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991.
PA Roberts 《Canadian Metallurgical Quarterly》1975,80(1):135-142
The frequency of recovered X-ray-induced (4000R) rearrangements that, in all probability mimic terminal deletions of the X chromosome was only one of, roughly, 10-5 X chromosomes screened for tip deficiencies. Although the single exception looks terminally deleted, it is probably capped by a very short or nonpolytene telomeric segment. It is apparent from these data that the probability of "healing" or stabilization of a terminally deleted X in the zygotic nucleus or developing embryo of Drosophila melanogaster is vanishingly small. The telomeric caps in two obviously interstitial deficiencies that were recovered represent, roughly, 1/500 of the length of a mitotic chromosome. These findings give some indication of the extreme difficulty of detecting short telomeric segments capping either deleted polytene chromosomes or deleted metaphase chromosomes of, for example, humans. 相似文献
992.
JS Greenspan DA Davis PA Russo MR Wolfson TH Shaffer 《Canadian Metallurgical Quarterly》1993,55(4):927-932
The tuberomammillary nucleus, a cluster of cells in the posterior hypothalamus, is the only known source of brain histamine. Although this nucleus is well described in terms of anatomy and neurochemistry, only little is known about its function. In the present study, the effect of a lesion in the region of this nucleus on intracranial self-stimulation was examined. Rats were implanted bilaterally with stimulating electrodes in the lateral hypothalamus and unilaterally with one lesion electrode in the region of this nucleus. After three days of baseline testing, half of the animals were given an electrolytic lesion. The animals were retested for six consecutive days, and thereafter weekly for another seven weeks. From the second day postlesion on, we unexpectedly found a gradual increase in response rate, which peaked on day 13 in the ipsilateral hemisphere only. Although there was no further increase over subsequent days, response rates remained elevated during the following seven weekly tests. The observed increase in lateral hypothalamic self-stimulation after an electrolytic lesion of the tuberomammillary nucleus is discussed in terms of an inhibitory system, possibly located in the region of this nucleus which, when removed by the lesion, increased reinforcing effects of the electrical brain stimulation. The fact that the effects on self-stimulation were lateralized to one hemisphere rules out an interpretation in terms of unspecific "performance" variables that could influence rate of lever pressing. 相似文献
993.
F Gigliani C Ciotta MF Del Grosso PA Battaglia 《Canadian Metallurgical Quarterly》1993,238(3):333-338
The aim of this study was to quantitate factors affecting the initial "peak" of the pulmonary artery (PA) drug concentrations after i.v. bolus drug administration, which is a determinant of the subsequent drug uptake into both the lungs and other well-perfused organs. Indocyanine green (ICG) was used as a marker drug in anaesthetized (1.5% halothane) sheep prepared with an inferior vena cava injection catheter and a large-gauge pulmonary artery blood sampling catheter. For three ranges of cardiac output, 2.5-mg doses of ICG were injected in the following combinations: 10 ml injected over 1, 5 or 10 s; 5 or 25 ml injected over 1 s. On-line PA ICG concentrations were recorded for approximately 60 s using a densitometer. The mean maximum PA ICG concentrations (2-8 mg litre-1), the mean times at which they occurred (7-18 s after injection) and the time lags before ICG was detected in the PA (4-9 s), were inversely related to cardiac output, but linearly related to the time over which the injection was made. The area under the curve of the peak was related inversely to cardiac output only, while the aspect ratio of the peak was related inversely to the time over which the injection was made only. The injectate volume had no effect on any of the measured values. We conclude that, in some circumstances, the rate of injection of drugs with narrow margins of safety should be tailored to the cardiac output of an individual. 相似文献
994.
The human uroplakin 1B (UPK1B) gene codes for a structural protein which is a terminal differentiation component of the asymmetric unit membrane on the apical surface of the mammalian bladder. UPK1B is a member of the tetraspan family of proteins, many of which have de-regulated patterns of expression in cancer. Using polymerase-chain-reaction techniques, we have cloned a partial human UPK1B cDNA which codes for the putative full open reading frame for the UPK1B protein. The deduced human UPK1B protein sequence has 92% and 93% amino-acid homology with bovine UPK1b and mink TI1 proteins respectively. Using Northern analysis, we show that the human UPK1B gene is highly expressed in normal human urothelium. However, expression of UPK1B mRNA was undetectable or markedly reduced in 11 out of 16 samples of transitional-cell-bladder-carcinoma tissue and in all 5 bladder-carcinoma cell lines when compared with normal urothelial tissue. The molecular mechanism of down-regulation of RNA expression does not appear to involve gross gene rearrangements or allelic loss. 相似文献
995.
Cancer epigenetics comes of age 总被引:1,自引:0,他引:1
The discovery of numerous hypermethylated promoters of tumour-suppressor genes, along with a better understanding of gene-silencing mechanisms, has moved DNA methylation from obscurity to recognition as an alternative mechanism of tumour-suppressor inactivation in cancer. Epigenetic events can also facilitate genetic damage, as illustrated by the increased mutagenicity of 5-methylcytosine and the silencing of the MLH1 mismatch repair gene by DNA methylation in colorectal tumours. We review here current mechanistic understanding of the role of DNA methylation in malignant transformation, and suggest Knudson's two-hit hypothesis should now be expanded to include epigenetic mechanisms of gene inactivation. 相似文献
996.
