bluuebunny/crossref_metadata_2025 huggingface dataset:
Rise of plasma myeloperoxidase during interferon therapy
Authors: NAKAMUTA MAKOTO , OHASHI MASAO , FUKUTOMI TAKAYOSHI , TANABE YUICHI , HIROSHIGE KAICHIRO , NAWATA HAJIME
Published: March 2008

Abstract The plasma myeloperoxidase (MPO) level was evaluated using a specific radio‐immunoassay (RIA) for MPO in α2b‐interferon (IFN)‐treated patients with chronic viral hepatitis. The plasma MPO was checked before and after the initial 2 weeks use of IFN at a dose of 6 × 106 U/day. The mean concentration of plasma MPO was found to be markedly higher after IFN therapy than that before the therapy (421.7 ± 34.3 vs 242.9 ± 23.0 ng/mL, P < 0.001). The plasma MPO negatively correlated with the granulocyte count (r= ‐0.37, P < 0.02) and the platelet count (r= 0.49, P < 0.01), while it positively correlated with serum alkaline phosphatase (ALP; r= 0.41, P < 0.03). The plasma MPO also showed a strong correlation with plasma polymorphonuclear granulocyte elastase (PMN elastase; r= 0.73, P < 0.001). Our study thus suggests that the increased release of MPO from destroyed granulocytes is responsible for the high concentrations of the plasma MPO in patients during IFN therapy, because the plasma MPO, PMN elastase and ALP abundant in granulocytes all increased in spite of a decrease in the granulocyte count. Granulocytopenia during IFN therapy may therefore be due to the increased destruction of granulocytes in addition to a direct suppression of the bone marrow by IFN.
Membranous obstruction of inferior vena cava in Taiwan
Authors: LU CHING‐LIANG , CHOU YI‐HONG , HWANG SHINN‐JANG , CHAN CHO‐YU , LEE SHOU‐DONG
Published: March 2008

Abstract Membranous obstruction of the inferior vena cava (MOVC) is a rare cause of Budd‐Chiari syndrome. When compared to the West, the incidence of MOVC was reported to be higher in the Orient, India and South Africa. From 1979 to 1993, 16 consecutive Chinese patients (mean age 50 years) with MOVC were retrospectively evaluated. The diagnosis in these MOVC patients was usually delayed with a meanlag time of lll months. Most of the cases were detected by a delicate ultrasonographic examination of the abdomen. Segmental narrowing of the inferior vena cava in 11 patients was the predominant type of MOVC, while five experienced a membranous obstructive type. Only one of five surgery‐treated patients had a postoperation survival > 5 years, while five out of the nine patients who received conservative treatment still survived after a 6‐15 year follow up. Two patients received percutaneous angioplasty (PTA). One survived 4 years and the other expired 5 years after the PTA. Two patients (12%) developed a hepatocellular carcinoma in their disease course, and the incidence was lower than in previous reports from Japan and South Africa. The incidence of hepatitis B surface antigen in MOVC did not increase in our patients compared with the general population. In conclusion, the inferior vena cava should be carefully evaluated in an ultrasonographic examination of the abdomen to increase the diagnosis rate of MOVC. Surgical intervention should be carefully justified according to the patient's symptoms and signs, the types of obstructive lesions and the expertise of the surgeons.
The role of colonoscopy in screening persons with family history of colorectal cancer
Authors: WU CHENG‐SHYONG , TUNG SHUI‐YI , CHEN PANG‐CHI , KUO YOW‐CHII
Published: March 2008

Abstract First‐degree relatives of colorectal cancer patients are at increased risk for developing colorectal neoplasms. In order to assess the potentiality of colonoscopy screening in this high‐risk population, 213 asymptomatic family members (age range 30‐69 years, mean 42.8 years) of those patients with colorectal cancer received colonoscopic examination at Chang‐Gung Memorial Hospital from April 1992 to May 1994. Twenty‐eight persons with 42 lesions (polyps or cancer) were identified, including 28 adenomas, nine hyperplastic polyps and five adenocarcinomas. The positive detection rate was 9.9% for adenoma and 2.3% for cancer. Colorectal neoplasms afflicted males more frequently than females (16.7 vs 5.7%, P < 0.05) and occurred less frequently in those < 40 years of age (5.5 vs 17.2%, P < 0.05). Forty‐two per cent of the detected neoplastic lesions were beyond the reach of 60 cm flexible sigmoidoscopy and 36% of adenomas were < 0.5 cm in size and would be missed if patients were screened by air contrast barium enema. Cost analysis revealed that the charges of both screening colonoscopy and screening flexible sigmoidoscopy/air contrast barium enema were approximate. Colonoscopy also has a high acceptability and safety. It appears appropriate to use colonoscopy, rather than flexible sigmoidoscopy or air contrast barium enema, as an initial screening procedure for persons with a family history of colorectal cancer, especially those > 40 years of age.
Clinical associations between thyroid and liver diseases
Authors: HUANG MIAU‐JU , LIAW YUN‐FAN
Published: March 2008

