Transcriptomic analysis of left ventricle myocardium in an SHR congenic line with ameliorated cardiac fibrosis.

Metabolic syndrome and one of its manifestations, essential hypertension, is an important cause of worldwide morbidity and mortality. Morbidity and mortality associated with hypertension are caused by organ complications. Previously we revealed a decrease of blood pressure and an amelioration of cardiac fibrosis in a congenic line of spontaneously hypertensive rats (SHR), in which a short segment of chromosome 8 (encompassing only 7 genes) was exchanged for a segment of normotensive polydactylous (PD) origin. To unravel the genetic background of this phenotype we compared heart transcriptomes between SHR rat males and this chromosome 8 minimal congenic line (PD5). We found 18 differentially expressed genes, which were further analyzed using annotations from Database for Annotation, Visualization and Integrated Discovery (DAVID). Four of the differentially expressed genes (Per1, Nr4a1, Nr4a3, Kcna5) belong to circadian rhythm pathways, aldosterone synthesis and secretion, PI3K-Akt signaling pathway and potassium homeostasis. We were also able to confirm Nr4a1 2.8x-fold upregulation in PD5 on protein level using Western blotting, thus suggesting a possible role of Nr4a1 in pathogenesis of the metabolic syndrome.

[Mutations in genes affecting fertility of men - current routine laboratory genetic diagnostics and searching for more DNA segments and genes influencing spermatogenesis]. / Mutace v genech ovlivnujících plodnost muzu - soucasná rutinní laboratorní genetická diagnostika a hledání dalsích úseku DNA a genu, ovlivnujících spermatogenezi.

OBJECTIVE: To present the results of molecular genetics analysis in men with reproductive disorders focusing on the DNA segments and genes which affect spermatogenesis. DESIGN: Original article. SETTING: Institute of Biology and Medical Genetics of the First Faculty of Medicine and General Teaching Hospital, Prague. METHODS: One hundred and twenty-three patients identified with a fertility disorder were screened for mutations of the CFTR gene. In all patients were performed cytogenic analysis and assessment of Y-chromosome microdeletions. In 107 patients where the fertility was not detected by routine examination we performed an analysis for X-chromosome microdeletions (CNV64, CNV67, CNV69) and in certain genes necessary for normal spermatogenesis (AGFG1, CAPZA3, CNTROB, HOOK1, GOPC, SPATA16). RESULTS: Our results did not reveal any negative efffects of X-chromosome microdeletion on spermatogenesis. Analysis of six genes showed in two patients in gene SPATA16 a homozygotic haplotype [1526C>T + 1577T>C] which can be most probably responsible for the fertility in two examined patients. CONCLUSION: According to our results we do not recommend introduction of X-chromosome microdeletions assays in areas CNV64 , CNV67 and CNV69 into routine diagnostic. Regarding the selected genes affecting spermatogenesis, our results showed that homozygotic haplotype [ 1526C>T + 1577T>C] in SPATA16 gene is very likely responsible for infertility in two of our patients. The above mentioned haplotype deserves attention in the investigation of male infertility.

[Cholecystectomy--the risk factors for endometrial carcinoma?]. / Cholecystektomie--rizikový faktor karcinomu endometria?

AIM: The aim of this study was to find out if the incidence of cholecystectomy is more frequent in patiens with endometrial carcinoma and if the incidence of the anamnestic information concerning cholecystectomy in patiens with endometrial carcinoma influences the course and the result of the treatment of the said tumorous disease. TYPE OF STUDY: Retrospective study. METHODS: 470 females with endometrial carcinoma were entered into the study, the group was divided into the patients who have had cholecystectomy and those who have not had it. There was a control group of 370 females. All the said patients were diagnosed and subsequently treated at the Department of Gynecology and Obstetrics Masaryk University affiliated Hospital, Brno between January 2004 and December 2006. RESULTS: We have not proved any statistically significant difference concerning the origin of the endometrial carcinoma after a performed cholecystectomy. There was no difference in grading as well as the stage according to the FIGO standards. Nonetheless, we can say that the patients with endometrial carcinoma and cholecystectomy have significantly higher BMI. CONCLUSION: The relation between cholecystectomy and the endometrial carcinoma can be influenced by various factors. However, we can assume that the pathological processes of cholelithiasis are pathophysiologically connected with the development of changes, which fall within the category of hormonal risk factors for the development of endometrial carcinoma.

PXO set of recombinant inbred strains of the rat: a new strain distribution pattern containing 448 markers.

A new PXO set of RIS represents a fixed F2 population derived from polydactylous (P) congenic strain SHR.Lx and oligodactylous (O) RI strain BXH2. The PXO strains were derived as a complementary set to current RIS (HXB, BXH) of the laboratory rat. All PXO strains are homozygous in the Lx allele and express different morphological phenotypes of the polydactyly-luxate syndrome (PLS) due to variable combinations of Lx modifying genes of either SHR or BN origin. The SDP is being built up by genotyping polymorphic microsatellite markers and several gene polymorphisms. The markers were ordered according to data from public mapping resources such as the Rat Genome Database (rgd.mcw.edu) and current SDP of the other RI strain sets (HXB, BXH). The resulting map corresponding to the common SDP of HXB, BXH RIS sets consists of 448 markers, from which 261 were proven to be polymorphic in the PXO set. The SDP of PXO strains with polymorphic markers arranged in approximately 5 cM intervals is ready for the association analysis and interval mapping in interconnection with the SDP of HXB/BXH strains.

Binding of thyroxine and triiodothyronine in solubilized nuclear extract of human leukocytes.

An in vitro study was carried out of the interaction of thyroidal hormones with leukocytes and with a solubilized extract of the nuclear fraction of human leukocytes. The respective association constants characterising the binding of triiodothyronine (T3) and thyroxine (T4) to whole leukocytes are roughly equal (for T3, KA = 3.1 X 10(11) 1/mol and for T4, KA = 4 X 10(11) 1/mol) but a 0.4 KCl extract of the nuclear fraction exhibits a different affinity to T3 (KA = 2.16 X 10(11) 1/mol) in comparison with T4 (KA = 1.3 X 10(10) 1/mol). In the nuclear extract, both hormones are bound with the affinity higher for T3 than for T4. The soluble nuclear binding protein in human leukocytes had a molecular weight 46 000, was chromatographically homogenous in chromatography on Sepharose 2B and Sephadex G200, and exhibited a longlasting stability at -25 degrees C, without any marked change in the binding affinity to thyroidal hormones.