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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 217 records · Page 12Linked to original sources
PubMed1999

Multiple brain infarcts: clinical and neuroimaging patterns using diffusion-weighted magnetic resonance.

The capability of diffusion-weighted (DW) magnetic resonance imaging (MRI) to identify very early ischemic brain injury better than conventional MRI is well known. This technique, which successfully discriminates acute from old infarcts, is particularly useful in patients with multiple brain infarcts (MBI). Among 142 patients with acute stroke consecutively admitted to our primary care center, we selected 43 patients with two or more brain infarcts on conventional MRI. All patients presented with clinical deficits consistent with acute cerebral ischemia and underwent conventional spin echo for T(1) (T1-WI) and T(2)-weighted images (T2-WI), T(1)-W gadolinium-enhanced images, and echo-planar technique for DW MRI sequences. Patients underwent DW MRI examinations within 15 days of stroke onset (mean +/- SD: 3 +/- 3 days). In all but 1 case, the infarcts detected on DW MRI were also visible on T2-WI. The different signal pattern on DW MRI, compared with T2-WI, facilitated the detection of acute infarcts in all patients. T1-WI with gadolinium enhancement was only helpful in 5 (11.6%) patients. DW MRI enabled precise clinicotopographic correlations in 79% of our patients and provided additional clinically relevant findings in 72% of the patients. Based on the neuroradiological findings, patients were divided into three clinicotopographic types of MBI as follows: 13 patients (30.2%) presented with multiple acute infarcts, 24 patients (55.8%) with a single acute infarct and multiple old infarcts, and 6 patients (13.9%) with multiple acute and old infarcts. In conclusion, DW MRI can easily be added to conventional MRI in order to be able to distinguish acute from old infarcts, and to identify acute multiple lesions. Therefore, a better correlation between clinical symptoms and the site of lesions can be obtained, considerably improving patient care.

Adolescent↗
PubMed1999

Cardiopulmonary exercise testing before and after lung and heart-lung transplantation.

Heart-lung (HLT) and lung transplantation (LT) have been shown to be effective procedures for patients with end-stage cardiopulmonary disorders. As yet, few data exist on the exercise performance of patients before and after thoracic transplantation except with regard to 6-min walk tests. In this article we report cardiopulmonary exercise test results of lung and heart-lung transplant recipients in comparison with their pretransplant values. We studied 103 consecutive recipients of single-lung (n = 46), bilateral lung (n = 32), and heart-lung (n = 25) transplants. Cardiopulmonary exercise testing with a cycle ergometer was performed before and shortly after surgery. Before transplantation, all patients showed severe exercise intolerance and markedly impaired parameters reflecting cardiopulmonary function (e.g., work capacity: 20 +/- 11% predicted; oxygen uptake: 34 +/- 12% predicted; oxygen pulse: 50 +/- 18% predicted; functional dead space ventilation: 57 +/- 10% of minute ventilation; alveolar-arterial oxygen difference during exercise: 79 +/- 15 mm Hg). At 55 +/- 9 d after transplantation, transplant recipients reached maximum oxygen uptakes in the range of 22 to 71% of predicted values; the peak oxygen uptake was increased after transplantation (13.1 +/- 3.4 ml/min/kg versus 10.4 +/- 3.8 ml/min/kg; p < 0.001). Work capacity, oxygen pulse, tidal volume, and peak minute ventilation did not differ in patients following single- or double-lung tranplantation or HLT. Ventilatory factors did not appear to limit exercise capacity in any group. Despite the persistent limitations in aerobic capacity and work rate seen in many of the recipients, cardiopulmonary performance is reasonably well restored shortly after LT and HLT.

Adult↗
PubMed1999

Lack of sex difference in cerebrospinal fluid (CSF) leptin levels and contribution of CSF/plasma ratios to variations in body mass index in children.

