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Biomedical subjects

Hiromitsu Saisho

Publications and source records attributed to Hiromitsu Saisho.

At least 145 records · Page 8Linked to original sources
PubMed2002

Portal-systemic encephalopathy in two patients without liver cirrhosis and portal hypertension.

The portal-systemic venous shunt is uncommon in patients without portal hypertension. We present two cases of portal-systemic encephalopathy due to extrahepatic shunt without liver cirrhosis and portal hypertension. Two women in their seventies were admitted to our hospital because of recurrent episodes of altered sensorium, drowsiness, slurred speech, disorientation, asterexis and high blood ammonia levels. There was no history of abdominal surgery or abdominal trauma. Clinical examination revealed no signs of portal hypertension or stigmata of chronic liver diseases. Brain CT and MRI scanning were unremarkable except for a high intensity signal in the basal ganglia on T1 weighted MRI images. Laboratory tests were almost normal except for the hyperammonemia occurring on several occasions. There was no evidence of liver cirrhosis by imaging. However, color Doppler showed an extra-hepatic shunt in both patients and pulsed Doppler showed decreased velocity and volume of the portal venous flow. These sonographic findings were confirmed during percutaneous transhepatic portography (PTP). Portal pressures measured during PTP were 9 and 11 mmHg. Needle biopsy ruled out idiopathic portal hypertension and liver cirrhosis. The diagnosis was portal systemic encephalopathy due to extra-hepatic portosystemic venous shunting. Both patients were treated by embolization of the shunting vessel with metallic coils.

Journal Article↗
PubMed2002

Hepatic graft-versus-host disease resembling acute hepatitis: additional treatment with ursodeoxycholic acid.

Hepatic graft-versus-host disease (GVHD) is a frequent complication after bone-marrow transplantation (BMT). The disease is often refractory to immunosuppressive therapy. We present a 30-year-old Japanese male, who developed an abrupt elevation of aminotransferases, on day 135 after allogeneic BMT. A liver biopsy specimen revealed degeneration of the small bile ducts and portal fibrosis, and the diagnosis of chronic hepatic GVHD was confirmed. No manifestation of chronic GVHD was observed except liver dysfunction. The administration of prednisolone (PSL) and cyclosporin (CsA) ameliorated laboratory data to a degree, but they did not return to normal. Treatment with ursodeoxycholic acid (UDCA), subsequently added to the immunosuppressive therapy, apparently normalized the levels of biliary tract enzyme and total bilirubin. His liver function test completely returned to normal on day 260. We believe that it is worthwhile to administer UDCA as an additional treatment for not only common hepatic GVHD but also atypical cases presenting as acute hepatitis.

Acute Disease↗
PubMed2002

Diagnosis and patient management of intraductal papillary-mucinous tumor of the pancreas by using peroral pancreatoscopy and intraductal ultrasonography.

BACKGROUND & AIMS: Intraductal papillary-mucinous tumor (IPMT) of the pancreas has attracted increasing interest because of its unique presentation. The differential diagnosis between malignant and benign tumors is extremely important in the determination of the therapy for IPMT. The aims of this study are to determine the usefulness of peroral pancreatoscopy (POPS) and intraductal ultrasonography (IDUS) in IPMT for the differentiation of malignant from benign disease, and to evaluate the significance of these techniques as new preoperative examinations. METHODS: Sixty histopathologically confirmed patients with IPMT underwent POPS and/or IDUS preoperatively. POPS was perfomed in all patients, and IDUS in 40. Findings of POPS and IDUS were compared with histopathology of resected specimens. The postoperative follow-up data were analyzed. RESULTS: Protruding lesions were detected by POPS in 40 patients. They were classified into 5 groups. Fish-egg-like type with vascular images, villous type, and vegetative type were considered to be malignant. By IDUS, lesions protruding 1 mm or more were observed in 36 patients. Of the lesions protruding 4 mm or more, 88% were malignant. Combination of POPS and IDUS improved the differential diagnosis between benign and malignant IPMT. The 3-year cumulative survival rate and disease-free survival rate were extremely high at 95% and 93%, respectively. CONCLUSIONS: The combination of POPS and IDUS results in a considerably improved differential diagnosis between malignant and benign IPMT and is useful for determining an effective therapeutic approach. These new techniques can contribute to improvements in postoperative results.

Adenoma↗
PubMed2002

Increased metabolizing activities of the tricarboxylic acid cycle and decreased drug metabolism in hepatocellular carcinoma.

