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  • 1995-1999  (9)
  • United States  (4)
  • hamster  (3)
  • Computational Chemistry and Molecular Modeling  (2)
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  • 1
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; hamster ; islet regeneration ; growth factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Partial pancreatic duct obstruction in the hamster leads to the induction of endocrine-cell differentiation and new islet formation. We prepared cytosolic extracts from the partially obstructed pancreas and identified one, which when administered i.p., produced significant increases in the incorporation of tritiated thymidine by ductular and islet cells, as well as a corresponding increase in islet mass. In this study, we evaluate the ability of this extract to reverse streptozotocin diabetes mellitus. Hamsters were treated i. p. twice daily for 7 weeks with either 0.9% NaCl (saline) (n=10) or a cytosol extract (n=10) prepared previously from partially obstructed hamster pancreata. All animals in the cytosol group survived vs only 60% of the saline group (p=0.02). Random blood glucose levels were greater than 22.2 mmol/l in 90% of the saline group vs 40% in the cytosol group (p〈0.05). Pancreatic tissue from the surviving saline animals and from persistently hyperglycaemic cytosol-treated animals, showed intra-cytoplasmic vacuolation of islet cells, a characteristic lesion of sustained hyperglycaemic states. Vacuolation was not observed in normoglycaemic extract treated animals. Islets in hyperglycaemic animals demonstrated a profound decrease or absence of immunoreactive insulin, compared to an abundance of immunoreactive beta cells in cytosol-treated animals that reverted to normoglycaemia. In this group, single cells or nests of cells stained for insulin or glucagon cells were identified in ductal epithelium in association with cells budding from the duct. Morphometric analysis of pancreata in reverted cytosol-treated animals showed a new population of small islets compared with saline controls and an increased islet mass. In summary, streptozotocin diabetes can be reversed by new islet formation induced by local pancreatic growth factors, the exact nature of which remains to be determined.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Diabetes mellitus ; hamster ; islet regeneration ; growth factors.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Partial pancreatic duct obstruction in the hamster leads to the induction of endocrine-cell differentiation and new islet formation. We prepared cytosolic extracts from the partially obstructed pancreas and identified one, which when administered i. p., produced significant increases in the incorporation of tritiated thymidine by ductular and islet cells, as well as a corresponding increase in islet mass. In this study, we evaluate the ability of this extract to reverse streptozotocin diabetes mellitus. Hamsters were treated i. p. twice daily for 7 weeks with either 0.9 % NaCl (saline) (n = 10) or a cytosol extract (n = 10) prepared previously from partially obstructed hamster pancreata. All animals in the cytosol group survived vs only 60 % of the saline group (p = 0.02). Random blood glucose levels were greater than 22.2 mmol/l in 90 % of the saline group vs 40 % in the cytosol group (p 〈 0.05). Pancreatic tissue from the surviving saline animals and from persistently hyperglycaemic cytosol-treated animals, showed intra-cytoplasmic vacuolation of islet cells, a characteristic lesion of sustained hyperglycaemic states. Vacuolation was not observed in normoglycaemic extract treated animals. Islets in hyperglycaemic animals demonstrated a profound decrease or absence of immunoreactive insulin, compared to an abundance of immunoreactive beta cells in cytosol-treated animals that reverted to normoglycaemia. In this group, single cells or nests of cells stained for insulin or glucagon cells were identified in ductal epithelium in association with cells budding from the duct. Morphometric analysis of pancreata in reverted cytosol-treated animals showed a new population of small islets compared with saline controls and an increased islet mass. In summary, streptozotocin diabetes can be reversed by new islet formation induced by local pancreatic growth factors, the exact nature of which remains to be determined. [Diabetologia (1996) 39: 256–262]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Reg gene ; islet neogenesis ; cellophane wrap ; hamster
