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Biomedical subjects

G Wasner

Publications and source records attributed to G Wasner.

31 records · Page 2Linked to original sources
PubMed1998

[Quantitative thermotest - investigations of thermal and nociceptive afferents in neuropathy. Is a multicentric approach useful to investigate rare painful neuropathies?].

Disturbances of small afferent nerve fibres play an important role in painful neuropathies. Quantitative thermotest offers a possibility to quantify these disturbances that can not be detected by conventional electrophysiology. It is a psychophysical method to investigate thermal and nociceptive afferents by determining thermal thresholds. Former experiences have shown that quantitative thermotest can be a helpful tool not only in daily routine but also for research work concerning pathophysiological mechanisms of neuropathy. Therefore a multicentric approach to investigate rare painful neuropathies seems to be useful.

English Abstract↗
PubMed1998

Traumatic neuralgias: complex regional pain syndromes (reflex sympathetic dystrophy and causalgia): clinical characteristics, pathophysiological mechanisms and therapy.

Complex regional pain syndromes (CPRS) may develop as a disproportionate consequence of a trauma affecting the limbs without (CRPS I, reflex sympathetic dystrophy) or with (CRPS II, causalgia) obvious nerve lesions. The clinical picture of CRPS consists of asymmetrical distal extremity pain, swelling, and autonomic (sympathetic) and motor symptoms. Changes in the peripheral and central somatosensory, autonomic and motor processing, and a pathologic interaction of sympathetic and afferent systems are discussed as underlying pathophysiologic mechanisms. Therapeutic strategies include pharmacologic pain relief, sympatholytic interventions, and rehabilitation.

Analgesics↗
PubMed1998

Optimal treatment of phantom limb pain in the elderly.

Phantom limb and stump pain is a common sequela of amputation. In geriatric patients with an amputated limb and multiple other illnesses, drug therapy may be problematic and invasive techniques may be risky. Interactions between pathophysiological mechanisms in the peripheral and central nervous systems may be responsible for the initiation and maintenance of chronic phantom limb and stump pain. These mechanisms include: (i) peripheral damage to nociceptive fibres and dorsal root ganglion cells, which acquire abnormal sensitivity to mechanical, thermal and chemical stimuli; (ii) the prolonged sensitisation of central nociceptive 'second order' neurons in the dorsal horn of the spinal cord, which become hyperexcitable and start responding to nonnoxious stimuli; and (iii) the degeneration of nociceptive neurons, which may trigger the anatomical sprouting of low threshold mechanosensitive terminals to form connections with central nociceptive neurons. This may subsequently induce functional synaptic reorganisation in the dorsal horn. The provision of a pain-free perioperative interval using regional anaesthetic techniques is likely to reduce the incidence of phantom limb pain. The therapy of manifest pain is difficult, and treatment should start as soon as possible to prevent chronic pain. In the acute state, the infusion of calcitonin and oral opioid analgesics have proven to be helpful, while established phantom limb pain may respond to antidepressants, anticonvulsants and drugs that mimic or enhance gamma-aminobutyric acid function. Pharmacological treatment should be combined with transcutaneous electrical nerve stimulation, sympathetic blockade and psychotherapy. In addition, new therapeutic strategies are now being tested; examples include capsaicin, new anticonvulsants and N-methyl-D-aspartate antagonists. Patients with severe pain should be referred to a pain specialist to ensure optimal and timely interventional pain management.

Amputation Stumps↗
PubMed1997

Interaction of sympathetic vasoconstriction and antidromic vasodilatation in the control of skin blood flow.

