Aims/hypothesis. Resistin is thought to be an important link between obesity and insulin resistance. It has been suggested that genetic polymorphism in the promoter of resistin gene is a determinant of resistin mRNA expression and possibly associated with obesity and insulin resistance. In this study, we investigated the association between the genotype of resistin promoter and its plasma concentrations. Methods. We examined g.-537A>C and g.-420C>G polymorphisms in the resistin promoter and measured plasma resistin concentrations in Korean subjects with or without Type 2 diabetes. We also did haplotypebased promoter activity assays and the gel electrophoretic mobility shift assay. Results. The −420G and the −537A alleles, which were in linkage disequilibrium, were associated with higher plasma resistin concentrations. Individuals with haplotype A-G (−537A and −420G) had significantly higher plasma resistin concentrations than the others. Haplotype A-G had modestly increased promoter activity compared to the other haplotypes. Electrophoretic mobility shift assay showed that the −420G allele is specific for binding of nuclear proteins from adipocytes and monocytes. However, none of the two polymorphisms were associated with Type 2 diabetes or obesity in our study subjects. Conclusions/interpretation. Polymorphisms in the promoter of resistin gene are major determinants of plasma resistin concentrations in humans. [Diabetologia (2004) . Moreover, obese mice given an antiresistin antibody had increased insulin-stimulated glucose uptake, whereas the treatment of normal mice with recombinant resistin impaired insulin action [4]. Resistin therefore could link obesity with insulin resistance and diabetes in mouse models. However, subsequent studies in rodent models have produced disparate findings on the role of resistin in obesity and insulin resistance [5,6,7].In humans, the expression of resistin in adipocytes is much lower than that seen in rodents and does not differ between normal, insulin-resistant or Type 2 diabetic patients [8,9,10]. Little is known about the relationship between circulating resistin concentrations Resistin belongs to a novel family of cystein-rich C-terminal domain proteins called resistin-like molecules, which are identical to those found in inflammatory
Aims/hypothesis This multinational study was conducted to investigate the association between a mitochondrial DNA (mtDNA) T16189C polymorphism and type 2 diabetes in Asians. The mtDNA 16189C variant has been reported to be associated with insulin resistance and type 2 diabetes. However, a recent meta-analysis concluded that it is negatively associated with type 2 diabetes in Europids. Since the phenotype of an mtDNA mutant may be influenced by environmental factors and ethnic differences in the nuclear and mitochondrial genomes, we investigated the association between the 16189C variant and type 2 diabetes in Asians. Methods The presence of the mtDNA 16189C variant was determined in 2,469 patients with type 2 diabetes and 1,205
Hepatocyte growth factor (HGF) is a multifunctional cytokine which acts as a mitogen, motogen, morphogen and angiogenic factor of epithelial cells. HGF receptor is encoded by a proto-oncogene, c-met, which is overexpressed in various cancers. The role of HGF and c-Met in prostate carcinogenesis, especially in the early stages, is undefined. In this study, prostatic dysplasia and carcinomas were induced by testosterone propionate and 17 beta-estradiol in Noble rats. The expression of HGF and c-Met was assessed at a protein level by immunohistochemistry and western blot analysis. Intense immunostaining for HGF alpha and c-Met beta-chain was co-localized in dysplastic lesions and in primary and metastatic cancer cells. The levels of HGF alpha expression were similar among normal control, dysplastic and cancerous prostate tissues, as determined by western blot analysis. Immunoblot study for c-Met under reducing conditions identified two bands at 145 kDa (beta-subunit of c-Met) and 170 kDa (precursor form of c-Met) in rat liver extracts. However, two bands at approximately 220 and 245 kDa were detected in hormone-treated dysplastic prostate tissues and primary tumors. Overexpression of the 220 kDa band was observed in long-term (10-12 months) hormone-treated prostate and primary tumor extracts. Metastatic tumors consistently exhibited up-regulation of a single 245 kDa band. Under non-reducing conditions, however, protein bands of 220, 280 or 300 kDa were seen in the blots. The hormone-treated prostate tissues and metastatic tumors expressed the 220 and 300 kDa proteins, respectively. The majority of primary tumors expressed the 280 kDa protein. In summary, HGF and its receptor, c-Met, were co-expressed in dysplastic and tumor cells, suggesting that an autocrine mode of action may be involved in prostate carcinogenesis. The close correlation of expression of the high-molecular-weight isoforms of c-Met with different stages of carcinogenesis implicates that they might play differential roles in the onset, progression, growth and metastasis in prostate cancer.
Propionibacterium acnes is a gram-positive anaerobic bacillus and a normal inhabitant of the skin. Although it is often considered a contaminant of blood cultures, it can occasionally cause serious infections, including postoperative central nervous system infections. Here, we report the case of a 70-yr-old man who developed a large cerebral abscess caused by P. acnes 13 months after neurosurgery. Immediate gram staining of the pus from his brain revealed the presence of gram-positive coccobacilli. However, colony growth was observed only after 5 days of culture. Therefore, we performed 16S rRNA gene sequencing of the pus specimen. The isolate was identified as P. acnes. The colonies developed 9 days after the initial culture. The API Rapid ID 32A test (bioMérieux, France) was performed using a colony, but an unacceptable profile was obtained. Then, the pus was transferred into the enrichment broths of the BACTEC FX (Becton Dickinson, USA) and BacT/Alert 3D (bioMérieux, Organon Teknika, USA) systems, but only the BACTEC FX system could detect growth after 5 days. We performed 16S rRNA gene sequencing and API Rapid 32A profiling with a colony recovered from Brucella agar, which was inoculated with the microbial growth in the enrichment broth from the BACTEC FX system. The organism was identified as P. acnes by both methods. This case suggests that 16S rRNA gene sequencing may be a useful alternative for identifying slowly growing P. acnes from specimens that do not show growth after 5 days of culture.
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