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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 163 records · Page 9Linked to original sources
PubMed2000

Autoantibodies to tissue transglutaminase are sensitive serological parameters for detecting silent coeliac disease in patients with Type 1 diabetes mellitus.

AIMS: To investigate the clinical significance of the determination of IgA antibodies to tissue transglutaminase (tTG) for the detection of silent coeliac disease in patients with Type 1 diabetes mellitus. METHODS: A total of 520 patients with diabetes (median age 14.2 years, range 1-27) were tested for IgA antibodies to tTG (IgA anti-tTG, ELISA), endomysium (EmA, indirect immunofluoresence) and gliadin (IgA-AGA, enzyme immunometric assay) after ruling out IgA deficiency. RESULTS: The prevalence of IgA anti-tTG among patients with diabetes was 4.4% (23 of 520), and that of EmA and IgA-AGA 3.5% (18 of 520, respectively). The coefficient of agreement between IgA anti-tTG and EmA was high (Cohen's kappa = 0.87, P < 0.001). Thirteen of the 23 IgA anti-tTG-positive patients underwent duodenal biopsy. Coeliac disease was confirmed in nine of 13 patients. One of them was negative for EmA and AGA, but positive for IgA anti-tTG. Retrospective annual determinations up to 8 years in six IgA anti-tTG-positive patients showed both permanent and transient elevations of the serological markers. CONCLUSIONS: These data show that a positive IgA antibody test to tTG is a more sensitive parameter than EmA for silent coeliac disease in patients with diabetes. Confirmatory small bowel biopsy, however, remains necessary for diagnosis as some patients with positive antibodies may be without histological changes.

Adolescent↗
PubMed2000

Gastrointestinal glutathione peroxidase prevents transport of lipid hydroperoxides in CaCo-2 cells.

BACKGROUND & AIMS: Gastrointestinal glutathione peroxidase (GI-GPx), 1 of the 4 types of selenium-dependent glutathione peroxidases, is expressed exclusively in the gastrointestinal system and has therefore been suggested to function as a barrier against the absorption of dietary hydroperoxides. METHODS: The selenium-dependent expression of GI-GPx and cytosolic GPx (cGPx) was analyzed by Western blotting. Transport of 13-hydroperoxy octadecadienoic acid (13-HPODE) was investigated in a CaCo-2 cell monolayer modulated in GI-GPx and cGPx by selenium restriction or repletion. Localization of GI-GPx in rat intestine was visualized by immunohistochemistry. RESULTS: Low but significant GI-GPx levels were detected in selenium-deficient CaCo-2 cells and in the gastrointestinal tract of selenium-deficient rats, whereas cGPx was completely absent. Selenium supplementation of CaCo-2 cells resulted in a 5-fold increase of GI-GPx protein, whereas total GPx activity increased by a factor of 13, with most of the GPx activity under selenium-adequate conditions being cGPx. Irrespective of the selenium status, 13-HPODE did not reach the basolateral side of an intact CaCo-2 cell monolayer. Depending on the selenium status, hydroperoxides damaged the monolayer as evidenced by loss of transepithelial resistance and paracellular diffusion of lucifer yellow. Only under these conditions was unmetabolized 13-HPODE detectable at the basolateral side. CONCLUSIONS: Low GI-GPx levels, as present in selenium deficiency, suffice to prevent transport of 13-HPODE. GI-GPx may thus function as a barrier against hydroperoxide absorption. cGPx contributes to balance major oxidative challenge.

Animals↗
PubMed2000

Hepatocellular carcinoma in Austria: aetiological and clinical characteristics at presentation.

BACKGROUND AND AIMS: The aetiology of chronic liver disease leading to hepatocellular carcinoma (HCC) and the clinical characteristics at the time of presentation vary considerably among different parts of the world and over time. The number of patients seen at our institution has increased as compared to a period 20 years earlier. We investigated baseline characteristics of patients with hepatocellular carcinoma such as cirrhosis, hepatitis virus markers, age at presentation and stage of the tumour in an area with low prevalence of viral hepatitis. METHODS: All 245 patients seen at the Department of Gastroenterology and Hepatology at the University of Vienna, Austria, from July 1991 to March 1998 were included in this retrospective study, and 19 different clinical characteristics were studied. RESULTS: The median age at detection of HCC was 63.3 years, and alcoholic liver disease (35.1%) and hepatitis C virus (HCV) infection (36.7%) were the most frequent underlying diseases. Both chronic alcoholism and HCV infection as risk factors were present in 6.9% of the patients. Liver cirrhosis was present in 86.5%. At the time of diagnosis, 43.5% had multi-nodular tumours. Of the remaining patients with a single nodule, only 10% had HCC < or =2 cm. Most of our patients presented at a late stage of the disease (TNM stage 3 29.4%, TNM stage 4 69.7%; Okuda stage 2 65.7%, Okuda stage 3 18.0%). Due to the late stage of the disease at the time of presentation, 145 patients (59.2%) received palliative care only, 24 (9.8%) underwent liver resection, 38 (15.5%) liver transplantation and 38 (15.5%) chemotherapy. CONCLUSIONS: In this large single-centre series of HCC, the dominant contribution of HCV infection and chronic alcohol abuse as the underlying aetiology is documented. Diagnosis is usually made very late as reflected in the high proportion of patients in TNM stages 3 and 4 or Okuda stages 2 and 3. This resulted in a high percentage of patients who received palliative care only and very few who were eligible for treatment modalities with curative potential such as resection and liver transplantation.

