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  • American Society of Hematology  (5)
  • Geological Society of London  (4)
  • American Association for the Advancement of Science (AAAS)  (3)
  • Amsterdam : Elsevier  (1)
  • Blackwell Science Ltd  (1)
  • American Institute of Physics (AIP)
  • 2000-2004  (14)
  • 2004  (14)
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  • 2000-2004  (14)
Year
  • 1
    Call number: ILP/M 06.0353
    In: Publication of the International Lithosphere Programme
    In: Tectonophysics
    Type of Medium: Monograph available for loan
    Pages: vi, 271 S. : Ill., graph. Darst.
    Series Statement: [Publication of the International Lithosphere Programme] 381,1-4 : special issue
    Language: English
    Location: Reading room
    Branch Library: GFZ Library
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  • 2
    Publication Date: 2004-11-16
    Description: Postmenopausal women have an increased risk of cardiovascular disease, and heart disease is the leading cause of death in postmenopausal American women. Conventional hormone replacement therapy has been shown to result in an increase in thrombotic events in large prospective clinical trials including HERS I, and the recently halted Women’s Health Initiative. One possible mechanism for this observed increase is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory factors. An estimated 50 million American women are peri or postmenopausal and clinical therapies for menopausal symptoms remain a significant challenge in light of the known thrombotic risks. In this prospective blinded study, we examined the short-term effect of topical progesterone cream on menopausal symptom relief in 30 healthy postmenopausal women. Potential adverse effects of topical progesterone on hemostatic and inflammatory factors and cortisol levels were also examined. Subjects were randomized to first receive either 20 mg of topical progesterone cream or placebo cream for 4 weeks. Following a subsequent 4-week washout period, subjects were crossed over to either placebo cream or active drug for an additional 4-week period. In each case, progesterone and cortisol levels were monitored by salivary sampling. Baseline values, 4-week follow-up values and end-of-study values were also obtained for the Greene Climacteric Scale, total factor VII:C, factor VIIa, factor V, fibrinogen, antithrombin, PAI-1, CRP, TNFα, and IL-6. For subjects receiving 20 mg of topical progesterone cream for 4 weeks, Greene Climacteric Scale scores were consistently and significantly improved (decreased) over baseline, demonstrating significant relief from menopausal symptoms. In addition, in a subpopulation of hypercortisolemic women, topical progesterone was associated with a favorable decrease in nocturnal cortisol. Surprisingly, and in sharp contrast to earlier studies with conventional hormone replacement therapy, topical progesterone had no effect on any of the hemostatic components examined: total factor VII:C, factor VIIa, factor V, fibrinogen, antithrombin, and PAI-1 levels were all unchanged. Levels of CRP, TNFα and IL-6 also remained unchanged. From this study we conclude that administration of topical progesterone cream at a daily dose of 20 mg significantly relieves menopausal symptoms in postmenopausal women without adversely altering prothrombotic potential. Since the thrombotic complications that are typically observed with conventional hormone replacement therapy do not seem to occur with topical progesterone, this treatment should be seriously considered as an effective and safe alternative clinical therapy for women suffering from menopausal symptoms.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Weed research 44 (2004), S. 0 
    ISSN: 1365-3180
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Classical Mendelian experiments were conducted to determine the genetics and inheritance of quinclorac and acetolactate synthase (ALS)-inhibitor resistance in a biotype of Galium spurium. Plants were screened with the formulated product of either quinclorac or the ALS-inhibitor, thifensulfuron, at the field dose of 125 or 6 g active ingredient (a.i.) ha−1 respectively. Segregation in the F2 generation indicated that quinclorac resistance was a single, recessive nuclear trait, based on a 1 : 3 segregation ratio [resistant : susceptible (R : S)]. Resistance to ALS inhibitors was due to a single, dominant nuclear trait, segregating in the F2 generation in a 3 : 1 ratio (R : S). The genetic models were confirmed by herbicide screens of F1 and backcrosses between the F1 and the S parent. F2 plants that survived quinclorac treatment set seed and the resulting F3 progeny were screened with either herbicide. Quinclorac-treated F3 plants segregated in a 1 : 0 ratio (R : S), hence F2 progenitors were homozygous for quinclorac resistance. In contrast, F3 progeny segregated into three ratios: 1 : 0, 3 : 1 and 0 : 1 (R : S) in response to ALS-inhibitor treatment. This segregation pattern indicates that their F2 parents were either homozygous or heterozygous for ALS-inhibitor resistance. Therefore, there were clearly two distinct resistance mechanisms encoded by two genes that were not tightly linked as demonstrated by segregation patterns of the F3.
