bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of P‐glycoprotein and p53 in advanced hepatocellular carcinoma treated by single agent chemotherapy: Clinical correlation
Authors: CHOU YUH‐YU , CHENG ANN‐LII , HSU HEY‐CHI 
Published: March 2008

ABSTRACTHepatocellular carcinoma (HCC), a chemoresistant tumour, is the most common fatal cancer in Taiwan. Hepatocellular carcinoma frequently expresses a high level of P‐glycoprotein (P‐gp), which is a specific phenotype of a multidrug‐resistance gene, and harbours mutations of the tumour suppressor gene p53. A modulatory relationship between p53 and P‐gp has been reported. In this study, we analysed the expression of P‐gp in relation to chemotherapeutic response and p53 protein expression in advanced HCC. Prechemotherapeutic tumour samples were obtained from 25 patients with HCC which had been treated with either etoposide (VP‐16) or doxorubicin. P‐glycoprotein and p53 in HCC were visualized by immunohistochemical staining using the monoclonal antibodies JSB‐1 and DO1, respectively. We investigated the correlation of P‐gp expression with chemotherapeutic responses, clinicopathological features and p53 protein expression. In our study, seven cases achieved partial remission, and the remaining 18 cases had a poor response to chemotherapy. Expression of P‐gp was observed in 13 tumours (52%). Positive P‐gp protein expression was significantly associated with non‐responders (8% or 1/13 vs 50% or 6/12, P= 0.03). Thus, P‐gp expression inversely correlated with chemotherapeutic response. Expression of p53 protein was seen in 12 cases and did not correlate with chemosensitivity or P‐gp expression. In summary, P‐gp expression correlates with the chemosensitivity of HCC that has been treated with VP‐16 or doxorubicin and p53 mutations do not appear to be a major determinant of P‐gp expression in advanced HCC.
Haemodynamic effects of chronic tetrandrine treatment in portal hypertensive rats
Authors: HUANG YI‐TSAU , CHENG YUH‐REN , LIN HAN‐CHIEH , CHEN CHIEH‐FU , HONG CHUANG‐YE 
Published: March 2008

ABSTRACTTetrandrine is a calcium channel antagonist with reported antihypertensive effect. However, the potential role of tetrandrine as a therapeutic agent in portal hypertension has yet to be explored. The present study aimed to investigate the haemodynamic effects of chronic tetrandrine treatment on portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation in Sprague‐Dawley rats. Animals were allocated into one of two groups: a tetrandrine group and a vehicle group. Tetrandrine (20 mg/kg) or vehicle was administered by gavage every 12 h for 8 consecutive days, starting 1 day before ligation and continuing thereafter. After 8 days of tetrandrine treatment, systemic haemodynamics, organ blood flows and the degree of portal‐systemic shunting were measured after an overnight fast. The portal venous pressure and portal tributary blood flow were significantly decreased, while portal territory as well as hepato‐collateral vascular resistance significantly increased in the tetrandrine group compared with the vehicle group. The cardiac index was increased, while systemic vascular resistance was decreased, in the tetrandrine group. Mean arterial pressure, heart rate, portalsystemic shunting and bodyweight were similar between the two groups. Renal blood flow was decreased in the tetrandrine group. In conclusion, long‐term treatment of tetrandrine reduced portal venous pressure and alleviated splanchnic hyperaemia in portal hypertensive rats without affecting the portal‐systemic shunting.
Radiological retrospective study of gastric cancer in humans: Two patterns of development in elevated type gastric cancer
Authors: MIWA HIROTO , IWAZAKI RYOZO , OHKURA RYUICHI , NAGAHARA AKIHITO , MURAI TOSHIO , OGIHARA TATSUO , WATANABE SUMIO , SATO NOBUHIRO 
Published: March 2008

