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Naondo Sohara

Publications and source records attributed to Naondo Sohara.

At least 19 recordsLinked to original sources
PubMed2006

The role of the nuclear receptor constitutive androstane receptor in the pathogenesis of non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease is a common liver injury, but the pathophysiological mechanisms leading to the development of non-alcoholic steatohepatitis (NASH) remain unclear. The pathological roles of the nuclear receptor constitutive androstane receptor (CAR), a key regulator of drug-metabolising enzymes, in the development of NASH were investigated. METHODS AND RESULTS: CAR(+/+) and CAR(-/-) mice were given a methionine and choline-deficient (MCD) diet to establish a dietary model of NASH. Increases in serum alanine aminotransferase (ALT) and in infiltration of inflammatory cells were dominant in CAR(+/+) mice at 8 weeks. There was no significant difference in the lipid concentration of the liver - namely, the first hit between CAR(+/+) and CAR(-/-) mice. The index of lipid peroxidation increased in liver of the CAR(+/+) mice, as demonstrated by 8-iso-prostaglandin F2alpha (F2-isoprostanes). Western blotting analysis showed that nuclear translocation of CAR occurred in CAR(+/+) mice fed the MCD diet. As a result, the CAR activation caused the lipid peroxidation - namely, the second hit. The expressions of cytochrome P450 (CYP)2B10, 2C29, 3A11 all increased considerably in the CAR(+/+) mice. Furthermore, alpha smooth muscle actin immunohistochemistry and Sirius red staining showed an increase in the degree of fibrosis in CAR(+/+) mice fed the MCD diet at 16 weeks. The mRNA expressions of collagen alpha1(1) and the tissue inhibitor of metalloproteinase-1 were found to be elevated in CAR(+/+) mice. CONCLUSION: CAR caused the worsening of the hepatic injury and fibrosis in the dietary model of NASH. Our results suggest that the CAR nuclear receptor may thus play a critical role in the pathogenesis of NASH.

Alanine Transaminase↗
PubMed2006

Integrative roles of transforming growth factor-alpha in the cytoprotection mechanisms of gastric mucosal injury.

BACKGROUND: Transforming growth factor alpha (TGFalpha) protects against gastric mucosal injury and facilitates wound healing. However, its overexpression is known to induce hypertrophic gastropathy resembling Menetrier's disease in transgenic (TG) mice on an FVB background, as one of the authors reported previously. We studied another TGFalpha-expressing mouse line on a CD1 background, whose gastric mucosa appears normal. Since this TG mouse had a strong resistance to ethanol-induced gastric injury, we considered the long-term effect of TGFalpha on several gastric protection mechanisms. METHODS: TGFalpha-expressing transgenic (TG) mouse lines bearing human TGFalpha cDNA under the control of the mouse metallothionein gene I promoter were generated on a CD1 mouse background, and analyzed their ethanol injury-resistant phenotypes produced by TGFalpha. RESULTS: In the TG mucosa, blood flow was well maintained after ethanol injury. Further, neural and inducible types of NO synthases were consistently and widely expressed in the TG mucosa, compared with the limited distribution of neural type NO synthase in the luminal pit region of the wild-type (WT) mucosa. COX-2 and its upstream transcription factor NfkB were constitutively elevated in the TG mucosa even before ethanol administration, whereas they were induced in the same region of the WT mucosa only after ethanol injury. Two anti-apoptotic proteins, HSP70 and Bcl-2, were upregulated in the TG mucosa even before ethanol administration, while they were not expressed in the WT mucosa before the injury. Furthermore, pro-caspase 3 activation was inhibited in the TG mucosa, while it was converted to the active form in the WT mucosa following ethanol administration. CONCLUSION: We conclude that TGFalpha maintains the gastric mucosal defense against gastric injury by integrating other cytoprotective mechanisms.

Animals↗
PubMed2006

Living-related liver transplantation for multiple liver metastases from rectal carcinoid tumor: a case report.

