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91.
Background: this study was designed to characterize some of the biochemical and molecular genetic changes during reversion
of human fat cells. Methods: mature adipocytes were isolated from greater omental fat tissue of eight lean and 14 massively
obese persons by established methodology. Results: at day 7 of adherence to Leighton tubes, there was appreciable depletion
of triacylglycerol, as well as assumption of an elongated contour. Relatedly, there was an increase in the expression of β-actin
mRNA and a significant decrease in the specific activity of cytosolic glycerophosphate dehydrogenase. The decrement in the
specific activity of glycerophosphate dehydrogenase, after 7 days in culture, was significant at p < 0.001. Basic fibroblast growth factor at 10 ngml-1 accelerated significantly (p < 0.03) the decrease in the specific activity of glycerophosphate dehydrogenase in adipose cells from lean subjects. In contrast,
basic fibroblast growth factor had no significant influence on cells from massively obese persons. Conclusion: such resistance
may contribute to the intractability of massive obesity. 相似文献
92.
93.
Fulminant hepatic failure is a serious condition with very high mortality. Development of new therapies designed to bridge the patient through the acute period of their disease has been hampered by the lack of a large animal model that closely reproduces the changes in humans. We have established an improved model of fulminant hepatic failure in the pig by administration of an aminosugar d-galactosamine hydrochloride. Galactosamine in a dose of 1.0 g/kg was dissolved in 5% dextrose in water (D5W) and given intravenously to seven young pigs weighing 8 to 15 kg. Seven control pigs received an equal volume of D5W alone. Two days prior to injection, a baseline ultrasound-guided liver biopsy was done in each pig under general anesthesia using isofluorane. Clinical data were recorded and blood for laboratory determinations was drawn at 0 h (baseline), 24 h, 48 h, and 72 h after infusion of galactosamine or D5W alone, under general anesthesia. Neurological data were recorded at the same intervals before inducing anesthesia. Galactosamine-treated animals showed 100% mortality. All of them died by 86 h after injection of galactosamine, with death resulting from fulminant hepatic failure characterized by marked increases in total bilirubin, liver enzymes, ammonia, and lactate; associated coagulopathy; hypoglycemia; and coma. Liver histology showed massive hepatocellular necrosis in all seven galactosamine-treated animals. This large and highly reproducible animal model appears promising for future evaluation of bioartificial liver support systems designed to treat fulminant hepatic failure in humans. 相似文献
94.
Two lines of rats, least affected (LA) and most affected (MA), had been selectively bred for their differential sensitivity to ethanol. Both males and females of the LA strain were observed to be less sensitive than their MA counterparts to the acute hypnotic and motor-impairing effects of ethanol. However, a lower ethanol metabolic rate of the MA males suggests that both CNS and metabolic factors contribute to their enhanced sensitivity to ethanol. By contrast, no differences were observed between the LA and MA males with respect to the hypnotic and subhypnotic effects of pentobarbital or to the clearance of this drug. MA females were more sensitive only to the hypnotic effects of pentobarbital, probably because of a smaller apparent volume of distribution. No strain difference was observed in the hypnotic effect or clearance of barbital. These observations suggest that, in spite of a differential sensitivity to ethanol, the LA and MA lines do not differ in their response to the barbiturates tested. 相似文献
95.
Conclusion From the above consideration we conclude that the stature of the boys and girls in all the age groups grew more rapidly than
the other body segments under consideration. On the other hand, the arm girth grew very slowly. The mean values were progressively
higher while the rate of growth and growth velocities were different in different age groups. The mean values of the lower
extremity and biacromial indices were nearly constant in all the age groups which showed relatively equal growth of the stature
in relation to lower extremity and shoulder breadth.
From the Department of Anthropology, Lucknow University, Lucknow-226001. 相似文献
96.
The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. 总被引:12,自引:0,他引:12
Thorir D Bjornsson John T Callaghan Heidi J Einolf Volker Fischer Lawrence Gan Scott Grimm John Kao S Peter King Gerald Miwa Lan Ni Gondi Kumar James McLeod R Scott Obach Stanley Roberts Amy Roe Anita Shah Fred Snikeris John T Sullivan Donald Tweedie Jose M Vega John Walsh Steven A Wrighton 《Drug metabolism and disposition》2003,31(7):815-832
Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches, to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (P450) probe substrates, inhibitors and inducers and for the development of classification systems to improve the communication of risk to health care providers and to patients. While existing guidances cover mainly P450-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently, and should also be addressed. This article was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers. 相似文献
97.
