bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous occurrence of autoimmune cholangitis in senescent mice
Authors: KANDA KIMITOSHI , ONJI MORIKAZU , OHTA YASUYUKI
Published: March 2008

Abstract The biliary lesions that developed spontaneously in senescent female C57BL/6NCrj mice were investigated. Degeneration of the bile duct epithelium was observed in 12 of 13 mice (92%), destruction of bile duct epithelial cells was seen in six of 13 mice (46%) and chronic non‐suppurative destructive cholangitis was found in three of 13 mice (23%). The biliary lesions were characterized by prominent round cell infiltrates in the portal areas. Extra‐hepatic lesions such as sialoadenitis were observed in six mice (46%) and pancreatitis in seven (53%). IgM class antipyruvate dehydrogenase antibody was positive in one of three C57BL/6NCrj mice not given anti‐Lyt 2 antibody and in three of six C57BL/6NCrj mice injected with anti‐Lyt 2 antibody. These lesions were not observed in male C57BL/6NCrj mice, young female C57BL/6NCrj mice, or ICR mice. However, by transferring the splenic cells of senescent female C57BL/6NCrj mice to 6 week old females, the biliary lesions could be transferred at the rate of 6/9. The lymphocytes infiltrating in the bile ducts were CD8 positive lymphocytes. Moreover, in the ultrastructural immunocytochemical analysis of lymphocytes infiltrating bile duct epithelia, CD8 positive lymphocytes often formed broad contacts with the epithelial cells. The biliary lesions developing spontaneously in these mice are similar to those found in human primary biliary cirrhosis.
Differential regulation of ferritin H and L subunit mRNA during inflammation and long‐term iron overload
Authors: LEGGETT B. A. , FLETCHER L. M. , RAMM G. A. , POWELL L. W. , HALLIDAY J. W.
Published: March 2008

AbstractIron overload, such as occurs in the genetic disease haemochromatosis, leads to synthesis of ferritin containing an increased proportion of L subunits. Inflammation also leads to clinically important increases in ferritin synthesis but the predominant subunit involved is unclear. Elevation of serum ferritin concentration during the acute phase response confounds its use as an indicator of body iron stores and identification of the major subunit involved may allow distinction of the ferritin associated with inflammation from that synthesized during iron overload. The present study examined H and L ferritin subunit mRNA levels in rats with: (i) longstanding iron overload, both parenteral and oral, in which changes should be maximal and stable; and (ii) inflammation of 24 and 48 h duration. A two‐fold increase in L mRNA level was found in both groups of iron loaded animals while H mRNA level was unchanged. This finding would account for the observed preponderance of L subunits in ferritin during iron overload. During the course of inflammation there was a progressive decrease in L mRNA level in the liver but not the spleen. H mRNA relative to total RNA level was unchanged in both liver and spleen. It is concluded that the differential regulation of the two ferritin subunits in response to different stimuli and in different tissues occurs at the level of alteration in mRNA concentration.
Bacterial biofilm, brown pigment stone and blockage of biliary stents
Authors: SUNG J. Y. , LEUNG J. W. C. , SHAFFER E. A. , LAM K. , COSTERTON J. W.
Published: March 2008

Abstract Bacterial pathogens gain access into the biliary system by descending via the portal venous circulation or ascending through the sphincter of Oddi in duodenal‐biliary reflux. Bacteria thrive as glycocalyx‐enclosed microcolonies, coalescing to form an adherent biofilm. The establishment of biofilm is a key event in the formation of biliary sludge and pigment gallstones, and the blockage of biliary stents. The biofilm mode of growth is very effective because it provides bacteria with a measure of protection from antibacterial agents and phagocytic leucocytes. Calcification of the matrix confers further protection for the micro‐organisms living inside the biofilm. To date, attempts to prevent blockage of biliary stent have employed physical methods by using large self‐expandable stents and stents without side hole. Incorporation of antibiotics within stents has not been successful presumably because bacteria once living in their biofilm are quite resistant to antimicrobial agents. Even the most toxic bile salts have no effect on the biofilm bacteria. Yet, hydrophobic bile salts reduce bacterial adhesion on biomaterial, suggesting that incorporation of such bile salts might prevent the formation of bacterial biofilm.
Emergency endoscopic nasobiliary drainage for acute calculous suppurative cholangitis and its potential use in chemical dissolution
Authors: LIN XI‐ZHANG , CHANG KUO‐KUAN , SHIN JENG‐SHIANN , LIN CHIN‐YIH , LIN PIN‐WEN , YU CHIN‐YING , CHOU TSE‐CHUAN
Published: March 2008

Abstract Acute suppurative cholangitis is one of the common causes of acute abdomen in Taiwan. Emergency decompression is a life‐saving procedure if patients fail to respond to antibiotic treatment. From July 1988 to June 1991, 224 patients were encountered with concomitant bile duct stones and cholangitis; 40 were brought to the emergency service with shock or mental confusion or responded poorly to antibiotic treatment. The patients consisted of 20 males and 20 females aged 21–81 years (mean age 64 years); 55% had intrahepatic duct stones, 50% had positive blood culture, 38% had undergone previous biliary surgery, 25% had concomitant medical illnesses and 20% presented with mental confusion. Emergent endoscopic nasobiliary drainage (ENBD) was performed within 48 h of each patient's arrival in the emergency room. In 3 days all the patients exhibited significant improvement as defined by body temperature, vital signs, white blood cell count, serum bilirubin and alkaline phosphates levels. When their condition had stabilized, 21 patients underwent elective surgery. Six patients received ethylenediaminetetraacetic acid infusion through an ENBD tube. Two of the patients’ stones dissolved completely. Six patients received papillotomy with stone removal. The remaining patients refused further treatment. There was no hospital mortality. It is therefore concluded that ENBD offers an effective treatment for acute calculus suppurative cholangitis and it is a potential route of administration for the chemical dissolution of bile duct stones.
Therapeutic upper gastrointestinal endoscopy in children: An audit of 443 procedures and literature review
Authors: GOENKA A. S. , DASILVA M. S. , CLEGHORN G. J. , PATRICK M. K. , SHEPHERD R. W.
Published: March 2008

