bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating atrial natriuretic peptide (ANP) and central blood volume (CBV) in cirrhosis
Authors: Henriksen Jens H. , Schütten Hans Jørgen , Bendtsen Flemming , Warberg Jørgen
Published: August 2010

ABSTRACT— Endogenous α‐atrial natriuretic peptide (ANP) in plasma is elevated in various hypervolaemic conditions. Possible relationships between circulating immunoreactive ANP and cardiovascular and splanchnic haemodynamics were therefore studied in patients with cirrhosis (n = 16) and controls (n = 12). Arterial plasma concentration of ANP in supine patients was (mean ± SEM) 33 ± 4 vs 41 ± 10 pg/ml (9.9 ± 1.2 vs 12.3 ± 3.0 fmol/l) in controls (n.s.), and there was a weak direct correlation with right atrial pressure (r = 0.36, P = 0.05). There was no relationship with the presence of ascites or diuretic treatment. Central blood volume (CBV, i.e. the blood volume in the heart cavities, lungs, and aorta), determined from the mean transit time of 125I‐labelled albumin and cardiac output, was significantly reduced in cirrhotics compared to controls (1.45 ± 0.12 vs. 1.83 ± 0.10 1, P < 0.02) and inversely correlated with portal pressure (r = –0.42, P < 0.05), whereas total plasma volume was somewhat increased (3.51 ± 0.2 vs 3.19 ± 0.2, 0.05 < P < 0.1). A high arterio‐venous extraction of ANP was found in the splanchnic system (extraction ratio 0.44 vs 0.28), kidney (0.45 vs 0.54), lower limb (0.53 vs 0.40), and forearm (0.27 vs 0.18) in patients and controls, respectively (n.s.). Our results suggest that the lack of elevation of circulating ANP in cirrhosis, even in the presence of actual fluid retention, may be explained by central hypovolaemia in these patients. Turnover and degradation of ANP is rapid and normal, as evaluated from the tissue extraction ratios.
Isolation and culture of biliary epithelial cells from the biliary tract fraction of normal rats
Authors: Kumar U. , Jordan T. W.
Published: August 2010

ABSTRACT— A method has been developed for the isolation of a population of cells enriched in epithelial lining cells from the bile ducts of normal rats. The procedure utilized digestion by pronase of the white strands of biliary and connective tissue which remained after hepatocytes had been mechanically removed from collagenase‐perfused liver. The resulting cell population was enriched in cells whose ultrastructure resembled that of the epithelial cells of intrahepatic bile ducts. Contamination with hepatocytes, hepatocyte nuclei and erythrocytes was less than 2%. The cells have been maintained in short‐term culture. The major morphological change during the first 2 days of culture was proliferation of microvilli, but cell protein composition was unchanged when analysed by polyacrylamide gel electrophoresis. A rabbit antiserum against bovine hoof prekeratin was used to immunohistochemically stain the intermediate filaments of biliary epithelium and was shown to stain more than 90% of the cells in the isolated cell population.
Effect of acetaldehyde on collagen synthesis by fat‐storing cells isolated from rats treated with carbon tetrachloride
Authors: Shiratori Yasushi , Ichida Takafumi , Kawase Tateo , Wisse Eddie
Published: August 2010

ABSTRACT‐ In an attempt to elucidate the role of fat‐storing cells (FSCs) in alcoholic liver fibrosis, we examined the effects of ethanol and acetaldehyde on collagen synthesis by FSCs isolated from CCl4‐treated or normal rats. Isolated FSCs from normal rats showed characteristic lipid droplets in the cytoplasm. FSCs from CCl4‐treated rats showed an abundant rough endoplasmic reticulum and a small number of lipid droplets. Collagen synthesis by the cells from CCl4‐treated rats was 4–5‐fold enhanced as compared with untreated rats. Though ethanol had an inhibitory effect on collagen synthesis by FSCs, acetaldehyde stimulated collagen production by the cells from CCl4‐induced hepatic fibrosis, whereas collagen synthesis by the cells from normal rats was not influenced by acetaldehyde. From these results, FSCs are morphologically and functionally changed in liver fibrosis, and the transitional state of FSCs might be important in the pathogenesis of alcoholic liver fibrosis.
Relationship of histologic grade of hepatocellular carcinoma (HCC) to tumor size, and demonstration of tumor cells of multiple different grades in single small HCC
Authors: Kenmochi Kunihiko , Sugihara Shigetaka , Kojiro Masamichi
Published: August 2010

ABSTRACT— The histologic features of 65 surgically resected cases of hepatocellular carcinoma (HCC) were studied, and the cellular differentiation was graded from I to IV according to Edmondson‐Steiner's classification. HCC cells of 2 or more grades were seen in 31 (47.7%) of the 65 cases. There was no significant difference in the proportion of HCC composed of tumor cells of more than one histologic grade between HCCs with association with liver cirrhosis and without cirrhosis. Among these 31 cases, extremely well‐differentiated HCC, corresponding to Edmondson‐Steiner's grade I carcinoma, was found in 9 of 11 tumors smaller than 3 cm in diameter, but it was not seen in 20 tumors larger than 3 cm in diameter. In the 34 HCCs with a uniform histologic pattern, all of two minute tumors smaller than 1 cm in diameter consisted of extremely well‐differentiated HCC, but there were no cases consisting of extremely well‐differentiated HCC in tumors larger than 2 cm in diameter. Taken together, these findings suggest that HCCs originate as relatively well‐differentiated tumors, which may be difficult to distinguish from adenomatous regenerative nodules, and become progressively less differentiated at a later stage of their development.
Congenital intrahepatic cholestasis with pigment deposits and abnormal bile acid metabolism. A variant of Dubin‐Johnson's syndrome?
Authors: Bremmelgaard A. , Ranek L. , Hage E. , Tyg‐strup N.
Published: August 2010

