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  • breast cancer
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  • 101
    ISSN: 1573-7217
    Keywords: breast cancer ; microsatellite instability ; microsatellite markers ; review ; survey
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Microsatellite markers may provide evidence of faulty DNA mismatch repair (MMR) via the detection of microsatellite instability (MSI). The choice of microsatellite markers may impact on the MSI detection rate. In hereditary non-polyposis colon cancer (HNPCC), several informative microsatellite markers have been recommended. Two of these, BAT 25 and BAT 26, are quasi-homozygous, enabling analysis of tumour DNA in the absence of paired normal DNA. Sixty-six breast cancer patients under 45 years of age at diagnosis were examined for MSI at BAT 25 and BAT 26. Tumour DNA was extracted from paraffin-embedded tissue. No MSI was detected at the BAT 25 or BAT 26 loci. An additional five microsatellite markers, known to be informative for HNPCC, were examined for MSI in these patients. Apparently-normal profiles were achieved. A tabulated survey of 306 microsatellite markers used to detect MSI in breast cancer revealed that only 35.5% of markers detected MSI at an average rate of 2.9%. The MSI detection rate at the specific HNPCC markers varied from 0% to 10% in breast cancer, with D175250 and TP53 being the HNPCC markers most suitable for analysis of breast cancer. The size of the microsatellite marker's repeat unit did not impact on MSI detection rates. Compiled data from large studies (n〉100) revealed D115988 as the marker with the highest MSI detection rate. Genomic instability pathways of carcinogenesis, characterised by MMR defects and MSI, appear to play a role in the genesis of some breast cancer types.
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  • 102
    ISSN: 1573-7217
    Keywords: aromatase inhibitor ; breast cancer ; liarozole ; retinoic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Liarozole is an imidazole compound that inhibits enzymes involved in steroid hormone aromatisation and retinoid metabolism. The IDBBC branch of the EORTC has performed a series of phase II studies of the agent in four groups of postmenopausal women with metastatic breast cancer. This paper reports the results of the first two groups: ‘Chemotherapy Resistant’ (unrestricted ER status, 1 or 2 prior chemotherapy regimens, 0–2 prior hormonal therapies) and ‘Potentially Hormone Sensitive’ (ER positive or unknown, 1 or 2 prior hormonal therapies with a substantial disease free interval or progression free survival, and no history of chemotherapy for metastatic disease). Liarozole was administered at 150–300 mg orally bid. The objective response rate was 12% in the ‘Chemotherapy Resistant’ group (n=34), and 22% in the ‘Potentially Hormone Sensitive’ group (n=37), with median response durations of 9 and 14 months, respectively. Median time to treatment failure was only 2 months in both groups, due largely to the significant percentage (24%) of patients who ceased treatment following excessive mucocutaneous and gastrointestinal toxicity. This adverse event profile will limit its use in breast cancer. Results of the ‘ER negative’ and ‘Tamoxifen Refractory’ groups will be reported in a future paper.
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  • 103
    ISSN: 1573-7217
    Keywords: active processed cathepsin D ; breast cancer ; prognostic indicator ; survival analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relative amounts of the precursor (52 kDa) and processed (31,27 kDa) forms of cathepsin D have been analyzed by Western blotting in biopsied breast tissue cytosols from 134 lesions from invasive breast cancer patients, 24 lesions from patients with ductal carcinoma in situ (DCIS), 227 lesions from benign breast disease patients, and 28 lesions from normal control subjects. The mean relative percentage amount of the 31 kDa form was significantly increased (p〈0.001) in the invasive breast cancer group compared to the other three groups. In addition, the mean relative percentage amount of the 31 kDa form was significantly increased (p〈0.05) in node-positive compared to node-negative breast cancer patients. In the benign breast disease group, patients with proliferative-type disease had a significantly increased (p=0.02) mean relative percentage amount of the 31 kDa form of cathepsin D compared to patients with nonproliferative-type disease. Invasive breast cancer patients were followed for up to 75 months to determine if the relative percentage amount of the 31 kDa form of cathepsin D was predictive of disease-free and overall survival. Although the amount of the 31 kDa form was not predictive of disease-free survival, patients in the ‘high’ 31 kDa group (〉18) were significantly (p〈0.05) more likely to die than patients in the ‘low’ 31 kDa group (≤18%). The 12 patients who died were all node-positive and in the high 31 kDa group. It thus appears that the relative amount of the processed, active 31 kDa form of cathepsin D is a useful prognostic indicator, at least in node-positive breast cancer patients.
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  • 104
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 60 (2000), S. 259-266 
    ISSN: 1573-7217
    Keywords: TSG101 ; breast cancer ; tumor suppressor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Functional inactivation of the tsg101 gene in mouse fibroblasts results in cell transformation and the ability to form metastatic tumors in nude mice. The human tsg101 gene was mapped to chromosome 11q15.1-2 and found to mutate in some cancer patients. To test the expression pattern of the tsg101 gene in Chinese breast cancer patients, we analyzed the mRNA by RT-PCR in 51 breast cancer patients. The full-length tsg101 and 7 truncated transcripts were detected in both normal and matched tumor tissues. A short transcript with a deletion of nucleotides 154–1054 is frequently presented in late-stage breast cancers. TSG101 protein expression was also detected by Western blot analysis in 30 breast cancer patients. A predicted full-length 46 kDa and three proteins with smaller molecular weight were detected. The full-length 46 kDa protein was less expressed in tumor specimens. Immunohistochemical stains from 10 patients of each stage 0–4 revealed that TSG101 protein was predominantly present in the cytoplasm. Cell nuclei were occasionally immunopositive and the chromosomes were deeply stained during cell division. The intracellular location and the expression of TSG101 protein were both not stage-dependent in primary breast cancers. In addition, normal mammary glands were more homogenously immunopositive than invasive ductal carcinoma. These results support the notion that the aberrant expression of TSG101 in breast cancer is associated with altered cell growth.
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  • 105
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 60 (2000), S. 201-209 
    ISSN: 1573-7217
    Keywords: breast cancer ; growth rates ; histological grade ; primary medical treatment ; radiotherapy fractionation ; ‘split-course’ radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract ‘Timing’ of treatment in breast cancer may refer to intervals within a single management or between different managements. Rates of shrinkage of breast cancers in response to treatment are related to histological grade and may be used as surrogates for growth rates. Histological grade should predict appropriate timing of treatment. Four cases of locally advanced breast cancer that illustrate a number of different types of interval are presented. Two tumours of differing histological grade (II and III) had been managed by historical ‘split-course’ radiotherapy and two similar grade III tumours were managed by primary medical treatment, followed at different intervals by radiotherapy. In the grade III tumours different radiotherapy fractionation régimes and effects of varying intervals between mangements are compared. The theoretical advantage of shrinkage (leading to reoxygenation) during the gap in ‘split-course’ radiotherapy is realized only in relatively slowly growing and shrinking tumours. Grade III tumours grow rapidly. They have the potential to shrink rapidly in response to appropriate treatment, namely intensive chemotherapy or radiotherapy but not hormones. Inadequate treatment leads to growth in intervals between individual doses, whether of drugs or radiation, and to failure of local control. The advantage of surgery or primary medical treatment will be lost if the interval between managements is too long in relation to the volume doubling time. Histological grade is a good guide of this parameter; the grade III tumours are particularly vulnerable to gaps in treatment.
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  • 106
    ISSN: 1573-7217
    Keywords: breast cancer ; 5-fluorouracil ; methotrexate ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A novel approach is described to simulate effect site pharmacodynamics of anticancer drugs. This approach is based on (i) the in vivo measurement of unbound, interstitial drug pharmacokinetics (PK) in solid tumor lesions in patients and (ii) a subsequent pharmacodynamic (PD) simulation of the time versus drug concentration profile in an in vitro setting. For this purpose, breast cancer cells (MCF-7) were exposed in vitro to the time versus interstitial tumor concentration profiles of 5-fluorouracil (5-FU) and methotrexate (MTX) from primary breast cancer lesions in patients. This led to a maximal reduction in the viable cell count of 69 on day 4, and of 71 on day 7 for 5-FU and MTX, respectively. This effect was dependent on the initial cell count and was characterized by a high interindividual variability. For 5-FU there was a significant correlation between the maximum antitumor effect and the intratumoral AUC (r = 0.82, p = 0.0005), whereas no correlation could be shown for MTX (r = 0.05, p = 0.88). We conclude, that the in-vivo-PK / in-vitro-PD model presented in this study may provide a rational approach for describing and predicting pharmacodynamics of cytotoxic drugs at the target site. Data derived from this approach support the concept that tumor penetration of 5-FU may be a response-limiting event, while the response to MTX may be determined by events beyond interstitial fluid kinetics.
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  • 107
    ISSN: 1573-7217
    Keywords: breast cancer ; database ; prognosis ; Taiwan ; young age
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Between April 1990 and December 1997, 811 consecutive patients with 830 newly diagnosed breast cancers having their primary treatments in our institution were included in this study. Sixty three percent of breast cancer patients were premenopausal. The early-onset breast cancer (age ≤ 40) composed 29.3% of all patients. The five-year survival rate of all patients was 80.4% (95% confidence interval [CI], 76.2–84.6%). The five-year overall survival rate for stage 0 was 95.7% (95% CI, 87.3–100%), stage I, 93.9% (95% CI, 88.9–98.9%), stage II, 88.5% (95% CI, 82.0–95.1%), stage III, 65.0% (95% CI, 54.0–75.9%), and stage IV, 18.5% (95% CI, 3.4–33.7%). Multivariate analysis of primary operable breast cancer revealed that axillary lymph node involvement, high nuclear grade and early-onset breast cancer (age ≤ 40) were poor prognostic factors. The early-onset breast cancer had a more aggressive clinical behavior than that of the older age group, their five-year disease-free survival rates for stage I, stage II and stage III diseases being only 64.7%, 66.5%, and 43.3%, respectively. In these patients the only meaningful prognostic factor was extensive axillary lymph node metastasis (≥10). In summary, breast cancer patients in Taiwan tend to be younger than their counterpart in western countries. The early-onset breast cancer had poorer prognostic features for all stages comparing to the older age group. Standard pathologic factors are not good predictors of their outcome. For these patients new biologic markers need to be sought to distinguish between high and low risk and the treatment strategy for them should be guided by the aggressive characteristics of the disease.
