Mikako Nakajima

Autoimmune hepatitis in primary Sjögren's syndrome: Pathological study of the livers and labial salivary glands in 17 patients with primary Sjögren's syndrome

Although primary Sjögrens syndrome (pSS) is an autoimmune exocrinopathy, the involvement of liver has been reported. Because no study focusing on autoimmune hepatitis (AIH) in pSS has been published, the purpose of the present study was to perform a clinical and histological examination of the liver, focusing on AIH, in 17 pSS patients. The patients had liver enzyme abnormalities without hepatitis virus infection. In all cases, biopsied livers were examined, and in 10 cases biopsied labial salivary glands were also examined histologically. Based on the authors’ diagnostic criteria for AIH in pSS, the liver diseases consisted of AIH (eight cases, 47%), primary biliary cirrhosis (PBC; six cases, 35%), non‐specified chronic hepatitis (two cases, 12%) and acute hepatitis (one case, 6%). Lymphoplasmacytic infiltrate, with predominancy of CD3+ T cells, was noted in both the liver and salivary glands in the patients with AIH. The patients with AIH with severe interface hepatitis had a good response to immunosuppressive therapy. The comparison of liver histology between the PBC with pSS group and the PBC without pSS group showed that the incidence of lymphoid non‐suppurative cholangitis was higher in PBC with pSS. In conclusion, the present study offers new information on the relatively common occurrence, diagnostic criteria and treatment effects of AIH in pSS.

Detection of IgA, IgM, and IgG subclasses of anti-M2 antibody by immunoblotting in autoimmune cholangitis: is autoimmune cholangitis an early stage of primary biliary cirrhosis?

Abstract: Autoimmune cholangitis (AIC) has been proposed as a distinct disease entity from primary biliary cirrhosis (PBC), without antimitochondrial antibody (AMA) and anti-M2 antibody but with a high titer of antinuclear antibody (ANA) in the serum. However, negativity for AMA and anti-M2 antibody was determined by different methods in different studies. We hypothesized that anti-M2 antibody negativity in AIC resulted from methodological differences, including selection of the immunoglobulin subclass of the autoantibody. Twenty-three patients compatible with AIC whose serum tested negative for AMA and positive for ANA (≧1 : 80) were compared with 71 AMA-positive PBC patients. Laboratory findings, histology, and the pattern of anti-M2 antibody assessed by immunoblotting were compared. Alkaline phosphatase, total bilirubin, total cholesterol, and IgM values were lower in patients with AIC (P < 0.05, 0.01, respectively). Anti-smooth muscle antibody was detected more frequently in patients with AIC (P < 0.01). However, anti-M2 antibody was detected using immunoblotting not only in PBC but also in AIC cases. IgA class alone, IgM class alone, or both IgA and IgM classes of anti-M2 antibody were detected in 13%, 17%, and 22% of AIC patients, respectively, whereas they were not detected in PBC patients (P < 0.05, P < 0.01, P < 0.01). IgG class anti-M2 was detected in all patients with PBC, whereas it was detected in 48% of patients with AIC (P < 0.01). Histological evaluation showed that the early stages of disease were found more frequently in AIC (78%) than in PBC patients (39%) (P < 0.01). Anti-M2 antibody was detected by immunoblotting in all AIC patients. Hence, AIC is not a distinct disease from PBC. For diagnosing AIC and/or PBC, anti-M2 antibody should be examined by the immunoblotting assay to detect not only IgG but also IgA and IgM subclasses.

A neurotrophic pyrimidine compound, MS-818, enhances EGF-induced restoration of gastric epithelial wounds in vitro

MS-818 is a novel synthetic pyrimidine compound that stimulates nerve regeneration and promotes synthesis of various growth factors and differentiation of astrocytes. Effects of MS-818 on gastric epithelial cells were assessed using a wound repair model with primary cultured gastric epithelial cells from rabbits. A round wound with a constant cell-free area was created and the process of restoration was monitored by measuring wound size every 12 h. Cell proliferation was monitored by sequential staining with BrdU. As previously reported, EGF (10 ng/ml) accelerated wound repair by promoting cell migration and proliferation. Although MS-818 alone had no effects, MS-818 (10-100 microM) enhanced EGF-induced acceleration of gastric epithelial restoration, including cell migration and proliferation. Although the detailed mechanism of action of this agent is still unclear, MS-818 might have favorable effects on in vivo gastric mucosal repair.

Case Report: Primary Gastric T-cell Lymphoma Accompanied by HTLV-I, HBV and H. pylori Infection

Primary gastrointe stinal lymphomas are the most common forms of extranodal non-Hodgkin’ s lymphoma (NHL), of which almost half are of the gastrointe stinal tract (1, 2). Most primary gastrointe stinal lymphomas are conside red to be of B-cell origin; those of T-cell origin are very rare (3± 8). Only 38 cases of primary gastric T-cell lymphoma have been reported in the lite rature . Recently, T-cell leukemia virus type I (HTLV-I) has received attention as an etiological factor, as approximate ly half of the reported cases are positive for HTLV-1 antibody. Furthermore , the close association of Helicobacter pylori infection with malignant lymphoma also has been recognized. Here we present a case of primary gastric T-cell lymphoma that was positive not only for HTLV-1 antibody but also HBV and H. pylori infection.

The novel histamine H2 receptor antagonist FRG-8813 prevents delay of wound repair induced by hydrogen peroxide in a rabbit gastric epithelial cell system

Abstract The effects of a novel histamine H2 receptor antagonist (FRG‐8813) on the restoration process of gastric epithelial wounds were assessed using an in vitro wound healing model. FRG‐8813 (1, 10 mol/L) was added to a complete confluent monolayer cell sheet after artificial wounding. The restoration process was analysed by a time‐lapse video system and cell migration, proliferation and apoptosis were assessed. Hydrogen peroxide (1, 3 mmol/L) inhibited restoration after wounding by suppressing cell migration and proliferation and induced epithelial cell apoptosis around the wound. The addition of FRG‐8813 abolished the hydrogen peroxide‐induced retardation and prevented apoptosis, although FRG‐8813 itself did not enhance wound healing. FRG‐8813 may act as a radical scavenger as well as having an anti‐secretory action and may have favourable effects on peptic ulcer healing.