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121.
Putative carcinogen-DNA adducts in human larynx tissues (n = 25) from smoker and non/ex-smoker patients were examined by 32P-postlabeling and compared with the metabolic activation capacity of larynx microsomes and cytosols from the same tissues. Hydrophobic DNA adducts were evident only in smokers, and chromatographic profiles of the adducts were similar using either the butanol extraction or nuclease P1 enhancement method, which suggested that the adducts may be derived from polycyclic aromatic hydrocarbons but not aromatic amines. Immunoblots of larynx microsomes using anti-cytochrome P450 1A1/1A2, 2C, 3A4, 2E1, and 2A6 antibodies showed intensities ranging from 1-10% of that typically observed with human liver microsomes. Enzymatic assays of larynx microsomes showed appreciable activity for benzo(a)pyrene hydroxylation (P450 1A1 and 2C) but not for 4-aminobiphenyl N-oxidation (P450 1A2), which indicated that the observed immunoreactivity was for P450 1A1; this represents the highest level of this P450 yet detected in human extrahepatic tissues. Accordingly, total DNA adduct levels in the larynx correlated strongly with levels of P450 2C, 1A1, and 3A4 but not with P450 2E1 or 2A6. Larynx cytosols also showed appreciable aromatic amine N-acetyl-transferase activity for p-aminobenzoic acid (NAT-1) but not for sulfamethazine (NAT-2); however, NAT-1 activity was not correlated with total DNA adducts, which is again consistent with the lack of aromatic amine-DNA adducts detected by 32P-postlabeling. Thus, these results suggest that the DNA adducts detected in human larynx are largely derived from metabolic activation of polycyclic aromatic hydrocarbons in cigarette smoke by P450 2C, 3A4, and/or 1A1.  相似文献   
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Development of auditory stimulation tests associated with single-photon emission tomography (SPET) shows evidence of variations in perfusion related to the stimuli. Three brain SPET examinations with technetium-99m hexamethylpropylene amine oxime were performed on eight right-handed adults with normal hearing, the first one without stimulation and the other two associated with a 500-Hz/30-dB stimulation of the right ear. Temporal regions of interest covering auditory areas, as well as parietal ones (internal control), were drawn on three successive coronal slices. A cortico-cerebellar index R was calculated, and the variation in activity was defined for each subject using the ratio R poststimulation--R prestimulation/R prestimulation. A significant increase in the temporal cortex count occurred in all subjects. This increase was bilateral, except for one subject in whom it was not significant on the right side. This result recurred during the second stimulation study. Overall the response of the left temporal cortex was stronger, although the asymmetry was not significant. The asymmetry repeated itself after each stimulation. The perfusion response is globally reliable in our study. We must ascertain how sensitive this test is with regard to deaf adults and adults with normal hearing before extending its use to children.  相似文献   
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Infection and undernutrition in young children are thought to act synergistically. However, studies of the relationship between low height-for age (stunting) and morbidity in young children have had inconsistent findings and there are few adequate data on the effects of nutritional supplementation on morbidity. 129 stunted and 21 non-stunted children aged between 9 and 24 months, from poor Kingston neighbourhoods, identified from a house-to-house survey, were studied. The stunted children were randomly assigned to supplementation or no supplementation. Every week for 24 months the mothers were asked about the occurrence of any symptoms of illness. Supplementation had no consistent effect on the incidence or duration of symptoms. The stunted children had significantly more attacks of diarrhoea, fever, anorexia and apathy than the non-stunted children. The differences remained after controlling for social background and previous attacks of diarrhoea. There was also some indication of more severe illness in the stunted than in the non-stunted children.  相似文献   
