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  • Electronic Resource  (157)
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  • 2000-2004  (157)
  • chemotherapy  (81)
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  • 1
    ISSN: 1569-8041
    Keywords: BEACOPP ; chemotherapy ; dose intensification ; hematotoxicity ; Hodgkin's disease ; practicability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Evidence is recently accumulating that the novelBEACOPP (bleomycin (B), etoposide (E), adriamycin (A), cyclophosphamide (C),vincristine (O), procarbazine (P), prednisone (P)) chemotherapy is a highlyeffective treatment for advanced stage Hodgkin's disease. Two dose variantsof BEACOPP are currently tested in a phase III randomized multicenter trialof the GHSG. To enable more extensive testing of BEACOPP we characterized itspracticability regarding schedule adherence, acute hematotoxicity and need forsupportive treatment. Patients and methods:Data of 858 patients (6592 therapy cycles)from 184 participating institutions were evaluated. Planned total drug dosesof the baseline variant (arm 1) were 80, 2400, 200, 5200, 11.2, 5600 and 4480mg/m2 for B, E, A, C, O, P and P, respectively. Compared to arm 1,the doses of E, A and C in the dose-intensified variant (arm 2) were escalatedby factor 2.0, 1.4, 1.92, respectively, using G-CSF assistance. Stepwise dosereductions were specified in case of dose-limiting toxicities. Both variantsare given in eight three-weekly courses. Results:Median dose adherence (dose actually given relative toplanned arm 1 dose) in arm 1 was 1.0 for all drugs. Relative dose escalationof E, A, and C actually maintained in arm 2 was 1.83, 1.37 and 1.77 (medians),respectively, and 70% of patients maintained elevated dose levelsthroughout the entire treatment. Dose-limiting toxicities occurred in25% of cycles in arm 2, most frequently due to leukocytopenia andthrombocytopenia. Time courses of leukocytes in arm 2 showed more severe butnot more prolonged leukocytopenia compared with arm 1. WHO grades 3–4infections were documented in 2.1% (arm 1) and 3.1% (arm 2) ofall cycles. Erythrocytes were transfused in 6% (arm 1) and 28%(arm 2), platelets in 〈1% (arm 1) and 6% (arm 2) of allcycles. Conclusions:Both BEACOPP schemes are practicable in a largemulticenter setting. Despite increased hematotoxicity, moderate doseescalation is safe for the majority of the patients with G-CSF assistance andstandard supportive treatment.
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  • 2
    ISSN: 1569-8041
    Keywords: chemotherapy ; 5-FU ; folinic acid ; gemcitabine ; Gemzar® ; pancreas cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Gemcitabine (Gemzar®) and 5-fluorouracil (5-FU)plus folinic acid (FA) both have proven activity in the treatment of patientswith advanced pancreatic cancer. The present study was initiated toinvestigate the efficacy of gemcitabine in combination with 5-FU–FA. Patients and methods:Thirty-eight patients, median age 60 years(range 34–70) with inoperable, stage IV, pancreatic cancer were enrolledinto the study and treated on an outpatient basis. All except one patientreceived at least one cycle of treatment with gemcitabine (1000mg/m2), followed by FA (200 mg/m2) and 5-FU (750mg/m2) administered as a 24-hour continuous infusion on days 1, 8,15 and 22 of a 42-day schedule. No patient had received prior chemotherapy orradiotherapy. All 38 patients were assessed for efficacy, toxicity and timeto progressive disease. Results:Two patients (5%), achieved a partial response andthirty-four patients (89%) achieved stable disease. There were twoearly deaths (≤4 weeks). The median time to progression was 7.1 months(range 0.4–18.1+; 95% confidence interval (95% CI):5.3–7.9 months). Three patients had a progression-free interval ofgreater than 12 months and 12 of 38 patients (32%) survived longer than12 months. The median overall survival was 9.3 months (range 0.5–26.5;95% CI: 7.3–13.0 months). The incidence of grade 3 and 4toxicities was low. Conclusions:The combination of gemcitabine and 5-FU–FA isactive and well tolerated and seems to offer an improvement inprogression-free interval over both gemcitabine monotherapy and 5-FU–FAtherapy.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 11 (2000), S. 217-220 
    ISSN: 1569-8041
    Keywords: chemotherapy ; Guillain–Barré syndrome ; lymphoma ; polyneuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We describe a case of Guillain–Barré syndrome (GBS) in apatient with non-Hodgkin's lymphoma (NHL). A 21-year-old woman with a newlydiagnosed stage IV high-grade lymphoma (precursor T-cell NHL according to theR.E.A.L. Classification) developed flaccid quadriparesis and bilateral facialdiplegia after three weeks of treatment with vincristine, daunorubicin,L-asparaginase and prednisolone. The clinical course and neurologicalexamination were consistent with GBS. Despite treatment with intravenousimmunoglobulins her neurological symptoms progressed. Plasmapheresis wastherefore initiated followed by intravenous immunoglobulins. After partialremission of neurologic symptoms, induction chemotherapy with cyclophosphamideand cytarabine was continued without any further complication. Three monthslater, the lymphoma was in complete remission. GBS has been described inHodgkin's disease and after bone marrow transplantation but is rare in NHL.In patients with NHL who develop neurological symptoms, drug toxicity andnervous system infiltration are the leading cause of neuropathology, but GBSshould be considered in the differential diagnosis.
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  • 4
    ISSN: 1569-8041
    Keywords: brain tumor ; chemotherapy ; encephalopathy ; late neurological toxicity ; leucoencephalopathy ; primary cerebral lymphoma ; radiochemotherapy ; systematic follow-up
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Primary cerebral non-Hodgkin's lymphomas (NHL) inimmunocompetent patients (PCL) are located exclusively in the central nervoussystem, the eye, or meninges. Clinical management of these patients remainscontroversial. Patients and methods:Clinical characteristics of the patients andparameters influencing their outcome as of December 1998 were investigated andregistered in a database of 226 patients treated in the French Federation ofCancer Centers between 1980 and 1995. Results:Most PCL are diffuse large-cell NHL with a B phenotype.The incidence of PCL has been steadily increasing over the past 20 years insome but not all countries. The overall survival of primary cerebral lymphoma(PCL) patients in the published series, a median of 12–16 months and afive-year survival of 5%–20%, is poor. Several series havenow reported long-term survivals of more than 10 years and PCL may thereforebe a curable tumor in some patients. The optimal treatment of PCL is notknown. Complete resection of the tumor does not improve outcome andmultidisciplinary approaches combining chemotherapy and radiotherapy are nowcommonly used, although the superiority of combination over radiotherapy- orchemotherapy-alone has never been demonstrated in a phase III trial. Theoptimal chemotherapy regimen, the dose and even the usefulness of brainradiotherapy after chemotherapy are therefore still matters of debate.Recently, several authors have reported a relatively high incidence of lateneurological sequelae after PCL treatment. Conclusions:The optimal treatment of PCL patients remains to bedefined. Large cooperative international phase III trials are now required todefine and improve the optimal treatment of PCL and reduce its sequelae.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Entomologia experimentalis et applicata 95 (2000), S. 141-149 
    ISSN: 1570-7458
    Keywords: ecology ; reproductive success ; fecundity ; intraspecific competition ; evolution ; pest outbreaks ; pest control ; chemical control ; economic threshold ; oilseed rape ; turnip rape
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Populations of the rapeseed pollen beetle Meligethes aeneus F. (Col., Nitidulidae) from areas with 0–16 years of history of intensive rapeseed growing were compared for key ecological characters. During the first 16 years of rapeseed cultivation the reproductive success of M. aeneus increased 200–300% over that of the beetles living on the natural host plants, cruciferous weeds. The increase was linear over time and statistically highly significant, and it did not appear to be related to food quality or to the size of the beetles. During the same period the tolerance to intraspecific competition decreased, possibly due to the relative absence of such competition on the new crop. Furthermore, the optimum population density for M. aeneus to maximize the size of its next generation on summer turnip rape was determined to be 0.5–1.0 beetles/plant, which is slightly below the economic threshold for chemical control (1 beetle/plant). Therefore the practical protection of the rapeseed yield also ensures the highest possible pest population size for the next year. These mechanisms may in part explain the particular noxiousness of the species as a pest all over Europe. In general these data show that after the introduction of a new crop plant into a region, significant changes during the recruitment process in a pestiferous insect may take place, contributing to the future pest status of the insect. It is suggested that such genetic and ecological changes in insects may be a more common mechanism than previously thought in initiating and sustaining pest outbreaks, and that conventional pest management methods may enhance that effect.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Entomologia experimentalis et applicata 97 (2000), S. 237-249 
    ISSN: 1570-7458
    Keywords: herbivores ; predators ; parasitoids ; mutualism ; induced defence ; behaviour ; ecology ; evolution ; sensory physiology ; plant fitness ; pathogens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Herbivorous and carnivorous arthropods use plant volatiles when foraging for food. In response to herbivory, plants emit a blend that may be quantitatively and qualitatively different from the blend emitted when intact. This induced volatile blend alters the interactions of the plant with its environment. We review recent developments regarding the induction mechanism as well as the ecological consequences in a multitrophic and evolutionary context. It has been well established that carnivores (predators and parasitoids) are attracted by the volatiles induced by their herbivorous victims. This concerns an active plant response. In the case of attraction of predators, this is likely to result in a fitness benefit to the plant, because through consumption a predator removes the herbivores from the plant. However, the benefit to the plant is less clear when parasitoids are attracted, because parasitisation does usually not result in an instantaneous or in a complete termination of consumption by the herbivore. Recently, empirical evidence has been obtained that shows that the plant's response can increase plant fitness, in terms of seed production, due to a reduced consumption rate of parasitized herbivores. However, apart from a benefit from attracting carnivores, the induced volatiles can have a serious cost because there is an increasing number of studies that show that herbivores can be attracted. However, this does not necessarily result in settlement of the herbivores on the emitting plant. The presence of cues from herbivores and/or carnivores that indicate that the plant is a competitor- and/or enemy-dense space, may lead to an avoidance response. Thus, the benefit of emission of induced volatiles is likely to depend on the prevailing faunal composition. Whether plants can adjust their response and influence the emission of the induced volatiles, taking the prevalent environmental conditions into account, is an interesting question that needs to be addressed. The induced volatiles may also affect interactions of the emitting plant with its neighbours, e.g., through altered competitive ability or by the neighbour exploiting the emitted information. Major questions to be addressed in this research field comprise mechanistic aspects, such as the identification of the minimally effective blend of volatiles that explains the attraction of carnivores to herbivore-infested plants, and evolutionary aspects such as the fitness consequences of induced volatiles. The elucidation of mechanistic aspects is important for addressing ecological and evolutionary questions. For instance, an important tool to address ecological and evolutionary aspects would be to have plant pairs that differ in only a single trait. Such plants are likely to become available in the near future as a result of mechanistic studies on signal-transduction pathways and an increased interest in molecular genetics.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Acta biotheoretica 48 (2000), S. 137-147 
    ISSN: 1572-8358
    Keywords: Sex ; sexual selection ; mate selection ; evolution ; ploidy ; assortative mating ; recombination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Using computer simulations I studied the simultaneous effect of variable environments, mutation rates, ploidy, number of loci subject to evolution and random and assortative mating on various reproductive systems. The simulations showed that mutants for sex and recombination are evolutionarily stable, displacing alleles for monosexuality in diploid populations mating assortatively under variable selection pressure. Assortative mating reduced excessive allelic variance induced by recombination and sex, especially among diploids. Results suggest a novel adaptive value for sex and recombination. They show that the adaptive value of diploidy and that of the segregation of sexes is different to that of sex and recombination. The results suggest that the emergence of sex had to be preceded by the emergence of diploid monosexual organisms and provide an explanation for the emergence and maintenance of sex among diploids and for the scarcity of sex among haploid organisms.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of ornithology 141 (2000), S. 263-274 
    ISSN: 1439-0361
    Keywords: Systematics ; evolution ; anagenesis ; genealogy ; reference system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Description / Table of Contents: Zusammenfassung Verglichen mit anderen Tiergruppen, scheint die artliche Bestandsaufnahme der rezenten Vögel nahezu abgeschlossen zu sein. Doch ist das System der Vögel weiterhin umstritten und mit vielen Neuerungen konfrontiert. Die Gründe dafür liegen hauptsächlich in neuen, vor allem molekularbiologischen Methoden und in den unerwartet reichen Fossilfunden der jüngsten Zeit. Als Beispiele werden Altgaumenvögel, Kranichvögel, Ibisse, Flamingos, Mausvögel, Hopfe und Sperlingsvögel kurz behandelt. Die hier erzielten Fortschritte lassen die Befürchtung Stresemanns, die Großsystematik der Vögel sei mit den vorhandenen Methoden phylogenetisch nicht interpretierbar, zunächst als unbergründet erscheinen. Doch erwachsen einer solchen Interpretation andere Hindernisse, deren Bedeutung bisher zu wenig beachtet wurde, nämlich Parallelentwicklungen, die viel verbreiteter sind als gemeinhin angenommen. Ihre Häufigkeit lässt sich sogar mit evolutionsbiologischen Argumenten begründen. Es ist deshalb nicht zu erwarten, dass die Diskussionen um das „richtige“ System bald verstummen. Um dennoch die Eindeutigkeit der Information in nicht-systematischen Veröffentlichungen zu wahren, wird empfohlen ein etabliertes Referenzsystem auf Zeit zu wählen.
    Notes: Summary Unlike in most animal classes the inventory of extant species of the class Aves seems to be almost complete. Nevertheless avian systematics is challenged by many novelties and seems far from being settled. This is caused mainly by the application of novel methods of molecular analysis to phylogenetic problems and by the unexpectedly rich fossil record collected within the last 10–20 years. Examples from the Palaeognathae, Gruiformes, Threskiornithidae, Phoenicopteridae, Coliiformes, Upupiformes and Passeriformes are briefly treated. The progress in the field seems to disprove Stresemann's pessimistic view that the phylogeny of higher categories (orders) cannot be reconstructed by the available methods. However, phylogenetic interpretations are impeded by obstacles not considered by Stresemann and highly underestimated in most cases, namely by multiple independent developments leading to identical features. Frequent parallel developments are to be expected for theoretical evolutionary reasons. The diagnosis of such homoplasies can be extremely difficult or even impossible. Therefore we cannot expect the discussion about the “best” system of birds to end in the near future. Considering this dynamic situation in systematics, it is recommended to maintain unambiguousness of information in not strictly systematic publications by refering to a well established system as a temporally limited reference.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of insect behavior 13 (2000), S. 71-86 
    ISSN: 1572-8889
    Keywords: copulatory courtship ; behavioral interactions ; songs ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract D. birchii and D. serrata, two endemic Australian Drosophila species, have a copulatory courtship. The males of these species begin to court the female after mounting her and often go on with the courtship after the copulation is over. In the present paper we have described behavioral interactions between the male and the female and analyzed acoustic signals produced by the flies during courtship. Species differences were more pronounced in female than in male behavior. Variation within the species was obvious in the relative proportions of time the flies spent in different behaviors. Even though courtship took place nearly solely during copulation, some remains of precopulatory courtship were observed in both species. It is suggested that copulatory courtship exhibited by D. birchii and D. serrata flies is a derived rather than a primitive character.
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  • 10
    ISSN: 1569-8041
    Keywords: Charcot–Marie–Tooth disease ; chemotherapy ; hereditary motor and sensory neuropathy ; PMP22 ; vincristine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Severe up to life-threatening neuropathy has beenobserved in patients with hereditary neuropathies receiving vincristine. Case report:A 52-year-old female painter suffering fromhigh-grade non-Hodgkin's lymphoma (stage IVB) was treated with a total of 4mg of vincristine during two courses of CHOP chemotherapy (cyclophosphamide,vincristine, adriamycin, prednisone). At onset of treatment no neurologicalproblems were reported. There was good lymphoma response to chemotherapy. Atthe same time, however, the patient gradually developed dysphagia, dysarthria,muscular weakness of both lower and upper extremities, areflexia, paraesthesiaof the fingertips and bilateral sensory impairment of feet and lower legs.These symptoms continually worsened over a period of seven weeks until she wasunable to walk or to perform her work. Electrophysiological studies showedperipheral axonal and demyelinative sensorimotor neuropathy in correlation tohistological findings. Molecular analysis revealed 17p11.2 duplication typicalfor Charcot–Marie–Tooth disease IA. While continuing chemotherapywithout the use of vincristine the patient's neurologic symptoms slowlyrecovered within six months. Conclusion:Prior to administration of vincristine family andpatient history as well as physical examination should be performed carefullyto look for underlying hereditary neuropathy. For those patients with aclinical history or symptoms suggestive for CMT nerve conduction velocitystudies and on an individual base even molecular genetic analysis areneccessary to prevent serious neurologic complications.