ABSTRACT— A congenital cholestatic disorder of long duration with heavy deposits of pigment in the liver cells is presented.
Possible infectious causes in 651 patients with acute viral hepatitis during a 10‐year period (1976–1985)
Authors: Kiyosawa Kendo , Gibo Yukio , Sodeyama Takeshi , Furuta Kiyoshi , Imai Haruhiko , Yoda Hidetoshi , Koike Yuriko , Yoshizawa Kaname , Furuta Seiichi
Published: August 2010

ABSTRACT— Six hundred and fifty‐one patients with acute viral hepatitis were identified serologically between January 1976 and December 1985. Of these, 109 (17%) had hepatitis A, 135 (21%) had hepatitis B, and 407 (62%) had hepatitis non‐A, non‐B. The possible infectious causes for acquisition of viral hepatitis occurring within 6 months before the onset of hepatitis were analysed. Approximately 80% of cases of hepatitis A and 70% of hepatitis B had no known risk factor, while in 67% of cases of hepatitis non‐A, non‐B possible risk factors for infection were documented. Infectious causes for hepatitis A were ingestion of raw shellfish (11%) and previous familial contact with patients with hepatitis A (10%). For hepatitis B, risk factors included medicare (24%), such as transfusion, surgical operation, accidental needle stick and acupuncture, and sexual contact (6%). For hepatitis non‐A, non‐B, the most important infectious cause was medical procedures (65%). The numbers of hospital employees were 2 (2%) with hepatitis A, 15 (11%) with hepatitis B and 14 (3%) with hepatitis non‐A, non‐B. These data suggest that hepatitis non‐A, non‐B can be a kind of nosocomial disease.
Hepatic venous oxygen content in alcoholic cirrhosis and non‐cirrhotic alcoholic liver disease
Authors: Bendtsen Flemming , Henriksen Jens H. , Widding Alice , Winkler Kjeld
Published: August 2010

ABSTRACT— Blood gas analyses and hepatic blood flow were determined during hepatic vein catheterization in order to establish a possible hypoxic component in alcoholic liver disease. Fifty‐six patients (9 non‐cirrhotic liver disease, 14 cirrhosis Child‐Turcotte class A, 23 class B, 10 class C) and 10 control subjects were studied. Mean hepatic venous oxygen saturation and tension were almost the same in all groups, and hepatic blood flow was inversely correlated to the arteriohepatic venous oxygen difference (r = –0.53, P < 0.01). Splanchnic oxygen uptake was similar in all groups studied. The arterio‐hepatic venous difference of base excess was small and of the same size in all groups, indicating no enhanced production of lactic acid in the liver. Our results do not support the concept that hepatic venous oxygen content is low in alcoholic liver disease and thereby contributes to hypoxic liver damage.
Elements in normal and cirrhotic human liver tissue II. Potassium, sulphur, chlorine and bromine measured by X‐ray fluorescence spectrometry
Authors: Milman N. , Laursen J. , Asnæs S. , Pøden‐Phant J.
Published: August 2010

ABSTRACT— Elements (K, S, Cl, Br) were measured by X‐ray fluorescence spectrometry in normal liver tissue obtained at autopsy from 74 subjects (44 ♂, 30 ♀), median age 62 years (range 20–87), and in cirrhotic liver tissue from 27 subjects (14 alcoholic, 13 non‐alcoholic cirrhosis). The element content (median and 5–95 percentile interval) in normal livers in mmol/kg dry tissue was: K, 198.75 (150.95–256.42); S, 147.60 (73.86–233.97); Cl, 98.73 (69.51–163.55); Br, 0.1101 (0.0701–0.4205). None of the elements displayed any sex difference. There were correlations between the content of Br and Cl (r = 0.26, P<0.05) and Br and K (r = 0.24, p<0.05). In both groups of cirrhotic livers, K, S and Cl content was within the normal range. Median Br content was above normal both in alcoholic (0.2265 mmol/kg, P<0.01) and non‐alcoholic cirrhotic livers (0.2228 mmol/kg, P<0.01).
Pattern of progression in liver injury following jejunoileal bypass for morbid obesity
Authors: Vyberg Mogens , Ravn Vibeke , Andersen Bjørn
Published: August 2010

ABSTRACT— Liver biopsies from 34 patients with morbid obesity, performed before and 5–9 months after jejunoileal bypass, were studied. The patients were divided into four groups according to preoperative findings: A: no or slight steatosis (15 patients), B: moderate‐severe steatosis (6), C: steatohepatitis (steatosis+lobular lymphocytic inflammation) (8), D: steatofibrosis (steatosis+pericellular fibrosis) (5). In Group A, 12 patients showed postoperative progression to either moderate/severe steatosis, steatohepatitis, or steatofibrosis. In Group B, all patients progressed to steatohepatitis or steatofibrosis, and one developed septate fibrosis. All patients in Group C progressed to steatofibrosis, and 5 developed septate fibrosis or cirrhosis. In Group D, 3 developed bridging fibrosis. Mallory bodies appeared postoperatively in 11 patients (32%), all of whom preoperatively had either severe steatosis, steatohepatitis, or steatofibrosis. Only patients with postoperative pericellular fibrosis and Mallory bodies developed deranged architecture: 6 septate/bridging fibrosis, and 3 cirrhosis. Five patients, all with deranged architecture, developed reversible liver insufficiency. Progressive liver injury after jejunoileal bypass appears to reflect aggravation of a preexisting liver lesion. The sequence of events: increasing steatosis, lobular lymphocytic inflammation, pericellular fibrosis, Mallory bodies, and deranged architecture is similar to that of the alcoholic liver lesion, indicating common pathogenetic mechanisms.
The characteristics of alcoholic liver disease in Japan. Clinicopathologic comparison with alcoholic liver disease in the United States
Authors: Uchida Toshikazu , Shikata Toshio , Govindarajan Sugantha , Kronborg Ian
Published: August 2010