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  • 108
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 63 (2000), S. 225-234 
    ISSN: 1573-7217
    Keywords: breast cancer ; cholesterol ; triglycerides ; tamoxifen ; toremifene
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tamoxifen decreases serum cholesterol (S-cholesterol) level about 10% and low-density lipoprotein cholesterol (S-LDL) 15–20%, but in most studies it has increased serum triglyceride levels and had little effect on serum high-density cholesterol (S-HDL). The effect of another antiestrogen, toremifene, on the serum lipid profile has not been completely studied. We monitored serum lipid levels longitudinally in 141 axillary node-positive postmenopausal breast cancer patients who received randomly either 40 mg toremifene or 20 mg tamoxifen as adjuvant therapy for 36 months, and in 34 postmenopausal women who received no adjuvant systemic therapy after surgery for axillary node-negative breast cancer. No significant differences were found between the drugs in their effects on S-cholesterol, LDL, HDL, or triglyceride levels, or on the cholesterol-to-HDL or LDL-to-HDL ratios. For both drugs the S-cholesterol and S-LDL absolute lowering effect was the greater the higher the pretreatment level. For a patient with a median pretreatment value, toremifene decreased S-cholesterol 6% and tamoxifen 13%, and S-LDL decreased by 13% and 23%, respectively, at 6 months of therapy. Six months after stopping three-year antiestrogen therapy S- cholesterol and S-LDL levels had returned to the pretreatment levels. In conclusion, we found no major differences between 40 mg toremifene and 20 mg of tamoxifen in their effect on the serum lipid levels, which return to the pretreatment levels within 6 months after cessation of therapy.
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  • 109
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 64 (2000), S. 201-209 
    ISSN: 1573-7217
    Keywords: alcohol ; breast cancer ; cohort ; women
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Available epidemiological evidence indicates that alcohol intake is associated with a higher risk of developing breast cancer. Plausible biological pathways include its effect on levels of estrogens, cell membrane integrity and cell-to-cell communication, inhibition of DNA repair, and congener effect. The present study evaluated the impact of alcohol on mortality from breast cancer, an area with relatively few studies in the literature. The subjects were participants in a Canadian prospective cohort study, the National Breast Screening Study (NBSS). Women were enrolled in the cohort from 1980 to 1985 to evaluate the efficacy of mammographic screening. Information on usual diet and alcohol intake at enrolment and other epidemiological variables was collected by means of a mailed, self-administered questionnaire. Mortality from breast cancer during follow- up to 31 December, 1993 was ascertained by record linkage to the Canadian Mortality Data Base maintained by Statistics Canada. During the follow-up period of 1980–1993 (average 10.3 years), 223 deaths from breast cancer were identified for this analysis. The hazard ratios for the risk of death from breast cancer increased with intakes of total alcohol of 10–20 g/day (1.039, 1.009–1.071) and 〉 20 g/day (1.063, 1.029–1.098). This increase was contributed largely by the intake of wine, a 15% increase in risk at intakes higher than 10 g/day of alcohol from wine. Alcohol from spirits was associated with a small decrease in risk of death (hazard ratio at 10 g/day, 0.945, 0.915–0.976). The effect of alcohol from beer was not significant in the two categories studied. Although our results were statistically significant, the magnitude of the change in risk was small.
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  • 110
    ISSN: 1573-7217
    Keywords: breast cancer ; EGF receptor ; erbB2 ; estrogen receptor ; LAR ; 13762NF tumor ; tyrosine phosphatase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Several prognostic indices in breast cancer, including c-erbB2, epithelial growth factor receptors (EGFR), estrogen and progesterone receptors are signal transduction molecules. Recently, expression of another signal transduction molecule, the protein tyrosine phosphatase LAR, has been suggested to be increased in breast cancer. The objective of the current investigation was to examine the relationship between LAR expression and prognostic parameters in breast cancer. LAR expression was associated with metastatic potential in the well-characterized 13762NF rat mammary adenocarcinoma clones. The metastatic MTLn3 and MTLn2 clones expressed sizable amounts of LAR. The essentially non-metastatic MTC clone had little LAR expression. C-erbB2 had highest expression in the highly metastatic MTLn3 clone, but c-erbB2 levels were sizeable in the weakly metastatic MTLn2 and non-metastatic MTC clone. EGFR expression had the strongest association with a clone's metastatic potential, being very high in MTLn3, weak in MTLn2, and undetectable in MTC. In human breast cancer specimens, LAR expression was strongly positive in 50% of metastatic cases but in only 21% of ‘non-metastatic’ cases. As with the 13762NF-derived clones, c-erbB2 expression was strongly positive independent of metastatic phenotype. However, 46% (6/13) of cases that were strongly positive for c-erbB2 were strongly positive for LAR. Only 17% (2/11) of negative or weakly c-erbB2 positive samples were strongly positive for LAR. All ER+ positive tumors (n = 15) were positive for LAR and 53% of these tumors were strongly positive for LAR. In ER− negative cases, only 1 of 11 was strongly positive for LAR. While the current data indicate a strong association between ER and LAR expression in breast cancer tissue (p = 0.003), additional studies are warranted to further explore the relationship between LAR and prognostic indices of breast cancer progression.
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  • 111
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 61 (2000), S. 33-43 
    ISSN: 1573-7217
    Keywords: breast cancer ; p21WAF1/CIP1 ; p53 ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract p21WAF1/CIP1 is transcriptionally activated by wt p53 and inhibits G1 associated cyclins, a major mechanism by which p53 inhibits cellular proliferation. Archival breast cancers (798) with a median follow-up of 16.3 years were used to explore the prognostic value of p2l immunohistochemical analyses. p21 immunostaining was detected in the majority (726/798: 91%) of breast cancers as well as adjacent in situ carcinomas (125/170: 74%), hyperplastic lesions (140/349: 40%) and normal breast epithelium adjacent to carcinoma (3/89: 3%). Complete immunonegativity was observed in only 9% of invasive cancers and was associated with p53 immunopositivity (p〈0.05). Univariate analysis of all patients showed that p21 negativity was associated with a longer disease specific survival (relative risk (RR) 1.5). Node positive p21 – patients also showed a longer disease free and disease specific survival as compared to tumor p21+ patients. In node negative patients, p53 positivity but not p21 alone, was significantly associated with a shortened disease free survival (RR = 1.6). Node negative patients who were p53 + p21−, in particular had the shortest disease free survival compared to other p53, p21 subgroups (i.e., p21 negativity was associated with a worse outcome). Multivariate analysis of lymph node negative patients (n〉300) demonstrated that tumor size and tumor grade were independently predictive of outcome, whereas neither p53 nor p21 were significant. For node positive patients, p21 positivity (p=0.05), p53 positivity (p=0.03), a higher number of positive nodes, larger tumor size, steroid receptor negativity, high proliferation rate, and erbB-2 expression were each independently associated with poor outcome. In summary, p21 negativity was inversely correlated with p53 immunopositivity in the majority of cases. p21 negative tumor patients had an improved outcome if they were node positive, whereas p21 status was not significantly associated with survival in node negative patients. This observation may be due to the reported ‘uncoupling of S phase and mitosis’ associated with a loss of p21 expression which may result in enhanced sensitivity to chemotherapy.
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  • 112
    ISSN: 1573-7217
    Keywords: ataxia telangiectasia ; ATM ; breast cancer ; mutation screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Based upon the results of several epidemiologic studies, it has been suggested that women who are carriers for a mutation in the ataxia telangiectasia-mutated (ATM) gene are susceptible for the development of breast cancer. Therefore, 37 consecutive breast cancer patients were screened for the presence of a germline ATM mutation using a non-isotopic RNase cleavage-based assay (NIRCA). This paper reports the first use of NIRCA for detection of ATM mutations in breast cancer patients. Using this assay, no ATM mutations were found in our patient population. This result is similar to the findings of other studies that have employed approaches complementary to NIRCA.
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  • 113
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 61 (2000), S. 45-57 
    ISSN: 1573-7217
    Keywords: androgen receptor ; apoptosis ; Bax ; Bcl-2 ; breast cancer ; estrogen receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have established a Noble rat model to explore the mechanisms of hormonal mammary carcinogenesis, in which the role of androgen in promoting mammary carcinogenesis was highlighted. We have also established that stromal-epithelial interactions may be responsible for the promotional effects of testosterone in mammary carcinogenesis. Based on these understandings, in the present study we examined the expression of Bcl-2 and Bax in pre-malignant mammary glands from rats treated with different protocols of sex hormones for 7 weeks as well as sex hormone induced mammary tumours. We observed that Bcl-2 was strongly expressed in most of mammary tumour cells, whereas weak or negative in adjacent normal or hyperplastic ductal structures. On the contrary, Bax immunoreactivity was weak in mammary tumour cells while strongly expressed in adjacent normal or hyperplastic ductal structures. More importantly, the results from comparative study of ‘pre-malignant’ glands further showed that when animals were treated with 17β-oestradiol, the mammary epithelial cells expressed high levels of Bcl-2. The results from rats treated with testosterone, either alone or in combination with oestrogen, give rise to high levels of Bax expression in ‘pre-malignant’ mammary glands. These observations indicate that in ‘pre-malignant’ mammary glands, treatment with testosterone, either alone or in combination with 17β-oestradiol, may induce high apoptotic activities. However, in fully developed mammary tumours, the apoptotic activities apparently decrease in tumour cells. TUNEL assay provides further data to support this conclusion. Our study, thus, suggests that androgens may play a promoting role in mammary carcinogenesis by upregulation of Bax expression and induction of high apoptotic activities in ‘pre-malignant’ stage, which would provide a selective pressure favouring the expansion of the initiated cells.