Adult↗
PubMed2000

Gastric perforation of a left lobe amoebic liver abscess.

Liver abscess is the most common extra-intestinal manifestation of invasive amoebiasis. Perforation of the abscess is a potential life-threatening complication. We report a case where perforation into the stomach was successfully managed conservatively. The initial diagnosis in this case was made by gastroscopy and biopsy. To our knowledge, only five cases of gastric perforation of an amoebic liver abscess have been reported in the English literature. In none of these cases was the diagnosis established by histology of gastric biopsy specimens.

Adult↗
PubMed2000

Methylation of the cyclin A1 promoter correlates with gene silencing in somatic cell lines, while tissue-specific expression of cyclin A1 is methylation independent.

Gene expression in mammalian organisms is regulated at multiple levels, including DNA accessibility for transcription factors and chromatin structure. Methylation of CpG dinucleotides is thought to be involved in imprinting and in the pathogenesis of cancer. However, the relevance of methylation for directing tissue-specific gene expression is highly controversial. The cyclin A1 gene is expressed in very few tissues, with high levels restricted to spermatogenesis and leukemic blasts. Here, we show that methylation of the CpG island of the human cyclin A1 promoter was correlated with nonexpression in cell lines, and the methyl-CpG binding protein MeCP2 suppressed transcription from the methylated cyclin A1 promoter. Repression could be relieved by trichostatin A. Silencing of a cyclin A1 promoter-enhanced green fluorescent protein (EGFP) transgene in stable transfected MG63 osteosarcoma cells was also closely associated with de novo promoter methylation. Cyclin A1 could be strongly induced in nonexpressing cell lines by trichostatin A but not by 5-aza-cytidine. The cyclin A1 promoter-EGFP construct directed tissue-specific expression in male germ cells of transgenic mice. Expression in the testes of these mice was independent of promoter methylation, and even strong promoter methylation did not suppress promoter activity. MeCP2 expression was notably absent in EGFP-expressing cells. Transcription from the transgenic cyclin A1 promoter was repressed in most organs outside the testis, even when the promoter was not methylated. These data show the association of methylation with silencing of the cyclin A1 gene in cancer cell lines. However, appropriate tissue-specific repression of the cyclin A1 promoter occurs independently of CpG methylation.

Animals↗
PubMed2000

Inhibition of CD95/Fas-induced DNA degradation by osmotic cell shrinkage.

Apoptosis (programmed cell death) is an active physiological mechanism from which removal of abundant or potentially harmful cells follows. Apoptosis of lymphocytes is critical for the development of the immune system and during the immune response. As we have shown previously, moderate osmotic cell shrinkage interferes with CD95(Fas/Apo-1)-induced cell death. The present study has been performed to further elucidate the underlying mechanisms. To this end, apoptosis in Jurkat T-lymphocytes was elicited by triggering the CD95-receptor with monoclonal CD95/Fas-antibody. Osmotic cell shrinkage which was induced by the addition of 100 mM NaCl, did not significantly interfere with CD95-induced phosphatidylserine exposure nor the activation of caspase 3 activity as determined by PARP cleavage, DEVD-AMC consumption, or the activation of PAK2-kinase. However, osmotic cell shrinkage almost abolished CD95-induced DNA fragmentation (as revealed by propidium iodide staining) and the activation of a DNase as evidenced from SDS-PAGE gel assay. Western blot analysis showed CD95-induced tyrosine phosphorylation of a nuclear protein of ca. 20 kD which comigrated with nuclease activity. This tyrosine phosphorylation was almost completely abolished by the addition of 100 mM NaCl. Furthermore, osmotic cell shrinkage blunted the CD95-induced activation of the Src-like kinase p56lck. It is concluded that different signaling pathways mediate FITC-Annexin-V binding and DNase activation. Only the latter is sensitive to osmotic cell shrinkage.

