bluuebunny/crossref_metadata_2025 huggingface dataset:
The Perfused Human Liver Wedge Biopsy: A New In Vitro Model for Morphological and Functional Studies
Authors: Burwen Susan J. , Jones Albert L. , Goldman Ira S. , Way Lawrence W. , Dejbakhsh Sussan
Published: July 2010

We developed a simple and inexpensive method of perfusing small specimens of human liver in vitro that maintains short–term tissue viability as judged by protein transport function and morphological features. The technique allows investigation of liver function at the cellular level in normal specimens and those with hepatobiliary disease. Electron microscopy of specimens perfused with this system demonstrates the presence of an incomplete basement membrane within the space of Disse and shows that human microbodies contain crystalline–like cores morphologically similar to those found in rat liver.
Hepatocellular Carcinoma in Women: Probable Lack of Etiologic Association With Oral Contraceptive Steroids
Authors: Goodman Zachary D. , Ishak Kamal G.
Published: July 2010

To investigate the possibility of an association between oral contraceptive steroids (CS) and hepatocellular carcinoma (HCC), we reviewed 128 cases of HCC in women collected between 1953 and 1980. There were 48 cases under the age of 40, and 13 of these (27%) had used CS. However, 62% of HCC associated with CS and 58% of HCC in women under 40 not using CS were classified histologically as “fibrolamellar” carcinoma. This subtype of HCC occurs predominantly in young people, both male and female. The apparent increase in HCC in young women can be explained by the presence of cases of fibrolamellar carcinoma in this age group, and the apparent association with CS is probably coincidental.
Dane Particle–Associated Hepatitis B E Antigen in Patients With Chronic Hepatitis B Virus Infection and Hepatitis B E Antibody
Authors: Raimondo Giovanni , Recchia Serafino , Lavarini Carla , Crivelli Osvaldo , Rizzetto Mario
Published: July 2010

A commercial radioimmunoassay was adapted to detect serum Dane particle–associated HBeAg in patients whose sera contained the homologous antibody. HBeAg was released from Dane particles with guanidine HC1.

Dane particles were separated from anti–HBe by gel–filtration (Sepharose 4B) and ultracentrifu–gation of the eluate. Dane particle–HBeAg was tested in 45 HBsAg carriers with anti–HBe and was present in 8 (18%) carriers, all of whom had chronic liver disease. By contrast, HBeAg was not found in 10 carriers with normal liver histology. Serum or liver HBeAg was found in 6 of 8 patients with Dane particle–HBeAg. None of the carriers without Dane particle–HBeAg had other markers of hepatitis B virion synthesis.

We conclude that Dane particle–HBeAg provides a sensitive index of active hepatitis B virus replication, a guide to the presence of chronic hepatitis in HBsAg carriers with anti–HBe, and a noninvasive method to follow infection in these patients.
The Spectrum of Hepatic Candidiasis
Authors: Lewis James H. , Patel Hasmukh R. , Zimmerman Hyman J.
Published: July 2010

The liver is affected in up 50 to 75% of compromised hosts with disseminated Candida albicans infection who come to autopsy. The antemortem diagnosis of hepatic candidiasis is rarely made. Blood cultures are negative in approximately 50% of cases, and biochemical parameters of hepatic injury may be of nonspecific value. Additionally, the more commonly seen renal, cardiac, and respiratory involvement may overshadow the hepatic lesion. In a review of 17 autopsy series of disseminated candidiasis, 92 cases with hepatic involvement were identified for a mean prevalence of 13.7%. Hepatic granulomas and microabscesses were the two most common histologic lesions attributable to Candida. Inflammatory aggregates, centrilobular congestion, bile stasis, and fatty change were seen less frequently. The diagnosis should be suspected in any compromised host with unexplained fever with or without elevated alkaline phosphatase or bilirubin levels. The diagnosis can be made by percutaneous needle biopsy or at laparoscopy in a majority of cases. Early treatment with Amphotericin is associated with prolonged survival.
Comparison of the Effects of A Cardioselective and A Nonselective β–Blocker on Portal Hypertension in Patients With Cirrhosis
Authors: Hillon Patrick , Lebrec Didier , Muńoz Cristina , Jungers Michel , Goldfarb Gerard , Benhamou Jean-Pierre
Published: July 2010

The effects on cardiac output and portal venous pressure of atenolol, a cardioselective β–blocker, and propranolol, a nonselective β–blocker, were compared in patients with portal hypertension due to cirrhosis. One hour after p.o. administration of 100 mg of atenolol, cardiac output decreased by 32%, and portal venous pressure by 16%; the decrease in cardiac output and the decrease in portal venous pressure were significantly correlated. One hour after p.o. administration of 40 mg of propranolol, cardiac output decreased by 32% and portal venous pressure by 24%; the decrease in cardiac output and the decrease in portal venous pressure were not correlated. Whereas the decrease in cardiac output was similar after atenolol or propranolol, the decrease in portal venous pressure was significantly less marked after the former than after the latter β–blocker. It is concluded that: (a) the decrease in portal venous pressure determined by atenolol results mainly from reduction in cardiac output; (b) the decrease in portal venous pressure determined by propranolol results not only from reduction in cardiac output, but also from extracardiac effects of this β–blocker, and (c) atenolol might be less efficient in the prevention of recurrent gastrointestinal bleeding in cirrhosis, since the decrease in portal venous pressure is less marked than that which occurs with propranolol.
Visual Evoked Potentials in Encephalopathy Induced by Galactosamine, Ammonia, Dimethyldisulfide, and Octanoic Acid
Authors: Zeneroli Maria L. , Ventura Ezio , Baraldi Mario , Penne Alessandro , Messori Elena , Zieve Leslie
Published: July 2010

