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Biomedical subjects

J De Keyser

Publications and source records attributed to J De Keyser.

At least 73 records · Page 4Linked to original sources
PubMed1993

Subtypes and localization of dopamine receptors in human brain.

Dopamine receptors in the human brain play an important role in the pathophysiology and treatment of psychosis and movement disorders. Pharmacological and biochemical studies, and more recently gene cloning techniques, have demonstrated that there are multiple receptors for dopamine in the brain. There is confusion in the literature as new subtypes (D3, D4 and D5 receptors) were classified according to unspecified criteria. At present, however, all subtypes of dopamine receptors that have been identified still fit in the traditional D1/D2 dopamine receptor classification scheme. In this article, a more hierarchical system of nomenclature is proposed and our insights into the distribution and localization of the dopamine receptor subtypes in human brain are summarized. Although the current status of the different subtypes of the D1 and D2 receptor families in human brain remains unclear, their discovery has created hope for the development of more efficacious and specific medicines with less side-effects.

Animals↗
PubMed1993

Alpha 2A adrenoceptors and non-adrenergic idazoxan binding sites in calf brain and retina are distinct from those in human brain.

alpha 2 Adrenoceptors in membrane preparations of human and calf frontal cortex and of calf retina can be labelled by the antagonists [3H]idazoxan, [3H]rauwolscine and [3H]RX 821002. Present and previous data indicate that [3H]idazoxan possesses the highest affinity for the alpha 2 adrenoceptors in the calf tissues, whereas [3H]rauwolscine displays the highest affinity for those in the human frontal cortex. Competition binding experiments with adrenergic and serotonergic drugs further support the notion that the alpha 2 adrenoceptors in calf frontal cortex and retina are similar, but distinct from the receptors in human frontal cortex. The alpha 2 adrenoceptors in the three investigated tissues display low affinity for the antagonist prazosin, which suggests that they all belong to the alpha 2A subclass. The competition binding curves of the alpha 2A adrenoceptor subtype-selective agonist oxymetazoline are shallow, but undergo a rightward shift and steepening in the presence of GTP. The shallow curves can therefore be attributed to the coupling of the alpha 2 adrenoceptors to G proteins. The different binding characteristics of the alpha 2A adrenoceptors from the investigated human and bovine tissues are likely to reflect species-related differences in protein structure. [3H]Idazoxan binds also to non-adrenergic sites in membrane preparations from the three tissues. However, the affinity of [3H]idazoxan for these sites in calf cortex and retina is appreciably lower than for those in human cortex. The species-related differences of the non-adrenergic idazoxan binding sites may be due to differences in protein structure or even to differences in gene-product.

Animals↗
PubMed1992

Serum concentrations of vitamins A and E and early outcome after ischaemic stroke.

Formation of free radicals and subsequent lipid peroxidation may have an important role in tissue injury and neuronal cell death after cerebral ischaemia. We conducted a prospective, controlled study to determine whether the endogenous antioxidant vitamins A and E had a protective function in acute ischaemic stroke. The study population consisted of 80 patients seen at the Free University Hospital in Brussels. Entry criteria were occurrence of sudden focal neurological deficit lasting more than 3 h; deficit due to acute ischaemia in the territory of the middle cerebral artery; and investigation within 24 h of onset of the episode. Outcome was assessed within the first 21 days. 80 controls matched for age and sex had various neurological disorders other than acute ischaemia. Serum concentrations of vitamins A and E were similar in the study and control groups. In the study population a serum vitamin A concentration higher than the mean of 2.27 mumol/l was associated with a higher frequency of complete recovery within the first 24 h (p less than 0.05), decreased mortality (p = 0.038), and a better outcome as assessed by the Mathew scale of neurological deficit (p less than 0.03) and the Barthel index. There was no significant difference in outcome between patients with vitamin E concentrations above or below the mean of 35.3 mumol/l. Our results suggest a beneficial effect of a high serum vitamin A concentration on early outcome in ischaemic stroke.

Aged↗
PubMed1992

Idiopathic hemiparetic parkinsonism, a syndrome distinct from idiopathic parkinsonism.

Two women had a syndrome of progressive parkinsonism with ipsilateral rigidity, mild resting tremor, paresis, hyperreflexia, and an extensor plantar response. Symptoms had started 24 and 3 months after a surgical procedure in the affected limb. Neuroimaging studies were unhelpful. Both the parkinsonian features and the pyramidal tract signs responded well to dopaminergic drug treatment. We propose that the syndrome be called "idiopathic hemiparetic parkinsonism".

Adult↗
PubMed1992

Regional distribution of alpha 2A- and alpha 2B-adrenoceptor subtypes in postmortem human brain.