ABSTRACT— Alcoholic liver disease (ALD) in Japan was compared clinicopathologically with the occurrence in the U.S.A. ALD found in Japan was more frequently complicated by other hepatic diseases including non‐A, non‐B chronic hepatitis than ALD found in the U.S.A. (9.9% versus 21.9%). Patients with such complications were excluded from this study. The chief complaints of the total of 51 alcoholics studied in the U.S.A. were abdominal distension or jaundice and those of 98 alcoholics studied in Japan were non‐specific: general fatigue, weakness or appetite loss. The U.S. patients exhibited more elevated levels of serum bilirubin (8.1±7.5 versus 1.9±2.4 mg/dl, mean±SD) and a higher incidence of leukocytosis (49.0% versus 5.1%). While the serum glutamic‐oxalacetic transaminase (GOT) levels were not significantly different between the two groups (146.5±116.8 versus 140.8±147.7 IU/L), the serum glutamic‐pyruvic transaminase (GPT) levels among Japanese alcoholics were higher (38.6±31.4 versus 87.4±99.1 IU/L) and in about one quarter of these patients, serum GPT was higher than serum GOT, a feature not seen in the patients in the U.S.A. Comparative histopathologic study of 337 U.S. patients and 210 Japanese patients disclosed a higher frequency of cirrhosis (46.9% versus 33.8%), the presence of Mallory bodies (58.5% versus 13.8%) and marked neutrophilic exudation (45.1% versus 6.2%). Thus, the majority of Japanese alcoholics exhibited progression of liver disease, eventually leading to cirrhosis, due to hepatocellular drop‐out and fibrosis caused by a mechanism different from alcoholic hepatitis. In addition, ALD in the U.S.A. revealed more striking extension of fibrosis. In conclusion, ALD appeared to be generally more severe clinicopathologically in the U.S.A. than in Japan.
Immunoglobulin on the surface of isolated hepatocytes is associated with antibody‐dependent cell‐mediated cytotoxicity and liver damage
Authors: Vergani D. , Mieli‐Vergani G. , Mondelli M. , Portmann B. , Eddleston A. L. W. F.
Published: August 2010

ABSTRACT— Hepatocytes isolated from patients with chronic liver disease are often covered by immunoglobulin. The aim of the present study was to establish whether this surface immunoglobulin (SIg) mediates liver cell damage. Freshly isolated hepatocytes from percutaneous liver biopsy of 16 patients with chronic active hepatitis (CAH) (6 HBsAg positive), 3 with HBsAg‐positive chronic lobular hepatitis (CLH), 5 with HBsAg‐positive chronic persistent hepatitis (CPH) and 12 with minor histological abnormalities (MHA) (5 HBsAg positive) were divided into two aliquots. One was studied for the presence of membrane‐bound immunoglobulin and the third component of complement by direct immunofluorescence and the other was incubated, in an allogeneic cytotoxic assay, with peripheral blood mononuclear cells prepared from healthy volunteers as a source of effectors for antibody‐dependent cell‐mediated cytotoxicity (ADCC). Liver biopsies were scored for portal and parenchymal inflammatory activity. The percentage of SIg positive hepatocytes was significantly higher in patients with CAH (median 52.5%) than in patients with CLH/CPH (20.5%) or in patients with MHA (1%). Percentages of SIg‐positive liver cells were significantly correlated with total liver biopsy scores and with both portal or parenchymal scores considered independently. SIg were found to belong to the IgG class in all groups of patients. When hepatocytes were cultured with normal human lymphocytes, allogeneic cytotoxicity values were significantly higher in patients with CAH (median 34%) than in patients with CLH and CPH (18%) or in those with MHA (12%). Percentage cytotoxicity was positively correlated with total biopsy scores and with portal activity but not with parenchymal activity, suggesting that ADCC might play a damaging role mainly in the portal areas. Our results show that in HBsAg‐positive and in HBsAg‐negative chronic liver disease IgG on the liver cell membrane is associated with increased susceptibility to in vitro cytotoxicity by killer cells and with increased severity of histological liver damage, suggesting a direct role for these antibodies in the generation of the liver injury.
Differential diagnosis of jaundice: junior staff experience with the Copenhagen pocket chart
Authors: Malchow‐Møller Axel , Mindeholm Linda , Rasmussen Henrik Sandvad , Rasmussen Bo , Wilhelmsen Flemming , Petersen Jørgen Schmidt , Jørgensen Susanne , Hilden Jørgen , Thomsen Carsten , Matzen Peter , Juhl Erik
Published: August 2010

ABSTRACT— Originally published in 1984, the Copenhagen Pocket Chart for early differentiation between causes of jaundice has been tested with success in centres outside Denmark. Using a logistic discrimination model, it estimates probabilities of obstruction and non‐obstruction in each case (and provides a further subdivision if desired). Here we evaluate its performance in the hands of young clinicians on a consecutive series of 173 jaundiced patients from two Danish hospitals. The chart performed as well as in the original series: confident diagnoses (probability ≥ 0.80) were assigned to 124 patients; of these 115 proved correct (93%). In 46 patients diagnostic probabilities were <0.80, and 3 patients had an unknown cause of jaundice. There were 108 cases in which physician and chart were in agreement, both with a confident diagnosis, and only one of these cases was wrong. In one hospital, contributing 107 cases, each patient was independently examined by a medical student in addition to the physician's examination. Student performance was equally good, practically speaking, in particular when taking the scores on the chart into consideration. As to observer disagreement, the student and the physician typically differed on 0–2 of the chart's 21 items. In no case, however, did this lead to a confident obstructive diagnosis being changed into a confident diagnosis of non‐obstruction, or vice versa.
Hepatic fibrosis in patients with idiopathic thrombocytopenic purpura
Authors: Lafon M. E. , Bioulac‐Sage P. , Balabaud C.
Published: August 2010