Visual evoked potentials were utilized to examine the neuronal transmission changes provoked by galactosamine–induced hepatic encephalopathy and by administration in normal animals of toxins presumably involved in the pathogenesis of hepatic encepalopathy. Separate acute administrations of ammonia, dimethyldisulfide, and octanoic acid induced lethargy, convulsions in the case of the first two, and coma with visual–evoked potential patterns that never resembled the evoked potentials recorded in hepatic coma. By contrast, single and repeated administrations of the three above–mentioned toxins together at lower doses induced lethargy and coma with visual–evoked potential patterns similar to those observed in galactosamine–induced hepatic coma. These observations, together with previously published data, are consistent with the concept that the synergistic interaction of these toxins plays a significant role in the pathogenesis of hepatic encephalopathy.
Geographic Distribution of Hbsag Carriers in China
Authors: BEASLEY Palmer R. , Lin Chia-Chin , Chien Chia-Siang , Chen Chien-Jen , Hwang Lu-Yu
Published: July 2010

We tested by radioimmunoassay the sera of 22,707 male Chinese government employees in Taiwan for HBsAg and found 15.2% to be positive. Almost all were confirmed as carriers by follow–up testing 1 year later. This paper presents HBsAg positivity rates of these men according to the province of China from which they originated, and compares the rates with published provincial mortality rates for primary hepatocellular carcinoma. Moderate variation in carrier rates between provinces was observed with high prevalence in men from provinces south of the Yangtze River. There was positive correlation between HBsAg prevalence and primary hepatocellular carcinoma incidence giving further support to the possibility of a causal relationship.
Hepatitis B Virus and Hla Antigen Display in the Liver During Chronic Hepatitis B Virus Infection
Authors: Montaño Luis , Miescher Guido C. , Goodall Alison H. , Wiedmann Karl H. , Janossy George , Thomas Howard C.
Published: July 2010

An analysis of the expression of the histocompatibility antigens in the livers of patients with chronic hepatitis B virus infection and normal subjects has demonstrated an increased expression of HLA–A,B,C antigens on the hepatocytes of patients with a low level of viral replication (HBe antibody positive) as compared with patients who exhibit a high level of viral replication (HBe antigen positive) and controls. This increase in the expression of histocompatibility antigens on the hepatocytes was associated with a decrease in the membrane expression of viral antigens by the same cells. These differences in the density of HLA and viral antigen display may influence the efficiency of T–cell cytolysis of hepatitis B virus–infected hepatocytes.
Histologic Observations in Human Hepatitis Non–A, Non–B
Authors: Dienes Hans P. , Popper Hans , Arnold Wolfgang , Lobeck Hartmut
Published: July 2010

Specimens from 57 patients with acute or chronic hepatitis non–A, non–B (HNANB), mostly mild to moderate, were studied by light and, in 22 instances, by electron microscopy. They were compared to specimens of hepatitis A and hepatitis B on file or obtained simultaneously with the HNANB cases. In the HNANB material, two types of light–microscopic lesions were noted in the lobular parenchyma singly or in combination. One was an eosinophilic alteration of the hepatocytic cytoplasm associated with many acidophilic bodies. Conspicuous alteration were often accompanied by microvesicular steatosis. This lesion was associated with nuclear particles detectable by electron microscopy. The second lesion consisted of sinusoidal cell activation which was prominent in some cases. From experiences with chimpanzees, these features were tentatively considered to be stages of the same process. Both lesions were associated with portal and usually mild periportal inflammation which was not related to the degree and type of parenchymal reaction. They were also observed in chronic stages, making the differentiation between acute and chronic HNANB difficult. Active hepatitis B seems to differ from HNANB primarily by the conspicuous presence of lymphocytes in the lobular parenchyma often in contact with hepatocytes, acidophilic bodies, and a more uniform portal inflammatory reaction. In hepatitis A, hepatocellular injury was conspicuously periportal. In HNANB, a cytopathic effect rather than lymphocytic immune attack appears to be of greater significance than in the other forms of viral hepatitis. The recurrence of lobular mainly eosinophilic changes may explain chronicity.
Biochemical Separation of Na+, K+–Atpase From A “Purified” Light Density, “Canalicular”–Enriched Plasma Membrane Fraction From Rat Liver
Authors: Boyer James L. , Allen Rose M. , Ng Oi Cheng
Published: July 2010

Cytochemical studies suggest that Na+, K+–ATPase is localized to sinusoidal and lateral portions of the hepatocyte plasma membrane whereas Mg++–ATPase and alkaline phosphatase are luminal or canalicular membrane markers. To validate further these cytochemical findings, we have isolated from the nuclear pellet of rat liver homogenates a liver plasma membrane (LPM) fraction enriched in all three enzyme markers, as previously described (Biochimica et Biophysica Acta 1975; 401:59-52). Following tight Dounce homogenization, the vesiculated membrane preparation was further separated on a multiple–step discontinuous sucrose density gradient (d 1.12 to 1.22). Na+, K+–ATPase activity “dissociated” from Mg++–ATPase activity, sedimenting at densities of 1.14 and greater. Further studies were carried out in two–step discontinuous sucrose gradients (1.13 and d ± 1.13), and a light density fraction (d 1.13) was further characterized in calcium–free media (since addition of calcium increased contamination with intracellular membranes). Electron microscopy demonstrated a homogeneous vesicular membrane population in contrast to the heavy density fraction (d ± 1.13) which contained membrane sheets and junction complexes as well as vesicles. The light density fraction was highly enriched in Mg++–ATPase (42.1 x homogenate specific activity) and alkaline phosphatase (64.6 X homogenate), 3 to 4 times their activities in the original LPM. In contrast, Na+, K+–ATPase activity in the light density fraction, diminished 16–fold from values in the original unfractionated LPM. All but 15% of total Na+, K+–ATPase activity in the original LPM could be accounted for in unwashed preparations. Neither cholesterol/phospholipid ratios nor an analysis of peptides on sodium dodecyl sulfate gel electrophoresis demonstrated differences in the composition of the light vs. heavy density subfractions, although there were relative increases in several peptide bands in the light density subtraction. These studies provide further supporting biochemical evidence for the concept that Na+, K+–ATPase resides on different membrane domains than does Mg++–ATPase and alkaline phosphatase and further characterizes a vesiculated membrane preparation highly enriched in putative “canalicular” enzyme markers.
Decreased Albumin and Increased Fibrinogen Secretion by Single Hepatocytes From Rats With Acute Inflammatory Reaction
Authors: Bernuau Dominique , Rogier Edith , Feldmann Gérard
Published: July 2010

