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Biomedical subjects

K Jellinger

Publications and source records attributed to K Jellinger.

At least 199 records · Page 11Linked to original sources
PubMed1985

Comparison of benzodiazepine receptor binding in membranes from human or rat brain.

Specific high affinity binding of [3H]flunitrazepam to membranes from human brain was stimulated by gamma-aminobutyric acid (GABA), pentobarbital, 1-ethyl-4-(isopropylidene-hydrazino)-1H-pyrazolo[3,4b]pyridine-5-carboxy lic acid ethyl ester hydrochloride (SQ 20009) and avermectin B1a and was unaffected by 2 microM 4'-chlorodiazepam (Ro 5-4864) indicating that [3H]flunitrazepam in human brain as well as in rat brain predominantly binds to benzodiazepine receptors specific to brain, which was associated with a GABA receptor and several modulatory binding sites for drugs. The potency of several selective and non-selective ligands for benzodiazepine receptors for inhibition of the binding of [3H]flunitrazepam was compared in membranes from human or rat brain cerebellum, hippocampus and cerebral cortex. It was demonstrated that all these compounds, derived from different chemical structures, had a remarkably similar potency for inhibition of the binding of [3H]flunitrazepam in the corresponding regions of the human or rat brain. However, irreversible labelling of benzodiazepine binding sites with [3H]flunitrazepam and subsequent SDS-polyacrylamide gel electrophoresis and fluorography revealed more photolabelled protein bands in human than in rat cerebellum and hippocampus. The results seem to indicate that, although the pharmacological properties of reversible binding of [3H]flunitrazepam are remarkably similar in membranes from rat or human brain, the molecular heterogeneity of benzodiazepine binding sites is even greater in human than in rat brain.

Animals↗
PubMed1985

[Changes in and modulation of receptor activity in hepatic encephalopathy].

In hepatic encephalopathy (HE) brain uptake of large neutral amino acids is impaired with tryptophan crossing the blood brain barrier (BBB) to a much larger extent than all other competing amino acids (AA). The disturbance in the steady-state of transmitter is paralleled to the change of their kinetic data. This is reflected by an increase in serotonin (5-HT) synthesis and turnover, while the number of post-synaptic 5-HT1-binding sites is decreased, 5-HT2-receptor activity is dropping to a much smaller extent. On the other hand, presynaptic dopaminergic activity remains unchanged with no change in D2-receptor activity. Valine (VAL) improves the postsynaptic 5-HT function via modulating activity due to a regulatory mechanism at the membranal level in vitro and ex vivo. Furthermore, VAL leads to a significant reduction of serum ammonia (NH4+) and brain NH4+ concentration. VAL is able to antagonize the binding density diminishing effects of NH4+ on 5-HT binding sites. This effect could be characterized by the measurement of VAL binding sites being 5 to 10 fold higher than the number of leucin (LEU)-sites. Considering the chemical bonds involved in the attachment of biogenic amines and aminoacids (Schiff-bases equilibria) the modulating action of NH4+ on neural transmission may be clarified. Tryptamine can displace the postsynaptic binding of 5-HT in brain tissue and is a possible antagonist to physiological and pharmacological effects of 5-HT. The dynamic changes of the kinetic behaviour of tryptamine-binding might demonstrate a compensating effect as shown in an increase of tryptaminergic receptor activity. As a working hypothesis, the different relative strengths of electron-pair donor and -acceptor sites of both compounds are suggested to their complementary physiological interaction. GABA, an inhibitory transmitter of the CNS is diminished in its maximal binding capacity in severe HE and is independent of NH4+ influence. Furthermore, glutamate and aspartate-receptors decrease in experimentally induced hepatic coma. L-LEU shows modulating effects of glutamine binding. Glycin-activity is increased, while naloxone- and D-ala2-methionine-encephalinamid binding are not different from controls. These data demonstrate a different influence of various brain receptors and binding sites by HE and indicate a differentiated disturbance of (neuronal) membrane activity. Therefore disturbed interneuronal dynamics might be important pathophysiological mechanisms underlying hepatic coma.

Ammonia↗
PubMed1984

Bimodal distribution of dopamine receptor densities in brains of schizophrenics.

The dopamine hypothesis of schizophrenia was examined by measuring the density of dopamine receptors in the postmortem brains of 81 control subjects and 59 schizophrenics from four different countries. The densities of dopamine receptors in the tissues from the schizophrenic patients had a bimodal distribution in the caudate nucleus, putamen, and nucleus accumbens. One mode occurred 25 percent above the control density, and a second mode occurred at a density 2.3 times that of the control density for all three regions. Although almost all the patients had been medicated with neuroleptics, the two modes had the same dissociation constant for the labeled ligand used, suggesting that the neuroleptic doses were similar for the two populations of schizophrenics. The results thus provide direct evidence for two distinct categories of schizophrenia.

