The human glycoprotein PC-1 codon Q121 allele has been correlated with insulin resistance, but not with type 2 diabetes or obesity. We investigated the prevalence of PC-1 Q121 in the Dominican Republic population (755 subjects studied) and whether this variant is associated with insulin resistance, obesity, or type 2 diabetes. The prevalence of PC-1 Q121 was high compared with that in other populations. The proportions of genotypes detected were: KK, 21.6%; KQ, 48.3%; and QQ, 30.1%. This compares to approximately 74%, 24%, and 2% in other populations. Among nonobese, nondiabetic subjects, the insulin response of KQ (P = 0.027) and QQ (P = 0.031) subjects was greater during the oral glucose tolerance test than that of KK subjects, whereas plasma glucose profiles were comparable. The Q allele was more prevalent in obese type 2 diabetics than in controls (P = 0.026; odds ratio = 1.56). Multiple regression analysis, after adjusting for age, gender, and body mass index, showed the QQ genotype to be associated with type 2 diabetes (P = 0.043; odds ratio = 2.74), but not obesity (P = 0.068). These results indicate that the PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic, contributing to both insulin resistance and type 2 diabetes.
Innate immunity plays important roles in the primary defense against pathogens, and epidemiological studies have suggested a role for Toll-like receptor 1 (TLR1) in Helicobacter pylori susceptibility. Microarray analysis of gastric biopsy specimens from H. pylori-positive and uninfected subjects showed that TLR10 messenger RNA (mRNA) levels were upregulated approximately 15-fold in infected subjects; these findings were confirmed by real-time quantitative polymerase chain reaction analysis. Immunohistochemical investigation showed increased TLR10 expression in the gastric epithelial cells of infected individuals. When H. pylori was cocultured with NCI-N87 gastric cells, both TLR10 and TLR2 mRNA levels were upregulated. We compared the ability of TLR combinations to mediate nuclear factor-κB (NF-κB) activation. Compared with other TLR2 subfamily heterodimers, the TLR2/TLR10 heterodimer mediated the greatest NF-κB activation following exposure to heat-killed H. pylori or H. pylori lipopolysaccharide. We conclude that TLR10 is a functional receptor involved in the innate immune response to H. pylori infection and that the TLR2/TLR10 heterodimer functions in H. pylori lipopolysaccharide recognition.
The aim of this study was to determine which morphological features of low-intensity lesions in the peripheral zone of the prostate are predictable of prostate cancer on pre-biopsy T2-weighted integrated endorectal phased-array MR images. The MR examinations were performed in 69 consecutive patients with elevated level of prostate-specific antigen (>4 ng/ml) and/or a positive digital rectal examination before transperineal 12-site biopsy. Two radiologists evaluated presence of lesions, their morphological features, and possibility of malignancy in divided into four sections of the peripheral zone. Imaging analysis findings were compared with biopsy results. Discriminative features were selected by stepwise logistic regression. Descriptive statistics and receiver operating characteristics (ROC) curves were also calculated. Sixty-eight benign lesions and 23 malignant lesions were found. Wedge shape and diffuse extensions without mass effect were significantly associated with benignity ( P=0.0105 and 0.002, respectively). Lesion size was significantly associated with malignancy ( P=0.0001). For evaluating probability of malignancy for lesions, regression model showed a comparable accuracy with the total impression for the readers in ROC analysis (Az 0.9095 vs 0.9266, respectively). Wedge shape, diffuse extension without mass effect, and size are the morphological features of low-intensity lesions in the peripheral zone on pre-biopsy T2-weighted MR images that give the best prediction of malignancy.
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