ABSTRACT— Three patients showing all the symptoms of idiopathic thrombocytopenic purpura underwent a splenectomy. A wedge liver biopsy revealed hepatic fibrosis around central veins and an increased perisinusoidal network on Sirius red staining. Fibrosis was moderate or mild. Liver histology was otherwise normal, as were liver function tests. Hepatic fibrosis could not be attributed to any known causes. Electron microscopy showed numerous Kupffer cells with intense phagocytic activity, and perisinusoidal cells with some of the characteristics of fibro/myofibroblasts. The mechanisms of fibrosis remain unknown but could be attributed, by analogy to agnogenic myeloid metaplasia, to the massive destruction of platelets liberating PDGF and to increased activation of macrophages.
Post‐transfusional vs. sporadic non‐A, non‐B chronic hepatitis. A clinico‐pathological and evolutive study
Authors: Jové J. , Sánchez‐Tapias J. M. , Bruguera M. , Mas A. , Costa J. , Barrera J. M. , Rodés J.
Published: August 2010

ABSTRACT— The clinical, morphological and evolutive features of 60 patients with chronic hepatitis, presumably caused by non‐A, non‐B virus infection, have been retrospectively analyzed. In all the cases the disease began as an acute episode of viral hepatitis that was followed by persistently abnormal liver function tests. No patient had evidence of current or past hepatitis B virus infection and other known causes of chronic liver disease were excluded. Thirty patients had received blood transfusions in the recent past, five were drug addicts and the source of the infection was not identified in the remaining 25, in whom the disease was considered to be sporadic. Clinical or biochemical differences between patients with post‐transfusional and sporadic non‐A, non‐B chronic hepatitis were not observed, but liver histology showed a higher proportion of patients with chronic persistent hepatitis in the sporadic (72%) than in the transfusional group (53%). On follow‐up, sustained normalization of liver function tests was observed in 46% of the cases with sporadic hepatitis but only in 13% of the cases with post‐transfusion hepatitis. These observations suggest that non‐A, non‐B chronic hepatitis is more severe in patients with transfusion‐related infection than in sporadic cases.
Biphasic form of hepatitis A virus infection: a frequent variant in Argentina
Authors: Tanno Hugo , Fay Oscar H. , Rojman José A. , Palazzi Jorge
Published: August 2010

ABSTRACT— In a retrospective study, we review here the clinical presentation of patients with the biphasic form of hepatitis A, a variant of viral hepatitis characterised by an increase in ALAT levels after an initial recovery in clinical condition and laboratory tests. Twenty‐one patients were diagnosed as having a biphasic form; they represent about 10% of a selected population of hepatitis A cases. Six patients were asymptomatic. Eleven patients were jaundiced, nine of them showing a “cholestatic” pattern. The second phase of the disease had a more protracted course and displayed higher ALAT levels than the first phase. The total duration of the disease was 120±28 (mean±SD) days, and its course was benign.
Serum proline and blood lactate levels in alcoholic patients without hepatic failure: relationship with alcohol ingestion and histological activity
Authors: Vargas‐Tank L. , Wolff C. , Castillo T. , Carrión Y. , Hoppe A. , Martínez V. , Armas‐Merino R.
Published: August 2010

ABSTRACT— It has not yet been established whether serum proline and blood lactate levels are increased in alcoholic liver disease. We measured serum proline and blood lactate in controls and in patients with different stages of alcoholic liver disease in the absence of hepatic failure. Samplings were done in both abstinent and drinking alcoholics. Compared to controls, there was a striking increase in serum proline levels in 52 abstinent alcoholics with little or no hepatic fibrosis by histological assessment (0.10 ± 0.01 vs. 0.155 ± 0.008; p<0.005). Blood lactate levels were within the normal range and did not correlate with serum proline levels. On the other hand, serum proline and blood lactate levels were independent of hepatic necrosis and inflammation scores. In addition, in 10 patients with blood alcohol concentrations between 0.3 mg/ml and 7.8 mg/ml, serum lactate and proline were significantly elevated (2.42 ± 0.29 mg/ml and 0.275 ± 0.0026 mg/ml, respectively; p<0.005). These results show that there is an association between serum proline levels and the abstinence period in alcoholic patients. They further suggest that in alcoholic patients neither serum proline nor blood lactate concentrations are reliable markers for liver histological activity (necrosis and inflammation) or fibrosis.
The streaming liver II. Hepatocyte life history
Authors: Arber N. , Zalicek G. , Ariel I.
Published: August 2010

ABSTRACT— Thirty male adult rats, were injected with [3H]‐thymidine, [3H]TdR. The animals were killed in groups of five, at the following times: 1 h, 14, 30, 60, 90 and 120 days. The livers were fixed in formalin, embedded in paraffin and cut into 5‐μ‐thick sections, which were then dipped into liquid emulsion and exposed for 3 weeks. The grain content of each sampled cell was counted and its distance from the nearest portal tract rim measured. Since the cells were labelled once and the label was available only for a short period, cell displacement could be followed with time. One hour after labelling, most labelled cells were confined within the 300 μm distance from the portal space rim. From then on, labelled cells advanced at a daily velocity of 2.5 μm toward the terminal hepatic vein. The liver acinus is composed of two compartments: a progenitor compartment extending up to 300 μm from the portal tract and a functional compartment covering the remaining acinus portion. Such an arrangement is known as a two‐compartment cell renewal system, and is found in renewing tissues like cryptvillus and epidermis. The hepatocyte moves from the portal space toward the terminal hepatic vein, proceeding along a trajectory, denominated as tissue radius. Since cells move in one direction, the further a cell is from the portal tract, the older it is. One may therefore estimate cell age by measuring its distance from the origin. Since the tissue radius portrays cells of all ages, it describes the entire life history of one cell. The advancing hepatocytes traverse the three acinus zones. Each represents, therefore, a differentiation stage of one cell, and since in each zone cells perform different functions, the metabolic activity of the hepatocyte is age‐dependent. When young it is engaged, among other activities, in gluconeogenesis, turning in old age to glycolysis.
An enzyme‐linked immunoassay for the possible detection of non‐A, non‐B viral antigen in patients with epidemic viral hepatitis
Authors: Gupta Hema , Joshi Y. K. , Tandon B. N.
Published: August 2010

