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  • 2020-2024
  • 1995-1999  (201)
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  • 1999  (201)
  • breast cancer  (126)
  • nitrogen  (75)
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  • 2020-2024
  • 1995-1999  (201)
  • 1990-1994
  • 1920-1924
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  • 1
    Electronic Resource
    Electronic Resource
    Effects of Experimental Chemoendocrine Therapy With a Combination of a Pure Antiestrogen and 5-Fluorouracil on Human Breast Cancer Cells Implanted in Nude Mice (1999)
    Springer
    Surgery today 29 (1999), S. 149-156 
    Details
    ISSN: 1436-2813
    Keywords: Key Words: chemoendocrine therapy ; pure antiestrogen ; 5-fluorouracil ; nude mouse ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s005950050376
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of experimental chemoendocrine therapy with a combination of a pure antiestrogen and 5-fluorouracil on human breast cancer cells implanted in nude mice (1999)
    Springer
    Surgery today 29 (1999), S. 149-156 
    Details
    ISSN: 1436-2813
    Keywords: chemoendocrine therapy ; pure antiestrogen ; 5-fluorouracil ; nude mouse ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The antitumor effects of an experimental chemoendocrine therapy combining a new pure antiestrogen ICI 182780 and 5-fluorouracil (5-FU) were studied on MCF-7 human breast cancer cells implanted in nude mice. ICI 182780 had a dose-dependent antitumor activity, which was potentiated by the concomitant use of 5-FU. When compared with the control group, the estrogen receptor (ER) level in the ICI 182780 group was lower and that in the combination group was markedly lower. Cell cycle analysis by flow cytometry (FCM) resulted in a lower percentage of S-phase cells (%S) in the treated mice. No significant difference was observed in the 5-FU concentrations in tumor cells, while the 5-FU content in RNA was significantly higher in the combination group. The changes in free thymidylate synthetase (TS) concentration indicated TS synthesis after the administration of 5-FU to be more greatly suppressed in the combination group than in the 5-FU group. These results suggest that ICI 182780 and 5-FU exert their combination effect mainly on ER-positive cells, and that the suppression of TS synthesis in tumor cells and the potentiation of the 5-FU-induced metabolic dysfunction of RNA are thus involved in the mode of action of this combination therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02482240
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  • 3
    Electronic Resource
    Electronic Resource
    Compensatory responses of Samea multiplicalis larvae when fed leaves of different fertilization levels of the aquatic weed Pistia stratiotes (1999)
    Springer
    Entomologia experimentalis et applicata 92 (1999), S. 205-216 
    Details
    ISSN: 1570-7458
    Keywords: Samea multiplicalis ; Spodoptera pectinicornis ; Pistia stratiotes ; waterlettuce ; nitrogen utilization efficiency ; compensatory feeding ; nitrogen ; biological control of weeds
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Compensatory responses of caterpillars fed low quality food include increased consumption and utilization of essential nutrients. Information about an insect's responses to nutritional challenges from their host plants could benefit weed biological control efforts in the selection and establishment of new agents. The target weed, Pistia stratiotes L. (Araceae) is a floating aquatic plant that has relatively low nitrogen levels which are further diluted with high water content. Efforts to establish the insect Spodoptera pectinicornis (Hampson) (Lepidoptera: Noctuidae) for biological control of P. stratiotes could benefit by examining the nutritional responses of a similar widely established lepidopteran species, Samea multiplicalis (Guenèe) (Lepidoptera: Pyralidae). Larvae of this species were fed leaves of P. stratiotes plants that had been fertilized (NPK) at high and low rates. The leaves of the fertilized plants had a 4.3-fold increase in nitrogen (dry weight) and a 1.6-fold increase in water content. The results suggest that no compensatory increases occurred in larvae fed leaves from the low fertilized plants as no changes were found in fresh mass consumption or nitrogen utilization efficiency. Consequently, development time from second-third instars to pupation was delayed about 3 days compared with larvae fed the high nitrogen leaves. Furthermore, consumption of nitrogen was only 30% and its accumulation into larval tissues was only 60% compared with the larvae fed the high fertilized leaves. The resulting larvae had both a final biomass and a growth rate that were reduced by 40%. Regardless of plant fertilizer level, the larvae fed at a rate 5–10 times greater than that of similar lepidopteran species consuming either low or high quality diets, suggesting that the S. multiplicalis larvae may be functioning at their biological limit for ingesting food.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003771512722
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  • 4
    Electronic Resource
    Electronic Resource
    Plant quality or quantity? Host exploitation strategies in three Chrysomelidae species associated with Asteraceae host plants (1999)
    Springer
    Entomologia experimentalis et applicata 92 (1999), S. 165-177 
    Details
    ISSN: 1570-7458
    Keywords: Chrysomelidae ; herbivory ; Asteraceae ; life history ; nitrogen ; plant quality ; season
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Phytophagous insects which feed on the leaves of herbaceous host plants have to adapt their life histories to the fact that protein nitrogen is usually highest in growing tissues in spring. We monitored field populations of larvae and adults of three chrysomelid species (Galeruca tanaceti (L.) (main host Achillea millefolium (L.) Yarrow), Cassida rubiginosa (Mueller) (main host Cirsium arvense (L.) Scop.) and Oreina luctuosa (Suffrian) (host Centaurea scabiosa (L.)) together with the amount of protein nitrogen of their food resources and host plant biomass. As expected, the development of host quality, measured as concentration of protein nitrogen, and host plant biomass showed inverse trends during the season. The euryphagous G. tanaceti attacks Achillea early and profits from high nitrogen concentrations in the leaves. Occasional overexploitations of local populations of Achillea are compensated by the capacity to move to other host species. In C. rubiginosa, a species with a host range restricted to the Cardueae, the main larval feeding activity is postponed to a period when the nitrogen content of the host leaves had dropped to 50% of its initial value, but when host plant biomass had increased by 30%. In the monophagous O. luctuosa the larval development is synchronized with a still later phase of host phenology, at which the nitrogen content is below 50% but plant biomass has reached its maximum. There seem to be selection factors, which oppose the use of high quality food in spring and which force the latter two species to postpone their larval development to a later time in the year. This could be caused by numerous factors like, for example, mean daytime temperature. Later in the season the larvae have to cope with the low quality of their host plants. They have, however, the advantage of large quantities of food available. A laboratory study with adults and mature larvae of O. luctuosa shows that this species can overcome low levels of protein nitrogen either by selecting younger leaves with higher nitrogen concentrations or by increasing the daily food consumption rate (RCR) on leaves with a low level of nitrogen and by a prolongation of the feeding period. In this way the larvae compensate the effect of lower daily growth rates (RGR) and a lower food conversion index (ECI) on poor food quality: Regardless of the level of protein nitrogen there was no statistically significant difference in total gain of weight during the third-instar feeding period and in the weight at the end of the third larval stage. The three investigated chrysomelids show that there exists a broad spectrum of adaptations to overcome the dilemma of variable food quality.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003709622409
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  • 5
    Electronic Resource
    Electronic Resource
    Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older (1999)
    Springer
    Annals of oncology 10 (1999), S. 397-402 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; old age ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Older patients with advanced breast cancer are less likely to receive chemotherapy than younger patients. Vinorelbine is an attractive alternative in this setting because of its clinical activity and low frequency of side effects. This multicenter, phase II trial was designed to assess the safety and efficacy of intravenous vinorelbine as first-line therapy in women ≥60 years old. Patients and methods: Fifty-six women (median age, 72 years; range 60–84 years), with measurable advanced breast cancer and no prior chemotherapy for metastatic disease, were enrolled and included in the analysis. Vinorelbine 30 mg/m2 was administered weekly for 13 weeks and then every two weeks until development of progressive disease; doses were reduced or delayed to manage toxicity. Results: The objective response rate was 38% (95% confidence interval (95% CI): 24%–51%); median duration of response, nine months; median time to disease progression in all patients, six months. The major dose-limiting toxicity was hematologic, which led to a median dose intensity of 20.6 mg/m2/week. Grade 3–4 nonhematologic toxicity consisted of asthenia (7%); nausea and generalized pain (5%); vomiting, chest pain, abdominal pain, and elevated AST (4%); fever, diarrhea, constipation, and injection site reaction (2%). Neurotoxicity and alopecia were grade 1–2 and relatively infrequent. Conclusions: Vinorelbine offers a promising alternative for the management of advanced breast cancer in elderly patients who are concerned about the subjective side effects of cytotoxic chemotherapy. The dose-limiting toxicity is neutropenia, which is readily managed with dose adjustment. Nonhematologic toxicity, including gastrointestinal side effects, is minimal. Randomized studies are warranted to compare the activity of vinorelbine with that of other regimens in elderly patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008364222793
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  • 6
    Electronic Resource
    Electronic Resource
    FTIR spectroscopic evidence of formation of geminal dinitrogen species during the low-temperature N2 adsorption on NaY zeolites (1999)
    Springer
    Catalysis letters 58 (1999), S. 21-26 
    Details
    ISSN: 1572-879X
    Keywords: adsorption ; adsorption isotherms ; dinitrogen ; FTIR spectroscopy ; geminal species ; NaY ; nitrogen ; zeolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Adsorption of N2 on NaY zeolites at 85 K and equilibrium pressures higher than 1 kPa results in the formation of geminal dinitrogen complexes characterized by an IR band at 2333.5 cm−1 (2255.4 cm−1 after adsorption of 15N2). With decreasing equilibrium pressure the complexes tend to loose one N2 ligand, thus forming linear species characterized by an IR band at 2336.8 cm−1 (2258.7 cm−1 after adsorption of 15N2). All species disappear completely after evacuation. Co-adsorption of N2 and CO revealed that the dinitrogen complexes are formed on Na+ cations. The changes in the concentrations of the linear and geminal N2 species with the changes in the equilibrium pressure are excellently described by equations of adsorption isotherms proposed earlier for mono- and di-carbonyls.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1019040825491
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  • 7
    Electronic Resource
    Electronic Resource
    Pure and Binary Gas Adsorption Equilibria and Kinetics of Methane and Nitrogen on 4A Zeolite by Isotope Exchange Technique (1999)
    Springer
    Adsorption 5 (1999), S. 145-158 
    Details
    ISSN: 1572-8757
    Keywords: kinetics ; isotope-exchange ; nitrogen ; adsorption ; methane ; zeolite ; equilibria
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Physics , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Abstract The Isotope Exchange Technique (IET) was used to simultaneously measure pure and binary gas adsorption equilibria and kinetics (self-diffusivities) of CH4 and N2 on pelletized 4A zeolite. The experiment was carried out isothermally without disturbing the adsorbed phase. CH4 was selectively adsorbed over N2 by the zeolite because of its higher polarizability. The multi-site Langmuir model described the pure gas and binary adsorption equilibria fairly well at three different temperatures. The selectivity of adsorption of CH4 over N2 increased with increasing pressure at constant gas phase composition and temperature. This curious behavior was caused by the differences in the sizes of the adsorbates. The diffusion of CH4 and N2 into the zeolite was an activated process and the Fickian diffusion model described the uptake of both pure gases and their mixtures. The self-diffusivity of N2 was an order of magnitude larger than that for CH4. The pure gas self-diffusivities for both components were constants over a large range of surface coverages (0 〈 θ 〈 0.5). The self-diffusivities of CH4 and N2 from their binary mixtures were not affected by the presence of each other, compared to their pure gas self-diffusivities at identical surface coverages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008917308002
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  • 8
    Electronic Resource
    Electronic Resource
    Upregulation of basic fibroblast growth factor in breast carcinoma and its relationship to vascular density, oestrogen receptor, epidermal growth factor receptor and survival (1999)
    Springer
    Annals of oncology 10 (1999), S. 707-713 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; fibroblast growth factor ; microvasculature
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Angiogenesis, the process whereby endothelial cells divide and migrate to form new blood capillaries, has been assessed in tumours by measuring microvessel density. High microvessel density is a significant adverse prognostic factor in breast cancer. The angiogenic factor, basic fibroblast growth factor (bFGF), has been associated with tumourigenesis and metastasis in several human cancers. There are few quantitative studies of bFGF expression in normal tissues compared to cancer. Patients and methods: We have measured bFGF levels in 149 human primary breast carcinomas and assessed the findings in relation to microvessel density, oestrogen receptor (ER) and epidermal growth factor receptor (EGFR). Basic FGF levels were measured by ELISA. Western blotting and immunohistochemistry were carreid out to confirm the presence of bFGF. Results: Levels of bFGF were more than 10-fold higher in tumour cytosols compared to reduction mammoplasty tissue and 3-fold compared to non neoplastic cytosols from the same breast as the tumour (P 〈 0.0001). Immunohistochemistry showed bFGF protein was localised exclusively in the stroma whereas no bFGF staining was observed in the epithelial cells. High bFGF levels were significantly related to high ER (P = 0.01). Similarly, high bFGF levels were significantly related to low grade (P = 0.046) and to small tumour size (P = 0.04). No significant relationship was observed between bFGF and microvessel count, EGFR or age. In univariate analysis and in a Cox proportional hazard model bFGF did not reach significance for overall or relapse free survival. Conclusions: Our results show that although bFGF is elevated in breast carcinomas compared to normal breast tissue it is not related to microvessel density and it is not an independent predictor of survival in breast cancer patients. Basic FGF may be one of multiple factors that synergise with other growth factors such as VEGF to enhance angiogenesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008303614441
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  • 9
    Electronic Resource
    Electronic Resource
    ESTIC position paper: High-dose chemotherapy for breast cancer, investigation should continue (1999)
    Springer
    Annals of oncology 10 (1999), S. 903-905 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; high-dose chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008396811371
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  • 10
    Electronic Resource
    Electronic Resource
    The influence of familial and hereditary factors on the prognosis of breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1163-1170 
    Details
    ISSN: 1569-8041
    Keywords: BRCA1 ; BRCA2 ; breast cancer ; family history ; survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Family history is a well recognized risk factor for breast cancer, but its impact in terms of breast cancer survival is uncertain. The recent identification of breast cancer predisposing genes has provided new clinical insights in this field. Design: English literature identified through Medline between 1976 and February 1999 was reviewed including search terms: breast cancer, survival, prognosis, family history, genetics, BRCA1, BRCA2, and related articles. Results: Publications were divided into three categories.Family history-based studies: eighteen articles were reviewed. Four studies showed a statistically significant better survival in patients with a family history of breast cancer, and two studies demonstrated a significantly worse prognosis in this context. The remaining articles showed no significant difference. Linkage studies: Two studies based on linkage to BRCA1 found that overall survival was better in linked families. A third one concluded to a worse outcome in BRCA2-linked tumors. Mutation-based studies: 10 studies looking at the association between germ-line mutations in BRCA1/BRCA2 and clinical outcomes were reviewed. Eight articles reported no significant difference in outcome, whereas two studies showed a worse outcome in patients with mutations. Conclusions: Conflicting data exist as to whether the prognosis of familial or hereditary breast cancer differs from that of sporadic cases. Some of the discrepancies may be explained by methodological differences or biases. However, no studies showed a survival advantage for BRCA1mutation carriers. This seems to indicate that BRCA1-related breast cancer is not associated with a survival advantage, and that in fact, certain BRCA1 germline mutations confer a worse prognosis. However, to adequately answer this question, more efficient molecular tools to identify all the genetic changes responsible for breast cancer predisposition, and large cohort studies to evaluate their clinical consequences, are needed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008301314812
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  • 11
    Electronic Resource
    Electronic Resource
    Local relapse in primary breast cancer patients with unexcised positive surgical margins after lumpectomy, radiotherapy and chemoendocrine therapy (1999)
    Springer
    Annals of oncology 10 (1999), S. 1451-1455 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; chemotherapy ; margins ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates. To reduce this risk positive margins are, therefore, usually excised. Systemic treatment with tamoxifen or chemotherapy reduces local recurrence, along with radiotherapy. However, no studies to date have examined the correlation between chemoendocrine treatment, together with radiotherapy, and local relapse in patients with unexcised involved resection margins, having had breast conservation treatment. Patients and methods: The histopathology reports were reviewed of 184 patients who were treated from June 1991 to August 1995 within our randomised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate (2M) ± mitomycin-C (3M) and tamoxifen, used concurrently with radiation following conservation surgical treatment. Histological resection margin was considered positive if ductal carcinoma in situ (DCIS) or invasive carcinoma was present microscopically less than 1mm from the excision margin. Results: Although 38% of patients had unexcised microscopically involved margins, local relapse rate as first site of relapse was only 1.9% after a median follow up of 57 months. There was no difference in distant relapse (P = 0.2) and survival (P = 0.5) between the positive and negative margins groups. Conclusions: The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with radiotherapy. Further clinical trials are required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008371318784
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  • 12
    Electronic Resource
    Electronic Resource
    Docetaxel in the community setting: An analysis of 377 breast cancer patients treated with docetaxel (Taxotere®) in the UK (1999)
    Springer
    Annals of oncology 10 (1999), S. 205-210 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; docetaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Given as first- or second-line chemotherapy, docetaxel appears to have great potential in advanced breast cancer. Patients and methods: Three hundred and seventy-seven locally advanced or metastatic breast cancer patients received docetaxel (Taxotere®) as part of a named patient programme under the care of 108 oncologists from 61 cancer units across the UK. The recommended starting dose was 100 mg/m2, but patients at higher risk of toxicity started at 75 mg/m2. All patients received corticosteroid premedication. The modal number of prior chemotherapy regimens was 2 (range 1–7), 342 patients (91%) had at least one prior anthracycline-based regimen. Results: Response was graded according to the managing clinician's best judgement without formal criteria. The overall response rate (ORR) was 46% among the 331 evaluable patients, 46% among the 299 patients who were 'anthracycline resistant' and 35% among the 82 patients who were 'anthracycline refractory' (progressive disease being the best response obtained to the most recent anthracycline containing regimen). One hundred and ninety-three patients started at the full dose of 100 mg/m2 with an ORR of 55% and 129 started at 75 mg/m2 with an ORR of 33%. In October 1997, some two years after the programme had started, 26 of 377 patients were still alive, although no complete remissions have lasted to this date. Kaplan–Meier survival analysis yielded a median survival of 194 days (95% CI: 178–218 days). Haematological parameters were checked before each course of docetaxel and additionally as clinically indicated. The safety data confirmed that docetaxel has a manageable, predictable side effect profile; 29 of 377 (7.7%) patients were hospitalised as a result of neutropenic sepsis. Conclusions: The results of this named patient programme over a two year timespan confirm that docetaxel is an effective chemotherapy option in patients with locally advanced and/or metastatic breast cancer, including an 'anthracycline refractory' population.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008370930599
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  • 13
    Electronic Resource
    Electronic Resource
    Phase II study of epirubicin and vinorelbine with granulocyte colony-stimulating factor: A high-activity, dose-dense weekly regimen for advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 937-942 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; dose-intensity ; epirubicin ; G-CS/kwd〉 ; vinorelbine ; weekly schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This study was designed to explore the effectiveness and tolerability of a weekly regimen of epirubicin and vinorelbine plus granulocyte colony-stimulating factor (G-CSF). Patients and methods: Fifty-two patients with previously untreated advanced breast cancer were treated with epirubicin (25 mg/m2/week) and vinorelbine (25 mg/m2/week) with G-CSF support, for 24 consecutive weeks. Results: The median number of courses per patient was 22 (range 10–24). The administered dose intensity was 23 mg/m2 for both epirubicin and vinorelbine. Ten complete responses (19%) and 30 partial responses (58%) were obtained, for an overall response rate of 77%. None of the patients progressed during treatment. The median response duration and time to progression were both 10 months. A total of 1065 courses were assessed for toxicity. Grade 3 neutropenia was the most common toxic manifestation, (39% of patients), without febrile neutropenia or neutropenic sepsis. Two patients had grade 3 cardiac toxicity, which regressed without sequelae. Median survival was 31 months, with a median follow-up of 24 months (range 9–40). Conclusions: Owing to its effectiveness and tolerability, the weekly regimen of epirubicin and vinorelbine plus G-CSF may represent an acceptable alternative for patients with untreated metastatic breast cancer. It could be tested in the adjuvant and neoadjuvant setting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008324329562
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  • 14
    Electronic Resource
    Electronic Resource
    Paclitaxel by 24-hour infusion with doxorubicin by 48-hour infusion as initial therapy for metastatic breast cancer: Phase I results (1999)
    Springer
    Annals of oncology 10 (1999), S. 403-411 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; doxorubicin ; paclitaxel-anthracycline combination ; schedule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: We and others have demonstrated the antineoplastic efficacy of paclitaxel as a single agent in metastatic breast cancer. We performed this phase I trial to evaluate the combination of paclitaxel with doxorubicin. Patients and methods: Eligible patients had measurable or evaluable metastatic breast cancer for which this was the initial cytotoxic treatment. They may have received adjuvant chemotherapy with other drugs. The study had four parts. In part 1, the patients received paclitaxel by 24-hour infusion followed by doxorubicin by 48-hour infusion. The paclitaxel dose was to be escalated from a starting dose of 125 mg/m2, and the doxorubicin dose was to remain constant at 60 mg/m2 with treatment repeated every three weeks. The results of part 1 prompted part 2 which was a study of the reverse sequence. Part 3 was a formal study of pharmacology and has been reported (J Clin Oncol 14: 2713–21, 1996). In part 4, patients received doxorubicin 50 mg/m2 by bolus followed by paclitaxel 150 mg/m2 by 24-hour infusion for courses 1 and 2. In all subsequent courses doxorubicin was administered by 48-hour infusion. All patients in all four parts of the study had baseline cardiac scans. All patients received standard premedication for paclitaxel. Results: Forty-eight patients were treated in all four parts of the study. In part 1 (10 patients), the maximum tolerated dose (MTD) was paclitaxel 125 mg/m2/24 hours followed by doxorubicin 48 mg/m2/48 hours as defined by dose-limiting mucositis and neutropenic fever which occurred at the starting dose. For part 2 (21 patients), the MTD was doxorubicin 60 mg/m2/48 hours followed by paclitaxel 160 mg/m2/24 hours. In part 4 (seven patients), the MTD was doxorubicin 50 mg/m2/bolus followed by paclitaxel 135 mg/m2/24 hours. In parts 2 and 4, the dose-limiting toxic effect was neutropenia. Of the entire cohort of 48 patients, seven (15%) had a complete response (one persists at five years without intervening therapy), 26 (54%) had a partial response for an objective response rate of 69% (95% confidence interval (95% CI): 54%–81%). The median follow-up of all living patients is 38+ months (range 20+ to 62+); the median response duration is seven months (range 2–33.7+); the median overall survival is 20.5 months (range 5–54+). The median time to progression is 9.6 months (range 1–33.7+ months). Two patients developed congestive heart failure, one at 24 months after her final dose of doxorubicin which amounted to a cumulative lifetime total doxorubicin dose of 870 mg/m2, one after a total of 660 mg/m2. In both, cardiac symptoms were controlled with medications. Conclusions: The combination of paclitaxel/24 hours with doxorubicin/48 hours is an effective antineoplastic treatment for metastatic breast cancer. However, the incidence of complete response, the median overall survival, and time to progression were not greater than for standard doxorubicin-based combinations. Additionally, a sequence-dependent interaction between paclitaxel and doxorubicin, given in the schedule described here, was defined. Other strategies and schedules should be evaluated to maximize the antineoplastic efficacy of these two potent agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008360406322
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  • 15
    Electronic Resource
    Electronic Resource
    Primary chemotherapy in operable breast cancer with favorable prognostic factors: A pilot study evaluating the efficacy of a regimen with a low subjective toxic burden containing vinorelbine, 5-fluorouracil and folinic acid (FLN) (1999)
    Springer
    Annals of oncology 10 (1999), S. 993-996 
    Details
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; breast cancer ; neoadjuvant ; primary chemotherapy ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Biological considerations support the use of primary chemotherapy in operable breast cancer; and despite wide variations of used regimens, clinical studies consistently show a significant tumor response allowing breast conservation in many patients otherwise canditates for mastectomy. We investigated the efficacy and the acceptance of a combination chemotherapy with vinorelbine, 5-fluorouracil and high-dose folinic acid in operable breast cancer with favorable prognostic factors and tested the relationship of hormone receptor status, Ki67, p53, c-erbB2 and bcl-2 with treatment response. Patients and methods: Thirty-nine patients (median age 51 years, range 36–71 years), eight with T1, twenty-eight with T2 and two with T3 lesions, were treated with 5-fluorouracil (350 mg/m2, i.v. on day 1 to 3) preceded by folinic acid (100 mg/m2 i.v. on day 1 to 3) and vinorelbine, given on days 1 and 3 at the dose of 20 mg/m2 (FLN regimen). Therapy was administered on an outpatient basis every three weeks. Non responders had surgery after three courses, while complete or partial responders underwent surgery after six courses. All but one were evaluable for response and toxicity. Results: Objective responses were observed in 23 of the 38 evaluable patients (61%; 95% CI: 46%–76%): three complete responses (8%) and 20 partial responses (53%). Fifteen patients (39%) had stable disease, of whom nine (23%) had minor response. None of the patients had disease progression during treatment. Objective responses were significantly associated with no expression of estrogen and/or progesteron receptors and 〉50% decrease in Ki67 after induction chemotherapy. Tolerance was excellent and none of the patients experienced grade 2 alopecia. Conclusions: The ‘moderate’ efficacy of this regimen might be partially due to the selection of patients with high expression of steroid hormone receptors and low proliferation rate, which have an unfavorable impact on response to this chemotherapy.
