Distribution of Abcg2 (BCRP) and Abcc2 (MRP2) mRNAs in rat small intestine and liver

The purpose of this study is to examine the distribution of Abcg2 and Abcc2 mRNAs in the intestine and liver of male Wistar rats, and any regional differences. Nine-week-old male rats were used, and their intestine divided equally into nine segments. The expression patterns of Abcg2 and Abcc2 mRNAs in the intestine and liver were examined using a reverse transcription-polymerase chain reaction (RT-PCR). PCR products for Abcg2 mRNA were readily detectable in the intestine, but no bands were detected in the liver. In addition, the level of Abcg2 mRNA increased significantly from the duodenum to ileum, indicating a regional difference in Abcg2 mRNA expression in the intestine. This regional difference was comparable to that of Abcb1/mdr1a as reported previously. On the other hand, Abcc2 mRNA was detected at a higher level in the liver than in the intestine. However, there was no regional difference in Abcc2 mRNA expression in the intestine. Collectively, Abcg2 was predominant in the intestine rather than liver in male Wistar rats, whereas Abcc2 was predominant in the liver. These findings will provide useful information for evaluating the gastrointestinal secretion of drugs as well as drug-drug interactions in rats

CLINICOPATHOLOGICAL STUDY OF CEREBRAL SUBCORTICAL CAVERNOUS ANGIOMA AS EPILEPTOGENIC FOCUS

The authors conducted a comparative histological study of two groups of patients with cerebral subcortical cavernous angioma. One group was composed of 5 asymptomatic cases detected accidentally. The other group was composed of 4 patients presenting as epilepsy. The results obtained may be summarized as follows ; 1) Hemosiderin deposit and gliosis were seen in all cases examined ; 2) Granulomatous change was a histological finding associated with epileptogenesis ; 3) The histological changes, starting with proliferation of collagen fibers and leading to hyaline degeneration, calcification, and then hemangioma calcificans, seem to represent a course of spontaneous healing, when viewed from epileptogenesis

Molecular characteristics of methicillin-resistant Staphylococcus aureus isolated from skin and soft tissue infections collected in the Japanese nationwide surveillance

Skin and soft tissue infections (SSTI) are a common infection among both outpatients and inpatients. The most frequently isolated bacterium in SSTI was Staphylococcus aureus, a quarter of which was methicillin-resistant S. aureus (MRSA). In this study, to investigate molecular epidemiology of the 141 MRSA strains collected in the Japanese nationwide surveillance, we performed multiplex real-time polymerase chain reaction to detect staphylococcal cassette chromosome mec (SCCmec) type and virulence genes. The percentage of SCCmec types I, II, III and IV was 1.4%, 52.5%, 5.7% and 40.4%, respectively. According to the SCCmec type, we classified the strains into health-care-associated (HA)-MRSA (n = 84) and community-associated (CA)-MRSA (n = 57). Among the virulence genes, the percentage of enterotoxin C gene-positive strains was significantly higher in CA-MRSA than in HA-MRSA. No significant differences were detected between the two groups in terms of antibiotic susceptibility and patients’ background information, classification of SSTI or symptoms of SSTI

The Shiga toxin 2 production level in enterohemorrhagic Escherichia coli O157:H7 is correlated with the subtypes of toxin-encoding phage

Enterohemorrhagic E. coli (EHEC) causes diarrhea and hemorrhagic colitis with life-threatening complications, such as hemolytic uremic syndrome. Their major virulence factor is Shiga toxin (Stx), which is encoded by bacteriophages. Of the two types of Stx, the production of Stx2, particularly that of Stx2a (a subtype of Stx2), is a major risk factor for severe EHEC infections, but the Stx2 production level is highly variable between strains. Here, we define four major and two minor subtypes of Stx2a-encoding phages according to their replication proteins. The subtypes are correlated with Stx2a titers produced by the host O157 strains, suggesting a critical role of the phage subtype in determining the Stx2a production level. We further show that one of the two subclades in the clade 8, a proposed hyper-virulent lineage of O157, carries the Stx2 phage subtype that confers the highest Stx2 production to the host strain. The presence of this subclade may explain the proposed high virulence potential of clade 8. These results provide novel insights into the variation in virulence among O157 strains and highlight the role of phage variation in determining the production level of the virulence factors that phages encode

Local Recurrence and Complications after Percutaneous Radiofrequency Ablation of Hepatocellular Carcinoma : A Retrospective Cohort Study Focused on Tumor Location