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  • 114
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 61 (2000), S. 121-129 
    ISSN: 1573-7217
    Keywords: breast cancer ; ex-smokers ; smoking ; smoking cessation ; tobacco
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract High plasma levels of oestrogens are associated with increased breast cancer risk. If smoking, as has been suggested, have both a tumour initiating mutagenic effect and a protective anti-oestrogenic effect, one would assume that smokers who give up smoking have the highest incidence of breast cancer. This was evaluated in the follow-up of a cohort of 10,902 women of whom 4,359 were premenopausal. Record-linkage with official cancer registries yielded 416 incident cases during an average follow-up of 13.6 years. The adjusted relative risk in all ex-smokers was 1.31 (1.02–1.69), as compared to never smokers, and in premenopausal ex-smokers it was 1.57 (1.07–2.30). Breast cancer incidence in premenopausal ex-smokers was inversely related to time since cessation, (p for trend = 0.01), and was highest among the women who had given-up smoking less than 12 months before screening: 2.76 (1.55–4.91). There was no significant association between current smoking and breast cancer risk. We conclude that incidence of breast cancer in premenopausal women who have given up smoking is higher than it is in smokers and never smokers. To what extent this may be related to endocrine effects associated with smoking cessation remains to be evaluated.
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  • 115
    ISSN: 1573-7217
    Keywords: breast cancer ; breast conserving surgery ; hospital practices ; mastectomy ; physician behavior
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied whether a hospital intervention utilizing medical opinion leaders and performance feedback reduced the proportion of women who reported that surgeons did not discuss options prior to surgery for early stage breast cancer. Opinion leaders provided clinical education to their peers using a variety of strategies and were selected for their ability to influence their peers. Performance feedback involved distributing performance reports that contained data on the outcomes of interest as well as on other treatment patterns. Twenty-eight hospitals in Minnesota were randomized to the intervention or to a control group that received performance feedback only. The proportion of patients at intervention hospitals who said that their surgeon did not discuss options decreased significantly (p〈0.001) from 33% to 17%, but a similar decrease was observed among control hospitals. Using medical opinion leaders to intervene in hospitals appeared as effective as performance feedback.
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  • 116
    ISSN: 1573-7217
    Keywords: androgen receptor ; breast cancer ; mutation ; polymorphism ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Prostate Specific Antigen (PSA) expression by breast epithelial cells is associated with favorable breast cancer prognosis. In preliminary studies, we found that a nucleotide variation (G → A) at position −158 in the androgen response element (ARE-1) of the PSA promoter was present in four out of 9 breast tumors examined and in a breast carcinoma cell line. We have now determined the nucleotide composition at position −158 of DNA extracted from 148 well-characterized breast tumors and compared tumor genotype with that of controls without cancer, with tumor PSA concentration and with clinicopathological variables, overall survival and disease free survival. The G → A base change at position −158 is a polymorphism. Allelotypes were similarly distributed in breast cancer patients and controls. The Mann–Whitney U Test showed a significantly higher tumor PSA concentration in tumors that presented a homozygous G as opposed to homozygous A genotype. Genotype at position −158 was not associated with clinicopathological variables in contingency table analysis. Univariate Cox regression models showed a 28% reduction in risk for death in patients with homozygous G genotype compared to those with homozygous A genotype (P=0.03). However, ARE-I genotype did not significantly add to the prognostic power in the multivariate model of overall survival. In summary, the base change at position −158 is a polymorphism that may affect breast cancer prognosis, but further studies are required to confirm this possibility and to investigate the relevance of this polymorphism in terms of breast cancer susceptibility.
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  • 117
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    Breast cancer research and treatment 61 (2000), S. 139-143 
    ISSN: 1573-7217
    Keywords: breast cancer ; mutation ; nipple aspirate fluid ; p53
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Nipple Aspirate Fluid (NAF) from patients with breast cancer is a potential source of exfoliated tumour material amenable to molecular biological study, but few such data have been reported. In this study we demonstrate that polymerase chain reaction (PCR) amplification of p53 gene DNA is achievable in a proportion of NAF samples from breast cancer patients. Subsequently four NAF samples from patients whose primary tumours were identified as having a defined p53 mutation were studied by single stranded conformational polymorphism analysis (SSCP). Two samples yielded PCR product indistinguishable from wild type and two yielded no product. Whilst no cancer-related genetic mutations were demonstrated in NAF samples, further study is warranted.
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  • 118
    ISSN: 1573-7217
    Keywords: adjustment disorders ; breast cancer ; first recurrence ; major depressive disorder ; psychological distress
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: To investigate the prevalence of, and risk factors for psychological distress following first recurrences of breast cancer. Patients and methods: The sample was drawn consecutively from the inpatient and outpatient populations of the National Cancer Center Hospital in Japan during an 18-month period from July 1996 to December 1997. Of the 56 eligible patients, 55 women aged 30–73 year with recurrent breast cancer participated in the study. The prevalence of psychological distress, including major depressive disorder and adjustment disorders was evaluated according to the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Third edition-revised (DSM-III-R). Risk factors for psychological distress were analyzed with a logistic regression model. Results: Of the 55 subjects, 42 met the DSM-III-R criteria for major depressive disorder or adjustment disorders. Major depressive disorder was seen in 4 (7%), and adjustment disorders in 19 (35%). Logistic regression analysis showed that a disease-free interval of less than 24 months significantly predicted a diagnosis of major depressive disorder or adjustment disorders (odds ratio 5.28, 95% confidence interval; 1.28–21.8, p=0.02). Conclusions: These results suggest that it is important for all oncology staff to pay careful attention to the psychological health of patients who have been informed of their cancer recurrence, and that some psychosocial intervention is necessary for preventing distress in patients facing early recurrence.
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  • 119
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    Breast cancer research and treatment 61 (2000), S. 161-170 
    ISSN: 1573-7217
    Keywords: breast cancer ; cell cycle ; ductal ; histologic subtypes ; lobular
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are similar in many respects and their histologic features occasionally overlap. Despite the many similarities, some clinical follow-up data and the patterns of metastasis suggest that ILC and IDC are biologically distinct. Unfortunately, most breast cancer research has focused almost exclusively on the ductal subtype or has not stressed the biologic or molecular genetic distinctions between breast carcinoma subtypes. Several reports have suggested the possibility that ILCs and IDCs differ with respect to expression of antigens involved in proliferation and cell cycle regulation. Therefore, we undertook an immunohistochemical evaluation of cell cycle related antigens in ILCs, including histologic variants thought to represent aggressive neoplasms, and IDCs matched for histologic grade (Modified Bloom–Richardson Grade I). We believe that different antigent expression profiles could elucidate the biological distinctiveness of breast carcinoma subtypes and possibly provide diagnostically relevant information. We studied the expression of the following antigents in 28 archived, formalin-fixed ILCs and 34 well-differentiated IDCs: estrogen receptor (ER), progesterone receptor (PR), Her 2-neu, mib-1, cyclin D1, p27, p53, mdm-2 and bcl-2. 94% of ILCs and 100% of IDCs expressed ER; 75% of ILCs and 76% of IDCs expressed PR; 4% of ILCs and 13% of IDCs expressed c cerb B-2; ILCs and IDCs both expressed mib-1 in approximately 10% of lesional cells; 82% of ILCs and 54% of IDCs expressed cyclin D1; 90% of ILCs and 83% IDCs expressed p27 strongly; 4% of ILCs and 4% of IDCs expressed p53, 25% of ILCs and 33% of IDCs expressed mdm-2; 96% of ILCs and 100% of IDCs expressed bcl-2. None of the apparent differences were statistically significant. The ILC variants demonstrated immunophenotypes that were essentially similar to ILCs of the usual type. We conclude that ILCs and well-differentiated IDCs show similar proliferation and cell cycle control antigen profiles. Despite their unusual histologic features, most ILC variants appear to maintain a characteristic ILC immunophenotype.
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  • 120
    ISSN: 1573-7217
    Keywords: breast cancer ; in vivo tumor models ; Her-2/neu ; metastasis ; SCID mice ; soluble Her-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract HER-2/neu is overexpressed on a variety of human adenocarcinomas and overexpression has been associated with a poor prognosis. For this reason, HER-2 has become an attractive target for immunotherapy. To facilitate testing of anti-HER-2-monoclonal antibodies (MAbs) and immunotoxins (ITs), we have evaluated the in vivo growth and metastatic spread of three HER-2-overexpressing human breast cancer cell lines (BT474, MDA-MB-453 and HCC1954) and one ovarian cancer cell line (SKOV3.ip1) in pre-irradiated male SCID mice using subcutaneous (s.c.), intravenous (i.v.) and intraperitoneal (i.p.) routes of injection. All the cell lines tested grew as s.c. tumors and the growth of BT474 and MDA-MB-453 cells after s.c. injection was improved by co-inoculation with Matrigel. Metastases to the lungs were detectable by PCR or histopathology after s.c. injection of BT474 and to a much lesser extent after s.c. injection of HCC1954, MD-MB-453 and SKOV3.ip1cells. I.P. injection of HCC1954 and SKOV3.ip1 cells produced fatal ascites while i.v. injection of SKOV3.ip1, but not BT474 or MDA-MB-453 cells, resulted in infiltration of lungs and death within 9–11 weeks.