ABSTRACTA better understanding of the process of gastric cancer development would undoubtedly be helpful in diagnosis and treatment. However, there is little literature available concerning the natural history of elevated type gastric cancer in humans and this disease has not been systematically investigated. In this study the natural history of elevated type human gastric cancer was retrospectively investigated in 12 radiologically followed‐up patients. The cases were divided into two groups according to whether obvious abnormal findings were absent (group A, n= 5) or present (group B, n= 7) at initial examination. Clinico‐pathological features, including outcomes and DNA content of the tumours in both groups, were investigated and compared. Although the mean period between the initial and final examinations was significantly shorter in group A (19.6±11.7 months) than in group B (43.4±17.3 months), tumour size was significantly larger in group A (5.5±2.5 cm) than in group B (2.4±2.5 cm). Furthermore, group A showed deeper neoplastic cell invasion and worse outcomes. The DNA content of two cases in group A and four cases in group B was examined. One case in group A showed an aneuploid pattern, while all of those in group B showed a diploid pattern. These results indicate that the tumours in group A grew much faster than those in group B, which suggests the presence of two different patterns of development in elevated type gastric cancer.
Fas system and apoptosis in viral hepatitis
Authors: HAYASHI NORIO , MITA EIJI 
Published: March 2008

ABSTRACTHepatitis C virus (HCV) and hepatitis B virus (HBV) are the major causative agents of chronic liver disease. However, the mechanisms responsible for liver cell injury remain to be clarified. Playing crucial roles in the clearance of viral infection are cytotoxic T lymphocytes. Recently, it has been demonstrated that perforin‐ and Fas‐based mechanisms account for all T cell‐mediated cytotoxicity. Therefore, we examined the correlation between liver cell damage and the Fas system in the liver of patients with chronic hepatitis C. Fas is a cell surface protein that mediates apoptosis with treatment of the Fas ligand or the anti‐Fas antibody. To investigate the role of Fas in type C hepatitis, we examined the correlation between liver cell damage and Fas expression. Fas expression was found mainly in the cytoplasm of hepatocytes and these positive cells were found particularly among infiltrating lymphocytes. A high prevalence of Fas expression was shown in liver tissue with more severe inflammation. The Fas system‐mediated death signal requires the interaction of Fas ligand with Fas on target cells. We isolated a 1.9 kb cDNA clone for the human Fas ligand and examined the expression of the Fas ligand in liver‐infiltrating mononuclear cells obtained from patients with chronic hepatitis C. The open reading frame encodes 281 amino acids. Next, we examined the expression of the Fas ligand in liver‐infiltrating mononuclear cells obtained from patients with chronic hepatitis C. The amplified products (231 bp) derived from Fas ligand transcripts were detected in liver‐infiltrating mononuclear cells, whereas no signal was observed in liver tissues. In HCV infection, Fas expression in hepatocytes is up‐regulated in accordance with the severity of liver inflammation. When HCV‐specific T cells migrate into hepatocytes and recognize the viral antigen via the T cell receptor, they become activated and express Fas ligand that can transduce the apoptotic death signal to Fas‐bearing hepatocytes. Thus, the Fas system plays an important role in liver cell injury by HCV infection.
Recent developments in autoimmune liver diseases
Authors: MANNS MICHAEL P 
Published: March 2008

ABSTRACTSeveral diseases are regarded as autoimmune liver diseases. Apart from the cholestatic liver diseases, primary biliary cirrhosis, primary sclerosing cholangitis, these include autoimmune hepatitis, hepatitis as part of the autoimmune polyendocrine syndrome type 1 (APS‐1) and particular overlap syndromes such as autoimmune cholangitis (also called antimitochondrial antibody negative primary biliary cirrhosis [PBC]), overlap syndrome chronic active hepatitis (CAH)/PBC and the overlap syndrome primary sclerosing hepatitis (PSC)/CAH. In addition, auto‐antibodies may be observed during the course of chronic viral hepatitis, in particular chronic hepatitis C and D. Finally, a small number of drug‐induced liver diseases is immune mediated. The following article will review our recent progress in the field of autoimmune hepatitis including APS‐1 and autoimmunity in viral hepatitis and immune‐mediated drug‐induced liver disease.
Living related donor liver transplantation
Authors: CHEN CHAO‐LONG , CHEN YAW‐SEN , LIU PO‐PING , CHIANG YUAN‐CHENG , CHENG YU‐FAN , HUANG TUNG‐LIANG , ENG HOCK‐LIEW 
Published: March 2008