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  • 11
    ISSN: 1569-8041
    Keywords: carboplatin ; chemotherapy ; gemcitabine ; non-small-cell lung cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The combination of paclitaxel (P) and carboplatin (C)is an effective treatment for advanced NSCLC. Gemcitabine (G) is an active newdrug. We planned a phase I study to find the maximum tolerated dose (MTD) ofthe PCG combination. A phase II study was subsequently conducted to evaluatethe activity and toxicity of PCG. Patients and methods:Forty-five patients entered the study.Twenty-eight had stage IIIA–B disease, 17 stage IV. In the phase Istudy, with a fixed dose of C at AUC = 6 on day 1, P was escalated usingincrements of 25 mg/m2 starting from 175 mg/m2 on day1 and G with increments of 200 mg/m2 starting from 800mg/m2 on day 1 and 8. Results:Fourteen patients entered the phase I study. The MTD wasreached at P 200 mg/m2, C AUC = 6 and G 1000 mg/m2.Neutropenic fever and grade 3 diarrhea were the dose limiting toxicities.Thirty-one patients were treated in the phase II study with P 175mg/m2, C AUC = 6 and G 1000 mg/m2. Response rate was57% (68% in stage III and 47% in stage IV).Myelosuppression was the main toxicity, with grade 3–4 leukopeniaoccurring in 35% of cases. Grade 3 anemia was observed in 24%of cases and grade 3–4 thrombocytopenia occurred in 34% ofpatients. Non-hematological toxicity was mild. Median survival and one-yearactuarial survival were 20.5 months and 74% for stage III and 11.5months and 47% for stage IV. Conclusions:PCG is a promising regimen for treating advancedNSCLC. A phase III study comparing PCG to paclitaxel plus carboplatin inadvanced NSCLC is ongoing. On the other hand, we are planning to introduce thePCG regimen in the treatment of stage II–III patients in the setting ofa multimodality treatment.
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  • 12
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 11 (2000), S. 1615-1616 
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; radiotherapy ; radiation myositis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 13
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 11 (2000), S. 1523-1530 
    ISSN: 1569-8041
    Keywords: androgen-independent prostate cancer ; chemotherapy ; metastatic prostate cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background and purpose:A great number of clinical researchstudies have been reported in the field of chemotherapy for advancedandrogen-independent prostate cancer during the last ten years. The aims ofthe present review were to assess their impact on management of the diseaseand on survival of patients. Methods:The review of full published reports was facilited by theuse of a MEDLINE computer search. Results:Clinical research studies have focused on definingguidelines for eligibility criteria and accurate endpoints for patients to beenrolled onto clinical trials and developing new agents or combinationof drugs including estramustine phosphate. Any combination of currentchemotherapy has no impact on overall survival of patients. Among drugs indevelopment, only the promising activity observed with docetaxel deservesrandomized trials to assess its impact on survival. The major innovativeadvance of the 90s is the demonstration of the impact of chemotherapy(mitoxantrone + prednisone) on quality of life as compared to prednisonealone. A greater and longer-lasting improvement in quality of life along witha concomitant decrease in costs was observed. Conclusions:At the present time, chemotherapy should beconsidered as a palliative treatment in patients with symptomaticandrogen-independent disease. The enrollment of patients into clinical trialsdealing with quality of life as primary endpoint is strongly solicited. Astandard methodology should be used in phase II trials with a primary goal ofselection of agents which should progress to randomized trials using survivalas an endpoint. Hopefully new specific strategies targeted to reverse themolecular changes that underlie prostate tumorigenesis should rapidly impactthe multimodality management of AIPC in the third millenium.
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  • 14
    ISSN: 1569-8041
    Keywords: cancer ; chemotherapy ; pleuropulmonary blastoma ; PPB ; soft tissue sarcoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pleuropulmonary blastoma (PPB) is a rare dysontogenetic tumor that usuallydevelops in the first decade of life and has been recognized as a distinctclinico-pathological entity different from the ordinary pulmonary blastoma ofadulthood. Since the tumor grows aggressively and tends to metastasize early,physicians have to be aware of late onset of symptoms and uncommonmanifestations. We report a case of PPB in a young adult and its recurrencein the pancreas after primary surgical treatment and adjuvant chemotherapy.Keeping in mind the moderate prognosis of PPB in children, accurate assessmentand treatment of PPB require a team approach of oncology, radiology andsurgery to establish new therapeutic guidelines in the future.
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  • 15
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; arterial access device ; chemotherapy ; colorectal cancer ; hepatic arterial chemotherapy ; liver metastases ; port-a-cath
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Hepatic arterial chemotherapy for liver metastases ofcolorectal cancer is still under discussion. Mainly because of the technicalcomplications of this mode of treatment and the lack of a survival benefit inrandomized studies. We performed an analysis of hepatic arterial5-fluorouracil (5-FU) chemotherapy in 145 consecutive patients treated at asingle institution. Patients and methods:One hundred forty-five patients withinoperable liver metastases from colorectal cancer were included. 5-FU, 1000mg/m2/day continuous infusion for five days every three weeks, wasdelivered in the hepatic artery by percutaneous catheter or arterial accessdevice. Results:The response rate was 34% for all patients,40% in patients with extrahepatic disease, and 15% in patientswith i.v. 5-FU-based pretreatment. TTP and OS for all patients were 7.5 and14.3 months, respectively. In patients with extrahepatic disease or i.v.5-FU-based pretreatment, OS was significantly shorter compared to patientswithout extrahepatic disease or 5-FU-based pretreatment (9.7 vs. 19.3 monthsand 10.1 vs. 17.4 months, respectively). forty-seven percent of patientsstopped treatment because of a complication. Complications most often seen inpatients with arterial ports were hepatic artery thrombosis (48%) anddislocation of the catheter (22%). Conclusions:The results of our analysis are in line with previousphase III studies. Extrahepatic disease and i.v. 5-FU-based pretreatment wereprognostic for reduced OS. The complication rate of hepatic arterial deliverywas worrisome, although, no negative impact on survival could be established.There is a strong need for improvement of hepatic arterial delivery methodsbefore further evaluation of hepatic arterial 5-FU will be worthwhile.
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  • 16
    ISSN: 1569-8041
    Keywords: advanced ovarian cancer ; chemotherapy ; docetaxel ; phase II trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:This phase II study was conducted to evaluate theefficacy and toxicity of docetaxel in Japanese patients with advanced ovariancancer. Patients and methods:Docetaxel was administered at a dose of 70mg/m2 intravenously to patients with platinum pre-treated advancedovarian cancer. Treatment was repeated every three weeks. No routinecorticosteroid premedication was given. Results:Ninety patients with advanced ovarian cancer were enteredand sixty were assessable for response. The overall response rate was28% in the assessable patients (95% confidence interval(95% CI): 17.5%–41.4%). CA125 responses were seenin 8 (24%) of 34 assessable patients for CA125 criteria. The 36platinum-refractory patients had a response rate of 25% compared with33% in the platinum-sensitive patients. The predominant toxicity wasneutropenia, with 86% of the patients experiencing grade 3 or 4.Hypersensitivity reactions occurred in 37% of the patients and were notlife threatening. Edema was mild and infrequent. Conclusion:Docetaxel at 70 mg/m2 demonstratedeffectiveness as a treatment of both platinum-sensitive andplatinum-refractory ovarian cancer patients, with a low incidence of severehypersensitivity reactions and edema.
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  • 17
    ISSN: 1569-8041
    Keywords: autologous stem-cell transplantation ; chemotherapy ; follicular lymphoma ; progression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Among the 566 patients with follicular lymphomas (FL)included in the GELF 86 prospective trials from October 1986 to September1995, 372 with progressive/relapsing disease were analyzed retrospectively toidentify prognostic factors at first relapse. Patients and methods:For progressive FL, patients received mono-(22%) or polychemotherapy (78%) followed by high-dose therapy(HDT) with ASCT for 83 patients (22%). The median time toprogression from initial treatment was 23 months (range 3–102 months)and 24% of documented patients (52 of 217) had histologicaltransformation (HT). Salvage therapy produced an overall response in64% of patients and the five-year survival from progression was42%. Results:For patients who underwent HDT with ASCT compared tostandard treatment, five-year freedom from second failure was at 42%vs. 16% (P = 0.0001) and five-year survival was58% vs. 38% (P = 0.0005), respectively. Thebenefit of HDT and ASCT remained if we consider only patients less than 65years (five-year survival at 60% vs. 40%; P =0.001). Multivariate analysis of parameters significant according tounivariate analysis found that no ASCT at first progression, age at relapse〉50 years, progression on-therapy were adversely significant onsurvival. Conclusions:HDT with ASCT compared to standard treatmentprolonged remission and survival after first progression of FL patients.
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  • 18
    ISSN: 1569-8041
    Keywords: 5-fluorouracil ; chemotherapy ; colorectal cancer ; cost/effectiveness analysis ; irinotecan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:It has been shown that irinotecan is superior toinfusional 5-fluorouracil (5-FU) in patients with advanced colorectal cancerafter 5-FU failure. In a recent trial, median survival was 10.8 months forpatients treated with irinotecan, compared to 8.5 months in patients receivinginfusional 5-FU. Considering the statistically significant but clinicallyrelatively small advantage of irinotecan over 5-FU, cost effectiveness shouldalso be part of treatment decision. Purpose:To relate the costs of each management approach tooverall survival in patients with metastatic colorectal cancer. Patients and methods:The healthcare costs and medical benefits(treatment-added survival) of second-line chemotherapy in patients (infusional5-FU: 129, irinotecan: 127) were compared. Data on overall survival were drawnfrom a multicenter randomised trial that compared infusional 5-FU (continuousinfusion, AIO, or LV5-FU2 regimens) to irinotecan alone. Costs were derivedfrom the accounting system in two university hospitals in Paris, France. Results:The range in total healthcare costs was 14,135 to 12,192US$ patient between management approaches, with irinotecan chemotherapycosting most and 5-FU-continuous infusion least. If survival was included asa treatment benefit, the cost-effectiveness ratio of irinotecan over 5-FUranged from 9,344 to 10,137 US$ per year of added survival. Conclusions:The least expensive management for metastaticcolorectal was 5-FU infusion but the additional cost of irinotecan wasbalanced by the added months of survival, with a cost-effectiveness ratioclose to that of other cancer treatments.
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  • 19
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    Springer
    Annals of oncology 11 (2000), S. 81-85 
    ISSN: 1569-8041
    Keywords: ABVD ; BEACOPP ; chemotherapy ; clinical trials ; COPP ; dose intensification ; Hodgkin's disease ; radiotherapy ; risk factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Treatment strategies in Hodgkin's disease (HD) arechanging fundamentally over the last decades. Both radiotherapy andcombination chemotherapy are effective treatment modalities. However, theoptimal choice of treatment or combinations of treatment is still debated fordifferent prognostic groups. Patients and methods:The German Hodgkin's Lymphoma Study Group(GHSG) initiated randomized clinical trials since 1978. Over the past 20years, more than 6000 patients with HD in all stages were randomized, treatedand followed by the GHSG. Patients are now being recruited from more than 300clinical centers. Results:As a consequence of different clinical trials, it is nowthe policy of the GHSG to tailor treatment to the individual risk of patients,giving favorable patients less intensive and less toxic therapy thanunfavorable patients. The treatment for early and intermediate stage HDbecomes quite similar with few cycles of polychemotherapy followed by involvedfield irradiation. In advanced stage HD, the introduction of dose intensifiedchemotherapy (BEACOPP), has improved treatment results and thus willsubstitute the MOPP or ABVD regimens. Conclusions:Although most of the patients with HD will be curedby modern treatment stategies, several questions are still subjects of ongoingclinical trials: 1) which chemotherapy regimen in which quantity will be thebest with respect to efficacy and toxicity and 2) which dose and field sizeof radiotherapy is adequate within the combined modality.
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  • 20
    ISSN: 1569-8041
    Keywords: chemotherapy ; docetaxel ; gastric cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:A multi-centric trial was performed to explore theclinical activity, in terms of response and toxicity (primary objectives),duration of response and survival (secondary objectives), of docetaxel withcisplatin in advanced gastric cancer (AGC). Patients and methods:Patients with measurable unresectable and/ormetastatic gastric carcinoma, performance status ≤1, normal hematological,hepatic and renal functions and not pretreated for advanced disease bychemotherapy received up to eight cycles of TC (docetaxel 85 mg/m2d1, cisplatin 75 mg/m2 d1) q3w. Dose escalation to 100mg/m2 was performed in five patients and was discontinued forexcessive toxicity. Results:Forty-eight patients were accrued. A median of 5cycles/patient was given. We observed 2 complete and 25 partial responses foran overall intent to treat response rate of 56% (95% CI:41%–71%). Twelve patients had stable disease for ≥9weeks (3 cycles). The median time to progression and overall survival were 6.6and 9 months, respectively. Grade ≥3 toxicities were neutropenia81%, anemia 32%, thrombocytopenia 4%, alopecia36%, fatigue 9%, mucositis 9%, diarrhea 6%,nausea/vomiting 4%, neurologic 2%, and one anaphylaxisprecluding treatment administration. We recorded nine episodes of non-fatalfebrile neutropenia in eight patients, two of them with docetaxel at 100mg/m2. There were no direct treatment-related deaths. Conclusions:TC is active in AGC with a high response rate in amulticentric trial. Despite its hematotoxicity, this regimen is well toleratedand can be recycled as originally planned in 78% of the cases. Theseresults may serve as basis for further developments of docetaxel containingregimens in this disease.
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  • 21
    ISSN: 1569-8041
    Keywords: chemotherapy ; concomitant chemoradiotherapy ; head and neck cancer ; paclitaxel ; radiation ; reirradiation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Concomitant chemoradiotherapy is an effectivetreatment modality for advanced head and neck cancer, but improved regimensare needed. We sought to define the toxicities, recommended phase II dose, andoutcome of a combination chemotherapy regimen with concomitanthyperfractionated radiotherapy in patients with poor prognosis cancers of thehead and neck, including those having received prior curative intentradiotherapy. Patients and methods:From 1995 until 1997, 54 patients weretreated, 25 of whom had received a prior full course of radiotherapy to thehead and neck. Patients were treated with 5-fluorouracil (5-FU) 600mg/m2/day continuous infusion × 5 days (days 1–5),hydroxyurea, 500 mg p.o. bid × 11 doses (days 1–6) and paclitaxel(60–150 mg/m2) by one-hour infusion on day 2 using a doseescalation strategy. Radiotherapy was given concomitantly on days 2–6,150 cGy bid. Each of 4–5 cycles was delivered every other week. Results:The MTD of paclitaxel was 100 mg/m2. Theregimen was feasible; radiotherapy was delivered at a median of 7300 cGy and83% of patients received ≥80% planned dose intensity.Hematological toxicity, with granulocyte colony stimulating factor, was verymild. Dose limiting toxicities were mucositis and dermatitis. Despite poorprognosis, two-year survival was 45%. Conclusions:The recommended phase II dose of this regimen is 5-FU600 mg/m2/day × 120 hours (days 1–5), hydroxyurea 500mg p.o. b.i.d. × 11 doses (days 1–6), paclitaxel 100mg/m2 over one hour on day 2, and radiotherapy 150 cGy b.i.d. days2–6. Concomitant chemotherapy and re-irradiation was feasible on thisprotocol and resulted in long-term survival in patients without other curativeintent options.