Abstract The liver has an important role in thyroid hormone metabolism and the level of thyroid hormones is also important to normal hepatic function and bilirubin metabolism. Besides the associations between thyroid and liver diseases of an autoimmune nature, such as that between primary biliary cirrhosis and hypothyroidism, thyroid diseases are frequently associated with liver injuries or biochemical test abnormalities. For example, thyroid diseases may be associated with elevation of alanine aminotransferase and alkaline phosphatase, which is mainly of bone origin, in hyperthyroidism and aspartate aminotransferase in hypothyroidism. Liver diseases are also frequently associated with thyroid test abnormalities or dysfunctions, particularly elevation of thyroxine‐binding globulin and thyroxine. Hepatitis C virus infection has been connected with thyroid abnormalities. In addition, antithyroid drug therapy may result in hepatitis, cholestasis or transient subclinical hepatotoxicity, whereas interferon (IFN) therapy in liver diseases may also induce thyroid dysfunctions. These thyroid‐liver associations may cause diagnostic confusions. Neglect of these facts may result in over or under diagnosis of associated liver or thyroid diseases and thereby cause errors in patient care. It is suggested to measure free thyroxine (FT4) and thyroid‐stimulating hormone (TSH) which are usually normal in euthyroid patients with liver disease, to rule out or rule in coexistent thyroid dysfunctions, and consider the possibility of thyroid dysfunctions in any patients with unexplained liver biochemical test abnormalities. It is also advisable to monitor patients with autoimmune liver disease or those receiving IFN therapy for the development of thyroid dysfunctions, and patients receiving antithyroid therapy for the development of hepatic injuries.
Budd‐Chiari syndrome due to pacemaker‐induced thrombosis
Authors: LU CHING‐LIANG , HWANG SHINN‐JANG , CHEN SHIH‐ANN , YU TARNG‐JENN , CHOU YI‐HONG , LEE SHOU‐DONG
Published: March 2008

Abstract We report a unique case of Budd‐Chiari syndrome caused by pacemaker leads‐induced thrombosis. A 34 year old female patient was subjected to a permanent pacemaker insertion because of refractory paroxysmal supraventricular tachycardia attacks related to Wolff‐Parkinson‐White syndrome. Three years later, another pacemaker was re‐implanted because of its dislodgement. Four episodes of skin infections at the implantation site were noted thereafter. The patient developed symptoms of abdominal pain and ascites 5 years after the second pacemaker implantation. Ultrasonography and computerized tomography of the abdomen revealed hepatomegaly with ascites and dilated inferior vena cava. An echocardiogram displayed thrombus formation in the superior vena cava, the right atrium and the inlet of the inferior vena cava into the right atrium. Inferior and superior venacavogram confirmed the above findings. With the impression that Budd‐Chiari syndrome was caused by pacemaker‐induced thrombus, we removed the pacemaker first and thoracotomy with thrombectomy was then performed. The clinical symptoms resolved after the operation. To our knowledge, this is the first case reported in the literature and this observation supported the thrombosis theory for membranous obstruction of inferior vena cava.
Clinicopathological study of minimum‐sized hepatocellular carcinoma: An approach to the definition of early hepatocellular carcinoma
Authors: KIM SOO RYANG , KANG KYONG BOO , SOH CHANG GYO , KIM JUNG HYO , HAYASHI YOSHITAKE , HANIOKA KEISUKE , ITOH HIROSHI
Published: March 2008

Clinicopathologic examination of 33 nodules from 23 cases of minimum‐sized hepatocellular carcinoma (HCC), less than 15 mm in diameter, was carried out by imaging and clinical follow up. On ultrasound (US), 16 hypoechoic nodules (48%) and 15 hyperechoic nodules (45%) on angiography 7 tumour stains (21%) and on computerized tomography (CT) 3 low density nodules (9%) were detected. Of 27 nodules on lipiodol CT (LpCT), 7 lipiodol‐deposited nodules (26%) were detected. Of 16 nodules on CO2US angiography (US‐angiography), 7 hypervascular (44%), 5 hypovascular (31%) and 4 isovascular nodules (25%) were detected. Of 13 nodules on CT during arterial portography (CTAP), 7 perfusion defect nodules (54%) were detected. The nodules were graded according to the Edmondson & Steiner Classification. Three nodules were resected; grossly, two were not distinct and one was poorly demarcated. Histologically, they were highly differentiated with irregularly‐thin trabecular‐patterned HCC where portal triads were detected. Cancer cells invaded the non‐cancerous liver cells by replacement, and the border between the cancerous and non‐cancerous regions was unclear; the latter region manifested chronic hepatitis or liver cirrhosis without hyperplasia. Minimum‐sized HCC is characteristically hypovascular in arterial and portal supply of blood, of multicentric origin and of a well‐differentiated pattern. Because the three resected nodules did not damage the liver acinus structure, they were considered to be an early stage of HCC.
Prediction of interferon‐alpha‐induced thyroid dysfunction in patients with chronic hepatitis C
Authors: MURAKAMI TSUKASA , MASUMOTO TOSHIKAZU , MICHITAKA KOJIRO , HORIIKE NORIO , HINO HISAKO , OKADA SHINICHI , KITAI KOICHIRO , ONJI MORIKAZU
Published: March 2008