During the acute inflammatory reaction (AIR), the plasma concentration of several plasma proteins, including fibrinogen, is increased as a result of enhanced production by the liver. Whether this increased production influences the production of the other plasma proteins at the single hepatocyte level is not known. Accordingly, we simultaneously measured albumin and fibrinogen secretion by single hepatocytes isolated from normal rats and from rats sacrificed 24 hr after a turpentine–induced AIR, using an hemolytic plaque test. In normal rats, 74, 82, and 98% of the hepatocytes were detected as secreting albumin, after 1, 2, and 4 hr of incubation, respectively. Simultaneously, 0, 32, and 62% of the hepatocytes were detected as secreting fibrinogen at the same incubation times. For secretion of both proteins, a significant correlation was established between the diameter of a plaque–forming hepatocyte and its hemolytic plaque. In rats with AIR, the formation of hemolytic plaques detecting albumin secretion was slowed down compared to normal rats, since only 0, 36, and 78% of the hepatocytes were forming hemolytic plaques after 1, 2, and 4 hr of incubation, respectively. Simultaneously, the formation of hemolytic plaques detecting fibrinogen secretion was increased compared to normal rats, since at the same incubation times, 52, 78, and 93% of the hepatocytes formed hemolytic plaques. A significant correlation between the diameter of a plaque–forming hepatocyte and its hemolytic plaque was still maintained for both protein secretion.

These results demonstrate that during the AIR enhanced fibrinogen production is the result of an increased secretion rate per cell, and decreased albumin secretion is the result of a lowered secretion rate per cell, generalized for all hepatocytes. These data strongly suggest that there is a reciprocal modulation of fibrinogen and albumin secretion at the single hepatocyte level during the AIR.
Effect of Chronic Ethanol Feeding on Hepatic Mitochondria in the Monkey
Authors: French Samuel W. , Ruebner Boris H. , Mezey Esteban , Tamura Tsunenobu , Halsted Charles H.
Published: July 2010

The effect of chronic ethanol feeding on hepatic mitochondrial morphology and histochemically measured succinic dehydrogenase activity was assessed. Five monkeys of the species Macaca radiata received a nutritionally adequate diet containing 50% of the calories as ethanol, while five others were pair–fed the same diet except that ethanol was isocalorically substituted by carbohydrate. Liver morphology was assessed at 12 and 24 months and at sacrifice after 40 to 48 months of ethanol feeding. The ethanol–fed animals developed mild to moderate fatty liver as did some of the controls. No necrosis or fibrosis developed. All ethanol–fed animals developed centrilobolar mega–mitochondria and centrilobular “shift” in histochemically assayed succinic dehydrogenase activity characteristic of animals fed ethanol for prolonged periods. These mitochondrial changes persisted throughout the 48–month test period without progressive increase in severity or accompanying pathology. It is concluded that the morphologic and histochemically assessed mitochondrial changes do not necessarily represent a progressive destructive effect of ethanol.
Effect of Chronic Ethanol Feeding on Hepatic Collagen in the Monkey
Authors: Mezey Esteban , Potter James J. , French Samuel W. , Tamura Tsunenobu , Halsted Charles H.
Published: July 2010

The effect of chronic ethanol feeding was determined on parameters of hepatic collagen metabolism in the monkey. Four monkeys of the species Macaca radiata received a nutritionally adequate diet containing 50% of the calories as ethanol, while four others were pair–fed a diet in which ethanol was isocalorically substituted by carbohydrate. Liver biopsies were obtained at 3, 12, and 24 months, and the animals were killed between 40 and 48 months after initiation of the diets. The ethanol–fed animals developed various degrees of fatty infiltration, but no necrosis, inflammation, or fibrosis. The amount and distribution of collagen Types I, III, and IV demonstrated by immuno–histochemical techniques was not altered after ethanol feeding. No changes were found in hepatic protein–bound hydroxyproline or in collagen prolyl hydroxylase activity at the various time intervals. Liver free proline and the incorporation of labeled proline into protein–bound hydroxyproline by liver slices were not altered after 40 to 48 months of ethanol feeding. This study shows that prolonged feeding of ethanol together with an adequate diet results in fatty infiltration but not deposition or alteration of hepatic collagen metabolism.
Hepatitis B Virus Status of Southern African Blacks With Hepatocellular Carcinoma: Comparison Between Rural and Urban Patients
Authors: Kew Michael C. , Rossouw Elizabeth , Hodkinson John , Paterson Alan , Dusheiko Geoffrey M. , Michael Whitcutt J.
Published: July 2010