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  • 22
    ISSN: 1569-8041
    Keywords: alkylating agents ; bendamustine ; chemotherapy ; phase I study ; solid tumours ; weekly chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The cytotoxic agent bendamustine combines apurine-like benzimidazol and alkylating nitrogen mustard group. The clinicallytolerated dose for single bolus bendamustine is 215 mg/m2, forfractionated therapy on four consecutive days 85 mg/m2. The maximumtolerated dose of a day 1 and 8 (q4w) 30 min infusion schedule was recentlyfound to be 160 mg/m2, mouth dryness and fatigue weredose-limiting. Our current phase I trial was designed to define therecommended dose of a new weekly short infusion schedule. Patients and methods:Patients with refractory malignant tumoursqualified for the trial after written informed consent was obtained.Bendamustine was given as a 30-min i.v. infusion weekly for up to eightconsecutive weeks. Results:Twelve patients (8 male, 4 female, median age 57.5 years,range 42–64) were enrolled in this trial. At the starting dose of 80mg/m2, two patients had dose-limiting toxicity (fatigue grade 3,mouth dryness grade 3, fever grade 4 Common Toxicity Criteria). Nodose-limiting events were observed in six patients treated at 60mg/m2. An intermediate dose level of 70 mg/m2 wasstudied in three younger, less heavily pre-treated patients, was welltolerated and not associated with dose-limiting events. Haematologicaltoxicity was mild except for grade 3–4 lymphocytopenia, occurring in 11of 12 patients. Bendamustine was found to induce long-lastingpanlymphocytopenia with predominant B-cell cytotoxicity. Conclusions:The maximum tolerated dose of weekly bendamustinegiven as a 30-min i.v. infusion is 80 mg/m2, mouth dryness, fatigueand fever are dose-limiting. The recommended dose for phase II trials is 60mg/m2.
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  • 23
    ISSN: 1569-8041
    Keywords: anthracycline ; chemotherapy ; liposomal daunorubicin ; lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Standard therapy for lymphoma consists of acyclophosphamide (C), doxorubicin, vincristine (V), and prednisone (P) (CHOP)combination regimen. Liposomal daunorubicin (DaunoXome®) is an alternativeto doxorubicin for patients with lymphoma because of its more favorable safetyprofile and potentially more selective uptake in lymphoma. The objectives ofthis study were to determine the maximum tolerated dose (MTD) of liposomaldaunorubucin with CVP (COP-X) and the tolerability of the regimen in patientswith indolent lymphoma. Patients and methods:Patients with low-grade andintermediate-grade lymphoma having adequate cardiac, hepatic, and renalfunction were enrolled. Patients received C 750 mg/m2, V 1.4mg/m2 (maximum 2.0 mg), and liposomal daunorubicin 50–100mg/m2 i.v. on day 1 and P 100 mg p.o. on days 1–5. MTD wasthe liposomal daunorubicin dose associated with 20% dose-limitingtoxicity (ANC 〈500/mm3 for 〉5 days or febrile neutropenia). Results:Twenty patients, median age 59 years, were treated. Theliposomal daunorubicin MTD combined with CVP was 70–80 mg/m2,depending on patient population. No significant non-hematologic toxicityoccurred. Response rate was 44% (2 complete and 5 partial responses). Conclusions:A liposomal daunorubicin dose of 80 mg/m2in the COP-X regimen was well tolerated with little non-hematologic toxicity.
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  • 24
    ISSN: 1569-8041
    Keywords: chemotherapy ; chromosome aberrations ; malignant germ-cell tumours
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 25
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    Annals of oncology 11 (2000), S. 11-16 
    ISSN: 1569-8041
    Keywords: chemotherapy ; gene therapy ; head and neck cancer ; immunotherapy ; radiotherapy ; recurrent ; surgery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Locoregional recurrence is the most common cause of failure after head andneck cancer surgery. It is a disease which causes significant morbidityespecially on speech and swallowing. There are many different treatmentsavailable including surgery, reirradiation and chemotherapy. However, none ofthese have produced any significant survival benefit. Because of this, therehas been considerable interest in the development of new biological therapiessuch as gene therapy and immunotherapy for this disease. The objectives ofthis article are to provide an overview of the currently available therapiesfor recurrent head and neck cancer including gene therapy and immunotherapy.Prevention of recurrent disease by the detection and treatment of minimalresidual disease is also discussed.
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  • 26
    ISSN: 1569-8041
    Keywords: chemotherapy ; hepatocellular carcinoma ; liposomal doxorubicin ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Pegylated liposomal doxorubicin has an enhancedefficacy and reduced toxicity compared with free doxorubicin. The efficacy andtoxicity of pegylated liposomal doxorubicin was investigated in patients withhepatocellular carcinoma. Patients and methods:Patients with histologically confirmed,locally advanced or metastatic hepatocellular carcinoma and a Karnofsky index〉60% were included in this prospective single-arm study. Exclusioncriteria were liver cirrhosis stage Child–Pugh C, previous chemotherapy,or chemoembolization. Pegylated liposomal doxorubicin was given in a dose of30 mg/m2 every three weeks until progression of disease. Afterinclusion of five patients the dose could be escalated to 40 mg/m2in absence of toxicity grade 3 and 4. Results:Sixteen patients were evaluable for response. Noobjective response was achieved. The median survival time was 140 days(95% confidence interval: 126–154 days). Treatment toxicitiesgrade ≥3 comprised increased liver enzymes in patients with preexistinggrade 1 or 2 elevation (n = 6), hematologic toxicity (n =5), and hypersensitivity (n = 2). Conclusions:Pegylated liposomal doxorubicin is not effective fortreatment of advanced hepatocellular carcinoma. The favorable toxicity profilewas confirmed even in patients with underlying liver disease.
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  • 27
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; non-small-cell lung cancer ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thirty patients with chemotherapy-naïve advanced non-small-cell lungcancer (NSCLC) were given escalating doses of paclitaxel (150, 175, 200mg/m2) on day 1 in three consecutive cycles, together with a fixeddose of gemcitabine 1000 mg/m2 on days 1 and 8; cycles wererepeated every three weeks. The dose escalation of paclitaxel was feasible inthe majority of patients. Subsequently, 30 other NSCLC patients received adose of 200 mg/m2 paclitaxel with gemcitabine 1000 mg/m2in a phase II study. The major side effect was mild myelosuppression. Aresponse rate of 24% was achieved in 49 fully evaluable patients. Thisregimen proved to be safe and easy to administer on an out-patient setting,and constitutes now one of the arms of the current EORTC randomized study foradvanced NSCLC.
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  • 28
    ISSN: 1569-8041
    Keywords: breast cancer ; carboplatinum ; chemotherapy ; continuous 5-fluorouracil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We performed a trial using the combination of epirubicin 50mg/m2/day 1, carboplatinum AUC 5/day 1 and continuous5-fluorouracil (5-FU) 200 mg/m2/day (every 4 weeks for6 months) to confirm the efficacy and low toxicity profile of thisregimen in breast cancer. In 51 patients with metastatic(n = 33) or locally advanced (n = 18)breast cancer the overall response rate was 86% (95% confidenceinterval (95% CI): 73%–94%): 94% in locallyadvanced and 81% metastatic disease. Grade 3–4 toxicity was low:4% of patients presented with febrile neutropenia, 16% withsevere palmar-plantar syndrome, 10% with Port-a-cath thrombosis. This study confirms the high efficacy of infusional 5-FU-based regimens andjustifies further research into novel promising oral 5-FU derivatives.
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  • 29
    ISSN: 1569-8041
    Keywords: chemotherapy ; ovarian cancer ; second-line
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Gemcitabine is active in patients with otherwiseresistant or refractory ovarian cancer. As the drug is well tolerated, studiesusing gemcitabine combined with other antineoplastic agents are needed. Theaim of the study was to determine the maximum tolerated dose (MTD) ofepirubicin combined with gemcitabine, with and without support of G-CSF. Patients and methods:Patients with platinum-resistant orrefractory ovarian cancer were eligible. Gemcitabine (G) (starting dose 800mg/m2 day 1 and 8; 200 mg/m2 escalation per level) andepirubicin (E) (starting dose 60 mg/m2 day 1; 15 mg/m2escalation per level) were given every 21 days for four to six cycles. G-CSF(filgrastim 5 µg/kg/die) was given in case of grade 4 neutropenia(levels without support) or from day 9 up to leukocyte count〉10,000/mm3 after nadir (levels with support). Cohorts of threepatients were enrolled at each level, and another three patients were planned,if one dose-limiting toxicity (DLT) was registered. MTD was determined firstwithout and then with G-CSF. Results:Four levels were studied (G 800 + E 60; G 1000 + E 60;G 1000 + E 75; G 1000 + E 75 + G-CSF) with four, four, three and threepatients enrolled, respectively. DLT (grade 4 febrile neutropenia) wasobserved in two patients at level 3. Thus, G1000 + E 60 mg/m2 wasthe MTD without G-CSF. The addition of prophylactic G-CSF did not allow afurther increase of the dose and grade 4 thrombocytopenia was the DLT at level4. Non-hematological toxicity was mild. Grade 2 mucositis was reported in fourpatients. Among the 13 patients with measurable or evaluable disease, 3partial responses were observed for an overall response rate of 23.1%. Conclusions:The combination of gemcitabine 1000 mg/m2(day 1, 8) and epirubicin at 60 mg/m2 (day 1) is a feasibletherapy. Grade 4 neutropenia is frequent and G-CSF support is often required.With prophylactic support of G-CSF, the DLT is thrombocytopenia.
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  • 30
    ISSN: 1569-8041
    Keywords: chemotherapy ; intra-arterial ; liver metastasis ; unresectable pancreatic cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:A phase II trial of a new intra-arterial chemotherapyregimen for unresectable pancreatic cancer (UPC). Patients and methods:Ninety-six patients with UPC were treatedwith intra-arterial chemotherapy at three-weekly intervals. The schedule usedwas FLEC: 5-fluorouracil 1000 mg/m2, folinic acid 100mg/m2, carboplatin 300 mg/m2; epirubicin 60mg/m2. Results:The overall response rates by CT-scan evaluation were:15% partial response (PR), 44% stable disease (SD), 17%progressive disease (PD). The overall median survival was 9.9 months, and 10.6and 6.8 for UICC stage III and IV, respectively. Pain reduction occurred in42% of patients. A weight gain 〉7% from baseline occurred in8% of patients. A total of 341 courses of FLEC were administered. Grade3–4 hematological toxicity was seen in 25% of patients;ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%; andgrade 3 alopecia in 16%. One sudden death, a pre-infarction angina, anda transitory ischemic attack were observed. The only complication related tothe angiographic procedure was an intimal dissection of the iliac artery. Conclusions:The intra-arterial FLEC regimen was well toleratedand active. It requires only one day of hospitalization. Efficacy could onlybe assessed in a randomized study against a gemcitabine containing regimen.
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  • 31
    ISSN: 1569-8041
    Keywords: chemotherapy ; combination ; etoposide ; ifosfamide ; ovarian cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The prognosis of platinum resistant ovarian cancer isvery poor and the treatment of choice has not been clearly defined. Patients and methods:We conducted a phase II study with thecombination of ifosfamide i.v. at 2.25 g/m2 (days 1, 2) andetoposide per os at 100 mg daily (days 1–10) every four weeks. To beeligible for the study patients had to be resistant to platinum and paclitaxelpretreated. Results:Forty-one patients entered the study. The median intervalfrom the previous chemotherapy was 3.9 months. The median number of previouschemotherapeutic regimens was 2. Severe toxicities included neutropenia(41% of patients), leukopenia (29%) and thrombocytopenia(13%). Thirty-five patients are assessable for response. Nine patientsresponded (22% of the eligible, 26% of the assessable), four ofthemdemonstrated complete response to chemotherapy (10% and 12%,respectively), while three patients demonstrated stabilization of theirprogressive disease. After a median follow-up of 18 months, time toprogression is 3 months (range 0.9–14.4), duration of response is 9months (2.5–11) and median survival is 13 months (2.5–37.4+). Conclusions:The combination of ifosfamide with oral etoposideappears to have significant but manageable toxicity and encouraging efficacyin platinum resistant ovarian cancer.
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  • 32
    ISSN: 1572-9737
    Keywords: conservation genetics ; Equus ; evolution ; mitochondrial DNA control region ; mitochondrial 12S rRNA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The evolution, taxonomy and conservation of the genus Equuswere investigated by examining the mitochondrial DNA sequences of thecontrol region and 12S rRNA gene. The phylogenetic analysis of thesesequences provides further evidence that the deepest node in thephylogeny of the extant species is a divergence between twolineages; one leading to the ancestor of modern horses (E.ferus, domestic and przewalskii) and the other to thezebra and ass ancestor, with the later speciation events of the zebrasand asses occurring either as one or more rapid radiations, or withextensive secondary contact after speciation. Examination of the geneticdiversity within species suggested that two of the E. hemionussubspecies (E. h. onager and E. h. kulan) onlyrecently diverged, and perhaps, are insufficiently different to beclassified as separate subspecies. The genetic divergence betweendomestic and wild forms of E. ferus (horse) and E.africanus (African ass) was no greater than expected within anequid species. In E. burchelli (plains zebra) there was anindication of mtDNA divergence between populations increasing withdistance. The implications of these results for equid conservation arediscussed and recommendations are made for conservation action.
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  • 33
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    Antonie van Leeuwenhoek 77 (2000), S. 235-239 
    ISSN: 1572-9699
    Keywords: Aspergillus section Fumigati ; β-tubulin gene ; evolution ; phylogenetic analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Isolates representing newly described Neosartorya species, and isolates with abnormal morphologies from Aspergillus section Fumigati were examined by phylogenetic analysis of sequences of part of their β-tubulin gene. Phylogenetic analyses supported the earlier suggestions that heterothallism is a derived character, and that sexuality was lost several times during the evolution of Aspergillus section Fumigati. The heterothallic N. fennelliae and N. udagawae strains were found to be closely related to the homothallic Neosartorya sp. NRRL 4179 and N. aureola, respectively. Aspergillus sp. FRR 1266, which was earlier described as a variant of A. fumigatus, was found to be closely related to A. viridinutans. Another abnormal asexual isolate was found to be closely related to A. fumigatus and N. fischeri. Phylogenetic relationships among newly described Neosartorya species and other taxa were successfully established based on phylogenetic analysis of β-tubulin sequences.
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  • 34
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    Journal of the history of biology 33 (2000), S. 457-491 
    ISSN: 1573-0387
    Keywords: J. B. S. Haldane ; biology ; politics ; genetics ; evolution ; population genetics ; physiology ; Darwinism ; experimental biology ; eugenics ; Britain ; Russia ; India ; Soviet ; Communism ; socialism ; philosophy ; vision ; literature ; popularization ; religion ; human experimentation ; bioethics ; Venus ; Mars ; science fiction ; technocracy ; futurology ; H. G. Wells ; Julian Huxley ; Olaf Stapledon ; C. S. Lewis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , History
    Notes: Abstract This paper seeks to reinterpret the life and work of J. B. S. Haldane by focusing on an illuminating but largely ignored essay he published in1927, “The Last Judgment” – the sequel to his better known work, Daedalus (1924). This astonishing essay expresses a vision of the human future over the next 40,000,000 years, one that revises and updates Wellsian futurism with the long range implications of the “new biology” for human destiny. That vision served as a kind of lifelong credo, one that infused and informed his diverse scientific work, political activities, and popular writing, and that gave unity and coherence to his remarkable career.
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  • 35
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    Journal of the history of biology 33 (2000), S. 221-246 
    ISSN: 1573-0387
    Keywords: August Weismann ; ciliates ; Clifford Dobell ; cytology ; death ; Emile Maupas ; evolution ; Herbert Spencer Jennings ; Otto Bütschli ; Paramecium ; rejuvenescence ; sex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , History
    Notes: Abstract In the period 1875–1920, a debate about the generality and applicability of evolutionary theory to all organisms was motivated by work on unicellular ciliates like Paramecium because of their peculiar nuclear dualism and life cycles. The French cytologist Emile Maupas and the German zoologist August Weismann argued in the 1880s about the evolutionary origins and functions of sex (which in the ciliates is not linked to reproduction), and death (which appeared to be the inevitable fate of lineages denied sexual conjugation), an argument rooted in the question of whether the ciliates and their processes where homologous to other cellular organisms. In the beginning of the twentieth century, this question of homology came to be less important as the ciliates were used by the British protozoologist Clifford Dobell and the American zoologist Herbert Spencer Jennings to study evolutionary processes in general rather than problems of development and cytology. For them, homology mattered less than analogy. This story illustrates two partially distinct problems in evolutionary biology: first, the question of whether all living things have common features and origins; and second, whether their history and current nature can be described by identical mechanisms. Where Maupas (contra Weismann) made the ciliates qualitatively the same as all other organisms in order to create a cohesive evolutionary theory for biology, Jennings and Dobell made them qualitatively different in order to achieve the same end.