ABSTRACT— An enzyme‐linked immunosorbent assay has been developed by using IgM antibodies from the acute stage as a source to capture the antigen in stools of patients with epidemic non‐A, non‐B (NANB) viral hepatitis. 29/69 (42.3%) of the patients and 3/9 (33.3%) contacts were positive for a suspected NANB viral antigen. However, only 1/27 (3.7%) of the negative controls drawn from amongst the patients with amoebiasis, giardiasis, hepatitis due to virus A and healthy individuals was positive for NANB antigen in the stool. The suspected NANB viral antigen was more frequently detected in stools collected between the 14th and 18th day of icteric hepatitis. The study suggests that IgM antibodies from patients with acute viral NANB hepatitis react with an antigen present in the stools of a high proportion of patients with epidemic NANB viral hepatitis. This serological test may be useful to establish the etiological diagnosis of non‐A, non‐B (fecal‐oral) viral hepatitis. ELISA‐positive stools contained 27 nm viral particles.
The effect of porta‐caval shunt, ammonia infusion and alcohol administration on rat plasma β‐hexosaminidase
Authors: Hultberg B. , Isaksson A. , Bugge M.
Published: August 2010

ABSTRACT— The activity of the lysosomal enzyme, β‐hexosaminidase, is increased in plasma of patients with various forms of liver disease as well as in plasma from rats with experimental cholestasis or cirrhosis. In this experimental study in the rat, the effect of porta‐caval shunt, ammonia infusion and ethanol feeding on plasma β‐hexosaminidase activity was studied. Porta‐caval shunted animals had significantly increased plasma β‐hexosaminidase activity compared to sham‐operated animals. Ammonia infusion in porta‐caval shunted rats resulted in a further increase of plasma enzyme activity. Ethanol feeding for different periods of time (1 day to 4 weeks) did not have any influence on plasma β‐hexosaminidase activity.
Propranolol reduces the response of serum bile acids to oral chenodeoxycholic acid, possibly as a reflex reaction to reduced portal blood flow in healthy and cirrhotic subjects
Authors: Testa Roberto , Dagnino Franco , Grasso Alessandro , Celle Guido
Published: August 2010

ABSTRACT— To evaluate if a drug that affects splanchnic and portal flow reduces intestinal bile acid absorption, we studied the effect of propranolol (40 mg oral dose) both on the response of total bile acids (SBA) to oral chenodeoxycholic acid (CDCA 250 mg) and on the estimated hepatic flow by indocyanine green kinetics in 10 healthy and 14 cirrhotic subjects. In 18 subjects who showed a reduction in resting heart rate of almost ‐5%, propranolol significantly reduced the SBA area under the curve after CDCA in both healthy (μmol/l/h m±SD from 181.7 times 144.9 to 56.5±36.4 p<0.02) and cirrhotic (from 1412.1±1044.8 to 1129.2±978.8 p<0.01) subjects. Variable but not significant modifications were observed in estimated hepatic flow. These results suggest that the propranolol‐induced changes in SBA response to CDCA could be a reflex reaction to changes in splanchnic/portal flow.
Long‐term follow‐up of chronic post‐transfusion non‐A, non‐B hepatitis: clinical and histological outcome
Authors: Mattsson Lars , Weiland Ola , Glaumann Hans
Published: August 2010

ABSTRACT— A chart review of chronic hepatitis cases at the Department of Infectious Diseases, Roslagstull Hospital, Karolinska Institute, Stockholm, Sweden, revealed 37 patients with chronic non‐A, non‐B hepatitis, caused by blood transfusions or intravenous gammaglobulin infusions. They had been followed up long‐term, mean 46 months (range 10–149). During the initial hepatitis episode most patients had been anicteric and 13/37 (35%) asymptomatic. Yet, the majority developed progressive liver disease with chronic active hepatitis, with or without histological signs of cirrhosis. Thus, 10/18 (56%) on whom a liver biopsy had been performed within 7–12 months had chronic active hepatitis, four (22%) with histological signs of cirrhosis, and of the five patients biopsied after ≥5 years of follow‐up, three (60%) had histological signs of cirrhosis. Accordingly, as the duration of follow‐up increases, an increasing number of patients with post‐transfusion non‐A, non‐B hepatitis seem to develop cirrhosis.
Dexamethasone increases the capacity of urea synthesis time dependently and reduces the body weight of rats
Authors: Sigsgaard Inga , Almdal Thomas , Hansen Bent A. , Vilstrup Hendrik
Published: August 2010

ABSTRACT— Rats of 230 g were treated with 0.1 mg of dexamethasone twice daily for 2 days (n = 5) and 14 days (n = 9). Controls received isotonic saline. During the first week of dexamethasone treatment the rats lost weight rapidly (up to 9 g/day). The weight loss diminished during the second week of treatment. The fasting blood insulin concentration increased sevenfold in the dexamethasone‐treated rats. Fasting blood glucagon and glucose concentrations were not different from controls. In the dexamethasone‐treated rats the fasting alpha‐amino‐N concentrations were lower: 4.0±0.3 mmol/l (mean ± SEM) versus 6.8±0.3 mmol/1 in controls. The capacity of Urea‐N Synthesis, determined during alanine loading was: after 2 days of treatment 14.7±1.7 μmol/(min 100 g), after 14 days of treatment 7.9±0.8 μmol/(min 100 g), and in controls 7.5±1.0 μmol/(min 100 g) (mean±SEM). In conclusion, glucocorticoid treatment leads to a transient change in the liver function as to hepatic amino‐N conversion, implying that more amino‐N than normal is eliminated as urea‐N after 2 days of treatment. This may contribute to the early, but not the late body weight loss.
Prevalence of HBcAg and delta‐Ag in liver tissue of patients with HBsAg positive chronic hepatitis
Authors: Di Sapio Mario , Caporaso Nicola , Del Vecchio‐Blanco Camillo , Coltorti Mario
Published: August 2010

