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51.
Parle-McDermott A Mills JL Kirke PN O'Leary VB Swanson DA Pangilinan F Conley M Molloy AM Cox C Scott JM Brody LC 《Journal of human genetics》2003,48(4):190-193
The thermolabile variant (677TT) of methylenetetrahydrofolate reductase (MTHFR) is a known risk factor for neural tube defects
(NTDs). The relationship between a second MTHFR polymorphism (1298A→C) and NTD risk has been inconsistent between studies.
We genotyped 276 complete NTD triads (mother, father and child affected with an NTD) and 256 controls for MTHFR 1298A→C. Our
findings do not support a role for the 1298A→C polymorphism in NTDs (OR 0.85 (95% CI 0.49–1.47), p= 0.55), nor do we observe a combined effect with the 677C→T polymorphism.
Electronic Publication 相似文献
52.
Traditional approaches to generating tissue-engineered arteries in vitro rely on expansion of cells in culture to seed appropriate scaffolds. In most envisioned applications, small autologous blood vessels would be harvested and used as a source for these cells. We propose that small autologous arteries, not the cells derived from them, may be an attractive starting point for engineered arteries. This approach capitalizes on the ability of intact arteries to grow and remodel in response to chronic changes in their mechanical environment. Carotid arteries from juvenile (approximately 30-kg) pigs were stretched longitudinally in an ex vivo perfusion system over 9 days. This resulted in a 40% increase in artery length at physiological longitudinal stress and a 20 +/- 3% increase when unstressed. Control arteries were perfused for 9 days ex vivo at their physiological loaded length. Control and elongated arteries displayed native appearance (macroscopic and histological), excellent viability (cellularity and mitochondrial activity), normal vasoactivity, and similar mechanical properties (ultimate stress and ultimate strain) as compared with freshly harvested arteries. Growth, as opposed to just redistribution of existing mass, contributed to elongation as evidenced by an increase in artery weight. Results on elongation of arteries from neonatal and adolescent pigs are also presented and discussed. 相似文献
53.
Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships 总被引:9,自引:0,他引:9
This review focuses on recent advances in the structure-function relationships of thyroid-stimulating hormone (TSH) and its receptor. TSH is a member of the glycoprotein hormone family constituting a subset of the cystine-knot growth factor superfamily. TSH is produced by the pituitary thyrotrophs and released to the circulation in a pulsatile manner. It stimulates thyroid functions using specific membrane TSH receptor (TSHR) that belongs to the superfamily of G protein-coupled receptors (GPCRs). New insights into the structure-function relationships of TSH permitted better understanding of the role of specific protein and carbohydrate domains in the synthesis, bioactivity, and clearance of this hormone. Recent progress in studies on TSHR as well as studies on the other GPCRs provided new clues regarding the molecular mechanisms of receptor activation. Such advances are a result of extensive site-directed mutagenesis, peptide and antibody approaches, detailed sequence analyses, and molecular modeling as well as studies on naturally occurring gain- and loss-of-function mutations. This review integrates expanding information on TSH and TSHR structure-function relationships and summarizes current concepts on ligand-dependent and -independent TSHR activation. Special emphasis has been placed on TSH domains involved in receptor recognition, constitutive activity of TSHR, new insights into the evolution of TSH bioactivity, and the development of high-affinity TSH analogs. Such structural, physiological, pathophysiological, evolutionary, and therapeutic implications of TSH-TSHR structure-function studies are frequently discussed in relation to concomitant progress made in studies on gonadotropins and their receptors. 相似文献
54.
The maternal dominance hypothesis has been derived from workwith humans which shows that women who are more dominant thanother women are more likely to conceive sons. In both animalsand humans dominance is a characteristic or personality trait,underpinned by testosterone and responsive to a range of environmentalchanges: physical, social and psychological. Studies of thesex ratio in the social sciences and animal behaviour eithersupport or are compatible with the idea that the sex-determiningrole of X- and Y-chromosome bearing spermatozoa may be precededby factors under maternal control which provide for differentialaccess of spermatozoa. Findings in reproductive physiology andphysiological psychology suggest that folh'cular testosteroneor a related hormone may play a critical role. Reproductivephysiologists have already identified maternal mechanisms whichcould provide the context for such a model. 相似文献
55.
Rapid detection of Candida albicans in clinical blood samples by using a TaqMan-based PCR assay 总被引:2,自引:0,他引:2
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Maaroufi Y Heymans C De Bruyne JM Duchateau V Rodriguez-Villalobos H Aoun M Crokaert F 《Journal of clinical microbiology》2003,41(7):3293-3298
We describe a rapid and reproducible PCR assay for quantitation of the Candida albicans ribosomal DNA (rDNA) in clinical blood samples based on the TaqMan principle (Applied Biosystems), in which a signal is generated by cleavage of a template-specific probe during amplification. We used two fluorogenic probes based on universal, fungus-specific primers, one for the detection of C. albicans species DNA and one for the detection of all Candida genus DNA. C. albicans blastoconidia mixed with whole blood in a titration experiment yielded a linear PCR signal over a range of 3 orders of magnitude. The TaqMan-based PCR assay for C. albicans exhibited a low limit of detection (5 CFU/ml of blood) and an excellent reproducibility (96 to 99%). While the C. albicans species-specific probe had 100% specificity for C. albicans, all Candida genus-specific probes cross-reacted with other organisms likely to coinfect patients with C. albicans infections. On the basis of these data, we determined the C. albicans loads with a species-specific probe from 122 blood samples from 61 hematology or oncology patients with clinically proven or suspected systemic Candida infections. Eleven positive samples exhibited a wide range of C. albicans loads, extending from 5 to 100,475 CFU/ml of blood. The sensitivity and specificity of the present assay were 100 and 97%, respectively, compared with the results of blood culture. These data indicate that the TaqMan-based PCR assay for quantitation of C. albicans with a species-specific probe provides an attractive alternative for the identification and quantitation of C. albicans rDNA in pure cultures and blood samples. 相似文献
56.