Hepatocellular carcinoma (HCC) is less common and occurs at a much older age in urban than in rural southern African Blacks. These differences may reflect differences in the etiology of the tumor in the two populations. The purpose of this study was to compare the hepatitis B virus (HBV) status of 150 HCC patients who were born and had lived all their lives in a rural environment with 158 patients who were born and brought up in a rural setting but then became urbanized. HBsAg and all markers of present or past HBV infection [HBsAg(+) or anti–HBc(+) or anti–HBs] were significantly less common in the urban patients when the two groups were considered as a whole (p < 0.001 and p < 0.05, respectively). However, because the rural patients were considerably younger (mean age 34.7 years; 66% less than 40 years of age) than the urban patients [mean age 50.9 years (p < 0.0005), 19.0% less than 40 years of age (p < 0.001)], an age–related analysis was performed. No significant difference in any HBV marker was found between rural and urban patients. The association between active HBV infection and HCC was similar in young patients, both rural and urban, and the prevalence of HBs antigenemia decreased in both groups with increasing age. We conclude that the differences in incidence and age of onset of HCC in rural and urban southern African Blacks cannot be attributable to differences in HBV status.
Arteriohepatic Dysplasia. Ii. Hepatobiliary Morphology
Authors: Kahn Ellen I. , Daum Fredric , Markowitz James , Aiges Harvey W. , Schneider Keith M. , So Henry B. , Altman Peter , Chandra Roma S. , Silverberg Mervin
Published: July 2010

Five children were noted to have arteriohepatic dysplasia (Alagille's syndrome) between 3 and 7 months of age. Prior to diagnosis, four underwent Kasai procedures after intraoperative cholangio–grams failed to demonstrate patency of the extrahepatic bile ducts. In three patients, a focal proximal hypoplasia of the common hepatic duct was demonstrated with fibrosis and increased vascularity. Hypoplasia of the gallbladder occurred in two patients.

Changes were observed in the porta hepatis. Eighty to 208 /tm bile ducts were associated with peripherally located gland–like structures. These changes are indistinguishable from those in fibrous remnants of extrahepatic biliary atresia.

Hepatic features of sequential liver biopsies obtained in the five patients were divided into early and late changes. From birth to 3 months of age, the pathology consisted of cholestasis and bile duct destruction. After 3 months of age, there was persistent cholestasis, paucity of interlobular bile ducts, and portal fibrosis. Ductular proliferation was not an intrinsic change. When present, it was related to a recent episode of cholangitis.
Serodiagnosis of Recent Hepatitis B Infection by Igm Class Anti–Hbc
Authors: Chau Kurt H. , Hargie Martha P. , Decker Richard H. , Mushahwarand Isa K. , Overby Lacy R.
Published: July 2010

time sequence, relative reactivity, and persistence of anti–HBc IgM were assessed in patients with HBsAg–positive viral hepatitis. A solid–phase immunoassay was developed using the IgM capture procedure with anti–m¨ated polystyrene beads. HBcAg was purified from serum Dane particles and used as a probe with 125I–labeled anti–HBc IgG. This immunoassay exhibited a pronounced prozoning phenomenon, and relative titers of sera differed widely depending upon the dilution of serum tested. When all sera were tested at 1:5,000 dilution, results were comparable in different patient groups.

HBc IgM persisted at detectable levels for up to 2 years, and it was necessary to establish relative titers to discriminate current from remote infections. A cut–off assay value was established, and in 12 cases of acute hepatitis B virus (HBV) infection, antibody exceeded this value for about 6 months after onset of HBs antigenemia. A similar profile of anti–HBc IgM persistence was observed in seven patients who developed an HBsAg chronic carrier state. Long–term viral replication did not sustain elevated IgM class–specific antibody levels.

studies suggest that anti–HBc IgM analyses may be useful for differentiating recent and current HBV infections from remote infections, eliminating HBV as the agent for non–A, non–B hepatitis in asymptomatic HBsAg carriers, and detecting HBV as the etiologic agent during silent (HBsAg negative) infections.
Hepatocyte Membrane–Bound Igg and Circulating Liver–Specific Autoantibodies in Chronic Liver Disease: Relation to Hepatitis B Virus Serum Markers and Liver Histology
Authors: Meliconi Riccardo , Miglio Federico , Stancari Valeria M. , Baraldini Mario , Stefanini Francesco G. , Gasbarrini Giovanni
Published: July 2010

Hepatocytes isolated from 101 biopsies were examined for membrane–bound IgG. The sera of the patients were tested for anti–liver–specific lipoprotein by radioimmunoassay and for liver membrane autoantibody (by indirect immunofluorescence on isolated rabbit hepatocytes. The seven patients with normal liver or minor nonspecific alterations were negative for membrane IgG and serum antibodies. Membrane IgG with granular distribution was found in 41 patients [21 hepatitis B virus–related chronic active hepatitis (CAH), 3 cryptogenic CAH, 3 chronic persistent hepatitis, 6 prolonged viral hepatitis, 1 alcoholic cirrhosis, and 6 primary biliary cirrhosis]. Membrane IgG with linear fluorescence pattern was detected in 12 cases (4 autoimmune CAH, 3 HBsAg–positive CAH, 2 alcoholic cirrhosis, 1 anti–HBc positive CAH, 1 cryptogenic CAH, and 1 prolonged viral hepatitis). A strong association between granular IgG and serum HBsAg was found. Nuclear localization of IgG was found in 34 patients and correlated with the positivity of granular membrane IgG.

The highest prevalence of anti–liver–specific lipoprotein was found in primary biliary cirrhosis and autoimmune CAH cases which were also positive for liver membrane autoantibody. No relationship was found between the presence of membrane IgG and circulating liver–specific autoantibodies.

Membrane IgG and anti–liver–specific lipoprotein correlated with the presence of moderate and severe portal inflammatory infiltration but not with piecemeal necrosis or transaminase levels. Eleven of the twelve patients with linear membrane IgG presented chronic active liver disease with moderate to severe signs of liver damage.

