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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 271 records · Page 15Linked to original sources
PubMed1998

Inhibition of tumor necrosis factor-alpha- and interleukin-1-induced endothelial E-selectin expression by thiol-modifying agents.

The expression of endothelial-leukocyte adhesion molecules has been postulated to be regulated by redox-sensitive events. Tumor necrosis factor-alpha (TNF-alpha)- and interleukin-1 (IL-1)-induced E-selectin expression was analyzed after pretreating human umbilical vein endothelial cells with different thiol-modifying agents, ie, diamide, phenylarsine oxide, N-ethylmaleimide, and diethyl maleate. E-selectin protein expression was quantified by indirect immunofluorescence. All compounds suppressed the cytokine-induced E-selectin expression in a concentration-dependent manner, whereas the antioxidant N-acetylcysteine showed no effect. The inhibitory effect of diamide (100 micromol/L, 1 hour) was reversible within 6 hours when the cells were allowed to recover before application of cytokines. Reversibility was strongly delayed when cells were deprived of glutathione by buthionine sulfoximine pretreatment. Glutathione depletion alone did not influence cytokine-induced E-selectin expression. Analysis of cellular glutathione status showed a 3-fold increase in oxidized glutathione after diamide treatment. Monochlorobimane labeling also revealed a decrease in total cellular thiols. During recovery, the glutathione status was restored within 1 hour, whereas total thiol content and E-selectin expression needed at least 6 hours to return to baseline. Complete inhibition of E-selectin expression by the vicinal thiol blocker phenylarsine oxide (0.5 micromol/L) was reversed by dithiols like dithiothreitol or dimercaptopropanol, but not by the monothiol 2-mercaptoethanol. These data suggest that proteins with essential thiols, most probably vicinal thiols. are involved in the IL-1- and TNF-alpha-mediated induction of E-selectin. These thiols must be in the reduced state; oxidation or other modification thereof attenuates or abolishes the cells' response to the cytokines.

Acetylcysteine↗
PubMed1998

Use of psychotropic drugs in gynecological, surgical, and medical wards of general hospitals.

OBJECTIVE: The purpose of the present study was to investigate the prevalence of psychotropic drug use and the predictors of use during hospitalization. METHOD: We investigated 728 patients admitted to medical, gynecological, and surgical wards of two non-university general hospitals in Austria for psychotropic drug use, psychiatric morbidity, and sociodemographic characteristics. RESULTS: The use of psychotropics was highest in medical wards (67.6%), followed by surgical (59.3%), and gynecological wards (37.8%). Older age, psychiatric caseness, consultation by psychiatrists and use of psychotropics before admission were predictors for psychotropic drug use. Psychotropics were given for a longer duration to psychiatric cases than to non-cases. Anxiolytics were prescribed most often (39.6%), followed by hypnotics (16.9%), neuroleptics (10.7%), and antidepressants (7.0%). CONCLUSIONS: The fact that psychiatric illness is a significant predictor of psychotropic drug use suggests that these drugs were prescribed aptly. The longer duration of use among psychiatric cases supports the idea of appropriate prescriptions.

Adult↗
PubMed1998

Flow cytometric analysis of protein phosphorylation in the hematopoetic system.

Cellular growth and differentiation in blood cells are regulated by the phosphorylation status of growth factor receptors and downstream proteins. Protein kinases and phosphatases balance the homeostasis of protein phosphorylation. Various diseases are associated with alterations in these tightly regulated processes. Aberrations have been proved to be of diagnostic value and might enhance the pathophysiological insight into the origin of the disease. However, quantitation of protein phosphorylation is currently not feasible in a clinical situation. We developed a flow cytometric methodology which enables for direct investigation of protein phosphorylation in cell populations defined by multi-color flow cytometry. This assay does not only overcome drawbacks of traditional methodologies (e.g. Western blotting) but also allows quantitative analyses even in rare cell populations. We accurately examined phosphorylation levels in different cell populations of hematological interest and especially analyzed CD34+ hematopoietic progenitor cells. CD34+ cells in bone marrow and in cord blood contained similar, low levels of phosphotyrosine. Circulating pheripheral blood system cells PBSC in patients exposed to G-CSF for stem cell mobilization exhibited significantly increased levels of phosphotyrosine. In vitro exposure of CD34+ progenitors to growth factors (G-CSF, IL-3, SCF) raised the levels of tyrosine phosphorylation in bone marrow and cord blood. Effects were dose and time dependent. Interestingly, in vivo stimulated CD34+ PBSC could not be further stimulated in vitro. In conclusion, we present a new powerful methodology for analysis of protein phosphorylation in hematological specimens. The method does not only allow for accurate detection of phosphorylation levels in vivo, but also enables for quantitative analysis of growth factor receptor stimulation in vitro and in vivo.