The aim of this study was to determine the metabolizing activities in the liver of patients with hepatocellular carcinoma (HCC). Thin-layer chromatography autoradioluminography was used to measure metabolizing activities. Succinate-producing activity (SPA) was used as an indicator of metabolizing activity of the tricarboxylic acid (TCA) cycle in mitochondria, and diazepam-N-demethylating activity (DZ-DA), diazepam-3-hydroxylating activity (DZ-HA) and tolbutamide-methyl-hydroxylating activity (TB-HA) as indicators of drug metabolizing activities by P-450. SPA and drug-metabolizing activity of HepG2 cells were examined to compare with those of human liver specimens. Liver biopsy specimens of 30 patients and surgical specimens of eight patients with HCC were studied. SPA of HepG2 cells was as high as that of human tumor tissue, and DZ-DA, DZ-HA and TB-HA were undetectable in HepG2 cells. SPA and DZ-HA of non-tumor tissue in biopsy samples were significantly higher than those in resected liver specimens (P < 0.05). In biopsy specimens, SPA was significantly higher in tumor tissue than in non-tumor tissue (P < 0.05), and DZ-DA, DZ-HA and TB-HA were significantly lower in tumor tissue (P < 0.01). SPA was significantly higher in large tumors (>/=30 mm) than in small tumors <30 mm (P < 0.05), and TB-HA was significantly lower in large tumors than in small tumors (P < 0.01). DZ-DA and TB-HA significantly decreased with the progression of the tumor differentiation (P < 0.05). In conclusion, HCC has increased metabolizing activities of the TCA cycle and decreased drug-metabolizing activities.

Carcinoma, Hepatocellular↗
PubMed2002

Evaluation of the Helicobacter pylori stool antigen test for monitoring eradication therapy.

OBJECTIVE: We aimed to clarify the time course of the Helicobacter pylori stool antigen (HpSA) level during and after eradication therapy and to determine the appropriate time of measurement of HpSA to evaluate eradication. METHODS: The subjects were 47 patients who were positive for H. pylori. The patients underwent a 1-wk regimen of triple therapy. The outcome of the eradication therapy was judged by urea breath test, culture, and histology 6 wk after the end of treatment. The HpSA level was serially measured nine times from before therapy until 12 wk after the end of therapy. RESULTS: In the group with successful eradication, HpSA became negative immediately after the end of therapy and the negativity persisted. In contrast, in the noneradication group HpSA became negative immediately after therapy, but became positive again within 2 wk after the end of therapy. The mean absorbance value of the HpSA test on the 4th day after the initiation of eradication therapy was significantly higher in the noneradication group than in the group with successful eradication. The diagnostic accuracy of the HpSA test increased to > or = 90% 2 wk after therapy and thereafter. Comparison of the diagnostic accuracy at 4 wk after the end of therapy showed no significant differences with that at 2, 6, 8, and 12 wk after the end of therapy. CONCLUSIONS: The course of the HpSA levels during and after eradication therapy in patients with successful eradication was quite different from that in noneradication patients. Measurement of HpSA was useful to evaluate eradication, and the appropriate evaluation of the outcome of treatment could be made as early as 2 wk after the end of therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2002

Irregularity of parenchymal echo patterns of liver analyzed with a neural network and risk of hepatocellular carcinoma in liver cirrhosis.

OBJECTIVE: In this study, we scored the hepatic parenchymal echo patterns as the coarse score (CS) analyzed with a neural network in cirrhosis patients and calculated the variations in CS as the coefficient of variation, and evaluate their usefulness as predictor of the development of hepatocellular carcinoma (HCC). METHODS: The relationship between the degree of variation in CS and histopathological findings was assessed in 10 autopsied livers fixed in formalin. The degree of intrahepatic variation in CS was calculated as the coefficient of variation of CS (CVCS). Irregular regeneration of liver cells in autopsied livers was classified into two categories, slight and severe. A total of 56 cirrhosis patients were prospectively followed to evaluate the predictors of HCC. RESULTS: A significant positive correlation was observed between CVCS and the coefficient of variation of the diameter of the regenerative nodules. Coefficient variation of nodule diameter and CVCS in patients in whom irregular regeneration was severe were significantly higher than those in patients in whom irregular regeneration was mild (p < 0.05). Concerning the relationship between hepatitis virus markers and CS or CVCS, CVCS was significantly higher in those who were hepatitis C virus antibody positive and those who were hepatitis B surface antigen negative (p < 0.01). Using a combination of CS and CVCS, the incidence of HCC, as determined by the Kaplan-Meier method, was significantly higher in patients whose CS was > or = 1.5 and CVCS was > or = 15%, as compared with that in patients whose CS was <1.5 and CVCS was <15% (p < 0.01) and whose CS was > or = 1.5 and CVCS was <15% (p < 0.05). Multivariate analysis of the predictors for HCC using the Cox's proportional hazards model showed a significant correlation between the risk of development of HCC and CVCS, CS and serum alpha-fetoprotein level. CONCLUSIONS: CVCS and CS can be calculated from liver echo patterns and are useful for identifying a high-risk group for HCC.

