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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 19 recordsLinked to original sources
PubMed1999

The urinary ratio of 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid in surgical patients with chronic alcohol misuse.

The urinary ratio of 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid was reported to be elevated for a period of up to 22 h following acute alcohol ingestion. Therefore, the ratio could detect continuous alcohol consumption, in what was considered to be a high-risk surgical group, on the evening prior to surgery. The aim of this study was to determine the preoperative ratio of 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid in patients with continuous preoperative alcohol misuse. Forty-two patients participated in this institutionally approved study, once their written informed consent had been obtained. Chronic alcoholics were defined by meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders criteria and an ethanol consumption > or =60 g/day. The urine samples were taken preoperatively and determined by means of gas chromatography-mass spectrometry and high performance liquid chromatography. The urinary ratio of 5-hydroxytryptophol to 5-hydroxyindole-3-acetic acid was significantly increased in chronic alcoholics. The ICU stay of these patients was significantly prolonged due to an increased incidence of pneumonia and sepsis. Five chronic alcoholics died, whereas no deaths occurred in the nonalcoholic group (p = 0.05). As the measurement of the urinary ratio of 5-hydroxy-tryptophol to 5-hydroxyindole-3-acetic acid could detect alcohol consumption immediately prior to operation, this marker could assist the carbohydrate-deficient transferrin in screening for patients with high-level dependency; these patients were considered to be at a high risk of developing intercurrent complications.

Adult↗
PubMed1999

Secretion of human meprin from intestinal epithelial cells depends on differential expression of the alpha and beta subunits.

Human meprin (N-benzoyl-l-tyrosyl-p-aminobenzoic acid hydrolase, EC 3.4.24.18), an astacin-type metalloprotease, is expressed by intestinal epithelial cells as a dimeric protein complex of alpha and beta subunits. In transfected cells, intracellular proteolytic removal of the membrane anchor from the alpha subunit results in its secretion, while the beta subunit and alpha/beta heterodimers are retained at the cell membrane. We investigated the consequence of differential intracellular processing of alpha and beta subunits in the human small and large intestine using subunit-specific immunohistochemistry, in situ hybridization and biosynthetic studies in organ culture. In the ileum, both subunits localize to the brush-border membrane of villus enterocytes. In contrast, the beta subunit is not expressed in the colon, which leads to the secretion of the alpha subunit. We conclude that differential expression of meprin alpha and beta subunits is a unique means of targeting the proteolytic activity of the alpha subunit either to the brush-border membrane in the ileum or to the lumen in the colon, suggesting dual functions of cell-associated and luminal meprin. Meprin alpha and beta subunits are also coexpressed in distinct lamina propria leukocytes, suggesting an additional role for this protease in leukocyte function in the intestinal mucosa.

Colon↗
PubMed1999

Lovastatin induces p21WAF1/Cip1 in human vascular smooth muscle cells: influence on protein phosphorylation, cell cycle, induction of apoptosis, and growth inhibition.

Morbidity, mortality and the incidence of myocardial revascularisation procedures can be reduced by simvastatin, an inhibitor of the HMG-CoA reductase (EC 1.1.1.34). It was hypothesised that inhibition of isoprenylation of signalling proteins by HMG-CoA reductase inhibitors (vastatins), especially of the p21ras proteins could be causative for suppression of vascular smooth muscle cell (SMC) proliferation. The primary pharmacological mechanism of vastatins on human vascular SMC still remains unexplained. To analyse the influence of vastatins, SMC grown in presence of endothelial cell growth supplement (ECGS) were exposed to different concentrations of lovastatin. At 10 microM concentration, inhibition of SMC proliferation was associated with induction of apoptosis in a large fraction of cells as at the 1 microM level apoptosis was induced only in a minority of SMC. Protein phosphorylation on tyrosine, serine and threonine residues demonstrated no differences to untreated controls. Lovastatin induced arrest of cells in G0/G1 phase of the cell cycle and DNA synthesis was reduced. Western blot analysis demonstrated a significant induction of p21WAF1/Cip1 protein expression. This led to strong inhibition of cyclin dependent kinases (cdks) resulting in a cell cycle arrest. Our study provides evidence for a pharmacological explanation for the inhibition of ECGS-driven proliferation of human SMC by lovastatin.

Apoptosis↗
PubMed1998

Effect of ribose on cardiac adenine nucleotides in a donor model for heart transplantation.