Acute Disease↗
PubMed1998

Lovastatin inhibits proliferation of pancreatic cancer cell lines with mutant as well as with wild-type K-ras oncogene but has different effects on protein phosphorylation and induction of apoptosis.

Besides its pharmacological effect on cholesterol biosynthesis, lovastatin inhibits p21ras proteins by substrate depletion for post-translational protein farnesylation and geranylation. This inhibition has previously been used to reverse cell proliferation after cellular transformation by the mutant p21ras oncogene. We investigated the biological effects of lovastatin on two pancreatic carcinoma cell lines. The SW-850 cell line contained the k-ras wild-type gene and the A818-4 cell line contained the mutant gene with a point mutation at codon 12 (GGTZCGT; glyZarg). Lovastatin inhibited the proliferation of pancreatic carcinoma cells dose-dependently showing an IC20-30 at 5 microM and IC40-50 at 10 microM. Proliferation of both cancer cell lines, A818-4 (p21ras-M) and SW-850 (p21ras-WT) were inhibited to a very similar extent. After 24 h of drug exposure, cell cycle arrest in G1 and G2/M-phase occurred in a large proportion of cells. At this time, neither cell line showed alteration of protein phosphorylation and did not undergo apoptosis. However, after 72 h of drug exposure, lovastatin significantly decreased protein phosphorylation on tyrosine, serine and threonine residues in A818-4 (p21ras-M) cells. Only a minute reduction of protein phosphorylation was detected in SW-850 (p21ras-WT) cells. Apoptosis occurred in both cell lines, but the SW-850 (p21ras-WT) showed a higher percentage of apoptotic cells than the A818-4 (p21ras-M). In conclusion, there is further evidence for a growth inhibitory effect on cancer cells regardless of the ras mutation status. However, as the effects on protein phosphorylation and induction of apoptosis differed between the mutant and wild-type cell lines, the mechanism of action of lovastatin may depend on partially different mechanisms.

Amino Acid Substitution↗
PubMed1998

Cloning and characterization of bone marrow cells from patients with acute lymphoid leukemia (ALL) in agar cultures.

UNLABELLED: Acute lymphoid leukemias (ALL) represent malignant clonal expansions of lymphoid hemopoietic cells arrested at different stages of B- or T-cell maturation. We studied surface marker profiles and cloning capability of bone marrow (BM) cells from 22 adult ALL-patients at diagnosis (n = 15) or relapse (n = 7) in agar cultures under different culture conditions in order to develop a screening system for the classification of ALL and the detection of residual leukemia. Immunophenotyping of those 22 BM-samples enabled a classification in B- or T-linear ALL. Colony growth of BM-cells could be obtained in four out of 20 cases of ALL at diagnosis and in one case at relapse. Different stimulating factors and their combinations (GM-CSF; IL-1; IL-2; IL-3; IL-4; IL-6; placenta conditioned media (PCM); Phytohemagglutinin (PHA, 40%) and lipopolisaccaride (LPS, 1.25%)--containing conditioned media ('B-ly'); IL-1+IL-3; IL-1+IL-4; IL-1+IL-6; IL-1+B-ly) did not show an overall significant difference in stimulating ALL-clones. Immunological phenotyping of ALL-clones in these 5 cases could prove the lymphoid leukemic character of the clones obtained. CONCLUSIONS: Our data show that colony growth of ALL-BM-cells is difficult. Nevertheless, in cases where colony growth could be obtained those clones showed the original surface marker profile of the leukemic cells proving the specificity of our colony assay.

Acute Disease↗
PubMed1998

[Studying minimally invasive osteosynthesis methods for distal radius fractures. Intra-focal vs. conventional wire osteosynthesis].