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  • 36
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    Journal of gastroenterology 35 (2000), S. 907-911 
    ISSN: 1435-5922
    Keywords: Key words: gastric cancer ; liver neoplasms ; secondary ; interventional radiology ; chemotherapy ; chemoembolization ; therapeutic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract: Little is known about the effectiveness of transcatheter chemotherapy in liver metastases from gastric cancer. The aim of this study was to evaluate the initial results of hepatic artery infusion and oily chemoembolization in these liver secondaries. Courses of transcatheter arterial infusion with 5-fluorouracil/doxorubicin (12 patients) and oily chemoembolization with doxorubicin-in-iodized oil and gelatin sponge (12 patients) were performed in 24 patients with histologically proven unresectable gastric cancer liver metastases. A positive effect of treatment (partial response + stabilization) was seen in 92% of the patients after chemoinfusion and in 50% after chemoembolization. The 1- and 2-year actuarial survival rates were 92% and 53% for infusion vs 50% and 17% for chemoembolization, respectively (log-rank test, P = 0.0009). For patients who had already died, the mean survival was 19.2 months vs 9.5 months (Student's t-test, P 〈 0.05) with median survivals of 23 months vs 8 months, respectively. The results with arterial infusion were very close to those reported for liver resection. Transcatheter therapy appears to be useful for the palliation of unresectable liver metastases from gastric cancer. If regional chemotherapy is used, arterial infusion should be the first-choice treatment, with oily chemoembolization being reserved for patients who do not respond to infusion.
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  • 37
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    Foundations of science 5 (2000), S. 429-456 
    ISSN: 1572-8471
    Keywords: awareness ; reflexive awareness and consciousness ; evolution ; experience and pattern matching ; symbolic language
    Source: Springer Online Journal Archives 1860-2000
    Topics: Natural Sciences in General
    Notes: Abstract An evolutionary point of view is proposed to make more appropriate distinctions between experience, awareness and consciousness. Experience can be defined as a characteristic linked closely to specific pattern matching, a characteristic already apparent at the molecular level at least. Awareness can be regarded as the special experience of one or more central, final modules in the animal neuronal brain. Awareness is what experience is to animals. Finally, consciousness could be defined as reflexive awareness. The ability for reflexive awareness is distinctly different from animal and human awareness and depends upon the availability of a separate frame of reference, as provided by symbolic language. As such, words have made reflexive awareness – a specific and infrequent form of awareness – possible. Conciousness might be defined as the experience evoked by considering, i.e. thinking about experiences themselves. If there is a hard problem of explaining consciousness, than this actually must be considered as the hard problem already met when trying to explain basic experience, since its nature remains elusive.
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  • 38
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    International journal of value-based management 13 (2000), S. 297-308 
    ISSN: 1572-8528
    Keywords: morality ; moral systems ; behavior ; evolution ; adaptation ; natural selection ; altruism ; reciprocal altruism ; fitness ; reciprocity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract The ethical and moral behavior of Homo sapiens is no longer the exclusive domain of religion and philosophy because we recognize that such behavior affects the reproductive success of individuals within the species. We are a social species and therefore our survival is influenced by our capacity for cooperation and our willingness to take risks for kin. Emotions, some of which are found in other species, help to mediate our altruistic behavior. The reproductive benefits of helping kin, especially offspring, are readily seen. Helping non-kin can be beneficial if individuals can differentiate between ‘reciprocators’ and ‘non-reciprocators’ and direct altruistic behavior toward reciprocators. Also, if third parties are favorably impressed by observing altruistic behavior, the rewards need not come from the recipient of the altruistic behavior.
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  • 39
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    Journal for general philosophy of science 31 (2000), S. 57-73 
    ISSN: 1572-8587
    Keywords: complex systems ; evolution ; nonlinearity ; pre-determination ; self-organization ; soft management ; structure-attractors ; synergetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Philosophy , Nature of Science, Research, Systems of Higher Education, Museum Science
    Notes: Abstract The philosophical consequences of synergetics, the interdisciplinary theory of evolution and self-organization of complex systems, are being drawn in the paper. The idea of discreteness of evolutionary paths is in the focus of attention. Although the future is open, and there are many alternative evolutionary paths for complex systems, not any arbitrary (either conceivable or desirable) evolutionary path is feasible in a given system. There are discrete spectra of possible evolutionary paths which are determined exclusively by inner properties of the corresponding systems. Synergetics allows us to reveal general laws of self-organization and, therefore, certain limits of arbitrariness of nature in choosing possible paths of evolution as well as in constructing of a complex evolutionary whole. A comparative analysis between the modern synergetic notions and a few ideas of the Western philosophy (F. Nietzsche, N. Hartmann, M. Heidegger) and of the Eastern teachings (Taoism, Buddhism) is made.
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  • 40
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    Annals of oncology 11 (2000), S. 927-937 
    ISSN: 1569-8041
    Keywords: brain lymphomas ; chemotherapy ; intrathecal chemotherapy ; methotrexate ; primary central nervous system lymphoma ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Primary central nervous system lymphomas (PCNSL) are aggressivemalignancies, exhibiting one of the worst prognoses among lymphomas. The besttreatment modality for PCNSL has not yet been identified. Several therapeuticquestions still remain unanswered, and some methodological pitfalls inclinical trials prevent definitive conclusions from being drawn. In thisreview, certain aspects of trial design as well as emerging therapeuticguidelines are analyzed, and future perspectives are discussed. In the vast majority of prospective trials, general criteria for treatmentof aggressive lymphomas were adopted, choosing primary chemotherapy (CHT)followed by radiotherapy (RT) as therapeutic modality. This strategy produceda five-year survival of 22%–40% in comparison to the3%–26% reported with RT alone. Systemic high-dosemethotrexate (HD-MTX) seems to be the most effective drug, producing aresponse rate of 80%–90% and a two-year survival of60%–65%. To date, the addition of other drugs atconventional doses have not consistently improved outcome. With a fewexceptions, any regimen without HD-MTX comprehensively performed no betterthan RT alone. In combined treatment, RT doses should be decided on the bases of responseto primary CHT and the number of lesions, and, until definitive conclusionsfrom well-designed trials are available, RT parameters should follow thewidely accepted principles used for other aggressive lymphomas. CHT asexclusive treatment, keeping RT for relapses or persistent disease, appearsto be an attractive strategy. However, the worldwide experience with thismodality is still limited, and corroborating data are needed. Intrathecal CHTstill has not found a defined role in PCNSL management. Preliminary data seemto indicate that adequate meningeal treatment with HD-MTX, but withoutintrathecal CHT, could also be suitable in positive-cerebrospinal fluidpatients. Future efforts should be addressed to identify new active drugs and moreefficient CHT combinations, to evaluate the efficacy of high-dose CHTsupported by autologous peripheral blood stem cells transplantation, and toclarify the impact of RT delay in complete responders, the usefulness ofintrathecal CHT, and the best management for elderly patients. The assessmentof impact of treatment on neuropsychological functions and quality of life isa mandatory endpoint in clinical trials.
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  • 41
    ISSN: 1569-8041
    Keywords: antifolate ; chemotherapy ; pancreatic cancer ; thymidylate synthase inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:To determine the safety and activity of LY231514(ALIMTA™, MTA, pemetrexed disodium, Eli Lilly and Co.,Indianapolis, IN) in chemotherapy-naïve patients with advanced pancreaticcancer. Patients and methods:Patients with unresectable or metastaticpancreatic cancer received LY231514 600 mg/m2 as a 10–minuteinfusion every three weeks. Results:Forty-two patients were enrolled in this phase II trial.The median age was 60.3 (range 37–77) years; 79% had metastaticdisease. Neutropenia was common (40% of patients ≥ grade 3) butinfectious complications were rare. Significant anemia or thrombocytopeniaoccurred in 〈20% of patients. Non-hematologic toxicities includedgrade 2 or 3 skin reaction which was ameliorated by dexamethasone. Elevationsof bilirubin or transaminases were infrequent (〈25% of patients) anddid not require dose reductions or treatment delays. Thirty-five patientsreceived two cycles of therapy and were evaluable for response. One complete(duration 16.2 months) and one partial (duration 6.9 months) were observedresulting in an objective response rate of 5.7% for evaluable patients.In addition, 17 patients (40%) had stable disease that lasted ≥6months in 5 patients. The median survival was 6.5 months, with 28% ofpatients alive at one year. Conclusions:LY231514 is a well-tolerated agent with minimalobjective antitumor activity in pancreatic cancer. The median and one yearsurvival times, which may be important indicators in phase II trials of newagents, are of interest. Combination trials of LY231514 in pancreatic cancerare planned.
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  • 42
    ISSN: 1569-8041
    Keywords: chemotherapy ; doxorubicin ; hepatocellular carcinoma ; liposome ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:There is lack of effective and safe chemotherapy foradvanced hepatocellular carcinoma. Polyethylene glycol-coated (pegylated)liposomal doxorubicin (PLD) has long circulation time and enhanced drugaccumulation in the tumor tissues. It has significant activity in Kaposi'ssarcoma, breast and ovarian cancers and the acute adverse effects of free drugare reduced. Patients and methods:A patient with advanced hepatocellularcarcinoma was treated with PLD and a pharmacokinetic study was performed.Initial serum total and direct bilirubin were 3.6 and 6.8 folds of uppernormal, respectively, and an indocyanine green clearance test at 15 minuteswas 26.3% (normal 〈 15%). Results:Compared to cases with normal liver function, increasedvolume of distribution of doxorubicin correlated with a large amount ofascites (P〈 0.05). The clearance of drug was unexpectedly higherthan in cases with normal liver function (P〈 0.05). According tothe pharmacokinetic studies, the disposition of PLD in this case has not beenretarded even in the presence of severe liver dysfunction. Only minimaltoxicities including grade 2 stomatitis and moderate leukopenia were observed.The tumor had a partial remission and the patient survived nine months afterPLD treatment. Conclusion:PLD could serve as a safe and effective treatment forhepatocellular carcinoma even in the presence of impaired liver function. Itsrole in treating advanced hepatocellular carcinoma is worthy of further study.
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  • 43
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; non-small-cell lung cancer ; phase II trial ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:The purpose of the present phase II trial was todetermine the efficacy and toxicity of vinorelbine–gemcitabine inpatients with advanced non-small-cell lung cancer (NSCLC). Patients and methods:From December 1997 to February 1999, 78chemotherapy-naive patients (median age 60 years, Karnofsky performance statusof 100, 90, 80 and 70 present in 5%, 41%, 36% and18% of the patients, respectively) with stage IIIB (17%) or IV(83%) NSCLC (65% adenocarcinomas, 22% squamous-cellcarcinomas, 10% large-cell carcinomas, 3% mixed-cell carcinomas)received 25 mg/m2 vinorelbine and 1200 mg/m2 gemcitabineon days 1, 8 and 15 of a four-week cycle. Results:In an intent-to-treat analysis, partial responses wereseen in 19% of the patients. The median duration of response was 4.4months. The median survival time was seven months and the one-year survivalrate was 32%. Myelosuppression was the main side effect with WHO grade3/4 neutropenia and thrombocytopenia in 35% and 11% of thepatients, respectively. Other side effects were usually mild to moderate. Conclusions:Vinorelbine–gemcitabine is active, welltolerated and easy to administer on an outpatient basis in advanced NSCLC.Thus a randomized comparison of this combination with platinum-based protocolsis warranted in patients with advanced NSCLC.
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  • 44
    ISSN: 1569-8041
    Keywords: chemotherapy ; esophageal cancer ; gemcitabine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:There were approximately 12,500 cases of esophageal carcinoma diagnosed in the US in 1992 and 12,200 deaths. The impact of chemotherapy on patients with metastatic disease is marginal with a median survival of only five months. Gemcitabine (LY188011,2,2,–difluorodeoxycytidine: dFdC), an analog of cytosine arabinoside (ara-C), is a pyrimidine antimetabolite. Gemcitabine has shown interesting clinical activity in initial phase II clinical trials in a variety of malignancies, including the aerodigestive malignancies, squamous-cell carcinoma of the head/neck and both non-small-cell and small-cell lung cancer. Patients and methods:A total of 21 patients with chemotherapy-naïve metastatic esophageal carcinoma were entered. Nineteen patients were evaluable for toxicity and seventeen patients were evaluable for response. Gemcitabine was administered intravenously at 1250 mg/m2 over 30–60 minutes on days 1, 8, and 15 followed by 1 week of rest. This four-week schedule defined a cycle of treatment. Patients may have received a maximum of six cycles. Results:Gemcitabine was well tolerated with minimal non-hematologic toxicity and grade 3–4 anemia, granulocytopenia, and thrombocytopenia occurring in 10.5%, 21%, and 0% of patients, respectively. No responses were seen in the seventeen evaluable patients. Conclusions:At the dose and schedule studied it would appear that gemcitabine has no activity in patients with chemotherapy-naïve esophageal carcinoma.
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  • 45
    ISSN: 1573-8604
    Keywords: vocalization ; sexual advertisement ; predator advertisement ; taxonomy ; evolution ; mouse lemur ; primate ; Madagascar
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Advertisement calls are often important noninvasive tools for discriminating cryptic species and for assessing specific diversity and speciation patterns in nature. We investigated the contribution of these calls to uncover specific diversity in nocturnal Malagasy lemurs. We compared sexual advertisement and predator advertisement calls of two mouse lemur species, western gray and eastern rufous mouse lemurs (Microcebus murinus and M. rufus, respectively) living in two contrasting habitats (dry deciduous vs. rain forest), and analyzed them statistically. Both species emitted several highly variable whistle calls in the context of predator-avoidance. Intrapopulation variation was high and overlapped interspecific variation. Sexual advertisement calls, given in the mating context, displayed a totally distinct, species-specific acoustic structure. Whereas gray mouse lemurs produced rapidly multifrequency modulated, long trill calls, rufous mouse lemurs gave slowly frequency-modulated short chirp calls. Our results suggest specific status for gray and rufous mouse lemurs and indicate the importance of predation and social needs in shaping vocal communication.
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  • 46
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    Anatomy and embryology 202 (2000), S. 281-290 
    ISSN: 1432-0568
    Keywords: Key words Extracellular matrix ; cartilage ; bone ; evolution ; lamprey ; agnathan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Previous evidence from our laboratories showed that collagen is not the major matrix protein of the cartilaginous endoskeleton of the lamprey (Petromyzon marinus). Here we have characterized the cartilage matrix proteins of the only other extant agnathan, the hagfish (Myxine glutinosa). Using morphological, immunochemical and biochemical methods, we show that the structural proteins of the cartilaginous endoskeleton of the hagfish are also non-collagenous in nature. Although these hagfish cartilage proteins share properties both with each other and with lamprey cartilage proteins, including resistance to solubilization with cyanogen bromide and an usual amino acid composition rich in glycine and non-polar amino acids, it is clear that at least two and probably more hagfish cartilage proteins can be distinguished, with distinct distributions in different cartilage structures. Furthermore, in spite of their similarities, matrix proteins from hagfish cartilage are not identical to the proteins we have previously characterized in lamprey cartilage. These results suggest the existence of a larger family of similar but not identical proteins that form the major structural elements of cartilage tissues of agnathans. These data also support our previous conclusion that type II collagen became the predominant structural protein of cartilage only after the divergence of the agnathans from the ancestral line of the vertebrates.
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  • 47
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    Annals of oncology 11 (2000), S. 133-149 
    ISSN: 1569-8041
    Keywords: chemotherapy ; dose ; dose-density ; dose-intensity ; high-dose chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Shortening the interval between cycles is one meansof increasing the dose intensity of chemotherapy, and can be supported bybiological and mathematical rationales. Our objective was to assess theclinical relevance of the rapid repetition of regimens (so-called `dose-densechemotherapy') in various solid neoplasms. Design:The medical literature was reviewed in accord withMulrow's recommendations. Randomised studies comparing frequently-repeatedchemotherapy to standard regimens as well as open studies are described andcritically examined. Results:Dose-dense regimens were widely found to be feasible. In small-cell lung cancer, survival of patients receiving dose-denseregimens was better than that of patients treated by standard chemotherapy inthree trials, two of which reached significance, when these intensive regimensallowed better dose intensity. In poor-prognosis germ-cell tumors, a dose-dense regimen was not betterthan standard therapy, perhaps because of an excessively high toxicity-relateddeath rate. However, recent phase II studies have provided encouragingresults. In early breast cancer, the one published randomized study in the adjuvantsetting showed only a trend towards better disease-free survival innode-positive women receiving a weekly-repeated regimen. Two randomized trialsfailed to show any benefit in the neoadjuvant setting with a dose-denseregimen. No evidence of a benefit was provided in metastatic breast cancer. In advanced colorectal cancer, evidence of an improvement in survival withweekly or bi-weekly 5-FU–leucovorin compared to a classic monthlyschedule has recently been shown in two randomized trials, and dose-denseregimens are recognized as standard therapy in many countries. Phase II studies of dose-dense regimens have also shown high response ratesand long survival in many neoplasms, including Ewing's sarcoma, gestationaltrophoblastic disease, ovarian carcinoma and gastric cancer. Conclusions:A considerable amount of experience has been gainedwith frequently-repeated regimens. A few randomized trials have demonstrateda benefit for survival on standard chemotherapy in small-cell lung cancer andadvanced colorectal cancer. However, this benefit appears to be weak. Thecombination of dose-dense chemotherapy regimens with new anti-cancerstrategies based on our insights into the mechanisms of oncogenesis is achallenge on the eve of the millennium.
