Clinical study of IgA antibody against hepatitis C virus core antigen in patients with type C chronic liver disease

Immunoglobulin A class antibody to hepatitis C virus core antigen (IgA anti-HCc) was measured in the serum of 128 patients with type C chronic liver disease. Fifty-eight patients (45.3%) were seropositive. IgA anti-HCc was detected in only one of 20 patients with chronic persistent hepatitis; however, 52.3% (46/88) of patients with chronic active hepatitis and 55% (11/20) of patients with liver cirrhosis were seropositive. Histological examination revealed that 22 (71.0%) of 31 patients with severe disease activity were seropositive compared to 35 (44.9%) of 78 patients with moderate (P<0.05) and one (5.3%) of 19 patients with mild (P<0.01) histological changes. IgA anti-HCc was measured sequentially in 65 patients who underwent interferon therapy. There was a significant difference between responders and other patients in the mean ratio of IgA anti-HCc titers one month after therapy. Three months after therapy, IgA anti-HCc was detectable in only two of 15 responders who were IgA anti-HCc seropositive at the start of therapy. In contrast, IgA anti-HCc reappeared three months after therapy despite a temporary decrease to undetectable levels in all nonresponders. We conclude that IgA anti-HCc is a useful marker to identify the presence of active type C liver disease and that the disappearance of IgA anti-HCc three months after interferon therapy predicts a good response in treated patients.     

Effectiveness of combined anticoagulant therapy for extending portal vein thrombosis in Crohn's disease

PURPOSE: Portal vein thrombosis is a rare complication of Crohn's disease, and its precise cause and appropriate treatment are not known. We describe a patient with extending portal vein thrombosis in Crohn's disease who was successfully treated with combined anticoagulant therapy. METHOD: Urokinase and tissue plasminogen activator were administered from a catheter inserted into the superior mesenteric artery, and heparin and a serine protease inhibitor also were given intravenously. RESULTS: On admission, thromboembolic occlusion was observed throughout the entire portal venous system in association with massive ascites and remarkable intestinal edema. After administration of combined anticoagulant therapy, thrombus rapidly decreased in size, and color Doppler ultrasonography showed a gradual increase in portal venous flow. The patient had no recurrence of symptoms while receiving warfarin after resolution of thrombus. CONCLUSION: This case report suggests that combined anticoagulant therapy is effective for patients with severe portal vein thrombosis in Crohn's disease and that color Doppler ultrasonography is useful for evaluation of portal venous flow.     

Characterization of complement C3, C4, and factor B molecules in human bile

We performed molecular analysis of complement components (C3, C4, and factor B) in human bile by sodium dodecyl sulfate-polyarylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Complement C3 was detected as a molecule composed of a 115-kDa α-chain linked to a 70-kDa β-chain by disulfide bonds, and C3 levels ranged from 45 to 650μg/ml (n=15). C4 was detected as a triple chain (98-kDa α-chain, 73-kDa β-chain, and 33-kDa γ-chain) molecule linked by disulfide bonds, and C4 levels ranged from 2.5 to 60μg/ml. Factor B, a component of the alternative pathway, was also detected, as an intact form. Factor B levels ranged from 0.3 to 8.0μg/ml. The sizes and subunit structures of complement components in human bile were compatible with those reported in human serum. The results of a hemolytic assay indicated that complement molecules in human bile were functionally active. These molecules may participate in local immune and inflammatory responses in the biliary tract.     

Activation of MIP-2 and MCP-5 Expression in Methylmercury-Exposed Mice and Their Suppression by N-Acetyl-L-Cysteine

Neurotoxicity Research - Methylmercury (MeHg) is a well-known neurotoxin of the central nervous system (CNS). Neuroinflammation is one of the main pathways of MeHg-induced CNS impairment. This...     

A case of scirrhous gastric cancer with peritonitis carcinomatosa controlled by TS-1(R) + paclitaxel for 36 mo after diagnosis

A 34-year-old female complaining of abdominal fullness was diagnosed as scirrhous gastric cancer (type 4')with peritonitis carcinomatosa in July 2002. A combined chemotherapy regimen was selected to control massive ascites; TS-1(R) 80 mg/m2 was given orally on d 1-14,22-35, and paclitaxel 50 mg/m2 was administered intravenously on d 1, 8, 22 and 29. After 2 courses of this regimen, the primary tumor was markedly reduced,and ascites completely vanished. Alopecia (grade 1,since d 30), leukocytopenia (grade 2, on d 34) and anemia (grade 2, on d 34) were the only adverse events throughout the following courses. The chemotherapy was effective for 28 mo, and then it was discontinued upon the patient's own request, and she survived for 36mo after diagnosis.     

