Serum albumin and mortality risk in a hyperendemic area of HCV infection in Japan

<p>Abstract</p> <p>Background</p> <p>Hypoalbuminemia has been shown to be associated with increased mortality. We reported a mass screening in 1990 of X town in Japan, which demonstrated a high prevalence of hepatitis C virus (HCV) infection. This follow-up study determined, through a period of 12 years, whether serum albumin levels impact on the life prognosis of the residents of X town.</p> <p>Results</p> <p>Of the 509 subjects, 69 had died and 55 had moved to other regions by 2002. Therefore, we analyzed 454 people for whom we could confirm life and death between 1990 and 2002. Albumin levels were assigned to two groups, low (<4.0 g/L, group A) and normal (≥4.0 g/L, group B). Of the 454 subjects analyzed, 25 were in group A and 429 in group B and the mortality was 68.0% (17/25 cases, P < 0.00001 vs. group B) and 12.1% (52/429), respectively. Mortality from hepatocellular carcinoma (HCC) was 66.7% in group A (6/9 cases, P = 0.01 vs. group B) and 15.8% (3/19) in group B. According to multivariate analysis, five factors - 50 years or older, low albumin level (<4.0 g/L), abnormal AST level, history of smoking, and absence of alcohol consumption - were associated with death. The adjusted odds ratios for these five factors were 20.65, 10.79, 2.58, 2.24 and 2.08, respectively, and each was statistically significant.</p> <p>Conclusions</p> <p>We show that the serum albumin level is an independent risk factor for mortality from all causes in the residents of X town and an important prognostic indicator. Improvement of hypoalbuminaemia should be considered for improvement of prognosis.</p

Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-ligand pathway in mice

Peer reviewedPublisher PD

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Interaction between maternal caffeine intake during pregnancy and CYP1A2 C164A polymorphism affects infant birth size in the Hokkaido study

BACKGROUND: Caffeine, 1,3,7-trimethylxanthine, is widely consumed by women of reproductive age. Although caffeine has been proposed to inhibit fetal growth, previous studies on the effects of caffeine on infant birth size have yielded inconsistent findings. This inconsistency may result from failure to account for individual differences in caffeine metabolism related to polymorphisms in the gene for CYP1A2, the major caffeine-metabolizing enzyme. METHODS: Five hundred fourteen Japanese women participated in a prospective cohort study in Sapporo, Japan, from 2002 to 2005, and 476 mother-child pairs were included for final analysis. RESULTS: Caffeine intake was not significantly associated with mean infant birth size. When caffeine intake and CYP1A2 C164A genotype were considered together, women with the AA genotype and caffeine intake of >= 300 mg per day had a mean reduction in infant birth head circumference of 0.8 cm relative to the reference group after adjusting for confounding factors. In a subgroup analysis, only nonsmokers with the AA genotype and caffeine intake of >= 300 mg per day had infants with decreased birth weight (mean reduction, 277 g) and birth head circumference (mean reduction, 1.0 cm). CONCLUSION: Nonsmokers who rapidly metabolize caffeine may be at increased risk for having infants with decreased birth size when consuming >= 300 mg of caffeine per day.This is the author's accepted version of their manuscript of the following article: Sasaki, et al. Pediatric Research (2017) 82, 19–28. The final publication is available at: http://dx.doi.org/10.1038/pr.2017.7

A retrospective case-control study of hepatitis C virus infection and oral lichen planus in Japan: association study with mutations in the core and NS5A region of hepatitis C virus

