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Biomedical subjects

G Ebinger

Publications and source records attributed to G Ebinger.

At least 109 records · Page 6Linked to original sources
PubMed1990

Recurrent brachial plexus neuropathy and giant cell arteritis.

A 73-year-old women presented with a recurrent form of sporadic brachial plexus neuropathy, the so-called Parsonage and Turner syndrome. This diagnosis is based on clinical and electromyographic findings. Interestingly a biopsy of the temporal artery demonstrated a giant cell arteritis. The clinical picture started 2 weeks after an upper respiratory tract illness. The possible viral etiology of giant cell arteritis is considered. We think an immunological rather than ischemic disturbance may have caused the recurrent brachial plexus neuropathy. This case report suggests that giant cell arteritis be considered in the investigation of the Parsonage and Turner syndrome.

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PubMed1990

Development of monoaminergic neurotransmitters in fetal and postnatal rat brain: analysis by HPLC with electrochemical detection.

The monoamines dopamine, norepinephrine, epinephrine, and serotonin and their major metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylethylene glycol, and 5-hydroxyindoleacetic acid were measured in the CNS of the rat during development from fetal day 18 to young adult. The catecholamines, serotonin, and their major metabolites remained low during fetal life. Concentrations measured in total brain started to increase around birth till the end of the fourth week of life after which steady-state levels were measured. Our results suggest that although monoamine systems are already morphologically well developed during late gestational life, they probably become a significant functional system only around birth and early postnatal life.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Evidence for a widespread dopaminergic innervation of the human cerebral neocortex.

The recent finding that D1 dopamine receptors are present in all neocortical areas of the human brain, does not fit in with the generally held view that the mesocortical dopaminergic pathway is restricted to prefrontal areas. We investigated the brains of 3 patients who died with a unilateral infarction in the ventral midbrain, including the substantia nigra and ventral tegmental area. Compared to the intact side, the D1 receptors in frontal, temporal, parietal and occipital cortices and caudate nucleus at the lesioned side were increased by 27-37%, which is consistent with an up-regulation in response to a depletion of dopamine. These data provide evidence for a more widespread dopaminergic innervation of the human neocortex.

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PubMed1989

Coupling of D1 dopamine receptors to the guanine nucleotide binding protein Gs is deficient in Huntington's disease.

Human brain contains two subtypes of D1 dopamine receptors, which both exist under high- (RH) and low-agonist affinity (RL) sites, but can be distinguished on the basis of the ability of GTP to convert RH into RL. The amygdala contains exclusively GTP-sensitive (GS) D1 receptors, frontal cortex exclusively GTP-insensitive (GI) D1 receptors, and putamen both GS and GI receptors. In contrast with controls, we were unable to detect RH sites in amygdala from patients with Huntington disease (HD). The amount of RH sites in normal and HD frontal cortex were similar. In putamen, the GTP-induced partial conversion of RH into RL, observed in controls, was absent in HD. The results suggest that coupling of GS-D1 receptors with the guanine nucleotide binding protein Gs may be deficient in HD.

Adult↗
PubMed1989

D2 dopamine receptors in the human brain: heterogeneity based on differences in guanine nucleotide effect on agonist binding, and their presence on corticostriatal nerve terminals.

In human brain, regulation of agonist binding to the D2 dopamine receptors by guanine nucleotides is different between several regions. In membranes of the anterior pituitary lobe, agonist binding is fully sensitive to GTP or Gpp(NH)p, whereas it is resistant in membranes of globus pallidus. Both guanine nucleotide-sensitive (G-S) and -insensitive (G-I) receptors are found in membranes of the striatum. The G-S and G-I type receptors display similar affinities for antipsychotic drugs of different classes, suggesting that they only differ in their effector-coupling system. We investigated the D2 receptors in striatal membranes of postmortem human brains in which corticostriatal pathways were unilaterally destroyed by an infarction. Compared to the intact side, D2 receptor densities in striata from the lesioned side were reduced by 46-65%, whereas the densities of the muscarinic cholinergic receptors, dopamine uptake sites, and D1 dopamine receptors were unchanged. In the deafferented striata all G-I, but also a substantial number of G-S receptors were lost, suggesting that both receptor subtypes are present on corticostriatal nerve terminals.

Adult↗
PubMed1989

Regional differences in the distribution of norepinephrine and epinephrine in human cerebral cortex: a neurochemical study using HPLC and electrochemical detection.

