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Biomedical subjects

B Bondy

Publications and source records attributed to B Bondy.

At least 55 records · Page 3Linked to original sources
PubMed1999

Relationship of substance P, 5-hydroxyindole acetic acid and tryptophan in serum of fibromyalgia patients.

The serotonergic system has repeatedly been discussed to be involved in the pathophysiology of fibromyalgia (FM), which is a syndrome of widespread pain and sleep disturbance. Elevated levels of substance P (SP), a mediator of nociception, have been described in FM. In this study the possible relationship between SP and serotonin (5-HT) together with its precursor tryptophan (TRP) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) was evaluated in 51 serum samples of fibromyalgia patients. These parameters were compared with clinical data such as pain intensity or sleep quality. A strong negative correlation between SP and 5-HIAA (P = .000) as well as between SP and TRP (P = .009) could be demonstrated. High serum concentrations of 5-HIAA and TRP showed a significant relation to low pain scores (5-HIAA: P = .030; TRP: P = .014). Moreover, 5-HIAA was strongly related to good quality of sleep (P = .000), while SP was related to sleep disturbance (P = .005). These data are valid to support the hypothesis of a systemic involvement of 5-HT and SP in fibromyalgia.

Adult↗
PubMed1999

Possible association of fibromyalgia with a polymorphism in the serotonin transporter gene regulatory region.

OBJECTIVE: To analyze the genotypes of the promoter region of the serotonin transporter gene (5-HTT) in patients with fibromyalgia (FM). METHODS: Genomic DNA from 62 patients meeting the American College of Rheumatology 1990 criteria for FM and 110 healthy controls was analyzed by polymerase chain reaction. Additionally, the psychopathologic state of 52 of the FM patients was evaluated using the Beck Depression Inventory (BDI) and the Symptom Checklist-90-Revised (SCL-90-R). RESULTS: The 5-HTTLPR genotypes in FM patients versus controls were distributed as follows: L/L 27% versus 34%, L/S 42% versus 50%, and S/S 31% versus 16%. FM patients with the S/S genotype had higher mean scores on the BDI and the SCL-90-R compared with those in the L/L and L/S groups. CONCLUSION: A higher frequency of the S/S genotype of 5-HTT was found in FM patients compared with healthy controls. The S/S subgroup exhibited higher mean levels of depression and psychological distress. These results support the notion of altered serotonin metabolism in at least a subgroup of patients with FM.

Adult↗
PubMed1999

The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia.

Based on a possible involvement of serotonergic dysfunction in the pathophysiology of fibromyalgia (FM) and on preliminary reports of a possible genetically driven vulnerability for this disorder we investigated the silent T102C polymorphism of the 5-HT2A-receptor gene in 168 FM patients and 115 healthy controls. Our results showed a significantly different genotype distribution in FM patients with a decrease in T/T and an increase in both T/C and C/C genotypes as compared to the control population (Fisher's Exact test, two-sided, P = 0.008). However, the increase in allele-C102 frequency felt short of significance (P = 0.07). Correlation of genotypes to clinical parameters revealed no influences on age of onset, duration of disease or psychopathological symptoms, measured with the Beck Depression Inventory and the symptom checklist SCL-90-R. In contrast to that the pain score, being a self reported information on pain severity, was significantly higher in patients of the T/T genotype (Mann-Whitney U test, P = 0.028). This suggests that the T102-allele might be involved in the complex circuits of nociception. However, the T102C polymorphism is not directly involved in the aetiology of FM but might be in linkage dysequilibrium with the true functional variant, which has to be unravelled.

Adult↗
PubMed1998

Phytohemagglutinin-stimulated calcium signal in lymphocytes of alcoholics before, during and after detoxification.

Acute and chronic exposure to ethanol influences intracellular calcium homeostasis via NMDA receptors, direct regulation of calcium channels or the phosphoinositide pathway. To explore the influence of alcohol withdrawal on calcium metabolism, we have investigated the resting and phytohemagglutinin (PHA) stimulated [Ca2+]i in lymphocytes of 10 alcoholics before, during and after withdrawal. Our findings suggest that both compartments of the PHA-stimulated signal are affected in alcoholics, with flattening of the initial peak and sustained calcium influx, as long as severe vegetative signs are present. MANOVA results showed significant interaction effects for both measurement points, for the initial peak, 40 s after stimulation (P = 0.05), and especially for the sustained influx at the end of the observation period (P = 0.001). The detailed mechanisms of this disturbed calcium homeostasis need further investigation.

