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Biomedical subjects

M Weber

Publications and source records attributed to M Weber.

At least 271 records · Page 15Linked to original sources
PubMed1999

Lesion-induced changes of electrophysiological properties in astrocytes of the rat dentate gyrus.

Reorganization of the adult dentate gyrus following unilateral entorhinal cortex lesion (ECL) is a well-established model for studying mechanisms of trauma-induced neuronal plasticity. The lesion induces deafferentiation of the outer molecular layer, which is accompanied by a strong astroglial reaction. This glial response is thought to contribute to subsequent repair processes, but the underlying mechanisms are poorly understood. In this study we addressed the question whether denervation leads to modifications in the electrophysiological properties of astrocytes, assuming that such changes might be involved in the remodeling of neural circuitry. Patch-clamp recordings were obtained from astrocytes in the dentate gyrus of adult rats that underwent ECL and compared to corresponding data from control animals. We observed a significant reduction of inward rectifier K(+) current densities, a positive shift of resting potentials, and an increase in input resistance in astrocytes of the denervated molecular layer. Current densities were reduced between 6 and 19 days postlesion (dpl), reaching a minimum at 10 dpl. Voltage-gated outward K(+) currents were not affected by the lesion. Inward rectifier K(+) currents increase with maturation in astrocytes. Thus, our results provide evidence that, following ECL, mature astrocytes dedifferentiated and readapted an immature current pattern. Presumably, these changes lead to stronger and prolonged depolarization of glial cells and neurons in response to activity-dependent K(+) release, which in turn might enhance the synthesis of neurotrophic factors and contribute to a permissive environment for neuronal reorganization.

Animals↗
PubMed1999

[Brief report of the working group OPD-CA (children and adolescents) Axis II: interpersonal relations].

Operationalization of relations is tried out following an interpersonal circular model (SASB) using observation and description of behavior in dyadic and triadic relationship configurations. On a vertical and on a horizontal axis the amount of loving kindness versus hostile aggressivity and of independence versus control is determined. Different dyadic and triadic relationship configurations (e.g. child to mother or researcher to child) and also the emotional resonance of the investigating person will be rated according to anamnestic data, observed and videotaped sequences of interaction, play episodes or symbolic relationships in projective tests. Such ratings can be performed in a module like form and will be used not only in clinical practice but also in settings of scientific research. The minimal standard for a clinical examination consists of the evaluation of the child with his parents.

Adult↗
PubMed1998

Potential benefit from implantable cardioverter-defibrillator therapy in patients with and without heart failure.

BACKGROUND: Whether patients with heart failure derive a benefit from therapy with implantable cardioverter-defibrillators (ICDs) has been questioned. The purpose of this study was to investigate whether New York Heart Association (NYHA) functional class had an impact on the potential benefit from ICD therapy as assessed from data stored in the memory of ICDs. METHODS AND RESULTS: Between 1989 and 1996, 603 patients (77% men; 59% with coronary artery disease and 16% with dilated cardiomyopathy; age, 57+/-13 years; ejection fraction, 44+/-18%) were treated with an ICD with extended memory function (storage of electrograms and/or RR intervals from treated episodes) in combination with endocardial lead systems. The stages of heart failure (NYHA functional class I through III) at implantation were correlated with overall mortality and the recurrence of fast ventricular tachyarrhythmias (>240 bpm) during follow-up. The potential benefit of the device was estimated as the difference between overall mortality and the hypothetical death rate had the device not been implanted. The latter was based on the recurrence of fast and, without termination by the devices, presumably fatal ventricular tachyarrhythmias. In the overall group, a significant difference between hypothetical death rate and overall mortality was observed (13.9%, 23.5%, and 26.6% at 1, 3, and 5 years, respectively) that suggested a benefit from ICD implantation. In patients in NYHA class I, the estimated benefit, which increased over time, was 15.2%, 29.2%, and 35.6% after 1, 3, and 5 years, respectively. In patients in NYHA class II or III, the estimated benefit increased until the third year (21.8% and 21.9%, respectively) and then remained constant until the fifth year (22.9% and 23.8%, respectively). Even those patients in NYHA class III with a history of decompensated heart failure benefited from ICD implantation. CONCLUSIONS: Analysis of stored ECG data suggests that in patients with a history of ventricular tachycardia or ventricular fibrillation, ICD therapy may lead to a prolongation of life in NYHA classes I through III. The initial benefit is greatest in patients in NYHA class II and class III, but the estimated benefit might persist longest for patients in NYHA class I.

