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51.
Genotypes of 17 patients with cystinuria were predicted from data based on excretion rates of the families' obligate carriers. The methodology differed from that used by other investigators as it did not employ intestinal biopsy studies or loading dose measurements. The Type I form was more common than either Type II or Type III and frequently occurred in combination to give compound heterozygous genotypes with the Type III form. 相似文献
52.
Distribution of Helicobacter pylori cagA, cagE and vacA in different ethnic groups in Kuala Lumpur, Malaysia 总被引:3,自引:0,他引:3
BACKGROUND AND AIMS: There is a geographic variation in Helicobacter pylori (HP) genotypes and virulence factors. Cytotoxin associated genes A (cagA) and E (cagE), and certain vacuolating cytotoxin (vacA) genotypes are associated with peptic ulcer disease (PUD). There is also a different prevalence of PUD among different ethnic groups in Malaysia. The present study compared the distribution of vacA alleles and cagA and cagE status in three ethnic groups residing in Kuala Lumpur, Malaysia, and their association with clinical outcome. METHODS: All patients with cultured positive HP were recruited prospectively. DNA was extracted and polymerase chain reaction was carried out to determine the cagA and cagE status and vacA alleles. RESULTS: The results of 127 patients (72 men and 55 women) were included. The mean age was 55.53 +/- 12.52 years. The ethnic distribution was 59 Chinese, 38 Indian and 30 Malay patients. The predominant genotype was s1a among the Malay (76.6%) and Indian patients (71.0%), and s1c among the Chinese patients (66.1%). The vacA middle region sequence m1 was detected in 66.7% of Malay, 54.2% of Chinese and 76.3% of Indian patients. Of the Malay, Chinese and Indian patients, 76.6%, 86.4% and 86.8%, respectively, were cagA positive, and 70.0%, 39.0% and 81.6%, respectively, were cagE positve. HP cagA, cagE and vacA were not associated with PUD. CONCLUSION: There is a distinctive difference in the HP strains among the three ethnic groups in Malaysia. There was no association between cagA, cagE or vacA genotypes and clinical outcome in the patients. None of these markers are helpful in predicting the clinical presentation of a HP infection. 相似文献
53.
Global genetic diversity of human metapneumovirus fusion gene 总被引:6,自引:0,他引:6
Boivin G Mackay I Sloots TP Madhi S Freymuth F Wolf D Shemer-Avni Y Ludewick H Gray GC LeBlanc E 《Emerging infectious diseases》2004,10(6):1154-1157
We analyzed 64 human metapneumovirus strains from eight countries. Phylogenetic analysis identified two groups (A and B, amino acid identity 93%-96%) and four subgroups. Although group A strains predominated, accounting for 69% of all strains, as many B as A strains were found in persons >3 years of age. 相似文献
54.
Modern molecular techniques make discovery of numerous single nucleotide polymorphims (SNPs) in candidate gene regions feasible. Conventional analysis relies on either independent tests with each variant or the use of haplotypes in association analysis. The first technique ignores the dependencies between SNPs. The second, though it may increase power, often introduces uncertainty by estimating haplotypes from population data. Additionally, as the number of loci expands for a haplotype, ambiguity in interpretation increases for determining the underlying genetic components driving a detected association. Here, we present a genotype-level analysis to jointly model the SNPs via a SNP interaction model with phase information (SIMPle) to capture the underlying haplotype structure. This analysis estimates both the risk associated with each variant and the importance of phase between pairwise combinations of SNPs. Thus, rather than selecting between genotype- or haplotype-level approaches, the SIMPle method frames the analysis of multilocus data in a model selection paradigm, the aim to determine which SNPs, phase terms, and linear combinations best describe the relation between genetic variation and a trait of interest. To avoid unstable estimation due to sparse data and to incorporate both the dependencies among terms and the uncertainty in model selection, we propose a Bayes model averaging procedure. This highlights key SNPs and phase terms and yields a set of best representative models. Using simulations, we demonstrate the utility of the SIMPle model to identify crucial SNPs and underlying haplotype structures across a variety of causal models and genetic architectures. 相似文献
55.