ABSTRACT— One hundred and twenty HBsAg positive patients with chronic liver disease, 94 with CAH and 26 with CPH, were studied in order to characterize chronic HBsAg positive hepatitis virologically. All patients came from a geographical area (Campania, Italy) with a high prevalence of HBV and HDV infection. Each patient was tested for the presence of HBsAg, HBeAg, anti‐HBe and anti‐delta in serum (by RIA techniques), and of HDV (by direct immunofluorescence) and HBcAg (by indirect immunofluorescence and PAP‐immunoperoxidase) in liver biopsy specimens. Anti‐delta serum positivity was remarkably more frequent in patients with CAH (40%) than in those with CPH (19%). Delta‐Ag was found in 94.7% of the anti‐delta positive patients with CAH, but in none of the five anti‐delta positive patients with CPH. In contrast, the frequency of HBcAg tissue positivity was similar in CAH and CPH. Positivity for HBcAg was less frequent in CAH with cirrhosis than in CAH without cirrhosis, while there was no difference in the prevalence of delta‐Ag.
Does a linear pattern of sinusoidal IgA deposition distinguish between alcoholic and diabetic liver disease?
Authors: Nagore N. , Scheuer P. J.
Published: August 2010

ABSTRACT— IgA deposition in hepatic sinusoids was demonstrated in liver biopsies from 26 patients with alcohol‐ or diabetes‐related fatty liver and fatty liver hepatitis, and from 13 patients with normal liver or chronic active hepatitis. The pattern and extent of IgA deposition were similar in alcoholic and diabetic patients, a linear, continuous pattern being the most common. Staining for IgA cannot therefore be used to evaluate aetiology of fatty liver hepatitis in these two groups of patients.
Pathologic study of primary biliary cirrhosis of early histologic stages presenting cholestatic jaundice
Authors: Nakanuma Yasuni , Hoso Masahiro , Mizuno Yasunori , Unoura Masashi
Published: August 2010

ABSTRACT— While cholestatic jaundice usually develops in the advanced stages of primary biliary cirrhosis, our series of this disease disclosed that 8 of the 88 cases presented cholestatic jaundice in the early histologic stages (stages 1 and 2). These patients frequently presented esophageal varices (57%) and showed a low incidence of positive mitochondrial antibodies compared to the non‐jaundiced cases in the same histologic stages. Histologic changes of livers from the jaundiced patients failed to show fundamental differences from those of the non‐jaundiced patients, except for the presence of bile plugs and extensive bile duct loss in the former. Deposition of orcein‐positive granules and increased hepatic copper content, suggesting prolonged cholestasis, were rather advanced, and inflammatory changes in the portal tracts and piecemeal necrosis were rather mild in the jaundiced patients. These data suggest that cholestatic jaundice occurs in a few patients in the early histologic stages on a biopsy with extensive bile duct loss and features of prolonged cholestasis; it is not clear whether such patients are a small separate cluster in PBC, or not.
Perivenous and perisinusoidal collagen content in the acinar zone 3 in the “normal” liver. A light microscopical study
Authors: Junge Jette , Vyberg Mogens , Horn Thomas , Christoffersen Per
Published: August 2010

ABSTRACT— The thickness of the terminal hepatic vein wall (TTHV) and the content of perisinusoidal collagen in 989 zone 3 areas in Picro‐Sirius‐stained sections from 117 liver biopsies with normal morphology or slight non‐specific changes were analyzed. TTHV varied from 0.4 μm to 21.3 μm (median 3.8 μm). A positive correlation was found between TTHV and the diameter of the terminal hepatic vein. The average TTHV of the individual biopsies was not correlated to age, sex or liver morphology. The average zone 3 collagen content did not exceed that of zones 2 and 1, with the exception of biopsies with slight steatosis, where a minimal increase in zone 3 collagen was found. The normal variability of TTHV and the correlation to the diameter of THV must be considered in the evaluation of perivenular fibrosis. Even a slight increase in perisinusoidal collagen content may be suggestive of a pathological condition.
Effects of sera from patients with obstructive jaundice on the generation of oxygen intermediates by normal polymorphonuclear leukocytes
Authors: Ohshio Gakuji , Miyachi Yoshiki , Kudo Hiroyuki , Niwa Yukie , Manabe Tadao , Tobe Takayoshi
Published: August 2010

ABSTRACT— Recently it has been suggested that oxygen intermediates play an important role in the pathogenesis of tissue damage. The effect of sera from patients with obstructive jaundice on the generation of oxygen intermediates by normal polymorphonuclear leukocytes (PMNs) was investigated. Sera from patients with obstructive jaundice increased superoxide anion (O2‐), hydrogen peroxide (H2O2) and hydroxol radical (OH) generation compared with sera from healthy individuals or patients with biliary tract stones and/or tumors of the biliary tract or pancreas (without obstructive jaundice). In particular, the hydroxyl radical, which is one of the most potent oxidants capable of causing tissue damage, was produced in large quantities. Sera from patients with obstructive jaundice have a strong capacity to induce production of oxygen intermediates from PMNs, and oxygen intermediates may play a role in the pathogenesis of hepatic and other organ injury in obstructive jaundice.
Tryglycylvasopressin‐reduced portal and systemic concentrations of serum bile acids after exogenous chenodeoxycholic acid load in rats as a reflection of reduced splanchnic blood flow
Authors: Testa R. , Ghia M. , Grasso A. , Mereto E. , Dagnino F. , Celle G.
Published: August 2010