Adult↗
PubMed1996

Beta 2-receptor density on mononuclear blood cells in patients suffering from neuroleptic-induced akathisia (NIA).

The effectiveness of beta-blockers in the treatment of neuroleptic-induced akathisia (NIA) suggests that beta-adrenergic overactivity is involved in the manifestation of NIA. As an approach to understanding this postulated overactivity, we investigated the beta 2-receptor density on mononuclear blood cells in 21 patients suffering from NIA as well as in 12 patients without NIA. The beta 2-receptor density in NIA-positive patients was significantly higher than that in NIA-negative patients (t = 2.84; p = .008). The NIA-positive patients were treated with 20 mg propranolol t.i.d. for 5 days. The beta 2-receptor density in treatment responders did not differ significantly from that in non-responders. Our results indicate that beta 2-receptors on mononuclear cells in patients with NIA may be of a certain degree of importance. With the prerequisites of replicability as well as correlation of this parameter with therapeutic success of beta-blockers, it may be considered as a predictor for treatment response.

Adolescent↗
PubMed1996

Human adenosine A2a receptor (A2aAR) gene: systematic mutation screening in patients with schizophrenia.

Several lines of evidence suggest an involvement of adenosine A2a receptor (A2aAR) mediated adenosinergic neuromodulation in the etiopathogenesis of schizophrenia. We therefore performed a systematic mutation scan of the complete coding region of the human A2aAR gene in a sample of 42 schizophrenic patients. We detected one rare naturally occurring receptor variant (Gly-340-Ser) and two silent mutations (405C/T and 1083C/T). To our knowledge the Gly-340-Ser substitution is the first naturally occurring molecular variant of the A2aAR identified. Determining the frequency of the three variants in 42 unrelated healthy controls, we observed a significant trend towards an overrepresentation of the 1083T variant in patients when compared to controls (p = 0.041). This trend was followed up in a large independent replication sample. However, we were not able to confirm the original trend in the second sample (p = 0.367). The Ser-340 variant was found in a single schizophrenic individual. Investigation of the patient's family revealed independent segregation between the Ser-340 variant and psychiatric illness. Our data suggest that genetically determined structural variation of the A2aAR does not play a major role in the development of schizophrenia.

Alleles↗
PubMed1996

Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: identification of two naturally occurring receptor variants and association analysis in schizophrenia.

A statistically significant association between a silent mutation (102T/C) in the serotonin-2A (5-HT2A) receptor gene and schizophrenia has recently been reported in a sample of Japanese patients and healthy controls. This finding suggests that genetic predisposition to schizophrenia may be affected by a functional 5-HT2A receptor variant that is in linkage disequilibrium with 102T/C. In the present study, we have sought to identify genetic variation in the 5-HT2A receptor gene by screening genomic DNA samples from 91 unrelated subjects comprising 45 patients with schizophrenia and 46 healthy controls by using single-strand conformation analysis. We have identified four nucleotide sequence variants. Two sequence changes would result in protein alterations: a substitution of threonine by asparagine at position 25 (Thr25Asn), and a substitution of histidine by tyrosine at position 452 (His452Tyr). In order to test for a possible contribution to the development of schizophrenia, we have determined allele frequencies in extended samples of unrelated patients and healthy controls. The two amino acid substitutions are found with similar frequencies in patients and controls, indicating that the presence of these variants is not causally related to the development of schizophrenia. However, the reported association of the non-coding polymorphism 102T/C with the disease has also been detected in our sample (P=0.041, odds ratio=1.28, 95% confidence interval 1.012-1.623).

Alleles↗
PubMed1996

Dopamine D3 receptor Gly9/Ser9 polymorphism and schizophrenia: no increased frequency of homozygosity in German familial cases.