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  • 121
    ISSN: 1573-7217
    Keywords: breast cancer ; chemotherapy ; cohort study ; radiotherapy ; second primary cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives and methods.The risk of second primary malignancies (SMN) was studied in a cohort of 4,416 one-year survivors of a breast cancer. The role of the menopausal status and of the initial treatment modalities (surgery, radiotherapy, and chemotherapy) was investigated. Results.Excluding second primary breast cancer and non-melanoma skin cancer, a total of 193 (4.4%) patients developed a SMN between 1973 and 1992, compared with 136 expected (Standardised Incidence Ratio, SIR = 1.4, 95% CI (1.2–1.6)). No trend towards either an increase or a decrease was noted in the SIR with time after treatment (p = 0.2). The greatest increase in the relative risk concerned soft tissue cancers (SIR = 13.0, 95% CI: 6.8–22.3), followed by leukaemia (SIR = 3.1, 95% CI: 1.7–5.0), melanoma (SIR  =  2.7, 95% CI: 1.4–4.8), kidney (SIR = 2.5, 95% CI: 1.2–4.5), ovary (SIR = 2.0, 95% CI: 1.2–3.1) and uterine tumours (SIR = 1.9, 95% CI: 1.4–2.5). The SIR was 3.0 (95% CI 1.8–4.7) in women under 40 at the time of the breast cancer, 1.9 (95% CI : 1.4 – 2.4) in those aged 40–49 and 1.2 (95% CI 1.0–1.4) in those aged 50 or more. In the 2,514 women who had received radiotherapy as initial treatment without chemotherapy, the SIR for all SMN was 1.6 (95% CI: 1.1–2.3) fold higher than in those who had not received radiotherapy as initial treatment. Conclusion.In conclusion, this study confirms the increased risk of second malignancies in women treated for a breast cancer, and particularly in those who were younger at the time of treatment for breast cancer. Our results also suggest that radiotherapy may play a role in the onset of these second lesions.
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  • 122
    ISSN: 1573-7217
    Keywords: apoptosis ; breast cancer ; melatonin ; retinoic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract It has been established that melatonin (Mlt) and retinoic acid, individually, inhibit the proliferation of the estrogen receptor-alpha (ERα)-positive MCF-7 breast cancer cell line. Our laboratory has previously demonstrated that Mlt and all-trans-retinoic acid (atRA) not only inhibit the proliferation, but also induce apoptosis of MCF-7 cells when used in a sequential regimen of Mlt followed 24 h later by atRA. Using this same MCF-7 breast cancer cell line, we investigated the potential pathways through which apoptosis is being induced. We found that treatment of MCF-7 cells with Mlt for 24 h before the addition of atRA decreased the protein levels of the death suppressor, Bcl-2, and increased, although with different time courses, the levels of the death promoters, Bax and Bak; however, there was no change in the levels of the tumor suppressor gene, p53. MCF-7 cells treated sequentially with Mlt and atRA also demonstrated an enhanced sensitivity to the apoptotic effects of atRA, which did not appear to be due to increased expression of the retinoic acid receptors, RARα or RXRα, but rather to enhanced transcriptional activity of the RARα. These data suggest that the sequential treatment regimen of Mlt and atRA may induce apoptosis by modulation of members of the Bcl-2 family of proteins. Thus, this combinatorial regimen, which reduces the concentration of atRA needed for clinical efficacy while enhancing its anti-tumorigenic activity, could be of great therapeutic benefit, and may, in fact, specifically induce the regression of established breast tumors due to its apoptosis-promoting effects.
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  • 123
    ISSN: 1573-7217
    Keywords: breast cancer ; intravenous digital subtraction angiography ; axillary lymph node metastasis ; neovascularization of lymph nodes ; microvascular density ; antibody to platelet/endothelial cell adhesion molecule
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Accurate predication of axillary node status by non-invasive diagnostic method would be of great value in cases of breast cancer. There have been few reports advocating digital subtraction angiography (DSA) as specifically advantageous for the detection of lymph node metastasis. IV (intravenous)-DSA was carried out on 42 patients with breast carcinoma using a DSA system with a matrix of 1024 × 1024×pixels. When a mass became stained in the axilla, it was considered to be metastatic. An immunohistochemical technique with JC70 antibody to platelet/endothelial cell adhesion molecules was used to evaluate the microvascular density (MVD) of the axillary lymph nodes. IV-DSA achieved a 76.2% sensitivity, 85.7% specificity, and 81.0% accuracy. The average MVD with JC70 antibody was 97.7 ± 44.4 in metastatic and 62.9 ± 23.6 in nonmetastatic nodes. MVD was significantly higher in the cancerous than in the noncancerous regions within lymph nodes. The MVD was 105 ± 38.4 in DSA-N(+) cases and was 57.8 ± 21.9 in DSA-N(−) cases, and the difference was statistically significant. In conclusion, IV-DSA is a useful diagnostic modality for detection of axillary lymph node metastasis. This new modality predicts lymph node status by assessing the neovascularization of the lymph node.
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  • 124
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    Cancer causes & control 11 (2000), S. 319-344 
    ISSN: 1573-7225
    Keywords: breast cancer ; endometrial cancer ; fertility drugs ; infertility ; melanoma ; ovarian cancer ; thyroid cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: Over the past decades the use of fertility drugs (FDs) has greatly increased. Recently, the possible association between the use of FDs and risk of cancer has aroused great concern. In this paper, we critically review the available epidemiologic studies. Methods: We identified papers published between 1966 and 1999 that examined FDs and specific causes of subfertility in relation to the risks of cancers of the ovary, breast, endometrium and thyroid, and melanoma. Results: Although present insights into the pathogenesis of hormone-related malignancies suggest a possible association between the use of FDs and the risk of specific cancers, this has not been convincingly demonstrated in epidemiologic studies. With regard to cancer risk in relation to the cause of subfertility, the only consistent association observed is an increased risk of endometrial cancer for women with subfertility due to hormonal disorders. While positive findings in some studies on FDs and ovarian cancer risk have aroused serious concern, the associations observed in most of these reports appear to be due to bias or chance rather than being causal. The most important sources of bias are inadequate confounder control for both parity and causes of subfertility. Conclusions: To discriminate between the possible carcinogenic effects of various ovulation induction regimens, subfertility disorders, and reproductive characteristics associated with subfertility, future studies should include large populations of subfertile women with sufficient follow-up time. In such cohort studies the cause of subfertility should be measured adequately (based on medical records) and information about reproductive characteristics should be collected for all cohort members. Such studies should also include a group of subfertile women with an indication for FD use but not so treated.
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  • 125
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    Cancer causes & control 11 (2000), S. 117-120 
    ISSN: 1573-7225
    Keywords: breast cancer ; cohort ; hydatidiform
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: The etiology of breast cancer is only partially understood. Based on the findings that pregnancies reduce breast cancer risk, a possible inverse association between exposure to the placental hormone human chorionic gonadotropin (hCG) and the risk of breast cancer has been suggested. Hydatidiform mole, a gestational trophoblastic disease, is associated with a high expression of hCG. We performed a population-based cohort study in which women with a history of hydatidiform mole were followed up for future cancer outcomes. Methods: All 3371 women with a notification of hydatidiform mole in the Swedish Cancer Registry between 1958 and 1993 were followed up for future cancer outcomes by record linkages within the registry. Results: In a total of 57,075 person-years of follow-up, 59 women had a diagnosis of breast cancer during follow-up, yielding an overall standardized incidence ratio of 1.3 (95% CI 1.0–1.7). Conclusion: This finding is not consistent with the hypothesis of a protective effect of hCG exposure on breast cancer risk, but rather suggests an adverse association.
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  • 126
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    Breast cancer research and treatment 59 (2000), S. 41-48 
    ISSN: 1573-7217
    Keywords: breast cancer ; bcg-1 ; L19 ; L34 ; MAGE-like ; MLN70 ; subtractive hybridization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A number of approaches have been used to identify genes important in breast cancer. In one approach the genes already shown to be involved in other tumors, such as p53 and Her2neu, were examined. A second approach examined genes detected through genetic screening of families with a high incidence of breast cancer, for example, BRCA-1 and BRCA-2. We used a third approach, subtractive hybridization, to identify and clone genes that were preferentially expressed in breast cancer cells compared to normal mammary epithelium. Instead of analyzing breast cancer cell lines, we examined fresh human breast cancer specimens. By subtracting normal mammary epithelial cDNA from breast cancer cDNA, we were able to clone several genes overexpressed in breast cancer. Two of these genes, L19 and MLN70, were previously reported to be overexpressed in breast cancer. Three of these genes, L19, L34, and MLN70, were localized to a region on chromosome 17 where Her2/neu and BRCA-1 are found. In addition, we isolated a gene we call breast cancer associated gene-1 that was expressed almost exclusively in fresh breast cancer tissue and not in normal mammary epithelium or breast cancer cell lines. We were unable to detect expression of breast cancer associated gene-1 in cell lines from melanoma, renal cell carcinoma, lymphoma, or leukemia. The full-length sequence from two separate breast cancer specimens revealed one amino acid difference compared to the sequence from normal breast epithelial tissue. Further studies are necessary to determine whether these genes contribute to breast cancer development or can be used as therapeutic targets.
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  • 127
    ISSN: 1573-7217
    Keywords: breast cancer ; lobular ; ductal ; conservative surgery ; radiation therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The role of conservative surgery and radiation therapy (CS and RT) in the treatment of patients with infiltrating ductal carcinoma is well established. However, the efficacy of CS and RT for patients with infiltrating lobular carcinoma is less well documented. The goal of this study was to examine treatment outcome after CS and RT for patients with infiltrating lobular carcinoma and to compare the results to those of patients with infiltrating ductal carcinoma and patients with mixed ductal–lobular histology. Methods: Between 1970 and 1986, 1624 patients with Stage I or II invasive breast cancer were treated with CS and RT consisting of a complete gross excision of the tumor and ≥6000 cGy to the primary site. Slides were available for review for 1337 of these patients (82%). Of these, 93 had infiltrating lobular carcinoma, 1089 had infiltrating ductal carcinoma, and 59 had tumors with mixed ductal and lobular feature these patients constitute the study population. The median follow-up time for surviving patients was 133 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. Additional histologic features assessed for patients with infiltrating lobular carcinoma included histologic subtype, multifocal invasion, stromal desmoplasia, and the presence of signet ring cells. Results: Five and 10-year crude results by site of first failure were similar for patients with infiltrating lobular, infiltrating ductal, and mixed histology. In particular, the 10-year crude local recurrence rates were 15%, 13%, and l3% for patients with infiltrating lobular, infiltrating ductal, and mixed histology, respectively. Ten-year distant/regional recurrence rates were 22%, 23%, and 20% for the three groups, respectively. In addition, the 10-year crude contralateral breast cancer rates were 4%, 13% and 6% for patients with infiltrating lobular, infiltrating ductal and mixed histology, respectively. In a multiple regression analysis which included established prognostic factors, histologic type was not significantly associated with either survival or time to recurrence. Conclusions: Patients with infiltrating lobular carcinoma have a similar outcome following CS and RT to patients with infiltrating ductal carcinoma and to patients with tumors that have mixed ductal and lobular features. We conclude that the presence of infiltrating lobular histology should not influence decisions regarding local therapy in patients with Stage I and II breast cancer.