To predict interferon‐alpha (IFN‐α)‐induced thyroid dysfunction, anti‐thyroglobulin (anti‐TgAb) and anti‐thyroid peroxidase antibodies (anti‐TPOAb) were determined by radio‐immunoassay (RIA) before IFN‐α treatment in 30 patients with chronic hepatitis C in whom the conventional haemagglutination test had failed to detect anti‐thyroid auto‐antibodies. Seven patients developed thyroid dysfunction during IFN‐α treatment (transient thyrotoxicosis in four patients, transient hypothyroidism in two, and Graves’ disease in one). Anti‐TgAb and/or anti‐TPOAb were detectable before IFN‐α treatment in six of these seven patients, while these antibodies were detected before treatment in only four of 23 patients who did not develop any thyroid dysfunction. The prevalence of these antibodies was significantly higher (P= 0.002) in the former group of patients than in the latter. In four patients with detectable anti‐TgAb before treatment but no subsequent thyroid dysfunction, the antibody disappeared during IFN‐α treatment. Haemagglutination tests for anti‐thyroid microsomal antibodies have previously been reported to be a useful predictive marker of IFN‐α‐induced thyroid dysfunction. In conclusion, sensitive detection of anti‐thyroid auto‐antibodies using RIA may also be useful for the prediction of IFN‐α‐induced thyroid dysfunction in patients with a negative haemagglutination test.
Restoration of gap junctions in the regenerative process of ethanol‐induced gastric mucosal injury
Authors: ENDO KEIICHIRO , WATANABE SUMIO , NAGAHARA AKIHITO , HIROSE MIYOKO , SATO NOBUHIRO
Published: March 2008

Gap junctions mediate intercellular communication and play an important role in cell proliferation and differentiation. The present study examined the expression of the gap junction protein connexin 32 in rat gastric mucosa during the regenerative process of ethanol‐induced gastric mucosal injury. Absolute ethanol (0.5 mL/100 g bodyweight) was administered to rats via gastric intubation. Following the treatment, rats were killed periodically, and gastric tissues were processed for indirect immunofluorescence microscopy using an anti‐connexin 32 antibody. Haematoxylin and eosin (H&E), periodic acid Schiff (PAS) and Bromodeoxyuridine (BrdU) staining were also performed in serial sections. Gastric injuries were limited in the mucosal layer. The injury was most severe 1 h after treatment, and was completely resolved by the 4th day after treatment. The number of immunoreactive spots for gap junctions was markedly decreased 1 h after the ethanol treatment. Reappearance of these immunostaining gap junctions occurred with repair of the injury. The reappearance of connexin 32 after injury was delayed in comparison with both the histologic resolution of the injury and the normalization of PAS‐stained mucus. In contrast, the time course of reappearance of gap junctions closely paralleled the appearance of BrdU‐labelled cells. These results indicate that morphologic repair is different to the recovery of cell maturity and cell proliferation in the regenerative gastric mucosa.
Primary liver cancer is of multifactorial origin: Importance of hepatitis B virus infection and dietary aflatoxin
Authors: SARACCO GIORGIO
Published: March 2008

Primary liver cancer has a variable incidence worldwide, occurring most frequently in South‐East Asia and China, which indicates that environmental factors are important in its aetiology. Although hepatitis B virus and chemical agents are the major risk factors for primary liver cancer, current evidence strongly suggests that it is of multifactorial origin. Aflatoxins are thought to be important because they are common food contaminants and are potent liver carcinogens in a wide variety of animal species. Evidence for the possible interactions between aflatoxin and hepatitis B infection, and their effects on the prevalence of primary liver cancer, is obtained from animal data and epidemiological studies. The risk of developing primary liver cancer following exposure to hepatitis B infection and aflatoxin is shown to be increased and the possible molecular mechanisms involved are discussed.
Aflatoxin and p53 abnormality in duck hepatocellular carcinoma
Authors: IMAZEKI FUMIO , YOKOSUKA OSAMU , OHTO MASAO , OMATA MASAO
Published: March 2008

Recent studies have revealed that a point mutation at codon 249 in the p53 gene predominates in hepatocellular carcinoma (HCC) cases from Southern Africa and China, where infection with hepatitis B virus (HBV) and contamination of aflatoxin B1 in food are risk factors for HCC. This unique mutation from G to T at the third base in codon 249 observed in human HCC cases is suggested to be linked to aflatoxin exposure. Six ducks with HCC, five of which were fed a diet containing aflatoxin B1 for 1–2 years, were analysed for the presence of point mutations at this codon of the p53 gene by polymerase chain reaction and direct nucleotide sequencing. None of the six ducks with HCC showed the change at this codon regardless of duck hepatitis B virus infection. This suggests that aflatoxin B1 itself might not be involved in the unique mutation at codon 249 in hepatocar‐cinogenesis, or that other factors coincident with aflatoxin may be responsible for this unique mutation.
Clinical and radiological pictures of hepatocellular carcinoma with intracranial metastasis
Authors: YEN FU‐SHUN , WU JAW‐CHUNG , LAI CHUNG‐RU , SHENG WEN‐YANG , KUO BENJAMIN ING‐TIAU , CHEN TRONG‐ZONG , TSAY SHYH‐HAW , LEE SHOU‐DONG
Published: March 2008

Hepatocellular carcinoma (HCC) with extrahepatic spreading is not uncommon. In order to delineate the clinical and radiological pictures of HCC with intracranial metastasis, 33 documented cases were analysed. Eighteen had brain parenchymal metastasis without skull involvement; the other 15 cases disclosed skull metastasis with brain invasion. The underlying HCC are mainly of expanding (13/33, 39.4%) and multifocal (13/33, 39.4%) types. Eighteen cases (18/33, 54.5%) had mental changes not related to hypoglycaemia or hepatic encephalopathy. Eighteen cases (18/20, 90%) disclosed hyperdense mass lesions by non‐contrast computed tomography (CT) scans and 17 cases showed homogeneous enhancement (17/22, 77.3%) by post‐contrast CT images. In the non‐skull involved group, five cases (5/12, 41.7%) disclosed ring‐shape enhancement and 14 cases (14/16, 87.5%) had perifocal oedema, which were not seen in the skull involved group. Eight cases (8/33, 24.2%) presented as intracerebral haemorrhage. Twelve (12/33, 36.4%) died of brain herniation. Most (14/18, 77.8%) non‐skull involved cases had simultaneous lung metastasis without bony metastasis, while the skull involved group often (10/15, 66.7%) disclosed extracranial bony metastasis without lung metastasis. The difference in extracranial metastasis was statistically significant (P<0.05). The multivariate survival analysis disclosed that lower lactate dehydrogenase level (≤316 U/L, P= 0.029) and treatments (surgery or radiation, P= 0.001) were positively associated with longer survival.