Antipsychotic Agents↗
PubMed1984

Cerebral granulomatous angiitis with atypical features.

A case of cerebral granulomatous angiitis of the left temporal lobe mimicking a brain tumour is presented. Following surgical removal of a glioma-imitating mass, histological examination disclosed a granulomatous vasculitis. Treatment consisted of dexamethasone given in tapering doses for 5 days after surgery. Clinical and morphological differences from other reported cases of granulomatous angiitis of the nervous system are described.

Adult↗
PubMed1984

Metastasis of solid tumors in extraocular muscles.

Three autopsy cases with discrete metastatic involvement of one or several extraocular orbital muscles by disseminated amelanotic melanoma (one case) and lobular mammary adenocarcinoma (two cases) associated with extensive meningeal involvement are reported. Clinical ocular symptoms including pain, exophthalamus, and diplopia occurred 6 months to almost 5 years after resection of the primary tumor; in two cases CT scan showed spindle-like enlargement of orbital muscles. Pathologic examination disclosed solid localized metastatic deposits in several extraocular muscles of one (breast carcinomas) or both orbits (melanoma), with diffuse invasion of striated muscle, but without necrosis, inflammation, or involvement of other orbital adnexa, eye ball, optic nerves, or orbital bone. Since no continuous invasion of orbital or intraocular structures by diffuse meningeal blastomatosis was histologically observed, rare metastatic involvement of extraocular muscles via hematogenic route is suggested.

Breast Neoplasms↗
PubMed1983

[Betamed in the treatment of psychogenic disorders with a somatic component].

52 patients with acute neurotic anxious and psychosomatic syndromes or chronic anxious and vegetative neuroses were treated orally with the combination drug Betamed (1 tablet contain 60 mg bupranolol and 2.5 mg diazepam). The optimum daily dosage are 2 to 3 tablets; duration of treatment ranged from 2 to 12 weeks. The most responsive target symptoms are psychogenic disorders of the cardiovascular system, anxiety and insomnia, while no antidepressive effect was observed. Clinical improvement is often observed 2 to 3 weeks after the onset of treatment, and dosage reduction is possible frequently. Rarely observed side effects are minimal and mainly occur within one week after onset of treatment. Controls performed 2 to 4 weeks after discontinuation of treatment revealed reactivation of symptoms only in some patients with chronic anxiety and vegetative syndromes. In addition to the easy application and excellent tolerance of the combination drug emphasis is given on the minimal danger of drug dependence.

Adolescent↗
PubMed1983

[Combined treatment of malignant gliomas].

A controlled study of 226 age-matched patients with histologically proven grade 3 and 4 supratentorial gliomas with maximum feasible tumour resection, postoperative Karnofsky performance over 50 and minimum survival of 8 weeks compares the results of supportive care (45 cases), high-dose irradiation of 40 to 66 Gy (59 cases), COMP protocol (CCNU, procarbazine, vincristine, methotrexate, prednisone in 15 day cycles-42 cases) and simultaneous irradiation and COMP chemotherapy (80 cases including 30 survivors). Median recurrent-free intervals in the treatment groups (7 to 11.7 months) were significantly longer than after supportive care (4.4 months). Median survival with supportive care (6.7 months) was significantly shorter than after radiation or COMP treatment (11.7 and 12.3 months) and 14.9 to over 19.9 months with combined treatment, where the two-year survival rates were 33 and 67% (for survivors), and the 3-year survival rates 13 to 30%. Toxic side effects of multimodality treatment were more frequent than after chemotherapy. In addition to space-occupying intracranial cysts often simulating tumour recurrence (12%) and rare radiation necrosis, about 15% of long-term survivors developed progressive intellectual dysfunction with brain atrophy, in the absence of tumour regrowth. Despite some promising results of multimodality approaches towards the management of malignant supratentorial gliomas, the overall results are unsatisfactory and need further optimization.

Adult↗
PubMed1983

Neurochemical insights into monoamine oxidase inhibitors, with special reference to deprenyl (selegiline).