Preservation time of explanted hearts is short. Cardiac function after transplantation declines dramatically in hearts that have been preserved for more than 4 to 6 hours. This has been linked to a critical decrease in high energy phosphates (HEP) after explantation. Ribose has previously been shown to stimulate HEP synthesis and to improve cardiac function. In this study, ribose was infused into 20 rats for 24 hours continuously before explantation (donor treatment) and also added to the solutions used for preservation. Saline was used in the control group. Myocardial tissue biopsies were taken after 24h of infusion and after 4h of preservation. High energy phosphates were determined by HPLC. Adenosine triphosphate content (ATP), energy charge and total adenine nucleotides (TAN) were significantly lower after 4h of preservation in both the ribose-treated and the control group compared to hearts before preservation. The difference in mean ATP concentrations between the 4 hours preserved ribose group and the control group was not significant. Single case analysis however revealed a minimum ATP level of 12.3 micromol/g dry weight in 10 ribose treated hearts whereas 2 out of 11 control hearts showed ATP levels below 10 micromol/g dry weight. - This study supports the hypothesis that ribose treatment is capable of maintaining ATP at a higher level in preserved rat hearts. Donor treatment and metabolic support with ribose during organ preservation may be suitable to prolong preservation time of donor hearts.

Adenine Nucleotides↗
PubMed1998

Prevalence of hepatitis G-virus infection in alcohol abusing patients with and without liver cirrhosis.

BACKGROUND: Hepatitis G (GBV-C/HGV) is an RNA-virus belonging to the flavivirus family and is capable of inducing hepatitis in rare cases. Its importance as a co-factor in the pathogenesis of liver disease needs to be clarified. AIMS: To determine the prevalence of HGV in chronic alcoholics with and without liver cirrhosis. PATIENTS: 86 alcoholics, 44 with liver cirrhosis and 42 without liver cirrhosis, were investigated; 93 healthy individuals served as controls. METHODS: Serum was tested for GBV-C/HGV-RNA by reverse-transcription polymerase chain reaction (RT-PCR) and for anti-E2, a marker of resolved GBV-C/HGV infection, by ELISA. GBV-C/HGV-RNA positive samples were sequenced and the GBV-C/HGV subtype determined. RESULTS: Eight out of 86 (9.3%) alcoholics were GBV-C/HGV-RNA positive, as compared to 2 out of 93 (2.2%) healthy controls (n. s.). Twenty-one (24.4%) alcoholics had anti-E2 in serum, whereas this antibody was found in 12 (12.9%) healthy persons only (n. s.). However, significantly more alcoholic patients (33.7%) than healthy controls (15.1%) had past or present contact with GBV-C/HGV (p = 0.006). 11.4% of alcoholic patients with liver cirrhosis and 7.1% of alcoholic patients without liver cirrhosis showed GBV-C/HGV-RNA. 34.1% of alcoholic patients with liver cirrhosis and 16.6% of alcoholic patients without liver cirrhosis had anti-E2. Among the 44 patients with liver cirrhosis, 8 out of 11 (72.7%) patients with variceal bleeding, but only 11 of 33 patients without bleeding had contact with GBV-C/HGV (p = 0.05). Seven out of 8 GBV-C/HGV-RNA positive alcoholics had genotype 2a, 1 had type 1a of GBV-C/HGV. CONCLUSION: Alcoholic patients have a significantly higher contact rate with GBV-C/HGV as compared to healthy controls. Alcoholics with liver cirrhosis tend to be more frequently infected than alcoholic patients without liver cirrhosis. A previous variceal bleeding episode is significantly associated with GBV-C/HGV infection.

Adult↗
PubMed1998

Postnatal development of neuron number and connections in the suprachiasmatic nucleus of the hamster.

