bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative risks of death due to liver disease among Japanese male adults having various statuses for hepatitis B s and e antigen/antibody in serum: A prospective study
Authors: Sakuma Koshi , Saitoh Nobuteru , Kasai Misako , Jitsukawa Hiroshi , Yoshino Izumi , Yamaguchi Momoko , Nobutomo Kouichi , Yamumi Makoto , Tsuda Fumio , Komazawa Tsutomu , Nakamura Tetsuo , Yoshida Yasuo , Okuda Kunio 
Published: March 2007

Taking advantage of the compulsory annual medical check-up at the Central Institute of Health, Japan National Railways, hepatitis B seromarkers were tested in male employees at work and their “dead and alive” status was followed for more than 6 years for their prognostic significance. Two prospective studies were carried out. In the first study, two groups (cohorts) of males age 40 to 55 years were tested in 1973 and 1978, respectively, for HBsAg and anti-HBs. The relative risk of dying from primary liver cancer in HBsAg-positive carriers (n = 126) as compared to the controls who were negative for both HBsAg and anti-HBs (n = 5,322) was 30.03 and significantly high, whereas those positive for anti-HBs (n = 1,470) had no increased risk of dying from primary liver cancer or from other liver diseases. The follow-up period ranged from 6.5 to 11.5 years, averaging 8.5 years.
In the second study, three male cohorts of the same ages were tested for HBsAg and HBeAg/anti-HBe (micro-Ouchterlony method) in 1977, 1978 and 1979, respectively. There were 513 HBsAg-positive carriers among 25,547 examinees, who were followed for an average of 7.3 (6 to 8) years. Among these HBsAg carriers, those who were positive for HBeAg on entry had the highest risk of dying from primary liver cancer (relative risk, 50.25) and from other liver diseases (78.06), followed by those negative for both (28.95 and 21.78, respectively) and those positive for anti-HBe (9.47 and 6.43) when compared with 25,034 noncarriers. There was no significant increase in the risk of dying from nonhepatic diseases among these three e-oriented carrier groups.
Alterations in the functional expression of receptors on cirrhotic rat hepatocytes
Authors: d’Arville Carolyn N. , Le Mysan , Kloppel Thomas M. , Simon Francis R. 
Published: March 2007

Reduced hepatic uptake and clearance of macromolecules in liver cirrhosis is due to two major factors: increased diffusional barriers, resulting primarily from the deposition of excessive connective tissue in the space of Disse, and hepatocellular dysfunction, manifested by receptor and/or postreceptor defects.
To probe the mechanisms underlying hepatocellular dysfunction in liver cirrhosis, we have investigated receptor-ligand interactions for asialoorosomucoid, insulin and epidermal growth factor in hepatocytes isolated from the livers of rats chronically exposed to phenobarbital and carbon tetrachloride for up to 12 weeks. Viable cells were allowed to attach at 37°C and the high-affinity cell surface binding sites for each ligand were assessed at 4°C in the presence of [125I]-ligand. In parallel incubations, digitonin (0.055%) was added to the binding medium to assess total cellular binding sites.
Results demonstrated that chronic treatment of rats with phenobarbital increased hepatocyte asialoorosomucoid surface receptor affinity (p < 0.05) but had no affect on the number of asialoglycoprotein binding sites. Treatment with CCl4 and phenobarbital significantly reduced the number of surface binding sites for asialoorosomucoid (p < 0.05) and epidermal growth factor (p < 0.02), although this treatment had no effect on either the binding affinity or the number of binding sites for insulin. The decrease in cell surface binding sites for asialoorosomucoid and epidermal growth factor was not due to a redistribution of the surface sites to intracellular locations, since the total number of cellular binding sites also was reduced. These results indicate that cirrhosis induced by phenobarbital and CCl4 results in a differential effect on one parameter of hepatocellular function: receptor-ligand interaction.
α-fetoprotein monitoring in chinese patients with chronic hepatitis B virus infection: Role in the early detection of hepatocellular carcinoma
Authors: Lok Anna S. F. , Lai Ching-Lung 
Published: March 2007

