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Biomedical subjects

K H Wiedmann

Publications and source records attributed to K H Wiedmann.

At least 19 recordsLinked to original sources
PubMed1994

Induction of autoimmune phenomena in patients with chronic hepatitis B treated with gamma-interferon.

All interferons display antiviral properties, but gamma-interferon especially has an immunomodulatory effect and may induce autoimmune phenomena. Therefore the formation of autoantibodies was investigated in patients with chronic hepatitis B treated with gamma-interferon. Eleven patients (all HBs-Ag and HBe-Ag positive) were treated for 6 months with recombinant gamma-interferon. The following antibodies were tested: anti-nuclear antibodies, smooth muscle antibodies, anti-actin, anti-mitochondrial antibodies of subgroup anti-M2 and anti-M9 as well as naturally occurring antibodies, antibodies to liver-kidney microsomes, vascular endothelial cell antibodies, sarcolemmal antibodies, parietal cell antibodies, thyroglobulin antibodies and antibodies to laminin and keratin. All patients produced autoantibodies during therapy. The maximum antibody formation and the highest titres were observed in the period between the 3rd and 6th month after therapy began. The cumulative frequencies of the different antibody specificities were as follows: n = 6 anti-nuclear antibodies, n = 7 smooth muscle antibodies, n = 1 anti-actin, n = 12 antibodies to laminin or keratin, n = 6 endothelial cell antibodies/sarcolemmal antibodies, n = 6 anti-mitochondrial antibodies, n = 1 antibodies to liver-kidney microsomes, n = 2 thyroglobulin antibodies, n = 4 parietal cell antibodies. Antibodies persisted in six patients over a period of 3 months (two cases of parietal cell antibodies and one case of antibodies to liver-kidney microsomes) and were still detectable in three patients 6 months after therapy. In three patients new antibody formation occurred 1 month after therapy. So far, clinical signs of an autoimmune disorder have not appeared in any of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1992

Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis.

The presence of perinuclear antibodies against neutrophils (pANCA) has been detected recently in sera of patients with inflammatory bowel disease and primary sclerosing cholangitis. In order to evaluate their clinical significance, sera from 126 patients with inflammatory bowel disease (80 Crohn's disease and 46 ulcerative colitis and 22 patients with primary sclerosing cholangitis were examined for pANCA by indirect immunofluorescence on liver sections and cytocentrifuge slides of neutrophils and by immunoblot. Perinuclear antibodies against neutrophils were found in 83% of patients with ulcerative colitis in 88% of patients with primary sclerosing cholangitis and inflammatory bowel disease, in 40% of patients with primary sclerosing cholangitis but without inflammatory bowel disease, and in 25% of patients with Crohn's disease using the immunofluorescence test. Titres of pANCA ranged from 1:10 to 1:1000 in ulcerative colitis and primary sclerosing cholangitis (median 1:100), whereas in Crohn's disease only four patients had titres of more than 1:10. The occurrence of pANCA did not correlate with clinical activity of Crohn's disease and primary sclerosing cholangitis whereas in ulcerative colitis high titres of pANCA were found mainly in active disease. Using an immunoblot system with sonified neutrophils as antigen, 82% of sera from patients with primary sclerosing cholangitis reacted with up to five different determinants, whereas only 12% of sera from patients with Crohn's disease and 11% of sera with ulcerative colitis detected one of the determinants, suggesting different antigens involved in pANCA reaction.

Adolescent↗
PubMed1991

[Cryptococcal meningitis in AIDS: successful long-term prophylaxis with fluconazole].

A 30-year-old, HIV-positive, man who had been repeatedly treated with amphotericin B for oral thrush, developed headaches, fever up to 38.5 degrees C, dizzy spells with falling tendency, as well as disorder of speech and word finding. Cerebrospinal fluid (CSF) contained 5700/3 cells, of which 90% were encapsulated yeast-fungus. Cryptococcal antigen titres were elevated both in serum (1:256) and CSF (1:1024), providing the diagnosis of cryptococcal meningitis. Intravenous treatment was started with amphotericin B, 0.3 mg/kg daily and flucytosine, 150 mg/kg daily. The clinical, microbiological and serological findings regressed after 4 weeks. After 8 weeks the creatinine concentration rose to 2.5 mg/dl. Because amphotericin B nephrotoxicity was suspected, further intravenous administration was stopped after a cumulative dosage of 2 g. He was placed on a prophylactic dosage of fluconazole, 100 mg by mouth twice daily. The cryptococcal antigen titre had fallen to normal within one year. The prophylactic regimen has been continued now for three years without recurrence or other fungal infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Methotrexate in the therapy of primary biliary cirrhosis].

