Wataru Yamamuro

Disappearance of HCV after cessation of immunosuppression in a patient with ulcerative colitis and renal transplantation

We report a patient, a 45-year-old Japanese woman, who underwent living-related donor renal transplantation in 1986 and 1988, with the second procedure being successful. Ulcerative colitis (UC) was diagnosed in 1987 while she was receiving immunosuppressive therapy after the renal transplantation. She became positive for serum anti-hepatitis C virus (HCV) in November 1990, although her serum aminotransferase levels were normal. In June 2001, she had frequent episodes of melena with abdominal pain, as control of her UC deteriorated. In July 2001, she was admitted to the Department of Surgery at our hospital, and her daily dose of prednisolone was increased from 40 mg to 80 mg. After 2 weeks of high-dose prednisolone therapy, there was a significant increase of serum aminotransferases, and serum HCV-RNA rose above 850 KIU/ml (by reverse transcription-polymerase chain reaction [RT-PCR]). Control of UC was still poor, so cyclosporine A (CyA) was added at a dose that maintained a high serum concentration. The daily dose of prednisolone was tapered and leukapheresis was performed three times weekly. As result, serum aminotransferases decreased to the normal range. However, total colectomy and colostomy were required because the UC could not be controlled by these therapies. Serum aminotransferase levels increased transiently 2 months after the cessation of immunosuppressive therapy (prednisolone, azathioprine [AZP], and CyA). Subsequently, serum aminotransferases rapidly declined below normal, and the serum level of HCV-RNA (by RT-PCR) fell from 480 KIU/ml to less than 0.5 KIU/ml. She was discharged on April 25, 2002. During follow-up as an outpatient, serum HCV-RNA became negative and remained negative for 7 months. To confirm clearance of HCV, liver biopsy was performed, and no HCV-RNA was detected in the liver tissue by RT-PCR. These findings suggested that HCV was cleared by the cessation of immunosuppressive therapy, as a rebound effect.

Distribution of 3α-hydroxysteroid dehydrogenase (bile acid binder) in rat small intestine: Comparison with glutathione S-transferase subunits

We identified and quantitated theY′ bile acid binder, i.e., 3α-hydroxysteroid dehydrogenase (3α-HSD), in rat small intestinal mucosa, and compared its longitudinal distribution with that of glutathione S-transferases (GST). The enzyme activity of 3α-HSD in intestinal mucosa was approximately one-third of that in liver, and it had similar activity in the proximal, middle, and distal portions of the intestine. Immunoreactive protein corresponding to hepatic bile acid binder was detected in all segments of rat small intestine mucosal cytosol by Western blot analysis. There was no significant difference in the concentration of bile acid binder, assayed by enzyme-linked immunosorbent assay (ELISA), between the proximal and the distal intestine, this being 2.93±0.03 and 3.29±0.95 nmol/g tissue, respectively (mean±SD of four animals). On the other hand, the concentration of GST 1-1 showed sharp longitudinal decline and that of GST 3–4 was negligible in the small intestine, as we previously reported, indicating that bile acid binder was a prominent cytosol binding protein in the distal intestine. These results suggested the possible role of bile acid binder in the intracellular transport of bile acids in the ileum.

Malignant transformation of Nakamura type IV gastric polyp with CA 19-9 production.

Abstract: In a 68-year-old Japanese man, a gastric polyp 24 mm in diameter with a stalk 15 mm in diameter was diagnosed as well differentiated adenocarcinoma and treated by endoscopic polypectomy. Histologically, most of the resected tissue was adenoma, and atypical cells were papillarily proliferating to form adenocarcinoma in adenoma, a Nakamura type IV gastric polyp. Infiltration of carcinoma was limited to within the mucosal layer. Immunohistochemical study with anti-CA19-9 antibody revealed positive staining in carcinoma cells. Serum CA19-9 level, which showed slight elevation, returned to the normal range 1 month after the polypectomy. The proliferating cell nuclear antigen (PCNA) labeling index and DNA ploidy pattern were analyzed in the resected tissue. The PCNA labeling index was 30% in carcinoma, 17% in adenoma, and 0.1% in the normal tissue. The DNA ploidy pat-tern was diploid in adenoma and aneuploid in adenocarcinoma. These findings suggest that gastric adenoma, as well as colonic adenoma, may have the potential for malignant transformation.

Laparoscopic Findings of Asymptomatic Primary Biliary Cirrhosis —Particular investigation in early PBC—

Abstract: of 17 cases of asymptomatic primary biliary cirrhosis (PBC), seven cases whose ALP (alkaline phosphatase) was less than twice the upper limit of the normal range were defined as being “early PBC”, and ten cases whose ALP was more than twice the upper limit of the normal range were defined as being “classical PBC” in order to investigate their clinical pictures and laparoscopic findings.

Effects of Probiotics on Serum Bile Acids in Patients With Ulcerative Colitis

BACKGROUND/AIM: Evaluation of bile acids (BA) is a useful method for assessing changes of the intestinal flora in patients with ulcerative colitis (UC). During enterohepatic circulation, conjugated BA is deconjugated to free BA by intestinal bacteria. The presence of intestinal microflora (Clostridium and Eubacterium) leads to 7 alpha-dehydroxylation of cholic acid (CA) and chenodeoxycholic acid (CDCA), yielding deoxycholic acid (DCA) and lithocholic acid, respectively. It was reported that the Lachnospiraceae subgroup of Firmicutes (including Clostridium) are decreased in the colon of UC patients compared to controls without inflammatory bowel disease. We have already reported that the serum%CDCA is significantly higher in patients with UC than in healthy volunteers (HV), while serum%DCA is significantly lower in UC patients than in HV, and these changes do not depend on the activity or extent of UC. The aim of the present study was to elucidate the effects of probiotics in patients with UC by examining the serum BA profile. PATIENTS/METHODS: The study population was 27 patients in whom UC was diagnosed from endoscopic and histological findings. All patients underwent ileocolonoscopy with appropriate biopsies. They were divided into the following 2 groups based on endoscopic findings: 15 patients with distal UC (dUC) and diffuse changes extending from the rectum to the splenic flexure, and 12 patients with more extensive UC or pancolitis (pUC). Treatment was givenwithmesalazine or salazosulfapyridine (5-ASA) and all patients achieved remission. After entering remission, they were treated with by 5-ASA plus the probiotic Clostridium butyricum Miyairi (MIYA) (3 g/day) for 4 weeks. The control group was composed of 8 HV. Routine laboratory tests were performed on the basis of clinical need, while fasting serum samples for measurement of BA were obtained before and after treatment with 5-ASA plus MIYA for 4 weeks. Serum BA fractions were analyzed by HPLC. RESULTS: There were no significant differences of serum total BA among the 3 groups. Before treatment, %CDCA was significantly higher in the dUC and pUC groups than in the HV group, while %DCA was significantly lower than in the HV group. In the pUC group, %CDCA was significantly higher and %DCA was significantly lower than in the HV group after 4 weeks of probiotic treatment. In the dUC group, however, there was no significant difference of %CDCA or %DCA after 4 weeks compared with the HV group. There were no significant differences in the ratio of conjugated BA to total serum BA among the three groups. CONCLUSIONS: These results suggest that intestinal bacteria involved in the deconjugation of BA are restored when patients achieve remission of UC by treatment with 5-ASA, and thatMIYA restoredmicroflora involved in 7 alpha-dehydroxylation in the dUC group, but not in the pUC group.