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  • 128
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    Breast cancer research and treatment 59 (2000), S. 1-14 
    ISSN: 1573-7217
    Keywords: breast cancer ; prostate-specific antigen ; prognostic indicators ; tumor markers ; breast cyst ; benign breast disease ; molecular forms of prostate-specific antigen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Although prostate-specific antigen (PSA) is the most valuable tumor marker for the diagnosis and management of prostate carcinoma, it is widely accepted that PSA is not prostate specific. Numerous studies have shown that PSA is present in some female hormonally regulated tissues, principally the breast and its secretions. In this review, we summarize the findings of PSA in the breast, and focus on its potential for clinical applications in breast disease. PSA is produced by the majority of breast tumors and is a favorable indicator of prognosis in breast cancer. Low levels of PSA are released into the female circulation, and while the level of serum PSA is elevated in both benign and malignant breast disease, the molecular form of circulating PSA differs between women with and without breast cancer. These findings indicate that PSA may have potential diagnostic utility in breast cancer. PSA may also have a clinical application in benign breast disease, as both the level and molecular form of PSA differ between Type I and II breast cysts. High levels of PSA have been reported in nipple aspirate fluid (NAF) and recent studies have shown that the concentration of PSA in NAF is inversely related to breast cancer risk, indicating that NAF PSA may represent a clinical tool for breast cancer risk assessment. Thus, PSA represents a marker with numerous potential clinical applications as a diagnostic and/or prognostic tool in breast disease.
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  • 129
    ISSN: 1573-7217
    Keywords: estrogen and progesterone receptor ; S-phase fraction ; tamoxifen ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A Swedish cooperative trial demonstrated that 5 years of adjuvant tamoxifen was more beneficial than 2 years of tamoxifen in the treatment of postmenopausal women with estrogen receptor (ER) positive, early stage, invasive breast cancer. The main aim of the present study was to investigate the importance of progesterone receptor (PgR) and ER concentration levels for patients participating in the trial and still distant recurrence free two years after the primary operation. Subgroup analyses revealed that only patients with ER positive and PgR positive breast cancer had improved distant recurrence free survival (DRFS) by prolonged tamoxifen therapy (p=0.0016). Patients with ER negative and PgR negative as well as ER positive and PgR negative tumors showed no significant effect of prolonged tamoxifen (p=0.53 and p=0.80, respectively). The percentage of ER negative and PgR positive breast cancers was too small (2.2%) for any meaningful subgroup analysis. There was a significant positive trend that the concentration level of PgR (high positive vs. low positive vs. negative) decreased the recurrence rate for those with prolonged therapy. No corresponding pattern was found for the ER content. S-phase fraction did not correlate to the recurrence rate of PgR positive breast cancers. Patients recurring during tamoxifen therapy had receptor negative tumors to a greater extent than those recurring after tamoxifen treatment. In conclusion, prolonged tamoxifen therapy for 5 years instead of 2 years was found to be beneficial for patients with ER positive and PgR positive breast cancer, whereas three extra years of tamoxifen had little or no effect for patients with ER positive but PgR negative tumors as well as for steroid receptor negative patients.
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  • 130
    ISSN: 1573-7276
    Keywords: BRCA1 ; breast cancer ; chemically modified tetracycline ; E-cadherin/catenin ; invasion ; migration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Chemically modified tetracyclines (CMTs) are promising anti-cancer agents. In this study, we found that CMT-3 and CMT-8 showed dose-dependent cytotoxicities in MDA-MB-468 human breast cancer cells. Moreover, both CMT-3 and CMT-8 significantly inhibited in vitro cell migration and invasion at non-cytotoxic concentrations. Anti-invasion and migration potentials of the CMTs were associated with an increased expression of E-cadherin/catenins (α, β and γ-catenin) and tumor suppressor BRCA1. In addition, CMT-3 and CMT-8 abolished or reduced spontaneous and HGF/SF-induced cell invasion and migration in U-373 MG human glioblastoma cells. Our current finding is the first demonstration that CMT-3 and CMT-8 can activate the function of invasion suppressor molecules associated with the suppression of breast cancer cell invasion and migration. Thus, clinical application of CMTs may provide potential benefit for suppression of breast cancer growth, invasion and metastasis.
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  • 131
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    Journal of mammary gland biology and neoplasia 5 (2000), S. 85-94 
    ISSN: 1573-7039
    Keywords: Mannose 6-phosphate/insulin-like growth factor 2 receptor ; tumor suppressor gene ; breast cancer ; loss of heterozygosity ; somatic mutation ; microsatellite instability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R)3 is considereda “candidate” tumor suppressor gene. This hypothesis has been provoked by the identificationof loss of heterozygosity (LOH) at the M6P/IGF2R locus on chromosome 6q26 in breast andliver cancer, accompanied by point mutations in the remaining allele. Somatic mutations incoding region microsatellites have also been described in replication error positive (RER+)tumors of the gastrointestinal tract, endometrium and brain. These genetic data are compelling,but a tumor suppressor gene candidate has to meet functional as well as genetic criteria. Thisreview weighs the evidence and discusses the observations that are necessary to promoteM6P/IGF2R from candidate to bona fide tumor suppressor gene.
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  • 132
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    Journal of mammary gland biology and neoplasia 5 (2000), S. 243-244 
    ISSN: 1573-7039
    Keywords: mouse mammary gland ; human breast ; oncogenes ; breast cancer ; CD-ROM ; histopathology ; ammary development
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This article introduces a CD-ROM containing whole-mount and histological images of normal growth and development of both the mouse mammary gland and the human breast. It also covers nonneoplastic lesions and neoplasias in both species including a catalog of lesions in genetically engineered mice. Instructions, with examples, on techniques such as whole-mount preparation, immunohistochemistry, in situ hybridization, and common histological stains are provided. The images are based on full-scale 1996 × 1640 pixel images at 300 pixels/inch and are annotated. Every genetically engineered model has one or more accompanying citations. Tables are provided for orientation and organization. The CD includes zoom capabilities, a search engine, and a help mode.
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  • 133
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    Journal of mammary gland biology and neoplasia 5 (2000), S. 259-270 
    ISSN: 1573-7039
    Keywords: estrogens ; 17β-hydroxysteroid dehydrogenase (17HSD) ; mammary gland ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Estrogen action in the target cells is dependent on estrogen receptor activity and intracellular estrogen concentration, which, in turn, is affected by the serum concentration and local metabolism in these cells. During the reproductive years the main source of estrogens is the ovarian follicles, but in postmenopausal women most of the estrogens are formed in peripheral tissues. 17β-hydroxysteroid dehydrogenases (17HSDs)6 catalyze the reaction between 17β-hydroxysteroids and 17-ketosteroids, and several distinct 17HSD isoenzymes have been characterized. 17HSD type 1 catalyzes the reaction from low-activity estrone to high-activity estradiol. The type 2 enzyme has an opposite activity, thereby reducing the exposure of tissues to estrogen action. 17HSD type 1 is expressed both in steroidogenic tissues and in the target tissues of steroid action, such as normal and malignant breast tissue, where it may be responsible for maintaining the high intracellular estradiol concentration seen in breast cancer specimens. Therefore, 17HSD type 1 inhibitors may be useful in the treatment and/or prevention of estrogen-dependent malignancies, such as breast cancer. This article deals mainly with 17HSD types 1 and 2 and their role in estrogen action in breast tissue.
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  • 134
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    Journal of mammary gland biology and neoplasia 5 (2000), S. 271-281 
    ISSN: 1573-7039
    Keywords: breast cancer ; estrogen receptor ; endocrine therapies ; resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Estrogens have long been recognized as being important for stimulating the growth of a large proportion of breast cancers. Now it is recognized that estrogen action is mediated by two receptors, and the presence of estrogen receptor α (ERα)3 correlates with better prognosis and the likelihood of response to hormonal therapy. Over half of all breast cancers overexpress ERα and around 70% of these respond to anti-estrogen (for example tamoxifen) therapy. In addition, the presence of elevated levels of ERα in benign breast epithelium appears to indicate an increased risk of breast cancer, suggesting a role for ERα in breast cancer initiation, as well as progression. However, a proportion of ERα-positive tumors does not respond to endocrine therapy and the majority of those that do respond eventually become resistant. Most resistant tumors remain ERα-positive and frequently respond to alternative endocrine treatment, indicative of a continued role for ERα in breast cancer cell proliferation. The problem of resistance has resulted in the search for and the development of diverse hormonal therapies designed to inhibit ERα action, while research on the mechanisms which underlie resistance has shed light on the cellular mechanisms, other than ligand binding, which control ERα function.
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  • 135
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    Journal of traumatic stress 13 (2000), S. 301-319 
    ISSN: 1573-6598
    Keywords: PTSD ; breast cancer ; symptom structure ; confirmatory factor analysis ; PCL-C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Psychology
    Notes: Abstract Identification of posttraumatic stress disorder (PTSD) symptoms and diagnoses in survivors of cancer is a growing area of research, but no published data exist regarding the symptom structure of PTSD in survivors of malignant disease. Findings from investigations of the PTSD symptom structure in other trauma populations have been inconsistent and have not been concordant with the reexperiencing, avoidance/numbing, and arousal symptom clusters specified in DSM-IV. The present study employed confirmatory factor analysis to evaluate the extent to which the implied second-order factor structure of PTSD was replicated in a sample of 142 breast cancer survivors. PTSD symptoms were measured using the PTSD Checklist—Civilian Version (PCL-C). Fit indices reflected a moderate fit of the symptom structure implied by the DSM-IV. These findings provide some tentative support for the DSM-IV clustering of PTSD symptoms and for the validity of cancer-related PTSD.
