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Biomedical subjects

M Manns

Publications and source records attributed to M Manns.

At least 73 records · Page 4Linked to original sources
PubMed1994

Anti-GOR in hepatitis D: specific association with hepatitis C virus superinfection.

A group of 113 patients with chronic hepatitis D was investigated for the presence of anti-GOR and liver kidney microsomal antibodies. Eight patients were anti-GOR positive and also positive for hepatitis C virus-infection. In sera from 16 patients liver-kidney microsomal antibodies were detectable by immunofluorescence. They were classified as LKM-3 due to their fluorescence pattern. Two of the LKM-3-positive sera were also anti-hepatitis C virus and anti-human immunodeficiency virus positive. None of these patients were positive for anti-GOR. Fourteen sera from LKM-3-positive patients reacted in Western blot with a microsomal protein at 55 kDa that differs from the 50-kDa LKM-1 (cytochrome P450IID6) antigen. Our studies demonstrate that hepatitis D virus itself does not induce an autoimmune reaction against the GOR antigen and that autoimmunity to the LKM-3 antigen induced by hepatitis D virus infection does not correlated with anti-GOR. These studies support the specificity of the anti-GOR response for hepatitis C virus infection.

Autoantibodies↗
PubMed1994

Tissue characterization using intelligent adaptive filter in the diagnosis of diffuse and focal liver disease.

In ultrasonic imaging an adaptive two-dimensional filter (ATDF) can suppress randomly generated speckle using the ratio of the local variance to the local mean as the speckle recognition feature (R). The degree of smoothing depends on the difference between the recognition feature in the region to be filtered and the selected reference tissue. We have investigated the clinical application of ATDF for ultrasound B-mode images of liver abnormalities. Using the R values of normal liver as reference values, the ATDF images were displayed. Normal livers (n = 17, R = 2.19 +/- 0.14 M +/- SEM), fatty livers (N = 16, R = 1.89 +/- 0.15) and those with acute hepatitis (N = 10, R = 2.25 +/- 0.18) appeared smooth after application of the adaptive filter, but those diseases with higher R values, such as chronic hepatitis (N = 10, R = 3.04 +/- 0.30), cirrhosis (n = 16, R = 4.44 +/- 0.30), metastases (N = 16, R = 6.43 +/- 0.53) and hepatocellular carcinomas (N = 8, R = 7.92 +/- 0.85), were largely unsmoothed. In conclusion, ATDF allows differentiation of some forms of liver disease and may be helpful in the detection of microfocal echogenic textural lesions.

Adult↗
PubMed1994

Is there recurrence of primary biliary cirrhosis after liver transplantation? A clinicopathologic study in long-term survivors.

Liver transplantation has been accepted as a successful therapeutic tool for irreversible liver diseases such as primary biliary cirrhosis. However, removal of the diseased liver may not eliminate this autoimmune disease, and recurrence of primary biliary cirrhosis in the liver graft has been reported as early as within the first posttransplant year. We studied whether or not primary biliary cirrhosis recurs after liver transplantation in follow-up biopsies of 19 primary biliary cirrhosis patients. Biopsies of 14 non-primary biliary cirrhosis patients served as controls. The median follow-up period was 5 years (range 1-11 years). Both groups of patients were selected according to strict criteria which excluded pre- and posttransplant diseases which could mimic primary biliary cirrhosis. The follow-up biopsies were taken according to a protocol at yearly intervals. Established histologic criteria for primary biliary cirrhosis were assessed semi-quantitatively in 119 biopsies in a coded fashion. A longitudinal study was performed after decoding the biopsies, to document the course of morphological changes in time per patient. In addition to data on liver tests and immunosuppression, anti-mitochondrial antibodies including the primary biliary cirrhosis specific subtypes (anti-PDH-E2 and BCKD-E2) were determined in freeze-stored serum samples. The biopsies showed a striking concordance between the primary biliary cirrhosis and non-primary biliary cirrhosis groups and few overt histologic abnormalities. There was no significant difference in liver-test results and immunosuppression. Overall anti-mitochondrial antibodies remained present in decreased titers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Helicobacter pylori infection and serum pepsinogen A, pepsinogen C, and gastrin in gastritis and peptic ulcer: significance of inflammation and effect of bacterial eradication.

