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Biomedical subjects

Minoru Shibata

Publications and source records attributed to Minoru Shibata.

26 records · Page 2Linked to original sources

A patient with hepatitis C-related cirrhosis and hepatocellular carcinoma who was cured with an orthotopic liver transplantation and interferon therapy.

A patient with hepatitis C virus (HCV)-related liver cirrhosis and hepatocellular carcinoma (HCC) was treated successfully with an orthotopic liver transplantation (OLT) followed by interferon therapy. The 36-year-old Japanese man was diagnosed as having liver cirrhosis in 1983. HCC was detected in 1991, and by 1994, jaundice and ascites had developed. The patient underwent OLT in June 1995, after which hepatitis C recurred, with elevated aminotransferases. His liver biopsy specimen showed chronic active hepatitis. He was given interferon-alpha three times weekly for 24 weeks in 1999. Six months after the end of the interferon treatment, the patient's serum HCV RNA became negative, with normalization of aminotransferases, and his liver histology exhibited amelioration of fibrosis and inflammation. At the present time, he remains free of HCC (more than 6.5 years after the OLT) and free of HCV RNA (more than 2.5 years since interferon therapy was completed). This is the first Japanese patient whose HCC was cured by OLT and HCV was eradicated by interferon therapy.

Adult↗

Disruption of a long-range cis-acting regulator for Shh causes preaxial polydactyly.

Preaxial polydactyly (PPD) is a common limb malformation in human. A number of polydactylous mouse mutants indicate that misexpression of Shh is a common requirement for generating extra digits. Here we identify a translocation breakpoint in a PPD patient and a transgenic insertion site in the polydactylous mouse mutant sasquatch (Ssq). The genetic lesions in both lie within the same respective intron of the LMBR1/Lmbr1 gene, which resides approximately 1 Mb away from Shh. Genetic analysis of Ssq reveals that the Lmbr1 gene is incidental to the phenotype and that the mutation directly interrupts a cis-acting regulator of Shh. This regulator is most likely the target for generating PPD mutations in human.

Animals↗

Characterization of DNA polymorphisms in the E-cadherin gene (CDH1) promoter region.

E-cadherin is a tumor suppressor involved in epithelial cell-cell interactions. Some of the nucleotide variation in the 5'-promoter region of the gene influences transcriptional efficiency. We investigated single nucleotide polymorphisms (SNPs) in the promoter-exon 1 region of the E-cadherin gene (CDH1) using fluorescence-based PCR-single-strand conformation polymorphism (PCR-SSCP) analysis. We detected four kinds of polymorphisms between nucleotides -516 and +12, numbering from the translation initiation site. SNPs were localized at -472G-->GA, -288T-->deltaT, -285C-->A, and -54G-->C. Variants -472GA and -285A were frequently found in controls, but the -288deltaT and -54C are rare variants. We examined the effects of these variants on transcription. The activity of promoters containing the variants -288deltaT, -285A, or -54C was lower than the activity of promoters with the major variants, as assayed by a luciferase reporter gene. Variants -472G and -472GA displayed the same promoter activity. The decreased transcriptional activity from variant promoters affects the expression of E-cadherin.

Alleles↗

Risk factors for infections in cirrhotic patients with and without hepatocellular carcinoma.

BACKGROUND: Patients with liver cirrhosis (LC) frequently have complications with bacterial infections, and these infections increase the mortality rate. However, a detailed analysis of infections associated with LC patients has not yet been performed. METHODS: We analyzed 325 patients with LC with and without hepatocellular carcinoma (HCC) who were hospitalized between 1997 and 1999. RESULTS: Infections developed in 70 (21.5%) patients and 48 (68.6%) of these developed infections during hospitalization. The mortality rate of 28.6% (20/70) in patients with infectious complications was higher than that of 12.5% (32/255) in patients without infectious complications. Forty (57.1%) of the 70 patients had infections of unknown causes; 11 (15.7%) had sepsis; 6 (8.6%) had intravenous hyperalimentation (IVH) infection; 3 (4.3%) each had spontaneous bacterial peritonitis (SBP), liver abscess, and cholecystitis; and 4 (5.7%) had other infections. Bacterial cultures of blood were prepared from 73 of the 325 patients (22.5%), and were positive in 22 of the 73 patients (30.1%). Of these 22 culture-positive patients, 11 had sepsis, 6 had IVH infection, 2 had liver abscess, 1 had cholecystitis, 1 had pneumonia, and 1 had decubitus ulcer. Gram-positive bacterial strains were detected most frequently, in 16 of the 24 strains isolated. Univariate analysis revealed significant differences between the groups with and without infectious complications with regard to hepatitis B virus infection, Child-Pugh classification, ascites, esophageal varices, survival rate, total-bilirubin (T-Bil), albumin (Alb), lactate dehydrogenase (LDH), total cholesterol (T-chol), and prothrombin time (PT). On multivariate analysis, the Alb level was selected as a significant independent factor contributing to the development of infections. CONCLUSIONS: Patients with advanced cirrhosis with low Alb levels should be carefully treated, and the administration of broad spectrum antibiotics covering gram-positive bacteria needs to be considered in the treatment of infections.