Two hundred ninety patients (203 men, 87 women), age 7 to 74 years (mean: 39.1 years), with chronic hepatitis B virus infection, were prospectively followed for a period of 1 to 4 years to determine the value of α-fetoprotein monitoring in the early detection of hepatocellular carcinoma. At presentation, 66% of the patients were asymptomatic, 19% had chronic hepatitis and 15% had established cirrhosis.
Forty-four (15%) patients had elevated α-fetoprotein levels on one or more occasions during the study period. Twenty patients with normal α-fetoprotein levels at presentation developed elevated α-fetoprotein levels during the course of follow-up, whereas 24 patients had elevated α-fetoprotein levels at presentation. Six (14%) of these 44 patients (five men and one woman), age 23 to 66 years, had persistent or progressive increase in α-fetoprotein levels and were confirmed to have hepatocellular carcinoma. In four patients, the α-fetoprotein levels were below 500 ng per ml at the time of tumor localization. Only three patients had resectable tumors. All six patients would have been missed if α-fetoprotein screening was restricted to men above the age of 40 with cirrhosis and anti-HBe. Of the remaining 38 patients, elevation in α-fetoprotein levels in 18 patients was associated with exacerbations of the underlying liver disease and/or significant changes in level of hepatitis B virus replication, but in 20 patients, no apparent cause could be identified. The elevation in AFP levels exceeded 200 ng per ml in 26% and persisted beyond 6 months in 15% of these patients.
We observed that elevation in α-fetoprotein levels occurred quite frequently in patients with chronic hepatitis B virus infection. The differentiation between benign and malignant causes of α-fetoprotein elevation was at times difficult. Thus, α-fetoprotein monitoring alone is not a satisfactory tool in the early diagnosis of hepatocellular carcinoma.
Studies of GB hepatitis agent in tamarins
Authors: Karayiannis Peter , Petrovic Lidija M. , Fry Mark , Moore Duncan , Enticott Mike , McGarvey Michael J. , Scheuer Peter J. , Thomas Howard C. 
Published: March 2007

Three tamarins (Saguinus labiatus), two of which had previously been infected with hepatitis A virus and parenteral non-A, non-B hepatitis, were inoculated intravenously with the agent of GB hepatitis. All three animals developed alanine aminotransferase abnormalities 2, weeks after inoculation. Peak alanine aminotransferase levels were recorded 4 weeks postinoculation. These declined thereafter but continued to fluctuate at abnormal levels for 32 weeks. Liver biopsies showed liver cell swelling and inflammation with focal necrosis. Portal tracts and areas around central veins were heavily infiltrated with mononuclear cells. A fourth animal (no previous exposure to hepatitis viruses) inoculated with GB was killed on Day 15 postinoculation. Serum and extracts of liver and feces from this day were used as inocula for three other animals. Only the serum and liver extract transmitted GB hepatitis. The fecal specimen did not transmit and a fecal extract taken at a later date from another animal was also noninfectious.
GB hepatitis virus is distinct from the viruses causing Type A and blood-borne non-A, non-B-hepatitis. Although the virus is present in serum and has previously been transmitted per os, it is not shed in feces.
The effect of age upon liver volume and apparent liver blood flow in healthy man
Authors: Wynne Hilary A. , Cope Lance H. , Mutch Elaine , Rawlins Michael D. , Woodhouse Kenneth W. , James Oliver F. W. 
Published: March 2007

The aim of this study was to determine the effect of aging upon liver volume and apparent liver blood flow in healthy man. Sixty-five subjects between 24 and 91 years of age were recruited. Liver volume was quantitated by a gray scale B ultrasound scan method. Apparent liver blood flow was determined from the plasma clearance of indocyanine green, based on an assumption of no change in hepatic extraction of the dye with age.
A significant negative correlation was observed between age and both liver volume and apparent liver blood flow (p <0.001), whether expressed in absolute terms or per unit body weight. Similarly, a significant negative correlation was observed between apparent liver blood flow per unit volume of liver (liver perfusion) and age (p<0.005).
The reduction in liver volume, apparent liver blood flow and perfusion may at least partly account for the decline in the clearance of many drugs undergoing liver metabolism which has been noted to occur with aging in man.
Localization of ammonia-metabolizing enzymes in human liver: Ontogenesis of heterogeneity
Authors: Moorman Antoon F. M. , Vermeulen Jacqueline L. M. , Charles Robert , Lamers Wouter H. 
Published: March 2007

