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排序方式: 共有78条查询结果,搜索用时 31 毫秒
61.
B. J. Wainwright L.-C. Tsui M. Leppert M. Buchwald X. Estivill P. O''''Connell M. Lathrop J.-M. Lalouel R. White R. Williamson M. Farrall 《American journal of human genetics》1987,41(5):944-947
We have conducted, in 64 affected families, a study of linkage between the anonymous DNA segment pB79a (D7S13) and the locus for cystic fibrosis (CF) on chromosome 7q. The maximum lod score was 12.60 at theta = .08 (confidence bounds .045-.135). Although D7S13 is not sufficiently close to CF for routine use in DNA-based prenatal diagnosis, it will be helpful in certain families when other nearby markers are uninformative. D7S13 will also be useful for refining the linkage map of the CF region. 相似文献
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64.
Rapid resolution of duck hepatitis B virus infections occurs after massive hepatocellular involvement. 总被引:9,自引:0,他引:9
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A R Jilbert T T Wu J M England P M Hall N Z Carp A P O''''Connell W S Mason 《Journal of virology》1992,66(3):1377-1388
A study was carried out to determine some of the factors that might distinguish transient from chronic hepadnavirus infection. First, to better characterize chronic infection, Pekin ducks, congenitally infected with the duck hepatitis B virus (DHBV), were used to assess age-dependent variations in viremia, percentage of DHBV-infected hepatocytes, and average levels of DNA replication intermediates in the cytoplasm and of covalently closed circular DNA in the nuclei of infected hepatocytes. Levels of viremia and viral DNA were found to peak at about the time of hatching but persisted at relatively constant levels in chronically infected birds up to 2 years of age. The percentage of infected hepatocytes was also constant, with DHBV replication in virtually 100% of hepatocytes in all birds. Next, we found that adolescent ducks inoculated intravenously with a large dose of DHBV also developed massive infection of hepatocytes with an early but low-level viremia, followed by rapid development of a neutralizing antibody response. No obvious quantitative or qualitative differences between transiently and chronically infected liver tissue were detected in the intracellular markers of viral replication examined. However, in the adolescent duck experiment, DHBV infection was rapidly cleared from the liver even when up to 80% of hepatocytes were initially infected. In all of these ducks, clearance of infection was accompanied by only a mild hepatitis, with no evidence that massive cell death contributed to the clearance. This finding suggested that mechanisms in addition to immune-mediated destruction of hepatocytes might make major contributions to clearance of infections, including physiological turnover of hepatocytes in the presence of a neutralizing antibody response and/or spontaneous loss of the capacity of hepatocytes to support virus replication. 相似文献
65.
Genetic linkage and heterogeneity in type I Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy type I). 总被引:10,自引:4,他引:6
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P F Chance T D Bird P O''''Connell H Lipe J M Lalouel M Leppert 《American journal of human genetics》1990,47(6):915-925
The segregation patterns of DNA markers from the pericentromeric regions of chromosomes 1 and 17 were studied in seven pedigrees segregating an autosomal dominant gene for Charcot-Marie-Tooth neuropathy type I (CMT I; hereditary motor and sensory neuropathy I). A multilocus analysis with four markers (pMCR-3, pMUC10, FY, and pMLAJ1) spanning the pericentromeric region of chromosome 1 excluded the CMT I gene from this region in six pedigrees but gave some evidence for linkage to the region of Duffy in one pedigree. Linkage of the CMT I gene to markers in the pericentromeric region of chromosome 17 (markers pA10-41, pEW301, p3.6, and pTH17.19) was established; however, in these seven pedigrees homogeneity analysis with chromosome 17 markers detected significant genetic heterogeneity. This analysis suggested that three of the seven pedigrees are not linked to this same region. Overall, two of the seven CMT I pedigrees were not linked to markers tested from chromosomes 1 or 17. These results confirm genetic heterogeneity in CMT I and implicate the existence of a third autosomal locus, in addition to a locus on chromosome 17, and a probable locus on chromosome 1. This evidence of etiological heterogeneity, supported by statistical tests, will have to be taken into consideration when fine-structure genetic maps of the regions around CMT I are constructed. 相似文献
66.
Diagnosis of neurofibromatosis I by using tightly linked, flanking DNA markers. 总被引:8,自引:5,他引:3
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K Ward P O''''Connell J C Carey M Leppert S Jolley R Plaetke B Ogden R White 《American journal of human genetics》1990,46(5):943-949
We tested 132 individuals from 21 families segregating an allele for neurofibromatosis type 1 (NF-1), by using nine RFLPs tightly linked to the NF-1 locus. Family members had requested DNA testing either to determine whether "at risk" children were carrying the NF-1 allele or to determine whether their respective families would be informative for prenatal testing. Predictions about whether a child carries the NF-1 mutation were possible for all 32 at-risk offspring (greater than 98% accuracy based on the recombination estimates currently available for these DNA markers). At least one informative probe was available for all 23 matings in these 21 families; flanking markers were informative for 10 matings. Pairwise analysis showed that several of the polymorphisms were in tight linkage disequilibrium; few recombination events were observed with these markers in the families under study. We conclude that the DNA probes used in this study perform well for diagnostic testing of NF-1 in familial cases. A subset of five probe-enzyme systems (pHHH202/RsaI, p11-3C4.2/MspI, pTH17.19/Bg/II, p11-2C11.7/BamHI, and p11-2F9.8/TaqI) provide reliable linkage information for both clinical testing and prenatal diagnosis. 相似文献
67.
