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71.
Krone N Grischuk Y Müller M Volk RE Grötzinger J Holterhus PM Sippell WG Riepe FG 《The Journal of clinical endocrinology and metabolism》2006,91(7):2682-2688
CONTEXT: Congenital adrenal hyperplasia is a group of autosomal recessive inherited disorders of steroidogenesis. The deficiency of steroid 11-hydroxylase (CYP11B1) resulting from mutations in the CYP11B1 gene is the second most frequent cause. OBJECTIVE: We studied the functional and structural consequences of two CYP11B1 missense mutations, which were detected in a 1.8-yr-old boy with acne and precocious pseudopuberty, to prove their clinical relevance and study their impact on CYP11B1 function. RESULTS: The in vitro expression studies in COS-7 cells revealed an almost complete absence of CYP11B1 activity for the P94L mutant to 0.05% for the conversion of 11-deoxycortisol to cortisol. The A368D mutant severely reduced the CYP11B1 enzymatic activity to 1.17%. Intracellular localization studies by immunofluorescence revealed that the mutants were correctly localized. Introducing these mutations in a three-dimensional model structure of the CYP11B1 protein provides a possible explanation for the effects measured in vitro. We hypothesize that the A368D mutation interferes with structures important for substrate specificity and heme iron binding, thus explaining its major functional impact. However, according to structural analysis, we would expect only a minor effect of the P94L mutant on 11-hydroxylase activity, which contrasts with the observed major effect of this mutation both in vitro and in vivo. CONCLUSION: Analyzing the in vitro enzyme function is a complementary procedure to genotyping and a valuable tool for understanding the clinical phenotype of 11-hydroxylase deficiency. This is the basis for accurate genetic counseling, prenatal diagnosis, and treatment. Moreover, the combination of in vitro enzyme function and molecular modeling provides valuable insights in cytochrome P450 structural-functional relationships, although one must be aware of the limitations of in silico-based methods. 相似文献
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A N Tulupov L V Filev I V Volchek V I Popov A N Bel'skikh 《Vestnik khirurgii imeni I. I. Grekova》1991,146(4):26-28
The antiviral cellular resistance was studied in 22 patients with acute sepsis of different etiology. The acute sepsis was found to develop as a rule against the background of substantially decreased antiviral cellular resistance. So, treatment of this category of patients should include not only antibacterial and antimycotic, but also antiviral methods of therapy. 相似文献
74.
Eugene. V. Shlyakhto Eugene. I. Shwartz Yulia. B. Nefedova Anna. V. Zukova Tatyana. A. Vinnic Alexandra. O. Conrady 《Blood pressure》2001,10(3):135-141
Objective: The aim of the present study was to determine if there is an association of different gene polymorphisms of renin-angiotensin system and left ventricular hypertrophy (LVH) in patients with essential hypertension (EH) in St Petersburg population. Patients and methods: We examined 156 patients (the mean age 49 ±8 years) with mild-to-moderate EH recruited from the general population of the outpatient clinic. Left ventricular mass was measured by echocardiography and left ventricular mass index (LVMI) was calculated. Subjects were genotyped for I/D polymorphism of the angiotensin-converting enzyme (ACE) gene, A1166C polymorphism of renin-of the AT1 receptor gene, M235T polymorphism of angiotensinogen gene and-6G/A polymorphism of its promoter region. Results: Genotype distribution of the sample obeyed Hardy-Weinberg equilibrium and was comparable to that reported previously for hypertensive individuals. Groups of patients with II, ID and DD polymorphism of ACE gene did not differ significantly in their LVMI levels. Furthermore, neither ID ACE-gene polymorphism nor AT1-receptor gene and angiotensinogen gene polymorphism was associated with LVH. Additionally, no any significant gene-gene interactions were found to be associated with LVH in the group studied. Conclusions: In the light of these observations it seems reasonable to make a preliminary conclusion about lack of association between LVH and distinct polymorphisms of renin-angiotensin system genes in the population studied. 相似文献
75.
Development of a group and family‐based cognitive behavioural therapy program for youth at risk for psychosis 下载免费PDF全文
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Yuriy K Bashmakov Nailya A Zigangirova Yulia P Pashko Lidia N Kapotina Ivan M Petyaev 《Comparative hepatology》2010,9(1):3
Background
Perihepatitis is rare but consistently occurring extragenital manifestation of untreated Chlamydia trachomatis infection. Despite of possible liver involvement in generalized C. trachomatis infection, the ability of the pathogen to propagate in the hepatic cells and its impact on liver functions is not thoroughly investigated. The effect of mevastatin, an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase, on C. trachomatis growth in human hepatoma cell line HepG2 has been studied. Bacterial growth was assessed by immunostaining with FITC-labeled monoclonal antibody against chlamydial lipopolysaccharide and by RT-PCR for two chlamydial genetic markers (16S rRNA and euo). 相似文献80.
Yulia M. Ulybina Ekatherina Sh. Kuligina Nathalia V. Mitiushkina Nathalia Yu. Sherina Grigoriy A. Yanus Tatiana V. Gorodnova Anna S. Katanugina Andrey V. Koloskov Alexandr V. Togo Evgeny N. Imyanitov 《Experimental gerontology》2010
Our previous studies, which included genotyping of multiple coding apoptotic gene polymorphisms, unexpectedly demonstrated a depletion of heterozygous CASP5 Ala90Thr (rs507879, c.268 G > A) genotypes in elderly subjects. Present investigation was aimed to validate this trend. An analysis of 510 subjects aged 75–103 years revealed 205 (40%) CASP5 Ala90Thr heterozygotes as compared to 254 (50%) expected from the minor allele frequency 0.470 (p = 0.000014). This deviation was not observed in 549 middle-aged (18–50 years) controls (270 (49%) heterozygotes observed vs. 274 (50%) expected; minor allele frequency 0.475; p = 0.743). Unfavorable significance of CASP5 heterozygous genotype may be explained by the role of the caspase-5 in inflammation-related processes. Almost all prior gene-longevity association studies focused on discrimination between “good” and “bad” gene variants. Here we present a distinct situation, where the combination of alternative alleles (i.e., heterozygosity) appears to be unfavorable as compared to the homozygous carriership of either gene variant. 相似文献