Annexin A5↗
PubMed2000

Prevalence and distribution of hepatitis C subtypes in patients with opioid dependence.

UNLABELLED: AIM AND SETTING: The drug addiction out-patient clinic at the University Hospital for Psychiatry in Vienna performed a study to identify the prevalence of hepatitis C virus (HCV) infections in a group of opiate-dependent patients, to detect the distribution of HCV subtypes and to calculate the comorbidity of human immunodeficiency virus (HIV) and hepatitis B virus (HBV). DESIGN AND PARTICIPANTS: We consecutively investigated unselected patients (n = 173) during an observation period of 2 months with the diagnosis of opioid dependence (DSM-IV: 304.0) and polysubstance dependence (DSM-IV: 304.9). MEASUREMENTS: Blood was investigated focusing on liver enzymes and on viral status including HIV, hepatitis B and hepatitis C, followed by subtyping of the virus. FINDINGS: In 80.3% hepatitis C antibodies were found, 66.5% were HCV RNA (PCR) positive. 3a was the most frequent subtype (35.6%), followed by 1a (28.8%) and 1b (22.0%). Four patients had both subtypes 1a and 1b (6.8%), 3 were 2b positive (5.1%) and 1 patient had subtypes 2a/2c (1.7%). No significant difference in aspartate (AST) and alanine aminotransferases (ALT) concerning the different subtypes (AST: p = 0.290; ALT: p = 0.260) could be calculated; 11.6% showed co-infection with HIV, 2 patients had a chronic infection with hepatitis B. CONCLUSIONS: The rate of HCV infection in substance-dependent patients at our drug addiction out-patient clinic is extremely high. The distribution of subtypes showed a relatively homogeneous distribution of the types 1a, 1b and 3a. The recommended therapy with alpha-interferon should be initiated in drug-dependent patients under considerations of an enrollment in oral maintenance with synthetic opioids.

Adolescent↗
PubMed2000

Expression of intercellular adhesion molecule 1 (ICAM-1) on the human oviductal epithelium and mediation of lymphoid cell adherence.

The epithelium of the human oviduct expresses the major histocompatibility complex (MHC) class II and shows endocytic properties towards luminal antigens. Therefore, the epithelial cells might behave as antigen-presenting cells, inducing a local immune response. The activation of antigen-specific T cells not only requires presentation of the peptide antigen by MHC class II, but also the presence of co-stimulatory molecules in the antigen-presenting cells. Therefore, the expression of the intercellular adhesion molecule 1 (ICAM-1) was examined in the epithelium of the human oviduct. Most oviducts showed epithelial ICAM-1 expression, as assessed by immunocytochemistry, western blot analysis and RT-PCR assay, and the expression was restricted to the luminal border of ciliated and secretory cells. Interferon gamma, interleukin 1 and lipopolysaccharide treatments increased the percentage of ICAM-1-positive cells in primary cultures, indicating that the expression of ICAM-1 in the oviduct might be upregulated in vivo by inflammatory cytokines or bacterial infections. Binding assays between allogenic phytohaemagglutinin-activated lymphocytes and epithelial monolayers expressing ICAM-1 demonstrated that this molecule stimulated lymphocyte adherence. The presence of ICAM-1, in addition to MHC class II, supports the putative role of the oviductal epithelium in antigen presentation. The exclusive apical distribution of ICAM-1 indicates that T-cell activation would occur in a polarized manner. Binding of lymphoid cells to the surface of the oviductal epithelium may help to retain these immune cells that are required for the clearance of pathogens.

Adult↗
PubMed2000

Insulin-like growth factor induces up-regulation of AT(1)-receptor gene expression in vascular smooth muscle cells.

BACKGROUND: Insulin-like growth factor-1 (IGF-1), as well as AT1-receptor activation, plays a central role in growth processes of cardiac and vascular cells. In order to assess relevant interactions of both systems, the effect of IGF-1 on AT1-receptor expression was evaluated in vascular smooth muscle cells. METHODS AND RESULTS: Incubation of cultured vascular smooth muscle cells (VSMC) with IGF-1 led to a dose- and time-dependent up-regulation of AT1-receptor mRNA, as measured by Northern hybridisations. The maximal AT1-receptor overexpression of 201 +/- 70% of control levels was reached after a 24-hour incubation with 100 ng/ml IGF-1. Consequently, AT,-receptor protein expression was increased to 231 +/- 35% of control levels. Experiments under transcriptional blockade showed that AT1-receptor mRNA stability was not altered by IGF-1, suggesting that transcriptional mechanisms may be involved in IGF-1-induced AT1-receptor regulation. Preincubation with various pharmacological inhibitors revealed that IGF-1 up-regulated AT1-receptor expression via activation of p42/44 MAP kinase,whereas tyrosine phosphorylation and Pl-3 kinase seemed not to participate in this regulative pathway. CONCLUSIONS: IGF-l-induced up-regulation of the AT1-receptor maybe an important interaction by which cellular grow this modulated in the heart as well as in the vasculature. This may have implications for the treatment regimen of patients suffering from hypertension, cardiac hypertrophy, and coronary heart disease.

