Search PubMed⌕ Search

Biomedical subjects

M Manns

Publications and source records attributed to M Manns.

At least 145 records · Page 8Linked to original sources
PubMed1987

Pre-S encoded surface proteins in relation to the major viral surface antigen in acute hepatitis B virus infection.

The role of pre-S encoded viral surface proteins in acute hepatitis B virus infection is still poorly understood. Binding sites for polymerized human serum albumin have been found to be encoded by the pre-s2 region of the hepatitis B virus genome. Recently, murine monoclonal antibodies against pre-s1 and pre-s2 encoded hepatitis B virus gene products were generated and used for their specific detection in serum. In sera from patients with acute hepatitis B, pre-s1 and pre-s2 antigen occurred in 16 of 20 and 15 of 20 patients, respectively. In the initial stage of the disease, pre-S gene products correlated with binding sites for polymerized human serum albumin, but not with hepatitis B surface antigen. Subsequently, pre-s1 and pre-s2 antigens were cleared from the serum of patients with acute hepatitis B before binding sites for polymerized human serum albumin and hepatitis B surface antigen. Possibly, the early clearance of pre-S markers can be of prognostic value in acute hepatitis B. The mechanisms of the early clearance of the pre-S antigens in acute hepatitis B remain to be elucidated. However, elimination by immunologic mechanisms appears likely.

Acute Disease↗
PubMed1987

Liver membrane autoantibodies in chronic active hepatitis. Studies on mechanically and enzymatically isolated rabbit hepatocytes.

Target antigens relevant for immune reactions in inflammatory liver diseases should be expressed on the hepatocellular membrane. Using mechanically or enzymatically isolated rabbit hepatocytes, we evaluated the influence of cell integrity on the detection of membrane-expressed antigens by sera from patients with chronic hepatitis and by murine monoclonal antibodies. Our results provide evidence that target antigens of liver membrane autoantibodies (LMA) as well as liver kidney microsomal antibodies (LKM) are not expressed on the hepatocellular membrane of viable and intact isolated rabbit hepatocytes. However, LMA were detected in the sera of 56% of patients with autoimmune chronic active hepatitis using mechanically isolated hepatocytes. These findings underline the diagnostic relevance of the autoantibodies. It is suggested that LMA are directed against constituents of the cytoskeleton. Therefore, it seems to be unlikely that this antibody is causally involved in the pathogenesis of autoimmune liver diseases.

Animals↗
PubMed1987

Liver cell damage caused by monoclonal antibody against an organ-specific membrane antigen in vivo and in vitro.

Monoclonal antibodies have been raised against different antigenic determinants of normal rabbit hepatocytes. One antibody (2D3) recognized a liver-specific 43 kDa protein displayed exclusively on the basolateral portion of the hepatocellular membrane. Purified monoclonal antibodies were injected intravenously into rabbits. Following the injection of antibody 2D3, a dose-dependent increase of liver enzyme activities in sera was observed. Within 8 h, marked morphological alterations of the hepatocytes, including multiple cell necroses, could be demonstrated by light and electron microscopy. When isolated vital rabbit hepatocytes in culture were used as targets, cytotoxic effects of this antibody could also be observed. This indicates that liver cell damage was not due to antibody-dependent cellular cytotoxicity, but was mediated by the antibody itself. Control antibodies did not show these effects. Thus, our results clearly demonstrate that humoral immune reactions against particular liver membrane antigens may play a role in the development of liver diseases, and provide a useful experimental approach for the investigation of their specificity.

Animals↗
PubMed1987

Analysis of liver-specific protein LSP using murine monoclonal antibodies.

We describe twenty murine monoclonal antibodies directed against different antigenic determinants of human and rabbit liver-specific protein LSP. Among them, nine were directed against liver-specific epitopes as judged from immunohistological studies. Immunoelectronmicroscopy revealed that seven of these monoclonals recognized membrane determinants differing in staining of distinct areas of the hepatocellular surface. Eleven antibodies were directed against intracellular structures. Western blot analysis showed that the epitopes detected were displayed on either single or multiple protein bands with apparent molecular weights between 24,000 and 60,000. Further differences were observed with respect to the species specificity and (among the non-organ-specific antibodies) pattern of tissue cross-reactivity. Our results demonstrate the presence of several liver-specific determinants and membrane components within LSP. There are, however, a very much greater number of non-organ-specific epitopes and numerous determinants displayed on intracellular structures. This emphasizes the remarkable heterogeneity of the antigen preparation named LSP and warrants the use of clearly defined antigens in further studies dealing with auto-immune phenomena in liver diseases.