Twin studies provide estimates of genetic and environmental contributions to cognitive ability differences, but could be based
on biased samples. Here we report whole-population estimates using twins from unique mental surveys in Scotland. The Scottish
Mental Surveys of 1st June 1932 (SMS1932) and 4th June 1947 (SMS1947), respectively, administered the same validated verbal
reasoning test to almost everyone born in 1921 or 1936 and attending school in Scotland. There were 572 twin pairs from the
SMS1932, and 517 pairs from the SMS1947. Information on zygosity was unavailable. A novel application of a mixture distribution
was used to estimate genetic and environmental components of verbal reasoning variation by maximum likelihood. We found consistent
heritability (~0.70) and shared environment (~0.21) estimates. The estimates did not change substantially when additional
quantitative traits (height and weight) were added in a multivariate analysis. More generally for studies in genetics, the
methodological innovation developed here implies that large (national) data collections can provide sufficient information
on twin pairs to estimate genetic parameters, even without zygosity. 相似文献
57.
Hentchel-Franks K Lozano D Eubanks-Tarn V Cobb B Fan L Oster R Sorscher E Clancy JP 《American journal of respiratory cell and molecular biology》2004,31(2):140-146
We investigated cystic fibrosis (CF) transmembrane conductance regulator (CFTR) regulation by A2 adenosine (Ado) receptors and beta2 adrenergic receptors in CFTR-corrected CFBE41o- airway cells and human subjects. CFBE41o- cells stimulated with Ado (10 microM), isoproterenol (Iso, 10 microM), or Ado + Iso (10 microM each) elevated cyclic AMP (cAMP) above control conditions (P < 0.001), with the Iso conditions increasing cAMP approximately 10-fold above that produced by Ado alone (P < 0.001). All agonist conditions had similar effects on short circuit current at 10 and 25 microM, with no further currents produced by subsequent stimulation with forskolin (20 microM). CFTR dependence was demonstrated by glybenclamide block of agonist-stimulated currents. Nasal potential difference studies in normal (n = 50) subjects demonstrated that Ado (10 microM) and Ado + Iso (10 microM each) produced more polarization compared with Iso (10 microM Ado increase = 44%, 10 microM Ado + Iso increase = 52%, P < 0.05 for each condition compared with Iso alone). Studies completed in patients with CF (n = 10, "severe" genotypes) confirmed that Ado-stimulated polarization was CFTR-dependent. Together, these results indicate that Ado is a potent Cl- secretagogue in vivo, with relatively small effects on cAMP levels despite strong effects on CFTR-dependent short circuit current and nasal Cl- transport. These findings support growing evidence indicating a role for Ado regulation of CFTR-dependent Cl- secretion in vivo. 相似文献
58.
Immunoassay targeting nonstructural protein 5 to differentiate West Nile virus infection from dengue and St. Louis encephalitis virus infections and from flavivirus vaccination
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Wong SJ Boyle RH Demarest VL Woodmansee AN Kramer LD Li H Drebot M Koski RA Fikrig E Martin DA Shi PY 《Journal of clinical microbiology》2003,41(9):4217-4223
West Nile virus (WNV) is an emerging flavivirus that has caused frequent epidemics since 1996. Besides natural transmission by mosquitoes, WNV can also be transmitted through blood transfusion and organ transplantation, thus heightening the urgency of development of a specific and rapid serologic assay of WNV infection. The current immunoassays lack specificity because they are based on detection of antibodies against WNV structural proteins and immune responses to structural proteins among flaviviruses cross-react to each other. Here, we describe microsphere immunoassays that detect antibodies to nonstructural proteins 3 and 5 (NS3 and NS5). In contrast to immunoassays based on viral envelope and NS3 proteins, the NS5-based assay (i) reliably discriminates between WNV infections and dengue virus or St. Louis encephalitis virus infections, (ii) differentiates between flavivirus vaccination and natural WNV infection, and (iii) indicates recent infections. These unique features of the NS5-based immunoassay will be very useful for both clinical and veterinary diagnosis of WNV infection. 相似文献
59.
60.
Stone VE 《Current HIV/AIDS reports》2005,2(4):189-193
Racial/ethnic minorities in the United States are disproportionately affected by HIV/AIDS. In addition to having higher rates
of HIV/AIDS, minorities with HIV/AIDS have higher mortality rates than others in the United States. Disparities in the care
received by minorities living with HIV/AIDS contribute to these higher mortality rates. This article provides a review of
HIV/AIDS health care disparities and explores providers’ contributions to these disparities. An important source of provider
contribution to disparities appears to be differential prescribing based on perceptions and assumptions that minority patients
may have lower adherence to highly active antiretroviral therapy. Literature regarding this topic is reviewed and strategies
for reducing disparities are suggested. 相似文献