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C Trautwein

Publications and source records attributed to C Trautwein.

119 records · Page 7Linked to original sources
PubMed1993

Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domain.

One of the members of the bZIP family of transcriptional activators is NF-IL6/LAP (IL-6 DBP, C/EBP beta, CRP2). NF-IL6/LAP protein is highly expressed in liver nuclei, where it has been implicated as a master regulator of the acute-phase response, induced by interleukin-6 (IL-6) and other inflammatory mediators. Also, NF-IL6/LAP is involved in the activation of the IL-6 promoter in response to IL-1 and bacterial lipopolysaccharide. The control of NF-IL6/LAP expression and activity is complex and poorly understood. Under some conditions the NF-IL6/LAP gene is transcriptionally activated by IL-1 and lipopolysaccharide, whereas in other instances, its binding to cognate DNA sequences is enhanced by cytokines. Additionally, the ability of constitutively expressed NF-IL6/LAP to activate transcription is strongly augmented by IL-6, through an unknown signalling pathway. We now show that stimulation of the protein kinase C pathway increases the phosphorylation of Ser 105 within the activation domain of NF-IL6/LAP, and enhances its transcriptional efficacy.

Animals↗
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↗
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↗
PubMed1991

Clonal analysis of liver-infiltrating T cells in patients with LKM-1 antibody-positive autoimmune chronic active hepatitis.

Autoantibodies against microsomal antigen of liver and kidney (LKM-1) are diagnostic markers for a subgroup of autoimmune chronic active hepatitis (AI-CAH). Cytochrome P450dbl, now classified as cytochrome P450 IID6, is the major antigen of LKM-1 antibodies. Immunohistological studies suggest that hepatic injury in AI-CAH is mediated by liver-infiltrating T cells. In the present study the specificity and function of liver-infiltrating T cells was analysed at the clonal level. Phenotypical characterization of 189 T cell clones isolated from four liver biopsies of LKM-1 antibody-positive patients showed an enrichment of CD4+ CD8- T cell clones proliferated specifically in the presence of recombinant human LKM-1 antigen (rLKM). This reaction was restricted to autologous antigen-presenting cells and to HLA class II molecules. In order to see whether rLKM was also recognized by peripheral blood T lymphocytes (PBL) we tested the proliferative response of PBL from several individuals. PBL from three of the four patients with LKM-1 antibody-positive AI-CAH proliferated to rLKM, whereas no response was seen with PBL from patients with LKM-1 antibody-negative chronic liver diseases and from healthy blood donors. These data demonstrate that the LKM-1 antigen is recognized by liver-infiltrating T cells in LKM-1 antibody-positive AI-CAH. For further functional characterization, liver-derived T cell clones were tested for their cytotoxic activity. In the presence of phytohaemagglutinin 24 out of 26 CD4- CD8+ but also 20 out of 63 CD4+ CD8- T cell clones lysed autologous as well as allogenic EBV-transformed B cell lines or K562 cells. Five CD4- CD8+ T cell clones lysed autologous but not allogenic B cell lines spontaneously in a HLA class I-restricted manner. Although the antigen specificity of these clones is still unknown the data show the presence of autoreactive T cells at the site of inflammation that could contribute in the pathogenesis of AI-CAH.

Adolescent↗
PubMed1991

Candida arthritis: cellular immune responses of synovial fluid and peripheral blood lymphocytes to Candida albicans.

A case of septic Candida albicans arthritis of the knee in a patient with systemic candidiasis is presented. Systemic and intra-articular cellular immune responses to C albicans and various bacterial antigens were monitored for 15 weeks. It is shown that the candida induced blastogenesis of synovial fluid lymphocytes was much more stimulated than that of peripheral blood lymphocytes, and that the proportion of activated cells expressing HLA class II antigens was markedly increased in the synovial fluid. Strong cellular immune responses to Candida albicans could still be shown many weeks after the synovial fluid aspirates had become sterile. For the first time synovial fluid derived, CD4 positive T lymphocyte clones with specificity for candida antigens were characterised and further propagated in vitro.

Antibodies, Monoclonal↗
PubMed1990

[Retractile mesenteritis. Diagnostic and therapeutic aspects].