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  • 48
    ISSN: 1569-8041
    Keywords: chemotherapy ; colorectal cancer ; oxaliplatin ; phase II
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Backround:Oxaliplatin is a novel platinum derivative, which,combined with 5-fluorouracil (5-FU), and folinic acid (FA), demonstratessynergistic activity in metastatic colorectal cancer (MCC). The HeCOGperformed a multicenter phase II study of a weekly oxaliplatin administrationschedule in patients with previously treated MCC to evaluate the antitumorefficacy and toxicity of this combination. Patients and methods:Eligible patients included those whorelapsed after or during chemotherapy with 5-FU and FA and/or irinotecan.Prior radiotherapy was accepted provided that measurable disease was outsidethe radiation fields. Other eligibility criteria included written informedconsent, a WHO performance status ≤2 and adequate bone marrow, liver andrenal function. Treatment consisted of Oxaliplatin 50 mg/m2 bytwo-hour intravenous (i.v.) infusion followed by FA 500 mg/m2(two-hour i.v. infusion) and 5-FU 2500 mg/m2 (24-hour continuousi.v. infusion) on days 1, 8, 15, 22, 29, 36. The regimen was repeated every50 days. Results:Thirty-two patients (Median age 61 years, range25–76) entered the trial. The majority (75%) had progressed afterreceiving first-line chemotherapy. Diarrhea was the main non-hematologic toxicity. More than half of thepatients (53%) developed grades 3 or 4 diarrhea. Due to this sideeffect only 29% of cycles were given with at least 90% of theplanned dose of 5-FU. Hematologic toxicity included grade 3 neutropenia andthrombocytopenia (10% for each), and grade 4 thrombocytopenia(3%). Two patients (6%) died of sepsis, one related toneutropenia and one due to urinary tract sepsis. Sixteen patients (50%)developed grades 1 and 2 neurotoxicity in the form of sensory neuropathy,which was mild and transient. The objective response rate was 13%(95% CI: 3%–29%). All four responses were partial.Twelve patients (38%) had stable disease and 8 (25%) progressivedisease. The median time to progression was three months and the mediansurvival was nine months from the start of therapy. The Kaplan–Meierestimated probability of one-year survival for the group as a whole was32%. Conclusions:The weekly administration of oxaliplatin with 5-FUand FA was associated with considerably less neurotoxicity than otherschedules. However, the high percentage of diarrhea suggests that a dosereduction of 5-FU in this regimen may result in better therapeutic synergy.
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  • 49
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    Annals of oncology 11 (2000), S. 887-889 
    ISSN: 1569-8041
    Keywords: chemotherapy ; lung metastases ; spontaneous pneumothorax
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Pneumothorax occurring in the absence of obvious lungdisease is defined as spontaneous pneumothorax. Spontaneous pneumothoraxoccurs in a variety of settings in patients with malignancies. Patients and methods:We present a case report of spontaneouspneumothorax in malignancy and review the literature. Results:No correlation was found between the occurrence ofpneumothorax with age, sex or smoking history. Pneumothorax occurred with avariety of primary tumors. However it was always associated with lungmetastases or lung involvement with tumor. In certain cases the metastaseswere detected after the occurrence of pneumothorax. Conclusions:The occurrence of pneumothorax in a patient withmalignancy should prompt a search for lung metastases.
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  • 50
    ISSN: 1569-8041
    Keywords: adjuvant ; chemotherapy ; gastric cancer ; meta-analysis ; randomised clinical trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Several studies have investigated the possible roleof the adjuvant chemotherapy after curative resection for gastric cancerfailing to show a clear indication; previous meta-analyses suggested smallsurvival benefit of adjuvant chemotherapy, but the statistical methods usedwere open to criticisms. Materials and methods:Randomised trials were identified by meansof Medline and CancerLit and by selecting references from relevant articles.Systematic review of all randomised clinical trials of adjuvant chemotherapyfor gastric cancer compared with surgery alone, published before January 2000,were considered. Pooling of data was performed using the fixed effect model.Death for any cause was the study endpoint. The hazard ratio and its95% confidence intervals (95% CI), derived according to themethod of Parmar, were the statistics chosen for summarising the relativebenefit of chemotherapyversuscontrol. Results:Overall 20 articles (21 comparisons) were considered foranalysis. Three studies used single agent chemotherapy, seven combination of5-fluorouracil (5-FU) with anthracyclin, ten combination of 5-FU withoutanthracyclines. Information on 3658 patients, 2180 deaths, was collected. Chemotherapy reduced the risk of death by 18% (hazard ratio 0.82,95% CI: 0.75–0.89, P 〈 0.001). Association ofAnthracyclines to 5-FU did not show a statistically significant improvementwhen compared with the effect of the other regimens. Conclusions:Chemotherapy produces a small survival benefit inpatients with curatively resected gastric cancer. However, taking into accountthe limitations of literature based meta-analyses, adjuvant chemotherapy isstill to be considered as an investigational approach.
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  • 51
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    Annals of oncology 11 (2000), S. 1343-1347 
    ISSN: 1569-8041
    Keywords: chemotherapy ; Her2/neu ; indolent ; malignant ; palliative care ; secretory breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Secretory carcinoma of the breast is a rare and indolent tumour originallydescribed in children but occurring equally in the adult population. Theprincipal management problems following primary surgical treatment are localrecurrence and axillary lymph node metastases. Distant metastases areextremely rare. We present the case of a 27-year-old woman with pulmonary metastases froma secretory breast cancer treated by mastectomy and axillary lymph nodedissection 12 years previously. There was no response to chemotherapy; however, the patient remained aliveand active two years from presentation with metastatic disease and one yearfrom cessation of all cytotoxic chemotherapy. She eventually died ofrespiratory failure two and a half years after presentation. To our knowledge, this is only the fourth reported case of distantmetastases from secretory breast cancer and the second reported case in whichcurrent active chemotherapy has been used. We review the literature anddiscuss the apparent chemoresistance of this tumour including the lack ofmembrane staining for Her2/neu. In the absence of any proven effective chemotherapy we believe that symptomcontrol becomes the focus of management and offers patients with metastaticsecretory breast cancer the greatest chance of a functional and good qualityexistence.
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  • 52
    ISSN: 1569-8041
    Keywords: chemotherapy ; drug interaction ; in vitroassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Chemotherapy using multi-drug regimens is consideredmore active than single-agent therapy. This may be due to synergisticinteractions or, simply, a higher probability of administering an activeagent. We investigated in vitrothe type of drug interactions in arecognized regimen in relationship to tumour type and drug sensitivity. Patients and methods: The possibility of synergistic and additiveinteractions between individual cytotoxic drugs was investigated for thecomponent drugs of the established FEC regimen, i.e., 5-fluorouracil,epirubicin and cyclophosphamide, in 243 patient tumour samples representingvarious drug sensitivity using the non-clonogenic fluorometric microculturecytotoxicity assay. Results: Using a cell survival of ≤50% as a limit fordrug activity and sample sensitivity, the overall response rates to the mostactive single drug (Dmax) and the combination were 56% and64%, respectively, with a distribution among diagnoses similar to thatin the clinic. For 86% of the samples there was concordance withrespect to judgement of activity using either Dmax or thecombination. For samples being sensitive to at least one single drug,95% were also sensitive to the combination whereas for samples withinsignificant Dmax effect, only 2% were sensitive to thecombination. In samples with modest Dmax effects, i.e., cellsurvival in the range 〉50%–≤80%, 45%responded to the combination. The effect of the combination was generally wellpredicted from the Dmax effect. Conclusions:The superior antitumour effect of drug combinationscompared with single drugs may be due to the higher chance of selecting anactive agent. However, for intermediately sensitive tumours, additionalinteraction effects of a combination may be of clinical significance.
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  • 53
    ISSN: 1569-8041
    Keywords: carcinosarcoma ; chemotherapy ; thyroid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thyroid carcinosarcoma is a rare and aggressive thyroid tumor. Histologicalexamination of a tumor showed the characteristic of epithelial carcinoma andmesenchymal differentiation. We retrospectively analyzed the course of thepatient and reviewed the literature in which only 19 other cases aredescribed. Carcinosarcoma of the thyroid is a very aggressive tumor with aclinical course similar to anaplastic thyroid carcinoma. Survival is veryshort despite aggressive multimodal treatment.
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  • 54
    ISSN: 1569-8041
    Keywords: acute myeloid leukemia ; chemotherapy ; chronic lymphocytic leukemia ; immunosuppression ; second neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An increased incidence of different malignancies associated to chroniclymphocytic leukemia (CLL) has been reported. The association of CLL and acuteleukemia is a rare event described in 〈1% of CLL, the type of acuteleukemia being either from the lymphoid or more often from the myeloidlineage. The coexistence of acute myeloid leukemia (AML) and CLL in the samepatient has been occasionally reported. Most of these cases have beenassociated with the administration of chemotherapy or radioterapy for CLL,suggesting that the former may be a secondary leukemia. On the other hand, CLLcould precede, but could also be diagnosed at the same, or delayed time asAML, suggesting the presence of other leukemogenic factors. We describe theexceptional development of AML and lung cancer in a patient with previouslydiagnosed CLL in minimal residual disease status after fludarabine treatmentfollowed by autologous peripheral blood stem-cell transplantation.
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  • 55
    ISSN: 1569-8041
    Keywords: chemotherapy ; interferon ; transitionall-cell carcinoma ; urothelial tract
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Based on the favorable results of the combination5-fluorouracil (5-FU), cisplatin and interferon-α as second-line treatmentin advanced metastatic transitional-cell carcinoma of the urothelial tract aconfirmatory study was executed in a multicenter setting. Patients and methods:In this open label phase II study 43patients failing adequate previous chemotherapy were treated with IFN-α2b5 MU/m2 subcutaneously for 5 consecutive days starting on day 1 and22 simultaneous with 5-FU 500 mg/m2 daily as a continuous infusion.In between the same dose of IFN-α2b was given 3 times weekly with CDDP 25mg/m2 on days 1, 8, 15 and 22. This cycle was repeated every sixweeks. Results:In 40 eligible patients 5 PR were seen (12.5%;95% confidence interval (95% CI):4.1%–26.8%). The major toxicity was hematological. Twotoxic deaths were seen due to gastro-intestinal hemorrhage. Conclusions:In view of these results this combination can not berecommended as second line treatment for metastatic transitional-cellcarcinoma of the urothelial tract.
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  • 56
    ISSN: 1569-8041
    Keywords: chemotherapy ; docetaxel ; gemcitabine ; non-small-cell lung cancer ; phase I trials ; taxanes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Docetaxel and gemcitabine are active in a broad rangeof malignancies. The objective of this phase I trial was to determine themaximally tolerated doses of the combination of docetaxel and gemcitabine. Patients and methods:Patients with advanced cancer, WHOperformance status 0–2, who had received up to one prior chemotherapyregimen were treated with gemcitabine on days 1 and 8 and docetaxel on day 8repeated every 21 days. Prophylactic ciprofloxacin was commenced on day 11 ofeach cycle and continued until the neutrophil count reached 1.0 ×109/l. G-CSF was not administered. Dose levels studied weredocetaxel/gemcitabine: 60/800, 60/1000, 75/1000, 75/1200, 85/1200 and 100/1200mg/m2. Results:Thirty-nine patients were entered and all were assessablefor toxicity. The highest administered dose level was 100 mg/m2docetaxel and 1200 mg/m2 gemcitabine with dose limiting toxicitiesof febrile neutropenia, grade 4 neutropenia ≥7 days, grade 4thrombocytopenia, grade 3 stomatitis and/or grade 3 fatigue in three out ofsix patients. Treatment was well tolerated (40 cycles) in the 10 patientstreated at the recommended dose level (85/1200) with only a single episode offebrile neutropenia and grade 3 or 4 non-hematologic toxicity was infrequent.There was no significant pulmonary toxicity. Responses were seen in a rangeof malignancies including non-small-cell lung cancer. Conclusions:The recommended dose level of 85 mg/m2docetaxel and 1200 mg/m2 gemcitabine has a favourable toxicityprofile and is suitable for further investigation in phase II trials. Thisnon-platinum containing regimen warrants further investigation as a potentialalternative to platinum containing regimens in non-small-cell lung cancer andother malignancies.
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  • 57
    ISSN: 1569-8041
    Keywords: cervical cancer ; chemotherapy ; phase I ; radiotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background.Cisplatin and paclitaxel are active in cervical cancerand both are able to potentiate the effects of radiotherapy. In this study weevaluated the maximum-tolerated dose (MTD) of paclitaxel in combination witha fixed dose of cisplatin when given weekly concurrently with pelvicradiotherapy to patients with carcinoma of the cervix uteri. Patients and methods:Eighteen patients with cervical cancer wereenrolled in this study. Cisplatin (30 mg/m2) and paclitaxel(starting dose 40 mg/m2; 5 mg/m2 escalation per level)were given on day 1 of radiotherapy and then weekly for six times.Radiotherapy was given to the pelvis with a four-field box technique for fivedays each week. Patients received 65 Gy in 1.8 Gy fractions. Cohorts of threepatients were enrolled at each level and three further patients were includedif one or two dose-limiting severe adverse events (SAE) were recorded. SAE wasdefined as grade 3 or 4 nonhematologic toxicity, excluding nausea or vomitingand alopecia, grade 4 neutropenia or thrombocytopenia, and prolonged (〉1week) neutropenia or thrombocytopenia. Results:Four levels were studied (paclitaxel 40, 45, 50, 55mg/m2) with three, five, four and six patients enrolled,respectively. The MTD of paclitaxel was found at 50 mg/m2/wk andcisplatin 30 mg/m2/wk. Diarrhea was the dose-limiting toxicity.Thirteen patients were evaluable for response: seven complete and five partialresponses were obtained with an overall response rate of 92.3%. Conclusions:The MTD of paclitaxel is 50 mg/m2/wk whenassociated to cisplatin 30 mg/m2/wk and concurrent pelvicradiotherapy. Diarrhea is the dose limiting side effect. Preliminary datasuggest that concurrent chemoradiotherapy with paclitaxel and cisplatin couldbe a very active treatment for patients with locally advanced carcinoma of thecervix.
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  • 58
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    Annals of oncology 11 (2000), S. 509-513 
    ISSN: 1569-8041
    Keywords: assessment ; chemotherapy ; eripheral neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 59
    ISSN: 1569-8041
    Keywords: advanced breast cancer ; chemotherapy ; gemcitabine ; vinorelbine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Gemcitabine and vinorelbine have shown activity inbreast cancer. A phase II trial was initiated in order to evaluate theresponse rate (RR) and time to progression (TTP) of the combination of the twodrugs in patients with metastatic breast cancer progressing after first-linetaxane-based chemotherapy. Patients and methods:Thirty-one patients were treated with thecombination of gemcitabine 1000 mg/m2 days 1 + 8 and vinorelbine30 mg/m2 days 1 + 8. The cycles were repeated every three weeks. Results:Of 27 evaluable patients 1 (4%, 95%confidence interval (95% CI): 0.1%–19%) achievedcomplete remission (CR), five (18%; 95% CI:6%–38%) partial remission (PR), eleven (40%;95% CI: 22%–61%) stable disease and ten patientsprogressed. The median duration of response was six months (range 4–10+)and the median duration of disease stabilization was five months (range2–22+). With a median follow-up of 16 months (range 0.4–22+) themedian TTP was 3.5 months (range 0.4–22+) and the median survival was9.5 months (range 0.4–22+). Grade 3–4 toxicities weregranulocytopenia 15 patients (48%), rash 3 patients (10%),neuropathy 1 patient (3%) and thrombocytopenia 1 patient (3%).In conclusion the combination of gemcitabine/vinorelbine in the dosesadministered in this group of patients had a response rate of 22% andneeds to be further evaluated in metastatic breast cancer.