In a pilot study 5 females with primary biliary cirrhosis (PBC), histological stages I-III, were treated with methotrexate (7.5-15.0 mg by mouth weekly) for 15 months. Pruritus and fatigue decreased in 3 patients and cholestyramine could be reduced or discontinued. The concentration of alkaline phosphatase decreased significantly until the 6th month of treatment (P less than 0.002), but only after the methotrexate dosage had been increased to 15 mg weekly. However, the improvement in cholestasis parameters persisted until the end of the period of observation in only 3 patients in stages I and II. In only one case, initially in stage III with increased serum bilirubin concentration of 3.5 mg/dl, was there a change in the histological stage, to stage IV, after treatment. These preliminary results indicate that methotrexate can influence the symptoms and cholestasis enzymes in the early stages of PBC. Controlled studies should therefore only be conducted on anicteric patients in an early stage of the disease.

Adult↗
PubMed1991

Antibodies to a trypsin sensitive pancreatic antigen in chronic inflammatory bowel disease: specific markers for a subgroup of patients with Crohn's disease.

The presence of antibodies against pancreatic juice (PAB) in patients with Crohn's disease has recently been reported. In our study sera from 273 patients with inflammatory bowel disease (222 with Crohn's disease, 51 with ulcerative colitis) have been examined for PAB and also for antibodies against gut tissues by means of indirect immunofluorescence. PAB were found in 68 of the 222 patients with Crohn's disease (31%), with titres ranging from 1/10 to 1/1280, and in only two patients with ulcerative colitis (4%), with titres of 1/20. None were found in 198 patients with various chronic inflammatory diseases and healthy control subjects. No differences were found between the PAB positive and negative patients when the following parameters were compared: disease activity (Crohn's disease activity index), involvement of bowel segments, incidence of extraintestinal disease, or treatment with anti-inflammatory drugs. Only seven of the patients with Crohn's disease had a history of pancreatic disease and of these, four had detectable pancreatic antibodies. Longitudinal observations of 40 patients with Crohn's disease showed a stable pattern for PAB, independent of disease activity and treatment. Partial characterisation of the PAB antigen, isolated from pancreatic juice, showed a trypsin sensitive macromolecular protein of more than 10(6) daltons not identical with a panel of defined exocrine pancreatic proteins. By contrast, antibodies against goblet cells (GAB) were found in 13 of 51 patients with ulcerative colitis (29%) and in none of the patients with Crohn's disease or control subjects. PAB were found as a highly specific serological marker for Crohn's disease and GAB for ulcerative colitis, but the relevance of PAB and GAB in the pathogenesis in Crohn's disease remains unclear.

Adolescent↗
PubMed1991

[Immunohistologic studies of differential HLA expression in patients with various intestinal diseases].

Histocompatibility antigens (HLA) play an important part in immunoregulation and in cell differentiation. This study analyses the expression of HLA class I and class II antigens (DR, DP, DQ) in intestinal biopsy specimen from patients with Crohn's disease, ulcerative colitis, GvHD, radiation colitis and intestinal adenomas using the indirect immunoperoxidase technique. 92 of 94 inflamed specimen from patients with inflammatory bowel disease showed a neoexpression of HLA II (DR greater than DP greater than DQ) on their epithelial cells. The intensity of HLA-DR neoexpression was significantly dependent on an endoscopic as well as a histological index of inflammation. All 75 non-inflamed specimen except 4 from patients with Crohn's disease did not show any evidence of HLA II display on the epithelium. 4 of 18 intestinal adenomas expressed HLA II on their epithelial cells without any correlation to the type of adenoma or the degree of cell dysplasia. Furthermore all specimen from a patient with intestinal GvHD showed an aberrant epithelial HLA II expression, but not that from radiation colitis. The expression of HLA class I antigens was similar in all biopsies studied. Our results suggest, that the epithelial neoexpression of HLA class II antigens may be an important event in the pathogenesis of various bowel diseases.

