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R Westermann

Publications and source records attributed to R Westermann.

At least 19 recordsLinked to original sources
PubMed2001

Effect of repeated treatment with high doses of selegiline on behaviour, striatal dopaminergic transmission and tyrosine hydroxylase mRNA levels.

The anti-parkinsonian drug selegiline is a monoamine oxidase B (MAO-B) inhibitor and a potential neuroprotective agent which facilitates dopaminergic transmission. Its metabolites (-)-amphetamine and (-)-metamphetamine might contribute to the pharmacological effects as they are also able to increase dopaminergic transmission and in addition might lead to behavioural sensitization after repeated administration. We investigated the effects of acute and repeated treatment with a high dose of selegiline on dopamine overflow in the striatum as well as on behaviour and on tyrosine hydroxylase (TH) mRNA levels in midbrain. Two experiments were performed. In the first one, rats were implanted with microdialysis probes into the striatum and received daily injections of selegiline (10 mg/kg, i.p.) for 1 or 8 days or a single dose of saline. In vivo microdialysis was carried out on days 1, 8 or 17 (after withdrawal of 9 days) to measure dopamine overflow. Motility was measured at the same time. In the second experiment, rats were injected daily with selegiline (10 mg/kg, i.p.) or saline over a time period of 6 weeks or only once before the brains were processed for in situ hybridization with a (35)S-radiolabelled probe for TH. Repeated treatment led to higher levels in motility scores than acute administration after administration of the same dose, indicating behavioural sensitization, which was still manifest after an interruption of 9 days in the supply of selegiline. In contrast, acute administration of selegiline increased dopamine levels to a similar degree as the same dose after subchronic treatment, with or without interruption of 9 days. The dopamine metabolite DOPAC was reduced by more than 50% after acute administration of selegiline and even more so on day 8 by the same dose, after repeated administration. The basal concentrations of dopamine (before challenge with selegiline) were not altered by the repeated administration, whereas the basal concentrations of DOPAC were decreased by more than 80% by the repeated administration of selegiline, suggesting a decrease in dopamine turnover. Acute administration did not have any influence on TH mRNA levels, whereas chronic treatment significantly reduced TH mRNA levels in substantia nigra and ventral tegmental area. In conclusion, repeated administration of selegiline leads to behavioural sensitization independent of altered dopamine levels. In addition, it leads to a decrease, probably due to a down-regulation, of dopamine turnover and tyrosine hydroxylase.

Animals↗
PubMed2001

Sensitization to the behavioural effects of cocaine: alterations in tyrosine hydroxylase or endogenous opioid mRNAs are not necessarily involved.

After repeated administration of cocaine at intervals, sensitization phenomena can be observed, so that its behavioural effects are enhanced. Since this phenomenon is long-lasting, it was of interest to study which persistent alterations in the activity of dopaminergic neurones or of endogenous opioid systems downstream of dopaminergic synapses in the basal ganglia are involved in the sensitization. Cocaine (10 mg/kg i.p.) was administered to rats on days 1, 3, 5 and 7 and saline on days 2, 4 and 6 ("repeated cocaine"), or saline was injected on days 1-6 and cocaine on day 7 ("acute cocaine"), or saline was injected on days 1-7 ("saline group"). The "repeated cocaine" schedule led to a significant sensitization to the locomotor activation produced by cocaine on day 7 or on day 17, 10 days after the end of sensitization protocol. Microdialysis in the nucleus accumbens which was performed after administration of cocaine (10 mg/kg i.p.) on day 7, or after an administration of the same dose 10 days after the last administration of cocaine, respectively, revealed significant acute increases of extracellular dopamine to about 200% of basal values. These increases were similar in "acute cocaine" and in "repeated cocaine" animals both after 7 days and after 17 days. For in situ hybridization studies, rats were sacrificed on day 7, 4.5 h after the last cocaine or saline administration. The mRNA for tyrosine hydroxylase (TH) in substantia nigra + ventral tegmental area was significantly elevated to about 140% of saline controls both in the "repeated cocaine" and the "acute cocaine" group as compared with the "saline group". In contrast, there were no differences between the three groups in the mRNAs of preprodynorphin or preproenkephalin levels measured in the nucleus accumbens (core and shell). These results suggest that sensitization phenomena to cocaine are not necessarily connected with alterations in the dopaminergic activity in the mesolimbic system or in the transcription of precursors of endogenous opioid peptides which are located downstream of the dopaminergic synapses.

Animals↗
PubMed1998

Inhibition of growth and induction of differentiation of glioma cell lines by oncostatin M (OSM).