We studied the interaction between the vasoconstriction evoked by postganglionic sympathetic neurones (sympathetic vasoconstriction) and the vasodilatation mediated by small-diameter afferent neurones (antidromic vasodilatation) in hairless skin of anaesthetized rats kept under controlled conditions. In all animals both the lumbar sympathetic trunk (LST) and the ipsilateral dorsal root (DR) L5 were surgically exposed, sectioned and electrically stimulated using different protocols. This experimental approach results in the exclusive and selective activation of sympathetic efferents and primary afferents respectively. Blood flow responses were measured using laser Doppler flowmetry. Sectioning the LST resulted in a pronounced increase in cutaneous blood flow by 112+/-15% (mean+/-SEM, n=25) indicating that ongoing sympathetic vasoconstrictor activity had been abolished. When a brief antidromic vasodilatation was produced by DR stimulation with 10-15 pulses at 1 Hz with C-fibre intensity during a sustained sympathetic vasoconstriction, peak blood flow reached preconstriction levels at LST stimulation frequencies of < or = 3 Hz. By contrast, antidromic vasodilatation was reduced at sympathetic stimulation frequencies of > or = 5 Hz and absent when stimulating the LST with 20 Hz. A similar response characteristic was obtained when LST and DR stimulation were started simultaneously. Continuous DR stimulation with 0.1 Hz evoked a substantial increase in cutaneous blood flow by 38+/-10% (mean+/-SEM, n=8) to a new baseline level. When sympathetic vasoconstriction was elicited on this background DR stimulation, the responses were smaller at all sympathetic frequencies. However, the maximum decrease in blood flow was significantly smaller than the controls at LST stimulation with < or = 3 Hz but not at higher frequencies. We conclude that sympathetic vasoconstriction and antidromic vasodilatation are competitive influences in the control of cutaneous blood flow. At low levels of cutaneous sympathetic vasoconstrictor activity, which probably prevail under resting conditions in the absence of cold stress, antidromic vasodilatation overrides sympathetic vasoconstriction. At high levels of cutaneous sympathetic activity, which may be reached in normal life under the conditions of severe cold, sympathetic vasoconstriction can suppress antidromic vasodilatation almost totally.

Animals↗
PubMed1997

Responses of rat postganglionic sympathetic vasoconstrictor neurons following blockade of nitric oxide synthesis in vivo.

The hypothesis was tested that the activation of postganglionic sympathetic neurons contributes to the peripheral vasoconstriction and the blood pressure increase which are observed in rats after systemic blockade of nitric oxide synthase by substituted L-arginine analogues. Single and multifiber postganglionic sympathetic activity supplying hindlimb hairy skin and the activity in the caudal lumbar sympathetic trunk supplying mainly hindlimb skeletal muscle were recorded in anaesthetized, paralysed and artificially ventilated Wistar rats before, during and up to 1 h after intravenous injection of a supramaximal dose (10 or 35 mg/kg) of N(G)-nitro-L-arginine methyl ester. This elicited a sustained rise of arterial blood pressure, a long-lasting decrease in heart rate and vasoconstriction in hindlimb skin and skeletal muscle as measured by laser Doppler flowmetry. With intact buffer nerves all sympathetic neurons analysed responded with a decrease in their ongoing activity in parallel with the vasoconstriction and the increased blood pressure, except for one neuron which was unresponsive. These responses were probably mediated by the arterial baroreceptors. since it was shown that N(G)-nitro-L-arginine methyl ester did not impair the function of both the afferent and the efferent limb of the reflex. Furthermore, baroreceptor denervation almost abolished the inhibitory responses in sympathetic neurons. In baroreceptor denervated animals, with a latency of about 15 min after N(G)-nitro-L-arginine methyl ester there was an increase in sympathetic activity without a further increase in blood pressure. It was concluded that sympathetic vasoconstrictor neurons which supply the rat hindlimb do not contribute by neurogenic means to the vasoconstriction and the blood pressure increase occurring after blockade of the nitric oxide synthase. Instead, the results suggest that sympathetic vasoconstrictor neurons, via the baroreceptor loop, counteract the vasoconstriction caused by the blockade of endothelium-derived nitric oxide. Therefore nitric oxide does not seem to play a role in the central regulation of activity in the sympathetic vasoconstrictor pathways studied here. The long latency increase in sympathetic activity observed after N(G)-nitro-L-arginine methyl ester in baroreceptor-denervated animals may be due to an impairment of blood flow in the brainstem.

Animals↗
PubMed1997

Attenuation of neurogenic vasoconstriction by nitric oxide in hindlimb microvascular beds of the rat in vivo.

There is evidence that sympathetic nerve activity leads to endothelium-derived nitric oxide release, which in turn attenuates neurogenic vasoconstriction. Here we tested in vivo (1) whether the magnitude of the vasoconstriction induced by N(G)-nitro-L-arginine methyl ester given systemically is altered when ongoing sympathetic activity is abolished by sectioning the lumbar sympathetic trunk, and (2) whether hindlimb sympathetic vasoconstriction elicited by electrical stimulation of the lumbar sympathetic trunk is enhanced after inhibition of nitric oxide synthesis. Blood flow in the microvascular beds of hairless skin and skeletal muscle of the rat hindlimb was measured with laser Doppler flowmetry. Sectioning the lumbar sympathetic trunk resulted in an increase of blood flow in both tissues, indicating that tonic neurogenic vasoconstriction was abolished. Inhibition of nitric oxide synthesis resulted in vasoconstriction in both vascular beds. This vasoconstriction was more pronounced after abolition of sympathetic activity than with intact sympathetic supply in skin but was smaller in skeletal muscle. The vasoconstriction elicited by graded electrical stimulation of the centrally sectioned lumbar sympathetic trunk with frequencies less than 5 Hz was significantly enhanced after blockade of nitric oxide in skeletal muscle but not in skin microvasculature. These findings suggest that under physiological conditions, sympathetic nerve impulses directly promote the release of nitric oxide in skeletal muscle but not in cutaneous blood vessels. Therefore, basal nitric oxide release is probably in part dependent on sympathetic activity in skeletal muscle, whereas it appears to be mainly due to flow-dependent shear stress in hairless skin microvasculature.