ABSTRACTLiving related liver transplantation (LRLT) has been developed in response to the paediatric organ donor shortage. According to the International Living Donor Registry, 521 transplants had been performed in 515 patients between December 8 1988 and January 19 1996 in 30 centres worldwide. The overall actuarial patient and graft survival rates were 82.7 and 80%, respectively. Between June 17 1994 and November 30 1996, the authors performed 11 LRLT at the Chung Gung Memorial Hospital. The living donors consisted of 10 mothers and one father. The mean graft weight was 303 g and the mean graft recipient weight ratio was 2.2%. Donor hepatectomy was performed without vascular inflow occlusion. The intra‐operative blood loss ranged from 30 mL to 120 mL with an average of 61 mL, and blood transfusion was not required in all donors both intra‐operatively and during the postoperative period. Underlying diseases of the recipients were biliary atresia (n= 10) and glycogen storage disease (n= 1). The mean graft cold ischaemia time was 106 min, the mean second warm ischaemia time was 51 min and the mean interval between portal and arterial reperfusion was 81 min. The initial LRLT results were promising with all donors having been discharged without complication. The recipients experienced a few complications, all of which were manageable with early intervention. All 11 recipients are alive and well. These are encouraging results and the authors hope to expand the use of live donors for liver transplantation to cope with demand.
Case Report: Congenital absence of the portal vein associated with nodular hyperplasia in the liver
Authors: MOTOORI SHIGEATSU , SHINOZAKI MASAMI , GOTO NOBUAKI , KONDO FUKUO 
Published: March 2008

ABSTRACTCongenital absence of the terminal portion of the portal vein with visceral venous return to the suprahepatic inferior vena cava, a rare malformation, was demonstrated in an 18‐year‐old Japanese woman. She had nodular hyperplasia in the liver and a non‐functioning pancreatic endocrine tumour. It is generally believed that reduction of portal venous flow causes atrophic changes and, subsequently, nodular hyperplasia occurs in a well‐perfused area in the liver. However, the liver was not perfused by the portal vein in this case. It is suggested that nodular hyperplasia can occur without portal blood flow.
Serum levels of sCD23, interleukin‐10 and interferon‐γ in patients with coeliac disease
Authors: BANSAL AS , BRUCE J , THOMSON A , KERLIN P 
Published: March 2008

ABSTRACTThe role of cellular and humoral immunity coeliac disease was investigated by the measurement of serum levels of interleukin‐10 (IL‐10), interferon‐gamma (IFN‐γ) and soluble CD23 (sCD23). Coeliac disease was diagnosed by duodenal biopsy and response to a gluten‐free diet (GFD). The results were compared with age and sex‐matched patients with non‐specific upper gastrointestinal symptoms and normal duodenal histology. While the levels of serum IL‐10 were significantly elevated (P < 0.01) in patients with coeliac disease taken as a whole, the levels of serum IFN‐γ were normal and sCD23 significantly decreased (P < 0.002). The median serum sCD23 was significantly lower in the coeliac disease patients not on a GFD compared with those asymptomatic on a GFD (P < 0.03) and the control group (P < 0.0004). The coeliac disease patients on a GFD also had significantly lower serum sCD23 and higher IL‐10 compared with the control group (P < 0.01 and P < 0.015). There was no significant difference in the serum IL‐10 between the coeliac disease patients on a GFD and those not on a GFD and between the latter and the control group. The low levels of serum sCD23 in coeliac disease suggest diminished humoral immunity and, conversely, exaggerated cellular immunity. The aetiology of the raised levels of IL‐10 in coeliac disease is unclear and similar to that observed in patients with inflammatory bowel disease. However, this may represent a regulatory response to the elevated levels of proinflammatory cytokines described in coeliac disease. A combination of diminished sCD23 and raised IL‐10 is clearly unusual as both are associated with Th2‐type functions. The possible causes of this finding are discussed.
Hepatitis viruses under immunosuppressive agents
Authors: LIAW YUN‐FAN 
Published: March 2008

