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Biomedical subjects

M Manns

Publications and source records attributed to M Manns.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Prevalence of antibodies to hepatitis C virus among patients with cryptogenic chronic hepatitis and cirrhosis.

Many cases of chronic hepatitis and cirrhosis cannot be attributed to a known cause and are collectively referred to as cryptogenic chronic liver disease. We have evaluated the role of the hepatitis C virus in the pathogenesis of this condition in a retrospective serum analysis for antibody to hepatitis C virus in 129 patients with cryptogenic liver disease. Other causes of chronic hepatitis and cirrhosis were ruled out by clinical, serum biochemical and serological techniques. All 129 patients were HBcAg negative, but 28 (22%) had antibody to HBcAg. Sera were tested by radioimmunoassays using recombinant peptides for antibodies to nonstructural (C100-3 and C33c) and structural regions (C22) of HCV. Among the 129 patients, 61 (47%) had antibody to C100-3, 76 (59%) had antibody to C33c and 74 (57%) had antibody to C22. Seventy-nine (61%) were reactive with at least one and 76 (59%) were reactive with at least two HCV peptides (this is the criterion used for hepatitis C virus antibody reactivity). A proportion of patients with chronic hepatitis and cirrhosis (55 of 91; 60%) similar to that of patients without cirrhosis (21 of 38; 55%) had hepatitis C virus antibody. No significant clinical, serum biochemical or histological differences were noted between the group of patients with hepatitis C virus antibody and those without this antibody reactivity. Thus more than half the patients with cryptogenic chronic liver disease had hepatitis C virus antibody, suggesting that chronic HCV infection plays a major role in the origin of cryptogenic chronic hepatitis and cirrhosis.

Adult↗
PubMed1992

Clinical significance of the polymerase chain reaction (PCR) assay in chronic HBV carriers.

PCR was evaluated as a clinical tool for use in accurate identification of the specific etiologic agent in chronic HBV carriers. The method was found to be valuable in diagnosis and for monitoring therapy, as well as for elucidation of genotypic variants of HBV in chronic HBV cases. By this means an HBV defective variant with alterations in the preS1/preS2 sequence was detected and is consequently described here.

Asia, Southeastern↗
PubMed1992

Hepatitis C virus (HCV) and autoimmune liver diseases.

Anti-HCV tests were positive in 18-45% of sera from patients with autoimmune chronic active hepatitis. High gammaglobulin levels may result in false positive results, however, some sera show true positivity. PCR testing of such sera is necessary in order to determine whether HCV is directly involved in specific forms of the disease.

Antigens, Viral↗
PubMed1992

Autoantibodies in experimental autoimmune hepatitis.

Experimental autoimmune hepatitis (EAH) can be induced in mice by immunization with syngeneic soluble liver antigens in complete Freund's adjuvant. It has previously been shown that autoreactive T cells play an important role in this animal model of autoimmune hepatitis. We have studied the occurrence of liver autoantibodies in EAH. Characteristic autoantibodies appeared several weeks after disease induction and antibody titres continued to rise when histological and biochemical signs of disease activity had already regressed. Autoantibodies in EAH seemed to recognize autoantigens other than those present in autoimmune chronic active hepatitis patients. We conclude that autoantibodies arise in experimental autoimmune hepatitis but that these autoantibodies do not play a critical role in the pathogenesis of the disease.

Animals↗
PubMed1992

Hepatitis C virus antibody secretion in vitro by peripheral blood lymphocytes.

A recombinant polypeptide corresponding to a virus-specific cDNA clone (c100-3) serves as the antigen for a hepatitis C virus (HCV) antibody assay. Previous investigations have shown an 80% prevalence of HCV antibodies in sera of patients suffering from post-transfusional chronic hepatitis non-A, non-B, but positive results were also obtained for 30 to 70% of sera from patients with chronic hepatitis B or autoimmune hepatitis. In this study we show that HCV antibodies are secreted by peripheral blood lymphocytes (PBL) in vitro. PBL from 12/35 patients with chronic non-A, non-B hepatitis and 1/6 patients with chronic active hepatitis B spontaneously secreted HCV antibodies in cell culture supernatants. The results were confirmed by neutralisation assay and ELISAs using recombinant and synthetic polypeptides derived from the c100-3 antigen and from the HCV core antigen. Two patients suffering from non-A, non-B hepatitis were negative for HCV antibodies in serum, but their PBL produced HCV c100-3 antibodies in vitro. PBL from patients suffering from autoimmune chronic hepatitis, primary biliary cirrhosis, toxic-liver injury and healthy blood donors did not produce antibodies to HCV c100 antigen irrespective of HCV antibody test results in their sera. Polyclonal B cell activation or mitogenic stimulation of T helper cells led to increased immunoglobulin synthesis by PBL in vitro, but did not lead to enhancement of specific HCV antibody production. In addition, HCV antibody production was not induced by these stimulation procedures in control lymphocytes. This spontaneous HCV antibody production in vitro suggests persistent antigenic stimulation of the B cells in vivo.