Therefore, it is suggested that, while granular membrane IgGs are related to hepatitis B virus, antigenic expression on the hepatocyte surface and/or the presence of immune complexes, linear membrane IgG could play a role in the immunopathogenesis of liver cell damage particularly in “autoimmune” cases which present high percentages of positive cells liver–specific autoantibodies.
Glutathione S–Transferase in Human Hepatocellular Carcinoma
Authors: Sherman Morris , Campbell John A.H. , Titmuss Sally A. , Kew Michael C. , Kirsch Ralph E.
Published: July 2010

Qualitative and quantitative changes in glutathione S–transferase (GSH–T) were studied in human hepatocellular carcinoma. GSH–T specific activity (/imoles per min per mg protein) was variably reduced in hepatocellular carcinoma. Similar changes were seen in “cationic” GSH–T (ligandin) concentration determined by radioimmunoassay. Immunohistochemical studies with antihuman liver ligandin suggest that positive staining was more frequently found in well–differentiated tumors.

The relative activities of “cationic,” “neutral,” and “anionic” transferases were estimated after separation by isoelectric focusing. Tumor “cationic” transferase (pI ± 7.5) activity ranged from virtually absent to near normal values. “Neutral” (pI 6 to 6.5) and “anionic” (pI < 5.4) species were present more often in tumors than in normal liver. In two cases, normal liver tissue and tumor were obtained from the same patient. In one, only quantitative differences were present, while in the other “cationic” and “neutral” GSH–Ts were present in the normal liver tissue while both “cationic” and “anionic” species were found in the tumor. Our studies indicate that qualitative as well as quantitative changes of GSH–T occur in human hepatocellular carcinoma.
Lipolysosomes in Human Hepatocytes: Their Increase in Number Associated With Serum Level of Cholesterol in Chronic Liver Diseases
Authors: Hayashi Hisao , Sameshima Yoichi , Lee Michio , Hotta Yasuhiro , Kosaka Toshihiko
Published: July 2010

The clinical significance of hepatocellular lipolysosomes in patients with various liver diseases was investigated. Of the 102 cases studied, lipolysosomes were found in 78 cases or 76%. In patients with fatty change of the liver, hepatocellular lipolysosomes were found in 62 of 68 or 91%. In patients without fatty change, lipolysosomes were found in 16 of 34 or 47%. The lipolysosome:.lipido ratio in the hepatocytes ranged from 0 to 10%. No differences were found in the lipolysosome:lipid ratios of patients with acute hepatitis, cholestasis, fatty liver, chronic hepatitis, or cirrhosis. In chronic hepatitis and cirrhosis with associated fatty change, the ratio was correlated with the serum level of cholesterol, whereas in fatty liver the ratio was not correlated with any parameters of patient's age, etiologic factors, or serum level of cholesterol. The findings suggest that lysosomal function is less significant as a pathogenesis of fat infiltration but lipolysosomes increase in number as a sequence of cholesterol overload to the liver.
The Amount of Ferritin and Hemosiderin in the Livers of Patients With Iron–Loading Diseases
Authors: Zuyderhoudt Floris M.J. , Sindram Jan W. , Marx Joannes J.M. , Jorning George G.A. , Van Gool Jacobus
Published: July 2010

Depot iron, ferritin iron, and ferritin protein were measured in 34 liver needle biopsy specimens obtained from patients with primary and secondary iron–loading diseases.

The patients were classified as idiopathic hemochromatosis (14), porphyria cutanea tarda (4), and iron–loading anemias (16). With accumulation of depot iron, the amount of liver ferritin protein increased, however, the ratio of ferritin protein to depot iron fell at concentrations of depot iron in excess of 1,000 m¨er gm of liver. The liver ferritin protein concentration was not influenced by the specific kind of the iron storage disorder. The mean iron content of ferritin molecules increased about 50% in profound iron overload.

In low grade iron overload, the bulk of depot iron was present as ferritin; however, in subjects with heavy iron overload, depot iron consisted of approximately equal amounts of hemosiderin (nonferritin iron) and ferritin iron.
Changes in Iga Following Varying Degrees of Biliary Obstruction in the Rat
Authors: Rank Jeffrey , Wilson Dodd I.
Published: July 2010

Polymeric IgA is rapidly transported from blood to bile by the rat liver. The effect of varying degrees of biliary obstruction on this transport process was studied. IgA concentrations were measured by radioimmunoassay. Serum IgA concentrations increased progressively, and IgA output in bile declined with increasing bile duct obstruction. The decline in bile IgA output was explained by both diminished bile flow and decreased concentrations of IgA in bile. Very little polymeric IgA was present in normal rat serum. In contrast, using column chromatography on Ultrogel AcA 22, increases in serum IgA associated with cholestasis were shown to be due to increments in polymeric IgA. Serum IgA was a more sensitive indicator of cholestasis than was serum alkaline phosphatase. IgA and secretory component were found, using indirect immunofluorescence, surrounding bile canaliculi and on or adjacent to the hepatocyte plasma membrane lining the sinusoids. With biliary obstruction, staining for IgA and secretory component intensified markedly near the bile canaliculi.