A 42-year-old woman was admitted to our hospital because of multiple liver tumors detected by ultrasonography. Colonoscopy revealed submucosal tumor in the rectum, which was considered the primary lesion. Endoscopic mucosal resection followed by histopathological examination revealed that the tumor was carcinoid. The resected margin of the tumor was positive for malignant cells. Two courses to transcatheter arterial chemotherapy for liver metastasis were ineffective. Accordingly, the rectal tumor and metastatic lymph nodes were surgically resected. One month after the operation, she received liver transplantation (left lateral segment and caudate lobe) from her son. No recurrent lesion has been observed at two years after the liver transplantation. Liver transplantation should be considered as a treatment option even in advanced case of carcinoid metastasis to the liver. We also discuss the literature on liver transplantation for metastatic carcinoid tumor.

Adult↗
PubMed2006

Spontaneous regression of hepatic inflammatory pseudotumor with primary biliary cirrhosis: case report and literature review.

Hepatic inflammatory pseudotumor (IPT) is a rare benign non-neoplastic lesion characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The exact etiology of IPT remains unclear. Although the association of IPT with systemic inflammatory disorders has been well established, a specific relationship with cholangitis is distinctly rare. We report a case of spontaneous regression of hepatic IPT with primary biliary cirrhosis (PBC). To date, only two cases of IPT with PBC have been reported. In our case, however, IPT developed during the course of improvement of cholangitis of PBC induced by effective treatment, differing from two previously reported cases. Our case indicates that the development of IPT does not also relate to the activity of cholangitis and/or hyper gamma-globulinemia, since our case was confirmed radiologically to be free of IPT when biliary enzymes and immunoglobulins were much higher than the corresponding values on admission. Comparison of our case with the two previously reported cases suggests that IPT occurring with PBC does not represent the same disease entity or be a bystander for PBC.

Aged↗
PubMed2006

Triple therapy of interferon and ribavirin with zinc supplementation for patients with chronic hepatitis C: a randomized controlled clinical trial.

AIM: To study the therapeutic effect of interferon (IFN) and ribavirin with zinc supplement on patients with chronic hepatitis C viral (HCV) infection. METHODS: A total of 102 patients confirmed histologically to have chronic HCV infection with genotype 1b and more than 100 KIU/mL of HCV were randomly assigned to each arm of the study and each received 10 million units of pegylated interferon (IFN-alpha-2b) daily for 4 wk followed by the same dose every other day for 20 wk plus ribavirin (600 or 800 mg/d depending on body weight), with or without polaprezinc (150 mg/d) orally for 24 wk. The primary endpoint was sustained virological response (SVR) defined as negative HCV-RNA in the serum 6 mo after treatment. RESULTS: There were no differences in the clinical background between the two groups except for more females in the dual therapy group than in the other group (P<0.05). SVR was observed in 33.3% of the triple therapy group and 33.3% of the dual therapy group. The side effects were almost the same in both groups except for gastrointestinal symptoms, which were less in the triple therapy group (P=0.019). CONCLUSION: Considered together, triple therapy of zinc plus IFN and ribavirin for HCV infection patients with genotype 1b and high viral load is not better than dual therapy except for lower incidence of gastrointestinal side effects.

Adult↗
PubMed2006

Randomized controlled trial of consensus interferon with or without zinc for chronic hepatitis C patients with genotype 2.

AIM: The beneficial effect of zinc supplementation on the efficacy of interferon as a treatment for chronic hepatitis C had been demonstrated in hepatitis virus genotype 1b of high viral load. This study focused on patients with genotype 2, which is more sensitive to interferon than genotype 1b, and used consensus interferon (CIFN) with or without zinc. METHODS: We randomized 83 patients with chronic hepatitis C to CIFN at 18 MIU six times/wk for 4 wk, followed by CIFN at 18 MIU six times/wk for another 20 wk, in combination with polaprezinc 300 mg (regimen A, n=41) or as monotherapy (regimen B, n=42). Thirty-one patients in regimen A and 33 patients in regimen B completed the clinical trial; the remaining patients withdrew because of side effects or a transfer to another hospital. RESULTS: Sustained biochemical response, defined as a normal aminotransferase level at the end of the 6-mo post-treatment observation, was 68% and 69%, and sustained virological response, defined as undetectable HCV-RNA at the end of the 6-mo post-treatment observation, was 54% and 67% for regimens A and B, respectively. CONCLUSION: CIFN treatment combined with zinc did not enhance the effect of CIFN as shown by biochemical, virological criteria. No side effects related to polaprezinc were noted.