Animals↗
PubMed1987

Relationship of pre-S encoded antigens in liver and clinical manifestations of chronic hepatitis B infection.

Pre-S1 and pre-S2 encoded antigens of hepatitis B virus were localized in liver tissue using monoclonal antibodies. They were found to be exclusively expressed in the cytoplasm of liver cells. Cell bound pre-S1 encoded protein was often detected in patients with chronic liver disease and viremia. Only a small number of the HBsAg positive cells also contained pre-S1 antigen. There was no correlation with nuclear HBcAg. Livers of non-viremic HBsAg carriers contained many HBsAg expressing liver cells, that were frequently also positive for pre-S2 encoded protein but contained no detectable pre-S1 encoded protein at all. It remains open whether cell bound pre-S2 containing proteins of middle size have a significance for pathogenesis, as they are present in individuals with chronic liver disease as well as in healthy HBsAG carriers, and may be associated with both increased and normal liver enzymes. Cell bound pre-S1 antigen with viremia may, however, be involved in the maintenance of viremia and liver disease.

Biopsy↗
PubMed1987

Discontinuation of immunosuppressive therapy in hepatitis B surface antigen-positive chronic hepatitis: effect on viral replication and on liver cell damage.

Immunosuppressive therapy was stopped in 12 individuals positive for hepatitis Be antigen (HBeAg) and hepatitis B surface antigen (HBsAg) and in 4 individuals positive for HBsAg but negative for HBeAg. Discontinuation of immunosuppressive therapy in HBeAg-positive patients was always associated with a bout of hepatitis and elimination of HBeAg in 8/12 patients. One patient died from liver failure and 2 patients experienced a decompensation of their liver disease indicating that this approach might be harmful if used therapeutically. A bout of hepatitis was not noted in any of the individuals negative for HBeAg when the immunosuppressive therapy was stopped, implying that this event is not potentially harmful to the patient.

Adult↗
PubMed1987

Virus-associated receptors for polymerized human serum albumin (RpHSA) in patients with chronic active hepatitis B treated with recombinant leukocyte A interferon.

Hepatitis B surface antigen (HBsAg)-associated receptors for polymerized human serum albumin (RpHSA) are assumed to mediate viral attachment to hepatocytes in hepatitis B virus (HBV) infection. RpHSA was found to be coded by the pre-S region of HBV genome. Recently, the antiviral effect of recombinant leukocyte alpha-interferon was shown in patients with hepatitis B. Our study evaluated the detection and the clinical implications of RpHSA in patients with chronic active hepatitis B under treatment with recombinant alpha-interferon. Two out of nine patients eliminated all HBV markers including RpHSA. Four out of nine patients became negative for markers of viral replication but remained positive for HBsAg and in part for RpHSA. In three out of nine patients HBV markers including RpHSA remained unchanged. In summary, the titer for RpHSA is a reliable indirect marker for infectivity and of prognostic value in patients with chronic active hepatitis B during interferon treatment. Future studies should evaluate a putative immune response to RpHSA-containing viral surface proteins, which could be relevant for viral clearance in HBV infection.

Adult↗
PubMed1987

Detection of hepatitis B virus markers in sera of asymptomatic hepatitis B surface antigen carriers with special emphasis to pre-S-encoded proteins.

Sera of asymptomatic hepatitis B surface antigen (HBsAg) carriers were analyzed for the presence of pre-S-encoded proteins. Four individuals with biopsy-proven chronic hepatitis uniformly expressed pre-S1- and pre-S2-encoded proteins. Individuals who had histologically normal or largely normal livers were heterogeneous with respect to expression of pre-S-encoded proteins. This heterogeneous expression of pre-S-encoded proteins occurred most likely due to difference in serum HBsAg concentration. Alternatively differences in pre-S gene expression need to be considered. Clinically the study indicates that expression of pre-S domains in serum is unrelated to viremia or chronic liver disease.

