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1.
P J Hayden C J Welsh Y Yang W H Schaefer A J Ward J L Stevens 《Chemical research in toxicology》1992,5(2):232-237
Nephrotoxic cysteine conjugates derived from a variety of halogenated alkenes are enzymatically activated via the beta-lyase pathway to yield reactive sulfur-containing metabolites which bind covalently to cellular macromolecules. Mitochondria contain beta-lyase enzymes and are primary targets for binding and toxicity. Previously, mitochondrial protein and/or DNA have been considered as molecular targets for cysteine conjugate metabolite binding. We now report that metabolites of nephrotoxic cysteine conjugates form covalent adducts with rat kidney mitochondrial phospholipids. Rat kidney mitochondria were incubated with the 35S-labeled conjugates S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFEC), S-(2-chloro-1,1,2-trifluoroethyl)-L-cysteine (CTFC), S-(1,2-dichlorovinyl)-L-cysteine, and S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine. Quantitation of metabolite binding to whole mitochondria and to mitochondrial protein and lipid fractions revealed that as much as 42% of the 35S-label associated with the mitochondria was found in the lipid fraction. Total lipids were also extracted from 35S-treated mitochondria and separated by thin-layer chromatography. 35S-Containing metabolites were found in the lipid fractions from mitochondria treated with each of the conjugates. Lipids from both [35S]CTFC- and [35S]-TFEC-treated mitochondria contained major 35S-labeled lipid adducts which had similar mobility by thin-layer chromatography. Fatty acid analysis, 19F and 31P NMR spectroscopy, and mass spectrometric analyses confirmed that the major TFEC and CTFC adducts are thioamides of phosphatidylethanolamine. 相似文献
2.
Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight. 相似文献
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4.
CM Reid M. Nelson P. Beckinsale P. Ryan LMH Wing LJ Beilin MA Brown GLR Jennings CI Johnston J. Marley JJ McNeil TO Morgan J. Shaw ID Steven MJ West 《Clinical and experimental pharmacology & physiology》1997,24(5):370-373
1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial. 相似文献
5.
Maternal serum and amniotic fluid alpha-fetoprotein testing has increased significantly in our laboratory and throughout the state since 1985. The results of this test are reported in a novel fashion as multiples of the median. The calculation and reporting of the test results are highly dependent upon gestational age, maternal weight, race and presence or absence of maternal diabetes. When properly interpreted alpha-fetoprotein determinations are a good screening test for early detection of neural tube defects and Trisomy 21 (Down Syndrome). Our approach to screening, diagnosis and counseling is discussed. 相似文献
6.
Background
Induction of apoptosis is one strategy for treatment of prostate cancer. The Shb adapter protein has been found to regulate apoptosis in various cell types and consequently human prostate cancer 3 (PC3) cells were transfected to obtain cells overexpressing Shb in order to increase our understanding of the mechanisms regulating PC3 cell apoptosis. 相似文献7.
K S Blumenfeld F A Welsh V A Harris M A Pesenson 《Journal of cerebral blood flow and metabolism》1992,12(6):987-995
Cerebral ischemia induces the expression of a number of proteins that may have an important influence on cellular injury. The purpose of this study was to compare the regional effects of hypoxia-ischemia on the expression of the proto-oncogene, c-fos, and the heat shock protein-70 (HSP-70) gene in developing brain. Unilateral hypoxia-ischemia was produced in the brain of immature rats (7, 15, and 23 days after birth) using a combination of carotid artery ligation and systemic hypoxia (8% O2). After recovery for 2 and 24 h, the regional expression of c-fos and HSP-70 mRNA was determined using in situ hybridization. Littermates were permitted to recover for 1 week for assessment of histologic injury. Hypoxia-ischemia increased the expression of both c-fos and HSP-70 mRNA, but the topography of expression varied with the age of the animal as well as the mRNA species. In the 7-day-old group, expression of c-fos at 2 h increased in multiple regions of the ipsilateral hemisphere in nearly one-half of the animals, while HSP-70 mRNA was not expressed until 24 h and, then, predominantly in the hippocampus. In 15- and 23-day-old rats, expression of c-fos was increased at 2 h in the entorhinal cortex and in the dendritic field of the upper blade of the hippocampal dentate gyrus, while HSP-70 mRNA was prominently expressed in neocortex and the cell layers of the hippocampus. Interestingly, the strong expression of HSP-70 mRNA in dentate granule cells did not occur in the innermost layer of cells.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
9.
C A Gaydos L Bobo L Welsh E W Hook R Viscidi T C Quinn 《Sexually transmitted diseases》1992,19(6):303-308
A portion of the major outer membrane protein (MOMP) gene from 15 Chlamydia trachomatis serovars was amplified by polymerase chain reaction (PCR) and the product was analyzed by restriction fragment length polymorphism (RFLP). A set of primers was used to amplify an 871 base pair gene fragment encompassing the 4 hypervariable regions of MOMP. AluI digestion of the product gave distinctive patterns for the 15 serovars as demonstrated on silver-stained polyacrylamide gels. A triple digest with EcoRI, HinfI, and HpaII allowed improved discrimination between closely related serovars (C, H, I, J, L3). PCR and RFLP were used to type 50 wild-type clinical isolates and results were compared to results of the solid-phase enzyme immunoassay typing method. These isolates represented the most prevalent genital serovars (D, E, F, K, I and J) in the local sexually transmitted diseases clinic population. For specimens containing 1 serovar, the results of the two methods were similar for 42 samples and discordant for 1 sample. In addition, two samples showed evidence of mixed infection with two serovars as identified by both methods. Five additional specimens contained two serovars, as shown by one or both methods. In all five such specimens, the two typing methods agreed on at least one of the two serovars. For both single and multiple serovar specimens, there was concordance between the two typing methods for 16/17 E serovars, 8/9 D serovars, 8/8 F serovars, 7/7 I serovars, 7/7 J serovars, 5/8 K serovars, and 0/2 G serovars.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献