We performed neurochemical quantitation of the catecholamines dopamine (DA), norepinephrine (NE) and epinephrine (E) and their major metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) in 22 cortical regions of 6 postmortem human brains. Statistical analysis indicated a clear regional difference for NE and E while DA and all the metabolites under study are homogeneously distributed over the cortex. These consistent regional differences suggest the possible role of NE and E as neurotransmitters or neuromodulators in human cerebral cortex.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

[3H]SCH 23390 labels a novel 5-hydroxytryptamine binding site in human blood platelet membranes.

In human blood platelet membranes, 5-HT displaced the binding of the putative selective D-1 dopamine receptor antagonist [3H]SCH 23390 in a competitive manner with a Ki value of 5.7 +/- 0.8 nM, which was about 1000-fold lower than the Ki value for dopamine (Ki = 4400 +/- 150 nM). Thus the 'D-1 dopamine-like' site in human blood platelet membranes described previously corresponds to a 5-HT1-type site. [3H]SCH 23390 competition experiments with a number of serotonergic drugs disclosed a pharmacological profile that was distinct from the four 5-HT1 site subtypes reported previously. We therefore propose that this novel 5-HT site be designated the 5-HT1E site. Binding of [3H]SCH 23390 to 5-HT1-type sites could not be detected in several regions of the human brain. In some regions, however, 5-HT displaced part of the [3H]SCH 23390 binding with a K1 value of 320-380 nM. These sites correspond to 5-HT2 receptors.

Antipsychotic Agents↗
PubMed1989

Vertical one-and-a-half syndrome. Supranuclear downgaze paralysis with monocular elevation palsy.

A patient with bilateral infarction in the mesodiencephalic region showed impairment of all downward rapid eye movements (including vestibulo-ocular movements) and foveal smooth pursuit (nondissociated downgaze paralysis) associated with monocular paralysis of elevation (vertical one-and-a-half syndrome). Bell's phenomenon and all types of horizontal eye movements were preserved. The lesions may have affected the efferent tracts of the rostral interstitial nucleus of the medial longitudinal fasciculus bilaterally and the premotor fibers to the contralateral superior rectus subnucleus and ipsilateral inferior oblique subnucleus, either before or after decussation in the posterior commissure.

Cerebral Infarction↗
PubMed1989

Lack of GTP-insensitive D2 dopamine receptors in Huntington's disease.

Previous studies have shown that the mammalian neostriatum contains two subtypes of D2 dopamine receptors, which can be distinguished on the basis of the ability of GTP to convert high (RH) into low (RL) affinity sites for dopamine: GTP-sensitive (GS) and GTP-insensitive (GI) D2 receptors. The GI-D2 receptors in rat and human neostriatum are confined to the corticostriatal terminals. In rats, these receptors mediate the inhibitory effect of dopamine on the release of glutamate in the striatum. Here we report that the putamen in Huntington's disease (HD) lacks GI-D2 receptors. Their absence might be responsible for an inappropriate release of glutamate, which is neurotoxic in high concentrations, and might thus contribute to striatal cell death in HD.

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PubMed1989

Monoaminergic neurotransmitters in Alzheimer's disease. An HPLC study comparing presenile familial and sporadic senile cases.

Norepinephrine, epinephrine, dopamine, serotonin and their major metabolites were measured in 20 regions of the left hemisphere in 4 presenile familial cases of Alzheimer-type dementia and 4 sporadic senile cases. Both groups were compared to values in normal brains obtained in our laboratory. Quantitative determination of the monoamines was performed by HPLC with electrochemical detection. The clinical diagnosis of Alzheimer-type dementia was confirmed by histological examination of the right hemisphere and brain stem. The serotonergic system was dramatically affected in the familial cases with very low or undetectable serotonin concentrations in most cortical and subcortical areas studied and an important cell loss in the nucleus raphe dorsalis, origin of the main ascending serotonergic system. In the senile demented patients the serotonergic deficit is less important but still clearly present. The noradrenergic, adrenergic and dopaminergic systems were less affected by the disease process in senile sporadic as well as in the presenile familial type of Alzheimer's disease.

Adult↗
PubMed1989

Clinical and pharmacokinetic evaluation of controlled-release levodopa/carbidopa (CR-4) in parkinsonian patients with severe motor fluctuations: a six month follow-up study.