Biopsy↗
PubMed1990

Immunohistochemical demonstration of mitochondria in routinely processed tissue using a monoclonal antibody.

We report results obtained using the monoclonal antibody M-II 68, which recognizes inner mitochondrial membrane in routinely processed (formalin-fixed and paraffin-embedded) tissue by light microscopic immunohistochemistry. In ten normal brains, the range of immunoreactivity in various cell types and locations was defined. The most intense staining was observed in Purkinje cells, in neurons of cranial nerve nuclei, pons and substantia nigra, as well as in choroid plexus epithelial cells. By comparison with this control group, one case of primary mitochondrial encephalomyopathy exhibited increased staining of endothelial and vascular smooth muscle cells, choroid plexus epithelial cells, and neurons of various locations. Scattered ragged-red fibres were heavily labelled in one case of mitochondrial myopathy, while ten muscles without mitochondriopathy were left unstained. Our method is able to detect accumulations of mitochondria and increases in mitochondrial cristae density. It could prove useful for differential diagnosis of routine biopsy material and for clarification of cell types involved in mitochondrial cytopathies.

Adolescent↗
PubMed1990

Clonal analysis of infiltrating T lymphocytes in liver tissue in viral hepatitis A.

The pathogenic mechanism leading to liver tissue injury in hepatitis caused by hepatitis A virus is unclear. We have randomly established T-cell clones from liver biopsies from four patients with hepatitis A. A total of 578 clones was phenotypically analysed. During the acute phase of the disease CD8+ clones dominated over CD4+ clones, whereas in a biopsy taken late after onset of clinical syndromes more CD4+ than CD8+ clones were obtained. Interestingly, in a patient with a second exacerbation of the disease, more than 20% of all clones had the CD3+ WT31- CD4- CD8- 'NK-like' phenotype. All CD8+ clones had cytotoxic activity and approximately 50% of all CD8+ clones showed specific cytotoxicity against autologous fibroblasts infected with hepatitis A virus. The CD8+ cells also produced IFN-gamma in response to these target cells. Variable IFN-gamma production was observed with all types of T-cell clones. These results suggest that the liver injury in hepatitis A is not caused by a viral cytopathogenic effect but is due to an immunopathological reaction of sensitized cytotoxic T lymphocytes against infected hepatocytes. In addition, these studies show an enrichment of CD4-8-T-cell receptor alpha beta-chain-negative T lymphocytes at the site of an inflammation and suggest a role of these cells in an anti-viral reaction.

Acute Disease↗
PubMed1989

Ragged-red fibres detected in paraffin sections by a monoclonal antibody to inner mitochondrial membrane.

An immunohistochemical method is reported using the M-II68 monoclonal antibody, which detects mitochondrial accumulations ("ragged-red fibres") in routinely processed (formalin-fixed, paraffin-embedded) muscle tissue. Ten cases with electron-microscopically and histochemically proven mitochondrial myopathy featured 4% to 24% ragged-red fibres. In a series of 50 muscle biopsies without mitochondrial myopathy, scattered ragged-red fibres (less than 0.1%) were present in a few normal and pathological muscles. The immunohistochemical method is specific for mitochondria, does not require frozen tissue and permits rapid examination of large areas.

Antibodies, Monoclonal↗
PubMed1989

[Pathogenesis and clinical aspects of primary liver cell carcinomas].

The hepatocellular carcinoma is the most frequent primary liver cell carcinoma. On account of its geographical distribution with preferential occurrence in China, SE Asia and South Africa, exogenic causes are thought to be mainly responsible for its aetiopathogenesis. Besides mycotoxins, the hepatitis B virus infection (HBV) is particularly important. Integration of HBV-DNS into the hepatic cell DNS is considered to be an initiatory step in hepatocarcinogenesis. Clinically the tumour usually becomes manifest by upper abdominal complaints. Curative treatment can be promising only with very small tumours which can be detected most safely via ultrasound examination and alpha-1-fetoprotein determination.

Carcinoma, Hepatocellular↗
PubMed1989

Liver-derived cytotoxic T cells in hepatitis A virus infection.