The neuropoietic cytokines of the interleukin-6 family are a group of structurally and functionally related polypeptides. We studied the effect of the multifunctional neuropoietic cytokines, including oncostatin M (OSM), leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), on anaplastic glioma cell lines. Growth and morphology of the glioma cell lines were affected differently. While IL-6 and LIF exerted no or only small minor morphological changes and growth retardation, OSM induced a marked change in morphology and a strong suppression of growth. OSM treated cells were characterized by enlargement and the formation of multiple, thin processes thus resembling mature cultured astrocytes. The growth inhibitory effects were dose dependent with a maximum exerted by addition of 50 ng/ml OSM. The inhibition of DNA synthesis by OSM could be abolished by antibodies blocking either the activity of OSM or the OSM-receptor component, gp130.

Antibodies↗
PubMed1994

Diagnostic value of pelvic examination, ultrasound, and serum CA 125 in postmenopausal women with a pelvic mass. An international multicenter study.

BACKGROUND: In a prospective study, the differential diagnostic potential of pelvic examination, ultrasound, and serum CA 125 assay in postmenopausal patients presenting with a pelvic mass was assessed. METHODS: A total of 228 patients were evaluated preoperatively in an international, multicenter, prospective study using a standard protocol for pelvic examination, transvaginal (occasionally additional abdominal) ultrasound, and serum CA 125 determination with a cut-off level of 35 U/ml. RESULTS: Ninety-five malignant (41.7%) and 127 benign (55.7%) pelvic tumors were found in addition to 6 borderline ovarian tumors (2.6%) in the 228 patients. Seventy-two patients had ovarian carcinoma, 49 of whom were International Federation of Gynecology and Obstetrics Stage III or IV. Borderline tumors were excluded from the statistical calculations. The individual accuracy of pelvic examination, ultrasound, and serum CA 125 in discriminating between benign and malignant pelvic masses was approximately the same (76, 74, and 77%, respectively). Using logistic regression analysis, the power of pelvic examination appeared to be the most relevant factor (adjusted odds ratio, 9.2), followed by serum CA 125 (odds ratio, 5.6), and ultrasound (odds ratio, 4.9). Age appeared to be nonpredictive. No cancer was found in any patient in whom all three methods scored negative (n = 53; positive predictive value for malignancy = 0 and 95%; confidence interval, 0-7). CONCLUSIONS: The combined use of pelvic examination, ultrasound, and serum CA 125 leads to improved discrimination between malignant and benign pelvic masses, because malignancy can be excluded when all three examination methods are negative. A change to a more patient-tailored surgical approach could be considered in those cases.

Aged↗
PubMed1992

Basic fibroblast growth factor promotes transmitter storage and synthesis in cultured chromaffin cells.

We have studied the effects of basic fibroblast growth factor (bFGF), which occurs in the adrenal medulla, on the survival, morphological phenotype, storage capacity for catecholamines and induction of the synthesizing enzymes tyrosine hydroxylase (TH) and phenylethanolamine-N-methyltransferase (PNMT) of cultured chromaffin cells from young postnatal rats. Basic FGF (40 ng/ml), like nerve growth factor (NGF; 40 ng/ml) prevented a drastic numerical decrease of chromaffin cells over a 4-day culture period, but, in contrast to NGF, did not induce neurite outgrowth, unless the cells were maintained for 7 days. Basic FGF was also more effective than NGF in maintaining the initial storage capacity for catecholamines, and even increased it under certain culture conditions (laminin instead of polyornithine, or 200 ng instead of 40 ng/ml). Basic FGF and NGF did not induce TH and PNMT activities beyond their initial levels, but partially prevented the reduction of TH activity seen after 4 days in culture. Based on the present data and the previously reported greater in vitro survival and transmitter stability of older chromaffin cells, which contain bFGF, and the relative instability of young postnatal chromaffin cells, which express no or very low levels of bFGF until 8 days postnatally, but respond to it, we hypothesize that bFGF is an important autocrine/paracrine maintenance factor for adult chromaffin cells.

Animals↗
PubMed1992

Developmental and strain-specific heterogeneity of rat adrenal chromaffin cells recognized by a monoclonal antibody against intact chromogranin B.