Disturbances in the dopaminergic transmission have been implicated in the etiology of schizophrenia. Recently, an association of schizophrenia with increased homozygosity of a Gly9/Ser9 polymorphism in the dopamine D3 receptor gene (DRD3) has been reported (Crocq et al., 1992; Mant et al., 1994). This finding reflected a departure from the Hardy-Weinberg equilibrium in the genotype distribution observed in schizophrenic patients. The effect was found to be at its strongest in patients with a high familial loading. In the present study, we tried to replicate this finding in a sample of 146 German patients with a DSM-III-R diagnosis of schizophrenia. All patients had a positive family history of major psychiatric disorder including 70 patients with a family history of schizophrenia. Given our sample size, we have a power of 99.8% to detect 2. deviation from the Hardy-Weinberg equilibrium of the reported magnitude. However, we found no evidence of an excess of homozygosity in our schizophrenic patients. This seems to indicate that homozygosity for the Gly9/Ser9 polymorphism at the DRD3 locus is unlikely to confer susceptibility to schizophrenia in the German population. This held true whether the psychiatric diagnoses in the affected relatives of the patient samples was established by the family history or family interview method.

Adult↗
PubMed1996

Identification of dopamine D4 receptor mRNA in circulating human lymphocytes using nested polymerase chain reaction.

There is a long standing controversy if dopamine receptors are present on human lymphocytes. In recent years the expression of dopamine D3 and D5 receptors was demonstrated with molecular biological methods. Using reverse transcription and polymerase chain reaction (RT-PCR) we were able to demonstrate the expression of the dopamine D4 receptor (DRD4) mRNA in human circulating lymphocytes. Direct sequencing of the RT-PCR product assured that it corresponds to the human DRD4 sequence. However, because of the unusual high G/C content of the DRD4, several precautions have to be applied for reliable results.

Base Sequence↗
PubMed1995

Linkage analysis between pericentrometric markers on chromosome 18 and bipolar disorder: a replication test.

Replication was attempted of a recent report on linkage between bipolar affective disorder and pericentrometric loci on chromosome 18. Linkage to these markers was excluded in a sample of five extended multiplex families using lod-score and affected-pedigree-member methods. In one family, however, the lod score exceeded 1.0. Although the proposed susceptibility genes are unlikely to have a major impact on the occurrence of bipolar disorder, they might modify the genetic risk in a minority of familial cases.

Adult↗
PubMed1995

Potential linkage for schizophrenia on chromosome 22q12-q13: a replication study.

In an attempt to replicate a potential linkage on chromosome 22q12-q13.1 reported by Pulver et al. [1994: Am J Med Genet 54:36-43], we have analyzed 4 microsatellite markers which span this chromosomal region, including the IL2RB locus, for linkage with schizophrenia in 30 families from Israel and Germany. Linkage analysis by pairwise lod score analysis as well as by multipoint analysis did not provide evidence for a single major gene locus. However, a lod score of Zmax = 0.612 was obtained for a dominant model of inheritance with the marker D22S304 at recombination fraction 0.2 by pairwise analysis. In addition, using a nonparametric method, sib pair analysis, a P value of 0.068 corresponding to a lod score of 0.48 was obtained for this marker. This finding, together with those of Pulver et al. [1994: Am J Med Genet 54:36-43] and Coon et al. [1994: Am J Med Genet 54:72-79], is suggestive of a genetic factor in this region, predisposing for schizophrenia in a subset of families. Further studies using nonparametric methods should be conducted in order to clarify this point.

Chromosomes, Human, Pair 22↗
PubMed1995

Sodium chloride in separation medium enhances cell compatibility of free flow electrophoresis.

Free flow electrophoresis of cell suspensions in buffers containing sodium chloride was investigated using a modified procedure and the new apparatus Octopus PZE. The major methodical innovations are upward fluid flow, margin buffers flowing through the electrophoresis chamber at both sides of a central cell suspension buffer, adjacent to the electrode membranes, and a sample injection device which focuses the cells hydrodynamically to the middle of the chamber thickness. Mononuclear leukocytes, suspended in a buffer containing 35 mM NaCl, could be fractionated with the same accuracy as by conventional free flow electrophoresis, operated with a single NaCl-free chamber buffer. However, testing the vitality of separated cells with the help of the calcium indicator FURA2-AM clearly demonstrated the biological importance of the presence of a minimum amount of sodium chloride during cell electrophoresis. Only if at least 35 mM NaCl were present could an undisturbed cytosolic Ca2+ metabolism be maintained for the time of a free flow electrophoresis cell separation experiment.

B-Lymphocytes↗
PubMed1995

Reduced beta-amyloid response in lymphocytes of patients with Alzheimer's disease.