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  • 60
    ISSN: 1569-8041
    Keywords: chemotherapy ; gemcitabine ; malignant glioma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose:We conducted a phase II multicentre study of gemcitabinein patients with anaplastic astrocytoma and glioblastoma multiforme at firstrelapse. Patients and methods:Patients with anaplastic astrocytoma orglioblastoma multiforme receiving a stable dose of steroids and ECOGperformance status ≤3 were eligible for this study at the time of firstrelapse. One adjuvant chemotherapy regimen was permissible. Patients receivedgemcitabine 1000 mg/m2 i.v. weekly × 3, repeated on afour-weekly cycle. Results:Of 20 patients enrolled, 15 were evaluable for response,19 for non-hematological toxicity and 18 for hematological toxicity. Sevenpatients had anaplastic astrocytoma (AA) and twelve glioblastoma multiforme(GBM). Age ranged from 28–71 years (median 50). Fifteen patientsdiscontinued therapy due to disease progression. The median number of cyclesadministered was 1 (range 1–11); only two patients received more thanthree cycles. Hematologic toxicity was acceptable and no grade 4 toxicity wasseen. One patient developed Pneumocystispneumonia and eventualpulmonary embolism; one died of gastric hemorrhage related to steroid therapy.No objective responses were seen. Nine patients had stable disease (medianduration 2.7 months, range 0.9–11.2). Conclusions:Gemcitabine given in this dose and schedule seemswell tolerated but is not active in patients with recurrent high-gradegliomas.
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  • 61
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    Reviews in endocrine & metabolic disorders 1 (2000), S. 225-231 
    ISSN: 1573-2606
    Keywords: thyroid neoplasms ; chemotherapy ; anaplastic carcinoma ; lymphoma ; therapeutics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 62
    ISSN: 1573-689X
    Keywords: bedside wellness system ; chemotherapy ; fatigue ; emesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The bedside wellness system (BSW) is effective for decreasing stress and improving mental well-being and should help relieve the side effects and mental disorders of patients during cancer chemotherapy. Methods: The study was a randomized clinical trial. After giving informed consent, patients were randomly assigned to the BSW intervention or control groups. The patients were given the Hospital Anxiety and Depression Scale (HADS) test before the trial to evaluate their emotional baseline. The Cancer Fatigue Scale, which was developed at our institute, and face visual analog scale were used to measure the emotional state and subjective feelings before and after the trial. The degree of emesis was measured using a visual analogue scale after the experience. We set up the system in a room in the outpatient clinic of the National Cancer Center New Hospital Building. Results: The decreases in the fatigue score and emesis score 3–5 days after chemotherapy were statistically significant (both p 〈 0.05) and carry-over effects were detected. Conclusions: BSW intervention therapy is an effective way to treat fatigue and emesis. This virtual reality system is a new therapeutic method that can be used in palliative medicine.
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  • 63
    ISSN: 1573-6857
    Keywords: evolution ; Oryza ; retrotransposon ; rice ; wild species
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The Oryza officinalis complex is a genetically diverse, tertiary genepool of rice. We analyzed part of the primary structure of the integrase coding domain (ICD) of a gypsy-like retrotransposon from species of the O. officinalis species complex. PCR was performed with degenerate primers that hybridized to conserved sequences in the integrase genes of gypsy-type retrotransposons, using total DNA from different species of the O. officinalis complex as templates. Cloning and sequencing of the PCR products showed that the amplified fragments are highly homologous to each other (75–90%) and belong to one family of retrotransposons that is related to the previously studied RIRE-2 element from rice. Two main subfamilies of 292 and 351 bp were distinguished. Analysis of primary sequence data supports previous reports that sequence divergence during vertical transmission has been the major influence on the evolution of gypsy-type retrotransposons in Oryza species. Based on sequence data phylogenetic relationships among species of the O. officinalis complex were estimated. The data suggests that O. eichingeri is more closely related to the ancestral species of the complex.
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  • 64
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    Journal of mammalian evolution 7 (2000), S. 1-22 
    ISSN: 1573-7055
    Keywords: Dasyurus ; marsupials ; control region ; mtDNA ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract There has been a great deal of interest in determining phylogenetic relationships within the family Dasyuridae due to the widespread distribution, ecological diversity, and relative plesiomorphy of this taxon within the Australasian marsupial radiation. In the past, it has been extremely problematic to determine the phylogenetic relationships among species within Dasyurus, with numerous studies using both morphological and molecular characters providing different topologies. Here, the mitochondrial DNA (mtDNA) control region is used as a novel set of characters in an attempt to identify relationships among the six closely related extant species. Sequences were obtained from multiple individuals representing all extant species of quolls including, when possible, individuals from different geographical regions. Sequences were analyzed using both parsimony criteria and neighbor-joining methods. Results presented here concur with those of Krajewski et al. (1997) in (1) placing D. geoffroii in a highly supported clade with D. spartacus, (2) resolving a monophyletic group of D. albopunctatus + D. geoffroii + D. spartacus, and (3) placing D. hallucatus as the sister taxon to all other species of quolls. Results also show two highly supported and geographically distinct clades of D. maculatus (Tasmanian and mainland) that do not correspond to the currently used subspecific nomenclature. Preliminary results also indicate that there are different clades among geographic groups of D. hallucatus that warrant further investigation. The mtDNA control region is a highly variable locus and may be used in forensic tests for species identification in this genus.
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  • 65
    ISSN: 1573-6849
    Keywords: cat ; chromosome painting ; comparative mapping ; dog ; evolution ; human
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Domestic cats and dogs are important companion animals and model animals in biomedical research. The cat has a highly conserved karyotype, closely resembling the ancestral karyotype of mammals, while the dog has one of the most extensively rearranged mammalian karyotypes investigated so far. We have constructed the first detailed comparative chromosome map of the domestic dog and cat by reciprocal chromosome painting. Dog paints specific for the 38 autosomes and the X chromosomes delineated 68 conserved chromosomal segments in the cat, while reverse painting of cat probes onto red fox and dog chromosomes revealed 65 conserved segments. Most conserved segments on cat chromosomes also show a high degree of conservation in G-banding patterns compared with their canine counterparts. At least 47 chromosomal fissions (breaks), 25 fusions and one inversion are needed to convert the cat karyotype to that of the dog, confirming that extensive chromosome rearrangements differentiate the karyotypes of the cat and dog. Comparative analysis of the distribution patterns of conserved segments defined by dog paints on cat and human chromosomes has refined the human/cat comparative genome map and, most importantly, has revealed 15 cryptic inversions in seven large chromosomal regions of conserved synteny between humans and cats.
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  • 66
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    Genetica 109 (2000), S. 105-111 
    ISSN: 1573-6857
    Keywords: Drosophila ; evolution ; heterochromatin ; Y chromosome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Y chromosome evolution is characterized by the expansion of genetic inertness along the Y chromosome and changes in the chromosome structure, especially the tendency of becoming heterochromatic. It is generally assumed that the sex chromosome pair has developed from a pair of homologues. In an evolutionary process the proto-Y-chromosome, with a very short differential segment, develops in its final stage into a completely heterochromatic and to a great extends genetically eroded Y chromosome. The constraints evolving the Y chromosome have been the objects of speculation since the discovery of sex chromosomes. Several models have been suggested. We use the exceptional situation of the in Drosophila mirandato analyze the molecular process in progress involved in Y chromosome evolution. We suggest that the first steps in the switch from a euchromatic proto-Y-chromosome into a completely heterochromatic Y chromosome are driven by the accumulation of transposable elements, especially retrotransposons inserted along the evolving nonrecombining part of the Y chromosome. In this evolutionary process trapping and accumulation of retrotransposons on the proto-Y-chromosome should lead to conformational changes that are responsible for successive silencing of euchromatic genes, both intact or already mutated ones and eventually transform functionally euchromatic domains into genetically inert heterochromatin. Accumulation of further mutations, deletions, and duplications followed by the evolution and expansion of tandem repetitive sequence motifs of high copy number (satellite sequences) together with a few vital genes for male fertility will then represent the final state of the degenerated Y chromosome.
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  • 67
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    Journal of bioenergetics and biomembranes 32 (2000), S. 227-236 
    ISSN: 1573-6881
    Keywords: NDP kinase ; subunit interaction ; quaternary structure ; evolution ; mixed oligomers ; Dictyostelium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Physics
    Notes: Abstract Nucleoside (NDP) diphosphate kinases are oligomeric enzymes. Most are hexameric, but somebacterial enzymes are tetrameric. Hexamers and tetramers are constructed by assemblingidentical dimers. The hexameric structure is important for protein stability, as demonstratedby studies with natural mutants (the Killer-of-prune mutant ofDrosophila NDP kinase andthe S120G mutant of the human NDP kinase A in neuroblastomas) and with mutants obtainedby site-directed mutagenesis. It is also essential for enzymic activity. The function of the tetrameric structure is unclear.
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  • 68
    ISSN: 1573-6849
    Keywords: evolution ; genome ; Gossypium ; polyploidization ; repetitive element ; retrotransposon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Retrotransposons constitute a ubiquitous and dynamic component of plant genomes. Intragenomic and intergenomic comparisons of related genomes offer potential insights into retrotransposon behavior and genomic effects. Here, we have used fluorescent in-situ hybridization to determine the chromosomal distributions of a Ty1-copia-like retrotransposon in the cotton AD-genome tetraploid Gossypium hirsutum and closely related putative A- and D-genome diploid ancestors. Retrotransposon clone A108 hybridized to all G. hirsutum chromosomes, approximately equal in intensity in the A- and D-subgenomes. Similar results were obtained by hybridization of A108 to the A-genome diploid G. arboreum, whereas no signal was detected on chromosomes of the D-genome diploid G. raimondii. The significance and potential causes of these observations are discussed.
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  • 69
    ISSN: 1573-7217
    Keywords: cerbB2 ; chemotherapy ; neoadjuvant ; prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent advances in the detection and treatment of breast cancer have led to an intensive search for new markers of both prognosis and chemoresponsiveness. The oncogene cerbB2 has proved to be one of the most promising markers currently under study, both as a predictor of chemoresponsiveness and as a marker of poor prognosis. In addition the increasing use of neoadjuvant chemotherapy has led to the loss of standard prognostic criteria. In order to study the potential role of cerbB2 expression as an indicator of chemoendocrine resistance and poor prognosis, both before and after chemotherapy, we obtained tumour sections from 283 women enrolled onto a neoadjuvant trial. In this trial patients were randomised to receive either primary surgery followed by adjuvant chemoendocrine treatment or neoadjuvant chemoendocrine therapy followed by surgery. CerbB2 status was determined immunohistochemically on all of these patients. Thirty-eight percent of the tumours were cerbB2 positive. There was no significant difference in expression between the adjuvant (41%) and neoadjuvant arms (35%). CerbB2 positive patients were much more likely to have shown non-response to chemoendocrine therapy (p〈0.001) and had a worse DES (p〈0.05). The best prognosis was seen in cerbB2 negative patients receiving neoadjuvant chemoendocrine therapy who showed a significantly better DFS (p〈0.05), than the cerbB2 negative patients receiving adjuvant therapy.
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  • 70
    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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  • 71
    ISSN: 1573-7217
    Keywords: breast cancer ; locally advanced ; neoadjuvant ; chemotherapy ; paclitaxel ; cisplatin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background.In an earlier study, we have demonstrated a high response rate in metastatic breast cancer using paclitaxel (P) and cisplatin (C). A phase II study using the same regimen (PC) has been conducted in locally advanced breast cancer (LABC). Methods.A total of 72 consecutive patients with non-inflammatory LABC (T2 ≥ 4 cm, T3 or T4, N0–N2, M0). Patients were scheduled to receive 3–4 cycles of the neoadjuvant PC (paclitaxel 135 mg/m2 and cisplatin 75 mg/m2 on day 1) every 21 days. Patients were then subjected to surgery and subsequently received 6 cycles of FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2) or 4 cycles of AC (doxorubicin 60 mg/m2, and cyclophosphamide 600 mg/m2). Patients then received radiation therapy, and those with hormone receptor positive tumors were given adjuvant tamoxifen intended for 5 years. Results.The median age was 39 years (range, 24–78). Clinically, 7%, 58%, and 35% of patients had T2 ≥ 4 cm, T3, and T4, respectively. Disease stage at diagnosis was IIB (33%), IIIA (27%), and IIIB (40%). Complete and partial clinical response to PC was demonstrated in 13 (18%), and 52 (72%) patients, respectively. Of those patients with evaluable pathologic response (68 patients), complete pathologic response (pCR) was achieved in 15 (22%) patients. At a median follow-up of 22 (± 3.5) months, 58 (81%) were alive with no recurrence, nine (12%) were alive with evidence of disease, and five (7%) were dead. None of the patients achieving pCR has developed any relapse. The median overall survival has not been reached for all 72 patients with a projected 3-year survival (± SE) of 90% (± 4%). The median progression-free survival (PFS) was 42.1 (± 4.8) months with a projected PFS of 74% ± 7% at 3-years (for 68 patients). Conclusions.PC regimen in LABC produced a high pCR. The contribution of the other added modalities to survival could not be assessed.
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  • 72
    ISSN: 1573-7217
    Keywords: adjuvant treatment ; breast cancer ; chemotherapy ; immunotherapy ; radiotherapy ; randomized trial
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract With a median follow-up of 14 years, the combination of polyadenylic–polyuridylic acid plus locoregional radiotherapy (257 patients) has significantly improved disease-free survival (p = 0.03) and significantly reduced the incidence of metastases (p = 0.04) when compared to CMF alone (260 patients), in women with operable breast cancer. The trial does not, however, permit an appreciation of the respective role of radiotherapy and PolyAU in these results.
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  • 73
    ISSN: 1573-7225
    Keywords: breast neoplasms ; chemotherapy ; female ; hormonal therapy ; invasive carcinoma ; multiple primary neoplasms ; radiation therapy ; thyroid neoplasms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:Breast and thyroid cancer have been observed to occur more frequently than expected as multiple primary tumors in women. The study presented herein focuses on the effects of age at diagnosis and treatment for the first cancer on the development of the second cancer. Methods:This retrospective cohort study used a study population consisting of 38,632 women diagnosed with primary invasive breast cancer and 2189 women diagnosed with primary invasive thyroid cancer between 1974 and 1994. Cases were identified from records of the Cancer Surveillance System of western Washington and followed for subsequent cancer development through 1995. Results:Seventy-one women were diagnosed during their lives with both breast and thyroid cancers. Including cancers diagnosed during the same month as or after the initial cancer, the relative risk (RR) of breast cancer among women with thyroid cancer was 1.5 (95% confidence interval [CI] 1.1–2.0), and the RR of thyroid cancer among women with breast cancer was 1.5 (95% CI 1.1–2.2). Among women with thyroid cancer, risk of breast cancer was greatest when the latter cancer was diagnosed under 45 years of age (RR = 2.3, 95% CI 1.1–4.4). First course of treatment, including radiation or hormonal therapy to treat thyroid cancer, and radiation, chemotherapy, or hormonal therapy to treat breast cancer, did not alter a woman's risk of developing the second cancer. Conclusions:The data suggest that the incidence of breast and thyroid cancer may be related, and that in particular women with thyroid cancer may be at a moderately increased risk of developing breast cancer before age 45.
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  • 74
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    Evolutionary ecology 14 (2000), S. 665-692 
    ISSN: 1573-8477
    Keywords: disease ; evolution ; frequency-dependent selection ; genetic diversity ; life history ; lifespan ; polymorphism ; reproduction rate ; resistance ; specificity ; virulence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Pathogens and parasites can be strong agents of selection, and often exhibit some degree of genetic specificity for individual host strains. Here we show that this host–pathogen specificity can affect the evolution of host life history traits. All else equal, evolution should select for genes that increase individuals' reproduction rates or lifespans (and thus total reproduction per individual). Using a simple host–pathogen model, we show that when the genetic specificity of pathogen infection is low, host strains with higher reproduction rates or longer lifespans drive slower-reproducing or shorter-lived host strains to extinction, as one would expect. However, when pathogens exhibit specificity for host strains with different life history traits, the evolutionary advantages of these traits can be greatly diminished by pathogen-mediated selection. Given sufficient host–pathogen specificity, pathogen-mediated selection can maintain polymorphism in host traits that are correlated with pathogen resistance traits, despite large intrinsic fitness differences among host strains. These results have two important implications. First, selection on host life history traits will be weaker than expected, whenever host fitness is significantly affected by genotype-specific pathogen attack. Second, where polymorphism in host traits is maintained by pathogen-mediated selection, preserving the genetic diversity of host species may require preserving their pathogens as well.