In adults, leptin seems to cross the blood-brain barrier by a saturable transporter. This may contribute to the development of obesity. The present study in healthy children investigates leptin levels in plasma and cerebrospinal fluid (CSF) in relation to body constitution. This prospective study analyzed leptin levels in plasma and CSF samples (stored at -80 C) of patients without CNS infection or blood-brain barrier dysfunction. Inclusion criteria included temperature less than 38.5 C, C-reactive protein levels below 10 mg/L, CSF leukocyte levels less than 10(7)/L, no need for neurosurgical or oncological treatment, and no history of trauma. Four groups were designated according to body mass index. Sixty-five children (28 girls and 37 boys) entered the study. Plasma leptin (median) was 7.4 in girls and 2.6 ng/mL in boys., CSF leptin was 0.273 and 0.204 ng/mL, respectively, leading to CSF/plasma ratios of 0.045 and 0.071, respectively. Ratios were clearly dependent on body mass index percentiles (r = -0.484; P < 0.01, significant differences between groups by ANOVA). Median plasma leptin levels in the 4 groups (body mass index, <10th, 10th-50th, 50th-90th, and >90th percentile) were 2.0, 2.3, 4.1, and 8.8 ng/mL; CSF/plasma ratios were inversely related: 8.2%, 7.6%, 5.5% and 3.6%. In healthy children, CSF leptin levels account for approximately 5% of plasma levels. CSF/plasma ratios in girls are lower than those in boys, explaining why calorie intake and energy expenditure are not grossly different despite large differences in circulating plasma leptin concentrations. CSF/plasma ratios of lean children are higher than those in obese children. The dynamic changes in the CSF/plasma ratios are more pronounced in lean children, i.e. the nonlinear transport characteristics of the leptin system amplifies the information about changes in body energy stores in this population, indicating that leptin is part of a mechanism to protect the body from critical weight loss rather than to avoid obesity.

Adolescent↗
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↗
PubMed1999

Tyrosine phosphorylation in peripheral T cells of kidney transplant recipients: analyses of baseline levels and response to T cell receptor stimulation.

Impaired immunosurveillance in recipients of organ transplants has been attributed to alleviation of T cell functions. We analyzed the phosphorylation of tyrosine residues in T cells of peripheral blood, and after T cell receptor (TCR) stimulation. The TCR was stimulated by OKT3 monoclonal antibody (mAb) in non-separated heparinized blood specimens of patients (n=64) and healthy controls (n=25). After fixation and red cell lysis, lymphocytes were permeabilized by saponin. Subsequently, intracellular phosphotyrosine residues and surface CD3 antigen were stained simultaneously with specific mAbs. We analyzed transplant recipients and healthy donors for baseline levels of total cellular tyrosine phosphorylation and for increase in phosphotyrosine content following stimulation by OKT3. Phosphotyrosine levels were significantly lower in non-stimulated T cells of kidney transplant recipients compared to controls (p=0.004). There was a marked variability in the levels of tyrosine phosphorylation among transplanted patients (p=0.02). T cell receptor stimulation by OKT3 mAb in vitro led to a strong increase of tyrosine phosphorylation in all specimens of patients and healthy controls. In conclusion, we demonstrated decreased phosphotyrosine levels in T cells of kidney transplant recipients compared to healthy donors. However, increase in tyrosine phosphorylation was not impaired in all patients as a result of TCR stimulation.

Adult↗
PubMed1999

[Voluntary testing procedures of farm animal housing equipment according to the Animal Welfare Act of 1998].

Before its broad application in practice, housing equipment should be tested, in particular with regard to animal welfare. The differing positions of the German Federal Council (Bundesrat) and the German Federal Parliament (Bundestag), whether such testing should be mandatory or voluntary, have been conciliated in the amended animal welfare act by empowering the Federal Ministry of Food, Agriculture and Fisheries (BML) to fix official standards for voluntary testing procedures by regulation. On request of the BML, a report as scientific basis for a draft regulation is currently prepared by the scientific animal welfare committee of the German Agricultural Society (DLG). The scientific animal welfare committee has been appointed by the DLG in order to provide support in the effort to strengthen animal welfare aspects in the DLG-utility testing procedure of housing equipment, which is in place since 1953. The committee elaborates standards concerning testing methods, assessment criteria and the necessary size of investigations. As required, the scientific animal welfare committee may support the DLG-testing bodies in the implementation of the animal welfare part of the testing procedure. It will, moreover, be involved in the welfare assessment based on the testing results. The amendments of the already established testing procedure will help to fulfill the general requirements on an acceptable animal welfare testing procedure. While keeping in mind that there are certain limits in what can be achieved by a voluntary testing procedure, the enhanced consideration of animal welfare aspects within the DLG-utility testing procedure has the advantage to be relatively unbureaucratic and in line with EU legislation, and is, therefore, an appropriate tool for a contibrution to improved animal welfare in livestock housing.

Agriculture↗
PubMed1999

[Equipment and aids in trotting races].

During the last years, trotting races met with massive criticism, because some of the numerous items of equipment were not to be reconciled with animal protection. In March 1998, the Trotting Association (HVT), as well as the list of authorized equipment. The so-called "positive list" includes harnesses, bridles, bits, auxiliary reins, driving reins, whips and other aids, among other things brushing boots, ear-muffs and head-pole. Especially criticized items are submitted to an assessment according to the present animal protection law. Moreover, possibilities are shown to make positive conditions in the surrounding area of the trotter more transparent, for instance horse keeping and training management, and to underline them in order to improve the reputation of the trotting sport.

Animal Welfare↗
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↗