Abstract The safety, effectiveness and capabilities of therapeutic upper fibreoptic endoscopy in children undergoing therapeutic endoscopic procedures (n= 443) was studied. Therapy for gastrointestinal bleeding formed the major group (injection sclerotherapy for varices, n= 197 procedures; thermocoagulation for haemorrhagic gastritis, n= 1; and photocoagulation for Dieulafoy's disease, n= 1). Sclerotherapy was 97% effective in controlling acute bleeding and 84% effective in obliterating varices with no serious complications or deaths. Oesophageal dilatations for surgical, caustic, congenital and peptic strictures and achalasia (n= 193) were performed with no oesophageal perforations or deaths. Foreign bodies were retrieved (n= 34) with no failures or complications. Percutaneous endoscopic gastrostomy was performed (n= 11) with one failure, proceeding to an unsuccessful surgical gastrostomy. Miscellaneous procedures included endoscopic transpyloric tube placement (n= 5) and endoscopic diathermy of pyloric web (n= 1). Therapeutic fibreoptic endoscopy is therefore concluded to be safe and effective in children, replacing rigid oesophagoscopy and some traditional surgical approaches.
Protective effect of a cephalosporin, Shiomarin, plus a new potent protease inhibitor, E3123, on rat taurocholate‐induced pancreatitis
Authors: HIRANO TETSUYA , MANABE TADAO , IMANISHI KATSUHIRO , TOBE TAKAYOSHI
Published: March 2008

Abstract The role of infectious factors in the pathogenesis of acute pancreatitis and the protective effect of combined therapy with a new potent synthetic protease inhibitor, E3123, and a new potent synthetic cephalosporin, Shiomarin were examined in rat acute pancreatitis. Sodium taurocholate injection into the pancreatico‐biliary duct of rats caused severe pancreatitis with a high mortality rate, characterized by hyperamylasaemia, high amylase activity in ascitic fluid, hyperendotoxaemia and a high serum level of fibrin degradation products (FDP) and redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction. Sodium taurocholate injection into the pancreatico‐biliary duct also caused the bacterial growth in the pancreas. In rats with E3123 infusion almost all parameters were improved, including mortality rate, serum and ascitic fluid amylase levels, plasma endotoxin and serum FDP levels, and distribution of lysosomal enzyme. But combination therapy with E3123 and Shiomarin was significantly more protective than E3123 therapy alone.

These results indicate that infection plays an important role in the development of severe pancreatitis and that combination therapy with a new synthetic protease inhibitor and a new potent antibiotic may be useful in the treatment of severe pancreatitis.
Gastrointestinal involvement in homocystinuria
Authors: ILAN Y. , EID A. , RIVKIND A. I. , WEISS D. , DUBIN Z. , YATZIV S.
Published: March 2008

Abstract Homocystinuria is frequently associated with severe multisystem involvement such as dislocated lenses, skeletal deformities, mental retardation and premature vascular occlusions. Surprisingly, gastro‐intestinal involvement has not been described in this disorder. We present a 17 year old boy with homocystinuria due to cystathionine beta‐synthase deficiency, who developed severe gastrointestinal involvement, manifested by chronic diarrhoea and acute pancreatitis. The diarrhoea was successfully treated with betaine. Possible pathophysiological mechanisms and suggested treatment are described.
Significant changes in intestinal lymphatic system and immune response elicited by Peyer's patch excision in adult rats
Authors: SERIZAWA HIROSHI , MIURA SOICHIRO , TASHIRO HIROKAZU , IMAEDA HIROYUKI , SHIOZAKI HIROSHI , TANAKA SHIN , YOSHIOKA MASAHIRO , OHARA MAKOTO , HIBI TOSHIFUMI , YAMASHITA AKIRA , TSUCHIYA MASAHARU
Published: March 2008

Abstract The effect of deprivation of Peyer's patches (PP) on transport of lymphocytes through intestinal lymph and intestinal mucosal immune responses was investigated in rats. All visible PP in the rat small intestine were excised in order to examine the roles of PP in the intestinal lymphatic system and mucosal immune responses of the intestine. Two weeks after the experimental excision of PP, lymphocyte transport in intestinal lymph was significantly decreased in PP‐excised rats without significant changes in lymphocyte subsets as compared with sham operated control rats. Lymphocyte subsets as determined morphometrically in the intestinal mucosa showed no significant alteration in PP‐excised rats. There was a significant decrease in the number of immunoglobulin A (IgA) containing cells in the intestinal mucosa of PP‐excised rats, while IgM and IgG containing cells showed no statistically significant changes in number. Conversely, the macrophages in the intestinal mucosa increased in number, suggesting the enhanced accessory functions of these macrophages. Antigen‐specific immune response was further studied in PP‐excised rats using intraduodenal priming and challenge with cholera toxin (CT). Both the determinations of cells producing antigen‐specific antibody in the intestinal mucosa using anti‐CT antibody and those of cells secreting anti‐CT Ig in the intestinal lymph by enzyme‐linked immunospot (ELISPOT) assay showed a significant reduction of CT‐specific antibody production in PP‐excised rats compared with controls. Peyer's patches appear to have an important role in lymphocyte transportation through intestinal lymph and also in mucosal immune responses.
Bacterial invasion into the colonic mucosa in ulcerative colitis
Authors: OHKUSA TOSHIFUMI , OKAYASU ISAO , TOKOI SHINSUKE , OZAKI YOSHINORI
Published: March 2008