We have raised a monoclonal antibody (MAB-1E10) reactive with the intact forms but not the processing products of the chromaffin cell vesicle protein chromogranin B (CgB). The antibody recognizes rat and human, but not bovine and chick adrenal chromaffin cells. In addition, MAB-1E10 immunoreactivity was detected in rat PC 12 pheochromocytoma cells and in pituitaries. Several other tissues, including pancreas, small intestine and superior cervical ganglia, which are known to contain CgB in endocrine cells or neurons, respectively, were found not to be reactive with MAB-1E10. Using short-term cultures of dissociated adrenal chromaffin cells from Hannover-Wistar rats, we found that the expression of intact CgB is developmentally regulated. Between embryonic day 19 and postnatal day 40, about 80% of adrenal chromaffin cells--identified by their reactivity with an antibody against the enzyme dopamine-beta-hydroxylase--were found to be reactive with MAB-1E10. The proportion of positive cells subsequently decreased to about 5% at postnatal day 90. In the presence of glucocorticoids, this decrease was reduced to about 45% CgB-positive cells at postnatal day 90. In another rat strain, Sprague-Dawley rats, the proportion of MAB-1E10-immunoreactive chromaffin cells (about 50%) remained constant from birth to adulthood. Our results indicate that CgB is differentially expressed and/or processed in different rat tissues, strains and during development, and furthermore, that expression or processing in rat chromaffin cells might be regulated by glucocorticoids. Intact CgB appears to be a marker for a subpopulation of chromaffin cells, but its function(s) remains to be clarified.

Adrenal Medulla↗
PubMed1992

Cytokines in neural regeneration.

Growth factors with already established multiple effects on non-neural cells continue to be of considerable interest to researchers with regard to the nervous system, where regulation of cell maintenance and plasticity in relation to lesion and regeneration is part of their functional repertoire. Fibroblast growth factors, interleukins, and type beta transforming growth factors are prominent representatives of such proteins. Ciliary neurotrophic factor is another multifunctional neurokine. The proposed role of this molecule as a 'lesion factor', however, is still not firmly settled.

Animals↗
PubMed1991

Calcium-dependent transient potassium outward current in the marine ciliate Euplotes vannus.

In the marine hypotrichous ciliate Euplotes vannus, the transient K+ outward current, IK fast, was studied by use of a single-microelectrode voltage-clamp equipment. Activation and inactivation kinetics, and steady-state inactivation are comparable to the properties of A-currents. Not typical for this type of current is its insensitivity to either 4-AP or 3,4-AP and its Ca2+ dependence which was derived from its inhibition by either extracellular Cd2+, La3+, D-600, or by intracellular BAPTA. Actual amplitudes of IK fast were obtained from a composite current, by subtraction of early parts of a slowly activating K+ current, IK slow, and of the early, transient Ca2+ inward current, ICa fast, that is typical for ciliates. IK fast counteracts ICa fast during the first milliseconds after onset of depolarization such that the composite current is purely outward directed.

Animals↗
PubMed1990

High molecular weight forms of basic fibroblast growth factor recognized by a new anti-bFGF antibody.

An antibody against basic fibroblasts growth factor (bFGF) was raised using purified bovine pituitary bFGF. Western blot analysis revealed immunoreactive bands at 18, 24, 30-33 and 46 kDa in immunoaffinity purified extracts of pituitary and adrenal gland using this antibody. A similar staining pattern was obtained with ovary extracts with the exception of the missing 18 kDa band. A second anti-bFGF antibody raised against a synthetic peptide comprising the 24 N-terminal amino acids of bFGF reacted with the 18 kDa and the 46 kDa band of immunoaffinity purified ovary and adrenal gland extracts.

Adrenal Glands↗
PubMed1990

Basic fibroblast growth factor (bFGF) and rat C6 glioma cells: regulation of expression, absence of release, and response to exogenous bFGF.

Basic fibroblast growth factor (bFGF) is a potent mitogen for several types of cells, including glial cells, which also seem to express bFGF. We have used rat C6 glioma cells as a model system to study the expression and release of bFGF by glioma cells, as well as the effects of exogenous bFGF on these cells. We have shown that C6 cells express 18 kD bFGF and several higher molecular weight immunoreactive forms. The expression of bFGF could be induced by a factor present in fetal calf serum. Subsequent to its initial appearance, bFGF is regulated in a cell density-dependent manner. Neither bFGF-like immunoreactive material, nor bFGF-like neurotrophic activity were found to be released by C6 cells. Exogenously applied bFGF changed C6 cell morphology similar to cyclic AMP induced alterations but had no significant influence on C6 cell proliferation and biochemical differentiation. From these results we conclude that bFGF in C6 cells might act as an endogenous (not autocrine) mitogen. Possible roles for bFGF in glial cells are discussed.

Animals↗
PubMed1990

Basic fibroblast growth factor (bFGF) immunoreactivity is present in chromaffin granules.