Immunohistochemical analysis of human liver (8 to 94 years) shows a compartmentation of ammonia-metabolizing enzymes across the acinus. The highest concentration of carbamoylphosphate synthetase (ammonia) is found in the parenchymal cells around the terminal portal venules. Glutamine synthetase is found in a small pericentral compartment two to three cells thick. In contrast to observations in rat liver, in human liver a well-recognizable intermediate zone can be distinguished in which neither enzyme can be detected. This intermediate zone is not yet established at the age of 8 years but can be recognized in livers from 25 years onward.
Carbamoylphosphate synthetase can already be detected in the liver of human fetuses at 5 weeks of development. The enzyme distribution reveals a random heterogeneity among the hepatocytes, suggesting that not all hepatocytes start to accumulate carbamoylphosphate synthetase at the same time. From 9 weeks of development onward, the enzyme becomes homogeneously distributed throughout the liver parenchyma until at least 2 days after birth. Glutamine synthetase cannot be detected during this period. In addition, the definitive architecture of the acinus is not yet completed at birth.
These results therefore support the idea that in human liver, metabolic zonation with respect to NH3 metabolism exists as it does in rat liver. Furthermore, the data show that this functional compartmentation becomes established concomitant with the development of the acinar architecture. The fact that enzymic zonation is not yet established in the perinatal period may have important consequences for the regulation of ammonia fixation and pH homeostasis in preterm infants and neonates.
The effect of biliary enteroenterostomy on the pharmacokinetics of enterally administered cyclosporine in rats†
Authors: Whitington Peter F. , Kehrer Beat H. , Whitington Susan H. , Shneider Benjamin , Black Dennis D. 
Published: March 2007

A major factor in poor bioavailability of cyclosporine in children undergoing orthotopic liver transplantation appears to be poor absorption of the drug. Our hypothesis is that the Roux-en-Y choledochojejunostomy used for biliary drainage in these children causes cyclosporine malabsorption by reducing the length of bowel available for absorption and by distally displacing the entry of bile into the intestine. In these experiments, we determined the effect of biliary enteroenterostomy on the pharmacokinetics of enterally administered cyclosporine in Sprague-Dawley rats.
Experimental rats (n = 24) were prepared for study by constructing self-emptying jejunal blind loops. Sham rats (n = 9) had jejunal transection and reanastomosis. Control rats (n = 26) had no operation. Two to 4 weeks later, chronic biliary-enteric fistulae were formed in all animals. In experiments, [3H]cyclosporine was delivered into the duodenum while the site of bile delivery varied. Hourly and cumulative [3H]cyclosporine excretion into bile was quantitated, which our preliminary data show to be a valid estimate of absorption. In control rats, bile was delivered into the duodenum or was replaced with saline and sucrose solution. In experimental rats, bile was infused either into the duodenum, which tested bowel shortening only, or into the proximal end of the blind loop, which tested the combined effects of bowel shortening and distal displacement of bile entry. In sham rats, bile was infused into the duodenum, which controlled for previous abdominal surgery, or into the mid-jejunum, which tested for distal bile entry only.
Two effects of biliary enteroenterostomy on cyclosporine absorption were observed. First, distal displacement of bile entry into the intestinal lumen reduced drug absorption by about 50%. Compared to control rats with duodenal bile (n = 15), which excreted 14.8 ± 3.3% of the label into bile in 24 hr, and sham rats with duodenal bile (n = 4), which excreted 14.6 ± 1.3%, experimental animals with loop bile (n = 13) excreted 7.7 ± 2.1% and sham rats with midjejunal bile (n = 5) excreted 7.2 ± 1.8%. Control rats with no bile (n = 11) excreted 3.2 ± 1.6%. Second, reduction of bowel length by constructing the enteroenterostomy reduced absorption by 25%. Experimental rats with duodenal bile (n = 11) excreted 11.2 ± 2.5%. These data suggest that the surgical approach to biliary reconstruction after orthotopic liver transplantation in children can contribute to poor cyclosporine bioavailability.
Elevated levels of 2′,5′-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum during acute exacerbation of chronic hepatitis B
Authors: Shindo Michiko , Okuno Tadao , Arai Ken , Matsumoto Masayuki , Takeda Makoto , Takino Tatsuro , Sokawa Yoshihiro 
Published: March 2007