From 1992 to 1995 126 patients were treated with percutaneous wire pinning. Sixty-one patients were treated by Kapandji's technique and 65 patients were treated conventionally. Forty-nine patients were examined by 3 different scores (Cooney, Castaing, Stewart). The analysis of the scores showed no differences between the Kapandji technique and the conventional method. Functional and radiological results showed no correlation. Furthermore we found out that the results depend on the score. We conclude that the Kapandji technique shows no benefit in comparison to the conventional method. Functional and radiological results are not divisible: a conclusion from X-ray to function and vice versa is not allowed. A comparison of results is senseless if someone does not use the same score.

Adult↗
PubMed1998

[Diagnosis and therapy of biliary complications after laparoscopic cholecystectomy by ERCP].

Biliary tract injury, although uncommon, is the most feared complication of laparoscopic cholecystectomy. Early identification or exclusion of such injury is essential for successful management. Over a two year period (1995-1996) twenty-one from a total of 413 ERCPs in this Surgical Endoscopy Unit were performed because of suspected biliary injury after laparoscopic cholecystectomy. 16 patients were referred from other units. No abnormality was demonstrated in two cases. A clip-related stenosis requiring reoperation was shown in twei patients. The remaining 17 cases had biliary leakage, related to an aberrant bile duct in 2 cases or a cystic duct leak in 15, all of which were treated endoscopically by nasobiliary tube (7), endoscopic papillotomy (5) or a combination of both (5). All of these biliary leaks healed uneventfully no ERCP-associated morbidity.

Biliary Fistula↗
PubMed1998

Elecsys TSH, FT4, T4, T-uptake, FT3 and T3. Clinical results of a multicentre study.

6 assays for the assessment of thyroid function (TSH, FT4, T4, T-uptake, FT3 and T3) were targets of the International Multicenter Study on the random access analyzer Elecsys 2010. The aim of the study was to characterize the clinical performance of the assay in method comparison and reference range studies. The assays under evaluation were compared to a broad variety of radio isotopic and non-radio isotopic assays. They are suitable for serum and plasma samples. In case of TSH the study include 2nd and 3rd generation TSH procedures. In general, good to excellent correlations were found between the Elecsys and the respective routine methods. Systematic deviations were extraordinary low in case of TSH, FT4 and T4. Regarding the analysis of T3 and FT3 some systematic deviations in terms of standardization have been observed. Results of Elecsys T4 and Elecsys FT4 were independent of the serum total protein or serum albumin concentrations. In T3 and FT3 Elecsys the results of samples from NTI (non-thyroidal-illness) patients were decreased, reflecting the physiological situation in these patients. Studies using samples from healthy euthyroid as well as untreated hypo- and hyperthyroid individuals enabled us to assess the assays reference ranges.

Humans↗
PubMed1998

Results of the multicentre evaluation of an electrochemiluminescence immunoassay for HCG on Elecsys 2010.

This study evaluated the performance of the HCG STAT Elecsys assay in 8 European laboratories using the Elecsys 2010 system. Analytical sensitivity was < 0.5 mlU/mL. The analysis of concentration series prepared by mixing serum pools with high and low HCG concentrations proved linearity up to 10.000 mIU/mL. A high-dose hook effect was not seen up to HCG concentrations of 430.000 mIU/mL. The medians of the within-run CVs (n = 21, 3 series) were 3.0% (2.1-5.8% CV; 10.4-14.4 mIU/mL), 2.4% (1.7-6.1% CV; 35.6-88.6 mIU/mL) and 2.3% (1.7-6.1% CV; 282.3-643.8 mIU/mL). The medians of the between-day imprecisions (n = 10-21) were 7.0% CV (5.2-12.0% CV; 4.0-14.0 mIU/mL), 5.5% CV (3.1-7.2% CV; 35.4-92.7% mIU/mL) and 4.1% CV (2.8-5.1% CV; 270.8-658.0 mIU/mL). The median recovery of two external quality control samples with assigned values of 9.39 and 10.40 mIU/mL) were 101.2 and 104.3% (ranges: 94.8-116.1%, 98.6-117.8%, n = 10). The assay was compared with five non-isotopic automated routine immunoassay systems (x). Slopes ranged from 0.87 to 1.15 and intercepts from-0.53 to 12.50 mIU/mL. The coefficients of correlation were with one exception (0.898) > or = 0.960. The distribution of HCG in samples from non-pregnant women and healthy men was very similar to that observed with other automated routine methods. The HCG Elecsys assay is very specific for the intact holo-hormone. Nicked HCG dimer, nicked and non-nicked beta-subunits are weakly recognised or not detected. Hemoglobin, bilirubin and lipemia (tested up to: Hb, 3.7 g/L; bilirubin, 500 mumol/L; triglyceride, 37.6 mmol/L) did not interfere the assay. The HCG Elecsys assay is well suited for the early and fast diagnosis of normal pregnancy and the detection of tubal pregnancy.