Adolescent↗
PubMed1998

Heme and the endothelium. Effects of nitric oxide on catalytic iron and heme degradation by heme oxygenase.

We studied the effects of nitric oxide (NO) on the control of excess cellular heme and release of catalytically active iron. Endothelial cells (ECs) exposed to hemin followed by a NO donor have a ferritin content that is 16% that of cells exposed to hemin alone. Hemin-treated ECs experience a 3.5-fold rise in non-heme, catalytic iron 2 h later, but a hemin rechallenge 20 h later results in only a 24% increase. The addition of a NO donor after the first hemin exposure prevents this adaptive response, presumably due to effects on ferritin synthesis. NO donors were found to reduce iron release from hemin, while hemin accumulated in cells. A NO donor, in a dose-dependent fashion, inhibited heme oxygenase activity, measured by bilirubin production. Using low temperature EPR spectroscopy, heme oxygenase inhibition correlated with nitrosylation of free heme in microsomes. Nitrosylation of cellular heme prevented iron release, for while there was heme oxygenase-dependent release of iron in cells incubated with hemin for 24 h, the addition of a NO donor blocked iron release. This indicates that NO readily nitrosylates intracellular free heme and prevents its degradation by heme oxygenase. Nitrosylation of heme was found to reduce sensitization of cells to oxidative injury.

Adaptation, Physiological↗
PubMed1998

Role for Bcl-xL in delayed eosinophil apoptosis mediated by granulocyte-macrophage colony-stimulating factor and interleukin-5.

Eosinophils are potent inflammatory cells involved in allergic reactions. Inhibition of apoptosis of purified eosinophils by certain cytokines has been previously shown to be an important mechanism causing tissue eosinophilia. To elucidate the role of Bcl-2 family members in the inhibition of eosinophil apoptosis, we examined the expression of the known anti-apoptotic genes Bcl-2, Bcl-xL, and A1, as well as Bax and Bcl-xS, which promote apoptosis in other systems. We show herein that freshly isolated human eosinophils express significant amounts of Bcl-xL and Bax, but only little or no Bcl-2, Bcl-xS, or A1. As assessed by reverse transcription-polymerase chain reaction, immunoblotting, flow cytometry, and immunocytochemistry, we show that spontaneous eosinophil apoptosis is associated with a decrease in Bcl-xL mRNA and protein levels. In contrast, stimulation of the cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-5 (IL-5) results in maintenance or upregulation of Bcl-xL mRNA and protein levels. Moreover, Bcl-2 protein is not induced by GM-CSF or IL-5 in purified eosinophils. Bcl-2 protein is also not expressed in tissue eosinophils as assessed by immunohistochemistry using two different eosinophilic tissue models. Furthermore, Bcl-xL antisense but not scrambled phosphorothioate oligodeoxynucleotides can partially block the cytokine-mediated rescue of apoptotic death in these cells. These data suggest that Bcl-xL acts as an anti-apoptotic molecule in eosinophils.

Apoptosis↗
PubMed1998

Crystallization in Polyamide 6/Polysulfone Blends: Effect of Polysulfone Particle Size.

By reactive blending of polyamide 6 (PA) with polysulfone (PSU) using a gram-scale mixer (Mini-Max Molder), we prepared a series of PA/PSU (80/20 wt.ratio) with various diameters of PSU particles: 90 nm by using phthalic anhydride-terminated PSU (PSU-PhAH), 0.2 µm by carboxylic acid-grafted PSU (PSU-COOH), and 1.0 µm by nonreactive PSU (nf-PSU). Isothermal crystallization was carried out at 200 degreesC. Light scattering studies showed that spherulites in the blends can grow to more than 10 µm in diameter, as in the case of neat PA. It suggests that crystal growth in the radial direction can be achieved by circumventing the PSU obstacles; i.e., it does not matter how big or small they are in the range of 90 nm to 1 µm. The smaller the PSU particles, the slower was the overall rate of crystallization. The slower rate may be caused by the higher population of brush PA chains attached to PSU particles as block or graft chains, since the brushes may be hard to organize into crystal lamellae, compared with free chains. The blends showed rather broad wide-angle X-ray diffraction profiles. The smaller the PSU particles, the broader was the profile. The scattering from the particles themselves should appear only at extremely low angles (<0.1 degrees) and hardly affects the wide-angle X-ray profiles so that the results may imply that the presence of smaller PSU particles renders the less perfection of the PA crystal. This may be caused also by the higher population of brush chains. Note that the brush chains are formed only in the reactive systems and the population may be higher in the smaller particle systems. Even for the blend with smallest particle size, a small-angle X-ray scattering peak appeared at a magnitude of scattering vector of approximately 0.8 nm-1, suggesting the evolution of interlamellar spacing of 8.7 nm. However, the scattering profile was much broader than that of neat PA. It implies a less ordered lamellar stacking in the blend.