Age Distribution↗

Hepatocellular carcinoma and survival in patients with primary biliary cirrhosis.

The incidence of hepatocellular carcinoma (HCC) in patients with primary biliary cirrhosis (PBC) is not well known. The aims of this study are to determine HCC incidence and survival, and to identify risk factors associated with these outcomes in patients with PBC. We collected information on 396 patients with PBC at enrollment and followed-up from 6 to 271 months. They were all negative for hepatitis B and C virus markers. HCC was detected by scanning with ultrasonography, computed tomography, or both every 4 to 6 months. Life expectancy (LE) was approximated with the declining exponential approximation of LE. A total of 14 patients developed HCC. The cumulative appearance rate of HCC in patients with advanced-stage PBC (Scheuer's stage III or IV) was significantly higher than that for patients with early-stage (stage I or II) (12.3% and 7.7% by the tenth year, respectively. P =.021). Proportional hazards analysis showed 3 factors are independently associated with the development of HCC: age at the time of diagnosis, male gender, and history of blood transfusion. Age, male gender, and advanced-stage PBC were associated with survival, but HCC development was not. The disease-specific annual mortality rate was estimated to be 0.008 for women and 0.028 for men with advanced-stage PBC. In conclusion, HCC develops in old patients with advanced-stage PBC, but HCC does not affect the patients' survival.

Adult↗

Analysis of background factors influencing long-term prognosis of patients with chronic hepatitis C treated with interferon.

OBJECTIVE: Interferon (IFN) therapy has been used as antiviral therapy for chronic hepatitis C (CH-C); however, complete response to the therapy is observed in only about 30% of patients in Japan. Background factors involved in the responsiveness to IFN therapy, and progression to liver cirrhosis (LC) and hepatocellular carcinoma (HCC) after IFN therapy have not yet been sufficiently investigated. METHODS: One hundred twenty-one patients with CH-C who received IFN therapy at Showa University Hospital between 1984 and 1999 were analyzed. RESULTS: At 6 months after the termination of IFN therapy, 53 patients achieved a complete response, 11 patients incomplete response, and 57 patients no response. During a mean follow-up of 52.7 months, 12 patients progressed to LC, and 10 patients developed HCC. Multivariate analysis showed that significant independent factors involved in progression to LC were platelet count and the efficacy of IFN therapy. The significant independent factor involved in the development of HCC was platelet count. The factor involved in the therapeutic effect at 6 months after the termination of IFN administration was the serum hepatitis C virus (HCV) RNA levels before IFN therapy. CONCLUSION: Patients with high HCV RNA levels and low platelet counts should be considered to be at high risk of progressing to LC and developing of HCC and should be carefully followed after IFN therapy using ultrasonography, CT scan and MRI.

Adult↗

Cyclosporin A treatment for membranoproliferative glomerulonephritis type II.

A nephrotic patient with membranoproliferative glomerulonephritis type II (MPGN II) was treated with cyclosporin A (CSA) and alternate-day low-dose prednisolone. This patient developed the nephrotic syndrome twice. The second episode of the nephrotic syndrome was steroid resistant, and therefore this patient was treated with a CSA regimen. During treatments with alternate-day low-dose prednisolone and CSA, this patient recovered from the nephrotic syndrome. We conclude that CSA therapy may be effective for patients with the steroid-resistant nephrotic syndrome caused by MPGN II.

Child↗

Efficacy and safety of prednisolone in patients with autoimmune hepatitis.

A retrospective cohort study involving 29 Japanese patients with autoimmune hepatitis (AIH) was performed to clarify factors that predict the efficacy of prednisolone and the occurrence of various serious adverse effects. Independent predictors were identified by logistic analysis and with use of the Cox proportional hazard model. Responses to prednisolone were noted in 28 patients, who were classified into the complete remission group (52%) or the relapse group (48%). Multivariate analysis identified alanine aminotransferase, alkaline phosphatase, and immoglobulin G levels as independent predictors of relapse. The adverse effects most frequently observed were diabetes mellitus (37.9%), psychiatric/ neurologic symptoms (34.5%), and circulatory symptoms (34.5%). Predictive factors included lactate dehydrogenase, albumin, and fasting blood glucose levels for diabetes mellitus, alkaline phosphatase and C-reactive protein for psychiatric/ neurologic symptoms, and autoimmune hepatitis score and lactate dehydrogenase for circulatory symptoms. Selection of an optimal treatment method for individual patients may be possible after the risks of relapse and adverse effects have been estimated.

Asian People↗