Anita Koushik Robert W Platt Eduardo L Franco 《Cancer epidemiology, biomarkers & prevention》2004,13(1):11-22
The Arg/Arg genotype versus Arg/Pro or Pro/Pro at codon 72 of the p53 gene has been implicated as a risk marker in cervical neoplasia. However, research on this topic has produced controversial results. We reviewed the published literature to summarize the association and to identify methodological features that may have contributed to the heterogeneity. Information on specific methodological features of studies addressing this topic published between 1998 and 2002 were obtained. Study-specific odds ratios (ORs) were combined in a meta-analysis, assuming random effects. To identify characteristics that significantly contributed to heterogeneity, we used meta-regression analysis. We identified 50 articles, of which 45 were included in the meta-analyses and regressions. No evidence of association or heterogeneity was detected for preinvasive lesions. For invasive cervical cancer with undefined histology, the Arg/Arg genotype was not found to affect risk (OR, 1.1; 95% confidence interval (CI), 0.9-1.3). However, a slightly increased risk was observed for squamous cell carcinoma (OR, 1.5; 95% CI, 1.2-1.9) and adenocarcinoma (OR, 1.7; 95% CI, 1.0-2.7). Meta-regression analysis identified that the most important factor contributing to heterogeneity among results for invasive lesions was departures from Hardy-Weinberg equilibrium in the control group. Summary ORs for studies in equilibrium were essentially null. A possible susceptibility role by the p53 codon 72 polymorphism at a late carcinogenetic stage in cervical cancer cannot be ruled out. However, various methodological features can contribute to departures from Hardy-Weinberg equilibrium and consequently to less than ideal circumstances for the examination of this polymorphism. Future investigations require appropriate attention to design and methodological issues. 相似文献
98.
Alcohol exposure and breast cancer: results of the women's contraceptive and reproductive experiences study. 总被引:2,自引:0,他引:2
Jill A McDonald Michele G Mandel Polly A Marchbanks Suzanne G Folger Janet R Daling Giske Ursin Michael S Simon Leslie Bernstein Brian L Strom Sandra A Norman Kathleen E Malone Linda K Weiss Ronald T Burkman Anita L Weber Robert Spirtas 《Cancer epidemiology, biomarkers & prevention》2004,13(12):2106-2116
OBJECTIVES: To explore associated biological outcomes and clarify the role of timing of exposure in the alcohol-breast cancer relationship.METHODS: In a population-based study of 4,575 women ages 35 to 64 years diagnosed with invasive breast cancer between 1994 and 1998 and 4,682 controls, we collected details of lifetime alcohol use and factors that could confound or modify the alcohol-breast cancer relationship. We used conditional logistic regression to compute the odds of breast cancer among drinkers relative to nondrinkers at all ages and at ages 35 to 49 and 50 to 64 years separately.RESULTS: Recent consumption (at reference age minus two) of >/=7 drinks per week was associated with increased risk [odds ratio (OR), 1.2; 95% CI, 1.01-1.3] and evidence of dose response was observed. Most of the excess was observed among women ages 50-64 years (OR 1.3; 95% CI, 1.1-1.6), although the test for age interaction was not statistically significant. Exposure later in life seemed more important than early exposure. Excess breast cancer associated with recent consumption was restricted to localized disease. When outcome was examined according to tumor hormone receptor status, highest risks were observed for estrogen receptor-positive/progesterone receptor-negative tumors (OR 1.6; 95% CI, 1.2-2.3).CONCLUSIONS: The effect of timing of alcohol exposure on breast cancer risk is complicated and will require additional study focused on this one issue. Further work is needed to explain how alcohol exposure, sex hormones, and tumor receptor status interact. 相似文献
99.
100.
This case report describes a primary hepatic leiomyoma presenting as a mass lesion detected on ultrasonography of the abdomen in an asymptomatic hepatitis B carrier on routine surveillance. Primary leiomyomata of the liver are rare occurrences, with only 9 cases reported in the literature. The presenting features of primary hepatic leiomyomata and diagnostic approach towards such lesions are discussed. The significance of such tumours in the immunocompromised is also mentioned. 相似文献