Animals↗
PubMed1989

Differential modulation of gene induction by glucocorticoids and antiglucocorticoids in rat hepatoma tissue culture cells.

Studies of glucocorticoid and antiglucocorticoid induction of tyrosine aminotransferase (TAT) in two rat hepatoma cell lines (Fu5-5 and HTC) are described. These studies revealed several phenomena that are not consistent with the current models of steroid hormone action: (a) TAT induction occurred at glucocorticoid levels below those required for comparable receptor occupancy in Fu5-5, but not in HTC, cells; (b) the ability of antiglucocorticoids to induce TAT is higher in Fu5-5 than in HTC cells; (c) the values of the amount of TAT agonist activity with the antiglucocorticoid dexamethasone 21-mesylate and of log10 of the dexamethasone concentration required for half-maximal induction of TAT were not constant over time but varied in a linear, reciprocal manner. This modulation was seen for several glucocorticoids and antiglucocorticoids at the level of both TAT enzyme and mRNA but not for two other glucocorticoid inducible genes in the same cells. These results, plus the fact that a similar difference in the concentration required for half-maximal TAT induction in Fu5-5 cells was seen for both glucocorticoids and cyclic AMP, argue that the modulation occurs at some point distal to receptor-steroid complex binding to the biologically active nuclear sites but proximal to translation of TAT mRNA. In order to explain these results, it is pointed out that models involving second messengers are entirely appropriate for steroid hormone action. The participation of a modulated trans-acting factor in such a model may explain the above results.

Animals↗
PubMed1988

Inverse correlation between dexamethasone 21-mesylate agonist activity and sensitivity to dexamethasone for induction of tyrosine aminotransferase in rat hepatoma cells.

Previous results demonstrated that both the level of induction of the liver specific enzyme tyrosine aminotransferase (TAT) by the irreversible antiglucocorticoid dexamethasone 21-mesylate (Dex-Mes) and the concentration of the reversible glucocorticoid dexamethasone (Dex) required for 50% of maximal TAT induction (i.e. EC50) were different in HTC and Fu5-5 rat hepatoma culture cells. In the present study, a retrospective analysis of these two parameters over an 8 yr period indicates that the absolute values of both parameters varied within each cell line over time in a reversible manner. The variation of both parameters appears to be causally related since a linear, reciprocal relationship exists between the amount of Dex-Mes agonist activity and log10 (Dex EC50) in both cell lines (correlation coefficient is -0.896 for n = 46). This relationship was independent of changes in basal TAT level, culture medium, and serum lot. Results with cloned HTC cells indicate that these temporal variations are not due to fluctuations in the relative abundance of two cell populations displaying either high or low amounts of agonist activity with Dex-Mes. While these analyses relied on the detection of enzyme levels, the amount of TAT mRNA is shown to parallel the enzyme levels. Thus the variation in parameters of TAT induction by Dex and by Dex-Mes appears to be modulated at a pre-translational step. Such variations have not previously been observed for the control of specific gene transcripts by other steroid hormones and may be related to the known differences in agonist activity seen for most antisteroids in various systems.

Animals↗
PubMed1988

Unlinked regulation of the sensitivity of primary glucocorticoid-inducible responses in mouse mammary tumor virus infected Fu5-5 rat hepatoma cells.

The enzyme tyrosine aminotransferase (TAT) is induced by unusually low concentrations of glucocorticoids in Fu5-5 cells. We have isolated clones of Fu5-5 cells infected with mouse mammary tumor virus (MMTV) in order to simultaneously compare the glucocorticoid regulation of the host cell gene, TAT, with that of another primary inducible gene, MMTV. In the two clones that were examined in detail, MMTV RNA induction occurred at 4- to 11-fold higher concentrations of dexamethasone than those needed for induction of TAT mRNA. Furthermore, the amount of agonist activity displayed by the irreversible antiglucocorticoid dexamethasone 21-mesylate was greater for the induction of TAT mRNA than for MMTV RNA. These results extend our previous observations of unequal sensitivity of induction of TAT enzyme activity in two hepatoma cell lines and show that differential glucocorticoid regulation of gene induction within the same cell can occur at a pretranslational step. The present data also indicate that the unusual properties of TAT gene induction are not shared by all primary, glucocorticoid-inducible responses of the same cell and imply that additional factors mediating differential regulation of glucocorticoid-responsive genes are involved.