ABSTRACTClinical and experimental studies have shown that T cell‐mediated immune mechanisms are involved in the pathogenesis of hepatitis B virus (HBV) and hepatitis C virus infection. Immunosuppressants may impair T cell function and thereby reduce immune‐mediated hepatocytolysis and virus clearance. In addition, corticosteroid may activate the glucocorticoid responsive element in the HBV genome to enhance HBV replication and gene expression. These combined effects result in an increase of viraemia in association with a decrease of serum aminotransferase and hepatic necroinflammation. In acute infection, use of immunosuppressants will increase the incidence of chronic evolution. In chronic infection, withdrawal of immunosuppressants will be followed by a clinical flare due to a rebound of immune attack to hepatocytes with increased viral load. This may lead to a subsequent decrease of the viraemia. Therefore, short‐term use of immunosuppressant before antiviral therapy may be beneficial in the treatment of chronic viral hepatitis. However, the clinical rebound may be extremely severe and lead to hepatitis failure; thus, the patients should be monitored closely upon tapering and after the withdrawal of immunosuppressants. Long‐term use of immunosuppressants in patients with hepatitis virus infection is usually deleterious, particularly in patients after organ transplantation. These findings suggest that clinicians should be cautious in the use of immunosuppressants in patients with hepatitis virus infection.
Combined hepatocellular‐cholangiocarcinoma: A clinicopathological study
Authors: NG IRENE OL , SHEK TONY WH , NICHOLLS JOHN , MA LILY T 
Published: March 2008

ABSTRACTCombined hepatocellular‐cholangiocarcinoma (HCC‐CC) is an uncommon form of primary liver cancer having features of both hepatocellular and biliary epithelial differentiation. We reviewed 21 cases of this tumour diagnosed between 1972 and 1996 (patient age range 16–79 years; mean patient age 49.7 years; 18 male and three female patients). Histologically, the majority (n= 18) of tumours were ‘mixed’ tumours, in which areas of hepatocellular and biliary epithelial differentiation were intimately mixed within the same tumours. Two patients had separate tumours in which discrete nodules of HCC and CC occurred in the same livers. One patient had a ‘fibrolamellar’ tumour that histologically simulated the fibrolamellar variant of HCC, but some of the tumour cells were mucin‐producing cells. Of the 21 cases, mucin was demonstrable in 16 and, in the few mucin‐negative tumours, electron microscopic studies confirmed the presence of the dual differentiation. The tumours frequently exhibited an invasive character with frequent venous permeation, direct invasion into adjacent liver parenchyma and tumour microsatellite formation, similar to that of ordinary HCC. Histological evidence of cirrhosis or chronic hepatitis was present in 77.8% of patients and 75% of patients were hepatitis B surface antigen positive. Raised serum α‐fetoprotein (AFP) levels (above 300 ng/mL) were present in 61.5% of patients and AFP was detected immunohistochemically in 55% of tumours. The overall survival times of patients with HCC‐CC were short. In conclusion, HCC‐CC showed clinical and pathological features more akin to those of ordinary HCC than to CC.
Intra‐arterial carbon dioxide‐enhanced ultrasonogram of hepatocellular carcinoma treated by transcatheter arterial embolization and percutaneous ethanol injection therapy
Authors: CHEN RAN‐CHOU , WANG CHUNG‐KWE , CHIANG LIANG‐CHUNG , LO HSIN‐YEN , DUH SHGI‐JYE , CHEN WEI‐TZUNG , TU HSING‐YANG , LIAO LI‐YING , WANG CHAUR‐SHINE , CHEN PAO‐HUEI 
Published: March 2008

ABSTRACTThe purpose of this study was to investigate the value of carbon dioxide‐enhanced ultrasonography (CO2‐US) in the evaluation of viable hepatocellular carcinomas (HCC) which were treated by transcatheter arterial embolization (TAE), percutaneous ethanol injection (PEI), or a combination treatment (TAE and PEI). Forty‐one patients with 66 HCC were included in the study. They underwent CO2‐US and angiography were performed in all tumours after they were treated by TAE, PEI or a combination treatment. Forty‐six tumours were positively enhanced by CO2‐US and 40 of them were positive by angiography. These 46 tumours were proved to be viable tumours either by biopsy or by follow‐up studies. The positive predictive value was 100% for CO2‐US and 87.8% in angiography. Twenty tumours were negative by CO2‐US and these were also negative by angiography. Carbon dioxide‐enhanced ultrasonography is a more reliable method for detecting the viable portion of the treated HCC compared with conventional angiography.
Changes in biliary excretory mechanisms in rats with ethinyloestradiol‐induced cholestasis
Authors: TAKIKAWA HAJIME , TAKAMORI YORIYUKI , SANO NAOYO , KUYAMA YASUSHI , YAMANAKA MASAMI 
Published: March 2008