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    URL: http://dx.doi.org/10.1023/A:1008389106575
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  • 16
    Electronic Resource
    Electronic Resource
    Cardiac effects of high-dose epirubicin and cyclophosphamide in women with poor prognosis breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 53-58 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cardiotoxicity ; cyclophosphamide ; epirubicin ; high dose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To prospectively evaluate the long term cardiac effects of high-dose epirubicin and cyclophosphamide given to women with early stage, poor prognosis breast cancer. Patients and methods: Women with stage 2 breast cancer and 10+ nodes or 4+ nodes and estrogen receptor negative tumor, or stage 3 breast cancer received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 gm/m2 with peripheral blood progenitor cell and filgrastim support. Treatment was given every 28 days (n = 79) or 21 days (n = 20). Fifty patients received radiotherapy to the chest wall or breast, 25 of to the left side. Patients were assessed clinically regularly during chemotherapy and at least three times yearly after completion of treatment. Cardiac left ventricular ejection fraction (LVEF) was assessed by radionuclide scan before therapy, after each cycle of chemotherapy, three months and six months after completion of chemotherapy, and yearly thereafter until relapse. Results: Ninety-nine women were treated, and 92 completed all three cycles of chemotherapy. The median age was 43 years (range 24 to 60 years). All patients were included in this analysis. The median relapse-free survival was 39 months (11 to 68 months). There was a significant fall in LVEF during chemotherapy. In general, there was no further deterioration in cardiac function from the third month after cessation of treatment, however there was substantial variation between individuals. 35 patients had at least one LVEF measure less than normal (〈50%), but the LVEF returned to normal in 20 of these with further follow-up. Cardiac dysfunction was not increased in women who received radiotherapy and was not different between cohorts given chemotherapy every three or every four weeks. One patient died of acute myocardial necrosis following the third cycle of chemotherapy. Two patients developed clinical evidence of cardiac failure, and another had radiological signs but was asymptomatic. One woman died of progressive cardiac failure, one recovered clinically but also developed recurrent breast cancer, while the third recovered after commencement of medical therapy. Conclusions: During follow-up after high-dose epirubicin and cyclophosphamide as delivered in this study, the LVEF fell to below normal in approximately one third of patients. However, in over half of these patients the LVEF subsequently recovered to the normal range, and the incidence of clinically evident chronic cardiac failure was low. Further follow-up is required to assess the long- term safety. A randomized comparison with standard-dose anthracycline-based chemotherapy is needed to determine whether this regimen is associated with an increased risk of clinical cardiac toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008390203340
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  • 17
    Electronic Resource
    Electronic Resource
    Effect of split applications of cattle slurry and mineral fertilizer–N on the yield of silage maize in a slurry-based cropping system (1999)
    Springer
    Nutrient cycling in agroecosystems 53 (1999), S. 209-218 
    Details
    ISSN: 1573-0867
    Keywords: cattle slurry ; fertilizer splitting ; nitrogen ; recovery ; residual nitrogen ; Zea mays L
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The recovery of soil mineral nitrogen (N) by crops, and its subsequent utilisation for dry matter (DM) production may be increased when the application of N is postponed until after crop emergence. The significance of this strategy for silage maize was studied in nine field experiments on Dutch sandy soils from 1983 to 1988. In five experiments the effect of slurry applied before planting at a rate of circa 66 m3 ha-1, was compared to the effect of a similar rate of which half was applied before planting and half at the 4–6 leaf stage. In the 4-6 leaf stage slurry was either injected or banded. In four other experiments the effect of mineral fertilizer-N splitting was studied. In these experiments, 30 m3 ha-1 cattle slurry, applied before planting, was supplemented with mineral fertilizer-N at rates ranging from 40 to 160 kg ha-1, either fully applied before crop emergence or split. When split, 40 kg ha-1 of the mineral fertilizer-N rate was banded at the 4–6 leaf stage. According to balance sheet calculations, substantial losses of slurry N and mineral fertilizer-N occurred during the growing season. Losses were compensated for, however, by apparent mineralization, ranging from 0.34 to 0.77 kg N ha-1 day-1. Split applications of cattle slurry had a significant positive effect on the DM yield in two out of five experiments compared to the conventional non-split application, but only when the post-emergence slurry application was banded which is no longer in accordance with present legislation. Split applications of mineral fertilizer-N had a significant positive effect in one experiment where rainfall was excessive but not in the others. The results provide insufficient evidence to recommend farmers to split applications. Soil mineral N sampling at the 4–6 leaf stage should hence be considered a control on the appropriateness of early N applications after exceptional weather conditions rather than a routine observation on which the post-emergence N dressing is to be based in a deliberate splitting strategy. Our data suggest that the financial return of a 40 kg ha-1 supplementation with mineral fertilizer-N, was questionable when more than 175 kg N ha-1 were found in the upper 0.6 m soil layer at the 4–6 leaf stage.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009796021850
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  • 18
    Electronic Resource
    Electronic Resource
    Using nitrogen budgets to indicate nitrogen use efficiency and losses from whole farm systems: a comparison of three methodological approaches (1999)
    Springer
    Nutrient cycling in agroecosystems 53 (1999), S. 259-267 
    Details
    ISSN: 1573-0867
    Keywords: farming systems ; nitrogen ; nitrogen budgets ; sustainability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Three approaches to nitrogen budgeting were developed and their ability to quantitatively describe nitrogen cycling in a fertilizer based and a grass–clover based beef system tested. Budgets ranged in complexity from the Economic Input:Output (EIO) budget, which accounted simply for purchases and sales of nitrogen over the farmgate, through the Biological Input:Output (BIO) budget, which included estimates of biological nitrogen fixation and attempted to partition losses into leaching and gaseous forms, to the Transfer:Recycle:Input:Output (TRIO) budget, which also accounted for key soil processes. Nitrogen unaccounted for in the fertilized system decreased with increasing budget complexity (285, 212 and 188 kg ha-1 yr-1 unaccounted for by the EIO, BIO and TRIO budgets, respectively). In the legume based grass–clover system, the EIO budget did not accurately describe total nitrogen inputs as it did not include 146 kg ha-1 yr-1 from symbiotic nitrogen fixation. In the grass–clover system, nitrogen unaccounted for was again greater using the BIO than the TRIO budget (103 and 79 kg ha-1 yr-1, respectively). In conclusion, the most complex budgeting approach (TRIO) was able to account for the fate of a greater proportion of nitrogen inputs than the simpler approaches. However, the perceived success of the different approaches was strongly dependent on the precise objective.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009793120577
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  • 19
    Electronic Resource
    Electronic Resource
    Nitrogen uptake and chlorophyll meter measurements in Spring Wheat (1999)
    Springer
    Nutrient cycling in agroecosystems 55 (1999), S. 1-6 
    Details
    ISSN: 1573-0867
    Keywords: chlorophyll meter ; irrigation ; LAI ; nitrogen ; Spring Wheat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract A Spring Wheat crop was grown using three irrigation levels and nitrogen rate applications to evaluate chlorophyll meter measurements as a possible nitrogen nutrition index for modelling. These measurements yielded the most reliable indications at Zadoks GS45. The lower limit indicating severe nitrogen deficiency in the leaves was approximately 35 SPAD units while the upper limit of 45 SPAD units, indicated an excess consumption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009843813004
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  • 20
    Electronic Resource
    Electronic Resource
    The fate of algal nitrogen in a flooded soil system (1999)
    Springer
    Nutrient cycling in agroecosystems 55 (1999), S. 89-94 
    Details
    ISSN: 1573-0867
    Keywords: algae ; flooded soils ; N cycling ; nitrogen ; 15N ; rice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Algal N labelled with 15N added to a flooded soil in laboratory columns without plants was studied to determine the changes over time in the fate of N assimilated by algae and to study how its fate is affected by (a) exclusion of light simulating complete closure of the rice canopy, and (b) addition of fertilizer-NH4 *. In the light but with no added fertilizer-N there was little net mineralization of the added algal N during the first 4 weeks, but after 8 weeks 42% had been mineralized, of which 95% was denitrified. Exclusion of light caused net mineralization to proceed more rapidly in the first 4 weeks due to the death of algal cells and lowered reassimilation. After 8 weeks 51% had been mineralized, of which 54% was denitrified, 16% volatilized and 30% was present as KCl exchangeable NH4 +-N. Application of fertilizer-NH4 + apparently caused mineralization of 25% of the algal N within one week but the results were probably affected by pool substitution in which labelled N mineralized to NH4 +-N was diluted with fertilizer – NH+ 4 and then immobilized leaving more labelled NH4–N in the mineral pool. After 8 weeks, 42% of algal N had been mineralized, of which 69% was estimated to have been denitrified, 19% lost through NH3 volatilization and 12% remained as extracted NH4 ++NO- 3. Uptake of N by a rice crop would reduce the gaseous losses. Algal N was mineralized quickly enough to be available during the growing season of a rice crop and, depending on field conditions, algae may have a role in assimilating N and protecting it from loss as well as being a major driving force for NH3 volatilization through diurnal increases in pH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009850915579
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  • 21
    Electronic Resource
    Electronic Resource
    Influence of Canopy Height and Fertilization Levels on the Resistance of Lycopersicon Hirsutum to Aculops Lycopersici (Acari: Eriophyidae) (1999)
    Springer
    Experimental and applied acarology 23 (1999), S. 633-642 
    Details
    ISSN: 1572-9702
    Keywords: tomato plants ; susceptibility ; mite ; tridecan-2-one ; nitrogen ; potasium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The objective of this work was to study the effect of NK fertilization levels and canopy height on the resistance of Lycopersicon hirsutum and Lycopersicon esculentum to Aculops lycopersici (Acari: Eriophydae). The effects of NK fertilization levels and canopy height in the leaf size and density of trichomes and their effects on tridecan-2-one (2-TD) and undecan-2-one (2-UD) limiting the attack of A. lycopersici on tomato plants were assessed. Different NK fertilization levels had no effect on the resistance of L. hirsutum to A. lycopersici. No significant differences were found in attack rates of this mite on leaves of the top and median parts of L. hirsutum canopy. The type and density of trichomes were the main determining factor of A. lycopersici attack on tomato plants. High trichome densities and type VI glandular trichomes which produce tridecan-2-one are important resistance factors on tomato plants. L. hirsutum showed a high resistance level to A. lycopersici due to high densities of type VI glandular trichomes and consequently higher levels of tridecan-2-one in its leaves.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006201915292
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  • 22
    Electronic Resource
    Electronic Resource
    Breast cancer screening by mammography in Norway. Is it cost- effective? (1999)
    Springer
    Annals of oncology 10 (1999), S. 197-203 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cost-effectiveness ; mammography ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Mammography screening is a promising method for improving prognosis in breast cancer. Patients and methods: In this economic analysis, data from the Norwegian Mammography Project (NMP), the National Health Administration (NMA) and the Norwegian Medical Association (NMA) were employed in a model for cost-effectiveness analysis. According to the annual report of the NMP for 1996, 60,147 women aged 50–69 years had been invited to a two-yearly mammographic screening programme. 46,329 (77%) had been screened and 337 (0.7%) breast cancers had been revealed. The use of breast conserving surgery (BCS) was in this study estimated raised by 17% due to screening, the breast cancer mortality decreased by 30% and the number of life years saved per prevented breast cancer death was calculated 15 years. Results: The cost per woman screened was calculated £75.4, the cost per cancer detected £10,365 and the cost per life year (LY) saved £8,561. A raised frequency of BCS, diagnosis and adjuvant chemotherapy brought two years forward, follow-up costs and costs/savings due to prevented breast cancer deaths were all included in the analysis. A sensitivity analysis documented mammography screening cost-effective in Norway when four to nine years are gained per prevented breast cancer death. Conclusion: Mammography screening in Norway looks cost- effective. Time has come to encourage national screening programmes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008376608270
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  • 23
    Electronic Resource
    Electronic Resource
    The third-generation non-steroidal aromatase inhibitors: A review of their clinical benefits in the second-line hormonal treatment of advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 377-384 
    Details
    ISSN: 1569-8041
    Keywords: anastrozole ; aromatase inhibitors ; breast cancer ; hormonal therapy ; letrozole ; review ; vorozole
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Three new aromatase inhibitors have recently completed phase III evaluation as treatment of metastatic breast cancer in post-menopausal women whose disease has progressed despite tamoxifen therapy: anastrozole (ARIMIDEX, Zeneca), letrozole (FEMARA, Novartis) and vorozole (RIVIZOR, Janssen). All belong to the third generation of non-steroidal aromatase inhibitors, and each is superior to previous generations in terms of potency and selectivity. The trials that have been performed compare each agent to megestrol acetate, and letrozole and vorozole to aminoglutethimide. Although the studies are not directly comparable due to differing study designs and patient populations, it has been demonstrated each of these drugs provides single agent, once-daily, oral palliation of hormone-responsive, post-menopausal metastatic breast cancer. Letrozole is clearly more effective than megestrol acetate, and anastrozole and vorozole are possibly so. All three are better tolerated than the progestin, particularly in terms of weight gain. Both letrozole and vorozole are significantly more effective, and better tolerated than aminoglutethimide. Overall, this most recent generation of aromatase inhibitors is a clear improvement on our current standard second-line therapies. In 1999, tamoxifen remains the first choice in the hormonal therapy of breast cancer. Following tamoxifen failure, the optimal second-line hormonal therapy remains undefined, but aminoglutethimide and megestrol acetate are no longer optimal therapy in this setting. The third-generation non-steroidal aromatase inhibitors must now be compared to each other, to the steroidal aromatase inhibitors, to the pure anti-oestrogens, and to tamoxifen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008368300827
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  • 24
    Electronic Resource
    Electronic Resource
    Synchronous inflammatory breast cancer and advanced ovarian carcinoma: A case with prolonged disease-free survival (1999)
    Springer
    Annals of oncology 10 (1999), S. 585-588 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cisplatin ; ovarian cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Despite the known association of these malignancies, the incidence of a synchronous presentation of breast and ovarian cancer is low, and the current literature does not address an approach to this clinical problem directly. We report a greater than 2.5 year disease-free survival in a patient treated for synchronous stage IIIB inflammatory breast cancer and stage IIIC epithelial ovarian cancer. The prolonged disease-free survival in our case may provide some guidance in this unusual clinical situation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008239124657
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  • 25
    Electronic Resource
    Electronic Resource
    Autologous stem-cell transplant after conventional dose adjuvant chemotherapy for high-risk breast cancer: Impact on the delivery of local-regional radiation therapy (1999)
    Springer
    Annals of oncology 10 (1999), S. 929-936 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; local regional therapy ; stem-cell transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: High-dose chemotherapy with autologous stem-cell transplantation is used increasingly in the treatment of poor-prognosis primary breast cancer. Because these patients may be cured with standard multimodality therapy, it is important to address both the efficacy of transplantation, and its effect on the delivery of standard treatments including local radiation therapy. Patients and methods: Patients with high risk primary breast cancer were treated with high-dose cyclophosphamide and thiotepa and stem-cell transplant following surgery and conventional-dose adjuvant chemotherapy. Outcome, including sites of failure and delivery of local radiation therapy, was assessed for 103 patients. Results: Overall and disease-free survival rates at 18 months were 83% (± 4%) and 77% (± 4%) respectively. Twenty patients (19.4%) received radiation therapy prior to transplant. Of the remaining 83, 77 received radiation therapy after transplant. Overall, 5 (19.2%) of 26 first sites of recurrence were local alone. For patients receiving radiation prior to transplant, 3 of 7 (43%, 95% CI: 6%–80%) sites of first recurrence were local, while 2 of 19 (10.5%, 95% CI: 0%–24.5%) sites of first recurrence were local alone in patients receiving post-transplant radiation or no radiation. Conclusion: Transplantation does not appear to significantly compromise the delivery or outcome of local radiation therapy for primary breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008393204854
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  • 26
    Electronic Resource
    Electronic Resource
    Adjuvant Therapy of Breast Cancer: Update (1999)
    Springer
    Annals of oncology 10 (1999), S. 129-137 
    Details
    ISSN: 1569-8041
    Keywords: adjuvant treatment ; breast cancer ; systemic therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The theoretical prediction that breast cancer is a systemic disease, and that patients may benefit from addition of systemic therapy to local treatment, has now been confirmed by three decades of clinical investigations. A long-term follow up of individual trials and the International Overview based on meta-analyses clearly showed the potential of both hormonal therapies and chemotherapy to prolong disease-free and overall survival in nearly all groups of patients. The benefits have been demonstrated for both premenopausal and postmenopausal patients, with both node-negative and node-positive disease. However, there is still considerable uncertainty regarding the most appropriate treatment for each individual patient. In the present review, the results of meta-analysis are highlighted in the context of the new trials supporting the value of chemoendocrine therapy and anthracycline-based therapy. The results of prospective randomised trials evaluating the role of dose intensification, drug sequencing and dose density are discussed. Also presented are new treatment strategies, such as preoperative chemotherapy and high-dose chemotherapy with stem cell support, the value of which remains to be confirmed. Future possibilities opened by inclusion of biologics into adjuvant therapy are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008362521127
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  • 27
    Electronic Resource
    Electronic Resource
    New Developments in Chemotherapy of Advanced Breast Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 139-146 
    Details
    ISSN: 1569-8041
    Keywords: anthracycline ; breast cancer ; chemotherapy ; HER-2 antibody ; N,N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-217380-01) ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anthracyclines and taxanes are the two most active classes of chemotherapy for the treatment of advanced breast cancer. Recent studies have investigated combination therapy including doxorubicin (Dox) and paclitaxel. The efficacy of this combination has been established in a phase III study conducted by ECOG, comparing Dox/paclitaxel versus Dox versus paclitaxel. The combination is superior to Dox or paclitaxel with respect to response rate and time to disease progression, indicating that the combination provides a new standard for the first line treatment of metastatic breast cancer [1]. Phase II studies using higher doses of Dox and using shorter infusions of paclitaxel have suggested the combination can be further optimised; Gianni reported a 94% objective response rate using Dox 60 mg/m2 followed by paclitaxel 175 mg/m2 given over three hours [2]. The more active regimens are associated with enhanced cardiotoxicity; this toxicity can be avoided, however, by limiting the exposure to doxorubicin. The newer regimens have now been moved into phase III studies. Future progress for this disease will depend on the introduction of new agents. Two novel drugs are currently being investigated in randomised phase III trials as potentiators of Dox and/or paclitaxel. One is a monoclonal antibody from Genentech (Herceptin, trastuzumab) directed at the HER-2/neu oncogene, which is overexpressed in 〉25% of breast cancers [3]. Recent results indicate that Herceptin in combination with paclitaxel (or with a Dox plus cyclophosphamide regimen) induces a higher response rate (RR) and prolongs the time to disease progression when compared to chemotherapy alone. The second agent N,N-diethyl-2[4-(phenylmethyl)-phenoxyl] ethanamine.HCl (DPPE, BMS-217380-01), when combined with Dox, was associated with a higher RR than previously observed with Dox alone [4]. A randomised trial of Dox versus Dox plus DPPE is ongoing. The possible mechanisms underlying chemo-potentiation by these agents are discussed. As new anthracycline/taxane combinations establish themselves in earlier stages of the disease, the need for effective, non-cross resistant salvage regimens will emerge.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008318725670
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  • 28
    Electronic Resource
    Electronic Resource
    Cowden disease and Lhermitte Duclos disease, markers of breast carcinoma: Report of two patients (1999)
    Springer
    Annals of oncology 10 (1999), S. 1241-1243 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; Cowden disease ; Lhermitte Duclos
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008317923860
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  • 29