N Shaffer A Roongpisuthipong W Siriwasin T Chotpitayasunondh S Chearskul NL Young B Parekh PA Mock C Bhadrakom P Chinayon ML Kalish SK Phillips TC Granade S Subbarao BG Weniger TD Mastro 《Canadian Metallurgical Quarterly》1999,179(3):590-599
To determine the rate and risk factors for human immunodeficiency virus (HIV)-1 subtype E perinatal transmission, with focus on virus load, pregnant HIV-infected women and their formula-fed infants were followed prospectively in Bangkok. Of 281 infants with known outcome, 68 were infected (transmission rate, 24.2%; 95% confidence interval, 19.3%-29.6%). Transmitting mothers had a 4.3-fold higher median plasma HIV RNA level at delivery than did nontransmitters (P<.001). No transmission occurred at <2000 copies/mL. On multivariate analysis, prematurity (adjusted odds ratio [AOR], 4.5), vaginal delivery (AOR, 2.9), low NK cell percentage (AOR, 2.4), and maternal virus load were associated with transmission. As RNA quintiles increased, the AOR for transmission increased linearly from 4.5 to 24.8. Two-thirds of transmission was attributed to virus load>10,000 copies/mL. Although risk is multifactorial, high maternal virus load at delivery strongly predicts transmission. This may have important implications for interventions designed to reduce perinatal transmission. 相似文献
997.
PA Sakkinen EM Macy PW Callas ES Cornell TE Hayes LH Kuller RP Tracy 《Canadian Metallurgical Quarterly》1999,149(3):261-267
CONTEXT: Central venous catheters impregnated with chlorhexidine and silver sulfadiazine have recently been introduced for the prevention of catheter-related infections. However, there remains some uncertainty regarding the efficacy of these catheters because of conflicting reports in the literature. OBJECTIVE: To evaluate the efficacy of chlorhexidine-silver sulfadiazine-impregnated central venous catheters in the prevention of catheter-related bloodstream infection. DATA SOURCES: Studies identified from a computerized search of the MEDLINE database from January 1966 to January 1998, reference lists of identified articles, and queries of principal investigators and the catheter manufacturer. STUDY SELECTION: Randomized trials comparing chlorhexidine-silver sulfadiazine-impregnated central venous catheters with nonimpregnated catheters were included. The outcomes assessed were catheter colonization and catheter-related bloodstream infection confirmed by catheter culture. DATA EXTRACTION: Twelve studies met the inclusion criteria for catheter colonization and included a total of 2611 catheters. Eleven studies with a total of 2603 catheters met the inclusion criteria for catheter-related bloodstream infection. Most patients in these studies were from groups considered to be at high risk for catheter-related infections. Summary statistics were calculated using Mantel-Haenszel methods under a fixed-effects model. DATA SYNTHESIS: The summary odds ratio for catheter colonization was 0.44 (95% confidence interval [CI], 0.36-0.54; P<.001), indicating a significant decrease in catheter colonization associated with impregnated catheters. The studies examining the outcome of primary interest, catheter-related bloodstream infection, had a summary odds ratio of 0.56 (95% CI, 0.37-0.84; P = .005). CONCLUSIONS: Central venous catheters impregnated with a combination of chlorhexidine and silver sulfadiazine appear to be effective in reducing the incidence of both catheter colonization and catheter-related bloodstream infection in patients at high risk for catheter-related infections. 相似文献
998.
999.
1000.
PA Romitti AC Lidral RG Munger S Daack-Hirsch TL Burns JC Murray 《Canadian Metallurgical Quarterly》1999,59(1):39-50
Previous studies suggest that the relationship between genes and nonsyndromic cleft lip +/- cleft palate (CLP) or cleft palate only (CP) may be modified by the environment. Using data from a population-based case-control study, we examined allelic variants for three genes, i.e., transforming growth factor alpha (TGFA), transforming growth factor beta 3 (TGFB3), and Msh (Drosophila) homeobox homolog 1 (MSX1), and their interactions with two exposures during pregnancy (maternal cigarette smoking and alcohol consumption) as risk factors for CLP and CP. For each cleft phenotype, risk estimates associated with most allelic variants tended to be near unity. Risk estimates for maternal smoking (> or = 10 cigarettes/day) were significantly elevated for CP and were most elevated among infants with allelic variants at the TGFB3 or MSX1 sites. By comparison, risk estimates for maternal alcohol consumption (> or = 4 drinks/month) were significantly elevated for CLP and were most elevated among infants with allelic variants at the MSX1 site. Our results suggest that development of CLP and CP may be influenced independently by maternal exposures but more significantly by interaction of such exposures and specific allelic variants. 相似文献