Alanine Transaminase↗
PubMed2002

Decreased expression of the CCAAT/enhancer binding protein alpha gene involved in hepatocyte proliferation in human hepatocellular carcinomas.

CCAAT/enhancer binding protein alpha (C/EBPalpha), expressed at a high level in liver, plays an important role in proliferation and differentiation of hepatocytes. Previous studies showed that an expression level of the C/EBPalpha gene in hepatocytes was downregulated in response to proliferation signals and that forced expression of the C/EBPalpha gene in a number of cells caused cell cycle arrest. We compared the expression level of the C/EBPalpha gene in surgical specimens between hepatocellular carcinoma and non-tumorous regions of the same patients. In 9 out of 13 cases, the expression level in the tumors was decreased compared with that in corresponding non-tumorous regions. Transfection of the C/EBPalpha gene into C/EBPalpha-negative human hepatocellular carcinoma HLF cells, however, did not influence the rate of cell proliferation or cell cycle. Our present data suggest that the expression of the C/EBPalpha gene was downregulated in the majority of human hepatocellular carcinoma but the expression may not be directly associated with impaired proliferative activity of hepatocellular carcinoma cells.

Animals↗
PubMed2002

MEKK1 induces c-Jun complexes that act as negative regulators for cell survival and proliferation of HCC cells.

c-Jun has a variety of functions including proliferation, differentiation and death. c-Jun is specifically phosphorylated by c-Jun N-terminal kinase (JNK) which is regulated by Ras-MEKK1-MKK4/7 pathway. Previous studies showed that c-Jun protein plays a positive role in cell proliferation of normal hepatocytes and was detected in hepatocellular carcinoma (HCC) tissues. However, the function of c-Jun in HCC cells has not been examined. The aim of this study was to investigate whether the MEKK1-JNK signaling pathway and c-Jun may be involved in the survival and proliferation of HCC. Surprisingly, an active not dominant negative form of MEKK1 (CA-MEKK1) remarkably inhibited the colony formation of HCC cells. Gel retardation assays indicated that CA-MEKK1 induces c-Jun DNA binding, and luciferase assays exhibited that CA-MEKK1 enhances the transactivating activity of c-Jun in HCC cells. These results suggested that the inhibitory effect of CA-MEKK1 on colony formation is likely to be mediated by c-Jun. As expected, when wild-type c-Jun was transfected, the colony formation was significantly reduced. Especially in HuH7 cells, c-Jun transfected cells failed to make any colonies. Our data suggested that c-Jun activation can induce negative effect on survival and proliferation of HCC cells.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

A promoter region of midkine gene can activate transcription of an exogenous suicide gene in human pancreatic cancer.

We examined a possible application of regulatory regions of the midkine (MK) gene for suicide gene therapy of pancreatic cancer. The expression of MK has been demonstrated in human pancreatic cancer tissues but scarcely in normal adult tissues. Northern blot analysis confirmed that human pancreatic cancer cell lines expressed the MK gene. A 609-bp genomic fragment in the 5'-regulatory region of the MK gene, when transfected into human pancreatic cancer cells, activated the transcription of a fused reporter gene to an extent greater than the SV40 promoter. In contrast, the 609-bp fragment-mediated promoter activity tested in fibroblast cells was significantly weak. Human pancreatic cancer cells (AsPC-1) that were transduced with the herpes simplex virus-thymidine kinase gene linked with the 609-bp promoter markedly increased their sensitivity to a prodrug, ganciclovir, compared with untransduced cells. The present study suggests that preferential cytotoxic effects for pancreatic tumors can be achieved by using the MK promoter.

Carrier Proteins↗
PubMedDate not supplied

Down-regulated expression of the CCAAT/enhancer binding protein alpha and beta genes in human hepatocellular carcinoma: a possible prognostic marker.