In conclusion, HCC with intracranial metastasis is symptomatic and life‐threatening. Half the cases may come from pulmonary metastasis and the other half may be from bony metastasis. Brain irradiation or surgery can prolong their survival.
Effect of hepatitis C antibody screening in blood donors on post‐transfusion hepatitis in Taiwan
Authors: WANG JIN‐TOWN , WANG TEH‐HONG , LIN JAW‐TOWN , LEE CHA‐ZE , SHEU JIN‐CHUAN , CHEN DING‐SHINN
Published: March 2008

A national screening programme for antibody to hepatitis C virus (HCV) in blood donors in Taiwan began in July 1992 using a second‐generation immunoassay. To study the impact of this screening on post‐transfusion hepatitis in Taiwan, a prospective study on post‐transfusion hepatitis, that was started in 1987, was continued. As of June 1994, 245 patients who received a blood transfusion after July 1992 had completed a follow‐up period for more than 6 months post‐transfusion. Of them, seven (2.8%) recipients developed acute post‐transfusion hepatitis. The hepatitis in six cases could not be attributed to infection by hepatitis A, B, C, D, E viruses or cytomegalovirus (CMV) or Epstein‐Barr virus (EBV). The remaining patient seroconverted to both IgG and IgM anti‐CMV. All seven patients recovered in 6 months without development of chronicity, and the mean peak alanine aminotransferase level was lower compared with that of the cases before anti‐HCV screening (i.e. pre‐July 1992). These results indicate that the current anti‐HCV screening has effectively interrupted HCV transmission through blood transfusion in Taiwan.
Effect of changes in vascular tone on the haemodynamic characteristics of the portal vascular bed of the isolated perfused rat liver
Authors: GROSSMAN HOWARD J , GROSSMAN VIRGINIA L , BHATHAL PRITHI S
Published: March 2008

The effect of altered vascular tone on the haemodynamic characteristics of the intrahepatic portal vascular bed was studied in the isolated perfused rat liver preparation. The relationship between portal venous inflow (Q) and portal perfusion pressure (P) was determined in the presence of a maximally effective concentration of a vasoconstrictor agent (noradrenaline, NAmax, 3 × 10−5mol/L), an intermediate concentration (NAmed, 1 × 10−6mol/L) or a vasodilator agent (papaverine, PAP, 6 × 10−4mol/L). At flow rates greater than 20 mL/min, the pressure‐flow relationship could be regarded as linear (P < 0.001), with mean values for the extrapolated intercept with the pressure axis (Po) of 6.8 ± 0.9 mmHg for NAmax, 4.5 ± 0.5 mmHg for NAmed, and 1.65 ± 0.05 mmHg for PAP‐treated preparations. Over the full flow range (0–70 mL/min), in both NA‐ and PAP‐treated preparations, portal vascular conductance (G = Q/P) was related directly to perfusion pressure. Thus, G = C.P, where C is a constant (mean values for NAmax, NAmed, and PAP‐treated preparations were 0.0090 ± 0.0020, 0.023 ± 0.005, and 0.26 ± 0.02 mL/min per g per mmHg2, respectively). It is concluded that both C and Po may be useful indices of tone in the isolated perfused rat liver, and that analysis of hepatic portal haemodynamics in this manner may have considerable practical value in studies of the action of vasoactive agents.
Hepatitis C and liver transplantation
Authors: CHAZOUILLERES OLIVER , WRIGHT TERESA L
Published: March 2008

Hepatitis C virus (HCV) is important to the liver transplant recipient for several reasons. First, chronic HCV infection is a frequent cause of end‐stage liver disease in North America and Europe, where the majority of liver transplants are performed. Second, recurrence of HCV after liver transplantation is almost universal so that many liver transplant recipients with and without overt hepatitis are viraemic. Third, HCV infection in the organ donor and/or in the blood transfused in the peri‐transplant period make acquisition of HCV possible. Finally, liver transplantation for chronic HCV infection represents a major financial burden to the health‐care system in the USA and worldwide.

Histological hepatitis not due to HBV or cytomegalovirus (CMV) is present in 14–35% of allografts from patients undergoing liver transplantation, and the majority of this is due to HCV infection. HCV infection recurs post‐transplant in almost all patients with pre‐transplant infection. Proof that HCV does recur has been provided by the sequencing of the hypervariable domain of the E2/NS1 region. The magnitude of HCV infection is underestimated by using serological assays in this immunosuppressed population. Using the b‐DNA assay, HCV‐RNA levels have been shown to increase in patients with recurrent infection.