    Electronic Resource
    Electronic Resource
    A randomized, open, parallel-group trial to compare the endocrine effects of oral anastrozole (Arimidex®) with intramuscular formestane in postmenopausal women with advanced breast cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 1219-1225 
    Details
    ISSN: 1569-8041
    Keywords: anastrozole ; Arimidex® ; aromatase inhibitor ; breast cancer ; formestane ; oestradiol ; tolerability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: This study provides a direct randomized comparison of a new-generation, non-steroidal aromatase inhibitor, anastrozole (Arimidex®), with a steroidal aromatase inhibitor (formestane) with respect to oestrogen (oestradiol, oestrone, and oestrone sulphate) suppression and tolerability. Patients and methods: Sixty postmenopausal women with advanced breast cancer were randomized to receive either anastrozole 1 mg once daily orally (n = 29), or formestane 250 mg once every two weeks by intramuscular injection (n = 31). Treatment was continued until progression of disease or withdrawal from the study. The primary endpoints of this study were oestradiol suppression and tolerability. The secondary endpoints included oestrone and oestrone sulphate suppression. All laboratory analyses were conducted ‘blind’ of the randomized drug treatment. Results: Anastrozole produced a greater and more consistent suppression of oestradiol levels compared with formestane. Based on two- and four-week measurements, the mean fall from baseline (pre-dose) in oestradiol level was 79% and 58% in the anastrozole and formestane groups, respectively (P = 0.0001). After four weeks of treatment, oestrone and oestrone sulphate levels were also suppressed to a greater extent by anastrozole compared with formestane (oestrone: 85% versus67%, respectively, P = 0.0043; oestrone sulphate: 92% versus 67%, respectively, P = 0.0007). No statistical differences were seen between the two drugs in the incidence of adverse events. Conclusions: Anastrozole provides a more consistent and significantly more effective suppression of oestradiol compared with formestane. Similar results were observed for oestrone and oestrone sulphate. The clinical significance of these differences in total oestrogen suppression remains to be established.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008308609325
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  • 30
    Electronic Resource
    Electronic Resource
    Screening Mammography for Early Detection of Breast Cancer (1999)
    Springer
    Annals of oncology 10 (1999), S. 121-127 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; mammography ; prevention ; screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract From numerous studies on breast cancer it can be concluded that no single measure can lessen the burden of this frequent cancer in women in all developed countries. Complex strategies including primary prevention by identification of risk factors and their modification, secondary prevention by earlier detection and tertiary prevention by improving treatment outcome are needed to control the disease. Besides age, the established breast cancer risk factors include certain benign breast diseases, family history, ionising radiation, some reproductive factors and obesity. Primary prevention includes general recommendation for healthy lifestyle, e.g., avoidance of obesity, proper diet, physical activity and moderate alcohol consumption. Randomised controlled trials conducted in the USA, Canada, Scotland and Sweden have shown that regular mammography, alone or in combination with clinical examination, is effective in reducing mortality for about 30% in women over the age of 50, and much less in younger population. However, mammography screening has several drawbacks, the major being its tendency towards false positive and false negative results with all their potential psychosocial consequences. High quality assurance and control, as well as effective and readily available treatment, all of which demand high investments, are indispensable for good results. Even in the absence of organised screening, the availability of effective treatment may contribute to reduction in breast cancer mortality.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008310503380
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  • 31
    Electronic Resource
    Electronic Resource
    Cytomegalovirus pneumonia in a patient with breast cancer on chemotherapy: Case report and review of the literature (1999)
    Springer
    Annals of oncology 10 (1999), S. 461-465 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; cytomegalovirus pneumonia ; dexamethasone ; ganciclovir ; standard dose chemotherapy regimen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cytomegalovirus (CMV) pneumonia in the setting of non-transplantation patients is a rarity. We present a case of CMV pneumonitis in a woman with stage IV breast cancer, with brain metastases, receiving both chemotherapy and systemic corticosteroids. A review of the literature reveals this as a unique case. Potential viral etiologies should therefore be considered in cancer patients with pneumonia receiving non-transplantation chemotherapy-regimens, particularly if steroids are a component of their therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008360927507
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  • 32
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    Electronic Resource
    Front-line treatment of metastatic breast cancer with docetaxel and epirubicin: A multicenter dose-escalation study (1999)
    Springer
    Annals of oncology 10 (1999), S. 547-552 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; docetaxel ; epirubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: To determine the maximum tolerable dose (MTD) and the dose-limiting toxicity (DLT) of docetaxel (D) in combination with epirubicin (Epi) in patients with advanced breast cancer. Patients and methods: Forty-seven chemotherapy-naïve metastatic breast cancer patients aged 〈75 years with PS (WHO) 0–2 and adequate bone marrow, renal, liver and cardiac function, were enrolled in the study. Epi was given as a five-min bolus i.v. infusion on day 1 (d1) in escalated doses with increments of 10 mg/m2; D was given in a one-hour infusion after appropriate premedication on either day 1 or on day 2 in escalated doses with increments of 10 mg/m2. The patients' median age was 60 years, 42 (89%) had a PS (WHO) 0–1, 16 (34%) were premenopausal and 25 (53%) had visceral disease. Results: When the two drugs were given on the same day, the MTD1 was reached at the doses of Epi 60 mg/m2 and D 80 mg/m2; administration of G-CSF could not result in a dose intensification. When the drugs were given on two consecutive days, the MTD2 was reached at the doses of Epi 80 mg/m2 (d1) and D 90 mg/m2 (d2). The dose-limiting events were febrile neutropenia and grade 4 neutropenia, which developed in 30 (64%) patients during the study; among 227 delivered cycles grade 3–4 neutropenia occurred in 64 (28%) cycles but only 22 (10%) of them were complicated by fever. There were no septic deaths. Grade 1–2 neurosensory toxicity occurred in nine (19%) patients, mild edema in eight (17%) and allergic reactions in five (11%). Four (9%) patients presented a greater than 10% decrease of LVEF and treatment discontinuation was required in two of them; none of the patients developed congestive heart failure. Nevertheless, one patient suddenly died 10 days after treatment initiation of myocardial ischemia, and this death is considered treatment-related. Five (14.7%) complete and thirteen (38.2%) partial responses (ORR: 53.9%; 95% confidence interval: 36.1%–69.7%) were observed in 34 evaluable patients. Ten (29.4%) and six (17.6%) patients had stable and progressive disease, respectively. The median duration of response and time to tumor progression were five and seven months, respectively. The median survival has not yet been reached. Conclusions: The combination of epirubicin and docetaxel is a feasible and well tolerated regimen, but the MTD depends on the administration schedule of the drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026441804889
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  • 33
    Electronic Resource
    Electronic Resource
    Depression in breast cancer patients: The need for treatment (1999)
    Springer
    Annals of oncology 10 (1999), S. 627-636 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; depression ; diagnosis ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008328005050
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  • 34
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    Electronic Resource
    A phase I study of sequential vinorelbine followed by paclitaxel (1999)
    Springer
    Annals of oncology 10 (1999), S. 861-863 
    Details
    ISSN: 1569-8041
    Keywords: breast cancer ; paclitaxel ; phase I ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: In vitro experiments suggest that administration of vinorelbine preceding paclitaxel results in synergistic cytotoxic effects. A phase I dose escalation trial of vinorelbine daily × 3 with paclitaxel on day 3 repeated every 28 days in metastatic breast cancer patients was completed. Patients and methods: Female patients, PS 0–2, without evidence of CNS disease or prior neuropathies were treated with vinorelbine at dose levels 7, 10, 13 mg/m2 per day and paclitaxel over three hours at dose levels of 135, 175, and 200 mg/m2. Results: Twenty-eight patients with six dose levels were studied. At dose level 1, patients developed intolerable but reversible neutropenia. Subsequent dose levels required filgrastim. Dose limiting toxicities were myalgia and fatigue at vinorelbine 13 mg/m2 /day and paclitaxel 200 mg/m2. Neuropathy was minor. Twelve of twenty-five patients with measurable disease had a rapid response which did not correlate with dose level. Conclusions: Sequential administration of these two agents demonstrates activity in breast cancer patients. Phase II dosing on this schedule should be vinorelbine 13 mg/m2/day × 3 and paclitaxel 175 mg/m2. With proper selection of patients, concern about neurologic toxicity should not impede future trials of vinorelbine with paclitaxel.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008351915582
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  • 35
    Electronic Resource
    Electronic Resource
    Ala99ser mutation in RIα Regulatory Subunit of protein kinase A causes reduced kinase activation by cAMP and arrest of hormone-dependent breast cancer cell growth (1999)
    Springer
    Molecular and cellular biochemistry 195 (1999), S. 77-86 
    Details
    ISSN: 1573-4919
    Keywords: protein kinase A ; site-directed mutagenesis ; breast cancer ; growth arrest ; cAMP response element
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Expression of the RIα regulatory subunit of protein kinase A type I is increased in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. Ala99 (the pseudophosphorylation site) of human RIα was replaced with Ser (RIα-p) for the structure-function analysis of RIα. MCF-7 hormone- dependent breast cancer cells were transfected with an expression vector for the wild-type RIα or mutant RIα-p. Overexpression of RIα-P resulted in suppression of protein kinase A type II, the isozyme of type I kinase, production of kinase exhibiting reduced cAMP activation, and inhibition of cell growth showing an increase in G0/G1 phase of the cell cycle and apoptosis. The wild-type RIα overexpression had no effect on protein kinase A isozyme distribution or cell growth. Overexpression of protein kinase A type II regulatory subunit, RIIβ, suppressed RIα and protein kinase A type I and inhibited cell growth. These results show that the growth of hormone-dependent breast cancer cells is dependent on the functional protein kinase A type I.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006934113439
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  • 36
    Electronic Resource
    Electronic Resource
    Agonist and antagonist-induced qualitative and quantitative alterations of progesterone receptor from breast cancer cells (1999)
    Springer
    Molecular and cellular biochemistry 199 (1999), S. 49-56 
    Details
    ISSN: 1573-4919
    Keywords: progesterone receptor ; breast cancer ; steroid receptor agonists ; antagonists ; T47D cells ; RU486
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract T47D cells, cultured in medium containing serum stripped of endogenous steroids, proliferate in response to treatment with the progesterone receptor (PR) agonist, R5020 or the PR agonist/antagonist, RU486, whereas the full PR antagonist, ZK98299 has no proliferative effects. Under estrogenized conditions, all of the PR ligands tested inhibit cell growth [23]. In order to determine whether the levels or phosphorylation state of PR are reflected in the growth patterns of T47D cells, we monitored the effects of these PR ligands on the immunoblotted PR band intensities, the relative intensities, of PR-A and PR-B, and their phosphorylation states that are reflected in their altered mobility during SDS-PAGE. Under conditions where the PR ligands inhibit cell proliferation, each ligand had distinctively different qualitative and quantitative effects on PR. Short term treatment of the cells with R5020 or RU486 induced a characteristic phosphorylation-dependent upshift of both PR-A and PR-B. The phosphorylated PR was stable for up to 4 days after treatment of the cells with RU486, but was down regulated between 6-24 h after treatment with R5020. No replenishment of PR in cells treated with R5020 was detected. ZK98299, at concentrations tested, had no qualitative or quantitative effects on PR. Culturing cells for 8 days in medium containing steroid-depleted serum caused a significant reduction in the PR band intensity without causing a change in the ratio of PR-A and PR-B or their phosphorylation states. This decrease in the PR band intensity was reversed by maintaining the cells in 1 nM estrogen, but was potentiated by RU486 or ZK98299. These observations support the view that decreased PR levels may play a role in the stimulatory effects of R5020 and RU486 when cells are cultured under non-estrogenized conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006982528297
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  • 37
    Electronic Resource
    Electronic Resource
    Nitrogen Addition to an O-1 Tool Steel (1999)
    Springer
    Journal of materials synthesis and processing 7 (1999), S. 311-319 
    Details
    ISSN: 1573-4870
    Keywords: Iron ; carbon ; nitrogen ; microstructure ; characterization ; HIP-drip
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Abstract A new processing technique makes nitrogen alloying possible by adding nitrogen under elevated nitrogen pressure to prealloyed Fe-C ingots during continuous casting, producing a whole new class of precipitation-free, iron–carbon–nitrogen alloys. When both carbon and nitrogen bulk concentration levels exceeded 0.5 wt%, a duplex fcc-/(bcc-bct-) Fe microstructure resulted that is iron carbide- and nitride-free. With increasing carbon and nitrogen concentrations, there was an increase in the retained fcc-Fe phase. In cooling rate studies, increasing carbon and nitrogen concentrations shifted the knee of the fcc-Fe-to-bcc-Fe phase time–temperature–transformation (T–T–T) curve to longer times. Hardness, compression strength, and wear resistance increased with increasing carbon and nitrogen concentrations and were superior to iron–carbon alloys without the nitrogen addition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1021877121902
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  • 38
    Electronic Resource
    Electronic Resource
    Effects of antiprogestins on the rate of proliferation of breast cancer cells (1999)
    Springer
    Molecular and cellular biochemistry 198 (1999), S. 141-149 
    Details
    ISSN: 1573-4919
    Keywords: T47D cells ; breast cancer ; cellular proliferation ; progesterone ; estradiol ; steroid receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract We have examined the influence of progestins (progesterone, R5020) and antiprogestins (RU486, ZK98299, Org 31710 and Org 31806) on the rate of proliferation of wild type T47D cells cultured in whole fetal bovine serum (FBS) or in single charcoal stripped fetal bovine serum (SSFBS). All of the progesterone antagonists RU486, ZK98299 and two novel antiprogestins Org 31710 and Org 31806 inhibited cell proliferation when cells were cultured in FBS. In contrast, all of the antiprogestins with the exception of ZK98299 enhanced cell growth when cells were cultured in SSFBS. This stimulatory effect of RU486 was observed only at a high concentration of the ligand (1 μM). The effect of R5020, however, was concentration independent. The number of cells in the presence of RU486 was ~ 600% followed by R5020 ~ 400% above control values after a 28 day culturing period. In contrast, when the cells were grown in the presence of medium containing non-stripped whole serum, RU486 inhibited the extent of cell proliferation by 45%. Estradiol (E2) stimulated the rate of proliferation in cells cultured in SSFBS. Similar to when cells were cultured in whole serum, the antiprogestins inhibited cell growth in E2-supplemented SSFBS. Detection of the growth enhancement effects of progesterone receptor (PR) ligands such as RU486 and R5020 on the cells grown in charcoal-stripped medium appear to require the removal of E2 by charcoal stripping of the serum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006945813508
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  • 39
    Electronic Resource
    Electronic Resource
    Improving the field performance of micro-and minitubers (1999)
    Springer
    Potato research 42 (1999), S. 559-568 
    Details
    ISSN: 1871-4528
    Keywords: plastic mulch ; transplanting ; nitrogen ; planting depth ; seed tuber weight ; physiological age ; radiation conversion efficiency ; harvest index
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary In many seed potato producing areas, micro- and minitubers are too small for direct planting as seed tubers in the field. Such use of these propagules can, however, be feasible if the crop's growth and development can be advanced. Increasing light interception, harvest index and yield of useable progeny tubers has been proved possible with plastic mulch and pre-planting of small tubers in a greenhouse. High amounts of nitrogen (up to 180 kg ha−1) or deep planting (up to 9 cm) were less effective. Using older or pre-sprouted micro- or minitubers may be beneficial, because this might increase the number of sprouts per mother tuber (and thus stems per plant) or advance the growth of sprouts or stems. However, this would require even more careful management, due to the weakness of these sprouts and stems. Micro- and minitubers should be as large as feasible when used for direct planting in the field.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02358172
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  • 40
    Electronic Resource
    Electronic Resource
    Retention of nutrients in river basins (1999)
    Springer
    Aquatic ecology 33 (1999), S. 29-40 
    Details
    ISSN: 1573-5125
    Keywords: denitrification ; nature restoration ; nitrogen ; phosphorus ; riparian areas ; sedimentation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In Denmark, as in many other European countries, the diffuse losses of nitrogen (N) and phosphorus (P) from the rural landscape are the major causes of surface water eutrophication and groundwater pollution. The export of total N and total P from the Gjern river basin amounted to 18.2 kg ha−1 and 0.63 kg P ha−1 during June 1994 to May 1995. Diffuse losses of N and P from agricultural areas were the main nutrient source in the river basin contributing 76% and 51%, respectively, of the total export. Investigations of nutrient cycling in the Gjern river basin have revealed the importance of permanent nutrient sinks (denitrification and overbank sedimentation) and temporary nutrient storage in watercourses. Temporary retention of N and P in the watercourses thus amounted to 7.2–16.1 g N m−2 yr−1 and 3.7–8.3 g P m−2 yr−1 during low-flow periods. Deposition of P on temporarily flooded riparian areas amounted from 0.16 to 6.50 g P m−2 during single irrigation and overbank flood events, whereas denitrification of nitrate amounted on average to 7.96 kg N yr−1 per running metre watercourse in a minerotrophic fen and 1.53 kg N yr−1 per linear metre watercourse in a wet meadow. On average, annual retention of N and P in 18 Danish shallow lakes amounted to 32.5 g N m−2 yr−1 and 0.30 g P m−2 yr−1, respectively, during the period 1989–1995. The results indicate that permanent nutrient sinks and temporary nutrient storage in river systems represent an important component of river basin nutrient budgets. Model estimates of the natural retention potential of the Gjern river basin revealed an increase from 38.8 to 81.4 tonnes yr−1 and that P-retention increased from −0.80 to 0.90 tonnes yr−1 following restoration of the water courses, riparian areas and a shallow lake. Catchment management measures such as nature restoration at the river basin scale can thus help to combat diffuse nutrient pollution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009947907811
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  • 41
    Electronic Resource
    Electronic Resource
    Variation in nutrient availability and plant species diversity across forb and graminoid zones of a Northern New England high salt marsh (1999)
    Springer
    Plant ecology 143 (1999), S. 219-228 
    Details
    ISSN: 1573-5052
    Keywords: mineralization ; nitrogen ; phosphorus ; salinity ; stress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Plant zonation patterns across New England salt marshes have been investigated for years, but how nutrient availability differs between zones has received little attention. We investigated how N availability, P availability, and plant N status varied across Juncus gerardii, Spartina patens, and mixed forb zones of a Northern New England high salt marsh. We also investigated relationships between several edaphic factors and community production and diversity across the high marsh. P availability, soil salinity, and soil moisture were higher in the mixed forb zone than in the two graminoid zones. NH+ 4-N availability was highest in the J. gerardii zone, but NO− 3-N availability and mid season net N mineralization rates did not vary among zones. Plant tissue N concentrations were highest in the mixed forb zone and lowest in the S. patens zone, reflecting plant physiologies more so than soil N availability. Community production was highest in the J. gerardii zone and was positively correlated with N availability and negatively correlated with soil moisture. Plant species diversity was highest in the mixed forb zone and was positively correlated with P availability and soil salinity. Thus, nutrient availability, plant N status, and plant species diversity varied across zones of this high marsh. Further investigation is needed to ascertain if soil nutrient availability influences or is a result of the production and diversity differences that exist between vegetation zones of New England high salt marshes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009887727465
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  • 42
    Electronic Resource
    Electronic Resource
    Denitrification in coastal ecosystems: methods, environmental controls, and ecosystem level controls, a review (1999)
    Springer
    Aquatic ecology 33 (1999), S. 41-54 
    Details
    ISSN: 1573-5125
    Keywords: denitrification ; eutrophication ; estuary ; nitrogen ; sediment-water exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In this review of sediment denitrification in estuaries and coastal ecosystems, we examine current denitrification measurement methodologies and the dominant biogeochemical controls on denitrification rates in coastal sediments. Integrated estimates of denitrification in coastal ecosystems are confounded by methodological difficulties, a lack of systematic understanding of the effects of changing environmental conditions, and inadequate attention to spatial and temporal variability to provide both seasonal and annual rates. Recent improvements in measurement techniques involving 15 N techniques and direct N2 concentration changes appear to provide realistic rates of sediment denitrification. Controlling factors in coastal systems include concentrations of water column NO 3 − , overall rates of sediment carbon metabolism, overlying water oxygen concentrations, the depth of oxygen penetration, and the presence/absence of aquatic vegetation and macrofauna. In systems experiencing environmental change, either degradation or improvement, the importance of denitrification can change. With the eutrophication of the Chesapeake Bay, the overall rates of denitrification relative to N loading terms have decreased, with factors such as loss of benthic habitat via anoxia and loss of submerged aquatic vegetation driving such effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009921414151