Adult↗
PubMed2006

Computed tomography-guided transpulmonary radiofrequency ablation for hepatocellular carcinoma located in hepatic dome.

AIM: To determine the feasibility of performing computed tomography (CT)-guided transpulmonary radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) located in the hepatic dome. METHODS: A total of seven patients with HCC comprising seven nodules located in the hepatic dome were treated from April 2004 to December 2004. CT-guided transpulmonary RFA was performed using a cool-tip type electrode (Radionics Company) based on a standardized energy protocol. All tumors located in the hepatic dome were not detectable by the usual ultrasound (US) methods. The lesion diameters ranged from 15 to 27 mm. RESULTS: RFA was technically feasible in all the patients. The puncture procedure was performed twice or less and the total average performance time was 40.6 min. Local tumor control was achieved in all the patients. The necrosis diameter ranged from 25 to 35 mm. The mean follow-up period was 9.6 (7-14 mo) mo. There was no local recurrence at the follow-up points. Pneumothorax requiring pleural drainage was the main complication, which was observed in two of the seven patients (28.6%). However, it improved with chest drainage tube, and the tube could be removed within 2-3 d. No other major complications were observed. CONCLUSION: CT-guided puncture is useful for the treatment of tumors located in the hepatic dome which are hardly detectable by US, even though pneumothorax sometimes may occur as a complication. In the cases with adhesion in the pleura for which artificial pleural effusion methods are not appropriate, CT-guided RFA is thus considered to be an alternative treatment for HCC located in the hepatic dome.

Aged↗
PubMed2006

Hepatic adenomatosis associated with hormone replacement therapy and hemosiderosis: a case report.

We have reported a case of hepatic adenomatosis associated with hormone replacement therapy (estrogen and progesterone) and hemosiderosis caused by excessive blood transfusion for the treatment of chronic myeloid leukemia. A 34-year-old woman was found to have several hepatic tumors on a routine medical examination. The general condition was good. Laboratory studies showed iron overload. Abdominal computed tomography and selective hepatic angiography showed several hypervascular tumors in the right lobe of the liver (up to 20 mm in diameter). Since hepatocellular carcinoma could not be ruled out, subsegmental hepatectomy was performed. Histopathological examination of the surgical specimen showed hepatic adenomatosis with hemosiderosis. Both hormone replacement therapy and iron overload could be the cause of hepatic adenomatosis.

Adenoma↗
PubMed2006

Different outcomes of nosocomial infection with hepatitis C virus from the same origin.

The outcome of infection with hepatitis C virus (HCV) varies substantially from self-limiting infection to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma among the individuals. The mechanisms that determine the clearance or the persistence of HCV have not yet been clarified. Here, we experienced two cases of hospital-related infection with HCV from the same origin but with quite different outcomes. One case resolved after an episode of acute hepatitis, while the other case developed a chronic hepatitis although they were infected with HCV of the same origin. Although infected with the virus of the same origin, the clinical and virological courses were completely different. This suggests that host factors play a major role in conditioning the outcome of acute HCV infection.

Adult↗
PubMed2006

Hepatocellular carcinoma in extremely elderly patients: an analysis of clinical characteristics, prognosis and patient survival.

AIM: To identify the clinical and prognostic features of patients with hepatocellular carcinoma (HCC) aged 80 years or more. METHODS: A total of 1310 patients with HCC were included in this study. Ninety-one patients aged 80 years or more at the time of diagnosis of HCC were defined as the extremely elderly group. Two hundred and thirty-four patients aged > or = 50 years but less than 60 years were regarded as the non-elderly group. RESULTS: The sex ratio (male to female) was significantly lower in the extremely elderly group (0.90:1) than in the non-elderly group (3.9:1, P < 0.001). The positive rate for HBsAg was significantly lower in the extremely elderly group and the proportion of patients negative for HBsAg and HCVAb obviously increased in the extremely elderly group (P < 0.001). There were no significant differences in the following parameters: diameter and number of tumors, Child-Pugh grading, tumor staging, presence of portal thrombosis or ascites, and positive rate for HCVAb. Extremely elderly patients did not often receive surgical treatment (P < 0.001) and they were more likely to receive conservative treatment (P < 0.01). There were no significant differences in survival curves based on the Kaplan-Meier methods in comparison with the overall patients between the two groups. However, the survival curves were significantly worse in the extremely elderly patients with stage I/II, stage I/II and Child-Pugh grade A cirrhosis in comparison with the non-elderly group. The causes of death did not differ among the patients, and most cases died of liver-related diseases even in the extremely elderly patients. CONCLUSION: In the patients with good liver functions and good performance status, aggressive treatment for HCC might improve the survival rate, even in the extremely elderly patients.