We measured 2′,5′-oligoadenylate synthetase activity in peripheral blood mononuclear cells and serum of 14 HBsAg- and HBeAg-positive patients with chronic hepatitis B with or without acute exacerbation. Elevated levels of 2′,5′-oligoadenylate synthetase in peripheral blood mononuclear cells and serum were found in seven chronic hepatitis B patients with acute exacerbation, whereas in the remaining seven chronic hepatitis B patients without acute exacerbation, both levels were similar to those of normal subjects despite active hepatitis B virus multiplication. 2′,5′-Oligoadenylate synthetase levels in peripheral blood mononuclear cells and serum, which were not statistically different from those of normal subjects prior to acute exacerbation, increased during acute exacerbation from 3-to 23-fold over initial levels following elevations in ALT activity. 2′,5′-Oligoadenylate synthetase levels fluctuated over a normal range while ALT levels were elevated, and they returned to a baseline with ALT normalization. This suggests that the in vivo interferon system may be activated during acute exacerbation, and that this activation may not be a result of hepatitis B virus multiplication alone, but also of a host-immune response to hepatitis B virus multiplication.
Three patients were treated with interferon during acute exacerbation. All three had elevated levels of 2′,5′-Oligoadenylate synthetase in peripheral blood mononuclear cells and serum just before treatment. 2′,5′-Oligoadenylate synthetase levels increased only 1.1 -to 2.2-fold over initial levels during treatment, with none of the patients clearing HBeAg during and after treatment. This suggests that interferon treatment may not be effective during acute exacerbation, since the in vivo interferon system has already been activated. Measurement of 2′,5′-oligoadenylate synthetase levels may be useful in evaluating the in vivo state of the interferon system and in determining the optimal timing of interferon treatment.
Cytoskeletal organization and functional changes in monocytes from patients with chronic hepatitis B: Relationship with viral replication
Authors: Prieto Jesús , Castilla Alberto , Subirá María-Luisa , Serrano Manuel , Morte Susana , Civeira María-pilar 
Published: March 2007

Monocytes play an important role in the initiation and regulation of the antiviral immune response. These cells have a dense framework of intermediate filaments composed of vimentin monomers. In 35 patients with chronic hepatitis B, 26 healthy controls, seven patients with acute liver damage and eight patients with inactive HBsAg-negative cirrhosis, we investigated the expression of vimentin filaments, C3b and IgGFc receptors, HLA-DR molecules and the phagocytic activity in monocytes purified from venous blood. In the same subjects, we also studied the display of CD2, CD3 and CD5 on lymphocytes.
In patients with chronic hepatitis B manifesting viral replication (n = 21; Group 1), the expression of vimentin filaments and the other functional monocyte parameters were decreased, whereas in patients in the nonreplicative phase of the disease (n = 14; Group 2) and in control cases with various forms of acute liver damage or inactive HBsAg-negative cirrhosis, they were similar to those found in healthy subjects. In Group 1, there was also a selective defect in the display of CD3 on lymphocytes. The expression of this molecule correlated with the functional state of monocytes. In three patients with chronic hepatitis B that changed from the replicative to the nonreplicative phase of the disease, the expression of vimentin filaments in monocytes and of CD3 on lymphocytes increased to normal levels. On the other hand, the incubation of patients’ monocytes with γ-interferon corrected the diminished expression of vimentin filaments and the other decreased functional parameters.
These findings show that in the replicative phase of chronic hepatitis B, there are alterations in the initial steps of activation of antiviral immune response and that γ-IFN is able to correct the monocyte dysfunction present in these patients. Furthermore, it is suggested that the expression of immunoreactive vimentin filaments may be a dynamic indicator of the functional state of monocytes.
The liver and IgA: Immunological, cell biological and clinical implications
Authors: Brown William R. , Kloppel Thomas M. 
Published: March 2007