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    Journal of behavioral medicine 23 (2000), S. 15-36 
    ISSN: 1573-3521
    Keywords: genetic risk ; breast cancer ; knowledge ; genetic testing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract Informed consent for genetic testing for breast–ovarian cancer susceptibility requires that women understand basic concepts about the inheritance of cancer susceptibility and the benefits and risks associated with genetic testing. Women awaiting routine medical services (N = 220) were surveyed about their knowledge of breast cancer and cancer genetics and their perceptions of genetic testing and personal risk. There were no racial differences in median income or mean level of education. Compared to Caucasian women, African American women knew significantly less about breast cancer and about genetic risk for breast cancer. African American women had different psychological, social, and economic concerns as evidenced by how they weighted the benefits and risks of genetic testing. This study is the first to assess several dimensions of informed consent for genetic testing among a sociodemographically diverse group. The findings should enable health professionals to target the African American and lower-income populations with the appropriate education and counseling.
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    Journal of behavioral medicine 23 (2000), S. 367-376 
    ISSN: 1573-3521
    Keywords: optimistic bias ; Health Belief Model ; breast cancer ; prostate cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract Why do people fail to engage in positive behaviors which will promote their health and well-being? Researchers addressing this question adopt primarily one of two perspectives, drawing either on theories of health behavior, such as the Health Belief Model (HBM), or on theories of risk perception, such as unrealistic optimism. To overcome this compartmentalization, two studies of cancer screening behavior assessed the extent to which unrealistic optimism occurred in relation to each of the elements of the HBM: severity and curability of cancer and the benefits of, and barriers to, having a screening test. Data were collected using telephone interviews, dialing numbers randomly selected from the telephone directory. In the first study 164 women aged 50 to 70 years responded to questions about breast cancer and screening mammography, while in the second study 200 men aged 45 to 60 years responded to questions about prostate cancer and screening using the prostate specific antigen test. Women had an optimistic bias in relation to breast cancer risk and severity and barriers to having a screening mammogram but not in relation to the benefits of screening. For prostate cancer, there was an optimistic bias for all HBM variables: risk and severity of prostate cancer and barriers to and benefits of screening. It was concluded that unrealistic optimism is broader than perceived risk, being evident for all elements of the HBM.
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  • 138
    ISSN: 1573-3599
    Keywords: BRCA1 ; motivation ; satisfaction ; coping, genetic counseling ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract Women with a strong family history of breast and/or ovarian cancer can now have genetic testing, that may identify mutations associated with increased cancer predisposition. Within the context of a clinical trial evaluating printed educational materials, we examined motivation, satisfaction, coping, and perceptions of genetic counseling and testing among 159 women who underwent pretest counseling and made a testing decision. Ninety-six percent of the participants elected to have BRCA1/2 testing. When making a decision about genetic testing, study participants were concerned less about the potential negative effects that could result from testing than the potential benefits. After counseling, participants said that they felt better able to make decisions that were right for them and that their questions and concerns were adequately addressed during the session. Ninety-five percent of the women were satisfied with their test decision. Participants used a range of strategies to cope with thoughts and feelings about cancer and/or genetic testing immediately following test decision. Results suggest that the genetic counseling session helped women make decisions about testing for BRCA1 and BRCA2, even in the setting of a trial in which all women also received detailed educational materials. Further, the results indicate that future research focusing on perceptions of risks and benefits of testing and of coping strategies immediately following test decision may be warranted.
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  • 139
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    Journal of clinical psychology in medical settings 7 (2000), S. 91-97 
    ISSN: 1573-3572
    Keywords: breast cancer ; breast cancer in men ; male breast carcinoma ; breast cancer treatment ; psychological effects of cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The occurrence of breast cancer in men is rare in comparison to women. Public knowledge that men can get breast cancer and of male breast self-examination are lacking. Research in the course and treatment of breast cancer in men is needed. Men generally present in more advanced stages of breast cancer than women, and have a poorer prognosis. In this article, the epidemiology, common symptoms, diagnostic methods, and current treatment of breast cancer in men are described. Gender differences in presentation and course of illness are discussed. Additionally, the psychological implications of breast cancer for male gender roles and masculine identity are explored. Directions for further investigation are given. Treatment providers are encouraged to educate themselves and their male patients on breast cancer in men and male breast examination techniques so that this disease may be identified earlier in its course and survival rates improved.
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  • 140
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    Clinical social work journal 28 (2000), S. 183-195 
    ISSN: 1573-3343
    Keywords: adolescent ; mother ; breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract While the literature supports the view that a parent's illness will have an impact on a child, less specific attention has been given to the impact of a mother's breast cancer on her adolescent daughter. In this paper, clinical vignettes derived from interviews with adolescent daughters (ages 12–19) living with mothers who have breast cancer are presented to illustrate some of the concerns daughters have about themselves and their mother's illness. The daughters express anxiety about changes in family roles, but seem more concerned about the potential loss of the mother/daughter relationship. They describe their fears of recurrence of the disease as well as getting the disease themselves. The girls also demonstrate great strength; resilience and hope in the face of the challenges presented by the changes in their lives. Girls who had mothers die of the disease are not included in this article. Implications for treatment are discussed.
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    Journal of behavioral medicine 2 (1979), S. 31-38 
    ISSN: 1573-3521
    Keywords: breast cancer ; breast self-examination ; denial of risk ; fear of cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract In a population of 158 women with a breast concern, two-thirds examined their own breasts. Most examiners (80%) practiced breast self-examination at least once a month, and over 60% had been regular examiners for more than 2 years. No significant difference in frequency of breast self-examination was found between women who had been examiners for longer and shorter time periods. Examiners had two main reasons for beginning and continuing breast self-examination: (1) an awareness that it is desirable to detect breast cancer early and (2) an awareness that they themselves could get breast cancer, while nonexaminers tended to deny this possibility. Therefore, to become examiners, nonexaminers may need to be convinced not only that early detection is effective but also that they too are at risk of breast cancer. The importance of informing, but not alarming, women about their breast cancer risk is discussed.
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    Journal of behavioral medicine 2 (1979), S. 239-250 
    ISSN: 1573-3521
    Keywords: breast cancer ; lump detection ; training ; BSE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract Forty-two female subjects, constituting 14 groups, palpated a silicone breast model in a lump detection task. Three variables, number of trials (amount of practice), search pattern requirement (restricted vs. unrestricted), and the presence or absence of lumps, were manipulated according to 3 X 2 X 2 design. The effect of all modes of practice on detection performance in posttest 1 was evidenced by an increase in percent of lumps detected and a decrease in detection threshold, but no form of practice was superior to the others. Following posttest 1 a brief search-training procedure was administered to 39 subjects which further lowered detection threshold, increased percent of lumps detected, and increased trial duration in posttest 2. The results indicate the effectiveness of the training procedure for improving detection ability and suggest the need for a more complex model to determine more specifically the effects of the practice models employed.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1851-1863 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The boundary control problem of optimal heating of an infinitely long slab with tempertue-dependent thermal conductivity, subjected to a convection and radiation boundary condition, is analysed by numerical methods.In order to reformulate the optimal control problem of distributed parameter systems as a mathematical programming problem of finite dimension, a space, co-ordinate is discretized by use of the finite element method, while the Runge-Kutta method is utilized for time integrations. Finally, the performance index of the optimal control problem is minimized by the conjugate gradient method of optimization.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1879-1879 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 37-50 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 11-35 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Finite element equivalents of the equations governing shearing and buoyancy driven flows are derived, and reduced to upwind forms suitable for the solution of problems in which the Reynolds and Rayleigh numbers are large. A modification to the central difference iterative method is studied which increases the Reynolds and Rayleigh numbers for which a central difference form may be used. A comparison is made between the results obtained using the central and upwind forms of the finite element method and those predicted by finite difference methods in the case of flow in a cavity. A mesh refinement study is made. The upwind forms of the finite element equations are applied to the solution of a complex flow problem involving the flow of glass in a throated furnace in the case of constant- and temperature- dependent viscosity and conductivity.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 51-68 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The 18 degree-of-freedom flat triangular shell element is reformulated by combining the well-known bending triangle with a plane stress triangle incorporating in-plane rotations at each vertex. Both elements are displacement formulated. The plane stress element's displacement interpolation is incomplete and hence convergence to exact solutions is precluded. Comprehensive test results are presented for several types of problem including plane stress, thin shells and folded plates. The results indicate that the element does produce rapidly convergent answers. However these answers are not the correct ones, although they may be acceptable engineering approximations in many applications. Further, the element seems to provide reasonably good results even for relatively coarse element grids.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 81-102 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The paper considers the finite element analysis of the free, undamped and the forced damped vibrations of rotationally periodic structures. Associated with every natural frequency (except for those for which the deflection is the same at corresponding points on every substructure) there are a pair of orthogonal mode shapes, with eigenvectors {u} and {ü}. The complex vector {z}={u}+i{ü} is also an eigenvector of the equations of motion, and represents a rotating normal mode. The deflection of one substructure has the same amplitude as, and a constant phase difference from the deflection of the preceding substructure. It is therefore possible to analysse the complete structure by considering only one substructure, and applying appropriate complex constraints at its boundary with the following substructure, so as to and applying appropriate complex constrainsts at its boundary with the following substructure, so as to impose this phase difference. The method has been implemented in a computer program and is illustrated by analyses of an alternator end winding, a cooling tower with legs, and a wheel of turbine blades.For forced vibration, it is shown that any arbitrary oscillatory force can be decomposed into a series of rotating forces. For any one of these rotating components, there is a fixed relationship between the amplitude and phase of the force acting on one substructure, and that acting on an adjoining substructure. This relationship, which does not involve any approximation, can be used to enable a series of calculations of the response of one substructure to be performed instead of one on the whole structure. A series of calculations on an individual substructure normally requires much less computer time and storage than a single calculation on the complete structure.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 115-124 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Load-free notch surfaces of bodies made of a linear-elastic, homogeneous, isotropic material are optimized within given variation domains by means of an interation procedure so that the occurring maximum tangéntial stress is reduced to a minimum. The hypothesis of a constant tangential stress distribution for obtaining minimal notch stresses proposed by R. V. Baud has been confirmed by means of the Fade-away Law of the notch stress theory. The finite element method is applied for calculating the displacement and stress field of the styructure. An increment procedure is used for determing the displacement field after every iteration step, which permits the calculation of the displacement quantities with sufficient accuracy in a single step. Numerical solutions and their comparison with analytical solutions and stress results obtained with the aid of photo-elasticity confirm the usefulness of this procedure. The known optimization methods1,2 differ from those used in the present paper.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 317-336 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: This paper presents a novel integral-equation technique for solving the steady-state wave-resistance problem. The free-surface condition is linearized, but the body condition is satisfied exactly. An integral relation describing the flow inside an arbitrarily truncated internal region is first obtained by applying Green's Theorem, using only the simple source function for an infinite fluid. The internal flow is next matched with eigen expansions in the upstream and downstream outer regions. The radiation condition can be satisfied exactly simply by a proper choice of the solution form in these outer regions. The method is applied to investigate flows about both lifting and non-lifting two-dimensional bodies. Agreement with existing results is excellent. The present formulation provides a simple yet rational basis for tackling the practical three-dimensional ship-wave problem, in which past workers have encountered considerable difficulties using a complicated free-surface Green function.