We conclude that: (a) polymeric IgA must be efficiently removed from serum by the normal rat liver; (b) even minimal cholestasis impairs IgA output into bile, and (c) impairment of IgA transport during cholestasis appears to occur at or near the canalicular membrane.
Hepatic and Ductus Venosus Blood Flows During Fetal Life
Authors: Rudolph Abraham M.
Published: July 2010

The course of the venous circulation in the fetal liver has been studied in fetal lambs by means of the radionuclide–labeled microsphere technique. About 50% of umbilical venous blood passes through the ductus venosus, while the remainder is distributed to both lobes of the liver. Portal venous blood is largely distributed to the right lobe of the liver, with a small proportion passing through the ductus venosus and none to the left lobe. Because of these flow patterns, oxygen saturation is lower in the right than in the left hepatic vein. Left hepatic venous blood joins the ductus venosus stream and these preferentially pass through the foramen ovale, whereas right hepatic venous blood joins the distal inferior vena caval stream and preferentially passes through the tricuspid valve. These patterns favor distribution of well–oxygenated blood to the fetal heart and brain. Hypoxia and reduced umbilical venous return are associated with reduced flow through the hepatic microcirculation with proportionately greater ductus venosus flow. In the fetus, the liver has a major role in influencing venous return to the heart and in regulating distribution of oxygen and energy substrate supply to different fetal organs.
Detection of Hepatitis B Virus DNA Directly in Human Serum by a Simplified Molecular Hybridization Test: Comparison to HBeAg/ Anti-HBe Status in HBsAg Carriers†
Authors: Lieberman Harvey M. , Labrecque Douglas R. , Kew Michael C. , Hadziyannis Stefanos J. , Shafritz David A.
Published: July 2010

A simple, direct molecular hybridization test was employed to detect hepatitis B virus (HBV) DNA sequences in human serum. In 61 HBsAg carriers, many with HBV-related diseases (chronic persistent hepatitis, chronic active hepatitis, or posthepatitic cirrhosis), 28/28 (100%) who were HBeAg* and 16/32 (50%) who were anti-HBe+ had HBV DNA sequences in their serum. Among 22 South African black patients with hepatocellular carcinoma, 7 (32%) had detectable HBV DNA in their serum but at reduced levels when compared to HBsAg carriers without hepatocellular carcinoma, suggesting that viral replication is suppressed or inactive in many hepatocellular carcinoma patients. Hybridization analysis also distinguished carriers with high, moderate, or low amounts of HBV DNA in serum. Ten to 20% of HBsAg+/HBeAg+ carriers showed high serum levels of HBV DNA but, surprisingly, a similar percentage of HBsAg+/anti-HBe+ carriers also showed relatively high serum levels of HBV DNA. Five patients who had undergone immunosuppression therapy and most of whom were on chronic hemodialysis had very high serum levels of HBV DNA, in the range observed during acute HBV infection. By epidemiologic analysis, two of these individuals were implicated in transmission of hepatitis to other hemodialysis patients, paramedical personnel, or intimate family contacts. Serum HBV DNA hybridization analysis identifies carriers with high serum levels of HBV irrespective of HBeAg/anti-HBe status and may define individuals with potentially high risk of transmitting infection to their immediate contacts.
Prevalence and Significance of Anti-HBc IgM (Radioimmunoassay) in Acute and Chronic Hepatitis B and in Blood Donors†
Authors: Banninger Peter , Altorfer Josef , Frösner Gert G. , Pirovino Mauro , Gudat Fred , Bianchi Leonardo , Grob Peter J. , Schmid Martin
Published: July 2010

Anti-HBc IgM was determined by a modified radioimmunoassay (RIA) in 35 patients with acute hepatitis B, 35 patients with chronic hepatitis B (7 with chronic persistent, and 28 with chronic active hepatitis), 157 HBsAg positive blood donors, and in 143 HBsAg negative but anti-HBc positive donors. The results of the RIA test were compared with those obtained by an ELISA technique. In chronic hepatitis, anti-HBc IgM was correlated with the occurrence of HBeAg, anti-HBe, Dane particles in the serum, HBsAg, and HBcAg in liver tissue and with biochemical and histological degrees of hepatic inflammatory activity.

In acute self-limited hepatitis B, anti-HBc IgM (RIA and ELISA) was initially positive in all 35 patients. Twelve months after the acute illness, 94% of the patients were negative for anti-HBc IgM in the RIA test with only one patient showing a persistence of up to 18 months, whereas in the ELISA test anti-HBc IgM persisted in 17% of the patients over 2 years. In chronic hepatitis, the occurrence of anti-HBc IgM (RIA) showed a strong relation with the inflammatory activity, the anti-HBc IgM positive patients revealing a significantly more severe liver disease than did anti-HBc IgM negative patients. Anti-HBc IgM (RIA), however, did not correlate with the occurrence of HBeAg and Dane particles in the serum and HBcAg in liver tissue of patients with chronic hepatitis. Of the 157 HBsAg positive blood donors, anti-HBc IgM (RIA) could be demonstrated in 10 (6%), but in none of the 143 HBsAg negative, but anti-HBc positive donors, as compared to 43 (27%) and 9 (6%), respectively, in the ELISA test.

Comparing the two test methods, the RIA exhibits higher specificity than did the ELISA due to a better blocking of nonspecific reactions, but possibly somewhat lower sensitivity. In this form, however, the RIA test is a more useful tool in the diagnosis of the different forms of hepatitis B virus infection and in determining the severity of chronic hepatitis B.
High-Density Lipoprotein Cholesterol and Liver Disease
Authors: Kanel Gary C. , Radvanand George , Peters Robert L.
Published: July 2010

