bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression Of β 2-Microglobulin on Hepatocytes in Acute and Chronic Type B Hepatitis
Authors: Nagafuchi Yukihisa , Scheuer Peter J. 
Published: March 2007

β2-Microglobulin display was examined in 131 liver biopsies from patients with acute and chronic type B hepatitis, using an indirect immunoperoxidase method. Enhanced expression of β2-microglobulin on hepatocyte membranes was observed in patients with acute hepatitis, chronic active hepatitis with moderate to severe activity and cirrhosis, when compared with normal liver. In acute hepatitis, β2-microglobulin–positive hepatocytes were mainly observed in perivenular areas in association with bridging necrosis. In chronic hepatitis, β2-microglobulin–positive hepatocytes were observed mainly in periportal zones and in some areas of lobular activty.
Diffuse–enhanced display of β2-microglobulin on hepatocytes was observed in 5 of 6 patients treated with lymphoblastoid interferon as part of a trial of antiviral therapy. The mechanism by which β2-microglobulin display is enhanced on hepatocytes in patients not treated with interferon is uncertain. However, display of β2-microglobulin on hepatocytes probably reflects display of HLA–A, B and C antigens and may influence the course of hepatitis B virus infection by increasing susceptibility of the affectedcells to T cell–mediated immune attack.
Ultrastructural Evidence for the Presence of Ferritin–Iron in the Biliary System of Patients With Iron Overload
Authors: Cleton Maud I. , Sindram Jan W. , Rademakers Louk H.P.M. , Zuyderhoudt Floris M.J. , De Bruijn Willem C. , Marx Joannes J.M. 
Published: March 2007

Ferritin–like particles were observed in bile canaliculi of patients with iron overload. These particles have been further investigated by: (1) a staining method enhancing the size and contrast of ferritin protein, and (2) electronprobe microanalysis detecting the presence of the elements iron and phosphorus.
Morphological observation of coated vesicles in the cytoplasm adjacent to the bile canaliculi and coated pits in the canalicular membrane suggests a transport mechanism via membrane–bound organelles.
Support is given to the theory that part of the iron, stored in the liver, leaves the hepatocyte by excretion of ferritininto the bile.
Hemostasis and Fibrinolysis in Severe Liver Failure and Their Relation to Hemorrhage
Authors: Boks Anton L. , Brommer Emile J.P. , Schalm Solko W. , Van Vliet Huub H.D.M. 
Published: March 2007

In a study of severe, decompensated liver failure, we tried to find a correlation between hemorrhage and parameters ofhemostasis and fibrinolysis. Three groups of patients were studied: alcoholic cirrhosis; nonalcoholic cirrhosis, and acute liver failure without known prior liver disease. The two cirrhotic groups did not differ significantly from each other in coagulation or in fibrinolytic parameters, although liver function was more impaired in nonalcoholic cirrhosis. The levels of clotting factors, antithrombin III, prekallikrein, plasminogen and α2-antiplasmin were significantly lower in the third group. Mean values of fibrinolytic activity (fibrin plate method) were slightly reduced as compared to normal in all three groups. Tissue plasminogen activator–related antigen tended to be elevated especially in alcoholic cirrhosis. The free fast–acting plasminogen activator inhibitor showed extremely high and extremely low levels in some patients among all three groups.
Nonvariceal, capillary–type bleeding, including mucosal bleeding, hematomas and bleeding from puncture sites correlated with low thrombotest and normotest levels (p < 0.01), low fibrinogen concentration (p < 0.05) and with a high quotient of fibrinolytic activity (square root of lysis area) and normotest (p < 0.001). The ratio between fibrinformation and dissolution appears to be an important parameter of hemorrhagic tendency in liver disease. Variceal bleeding appeared not to be related to impairment of hemostasis or fibrinolysis.
Portal Venous–Esophageal Luminal Pressure Gradient in Cirrhosis
Authors: Reding Pierre , Urbain Daniel , Grivegnee André , Frere Daniel 
Published: March 2007