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  • 43
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    Electronic Resource
    Toward Checkmate: Biology and Breast Cancer Therapy for the New Millennium (1999)
    Springer
    Investigational new drugs 17 (1999), S. 417-427 
    Details
    ISSN: 1573-0646
    Keywords: breast cancer ; growth factors ; metalloproteinase ; angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract A better understanding of the biology of breast cancer should leadto the rational development of new treatments and the ability tocustomize therapy for individual patients. Though promising intheory, translating advances in biological knowledge to the clinichas been difficult. Recently several areas of research haveproduced treatments which have entered clinical trials; three willbe reviewed here. The growth of breast cancer is regulated bygrowth factors and their receptors; amplification or overexpressionis associated with poor prognosis. As such inhibition of growthfactors and/or growth factor receptors may provide an idealtherapeutic target. Herceptin binds to c-erbB-2, a member of theepidermal growth factor receptor family. Significant responses wereseen in patients with c-erbB-2 overexpressing breast cancer withHerceptin administered as a single agent or in combination withchemotherapy. Herceptin was approved by the Food and DrugAdministration in late 1998. Breast cancer invasion and metastasisrequires degradation of the surrounding basement membrane by matrixmetalloproteinases and other proteolytic enzymes. Syntheticinhibitors of these enzymes are now in clinical trials. Breastcancers must stimulate angiogenesis, the growth of new bloodvessels, in order to grow beyond a few millimeters in diameter.This nascent vascular network provides another opportunity fortherapy. Preclinical models support the critical role ofangiogenesis and the therapeutic benefit of angiogenesisinhibition; clinical trials are underway.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006311227965
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  • 44
    Electronic Resource
    Electronic Resource
    Effect of meteorology and nutrient load on oxygen depletion in a Danish micro-tidal estuary (1999)
    Springer
    Aquatic ecology 33 (1999), S. 55-64 
    Details
    ISSN: 1573-5125
    Keywords: estuaries ; nitrogen ; oxygen depletion ; phosphorus ; regression model ; vertical mixing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In a detailed analysis of oxygen saturation in a shallow Danish estuary it was possible to separate the effect of meteorological forcings (i.e. wind and solar radiation) and nutrient loads on oxygen depletion in bottom water. Regression analysis showed that oxygen saturation tied to nitrogen load rather than to phosphorus load. During summer periods of stratification the oxygen saturation could be attributed to the time elapsed after the onset of stratification and the accumulated nitrogen loading 10 month prior to measurement. Using a 10-year meteorological database and an empirical model it was calculated that a 25% reduction in nitrogen loading would reduce the number of days with severe oxygen depletion (i.e. 〈15% of saturation) by more than 50%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1009956210537
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  • 45
    Electronic Resource
    Electronic Resource
    Evaluation of seprase activity (1999)
    Springer
    Clinical & experimental metastasis 17 (1999), S. 67-72 
    Details
    ISSN: 1573-7276
    Keywords: breast cancer ; extracellular matrix ; gelatinase ; invasion ; matrix metalloproteinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Seprase is a serine protease that is integral to the plasma membrane and is overexpressed by invasive tumor cells (Piñeiro-Sánchez et al., J Biol Chem 1997; 272: 7595–601; Monsky et al., Cancer Res 1994; 54: 5702–10). Seprase activity is most often assessed by zymography, which is not a quantitative assay. This study establishes a relatively simple and quantitative method for determining seprase activity. The degradation of a 3H-gelatin substrate is measured in the presence of 5 mM EDTA which inhibits matrix metalloproteinases but not seprase. The quantitative character of the assay was demonstrated using partially purified seprase from chicken embryos, a preparation that lacks detectable matrix metalloproteinase activity. In this assay, release of 3H-gelatin fragments is linear over time for 1.5 μg/assay seprase concentration as well as for preparations concentrated or diluted by five fold (7.5 μg/assay and 0.3 μg/assay respectively). Additional experiments were performed to validate the quantification of seprase activity using the radiographic assay by comparing the results to zymography. Exposure to 22 or 37 °C results in maximal seprase activity while exposure to 80 or 100 °C completely abolishes seprase activity in both zymography and the radiographic assay. Exposure to 60 °C abolished seprase activity as judged by zymography, but about 50% gelatinase activity was observed using the 3H-gelatin substrate. Immunopreciptiation with seprase-specific antibody specifically removed seprase and lowered the seprase activity remaining in the extracts as judged by both assays. Investigation of the seprase that was partially purified from human breast cancer tissue revealed that its specific activity (cpm gelatin fragments released/ {mg protein×h}) is five times greater than that of seprase purified from chicken embryos. This assay will be useful for determining the seprase activity in extracts of tumor tissues and cells as well as for identifying inhibitors of seprase.
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    URL: http://dx.doi.org/10.1023/A:1026430206274
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  • 46
    Electronic Resource
    Electronic Resource
    Effects of Potato-cyst Nematodes (Globodera pallida) and Soil pH on Root Growth, Nutrient Uptake and Crop Growth of Potato (1999)
    Springer
    European journal of plant pathology 105 (1999), S. 61-76 
    Details
    ISSN: 1573-8469
    Keywords: core sampling ; foliar nutrient concentrations ; minirhizotrons ; nitrogen ; phosphorus ; potassium ; Rhizolab
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Potato-cyst nematodes (Globodera pallida) cause severe yield losses in potato. Plants infected with potato-cyst nematodes generally have reduced concentrations of nitrogen, phosphorus and potassium in the foliage. This study investigated whether reduced growth of nematode-infected potato is caused by nutrient limitation. Experiments in the field and in containers showed that phosphorus concentration correlated best with total crop biomass at early stages of growth. The role of phosphorus in nematode damage was further investigated in the field and in the Wageningen Rhizolab. The experimental field was infested with potato-cyst nematodes and two levels of nematode density were established by fumigation with a nematicide. Prior applications of calcium carbonate resulted in pHKCl levels of 4.8 and 6.1. Two levels of phosphorus fertiliser were applied: either 0 or 225 kg P ha−1. In the Wageningen Rhizolab, soil of both pH levels from the field was used after treatment with 1 MRad gamma irradiation to kill the nematodes. Subsequently, half of the soil was inoculated with cysts to give a nematode density of 30 viable juveniles per gram of soil. In the field, nine weeks after planting, the total crop biomass ranged from 107 g m−2 for the treatment with nematodes at pHKCl 6.1 without phosphorus fertiliser to 289 g m−2 for the fumigated treatment at pHKCl 4.8 with phosphorus fertiliser. The differences in total biomass for the various treatments were explained by differences in foliar phosphorus concentration. Nematodes induced or aggravated P deficiency and reduced total biomass. This was not the only damage mechanism as at high, non-limiting levels of foliar phosphorus concentration, nematodes still reduced total biomass. In the Wageningen Rhizolab, directly after planting, the number of roots visible against minirhizotrons was reduced by nematodes. However, the increase of root number in the nematode treatment continued longer than in the control, until root number was higher than that of the control. The compensary root growth of the nematode treatment was restricted to the top 30 cm and nematodes reduced rooting depth. High soil pH reduced growth, mainly by reducing the availability of phosphate. Both nematodes and high soil pH reduced nutrient uptake per unit root length. Our results lead us to suggest an interaction between nematodes and soil pH, with nematode damage being higher at pHKCl 6.1 than at pHKCl 4.8.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008641511688
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  • 47
    Electronic Resource
    Electronic Resource
    Deposition Rates of Terrestrial and Marine Organic Carbon in the Osaka Bay, Seto Inland Sea, Japan, Determined Using Carbon and Nitrogen Stable Isotope Ratios in the Sediment (1999)
    Springer
    Journal of oceanography 55 (1999), S. 1-11 
    Details
    ISSN: 1573-868X
    Keywords: Osaka Bay ; sediment ; carbon ; nitrogen ; organic matter ; stable isotope ratio ; terrestrial organic matter ; TOC ; POC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Geosciences
    Notes: Abstract Carbon and nitrogen stable isotope ratios (δ13C and δ15N) of surface sediments were measured within Osaka Bay, in the Seto Inland Sea in Japan, in order to better understand the sedimentation processes operating on both terrestrial and marine organic matter in the Bay. The δ13C and δ15N of surface sediments in the estuary of the Yodo River were less than −23‰ and 5‰ respectively, but increased in the area up to about 10 km from the river mouth. At greater distances they became constant (giving δ13C of about −20‰ and δ15N about 6‰). It can be concluded that large amounts of terrestrial organic matter exist near the mouth of the Yodo River. Stable isotope ratios in the estuary of the Yodo River within 10 km of the river mouth were useful indicators allowing study of the movement of terrestrial organic matter. Deposition rates for total organic carbon (TOC) and total nitrogen (TN) over the whole of the Bay were estimated to be 63,100 ton C/year and 7,590 ton N/year, respectively. The deposition rate of terrestrial organic carbon was estimated to be 13,200 (range 2,000–21,500) ton C/year for the whole of Osaka Bay, and terrestrial organic carbon was estimated to be about 21% (range 3–34) of the TOC deposition rate. The ratio of the deposition rate of terrestrial organic carbon to the rate inflow of riverine TOC and particulate organic carbon (POC) were estimated to be 19% (range 3–31) and 76% (range 12–100), respectively.
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    URL: http://dx.doi.org/10.1023/A:1007850003262
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  • 48
    Electronic Resource
    Electronic Resource
    Wastewater Irrigation-Economic Concerns Regarding Beneficiary and Hazardous Effects of Nutrients (1999)
    Springer
    Water resources management 13 (1999), S. 303-314 
    Details
    ISSN: 1573-1650
    Keywords: economics ; irrigation ; nitrogen ; nutrients ; wastewater
    Source: Springer Online Journal Archives 1860-2000
    Topics: Architecture, Civil Engineering, Surveying , Geography
    Notes: Abstract The optimal wastewater treatment level is affected by costs, hazards and benefits. Lowering the wastewater treatment level decreases fertilization costs because of the increased levels of available nutrients left in the water, and irrigation costs decrease if water prices reflect the lower treatment costs. Agricultural yields and/or prices may decrease according to differences between levels of nutrients needed by crops and those available in wastewater. The present article focuses on determination of monthly optimal treatment levels and of the mix of crops calculated to maximize agricultural incomes, according to farmers' point of view. It does not reflect the national point-view focusing on maximization of net national benefits considering also environmental hazards. The methodology appears in Haruvy (1994) and application will be presented in another article (Haruvy et al., 1999).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008114225469
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  • 49
    Electronic Resource
    Electronic Resource
    Do top-down and bottom-up controls interact to exclude nitrogen-fixing cyanobacteria from the plankton of estuaries? An exploration with a simulation model (1999)
    Springer
    Biogeochemistry 46 (1999), S. 203-231 
    Details
    ISSN: 1573-515X
    Keywords: Baltic Sea ; cyanobacteria ; estuaries ; grazing ; iron ; lakes ; molybdenum ; nitrogen ; nitrogen fixation ; nitrogen limitation ; Zooplankton
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Explaining the nearly ubiquitous absence of nitrogen fixation by planktonic organisms in strongly nitrogen-limited estuaries presents a major challenge to aquatic ecologists. In freshwater lakes of moderate productivity, nitrogen limitation is seldom maintained for long since heterocystic, nitrogen-fixing cyanobacteria bloom, fix nitrogen, and alleviate the nitrogen limitation. In marked contrast to lakes, this behavior occurs in only a few estuaries worldwide. Primary production is limited by nitrogen in most temperate estuaries, yet no measurable planktonic nitrogen fixation occurs. In this paper, we present the hypothesis that the absence of planktonic nitrogen fixers from most estuaries is due to an interaction of bottom-up and top-down controls. The availability of Mo, a trace metal required for nitrogen fixation, is lower in estuaries than in freshwater lakes. This is not an absolute physiological constraint against the occurrence of nitrogen-fixing organisms, but the lower Mo availability may slow the growth rate of these organisms. The slower growth rate makes nitrogen-fixing cyanobacteria in estuaries more sensitive to mortality from grazing by Zooplankton and benthic organisms. We use a simple, mechanistically based simulation model to explore this hypothesis. The model correctly predicts the timing of the formation of heterocystic, cyanobacterial blooms in freshwater lakes and the magnitude of the rate of nitrogen fixation. The model also correctly predicts that high Zooplankton biomasses in freshwaters can partially suppress blooms of nitrogen-fixing cyanobacteria, even in strongly nitrogen-limited lakes. Further, the model indicates that a relatively small and environmentally realistic decrease in Mo availability, such as that which may occur in seawater compared to freshwaters due to sulfate inhibition of Mo assimilation, can suppress blooms of heterocystic cyanobacteria and prevent planktonic nitrogen fixation. For example, the model predicts that at a Zooplankton biomass of 0.2 mg l−1, cyanobacteria will bloom and fix nitrogen in lakes but not in estuaries of full-strength seawater salinity because of the lower Mo availability. Thus, the model provides strong support for our hypothesis that bottom-up and top-down controls may interact to cause the absence of planktonic nitrogen fixation in most estuaries. The model also provides a basis for further exploration of this hypothesis in individual estuarine systems and correctly predicts that planktonic nitrogen fixation can occur in low salinity estuaries, such as the Baltic Sea, where Mo availability is greater than in higher salinity estuaries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01007580
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  • 50
    Electronic Resource
    Electronic Resource
    Nitrogen stable isotopic composition of leaves and soil: Tropical versus temperate forests (1999)
    Springer
    Biogeochemistry 46 (1999), S. 45-65 
    Details
    ISSN: 1573-515X
    Keywords: N15 ; nitrogen ; nutrient cycling ; plants ; stable isotopes ; soil ; temperate forest ; tropical forest
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Several lines of evidence suggest that nitrogen in most tropical forests is relatively more available than N in most temperate forests, and even that it may function as an excess nutrient in many tropical forests. If this is correct, tropical forests should have more open N cycles than temperate forests, with both inputs and outputs of N large relative to N cycling within systems. Consequent differences in both the magnitude and the pathways of N loss imply that tropical forests should in general be more 15N enriched than are most temperate forests. In order to test this hypothesis, we compared the nitrogen stable isotopic composition of tree leaves and soils from a variety of tropical and temperate forests. Foliar δ15N values from tropical forests averaged 6.5‰ higher than from temperate forests. Within the tropics, ecosystems with relatively low N availability (montane forests, forests on sandy soils) were significantly more depleted in 15N than other tropical forests. The average δ15N values for tropical forest soils, either for surface or for depth samples, were almost 8‰ higher than temperate forest soils. These results provide another line of evidence that N is relatively abundant in many tropical forest ecosystems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006100128782
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  • 51
    Electronic Resource
    Electronic Resource
    The impact of accelerating land-use change on the N-Cycle of tropical aquatic ecosystems: Current conditions and projected changes (1999)
    Springer
    Biogeochemistry 46 (1999), S. 109-148 
    Details
    ISSN: 1573-515X
    Keywords: estuaries ; lakes ; marine ; nitrogen ; phosphorus ; rivers ; streams ; temperate ; tropics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Published data and analyses from temperate and tropical aquatic systems are used to summarize knowledge about the potential impact of land-use alteration on the nitrogen biogeochemistry of tropical aquatic ecosystems, identify important patterns and recommend key needs for research. The tropical N-cycle is traced from pre-disturbance conditions through the phases of disturbance, highlighting major differences between tropical and temperate systems that might influence development strategies in the tropics. Analyses suggest that tropical freshwaters are more frequently N-limited than temperate zones, while tropical marine systems may show more frequent P limitation. These analyses indicate that disturbances to pristine tropical lands will lead to greatly increased primary production in freshwaters and large changes in tropical freshwater communities. Increased freshwater nutrient flux will also lead to an expansion of the high production, N- and light-limited zones around river deltas, a switch from P- to N-limitation in calcareous marine systems, with large changes in the community composition of fragile mangrove and reef systems. Key information gaps are highlighted, including data on mechanisms of nutrient transport and atmospheric deposition in the tropics, nutrient and material retention capacities of tropical impoundments, and N/P coupling and stoichiometric impacts of nutrient supplies on tropical aquatic communities. The current base of biogeochemical data suggests that alterations in the N-cycle will have greater impacts on tropical aquatic ecosystems than those already observed in the temperate zone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006156213761
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  • 52
    Electronic Resource
    Electronic Resource
    Do top-down and bottom-up controls interact to exclude nitrogen-fixing cyanobacteria from the plankton of estuaries? An exploration with a simulation model (1999)
    Springer
    Biogeochemistry 46 (1999), S. 203-231 
    Details
    ISSN: 1573-515X
    Keywords: Baltic Sea ; cyanobacteria ; estuaries ; grazing ; iron ; lakes ; molybdenum ; nitrogen ; nitrogen fixation ; nitrogen limitation ; zooplankton
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Explaining the nearly ubiquitous absence of nitrogen fixation by planktonic organisms in strongly nitrogen-limited estuaries presents a major challenge to aquatic ecologists. In freshwater lakes of moderate productivity, nitrogen limitation is seldom maintained for long since heterocystic, nitrogen-fixing cyanobacteria bloom, fix nitrogen, and alleviate the nitrogen limitation. In marked contrast to lakes, this behavior occurs in only a few estuaries worldwide. Primary production is limited by nitrogen in most temperate estuaries, yet no measurable planktonic nitrogen fixation occurs. In this paper, we present the hypothesis that the absence of planktonic nitrogen fixers from most estuaries is due to an interaction of bottom-up and top-down controls. The availability of Mo, a trace metal required for nitrogen fixation, is lower in estuaries than in freshwater lakes. This is not an absolute physiological constraint against the occurrence of nitrogen-fixing organisms, but the lower Mo availability may slow the growth rate of these organisms. The slower growth rate makes nitrogen-fixing cyanobacteria in estuaries more sensitive to mortality from grazing by zooplankton and benthic organisms. We use a simple, mechanistically based simulation model to explore this hypothesis. The model correctly predicts the timing of the formation of heterocystic, cyanobacterial blooms in freshwater lakes and the magnitude of the rate of nitrogen fixation. The model also correctly predicts that high zooplankton biomasses in freshwaters can partially suppress blooms of nitrogen-fixing cyanobacteria, even in strongly nitrogen-limited lakes. Further, the model indicates that a relatively small and environmentally realistic decrease in Mo availability, such as that which may occur in seawater compared to freshwaters due to sulfate inhibition of Mo assimilation, can suppress blooms of heterocystic cyanobacteria and prevent planktonic nitrogen fixation. For example, the model predicts that at a zooplankton biomass of 0.2 mg l−1, cyanobacteria will bloom and fix nitrogen in lakes but not in estuaries of full-strength seawater salinity because of the lower Mo availability. Thus, the model provides strong support for our hypothesis that bottom-up and top-down controls may interact to cause the absence of planktonic nitrogen fixation in most estuaries. The model also provides a basis for further exploration of this hypothesis in individual estuarine systems and correctly predicts that planktonic nitrogen fixation can occur in low salinity estuaries, such as the Baltic Sea, where Mo availability is greater than in higher salinity estuaries.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006189121030
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  • 53
    Electronic Resource
    Electronic Resource
    The effect of regeneration burns on the growth, nutrient acquisition and mycorrhizae of Eucalyptus regnans F. Muell. (mountain ash) seedlings (1999)
    Springer
    Plant and soil 210 (1999), S. 273-283 
    Details
    ISSN: 1573-5036