Abstract This study investigated interactions between mucosal lesions and bacterial invasion in ulcerative colitis using the acridine‐orange staining method. In all 16 cases of ulcerative colitis, the mucosa was found to be invaded by small rods and cocci. In five of 10 controls, bacteria were seen only adhering to the mucosa and no bacteria were detected in the five remaining cases. It is suggested that the presence of bacteria in the colonic mucosa may be a factor responsible for the persistence or aggravation of ulcerative colitis.
Abnormal prothrombin: Evaluation as a tumour marker and localization in tissues of patients with hepatocellular carcinoma
Authors: KODA T. , YAMAZAKI S. , TAMURA I. , NAKABA H. , TAKAO T. , KATAYAMA S. , KURIMURA O.
Published: March 2008

Abstract In this study, the diagnostic significance of PIVKA‐II concentrations in various liver diseases was evaluated, and the use of PIVKA‐II as a tumour marker for hepatocellular carcinoma (HCC) was discussed. Also, the location of abnormal prothrombin (PIVKA‐II) production in HCC by indirect immunoperoxidase staining was examined. There was a good correlation between plasma and serum PIVKA‐II concentrations, indicating that serum samples are adequate for PIVKA‐II measurements. Fifty‐four of 97 (55.7%) patients with HCC, one of 10 (10%) patients with metastatic liver cancer and two of 47 (4.3%) patients with liver cirrhosis had positive serum PIVKA‐II concentrations. Positive serum PIVKA‐II concentrations were found more frequently in patients with HCC than in any other liver disease (P < 0.01). Of the 97 patients with HCC, 54 (55.7%) were PIVKA‐II positive, 76.3% had serum concentrations of either PIVKA‐II or α‐fetoprotein, indicating the usefulness of both tumour markers in the diagnosis of HCC.

Using frozen sections of tissue specimens obtained at autopsy or during surgery, the localization of PIVKA‐II was examined by indirect immunoperoxidase staining with specific anti‐PIVKA‐II antibodies. Tissues from 12 of 22 patients with HCC had positive PIVKA‐II indirect immunoperoxidase staining only in the cancer cells. Cells with greater atypia tended to have stronger cytoplasmic staining. No specific staining was observed in non‐cancerous cells.

These findings suggest that PIVKA‐II is synthesized specifically in hepatic cancer cells.
Epidemiological characteristics of the incidence of hepatitis C virus (C100‐3) antibodies in patients with liver diseases in the Inshore Area of the Yangtze River
Authors: ITO S. , YAO D‐F. , NII C. , HIBINO S. , KAMAMURA M. , NISIKADO T. , HONDA H. , SHIMIZU I. , MENG X‐Y.
Published: March 2008

Abstract The Nantong area is an endemic region of hepatitis B virus (HBV) infection in the inshore area of the Yangtze River. However, no detailed data are available about hepatitis C virus (HCV) infection in this area. In this study recent reports are reviewed about the incidence of viral hepatitis and primary hepatocellular carcinoma (PHC) in China, and it is shown that the Nantong area is a high risk region for PHC. This study reports on the incidence of antibody to HCV (anti‐HCV) in patients with chronic liver diseases in the Nantong area; investigated in collaboration with members of the Nantong Medical College, Jiangsu Province, the People's Republic of China. The incidence of anti‐HCV (C100‐3) in the Nantong area was: 0.67% (three of 451) in donor blood; 0.0% (none of 89) in patients with acute hepatitis; 2.7% (five of 186) in those with chronic hepatitis, 4.5% (two of 44) in those with liver cirrhosis; 6.3% (one of 16) in those with PHC; and 1.3% (one of 78) in patients without liver disease. The incidence of hepatitis B surface antigen in the Nantong area was: 15.7% (14 of 89) in patients with acute hepatitis; 81.2% (151 of 186) in those with chronic hepatitis; 81.8% (36 of 44) in those with liver cirrhosis; 87.5% (14 of 16) in those with PHC; and 20.5% (16 of 78) in patients without liver disease. Although the Nantong area is a high risk region for PHC, these data suggest that HCV infection is not an important aetiological factor for PHC in this area.
Persistent childhood diarrhoea: Patterns, pathogenesis and prevention
Authors: GRACEY M.
Published: March 2008

Abstract With improved management of acute episodes of infectious diarrhoea, increased attention is now being given to persistent diarrhoea and its nutritional consequences and associated mortality. Risk factors for the development of persistent diarrhoea include young age, malnutrition, impaired immune function, recent introduction of milk feedings, prior antimicrobial therapy and infection with pathogenic strains of Escherichia coli. Descriptive epidemiology indicates that 3–20% of episodes of acute diarrhoea in children in developing countries become persistent and cause about one‐third to one‐half of all deaths from diarrhoea. Environmental factors may be very important in causing persistent diarrhoea: these include undernutrition combined with the impact of living in highly contaminated environments and their effects on gastrointestinal microecology. Development of effective preventive strategies will depend on improved understanding of causes and pathogenesis of persistent diarrhoea.
Doppler‐controlled injection treatment of Dieulafoy's disease
Authors: JASPERSEN D. , GASTER C. B. , KOERNER TH. , HAMMAR C‐H.
Published: March 2008