OBJECTIVES: To study the relationship between Helicobacter pylori infection, gastric inflammatory scores, and fasting gastrin and pepsinogen A and C concentrations, and to evaluate the effect of treatment on these parameters. METHODS: Gastrin and pepsinogen A and C concentrations were measured in 36 patients with gastritis, 10 gastric ulcer patients, 12 duodenal ulcer patients, and in 15 subjects with normal gastric mucosa, by standard radioimmunoassay techniques. Fifteen patients with H. pylori infection underwent triple therapy (bismuth subsalicylate, amoxicillin, metronidazole) and were reassessed 1 month later. RESULTS: Fasting gastrin and pepsinogen A and C concentrations were significantly higher in H. pylori-positive gastritis and peptic ulcer patients than in subjects with normal mucosa and in patients with H. pylori-negative gastritis. There was a significant correlation between inflammatory scores and serum gastrin (r = 0.45, p < 0.0001), and pepsinogen A (r = 0.33, p < 0.006) and pepsinogen C (r = 0.55, p < 0.0001) concentrations. Neither sex nor age affected basal gastrin and pepsinogen concentrations. Eradication of H. pylori infection was successful in 12 patients and resulted in a significant fall in serum gastrin and in pepsinogen A and C concentrations, and in a concomitant improvement of the inflammatory scores. Serum peptide levels and gastritis scores were unchanged in those patients in whom H. pylori infection persisted. CONCLUSIONS: These findings suggest that hypergastrinemia and hyperpepsinogenemia are secondary to H. pylori infection and are related to mucosal inflammation.

Amoxicillin↗
PubMed1994

Strong transient expression of the type I interferon-induced MxA protein in hepatitis A but not in acute hepatitis B and C.

The human MxA protein is a new specific marker for type I interferon activity both in vitro and in vivo. In the study presented here, this interferon-induced marker, as well as the 2',5'-oligoadenylate synthetases, was measured in circulating mononuclear cells from 21 patients with acute hepatitis A, 20 patients with acute hepatitis B and 14 patients with acute hepatitis C for determination of the activation of the interferon system in these viral diseases. In acute hepatitis A a strong expression (10 of 10 patients) of the MxA protein and the 2',5'-oligoadenylate synthetase activity in peripheral-blood mononuclear cells was observed during the first 2 wk after onset of clinical symptoms. In this period the MxA protein concentrations reached levels similar to those measured in patients treated with up to 5 x 10(6) IU interferon-alpha three times a week. Beyond wk 3, in eight of eight patients with hepatitis A no increased MxA protein levels were found. In contrast, peripheral-blood mononuclear cells from patients with acute hepatitis B contained either no measurable MxA protein or only slightly higher levels of the MxA protein, as did those of most patients (12 of 14) with acute hepatitis C. The MxA protein levels of both hepatitis B and C patients were significantly lower (p < 0.05) than those found in hepatitis A patients. Furthermore, sera from 6 of 10 patients with hepatitis A, but none of 10 patients with acute hepatitis B and C, contained measurable MxA protein. This serum MxA protein may originate from interferon-exposed and subsequently damaged liver cells.(ABSTRACT TRUNCATED AT 250 WORDS)

2',5'-Oligoadenylate Synthetase↗
PubMed1993

IgA deficiency associated with chronic hepatitis C virus infection. A cause or an effect?

OBJECTIVE: To evaluate the role of IgA in hepatitis C virus (HCV) infection. We have tested serum IgA levels in patients with antibodies to HCV. DESIGN: A retrospective study. PATIENTS: The IgA levels were tested in serum samples from 94 patients with antibodies to HCV examined during 1989-1990. RESULTS: Low IgA levels were found in 16/94 (17%) patients. In three of these 16 patients (3.2% of the original 94), no IgA was detected by radial immunodiffusion. In nine of 16 patients, previous pre-HCV infection serum samples with undetectable anti-HCV antibodies were available. In four of these nine patients, IgA deficiency was found in the preinfection serum, while in the remaining five patients, previous IgA levels were normal and the occurrence of anti-HCV was associated with the recent development of IgA deficiency. CONCLUSIONS: The results of this study indicate that IgA deficiency is a risk factor for HCV infection in some patients, whereas in others it might be caused by the viral disease.

