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Biomedical subjects

M Manns

Publications and source records attributed to M Manns.

At least 181 records · Page 10Linked to original sources
PubMed1982

[Antimitochondrial antibodies against the M2-antigen with immune vasculitis and discoid lupus erythematosus without proof of liver disease].

We have seen a 54-year-old patient with discoid lupus erythematosus and biopsy-proven vasculitis with granular deposits of complement and immunoglobulins in small subcutaneous vessels of clinically normal skin. Serologically, neither antinuclear antibodies nor antibodies against double-stranded DNA, Sm-Ag nor ribonucleoprotein could be demonstrated whereas the immunofluorescence test for antimitochondrial antibodies was positive during the whole observation period of 15 months. The further characterisation of the antimitochondrial antibodies by a newly described radio-immuno-assay demonstrated that the antibodies are directed against the primary biliary cirrhosis specific M2-antigen of mitochondria. So far, the patient, however, does not show any clinical or laboratory signs of primary biliary cirrhosis and a liver biopsy showed no evidence of that disease. It is discussed whether there is a coincidence of different autoimmunopathies or if the findings are symptoms of a single disease. Follow-up study might solve this open question.

Antigens↗
PubMed1982

Liver membrane autoantibodies: methods for their detection and clinical significance.

There is a growing evidence suggesting that immunological reactions against liver membrane antigens are involved in the process of ongoing hepatic injury in chronic active liver diseases (CALD). Liver specific lipoprotein (LSP) has been described as one of the target antigens of the liver cell membrane. Autoantibodies against LSP (anti-LSP) are predominantly directed against organ-specific determinants of a low density LSP subfraction (1.08-1.10 g/ccm). Anti-LSP detected in acute viral hepatitis are mainly directed against species-specific, whereas those in chronic active hepatitis are mainly directed against non-species-specific, determinants of the LSP complex. Further liver membrane autoantibodies were found to react with additional antigens of the hepatocellular membrane (LM-Ag). These liver membrane autoantibodies (LMA) are disease-specific for autoimmune type CALD. The detection of liver membrane autoantibodies by indirect immunofluorescence on isolated rabbit hepatocytes (LMA-test) is clinically important since this subgroup of CALD does well respond to immunosuppressive therapy. It is still unknown, however, whether these liver membrane autoantibodies are really involved in the immunopathogenesis of CALD via antibody dependent cellular cytotoxicity (ADCC) or whether they are a phenomenon secondary to liver cell destruction. Nevertheless they represent diagnostic markers by which one can classify subgroups of CALD with different etiologies. A further characterization of liver membrane antibody-antigen systems could lead to a more precise evaluation of the clinical relevance of liver membrane autoantibodies.

Antigen-Antibody Complex↗
PubMed1981

Studies on anti LSP autoantibodies in acute and chronic non-B hepatitis -- evidence for the lack of anti LSP in non-A, non-B (NANB) viral hepatitis.

The prevalence of autoantibodies against the liver membrane antigen LSP (anti LSP) has been studied in acute and chronic non-B hepatitis. Anti LSP autoantibodies were detected in five of eight patients with type A and in two of 18 patients with type non-A, non-B (NANB) acute hepatitis. No statistically significant difference was observed between the group of anti LSP positive and anti LSP negative cases of acute non-B hepatitis concerning age, serum glutamic pyruvic transaminase (SGPT), and serum bilirubin levels. In hepatitis A SGPT and bilirubin levels were significantly higher as compared to type NANB acute hepatitis. Sera which were positive for anti LSP in the acute phase were negative within 2 months from onset although the two anti LSP positive patients hepatitis (CPH). None of 27 patients with chronic NANB hepatitis displaying the morphology of CPH were anti LSP positive; in contrast, six of nine patients with autoimmune type chronic hepatitis were anti LSP positive, displaying the morphology of chronic active hepatitis. In conclusion, in acute hepatitis anti LSP autoantibodies are a consequence of liver cell destruction rather than being involved in the mechanism of liver cell necrosis. Anti LSP autoantibodies are unlikely to play an important role in the development of chronic NANB hepatitis.