Abstract Dieulafoy's anomaly is a vascular malformation of the upper stomach, which typically causes massive and recurrent haemorrhage. Emergency endoscopy is the most effective method of diagnosing the disease. Until recently, the therapy of choice was surgical resection. Five patients with spontaneously stopped bleeding from Dieulafoy's ulceration were investigated. Transendoscopic Doppler ultrasound was used to identify arterial blood flow from the lesions. Local injection treatment was performed. Successful therapy resulted in the disappearance of arterial pulsations and no rebleeding occurred. The endoscopic Doppler is of diagnostic value in the evaluation of Dieulafoy's ulcer and enables control of endoscopic sclerotherapy.
Prevalence of primary sclerosing cholangitis and other liver diseases in Japanese patients with chronic ulcerative colitis
Authors: HASHIMOTO E. , IDETA M. , TANIAI M. , WATANABE U. , OKUDA H. , NAGASAKO K. , HISAMITSU T. , OBATA H.
Published: March 2008

An association between primary sclerosing cholangitis (PSC) and chronic ulcerative colitis (CUC) is well known in Western countries, but there have been no reports on this association in Japan. We reviewed 163 consecutive CUC patients (91 males and 72 females) diagnosed from 1984 to 1990 at Tokyo Women's Medical College. Abnormal liver function tests were found in 42 patients with CUC (25.8%), but chronic liver disease was only diagnosed in seven patients (4.3%). Among these seven patients, there were four with PSC, one with small‐duct PSC, one with transfusion‐associated chronic hepatitis and one with Type B liver cirrhosis. No relationship was found between the documented colonic manifestations of CUC and the presence of PSC. The four PSC patients did not have a longer history of CUC at the time of diagnosis of PSC than CUC patients without PSC. At the time of PSC diagnosis, two patients were asymptomatic, one presented with right upper quadrant pain, and the other had fatigue. Three patients were diagnosed as having CUC before the onset of PSC (range 2–13 years), and the other patient had both diseases simultaneously. All four had a good prognosis. Thus PSC was the most common chronic liver disease associated with CUC in our series, and it was present in all our CUC patients with alkaline phosphatase levels exceeding twice the upper limit of normal and mild transaminase elevation.
Genotypic subtyping of hepatitis C virus
Authors: CHAYAMA KAZUAKI , TSUBOTA AKIHITO , ARASE YASUJI , SAITOH SATOSHI , KOIDA ISAO , IKEDA KENJI , MATSUMOTO TOYOMI , KOBAYASHI MARIKO , IWASAKI SATOMI , KOYAMA SHIMA , MORINAGA TSUTO , KUMADA HIROMITSU
Published: March 2008

Four subtypes of hepatitis C virus (HCV), Pt(I), K1(II), K2a(III) and K2b(IV), have been suggested based on the nucleotide sequences of the non‐structural (NS) 5 region. A fifth subtype from Japanese patients, Tr(V), which shows a less than 68% homology in nucleotide sequence when compared with other subtypes has been identified. A one‐step method which enables a quick determination of subtype using polymerase chain reaction with a mixed primer set deduced from the sequence of each subtype has been developed. Using this technique, the subtypes of 418 out of 478 Japanese patients (87.4%) were determined. The incidence of each subtype in Japan was as follows: K1(II), 307 (73.4%); K2a(III), 74 (17.7%); K2b(IV), 28 (6.7%); and Tr(V), 3 (0.7%). This one‐step subtyping technique should be useful for studying the epidemiology or biology of the HCV.
Combination antiviral therapy controls severe post‐liver transplant recurrence of hepatitis B virus infection
Authors: ANGUS PETER , RICHARDS MICHAEL , BOWDEN SCOTT , IRETON JOHN , SINCLAIR ROGER , JONES ROBERT , LOCARNINI STEPHEN
Published: March 2008

The authors have successfully used combination ganciclovir and foscarnet chemotherapy to control viral replication following liver transplantation in a patient with severe recurrence of hepatitis B virus (HBV) infection. The disease was characterized by extremely high viraemias, deteriorating liver function, and high levels of intra‐hepatic hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg). Treatment resulted in a greater than 30‐fold reduction in serum HBV DNA and HBsAg levels. Liver function tests returned to normal and the histological progression of the disease was arrested. Hepatic cytoplasmic HBsAg decreased substantially but there was little change in HBcAg, implicating HBsAg rather than HBcAg in the liver injury. Combination antiviral chemotherapy using agents such as ganciclovir and foscarnet may offer a new approach to the management of post‐transplant recurrence of HBV.
Retroperitoneal haematoma due to ruptured microaneurysm of the pancreaticoduodenal artery
Authors: FUJII T. , FUJINAMI S. , TAKEUCHI Y. , SHIRO T. , KITAGAWA S. , FUKUI Y. , OKUNO H. , KUBOTA Y. , SHIOZAKI Y. , INOUE K. , UEHARA M. , UETSUJI S.
Published: March 2008

A case of retroperitoneal haematoma due to a ruptured microaneurysm of the posterior superior pancreaticoduodenal artery in a 61 year old man is described. Ultrasonography and computed tomography revealed cystic masses near the gall‐bladder. Selective coeliac angiography disclosed a microaneurysm of the posterior superior pancreaticoduodenal artery. Surgical extirpation of the cystic masses was performed, and the histological finding was an encapsulated old haematoma.
Changing prevalence of hepatitis B virus in urbanized Australian Aborigines
Authors: PATTERSON FRANKIE , BUMAK JAMES , BATEY ROBERT
Published: March 2008

Serological surveys of desert or rural Australian Aboriginal settlements report up to 85% positivity for hepatitis B virus (HBV) markers. We report the results of two cross‐sectional HBV surveys carried out 5 years apart in the bi‐racial town of Condobolin, New South Wales (population 3086; 14% Aborigines).