    Keywords: ectomycorrhizae ; Eucalyptus regnans ; forest burns ; nitrogen ; phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract This study was conducted to compare the effects on the growth of Eucalyptus regnans seedlings of unheated soil and soil heated to different extents (as indicated by soil colour–bright red or black) in burnt logging coupes, and to separate the effects of heating of the soil on direct nutrient availability and on morphotypes and effectiveness of ectomycorrhizae. Burnt soils were collected from three logging coupes burnt 2, 14 and 25 months previously and unbumt soil from adjacent regrowth forests. Compared to unburnt soil, the early seedling growth was stimulated in black burnt soil from all coupes (burnt 2, 14 and 25 months previously). Seedling growth was generally poor in red burnt soil, especially in soil collected 2 months after burning. However, the concentration of extractable P was extremely high in red burnt soil, especially in soil collected 2 months after burning. In black burnt soil, extractable P was increased in soil 2 months after burning, but not in the soils collected 14 or 25 months after burning. However, both total P content and concentration in seedlings were increased in all collections of black burnt soil. Frequency of ectomycorrhizae was high in seedlings grown in all black burnt soils, but the mycorrhizal mantles were poorly developed in seedlings in black burnt soil collected 2 months after burning. Seedlings were also ectomycorrhizal in red burnt soil, except in soil collected 2 months after burning. Fine root inocula from seedlings grown in black burnt soils collected 14 and 25 months after burning significantly stimulated both seedling growth and P uptake compared with the uninoculated control, whereas the fine root inocula from the seedlings grown in all the other soils did not. These results suggest that, in black burnt soil, both direct nutritional changes and changes in the ectomycorrhizae may contribute to seedling growth promotion after regeneration burns. The generally poor seedling growth in red burnt soils is likely to have been due to N deficiency as the seedlings in these soils were yellow-green and the tissue concentrations of N were significantly lower than in other treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1004609912315
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  • 54
    Electronic Resource
    Electronic Resource
    A comparison of direct and indirect 15N isotope techniques for estimating crop N uptake from organic residues (1999)
    Springer
    Plant and soil 208 (1999), S. 259-270 
    Details
    ISSN: 1573-5036
    Keywords: crop residues ; isotope dilution ; 15N ; nitrogen ; organic matter ; pool substitution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Experiments were carried out to compare the direct approach for estimating crop N uptake from 15N labelled organic inputs, to two indirect approaches, 15N isotope dilution and A value. In the first experiment soils received 25, 50, 75, or 100 mg N kg soil−1 in the form of Casuarina equisitifolia residues in addition to ammonium sulphate fertiliser, to give a total of 100 mg N kg soil−1 added. This was a cross labelling design, thus two matching sets of treatments, were set up, identical in all but the position of the 15N label. Maize (Zea mays L.) plants were grown in the soils amended with residues for 11 weeks and N derived from residues (Ndfr) estimated using the A-value or the direct approach. The A-value approach appeared to significantly overestimate %Ndfr compared to the direct method. In the second experiment contrasting residues were added to soil, fababean (Vicia faba L. var. minor), alfalfa (Medicago sativa L.), soyabean fixing, (Glycine max (L.) Merrill), soyabean non-fixing, barley (Hordeum vulgare L.) and maize. This was also cross-labelling design, labelled and unlabelled residues were used. Maize plants were grown in these soils for 11 weeks and %Ndfr in the maize plants estimated using 15 N isotope dilution and the direct approach. The 15 N isotope dilution approach also overestimated %Ndfr compared to the direct method in this experiment. Pool substitution appeared to be responsible for the discrepancy between the direct and indirect techniques. It was concluded that 15N isotope dilution and A-value approaches as used in these experiments (i.e where residues and 15N label are added simultaneously) were not appropriate techniques for estimating N derived from organic residues in soils.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1004529711231
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  • 55
    Electronic Resource
    Electronic Resource
    Timing of nitrogen uptake affects winter storage and spring remobilisation of nitrogen in nectarine (Prunus persica var. nectarina) trees (1999)
    Springer
    Plant and soil 211 (1999), S. 149-153 
    Details
    ISSN: 1573-5036
    Keywords: nitrogen ; Prunus ; remobilisation ; storage ; uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Two-year old nectarine trees (Prunus persica, Batsch, var. nectarina, cv. Starkredgold on GF305 rootstock) planted in pots each received five applications of 1.0 g 15N labelled urea either from mid May to mid July (early uptake) or from mid August to the beginning of October (late uptake). All trees were supplied with a corresponding amount of unlabelled urea when they did not receive the labelled N. In autumn, all abscised leaves were collected and during winter randomly selected trees were harvested and divided into main organs. The remaining trees were transplanted into similar pots filled with sand; they received no N fertiliser and were harvested in May to evaluate the remobilisation of N. Total N and 15N abundance were determined in each organ. Nectarine trees took up similar amounts of N in the 'early' and in the 'late' period; however, more labelled nitrogen was recovered in the perennial organs during the winter when trees received the labelled N in the 'late' than in the 'early' period. Some 73–80% of the N present in the dormant trees was stored in the roots, which contained almost twice the amount of labelled N taken up 'late' than that absorbed 'early'. Nitrogen for spring growth was remobilised predominantly from the roots and accounted for some 43–49% of the labelled N recovered in the tree during winter. Results suggest that the nitrogen taken up 'late' in the season is preferentially stored in roots and used by peach trees to sustain new growth the following spring.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1004698422522
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  • 56
    Electronic Resource
    Electronic Resource
    Effects of sulphur nutrition on growth and nitrogen fixation of pea (Pisum sativum L.) (1999)
    Springer
    Plant and soil 212 (1999), S. 207-217 
    Details
    ISSN: 1573-5036
    Keywords: legume ; nitrogen ; N2-fixation ; pea ; sulphur
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract A S-deficient soil was used in pot experiments to investigate the effects of S addition on growth and N2-fixation in pea (Pisum sativum L.). Addition of 100 mg S pot−1 increased seed yield by more than 2-fold. Numbers of pods formed were the most sensitive yield component affected by S deficiency. Sulphur addition also increased the concentration of N in leaves and stems, and the total content of N in the shoots. The amounts of N fixed by pea were determined at four growth stages from stem elongation to maturity, using the 15N dilution technique. Sulphur addition doubled the amount of N fixed at all growth stages. In contrast, leaf chlorophyll content and shoot dry weight were increased significantly by S addition only after the flowering and pod fill stage, respectively. Pea roots were found to have high concentrations of S, reaching approximately 10 mg g−1 dry weight and being 2.6–4.4 times the S concentration in the shoots under S-sufficient conditions. These results suggest that roots/nodules of pea have a high demand for S, and that N2-fixation is very sensitive to S deficiency. The effects of S deficiency on pea growth were likely to be caused by the shortage of N, due to decreased N2-fixation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1004618303445
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  • 57
    Electronic Resource
    Electronic Resource
    Persistence of tree related patterns in soil nutrients following slash-and-burn disturbance in the tropics (1999)
    Springer
    Plant and soil 209 (1999), S. 137-157 
    Details
    ISSN: 1573-5036
    Keywords: fire ; nitrogen ; phosphorus ; soil nutrient heterogeneity ; tree effects ; tropical dry forest
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Individual trees are known to influence soil chemical properties, creating spatial patterns that vary with distance from the stem. The influence of trees on soil chemical properties is commonly viewed as the agronomic basis for low-input agroforestry and shifting cultivation practices, and as an important source of spatial heterogeneity in forest soils. Few studies, however, have examined the persistence of the effects of trees on soil after the pathways responsible for the effects are removed. Here, we present evidence from a Mexican dry forest indicating that stem-related patterns of soil nutrients do persist following slash-and-burn removal of trees and two years of cropping. Pre-disturbance concentrations of resin extractable phosphorus (P), bicarbonate extractable P, NaOH extractable P, total P, total nitrogen (N) and carbon (C), KCl extractable nitrate (NO3 -), and net N mineralization and nitrification rates were higher in stem than dripline soils under two canopy dominant species of large-stemmed trees with contrasting morphologies and phenologies (Caesalpinia eriostachys Benth. and Forchhammeria pallida Liebm.). These stem effects persisted through slash burning and a first growing season for labile inorganic and organic P, NaOH inorganic P, and plant-available P, and through a second growing season for labile organic P, NaOH organic P, and plant-available P. While stem effects for extractable NO3 -, net nitrification rates, total N and C disappeared after felling and slash burning, these stem effects returned after the first growing season. These results support the view that tree-influenced patterns of soil nutrients do persist after tree death, and that trees contribute to the long-term spatial heterogeneity of forest soils.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1004503023973
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  • 58
    Electronic Resource
    Electronic Resource
    Nitrogen and phosphorus requirement of the microbiota in soils of the Bornhöved Lake district (1999)
    Springer
    Plant and soil 212 (1999), S. 173-181 
    Details
    ISSN: 1573-5036
    Keywords: nitrogen ; phosphatase activity ; phosphorus ; protease activity ; soil microbial biomass ; substrate-induced respiration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Estimating in situ N and P status of the soil microbiota is complicated because microbiological features reflect potentials rather than field conditions. Complementary microbiological assays were, therefore, combined to evaluate the N and P requirement of the microbiota in seven agricultural, grassland and forest topsoils of the Bornhöved Lake district as follows: (i) the sensitivity of the substrate-induced respiration (SIR) to supplemental addition of N and P was monitored during microbial growth and (ii) soil protease and phosphatase activities were analysed and related to soil mass and microbial biomass content. Nitrogen addition increased the maximal SIR rate in all except one soil indicating that the growth of organisms is restricted by this element when easily degradable C source is present. Supplemental N (and in some cases also P) retarded the respiratory response within the first 24 h which suggests microbial sensitivity and/or greater anabolic efficiency. With additional N the maximal SIR rate was most strongly enhanced in topsoils of the beech forest and the dystric alder forest. Thus, the microbial growth in these soils that were below litter horizons seems to be mostly restricted by N. Supplemental P positively affected respiratory response of soils under monoculture, wet grassland and dystric alder forest. In the dystric alder forest soil, high rates of alkaline and unbuffered phosphatase activity were observed when activity was related to either soil mass or microbial biomass content. The data of proteolytic and phospholytic enzymes are discussed with reference to nutrient deficiency and microbial strategy for N and P adsorption.
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    URL: http://dx.doi.org/10.1023/A:1004677427165
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  • 59
    Electronic Resource
    Electronic Resource
    Contributions to nitrogen leaching and pasture uptake by autumn-applied dairy effluent and ammonium fertilizer labeled with 15N isotope (1999)
    Springer
    Plant and soil 210 (1999), S. 189-198 
    Details
    ISSN: 1573-5036
    Keywords: effluent ; leaching ; 15N isotope ; nitrogen ; pasture ; uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The objective of this study was to compare the N leaching loss and pasture N uptake from autumn-applied dairy shed effluent and ammonium fertilizer (NH4Cl) labeled with 15N, using intact soil lysimeters (80 cm diameter, 120 cm depth). The soil used was a sandy loam, and the pasture was a mixture of perennial ryegrass (Lolium perenne) and white clover (Trifolium repens). The DSE and NH4Cl were applied twice annually in autumn (May) and late spring (November), each at 200 kg N ha-1. The N applied in May 1996 was labeled with 15N. The lysimeters were either spray or flood irrigated during the summer. The autumn-applied DSE resulted in lower N leaching losses compared with NH4Cl. However, the N applied in the autumn had a higher potential for leaching than N applied in late spring. Between 4.5–8.1% of the 15N-labeled mineral N in the DSE and 15.1–18.8% of the 15N-labeled NH4Cl applied in the autumn were leached within a year of application. Of the annual N leaching losses in the DSE treatments (16.0–26.9 kg N ha-1), a fifth (20.3–22.9%) was from the mineral N fraction of the DSE applied in the autumn, with the remaining larger proportion from the organic fraction of the DSE, soil N and N applied in spring. In the NH4Cl treatments, more than half (53.8–64.8%) of the annual N leaching loss (55.9–57.6 kg N ha-1) was derived from the autumn-applied NH4Cl. DSE was as effective as NH4Cl in stimulating pasture production. Since only 4.4–4.5% of the annual herbage N uptake in the DSE treatment and 12.3–13.3% in the NH4Cl treatment were derived from the autumn-applied mineral N, large proportions of the annual herbage N uptake must have been derived from the N applied in spring, the organic N fraction in the DSE, soil N and N fixed by clover. The recoveries of 15N in the herbage were similar between the DSE and the NH4Cl treatments, but those in the leachate were over 50% less from the DSE than from the NH4Cl treatment. The lower leaching loss of 15N in the DSE treatment was attributed to the stimulated microbial activities and increased immobilization following the application of DSE.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1004677902049
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  • 60
    Electronic Resource
    Electronic Resource
    Relationships between eutrophication variables: from nutrient loading to transparency (1999)
    Springer
    Hydrobiologia 408-409 (1999), S. 375-387 
    Details
    ISSN: 1573-5117
    Keywords: eutrophication ; multi-lake studies ; phosphorus ; nitrogen ; chlorophyll-a ; transparency ; zooplankton ; macrophytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Monitoring data obtained from 231 freshwater lakes and ponds in the Netherlands, covering the period 1980–1996, were used to analyse the relationships between (a) transparency and chlorophyll-a, and the effect of system characteristics on this relationship, (b) chlorophyll-aand nutrient concentrations, and the effect of biological variables and (c) nutrient concentrations and nutrient loading. (a) Chlorophyll-aimposes a maximum on water transparency, but deviations from this maximum can be large. Reducing chlorophyll-a, therefore, does not guarantee a sufficient improvement of transparency. Soil type and the average depth of a lake were shown to influence the relationship between chlorophyll-aand transparency. (b) The maximum ratios of both chlorophyll-a: total-P and chlorophyll-a: total-N were higher in systems dominated by filamentous cyanobacteria than in systems dominated by other algae, indicating the efficiency of the former group with respect to nutrients. In systems with an areal coverage with submersed macrophytes above 5%, concentrations of chlorophyll-aand nutrients were lower than in systems with lower coverages. The ratios between chlorophyll-aand nutrients were lower at coverages larger than 10%. This indicates both bottom-up and top-down control of algae by macrophytes. Grazing pressure by zooplankton was also found to lower the chlorophyll-a: nutrient ratios. (c) System specific linear relationships were found between the average concentrations of total-P and total-N in the incoming water and the summer mean concentration in the lake. This allows the assessment of admissible loads for individual lakes, with narrower confidence limits compared to traditional relationships based on combined data from many lakes. From the analysis, it is concluded that the chain of relationships from nutrient loading to transparency is complex, and depends on biological variables as well as system characteristics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1017090931476
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  • 61
    Electronic Resource
    Electronic Resource
    A simulation model of organic matter and nutrient accumulation in mangrove wetland soils (1999)
    Springer
    Biogeochemistry 44 (1999), S. 93-118 
    Details
    ISSN: 1573-515X
    Keywords: Everglades National Park ; mangrove soils ; organic matter ; nitrogen ; phosphorus ; sedimentation ; simulation model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract The distribution and accumulation of organic matter, nitrogen (N) and phosphorus (P) in mangrove soils at four sites along the Shark River estuary of south Florida were investigated with empirical measures and a process-based model. The mangrove nutrient model (NUMAN) was developed from the SEMIDEC marsh organic matter model and parameterized with data from mangrove wetlands. The soil characteristics in the four mangrove sites varied greatly in both concentrations and profiles of soil carbon, N and P. Organic matter decreased from 82% in the upstream locations to 30% in the marine sites. Comparisons of simulated and observed results demonstrated that landscape gradients of soil characteristics along the estuary can be adequately modeled by accounting for plant production, litter decomposition and export, and allochthonous input of mineral sediments. Model sensitivity analyses suggest that root production has a more significant effect on soil composition than litter fall. Model simulations showed that the greatest change in organic matter, N, and P occurred from the soil surface to 5 cm depth. The rapid decomposition of labile organic matter was responsible for this decrease in organic matter. Simulated N mineralization rates decreased quickly with depth, which corresponded with the decrease of labile organic matter. The increase in organic matter content and decrease in soil bulk density from mangrove sites at downstream locations compared to those at upstream locations was controlled mainly by variation in allochthonous inputs of mineral matter at the mouth of the estuary, along with gradients in mangrove root production. Research on allochthonouns sediment input and in situ root production of mangroves is limited compared to their significance to understanding nutrient biogeochemistry of these wetlands. More accurate simulations of temporal patterns of nutrient characteristics with depth will depend on including the effects of disturbance such as hurricanes on sediment redistribution and biomass production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00993000
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  • 62
    Electronic Resource
    Electronic Resource
    Nutrient budgets and biogeochemistry in an experimental agricultural watershed in Southeastern China (1999)
    Springer
    Biogeochemistry 45 (1999), S. 1-19 
    Details
    ISSN: 1573-515X
    Keywords: Chaohu Lake ; chemical fertilizer ; cycling ; denitrification ; multipond system ; nitrogen ; nutrient budget ; phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract During a two-year field study, an annual nutrient budget and cycles were developed for a small agricultural watershed. The study emphasized the integrated unit of the watershed in understanding the biogeochemistry. It was found that the total nutrient input was 39.1× 104 kg nitrogen and 3.91×104 kg phosphorus in the year 1995, of which the greatest input of nutrients to the watershed was chemical fertilizer application, reaching 34.7×104 kg (676 kg/ha) nitrogen and 3.88×104 kg (76 kg/ha) phosphorus. The total nutrient output from the watershed was 13.55×104 kg nitrogen and 0.40×104 kg phosphorus, while the largest output of nitrogen was denitrification, accounting for 44.1% of N output; the largest output of phosphorus was sale of crops, accounting for 99.4% of P output. The results show that the nutrient input is larger than output, demonstrating that there is nutrient surplus within the watershed, a surplus which may become a potential source of nonpoint pollution to area waters. The research showed that both denitrification and volatilization of nitrogen are key ways of nitrogen loss from the watershed. This suggests that careful management of fertilizer application will be important for the sustainable development of agriculture. The research demonstrated that a multipond system within the watershed had high retention rate for both water and nutrients, benefiting the water, nutrient and sediment recycling in the terrestrial ecosystem and helping to reduce agricultural nonpoint pollution at its source. Therefore, this unique watershed system should be recommended due to its great potential relevance for sustainable agricultural development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00992870
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  • 63
    Electronic Resource
    Electronic Resource
    Nutrient losses in runoff from grassland and shrubland habitats in Southern New Mexico: I. rainfall simulation experiments (1999)
    Springer
    Biogeochemistry 45 (1999), S. 21-34 
    Details
    ISSN: 1573-515X
    Keywords: Chihuahuan desert ; desert ; desertification ; grassland ; nitrogen ; nutrient budgets ; phosphorus ; runoff
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Rainfall simulation experiments were performed in areas of semiarid grassland (Bouteloua eriopoda) and arid shrubland (Larrea tridentata) in the Chihuahuan desert of New Mexico. The objective was to compare the runoff of nitrogen (N) and phosphorus (P) from these habitats to assess whether losses of soil nutrients are associated with the invasion of grasslands by shrubs. Runoff losses from grass- and shrub-dominated plots were similar, and much less than from bare plots located in the shrubland. Weighted average concentrations of total dissolved N compounds in runoff were greatest in the grassland (1.72 mg/1) and lowest in bare plots in the shrubland (0.55 mg/1). More than half of the N transported in runoff was carried in dissolved organic compounds. In grassland and shrub plots, the total N loss was highly correlated to the total volume of discharge. We estimate that the total annual loss of N in runoff is 0.25 kg/ha/yr in grasslands and 0.43 kg/ha/yr in shrublands — consistent with the depletion of soil N during desertification of these habitats. Losses of P from both habitats were very small.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00992871
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  • 64
    Electronic Resource
    Electronic Resource
    Pore water N and P concentration in a floodplain marsh of the Lower Paraná River* (1999)
    Springer
    Hydrobiologia 392 (1999), S. 65-71 
    Details
    ISSN: 1573-5117
    Keywords: nitrogen ; phosphorus ; pore water ; macrophyte ; floodplain ; Paraná River
