Yusuke Kajiyama

Ursodeoxycholic acid reduces CpG‐induced IgM production in patients with primary biliary cirrhosis

Aim:  Ursodeoxycholic acid (UDCA) treatment reduces IgM serum levels in patients with primary biliary cirrhosis (PBC) without affecting serum antimitochondrial antibody (AMA) titers. We previously reported that PBC‐associated hyper‐IgM is secondary to a disease‐specific hyperproduction following bacterial stimulation by B cells.

Splenic lymph follicles generate immunoglobulin M-producing B cells in primary biliary cirrhosis

To reveal the site of immunoglobulin (Ig)M production in primary biliary cirrhosis (PBC) we performed immunohistochemical analysis on spleens collected from patients with PBC.

B-cell-activating factor affects the occurrence of thyroid autoimmunity in chronic hepatitis C patients treated with interferon alpha.

Chronic hepatitis C (CHC) patients frequently suffer from thyroid disorders during interferon therapy. However, the mechanism remains unclear. In this study, we investigated the association between serum B-cell-activating factor belonging to the TNF family (BAFF) levels and the presence of antithyroid peroxidase antibody (anti-TPO) in CHC patients treated with pegylated interferon alpha and ribavirin combination therapy. Six months after the therapy, anti-TPO antibody was detected in 10 (males, 1; females, 9) of 50 patients. The mean age of these patients was higher than that of the anti-TPO-negative patients (61 yr versus 55 yr). Before treatment, the serum BAFF levels of the anti-TPO-positive patients were higher than those of the anti-TPO-negative patients. After starting therapy, the serum BAFF levels of both the anti-TPO-positive and -negative patient groups were elevated. Our findings suggest that the serum BAFF concentration before therapy can predict the risk of thyroid autoimmunity in elderly female patients with CHC.

Autoantibody IgG subclasses to recombinant antigens and the role of bacterial stimuli in primary biliary cirrhosis

Aim:  Serum antimitochondrial antibody (AMA) of the IgG2 and IgG3 subclasses has been reported to be predominant in patients with primary biliary cirrhosis from developed countries. No data are available as to the significance of AMA subtypes in Japanese primary biliary cirrhosis (PBC) patients who have previously manifested unique serological features, nor it is known whether AMA subclasses are influenced by bacterial stimuli, as suggested by the molecular theory of PBC. We undertook a three‐step study to address these questions.

Serological and Histological Examination of a Nonalcoholic Steatohepatitis Mouse Model Created via the Administration of Monosodium Glutamate

The administration of monosodium glutamate (MSG) to mice induces hepatic steatosis and inflammation. In this study, we investigated the metabolic features of MSG-treated mice and the histological changes that occur in their livers and adipose tissue. MSG mice were prepared by subcutaneously injecting MSG into newborn C57BL/6J male mice. The control mice were subcutaneously injected with saline. Another group of mice was fed a methionine- and choline-deficient diet (MCD). Compared with the control mice, the MSG mice had higher serum levels of insulin and cholesterol than the control mice, whereas the opposite was true for the MCD mice. Microvesicular steatosis and inflammatory cell infiltration were detected in both the MSG and MCD mouse livers. Enlarged adipocytes and crown-like structures were observed in the epididymal fat of the MSG mice, whereas neither of these features was seen in the MCD mice. Flow cytometric analysis revealed increased frequencies of monocytes and M1 macrophages in the livers and epididymal fat tissue of the MSG mice, respectively. The MSG mice exhibited the characteristic liver histopathology of nonalcoholic steatohepatitis (NASH) as well as metabolic syndrome-like features, which suggested that MSG mice are a better model of human NASH than MCD mice.

Su1218 Combination Therapy of Intraarterial 5-Fluorouracil and Pegylated Interferon-Alpha Subcutaneous Injection for Unresectable Biliary Tract Adenocarcinoma

malignancy. High grade dysplasia (OR 6.66 [95% CI, 1.52-29.08]) and ductal dilatation (OR 10.96 [95% CI, 2.25-53.42]) were independently associated with malignancy in multivariate analysis. Fourteen (56%) of 25 patients with high grade dysplasia on endoscopic biopsy were revealed as carcinoma after resection. Conclusions The malignancy rate in ampullary adenomas on endoscopic biopsy was 26.4%. Adenoma with high grade dysplasia and ductal dilatation are significant predictors of malignancy in the ampullary adenoma.