The portal venous–esophageal luminal pressure gradient may be more important than the absolute portal venous pressure in explaining hemorrhages caused by esophageal varices. A continuous recording of portal venous pressure and the esophageal luminal pressure enabled the authors to study the gradient between these pressures in 12 cirrhotic patients with varices of different size and under different circumstances, in particular inspiration, expiration, coughing and a Valsalva maneuver.
A significant increase of portal venous pressure occurred during inspiration (+15%), coughing (+77%) and Valsalva maneuver (+157%). The value of portal venous–esophageal luminal pressure gradient increased during inspiration (+38%), coughing (+90%) and Valsalva maneuver (+69%) while it decreased during expiration (-14%).
Studies of Gene Transcription and Translation in Regenerating Rat Liver
Authors: Huber Brian E. , Heilman Carole A. , Wirth Peter J. , Miller Mark J. , Thorgeirsson Snorri S. 
Published: March 2007

Specific transcriptional and translational products associated with regenerating liver were analyzed by differential hybridization to a cDNA library and by two–dimensional electrophoresis of hepatic proteins, respectively. Comparisons of approximately 800 soluble and 800 particulate liver proteins from normal and 70% partially hepatectomized Fischer rats resulted in the identification of only three apparently unique polypeptides in 70% partially hepatectomized livers, although many quantitative changes were observed. A subset of these quantitative changes were also observed after sham operation. A cDNA library was generated from polyadenylated RNA isolated 18 hr post–70% partial hepatectomy. Comparative analysis of 6,000 transformantswith single–stranded cDNA probes prepared from 18 hr post–70% partial hepatectomy and sham–operated animals identified three clones whose sequences were preferentially expressed 4– to 6–fold 18 hr post–70%partial hepatectomy. Southern blot analysis of one clone, REG–A, showed no homology to albumin, α–fetoprotein, three different forms of cytochrome P–450, ornithine decarboxylase, globin, or to a putative tumor promotion associated gene called PRO–2. A single, REG–A specific 2.5 kb band was identified by Northern blot analysis of liver samples. REG–A expression was increased 2–fold 18 hr postsham operation; 4–fold 18 hr post–70% partialhepatectomy and following chronic 2,3,7,8–tetrachlorodibenzo–p–dioxin or phenobarbital treatment. REG–A expression returned to control levels 1 week after 70% partial hepatectomy. Furthermore, expression of REG–Awas reduced in chemically induced preneoplastic nodules and in primary and transplantable hepatomas. Hybrid selection studies indicated that the REG–A sequence selected a mRNA(s) species, that in an in vitro translation assay, produced two major polypeptides of 21,000 and 25,000 molecular weight with a pI of 6.9.
Thus, these data support the hypothesis that liver regeneration is characterized byquantitative changes in genes normally expressed at low levels in the Go hepatocyte andis not the result of major qualitative changes in gene expression.
Cell Types Involved in Collagen and Fibronectin Production in Normal and Fibrotic Human Liver
Authors: Clement Bruno , Grimaud Jean-Alexis , Campion Jean-Pierre , Deugnier Yves , Guillouzo Andre 
Published: March 2007

Three collagen types (I, III and IV) and fibronectin were localized in normal and alcoholic human liver by light and electron microscopy using the indirect immunoperoxidase technique. In normal liver, most of the bundles of collagen fibers stained for type pro–III collagen while only a few reacted for type I. Basement membranes stainedfor type IV collagen which formed discontinuous discrete deposits in sinusoids. Only fibronectin appeared as an almost continuous layer in the space of Disse. At the intracellular level, hepatocytes were found to contain little type I collagen and large amountsof fibronectin. Fat–storing cells strongly stained for type IV collagen and expressed low amounts of types I and III collagen and fibronectin. Endothelial cells contained low amounts of all the components.
Alcoholic livers were studied at three stages: steatosis, fibrosis and cirrhosis. Qualitative and quantitative differences were observed in extracellular and intracellulardistributions of matrix proteins. Increased amounts of all components were usually found in fibrotic and cirrhotic livers compared to normal liver. In two fibrotic livers which contained numerous bundles of collagen in the sinusoids, fat–storing cells stained more intensely for type III collagen. In a cryptogenic fibrotic liver, abundant type IV collagen was observed in hepatocytes.
These results suggest that hepatocytes, fat–storing cells and endothelial cells are engaged in production of extracellular matrix components in normal human liver. In fibrosis, hepatocytes which normally did not synthesize types III and IV collagen mayproduce these collagens.
Abnormalities of Neutrophil Phagocytosis, Intracellular Killing and Metabolic Activity in Alcoholic Cirrhosis and Hepatitis
Authors: Rajkovic I. A. , Williams Roger 
Published: March 2007