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 379-408 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: In this paper we present an algorithm for adaptively computing smooth piecewise polynomial approximations using restricted range uniform approximations on a finite point set. We also present several numerical examples and offer suggestions for the effective use of this algorithm. We have found the algorithm to be effective for approximating a wide class of functions, either with or without significant levels of noise. Furthermore, since the user of this algorithm actually defines tolerance bands within which the approximation will lie, the algorithm allows the user a great deal of flexibility and control over the shape of the resulting approximations.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 337-357 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The use of contacting components such as gear teeth in mesh and shrink-fitted shafts is very common in engineering practice. This paper deals with the development of a theoretical method which gives a solution for non-linear contact problems with irreversibility resulting from stick-slip phenomenon.The method is based on the finite element method and load incremental theory. The geometrical and the statical boundary conditions on contact surfaces are treated as additional conditions being independent of stiffness equations. As a result, the algorithm of calculation is simplified and only a part of the simultaneous equations related to the contact surfaces is required to be solved instead of the overall stiffness equations at each step. Furthermore, the magnitude of load causing a change in a contact condition of one contact nodepair is taken as a load increment, in analogy with the incremental iterative procedure for elastic-plastic problems. Therefore, the method provides a general and efficient method for analysis and design of such problems.As illustrative examples, the stick-slip behaviour of turbo-alternator end-bells and other problems are discussed. The calculated results show a reasonable agreement with experimental data and other solutions.
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    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 507-513 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 499-505 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The method for the evaluation of the thermal loads used in the incremental finite element analysis of elasto-plastic stress is presented. The stress distributions obtained by two apparently possible methods for evaluation of the thermal loads are compared.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 475-497 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: This paper presents an isoparametric finite element formulation for the torsion and the flexure due to end shears for the beam cross-sections of arbitrary shape. Isoparametric line elements are developed using this formulation for the beam cross-sections consisting of very thin wall open or close multicells. Isoparametric transition elements are also developed for the beam cross-sections consisting of both thin wall sections and solid like sections. Numerical examples are presented to demonstrate the accuracy and the applications of such elements.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 515-529 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A new element stiffness matrix is derived for straight cable elements subjected to tension and torsion. The cross-section of a cable, which may consist of many different structural components, is treated in the following as a single composite element. The derivation is quite general; consequently, the results can be used for a broad category of cable configurations. Individual helical armourning wires, for instance, may have unique geometric and material properties. In addition, no limit is placed on the number of wire layers. Furthermore, compressibility of the central core element can also be considered. The equations of equilibrium are first derived to include ‘internal’ geometric non-linearties produced by large deformations (axial elongation and rotatioin) of a straight cable element. These equations are then linearized in a consistent manner to give a liner stiffness matrix. Linear elasticity is assumed throughout. Excellent agreement with experimental results for two different cables validates the correctness of the analysis.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 531-544 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A high precision triangular thick orthotropic plate bending element on an elastic foundation is developed for the free vibration analysis of thick plates on elastic foundation. The element has three nodes with twelve degrees-of-freedom per node, and takes into account the shear deformation and rotatory inertia. The accuracy of the element is established by comparison of the natural frequencies of certain thick and thin plates, determined from a consistent mass matrix formulation, with available results.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 545-565 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A finite element simulation of the equations of momentum and energy transport in fluids has been implemented with triangular elements. An attempt is made to single out the reasons for numerical instabilities reported by other investigators for convection-diffusion transport operations in fluid mechanics when the ratio of the convective to the diffusive terms, measured by the Reynolds and Peclét numbers, is of the order of a hundred. To this end, the equations are solved for several problems to permit a direct comparison with results of other formulations. It is shown that the appearance of instability can be delayed by a proper choice of boundary conditions, and its intensity can be reduced through the use of triangular finite elements. Results agree very well with theoretical solutions for particular test problems including flows with large convection effects, large dissipation effects and fluids with temperature dependent properties.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 567-580 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Methods are described and reviewed for the accurate numerical evaluation of improper integrals encountered in conformal transformation solutions involving boundaries of relatively complicated shape. Four methods are reviewed for the solution of integrals containing end-point singularities. Two new methods are discussed for the solution of integrals containing both end point singularities and simple poles within the range of integration. One method uses a combination of a simple recursive formula and the coefficients of a Chebyshev series and a second method involves subtracting out the singularity and the use of Gauss-Jacobi quadrature. Both methods can give results of high accuracy and an upper limit of the error is readily found. A numerical example is taken which is typical of the application to practical problems and this brings out a comparison of the two methods.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 633-645 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: This paper present an algorithm and its corresponding FORTRAN IV program which solves a system of simultaneous equations of the type generated in structural analysis. It is based on the Gauss elimination method, so it is a direct method. But it only needs to have in core as many equations as it can contain, with a minimum of two. The program offers the following advantages: (a) Takes into account zeros to avoid operations. (b) Considers very big numbers in the diagonal, corresponding to boundary conditions, to avoid operations. (c) It can handle several load cases either simultaneously or in groups, at choice.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 786-786 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 787-790 
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    Keywords: Engineering ; Engineering General
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 785-786 
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    Keywords: Engineering ; Engineering General
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    International Journal for Numerical Methods in Engineering 14 (1979) 
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    International Journal for Numerical Methods in Engineering 14 (1979), S. i 
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    Keywords: Engineering ; Engineering General
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    International Journal for Numerical Methods in Engineering 14 (1979), S. ii 
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 791-812 
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    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: The essence of the proposed curvilinear finite difference solution method is the direct solution of the transformed fourth order partial differentiall equation using the finite difference expressions based on the flexible structure so that the geometry generality of the finite element method can be approached. The examples of applications indicte that the curvilinear mesh can be used and the boundary condition on the curved boundary can be easily and accurately prescribed.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 813-836 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: An interactive computer graphics system has been developed for generating the geometric description of an arbitrary shell surfface. The various difficulties facing the user of sophisticated, doubly-curved shell finite elements and the inefficiency of preprocessing for shell analysis are discussed to explain the benefits of this system. The method is a synthesis of spline theory and algorithms, and an interactive means for man-machine communication. The basic technique employed is a modified lofting method in which cardinal splines. An inversion procedure is incorporated which increases significantly the efficiency of the B-spline approximation process. Static and dynamic graphic displays greatly enhance visualization at any stage of the procedure. Two examples of practical interest are presented in some detail to demonstratge the flexibility and usefulness of this approach. Some natural extensions of this system for interactive mesh generation on the surface are also demonstrated.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 837-853 
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    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: Three widely-used nodal resequencing algorithms were tested and compared for their ability to reduce matrix profile and root-mean-square (rms) wavefront, the latter being the most critical parameter in determining matrix decomposition time in the NASTRAN finite element computer program. The three algorithms are Cuthill-McKee (CM), Gibbs-Poole-Stockmeyer (GPS), and Levy. Results are presented for a diversified collection of 30 test problems ranging in size from 59 to 2680 nodes. It is concluded that GPS is exceptionally fast, and, for the conditions under which the test was made, the algorithm best able to reduce profile and rms wavefront consistently well. An extensive bibliography of resequencing algorithms is included.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 855-870 
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    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: A simple computer method is presented for analysing statically indeterminate beams having sectionally constant EI values and loads consisting of any number of arbitrarily placed concentrated forces and couples as well as any number of uniform and ramp loads. Unknown reactions are treated as parameters which are determined by simulataneous imposition of end conditions and interior constraints. Support locations are specified independently of any discontinuites of load or cross-section. A computer program implementing this method is described which has very concise data input considerably shorter than tupically required in programs based on the stiffness method.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 871-903 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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    Notes: In References 1 and 2, algorithms were introduced for adaptively computing smooth piecewise polynomial approximations using uniform, least-squars (l2) and restricted-range uniform approximations. This present paper introduces a FORTRAN program for computing smooth piecewise polynomial approximations to data and/or precise mathematical functions (in discrete form) which allows the user the option of using best l1 of best l2 approximations. (The l2 option of this newly developed l1-l2 adaptive curve-fitting package supersedes the code listed in Reference 1 for the old least-squares program.) In this paper, adaptive curve-fitting algorithm used in this l1-l2 package is described in detail, the FORTRAN program is the given (in the Appendix) and discussed, the numerical results are presented in an effort to illustrate how the l1 and l2 versions of this algorithm may be used most effectively.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 905-911 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A numerical experiment has been conducted to check theeffectiveness and reliablity of the orthnormalization process tosolve two-point boundary value problems. This process in usedalong with the method of superposition in the linear case andwith the quasilinearization and then the method of superpositionin the non-linear case.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 921-931 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Truncation errors introduced by operator splittingtechniques, such as the ADI scheme, are discussed in the contextof the two-dimensional shallow-water equations. Numericalexamples of flow along a uniform channel, with and withoutfriction, illustrate the practical significance of these errors when the boundary is not aligned with the computational gridaxes. With irregular boundaries the maximum time step aceptable ismore severely restricted than has been realized hitherto. The problem, which is shown to stem from the treatment of the boundary conditons, is inherent in any splitting scheme and is difficult to circumvent.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 913-920 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Long thin test specimens of orthotropic material are modelledby quadratic isoparametric finite elements in plane strain. Displacement oscillations occur down the long free edge of themodel with both reduced (2 × 2) and full (3 × 3) integration, themagnitude of the oscillations being affected by element aspectratio and the elastic constants of the material. The rate ofdiffusion of stress as predicted by the classical shear-lag theory, being dependent on the material constants, is reflectedin the displacement oscillations near the load in 3 × 3integration. In 2 × 2 integration, however, this effect is swampedby the build-up of oscillations away from the restraints in alowenergy deformation mode which becomes dominant as the elementaspect ration is increased. These latter voscillations arepredicted by the illconditioning of the structural stiffnessmatrix measured by a solution diagonal decay factor.