Secretory immunoglobulin A is the characteristic and predominant immunoglobulin of the mucosal immune system; it participates in immunological protection at the level of mucous membrane surfaces. During the past 10 to 15 years, a great deal of experimental and clinical evidence has shown that the liver is very much involved in the sIgA system.
In certain animals (rats, mice, rabbits), polymeric forms of IgA are efficiently cleared by the liver and transported into bile by a receptor-mediated vesicular pathway across hepatocytes. Taking advantage of this easily accessible pathway, investigators have defined many of the events in the external secretion of pIgA, including details about the synthesis and secretion of its receptor, secretory component. In the rat hepatocyte, secretory component is synthesized as a transmembrane glycoprotein and is expressed preferentially on the sinusoidal plasma membrane; circulating pIgA that binds to secretory component is internalized into endocytic vesicles and transported across the hepatocyte to the bile canalicular membrane, where the pIgA is released into bile as a soluble complex with a portion of the secretory component, the complex being secretory IgA. In some other animals (dog, guinea pig, sheep) as well as man, biliary epithelial cells, not hepatocytes, express secretory component and perform the transcytosis and secretion of pIgA into bile. In those species, much of the pIgA that reaches bile is synthesized locally in plasma cells that populate the biliary tree; this design is analogous to the release of sIgA into various mucosae in the body.
The major biological functions ascribed to the secretion of IgA into bile are enhancement of immunological defense of the biliary and upper intestinal tracts and the clearance of harmful antigens from the circulation as IgA-antigen complexes. However, the importance of biliary IgA antibodies is largely unclarified, and man lacks the capacity for effective clearance of IgA-antigen complexes via the secretory component-mediated transhepatocellular pathway; whether this deficit contributes to the propensity for man to develop IgA immune complex diseases should be clarified.
Among liver diseases, alcoholic disease is most closely linked to alterations in IgA metabolism. This association is manifested principally by the deposition of IgA along the sinusoids in the livers of the majority of alcoholics and in the renal mesangium of many. The IgA1 subclass of IgA predominates in the IgA deposits in both tissues; the possibility that this predominance is related to abnormalities in the removal of circulating IgA1 by asialoglycoprotein receptors on hepatocytes is an intriguing consideration.
Thus, the liver plays a unique role in mucosal immunity and in the physiology of IgA in normal and disease states. Further study of the associations between the liver and IgA, particularly in man, is clearly needed.
Binding and uptake of native and modified low-density lipoproteins by human hepatocytes in primary culture
Authors: Babaev Vladimir R. , Kosykh Vladimir A. , Tsibulsky Vladimir P. , Ivanov Vadim O. , Repin Vadim S. , Smirnov Vladimir N. 
Published: March 2007

The binding and uptake of native low-density lipoproteins and malondialdehyde-treated low density lipoproteins by human hepatocytes in primary culture has been analyzed. Experiments with 125I-labeled malondialdehyde-treated low-density lipoproteins showed that cultured liver cells took up and degraded malondialdehyde-treated low-density lipoproteins, but the cell type(s) responsible for this action remain unclear. Immunofluorescent visualization of receptor-bound low-density lipoproteins revealed that low-density lipoprotein binding sites were distributed on the surface of nearly all cells of the culture. Binding sites for malondialdehyde-treated low-density lipoproteins were found in only 5% of the cultured cells, and these cells differed from hepatocytes in shape and size. Cultured hepatocytes internalized and native low-density lipoproteins, but not malondialdehyde-treated low-density lipoproteins, labeled with the fluorescent dye 3′,3′-dioctadecylindocarbocyanine. About 15% of the cells that take up 3′,3′-dioctadecylindocarbocyanine-labeled malondialdehyde-treated low-density lipoproteins could be identified as liver endothelial cells and macrophages, since they internalized formaldehyde-treated human albumin and fluorescent carboxylated microspheres.
Our results indicate that human hepatocytes in primary culture express surface receptors for native low-density lipoproteins but not for modified low-density lipoproteins.