Neutrophil functions of phagocytosis and intracellular killing of bacteria were examined in 40 patients with alcoholic cirrhosis of whom 18 had a superimposed acute alcoholic hepatitis. In 65% of these, defective neutrophil phagocytosis was demonstrable, and in 62.5% there was a defect of intracellular killing of either Staphylococcus aureus or Escherichia coli. Studies of the patients' serum failed to reveal inhibitors of neutrophil function. Additional assays of superoxide (O2
-) and hydrogen peroxide production, hexose monophosphate shunt activity, degranulation and cellular levels of granule enzymes and glutathione revealed that these neutrophil defects are caused by both reduced production of superoxide and defects of degranulation. The hydrogen peroxide/superoxide molar ratio was raised in patients' neutrophils, and the strong inverse correlation found between the value of this ratio and intracellular levels of reduced glutathione would be consistent with thehypothesis that the neutrophils from patients with cirrhosis are unable to detoxify hydrogen peroxide effectively and that this is a result of reduced levels of glutathione in the cells. The consequent increase in oxidant stress, both intra–and extracellularly, may be the cause of phagocytic and degranulation defects. The reduced responsesof patients' neutrophils may be caused by previous exposure of the cells to activating stimuli in circulation, as evidenced by depleted intracellular levels of granule enzymes and glutathione.
Neutrophils from the patients with a superimposed acute alcoholic hepatitis had depressed phagocytosis in the early stages of incubation but, on the whole, neutrophils from these patients had a greater capacity for ingestion and killing of bacteria than neutrophils from patients with cirrhosis alone. Other neutrophil functions and metabolic activities were also significantly better than in patients with cirrhosis alone, and the reason for this may lie in the greater proportion of young neutrophils in the circulation of patients with superimposed acute alcoholic hepatitis.
The exhaustion of the neutrophils' bactericidal capacity in severe alcoholic liver disease, most marked in patients with cirrhosis alone, could be a significant factor in the well–described increased susceptibility of these patients to bacterial infection.
HLA class I antigens on the hepatocyte membrane during recovery from acute hepatitis B virus infection and during interferon therapy in chronic hepatitis B virus infection†
Authors: Pignatelli Massimo , Waters Jenny , Brown Dave , Lever Andrew , Iwarson Sten , Schaff Zsuzsa , Gerety Robert , Thomas Howard C. 
Published: March 2007

In a chimpanzee model of acute type B hepatitis, at the time of onset of hepatitis B virus replication and before the development of immunity to hepatitis B virus, interferon is present in the plasma. This is followed by an increase in the display of HLA class I, but not class II proteins, on the hepatocyte membrane.
In chronic hepatitis B virus infection, there is a low density of HLA class I protein display on the infected hepatocyte. Administration of α-interferon enhances HLA display and in many cases is followed by a transaminase elevation, seroconversion of HBe antigen to antibody and disappearance of hepatitis B virus DNA from serum, changes implying clearance of infected hepatocytes. Successful response to interferon therapy may be predicted by a rapidly rising serum β-microglobulin, a component of the HLA class I molecule, during the first 2 weeks of therapy, before the rise in transaminases.
Transgenic mouse models for the chronic hepatitis B surface antigen carrier state: Transfection a deux
Authors: Di Bisceglie Adrian M. , Hoofnagle Jay H. 
Published: March 2007