Adult↗
PubMed1998

[The rotatory machines in the history of psychiatry].

The history of the rotatory machine shows a distinct transformation during its short-lived use in psychiatric therapy from about 1806 to 1836. Initially a variety of hypotheses were offered to explain its mode of action. Gradually the use of the method became a plain disciplinary measure. The technical features of the machine also changed. The adherents of both psychic and somatic treatment in psychiatry did not object to the method. Obviously, as a result of Conolly's no-restraint the use of the machine fell into disrepute. The scant case histories suggest that the machine was mainly used as a means of intimidation and deterrent. It is worth to be remembered that humane physicians in the middle of the 20th century still used deterring methods such as the aversion treatment of alcoholics.

Complementary Therapies↗
PubMed1998

[Definition of predictors of a complicated course in acute pancreatitis].

It is of utmost importance to assess the severity of acute pancreatitis immediately in order to identify patients with severe or necrotising disease who can benefit from early intensive care therapy. Additionally, in face of new therapeutic concepts (e.g., antibiotic therapy) and for the evaluation of new drugs (e.g. PAF antagonist) patients should be staged as soon as possible into mild and severe disease. At hospital admission it is not possible to assess the severity on a clinical basis. The "gold standard" up to now has been imaging procedures (contrast-enhanced CT and MRI) which should be preserved for the severe cases to estimate the extent of pancreatic necrosis. The ideal predictor in blood/urine should be objective, reliable, cheap, easy to measure, and available every time and should have on hospital admission a high efficacy and independence from other diseases. As single factors there are a variety of mediators of the "systemic inflammatory response syndrome" which are elevated in this disease (C-reactive protein, antiproteases, enzyme activation peptides, PMN-elastase, complement factors, interleukines and chemokines, etc.). Among all these prognostic indicators, C-reactive protein is now the best analyzed parameter. However, one should take into account that its highest efficacy is reached 3-4 days after onset of disease.

Biomarkers↗
PubMed1997

The CD40 ligand directly activates T-lymphocytes via tyrosine phosphorylation dependent PKC activation.

The activation of B-lymphocytes depends critically on the interaction of the CD40 receptor with its ligand. Here, we provide evidence that the CD40 ligand (CD40L) also functions as a direct stimulatory molecule for T-lymphocytes. Activation of T-lymphocytes via CD40L induces tyrosine phosphorylation of cellular proteins including PLC gamma. Tyrosine phosphorylation of PLC gamma correlates with an IP3- and Ca(2+)-release and an activation of PKC. Inhibition of src-like tyrosine kinases by Herbimycin A prevents these activation events suggesting a crucial role of tyrosine phosphorylation in T-lymphocyte activation via CD40L.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1997

Incorporation of 1-deoxy-D-xylulose into isoprene and phytol by higher plants and algae.

In further substantiating the novel mevalonate-independent pathway for isoprenoid biosynthesis, which generates isopentenyl diphosphate (IPP) via 1-deoxy-D-xylulose-5-phosphate, labeling experiments with 1-[2H(1)]deoxy-D-xylulose were performed with various higher plants and algae: efficient incorporation was observed into isoprene emitted by Populus, Chelidonium, and Salix, into the phytol moiety of chlorophylls in a red alga (Cyanidium), in two green algae (Scenedesmus, Chlamydomonas), and a higher plant (Lemna). By contrast, 13C-mevalonate applied was incorporated into isoprene and phytol to a much lower extent or not at all. This demonstrates that this '1-deoxy-D-xylulose-5-phosphate pathway' for biosynthesis of plastidic isoprenoids is widely distributed in photosynthetic organisms.

Butadienes↗