Schirmbeck R Böhm W Fissolo N Melber K Reimann J 《European journal of immunology》2003,33(9):2429-2438
The small hepatitis B surface antigen (HBsAg) of hepatitis B virus (HBV) has limited variability, but some serotypes and genotypes have been defined. Although no biological or pathogenetic differences could be traced to HBV serotypes, the clinical picture, response to treatment and long-term prognosis of HBV infection may vary with the HBV genotype, possibly due to differences in specific T cell recognition of HBV antigens from different genotypes. We analyzed murine CD8(+) T cell responses to two K(b)-restricted HBsAg epitopes primed by four different HBsAg variants using protein- and DNA-based vaccination protocols. The K(b)-binding S(208-215) epitope 1 is processed from exogenous but not endogenous HBsAg. Variants of epitope 1 differing at two positions within the epitope (ILSPFLPL in ayw/adr versus IVSPFIPL in adw2) efficiently primed cross-reactive CD8(+) T cell responses. In contrast, the exchange of an N-terminal flanking residue (S to N) completely eliminated the immunogenicity of epitope 1. The K(b)-binding S(190-197) epitope 2 is processed from endogenous but not exogenous HBsAg. A single-residue exchange within the epitope (VWLSVIWM in ayw/adr versus VWLSAIWM in adw2) completely eliminated the immunogenicity of epitope 2. Single, conservative residue exchanges can thus give rise to diverging CD8(+) T cell repertoires, suggesting an impressive complexity and flexibility of the CD8(+) T cell repertoire to antigen variants from viruses with limited diversity. 相似文献
56.
Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease 总被引:11,自引:0,他引:11
Sugauchi F Ohno T Orito E Sakugawa H Ichida T Komatsu M Kuramitsu T Ueda R Miyakawa Y Mizokami M 《Journal of medical virology》2003,70(4):537-544
Hepatitis B virus (HBV) mutants with deletions in the preS region have not been evaluated for association with viral genotypes. In a case-control study, HBV DNA samples collected from 80 each of carriers infected with HBV genotype B or C were examined for preS deletions. PreS deletion mutants were found in a total of 37 of 160 (23%) HBV carriers. Carriers with preS deletion mutants were older (56.0 +/- 12.7 vs 49.3 +/- 16.9 years, P < 0.05), were infected more frequently with HBV genotype C (84% vs 40%, P < 0.05), and had more advanced disease, such as liver cirrhosis and hepatocellular carcinoma (54% vs 31%; P < 0.05), than did those without such mutants. In a multivariate analysis, genotype C (odds ratio [OR] = 9.3, P < 0.001) and advanced liver disease (OR = 3.1, P < 0.01) were the most significant variables in association with preS deletions. A direct repeat sequence (TCAGG) was found at the start or at the end of preS1 deletions in 6 of the 20 (30%) cases examined, and preS2 deletions in these cases were clustered over the 5'-terminal half of this region. These results indicate that the development of preS deletion mutants depends on HBV genotypes and that it may be associated with progressive liver disease. 相似文献
57.