Vesicular glutamate transporter 3‐expressing nonserotonergic projection neurons constitute a subregion in the rat midbrain raphe nuclei

We previously reported that about 80% of vesicular glutamate transporter 3 (VGLUT3)‐positive cells displayed immunoreactivity for serotonin, but the others were negative in the rat midbrain raphe nuclei, such as the dorsal (DR) and median raphe nuclei (MnR). In the present study, to investigate the precise distribution of VGLUT3‐expressing nonserotonergic neurons in the DR and MnR, we performed double fluorescence in situ hybridization for VGLUT3 and tryptophan hydroxylase 2 (TPH2). According to the distribution of VGLUT3 and TPH2 mRNA signals, we divided the DR into six subregions. In the MnR and the rostral (DRr), ventral (DRV), and caudal (DRc) parts of the DR, VGLUT3 and TPH2 mRNA signals were frequently colocalized (about 80%). In the lateral wings (DRL) and core region of the dorsal part of the DR (DRDC), TPH2‐producing neurons were predominantly distributed, and about 94% of TPH2‐producing neurons were negative for VGLUT3 mRNA. Notably, in the shell region of the dorsal part of the DR (DRDSh), VGLUT3 mRNA signals were abundantly detected, and about 75% of VGLUT3‐expressing neurons were negative for TPH2 mRNA. We then examined the projection of VGLUT3‐expressing nonserotonergic neurons in the DRDSh by anterograde and retrograde labeling after chemical depletion of serotonergic neurons. The projection was observed in various brain regions such as the ventral tegmental area, substantia nigra pars compacta, hypothalamic nuclei, and preoptic area. These results suggest that VGLUT3‐expressing nonserotonergic neurons in the midbrain raphe nuclei are preferentially distributed in the DRDSh and modulate many brain regions with the neurotransmitter glutamate via ascending axons. J. Comp. Neurol. 518:668–686, 2010. © 2009 Wiley‐Liss, Inc.     

Epithelial-cadherin Gene Is Not Mutated in Ductal Carcinomas of the Breast

We investigated mutations of the epithelial (E)-cadherin gene and loss of heterozygosity (LOH) at flanking loci using three microsatellite markers on the long arm of chromosome 16 in 25 ductal carcinomas of the breast. Expression of E-cadherin was also investigated immunohistochemically. No mutations were detected in exons 6 through 9 of the E-cadherin gene. LOH was observed more frequently (42%) at D16S402 (16q-ter) than at D16S421 (16q22.3-q23.1) (17%), which is located near the E-cadherin gene. Expression of E-cadherin was observed at the cell borders in 92% (11/12) of the tumors examined. The absence of mutations in the E-cadherin gene and its conserved expression suggest that inactivation of E-cadherin does not contribute significantly to the invasion or metastatic potential of ductal carcinomas of the breast. Furthermore, the high frequency of LOH at 16q-ter suggests the existence of another tumor suppressor gene which may play a crucial role in the genesis of ductal carcinomas of the breast.     

Detection of sentinel lymphatic region with activated carbon particles in lymph node dissection for colorectal cancer

Sentinel node navigation surgery (SNNS) for gastrointestinal cancer has been examined using various methods, but the SN concept has not been established. For 18 patients who had colorectal cancer without macroscopic nodal metastases, we had attempted to detect sentinel lymph nodes (SNs) with activated carbon particles and investigate the existence of nodal metastases histologically. SNs were detected in 17 of 18 patients. Thus activated carbon particles are a useful tracer for SN detection. Three patients had microscopic nodal metastases, and two had nodal metastases in SNs. Although the remaining patient was a false negative case which had nodal metastases in non-SNs only, the nodal metastases were within the sentinel lymphatic region (SLR) which includes SNs. It is considered possible to safely perform minimally invasive lymphadenectomy for colorectal cancer without macroscopic nodal metastases, by means of SLR dissection using activated carbon particles.     

Analysis of effect of dextran sulfate on cancer cells

Peritoneal recurrence is one of the critical problems that occurs after surgery for gastrointestinal cancers. Since no curative treatment has been established for peritoneal recurrence, many efforts have been made to develop an effective method for preventing such recurrence. We focused on dextran sulfate, an anti-cell-adherence agent, to prevent peritoneal metastasis. Our previous studies in vitro and in vivo clarified that dextran sulfate prevents cancer cells from adhering to plastic flasks and the abdominal wall. In this study, we investigated the effects of dextran sulfate on cancer cells from the viewpoint of the cell cycle. Changes in gene expression caused by dextran sulfate were analyzed by cDNA microarrays. Analysis by cDNA microarray revealed the decreased expression of the genes essential to the progression of G1 and S phases. Our results indicate that dextran sulfate suppresses progression of the cell cycle as well as cell adhesion, suggesting that dextran sulfate could be used as an antimetastatic agent. Anti-cell-adherence agents with such mechanisms of action could be effective drugs for treatment during and after operation to prevent peritoneal metastases induced by surgical operation.