Adult↗
PubMed1993

Autoreactive liver-infiltrating T cells in primary biliary cirrhosis recognize inner mitochondrial epitopes and the pyruvate dehydrogenase complex.

Primary biliary cirrhosis (PBC) is characterized by lymphoid infiltrates in the portal tracts of the liver and the occurrence of antimitochondrial autoantibodies in serum directed against components of the pyruvate dehydrogenase complex and the other alpha-keto acid dehydrogenase complexes. These enzymes are located on the inner mitochondrial membrane. The destruction of the biliary tract in PBC is thought to be mediated by autoreactive liver-infiltrating T cells exerting cytotoxic activity or releasing certain lymphokines. In this study the reactivity of liver infiltrating T cells was shown to a bovine pyruvate dehydrogenase complex (PDH), a purified E2 subunit (PDH-E2) and a crude preparation of human liver mitoplasts (HLM), i.e. mitochondria depleted of their outer membranes. Peripheral blood lymphocytes (PBL) from 11 of 15 patients (73.3%) with PBC showed a HLA class II-restricted proliferative response to the PDH complex whereas PBL from patients with chronic viral hepatitis, autoimmune hepatitis or extrahepatic cholestatic icterus (n = 20) and healthy controls (n = 5) did not. In addition 13 of 15 PBL from patients with PBC (86.6%) and three of nine PBL from patients with autoimmune hepatitis (33.3%) reacted with the crude HLM preparation whereas no reactivity was found with PBL from eight patients with chronic viral hepatitis, three patients with extrahepatic cholestasis or five healthy controls. Clonal analysis of 115 liver-infiltrating T cells derived from two diagnostic liver biopsies of patients with PBC revealed a predominance of activated CD4+CD8- T helper cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[Infiltrating T-cells in primary biliary cirrhosis recognize mitochondrial epitopes].

The primary biliary cirrhosis (PBC) is characterized by lymphoid infiltrates in the portal tracts of the liver and occurrence of antimitochondrial autoantibodies (AMA) in serum directed against the pyruvate dehydrogenase complex or other enzyme complexes that are located on the inner mitochondrial membranes. The destruction of the biliary tracts is thought to be mediated by autoreactive liver infiltrating T-cells. In this study we demonstrate the reactivity of peripheral and liver-infiltrating T-cells against a crude preparation of human liver subcellular fractions measured by the tritium-thymidine uptake. Peripheral blood mononuclear cells (PBMC) from 13 of 15 patients with PBC and from 3 of 9 patients with chronic autoimmune hepatitis recognized human liver mitoplasts, i.e. mitochondria depleted of their outer membranes. PBMC from patients with chronic viral hepatitis B and C or with extrahepatic cholestatic icterus and PBMC from healthy controls did not recognize this antigen. Monoclonal antibodies against HLA-class II molecules blocked this proliferative response. Clonal analysis of 115 liver-infiltrating T-cells derived from two diagnostic liver biopsies of patients with PBC revealed a predominance of activated CD4+CD8- T helper cells. Six CD4- positive T-cell clones were reactive to the HLM preparation when the antigen was presented by autologous B cell lines. MAb against HLA-class II or HLA-DR inhibited the response whereas mAb against HLA-DP did not. These clones did not respond to other subcellular fractions of human liver tissue. We conclude that among liver-infiltrating T-cells in PBC autoreactive T-cells exist that recognize some epitopes on the inner mitochondrial membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Presenting Cells↗
PubMed1993

Lack of surface expression for the B-cell autoepitope of cytochrome P450 IID6 evidenced by flow cytometry.

The major target antigen of LKM-1 autoantibodies in chronic active hepatitis is cytochrome P450 IID6. The role of LKM-1 autoantibodies in the pathogenesis of the disease is not clear. A crucial point is the expression of the target epitope on the hepatocyte membrane. Cultured rat hepatocytes were used in this study. Time dependent analysis of cytochrome P450 IID6 specific RNA-level revealed a constant decrease in culture. A high amount of the specific RNA-level was present after culturing the hepatocytes for 24 hours at the time of the membrane studies. To investigate membrane surface expression, we used recombinant human cytochrome P450 IID6 to affinity purify the specific autoantibody from patients sera. Indirect immunofluorescence studies and flow cytometry analysis were performed with viable, unfixed rat hepatocytes. As positive control, a monoclonal antibody against rat MHC class I antigens was used. More than 85% of viable hepatocytes showed a positive membrane staining after the incubation with the monoclonal antibody to MHC class I antigens. Affinity purified monospecific LKM-1 autoantibody, sera from control subjects and from patients with liver diseases showed a membrane staining of less than 10%. Thus, no significant expression of the B cell autoepitope of LKM-1 antigen was found on the plasma membrane of viable hepatocytes with the methods applied.