Journal Article↗
PubMed1998

Solitary enchondroma with clonal chromosomal abnormalities.

We report a case of a solitary enchondroma located in the head of the left fibula in a 50-year-old patient and present the findings of histopathologic investigation and cytogenetic analysis. The tumor revealed simple karyotypic abnormalities with t(8;17)(q23;p13) and loss of chromosomes 9, 19, and 22 as clonal chromosomal changes. Only a few enchondromas with chromosome aberrations have been published previously; nevertheless, it appears that benign and malignant cartilaginous tumors may have similar chromosomal abnormalities.

Bone Neoplasms↗
PubMed1998

Role for tyrosine phosphorylation and Lyn tyrosine kinase in fas receptor-mediated apoptosis in eosinophils.

Fas ligand/Fas receptor molecular interactions have been implicated as having an important function for the regulation of eosinophil apoptosis. The purpose of the present study was to investigate biochemical events triggered by the engagement of the Fas receptor in freshly isolated human and mouse eosinophils. Activation of the Fas receptor on eosinophils with the agonistic anti-Fas monoclonal antibody (MoAb) resulted in increased tyrosine phosphorylation of several intracellular proteins. The tyrosine kinase inhibitors lavendustin A and genistein inhibited Fas receptor-induced cell death in both human and mouse eosinophils in vitro and prevented, at least partially, Fas receptor-mediated resolution of eosinophilic inflammation in a mouse in vivo model of lung eosinophilia. In addition, in freshly purified human eosinophils, lavendustin A prevented anti-Fas MoAb-induced proteolytic cleavage of lamin B, suggesting that tyrosine kinases may amplify the proteolytic signaling cascade within interleukin-1beta converting enzyme (ICE) family proteases. Moreover, the tyrosine kinase Lyn was identified as being involved in Fas receptor-mediated cell death. Collectively, these results demonstrate that tyrosine phosphorylation is an important step in the generation of the Fas receptor-linked transmembrane death signal in eosinophils and that Lyn participates in this pathway.

Animals↗
PubMed1998

Cloning and expression of odorant-binding proteins Ia and Ib from mouse nasal tissue.

We had previously reported the purification and partial characterisation of four distinct odorant-binding proteins from male mouse nasal epithelium. One of these, named OBP-I appeared to be a heterodimer, whose subunits, Ia and Ib showed significant similarity in their N-terminal amino acid sequences with hamster aphrodisin. In this paper, we report the complete amino acid sequences of these two polypeptide chains, as deduced from nucleotide sequences of their relative cDNA. These data confirm the high similarity of both proteins with hamster aphrodisin. A comparison with the sequences of other known OBPs indicate that they are more closely related to members of class I, including bovine OBP, rat OBP-I and pig OBP-I. A putative odorant-binding site is indicated by the presence of amino acid residues conserved with respect to the bovine protein, whose three-dimensional structure has been recently resolved. In-situ hybridisation has revealed identical expression patterns for the two proteins, further supporting the heterodimeric structure of these proteins in the nasal mucus.

Amino Acid Sequence↗
PubMed1998

Syncope in patients with an implantable cardioverter-defibrillator: incidence, prediction and implications for driving restrictions.

OBJECTIVES: This retrospective study was undertaken to provide information on occurrence, risk prediction and prevention of syncope in patients with an implantable cardioverter-defibrillator (ICD). BACKGROUND: ICDs effectively terminate ventricular tachycardia and fibrillation (VT/VF). Incapacitating symptoms, such as syncope, may still occur. METHODS: We performed a retrospective analysis of data from 421 patients (clinical history, outpatient chart reviews and episode data) with mean (+/-SD) follow-up of 26 +/- 18 months. RESULTS: Of 421 patients, 229 (54.4%) had recurrent VT/VF, and 62 (14.7%) had syncope. The actuarial survival rate free of VT/VF was 58%, 45% and 37% and that for survival free of syncope was 90%, 85% and 81% at 12, 24 and 36 months after implantation, respectively. Once VT/VF had occurred, 76%, 68% and 62% of patients remained free of syncope during the following 12, 24 and 36 months, and 68%, 64% and 56% remained free of second syncope 12, 24 and 36 months after first syncope, respectively. In cases of syncope, the mean cycle length (CL) of VT was 251 +/- 56 ms. A low baseline left ventricular ejection fraction (LVEF), induction of fast VT (CL <300 ms) during programmed ventricular stimulation and chronic atrial fibrillation (AF) were associated with an increased risk of syncope. If the LVEF was >40%, fast VT had not been induced, and patients had no chronic AF; 96%, 92% and 92% of patients remained free of syncope after 12, 24 and 36 months, respectively. Once patients had a VT recurrence, syncope during the first VT and a high VT rate were the strongest risk predictors of future syncope. CONCLUSIONS: Identification of patients with an ICD with a low and high risk of syncope seems to be feasible and might help as a guide to driving restrictions in such patients.