We had previously found a ca. 30% cell death during the prenatal ontogeny of the suprachiasmatic nucleus (SCN) of lambs. The period of neuron death was preceded by the establishment of the retinohypothalamic connections, a major input to this nucleus that allows the entrainment to light of the circadian rhythms generated by the SCN. The present study determined the temporal relationship between the period of ontogenetic neuron death and the establishment of the principal afferent and efferent connections of the SCN in hamsters. We found that during the first 3 postnatal days the SCN volume increases mainly by the addition of cells. After a peak 6140 neurons on each side during the third postnatal day, the SCN underwent an acute decrease of about 40% in neuron number, which led to the final adult complement of neurons, estimated in 3400 neurons per nucleus. The connections of the SCN were studied by placing DiI crystals either into the optic nerve, or into the SCN of brains fixed at different ages. We found, in agreement with previous studies, that retinal axons can be detected after the fifth postnatal day, that is, after the large decrease in neuron number. As for the SCN efferents, they began to invade the appropriate targets during the second postnatal day, followed by a large increase in the density of these efferent projection in the subsequent days. In conclusion, the massive neuronal death in the SCN was preceded by the formation of efferent connections, and followed by the formation of the retinohypothalamic tract.

Aging↗
PubMed1998

L-selectin stimulates the neutral sphingomyelinase and induces release of ceramide.

Selectins have been shown to be crucial in the rolling process of leukocytes during lymphocyte homing and in the early phase of inflammatory processes. Recently, we and others have shown that binding of L-selectin to its ligands correlates with a rapid induction of several intracellular signaling molecules, in particular, Src-like tyrosine kinases, MAP-kinases, Jun NH2-terminal kinase, the small G-proteins Ras and Rac, and a release of Ca2+ in leukocytes. Here, we demonstrate the activation of a novel signaling pathway by L-selectin. Stimulation of Jurkat T-lymphocytes via L-selectin results in an increase of neutral sphingomyelinase activity. This activity correlates with a consumption of cellular sphingomyelin and a release of ceramide. The activation of the neutral sphingomyelinase by L-selectin does not depend on tyrosine kinase activity and, therefore, represents an alternative and novel pathway to stimulate lymphocytes via L-selectin.

Ceramides↗
PubMed1998

Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice.

Induction of differentiation and apoptosis in cancer cells through ligands of nuclear hormone receptors (NHRs) is a novel and promising approach to cancer therapy. All-trans-retinoic acid (ATRA), an RA receptor-specific NHR ligand, is now used for selective cancers. The NHR, peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in breast cancer cells. Activation of PPARgamma through a synthetic ligand, troglitazone (TGZ), and other PPARgamma-activators cause inhibition of proliferation and lipid accumulation in cultured breast cancer cells. TGZ (10(-5) M, 4 days) reversibly inhibits clonal growth of MCF7 breast cancer cells and the combination of TGZ (10(-5) M) and ATRA (10(-6) M, 4 days) synergistically and irreversibly inhibits growth and induces apoptosis of MCF7 cells, associated with a dramatic decrease of their bcl-2 protein levels. Similar effects are noted with in vitro cultured breast cancer tissues from patients, but not with normal breast epithelial cells. The observed apoptosis mediated by TGZ and ATRA may be related to the striking down-regulation of bcl-2, because forced over-expression of bcl-2 in MCF7 cells cultured with TGZ and ATRA blocks their cell death. TGZ significantly inhibits MCF7 tumor growth in triple immunodeficient mice. Combined administration of TGZ and ATRA causes prominent apoptosis and fibrosis of these tumors without toxic effects on the mice. Taken together, this combination may provide a novel, nontoxic and selective therapy for human breast cancers.

Adenocarcinoma↗
PubMed1998

Distribution of the mevalonate and glyceraldehyde phosphate/pyruvate pathways for isoprenoid biosynthesis in unicellular algae and the cyanobacterium Synechocystis PCC 6714.

Isopentenyl diphosphate, the universal isoprenoid precursor, can be produced by two different biosynthetic routes: either via the acetate/mevalonate (MVA) pathway, or via the more recently identified MVA-independent glyceraldehyde phosphate/pyruvate pathway. These two pathways are easily differentiated by incorporation of [1-13C]glucose and analysis of the resulting labelling patterns found in the isoprenoids. This method was successfully applied to several unicellular algae raised under heterotrophic growth conditions and allowed for the identification of the pathways that were utilized for isoprenoid biosynthesis. All isoprenoids examined (sterols, phytol, carotenoids) of the green algae Chlorella fusca and Chlamydomonas reinhardtii were synthesized via the GAP/pyruvate pathway, as in another previously investigated green alga, Scenedesmus obliquus, which was also shown in this study to synthesize ubiquinone by the same MVA-independent route. In the red alga Cyanidium caldarium and in the Chrysophyte Ochromonas danica a clear dichotomy was observed: as in higher plants, sterols were formed via the MVA route, whereas chloroplast isoprenoids (phytol in Cy. caldarium and O. danica and beta-carotene in O. danica) were synthesized via the GAP/pyruvate route. In contrast, the Euglenophyte Euglena gracilis synthesized ergosterol, as well as phytol, via the acetate/MVA route. Similar feeding experiments were performed with the cyanobacterium Synechocystis PCC 6714 using [1-13C]- and [6-13C]-glucose. The two isoprenoids examined, phytol and beta-carotene, were shown to have the typical labelling pattern derived from the GAP/pyruvate route.