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  • 75
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    Evolutionary ecology 14 (2000), S. 25-38 
    ISSN: 1573-8477
    Keywords: animal coloration ; body temperature ; ectotherm ; evolution ; Orthoptera ; poly-morphism ; Tetrix subulata ; thermoregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Ectothermic animals rely on external heat sources and behavioral thermoregulation to control body temperature, and are characterized by possessing physiological and behavioural traits which are temperature dependent. It has therefore been suggested that constraints on the range of body temperatures available to individuals imposed by phenotypic properties, such as coloration, may translate into differential fitness and selection against thermally inferior phenotypes. In this paper, I report an association between thermal preferences and thermal capacity (the ability to warm up when insolated) across different genetically coded color morphs of the pygmy grasshopper Tetrix subulata. Data on behavioral thermoregulation of individuals in a laboratory thermal gradient revealed a preference for higher body temperatures in females than in males, and significant variation among colour morphs in preferred body temperatures in females, but not in males. The variation in females was in perfect accordance with estimates of morph-specific differences in thermal capacity. Thus, dark morphs not only attain higher temperatures when exposed to augmented illumination, but also prefer higher body temperatures, compared to paler morphs. This intra-population divergence probably reflects an underlying variation among colour morphs in temperature optima, and is consistent with the notion that coloration, behaviour and physiology evolve in concert.
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  • 76
    ISSN: 1572-9028
    Keywords: rutile supported V2O5–WO3 catalyst ; evolution ; NO reduction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This paper concerns the relation between surface structure of crystalline vanadia-like active species on vanadia–tungsta catalyst and their activity in the selective reduction of NO by ammonia to nitrogen. The investigations were performed for Ti–Sn-rutile-supported isopropoxy-derived catalyst. The SCR activity and surface species structure were determined for the freshly prepared catalyst, for the catalyst previously used in NO reduction by ammonia (320 ppm NO, 335 ppm NH3 and 2.35 vol% O2) at 573 K as well as for the catalyst previously annealed at 573 K in helium stream containing 2.35 vol% O2. The crystalline islands, exposing main V2O5 surface, with some tungsten atoms substituted for V-ones, were found, with XPS and FT Raman spectroscopy, to be present at the surface of the freshly prepared catalyst. A profound evolution of the active species during the catalyst use at 573 K was observed. Dissociative water adsorption on V5+OW6+ sites is discussed as mainly responsible for the catalyst activity at 473 K and that on both V5+OW6+ and V4+OW6+ sites as determining the activity at 523 K.
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  • 77
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    Journal of chemical ecology 26 (2000), S. 1773-1794 
    ISSN: 1573-1561
    Keywords: Grasshoppers ; polyphagy ; graminivory ; evolution ; secondary compound ; peritrophic envelope ; midgut ceca ; learning
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Modern grasshoppers probably evolved from polyphagous ancestors endowed with the ability to tolerate many plant secondary compounds. This tolerance involves various behavioral and anatomical adaptations. Polyphagous grasshoppers have a relatively low level of sensitivity to the taste of many secondary compounds, and, if they do respond to the taste, have the capacity to habituate. This gives time for the induction of detoxifying enzymes so that unpalatable but potentially nutritious plants may be eaten safely. Associative learning involving secondary compounds may be important in food aversion learning, enabling the insects to avoid foods that have inappropriate nutrients, for example. Learning is also involved when grasshoppers develop associations between the taste of chemicals in the surface waxes of plants and internal leaf chemistry, enabling them to make faster decisions about the acceptability of a plant. Anatomically, the midgut ceca of polyphagous grasshoppers have well-developed posterior arms, and it is possible that these are especially important in detoxification, while some species, in addition, have a specialized pocket region in which macromolecules accumulate to be eliminated from the body when the lining of peritrophic envelope is drawn out. Polyphagous species also have thick peritrophic envelopes to which various phenolics become adsorbed. Finally, the midgut environment contains surfactants that reduce tannin–protein complexing except at very high tannin concentrations. Some polyphagous species can utilize secondary compounds as defensive substances or, in one case, in cuticular sclerotization. Grass feeding has evolved on numerous occasions from these polyphagous ancestors, and it has been associated with a loss of many of the characters providing protection from secondary compounds.
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  • 78
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    Origins of life and evolution of the biospheres 30 (2000), S. 459-466 
    ISSN: 1573-0875
    Keywords: biogenesis ; biological ; coevolution ; evolution ; models ; origin of life
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: Abstract What was the first living molecule – RNA or protein?This question embodies the major disagreement instudies on the origin of life. The fact that incontemporary cells RNA polymerase is a protein andpeptidyl transferase consists of RNA suggests theexistence of a mutual catalytic dependence betweenthese two kinds of biopolymers. I suggest that thisdependence is a `frozen accident', a remnant from thefirst living system. This system is proposed to be acombination of an RNA molecule capable of catalyzingamino acid polymerization and the resulting proteinfunctioning as an RNA-dependent RNA polymerase. Thespecificity of the protein synthesis is thought to beachieved by the composition of the surrounding mediumand the specificity of the RNA synthesis – by Watson– Crick base pairing. Despite its apparent simplicity,the system possesses a great potential to evolve intoa primitive ribosome and further to life, as it isseen today. This model provides a possible explanationfor the origin of the interaction between nucleicacids and protein. Based on the suggested system, Ipropose a new definition of life as a system ofnucleic acid and protein polymerases with a constantsupply of monomers, energy and protection.
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  • 79
    ISSN: 1573-5028
    Keywords: evolution ; C4 plant ; maize ; ribulose-bisphosphate carboxylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The small subunit of ribulose-bisphosphate carboxylase (Rubisco), encoded by rbcS, is essential for photosynthesis in both C3 and C4 plants, even though the cell specificity of rbcS expression is different between C3 and C4 plants. The C3 rbcS is specifically expressed in mesophyll cells, while the C4 rbcS is expressed in bundle sheath cells, and not mesophyll cells. Two chimeric genes were constructed consisting of the structural gene encoding β-glucuronidase (GUS) controlled by the two promoters from maize (C4) and rice (C3) rbcS genes. These constructs were introduced into a C4 plant, maize. Both chimeric genes were specifically expressed in photosynthetic organs, such as leaf blade, but not in non-photosynthetic organs. The expressions of the genes were also regulated by light. However, the rice promoter drove the GUS activity mainly in mesophyll cells and relatively low in bundle sheath cells, while the maize rbcS promoter induced the activity specifically in bundle sheath cells. These results suggest that the rice promoter contains some cis-acting elements responding in an organ-pecific and light-inducible regulation manner in maize but does not contain element(s) for bundle sheath cell-specific expression, while the maize promoter does contain such element(s). Based on this result, we discuss the similarities and differences between the rice (C3) and maize (C4) rbcS promoter in terms of the evolution of the C4 photosynthetic gene.
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  • 80
    ISSN: 1573-5117
    Keywords: population genetics ; evolution ; allozymes ; DNA ; marine genetics ; Acanthaster planci
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The basic assumptions that widespread marine species should show little spatial variation in genetic structure, given their high potential for dispersal on ocean currents, is being questioned. This has taken some time because there are few studies of widespread marine species over oceanic scales, few data sets that have the high density of sampling required for the detection of fine population structure, and there is little incentive to look further if initial analyses suggest the expected result. The interpretation of the population genetic structure of crown-of-thorns starfish (Acanthaster planci) has been found to vary considerably depending on the sample set included in the analyses and on the method of analysis used. Scatter plots of genetic distance or θ, and spatial autocorrelation approaches gave markedly different results ranging from no structure to isolation by distance. Only visual examination of maps of patterns of variation in allele variation first detected that crown-of-thorns starfish occupy large regions with little between population differentiation, but between which there are markedly higher levels of differentiation. These findings highlight the care required in interpreting population structure, particularly where there are few sample points. Many marine species may have population structures where sharp genetic disjunctions, not associated with any obvious environmental boundaries, separate regions of relative genetic homogeneity. Such population structures are very different from those traditionally assumed and are not yet understood. Further advances in understanding the genetic structure of marine species will demand an iterative approach where a greater number of samples are collected over particular regions identified by earlier interpretations.
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  • 81
    ISSN: 1573-5117
    Keywords: cladocerans ; life history ; demography ; size structure ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Daphnia models for individual growth and population dynamics have been developed in the manner of models developed by Gurney, McCauley, Andersen and others. All or most of the earlier models were parameterized for Daphnia pulex; we have used the D. pulex model as a baseline model for other species of Daphnia such as magna, galeata and also Bosmina longirostris. Because of the lack of ample data for D. magna, D. galeata and B. longirostris, some of the physiological data had to be relied on the other species whose data were available and in some case calibrated. We were able to produce reasonable results for individual growth as well as population dynamics under the controlled laboratory conditions. Most of the results were compared with the available laboratory data for population as well as growth. All the simulations have been done under high and low food concentrations. The animals are assumed to be feeding on green algae (Chlamydomonas reinhardtti) under the laboratory conditions of 18–20°C. The continuous growth until the end of the life was observed in smaller B. longirostris, whereas rapid growth in the beginning and slower after the start of the reproduction was observed in Daphnia species. The smaller species matured earlier than larger species. B. longirostris population sustained better than Daphnia species in medium food concentrations.
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  • 82
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    Hydrobiologia 417 (2000), S. 91-99 
    ISSN: 1573-5117
    Keywords: evolution ; phylogeny ; larval characters ; morphology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The plesiomorphic mode of crustacean development is widely accepted to be via a larva called the nauplius. Extant taxa like the Cephalocarida, Branchiopoda, Ostracoda, Mystacocarida, Copepoda, Cirripedia, Ascothoracida, Facetotecta, Euphausiacea and Penaeidea hatch from an egg as a free-living nauplius. Other crustaceans show an embryonic phase of development suggestive of a naupliar organization. Several features of the nauplius larva have been proposed as diagnostic characters for the Crustacea: a median (nauplius) eye; at least three pairs of head appendages (antennules, antennae, mandibles); a posteriorly directed fold (the labrum) extending over the mouth and a cephalic (nauplius) shield. The relationship between trilobite protaspis with at least four appendages and the crustacean nauplius remains unclear, but reports of a copepod orthonauplius with four appendages are rejected. Swimming is suggested to represent the underived mode of locomotion for the crustacean nauplius, and that naupliar swimming directly results in naupliar feeding which also is underived.
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  • 83
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    Hydrobiologia 420 (2000), S. 55-62 
    ISSN: 1573-5117
    Keywords: chromosomes ; evolution ; nucleolar organizer region
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The number of cytogenetic studies of marine fish has increased in recent years. Fish groups, such as Perciformes, which comprises many of the extant marine teleosts of economic importance, show little divergence in chromosome number and most species display a diploid number of 48 acrocentric chromosomes. In the Serranidae, Sparidae, Sciaenidae (Perciformes) and Mugilidae (Mugiliformes) small chromosome variations are restricted to subtle heterochromatin or nucleolar organizer region (NOR) modifications. There appears to exist a strict relationship between both absence of geographic barriers throughout the marine environment and high mobility of these animals (eggs, larvae, or adults), with a rarity of chromosome rearrangement at the macrostructural level. Moreover, a cellular homeostasis might also be important to karyotype maintenance among these fishes, limiting changes in the chromosome complement to cryptic chromosome rearrangements. Other groups, such as Blenniidae, Gobiidae and Scorpaenidae, for instance, show more extensive chromosome diversity, which is probably related to limited mobility. Numerical and structural chromosome polymorphisms and several sexual chromosome systems are recurrent among these fishes. A wide karyotypic diversification also characterizes the Tetraodontiformes, an interesting fish group with peculiar morphological, physiological and ecological characteristics.
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  • 84
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    Hydrobiologia 420 (2000), S. 15-27 
    ISSN: 1573-5117
    Keywords: phylogeny ; evolution ; allozymes ; rDNA ; DNA sequence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The first application of molecular systematics to sponges was in the 1980s, using allozyme divergence to dis-criminate between conspecific and congeneric sponge populations. Since this time, a fairly large database has been accumulated and, although the first findings seemed to indicate that sponge species were genetically more divergent than those of other marine invertebrates, a recent review of the available dataset indicates that levels of interspecific gene identities in most sponges fall within the normal range found between species of other invertebrates. Nevertheless, some sponge genera have species that are extremely divergent from each other, suggesting a possible polyphyly of these genera. In the 1990s, molecular studies comparing sequences of ribosomal RNA have been used to reappraise the phylogenetic relationships among sponge genera, families, orders and classes. Both the 18S small subunit and the 28S large subunit rRNA genes have been sequenced (41 complete or partial and 75 partial sequences, respectively). Sequences of 18S rRNA show good support for Porifera being true Metazoa, but they are not informative for resolving relationships among genera, families or orders. 28S rRNA domains D1 and D2 appear to be more informative for the terminal nodes and provide resolution for internal topologies in sufficiently closely related species, but the deep nodes between orders or classes cannot be resolved using this molecule. Recently, a more conserved gene, Hsp70, has been used to try to resolve the relationships in the deep nodes. Metazoan monophyly is very well supported. Nevertheless, the divergence between the three classes of Porifera, as well as the divergence between Porifera, Cnidaria and Ctenophora, is not resolved. Research is in progress using other genes such as those of the homeodomain, the tyrosine kinase domain, and those coding for the aggregation factor. For the moment the dataset for these genes is too restricted to resolve the phylogenetic relationships of these phyla. However, whichever the genes, the phylogenies obtained suggest that Porifera could be paraphyletic and that the phylogenetic relationships of most of the families and orders of the Demospongiae have to be reassessed. The Calcarea and Hexactinellida are still to be studied at the molecular level.
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  • 85
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    Environmental biology of fishes 57 (2000), S. 443-449 
    ISSN: 1573-5133
    Keywords: parental care ; feeding behaviour ; evolution ; trade-off ; individual differences ; fish
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The function of the fin digging behaviour in increasing food availability for the offspring was analysed in the convict cichlid, Cichlasoma (Archocentrus) nigrofasciatum. Consistent individual differences in the frequency of fin digging were found in the parental fish. Examination of the gastrointestinal tract of young revealed that higher frequency of parental fin digging was associated with higher consumption of large and more profitable prey (Diptera larvae), which inhabited deep horizons of the bottom substrate and possibly were difficult to access without parental assistance. Thus, parental fin digging was initially associated with a significant increase of the offspring growth rate. However, at later brood intervals, when parental care ceased, the young of the high-digging parents were characterised by a poorer consumption of small larvae that were most accessible for them without parental aid and represented an increasingly more important component of their ration than large larvae. Offspring of the low-digging parents, on the other hand, presumably as a result of their individual experience, showed a considerably better consumption of small larvae, increasing their growth rate. As a consequence, prior parental fin digging did not affect the offspring body size after independence. Thus, there exist pronounced individual differences and alternative parental styles in the convict cichlid.
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  • 86
    ISSN: 1573-5133
    Keywords: Cyprinidae ; piscivores ; prey fish ; small barbs ; species flock ; evolution ; speciation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The endemic cyprinid species flock in Lake Tana consists of 15 species of large hexaploid barbs, eight of which are piscivorous. Previously, it was assumed that all piscivores preyed on the same small barb species, Barbus trispilopleura. In this paper we present a description of morphology and ecology of a new abundant small barb species, Barbus tanapelagius sp. nova (holotype RMNH 33731) from Lake Tana, Ethiopia, which appears to be the major prey species for the large pelagic piscivorous barbs. B. tanapelagius differs clearly in morphology from the other 3 small, diploid Barbus species known from Lake Tana, B. trispilopleura Boulenger, 1902, B. humilis Boulenger, 1902 and B. pleurogramma Boulenger, 1902. Conspicuous differences are its elongated body, large eye diameter, prominent and hooked lower jaw contour and colouration. Preliminary data suggest that B. tanapelagius also differs ecologically from the other small Barbus spp. by its pelagic, strictly zooplanktivorous feeding and its occurrence mainly in the deeper, offshore waters. The other small Barbus species are most probably largely benthic feeders and dominant in the shallow inshore waters. Previous views about the evolution of the present 8 endemic piscivorous large barb species therefore require reconsideration, as the present paper shows a more complex scenario including several prey species.