    Type of Medium: Electronic Resource
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  • 4
    Publication Date: 2004-11-30
    Description: The widespread extinctions of large mammals at the end of the Pleistocene epoch have often been attributed to the depredations of humans; here we present genetic evidence that questions this assumption. We used ancient DNA and Bayesian techniques to reconstruct a detailed genetic history of bison throughout the late Pleistocene and Holocene epochs. Our analyses depict a large diverse population living throughout Beringia until around 37,000 years before the present, when the population's genetic diversity began to decline dramatically. The timing of this decline correlates with environmental changes associated with the onset of the last glacial cycle, whereas archaeological evidence does not support the presence of large populations of humans in Eastern Beringia until more than 15,000 years later.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shapiro, Beth -- Drummond, Alexei J -- Rambaut, Andrew -- Wilson, Michael C -- Matheus, Paul E -- Sher, Andrei V -- Pybus, Oliver G -- Gilbert, M Thomas P -- Barnes, Ian -- Binladen, Jonas -- Willerslev, Eske -- Hansen, Anders J -- Baryshnikov, Gennady F -- Burns, James A -- Davydov, Sergei -- Driver, Jonathan C -- Froese, Duane G -- Harington, C Richard -- Keddie, Grant -- Kosintsev, Pavel -- Kunz, Michael L -- Martin, Larry D -- Stephenson, Robert O -- Storer, John -- Tedford, Richard -- Zimov, Sergei -- Cooper, Alan -- New York, N.Y. -- Science. 2004 Nov 26;306(5701):1561-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Henry Wellcome Ancient Biomolecules Centre, Oxford University, South Parks Road, Oxford OX13PS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15567864" target="_blank"〉PubMed〈/a〉
    Keywords: Alaska ; Animals ; Bayes Theorem ; *Bison/classification/genetics ; Canada ; China ; *Climate ; DNA, Mitochondrial/genetics ; Environment ; *Fossils ; Genetic Variation ; Genetics, Population ; Human Activities ; Humans ; North America ; Phylogeny ; Population Dynamics ; Sequence Analysis, DNA ; Time
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2004-06-12
    Description: Understanding the suppression of ferroelectricity in perovskite thin films is a fundamental issue that has remained unresolved for decades. We report a synchrotron x-ray study of lead titanate as a function of temperature and film thickness for films as thin as a single unit cell. At room temperature, the ferroelectric phase is stable for thicknesses down to 3 unit cells (1.2 nanometers). Our results imply that no thickness limit is imposed on practical devices by an intrinsic ferroelectric size effect.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fong, Dillon D -- Stephenson, G Brian -- Streiffer, Stephen K -- Eastman, Jeffrey A -- Auciello, Orlando -- Fuoss, Paul H -- Thompson, Carol -- New York, N.Y. -- Science. 2004 Jun 11;304(5677):1650-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Materials Science Division, Argonne National Laboratory, Argonne, IL 60439, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15192223" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2004-08-25
    Description: Intracellular acidification of skeletal muscles is commonly thought to contribute to muscle fatigue. However, intracellular acidosis also acts to preserve muscle excitability when muscles become depolarized, which occurs with working muscles. Here, we show that this process may be mediated by decreased chloride permeability, which enables action potentials to still be propagated along the internal network of tubules in a muscle fiber (the T system) despite muscle depolarization. These results implicate chloride ion channels in muscle function and emphasize that intracellular acidosis of muscle has protective effects during muscle fatigue.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pedersen, Thomas H -- Nielsen, Ole B -- Lamb, Graham D -- Stephenson, D George -- New York, N.Y. -- Science. 2004 Aug 20;305(5687):1144-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, University of Aarhus, DK-8000, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15326352" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Calcium/metabolism ; Chloride Channels/*metabolism ; Chlorides/metabolism ; Electric Stimulation ; Hydrogen-Ion Concentration ; In Vitro Techniques ; Lactic Acid/metabolism ; Membrane Potentials ; Muscle Contraction ; *Muscle Fatigue ; Muscle Fibers, Skeletal/metabolism/*physiology ; Muscle, Skeletal/metabolism/*physiology ; Permeability ; Potassium/metabolism ; Rats ; Sarcoplasmic Reticulum/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2004-11-16