ABSTRACT— The effect of triglycylvasopressin (TGVP) on the absorption of chenodeoxycholic acid (CDCA) was investigated in three groups of six rats (controls, CDCA, CDCA + TGVP) through the evaluation of portal and caval serum bile acids (SBA) concentrations after an oral load with CDCA to investigate whether changes in this parameter reflect variations in splanchnic blood flow induced by a vasoconstrictor. The results indicate that CDCA was absorbed and led to a significant increase in SBA. This increase was reduced by TGVP administration: portal blood 380.0 ± 61.2 vs 279.7 ± 45.3; caval blood 151.8 ± 45.7 vs 41.7 ± 12.5 (μmol/1; mean ± s.d.). This suggests that variations in SBA concentrations could reflect changes in splanchnic circulation.
Caroli's disease and adult polycystic kidney disease: a rarely recognized association
Authors: Jordon Deanna , Harpaz Noam , Thung Swan N.
Published: August 2010

ABSTRACT— Caroli's disease is a rare form of fibropolycystic disease of the hepatobiliary system characterized by segmental cystic dilatation of intrahepatic ducts. It is associated with intrahepatic cholelithiasis, cholangitis and hepatic abscesses. Like other forms of fibropolycystic disease of the liver, Caroli's disease is often accompanied by cystic renal disease, specifically renal tubular ectasia or medullary sponge kidney. Adult‐type polycystic kidney disease associated with Caroli's disease is rare, only one such case having appeared in the literature to our knowledge. We present a second instance of this association.
Hepatocellular transferrin receptor expression in secondary siderosis
Authors: Sciot Raf , Van Eyken Peter , Facchetti Fabio , Callea Francesco , van der Steen Kris , van Dijck Herwig , van Parys Geert , Desmet Valeer J.
Published: August 2010

ABSTRACT— We investigated the hepatocellular transferrin receptor expression in 55 human liver specimens with secondary siderosis, with an indirect immunoperoxidase technique on frozen sections using 3 monoclonal anti‐transferrin receptor antibodies. For comparison, specimens were also stained with the monoclonal antibody BK 19.9, recognizing an antigen which is biochemically similar to the transferrin receptor, and with a monoclonal antibody against the epidermal growth factor receptor. The degree of iron overload was estimated semi‐quantitatively, taking into account hepatocellular and Kupffer cell iron deposition. In 47 out of 55 specimens hepatocellular transferrin receptor expression was present. The positivity was predominantly localized on hemosiderin‐free hepatocytes. With increasing hepatocellular iron deposition, the proportion of cases with absent transferrin receptor immunoreactivity increased. This supports the previously reported disappearance of hepatocellular transferrin receptor expression in primary hemochromatosis cases with severe iron deposition. However, the transferrin receptor negative cases included four specimens in which Kupffer cell iron deposition clearly exceeded hepatocyte iron load. This finding suggests that in addition to hepatocellular iron load other factors may regulate the expression of parenchymal transferrin receptors in iron overload diseases. These may include plasma levels of various iron sources and/or Kupffer cell iron load. The iron deposition did not influence the staining of the hepatocellular epidermal growth factor receptor nor the Kupffer cell staining by the BK 19.9 antibody. This confirms the specificity of the findings concerning the behaviour of the transferrin receptor in secondary siderosis.
The streaming liver IV: DNA content of the hepatocyte increases with its age
Authors: Schwartz‐Arad D. , Zajicek G. , Bartfeld E.
Published: August 2010

Hepatocyte age was estimated from its distance from the portal tract. We have previously shown that hepatocytes are formed adjacent to the portal tract and stream toward the terminal hepatic vein, advancing at a daily velocity of 2 μm. Thus, the farther a cell from the portal tract, the older it is. This relationship between cell age and distance served here for the study of age‐dependent changes in the hepatocyte, particularly nuclear area and DNA content. DNA content was derived from the absorbance of Feulgen‐stained nuclei in 5‐μm‐thick tissue sections. Absorbance and nuclear area were measured with a cytophotometer. Since most nuclei of the tissue section were sliced, DNA content was estimated also in intact nuclei which were sampled by fine needle aspiration, and stained with either Feulgen or propidium iodide. Feulgen‐stained nuclei were scanned by a cytophotometer, while the DNA content of propidium iodide‐stained nuclei was measured by flow cytometry. Absorbance was expressed in relationship to the mean absorbance of diploid periportal littoral cells. Littoral absorbance was defined as one absorbance unit. A high correlation between nuclear absorbance and area was observed in nuclear suspensions (adjusted r‐square 0.79), so that nuclear area may serve as a good predictor of nuclear DNA content, which is valuable in routine sections which are stained with H and E. Most periportal hepatocytes were polyploid and their mean absorbance was 1.68 units. Nuclear absorbance increased with cell distance from the portal tract. Within 100 μm it rose from 1.68 to 1.92 units. Nuclear area increased by 13%. Since the cell covers the 100 μm distance in 50 days, its absorbance increases daily by 0.005 units. Yet since the advancing hepatocyte gets older as it advances, nuclear absorbance increases with hepatocyte age, and so does nuclear area.
Intrahepatic bile duct changes in human hepatosplenic schistosomiasis mansoni
Authors: Vianna M. Regina , Gayotto L. C. C. , Telma R. , Santos M. , Alves V. A. Ferreira , Fukushima Julia , De Brito T.
Published: August 2010