The long‐term consequences remain to be defined but post‐transplantation HCV infection is generally much less devastating than post‐transplantation HBV infection, and many patients have clinically silent disease. It is likely that a carrier state exists in immunosuppressed transplant recipients since high HCV‐RNA levels occur in the absence of liver damage. In one study, 1, 2 and 3 year patient survival rates were shown to be comparable in patients with chronic active HCV infection and with cryptogenic cirrhosis (94, 89 and 87%, and 84, 84 and 73%, respectively). A more recent study from the University of Pittsburgh which compared the outcome of a larger number of HCV‐infected patients (n= 237) with a large number of control patients with non‐viral disease (n= 801), showed that indeed HCV infection does impact negatively on both patient and graft survival (1, 2 and 3 year patient survival in the study and control groups of 78, 68 and 66% and 84, 82 and 78%, respectively, P= 0.001). Undoubtedly with time, the full impact of recurrent HCV infection will become apparent, although short‐term survival is sufficiently good to warrant continued transplantation of this group of patients.

While the disease course in many patients is benign, aggressive post‐transplant HCV infection leading to liver failure is well documented. Factors which determine why some patients are more susceptible to liver damage than others are currently under study. It is likely that many interrelated variables are involved, including the level of pre‐transplant viraemia, genotype of the virus, amount of post‐transplantation immunosuppression, and ability of the host immune system to recognize HCV and mount an immune response.
New observations on cytoskeleton and fenestrae in isolated rat liver sinusoidal endothelial cells
Authors: BRAET FILIP , ZANGER RONALD DE , CRABBÉ EVELYNE , WISSE EDDIE
Published: March 2008

Fenestrae control the exchange of fluids, dissolved compounds and small particles between the blood and the space of Disse, and are primarily limited at one side by parenchymal cells. We recently described a simple and rapid method for the isolation, purification and cultivation of rat liver sinusoidal endothelial cells. With regard to the purity and morphology of liver endothelial cells, a detailed microscopic study was performed. Purity and viability after selective adherence was 74 and 95%, respectively. Liver endothelial cell purity was further enhanced to about 95% during adherence and spreading on collagen after 8 h of culture. Liver endothelial cells isolated by this method provide a viable cell population, enabling the study of structure and function of these cells in vitro. We investigated the cytoskeleton associated with fenestrae and sieve plates of liver endothelial cells. Cultured cells were slightly fixed and treated with cytoskeleton extraction buffer containing 0.1 % Triton. Whole mounts of extracted liver endothelial cells were prepared for scanning and transmission electron microscopy. Extracted liver endothelial cells show an integral, intricate cytoskeleton. Sieve plates and fenestrae are clearly delineated by cytoskeleton elements. Fenestrae are surrounded by a filamentous, fenestrae‐associated cytoskeleton ring with an average filament thickness of 16 nm. Additionally, sieve plates are surrounded and delineated by microtubuli, which form a network together with additional branching cytoskeletal elements. Microtubuli are sometimes found delineating linear arrangements of fenestrae. In conclusion, liver endothelial cells possess a cytoskeleton, that defines and supports sieve plates and fenestrae. Fenestrae‐associated cytoskeleton rings are involved in determining the size of fenestrae. The fenestrae‐associated cytoskeleton therefore probably controls the important hepatic function of endothelial filtration.
Role of Ito cells in the degradation of matrix in liver
Authors: ARTHUR MICHAEL JP
Published: March 2008

Liver fibrosis is a dynamic process caused by changes in not only the synthesis of matrix proteins but also their degradation. Current evidence indicates that Ito cells, when activated to a myofibroblastic phenotype, play a very active role in regulating matrix degradation in liver. This is mediated via their ability to synthesize and release several members of the matrix metalloproteinase family, a class of enzymes which are responsible for degradation of matrix proteins in the extracellular space. Activated Ito cells have been demonstrated to release prostromelysin, progelatinase A and the pro‐enzyme form of interstitial collagenase. In addition, these cells can express appropriate systems for cleaving pro‐metalloproteinases to active forms (e.g. the plasminogen activator system, urokinase) as well as specific tissue inhibitors of the activated metalloproteinases (TIMP). In the early phases of liver injury, enzymes with the ability to degrade components of normal liver matrix are expressed (stromelysin and gelatinase A). In contrast, in the fibrotic phase of liver injury, during which fibrillar collagens accumulate, there is little (if any) expression of interstitial collagenase but marked expression of TIMP. These findings suggest that metalloproteinases and their inhibitors play a significant role in liver injury and fibrosis.
Non‐invasive means to study the functional status of sinusoidal liver endothelial cells
Authors: SMEDSRØD BÅRD
Published: March 2008

Circulating connective tissue macromolecules are efficiently eliminated by receptor‐mediated endocytosis in liver endothelial cells (LEC). In patients with a seriously diseased liver, for example in liver cirrhosis or when a transplanted liver is about to be rejected, dysfunctional LEC or altered blood perfusion through the liver results in significantly increased serum levels of connective tissue macromolecules and other substances that are normally taken up by LEC. With the aid of high affinity antibodies or other kinds of binding proteins it has been possible to measure a number of connective tissue macromolecules in the blood, and some of these substances have been used to diagnose serious liver disease. However, the metabolic patterns of these molecules are such that it is difficult to extrapolate directly on the basis of increased serum levels to conclude that the main underlying cause of increased serum levels is dysfunctional LEC. Elevated serum levels of many connective tissue proteins may reflect either increased synthesis, increased release from cell or tissue depots, and/or decreased removal by LEC. Therefore, to use measurement of serum connective tissue molecule levels as indicators of LEC function, it is imperative to know the catabolic routes of these substances in health and disease. Due to the fact that we presently know more about the total metabolic pattern of hyaluronan (HYA) than of other connective tissue macromolecules that are cleared solely by LEC, serum HYA should be preferentially used to monitor the function of LEC, in particular in liver transplantation and cirrhosis.
Construction of retroviral vectors to induce strong hepatoma cell‐specific expression of cytokine genes
Authors: CAO GUANGWEN , KURIYAMA SHIGEKI , DU PING , SAKAMOTO TAKEMI , YANG WENGUO , MASUI KAZUHIRO , QI ZHONGTIAN
Published: March 2008