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  • 176
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 937-941 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 177
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 933-936 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 178
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 946-948 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 179
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 942-945 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Additional Material: 3 Ill.
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  • 180
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    International Journal for Numerical Methods in Engineering 14 (1979) 
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    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 181
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 949-959 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A modification of the collocation method for the numerical solution of Cauchy-type singular integral equations appearing in plane elasticity and, especially, crack problems is proposed. This modification, based on a variable transformation, applies to the case when the unknown function of the singular integral equation behaves like A(x - c)α + B(x - c)β, where α 〈 0, 0 〈 β - α 〈 1, near an endpoint c of the integration interval. In plane elasticity such a point is either a crack tip or a corner point of the boundary of the elastic medium. Thus the method seems to be quite efficient for the numerical evaluation of generalized stress intensity factors near such points. A successful application of the method to the classical plane elasticity problem of an antiplane shear crack terminating at a bimaterial interface was also made.
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  • 182
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 961-986 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: An updated Lagrangian and a total Lagrangian formulation of a three-dimensional beam element are presented for large displacement and large rotation analysis. It is shown that the two formulations yield identical element stiffness matrices and nodal point force vectors, and that the updated Lagragian formulation is computationally more effective. This formulation has been implemented and the resulted of some sample analyses are given.
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  • 183
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 987-1000 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A new numerical method of calculating unsteady-state heat conduction and thermal stresses by using improved coefficient matrix patterns on the nodal points of a structure is given. Good agreement is obtained between our results and the rigorous results, and this method seems to yield better accuracy than other well-known approximate methods for two-dimensional transient thermal stress problems.
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  • 184
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1001-1019 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The homogeneous Dirichlet problem for the biharmonic operator is solved as the variational formulation of two coupled second-order equations. The discretization by a mixed finite element model results in a set of linear equations whose coefficient matrix is sparse, symmetric but indefinite. We describe a class of preconditioned conjugate gradient methods for the numerical solution of this linear system. The precondition matrices correspond to incomplete factorizations of the coefficient matrix. The numerical results show a low computational complexity in both number of computer operations and demand of storage.
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  • 185
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1021-1035 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Methods for comparing the accuracy of numerical methods for the solution of parabolic partial differential equations are briefly surveyed. Criteria for a more systematic comparison are proposed and applied to an accuracy comparison of the classical and the modified Saul'yev methods and the Crank-Nicholson method on a simple linear problem. The results obtained, which include observation of the existence of optimal spatial mesh size for the two Saul'yev methods, are discussed.
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  • 186
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1051-1061 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The application of finite element methods to parabolic partial differential equations leads to large linear systems of first-order ordinary differential equations. Very often these systems are stiff and difficulties arise in their numerical solution. We attempt to analyse the problem of how to select numerical methods for the solution of such linear systems.
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  • 187
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1037-1050 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The nonlinear impact of a vehicle against a deformable barrier and its subsequent rebound from that barrier are simulated. A one-dimensional elastoplastic model represents the vehicle as a series of rod finite elements and the barrier as a single mass, nonlinear spring. The solution procedure utilizes variable time step integration, contains an error control and eliminates numerical instabilities. A limited study assesses the influence of system parameters on both structure and occupants. The chief objective, however, is to establish the feasibility of the proposed treatment of this class of problems. Some results obtained appear, at first, to contradict intuition. It is observed that modelling a deformable barrier as rigid can lead to unconservative results with respect to structural response of the vehicle.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1063-1072 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: Similar and similarly oriented CST elements have the same stiffness matrix, and therefore similar shapes generated by the assembly of such elements possess the same stiffness matrix. This property and the matrix condensation technique may be judiciously combined to simplify the study of large structures, which may otherwise incur large core requirements and time and involve the solution of a great number of equations. In this paper the idea is developed to indicate its full potential. In illustration, results from examples on the determination of stresses around a small hole in a large plate are presented.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1073-1078 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A technique for smoothing the transition between structural components modelled with dissimilar finite element meshes is presented. The interface mismatch is assigned a potential of dislocation, which is minimized with respect to selected kinematic parametes of the mating surface. This leads to linear constraints between the caididate representations of the mating surface which essentially dictate a least-square error in dislocaiton. The constraints are enforced by the Lagrange multiplier or reduced stiffness technique. Numerical results indicate gradual transition in the predicted stresses neighbouring the interface. Existing computer codes which permit multipoint constraint specifications are readily available to implement the technique.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1085-1089 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: In this paper the order of certain two-dimensional quadrature formulae is discussed and it is shown that their degree and order are not related in the same simple way as they are for one-dimensional rules.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1079-1084 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: The decomposition of a block tridiagonal matrix into the product of block lowe and upper matrices is described. The cost of solving a block tridiagonal system of equations is given and compared to profile gaussian elimination. The desirability of a less expensive method is coupled to physical intuition about a common problem of solving a slowly varying sequence of such systems to motivate an iterative method based on residual correction. The method is described and convergence criteria are derived. An expression of the cost is developed and is shown to compare favourably with decomposition in many cases. Problems and advantages in computer implementation of the method are discussed and results of tests of a particular implementation on a well-known problem are given.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1090-1094 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: For the two-dimensional isoparametric 8-node element an additive condition is formulated, so that the function describing the domain boundary is continually differentiable at the common nodes on the boundary. This condition will be satisfied by moving the mid-side nodes into a special position. The advantage in using this modified element will be shown by an example of the elasto-plastic calculation of a double-edge notched specimen.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1095-1099 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: A mathematical description of the numerical approximation to incompressibility with nearly incompressible displacement finite elements is presented. By the way of functional analysis, it leads to a condition of convergence to the incompressible problem when v is increased up to 0.5, which can be identified with Fried's K1 criterion.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1100-1104 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: This communication presents a simple algorithm to compute the stiffness matrix for a triangular plate bending element, without numerical integration. This brings about a substantial saving in computer time.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1105-1105 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
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  • 196
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    International Journal for Numerical Methods in Engineering 14 (1979) 
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    Keywords: Engineering ; Engineering General
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1107-1126 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: This paper describes an optimization procedure for the minimum weight design of complex structures. The procedure is based on a new cubic extended interior penalty function (CEIPF) used with the sequence of unconstrained minimization technique (SUMT) and Newton's method. The Hessian matrix of the penalty function is approximated using only constraints and their derivatives. The CEIPF is designed to minimize the error in the approximation of the Hessian matrix, and as a result the number of structural analyses required is small and independent of the number of design variables. Three example problems are reported. The number of structural analyses is reduced by as much as 50 per cent below previously reported results.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1127-1140 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: In Reference 1 a class of first-order factorization methods for the solution of large, sparse systems of equations, of which the coefficient matrix is a symmetric M-matrix, was introduced. Asymptotic results for the computational complexity was proved in the case of systems arising from finite difference approximation of second-order self-adjoint elliptic partial differential equation problems in two dimensions with Dirichlet boundary conditions. In this paper the result is extended to cover even mixed boundary conditions and problems with discontinuous material coefficients. Results from numerical experiments with various finite difference and finite element approximations are presented and comparisons with direct and other interative methods are made.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1165-1182 
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    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: This paper describes a numerical procedure for the solution of metalworking problems of a strain-hardening material. The overall metalworking process is split up into a number of stages and the governing equations for a typical stage are set up in terms of incremental displacements. The incremental deformation occurring in each successive stage is found by an interative numerical procedure based on the concept of piecewise linearization. The ‘composite’ solution yields the distribution of stress and strain in the work material at various stages of the process. Finally, application of the method to finite axisymmetric compression is described.
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    International Journal for Numerical Methods in Engineering 14 (1979), S. 1141-1163 
    ISSN: 0029-5981
    Keywords: Engineering ; Engineering General
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Mathematics , Technology
    Notes: This paper describes an explicit numerical method for solving transient combined heat conduction and convection problems. Applications include the cooling of many types of engineering plant; for example, stator and rotor windings of turbogenerators and high voltage underground cables. The Du Fort-Frankel and the fully implicit finite difference schemes have been used to solve the conduction and convection equations, respectively. It is shown that, with a suitable order of calculation, the overall method becomes explicit. Computational procedures are outlined and stability, accuracy and convergence are considered. Numerical examples are given to illustrate the use of the method and to validate some of the theoretical points. Results have also been obtained using existing numerical methods and have been compared with those from the proposed method. For certain problems, it is shown that the proposed method uses less overall computing time than other methods such as that devised by Crank and Nicolson.
    Additional Material: 6 Ill.
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