In an attempt to establish a model of the healthy carrier state in hepatitis B virus (HBV) infections, transgenic mice expressing HBV genes were produced. Fertilized one-cell eggs were microinjected with subgenomic fragments of HBV DNA containing the coding regions for the HBV surface antigen (HBsAg) and pre-S and×antigens. Either the normal (HBV) or metallothionein promoters were used to obtain expression of the HBV genes. There was no evidence of viral replication or tissue pathology. The integrated HBV DNA sequences were inherited in a normal Mendelian fashion. Three of 16 transgenic mice expressed HBV-encoded gene products to which they were immunologically tolerant. Expression was not tissue specific and may be influenced by the genomic integration site and cellular factors. Both HBsAg and pre-S antigen were detectable within the cytoplasm of hepatocytes and renal tubular epithelial cells. High serum concentrations of HBsAg were detectable and the secreted product appeared authentic as judged by mean density, morphology, mean particle diameter, polypeptide composition, and antigenicity. The absence of tissue pathology in these immunologically tolerant animals supports the hypothesis that cellular injury under these conditions is not a direct consequence of expression of the pre-S or HBs regions of the HBV genome.
Two transgenic mice were obtained that contain in their chromosomes the complete hepatitis B virus (HBV) genome except for the core gene. These mice secrete particles of HBV surface antigen (HBsAg) in the serum. In one mouse, HBV DNA sequences that had integrated at two different sites were shown to segregate independently in the first filial generation (F1) and only one of the sequences allowed expression of the surface antigen. Among these animals the males produced five to ten times more HBsAg than the females. A 2.1-kilobase messenger RNA species comigrating with the major surface gene messenger RNA is expressed specifically in the liver in the two original mice. The results suggest that the HBV sequences introduced into the mice are able to confer a tissue-specific expression to the S gene. In addition, the HBV transgenic mice represent a new model for the chronic carrier state of hepatitis B virus infection.
Characterization and clinical relevance of a new complement-fixing antibod-anti-m8-in patients with primary biliary cirrhosis
Authors: Weber Paul , Brenner Judith , Stechemesser Ernst , Klein Reinhild , Weckenmann Ulrike , Klöppel Günter , Kirchhof Manfred , Fintelmann Volker , Berg Peter A. 
Published: March 2007

A new complement-fixing antimitochondrial antibody-anti-M8-was detected in patients with primary biliary cirrhosis. Anti-M8 was only found in association with anti-M2, however, not all anti-M2 positive patients had anti-M8. Thus, among 66 anti-M2 positive patients, 29 were also positive for anti-M8, whereas sera from patients who had the complement-fixing anti-M2 and anti-M4 antibodies in parallel always strongly reacted with the M8 antigen. This group was previously described as mixed form. The M8 antigen was isolated either from human liver mitochondria or pig kidney microsomes and could be clearly distinguished from the M4 antigen. In contrast to M4, M8 was trypsin sensitive and banded at sucrose densities from 1.16 to 1.24, while M4 was found at densities from 1.08 to 1.14. Like M4, the M8 antigen also co-purified with outer mitochondrial membranes.
Fifty-three patients with primary biliary cirrhosis have been followed over a period of up to 16 years and were classified according to their complement-fixing antimitochondrial antibody profile. At the time of the first diagnosis, 95% of 31 patients being anti-M2 positive, but anti-M8 negative (antimitochondrial antibody Profile I) were in Stage I or II. In contrast, only 61% of 13 patients being anti-M2 and anti-M8 positive (antimitochondrial antibody Profile II) and 44% of 9 patients with anti-M2, anti-M8 and anti-M4 in parallel (antimitochondrial antibody Profile III) belonged to Stage I or II. At the end of the observation period, only 24% of patients with antimitochondrial antibody Profile I (anti-M8 negative) had reached Stage III or IV, while 75% of patients with antimitochondrial antibody Profile II or III (anti-M8 positive) had a progression to Stage III or IV.
It is concluded that the presence of complement-fixing anti-M8 antibody may herald a more progressive course of primary biliary cirrhosis.
Receptor-mediated uptake of asialoglycoprotein by the primate liver initiates both lysosomal and transcellular pathways
Authors: Schiff Michael J. , Huling Sandra L. , Jones Albert L. 
Published: March 2007