Animals↗
PubMed1987

Differential sensitivity of HTC and Fu5-5 cells for induction of tyrosine aminotransferase by 3',5'-cyclic adenosine monophosphate.

The two independently derived hepatoma cell lines (HTC and Fu5-5) have previously been shown to display different sensitivities for the induction of tyrosine aminotransferase (TAT) enzyme activity and mRNA levels by glucocorticoids with the enzyme being half-maximally induced at approximately 7-fold higher concentrations of dexamethasone in HTC cells than in Fu5-5 cells. In the present study we investigated the induction of TAT activity by cAMP in order to see whether the difference is limited to the steroidal induction. Using the stable cAMP derivative (8-(4-chlorophenylthio)-cAMP) as an inducer, we found that a 6-fold higher cAMP concentration was needed in HTC cells to achieve the same extent of enzyme induction as in Fu5-5 cells. The induction of TAT enzyme activity could be accounted for by an increased amount of TAT mRNA. Further experiments involving sequential addition of both inducers in general showed a synergism of steroids and cAMP for TAT induction in HTC cells only at submaximal concentrations of steroid; in Fu5-5 cells, the occurrence of synergism depended on the order of addition of inducers. The maximal response in HTC cells was limited to the value that could be achieved by induction with steroid alone. In Fu5-5 cells, however, the steroid response could be augmented when cAMP was added to cells already maximally induced by steroid. This demonstrates that the effect of a combination of cAMP and steroids depends on their concentration, the sequence of their addition, and the rat hepatoma cell line used. Collectively the data suggest that a common pretranslational event determines the differential sensitivity of TAT induction by glucocorticoids and by cAMP in HTC and Fu5-5 cells. Furthermore a second, or possibly the same, common event also regulates the maximum level of TAT induction that is obtainable under most conditions with glucocorticoids and/or cAMP.

Animals↗
PubMed1983

Ontogeny of mesenchymal androgen receptors in the embryonic mouse mammary gland.

We demonstrate the presence of a high affinity androgen-binding site in the embryonic mouse mammary gland, and describe its appearance and development from the initial formation of the gland bud (day 12) through the androgen-responsive stage (day 14) until term (day 19). Binding assays were done on entire organ rudiments exposed to the ligand [( 3H] testosterone, [3H]5 alpha-dihydrotestosterone, or [3H]methyltrienolone) in vitro, and receptor levels are expressed per gland. In competition experiments, the binding site shows a ligand specificity of a typical rodent androgen receptor. Scatchard analysis yielded a figure of 90-100 million binding sites for one 14-day gland, or approximately 30,000 per target cell. The apparent dissociation constant Kd for ligand binding by the intact tissue was between 0.55 and 0.75 X 10(-9) M. The first binding sites become detectable at the time of mammary bud formation (day 12); their number increases about 20-fold towards the responsive stage (day 14), and they persist at high levels at least until birth. The loss of androgen responsiveness on day 15 is neither accompanied by a loss of receptors nor by a change of their binding affinity.

Animals↗
PubMed1982

Induction of androgen receptor formation by epithelium-mesenchyme interaction in embryonic mouse mammary gland.

The role of tissue interaction in the development of hormone responsiveness was studied in the embryonic mammary gland of the mouse, which becomes sensitive to testosterone on day 14. Previously, the mesenchyme had been identified as the sole target tissue for the hormone, although it was also demonstrated that its response to testosterone required the presence of mammary epithelium. Using autoradiography, we now show that [3H]testosterone or [3H]5 alpha-dihydrotestosterone is bound only by those mesenchymal cells closest to the epithelial mammary bud. When mammary epithelia were experimentally associated with mesenchyme of the mammary region and cultured together for 3 days in vitro, they also became surrounded by several layers of [3H]testosterone-binding mesenchymal cells. Correspondingly, this tissue association was accompanied by a substantial increase of androgen-binding sites in the explants. No hormone-building mesenchymal cells were seen in combinations with epidermis or pancreas epithelium; only salivary epithelium showed a weak positive effect. From these results we conclude that mammary epithelium induces the formation of androgen receptors in adjacent mesenchyme and thereby controls the development of androgen responsiveness in this tissue.

Animals↗