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Inorganic nitrogen and soluble reactive phosphate (o-P) concentrations were measured in the water of a marsh and in its interstitial water at two sites, and in the river water of a floodplain marsh of the Lower Paraná River. These values were compared with the N and P concentration in sediments and macrophyte biomass in order to assess nutrient availability, fate and storage capacity. High variability was found in the interstitital water using a 1 cm resolution device. Nitrate was never detected in the pore water. Depth averaged NH4 + concentrations in the upper 30 cm layer often ranged from N = 1.5 to 1.8 mg l-1, but showed a pronounced minimum (0.5–0.7 mg l-1), close to (March 95), or relatively soon after (May 94) the end of the macrophyte growing season. Soluble phosphate showed a large variation between P = 0.1–1.1 mg l-1 without any discernible seasonal pattern. NH4 + depletion in the pore water concentration and low N/P ratios (3.7 by weight) within the macrophyte biomass at the end of the growing period suggest that available N limits plant growth. NH4 + and o-P concentrations were 35 and 7 times higher, respectively, in the pore water than in the overlying marsh, suggesting a permanent flux of nutrients from the sediments. o-P accumulate in the marsh leading to higher concentrations than in the incoming river. NH4 + did not accumulate in the marsh, and no significant differences were observed between the river and the marsh water, while the NO3 - contributed by the river water was depleted within the marsh, caused probably by coupled nitrification-denitrification at the sediment–water interface. Although an order of magnitude smaller, the pore water pool can supply enough nutrients to build up the macrophyte biomass pool, but only if a fast turnover is attained. The Paraná floodplain marsh retains a large amount of nutrients being stored mainly in the sediment compartment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1003505424569
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  • 65
    Electronic Resource
    Electronic Resource
    The N and P budget of the shallow, flushed lake Müggelsee: retention, external and internal load (1999)
    Springer
    Hydrobiologia 408-409 (1999), S. 159-166 
    Details
    ISSN: 1573-5117
    Keywords: shallow lake ; nutrient loading ; retention ; nitrogen ; phosphorus ; release
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The shallow (mean depth 4.9 m), polymictic and eutrophic lake Müggelsee was highly loaded with phosphorus (6 gP m-2a-1) and nitrogen (170 gN m-2a-1) by the river Spree up to the end of the 1980s. Annual load declined by 40–50% during the last years (1991–97). Phosphorus retention fluctuated strongly during the seasonal cycle between −200 and +100 kgP d-1and from year to year between −44% and + 26% of the P import. At the end of the eighties, the P retention capacity of the sediment was exceeded and Müggelsee became a source of phosphorus. The lake regained its ability to retain P in the sediments after external load reduction in the 1990s. However, the internal load of P reached the level of the external one. The release of P during summer was strongly related to the import of nitrate. On long-term average (1979–1997), less than 1% of the P input was retained in Müggelsee. About 24% of the nitrogen load were removed in the lake on annual mean. This rate decreased during the last years.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1017023717324
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  • 66
    Electronic Resource
    Electronic Resource
    Legislative challenges for lake eutrophication control in Europe (1999)
    Springer
    Hydrobiologia 395-396 (1999), S. 389-401 
    Details
    ISSN: 1573-5117
    Keywords: legislation ; eutrophication ; phosphorus ; nitrogen ; wildlife conservation ; SSSI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract There is no single piece of legislation which comprehensively addresses the problem of eutrophication of freshwater lakes. An examination is made of the extent to which national and EU laws applicable in England and Wales may be used to reduce phosphorus inputs to eutrophicated lakes. This case study is then used to outline the shortcomings of existing legislation and the future challenges for lake eutrophication control. Applicable legislation may be divided into that relating to nature conservation, to water quality and to agricultural extensification. Nature conservation laws are applicable, in that lakes designated as Sites of Special Scientific Interest (SSSIs), are theoretically safeguarded from degradation. The main limitation of the SSSI system lies in the boundary definition process under which, as a rule, no other category of legally protected land may be designated. Thus, the use of surrounding buffer land to protect water quality at the catchment level is generally precluded. The introduction of consultation areas around SSSIs of international importance under the EU Directive on Habitats is unlikely to alleviate the problem, since the area involved remains minimal compared to the extent of the majority of catchments. Intensive agricultural practices are responsible for significant nutrient enrichment of rivers and lakes, so that legislation aimed at extensification is also relevant. Examples of agricultural extensification include the Environrnentally Sensitive Areas programme and various options available for Set-Aside land. However, the prime purpose of such initiatives is the alleviation of surplus and budgetary problems and, as such, they fall short of a fully integrated approach to the ecological management of farmland. Nutrient enrichment is, essentially, a water quality issue, but policy and legislation in this area are not yet sufficiently developed to address the problem comprehensively. The current regulatory process for water quality carries the potential to work comparatively well for point sources under the system of consents to discharge. This potential is limited, however, by the paucity of information available on ecologically acceptable concentrations of phosphorus in discharges. In addition, the consents system is not constructed to deal effectively with diffuse agricultural losses of phosphorus, since, unlike point sources, these tend to arise from the cumulative effect of many activities. The main legislative challenge for lake eutrophication control lies in the area of diffuse agricultural losses of phosphorus. In this respect, experience in the U.S.A. reveals that the use of comprehensive and catchment-wide ‘Best Management Practices’ is capable of producing significant water quality improvements, providing that some degree of mandatory compliance is incorporated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1017007315753
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  • 67
    Electronic Resource
    Electronic Resource
    Lake and catchment management in Denmark (1999)
    Springer
    Hydrobiologia 395-396 (1999), S. 419-432 
    Details
    ISSN: 1573-5117
    Keywords: Integrated lake management ; biomanipulation ; lake recovery ; phosphorus ; nitrogen ; eutrophication ; restoration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The majority of Danish lakes are highly eutrophic due to high nutrient input from domestic sources and agricultural activities. Reduced nutrient retention, and more rapid removal, in catchments as a result of agricultural drainage of wetlands and lakes and channelisation or culverting of streams also play a role. Attempts have recently been made to reduce nutrient loading on lakes by intervening at the source level and by improving the retention capacity of catchment areas. The former measures include phosphorus stripping and nitrogen removal at sewage works, increased use of phosphate-free detergents, and regulations concerning animal fertiliser storage capacity, fertiliser application practices, fertilisation plans and green cover in winter. In order to improve nutrient retention capacity of catchments, wetlands and lakes have been re-established and channelised streams have been remeandered. In addition, cultivation-free buffer strips have been established alongside natural streams and there has been a switch to manual weed control. These measures have resulted in a 73% reduction of the mean total phosphorus concentration of point-source polluted streams since 1978; in contrast, there has been no significant change in the total nitrogen concentration. Despite the major reduction in stream phosphorus concentrations, lake water quality has often not improved. This may reflect a too high external or internal phosphorus loading or biological resistance. Various physico-chemical restoration measures have been used, including dredging and oxidation of the hypolimnion with nitrate and oxygen. Biological restoration measures have been employed in 17 Danish lakes. The methods include reducing the abundance of cyprinids, stocking with 0+ pike ( Esox lucius) to control 0+ cyprinids, and promoting macrophyte recolonization by protecting germinal submerged macrophyte beds against grazing waterfowl and transplanting out macrophyte shoots. In several lakes, marked and long-lasting improvements have been obtained. The findings to date indicate that fish manipulation has a long-term effect in shallow lakes, providing nutrient loading is reduced to a level so low as to ensure an equilibrium lake water phosphorus concentration of less than 0.05–0.1 mg phosphorus l−1. If nitrogen loading is very low, however, positive results may be obtained at higher phosphorus concentrations. Macrophyte refuges and transplantation seem to be the most successful as restoration measures in the same nutrient-phosphorus regime as fish manipulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1017071602549
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  • 68
    Electronic Resource
    Electronic Resource
    A simulation model of organic matter and nutrient accumulation in mangrove wetland soils (1999)
    Springer
    Biogeochemistry 44 (1999), S. 93-118 
    Details
    ISSN: 1573-515X
    Keywords: Everglades National Park ; mangrove soils ; organic matter ; nitrogen ; phosphorus ; sedimentation ; simulation model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract The distribution and accumulation of organic matter, nitrogen (N) and phosphorus (P) in mangrove soils at four sites along the Shark River estuary of south Florida were investigated with empirical measures and a process-based model. The mangrove nutrient model (NUMAN) was developed from the SEMIDEC marsh organic matter model and parameterized with data from mangrove wetlands. The soil characteristics in the four mangrove sites varied greatly in both concentrations and profiles of soil carbon, N and P. Organic matter decreased from 82% in the upstream locations to 30% in the marine sites. Comparisons of simulated and observed results demonstrated that landscape gradients of soil characteristics along the estuary can be adequately modeled by accounting for plant production, litter decomposition and export, and allochthonous input of mineral sediments. Model sensitivity analyses suggest that root production has a more significant effect on soil composition than litter fall. Model simulations showed that the greatest change in organic matter, N, and P occurred from the soil surface to 5 cm depth. The rapid decomposition of labile organic matter was responsible for this decrease in organic matter. Simulated N mineralization rates decreased quickly with depth, which corresponded with the decrease of labile organic matter. The increase in organic matter content and decrease in soil bulk density from mangrove sites at downstream locations compared to those at upstream locations was controlled mainly by variation in allochthonous inputs of mineral matter at the mouth of the estuary, along with gradients in mangrove root production. Research on allochthonouns sediment input and in situ root production of mangroves is limited compared to their significance to understanding nutrient biogeochemistry of these wetlands. More accurate simulations of temporal patterns of nutrient characteristics with depth will depend on including the effects of disturbance such as hurricanes on sediment redistribution and biomass production.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006076405557
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  • 69
    Electronic Resource
    Electronic Resource
    Nutrient budgets and biogeochemistry in an experimental agricultural watershed in Southeastern China (1999)
    Springer
    Biogeochemistry 45 (1999), S. 1-19 
    Details
    ISSN: 1573-515X
    Keywords: Chaohu Lake ; chemical fertilizer ; cycling ; denitrification ; multipond system ; nitrogen ; nutrient budget ; phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract During a two-year field study, an annual nutrient budget and cycles were developed for a small agricultural watershed. The study emphasized the integrated unit of the watershed in understanding the biogeochemistry. It was found that the total nutrient input was 39.1 × 104 kg nitrogen and 3.91 × 104 kg phosphorus in the year 1995, of which the greatest input of nutrients to the watershed was chemical fertilizer application, reaching 34.7 × 104 kg (676 kg/ha) nitrogen and 3.88 × 104 kg (76 kg/ha) phosphorus. The total nutrient output from the watershed was 13.55 × 104 kg nitrogen and 0.40 × 104 kg phosphorus, while the largest output of nitrogen was denitrification, accounting for 44.1% of N output; the largest output of phosphorus was sale of crops, accounting for 99.4% of P output. The results show that the nutrient input is larger than output, demonstrating that there is nutrient surplus within the watershed, a surplus which may become a potential source of nonpoint pollution to area waters. The research showed that both denitrification and volatilization of nitrogen are key ways of nitrogen loss from the watershed. This suggests that careful management of fertilizer application will be important for the sustainable development of agriculture. The research demonstrated that a multipond system within the watershed had high retention rate for both water and nutrients, benefiting the water, nutrient and sediment recycling in the terrestrial ecosystem and helping to reduce agricultural nonpoint pollution at its source. Therefore, this unique watershed system should be recommended due to its great potential relevance for sustainable agricultural development.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006073408623
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  • 70
    Electronic Resource
    Electronic Resource
    The fate of NH4NO3 added toSphagnum magettanicum carpets at five European mire sites (1999)
    Springer
    Biogeochemistry 45 (1999), S. 73-93 
    Details
    ISSN: 1573-515X
    Keywords: atmospheric deposition ; moss ; bog ; nitrogen ; phosphorus ; water table
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Nitrogen additions as NH4NO3 corresponding to 0 (N0), 1 (N1), 3 (N3) and 10 (N10) g N m−2 yr−1 were made toSphagnum magellanicurn cores at two-week intervalsin situ at four sites across Europe, i.e. Lakkasuo (Finland). Männikjärve (Estonia), Moidach More (UK) and Côte de Braveix (France). The same treatments were applied in a glasshouse experiment in Neuchâtel (Switzerland) in which the water table depth was artificially maintained at 7, 17 and 37 cm below the moss surface. In the field, N assimilation in excess of values in wet deposition occurred in the absence of growth, but varied widely between sites, being absent in Lakkasuo (moss N∶P ratio 68) and greatest in Moidach More (N∶P 21). In the glasshouse, growth was reduced by lowering the water table without any apparent effect on N assimilation. Total N content of the moss in field sites increased as the mean depth of water table increased indicating growth limitation leading to increased N concentrations which could reduce the capacity for N retention. Greater contents of NH4 + in the underlying peat at 30 cm depth, both in response to NH4NO3 addition and in the unamended cores confirmed poor retention of inorganic N by the moss at Lakkasuo. Nitrate contents in the profiles at Lakkasuo, Moidach More, and Côte de Braveix were extremely low, even in the N10 treatment, but in Männikjärve, where the mean depth of water table was greatest and retention absent, appreciable amounts of NO3 − were detected in all cores. It is concluded that peatland drainage would reduce the capture of inorganic N in atmospheric deposition bySphagnum mosses.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00992874
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  • 71
    Electronic Resource
    Electronic Resource
    Nitrogen stable isotopic composition of leaves and soil: Tropical versus temperate forests (1999)
    Springer
    Biogeochemistry 46 (1999), S. 45-65 
    Details
    ISSN: 1573-515X
    Keywords: N15 ; nitrogen ; nutrient cycling ; plants ; stable isotopes ; soil ; temperate forest ; tropical forest
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Several lines of evidence suggest that nitrogen in most tropical forests is relatively more available than N in most temperate forests, and even that it may function as an excess nutrient in many tropical forests. If this is correct, tropical forests should have more open N cycles than temperate forests, with both inputs and outputs of N large relative to N cycling within systems. Consequent differences in both the magnitude and the pathways of N loss imply that tropical forests should in general be more15N enriched than are most temperate forests. In order to test this hypothesis, we compared the nitrogen stable isotopic composition of tree leaves and soils from a variety of tropical and temperate forests. Foliar δ15N values from tropical forests averaged 6.5‰ higher than from temperate forests. Within the tropics, ecosystems with relatively low N availability (montane forests, forests on sandy soils) were significantly more depleted in15N than other tropical forests. The average δ15N values for tropical forest soils, either for surface or for depth samples, were almost 8‰ higher than temperate forest soils. These results provide another line of evidence that N is relatively abundant in many tropical forest ecosystems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01007573
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  • 72
    Electronic Resource
    Electronic Resource
    The impact of accelerating land-use change on the N-Cycle of tropical aquatic ecosystems: Current conditions and projected changes (1999)
    Springer
    Biogeochemistry 46 (1999), S. 109-148 
    Details
    ISSN: 1573-515X
    Keywords: estuaries ; lakes ; marine ; nitrogen ; phosphorus ; rivers ; streams ; temperate ; tropics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract Published data and analyses from temperate and tropical aquatic systems are used to summarize knowledge about the potential impact of land-use alteration on the nitrogen biogeochemistry of tropical aquatic ecosystems, identify important patterns and recommend key needs for research. The tropical N-cycle is traced from pre-disturbance conditions through the phases of disturbance, highlighting major differences between tropical and temperate systems that might influence development strategies in the tropics. Analyses suggest that tropical freshwaters are more frequently N-limited than temperate zones, while tropical marine systems may show more frequent P limitation. These analyses indicate that disturbances to pristine tropical lands will lead to greatly increased primary production in freshwaters and large changes in tropical freshwater communities. Increased freshwater nutrient flux will also lead to an expansion of the high production, N- and light-limited zones around river deltas, a switch from P- to N-limitation in calcareous marine systems, with large changes in the community composition of fragile mangrove and reef systems. Key information gaps are highlighted, including data on mechanisms of nutrient transport and atmospheric deposition in the tropics, nutrient and material retention capacities of tropical impoundments, and N/P coupling and stoichiometric impacts of nutrient supplies on tropical aquatic communities. The current base of biogeochemical data suggests that alterations in the N-cycle will have greater impacts on tropical aquatic ecosystems than those already observed in the temperate zone.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01007576
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  • 73
    Electronic Resource
    Electronic Resource
    ATP levels of chinook salmon (Oncorhynchus tshawytscha) sperm following in vitro exposure to various oxygen tensions (1999)
    Springer
    Fish physiology and biochemistry 20 (1999), S. 389-397 
    Details
    ISSN: 1573-5168
    Keywords: adenosine triphosphate ; fertility ; nitrogen ; salmonid ; semen ; spermatocrit ; viability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Adenosine triphosphate (ATP) levels in sperm from chinook salmon (Oncorhynchus tshawytscha) were found to be 12.1±1.9 pmol ATP per 106 sperm cells (mean±SEM, n=18). Sperm were stored at 0–2 °C for up to 72 h under 100, 21, and 0% O2. Changes in sperm ATP content of samples maintained under 100 and 21% O2 were indistinguishable, decreasing to 50% of initial values after 72 h. ATP levels of sperm stored under 0% O2 decreased to 10% of initial values within 8 h and remained unchanged throughout the following 64 h. The initial percent of living sperm (sperm viability) was 94.7±1.7% (mean±SEM, n=12) and was unaltered at 24 h under all O2 tensions. At 72 h, sperm viability remained unchanged under 21% O2 and had decreased by 20% under 100% O2 and by 30% under 0% O2. Therefore, reductions in sperm ATP levels could not be attributed to cell lysis, as viability decreased only modestly over these durations. Fertilizing ability correlated positively with sperm ATP levels. Spermatocrit values increased by 20% for the samples maintained under 100 and 21% O2 after 72 h. However, a 20% increase in spermatocrit occurred within 24 h in samples maintained under 0% O2, rising 70% after 72 h under 0% O2. These data indicate that chinook sperm ATP (1) can be altered and manipulated without significant loss of viability, (2) is positively associated with fertilization, and (3) probably plays a role in sperm packing and cell flexibility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1007749703803
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  • 74
    Electronic Resource
    Electronic Resource
    Effect of soil characteristics on sequential reduction and methane production in sixteen rice paddy soils from China, the Philippines, and Italy (1999)
    Springer
    Biogeochemistry 47 (1999), S. 267-293 
    Details
    ISSN: 1573-515X
    Keywords: acetate ; carbon dioxide ; hydrogen ; methanogenesis ; iron ; organic carbon ; nitrogen ; redox balance ; rice paddy soil ; sulfate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract The potentials for sequential reduction of inorganic electron acceptors and production of methane have been examined in sixteen rice soils obtained from China, the Philippines, and Italy. Methane, CO2, Fe(II), NO 3 - , SO 4 2 , pH, Eh, H2 and acetate were monitored during anaerobic incubation at 30 °C for 120 days. Based on the accumulation patterns of CO2 and CH4, the reduction process was divided into three distinct phases: (1) an initial reduction phase during which most of the inorganic electron acceptors were depleted and CO2 production was at its maximum, (2) a methanogenic phase during which CH4 production was initiated and reached its highest rate, and (3) a steady state phase with constant production rates of CH4 and CO2. The reduction phases lasted for 19 to 75 days with maximum CO2 production of 2.3 to 10.9 μmol d-1 g-1 dry soil. Methane production started after 2 to 87 days and became constant after about 38--68 days (one soil 〉120 days). The maximum CH4 production rates ranged between 0.01 and 3.08 μmol d-1 g-1. During steady state the constant CH4 and CO2 production rates varied from 0.07 to 0.30 μmol d-1 g-1 and 0.02 and 0.28 μmol d-1 g-1, respectively. Within the 120 d of anaerobic incubation only 6--17% of the total soil organic carbon was released into the gas phase. The gaseous carbon released consisted of 61--100% CO2, 〈0.1--35% CH4, and 〈5% nonmethane hydrocarbons. Associated with the reduction of available Fe(III) most of the CO2 was produced during the reduction phase. The electron transfer was balanced between total CO2 produced and both CH4 formed and Fe(III), sulfate and nitrate reduced. Maximum CH4 production rate (r = 0.891) and total CH4 produced (r = 0.775) correlated best with the ratio of soil nitrogen to electron acceptors. Total nitrogen content was a better indicator for “available” organic substrates than the total organic carbon content. The redox potential was not a good predictor of potential CH4 production. These observations indicate that the availability of degradable organic substrates mainly controls the CH4 production in the absence of inorganic electron acceptors.