PRB2/1 fusion gene: a product of unequal and homologous crossing-over between proline-rich protein (PRP) genes PRB1 and PRB2.
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The PRB2/1 fusion gene is produced by homologous and unequal crossing-over between PRB1 and PRB2 genes that code for basic salivary proline-rich proteins (PRPs). To determine the molecular basis for the PRB2/1 fusion gene, the DNA sequence was determined for the PRB2/1 gene and was compared with those of the PRB1 and PRB2 genes. From these comparisons, the crossing-over is postulated to occur in a 743-bp region of identity, with only 1-bp mismatch between the PRB1 and PRB2 genes, in the third intron outside the coding region of the two genes. This region of virtual complete identity is the largest found between any of the six closely linked PRB genes and may facilitate recombination. Since the coding region of PRB1 is completely absent from the PRB2/1 gene, salivas from two white PRB2/1 homozygotes were studied to determine which polymorphic PRPs were missing from the salivas. Polymorphic PRPs Pe, PmF, PmS, and Ps were found to be missing from the salivas. However, a white individual lacking the same salivary PRPs is a PRB2/1 heterozygote with one PRB1 allele. The explanation for the missing salivary proteins in this individual is unknown. The PRB2/1 gene is relatively frequent in several populations of unrelated individuals, including American blacks (n = 41), American Utah whites (n = 76), and mainland Chinese (n = 131), with gene frequencies of .22, .06, and .09, respectively. Evidence for the occurrence of PRB1/2 heterozygotes is also presented. 相似文献
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69.
We recently reported that bile salts play a role in the regulation of mucin
secretion by cultured dog gallbladder epithelial cells. In this study we
have examined whether bile salts also influence mucin secretion by the
human epithelial colon cell line LS174T. Solutions of bile salts were
applied to monolayers of LS174T cells. Mucin secretion was quantified by
measuring the secretion of [3H]GlcNAc labeled glycoproteins. Both
unconjugated bile salts as well as taurine conjugated bile salts stimulated
mucin secretion by the colon cells in a dose-dependent fashion. Hydrophobic
bile salts were more potent stimulators than hydrophilic bile salts. Free
(unconjugated) bile salts were more stimulatory compared with their taurine
conjugated counterparts. Stimulation of mucin secretion by LS174T cells was
found to occur at much lower bile salt concentrations than in the
experiments with the dog gallbladder epithelial cells. The protein kinase C
activators PMA and PDB had no stimulatory effect on mucin secretion. We
conclude that mucin secretion by the human colon epithelial cell line
LS174T is regulated by bile salts. We suggest that regulation of mucin
secretion by bile salts might be a common mechanism, by which different
epithelia protect themselves against the detergent action of bile salts, to
which they are exposed throughout the gastrointestinal tract.
相似文献
70.
Oliver Beckstein Ekaterina Ivanova Tian Geng Simone Weyand David Drew Joseph Lanigan David J Sharples Mark SP Sansom So Iwata Colin WG Fishwick A Peter Johnson Alexander D Cameron Peter JF Henderson 《The EMBO journal》2014,33(16):1831-1844
The hydantoin transporter Mhp1 is a sodium‐coupled secondary active transport protein of the nucleobase‐cation‐symport family and a member of the widespread 5‐helix inverted repeat superfamily of transporters. The structure of Mhp1 was previously solved in three different conformations providing insight into the molecular basis of the alternating access mechanism. Here, we elucidate detailed events of substrate binding, through a combination of crystallography, molecular dynamics, site‐directed mutagenesis, biochemical/biophysical assays, and the design and synthesis of novel ligands. We show precisely where 5‐substituted hydantoin substrates bind in an extended configuration at the interface of the bundle and hash domains. They are recognised through hydrogen bonds to the hydantoin moiety and the complementarity of the 5‐substituent for a hydrophobic pocket in the protein. Furthermore, we describe a novel structure of an intermediate state of the protein with the external thin gate locked open by an inhibitor, 5‐(2‐naphthylmethyl)‐L‐hydantoin, which becomes a substrate when leucine 363 is changed to an alanine. We deduce the molecular events that underlie acquisition and transport of a ligand by Mhp1. 相似文献