Chaudhuri S Chowdhury A Datta S Mukhopadhyay AK Chattopadhya S Saha DR Dhali G Santra A Nair GB Bhattacharya S Berg DE 《Journal of gastroenterology and hepatology》2003,18(2):190-195
BACKGROUND AND AIMS: The efficiency of Helicobacter pylori eradication varies geographically, as do many parameters that might affect therapeutic efficiency, including bacterial genotype. The aim of the present study was to determine the efficiency of H. pylori eradication using a 10-day proton pump inhibitor-based triple-therapy regimen (omeprazole, clarithromycin and amoxycillin) in an eastern Indian patient population, and to find out the relationship, if any, of the success or failure of the therapy to known features of bacterial genotype. METHODS: Helicobacter pylori infections were analyzed in 66 duodenal ulcer patients by upper gastrointestinal endoscopy, rapid urease tests, histology and culture. The cytotoxin-associated gene (cagA) and vacuolating cytotoxin (vacA) gene status of cultured strains were studied by polymerase chain reaction. Treatment was given for 10 days and endoscopy was repeated at 4 and 12 weeks post therapy to monitor ulcer healing and H. pylori eradication. RESULTS: Ulcer healing was observed in 60 patients (96.77%). Helicobacter pylori was eradicated in 41 (62.12% intention to treat, 66.13% per protocol) of the 66 duodenal ulcer patients, but not in the other 25. The bacteria from 47 patients were genotyped. The only significant disease-associated difference in patterns observed was that the vacA m1 allele was represented more disproportionately among patients with eradication failures (68%) than in those with successful eradication (39%) (P < 0.05) No significant association of vacAs1 (signal sequence allele) or cag pathogenicity island status with persistence was detected. CONCLUSIONS: This study highlights the public health need for cheaper, more cost-effective anti-H. pylori therapies for developing countries, and suggests that subtle features of bacterial genotype can influence therapeutic efficiency. The possibility that particular vacA mid region alleles affect persistence, perhaps through toxin action on particular gastric cell types, merits further study. 相似文献
58.
Polymorphisms of four bone mineral density candidate genes in Chinese populations and comparison with other populations of different ethnicity 总被引:13,自引:0,他引:13
Lei SF Deng FY Liu XH Huang QR Qin Y Zhou Q Jiang DK Li YM Mo XY Liu MY Chen XD Wu XS Shen H Dvornyk V Zhao L Recker RR Deng HW 《Journal of bone and mineral metabolism》2003,21(1):34-42
Studies on polymorphisms of candidate genes and their association with bone mineral density (BMD) have been reported in many
populations, but few have been reported in Chinese populations. We investigated polymorphisms of the following five commonly
used markers of four prominent BMD candidate genes with the purpose of identifying useful genetic markers for osteoporosis
genetic research in Chinese: the Sp1 and RsaI polymorphisms of the collagen type 1 alpha l (Col1a1) gene, the −174G/C promoter
polymorphism of the interleukin 6 (IL-6) gene, the Asn363Ser polymorphism of the glucocorticoid receptor (GR) gene, and the
T → C polymorphism in intron 5 of the transforming growth factor β1 (TGF-β1) gene. We evaluated these polymorphisms using PCR-RFLP in samples of at least 124 random individuals. We compared the polymorphisms
of these five markers with other populations using the χ2 test and Fisher's exact two-tailed test. For the RsaI polymorphism, only three heterozygotes but no variant homozygote were
identified. For the −174G/C polymorphic site, only one GC heterozygote and no CC homozygote were found. Alleles s, Ser, and A
1
at the Sp1, Asn363Ser, and T → C marker sites that have been found to be polymorphic in other populations were not found
in Chinese. Significant differences of allele and genotype frequency distributions were observed at these polymorphisms (P < 0.001) after comparing with other populations. Our results suggest that variant alleles of the five markers are absent
or too rare to be useful genetic makers in Chinese, despite the fact that they have been commonly used as polymorphic markers
in osteoporosis genetic research in other populations.
Received: April 22, 2002 / Accepted: July 2, 2002
Acknowledgments. The study was partially supported by the Hunan Province Special Professor Start-up Fund (25000612), Chinese National Science
Foundation (CNSF) Outstanding Young Scientist Award (30025025), CNSF Grant (30170504), a grant from Huo Ying-Dong Education
Foundation, and a Seed Fund from the Ministry of Education of P.R. China (25000106). Some investigators (R.R.R., V.D., H.W.D.)
were partially supported by grants from the Health Future Foundation of USA, grants of National Health Institute (K01 AR02170-01,
R01 GM60402-01A1), grants from the State of Nebraska Cancer and Smoking Related Disease Research Program, and U.S. Department
of Energy grant (DE-FG03-00ER63000/A00). We thank all the study subjects for volunteering to participate in the study.
Offprint requests to: H.-W. Deng 相似文献
59.