Acute Disease↗
PubMed1980

Treatment of diabetes insipidus complicated by diabetes mellitus with chlorpropamide and clofibrate.

A patient with severe idiopathic diabetes insipidus, complicated by diabetes mellitus, was first treated with a combination o clofibrate and chlorpropamide. Urine volume dropped from 18 litres/day (CH2O = 10.5 ml/min) to 3.1-5.1 litres/day (CH2O = -0.1 -+1.1 ml/min) under treatment. Ten months after the beginning of therapy treatment was maintained with chlorpropamide alone; no significant rise in urine volume was observed. After 18 months when therapy was stopped for 5 days urine volume rose to 11.7 litres/day maximum (CH2O = 6.6 ml/min). No obvious side effects occurred under treatment during a follow up for over 18 months. Serum levels for arginine vasopressin before and under treatment were below 1.0 pg/ml. Determination of free water clearance (CH2O) proved to be a highly sensitive and simple method for follow up controls. It is discussed whether the coincidental manifestation of diabetes insipidus and diabetes mellitus may be caused by a single molecular lesion. This hypothesis is supported by data which imply that in both disease chlorpropamide acts via a common molecular mechanism, the blocking of endogenous prostaglandin E2 biosynthesis. Finally a treatment with oral "non-hormonal" drugs like clofibrate and chlorpropamide should be taken into consideration in some cases of diabetes insipidus as is demonstrated by this case report.

Adult↗
PubMed1980

Autoantibodies against liver-specific membrane lipoprotein in acute and chronic liver diseases: studies on organ-, species-, and disease-specificity.

A double antibody radioimmunoprecipitation test was used to detect anti-human LSP, anti-rabbit LSP, and autoantibodies against the human kidney equivalent of LSP (anti-HKP) in patients' serum. Anti-human LSP was found in 27/62 cases with chronic active liver disease (CALD), 9/16 cases with chronic persistent hepatitis (CPH), and 14/33 patients with acute viral hepatitis (AVH), 2/10 patients with ;inactive' cirrhosis of the liver (Ci), 4/14 patients with alcohol induced liver disease (ALD), 1/7 patients with miscellaneous liver diseases (MLD), and in 6/58 patients with primary non-hepatic autoimmune disease (PNHA). Frequencies of anti-LSP did not depend on HBsAg status. Anti-rabbit LSP was detected in only 9% of patients with AVH as compared with 42% for anti-human LSP. No such difference was observed in the other groups of patients. Anti-HKP was found in 6/62 patients with CALD, 1/7 patients with MLD, and 2/58 patients with PNHA; no anti-HKP occurred in patients with CPH, AVH, ALD, and Ci. The frequency of anti-LSP was not correlated with the presence of non-organ-specific autoantibodies in patients with CALD; furthermore, no correlation with sex-distribution, age, gammaglobulin levels, and SGOT occurred in this group of patients. No correlation existed between anti-LSP and liver membrane autoantibodies detected by indirect immunofluorescence on isolated rabbit hepatocytes (LMA). The reported data show that naturally occurring anti-LSP, characteristic for acute and chronic inflammatory liver diseases, are mostly directed against organ-specific determinants of the LSP complex. It is suggested that the occurrence of antibodies to species-specific determinants of LSP reflects a transient state of autoimmunity. The LMA immunofluorescence test seems to detect antibodies against other liver membrane antigens as well as LSP.

Antibody Specificity↗
PubMed1980

The liver specific protein: evidence for species-specific and non-species-specific determinants.