The newly available and highly selective radiolabeled antagonist [3H]RX 821002 was used to examine the distribution of alpha 2 adrenoceptors in human brain. High densities of alpha 2 adrenoceptors were found in the hippocampus, frontal cortex, thalamus, amygdala, pons, and medulla oblongata. Intermediate densities were observed in the striatum (nucleus accumbens, nucleus caudatus, and putamen), globus pallidus, and substantia nigra. The KD values for [3H]RX 821002 were similar in all regions (ranging from 2.8 to 7.5 nM). On the basis of their different affinities for prazosin and oxymetazoline, the alpha 2 adrenoceptors have been divided into alpha 2A and alpha 2B subtypes. To examine the alpha 2A/alpha 2B-adrenoceptor ratio in the different brain regions, we performed oxymetazoline and prazosin/[3H]RX 821002 competition binding experiments. In frontal cortex membranes, the competition curves with prazosin were steep, indicating a single class of binding sites, whereas the competition curves with oxymetazoline were shallow and fitted by computer best to a two-site model. However, in the presence of GTP, the high-affinity sites for oxymetazoline were partially converted into low-affinity sites, indicating that this agonist interacts with high- and low-affinity states of the alpha 2 adrenoceptors. This implies that oxymetazoline is not very suitable for discriminating the alpha 2A- and alpha 2B-receptor subtypes in radioligand binding studies. Therefore, prazosin/[3H]RX 821002 competition binding experiments were used to investigate the distribution of the alpha 2-adrenoceptor subtypes in human brain. The alpha 2A-receptor subtype was detected in all brain regions examined. In contrast, alpha 2B receptors were only observed in striatum and globus pallidus.

Adrenergic alpha-Antagonists↗
PubMed1991

Autoradiographic distribution of alpha 2 adrenoceptors, NAIBS, and 5-HT1A receptors in human brain using [3H]idazoxan and [3H]rauwolscine.

The regional distribution of [3H]idazoxan and [3H]rauwolscine was studied autoradiographically in human brain. [3H]Idazoxan binds with high affinity to alpha 2 adrenoceptors as well as to non-adrenergic sites (NAIBS). [3H]Rauwolscine, besides binding to alpha 2 adrenoceptors, also binds to 5-HT1A receptors. Both radioligands labelled the same population of alpha 2 adrenoceptors, defined as the epinephrine-displaceable binding component. The highest densities of alpha 2 adrenoceptors occur in the leptomeninges, cerebral cortex and claustrum; lower densities were visualised in the basal ganglia, thalamus, pons, substantia nigra, cerebellum and medulla oblongata; no alpha 2 adrenoceptors were detected in amygdala and nucleus ruber. NAIBS were present in all the examined brain areas, with the highest densities found in the basal ganglia and substantia nigra. The finding that certain brain regions, such as the amygdala, contained NAIBS but no detectable alpha 2 adrenoceptors, suggests that the binding sites are independent from each other. The regional distribution of 5-HT1A receptors labelled by [3H]rauwolscine is in agreement with previous studies using [3H]8-OH-DPAT.

Adult↗
PubMed1991

Meningoencephalitis caused by Rickettsia conorii.

Case report of Mediterranean spotted fever in an 18 year old male heroin addict, caused by Rickettsia Conorii. The typical "tache noir" was absent. The patient developed meningoencephalitis within 5 days after onset of the systemic symptoms. Diagnosis was based on serological findings. Treatment with doxycycline led to rapid recovery without sequelae.

Adolescent↗
PubMed1991

Sudden hypotonic paraparesis caused by tophaceous gout of the lumbar spine.

Gouty arthritis of the axial skeleton is rare, and neurological complications due to spinal cord or nerve root compression secondary to tophaceous deposits have been seldom reported. We describe a patient with chronic gouty arthritis who developed an acute paraparesis caused by tophaceous cauda equina compression. Surgical removal of the mass resulted in complete recovery.

Arthritis, Gouty↗
PubMed1991

Increase in serum myoglobin, creatine kinase, and free fatty acids, during recovery from a paralytic attack in hypokalemic periodic paralysis.

In a patient with hypokalemic periodic paralysis (HPP), recovery from a paralytic attack, coinciding with the restoration of plasma potassium, was associated with a rise in serum myoglobin (Mb) and creatine kinase (CK). The increase of muscle proteins in serum was preceded by an increase in serum free fatty acids (FFA). An increased permeability of the sarcolemma, caused by an accumulation of FFA within the muscle cell, might underly the reflux of potassium into the circulation. This might represent a mechanism by which the paralytic attacks in HPP terminate.

Adolescent↗