Continuing advances in molecular biology have provided tools for a promising approach to the treatment of cancer. Among the various strategies of gene therapy for cancer, many are aimed at killing tumour cells indirectly by the induction or reinforcement of a host immune response by gene transduction of various cytokines, major histocompatibility complex or immune accessory molecules. In the present study, we selected the tumour necrosis factor‐α, interleukin‐2 and interleukin‐3 genes as potential cytokine genes to induce antitumour effects. We constructed retroviral vectors carrying these cytokine genes under the control of the murine albumin enhancer and promoter and retrovirally transduced these genes into hepatoma and non‐hepatoma cell lines. Strong expression of the cytokine genes was induced in transduced hepatoma cells, while no evident expression was detected in transduced non‐hepatoma cells. These results demonstrate the hepatoma‐specific expression of cytokine genes and imply the feasibility of in vivo gene transfer into hepatomas without affecting any other tissues. Furthermore, these cytokine genes were expressed much more intensively when they were derived from the albumin enhancer and promoter than when derived from the simian virus 40 early region promoter. These results indicate that transcriptional regulatory sequences specific for the target tissues could be preferable to viral promoters for the gene therapy of cancer.
Effect of the microtubular inhibitor vinblastine on ferritin clearance and release in the rat
Authors: RAMM GRANT A. , POWELL LAWRIE W. , HALLIDAY JUNE W.
Published: March 2008

We have previously demonstrated that colchicine inhibits ferritin clearance from the circulation of normal and iron‐loaded rats and stimulates endogenous ferritin release into both the serum and bile of iron‐loaded rats. The aim of the present study was to determine the effect of vinblastine on ferritin clearance and release in normal and iron‐loaded rats. Vinblastine was administered at either 1 or 10 mg/kg to both normal and iron‐loaded rats, infused over a 5 h period with either a rat liver ferritin or saline solution. Serum and biliary ferritin levels were determined every 30 min. After 5 h, 90% of the infused ferritin was cleared from the circulation in the absence of vinblastine. Low‐dose vinblastine decreased ferritin uptake by 10–20% in iron‐loaded rats. High‐dose vinblastine inhibited ferritin clearance by 25% in normal rats and 20–40% in iron‐loaded rats. Vinblastine administration caused a 2–3‐fold increase in the serum ferritin concentration and a 3–5‐fold peak in biliary ferritin levels. Thus, vinblastine caused the release of endogenous ferritin into both the serum and bile of iron‐loaded rats in the presence of a ferritin load. We therefore conclude that disturbed microtubule function accounts for the observed inhibition of ferritin uptake and intracellular transport; however, the mechanism of increased ferritin release remains unclear.
Cyclic AMP‐dependent anion secretion in human small and large intestine
Authors: BRZUSZCZAK IM , ZHAO J. , BELL C. , STIEL D. , FIELDING I. , PERCY J. , SMITH R. , O'LOUGHLIN EV
Published: March 2008

Cyclic AMP‐dependent Cl secretion is the major secretion pathway in human intestine. The aim of the present study was to examine mechanisms involved in cAMP‐dependent anion secretion in human small and large intestine. Surgical resection specimens from both jejunum and distal colon were studied under short circuited conditions. Addition of the phosphodiesterase inhibitor IBMX induced an increase in the short‐circuit current (Isc) equivalent to the net increase in Cl secretion. The Isc was inhibited by diphenylamine decarboxylate (DPC; Cl channel blocker), bumetanide (basolateral Na+/K+/2Cl cotransporter), BaCl2 (basolateral K+ channel) and Cl free buffer in both segments and indomethacin (cyclo‐oxygenase inhibitor) in colon alone. Diphenylamine decarboxylate appears to directly inhibit secretion in jejunum, although its inhibitory effect is possibly mediated by inhibition of cyclo‐oxygenase in the colon. A small component of IBMX‐stimulated Isc was inhibited by acetazolamide. Cyclic AMP‐dependent secretion is largely apical Cl secretion, although a small component appears to be HCO3. Secretion is dependent on basolateral K+ channels and Na+/K+/2Cl cotransporters and, in the colon, is inhibited by indomethacin, implying a role for cyclo‐oxygenase metabolites. The chloride channel blocker DPC inhibits secretion in both areas. This class of compounds may have potential for treatment of secretory diarrhoea.
Endoscopic laser therapy for watermelon stomach
Authors: BOURKE MICHAEL J. , HOPE RICHARD L. , BOYD PETER , GILLESPIE PETER E. , WARD MICHAEL , COWEN ALISTAIR E. , WILLIAMS STEPHEN J.
Published: March 2008

Eleven patients (nine females, two males) with anaemia due to acute and chronic gastrointestinal blood loss were found to have gastric antral vascular ectasia (watermelon stomach). Nine patients were transfusion‐dependent, receiving a mean of 13.1 units over a mean period of 12.3 months. All patients received neodymium:yttrium‐aluminium‐garnet laser coagulation with a median of 3.0 treatment sessions. Post‐treatment transfusion needs were abolished in six patients and minimal in two patients during a mean follow up of 27.3 months (range 12–60 months). Overall there was a mean reduction in transfusion requirement with treatment from 2.5 units per month to 0.4 units per month (P<0.02). Mean pretreatment haemoglobin improved from 7.7 to 11.9g/dL after treatment (P< 0.001). No complications occurred. Laser coagulation is safe and effective treatment for anaemia due to watermelon stomach and should be considered as first line therapy.
Career paths for medical research. The proceedings of a Festschrift for Professor June Halliday (Part 1)
Authors: FARRELL GEOFFREY C. , POWELL LAWRIE W.
Published: March 2008