Liver specific protein (LSP) is known to be a macrolipoprotein of complete organ-specificity but without complete species-specificity. This membrane antigen is believed to play an important role in the pathogenesis of human and experimental chronic active hepatitis (CAH). In the present study, we investigated the species-crossreactivity of LSP by crossed immunoelectrophoresis, tandem crossed immunoelectrophoresis and fused rocket immunoelectrophoresis. With a sheep anti human LSP serum, two determinants of human LSP could be detected--one was found to be species-specific, the other crossreacted with rabbit, rat, swine and mouse LSP; no reaction was found with bovine and sheep LSP. A rabbit anti human LSP serum, after short term immunization, reacted only with a species-specific determinant of human LSP, no species-crossreactivity was observed. In contrast, rabbits with experimentally induced CAH, after longterm immunization with human LSP, had developed an autoantibody to rabbit LSP in addition to antibodies to the species-specific determinant of human LSP. Antibodies to the liver membrane antigen (LM-Ag) could not be detected. In conclusion human LSP contains a species-specific and a non-species-specific determinant. CAH in rabbits is induced by the loss of tolerance to the non-species-specific determinant.

Animals↗
PubMed1980

Detection and characterization of liver membrane autoantibodies in chronic active hepatitis by a solid-phase radioimmunoassay.

A solid-phase radioimmunoassay was developed to detect antibodies to liver membrane antigens in sera of patients with HBsAg-negative and -positive liver diseases and primary non-hepatic autoimmune diseases. Ten of fourteen patients with HBsAg-negative CAH had autoantibodies detected by RIA; negative results were obtained with sera of seven patients with HBsAg-positive acute and chronic liver diseases, six patients with miscellaneous liver diseases, including two patients with PBC, two healthy blood donors and seven patients with primary non-hepatic autoimmune diseases. Antibodies detected by RIA correlated with liver membrane autoantibodies (LMA) found by indirect immunofluorescence; no correlation was observed with AMA, ANA and SMA. Species-cross-reacting antibodies could be absorbed by preincubation with isolated plasma cell membranes prepared from rabbit livers. Liver membrane autoantibodies detected by RIA were directed against three different antigen fractions obtained from Sepharose 6B chromatography including LSP and LM-Ag. Only three of ten antibodies were directed against species-specific determinants; others cross-reacted with rabbit antigens. Only the antibody to LSP was organ-specific, all others cross-reacted with kidney proteins. Ferritin, human serum albumin and human plasma lipoprotein were excluded as target antigens. Although several sera reacted with identical molecules a remarkable heterogeneity of liver membrane autoantibodies was observed.

Adult↗
PubMed1980

[Induction and pathogenesis of chronic hepatitis experimentally induced in rabbits (author's transl)].

Studies of recent years have focussed on the immunopathogenesis of chronic liver diseases. Long-term immunization of rabbits with human liver proteins leads to liver lesions typical for human CAH. Delayed hypersensitivity against rabbit liver proteins, tested by skintest, correlated with the morphological changes of the liver. Circulating autoantibodies to liver specific protein, circulating immune complexes and IgG fixed in vivo to isolated hepatocytes could be observed before the liver lesions had developed histologically. The main target antigen in experimentally induced CAH seems to be an organ-specific but species-crossreacting macrolipoprotein with a molecular weight above 1 million, which is localized on the outer surface of the hepatocyte membrane. The liver specific protein (LSP) contains species-specific and non-species-specific determinants. Autoantibodies to non-species-specific determinants of LSP could only be detected in animals which had already developed CAH. Thus experimentally CAH in rabbits may be induced by the loss of tolerance to non-species-specific determinants of the LSP complex. Cell mediated and humoral immunity to LSP in man is found in HBsAg positive and HBsAg negative inflammatory liver diseases. Thus experimental CAH in rabbits seems to be a model for virus-induced and non-virus-induced chronic inflammatory liver diseases.

Animals↗
PubMed1979

LM-Ag and LSP--two different target antigens involved in the immunopathogenesis of chronic active hepatitis?