<p>Abstract</p> <p>Background</p> <p>The aims of this study were to assess the prevalence of hepatitis C virus (HCV) infection in Japanese patients with oral lichen planus and identify the impact of amino acid (aa) substitutions in the HCV core region and IFN-sensitivity-determining region (ISDR) of nonstructural protein 5A (NS5A) associated with lichen planus.</p> <p>Methods</p> <p>In this retrospective study, 59 patients (group 1-A) with oral lichen planus among 226 consecutive patients who visited our hospital and 85 individuals (group 1-B, controls) with normal oral mucosa were investigated for the presence of liver disease and HCV infection. Risk factors for the presence of oral lichen planus were assessed by logistic regression analysis. We compared aa substitutions in the HCV core region (70 and/or 91) and ISDR of NS5A of 12 patients with oral lichen planus (group 2-A) and 7 patients who did not have oral lichen planus (group 2-B) among patients (high viral loads, genotype 1b) who received interferon (IFN) therapy in group1-A.</p> <p>Results</p> <p>The prevalence of anti-HCV and HCV RNA was 67.80% (40/59) and 59.32% (35/59), respectively, in group 1-A and 31.76% (27/85) and 16.47% (14/85), respectively, in group 1-B. The prevalence of anti-HCV (<it>P </it>< 0.0001) and HCV RNA (<it>P </it>< 0.0001) in group 1-A was significantly higher than those in group 1-B. According to multivariate analysis, three factors - positivity for HCV RNA, low albumin level (< 4.0 g/dL), and history of smoking - were associated with the development of oral lichen planus. The adjusted odds ratios for these three factors were 6.58, 3.53 and 2.58, respectively, and each was statistically significant. No significant differences in viral factors, such as aa substitutions in the core region and ISDR of NS5A, were detected between the two groups (groups 2-A and -B).</p> <p>Conclusion</p> <p>We observed a high prevalence of HCV infection in patients with oral lichen planus. Longstanding HCV infection, hypoalbuminemia, and smoking were significant risk factors for the presence of oral lichen planus in patients. It is advisable for Japanese patients with lichen planus to be tested for HCV infection during medical examination.</p

Carcinoma Arising from Brunner's Gland in the Duodenum after 17 Years of Observation – A Case Report and Literature Review

A 60-year-old man presented with melena and hematemesis in 1984. Esophagogastroduodenoscopy (EGD) detected a small protruding lesion in the duodenal bulb, which was diagnosed as Brunner's adenoma. No significant change was detected in subsequent annual EGD and biopsies for 10 years, after which the patient was not observed for 7 years. The patient presented with melena again in 2001. The lesion had changed shape to become a 10 mm sessile tumor with a central depression, and following a biopsy was diagnosed as an adenocarcinoma. The patient underwent partial resection of the duodenum. Histopathological assessment showed acidophilic cells with swollen nuclei, and clear cells forming a tubular or papillary tubule in the mucosal lamina propria and submucosal layer. The tumor cells stained positive for lysozyme, indicating that they arose from Brunner's gland. The patient showed no sign of recurrence and was disease-free for more than 34 months after surgery. The patient died of pneumonia. This is an extremely rare case of primary duodenal carcinoma arising from Brunner's gland in a patient observed for 17 years

CYP3A4 and CYP3A5 genotyping by Pyrosequencing

BACKGROUND: Human cytochrome P450 3A enzymes, particularly CYP3A4 and CYP3A5, play an important role in drug metabolism. CYP3A expression exhibits substantial interindividual variation, much of which may result from genetic variation. This study describes Pyrosequencing assays for key SNPs in CYP3A4 (CYP3A4*1B, CYP3A4*2, and CYP3A4*3) and CYP3A5 (CYP3A5*3C and CYP3A5*6). METHODS: Genotyping of 95 healthy European and 95 healthy African volunteers was performed using Pyrosequencing. Linkage disequilibrium, haplotype inference, Hardy-Weinberg equilibrium, and tag SNPs were also determined for these samples. RESULTS: CYP3A4*1B allele frequencies were 4% in Europeans and 82% in Africans. The CYP3A4*2 allele was found in neither population sample. CYP3A4*3 had an allele frequency of 2% in Europeans and 0% in Africans. The frequency of CYP3A5*3C was 94% in Europeans and 12% in Africans. No CYP3A5*6 variants were found in the European samples, but this allele had a frequency of 16% in the African samples. Allele frequencies and haplotypes show interethnic variation, highlighting the need to analyze clinically relevant SNPs and haplotypes in a variety of ethnic groups. CONCLUSION: Pyrosequencing is a versatile technique that could improve the efficiency of SNP analysis for pharmacogenomic research with the ultimate goal of pre-screening patients for individual therapy selection