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T Goeser

Publications and source records attributed to T Goeser.

49 records · Page 3Linked to original sources
PubMed1992

Liver transplantation for acute or chronic liver failure by hepatitis non-A, non-B and hepatitis C viral infections: a postoperative follow-up.

Orthotopic liver transplantation (OLT) was performed for liver failure related to hepatitis non-A, non-B (HNANB) or hepatitis C (HCV) infections in 12 patients. Of those, 8 patients had chronic and 4 acute hepatic failure. To determine the incidence of recurrent infection, the clinical course, histological findings and serological HCV markers (HCV-RNA and detection of anti HCV antibodies, respectively) were comparatively studied in these patients. Recurrent infection was apparent in 5 of 6 patients transplanted for liver cirrhosis attributable to chronic HCV infection and with HCV-RNA detectable in serum. The clinical course of infection after OLT varied considerably. Chronic active hepatitis, progressing to liver cirrhosis 13 months postoperatively and an acute hepatitis, resolving spontaneously were seen in one case each. Recurrent infection led to chronic persistent hepatitis in the remainder. None of the patients with acute liver failure experienced recurrent infection. HCV-RNA was detectable in all the patients after OLT, with HCV-RNA present pretransplant, however the presence of HCV-RNA in serum was not necessarily associated with clinical illness.

Budd-Chiari Syndrome↗
PubMed1991

Organic anion transport in HepG2 cells: absence of the high-affinity, chloride-dependent transporter.

In previous studies, we identified a 55 kD organic anion-binding protein in liver cell sinusoidal plasma membrane subfractions. Other investigators identified another 55 kD bromosulfophthalein/bilirubin binding protein on the surface of rat hepatocytes and HepG2 cells and suggested that this protein served as a transporter for these ligands. In this study, transport of 35S-sulfobromophthalein by the human hepatoma cell line, HepG2, was quantified in the presence and absence of bovine serum albumin to further clarify the possible function of these plasma membrane binding proteins. In contrast to results in normal rat hepatocytes, virtually no uptake of 35S-sulfobromophthalein by HepG2 cells in the presence of bovine serum albumin was found. In the absence of albumin, HepG2 cells expressed temperature-dependent uptake of 35S-sulfobromophthalein. However, the high-affinity Cl(-)-dependent sulfobromophthalein transport that characterizes normal rat hepatocytes was absent, as indicated by an approximately 95-fold lower affinity and 170-fold higher capacity of HepG2 cells for sulfobromophthalein compared with previous results with rat hepatocytes. These results suggest that 55 kD sulfobromophthalein/bilirubin-binding protein on the liver cell surface differs from organic anion-binding protein and is not responsible for sulfobromophthalein extraction in the presence of albumin, although it may play some role in lower affinity transport by cells. Immunoblot analysis and metabolic labeling of HepG2 cells demonstrated synthesis of organic anion-binding protein. However, light microscopic immunocytochemistry and immunoprecipitation of surface iodinated rat hepatocytes and HepG2 cells with antibody to a recombinant organic anion-binding protein fusion protein indicated absence of organic anion-binding protein on the surface of HepG2 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Interactions of hepatitis B virus with hepatocytes: mechanism and clinical relevance.

A receptor for hepatitis B virus (HBV) on hepatocytes has been postulated. There is increasing evidence that the binding of the virus to the target cell surface is mediated by epitopes of the pre-S proteins of the HBV envelope. In contrast to vaccination with HBsAg, passive immunization for the prevention of HBV infection is less effective. Using antibodies against the pre-S proteins, representing the putative attachment site for HBV binding to hepatocytes, a more efficient means of protection might be achieved.

Epitopes↗
PubMed1990

Transport of chenodeoxycholic acid and its 3-alpha- and 7-alpha-sulfates by isolated perfused rat liver.

In patients with cholestasis, levels of sulfated bile acids rise. Sulfate esters of chenodeoxycholic acid are the most abundant of these bile acid sulfates. These compounds are taken up by the liver and excreted into bile, although their plasma clearance and biliary excretion are reduced compared with that of unsulfated bile acids. It is not clear whether this is due to differences in intrinsic hepatic uptake or biliary excretion. In the present study, single-pass transport kinetics of chenodeoxycholic acid 3-alpha-sulfate, chenodeoxycholic acid 7-alpha-sulfate and unsulfated chenodeoxycholic acid were quantified in isolated perfused rat liver. Influx of the 7-alpha- and 3-alpha-sulfated derivatives was 57% and 20% that of chenodeoxycholic acid, respectively. These three compounds bound to albumin equally well, indicating that this was not a factor in their differential uptake. Although single-pass extraction of material taken up by the liver was identical. There was no difference in bile flow or biliary excretion of material taken up by the liver was identical. There was no difference in bile flow or biliary excretion rate, regardless of which bile acid sulfate was tested. These results indicate that the low plasma elimination of sulfated bile acids previously observed by others can be explained by low hepatic influx. The diminished transport into liver resulting from sulfation could lead to enhanced elimination of bile acids by the kidney.

Animals↗
PubMed1990

The rat hepatocyte plasma membrane organic anion binding protein is immunologically related to the mitochondrial F1 adenosine triphosphatase beta-subunit.