Animals↗
PubMed2000

Acute effects of ACE inhibition on coronary endothelial dysfunction.

The prerequisite of atherosclerosis, endothelial dysfunction, is characterised by impaired endothelium-dependent vasodilation caused by the reduced bioavailibility of nitric oxide (NO). In order to assess the role of acute ACE inhibition in this setting, coronary arterial endothelial function was quantified following acute intracoronary administration of the angiotensin-converting enzyme (ACE) inhibitor quinapril. Twenty-one patients with non-limiting coronary artery disease were studied before and after acute intracoronary administration of 10 mg quinapril. Nine patients received pre-treatment with the angiotensin AT(1)-receptor antagonist losartan (2 x 50 mg, p.o.). Coronary cross-sectional diameter was measured via quantitative angiography and microvascular reaction was investigated by intracoronary Doppler flow measurement during intracoronary infusion of 0.1 to 10 micromol/l acetylcholine. Quinapril acutely improved endothelial dysfunction on the macro- as well as the microvascular level. Losartan did not alter macrovascular function but facilitated microvascular endothelial function. Acute quinapril application led to no further improvement of endothelial dysfunction in patients pre-treated with losartan. Acute quinapril infusion improved endothelial function in patients with coronary heart disease. Treatment with the AT(1)-receptor antagonist losartan led to a slight improvement in microvascular endothelial function, but pre-treatment with losartan blunted the vascular effect of quinapril, suggesting that the combination of ACE inhibition and AT(1)-receptor antagonism may not exert a synergistic benefical impact on the coronary vasculature.

Angiotensin Receptor Antagonists↗
PubMed2000

[Rabies-free status of Switzerland following 30 years of rabies in foxes].

The European fox rabies epizootic starting in 1939 at the eastern border of Poland reached Switzerland on March 3, 1967. Rabies spread over large parts of the country until 1977, the year it caused three human deaths. In 1978 the first field trial world-wide for the oral immunization of foxes against rabies was conducted in Switzerland. Initially, the expansion of the vaccination area led to a rapid reduction in rabies cases. However, the 1990s were characterized by a recrudescence of rabies in spite of regular oral immunization of foxes. The last endemic case of rabies was diagnosed in 1996 after an adaptation of the vaccination strategy. A total of 17,109 rabies cases, of which 73% in foxes and 14% in domestic animals were diagnosed, leading to an estimated number of some 25,000 postexposure treatments in humans. To eliminate rabies, a total of 2.8 million baits containing a modified live virus were distributed--mostly by hand--in the field.

Animals↗
PubMed2000

[Isolation of Listeria spp. and Aspergillus fumigatus--two case reports from mastitis diagnosis].

Two rare cases of a bovine listeria mastitis and a mould mastitis are being described and discussed. The L. monocytogenes strains isolated from milk as well as silage samples were further genotyped by means of Pulsed-Field Gel Electrophoresis (PFGE) and macrorestriction analysis (ApaI). Three strains from the silage and four strains from quarter milking showed an identical PFGE-pattern.

Animals↗
PubMed2000

Idiothetic orientation and path integration in unilateral hippocampal atrophy and sclerosis.

We determined the effects of hippocampal lesions on idiothetic spatial orientation by exposing 14 patients with unilateral hippocampal atrophy and/or sclerosis (HAS) and 10 normal controls to random rotational displacements (+/-30 degrees -180 degrees ) in darkness and examined their ability to rotate themselves back to the initial position. In comparison to controls, the patients responses were distinctly hypometric (p<0.005). Patients with right hippocampal lesions showed a trend towards higher come back errors p = 0.08). Normal controls could maintain their accuracy over five consecutive trials. Patients, beginning with less accuracy, showed significant improvement after each trial (p<0.001). The findings suggest that unilateral HAS impair the immediate recall of idiothetic spatial information, but does not affect long-term spatial learning.

Adult↗
PubMed1999

c-myb transactivates the human cyclin A1 promoter and induces cyclin A1 gene expression.