Adolescent↗
PubMed1998

Cardiovascular evaluation of lowland gorillas.

OBJECTIVE: To design a diagnostic protocol that uses appropriate techniques, including ultrasonography, to assess cardiovascular health and detect primary cardiac diseases in gorillas and to establish a database of reference values for cardiac measurements in clinically normal gorillas. DESIGN: Prospective study. ANIMALS: 5 adult male lowland gorillas from 11 to 18 years old. PROCEDURE: A complete cardiac evaluation was performed on anesthetized gorillas, including physical examination, thoracic radiography, electrocardiography, echocardiography, blood pressure determination, CBC, serum biochemical analyses, and serologic assay for viral diseases. Standard cardiac measurements were made from images collected during ultrasonography. RESULTS: Cardiac measurements derived from ultrasonographic images were consistent with those considered normal in human beings. Results of other diagnostic tests were also considered normal. CLINICAL IMPLICATIONS: Cardiac disease is the primary cause of mortality in old captive gorillas. The technique used here provided excellent evaluation of cardiac function. Use of these techniques will allow early detection of cardiac disease, making treatment or medical management possible.

Animals↗
PubMed1998

Expression of Rab3D N135I inhibits regulated secretion of ACTH in AtT-20 cells.

Rab proteins are small molecular weight GTPases that control vesicular traffic in eucaryotic cells. A subset of Rab proteins, the Rab3 proteins are thought to play an important role in regulated exocytosis of vesicles. In transfected AtT-20 cells expressing wild-type Rab3D, we find that a fraction of the protein is associated with dense core granules. In the same cells, expression of a mutated isoform of Rab3D, Rab3D N135I, inhibits positioning of dense core granules near the plasma membrane, blocks regulated secretion of mature ACTH, and impairs association of Rab3A to membranes. Expression of Rab3D N135I does not change the levels of ACTH precursor or the efficiency with which the precursor is processed into ACTH hormone and packaged into dense core granules. We also find that cells expressing mutated Rab3D differentiate to the same extent as untransfected AtT-20 cells. We conclude that expression of Rab3D N135I specifically impairs late membrane trafficking events necessary for ACTH hormone secretion.

Adrenocorticotropic Hormone↗
PubMed1998

Pulmonary evolution of cystic fibrosis patients colonized by Pseudomonas aeruginosa and/or Burkholderia cepacia.

UNLABELLED: We analysed the pulmonary evolution (radiological scores and pulmonary function) of 81 cystic fibrosis (CF) patients colonized by Pseudomonas aeruginosa (PA), by Burkholderia cepacia (BC) or by both these bacteria, compared to a control group. Pulmonary function was compared in the age bracket 6-13 years. Functional vital capacity (FVC) and forced expiratory volume (FEV1) values for PA colonized patients were significantly worse than for the control group but better than for children colonized by both organisms. In this last group, the evolution of radiological scores and pulmonary function showed a greater decline 2 years after the first colonization compared to the other groups. FVC and FEV1 values in patients colonized by BC were not worse than these of patients colonized by PA. Moreover, BC affected older patients with advanced lung disease and often previously colonized with PA. These results suggested that co-colonization by PA and BC could be a more deleterious factor on the pulmonary evolution than the isolated colonization by PA or BC, and that BC could be a severity marker rather than a cause. In addition, after starting the utilization of mouthpieces with filter at single use for spirometry in 1993 (without any other change in preventive measures already taken during hospitalization), incidence of BC decreased from 8.2% to zero, and no new case of BC colonization has been observed over the last 4 years. CONCLUSION: Co-colonization of CF patients by PA and BC is more deleterious for pulmonary evolution than colonization by one of these bacteria alone. Re-inforcement of environmental measures during hospitalization (e.g. use of disposable mouthpieces for spirometry) was sufficient to reduce the transmission of BC.

Adolescent↗