A 55-kD organic anion binding protein (OABP) was identified previously in liver cell plasma membrane sinusoidal subfractions. Although this protein was localized to the surface of hepatocytes by immunofluorescence, immunoblot analysis revealed reactivity toward both plasma membrane and mitochondrial fractions. To clarify these findings, an immunoreactive clone from a rat liver cDNA expression library was isolated, the 1,500-base pair cDNA insert was sequenced, and the corresponding beta-galactosidase fusion protein was expressed and purified. The resulting sequence corresponded to that of the rat mitochondrial F1-adenosine triphosphatase (F1-ATPase) beta-subunit. This protein and OABP are of similar size and are mutually immunologically cross-reactive. That the antigen was present on the cell surface as well as in mitochondria was suggested from studies of immunoprecipitation after cell-surface iodination, and light- and electron-microscopic immunocytochemistry. Photoaffinity labeling of bovine F1-ATPase with high-specific-activity [35S]sulfobromophthalein revealed binding only to the beta-subunit. Hepatocyte uptake of bilirubin and sulfobromophthalein requires cellular ATP and mitochondria also transport these organic anions, which at high doses inhibit respiration. The presence of an organic anion binding site on the F1-ATPase beta-subunit suggests that it may play a role in these processes.

Affinity Labels↗
PubMedDate not supplied

Expression of apoptosis and apoptosis-related peptides in various stages of rejection in the human transplanted liver.

BACKGROUND/AIMS: In the transplanted liver, the role of apoptosis and apoptosis-related proteins are largely unknown. This study addresses the question whether hepatocyte or leukocyte apoptosis plays an important role in acute rejection of the transplanted human liver and which pathways are involved. METHODOLOGY: Cryosections from liver biopsies with acute rejection were stained with the TUNEL technique for detection of apoptosis and labeled immunohistochemically with antibodies against CD95, bcl-2, TGF-beta and iNOS. A double-labeling protocol was developed for simultaneous detection of iNOS and apoptosis. Liver tissue with chronic viral hepatitis, with hepatitis reinfection and tissue without pathological findings served as a control. RESULTS: Leukocyte apoptosis was markedly reduced in severe compared to mild or moderate acute rejection. Hepatocyte apoptosis is detected rarely in acute rejection with a slight increase from mild to severe despite a strong expression of CD95 and TGF-beta on hepatocytes. The hepatocyte expression of iNOS is weak in acute rejection but strong in control slides with hepatitis B/C reinfection. In acute rejection, simultaneous expression of iNOS and apoptosis could be demonstrated in Kupffer-cells. CONCLUSIONS: Severe acute rejection in the human transplanted liver is characterized by a lack of apoptosis of infiltrating portal lymphocytes probably caused by a reduced downregulation of lymphocyte function. Secondly, in spite of the strong expression of CD95 and TGF-alpha, hepatocyte apoptosis plays a limited role for liver damage in acute rejection. Finally, Kupffer cell apoptosis is increased in acute rejection and seems to be induced by nitric oxide.

Apoptosis↗
PubMedDate not supplied

Prevalence and serological manifestation of hepatitis C virus infection in patients with hepatitis non-A, non-B: a follow-up study.

OBJECTIVES: Sera of patients with acute hepatitis non-A, non-B prospectively followed for a mean of 11.4 years (range 9 to 15 years) were assayed for anti-hepatitis C virus (HCV) by first- and second-generation enzyme-linked immunosorbent assay (ELISA) and second-generation recombinant immunoblot assay (RIBA) to study the patterns of antibody response in relation to the outcome of disease. METHODS: From 1974 through 1981, 112 patients with acute hepatitis non-A, non-B were enrolled in a prospective study. Sera of 45 patients taken during the acute phase of hepatitis, as well as taken during follow-up in 1983 and 1990 were still available for evaluation. Sera were assayed by first- (ELISA-1) and second-generation (ELISA-2) anti-HCV ELISA, second-generation RIBA (RIBA-2) and HCV RNA by RT-polymerase chain reaction (PCR). RESULTS: Based on anti-HCV seropositivity by RIBA-2 in acute hepatitis and/or during follow-up, a total of 22/45 patients with HNANB (48.8%) were considered to have confirmed HCV infection. By ELISA-1, 11/22-patients with HCV infection (50%) were positive for anti-HCV within 6 weeks of the onset of illness, 18/22 sera (82%) were reactive by ELISA-2. Confirmation by RIBA-2 was obtained in 12 (55%) cases, while one additional patient was RIBA-2 indeterminate. In 1983, a disappearance of anti-HCV tested by RIBA-2 was observed in 7/12 resolved patients but in none of the patients with chronic hepatitis (p = 0.0018) while loss of anti-HCV was observed in 2/12 cases with resolved hepatitis and none with chronic hepatitis by ELISA (not significant). In 1990, all patients with chronic hepatitis were still positive by either ELISA or RIBA-2 but 9/12 (75%), 6/12 (50%) and 10/11 (91%) patients with resolved hepatitis had lost anti-HCV seropositivity tested by ELISA-1 (p = 0.0004), ELISA-2 (p = 0.0124) or RIBA-2 (p < 0.0001), respectively. Mostly, RIBA-2 reactivity was lost prior to ELISA-2 reactivity during follow-up. Rates of antibody loss as detected by ELISA-1, ELISA-2 and RIBA-2 were 4.1, 2.9 and 5.8 per 100 person years, respectively. CONCLUSIONS: This study shows that the continuing presence of HCV is necessary to maintain anti-HCV seropositivity. In contrast, anti-HCV reactivity is progressively lost over time in resolved patients. In addition, albeit more specific, the RIBA-2 is less sensitive than the ELISA and RIBA seroconversion to negative seems to be the earliest serological marker of a resolved HCV infection.

Adult↗