To establish whether there is any significant relationship between high-density lipoprotein cholesterol (HDLC) concentrations and biopsy-documented liver disease, 169 patients had needle biopsies, serum cholesterol, and HDLC evaluated. Twenty-four patients had serial cholesterol, HDLC, prothrombin, and aminotransferase levels and activities examined. In both men and women, HDLC decreased strikingly and significantly in acute alcoholic hepatitis and in acute viral hepatitis, compared to controls (p < 0.001). Men and women with inactive alcoholic liver disease and chronic active hepatitis showed moderate decreases in HDLC (p < 0.001). Patients with primary and metastatic hepatic neoplasms also had strikingly decreased HDLC (p < 0.001). Serial testing showed an excellent direct correlation between HDLC and prothrombin activity, r values ranging from 0.71 to 0.98. Although alcohol intake is known to correlate positively with HDLC concentrations, our data shows that this association is not absolute, and in most cases is reversed once liver disease becomes apparent.
The Effect of Progesterone on the Regulatory Mechanisms of Biliary Cholesterol Secretion in the Rat† ‡
Authors: Nervi Flavio O. , Del Pozo Reginald , Covarrubias Carmen F. , Ronco Beatriz O.
Published: July 2010

We tested the hypothesis that progesterone, an inhibitor of cholesterol esterification in liver microsomes, increases biliary cholesterol output by increasing the availability of cholesterol. Initial bile samples of 20 min were obtained from acute bile fistula rats after seven daily doses of progesterone (5 to 55 mg per kg of body weight). Biliary cholesterol output correlated with the doses of progesterone, r = 0.64 (p < 0.005). A 100% increment in biliary cholesterol output was obtained with progesterone doses of 30 to 55 mg per kg of body weight. Under these conditions, biliary phospholipid output increased 50% (p < 0.02), but bile salt output remained normal. The relationship between biliary cholesterol and phospholipids as a function of bile salt output was studied after acute depletion of the bile salt pool. A rectangular hyperbola was the best curve fitting for the experimental data in control and progesterone-injected rats. In the physiological range of bile salt output, between 60 and 120 nmoles per gm per min, progesterone-injected rats secreted 100% more biliary cholesterol than did cntrols. The calculated theoretical maximal cholesterol and phospholipid outputs were significantly increased in progesterone-injected animals. Serum and hepatic cholesterol pool, free and ester fractions, remained normal. The acyl-CoA: cholesterol acyltransferase reaction was 30% inhibited in hepatic microsomes of progesterone-injected rats, (p < 0.05). The changes in biliary phospholipids and cholesterol output produced by progesterone were rapidly reversed by either 0.5% cholesterol feeding or 2 mg per kg of body weight ethynyl estradiol injection. These manipulations simultaneously produced a 100% increment in the microsomal acyl-CoA: cholesterol acyltransferase activity (p < 0.005) and increased 4-fold the concentration of hepatic cholesterol esters. This experimental model suggests a functional interrelationship between biliary cholesterol output and the rate at which the liver esterifies cholesterol.
Familial Benign Chronic Intrahepatic Cholestasis
Authors: Eriksson Sten , Larsson Christer
Published: July 2010

Three of four adult siblings in a family which was studied for three generations had clinical and/ or laboratory signs of slowly progressive intrahepatic cholestasis. Slight hyper pigmentation, facial hypertrichosis, and hypothyroidism were seen in affected individuals who also had prolonged increase in serum transaminase, γ-glutamyltranspeptidase, and alkaline phosphatase activities. Asymptomatic intervals were characterized by abnormal bromosulfophthalein retention, reduced N-demethylation capacity, elevated fasting total serum bile acid levels, and normal light microscopic findings. A high serum α-lipoprotein level was found in individuals affected with this hitherto unknown entity which appears to have an autosomal recessive mode of inheritance.
Cholic Acid Amelioration of Light and Electron Microscopic Hepatic Lesions in Experimental Protoporphyria†
Authors: Lefkowitch Jay H. , Feng-Chen Kuo-Ching , Sklar Jeffrey A. , Poh-Fitzpatrick Maureen B.
Published: July 2010

We studied the effects of cholic acid treatment on hepatic histology and ultrastructure in mice with griseofulvin-induced protoporphyria. After 5 weeks of feeding griseofulvin alone, control mice developed darkly pigmented livers which by light microscopy showed birefringent, brown pigment deposits in bile ducts and ductules, sinusoidal Kupffer cell aggregates, and occasionally in hepatocytes and bile canaliculi. Electron microscopy demonstrated aggregated protoporphyrin crystals at these sites as well as membrane blebs and reduction of microvilli in bile canaliculi. In contrast, experimental mice that were concomitantly fed cholic acid and griseofulvin developed no detectable pigment on light microscopy, only rare protoporphyrin crystals on electron microscopy and minimal bile canalicular abnormalities. This study suggests that protoporphyrin transport into bile is enhanced by cholic acid treatment and results in a significant reduction in hepatic protoporphyrin deposition and associated abnormalities of liver morphology.
Seroimmunologic Classification of Chronic Hepatitis in 57 Children
Authors: Odièvre Michel , Maggiore Giuseppe , Homberg Jean-Claude , Saadoun Fabrice , Courouce Anne-Marié , Yvart Jeannine , Hadchouel Michelle , Alagille Daniel
Published: July 2010

A seroimmunologic evaluation of 57 children with chronic hepatitis is presented. Twenty-one patients had chronic persistent hepatitis and 36 had chronic active hepatitis. Serum samples obtained before treatment were tested for HBsAg, anti-HBs, anti-HBc, smooth muscle antibody, and antibody to endoplasmic reticulum. A persistently positive HBsAg was observed in the serum of 18 of the 21 patients with chronic persistent hepatitis. The chronic active hepatitis group was divided into three subgroups according to the presence of hepatitis B-virus markers (7 patients), smooth muscle antibody (10 patients), and endoplasmic reticulum antibody (9 patients). Determination of these markers could be useful for classifying children with chronic hepatitis.
Spironolactone- and Canrenone-Induced Changes in Hepatic (Na+, K+)ATPase Activity, Surface Membrane Cholesterol and Phospholipid, and Fluorescence Polarization in the Rat†
Authors: Miner Philip B. , Sneller Michael , Crawford Synda S.
Published: July 2010