Wedge liver biopsies of 132 patients with hepatosplenic mansonian schistosomiasis were studied and divided in two groups according to the presence (Group I – 69 cases) or absence (Group II – 63 cases) of markers of the actual presence of the parasite in the liver tissue. Histological variables indicating bile duct injury were analysed in each case: periductal fibrosis, hyperplasia of the bile duct epithelium, bile duct degeneration, and marginal ductular proliferation. The presence of one or more of these variables defined two sub‐groups: A – bile duct lesions present (73 cases), and B – bile duct lesions absent (59 cases). The variables “bile duct degeneration” and “ductular proliferation” were related to the actual presence of the parasite in the host. In 55.3% of all cases of human mansonian schistosomiasis a spectrum of injuries to the bile ducts was present. Epithelial hyperplasia alone or associated with patterns of mucopolysaccharide production was observed in 87.6% cases of the Sub‐group A. The bile ducts changes in mansonian schistosomiasis are close to those described in liver fluke infestations such as clonorchiasis, fascioliasis and opistorchiasis. Statistical analysis revealed that high mucopolysaccharide production was associated with epithelial hyperplasia. The pathogenesis of the bile duct changes in human mansonian schistosomiasis and its relation to the parasitic infestations and their antigens is discussed.
Enterically transmitted non‐A, non‐B hepatitis in cynomolgus monkeys: morphology and probable mechanism of hepatocellular necrosis
Authors: SOE SOE , UCHIDA TOSHIKAZU , SUZUKI KOYU , KOMATSU KOUHEI , AZUMI JUN‐ICHI , OKUDA YASUNORI , IIDA FUSAE , SHIKATA TOSHIO , RIKIHISA TETSUJI , MIZUNO KYOSUKE , WIN KHIN MAUNG , TIN KHIN MAUNG
Published: August 2010

Two cynomolgus monkeys were inoculated with a stool extract originally derived from patients suffering from enterically transmitted non‐A, non‐B hepatitis. Subsequently, the primates developed self‐limiting acute hepatitis and their liver tissues were obtained sequentially by needle biopsy or at sacrifice. Histologically, the liver tissues exhibited necroinflammation which appeared in parallel, both in time and magnitude, with elevation in serum aminotransferases. Necroinflammation was characterized by focal dropout of hepatocytes with accumulation of lymphocytes and macrophages. These lymphocytes were positive for a cytotoxic/suppressor immunophenotype. The hepatocytes surrounding these focal necroses showed depletion of glycogen granules and decrease in glucose‐6‐phosphatase and succinic dehydrogenase activities. Ultrastructurally, damaged hepatocytes around the focal necroses revealed marked dilatation of both rough and smooth endoplasmic reticula, swelling and disruption of the mitochondria and leakage of nuclear materials into the cytoplasm. Frequently, direct contact between the damaged hepatocytes and lymphocytes was noted. Virus‐like particles measuring about 27 nm in diameter were observed singly or in small groups within the cytoplasm of damaged hepatocytes. Primary hepatocyte culture of a cynomolgus monkey, inoculated with a transmissible stool extract did not show any cytopathic change, although similar virus‐like particles were recognized ultrastructurally in the cultured hepatocytes. Morphological analysis of in vitro and in vivo transmission studies in cynomolgus monkeys strongly supported the hypothesis of immune‐mediated hepatocytolysis rather than a direct cytopathic effect of this hepatitis virus.
The streaming liver V: Time and age‐dependent changes of hepatocyte DNA content, following partial hepatectomy
Authors: ZAJICEK G. , SCHWARTZ‐ARAD D. , BARTFELD E.
Published: August 2010

Two processes contribute to the change in hepatocyte ploidy following partial hepatectomy: one is age‐dependent, while the other depends on the time which has elapsed since hepatectomy. While in the normal liver hepatocyte DNA content increases with the age of the cell, following hepatectomy the average DNA content (or ploidy) for the entire population rises as well. Hepatocyte age was derived from the cell's distance from the portal tract. We have previously shown that hepatocytes are formed adjacent to the portal tract and stream toward the terminal hepatic vein, advancing 2 μm/day. This finding enables the estimation of hepatocyte age from its location, since the older a cell the more remote it is from the portal tract. Twenty‐four young male random‐bred rats were partially hepatectomized and killed in groups of four animals at the following times: 1 h and 1, 2, 3, 7 and 14 days. Liver sections and nuclear suspensions which were collected by fine needle aspiration were stained with Feulgen and measured with the aid of computerized image cytometry. Part of the suspension which was aspirated with a fine needle was stained with propidium iodide and measured by flow cytometry. Both nuclear area and the DNA content increase with the age of the cell. The older a cell, the higher its ploidy. Generally, young hepatocytes which synthesized DNA did also divide, while older cells tended to accumulate DNA and became polyploid. The average nuclear DNA content of the entire population increased by 14% in 3 days. Partial hepatectomy thus triggers cells to synthesize DNA and proliferate. Since not all cells which synthesize DNA divide, it is proposed to distinguish between two triggers, one initiating DNA synthesis and the other, proliferation.
Iron induction of ferritin synthesis and secretion in human hepatoma cell (Hep G2) cultures
Authors: LESCOAT G. , LOREAL O. , MOIRAND R. , DEZIER J. F. , PASDELOUP N. , DEUGNIER Y. , BRISSOT P.
Published: August 2010

In order to determine if iron was able to stimulate specifically ferritin synthesis and secretion in transformed human hepatocytes in culture, human hepatoma cell (HepG2) cultures were submitted to increasing doses of ferric nitrilotriacetate. Iron uptake by the cells was demonstrated by incorporation of 59 Fe and the staining method of Perls. The following results were obtained: 1. iron incorporation within the hepatocytes increased as a function of culture time; 2. during the first 24 h of treatment, ferritin synthesis increased progressively, in parallel to the iron uptake; 3. a dose‐dependent significant stimulation of ferritin synthesis and secretion were observed when the medium iron concentration increased from 5 to 20 μmol/l; 4. albumin, transthyretin and transferrin secretions were unaffected. These data demonstrated that, in our hepatocyte culture model, iron load increased the expression of ferritin in a highly specific manner.