Clinical Significance of Telomerase Activity and Telomere Length in Various Liver Diseases

We investigated the clinical significance of telomerase activity and telomere length in hepatocellular carcinomas (HCCs) and chronic liver diseases. Telomerase activity was assessed quantitatively using \u27Stretch PCR\u27 assay and telomere length by Southern blotting in 24 HCCs, 2 focal nodular hyperplasia, 8 liver cirrhosis, 10 chronic hepatitis and 8 histologically normal livers. The latter were obtained from normal sections of resected specimens of cholangiocellular carcinoma, metastatic liver tumor or hemangioma. The relative titers of telomerase activity (RTA) were significantly higher in HCCs (average, 54 units) than in chronic liver diseases (average, 0.6 units) (P<0.001). In comparison, RTA was less than 2 units in non-malignant liver tissues. Telomere length in cirrhotic liver tissues was significantly shorter than in normal livers and tended to be shorter than those in chronic hepatitis. Telomere length and RTA correlated with the grading of tissue derangement in chronic liver diseases. Our results suggest that RTA estimated by Stretch PCR assay might be clinically useful for accurate diagnosis of liver diseases, particularly HCCs. In addition, telomere length seems to having a possibility as a useful predictor for risk of hepatocarcinogenesis

The impact of obesity and adiponectin signaling in patients with renal cell carcinoma: A potential mechanism for the obesity paradox

Although obesity increases the risk of renal cell carcinoma (RCC), obese patients with RCC experience longer survival than non-obese patients. However, the mechanism of this obesity paradox is unknown. We examined the impact of preoperative BMI, serum total adiponectin (sAd) level, total adiponectin secretion from perinephric adipose tissue, and intratumoral expression of adiponectin receptors on RCC aggressiveness and survival. We also investigated the mechanism underlying enhanced cancer aggressiveness in RCC cells stimulated with exogenous adiponectin. Overweight and obese patients had significantly lower grade cancers than normal patients in all patients and in those without metastasis (p = 0.003 and p = 0.027, respectively). Cancer-specific survival was significantly longer in overweight and obese patients than in normal patients in all patients (p = 0.035). There was a weak inverse correlation between sAd level and BMI in RCC patients (r = -0.344, p = 0.002). Tumor size was slightly correlated with sAd level, and high sAd was significantly associated with poor overall survival rates in patients with non-metastatic RCC (p = 0.035). Adiponectin levels in perinephric adipose tissue and intratumoral AdipoRl/R2 expression were not correlated with RCC aggressiveness or survival. Proliferation significantly increased in 786-0 and Caki-2 cells exposed to exogenous adiponectin, whereas cell invasion and migration were unaffected. In addition, exogenous adiponectin significantly inhibited starvation-and metformin-induced apoptosis, and up-regulated p-AMPK and Bcl-xL levels. In summary, low BMI and high adiponectin levels are associated with aggressive cell behaviors and poor survival in surgically-treated RCC patients. The effects of adiponectin on proliferation and apoptosis might underlie the obesity paradox of RCC

Whole-cell circular dichroism difference spectroscopy reveals an in vivo-specific deca-heme conformation in bacterial surface cytochromes

We established whole-cell circular dichroism difference spectroscopy to identify the inter-heme interaction in deca-heme cytochrome protein MtrC in whole cell. Our data showed that the heme alignment of reduced MtrC in whole cell is distinct from that in purified one, suggesting the in vivo specific electron transport kinetics

Congenital limb deficiency in Japan: a cross-sectional nationwide survey on its epidemiology

Abstract Background Congenital limb deficiency is a rare and intractable disease, which impairs both function and appearance of the limbs. To establish adequate medical care, it is necessary to reveal the actual conditions and problems associated with this disease. However, there have been no extensive epidemiological surveys in Japan addressing this disease. This is the first nationwide epidemiological survey of congenital limb deficiency in this country. Methods With the cooperation of epidemiology experts, we performed a two-stage nationwide survey to estimate the number of patients with congenital limb deficiency and reveal basic patient features. We targeted orthopaedic surgery, paediatric, and plastic surgery departments. Hospitals were categorized according to the institution type and the number of hospital beds; hospitals were randomly selected from these categories. We selected 2283 departments from a total 7825 departments throughout Japan. In this study, we defined congenital limb deficiency as partial or total absence of the limbs, proximal to the proximal interphalangeal joint of the fingers/lesser toes or interphalangeal joint of the thumb/great toe. We distributed the first survey querying the number of initial patient visits from January 2014 to December 2015. Targets of the second survey were departments that reported one or more initial patient visits in the first survey. Results In the first survey, 1767 departments responded (response rate: 77.4%). Among them, 161 departments reported one or more initial patient visits. We conducted the second survey among these 161 departments, of which 96 departments responded (response rate: 59.6%). The estimated number of initial visits by patients with congenital limb deficiency was 417 (95% confidence interval: 339–495) per year in 2014 and 2015. The estimated prevalence of congenital limb deficiency in Japan was 4.15 (95% confidence interval: 3.37–4.93) per 10,000 live births. The sex ratio was 1.40. Upper limbs were more affected than lower limbs. Conclusions We revealed the estimated number of initial patient visits per year and birth prevalence of congenital limb deficiency in Japan. Our results will contribute to establishing the disease concept and grades of severity of congenital limb deficiency