Cyclin A1 differs from other cyclins in its highly restricted expression pattern. Besides its expression during spermatogenesis, cyclin A1 is also expressed in hematopoietic progenitor cells and in acute myeloid leukemia. We investigated mechanisms that might contribute to cyclin A1 expression in hematopoietic cells. Comparison of cyclin A1 and cyclin A promoter activity in adherent and myeloid leukemia cell lines showed that the cyclin A1 promoter is preferentially active in myeloid cell lines. This preferential activity was present in a small, 335-bp cyclin A1 promoter fragment that contained several potential c-myb binding sites. Coexpression of a c-myb expression vector with the cyclin A1 promoter constructs significantly increased the reporter activity in adherent CV-1 as well as in myeloid U937 cells. Gel-shift assays demonstrated that c-myb could bind to the cyclin A1 promoter at a binding site located near the transcription start site. Site-directed mutagenesis of this site decreased promoter transactivation by 50% in both KCL22 cells that express high levels of c-myb and in CV-1 cells that were transfected with c-myb. In addition, transfection of primary human embryonic fibroblasts with a c-myb expression vector led to induction of the endogenous cyclin A1 gene. Taken together, c-myb can directly transactivate the promoter of cyclin A1, and c-myb might be involved in the high-level expression of cyclin A1 observed in acute myeloid leukemia. These findings suggest that c-myb induces hematopoiesis-specific mechanisms of cell cycle regulation.

Base Sequence↗
PubMed1999

Lung procurement by low-potassium dextran and the effect on preservation injury. Munich Lung Transplant Group.

BACKGROUND: This clinical study was performed to evaluate the effect of low-potassium dextran (LPD) solution on organ function in human lung transplantation. METHODS: A total of 80 patients were included in this study. Donor lungs were flushed with Euro-Collins (EC) solution in 48 cases or LPD (Perfadex) in 32 cases. Subsequently, single- (EC: n = 31; LPD: n = 15) or double-lung transplantations (EC: n = 17; LPD: n = 17) were performed. The evaluation parameters of transplant function were the reperfusion injury score (grade I to V); the alveolar/arterial oxygen ratio; the duration of respirator therapy; and the length of intensive care treatment and survival. RESULTS: Incidence and severity of reperfusion injury score were more severe in the EC group (31 of 48: grade I: n = 13; II: n = 8; III: n = 5; IV: n = 2; V: n = 3; LPD group: 17 of 32 patients; grade I: n = 12; II: n = 1; III: n = 3; IV: n = 0 grade V: n = 0), leading to death in three patients. In the LPD group, despite of the use of cardiopulmonary bypass, alveolar/arterial oxygen ratio values were significantly (P = 0.009) better during the early postoperative phase. Thirty-day mortality was 12% in the EC group and 6% in the LPD group. The one-year survival rate was 79% after the use of LPD (vs. EC: 62%). CONCLUSIONS: Graft preservation using LPD leads to better immediate and intermediate graft function after pulmonary transplantation and also results in better long-term survival.

Adult↗
PubMed1999

[Angioplasty in heart arrest].

Early onset of cardiopulmonary resuscitation (CPR) and defibrillation are the most important factors for improving outcome after cardiac arrest. Many patients do not receive thrombolytic therapy after prolonged CPR, as there is a fear of serious bleeding complications. Ten patients with cardiac arrest and acute myocardial infarction were treated with primary angioplasty after prolonged CPR. Angioplasty was successful in nine of the patients, and left ventricular function was well preserved after six weeks. Primary angioplasty is highly effective and safe in establishing reperfusion in selected patients with acute myocardial infarction and cardiac arrest.

Adult↗
PubMed1999

Renaturation of heterodimeric platelet-derived growth factor from inclusion bodies of recombinant Escherichia coli using size-exclusion chromatography.

A procedure for renaturation of heterodimeric platelet-derived growth factor (PDGF-AB) from inclusion bodies of recombinant Escherichia coli using size-exclusion chromatography is described. Either prepurified or crude PDGF-AB inclusion bodies solubilized with guanidinium hydrochloride were subjected to buffer exchange from denaturing to renaturing conditions during chromatography. Renaturation of PDGF-AB involves folding of the solubilized and unfolded molecules into dimerization competent monomers during size-exclusion chromatography and subsequent dimerization of folded monomers into the biologically active heterodimeric growth factor. Optimized conditions result in an overall yield of 75% active PDGF-AB with respect to size-exclusion chromatography and subsequent dimerization. The described approach allows renaturation at high protein concentrations and circumvents aggregation which is observed when refolding is carried out by dilution.

Chromatography, Gel↗