Biomedical subjects

B Bondy

Publications and source records attributed to B Bondy.

78 records · Page 5Linked to original sources

PubMedDate not supplied

The PHA-induced calcium signal in lymphocytes is altered after blockade of K(+)-channels in Alzheimer's disease.

Several lines of evidence indicate that alterations in intracellular calcium homeostasis with sustained elevation of free calcium ions ([Ca2+]i) might be important in the pathophysiology of Alzheimer's disease (AD). Recent studies with peripheral blood-cells have demonstrated that investigation of regulatory mechanisms in calcium homeostasis might be more promising than determining only resting or stimulated [Ca2+]i values. With respect to the importance of potassium (K+)-channels in intracellular calcium regulation we have investigated whether a potassium channel dysfunction, already demonstrated for AD fibroblasts (Etcheberrigaray et al., 1993, Proceedings of National Academy of Sciences USA, 90, 8209-8213), could be observed in circulating lymphocytes as well. Thus, we studied the influence of the K(+)-channel inhibitor tetraethylammonium (TEA) on basal and PHA-stimulated [Ca2+]i in lymphocytes from AD (n = 20), non-demented depressed patients (n = 15) and age-related healthy controls (n = 23). Preincubation of lymphocytes with 100 mmol/l TEA resulted in a 45.5 +/- 8.8% inhibition (mean +/- SD) of the PHA induced rise in [Ca2+]i in healthy controls and 37.3 +/- 11.3% inhibition in depressed patients. With lymphocytes of AD patients, this effect of TEA was significantly reduced (23.2 +/- 8.8%, p < .001). If the individual data are considered there was almost no overlap between AD patients and healthy controls, since only three (15%) AD patients responded to TEA with > 30% inhibition, but only one of the controls (5%) responded with < 30% inhibition. Besides the reduced signal-inhibition by blockade of K(+)-channels we have observed a delayed response of AD lymphocytes in [Ca2+]i rise after PHA stimulation, suggesting that functional plasticity of the cells is reduced. Although the significance and molecular basis of this K(+)-channel dysfunction are not yet determined, the presented data are of great significance because of diagnostic reasons and especially because this model thus offers a possibility to investigate functional cellular alterations in vivo.

Adult↗

PubMedDate not supplied

Dopamine D 4 receptor gene polymorphism and extraversion revisited: results from the Munich gene bank project for alcoholism.

In 1998 a gene bank project for association studies in alcoholism was initiated at the Psychiatric Hospital of Munich. The research instruments used were partly adopted from the US collaborative study of the genetics of alcoholism and include the family history assessment module (FHAM), the semi-structured interview for assessment of genetics in alcoholism (SSAGA) and a number of personality inventories such as the Zuckerman's sensation-seeking scale, the NEO Five factor inventory and the temperament and character inventory. Based on the examination of 181 alcoholic subjects, no association was found between Dopamine D4 receptor gene polymorphism and novelty-seeking or extraversion as assessed by the three personality inventories. These findings are in line with a number of more recent studies questioning the association between novelty-seeking and DRD4 dopamine receptor gene polymorphism. Possible implications of these findings are discussed.

Adult↗

PubMedDate not supplied

Ionotropic glutamate receptor gene GRIK3 SER310ALA functional polymorphism is related to delirium tremens in alcoholics.

Upregulation of glutamatergic neurotransmission resulting from chronic ethanol intoxication may cause a hyperexcitable state during alcohol withdrawal, which may lead to seizures and delirium tremens. The aim of our study was to evaluate the association between a history of alcohol withdrawal-induced seizures and delirium tremens, and a functional polymorphism (Ser310Ala) of the GRIK3 gene coding for the glutamatergic kainate receptor subunit GlurR7 in a sample of well-characterized alcoholics compared to controls. In total, 233 patients meeting DSM-IV alcohol dependence criteria and 309 controls, all of German descent, were investigated. GRIK3 functional polymorphism was determined using PCR (polymerase chain reaction) of lymphocyte DNA. History of alcohol withdrawal-induced delirium tremens and seizures were obtained using the SSAGA (Semi-Structured Assessment for the Genetics of Alcoholism). Data were cross-checked with in-patients' clinical files. While a significant relationship between history of delirium tremens and the Ser310 allele was detected, no significant results were obtained for alcohol withdrawal-related seizures. Although this result is suggestive for a significant role of this polymorphism in the pathogenesis of delirium tremens in alcohol-dependent individuals, further investigation and confirmation are warranted.