The beta-amyloid peptide (beta A4) is a principal constituent of senile plaques and is thought to play a major role in the pathophysiology of Alzheimer's disease (AD). Although the mechanism of beta-A4 neurotoxicity is still a matter of debate, one of its effects might be a destabilization of cellular calcium homeostasis, thus promoting neuronal damage. The influence of the toxic fragment beta A25-35 on the mitogen-induced rise in the intracellular calcium concentration ([Ca2+]i) in lymphocytes of AD (n = 13) and depressive patients (n = 14) as well as in healthy controls was therefore investigated (n = 16). The results showed a significant increase in the mitogen-induced calcium signal with lymphocytes of healthy controls and depressive patients. This beta A25-35-induced amplification was significantly lower in AD patients as compared to healthy controls but not as compared to depressive patients. The results thus confirm a postulated decreased beta-amyloid sensitivity in AD lymphocytes. However, this effect might not be as pronounced or as specific as recently described by Eckert et al., (1993b).

Aged↗
PubMed1994

Cytosolic free [Ca2+] in mononuclear blood cells from demented patients and healthy controls.

There is increasing evidence that the neurodegenerative processes in Alzheimer's disease (AD) may be related to alterations in calcium homeostasis and that these metabolic changes are not necessarily restricted to the central nervous system. However, previous studies investigating [Ca2+]i in fibroblasts, lymphoblasts, platelets and lymphocytes of AD patients gave inconclusive results, since increase, decrease and no alteration in [Ca2+]i were found in AD patients compared with controls. With respect to the importance of establishing altered Ca2+ homeostasis in peripheral cells, we have investigated [Ca2+]i in circulating mononuclear cells of patients with AD, multi-infarct dementia, age-associated memory impairment and healthy controls. [Ca2+]i was evaluated using the fluorescent dye fura-2 before and during stimulation with phythaemagglutinin (PHA). In our study we failed to find major differences in resting [Ca2+]i and in response to stimulation with 25 micrograms/ml and 100 micrograms/ml PHA in cells of AD patients as compared with all other groups investigated. There was only a tendency towards a decrease in [Ca2+]i in AD after stimulation with PHA. Thus the present findings suggest that [Ca2+]i evaluation in mononuclear cells does not have diagnostic value in discriminating AD patients from other demented patients. However, there might be some difference in [Ca2+]i values between early- and late-onset AD, which could have pathophysiological importance.

Adult↗
PubMed1994

Spiperone binding capacity in lymphocytes of patients with alcohol- and drug-induced psychosis: preliminary results.

An increased spiperone binding capacity in lymphocytes has been proposed as a possible biological marker for schizophrenia while in previous studies patients with alcohol dependence were shown to have a normal binding capacity. In a pilot study the spiperone binding capacity was studied in 8 patients with alcohol hallucinosis, 11 patients with acute drug-induced psychosis and 12 patients with other organic psychosis. An increased binding capacity, defined as > 4 fmol/l E6 cells, was found in only 1 patient with alcohol hallucinosis, 3 patients with drug-induced psychosis and 2 patients with other organic psychosis. Possible implications of these findings for future research are discussed.

Adult↗
PubMed1994

Clinical experience with the Greenfield filter in 193 patients and description of a new technique for operative insertion.

Transvenous inferior vena cava (IVC) interruption using the Greenfield filter was performed upon 193 patients from January 1982 to December 1988. Placement of a filter in the IVC was indicated for prophylaxis (23.8 percent), contraindication to anticoagulation (22.8 percent), pulmonary embolism despite anticoagulation (18.7 percent), complications of anticoagulation (26.9 percent) and free-floating thrombus (7.8 percent). Filters were placed in an infrarenal location in 92 percent of the patients. The remaining 8 percent of patients had placement of a suprarenal filter for specific indications, without complication. Most (97.4 percent) of the patients had filters placed through internal jugular or femoral vein cutdown. Five patients required filter placement through a retroperitoneal approach to the right common iliac vein and IVC junction. This new technique of filter insertion is described. The operative morbidity rate was 4.7 percent, with an additional 8.8 percent having postoperative thrombotic complications. The 30 day operative mortality rate (6.7 percent) was related to preexisting associated disease. Nonfatal, late, recurrent pulmonary embolism occurred in 2.6 percent of the patients despite filter placement. Caval patency remains at 97.9 percent in long term follow-up evaluation. The Greenfield filter is an effective and safe adjunct in the treatment of venous thromboembolic disease and a satisfactory prophylactic measure in specific high-risk patients.

Adolescent↗