The results of a six month open-label study comparing the efficacy of controlled-release levodopa-carbidopa (Sinemet CR-4 200 mg/50 mg) with standard levodopa/carbidopa (250 mg/25 mg) in 17 patients with idiopathic Parkinson's disease and severe response fluctuations, are reported. Major clinical benefits included; improvement of disability, reduction of the number of 'off' periods (predominantly end-of-dose hypokinesia) and a slight increase in 'on' time. No improvement was observed in two of our patients. Mean levodopa plasma levels were comparable between the two types of formulations during optimal treatment, however systemic bioavailability was significantly higher with CR-4. Delayed onset of antiparkinsonian effect of CR-4, resulting from an increase of Tmax for levodopa, was one of the major complaints and required additional small amounts of standard levodopa in three patients.

Adult↗
PubMed1989

In human brain two subtypes of D1 dopamine receptors can be distinguished on the basis of differences in guanine nucleotide effect on agonist binding.

D1 dopamine receptors were identified in membranes of human nucleus caudatus, nucleus accumbens, amygdala, and globus pallidus, by the specific binding of [3H](+)-R-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-benzazepine-7 -ol [( 3H]SCH 23390). In these four brain regions, dopamine/[3H]SCH 23390 competition binding curves were computer-analyzed to a two-site model, distinguishing a high- (RH) and low- (RL) affinity site for dopamine. The ability of guanine nucleotides (0.4 mM GTP or 0.1 mM 5'-guanylylimidodiphosphate) to provoke a conversion of RH into RL was different between these brain regions. In amygdala, a complete conversion was seen, whereas there was no guanine nucleotide-effect on RH in globus pallidus. In nucleus caudatus and nucleus accumbens, guanine nucleotides provoked only a partial conversion of RH into RL, suggesting that these brain regions may contain guanine nucleotide-sensitive and -insensitive receptors. Heating of the membranes at 60 degrees C for 5 min had the same effect as guanine nucleotides. The pharmacological profiles of the guanine nucleotide-sensitive and -insensitive D1 receptors were similar, suggesting that D1 receptors in human brain are heterogeneous only with respect to their effector-coupling mechanism: guanine nucleotide-sensitive receptors, which are capable of undergoing functional coupling with Gs, and guanine nucleotide-insensitive receptors, which are not.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1989

[3H]GBR 12935 binding to dopamine uptake sites in the human brain.

Binding of 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine ([3H]GBR 12935) was studied in membrane preparations of several human brain regions. In putamen, the substituted piperazine derivates cis- and trans-flupenthixol displaced 90% of the total [3H]GBR 12935 binding. Computer-assisted analysis of the competition curves revealed a high-affinity site (30%; KiH = 54 nM) and a low-affinity site (60%; KiL = 4.5 microM). The dopamine uptake blockers mazindol and nomifensine only displaced 30% of the total [3H]GBR 12935 binding in a monophasic way. Binding of [3H]GBR 12935 to the dopamine uptake sites, i.e., that displaced by dopamine uptake blockers, corresponded to part of the binding having low affinity for flupenthixol and was only detected in putamen, nucleus caudatus, nucleus accumbens, and substantia nigra. Even after masking the high-affinity binding site for flupenthixol by including 1 microM cis-flupenthixol in the binding assays, no dopamine uptake sites could be detected in globus pallidus, amygdala, thalamus, hippocampus, and cerebral cortex. Binding of [3H]GBR 12935 to dopamine uptake sites was lost in the nucleus caudatus ipsilateral to ventral midbrain infarctions, confirming their location on nigrostriatal nerve endings. Gross unilateral lesions of the striato- and pallidonigral pathways did not affect the number of dopamine uptake sites in the ipsilateral substantia nigra, suggesting that they may reside on the soma or dendrites of nigral neurons.

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PubMed1989

Controlled-release carbidopa/levodopa (CR) in parkinsonian patients with response fluctuations on standard levodopa treatment: clinical and pharmacokinetic observations.

The efficacy of an oral controlled-release preparation of carbidopa/levodopa (Sinemet CR 50/200 mg) was compared with conventional carbidopa/levodopa (25/250 mg) in an open-label study. Twenty patients with idiopathic Parkinson's disease and severe response fluctuations participated. At the end of 6 months of CR treatment, the major clinical benefits included improvement of disability, reduction in number of "off" periods (predominantly end-of-dose hypokinesia), and increase in percentage of "on" time. Although dosages of CR required for an optimal therapeutic response were not significantly higher compared with conventional levodopa, bioavailability significantly increased. Delayed onset of antiparkinsonian effect of CR, resulting from an increase of Tmax for levodopa, was one of the major patient complaints and required additional small amounts of standard levodopa in some patients.

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