Basic fibroblast growth factor (bFGF) has recently been isolated from bovine adrenal glands. Immunohistological data revealed its presence in both adrenal cortex and adrenal medulla. Using immuno-electronmicroscopy, we found that in medullary chromaffin cells bFGF-immunoreactivity is localized in the secretory granules. Immunoreactivity also was observed by electronmicroscopy in isolated granules. Western blot analysis revealed the presence of the typical 18-kDa bFGF and additional immunoreactive materials with molecular masses of approximately 24, 30, and 46 kDa in whole bovine adrenal, and in cortex and medulla. Similar results were obtained with proteins from bovine chromaffin granules, with the following two exceptions: the 46-kDa immunoreactivity was found to be highly enriched when compared with medulla or cortex, and the 18-kDa band could be detected with only an antiserum against a synthetic peptide comprising the 24 NH2-terminal amino acids of bFGF, and not with an antiserum against purified bovine pituitary bFGF. All fractions enriched for bFGF-immunoreactivity showed neurotrophic activity for chick ciliary ganglion neurons, which could be blocked by antibodies. These results demonstrate for the first time the localization and occurrence of bFGF in a cellular secretory organelle, and present further evidence for the existence of higher molecular weight immunoreactive forms of bFGF.

Adrenal Cortex↗
PubMed1990

Basic fibroblast growth factor (bFGF), a multifunctional growth factor for neuroectodermal cells.

Basic fibroblast growth factor (bFGF), a heparin-binding mitogen for mesoderm-derived cells, also acts as a mitogen, differentiation inducing and maintenance factor for many neuroectodermal cells including glial cells, neurons, paraneurons, and their tumor counterparts. The molecule is expressed in several types of neuroectodermal cells in vitro and in vivo. Furthermore, bFGF occurs in many neuronal target tissues, and can prevent ontogenetic as well as lesion-induced neuron death. Thus, in terms of its wide range of functions, bFGF is apparently more than a 'classical' neurotrophic factor. Some of its essential features, such as regulation of expression, local availability and transport in the nervous system remain to be studied.

Animals↗
PubMed1989

Laminin and other basal lamina proteins with neurite promoting activity in medium conditioned by C6 glioma cells.

Neurite promoting activities (NPFs) are essential factors in neuronal differentiation. Some of them are associated with proteins of the extracellular matrix (ECM). C6 cells, a rat glioma cell line, release NPF activities into the cell culture medium. We used antibodies against ECM-proteins for enrichment and partial characterization of these activities. Results show that, (1) C6 cells express and release laminin; (2) the C6-laminin consists of 260 kD chains only and is therefore different from typical basal lamina laminin (220 and 440 kD chains), but comparable to other laminins of glial origin (chains in the 200 kD range only); (3) C6-laminin partially purified by affinity chromatography shows NPF-activity; (4) laminin concentration in C6 cell-conditioned medium is not sufficient to account for the total neurite promoting activity of the medium, and (5) in addition to laminin C6 cells express and release fibronectin and possibly type IV collagen.

Animals↗
PubMed1988

Calcium-dependence of chromogranin A-catecholamine interaction.

Major components of the secretory organelle of bovine adrenal medullary cells, the chromaffin vesicles, are the acidic protein chromogranin A, catecholamines and Ca2+. The binding of Ca2+ to chromogranin A has been established. To study the interaction between chromogranin A and catecholamines and its dependence on Ca2+ we immobilized chromogranin A to a newly raised monoclonal antibody. It is shown that chromogranin A can bind (i) about 0.5 mol catecholamines per mol in a non-calcium-dependent manner and (ii) about 5 mol per mol in the presence of calcium. These results further support the notion that chromogranin A may act as a secretory granule-condensing protein.

Adrenal Medulla↗
PubMed1988

Neuronotrophic factors released by C6 glioma cells.

Glial cells have been shown previously to release factors that promote survival of central and peripheral neurons [neuronotrophic factors (NTFs)]. We have investigated the release of NTFs by C6 cells, a rat glioma cell line, under different modes of conditioning. Media conditioned in the presence or absence of serum [C6 cell conditioned media (C6CMs)] were analyzed using biological, biochemical, and immunological assays. We report that (a) nuclear and cytoskeletal proteins were not present in C6CMs, indicating that C6CM proteins result from release by C6 cells rather than from cell death; (b) C6CM contained 1-3 micrograms protein/ml, corresponding to a secretion rate of about 0.5 pg protein per cell and day; (c) C6CM contained the neurite-promoting factor laminin and low amounts of nerve growth factor; (d) the presence of fetal calf serum in the culture medium was essential for synthesis and release of NTFs; and (e) our C6CM contained at least three NTFs differing by their temporal secretory patterns and three NTFs differing by biochemical properties, indicating that C6 cells produce and secrete six different NTFs. Within these, nerve growth factor seems to be the only established NTF.

Animals↗