Carrier State↗
PubMed1987

Characterization of primary biliary cirrhosis (PBC) specific mitochondrial determinants by immunoblotting.

Antimitochondrial antibodies (AMA) are detected in up to 100% of patients with primary biliary cirrhosis (PBC); subtypes of AMA are disease specific. Sera from 21 patients with PBC and from 50 patients with various hepatic and non-hepatic diseases were tested for AMA by indirect immunofluorescence, radioimmunoassay for PBC-specific subtype anti M2 and characterized by western blot analysis and agarose-IEF-immunoblotting. Sera from patients with PBC reacted with up to 7 different mitochondrial polypeptides on western blots, mol. wt. 24,000-62,000 dalton. Sera from 50 patients with various hepatic and non-hepatic diseases did not react with these polypeptides. Sera with other AMA subtypes were included in this study (anti M1, anti M3, and anti M5). These mitochondrial polypeptides were associated with inner mitochondrial membranes (mitoplasts). Sonification led to a solubilization of several mitochondrial polypeptides (p 62, p 48, p 40, p 24). On agarose-IEF-immunoblotting sera from patients with PBC and 3 sera from patients with AMA positive cholestatic CAH but no other sera reacted with a protein band at pI 4.0; seven PBC sera reacted in addition with a protein band at pI 4.4. Western blot and agarose-IEF-immunoblotting are sensitive and specific tools to identify and characterize mitochondrial target antigens in PBC. Furthermore these techniques allow to study the clinical relevance of the heterogeneity of AMA in cholestatic liver disease.

Autoantibodies↗
PubMed1987

Identification of Goodpasture target antigens in basement membranes of human glomeruli, lung, and placenta.

Collagenase-digests of human glomerular (GBM), alveolar (ABM), and placenta basement membranes (PBM) were separated by gel filtration columns and the pools rich in Goodpasture antigens (GP) were identified by an antibody inhibition-ELISA. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting on nitrocellulose membranes was performed with each basement membrane preparation. Sera from patients with florid GP-syndrome and antibodies to glomerular basement membrane (anti-GBM antibodies) were incubated with nitrocellulose strips of GBM, ABM, and PBM. Immunoperoxidase staining revealed reactivity with target antigens of 24, 26, 44, and 50 kD in the GBM and of 44 and 50 kD in the ABM and PBM, respectively. No corresponding reactivity was observed using convalescent GP-sera, sera from patients with other immunological diseases or sera from healthy blood donors. The antigens were sensitive to reduction. We conclude, that antigens of similar molecular-weights can be identified by anti-GBM positive sera in human glomerular, alveolar and placenta basement membranes.

Adult↗
PubMed1987

Distinction between natural and pathological autoantibodies by immunoblotting and densitometric subtraction: liver-kidney microsomal antibody (LKM) positive sera identify multiple antigens in human liver tissue.

Using one-dimensional and two-dimensional immunoblotting techniques the reactions of sera from 14 patients with liver-kidney microsomal (LKM) antibody positive chronic active hepatitis (CAH) with human liver microsomal preparations was compared with the reaction of sera from 12 healthy persons and from five patients with systemic lupus erythematosus (SLE). All sera displayed a multiplicity of reactions. This demonstrates the presence of many autoantibodies in normal human sera. It could be shown that all sera react with the cytoskeletal antigens cytokeratin, actin and actomyosin. These reactions were more marked in the autoimmune sera, i.e. LKM-positive CAH and SLE. Densitometric subtraction was found to be a reliable technique to distinguish the natural antigen/autoantibody reactions from pathological, disease-characteristic autoantibodies. It was shown that the pathological LKM autoantibodies recognize non species-specific microsomal proteins at 50 kD of pI 7.5-8.0 at high titres, which are only very weakly recognized by normal or SLE sera. We recommend sensitive immunoblotting techniques and densitometric subtraction as the currently most accurate method to distinguish natural from pathological autoantibodies.

Autoantibodies↗
PubMed1986

[Myxoma of the right atrium. Rare differential diagnosis of fever of unknown origin].