Adult↗
PubMed2006

Solitary mandibular metastasis as an initial manifestation of hepatocellular carcinoma.

Oral metastases from hepatocellular carcinoma are very rare. We encountered a case of hepatocellular carcinoma with a solitary metastasis to the mandible as an initial manifestation. The patient was a 76-year-old man who was admitted for left mandibular swelling. A biopsy specimen of mandible was suspected to be a metastatic tumor. The histological findings, abdominal computed tomography, bone scintigraphy, and F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed it to be a solitary metastasis from hepatocellular carcinoma. As a result, he was diagnosed to have liver cirrhosis due to a hepatitis C virus infection and hepatocellular carcinoma with a solitary metastasis to the mandible. The primary lesion was treated with transcatheter arterial embolization (TAE), and the metastasis to the mandible was surgically resected. The patient survived for 9 months after treatment without recurrence.

Aged↗
PubMed2006

Ectopic varices in a right diaphragm that ruptured into the pleural cavity.

The term ectopic varices is used to describe dilated portosystemic collateral veins in unusual locations other than the gastroesophageal region. We recently experienced a rare case of ectopic varices that developed in the right diaphragm and ruptured into the pleural cavity. A 68-year-old female with hepatocellular carcinoma complicated with liver cirrhosis was admitted due to an acute onset of dyspnea and right bloody pleural effusion. Because of the patient's advanced hepatocellular carcinoma and poor condition, conservative therapies such as hemostats and blood transfusion were selected. Even though the bleeding to the pleural cavity stopped spontaneously, the patient died due to a progression of liver failure. Autopsy revealed a huge collateral vein in the right diaphragm. The etiology, prevalence, relationship with portal hypertension, and treatment of ectopic varices are discussed herein.

Aged↗
PubMed2005

Overexpression of NK2 inhibits liver regeneration after partial hepatectomy in mice.

AIM: To investigate the in vivo effects of NK2 on liver regeneration after partial hepatectomy (PH). METHODS: Survival after PH was observed with 21 NK2 transgenic mice and 23 wild-type (WT) mice over 10 d. Liver regeneration was analyzed using histology and immunohistochemistry. Expressions of genes were analyzed using Northern blot analysis, immunoprecipitation and immunoblotting, and reverse transcriptase polymerase chain reaction assay. Kaplan-Meier method and the log-rank test were used for analyzing the survival after PH. Differences in the results of immunohistochemistry and percentage of liver regeneration was determined by the Student's t-test. RESULTS: More than half of NK2 transgenic mice died within 48 h after PH. After PH, increased deposition of small lipid droplets in hepatocytes was evident and hepatic proliferation was inhibited in NK2 transgenic mice. The hepatic expression and kinase activity of HGF receptor, c-Met, were unchanged among WT mice and NK2 transgenic mice after PH. The expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in liver tissues were prolonged in NK2 transgenic mice that died after PH. CONCLUSION: Our findings indicate that over-expression of NK2 inhibits liver regeneration after PH.

Animals↗
PubMed2005

Adult onset type II citrullinemia as a cause of non-alcoholic steatohepatitis.

Adult onset type II citrullinemia (CTLN2) is an autosomal recessive disease accompanied with hyperammonemia and a sudden onset of psychiatric disorders. We demonstrated three male patients with CTLN2 having a liver histology of non-alcoholic steatohepatitis (NASH). Patients with NASH were analyzed for the causative gene of CTLN2, SLC25A13 and discussed.

Adolescent↗