In 1983–84, none of the 310 non‐Aborigines tested were hepatitis B surface antigen (HBsAg) positive but 7.2% were positive for hepatitis B core antibody (anti‐HBc). Among Aboriginal subjects, 57.6% had detectable HBV markers and 16.9% were HBsAg positive. In 1987–88, no non‐Aborigines were HBsAg positive and only 1% (of 422 individuals) had anti‐core antibodies. In contrast, 36% of Aboriginal subjects had HBV markers and 6% were HBsAg positive. No significant difference in detectable HBV markers was found among 98 Aborigines who were included in both surveys. Migration was the main factor influencing the HBV prevalence between the two surveys. Clustering of HBsAg carriers occurred within households and the likely mode of infection was intrafamilial horizontal childhood transmission.

There was a significant association between HBV markers and tattooing in Aborigines (P≤ 0.02). Overall, HBV markers were less frequent in this population than in other desert or rural Aboriginal populations surveyed. The prevalence of HBV infection in non‐Aboriginal households was not significantly different from that in the Australian Caucasian population.
Immunohistochemical detection of proliferating cell nuclear antigen in hepatocellular carcinoma: Relationship to histological grade
Authors: TANIAI M. , TOMIMATSU M. , OKUDA H. , SAITO A. , OBATA H.
Published: March 2008

Proliferating cell nuclear antigen (PCNA), also known as cyclin, is an auxiliary protein of DNA polymerase‐δ and is found only in the nuclei of proliferating cells in the late G1 and S phases. The proliferation of hepatocellular carcinoma (HCC) by immunohistochemical staining for PCNA using paraffin sections of 20 surgically resected HCC specimens was analysed. The mean percentage of PCNA‐positive nuclei in the HCC tissue was 10.3% in grade I of Edmondson and Steiner's classification, 25.5% in grade II, 28.4% in grade III and 41.5% in grade IV. In early HCC, we observed only a few PCNA‐positive tumour cells. However, PCNA‐positive nuclei were numerous in the tumour thrombi found in portal vein branches, in regions of extracapsular tumour growth, and in the inner nodules of tumours with a nodule‐in‐nodule formation. Proliferating cell nuclear antigen positivity was correlated with an increase of the nucleocytoplasmic ratio of tumour cells as determined by image analysis. Our findings showed that PCNA positivity was correlated with the histological grade and invasiveness of HCC, suggesting that this antigen may be used as an indicator to predict tumour invasion in patients with HCC.
Immunohistochemical demonstration of the p53 tumour suppressor gene product in cancer of the pancreas and chronic pancreatitis
Authors: LEE C. SOON , RUSH MOIRA , CHARALAMBOUS DORA , RODE JÜRGEN
Published: March 2008

The p53 tumour suppressor gene and its protein products after point mutations are currently attracting wide attention in the investigation of human tumours. In this study we present the findings on percutaneous pancreatic biopsies of 82 cases after routine processing and immunostaining for the polyclonal p53 antibody CM1, an antibody directed against both wild and mutant forms of p53 protein. There were 51 carcinomas, 5 islet cell tumours, 16 cases of chronic pancreatitis (including one with atypical ductal epithelium) and seven histologically normal pancreatic biopsy specimens. None of the seven normal cases showed any definite nuclear immunostaining for p53. Thirty‐two (63%) of the pancreatic adenocarcinomas showed moderate to intense immunoreactivity. Of the 16 cases of chronic pancreatitis, 11 were negative and three showed equivocal immunostaining. The one case with ductal epithelial atypia showed mild to moderate immunoreactivity. All islet cell tumours were negative. The expression of the p53 gene, therefore, appears increased in the majority of pancreatic adenocarcinomas while this is not observed in chronic pancreatitis or normal pancreatic tissue. Nuclear immunoreactivity for p53 protein may represent mutant forms because of the short half‐life of the wild‐type protein. The lack of p53 expression in some cases of pancreatic adenocarcinoma may be due to different types of mutant proteins not detectable by the CM1 antibody. Nuclear immunoreactivity to the p53 protein in pancreatic biopsy is more suggestive of a malignant tumour than chronic pancreatitis.
Hepatic angiomyolipoma pre‐operatively diagnosed by imaging
Authors: KUDO MASATOSHI , OKUNO TOSHITAKA , TOMITA SHUSUKE , KAJIWARA TATEHIRO , SHIRANE HIROBUMI , USUKI NORIROU , TODO AKIO
Published: March 2008

An asymptomatic patient with pre‐operatively diagnosed solitary angiomyolipoma is reported. The tumour was a well defined, fat density mass on computerized tomography (CT) and magnetic resonance imaging (MRI), and a hyperechoic nodule with a sharp margin on ultrasonography (US). The lesion was hypervascular on arteriography and CT during hepatic angiography. Chemical shift MRI confirmed the fat component within the lesion. Although a review of the literature shows this tumour to be rare and difficult to differentiate from a malignant lesion pre‐operatively, the pre‐operative diagnosis of angiomyolipoma is considered feasible when the characteristic findings as described here are present.
Immunological responses against an autologous human hepatocellular carcinoma cell line
Authors: USUDA SEIICHI , YOSHIZAWA KANAME , YABU KOJI , KIYOSAWA KENDO
Published: March 2008