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    URL: http://dx.doi.org/10.1023/A:1006186420644
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  • 75
    Electronic Resource
    Electronic Resource
    Effect of soil characteristics on sequential reduction and methane production in sixteen rice paddy soils from China, the Philippines, and Italy (1999)
    Springer
    Biogeochemistry 47 (1999), S. 269-295 
    Details
    ISSN: 1573-515X
    Keywords: acetate ; carbon dioxide ; hydrogen ; methanogenesis ; iron ; organic carbon ; nitrogen ; redox balance ; rice paddy soil ; sulfate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Geosciences
    Notes: Abstract The potentials for sequential reduction of inorganic electron acceptors and production of methane have been examined in sixteen rice soils obtained from China, the Philippines, and Italy. Methane, CO2, Fe(II), NO 3 − , SO 4 2− , pH, Eh, H2 and acetate were monitored during anaerobic incubation at 30 °C for 120 days. Based on the accumulation patterns of CO2 and CH4, the reduction process was divided into three distinct phases: (1) an initial reduction phase during which most of the inorganic electron acceptors were depleted and CO2 production was at its maximum, (2) a methanogenic phase during which CH4 production was initiated and reached its highest rate, and (3) a steady state phase with constant production rates of CH4. and CO2. The reduction phases lasted for 19 to 75 days with maximum CO2 production of 2.3 to 10.9μmol d−1 g−1 dry soil. Methane production started after 2 to 87 days and became constant after about 38–68 days (one soil 〉120 days). The maximum CH4 production rates ranged between 0.01 and 3.08μmol d−1 g−1. During steady state the constant CH4 and CO2 production rates varied from 0.07 to 0.30μmol d−1 g−1 and 0.02 and 0.28μmol d−1 g−1, respectively. Within the 120 d of anaerobic incubation only 6–17% of the total soil organic carbon was released into the gas phase. The gaseous carbon released consisted of 61–100% CO2, 〈0.1–35% CH4, and 〈5% nonmethane hydrocarbons. Associated with the reduction of available Fe(III) most of the CO2 was produced during the reduction phase. The electron transfer was balanced between total CO2 produced and both CH4 formed and Fe(III), sulfate and nitrate reduced. Maximum CH4 production rate (r=0.891) and total CH4 produced (r =0.775) correlated best with the ratio of soil nitrogen to electron acceptors. Total nitrogen content was a better indicator for “available” organic substrates than the total organic carbon content. The redox potential was not a good predictor of potential CH4 production. These observations indicate that the availability of degradable organic substrates mainly controls the CH4 production in the absence of inorganic electron acceptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00992910
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  • 76
    Electronic Resource
    Electronic Resource
    Loss of heterozygosity in BRCA1 and BRCA2 markers and high‐grade malignancy in breast cancer (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 9-17 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; microsatellites ; prognostic factors ; 17q21 region ; 13q12‐13 region
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Loss of heterozygosity (LOH) in loci of the 17q21 and 13q12‐13 regions can collaborate in the inactivation of BRCA1, BRCA2, and possibly other genes implicated in the pathogenesis of breast carcinomas. We investigate allelic losses in microsatellites of the BRCA1 and BRCA2 regions, and their correlations with seven pathologic parameters in 140 breast carcinomas. Those cases showing LOH in the region of the RB gene, 13q14, were excluded from the study. The LOH analysis was performed by amplifying DNA by PCR, using four markers of the 17q21 region (D17S856, D17S855, D17S1323, and D17S1327) and four markers of the 13q12‐13 region (D13S290, D13S260, D13S310, and D13S267). LOH in the BRCA1 region was found in 47% of tumors, correlating significantly with estrogen receptor content (p = 0.025), progesterone receptors (p = 0.004), higher grade (p = 0.0008), peritumoral vessel invasion (p = 0.001), and lymph node metastases (p = 0.002). When we excluded the cases with LOH in the BRCA2 region and those not informative for it, the significance disappeared. In the BRCA2 region, a rate of LOH of 51% was found; it correlated significantly with estrogen receptor content (p = 0.002), progesterone receptors (p =0.03), peritumoral vessel invasion (p = 0.005), higher grade (p =0.002), and lymph node metastases (p = 0.001). When cases with BRCA1 losses and those not informative were excluded, again the significance disappeared. Concomitant losses in the BRCA1 and BRCA2 regions were found in 32% of cases, correlating significantly with lymph node metastases (p = 0.0002), estrogen receptor content (p = 0.003), progesterone receptors (p = 0.001), histologic grade (p =0.01), and peritumoral vessel invasion (p = 0.0004). These results suggest that concomitant losses in both regions could have a functional effect, influencing the presence of a poor tumor pathophenotype in breast carcinomas.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006082117266
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  • 77
    Electronic Resource
    Electronic Resource
    Quantitative changes in cytological molecular markers during primary medical treatment of breast cancer: A pilot study (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 51-59 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; neoadjuvant therapy ; FNA ; estrogen receptor ; progesterone receptor ; p53 ; Bcl‐2 ; Ki67 ; SPF ; ploidy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aim: To quantify the changes in biological molecular markers during primary medical treatment in patients with operable breast cancer and to assess their possible relationship with response to treatment. Methods: The treatment group consisted of 31 patients with operable breast carcinomas, median age 57 years (range 41–67), treated with four 3‐weekly cycles of chemotherapy with Mitoxantrone, methotrexate (± mitomycin C), and tamoxifen before surgery. Fine needle aspiration (FNA) was used to obtain samples from patients prior to and at 10 or 21 days post‐treatment. The following molecular markers were assessed: estrogen receptor (ER), progesterone receptor (PgR), p53, Bcl‐2, and Ki67 measured by immunocytochemistry, and ploidy and S‐phase fraction (SPF) by flow cytometry. To evaluate the reproducibility of the technique, repeat FNA was performed in a separate non‐treatment control group of 20 patients and the same molecular markers assessed, two weeks after the first sample with no intervening treatment. Results: The non‐treatment control group showed a high reproducibility for the measurement of molecular markers from repeat FNA. In the treatment group there was a non‐significant reduction in SPF and a significant reduction (p = 0.005) in Ki67. Patients who responded to neoadjuvant therapy were more likely to have a reduction in these two markers than those who failed to respond. Similarly, a reduction in ER scores was observed between the first and second samples (p = 0.04). For PgR, the change between the first and second samples was not significant although there was a significant difference between responders and non‐responders (p = 0.03). All nine patients with an increase in PgR were responders. No significant changes in p53 or Bcl‐2 were observed during treatment. Conclusion: Molecular markers can be adequately measured from FNA samples prior to and during neoadjuvant therapy. Changes in cellular proliferation and hormone receptors have been shown that may be related to tumour response. These relationships should be assessed in a larger cohort of patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006179511178
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  • 78
    Electronic Resource
    Electronic Resource
    Human papillomavirus 16 in breast cancer of women treated for high grade cervical intraepithelial neoplasia (CIN III). (1999)
    Springer
    Breast cancer research and treatment 53 (1999), S. 121-135 
    Details
    ISSN: 1573-7217
    Keywords: HPV 16 ; breast cancer ; CIN III ; PCR ; southern blot ; in situ hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Women with both a history of high grade cervical intraepithelial neoplasia (CIN III) and breast carcinoma as second primary cancer were selected for studying the presence of HPV in breast carcinomas. Paraffin embedded material from 38 patients with 41 breast carcinoma cases after CIN III were examined by polymerase chain reaction (PCR) and in situ hybridization. By PCR we detected HPV 16 DNA in 19 out of 41 cases (46%) of the breast carcinomas. One case proved to be HPV 16 positive also by in situ hybridization. HPV 16 was also detected in 32 out of the 38 patients with CIN III (84%). All HPV 16 positive breast carcinomas were HPV 16 positive in their corresponding CIN III lesions. Eight patients with diagnosed breast cancer before the CIN III lesions were used as controls. None of these had HPV positive breast carcinomas. No cases were positive for HPV 11, 18, or 33. HPV 16 was detected in the primary tumours, in local metastases from HPV 16 positive tumours, in a distant HPV 16 positive breast carcinoma metastasis to the colon, and in other primary cancers in patients with HPV 16 positive breast carcinomas and HPV 16 positive CIN III. Estrogen and progesterone receptors were quantified in the HPV positive and HPV negative breast carcinomas, and there was no significant difference in the fraction positive in the two groups. Oncogenic HPV DNA might be transported from an original site of infection to other organs by blood or lymph, and possibly be a factor in the development of cancer in different organs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006162609420
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  • 79
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    Electronic Resource
    Genetic anticipation and breast cancer: a prospective follow‐up study (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 21-28 
    Details
    ISSN: 1573-7217
    Keywords: age of diagnosis ; ascertainment ; breast cancer ; genetic anticipation ; prospective cohort family study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Genetic anticipation is characterized by an earlier age of disease onset, increased severity, and a greater proportion of affected individuals in succeeding generations. The discovery of trinucleotide repeat expansion (TRE) mutations as the molecular correlate of anticipation in a number of rare Mendelian neurodegenerative disorders has led to a resurgence of interest in this phenomenon. Because of the difficulties presented to traditional genetics by complex diseases, the testing for genetic anticipation coupled with TRE detection has been proposed as a strategy for expediting the identification of susceptibility genes for complex disorders. In the case of breast cancer, a number of previous studies found evidence consistent with genetic anticipation. It is known that a proportion of such families are linked to either BRCA1 or BRCA2, but no TRE mutations have been identified. It has been shown that the typical ascertainment employed in studies purporting to demonstrate genetic anticipation combined with unadjusted statistical analysis can dramatically elevate the type I error. We re‐examine the evidence for anticipation in breast cancer by applying a new statistical approach that appears to have validity in the analysis of anticipation to data ascertained from a recent follow‐up of a large prospective cohort family study of breast cancer. Using this approach, we find no statistically significant evidence for genetic anticipation in familial breast cancer. We discuss the limitations of our analysis, including the problem of adequate sample size for this new statistical test.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006151132592
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  • 80
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    Electronic Resource
    Differential regulation of normal and tumoral breast epithelial cell growth by fibroblasts and 1,25‐dihydroxyvitamin D3 (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 29-39 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cell interactions ; 1,25‐dihydroxyvitamin D3 ; fibroblast ; normal epithelial cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mesenchymal‐epithelial interactions are of paramount importance during normal and tumoral breast developments. We have investigated the paracrine growth regulation of normal and tumoral breast epithelial cells by fibroblasts derived from normal or pathological breast tissues. In some cases, breast cancer MCF‐7 cells or normal epithelial cells in primary culture were cocultured with fibroblasts in a Transwell system allowing diffusible factor exchanges. Alternatively, conditioned medium produced by fibroblast cultures was added to epithelial cell cultures. Fibroblasts were shown to stimulate the proliferation of normal and carcinoma cells through paracrine mechanisms. However, the paracrine exchanges appeared to be different in normal versus tumoral breast epithelial cell growth regulation. Moreover, vitamin D‐related compounds that have been proposed as anti‐tumoral drugs were studied for their ability to affect normal and tumoral mammary epithelial cell proliferation and to interfere with the growth‐regulatory activity of fibroblasts. Whereas vitamin D compounds inhibited MCF‐7 cell growth, they led to a marked stimulation of the proliferation of normal mammary epithelial cells. Moreover, it was shown that the vitamin D analog EB 1089 can block the mitogenic effect of fibroblast‐conditioned medium on tumoral but not normal breast epithelial cells. The differential effects of vitamin D compounds on cell proliferation provide further data in favor of the different behaviours of normal and tumoral mammary epithelial cells. The potential therapeutic use of vitamin D derivatives in the treatment of breast cancer is supported by these results but their growth‐stimulatory properties on normal epithelial cells cannot be overlooked.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006163418479
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  • 81
    Electronic Resource
    Electronic Resource
    Regulation of BAX and BCL‐2 expression in breast cancer cells by chemotherapy (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 107-117 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; Bax ; Bcl‐2 ; breast cancer ; chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Optimizing chemotherapeutic drug delivery strategies relies, in part, on identification of the most clinically effective sequence, dose, and duration of drug exposure. The combination of dose intensive etoposide (VP‐16) followed by cyclophosphamide has clinical efficacy in the treatment of advanced breast cancer. However, molecular mechanisms that underlie the effectiveness of this combination of chemotherapeutic agents have not been investigated. In this study we investigated regulation of BAX and BCL‐2 expression by VP‐16 and cyclophosphamide as a potential mechanism for the induction of breast cancer cell death induced by this regimen. There was a dose and time dependent increase in BAX expression in the breast cancer cell lines MCF‐7, MDA‐MB‐435S, and MDA‐MB‐A231 following in vitro treatment with 50–100 μM VP‐16. Elevation of BAX protein expression in the presence of VP‐16 alone did not correlate with reduced viability or induction of apoptosis in MCF‐7, MDA‐MB‐435S, or MDA‐MB‐A231. VP‐16 did effectively block the breast cancer cell lines evaluated (MCF‐7 and MDA‐MB‐435S) at G2/M phase of the cell cycle, confirming activity of the drug in vitro. MCF‐7 and MDA‐MB‐435S cells that were pre‐treated with VP‐16 and subsequently exposed to 1.0–12.0 μg/m1 4‐hydroperoxycyclophosphamide (4HC), an active metabolite of cyclophosphamide, had markedly reduced viability when compared to matched controls treated with either VP‐16 or 4HC individually. Consistent with this loss of viability, exposure of all three cell lines to the combination of VP‐16 and 4HC resulted in higher BAX protein levels than those observed following treatment with either single agent. This combination of chemotherapeutic agents also resulted in reduced BCL‐2 expression. These observations suggest that combination chemotherapy may derive its efficacy, in part, through coordinated regulation of specific gene products associated with apoptosis. Characterization of molecular events that underlie susceptibility of specific tumor cells to combination chemotherapeutic regimens may lead to additional improvements in treatment strategies for this disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006175811676
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  • 82
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    Electronic Resource
    Cathepsin D expression by cancer and stromal cells in breast cancer: an immunohistochemical study of 1348 cases (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 135-145 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cathepsin D ; immunohistochemistry ; protease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was aimed at investigating the influence of cathepsin D (CD) expression by cancer cells and stromal cells on breast cancer prognosis. This is a study of 1348 node‐positive (NPBC) and node‐negative (NNBC) breast cancers diagnosed between 1980 and 1986 and with a minimum follow‐up of 5.2 years. CD expression was assessed by immunohistochemistry on archival material using a polyclonal antibody. The expression by cancer and stromal cells was assessed separately and correlated with distant metastasis free (DMFS) and overall survival (OS). Cancer cells expressed CD (more than 10% cells expressing CD) in 38.9% of cases and reactive stromal cells in 43.6%. CD expression by reactive stromal cells, and not cancer cells, correlated with several factors of poor prognosis by cancer cells. A strong association was also found with expression of other proteases (stromelysin‐3, gelatinase A, and urokinase Plasminogen Activator) by these same reactive stromal cells. CD expression by cancer cells did not predict DMFS or OS but, by univariate analysis, CD expression by reactive stromal cells was associated with earlier recurrence and shorter survival in NNBC (p = 0.0425) and NPBC patients submitted to adjuvant chemotherapy (p = 0.0234). However, CD expression by reactive stromal cells remained a significant predictor of recurrence by multivariate analyses only in a subgroup of NPBC submitted to adjuvant chemotherapy. Overall, those data support the concept that proteases produced by reactive stromal cells are under cancer cell stimulation and that CD by stromal cells, and not cancer cells, influences the prognosis, but only in a subgroup of patients with breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006140213493
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  • 83
    Electronic Resource
    Electronic Resource
    Assessment of quality of life in women undergoing hormonal therapy for breast cancer: validation of an endocrine symptom subscale for the FACT‐B (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 187-197 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; endocrine therapy ; FACT‐B ; FACT‐ES ; quality of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Existing quality of life instruments do not include adequate items to measure the side effects and putative benefits of hormonal treatments given in breast cancer. We report the development and validation of an 18 item endocrine subscale (ES) to accompany a standardised breast cancer quality of life measure, the Functional Assessment of Cancer Therapy (FACT‐B) [1]. The FACT‐ES (FACT‐B plus ES) was tested initially on 268 women with breast cancer receiving endocrine treatments. Alpha coefficients for all subscales demonstrated good internal consistency (range α = 0.65–0.87). Test‐retest reliability of the ES indicated good stability (r = 0.93, p 〈 0.001). Advanced breast cancer patients' quality of life was high, showing the efficacy of endocrine therapy, but women with primary disease reported better physical, social, and functional well‐being and fewer breast cancer concerns. Most frequently reported symptoms were loss of sexual interest (31%), weight gain (25%), and hot flushes (24%). Significant differences were found between treatment groups for hot flushes and vaginal dryness. Two assessments of the instrument's responsiveness to change were made; 32 women in a clinical trial of endocrine therapy and 18 women without breast cancer taking HRT completed the FACT‐ES at baseline, 4, 8, and 12 weeks. Trial patients reported significantly more symptoms at 8 and 12 weeks than at baseline. Women taking HRT reported significantly fewer or less severe symptoms than at baseline. In conclusion the FACT‐ES has acceptable validity and reliability and is sensitive to clinically significant change, making it suitable for clinical trials of endocrine therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006263818115
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  • 84
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    Electronic Resource
    Induction of insulin‐like growth factor binding protein expression by ICI 182,780 in a tamoxifen‐resistant human breast cancer cell line (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 231-242 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; ICI 182 ; 780 ; IGFBPs ; tamoxifen resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Earlier studies in our laboratory demonstrated that the steroidal antiestrogen ICI 182,780 is very effective in abolishing the tamoxifen‐resistant proliferation of MCF 7/5‐23 cells [1]. In addition, preliminary binding studies showed that ICI 182,780 increased the binding of insulin‐like growth factor (IGF)‐I to the MCF 7/5‐23 cells, although this finding was not the result of an increase in the expression of the insulin‐like growth factor‐I receptor (IGF‐IR). Hence, we reasoned that the inhibition of tamoxifen‐resistant cell growth by ICI 182,780 might have been due to increased expression of insulin‐like growth factor binding proteins (IGFBPs). We observed the up‐regulation of non‐insulin‐suppressible IGF‐I binding in both the tamoxifen‐sensitive MCF 7/5‐21 cell line (1.5‐fold) and the tamoxifen‐resistant MCF 7/5‐23 cell line (2.5‐fold) after 5 days of treatment with ICI 182,780 (10−7 M) in serum‐free medium, suggesting a role for cell‐associated IGFBPs. Affinity cross‐linking experiments confirmed the presence of an IGF‐I:IGFBP complex of approximately 38‐kDa in tamoxifen or ICI 182,780‐treated cells. Western ligand blots showed higher levels of a soluble 30‐kDa IGFBP in media conditioned by either of the subclones that had been treated with ICI 182,780, an effect consistently opposed by estrogen (E2:10−9 M). RT‐PCR showed higher levels of IGFBP‐5 mRNA than any of the other known IGFBPs, suggesting that this was the major IGFBP subtype. The protein was subsequently identified by Western immunoblotting as IGFBP‐5. In conclusion, we postulate that this may be a mechanism contributing to the greater potency of ICI 182,780 in the growth inhibition of the MCF 7/5‐23, tamoxifen‐resistant cell line.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006274712664
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  • 85
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    Electronic Resource
    A study on the cost effectiveness of sestamibi scintimammography for screening women with dense breasts for breast cancer (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 243-258 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; cost effectiveness ; dense breasts ; mammographic parenchymal patterns ; Sestamibi scintimammography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The potential impact of Sestamibi scintimammography (SSMM) on the cost effective management of women with dense breasts is not known. This study addresses this issue quantitatively by examining the impact of SSMM based screening strategies on the ∼3,000,000 women over 40 with very dense breasts (DY patterns) without palpable masses and who have had one or more prior mammograms, who undergo routine screening each year. Quantitative decision tree sensitivity analysis was used to compare the conventional mammography (MM) strategy (strategy A), which does not subject patients with negative mammograms to any further examination until their next screening, with two decision strategies for screening with SSMM SSMM after a negative mammogram (strategy B) or SSMM as the only screening test for women already identified as having dense breasts by a previous mammogram (strategy C). Cost effectiveness was measured by calculating the incremental cost effectiveness ratio (ICER) of strategies B and C, which is the cost of achieving an additional year of life in the screening population by choosing a SSMM based decision strategy rather than the conventional strategy. Strategies B and C reduced the number of false negative diagnoses by 62% and 8%, respectively. The ICER was $632,000 and $3.18M per life year for strategy B and C, respectively. To be cost effective, the pre‐test probability of cancer in the study population must be greater than 3% for strategy B or the cost of SSMM must be less than $50 for strategy C. These results show the ICER of an SSMM based breast cancer screening strategy in the management of patients with dense breasts is not currently within the range (∼$50,000 per year life saved) of other commonly performed medical interventions that are considered cost effective.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006211817207
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  • 86
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    Electronic Resource
    Vorozole results in greater oestrogen suppression than formestane in postmenopausal women and when added to goserelin in premenopausal women with advanced breast cancer (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 25-34 
    Details
    ISSN: 1573-7217