    Description: Background: Talabostat (PT-100), an orally available inhibitor of dipeptidyl peptidases, is in Phase 2 studies for B-cell malignancies and solid tumors. Talabostat increases production of cytokines and chemokines in lymph nodes and spleen, stimulating both adaptive and innate immune responses (Adams S, Cancer Research, 2004;64:5471). Talabostat may thus enhance the antibody-dependent cytotoxicity of MAbs such as rituximab. Methods: This is a Phase 1 study to evaluate the safety and activity of talabostat and rituximab in patients with indolent NHL who did not respond or progressed following rituximab. Rituximab 375mg/m2 was administered weekly x 4. Total daily doses of talabostat 400μg (n=6), 600μg (n=3), or 800μg (n=6) were administered BID for 6 days following each dose of rituximab. Cytokines and chemokines were assessed pre-, 2, and 6 hours post-talabostat on Days 1, 6, 13, 20, and 27. Flow cytometry was performed at baseline and Day 28. Clinical and laboratory evaluations were performed at specified times. Adverse events (AEs) were graded per NCI-CTC and recorded throughout the study. Disease assessments were performed on Days 28 and 84. Results: 11 men and 4 women aged 48–82 with NHL (n=10) or SLL/CLL (n=5) have been treated. 9 patients completed the 28-day study: 4 at 400μg, 1 at 600μg, and 4 at 800μg. Enrollment continues at 400μg/day. The most frequent AEs have been edema (67%), nausea (47%), dizziness (40%), hypotension (33%), fatigue (33%), vomiting (33%), constipation (33%), thrombocytopenia (27%), and weight gain (27%). Grade 3 toxicities include: dizziness, myopathy (400μg/day), and 2 events of thrombocytopenia (600μg/day). Grade 3 peripheral edema, myalgia, dehydration, electrolyte imbalance, hypereosinophilia, elevated CPK (primarily CK-MM), and rhabdomyolysis were seen in 2/6 patients at 800μg/day; these events were DLTs. One partial response (PR) lasting 7 months was seen in one patient (800μg/day). A PR was seen in a second patient at 800μg/day but did not meet the strict NCI-WG criteria for response. Elevations in cytokines 〉ULN were reported across all doses following talabostat: G-CSF (13/15), IL-1β (10/15), IL-2 (7/15), IL-6 (8/15), IL-8 (8/15), IL-10 (11/15), TNF-α (11/15), and IFN-γ (3/15). At Day 28 or early termination, CD20 was decreased in most (12/15) patients. Increases were seen in the percentage of CD3 (12/15), CD3/4 (11/15) and CD3/8 (9/15). In all 5 patients with SLL/CLL, CD5+/CD20+ was
    Print ISSN: 0006-4971
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  • 8
    Publication Date: 2004-11-16
    Description: Background: T cells can be activated and expanded ex vivo using the Xcellerate™ Process, in which peripheral blood mononuclear cells (PBMC) are incubated with anti-CD3 and anti-CD28 antibody-coated magnetic beads (Xcyte™-Dynabeads®). In an ongoing trial of Xcellerated T Cells in subjects with chronic lymphocytic leukemia, marked and sustained reductions in lymphadenopathy and splenomegaly were observed (Wierda et al., ASCO 2004). Increases in neutrophil, platelet and NK cell counts were also documented. This study is designed to determine if similar effects can be observed in subjects with indolent non-Hodgkin’s lymphoma (NHL). Methods: Subjects must have indolent NHL (follicular, small lymphocytic, marginal zone, or mantle cell lymphoma), have relapsed or refractory disease, and have received at least 1 but not more than 4 prior treatment regimens. PBMC are collected by leukapheresis for the Xcellerate Process, and subjects subsequently receive two infusions of 20–60 x 109 Xcellerated T Cells separated by 6–8 weeks. Approximately 40 subjects will be treated. Results: Seven subjects have been enrolled and Xcellerated T Cells have been manufactured in 5 subjects to date. T cells expanded 181.8 ± 88.5 fold and the final product was 〉99.0 ± 0.0% T cells (mean + SD). One subject with small lymphocytic lymphoma has been treated with two infusions of 38.6 x 109 Xcellerated T Cells. There have been no serious adverse events to date. Following the first treatment, the lymphocyte count increased from 1.8 x 109/L to 2.9 x 109/L on Day 28. The neutrophil count also increased from 2.9 x 109/L to 5.5 x 109/L six weeks following infusion. The subject had a significant reduction in cervical lymphadenopathy and a slight decrease in bulky mesenteric lymphadenopathy six weeks following the first infusion. Conclusions: Xcellerated T Cells can be manufactured in subjects with indolent NHL. Treatment leads to significant increases in T cell and neutrophil counts. Preliminary data suggest a reduction in peripheral lymphadenopathy. Data on additional subjects will be presented.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
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  • 9
    Publication Date: 2004-11-16