An 18-year-old boy, who had severe abdominal pain for 18 months associated with marked weight loss, was found to have a stenosed ileal sling on double-contrast radiology of the small intestine. At operation a plate-like tumour was extending from the pancreas to the aortic bifurcation. Histological examination of removed tissue revealed retractile mesenteritis (mesenteric panniculitis; liposclerotic mesenteritis). The symptoms regressed and the patient again gained weight under immunotherapy with 1 mg/kg of prednisone and 2 mg/kg of cyclophosphamide daily. Subsequently, under prednisone alone, there was a recurrence, which responded within five weeks to daily 60 mg prednisone and 125 mg cyclophosphamide. The patient remains symptom-free on 125 mg cyclophosphamide and 10 mg prednisone daily.

Abdominal Pain↗
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↗
PubMedDate not supplied

Two different subtypes of antimitochondrial antibodies are associated with primary biliary cirrhosis: identification and characterization by radioimmunoassay and immunoblotting.

Antimitochondrial antibodies from patients with primary biliary cirrhosis react with different mitochondrial polypeptides as demonstrated by Western blots. The IgG fractions of a patient with primary biliary cirrhosis Stage I reacting exclusively with a pair of polypeptides at 48,000 daltons (p 48) on Western blot and from a patient with Stage III primary biliary cirrhosis reacting exclusively with a single 62,000 dalton polypeptide (p 62) were labeled with 125I; two radioimmunoassays were established detecting antimitochondrial antibodies against p 62 and p 48, respectively. Autologous sera blocked the assay, but the two reference sera did not block each other. Fourteen of 40 patients with primary biliary cirrhosis reacted with p 62, 6/40 with p 48 and 20 sera with both antigens. Sera from 200 patients with various hepatic and nonhepatic diseases were negative for anti-p 62 and anti-p 48. This collection of sera included 5 patients with nonhepatic autoimmune disorders, 3 with drug-induced pseudolupus syndrome and 2 with syphilis II, which were positive for antimitochondrial antibodies by immunofluorescence. Mitochondrial autoantigens p 62 and p 48 were both localized on mitoplasts, presumably inner mitochondrial membranes; they were thermolabile, trypsin- and chymotrypsin-sensitive, but resistant to DNAase, RNAase and neuraminidase treatments. In cesium chloride density gradients, p 62 floated at 1.28 gm per cm3 and p 48 at 1.30 gm per cm3. Thus, radioimmunoassays have been developed that specifically detect two distinct primary biliary cirrhosis-specific subtypes of antimitochondrial antibodies: anti-p 62 and anti-p 48. All primary biliary cirrhosis sera were positive for at least one of these antimitochondrial antibodies subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Perihepatic lymphadenopathy: a marker of response to interferon alpha in chronic hepatitis C.

BACKGROUND/AIMS: Recently it was shown that perihepatic lymphadenopathy (PHL) correlates with histological activity in chronic hepatitis C. However, the question whether there is a correlation between the response to interferon alpha and PHL has not yet been raised. METHODOLOGY: We examined 103 patients who had been treated with interferon alpha for hepatitis C. Prior to treatment all patients had undergone high resolution ultrasonography. Thirty-six patients had follow up ultrasound scans during the course of the treatment. According to size and number of lymph nodes we introduced a grading of the PHL and determined grade I as minimal, grade II as medium and grade III as extensive PHL. RESULTS: Classification of PHL prior to treatment revealed 40 patients with PHL I, 30 with grade II and 33 with grade III. Hepatic inflammatory activity according to the Ishak score was increased in patients with PHL III (9.1+/-2.4) compared to PHL II (6.7+/-2.9) and PHL I (7.3+/-3.1) (p=0.01). In patients with PHL grade I prior to treatment 45% were initial responder, patients with grade II or III showed response rates of 40% and 33%, respectively. During therapy we found an increase of PHL in one out of 13 primary responder vs. 10 out of 23 non-responder (p=0.03). CONCLUSIONS: In conclusion, monitoring of PHL by abdominal ultrasonography is a simple, non-invasive and cheap additional marker of response to interferon alpha.

Adolescent↗