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The NAM2 gene of Saccharomyces cerevisiae encodes the mitochondrial leucyl tRNA synthetase (mLRS), which is necessary for the excision of the fourth intron of the mitochondrial cytb gene (bI4) and the fourth intron of the mitochondrial coxI gene (aI4), as well as for mitochondrial protein synthesis. Some dominant mutant alleles of the gene are able to suppress mutations that inactivate the bI4 maturase, which is essential for the excision of the introns aI4 and bI4. Here we report mutagenesis studies which focus on the splicing and suppressor functions of the protein. Small deletions in the C-terminal region of the protein preferentially reduce the splicing, but not the synthetase activity; and all the C-terminal deletions tested abolish the suppressor activity. Mutations which increase the volume of the residue at position 240 in the wild-type mLRS without introducing a charge, lead to a suppressor activity. The mutant 238C, which is located in the suppressor region, has a reduced synthetase activity and no detectable splicing activity. These data show that the splicing and suppressor functions are linked and that the suppressor activity of the mutant alleles results from a modification of the wild-type splicing activity.  相似文献   
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Recent studies have implicated herpesvirus 8 and Epstein-Barr virus in the development of cutaneous malignancies in immunosuppressed patients. In order to examine the strength of this association, we examined 37 malignant, pre-malignant and benign cutaneous epithelial neoplasms removed from immunosuppressed organ recipients for the presence of human herpesvirus 8 and Epstein-Barr viral genome sequences using polymerase chain reaction (PCR) and in situ hybridization. We examined 2 actinic keratoses, 1 benign keratosis, 11 invasive squamous cell carcinomas, 17 squamous cell carcinomas in situ and 6 basal cell carcinomas. We also examined 4 basal cell carcinomas, 1 invasive squamous cell carcinoma and 3 squamous cell carcinomas in immunocompetent hosts. In contrast to findings reported by other investigators, we were unable to detect viral genome sequences in any of the biopsies examined. Our findings suggest that human herpesvirus 8 and Epstein-Barr virus likely do not play an etiologic role in cutaneous epithelial oncogenesis in immunocompromised patients.  相似文献   
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Thrombomodulin (TM), recognized as an essential vessel wall cofactor of the antithrombotic mechanism, is also expressed by a wide range of tumor cells. Tumor cell lines subcloned from four patients with malignant melanoma displayed a negative correlation between TM expression and cell proliferation in vitro and in vivo. Overexpression of wild-type TM decreased cell proliferation in vitro and tumor growth in vivo. TM mutants with altered protein C activation capacity lead to a similar effect. In contrast, transfection of melanoma cells with mutant TM constructs, in which a portion of the cytoplasmic or lectin domain was deleted, abrogated the antiproliferative effect associated with overexpression of wild-type TM. Experiments performed with either peptide agonists/antagonists of the thrombin receptor, with hirudin, or with inhibitors of thrombin-TM interaction did not alter the growth inhibitory effect of TM overexpression. These data suggest that TM exerts an effect on cell proliferation independent of thrombin and the thrombin receptor, possibly related to the binding of novel ligands to determinants in the lectin domain which might trigger signal transduction pathways dependent on the cytoplasmic domain.  相似文献   
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OBJECTIVE: The goal of this study was to compare the effects of nitrous oxide (N2O), isoflurane (ISO), fentanyl (FENT), and propofol (PROP) on the tongue mucosal blood flow (TMBF) in rabbits. STUDY DESIGN: TMBF was measured with a laser Doppler flow meter before and after the administration of 50% N2O (n = 7), 1.0 and 1.5 minimum alveolar concentration ISO (n = 6), 10, 20, and 40 micrograms/kg FENT (n = 8) or 100, 200 and 400 micrograms/kg/min PROP (n = 7). Hemodynamic variables including heart rate, systolic blood pressure (SBP), mean arterial pressure (MAP) and aortic blood flow (AoF) were continuously monitored. Total peripheral resistance (TPR) was calculated as MAP divided by AoF. RESULTS: An increase in TMBF along with reductions in SBP, MAP and TPR were observed in ISO group. In FENT group, TMBF was decreased, whereas other hemodynamic variables showed no change. TMBF in groups N2O and PROP did not change. CONCLUSION: These results indicate that TMBF depends on the anesthetic used.  相似文献   
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