CCAAT/enhancer binding protein alpha (C/EBP alpha) and C/EBP beta, liver specific transcription factors, are involved in hepatocyte proliferation and differentiation. The expression level of the C/EBP alpha and C/EBP beta genes were examined between tumor and non-tumorous tissues of the same hepatocellular carcinoma patients with quantitative real-time polymerase chain reactions. The expression of both the C/EBP alpha and C/EBP beta genes was down-regulated in the majority of the tumor specimens compared with corresponding non-tumorous tissues. Patients whose expression of either C/EBP alpha or C/EBP beta was higher in tumors than non-tumorous tissues survived longer than those whose expression was lower in tumors. Higher expression of C/EBP alpha or C/EBP beta in tumors was reversibly correlated with the tumor size and progression of the clinical stage. These data imply that the comparison of C/EBP alpha and C/EBP beta expression between tumors and non-tumorous regions could be a prognostic marker for patients with hepatocellular carcinoma.

CCAAT-Enhancer-Binding Protein-alpha↗
PubMedDate not supplied

Regulatory regions of growth-related genes can activate an exogenous gene of the alpha-fetoprotein promoter to a comparable degree in human hepatocellular carcinoma cells.

We examined the transcriptional activation by the regulatory regions of the midkine (MK), survivin (SUR), cyclooxygenase-2 (COX-2), telomerase reverse transcriptase (TERT) and alpha-fetoprotein (AFP) genes in human hepatocellular carcinoma cells. Luciferase assays showed that the SUR regulatory region exhibited the greatest activity and that the MK regulatory region activated the reporter gene better than the enhancer-linked AFP promoter even in high-AFP-producing cells. The COX-2 and TERT regulatory regions also activated the reporter gene better than the AFP enhancer/promoter in intermediate-AFP-producing cells. Combination of the regulatory regions arranged in tandem modulated their transcriptional activities, depending on the arrangement of the promoters and cells examined. These data suggested that the regulatory regions of the growth-related genes could be useful to activate a therapeutic gene in hepatocellular carcinoma cells irrespective of the amounts of AFP production but combinatory use of the promoter regions could not always contribute to enhanced activity.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Acute hepatitis C virus infection, 1986-2001: a rare cause of fulminant hepatitis in Chiba, Japan.

BACKGROUND/AIMS: Hepatitis C virus (HCV) is the most common cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. It is controversial whether HCV causes fulminant hepatitis. METHODOLOGY: To determine the clinical features and etiology of acute hepatitis and fulminant hepatitis in Japan, an endemic area of hepatitis C, between 1986 and 2001 inclusively, a retrospective study of consecutively referred patients was performed. Two hundred and sixty-three patients admitted to a liver clinic after diagnosis of acute hepatitis or fulminant hepatitis, were evaluated. RESULTS: We found 181 cases of acute hepatitis and 82 cases of fulminant hepatitis/late onset hepatic failure. No cases of fulminant hepatitis were positive for HCV RNA. Only three cases had positive anti-HCV antibody, and they were thought to indicate past HCV infection. The main cause of infection in these three patients was hepatitis A virus in one,hepatitis B virus in one, and drugs in the remaining one. HCV did not seem to be the major cause. The three cases died without receiving liver transplantation. CONCLUSIONS: It was revealed that fulminant hepatitis C rarely occurs in Japan, as well as in the USA and European countries. Investigators should search for other causes in fulminant cases presenting an HCV marker.

Adult↗
PubMedDate not supplied

Prevalence of obesity in patients with acute hepatitis; is severe obesity a risk factor for fulminant hepatitis in Japan?

BACKGROUND/AIMS: The prevalence of obesity in acute convalescent hepatitis and fulminant hepatitis has not been reported. The aim of this study was to investigate whether obesity affected the disease severity in Japanese patients with acute hepatitis. METHODOLOGY: 31 non-severe acute hepatitis (NS-AH) and 24 severe acute hepatitis and 14 fulminant hepatitis patients (S-AH) between January 1995 and December 2001 were analyzed retrospectively. Height and weight were used to calculate the body mass index (BMI) in these 69 patients. RESULTS: Mean height, weight and BMI were not significantly different between S-AH and NS-AH patients. Two severely obese (BMI greater than 35kg/m2) patients had developed S-AH. CONCLUSIONS: Severe obesity may be one of the prognostic factors in acute hepatitis. Further studies are needed.

Acute Disease↗
PubMedDate not supplied

Acute-onset autoimmune hepatitis resembling acute hepatitis: a case report and review of reported cases.

We report a 54-year-old Japanese man, whose ALT level was 1689 IU/L, without increased gamma-globulin level or autoantibodies. He could not be diagnosed as autoimmune hepatitis (AIH) using scoring systems, and his liver function became normalized after steroid treatment. Recently, AIH with acute presentation of disease and acute-onset AIH without bridging fibrosis have been increasingly reported but cases without the character of increasing gamma-globulin level or autoantibodies before immunosuppressive treatment are extremely rare. This is the third such case report in the literature.

Acute Disease↗