Antigens, Surface↗
PubMed1993

Sonographic aspects of the Cruveilhier Baumgarten syndrome.

A rare case of Cruveilhier-Baumgarten syndrome with exceptional deep subcutaneous portosystemic collaterals is reported. Undetected these anastomoses represent potentially dangerous sites for hemorrhage complications. Ultrasound in combination with color-coded duplex sonography is a reliable technique in identifying portosystemic anastomoses as well as in providing valuable information about the etiology of portal hypertension.

Aged↗
PubMed1992

Retinoic acid affects the organization of reticulospinal neurons in developing Xenopus.

The effects of all-trans retinoic acid (RA) on the differentiation of the reticulospinal system were studied in Xenopus. RA was applied in concentrations of 10(-5) and 10(-6) M for 30 min at stage 12. When siblings had reached stages 46-48, the spinal cord was transected in anesthetized control and experimental animals and the reticulospinal cells were visualized through retrograde transport of fluorescing dextran amines. The lower concentration of RA led in many animals (22%) to the formation of multiple Mauthner-like cells. Higher concentrations resulted in the formation of two uninterrupted longitudinal columns of rather uniform reticulospinal cells. These data suggest that the normal expression of Hox genes pattern--known to be altered by RA--may be necessary for the differential specification of compartments of the reticulospinal system.

Animals↗
PubMed1992

Identification and characterization of a monoclonal antibody to the membrane fatty acid binding protein.

A monoclonal antibody to the rat liver membrane fatty acid binding protein (MFABP) was prepared by immunizing mice with purified MFABP isolated from solubilized rat liver plasma membrane proteins by oleate-agarose affinity chromatography technique. The monoclonal antibody K15/6 identified a single 40 kDa protein in rat liver plasma membranes with pI values of 8.5, 8.8 and 9.0, which is identical to the authentic MFABP, but clearly distinct from rat mitochondrial GOT. The antibody K15/6 selectively inhibited cellular influx as well as membrane binding of fatty acids, but not of cholesterol or vitamin E. The same antibody was used in immunofluorescence, ELISA and Western blot analysis to determine the subcellular and organ distribution pattern of MFABP. The protein was identified in rat liver plasma membranes and mitochondria, but in no other cell compartment. It was detectable in homogenates of rat liver but not in homogenates of other organs. Therefore, the monoclonal antibody K15/6 represents an organ specific antibody to MFABP which reveals inhibitory action on membrane binding/transport of fatty acids.

Animals↗
PubMed1992

Regulation of cytochrome P450 IID by acute phase mediators in C3H/HeJ mice.

Cytochrome P450 IID6 is a drug metabolizing enzyme and the major target antigen in LKM-1 antibody positive chronic active hepatitis. The histological hallmark of chronic active hepatitis is a lymphocytic infiltrate in the liver. It is unknown whether and how cytokines produced and secreted by these tissue infiltrating mononuclear cells regulate the cellular expression of cytochrome P450 IID6. To study the effect of interleukin 1, tumor necrosis factor and interleukin 6 on the hepatocellular RNA expression of cytochrome P450 IID, we injected each of the cytokines in C3H/HeJ mice. We found a time-dependent suppression of the cytochrome in the liver. Six hours after the intraperitoneal injection of 0.5 micrograms interleukin 1 beta the specific RNA-expression was reduced to 25% of the original level. A similar reduction was found after the injection of 2 micrograms tumor necrosis factor alpha. A mild suppression to 65% of the original level was seen six hours following the dose of 100 ng interleukin 6. Our studies show how immune mediators can change the expression of an autoantigen. Further studies in the human system are necessary to estimate this regulation for the elimination of drugs and in LKM-1 antibody positive chronic active hepatitis.

Animals↗