ABSTRACTSeveral excretory pathways for cholephilic compounds have been known. To examine the changes in excretory pathways in cholestasis induced by ethinyloestradiol, various bile acids, organic anions and organic cations were intravenously administered to ethinyloestradiol‐treated rats and their biliary excretion was studied. Biliary excretion of taurocholate was slightly delayed, but its excretory maximum was markedly decreased. Biliary excretion of lithocholate‐3‐O‐glucuronide, leukotriene C4, sulphobromophthalein and pravastatin was markedly impaired to a similar extent. Biliary excretion of vinblastine, a P‐glycoprotein substrate, was increased, suggesting increased expression of P‐glycoprotein. In contrast, biliary excretion of erythromycin, a cationic antibiotic, was markedly impaired. In conclusion, ethinyloestradiol treatment altered the biliary excretion of organic compounds, which may partly be related to changes of the canalicular transporters.
Acute in vivo effect of octreotide acetate, a somatostatin analogue on the cellular function of gastric mucosa in the rat
Authors: MOTEGI MASAHIKO , NAGAMACHI YUKIO , KANEKO TETSUYA , MATSUZAKI SHIGERU 
Published: March 2008

ABSTRACTSomatostatin is known to suppress various cellular functions of the gastrointestinal tract. In the present study, octreotide acetate, a synthetic long‐acting somatostatin analogue was tested for its effects on some cellular functions of gastric mucosa. Octreotide raised the gastric mucosal pH within 1 h after a single subcutaneous injection to rats at doses of 1–100 μg/kg bodyweight. Serum gastrin levels increased transiently at a dose of 10 μg/kg bodyweight but not at 100 μg/kg. Basal levels of serum gastrin were not affected, while famotidine‐induced gastrin secretion was suppressed by octreotide at a single dose of 100 μg/kg. The increase in the intragastric acidity and histidine decarboxylase activity following pentagastrin treatment was significantly reduced by octreotide. These results suggested that this somatostatin analogue inhibits the function of not only the parietal cell and G cell but also the enterochro‐maffin‐like (ECL) cell, resulting in intraluminal hypoacidity.
Low‐dose recombinant interferon therapy in anti‐HBe‐positive chronic hepatitis B in Asian Indians*
Authors: GUPTAN RAJ KUMAR C , THAKUR VARSHA , MALHOTRA VEENA , SARIN SHIV K 
Published: March 2008

ABSTARACTApproximately 15% of Indian patients with hepatitis B virus (HBV)‐related chronic liver disease (CLD) have infection with precore mutant forms. These patients are likely to have an aggressive course. There are equivocal reports of success with interferon therapy of mutant infection in the West. This therapy has not been evaluated in precore mutant‐related CLD in Asian Indians. Eighteen patients (mean age 38.2 ± 12 years, M: F: 17: 1) with biopsy proven CLD and precore mutant HBV infection (hepatitis B surface antigen (HBsAg) positive, hepatitis B e antigen (HBeAg) negative, anti‐HBe positive, HBV‐DNA positive) were included. Interferon alpha 2b was given at 3 mIU on alternate days for 4 months. Serology, determination of HBV‐DNA (both by dot‐blot hybridization and polymerase chain reaction) and liver biopsy were repeated after completion of the therapy. Response to interferon therapy was defined as loss of HBV‐DNA by dot‐blot hybridization. Thirteen (72.2%) patients responded to the treatment (responders). Mean alanine aminotransferase levels (83 ± 12 vs 55 ± 29 IU/L, P < 0.01) and the histological activity index (15 ± 1.4 vs 12 ± 1.3, P < 0.01) significantly decreased in the responders compared with initial values. Serum albumin levels also improved at the end of the therapy (3.5 ± 0.4 g/dL vs 3.8 ± 0.4 g/dL, P= 0.07). During follow up, seven of the 13 (54%) responders relapsed; cirrhotics relapsed more often than chronic hepatitis patients (P < 0.05). All 18 patients, however, continued to be HBV‐DNA positive at the end of follow up. This study concluded that:1. Interferon therapy is beneficial, albeit to a limited extent, in HBV precore mutant‐related chronic liver disease in Asian Indians.2. It is ineffective in eliminating the mutant HBV infection, which explains the high relapse rate.3. Prolonged low‐dose interferon therapy alone or in combination with newer nucleoside analogues should be evaluated in these patients.