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have reported previously that cellophane wrapping of the hamster pancreas is a stimulus that leads to the induction of duct epithelial cell proliferation, followed by endocrine cell differentiation and new islet formation. Reg is a candidate gene that has been reported to be expressed in regenerating pancreatic islets, suggesting a role in islet growth. We examined Reg gene expression in the cellophane-wrap model by isolating total RNA from hamster pancreata at various times after wrapping. Northern blot analysis using a rat cDNA Reg probe showed no expression of Reg in control non-wrapped hamster pancreas, whereas a strong signal was detected in control wrapped rat pancreas. Using reverse transcription of RNA followed by polymerase chain reaction (PCR) we amplified, isolated and sequenced a 194 base pair product which showed homology to rat Reg in both control and wrapped hamster pancreas. When the PCR product was used as a probe for Northern blot analysis, no signal was detected in control non-wrapped pancreata. In contrast, a strong signal was detected 1 and 2 days after wrapping, which then returned to basal between 4 and 6 days after wrapping. A similar temporal pattern was observed using in situ hybridization to localize the Reg gene. One- and 2-day wrapped but not control pancreas expressed Reg in acinar cells, but not in islets. In conclusion, (a) Reg expression is low in the control hamster pancreas; (b) in the cellophane-wrap model of islet neogenesis, increased Reg mRNA is found within acinar tissue; (c) Reg gene may thus be involved as an acinar paracrine effector of duct cell proliferation in the initial step of islet neogenesis, but may also participate in the inflammatory response to traumatic stimuli.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7225
    Keywords: Blacks ; breast carcinoma ; oral contraceptives ; United States
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Recent epidemiologic studies, most of them in predominantly White populations, have suggested that long duration of oral contraceptive (OC) use may increase the risk of breast cancer at young ages. We assessed the relationship of OC use to the risk of breast cancer in African-American women aged 25 to 59 years, using interview data from a multipurpose hospital-based case-control study. Five hundred and twenty-four cases hospitalized for invasive breast cancer were compared with 1,021 controls with nonmalignant conditions unrelated to OC use. Relative risks (RR) and 95 percent confidence intervals (CI) were estimated relative to a reference category of use for less than 12 months; potential confounders were controlled by multiple logistic regression analysis. Among women under age 45, three or more years of OC use was associated with an increased risk of breast cancer: the RR estimate was 2.8 (CI=1.5–5.0) for three to four years of use, and declined to 1.5 (CI=0.8.3.0) for 10 or more years of use. Recency and timing of use did not explain the observed association. Among women aged 45 to 59, OC use was associated with little or no increase in risk: the RR estimate for three or more years of use was 1.3 (CI=0.7–2.4). The findings add to the evidence from studies of White women and a recent study of Black women which have suggested an increased risk of breast cancer at young ages for moderate or long duration use of OCs.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-7225
    Keywords: Breast neoplasms ; cohort study ; daughters ; maternal age ; paternal age ; United States
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Data from the Framingham Heart Study, collected in Framingham, MA (United States) during 1948–86, were used to evaluate the relation of parental age at birth to the risk of breast cancer among daughters. After 38 years of follow-up, 149 breast cancer cases occurred among 2,662 women. All but two cases were confirmed by histologic report. The rate of breast cancer increased among daughters with increasing maternal age at birth up to the mid-30s, where the rate levelled off. A similar pattern was observed with paternal age. After adjustment for other confouding factors and paternal age, the rate ratios for breast cancer in daughters whose mothers were aged 26 to 31 years and 32 or more years at their birth, relative to women whose mothers were aged 25 years or younger, were 1.5 (95 percent confidence interval [CI]=1.0–2.4) and 1.3 (CI=0.8–2.2), respectively. However, there was no longer an association between paternal age at birth and risk of breast cancer after controlling for maternal age and other risk factors.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-7225
    Keywords: Acetaminophen ; kidney neoplasms ; renal cell carcinoma ; United States