Recruitment and training for careers in medical research is an important issue that has direct relevance for advances in gastroenterology and hepatology in the Asia‐Pacific region. In November 1995, a symposium on aspects of medical research careers was convened at The Queensland Institute of Medical Research (QIMR) as part of a Festschrift to celebrate the distinguished career of Professor June Halliday. In addition to her many contributions to scientific knowledge about iron metabolism and haemochromatosis, Professor Halliday has played a major role in the development of medical research careers. As a woman scientist within a clinical department of an Australian university medical school, she has been and remains an important role model, particularly for scientists within such departments and for women, whose participation and leadership in medical research careers is greatly under‐represented. Professor Halliday's contributions to hepatology are summarized in the companion special article on aspects of iron metabolism and the liver (to be published in issue 11).
The basic scientist in a clinical department
Authors: EADIE MJ
Published: March 2008

The basic scientist in a clinical department is a relatively recent phenomenon in the long course of the development of academic medicine. It came about as a response to the enormous growth in medical and scientific knowledge in comparatively recent times, coupled with the relative inability of medically educated clinicians to use the conceptual tools and investigational methods that were being made available by modern chemistry and statistics. The juxtaposition of basic scientists and clinicians in a common environment produces tensions, but also rich dividends for both parties. Whatever ways medicine develops in the future, it seems unthinkable that it will be able to advance very far unless basic scientists and clinicians continue to work in collaboration, side by side.
Women in medical research: Headaches and hurdles
Authors: HART PRUE
Published: March 2008

Very few women have professorial status in Australian medical schools. However, there are approximately equal numbers of male and female PhD students in biomedical research at Australian universities. At Flinders University of South Australia, females comprise approximately 25% of academics in the School of Medicine, with 75% of general staff (including research staff without academic status, e.g. research assistants, research officers) being female. Females comprise 29% of Fellows in the highly competitive Career Awards Scheme of the National Health and Medical Research Council of Australia (NHMRC; 26% excluding those of the lowest rank, namely RD Wright Fellows). In both systems, a higher percentage of women are appointed to the lower levels. The statistics suggest that the main hurdle for women in medical research is the inability to progress in the postdoctoral ranks (e.g. appointment to, or promotion from, academic Level A/B positions (Tutor/Lecturer) or appointment to the NHMRC Research Fellowships Scheme). This may reflect the conflicts that women face in their debate of the priorities of family (children and partner) versus career, or research versus teaching and professional activities. All medical research is time‐demanding and continuing research funds are difficult to obtain. Women and men have similar success rates for obtaining funds from the NHMRC. However, a greater percentage of women academics do not apply for grants. Why? Can women be helped to play a larger role in medical research?
ENDOSCOPY
Authors: SMITH BELINDA C. , ALQAMISH JEHAD R. , WATSON KATRINA JR. , SHAW R. GIDEON , ANDREW JOHN H. , DESMOND PAUL V.
Published: March 2008

Abstract  Current antibiotic prophylaxis for endoscopic retrograde cholangiopancreatography (ERCP) is not standardized and may be inadequate. We aimed to evaluate the efficacy of 3 days of additional oral antibiotics in the prevention of ERCP‐related sepsis. One hundred and fifty‐six patients were randomized prospectively to receive either intravenous ticarcillin and clavulinic acid (Timentin® SmithKline Beecham, Dandenong, Victoria, Australia), pre‐ERCP (group I) or Timentin® and 3 days of oral amoxycillin and clavulinic acid (Augmentin®; SmithKline Beecham, Dandenong, Victoria, Australia), group II). Blood cultures were taken 30 min after the procedure. The occurrence of sepsis, defined as a temperature over 38°C, occurring in the first 7 days was recorded and the risk factors for the development of sepsis were evaluated. Four patients had significant positive blood cultures despite the prior administration of Timentin.® Sepsis occurred in 10% of group I patients, but only 3% of group II patients (relative risk 3.30; 95% confidence intervals 0.74‐14.8). The performance of sphincterotomy and the presence of common bile duct stones were significant risk factors for the development of sepsis. We would recommend 3 days of additional oral Augmentin® after a single dose of intravenous antibiotics in patients at increased risk of sepsis, which would include those with bile duct stones and/or those undergoing a therapeutic procedure.
Proliferative activity in intrahepatic metastasis of hepatocellular carcinoma
Authors: MAEDA TAKASHI , ADACHI EISUKE , KAJIYAMA KIYOSHI , TAKENAKA KENJI , SUGIMACHI KEIZO , TSUNEYOSHI MASAZUMI
Published: March 2008