The degradation of asialoglycoproteins in hepatocytes has been well described in several animal models, but no direct evidence has yet been obtained for asialoglycoprotein processing in the primate liver. A double radiolabeling strategy was employed in the experiments described in this paper to evaluate the fate of asialoorosomucoid in the squirrel monkey. Intravenously injected asialoorosomucoid was taken up by the liver with a half-time of 1 min. Electron microscopic autoradiography showed progression of asialoorosomucoid from the hepatocyte plasma membrane through vesicles to multivesicular bodies and then to secondary lysosomes near the Golgi-rich area of the cell. Over 75% of the grains initially associated with clear endocytic compartments after injection had moved to these later organelles within 20 min. Following degradation of asialoorosomucoid labeled with the Bolton and Hunter reagent, radiocatabolites were secreted into bile, peaking ˜47 min after injection.
We also found that 7 to 8% of the injected protein entered an alternative pathway which led to resecretion of the ligand at the bile canaliculus. This was considerably more than in rats (1 to 3%), but roughly comparable to the amount in guinea pigs (10 to 17%). Intact asialoorosomucoid peaked in monkey bile˜27 min after injection and was 3 to 4 times more concentrated than the initial plasma concentration, indicating receptor-mediated transport. Gel filtration chromatography and polyacrylamide gel analysis of the secreted protein indicated that it had arrived in bile unaltered. Since <1% of the autoradiographic grains were localized to nonparenchymal cells, the hepatocyte was identified as the cell type simultaneously responsible for both pathways. We propose that missorting of some of the asialoglycoprotein to bile reflects diffusion within intracellular sorting compartments to areas primarily dedicated to the processing of unrelated ligands, such as those newly synthesized for biliary secretion.
Determination of iron to phosphorus ratios of iron storage compounds in patients with iron overload: A chemical and electron probe X-ray microanalysis
Authors: Cleton Maud I. , Frenkel Erik J. , de Bruijn Willem C. , Marx Joannes J. M. 
Published: March 2007

The amounts of phosphorus and iron in various isolated ferritin preparations were investigated by: (i) chemical analysis on ferritin samples and (ii) electron probe X-ray microanalysis on ferritin particles from the same preparations. A high correlation was found between iron to phosphorus ratios obtained by both methods.
Further investigation by electron probe X-ray microanalysis on lysosomes of hepatic cells of patients with idiopathic and secondary hemochromatosis revealed lysosomal iron to phosphorus ratios which were very similar in all parenchymal cells but different from ratios obtained in Kupffer cells. Lysosomal iron to phosphorus ratios in hepatocytes did not change after intensive phlebotomy treatment. It is postulated therefore that, during phlebotomy, iron and phosphorus are concomitantly lost from the hepatic lysosomes.
Morphological findings in the liver of children with cystic fibrosis: A light and electron microscopical study
Authors: Hultcrantz Rolf , Mengarelli Silwa , Strandvik Birgitta 
Published: March 2007

Liver tissue from five children with cystic fibrosis, obtained through percutaneous liver biopsies, have been investigated via light and electron microscopy. None of the patients had clinical evidence of liver disorder, and their blood chemistry was mainly normal.
Light microscopy showed slight fibrosis in three cases, more advanced fibrosis in one case and focal cirrhotic changes in one case. All patients had fatty infiltration in the hepatocytes and glycogen in the nuclei of these cells.
Electron microscopy showed an increase in the number of Ito cells around the portal tracts and also fibrosis in all patients. In the majority of hepatocytes, no evident necrosis was seen. Hypertrophy of the smooth endoplasmic reticulum and the Golgi apparatus were noted. Large lysosomes containing lipofuscin and lipids were also present. No direct evidence of cholestasis could be seen in the hepatocytes. The bile canaliculi were not dilated and did not contain bile plugs. No bile pigment was seen in the cells, and direct evidence of cholestasis was thus not found in the hepatocytes. Other organelles, such as the rough endoplasmic reticulum, peroxisomes and mitochondria, had a normal appearance. Bile ducts, even when seen in fibrotic portal tracts, were not dilated.
The ultrastructural findings cannot explain the basis for the liver cell damage. Cholestasis does not seem to be a presumable etiological factor as judged from the findings in the present study.