We studied changes in hepatic membrane (Na+,K+)ATPase activity and membrane lipids induced by canrenoate, the water-soluble congener of canrenone, the active metabolite of spironolactone. (Na+,K+)ATPase activity was decreased after canrenoate in a dose- and time-dependent manner. Decreased activity was demonstrated at the lowest dose (91% of control after 5 μmoles per 100 gm body weight per day × 3 days); the maximum dose (30 μmoles per 100 gm body weight per day × 3 days) resulted in activity 38% of untreated control values. A 20 μmoles per 100 gm body weight per day dose decreased enzyme activity to 89 and 55% of control after 24 and 72 hr, respectively. The nonionic detergent Triton WR- 1339 partially reversed drug-induced inhibition, suggesting that the enzyme changes may be related to altered membrane lipids.

Membrane cholesterol increased 17% after 3 days of 30 μmoles canrenoate per 100 gm body weight per day; phospholipids decreased by 12%. The cholesterol to phospholipid molar ratio increased from 0.419 to 0.555. Membrane fluidity, as measured by the fluorescent probe 1,6- diphenyl- 1,3,5-hexatriene decreased after treatment with 20 μmoles canrenoate per 100 gm body weight per day for 3 days.

These results describe in vivo and in vitro inhibition of hepatic (Na+,K+)ATPase activity. Increased membrane cholesterol with decreased phospholipid alters membrane fluidity and may be partially responsible for the change in (Na+,K+)ATPase activity.
Hemodynamic Changes in Patients with Portal Venous Obstruction
Authors: Lebrec Didier , Bataille Christian , Bercoff Eric , Valla Dominique
Published: July 2010

Splanchnic and systemic hemodynamics were evaluated in five adult patients with portal hypertension due to portal venous obstruction and were compared with those of patients with cirrhosis and those of a control group. In patients with portal venous obstruction, the gradient between wedged and free hepatic venous pressures ranged from 2 to 3 mm Hg, as in the control group, and was significantly lower than in patients with cirrhosis. Hepatic blood flow averaged 0.521 ± 0.127 liter per min per m2 (mean ± S.D.) and was significantly lower than that measured in cirrhotic and normal patients. Cardiac index averaged 3.788 ± 0.629 liters per min per m2; this high value for cardiac index was not significantly different from that measured in cirrhotic patients, but was significantly higher than in patients of the control group.

It is suggested that a hyperkinetic circulatory state may result from the development of portal-systemic venous collateral circulation in patients with portal venous obstruction having normal liver and hepatic venous pressures
Elevated Plasma Carnitine in Hepatic Cirrhosis
Authors: Fuller Richard K. , Hoppel Charles L.
Published: July 2010

Carnitine is essential for the oxidation of fatty acids. The liver is a major site of fatty oxidation. To determine if there are alterations in plasma carnitine in patients with alcoholic cirrhosis, we measured plasma carnitine and its metabolites by a specific radioenzymatic method in 20 men with hepatic cirrhosis and 30 healthy volunteers. We found total carnitine, free carnitine, short-chain acylcarnitines, and long-chain acylcarnitines to be significantly elevated in the cirrhotic subjects. The mean values for total carnitine, free carnitine, short-chain acylcarnitines, and long-chain acylcarnitines for the cirrhotic patients and the control subjects were 73.1 vs. 46.1, 47.0 vs. 36.7, 17.9 vs. 5.7 and 8.2 vs. 3.7 μM, respectively. The greatest increases were noted in the acylcarnitines; 3-fold for short-chain acylcarnitines and over 2-fold for long-chain acylcarnitines. We conclude that alcoholic cirrhosis is a hypercarnitinemic condition.
Extrahepatic Biliary Atresia in a Rhesus Monkey (Macaca mulatto)
Authors: Rosenberg Daniel P. , Morecki Rachel , Lollini Lance O. , Glaser Joy , Cornelius Charles E.
Published: July 2010

Extrahepatic biliary atresia was observed in a 6-week-old female rhesus monkey. Jaundice and conjugated hyperbilirubinemia were detected at the age of 6 days and persisted throughout life. At 6 weeks of age, the diagnosis of extrahepatic biliary atresia was established at exploratory laparotomy, and bile duct remnants were biopsied. Histological examination of these specimens showed inflammatory and fibrosing lesions similar to those observed in humans with extrahepatic biliary atresia.

Because of serologic evidence of Reovirus 3 infection in human patients with extrahepatic biliary atresia, serum of the affected monkey was tested for antibodies to this virus. Three sequential serum samples obtained during the course of illness showed persistently high Reovirus 3 titers which are consistent with but do not prove concurrent Reovirus 3 infection.

This report represents the first documented case of spontaneous extrahepatic biliary atresia in a nonhuman primate and suggests that this species may be suitable for further investigation of the pathogenesis of this disease.
Primary Pulmonary Hypertension: An Unusual Case Associated with Extrahepatic Portal Hypertension
Authors: Cohen Mark D. , Rubin Lewis J. , Taylor Wayne E. , Cuthbert Jennifer A.
Published: July 2010

A patient with both extrahepatic portal hypertension and primary pulmonary hypertension is reported. The pulmonary hypertension developed without a surgical portal-systemic shunt, and at autopsy there was no evidence of a large spontaneous shunt. This association of pulmonary arterial hypertension and portal venous hypertension without either intrinsic liver disease or a large portal-systemic anastomosis has not been reported previously. Our case supports the concept that portal hypertension with its attendant portal-systemic collateral circulation may be the major predisposing cause of pulmonary hypertension both in intrinsic liver disease and extrahepatic portal vein obstruction.