Coexisting high-grade glandular and squamous cervical lesions and human papillomavirus infections 总被引:3,自引:0,他引:3
Bekkers RL Bulten J Wiersma-van Tilburg A Mravunac M Schijf CP Massuger LF Quint WG Melchers WJ 《British journal of cancer》2003,89(5):886-890
The frequency of high-risk human papillomavirus (hr-HPV) genotypes in patients with adenocarcinoma in situ (ACIS) with coexisting cervical intraepithelial neoplasia (CIN), ACIS without coexisting CIN, and high-grade CIN (CIN II/III) was studied, in order to gain more insight into the relation between hr-HPV infections and the development of coexisting squamous and glandular lesions. The SPF(10) LiPA PCR was used to detect simultaneously 25 different HPV genotypes in biopsies obtained from 90 patients with CIN II/III, 47 patients with ACIS without coexisting CIN, and 49 patients with ACIS and coexisting CIN. hr-HPV was detected in 84 patients (93%) with CIN II/III, 38 patients (81%) with ACIS without CIN, and in 47 patients (96%) with ACIS and coexisting CIN. A total of 13 different hr-HPV genotypes were detected in patients with CIN II/III, and only five in patients with ACIS with/without coexisting CIN. HPV 31, multiple hr-HPV genotypes, and HPV genotypes other than 16, 18, and 45 were significantly more often detected in patients with CIN II/III, while HPV 18 was significantly more often detected in patients with ACIS with/without CIN. There were no significant differences in the frequency of specific hr-HPV genotypes between patients with ACIS with or without coexisting CIN. In conclusion, the frequency of specific hr-HPV genotypes is similar for patients with ACIS without CIN and patients with ACIS and coexisting CIN, but is significantly different for patients with CIN II/III without ACIS. These findings suggest that squamous lesions, coexisting with high-grade glandular lesions, are aetiologically different from squamous lesions without coexisting glandular lesions. 相似文献
60.
A high throughout assay for human papillomavirus genotypes with fluorescence polarization 总被引:7,自引:0,他引:7
Objective To develop a simple, cheap, quick, accurate and practical method for a high throughout genotypes assay of human papillomavirus (HPV) DNA.Methods Crude DNA was extracted by a simplified proteinase K digesting method. HPV common conservative primers: GP5 /6 system was used to amplify HPV DNA in 127 samples of condylomata acuminatum (CA) and cervical scrapes by PCR, then the PCR product was assayed using a template directing terminator incorporation (TDI) and genotypes were detected with fluorescence polarization (FP). Major HPVs type-specific probes (HPV6, 11, 16, 18, 31, 33, 35 and 58) designed by us were hybridized with the specific PCR products and a special fluorescent ddNTP terminator was directly added to the end of the probe under direction of specific PCR products.The results were measured with FP and compared with the results of the DNA sequence.Results Compared with the results of DNA sequencing, the results detected with fluorescence polarization were all correct. The proposed method could detect more than one type of HPV infection,but DNA sequencing method could not. The positive rate of HPV was 100% in 78 CA biopsies.Among them, there were 14 HPV double infections [HPV6B and 11(9 cases), HPV11 and 16(4),HPV11 and 18(1)], 5 HPV triple infections [HPV6B,11 and 16(4), HPV11,16 and 18(1)], and one HPV quadruple infection (HPV6B, 11,16 and 18). The positive rate of HPV was 77% in the 49cervical scrapes. Six HPV double infections [HPV6B and 11(2), HPV11 and 16(1), HPV6B and 16(1), HPV16 and 18(1), HPV18 and 58 (1)], 3 HPV triple infections [HPV6B, 11 and 16(2),HPV11,16 and 18(1)] and one HPV quadruple infection (HPV6B,11,16 and 18) were detected incervical cancer scrapes.Conclusions The proposed method allowed a high throughout, special, simple, rapid, automatic and economical detection of HPV-DNA genotyping without a use of labeling probes. It can detect multiple HPV genotype infection and will be and useful tool in HPV genotype screening. 相似文献