We performed a detailed analysis of immune responses in a hepatocellular carcinoma (HCC) cell line and effector cells obtained from a patient with HCC. We examined the cytotoxic activity of natural killer (NK) cells, lymphokine‐activated killer (LAK) cells and cytotoxic T lymphocytes (CTL) against an autologous tumour cell line (SUHC‐1) to investigate the immune mechanism of human lymphocytes against HCC cells. Cytotoxic T lymphocytes were induced by co‐culturing of peripheral blood lymphocytes (PBL) and SUHC‐1 cells, mixed lymphocyte and tumour cell culture (MLTC). The susceptibility of SUHC‐1 to NK and LAK cells was similar to that of other allogeneic cell lines, such as K562, PLC/PRF/5 and Mahlavu. Effector cells induced in the primary MLTC had high cytotoxic acitivity but were not specific for SUHC‐1. Cytotoxic T lymphocytes with specific activity against SUHC‐1 were induced after PBL were stimulated five times at 7–10 day intervals with SUHC‐1 and low‐dose recombinant interleukin‐2 (rIL‐2), suggesting that as the culture progressed, broadly reactive effector cells disappeared and specific effector cells survived. The specific effector cells were identified as CD3+/CD4+ and CD+/CD8+ T‐lymphocyte subsets. The recognition mechanisms of CD3+/CD4+ CTL remain unresolved because the cytotoxicities were not inhibited by anti‐CD4 and anti‐major histocompatibility complex (MHC) class II monoclonal antibodies (MoAb). Treatment of cells with anti‐CD3, anti‐CD8 and anti‐MHC class I MoAb partially inhibited lysis. These results demonstrated that the T‐cell receptor (TCR)/CD3 complex appeared to be involved in SUHC‐1 specific antigen recognition and antigen recognition of CD3+/CD8+ CTL was MHC class I restricted.
Role of the oestrogen receptor in liver regeneration in the male rat
Authors: LIDDLE CHRISTOPHER , FARRELL GEOFFREY C.
Published: March 2008

Partial hepatectomy in male rats results in raised serum oestrogen levels, nuclear binding of oestrogen receptor (ER) and feminization of certain aspects of hepatic metabolism. It has been proposed that these changes may have an important role in liver regeneration. The present study was performed to ascertain the effects of the oestrogen agonist diethylstilbestrol (DES), 2 mg/kg, and the oestrogen antagonist tamoxifen (TAM), 2 mg/kg, on liver regeneration induced by partial hepatectomy in the male rat. Regenerative activity was determined by incorporation of [3H]‐thymidine into hepatic DNA as well as by measurement of liver remnant weight. Following partial hepatectomy, there was a trend towards an increase in liver remnant weight at 24 h in rats treated with DES (DES, 5.95 ± 1.52 g; vehicle, 4.87 ± 0.66 g; P= 0.06) though by 48 h no effect was found. Tamoxifen treatment did not significantly affect liver weight at 24 h but by 48 h there was a highly significant reduction in liver remnant weight (TAM, 5.41 ± 0.85 g; vehicle, 7.31 ± 1.43 g; P < 0.001). Neither DES nor TAM treatment influenced liver regeneration as determined by [3H]‐thymidine incorporation into hepatic DNA. We conclude that pharmacologic manipulation of oestrogens does not influence the initiation of the regenerative process but that oestrogen may facilitate later phases of hepatic growth.
Pathogenesis of centrilobular necrosis following congestion of the liver
Authors: SHIBAYAMA YURO , URANO TORU , ASAKA SHOSAKU , HASHIMOTO KAZUAKI , NAKATA KATSUJI
Published: March 2008

The exact pathogenesis of centrilobular necrosis following congestion of the liver is still unknown. We reviewed the clinical data related to systemic circulatory disturbance and histopathology of the liver and the gut in 320 autopsy subjects. Congestion of the liver alone was associated only with atrophy and loss of hepatocytes in centrilobular areas, but not with hepatocellular coagulative necrosis. In many patients with coagulative necrosis of centrilobular hepatocytes and congestion of the liver, fibrin thrombi and neutrophil infiltration in the sinusoids, which are the characteristic histopathological features of the liver in endotoxaemia, were found in and around the necrotic area. Congestion, erosion or haemorrhage of the intestinal mucosa, which may allow entrance of endotoxin into the liver through the portal vein, was seen in such patients. Prolonged hypotension or shock, which may lead to portal endotoxaemia, was present in half the patients with centrilobular necrosis and congestion of the liver. These results suggest that not only congestion of the liver but also portal endotoxaemia may be involved in the pathogenesis of centrilobular necrosis in patients with congestion of the liver.
Factors useful in predicting the response to interferon therapy in chronic hepatitis C
Authors: TSUBOTA AKIHITO , CHAYAMA KAZUAKI , ARASE YASUJI , KOIDA ISAO , SAITOH SATOSHI , IKEDA KENJI , IWASAKI SATOMI , MATSUMOTO TOYOMI , KOBAYASHI MARIKO , KUMADA HIROMITSU
Published: March 2008

To determine how various factors influence the response to interferon (IFN) therapy, we retrospectively studied 157 consecutive Japanese patients with chronic hepatitis C who received various treatment schedules of IFN. They were divided into two groups on the bases of outcome. One group was comprised of 65 patients who achieved a sustained normalization of serum alanine aminotransferase (ALT) levels for at least 6 months after treatment, while the other group was comprised of 84 patients with persistent elevation of serum ALT levels, despite treatment. Genotyping of hepatitis C virus (HCV) was done by polymerase chain reaction (PCR) with genotype specific primers, analysing the variations in nucleotide sequence within the NS 5 region of the HCV genome, namely genotypes PT, K1, K2a and K2b. We then used a multivariate analysis to determine the factors related to mode of treatment, patient characteristics and HCV genotype in relation to the response to IFN therapy. Of the 16 factors analysed, the HCV genotype (genotype K2a or K2b, P < 0.0008), treatment schedule (intermittent administration following a daily schedule, designated as combined schedule, P > 0.0014) and liver histology just before treatment (chronic persistent hepatitis or mild chronic aggressive hepatitis, P < 0.0324) were the most strongly correlated with a normalizing response to IFN therapy. These results suggest that not only are the IFN treatment schedule and patient profile significant, but the properties of the virus also influences the response. However, as the IFN treatment schedule is the only changeable factor, it should be designed to maximize the benefit of IFN therapy.
Endotoxaemia in patients with liver cirrhosis and upper gastrointestinal bleeding: Detection by the chromogenic assay with plasma Tween 80 pretreatment
Authors: FUKUI HIROSHI , MATSUMOTO MUNESUKE , BODE CHRISTIANE , BODE J. CHRISTIAN , TSUJITA SHIGENOBU , TSUJII TADASU
Published: March 2008