Two different types of immune reactions against liver membrane antigens have been described: firstly, cell-mediated immunity and autoantibodies against the liver-specific protein (LSP) in HBsAg-negative and HBsAg-positive chronic active hepatitis (CAH), and secondly, a liver membrane autoantibody (LMA) in HBsAg-negative CAH. Using 100,000 g supernatants of human and rabbit liver homogenates, the corresponding antigen of LMA could be separated by affinity chromatography on insolubilized LMA-positive sera from patients with HBsAg-negative CAH. A further characterization by crossed immunoelectrophoresis showed that LMA is directed against a soluble liver membrane antigen (LM-Ag) that is not a constituent of the purified LSP. LM-Ag seems to be species-unspecific and moves faster than LSP and serum albumin in crossed immunoelectrophoresis. While LSP is believed to be involved in the pathogenesis of HBsAg-negative and HBsAg-positive chronic active hepatitis, LM-Ag may be a target antigen only in cases of HBsAg-negative autoimmune CAH.

Antigens↗
PubMed1978

Digoxin and digitoxin elimination in man by charcoal hemoperfusion.

Since there is no widely used causal means of reducing the severity of massive digitalis intoxication the capability of hemoperfusion with coated activated charcoal to remove toxicologically relevant amounts of digoxin and digitoxin was evaluated in vitro and in man. At a blood flow rate of 100 ml/min the digoxin clearance by hemoperfusion in vitro was 51 +/- 8 ml/min in comparison to 24.3 +/- 11.3 ml/min by hemodialysis. The average hemoperfusion clearance of digitoxin was 31.7 +/- 13.4 ml/min, whereas almost no digitoxin was removed by hemodialysis. These clearance values point to the ability of hemoperfusion of eliminating digitalis glycosides from the blood. They do not clarify the essential question whether it is possible to lower the toxic concentrations in the tissues.

Charcoal↗
PubMed1975

Arrhythmias and inhibition of noradrenaline uptake caused by tricyclic antidepressants and chlorpromazine on the isolated perfused rabbit heart.

1. Isolated rabbit hearts were perfused with a modified Tyrode solution containing noradrenaline in concentrations increasing stepwise from 5.9 nM to 5.9 muM at 5 min intervals. This dose regime was applied twice before and once 20 min after starting perfusion with one of 9 tricyclic drugs. Ventricular rate and right atrial and ventricular tensions were recorded using the transverse method. 2. Infusions of noradrenaline evoked ventricular arrhythmias in hearts perfused with amitriptyline 4.8 muM, chlorpromazine 5.0 muM, desipramine 5.0 muM, dibenzepine 34.7 muM, doxepin 4.7 muM, imipramine 4.7 muM, noxiptiline 9.1 muM and opipramole 9.2 muM. The incidence of arrhythmias increased with the concentration of noradrenaline applied and the dose of tricyclic drug administered. Whenever arrhythmias had started they continued as long as noradrenaline was infused. Noradrenaline failed to produce arrhythmias in hearts not exposed to drugs and after iprindole 4.7 muM or cocaine 2.9-18 muM. 3. Propranolol 0.1 muM inhibited the incidence of arrhythmias after doxepin 4.7 muM plus noradrenaline 5.9-190 nM. 4. Neuronal uptake of exogenous noradrenaline in the rabbit heart was inhibited by the tricyclic drugs in the following order of declining p potency: doxepin, noxiptiline, amitriptyline, desipramine, chlorpromazine, imipramine, dibenzepine, opipramole and iprindole. 5. Among tricyclic drugs the potency to inhibit amine uptake is related to the incidence of arrhythmias evoked by a submaximal concentration of noradrenaline. It appears, however, that these two parameters are not causally linked. 6. The isolated rabbit heart perfused with noradrenaline might be used as a model for testing the arrhythmogenic actions of tricyclic drugs and the treatment of such arrhythmias.

Animals↗
PubMedDate not supplied

A mitochondrial antigen-antibody system in cholestatic liver disease detected by radioimmunoassay.