    Description: Cytogenetics has proven an essential tool not only for confirming a diagnosis/classification, but for providing prognostic value as well in myelodysplastic syndromes (MDS). However, approximately 50% of primary MDS do not show discernible chromosome changes. In recent years, the fluorescence in situ hybridization (FISH) technique using gene or chromosome locus/region specific probes has emerged as a promising test in various hematopoietic and lymphoid neoplasms. To evaluate the application of FISH panels and cytogenetic studies in MDS, we retrospectively analyzed 1,885 consecutive bone marrow results from patients with suspected MDS due to cytopenia(s). In particular, we assessed the additional information a FISH reflex testing might have given in cytogenetically normal cases. The probes used in the panel included the EGR1 at 5q31, the D7S522 at 7q31, the D8Z2 for the centromere of chromosome 8, the MLL at 11q23 and the D20S108 at 20q12 (Vysis, Inc.). Among all patients, 190 (10%) had clonal chromosome abnormalities, mostly as reported in the literatures, eg, -5/5q- accounted for 34.7% of abnormalities, trisomy 8 29.5%, -7/7q- 14.2%, 20q- 13.7%. Of 345 cases with a FISH reflex test ordered and performed, only 3 (0.87%) showed positive results: a deletion of 7q31, a deletion of 20q12 and a deletion of 5q31 in 9.6%, 8.2% and 71.5% of interphase cells respectively. For the case with 5q- detected by FISH, only 12 metaphases were available for cytogenetic analysis. From our data and experience, at present, interphase FISH panel testing seems not to be an efficient and cost-effective method used as a screening test for cytopenia(s) in the diagnosis of MDS, different from its applications in B-cell chronic lymphoid leukemias, non-Hodgkin lymphomas and plasma cell neoplasms where neoplastic cells inherited not to divide easily in culture for metaphase analysis. Rather, it should be used for suspected MDS cases as a technique of choice for problematic specimens compromised for cytogenetic analysis such as cellular insufficiency, extended transit time and extremely low mitotic index or poor chromosome morphology. Until more genetic defect targeted probes become available with a better understanding of the stem cell biology and pathogenesis in MDS, cytogenetics is still the best and a “must” technique for detecting genomic aberrations in MDS and nearly all other myeloid hematopoietic neoplastic disorders.
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  • 10
    Publication Date: 2004-11-16
    Description: Oral mucositis (OM) is a common complication in cancer patients receiving chemotherapy (CT). OM is characterized by damage to the epithelium of the oral-pharyngeal cavity. CG53135-05, a recombinant human fibroblastic growth factor 20 (rhFGF-20) protein, has demonstrated epithelial and mesenchymal cell proliferation stimulating activity in vitro and reduces OM using single doses in a hamster mucositis model. The goal of this dose-escalating tolerance study was to assess the safety, tolerability and pharmacokinetics of CG53135-05 in cohorts of four patients (pts) at 0.03, 0.1, 0.33, and 1mg/kg (concentrations are determined by the UV method which are equivalent to 0.1, 0.3, 1.0, and 3.0 mg/kg by the Bradford method previously used). Dose escalation was stopped due to tolerability information at 0.33 mg/kg delivered in 15 min (reported in another Phase I study) and the protocol was amended to add a 0.2 mg/kg dose. The World Health Organization (WHO) OM and OMAS scoring systems were used to measure the incidence and severity of OM. The interim results are reported: Ten pts received CG53135-05 at 0.03 mg/kg (n=4) or 0.1 mg/kg (n=6) as a single 100-ml intravenous infusion administered 3 days after completion of the CT. After infusion, CG53135-05 reached maximum plasma concentration within 1h. The mean terminal exponential half-life was 49 min (range: 16.2–87 min, n=5). No pts discontinued the trial due to adverse experiences. Adverse events (number pts) that may be related to the study drug include: nausea (2); chills (2); fever (2); vomiting (1); dizziness (1); vision - “lights flashing” (1) and astigmatism (1); neuropathy (1); tachycardia (1); headache (1); and premature atrial complex (1). All reported incidences were mild to moderate. No grade 3 or 4 laboratory toxicity associated with the study drug was noted. Three serious adverse events deemed unrelated to study drug were noted from two pts including cancer progression, catheter infection, and small intestinal obstruction. Among the treated pts, no grade 3 or 4 OM was observed. Three pts developed Grade 2 mucositis that lasted between 1–5 days. No pts required total parenteral nutrition. Approximately 72–84% of pts receiving CPT-11 experience diarrhea. Of the six pts who received CPT-11 as part of CT in this trial, two pts (both receiving 0.03mg/kg of CG53135-05) experienced mild to moderate diarrhea. Conclusions: CG53135-05 is well tolerated with single dose administration at 0.03 and 0.1 mg/kg. Dosing at 0.2 mg/kg is ongoing. The full results of this study will be presented.
    Print ISSN: 0006-4971
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