A recently developed chromogenic endotoxin assay with plasma Tween 80 pretreatment was compared with the conventional dilution and heating method. Plasma endotoxin was measured in patients with liver cirrhosis and upper gastrointestinal (GI) bleeding by these methods. Plasma endotoxin concentration was calculated from an individual internal standard curve by adding three different standard endotoxin solutions to each sample. By the conventional heating method, added standard endotoxin gave different OD values in each sample and the slope of the standard curve showed interindividual variations. When sample plasma from chronic alcoholics was pretreated with 1% Tween 80 and ultrasonification after heating, the slope of standard curves was somewhat increased and interindividual variation was minimized. Significantly higher plasma endotoxin levels in cirrhotics with upper GI bleeding compared with those without upper GI bleeding was detected by this Tween 80 method. There was a strongly positive correlation between the endotoxin levels determined by this method and those determined by the perchloric acid method and endotoxin‐specific substrate in patients with upper GI bleeding. Endotoxin levels, which were elevated 1–2 days after the bleeding, tended to decrease as patients recovered.

In summary, the recovery of endogenous and exogenous endotoxin from plasma sample was increased by adding Tween 80 before the chromogenic substrate assay. Transient elevation of plasma endotoxin was demonstrated by this Tween 80 method in patients with liver cirrhosis and upper GI bleeding.
Intestinal pseudo‐obstruction, type 1 anti‐neuronal nuclear antibodies and small‐cell carcinoma of the lung
Authors: CHU G. , WILSON P. C. , CARTER C. D. , LENNON V. A. , ROBERTS‐THOMSON I. C.
Published: March 2008

Intestinal pseudo‐obstruction is a rare paraneoplastic manifestation of small‐cell carcinoma of the lung. This report documents a further case associated with neuronal degeneration of enteric neural plexuses and a high serum titre of immunoglobulin G (IgG) type 1 anti‐neuronal nuclear antibodies (ANNA‐1).
Epidemiology and clinical aspects of hepatocellular carcinoma
Authors: OKUDA K.
Published: March 2008

In this paper, the recent development in the study of the epidemiology of hepatocellular carcinoma (HCC) and the diagnosis of adenomatous hyperplastic nodules as a putative preneoplastic lesion are discussed. Other clinical features of HCC will not be included here.
The protooncogene c‐jun is transactivated by the X protein of hepatitis B virus and highly expressed in liver cancer
Authors: ROBINSON W. S. , TWU J‐S. , LAI M‐Y. , CHEN D‐S.
Published: March 2008

A specific viral oncogenic mechanism has not been shown for hepatitis B virus (HBV), although persistent HBV infection has been strongly associated with the development of hepatocellular carcinoma (HCC). Most HCC in HBV carriers contain integrated viral sequences in host DNA and this raises the question of whether such integrations ever contribute to oncogenesis. HBV contains a gene (designated the hbx gene), which encodes a transcriptional transactivator protein capable of activating homologous and heterologous cis‐acting regulatory sequences. Among the regulatory sequences that are responsive to hbx are those of HBV and heterologous regulatory sequences in the long terminal repeat (LTR) of human immunodeficiency virus type 1 (HIV‐1) and Rous sarcoma virus, and regulatory sequences of simian virus 40 and the human β interferon gene. The diversity of regulatory sequence that appear to be activated by hbx suggests that the hbx protein acts by a general mechanism that is not DNA sequence specific and other cellular genes may be similarly transactivated. This property of hbx raises the question of whether hbx expression in infected hepatocytes may activate cellular genes that could play a role in HCC, and hbx has been shown to be expressed from integrated viral genomic DNA in some HCC. In this regard, hbx was found to activate transcription regulated by the promoter of the protooncogene c‐jun. c‐jun was found to be expressed at a very low level in normal liver tissue but at high levels in HCC of HBV‐infected patients.
Use of recombinant HCV antigen in the serodiagnosis of hepatitis C virus infection: Significant improvement in HCV antibody detection as compared with the first generation HCV C100‐3 ELISA and the synthetic peptide EIA tests
Authors: CHIEN D. Y. , CHOO Q‐L. , TABRIZI A. , KUO C. , McFARLAND J. , BERGER K. , LEE C. , SHUSTER J. R. , NGUYEN T. , MOYER D. L. , TONG M. , FURUTA S. , OMATA M. , FONG C. T. , TEGTMEIER G. , ALTER H. , SCHIFF E. , JEFFERS L. , HOUGHTON M. , KUO G.
Published: March 2008

Hepatitis C virus (HCV) infection can be detected by using immunoassay techniques that measure reactivity to viral protein antigens. In this study seven discreet proteins derived from HCV genomic coding sequences have been expressed, purified and characterized. Six proteins represent the structural regions of the core (C22‐3), the envelope (E1 and E2), and the non‐structural regions NS3 (C33C), NS3–NS4 (C100‐3) and NS5. The seventh, C25, is a chimeric fusion protein containing C33C, C100‐3 and C22‐3 regions. Using these recombinant proteins, multi‐antigen radioimmunoassays and enzyme immunoassays (EIA) were designed. The fusion protein, C25, was demonstrated to be an improved antigen for serodiagnosis of HCV antibody. Use of the C25 protein accelerated HCV antibody detection by 3–46 weeks in non‐A, non‐B hepatitis seroconversion cases and significantly increased the rate of detection in a paid donor population by 20%. The C25 assay also demonstrated excellent specificity in 2446 randomly selected low prevalence samples. The repeated reactive rate in this group of samples was 0.5%.