Animals↗
PubMed1998

Over-expression of ICAM-1, VCAM-1 and ELAM-1 might influence tumor progression in colorectal cancer.

Adhesion molecules might play a role in tumor progression. We investigated expression of the adhesion molecules ICAM-1, VCAM-1 and ELAM-1 in 24 primary colorectal carcinomas using immuno-histochemistry and Northern blot analysis. Normal colonic tissue from the same patients served as controls. ICAM-1 immunostaining was restricted to the intercellular matrix and vascular endothelial cells. The vast majority of normal tissue samples revealed only faint ICAM-1 immunoreactivity. However, moderate to strong immunostaining was found in 86% of cancerous sections. The ICAM-1 immunoreaction was more intense in well-differentiated carcinomas as well as in the adenomatous parts and transition zones of cancers. Similarly, the cancers exhibited markedly enhanced VCAM-1 and ELAM-1 immunostaining in the endothelial cells of small blood vessels. The intense vascular immunostaining by ICAM-1 and VCAM-1 was associated with a strong presence of CD3-positive T lymphocytes, whereas ELAM-1 immunoreactivity did not correlate with round cell infiltration. On Northern blot analysis, ICAM-1, VCAM-1 and ELAM-1 mRNA levels were increased in 67%, 57% and 63% of carcinomas, respectively, in comparison with normal tissue samples. Densitometric analysis of Northern blots revealed an increase in ICAM-1 by 2.1-fold, an increase in VCAM-1 by 3.4-fold and an increase in ELAM-1 by 2.2-fold in cancerous tissues compared to normal controls. Over-expression of ICAM-I might prevent cell-cell disruption and, hence, tumor dissemination. Furthermore, over-expression of ICAM-1 and VCAM-1, but not ELAM-1, might favor host anti-tumor defense by trafficking of lymphocytes.

Adenocarcinoma↗
PubMed1998

[Angioplasty in acute myocardial infarction].

20 patients with acute myocardial infarction and a medical history of less than six hours were treated with immediate percutaneous transluminal coronary angioplasty. The median time from start of symptoms until establishment of reperfusion of the infarct related artery was 190 minutes, and the time from admission to insertion of the balloon was 52 minutes. Angioplasty was successful in all patients, with no serious complications. All patients experienced pain relief immediately after angioplasty. No patients died or had further infarctions. None needed hospitalization during the first three months of follow up. Eight patients had an exercise test between five and seven days after angioplasty and the other 12 at their six-week check up; there were no signs of ischemia or anginal pain. Measurement of global ejection fraction one week and six weeks after treatment showed median normal values and no significant changes (58% versus 57%). Myocardial perfusion imaging was carried out in eight patients both before hospital discharge and six weeks later. Normalization and improvement was seen in six patients using this method, whereas the perfusion was found unaltered in two patients. Hibernation or stunning, or both are suggested as possible explanations for this. We found the method highly effective and safe in selected patients.

Adult↗
PubMed1998

Alternative macrophage activation-associated CC-chemokine-1, a novel structural homologue of macrophage inflammatory protein-1 alpha with a Th2-associated expression pattern.