To assess the characteristics of intrahepatic metastatic lesions (IML) in hepatocellular carcinoma (HCC), we analysed both the histological features and proliferative activities of 15 resected cases of HCC accompanied by IML. The histological features of the IML were essentially the same as those observed in the main nodules in 12 (80%) of 15 cases. In 13 (87%) of 15 cases, the labelling index of proliferating cell nuclear antigen (PCNA) in the IML was either higher than or the same as in the main nodules. In 10 (77%) of 13 cases, the MIB‐1 labelling index in the IML was either higher than or the same as in the main nodules. The results indicate that the histological features of the IML are essentially the same as those of the main nodules, while the proliferative activities in the IML were generally higher than those in the main nodules. Such characteristics may thus provide a clue to help distinguish intrahepatic metastasis from the multicentric occurrence of HCC.
Case Report: Gastrointestinal bleeding from a hepatocellular carcinoma invading the transverse colon
Authors: HASHIMOTO MASAJI , WATANABE GORO , MATSUDA MASAMICHI , YAMAMOTO TAIRA , TSUTSUMI KENJI , TSURUMARU MASAHIKO
Published: March 2008

A 72‐year‐old woman with cirrhosis of the liver was treated repeatedly by transcatheter arterial embolization for multifocal hepatocellular carcinomas. She developed gastrointestinal bleeding secondary to direct invasion of the wall of the transverse colon. The diagnosis was made pre‐operatively by colonoscopy and the patient was treated successfully. This rare complication of hepatocellular carcinoma was due to the protrusive type of growth exhibited by this tumour and may have been affected by the transcatheter arterial embolization.
Case Report: Fibrolamellar hepatocellular carcinoma in a Japanese woman: A case report and review of Japanese cases
Authors: HOSHINO HIROSHI , KATADA NAOYUKI , NISHIMURA DAISAKU , IMADA JUNKO , MORITA KIYOSHI , YOSHIDA NORIO , SANO HIROSHI , OKAMOTO KATSUSHI , KATO KATSUMOTO
Published: March 2008

Fibrolamellar hepatocellular carcinoma (FLHCC) is an entity distinct from ordinary hepatocellular carcinoma and is very rare in Oriental countries. We present here a Japanese case of FLHCC in a 25 year old woman, and review Japanese cases of FLHCC. The patient had mild abdominal pain when the hepatic tumour was revealed by ultrasonography. Hepatitis B surface antigen (HBsAg) and anti‐hepatitis C antibody were negative and serum alpha‐fetoprotein (AFP) was within the normal limit. Ultrasound‐guided fine needle biopsy was performed and the tumour was histologically diagnosed as FLHCC. A right lobectomy of the liver was then performed. Macroscopically, the tumour (10 × 10 times 8 cm) was circumscribed, rather hard and yellowish white. Microscopically, neoplastic hepatocytes were polygonal and large with eosinophilic cytoplasm, which contained pale bodies. A number of fibrous stroma were arranged in thin parallel bands. Consequently, the case was diagnosed as FLHCC. In Japan, approximately 18 000 people die of ordinary hepatocellular carcinoma annually, while only nine cases (including the present case; six males, three females) of FLHCC in Japanese subjects have been reported previously. The mean age of the Japanese cases of FLHCC is 20.9 years old. One case with positive HBsAg, liver cirrhosis and high level of AFP was observed of nine cases. The nature of FLHCC in Japanese subjects may not be significantly different from that in Caucasians, except for male predominance.
Case Report: Hepatic adenoma with bone marrow metaplasia in a patient with glycogen storage disease type 1a
Authors: MORIURA SHIGEAKI , KURODA MAKOTO , KIMURA ATSUSHI , IWATSUKA YASUSHI , IKEDA SHUHEI , SAKAI TAKASHI , USUI AKIHIKO
Published: March 2008

A 34 year old man with glycogen storage disease type 1a had two hepatic tumours since 18 years of age. They had continued to grow until he was 24 years old, but showed no further growth since then. He underwent a right hepatic trisegmentectomy with caudate lobectomy under veno‐venous bypass. The tumour in the posterior segment showed nodule‐within‐nodule appearance. Histologically, the inner adenoma with dysplasia, bone marrow metaplasia and lymphocytic infiltration was separated by a fibrous band from the outer adenoma of usual histology.
Pravastatin transport across the hepatocyte canalicular membrane requires both ATP and a transmembrane pH gradient
Authors: ADACHI YUKIHIKO , OKUYAMA YOSHIFUMI , MIYA HIROHISA , MATSUSITA HIROAKI , KITANO MOTOKAZU , KAMISAKO TOSHINORI , YAMAMOTO TOSHIO
Published: March 2008

Hepatic excretion of non‐bile acid organic anions is reported to be ATP‐dependent and a defect of this transport has been reported in congenitally jaundiced rats, animal models of human Dubin‐Johnson syndrome. To investigate the effect of the transmembrane pH gradient on hepatocyte canalicular membrane transport of ATP‐dependent organic anions, uptake of pravastatin, a 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG CoA) reductase‐inhibiting organic anion, by hepatocyte canalicular membrane vesicles was observed in the presence or absence of transmembrane pH gradients. Uptake was assessed by a rapid filtration technique. ATP‐dependent pravastatin uptake was stimulated in the presence of a transmembrane pH gradient (in > out) in Sprague‐Dawley (SD) rats. Uptake was dependent on both pravastatin and ATP concentrations and showed saturation kinetics. After intravenous injection of [14C]‐pravastatin (0.3 μmol), 81% of the dose was excreted in the bile within 35 min in SD rats, whereas only 20% was excreted in the bile in Eisai hyperbilirubinuria rats. ATP and the pH gradient also co‐stimulated the uptake of pravastatin in Eisai hyperbilirubinuria rats, although the Km was much higher and Vmax was much lower than corresponding values in SD rats. This coincided well with the marked reduction in in vivo biliary excretion of pravastatin in jaundiced rats.