Cholecystectomy had been performed in a 52-year-old woman because of upper abdominal pain with nausea, fever and accelerated ESR and known cholelithiasis. Attacks of fever up to 39.5 degrees C persisted and she lost 10 kg in weight, requiring re-admission after eight months. Transoesophageal echocardiography revealed an echo-dense space-occupying lesion, 3.0 X 3.5 cm, in the right atrium. Due to contrast medium allergy angiography was omitted. M-mode and 2D echocardiography and computed tomography of the heart failed to demonstrate any space-occupying body. Thoracotomy revealed a fibro-angio-myxoma attached to the right side of the interatrial septum, and it was removed in toto. The postoperative course was without complications and the patient left hospital free of symptoms. It is suggested that transoesophageal echocardiography should be considered in case of "fever of unknown origin".

Diagnosis, Differential↗
PubMed1986

[Neurocysticercosis. Diagnostic and therapeutic advances].

A 42-year-old man of Croatian birth, with long-standing neurological symptoms, was found to have neurocysticercosis (a rare disease in Central Europe), as proven by positive antibody titres in serum and CSF and typical foci by computed tomography (CT). Ventriculo-cisternal drainage (after Torkildsen) controlled the acute symptoms of raised intracranial pressure. Postoperatively the CT revealed new low-density intracerebral foci, which responded to praziquantel.

Adult↗
PubMed1986

[Pancreas divisum: predisposition to chronic pancreatitis caused by chronic secretory stasis? Results of endoscopic intraductal pressure measurements].

In 6 patients with upper abdominal pain of unknown origin presenting with pancreas divisum, the pressure in the pancreatic duct was measured via the minor papilla into which in these patients the main part of the pancreatic duct system drains. For comparison intraductal manometry via the major papilla (papilla of Vater) was performed in 8 patients with normal pancreatic duct system. The pressure in the pancreatic duct of the control group was 10.5 +/- 0.9 (8-14) mm Hg, whereas in the patients with pancreas divisum it was 23.7 +/- 1.3 (20-28) mm Hg. The results demonstrate that in patients with pancreas divisum intraductal pressure may be largely increased even in the fasting state.

Adult↗
PubMed1986

Effect of modern analgesic drugs (tramadol, pentazocine, and buprenorphine) on the bile duct sphincter in man.

Modern narcotic analgesic drugs, such as tramadol, pentazocine, and buprenorphine share similarities of molecular structure with morphine which is widely believed to cause spasm of the bile duct sphincter and so impede bile flow. This study assessed the effects of intravenously administered analgesics on bile duct sphincter motor activity measured by ERCP manometry. Ten minutes after pentazocine injection the duration of contractions and baseline pressure of the bile duct sphincter rose from 6.2 +/- 0.2 to 8.2 +/- 0.27 s and from 5.1 +/- 0.6 to 8.8 +/- 0.4 mmHg respectively. Tramadol, buprenorphine and saline showed no such effect. These data indicated that the effects of such drugs on bile duct sphincter function can be safely assessed by ERCP manometry and that pentazocine adversely affects the bile duct sphincter, whilst tramadol and buprenorphine do not. We consider therefore that pentazocine is not the premedication of first choice for endoscopic procedures involving the sphincter of Oddi and should also be avoided in patients with pancreatic and biliary disorders.

Adult↗
PubMed1986

HBsAg clearance in patients with long-standing chronic active hepatitis B and hepatitis B virus-induced liver cirrhosis.

During a period of 3 years we observed 5 patients with chronic active hepatitis B and 2 with hepatitis B virus-induced liver cirrhosis who cleared HBsAg from their sera after 2-14 years of HBsAg carriership. 4 of them developed anti-HBs. After HBsAg clearance there was no evidence of persisting inflammatory activity within their livers. 5 of the 7 patients had been treated for 1-39 months with prednisolone, sometimes in combination with azathioprine. This therapy, however, had been stopped more than 3 years before these patients terminated their HBsAg carriership. Our observations indicate that even after long-standing chronic active hepatitis B or hepatitis B virus-induced liver cirrhosis HBsAg may be eliminated in a considerable number of patients.

Adult↗