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  • 87
    ISSN: 1573-5109
    Keywords: evolution ; genetic resources ; RAPDs ; seed protein electrophoresis ; taxonomy ; Vicia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract The genetic diversity of 58 wild and weedy populations representing taxa within the V. sativa aggregate from the former USSR, 4 cultivars of V. sativa, 2 accessions of V. cordata and 3 accessions of V. macrocarpa from Mediterranean countries were analysed using randomly amplified DNA fragments (RAPDs) and seed protein electrophoresis (SDS-PAGE). Interspecific variation between taxa in the V. sativa aggregate could readily be detected using both techniques. RAPDs and seed protein patterns were found to be an effective means of identifying accessions that cannot be identified clearly by morphological criteria alone. RAPD and seed protein analysis revealed a clear relationship between observed genetic variation of populations and their geographical distribution. Populations from each region had their own gene pools. Geographical variation was detected in V. segetalis. The degree of genetic divergence between local populations was usually related to proximity. In several locations where wild and weedy populations of different V. sativa agg. taxa grow sympatrically, intermediate forms could be detected at the DNA and protein levels. Both RAPD and seed protein analysis support the view that the V. sativa aggregate consists of 8 taxa warranting recognition at the species level. Several species in this aggregate are evolving intra-specific groups which can readily be detected at the molecular level.
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  • 88
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    Genetic resources and crop evolution 47 (2000), S. 385-393 
    ISSN: 1573-5109
    Keywords: Citrullus lanatus ; cluster analysis ; evolution ; morphology ; watermelon
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Morphological data recorded from field trials using Citrullus lanatus germplasm collected in Namibia were used to analyse and compare the various morphotypes of this species. The experiment comprised wild types and local landraces as well as commercial cultivars. Cluster analysis supported the indigenous classification system used in Namibia, in which Citrullus types are distinguished based on gross morphology, ecology and usage and grouped into seed, cooking and fresh-eating (watermelon) types. Commercial watermelon cultivars formed a distinct cluster. Wide variation was found within the local types whereas the genetic basis of the commercial type appears to be narrow. The commercial cultivars were most closely related to local watermelon types and more distantly related to the wild types, whereas the cooking melons form an intermediate group.
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  • 89
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    Hydrobiologia 419 (2000), S. 7-11 
    ISSN: 1573-5117
    Keywords: morphology ; palaeontology ; ecology ; genetics ; Ostracoda ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Morphology, palaeontology, genetics and ecology are the main scientific domains contributing theories, concepts and new data to evolutionary biology. Ostracods are potentially very good model organisms for evolutionary studies because they combine an excellent fossil record with a wide extant distribution and, therefore, allow studies on both patterns and processes leading to extant diversity. This preface provides an overview of the 15 contributions to the present volume and concludes that this set of papers supports the claim that ostracod studies are situated in all main evolutionary domains.
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  • 90
    ISSN: 1573-5117
    Keywords: reflecting organ ; upper lip ; Myodocopa ; chemical cues ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Multifunctions of the upper lip in a bioluminescent myodocopid Vargula hilgendorfii were studied by video observation and histological method. The localization of luciferin and luciferase gland cells within the upper lip was partly successful. Two long protrusions of the upper lip, both of V. hilgendorfii and a non-luminescent species of the same family, immediately anterior to the mouth, were found to show very flexible movement especially while eating, as if smearing on the food surface a secretion from the protrusions (glands), which may support the hypothesized secretion of digestive enzymes from the upper lip. This hypothesis is further supported by the new finding of a pair of ducts which connect the basal part of the upper lip with the posterior digestive duct (stomach). Comparative studies of V. hilgendorfii with several sympatric non-luminescent species of the same family have also revealed that it has a characteristic reflecting organ immediately posterior to the anus. It is a conical small protrusion, as if dangling from the ventral edge of the abdomen at the apex of the cone. It is observable only in live specimens, when the furca, which is located outwardly to the organ, is sufficiently transparent. When illuminated, the reflecting organ reflects the distinct light. The diameter of the mirror (chemical composition provisionally analyzed) is about 6–8% of the carapace length. The organ develops from the very first stage of its ontogeny without reference to sex, which suggests that the function may be related to intraspecific signaling or predatory deterrence.
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  • 91
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    Hydrobiologia 419 (2000), S. 31-63 
    ISSN: 1573-5117
    Keywords: morphology ; ontogeny ; Ostracoda ; evolution ; fifth limb ; crustacean phylogeny
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The chaetotaxy (shape, structure and distribution of setae) of appendages and valve allometry during the post embryonic ontogeny of the cyprididine ostracod Eucypris virens are described. It is shown that the basic ontogenetic development of E. virens is very similar to that of other species of the family Cyprididae. During ontogeny, the chaetotaxy shows continual development on all podomeres of the limbs with the exception of the last podomere on the antennulae. The long setae on the exopodite and protopodite of the antennae have a natatory function until the actual natatory setae develop in later instars. Aesthetascs (presumed chemoreceptors) ya and y3 are the first to develop and may have an important function in the first instars. Cyprididae require a pediform limb in the posterior of the body presumably to help them to attach to substrates and this is reflected by the pediform nature of one limb at all times throughout all instars. This study has also shown that the fifth limb is most probably of thoracic origin and hence ostracods have only one pair of maxillae.
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  • 92
    ISSN: 1573-5079
    Keywords: chlorophyll a ; Chl a-binding protein ; evolution ; light-harvesting complex ; LHC I ; Porphyridium cruentum ; reconstitution ; red alga ; zeaxanthin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The Porphyridium cruentum light harvesting complex (LHC) binds Chl a, zeaxanthin and β-carotene and comprises at least 6 polypeptides of a multigene family. We describe the first in vitro reconstitution of a red algal light-harvesting protein (LHCaR1) with Chl a/carotenoid extracts from P. cruentum. The reconstituted pigment complex (rLHCaR1) is spectrally similar to the native LHC I, with an absorption maximum at 670 nm, a 77 K fluorescence emission peak at 677 nm (ex. 440 nm), and similar circular dichroism spectra. Molar ratios of 4.0 zeaxanthin, 0.3 β-carotene and 8.2 Chl a per polypeptide for rLHCaR1 are similar to those of the native LHC I complex (3.1 zeaxanthin, 0.5 β-carotene, 8.5 Chl a). The binding of 8 Chl a molecules per apoprotein is consistent with 8 putative Chl-binding sites in the predicted transmembrane helices of LHCaR1. Two of the putative Chl a binding sites (helix 2) in LHCaR1 were assigned to Chl b in Chl a/b-binding (CAB) LHC II [Kühlbrandt et al. (1994) Nature 367: 614–21]. This suggests either that discrimination for binding of Chl a or Chl b is not very specific at these sites or that specificity of binding sites evolved separately in CAB proteins. LHCaR1 can be reconstituted with varying ratios of carotenoids, consistent with our previous observation that the carotenoid to Chl ratio is substantially higher in P. cruentum grown under high irradiance. Also notable is that zeaxanthin does not act as an accessory light-harvesting pigment, even though it is highly likely that it occupies the position assigned to lutein in the CAB LHCs.
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  • 93
    ISSN: 1573-5079
    Keywords: anatomy ; C3 and C4 photosynthesis ; Chenopodiaceae ; cotyledon ; deserts ; evolution ; leaf ; Salsola
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Most species of the genus Salsola (Chenopodiaceae) that have been examined exhibit C4 photosynthesis in leaves. Four Salsola species from Central Asia were investigated in this study to determine the structural and functional relationships in photosynthesis of cotyledons compared to leaves, using anatomical (Kranz versus non-Kranz anatomy, chloroplast ultrastructure) and biochemical (activities of photosynthetic enzymes of the C3 and C4 pathways, 14C labeling of primary photosynthesis products and 13C/12C carbon isotope fractionation) criteria. The species included S. paulsenii from section Salsola, S. richteri from section Coccosalsola, S. laricina from section Caroxylon, and S. gemmascens from section Malpigipila. The results show that all four species have a C4 type of photosynthesis in leaves with a Salsoloid type Kranz anatomy, whereas both C3 and C4 types of photosynthesis were found in cotyledons. S. paulsenii and S. richteri have NADP- (NADP-ME) C4 type biochemistry with Salsoloid Kranz anatomy in both leaves and cotyledons. In S. laricina, both cotyledons and leaves have NAD-malic enzyme (NAD-ME) C4 type photosynthesis; however, while the leaves have Salsoloid type Kranz anatomy, cotyledons have Atriplicoid type Kranz anatomy. In S. gemmascens, cotyledons exhibit C3 type photosynthesis, while leaves perform NAD-ME type photosynthesis. Since the four species studied belong to different Salsola sections, this suggests that differences in photosynthetic types of leaves and cotyledons may be used as a basis or studies of the origin and evolution of C4 photosynthesis in the family Chenopodiaceae.
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  • 94
    ISSN: 1573-5036
    Keywords: evolution ; glutamine synthetase ; sequences ; subunit composition ; Trientalis europaea
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Ion-exchange chromatography of extracts from Trientalis europaea L. leaf tissue have been shown to contain two distinct isoforms of glutamine synthetase (GS). However, analysis by Western blotting has shown that the first peak to elute contains a mixture of large and small GS subunits, whilst the second peak is comprised entirely of a smaller subunit. This is contrary to the widespread assumptions concerning plant GS biochemistry. Isolation of intact chloroplasts and subsequent extraction of GS, followed by ion-exchange chromatography, has shown that the first peak to elute contains a large subunit, and the second chloroplastic peak is composed entirely of the small subunit. This smaller subunit may be present due to it being encoded by a separate chloroplastic GS gene, or it may be present as a product of post-translational modification. DNA sequencing has been used to try and determine which of these may be occurring. The three partial DNA sequences (505 nucleotides) we have obtained from T. europaea have been compared with 64 other sequences available on the NCBI database, which have mainly been obtained from crop species. Neighbour joining and parsimony analysis (1000 bootstrap) has shown support (∼30%) for the separation of plant GS from all other phyla. Within the plant phylum, there is total support for the separation of chloroplastic and cytosolic GS (100%), whilst the cytosolic sequences divide further into monocot and dicot species (77% support by NJ). Further subgroups of plants from the same families is also suggested. This is consistent with previous work containing fewer, but longer (∼1000 nucleotides) GS sequences. The addition of GS sequences obtained from wild plant species, such as T. europaea, to the large amount of information already available on the database, will permit a better understanding of the evolution of this important enzyme.
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  • 95
    ISSN: 1573-4927
    Keywords: ancient endogenous provirus ; evolution ; retrotransposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract A new family of murine endogenous proviruses (VL6.0) is described here. The intact provirus is near 6 kb in length and shows a genomic organization of 5" LTR, gag, pol, env, and 3" LTR. The primer binding site (PBS) is that of a tRNAgly. The lack of functional open reading frames and occurrence of significant gaps in most, if not all, members of this group show it to be ancient. Our estimate of copy number per haploid genome is 30+. Members of this group have been isolated from Mus musculus domesticus, M. m. casteneus, M. m. hortulanus, M. caroli, and M. spretus. The occurrence of these sequences throughout such diverse members of the genus Mus may indicate that the date of the original infection predated the divergence of the extant Mus lineages at around 2.5 million years ago. Analysis of gap (deletion/insertion) patterns indicates that these sequences may have proliferated within the Mus genome by a mechanism of reverse transcriptase-mediated transposition. As yet, there are no closely related murine retroviruses described. The closest mammalian retrovirus based on sequence similarity is from the miniature swine (Sus scrofa).
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    Journal of the Gay and Lesbian Medical Association 4 (2000), S. 19-29 
    ISSN: 1573-3637
    Keywords: sexual orientation ; homosexuality ; instinct ; intelligence ; evolution
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There exists an unfounded and unproven ‘common sense’ belief that human beings possess the innate mechanistic urge to reproduce clearly evident in the behavior of all other sexually reproducing animals. As such, the heterosexual component of human behavior is by and large viewed as being genetic, whereas it is homosexuality that is primarily the focus of scientific investigations into human sexual orientation. A historical review of homosexuality in diverse cultures reveals that significantly many cultures have existed where (male) bisexuality has been rather universal and that all cultures have condemned exclusive homosexuality, either legally or with the threat of social rejection. Neither of these facts can be rationalized using the ballpark ‘10%’ statistic for homosexuality believed to be representative of human beings. This paper will attempt to provide a general underlying explanation for human sexuality as a whole. It will be argued that the varied forms of human sexual expression may be explained to some extent with the view that by virtue of their supreme intelligence, human beings do not possess an instinct to engage in heterosexual intercourse, human sexual orientation is fully determined by environment alone, and that due to rather universal childhood behavioral tendencies, human beings have a bias for acquiring a homosexual orientation over a heterosexual one or a bisexual one. Controlling this dominant homosexual tendency has always been a basic requirement for the propagation of societies.
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    Journal of the Gay and Lesbian Medical Association 4 (2000), S. 57-83 
    ISSN: 1573-3637
    Keywords: intelligence ; instinct ; evolution ; sexual orientation ; homosexuality
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intelligence is of greater species survival value than instincts over long evolutionary periods. Sufficient increases in the intelligence of a species cause natural selection to favor a corresponding decrease in the species' instinctive makeup. The human line uniquely crossed a threshold of intelligence during evolution that allowed humans to lose their sexual instinct. Devoid of a sexual instinct, human sexual orientation is fully a function of individual experience. Exploratory behaviors that infants innately display involving their own body have the greatest potential to bias the formation of a homosexual orientation. To survive, societies have always had to counter this natural developmental pathway with a social environment that has encouraged heterosexuality and to varying extents restricted the expression of homosexuality.
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    Archives of sexual behavior 29 (2000), S. 1-34 
    ISSN: 1573-2800
    Keywords: homosexuality ; birth order ; evolution ; genetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract The survival of a human predisposition for homosexuality can be explained by sexual orientation being a polygenetic trait that is influenced by a number of genes. During development these shift male brain development in the female direction. Inheritance of several such alleles produces homosexuality. Single alleles make for greater sensitivity, empathy, tendermindedness, and kindness. These traits make heterosexual carriers of the genes better fathers and more attractive mates. There is a balanced polymorphism in which the feminizing effect of these alleles in heterosexuals offsets the adverse effects. (on reproductive success) of these alleles' contribution to homosexuality. A similar effect probably occurs for genes that can produce lesbianism in females. The whole system survives because it serves to provide a high degree of variability among the personalities of offspring, providing the genotype with diversification and reducing competition among offspring for the same niches. An allele with a large effect can survive in these circumstances in males, but it is less likely to survive in females. The birth order effect on homosexuality is probably a by-product of a biological mechanism that shifts personalities more in the feminine direction in the later born sons, reducing the probability of these sons engaging in unproductive competition with each other.
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    Archives of sexual behavior 29 (2000), S. 35-66 
    ISSN: 1573-2800
    Keywords: evolution ; sex differences ; language ; visual spatial skills ; Homo erectus ; Cro-Magnon ; inferior parietal lobe ; Broca's area
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Psychology
    Notes: Abstract The evolutionary neurological and physical foundations for human sex differences in language, sexuality, and visual spatial skills are detailed and primate and human studies are reviewed. Trends in the division of labor were established early in evolution and became amplified with the emergence of the “big brained” Homo erectus. A bigger brain necessitated a size increase in the birth canal and female pelvis. These and other physical changes, e.g., the swelling of the breasts and buttocks, may have paralleled the evolution of full-time sexual receptivity, the establishment of the home base, and exaggerated sex differences in the division of labor (hunting vs. gathering), which in turn promoted innate sex differences in visual spatial vs. language skills. For example, female primates produce more social and emotional vocalizations and engage in more tool use and gathering activities, whereas males tend to hunt and kill. Similar labor divisions are evident over the course of human evolution. “Woman's work” such as child rearing, gathering, and domestic tool construction and manipulation contributed to the functional evolution of Broca's speech area and the angular gyrus—which injects temporal sequences and complex concepts into the stream of language and thought. These activities gave rise, therefore, to a female superiority in grammatical (temporal sequential) vocabulary-rich language. Hunting as a way of life does not require speech but requires excellent visual–spatial skills and, thus, contributed to a male visual–spatial superiority and sex difference in the brain. Over the course of evolution males acquired modern human speech through genetic inheritance and because they had mothers who taught them language.
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    The environmentalist 20 (2000), S. 257-271 
    ISSN: 1573-2991
    Keywords: evolution ; tides ; sea level ; time series
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract The increasing use of computers since the 1960s, has implied the digitization of observations in meteorology, oceanography and other observational sciences. Enough data has been accumulated to suggest that some patterns of evolution in the world may be discernable. The present article deals with what appears as changing tides around Canada.
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