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排序方式: 共有166条查询结果,搜索用时 15 毫秒
91.
92.
MH Wu KE Lohrbach OI Olopade DM Kokkinakis HS Friedman ME Dolan 《Canadian Metallurgical Quarterly》1999,5(1):209-213
O6-benzylguanine (BG) is a potent, specific inactivator of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT), which enhances sensitivity to nitrosoureas in cells and tumor-bearing animals. BG is presently undergoing clinical trials for development as an agent to enhance the therapeutic index of alkylating agent chemotherapy. It has been reported that a polymorphism exists in the human agt gene, with about 15% of the Japanese population having arginine at codon 160 instead of glycine on the polypeptide (Y. Imai et al., Carcinogenesis, 16: 2441-2445, 1995). The resultant mutant AGT protein is equally effective against both methylated DNA as compared with wild type protein. However, this mutant AGT protein was less sensitive to inactivation by BG with a 20-fold increase in the ED50 value. This observation raised the possibility that a subpopulation of patients may be resistant to BG due to a single base change. We have demonstrated that this alteration also reduces the sensitivity to O6-benzyl-8-oxoguanine, an equally potent, yet much longer-lived human metabolite of BG. To test the possibility that this germ-line mutation of the agt gene might explain resistance to BG and O6-benzyl-8-oxoguanine of patients on our Phase I clinical trials, we evaluated the DNA from lymphocytes of 18 patients. The G160R mutation was not found in any of the 18 patients. To determine the frequency of this mutation in the United States population, DNA from 181 healthy individuals were investigated and, again, the mutation was not observed in this cohort. Therefore, if the mutation exists, it is in statistically <1.6% of the United States noncancerous population. To investigate the possibility that this mutation might be somatic, we evaluated genomic DNA samples from 94 human primary cancers of four different histological subtypes (brain, colon, esophageal, and head and neck). Again, none were found to have the G160R mutation. 相似文献
93.
A case of multiple pyogenic granuloma affecting the penis of a 28 year old man is reported. The lesions were arranged in a floret-like fashion around the inner aspect of the prepuce and developed after circumcision for congenital phimosis. Histopathological examination of sections from a biopsy specimen of the papillomatous growths revealed the findings of pyogenic granuloma. In this patient, the pathogenesis of the lesions is probably related to the failure in surgical wound repair that followed circumcision. Problems of clinical and histopathological differential diagnosis are discussed. 相似文献
94.
95.
The identification of telomere-binding protein on the nuclear envelope (NE) of the frog oocyte is reported here. Nuclei and the NE were isolated manually and extracted, and the extracts were used to search for DNA-protein specific interactions. Fragment of the Tetrahymena telomere sequence (T2G4)130 from the plasmid YAC4 was used as a labeled probe. DNA-protein complexes revealed by gel shift assay were cut out of the gel and injected into a guinea pig. The antibodies obtained have common antigenic determinants with keratins; this was shown on Western-blot under conditions of competitive binding. Antibodies were purified on an affinity column with keratins attached and used in the following work. Antibodies recognize one protein with molecular weight 70 kD among the NE proteins; no signal was obtained to proteins isolated from the inner part of the oocyte, but two polypeptides of 70 and 120 kD were detected in the proteins from frog liver nuclei. The 70-kD protein is situated on the NE in a distinct pattern that looks like a network, probably of double-dots as was shown by immunofluorescence of the NE. Electron-microscope immunogold staining showed that the protein is localized in the outer surface of the oocyte NE within cup-like structures attached to the membrane. Combined in situ hybridization using the mammalian telomeric DNA sequence (T2AG3)135 and immunocytochemistry using antibodies showed them to be colocalized in the frog blood cells, so telomere sequence coexists with the protein in the interphase nuclei. Most of the telomeres are fused in highly differentiated blood cells though a double dot signal is visible. The signal appears to be localized in the outer part of the nuclei. The existence of membrane telomere-binding protein allows a discussion of the attachment of the telemeters to the membrane. 相似文献
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97.
Minisatellites are tandemly repeated DNA sequences with repeat units in the range 6-100 bp. They are preferentially located in subtelomeric euchromatin of chromosomes of higher eukaryotes. Minisatellite loci frequently show variability in allele length. This variability is a consequence of high frequency of mutations which change repeat copy number of locus. The most part of minisatellite mutations are germline specific and possibly meiotic. Examples of different mutations and involved genomic mechanisms are reviewed in this paper. A possible biological role of minisatellites is discussed. 相似文献
98.
JS Brunet P Ghadirian TR Rebbeck C Lerman JE Garber PN Tonin J Abrahamson WD Foulkes M Daly J Wagner-Costalas A Godwin OI Olopade R Moslehi A Liede PA Futreal BL Weber GM Lenoir HT Lynch SA Narod 《Canadian Metallurgical Quarterly》1998,90(10):761-766
BACKGROUND: Smoking has carcinogenic effects, and possibly antiestrogenic effects as well, but it has not been found to be a risk factor for breast cancer in women in the general population. However, hereditary breast cancer is primarily a disease of premenopausal women, and interactions between genes and hormonal and environmental risk factors may be particularly important in this subgroup. METHODS: We conducted a matched case-control study of breast cancer among women who have been identified to be carriers of a deleterious mutation in either the BRCA1 or the BRCA2 gene. These women were assessed for genetic risk at one of several genetic counseling programs for cancer in North America. Information about lifetime smoking history was derived from a questionnaire routinely administered to women who were found to carry a mutation in either gene. Smoking histories of case subjects with breast cancer and age-matched healthy control subjects were compared. Odds ratios for developing breast cancer were determined for smokers versus nonsmokers by use of conditional logistic regression for matched sets after adjustment for other known risk factors. RESULTS: Subjects with BRCA1 or BRCA2 gene mutations and breast cancer were significantly more likely to have been nonsmokers than were subjects with mutations and without breast cancer (two-sided P = .007). In a multivariate analysis, subjects with BRCA1 or BRCA2 mutations who had smoked cigarettes for more than 4 pack-years (i.e., number of packs per day multiplied by the number of years of smoking) were found to have a lower breast cancer risk (odds ratio = 0.46, 95% confidence interval = 0.27-0.80; two-sided P = .006) than subjects with mutations who never smoked. CONCLUSIONS: This study raises the possibility that smoking reduces the risk of breast cancer in carriers of BRCA1 or BRCA2 gene mutations. 相似文献
99.
AV Dreval' VG Vysotski? TA Iatsyshina OA Plotnikova DP Tishin NV Anykina OI Cherniak 《Canadian Metallurgical Quarterly》1993,39(2):4-7
Twenty-one obese patients with non-insulin dependent diabetes mellitus, 16 female and 5 male ones, were fed similar isocaloric rations, differing only by the share of substitution of the traditional protein products (0%, 60%, 30%, 45%) in the Danpro-S, Danpro-Fibre soybean protein concentrate. The parameters tested were daily glycemia, C-peptides, blood hydrocortisone, and urinary excretion of nitrous metabolites. Indirect calorimetry was used to assess the protein, fat, and carbohydrate oxidation rates at rest. Addition of proteins of a plant origin to the diets of such patients was associated with significant changes of the energy metabolism at rest at the expense of increased oxidation of carbohydrates and reduced protein catabolism, that may be regarded as a favorable effect. In this patient population a 30% soybean diet brings about an almost maximal positive effect in patients with the first degree of obesity, whereas in those with the second degree of obesity such effect is attained by the 45% soybean diet. 相似文献
100.