A radioimmunoassay (RIA) was established for the detection of antimitochondrial autoantibodies (AMAs) in patient sera. AMAs were detected by RIA in 12 of 14 patients with primary biliary cirrhosis and in 3 of 29 patients with chronic active hepatitis. AMAs were detected by indirect immunofluorescence in all sera positive by RIA. In addition, two patients with primary biliary cirrhosis and one patient with chronic active hepatitis were AMA positive when tested by indirect immunofluorescence, but negative when tested by RIA. AMAs were not detected by RIA or indirect immunofluorescence in 121 further patients with various hepatic and nonhepatic diseases, including healthy controls. The RIA detects an AMA directed against one determinant of a mitochondrial antigen which bears the characteristics of the previously described primary biliary cirrhosis antigen (M2 antigen). The RIA described is a sensitive and specific test for the detection of one mitochondrial autoantibody associated with chronic cholestatic liver diseases displaying the morphology of primary biliary cirrhosis in chronic active hepatitis or liver biopsy specimens. Antibodies against other mitochondrial antigens do not react in this assay system.

Adult↗
PubMedDate not supplied

Subtypes of antimitochondrial antibodies in primary biliary cirrhosis before and after orthotopic liver transplantation.

Antimitochondrial antibodies are markers for primary biliary cirrhosis and probably reflect a specific defect in immunoregulation underlying this disease. Antimitochondrial antibodies and their primary biliary cirrhosis-specific subtypes were tested before and up to 6 years after orthotopic liver transplantation. Sera from 31 consecutive patients were tested, 15 patients had primary biliary cirrhosis and 16 non-primary biliary cirrhosis. Antimitochondrial antibodies were investigated under code by immunofluorescence, and primary biliary cirrhosis-specific subtypes were determined by radioimmunoassay (anti-p62, anti-p48) and complement fixation test (anti-M2, anti-M4, anti-M8). Before orthotopic liver transplantation, antimitochondrial antibodies were detected by immunofluorescence in 13 of 15 patients with primary biliary cirrhosis. Of these patients, 12 were positive for anti-p62 and 8 for anti-p48. Ten patients were positive for anti-M2, 4 patients for anti-M4 and 7 patients for anti-M8. Two primary biliary cirrhosis patients and all non-primary biliary cirrhosis patients were negative with all tests. One month after orthotopic liver transplantation, antimitochondrial antibodies titers declined or became negative by antimitochondrial antibodies immunofluorescence, 3 patients became negative by radioimmunoassay for anti-p62 and 1 for anti-p48. With complement fixation test, 4 patients became negative for anti-M2, 2 for anti-M4 and 4 for anti-M8. Antimitochondrial antibody titer reduction observed 1 month after orthotopic liver transplantation remained unchanged in most sera during the following years. A rise was observed in two patients after 4 and 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

The effect of recombinant alpha-interferon treatment on serum levels of hepatitis B virus-encoded proteins in man.

The effect of alpha-interferon treatment on serum levels of hepatitis B virus-encoded proteins was analyzed in eight patients with chronic type B hepatitis who participated in a pilot study of interferon therapy. Three individuals became HBsAg-negative, 4 lost HBeAg but remained HBsAg-positive and 1 remained positive for both HBsAg and HBeAg. Initiation of interferon treatment was rapidly followed by reduction or loss of hepatitis B virus DNA in the serum but by little immediate change in hepatitis B virus antigen levels. Changes in hepatitis B virus antigens were usually delayed. Loss of HBsAg from the serum was preceded by the sequential disappearance of pre-S-encoded proteins (pre-S1 and polymerized human serum albumin) and HBeAg. In patients who lost HBeAg but remained HBsAg-positive, serum levels of pre-S1 and polymerized human serum albumin usually, but did not always, decrease. The individual who remained HBsAg- and HBeAg-positive had unchanged serum levels of pre-S1, polymerized human serum albumin and HBsAg. These results suggest that alpha-interferon inhibits hepatitis B virus DNA replication but has little direct effect on synthesis of hepatitis B virus gene products.

Adult↗