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Experimental and epidemiologic evidence have suggested that phenacetin use increases the risk of transitional cell cancers of the urinary tract. The drug is no longer marketed but a commonly used metabolite, acetaminophen, has been linked recently to an increased risk of renal cancer. We assessed the relation of acetaminophen use to the risk of transitional cell cancer of the urinary tract and of renal cell cancer with data from a hospital-based study of cancers and medication use conducted from 1976-96 in the eastern United States. We compared 498 cases of transitional cell cancer and 383 cases of renal cell cancer with 8,149 noncancer controls and 6,499 cancer controls and controlled confounding factors with logistic regression. For transitional cell cancer, the relative risk (RR) estimate for regular acetaminophen use that had begun at least a year before admission was 1.1 (95 percent confidence interval [CI] = 0.6-1.9) based on noncancer controls, and 0.9 (CI = 0.5-1.6) based on cancer controls. RR estimates for use that lasted at least five years, and for nonregular use, were also close to 1.0. For renal cell cancer, the corresponding estimates were again close to 1.0. Our results suggest that acetaminophen, as used in present study population, does not influence the risk of transitional cell cancer of the urinary tract or of renal cell cancer.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1573-7225
    Keywords: Abortion ; breast carcinoma ; risk factors ; United States ; women
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The relation of induced and spontaneous abortion to the risk of breast cancer is evaluated in a hospital-based case-control interview study conducted in three cities in the United States from 1985 through 1995. Cases were 1,803 women aged 25 to 64 years with newly diagnosed invasive breast cancer; controls were 4,182 women of the same ages admitted for conditions unrelated to reproductive factors. Other breast cancer risk-factors were controlled through multiple logistic regression. The reference for allanalyses was women who had never had an abortion, either induced or spontaneous. Among parous women, the relative risk (RR) estimate was 1.1 (95percent confidence interval [CI] = 0.9-1.5) for induced abortion overall, 1.0(CI = 0.7-1.4) for abortion before the first birth, and 1.3 (CI = 1.0-1.8)for abortion after at least one birth. Among nulliparous women, the relative risk estimate for induced abortion was 1.3 (CI = 0.9-1.9). There was no trend of increased risk with number of abortions, nor was there consistent evidence of an increased risk in any particular subgroup. Spontaneous abortion was not associated with increased risk of breast cancer, either among nulliparous women or among parous women. These findings provide little support for the hypothesis that induced abortion increases breast cancer risk overall or in particular subgroups.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Computational Chemistry 16 (1995), S. 1339-1350 
    ISSN: 0192-8651
    Keywords: Computational Chemistry and Molecular Modeling ; Biochemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Computer Science
    Notes: The recently formulated weighted histogram analysis method (WHAM)1 is an extension of Ferrenberg and Swendsen's multiple histogram technique for free-energy and potential of mean force calculations. As an illustration of the method, we have calculated the two-dimensional potential of mean force surface of the dihedrals gamma and chi in deoxyadenosine with Monte Carlo simulations using the all-atom and united-atom representation of the AMBER force fields. This also demonstrates one of the major advantages of WHAM over umbrella sampling techniques. The method also provides an analysis of the statistical accuracy of the potential of mean force as well as a guide to the most efficient use of additional simulations to minimize errors. © 1995 John Wiley & Sons, Inc.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Computational Chemistry 16 (1995), S. 1351-1356 
    ISSN: 0192-8651
    Keywords: Computational Chemistry and Molecular Modeling ; Biochemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Computer Science
    Notes: Current macromolecular energy minimization algorithms become inefficient and prone to failure when bond length constraints are imposed. They are required to relieve steric stresses in biomolecules prior to a molecular dynamics simulation. Unfortunately, the latter often require constraints, leading to difficulties in initiating trajectories from unconstrained energy minima. This difficulty was overcome by requiring that the components of the energy gradient vanish along the constrained bonds. The modified energy minimization algorithm converges to a lower energy in a fewer number of iterations and is more robust than current implementations. The method has been successfully applied to the Dickerson DNA dodecamer, CGCGAATTCGCG. © 1995 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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