Monoamine oxidase (MAO) is distributed in neurons and non-neuronal tissue in the human central nervous system. It occurs there as MAO type A and MAO type B. It is not, however, established where both types are located intra- and/or extra-neuronally. Recently, the use of selective MAO-B blockers has shown beneficial effects in the treatment of Parkinson's disease (PD). Knowledge about the locus of action of MAO inhibitors is therefore of great importance. Our findings indicate that MAO-B inhibitors like deprenyl act by blocking neuronal and extra-neuronal MAO-B. This demonstrates that in the early stages of PD the action of deprenyl improves dopamine neurotransmission and hormonal action, whereas in the advanced stages of the disease, when there is progressive loss of dopaminergic neurons accompanied by gliosis, the drug seems to exert beneficial effects via the hormonal route.

Aged↗
PubMed1983

Correlation between EEG changes indicative of sedation and subjective responses.

The central activity of ketotifen ( Zaditen ), a benzocycloheptathiophene derivative for use in the prophylaxis of asthma, was determined by quantitative pharmaco-EEG in 7 healthy volunteers in a single-blind trial. During the 1st week of the trial, placebo was given twice daily followed by ketotifen 1 mg twice daily for 3 weeks. Placebo was again given for a further week. 15-min resting EEGs were taken immediately before and 3 and 6 h after medication on 8 defined days during the study, and the subjects were asked for side effects. Lead O2-Cz was analyzed by spectral analysis, and the relative power of the delta, theta, and fast and slow alpha bands as well as the dominant alpha frequency were calculated. The mean of each of these parameters was calculated per subject for each of the three measurements on each study day and compared with the baseline by means of one-way analysis of variance. A statistically significant slowing of the dominant alpha frequency, a decrease of the relative power of the fast alpha activity, and an increase of the relative power of the theta rhythm were found. These effects, indicative of a mild sedation, were highest during the 1st week of treatment with ketotifen, with a peak at the 3rd day, and gradually decreased thereafter. In contrast to the sensitive pharmaco-EEG method, none of the subjects complained of sedation or tiredness while taking ketotifen.

Adult↗
PubMed1983

Studies on the neurotransmitter binding to pig brain microvessels.

Microvessels from pig brain areas were prepared by differential centrifugation techniques. These fractions were assayed for purity and structural unity by marker enzyme determination, light and electron microscopy. Binding properties of 3H-flunitrazepam were studied in different brain regions. Kinetic studies of 3H-flunitrazepam showed BMax-values of 0,42 +/- 0,3 pmol/mg protein and KD-values of 1,26 +/- 0,6 nM and were compared to a synaptosomal membrane fraction (P2-fraction) with BMax = 2,68 +/- 0,5 pmol/mg protein and a KD of 1,95 +/- 0,3 nM. GABA kinetic studies gave IC50-values of 250 nM in the microvessel fraction and 40 nM in the P2-fraction.

Animals↗
PubMed1983

General properties of 14C-L-Valine-binding to human brain tissue.

L-Valine (VAL) binding is saturable, reversible, linear within a protein concentration of 0.2 to 0.8 mg prot./ml, pH dependent (pH-optimum 7.1 to 7.4), temperature dependent with extremely low binding at 0-4 degrees C; the assay runs at 37 degrees C; it is ion dependent (Bmax:CaCl2 (5mM): + 100%; NaCl (5 mM): -50%); very sensitive to TRITON X-100 (Bmax at 0.01%; -70%); N-ethylmaleimide (0.5 mM): Competitive inhibition; no change in non-specific binding; there are no effects by puromycin plus GTP; VAL binds to synaptic membranes of human frontal cortex with KD-values several fold lower than that observed with homogenates, the distribution of VAL-binding is different in various human brain areas and can be inhibited by L-leucine, L-isoleucine, L-serine, DL-threonine, glycine and D-valine, while aromatic amino acids, beta-alanine, GABA, taurine, glutamate, proline and gamma-glutamyltaurine have no effects of 10(-3) M.

Aged↗
PubMed1982

[Long-term treatment of depressive syndromes with Psyton (author's transl)].

23 patients (in-patients and out-patients) with anxious-depressive symptoms were treated orally with the combination drug Psyton (nomifensine/clobazam) up to 6 months. Significant improvement of both anxiety and depression were observed by both the patients' and physician's assessment, particularly during the first month of treatment. Physical examination and laboratory investigations (weight, pulse rate, blood pressure, EKG, ophthalmology, blood and urine analysis, liver function tests) were not influenced by Psyton. Drug tolerance was good, and side effects observed in 39% of the patients were minimal and mainly occurred within 4 weeks after onset of treatment. There was no tendency to physical drug dependence during treatment and during a one-week placebo phase after discontinuation of Psyton. Hence, a long-term treatment of anxious depressive syndromes with this combination drug appears justified without development of drug dependence.

Adolescent↗