An autologous in vitro model was developed to analyze the immunologic cause of liver tissue injury during hepatitis A virus (HAV) infection. Human T lymphocytes infiltrating the livers of two patients with acute HAV infection were isolated from liver biopsy cores, cloned, and expanded in vitro. Procedures using a cell culture system with HAV-infected autologous skin fibroblasts demonstrated that 42% and 53% of the liver-infiltrating CD8+ clones were HAV-specific and that they kill HAV-infected skin fibroblasts in a human leukocyte antigen-restricted manner. Data show virus-specific killing by liver-infiltrating T lymphocytes in man and support the hypothesis that liver cell injury in acute HAV infection is mediated by HAV-specific CD8+ T lymphocytes and is not caused by a cytopathic effect of the virus itself.

Adult↗
PubMed1988

Human gamma interferon production by cytotoxic T lymphocytes sensitized during hepatitis A virus infection.

The production of interferon (IFN) during a chromium-51 release assay with hepatitis A virus (HAV)-infected fibroblasts and autologous peripheral blood lymphocytes from patients with acute HAV infection was studied to determine whether IFN plays a role in immunopathogenesis of hepatitis A infection in humans. Skin fibroblasts of eight patients after acute HAV infection and from two control persons without history of current or past HAV infection were infected with HAV. Peripheral blood lymphocytes were collected at different times after the onset of icterus and tested in a chromium-51 release assay against autologous HAV-infected skin fibroblasts for their cytolytic and IFN-producing activity. The IFN produced during the assay was characterized and found to have the properties of human gamma IFN. Cytotoxicity and gamma IFN release were virus specific. The cell types responsible for both functions were characterized and found to be in the HLA-dependent T8+ lymphocyte subset. Considering that gamma IFN has an antiviral effect on persistent HAV infection in vitro and that it probably accounts for stimulation of HLA class I antigen expression on hepatocytes, our experimental results presented here demonstrate that human gamma IFN produced by HAV-specific T cells may participate in pathogenesis of hepatitis A infection in humans.

Cells, Cultured↗
PubMed1985

Serum inhibitory factors (SIF) are of prognostic value in acute viral hepatitis.

Serum inhibitory factors (SIF) were analysed in relation to the natural course of acute viral hepatitis in 81 patients followed over a period of 1 year. 63 patients recovered completely (group 1), and 18 had a protracted course of hepatitis (group 2) as shown by persistent transaminase activity 6 months after onset. 11 patients in group 2 still had signs of liver disease after 1 year. A gradual fall of SIF activity (in 47 patients) heralded resolving hepatitis, whereas persistence of SIF (in 8 patients) correlated with inflammatory activity and failure of hepatitis B viral antigen elimination. Absence of SIF activity was associated with either an uncomplicated or a chronic course of hepatitis in 23 and 3 patients, respectively. Repeated determination of SIF may help to predict the final outcome of hepatitis. Both excessive and failure of SIF production may result in the development of chronic liver disease.

Acute Disease↗
PubMed1985

Basement membrane proteins and type III procollagen in murine schistosomiasis.

The livers of female CBA mice were examined 9 to 10 weeks after subcutaneous infection with Schistosoma mansoni. Cryostat liver sections and isolated liver cells were examined by indirect immunofluorescence using specific antibodies against basement membrane proteins (laminin, fibronectin and type IV collagen and type III collagen precursor. Liver cells were isolated by collagenase digestion, purification on Percoll density gradients and centrifugal elutriation to yield enriched fractions of hepatocytes, endothelial and Kupffer cells (Fractions I, II, III respectively). Infected animals yielded more than three times the control number of non-parenchymal cells; electron microscopy revealed that the increase in Fraction II was due mainly to eosinophilic leucocytes and in Fraction III due to Kupffer cells and macrophages from the schistosomal granulomata. Studies of cryostat liver sections showed that the schistosomal granulomata contained dense deposits of type III collagen precursor and fibronectin in the distribution of the reticulin fibres but laminin and type IV collagen were conspicuous only in new vessels in the periphery of the granuloma. Isolated liver cells showed fibronectin on their surface. Immunofluorescence studies could not be performed on Kupffer and endothelial cell fractions because of marked non-specific fluorescence. These experiments indicate that centrifugal elutriation is a useful method for isolating the constituent cells of murine schistosomal granulomata.

Animals↗