We have cloned a novel human CC-chemokine, alternative macrophage activation-associated CC-chemokine (AMAC)-1. The isolated cDNA clone (803 bp) shows a single open reading frame of 267-bp coding for 89 amino acid residues; mature AMAC-1 protein is predicted to consist of 69 amino acids with a m.w. of 7855. Sequence alignment and 3D-modeling show the typical structural characteristics of CC-chemokines with special features in the receptor-activating domain. AMAC-1 is most closely related to MIP-1 alpha with a cDNA and protein sequence homology of 55% and 59%, respectively. However, the expression pattern of AMAC-1 is directly opposite to that of MIP-1 alpha. While MIP-1 alpha is induced by classical macrophage mediators such as LPS and is inhibited by IL-4 and glucocorticoids, AMAC-1 is specifically induced in macrophages by alternative macrophage mediators such as IL-4, IL-13, and IL-10. Expression of AMAC-1 is inhibited by IFN-gamma while glucocorticoids exert a slightly positive synergistic effect in combination with IL-4. Peripheral blood monocytes do not express AMAC-1; time course experiments show that monocyte-to-macrophage differentiation is a prerequisite for AMAC-1 expression. Expression of AMAC-1 by granulocyte-macrophage CSF/IL-4-induced, monocyte-derived dendritic cells is complex; in mature adherent dendritic cells, however, only minor AMAC-1 mRNA expression was found. In vivo, AMAC-1 is expressed by alveolar macrophages from healthy persons, smokers, and asthmatic patients. In conclusion, AMAC-1 is a novel CC-chemokine whose expression is induced in alternatively activated macrophages by Th2-associated cytokines; thus, AMAC-1 may be involved in the APC-dependent T cell development in inflammatory and immune reactions.

Amino Acid Sequence↗
PubMed1998

Beta-galactoside-binding protein secreted by activated T cells inhibits antigen-induced proliferation of T cells.

We have used mRNA differential display PCR to search for genes induced in activated T cells and have found the LGALS1 (lectin, galactoside-binding, soluble) gene to be strongly up-regulated in effector T cells. The protein coded by the LGALS1 gene is a beta-galactoside-binding protein (betaGBP), which is released by cells as a monomeric negative growth factor but which can also associate into homodimers (galectin-1) with lectin properties. Northern blot analysis revealed that ex vivo isolated CD8+ effector T cells induced by a viral infection expressed high amounts of LGALS1 mRNA, whereas LGALS1 expression was almost absent in resting CD8+ T cells. LGALS1 expression could be induced in CD4+ and CD8+ T cells upon activation with the cognate peptide antigen and high levels of LGALS1 expression were found in concanavalin A-activated T cells but not in lipopolysaccharide-activated B cells. Gel filtration and Western blot analysis revealed that only monomeric betaGBP was released by activated CD8+ T cells and in vitro experiments further showed that recombinant betaGBP was able to inhibit antigen-induced proliferation of naive and antigen-experienced CD8+ T cells. Thus, these data indicate a role of betaGBP as an autocrine negative growth factor for CD8+ T cells.

Animals↗
PubMed1998

[Virtual and three-dimensional bronchoscopy with spiral and electron beam computed tomography].

PURPOSE: To compare spiral computed tomography (CT) and electron-beam CT (EBT) for 3D and virtual CT-bronchoscopy. MATERIALS AND METHODS: 17 patients with various disorders of the tracheobronchial system were examined using fiberoptic bronchoscopy, spiral CT and EBT. 3D images were reconstructed from CT data sets using automated segmentation based on volume-growing methods. Surface-rendered, volume-rendered, and hybrid reconstructions were visualized in real time using a data helmet. RESULTS: All data sets could be processed to high-quality three-dimensional (3D) and virtual reconstructions. The reduction of motion artifacts due to shorter scan times made EBT data sets better suited for automated segmentation and less susceptible to motion artifacts. 3D and virtual reconstructions did not increase the diagnostic sensitivity of CT compared to axial reconstructions alone. CONCLUSIONS: Shorter scan times of CT imaging yield higher-quality 3D and virtual reconstructions. Modern reconstruction techniques are valuable visualization tools for select indications and are the prerequisite for future developments in computer-aided medicine.

Bronchial Neoplasms↗
PubMed1998

Prevalence and course of psychiatric disorders among nursing home admissions.

Several studies have shown that psychiatric disorders are common in nursing homes, but information on the course of psychiatric morbidity shortly after admission is still lacking. Therefore, we interviewed 262 residents of Austrian nursing homes within 2 weeks following admission, and a second time after 6 months. Using the Clinical Interview Schedule and its case criteria, prevalence was 76.3% at admission, and 69.9% 6 months later. In the intervening period, the mortality rate was markedly higher among psychiatric cases, and the incidence of new psychiatric cases (5.9%) was slightly lower than the rate of remission (8.6%). At both assessments, organic mental illness was the most frequent diagnosis. Nursing home residents suffering from psychiatric disorders were treated predominantly by general practitioners applying a psychotropic drug regimen.

Aged↗