    Keywords: aromatase inhibition ; breast cancer ; formestane ; GnRH agonist ; goserelin ; pharmacology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The high potency and selectivity of new aromatase inhibitors has translated to greater efficacy and improved tolerability in comparison with established second‐line hormonal agents for advanced breast cancer in phase III clinical trials. Two pharmacological studies are reported which assess the use of one of these inhibitors, vorozole, in combination or comparison with well‐established methods of oestrogen deprivation in pre and postmenopausal patients. When combined with the gonadotrophin‐releasing hormone agonist (GnRHa) goserelin in 10 premenopausal patients, vorozole markedly enhanced the suppression of serum levels of oestrone, oestradiol and, oestrone sulphate beyond that achieved by goserelin alone (by a mean 74%, 83%, and 89%, respectively). The combination was well‐tolerated and had no significant effects on androgen levels. Vorozole was compared with formestane in 13 postmenopausal women and serum oestrone, oestradiol, and oestrone sulphate levels were suppressed by 47%, 30%, and 70%, respectively, more by vorozole than by the steroidal aromatase inhibitor. Again the tolerability was excellent. The plasma oestrogen levels in the postmenopausal patients on vorozole were lower than in the premenopausal patients on goserelin plus vorozole, indicating that ovarian oestrogen synthesis may be relatively resistant to aromatase inhibition, even during GnRHa treatment. Thus, in both pre and postmenopausal patients substantially greater suppression of oestrogen can be achieved by vorozole compared with alternative approaches. Existing clinical–pharmacological correlates suggest that these increases in pharmacological effectiveness may result in enhanced clinical effectiveness.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006289811540
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  • 87
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    Electronic Resource
    Hsp27 overexpression inhibits doxorubicin–induced apoptosis in human breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 185-194 
    Details
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; doxorubicin ; hsp27 ; topoisomerase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previously we demonstrated that heat shock protein 27 (hsp27) overexpression confers resistance to the chemotherapeutic agent doxorubicin in MDA–MB–231 breast cancer cells. Since induction of apoptosis is one underlying mechanism of chemotherapeutic drug action, we investigated the effect of hsp27 overexpression on doxorubicin–induced apoptosis, finding that hsp27 protects MDA–MB–231 cells from apoptosis. We also examined expression of the doxorubicin target, topoisomerase II (topo II), in control and hsp27–overexpressing stable transfectants, as topo II expression is important for both drug sensitivity and the initiation of apoptosis by doxorubicin. The relative levels of both topo IIα and β were higher in the controls than the hsp27–overexpressing clones, suggesting that the apoptotic protective effect of hsp27 overexpression in MDA–MB–231 cells is associated with altered topo II expression.abstract
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006207009260
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  • 88
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    Electronic Resource
    pS2 (TFF1) levels in human breast cancer tumor samples: correlation with clinical and histological prognostic markers (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 251-263 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; mRNA ; pS2 ; prognostic marker ; RT–PCR ; TFF1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The expression of pS2 (TFF1) has been previously shown to identify patients with improved response to anti–hormonal therapy and more favorable outcome. In the current study, 100 human breast carcinoma samples obtained from the Manitoba Breast Tumor Bank were analyzed for pS2 mRNA using a quantitative, competitive reverse transcriptase–polymerase chain reaction (qcRT–PCR) assay. A pS2/ß–actin cut–off criterion of 0.010 was established to classify tumors as either pS2 positive or pS2 negative. pS2 mRNA levels were positively associated with both ER and PR, with the majority of ER+ (59) and PR+ (60) tumors also being positive for pS2. In addition, a significant linear correlation was observed between the amount of pS2 mRNA and ER (p〈0.0001) and PR (p〈0.0001) protein. pS2 mRNA levels also exhibited an inverse association with tumor size and histological grade, consistent with the observation that pS2 is primarily expressed in small (T 〈 2.0 cm), but well differentiated tumors (Grades I and II). No associations were observed with tumor cell type, patient age, or lymph node status. The strong correlation displayed between pS2 and a number of currently used breast cancer prognostic markers supports the clinical use of pS2 to further assess tumor status and patient outcome.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006215310169
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  • 89
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    Electronic Resource
    Synergistic action of apoptosis induced by eicosapentaenoic acid and TNP‐470 on human breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 147-158 
    Details
    ISSN: 1573-7217
    Keywords: angiogenesis inhibitor ; apoptosis ; Bcl‐2 ; breast cancer ; eicosapentaenoic acid ; TNP‐470
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of eicosapentaenoic acid (EPA) and an angiogenesis inhibitor (TNP‐470) on the suppression of breast cancer cell growth were examined in five human breast cancer cell lines (MDA‐MB‐231, T‐47D, MCF‐7, KPL‐1, and MKL‐F). In all five cell lines, EPA and TNP‐470 alone both showed tumor growth inhibition in a time‐ and dose‐dependent manner, and in combination, a synergistic effect was seen at high concentrations. EPA plus TNP‐470 treatment evoked apoptosis as confirmed by the appearance of sub G1 populations, by DNA fragmentation, and by cell morphology. With the combination, the expression of Bax and Bc1‐xS, the apoptosis‐enhancing proteins, was more up‐regulated and that of Bcl‐2 and Bcl‐xL, the apoptosis‐suppressing proteins, was more down‐regulated compared to the use of EPA or TNP‐470 alone, suggesting that their synergistic effect was due to an acceleration of apoptosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006283131240
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  • 90
    Electronic Resource
    Electronic Resource
    Down‐regulation of gelsolin expression in human breast ductal carcinoma in situ with and without invasion (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 177-186 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; ductal carcinoma in situ (DCIS) ; gelsolin ; prognostic features
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Expression of gelsolin, an actin filament regulatory protein, in human breast ductal carcinoma in situ (DCIS) was analyzed by immunohistochemistry using a monoclonal antibody. Formalin‐fixed paraffin‐embedded tissues from 59 pure DCIS specimens and 33 DCIS specimens with associated invasive components were evaluated for gelsolin reactivity and compared to eight normal breast cases and 76 invasive breast cancers. The proportion of cases exhibiting negative/low expression of gelsolin in the epithelium was as follows – normal, 0%; pure DCIS, 56%; DCIS associated with invasion, 58% in the DCIS component and 66% in the invasive component; invasive carcinoma, 70%. These data demonstrate that down‐regulation of gelsolin expression in breast epithelium frequently parallels progression to malignancy. Testing gelsolin expression (normal vs. negative/low levels) in the DCIS lesions for associations with patient age or any of the following histopathologic parameters revealed no significant (95% probability level) correlations – tumor size; pathologic (Van Nuys system) grade; nuclear grade; necrosis; presence of histologic calcifications; presence or type of adjacent benign lesions; architectural histologic pattern; and mammographic extent. Gelsolin loss was more commonly associated with mammographic soft tissue lesions as compared to calcified lesions (P = 0.009). A positive trend of borderline significance (P = 0.06) found in the DCIS with invasion group was a correlation between down‐regulated gelsolin expression in the DCIS component and size (〈 versus ≥ 15 mm) of the invasive tumor. In conclusion, reduced gelsolin protein is detectable in at least half of breast lesions which have progressed to DCIS. The trend between increasing gelsolin loss and malignant progression from normal epithelium to DCIS to invasive breast cancer (P 〈 0.0001) suggests additional investigation is needed to determine the potential of altered gelsolin expression as a marker for prognosis and for therapeutic interventions in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006203632228
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  • 91
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    Electronic Resource
    Anti‐human procathepsin D activation peptide antibodies inhibit breast cancer development (1999)
    Springer
    Breast cancer research and treatment 57 (1999), S. 261-269 
    Details
    ISSN: 1573-7217
    Keywords: activation peptide ; antibodies ; breast cancer ; immunotherapy ; procathepsin D
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Enzymatically inactive procathepsin D secreted from cancer cells has been confirmed to play a role in development of human breast cancer. In the present study, we focused on the role of activation peptide which was in our preliminary studies suggested to be most probably responsible for mitogenic activity of procathepsin D. Using synthetic fragments and antibodies raised against individual fragments, we demonstrated that the growth factor activity of activation peptide is localized in a nine amino acid stretch (AA 36–44) of activation peptide and moreover both anti‐activation peptide and anti‐ 27–44 peptide antibodies administered in vivo inhibited the growth of human breast tumors in athymic nude mice. Taking into account our previous results and presented data, we hypothesize that the interaction of procathepsin D activation peptide with an unknown surface receptor is mediated by a sequence 36–44 plus close vicinity. We also propose that this interaction leads in certain types of tumor derived cell lines to proliferation and higher motility. Blocking of the interaction of activation peptide by specific antibodies or antagonists might be a valuable tool in breast cancer inhibition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006238003772
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  • 92
    Electronic Resource
    Electronic Resource
    Coexpression of c-kit and stem cell factor in breast cancer results in enhanced sensitivity to members of the EGF family of growth factors (1999)
    Springer
    Breast cancer research and treatment 58 (1999), S. 1-10 
    Details
    ISSN: 1573-7217
    Keywords: Akt ; breast cancer ; c-kit ; EGF ; ERK ; heregulin ; stem cell factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Kit, a tyrosine kinase growth factor receptor, and its ligand, stem cell factor (SCF), are commonly coexpressed in breast cancer. We have previously shown that MCF7 cells (that naturally express SCF) transfected with a c-kit expression vector exhibit enhanced growth in serum-free medium supplemented with IGF-1. Consequently, we wished to examine the interaction of Kit/SCF with additional growth factors important in the biology of breast cancer. MCF7 transfectants expressing Kit, cultured in serum-free medium supplemented with EGF, displayed more than twice the growth of controls at identical EGF concentrations. Similar responses were seen in the presence of heregulin. The specificity of the Kit-mediated response was illustrated by a reduction in heregulin-stimulated growth in the presence of a monoclonal antibody directed against the Kit receptor. In addition, EGF- and heregulin-stimulated growth of the ZR75-1 cell line that naturally coexpresses Kit and SCF was also inhibited by the Kit blocking antibody. Preliminary investigations into the signal transduction pathways activated by these growth factors revealed that SCF activated both the Ras-MAP kinase and phosphatidyl-inositol-3-kinase (PI3 kinase) pathway. Both EGF and heregulin activated MAPK but to a lesser degree than SCF, and combination of SCF with these growth factors resulted in enhanced MAPK activation. Assessment of PI3K pathway activation using anti-phospho-Akt antibodies revealed that EGF was a poor activator of Akt; activation of this pathway was markedly enhanced by the addition of SCF. Heregulin activated Akt and addition of SCF provided no further activation. Taken together these results suggest that coexpression of SCF and Kit may enhance responsiveness to erbB ligands by enhancing activation of the MAPK and PI3K pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006272527435
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  • 93
    Electronic Resource
    Electronic Resource
    Hypermethylation of the Wilms' tumor suppressor gene CpG island in human breast carcinomas (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 35-43 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; CpG island ; DNA hypermethylation ; Wilms' tumor suppressor gene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract CpG island hypermethylation is known to be associated with transcriptional silencing of tumor suppressor genes in neoplasia. We have previously detected aberrantly methylated sites in the first intron of the Wilms' tumor suppressor (WT1) gene in breast cancer. In the present study, we extended the investigation to a CpG island located in the promoter and first exon regions of WT1. Methylation of this CpG island was found to be extensive in MCF‐7 and MDA‐MB‐231 breast cancer cells, as well as in 25% (five of 20 patients) of primary breast tumors. While levels of the known 3.0‐kb WT1 mRNAs were decreased or not detected in these cell lines, the expression could be partially restored following treatment with a demethylation agent, 5‐aza‐2′‐deoxycytidine. Surprisingly, a novel 2.5‐kb WT1 transcript was expressed at high levels in both untreated and treated MDA‐MB‐231 cells. This novel transcript was likely a WT1 variant missing the first exon, and therefore escaped the methylation control present in the normal transcript. Our study implicates the future need to investigate the significance of this aberrant transcript as well as the role of WT1 CpG island hypermethylation in breast neoplasia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006222803788
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  • 94
    Electronic Resource
    Electronic Resource
    Breast cancer and timing of surgery during menstrual cycle: a 5‐year analysis of 248 premenopausal women (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 259-266 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; menstrual cycle phase ; premenopausal ; prognosis ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present report, we retrospectively analyzed the impact of the timing of surgery during menstrual cycle on disease‐free and overall survival of 248 premenopausal patients with stage I/Il breast cancer who underwent surgery followed by anthracycline‐containing adjuvant chemotherapy. With a median follow‐up of 5 years, no statistically significant differences were observed in disease‐free or overall survival between women operated upon during the follicular (days 0–14) and the luteal (days 15–32) phase of the menstrual cycle. The impact on disease‐free and overall survival of lymph‐node status, tumor size and hormone receptor expression, but not of the phase of the menstrual cycle at the time of surgery, was confirmed by univariate and multivariate analysis. However, when combined with hormone receptor status, the phase of the menstrual cycle at the time of surgery proved useful to better define the prognosis of primary breast cancer patients, with significantly longer disease‐free and overall survival for patients operated upon during the follicular phase and with positive hormone receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006276120841
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  • 95
    Electronic Resource
    Electronic Resource
    Early age at menopause and breast cancer: are leaner women more protected? A prospective analysis of the Dutch DOM cohort (1999)
    Springer
    Breast cancer research and treatment 55 (1999), S. 285-291 
    Details
    ISSN: 1573-7217
    Keywords: body mass index ; breast cancer ; menopause ; smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To investigate the relationship between age at menopause, body mass index, and breast cancer risk, we used data from a prospective cohort study (DOM cohort) in the Netherlands. Participants in this breast cancer‐screening project included 10,591 women living in Utrecht, aged 49–66 years at enrolment. During a median follow‐up period of 19 years, women attended screening rounds at which anthropometric measurements were taken and questions were asked about menopausal status, age at menopause, medication use and other risk factors for breast cancer. Cox regression analysis was used to investigate the relationship between age at menopause and subsequent breast cancer risk. Breast cancer incidence decreased with an earlier age at menopause. Women with a menopausal age of 44 years or younger had a 34% lower risk of breast cancer, than women with a menopausal age over 54 years (hazard ratio is 0.66 (95% confidence interval 0.43–0.91)). The annual hazard of breast cancer incidence decreased by 2.6% per year reduction in age at menopause. The protective effect of an early age at menopause was stronger for women with a low body mass index (≤27 kg/m2; reduction of 44%) than for women with a high body mass index (〉27 kg/m2; reduction of 24%), although this difference was not statistically significant (P for interaction = 0.58). This difference was most pronounced in women who had ever smoked. Adjustment for known breast cancer risk factors did not alter the crude risk estimates significantly. In conclusion, this study provides evidence of the protective effect of lower age at menopause on subsequent breast cancer risk. This protective effect may be even stronger in leaner women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006277207963
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  • 96
    Electronic Resource
    Electronic Resource
    Suppression of parathyroid hormone‐related protein messenger RNA expression by medroxyprogesterone acetate in breast cancer tissues (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 11-23 
    Details
    ISSN: 1573-7217
    Keywords: androgen receptor ; bone metastasis ; breast cancer ; medroxyprogesterone acetate ; parathyroid hormone‐related protein ; progesterone receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The level of parathyroid hormone‐related protein (PTHrP) expressed in breast cancer tissue is closely related to the incidence of bone metastasis. We examined the PTHrP mRNA expression in breast cancer tissues by coamplification polymerase chain reaction (PCR) in mole ratio to internal standard β‐actin mRNA. The PTHrP expression was higher in premenopausal patients than in postmenopausal patients (P〈0.05). More pronounced difference by menopause found in estrogen receptor (ER) positive groups (P〈0.001) indicated that the PTHrP expression in breast cancer tissue is hormonally regulated and might be altered by endocrine agents. To clarify the changes of PTHrP expression by endocrine therapy of breast cancer, we measured PTHrP expression in the breast cancer tissue incubated for 24 h with 1 × 10−8 M of estradiol (E2), 1 × 10−6 M of tamoxifen (TAM) and 1 × 10−5 M of medroxyprogesterone acetate (MPA). The PTHrP expression was decreased significantly by MPA (P〈0.005), while E2 and TAM did not change the PTHrP expression. Progesterone receptor (PgR) mRNA expression was also examined to confirm that the breast cancer tissue responds to E2 and TAM. The results were well compatible with the better therapeutic effect of MPA reported for the treatment of breast cancer with bone metastases. As a potential candidate for the receptor that mediates the suppressive effect of MPA, androgen receptor (AR) is suggested most probable. Present results also demonstrated that the clinical response of individual tumors is closely associated with the early in vitro changes of gene expression detected in the cancer specimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006254006088
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  • 97
    Electronic Resource
    Electronic Resource
    Quality of life in the first year after breast cancer surgery: rehabilitation needs and patterns of recovery (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 45-57 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; psychological distress ; quality of life ; rehabilitation needs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background. Although mortality rates from breast cancer are declining, many breast cancer survivors will experience physical and psychological sequelae that affect their everyday lives. Few prospective studies have examined the rehabilitation needs of newly diagnosed breast cancer patients, and little is known about the predictors of health‐related quality of life (QOL) in this population. Methods. Between 1987 and 1990, 227 women with early stage breast cancer participated in a prospective longitudinal study in which detailed information was collected through interviews, standardized measures of QOL and psychological distress, and clinical evaluation. Comparisons of physical and treatment‐related problems were made according to type of surgical treatment. Multivariate regression analysis was performed to examine the predictors of QOL at one year after surgery. Results. Physical and treatment‐related problems were reported frequently one month after breast cancer surgery, and occurred with equal frequency in women receiving modified radical mastectomy or breast conservation treatment. There were no significant differences in problems reported at one year by type of surgery; however, frequently reported problems include ‘numbness in the chest wall or axilla,’ ‘tightness, pulling or stretching in the arm or axilla,’ ‘less energy or fatigue,’ ‘difficulty in sleeping,’ and ‘hot flashes’. There was no relationship between the type of surgery and mood or QOL. Poorer QOL one year after surgery was significantly associated with greater mood disturbance and body image discomfort one month after surgery, as well as positive lymph node involvement. Although the majority of patients experienced substantial disruptions in the physical and psychosocial dimensions of QOL post‐operatively, most women recovered during the year after surgery, with only a minority (〈10%) significantly worsening during that time. Conclusions. At one year after surgery, most women report high levels of functioning and QOL, with no relationship between the type of surgery and QOL. Women who reported lower levels of QOL at one year after diagnosis had greater mood disturbance and poorer body image one month after surgery, as well as lower income and positive axillary nodes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006214830854
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  • 98
    Electronic Resource
    Electronic Resource
    Postoperative chemo–endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor–positive stage II breast cancer (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 111-122 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; estrogen receptor ; mitomycin C ; postoperative chemotherapy ; tamoxifen ; UFT
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991, we studied the effects of postoperative adjuvant therapy for Japanese women with stage II breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER− tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER− patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease–free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments 〈0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P〈0.0 1). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006221425652
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  • 99
    Electronic Resource
    Electronic Resource
    Expression of inducible nitric oxide synthase in human breast cancer depends on tumor grade (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 143-149 
    Details
    ISSN: 1573-7217
    Keywords: breast cancer ; immunohistochemistry ; nitric oxide synthases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Expression of inducible nitric oxide synthase (iNOS) by tumor cells has been suggested to abrogate metastasis in several tumor models, whereas constitutive NOS expression correlated positively with tumor grade in human breast carcinoma. Whether or not expression of one of the various NOS isoforms could predict the prognosis of breast cancer, however, has not been established. In the present report we investigated the cellular distribution of NOS isoforms in a series of benign and malignant breast tumors and in normal breast tissue. Immunohistochemistry revealed that in samples of benign disease the number of iNOS + epithelial cells or total epithelial cells was 69 ± 16% (n=50). In samples of grade II invasive ductal breast carcinomas the number of iNOS+ tumor cells or total tumor cells was 62 ± 20 (n=40), compared to 12 ± 9 (n=40) in samples of grade III carcinomas (P 〈 0.0001). iNOS protein was also identifiable in most of the epithelial cells of normal breast tissue (n=4). In contrast, eNOS protein was restricted to vascular endothelial cells in all of the specimens studied. Since the presence of tumor cell iNOS protein is inversely related to the tumor’s metastatic potential, we conclude that endogenous tumor cell mediated iNOS expression might have an inhibitory effect on the metastatic process in breast cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006288526311
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  • 100
    Electronic Resource
    Electronic Resource
    PACAP (6–38) is a PACAP receptor antagonist for breast cancer cells (1999)
    Springer
    Breast cancer research and treatment 56 (1999), S. 175-184 
    Details
    ISSN: 1573-7217
    Keywords: PACAP ; VIP ; breast cancer ; proliferation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of pituitary adenylate cyclase activating polypeptide (PACAP) analogs were investigated using breast cancer cells. 125I–PACAP–27 bound with high affinity (Kd=5 nM) to T47D cells (Bmax = 29,000 per cell). Specific 125I–PACAP–27 binding was inhibited half maximally by PACAP–27, PACAP–38, PACAP(6–38) and PACAP(28–38) with IC50 values of 8, 17, 750 and 〉3000 nM, respectively. By RT–PCR, PACAP receptor mRNA was present in MCF–7 and T47D cell lines. Polyclonal antibodies to a PACAP receptor fragment (A–8–C) were elicited. The antibodies were affinity purified, recognized a 60–kDa protein by western blot, and stained malignant cells in breast cancer biopsy specimens by immunohistochemistry. PACAP–27 elevated the cAMP in T47D cells and the increase in cAMP caused by PACAP was inhibited by PACAP(6–38). PACAP–27 stimulated c–fos mRNA in T47D cells and the increase in c-fos gene expression caused by PACAP was reversed by PACAP (6–38). PACAP (6–38) inhibited colony formation using a soft agar assay and inhibited breast cancer xenograft growth in nude mice. These data suggest that PACAP (6–38) functions as a breast cancer PACAP receptor antagonist.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1006262611290
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