Adolescent↗

PubMedDate not supplied

No association between metabotropic glutamate receptors 7 and 8 (mGlur7 and mGlur8) gene polymorphisms and withdrawal seizures and delirium tremens in alcohol-dependent individuals.

- Up-regulation of the glutamatergic neurotransmission from chronic ethanol intoxication may cause a hyperexcitable state during alcohol withdrawal that may lead to seizures and delirium tremens. The aim of our study was to evaluate the association between a history of alcohol withdrawal-induced seizures and delirium tremens and a mGlurR7 (Tyr433Phe); and a mGlurR8 (C2756T) metabotropic glutamate receptor polymorphism in alcoholics compared to controls. A total of 182 patients meeting DSM-IV alcohol dependence criteria and 117 controls, both groups being of German descent, were investigated. mGluR7 and mGluR8 polymorphisms were determined using polymerase chain reaction of lymphocyte DNA. History of alcohol withdrawal-induced delirium tremens and seizures were obtained using the Semi-Structured Assessment of Genetics in Alcoholism (SSAGA). Data were cross-checked with inpatients' clinical files. No significant associations were obtained between both receptor polymorphisms and alcohol withdrawal-induced seizures and delirium tremens. The negative results in this study question the role of these polymorphisms in the pathogenesis of alcohol withdrawal-induced seizures and delirium tremens.

Adult↗

PubMedDate not supplied

No association between a polymorphism in the promoter region of the MAOA gene with antisocial personality traits in alcoholics.

AIMS: We analysed the MAOAuVNTR functional polymorphism in the promoter region of the X-chromosomal monoamine oxidase A (MAOA) gene. Genotypes with three-repeat alleles were reported to be associated with antisocial as well as impulsive traits. METHODS: The repeat number (3-5) of the MAOA polymorphism was determined in 169 male alcoholic subjects and 72 controls of German descent. Behavioural and personality traits were evaluated using the Brown-Goodwin Assessment for History of Lifetime Aggression, the Buss Durkee Hostility Inventory, as well as the Barrat Impulsiveness Score. A median split in Brown-Goodwin, Buss Durkee Irritability, Buss Durkee Assault and Barrat Impulsiveness Score was conducted. RESULTS: High scores were found, i.e. 47.9% in Brown-Goodwin, 65.7% in Buss Durkee Irritability, 63.3% in Buss Durkee Assault and 59.8% in Barrat Impulsiveness Scale, indicating high impulsiveness, irritability and antisocial behaviour. Based on the results of these questionnaires, we detected no significant differences between the frequency of the three-repeat allele and high or low scores in alcoholics and controls. CONCLUSIONS: Taken together, these findings suggest that the three-repeat allele of the MAOAuVNTR 30-bp polymorphism is not associated with impulsive and aggressive personality traits.

Adult↗

PubMedDate not supplied

[Catecholaminergic receptors of the blood cells of schizophrenics].

The simultaneous determination of serum CA and their receptors in blood cells offers a possibility to evaluate disturbances of the DA and NA neuronal systems in man. High affinity binding sites for 3H-yohimbine in platelets, 3H-DHA on granulocytes and 3H-spiperone in lymphocytes from healthy control persons, unmedicated (n = 28), and medicated (n = 8) schizophrenics as well as from an unmedicated psychiatric control (n = 14) were investigated. Furthermore, the actual concentration of the circulating CA was determined with HPLC-ECD. In unmedicated schizophrenics as compared to controls, specific binding of 3H-spiperone to lymphocytes was markedly elevated in capacity and less in affinity as compared to controls. For beta2-receptors a significant decrease was found in capacity with no change in affinity. The changes in alpha2-receptors with a slight decrease in capacity were less distinct. The concentrations of circulating CA ranged from normal values up to a more than 3 fold increase in NA and DA, whereas A concentrations were practically unchanged. No overall change in these data was found in the medicated schizophrenic patients. 3H-spiperone binding was characteristically increased only in schizophrenics, but did not elevate above control data in the non-schizophrenic psychiatric control group. Preliminary experiments of family studies suggest that this model could be valuable as a vulnerability marker.

Adult↗