B-Lymphocytes↗
PubMed1992

In vitro secretion of specific antimitochondrial antibodies in primary biliary cirrhosis.

Antimitochondrial antibodies are present in the serum of virtually all patients with primary biliary cirrhosis. They have a well-defined antigen reactivity that is diagnostic for the disease. The role of these autoantibodies in the disease process remains to be defined. In this study we show that antimitochondrial antibodies can be produced in vitro by peripheral blood lymphocytes, that the cells producing antimitochondrial antibodies are present in the peripheral blood in a high frequency and seem to be maximally activated. Stimulation with pokeweed mitogen did not augment the in vitro production of antimitochondrial antibodies in patients nor did it induce the production of these antibodies by control lymphocytes. Thus, antimitochondrial antibodies are not simply an expression of polyclonal B-cell stimulation. The high frequency of maximally activated B-cells producing antimitochondrial antibodies suggests active antigenic stimulation.

Antibody Specificity↗
PubMed1992

Liver-infiltrating T helper cells in autoimmune chronic active hepatitis stimulate the production of autoantibodies against the human asialoglycoprotein receptor in vitro.

Autoantibodies against the human asialoglycoprotein receptor (ASGPR) occur in the sera of patients with autoimmune liver disorders. Liver-infiltrating T cell clones that specifically recognize the ASGPR have been described in patients with autoimmune chronic active hepatitis (AI-CAH) and primary biliary cirrhosis (PBC). Recently, we have shown that peripheral blood mononuclear cells (PBMC) from patients with AI-CAH or PBC but not chronic viral hepatitis secreted anti-ASGPR antibodies in vitro. In this study we characterized the influence of liver-infiltrating T cells on the secretion of ASGPR-specific autoantibodies by autologous B cells in cell culture supernatants. T cell clones from liver biopsies of three patients with chronic autoimmune liver disorders (one with AI-CAH, two with PBC) were isolated and investigated for their proliferative response to soluble ASGPR and their helper function provided to autoantibody-secreting B lymphocytes. PBMC from these patients secreted autoantibodies spontaneously in their cell culture supernatants and showed a proliferative response to ASGPR. T cell-depleted PBMC, however, lacked spontaneous antibody secretion. Four CD4+CD8- liver-infiltrating T cell clones showed a proliferative response to ASGPR and also induced spontaneous anti-ASGPR antibody production in cell culture supernatants when added to autologous T cell depleted PBMC. Activated supernatants of these T cell clones failed to induce antibody production. None of seven CD4+CD8- and two CD4-CD8+ T cell clones non-responding to ASGPR provided this help for antibody secretion. Anti-ASGPR secretion in vitro could not be inhibited by the addition of MoAbs raised against monomorphic determinants on HLA class II molecules. The addition of purified ASGPR or polyclonal-activating pokeweed mitogen showed no influence on the production of autoantibodies in these cultures. These data show that B lymphocytes require T cell help for the production of ASGPR-specific antibodies. This help can be provided by ASGPR-responsive T helper cells via cellular interactions.

Adult↗
PubMed1992

M4 and M9 antibodies in the overlap syndrome of primary biliary cirrhosis and chronic active hepatitis: epitopes or epiphenomena?

Before the identification of the major mitochondrial antigens of primary biliary cirrhosis as components of the 2-oxo-acid dehydrogenase enzyme family, mitochondrial autoantigens were believed to be extremely heterogeneous and were divided into nine subtypes termed M1 to M9. This classification was based on the data derived from the relatively nonspecific biochemical and immunological techniques that were available. After the cloning and definition of the major autoantigens, more than 95% of the sera of patients with primary biliary cirrhosis were found to react with components of the 2-oxo-dehydrogenase enzymes; these enzymes correspond to the old M2 classification. Two other "M" species, dubbed M4 and M9, have attracted significant attention because they have been postulated to be prognostic indicators and more recently have been tentatively identified respectively as sulfite oxidase (EC 1.8.3.1) and glycogen phosphorylase (EC 2.4.1.1). Indeed, patients with the "overlap syndrome" are reported to have antibodies to M4 and a poor prognosis, whereas patients with antibodies to M9 have a favorable prognosis. To address the significance and definition of M4 and M9, we performed in-depth studies of sera from 11 patients with the overlap syndrome, 75 patients with primary biliary cirrhosis, 19 chronic active hepatitis patients, 13 patients with primary sclerosing cholangitis, 10 patients with cholangiocarcinoma, 20 patients with systemic lupus erythematosus, 20 patients with alcoholic cirrhosis, 17 patients with scleroderma and 30 normal individuals, using techniques of ELISA, complement fixation, immunoblotting and enzyme inhibition. We report herein that we were unable to show any disease-specific reactivity toward the proposed M4 and M9 antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Bile Duct↗
PubMed1992

[Eosinophilic gastroenteritis with serosa involvement. A rare differential diagnosis of ascites].