We conducted a retrospective cohort study to investigate the predisposing factors for local recurrence and complications after percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). HCC patients (n＝397) consecutively treated with RFA (256 males, 141 females, median age 69 years) were enrolled. In these patients, 1,455 nodules (median size 17mm) were ablated. Predisposing factors for overall recurrence and local recurrence in the context of tumor location and complications were examined. Local recurrence was observed for 113 of the 1,455 nodules. The 1-, 3- and 5-year local recurrence rates were 2.2ｵ, 7.4ｵ and 9.5ｵ, respectively. A multivariate Cox proportional hazard analysis revealed that large tumor size (＞2cm), tumor location (adjacent to the major portal branch or hepatic vein), and small ablated margin (＜3mm) were independent predisposing factors for local recurrence after RFA (HR＝1.70-2.81). Tumor location (adjacent to the major portal branch, hepatic vein, or diaphragm) was also revealed as a risk factor for liver damage due to RFA. HCC adjacent to the major portal vein or hepatic vein was associated with a higher risk for local recurrence and for complications;therefore, special precautions are necessary when applying RFA to HCC near vessels even when the tumors are located at an easy-to-puncture site

The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis

The single nucleotide polymorphism (SNP) rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with hepatic fat accumulation and disease progression in patients with non-alcoholic fatty liver disease and alcoholic liver disease (ALD). This study was conducted to determine whether PNPLA3 rs738409 SNPs affect development and prognosis of hepatocellular carcinoma (HCC) in patients with various liver diseases. We enrolled 638 consecutive Japanese patients newly diagnosed with HCC between 2001 and 2010: 72 patients with hepatitis B virus (HBV), 462 with hepatitis C virus (HCV), and 104 with non-B non-C (NBNC). NBNC patients exhibited large tumors of advanced TNM stages at HCC diagnosis, and had significantly poorer prognosis than HBV or HCV patients (P < 0.001 and < 0.001, respectively; log-rank test). The G/G genotype of PNPLA3 rs738409 SNP had significantly higher distribution in NBNC patients (P < 0.001) and was significantly associated with higher body mass index (BMI) and an increased aspartate aminotransferase to platelet ratio index. No significant differences were observed in survival with differences in PNPLA3 SNP genotypes among the patients, although ALD patients with the G/G genotype of PNPLA3 SNP and low BMI had significantly poorer survival than those with high BMI (P = 0.028). The G/G genotype of PNPLA3 rs738409 SNP was more frequently distributed, and associated with BMI and fibrosis among NBNC-HCC patients but not among HBV or HCV patients. These genotypes might affect HCC prognosis in ALD patients, but not in HBV, HCV, or NAFLD patients

Impact of Comorbid Hepatic Steatosis on Treatment of Chronic Hepatitis C in Japanese Patients and the Relationship with Genetic Polymorphism of IL28B, PNPLA3 and LDL Receptor

The impact of hepatic steatosis on interferon therapy for patients with chronic hepatitis C (CHC) has been associated with single-nucleotide polymorphisms (SNP) of IL28B, patatin-like phospholipase domain-containing protein 3 (PNPLA3), and low-density lipoprotein (LDL) receptor. Whether this holds true for Japanese patients, however, remains unresolved. The present study prospectively enrolled 226 Japanese patients with CHC, and investigated the impact of hepatic steatosis and its related SNPs, including rs8099917 of IL28B, rs738409 of PNPLA3, and rs14158 of LDL receptor, on outcomes of peg-interferon and ribavirin therapy. In multivariate logistic regression analysis, significant factors affecting the severity of hepatic steatosis were high body mass index and the minor alleles of IL28B SNP (p＝0.020 and 0.039, respectively). The risk alleles of PNPLA3 SNP also showed weak association (p＝0.059). Severe steatosis and the minor alleles of IL28B SNP were significantly associated with null or partial virological response in patients with HCV genotype 1, as were female gender, and low LDL cholesterol (p＝0.049, and ＜0.001, respectively). The SNP genotype of PNPLA3 and LDL receptor did not have a significant impact on therapeutic outcomes. With respect to the SNP sites examined, the SNP of PNPLA3 has a weak association with severe hepatic steatosis, but not with the outcome of interferon therapy

A complete view of the genetic diversity of the Escherichia coli O-antigen biosynthesis gene cluster.

The O antigen constitutes the outermost part of the lipopolysaccharide layer in Gram-negative bacteria. The chemical composition and structure of the O antigen show high levels of variation even within a single species revealing itself as serological diversity. Here, we present a complete sequence set for the O-antigen biosynthesis gene clusters (O-AGCs) from all 184 recognized Escherichia coli O serogroups. By comparing these sequences, we identified 161 well-defined O-AGCs. Based on the wzx/wzy or wzm/wzt gene sequences, in addition to 145 singletons, 37 serogroups were placed into 16 groups. Furthermore, phylogenetic analysis of all the E. coli O-serogroup reference strains revealed that the nearly one-quarter of the 184 serogroups were found in the ST10 lineage, which may have a unique genetic background allowing a more successful exchange of O-AGCs. Our data provide a complete view of the genetic diversity of O-AGCs in E. coli showing a stronger association between host phylogenetic lineage and O-serogroup diversification than previously recognized. These data will be a valuable basis for developing a systematic molecular O-typing scheme that will allow traditional typing approaches to be linked to genomic exploration of E. coli diversity