Samples from volunteer blood donors pre‐selected for repeat reactivity with the first generation C100‐3‐based HCV antibody tests (n= 175) were tested using the C25 assay. The C25 assay detected 37.7% samples as reactive and 53.1% samples as non‐reactive. This result was in agreement with all other supplementary tests that include RIBATM, multi‐antigen assay, Abbott neutralization and peptide assay. The other 9.2% samples were classified as ‘indeterminant’ because these samples were only partially in agreement with some of the above supplementary tests.

The C25 enzyme‐linked immunosorbent assay (ELISA), with its improved assay sensitivity, can identify additional HCV antibody reactive cases in both hepatocellular carcinoma and cryptogenic cirrhosis patients. The C25 and multi‐antigen EIA assays were used to investigate the vertical transmission of HCV. It was observed that these improved assays are able to detect antibodies in a vertical transmission case. The C25 ELISA was also compared with a synthetic peptide assay. The C25 assay was found to be superior to the peptide assay that performed poorly in the detection of the C33C only reactive samples.
Quantitative analysis of hepatitis C virus RNA by competitive nested polymerase chain reaction
Authors: CHAYAMA K. , TSUBOTA A. , ARASE Y. , SAITOH S. , IKEDA K. , SAKAI Y. , MATSUMOTO T. , KOBAYASHI M. , UNAKAMI M. , MORINAGA T. , KUMADA H.
Published: March 2008

A method that allows the quantitation of hepatitis C virus (HCV) RNA is described. The RNA was extracted from serum samples and reverse transcribed. Target cDNA was then co‐amplified by nested polymerase chain reaction with a known amount of competitive template at various concentrations. Since this internal control DNA uses the same primers as those of the target and is distinguishable from the target cDNA after amplification by size, the initial concentration of the target could be estimated by comparing the intensity of the two bands of amplified DNA fragments. That is, if the starting amount of the cDNA and the competitive template are equal, the intensity of the two bands should also be equal. Using this method the amount of HCV RNA in serum samples obtained from 85 patients with chronic hepatitis type C was determined. There was as much as a 100 000‐fold difference in the levels of HCV RNA from patient to patient. A rapid decrease of HCV RNA in a patient treated with interferon is also described.
Translational regulation of hepatitis B viral gene expression
Authors: LO S. J. , SHEU S. Y. , LIN C‐G.
Published: March 2008

At least five species of unspliced mRNA of the hepatitis B virus (HBV), which are 3.5, 3.4, 2.4, 2.1 and 0.8 kb, have been identified. To study this amount of HBV proteins they were translationally regulated and both in vitro and in vivo experiments performed. The four in vitro synthesized RNA corresponding to the 2.1, 2.4, 3.4, and 3.5 kb mRNA, respectively, were translated in a rabbit reticulocyte lysate. In conjunction with in vivo transfection experiments, it was demonstrated that: (i) a preferential translational initiation is involved in the differential amount of surface antigens; (ii) the 2.1 kb mRNA is the template for the synthesis of the middle and major surface antigens in a ratio of about 1 : 4; (iii) the 2.4 kb mRNA, although containing sequences for coding the large, middle and major surface antigen, is primarily used for the synthesis of large surface antigens; (iv) both the core and pol proteins can be independently synthesized from the 3.4 kb mRNA (pregenome RNA) and the synthesis of pol protein is favourably carried out via a leaky scanning mechanism; (v) the 3.5 kb mRNA (pre‐C mRNA) is the template for the production of precore protein (the precursor of hepatitis B e antigen) but not for the synthesis of both core and pol proteins. Taken together, the results indicate that: (i) the translational initiation context of each HBV‐encoded protein plays a key role in determining the level of protein synthesis; (ii) the occurrence of bifunctional mRNA of pregenome RNA and 2.1 kb mRNA provides another alternative means for minimization of the viral genome size; (iii) the leaky scanning mechanism is involved in the expression of the second protein in bifunctional mRNA.
The functions of the p53 gene and gene product
Authors: QUARTIN R. S. , LEVINE A. J.
Published: March 2008

p53 is a tumour suppressor protein involved in the regulation of the cell cycle. Mutation of the p53 gene and expression of mutant p53 protein are associated with many types of human neoplasia. Mutational hot spots at specific amino acid residues have been identified, and these hot spot mutations are differentially expressed in tumours of different tissue origins. Mutant p53 proteins exhibit properties that are functionally and biochemically altered from those of the wild‐type protein, including increased metabolic stability, loss of DNA and SV40 T antigen‐binding ability, and loss of growth suppressive functions. Further characterization of both wild‐type and mutant p53 proteins will provide insights into the mechanisms of tumour development.
Expression and stability of the hepatitis B pol protein in Escherichia coli
Authors: LIN C‐G. , YOU L‐R. , LO S. J.
Published: March 2008

The pGEX plasmid containing the gene of glutathione S‐transferase (GST) was employed to express various lengths of the hepatitis B virus pol protein in a form of fusion protein in Escherichia coli. Results of SDS‐PAGE and Western blot analyses indicated that: (i) expression of GST‐pol fusion proteins varied from undetectable to 30% of total protein in different clones; (ii) presence of the carboxyl terminus of the pol protein apparently lowered the expression amount of fusion proteins; (iii) some distinct pol protein bands of lower molecular weight were constantly detected in several clones. The presence of the smaller pol protein therefore raises a possibility that the pol protein contains protease cutting sites.