A 21 year old caucasian male suffered for 14 days from cramping abdominal pain, associated with nausea and vomiting. 6 weeks later he was admitted to our hospital because of rapidly increasing ascites. Further examinations led to the following decisive findings: Marked eosinophilia in the white cell count; marked eosinophilia in protein rich ascitic fluid; infiltration of serosal layer with eosinophils; no evidence for parasites in blood, faeces and ascites in multiple probes; no evidence for malignant or rheumatoid disease. Histology and cytology of probes obtained at laparoscopy led to the diagnosis of eosinophilic gastroenteritis with ascites. After low dose prednisolone therapy we observed a complete relief of symptoms and ascites disappeared.

Adult↗
PubMed1992

[Differential diagnosis of peptic ulcer].

Although new pathogenetic findings of peptic ulcers have been detected, there still remain some open questions. Accurate anamnestic evaluation will find out risk factors as cigarette-smoking, stress and therapy with nonsteroidal antiinflammatory drugs (NSAIDs), and will be helpful in differential diagnosis. Endoscopy is the diagnostic means of choice, and enables to easy helicobacter pylori detection. Since some gastric ulcers are actually carcinomas, it is absolutely necessary to obtain multiple biopsies. The Zollinger-Ellison syndrome and symptoms of other rare diseases of the upper intestine are discussed.

Diagnosis, Differential↗
PubMed1992

[Helicobacter pylori. New apsects in the pathogenesis of peptic ulcer disease].

Antral gastritis and peptic ulcer disease are closely related to gastric Helicobacter pylori (HP) infection. HP possesses several pathogenic features which point to a causal role of HP in the development of gastroduodenal lesions. It is now generally accepted that HP causes type B gastritis, while its role in the pathogenesis of peptic ulcers is still unsolved. According to the classical ulcer concept, peptic ulceration is the result of an imbalance between protective mucosal mechanisms and aggressive digestive factors. The identification of HP does not disprove this concept, however, HP has to be added as a major pathogenic factor.

Gastric Mucosa↗
PubMed1992

[Methodology and clinical significance of intragastric long-term pH measurement].

Intragastric long-term pH-metry is a suitable method of assessing gastric acidity under conditions of real life. The pH-metry system consists of three components: pH electrode, solid state recorder, and data analyzing system. Combined glass electrodes are recommended for gastric pH studies. Up to now, there are no generally accepted normal values in gastric pH-metry and thus data analyzing is not uniformly standardized. Intragastric pH-metry is the method of choice for monitoring of antisecretory treatment. This method enables the recognition of non-responders and improves dosing of antisecretory drugs. The prognostic value of gastric pH-metry in the assessment of acid-related diseases, if any, has still to be defined.

Gastric Acidity Determination↗
PubMed1992

[Complications of peptic ulcer].

The complication rate of peptic ulcer disease is 2 to 5% a year. Hemorrhage occurs four times more often than perforation and penetration. High age and the use of nonsteroidal antiinflammatory drugs (NSAID) are the most important risk factors. The incidence of rebleeding is twice as high after a first complication. About 15 to 30% of bleeding patients die because of this complication. Endoscopy is the means of choice in diagnosis and primary therapy. Gastric retention and vomiting of stale food are typical symptoms of gastric outlet obstruction.

Humans↗
PubMed1991

The eye in the brain: retinoic acid effects morphogenesis of the eye and pathway selection of axons but not the differentiation of the retina in Xenopus laevis.

We have analyzed the effects of all-trans retinoic acid (RA) on the morphogenesis, differentiation and projection of the eye of Xenopus. RA was applied in concentrations of 10(-5), 5 x 10(-6) and 10(-6) M at stages 9-17. Animals were reared until stages 40-48. RA applied before stage 11 1/2, abated completely formation of an eye or a retina, at later stages it led to the formation of microphthalmic eyes. Even in the absence of an eye parts of the forebrain had characteristics of the retina, but rods and cones reached then into the lumen of the third ventricle. The projection of eyes of RA-treated animals was revealed with rhodamine dextran amine. Ganglion cell axons projected bilaterally to the tectum, to the hindbrain, the contralateral retina and, occasionally, to the olfactory bulb. RA affects both morphogenesis of the eye and pathway selectivity of ganglion cell axons but not differentiation of the neural retina.

Animals↗