Further RFLPs at the human tyrosine hydroxylase locus.
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Bacterial Proteins↗
Biomedical subjects
P Propping
Publications and source records attributed to P Propping.
The shark GABA-benzodiazepine receptor: further evidence for a not so late phylogenetic appearance of the benzodiazepine receptor.
Whilst the brain-specific benzodiazepine receptor has been assumed to show a late evolutionary appearance, we present evidence for the presence of a central benzodiazepine binding site in sharks, which shows a high affinity for [3H]Ro 15-1788. However, the receptor density and the affinities of several benzodiazepine receptor ligands are lower than in mammals, thus presumably explaining why the benzodiazepine binding sites had previously escaped detection in elasmobranchs. Additionally, radio- and immunohistochemistry were performed to localize the radioligand binding sites and the antigenic sites of the shark gamma-aminobutyric acid (GABA)-benzodiazepine receptor. In cerebellum, the granular layer reveals a high density of [3H]muscimol binding sites. The immunoreaction obtained with the beta-subunit-specific monoclonal antibody bd-17 seemingly parallels the distribution of high-affinity GABA binding sites. In contrast, [3H]Ro 15-1788 binding sites are evenly distributed in the molecular and granular layers, thus the results are similar to those previously described for rat cerebellum. Apparently, the respective distributions in this brain region are well conserved throughout vertebrate evolution.
Animals↗
Probable metachromatic leukodystrophy/pseudodeficiency compound heterozygote at the arylsulfatase A locus with neurological and psychiatric symptomatology.
Metachromatic leukodystrophy (MLD) is an autosomal recessive progressive demyelination disorder caused by the deficiency of arylsulfatase A (ASA). However, there exist individuals with low ASA activity without clinical symptoms. This state is described as ASA pseudodeficiency (PD). A number of patients with low ASA activity and various neuropsychiatric symptoms have been observed. It is controversial to what extent low ASA activity predisposes for neurological and/or psychiatric symptomatology. Therefore, persons with low ASA activity who were collected from a large-scale screening among neuropsychiatric patients and healthy controls are presently being extensively evaluated using biochemical, genetic, and clinical methods. Here we present a female patient, who had been first hospitalized with the diagnosis encephalomyelitis disseminata. Her ASA activity determined in fibroblast extracts is intermediate between adult MLD and PD. Sulfatide degradation in cultured fibroblasts is diminished. The subunit pattern obtained after SDS-polyacrylamide gel electrophoresis and immunoblotting was determined in the index patient and 2 sibs. It is compatible with a compound genotype ASA-/ASAp in the index case. It appears probable that in this patient low ASA activity leads to the accumulation of sulfatide and either causes the appearance of neuropsychiatric symptoms or at least contributes to the demyelination process.
Adult↗
Alcohol effects on the percentage of beta waves in the electroencephalograms of twins.
Electroencephalogram (EEG) recordings were made from 26 pairs of monozygotic (MZ) and 26 pairs of dizygotic (DZ) adult male twins, before and after alcohol ingestion. After a baseline EEG and a light breakfast, 1.2 ml/kg of ethanol was given orally over 15 min and the EEG repeated four times at hourly intervals. Alcohol caused a significant drop in the percentage of beta waves (14-30 cycles/sec) during the 1st hr. For the percentage of beta waves in 38 pairs of twins with complete data, MZ twin beta-wave intraclass correlations (RMZ) ranged between 0.85 and 0.91 before and after alcohol, but the DZ intraclass correlations (RDZ) started at 0.54 and fell to 0.05 at 2 hr after alcohol before recovering to baseline levels. These correlations resulted in heritability estimates [2(RMZ-RDZ)] of 0.68 at baseline and 1.73 at 2 hr. A heritability of 1.43 was found for the 1st hr drop in percentage of beta waves (RMZ = 0.78, RDZ = 0.06). These unrealistically high heritabilities, due to RDZ's approaching 0.0, suggest a failure of assumptions in the linear twin model that was used. Also, these findings are similar to, but more exaggerated than, findings in resting EEG's and visually evoked EEG potentials of twins and are compatible with the influence of gene interactions.
Adult↗
Genetic determination of the human EEG. Survey of recent results on twins reared together and apart.
In this article, we have discussed recent progress in quantifying the genetically determined component of the resting EEG. This progress has been made possible in particular by the application of advanced information processing techniques such as "supervised learning," and the development of a problem-oriented "similarity" concept. Our work aimed at modeling previous findings regarding the distinct individuality of human brain-wave patterns, the high similarity between the EEGs of monozygotic twins, and the average within-pair similarity of dizygotic twins. Thus, we had three objectives: First, we wanted to improve the quantification of EEG characteristics with respect to reproducibility and specificity by means of adaptive procedures and repeated measurements. Second, we wanted to compare the "typical" within-subject EEG similarity with the "typical" within-pair EEG similarity of monozygotic and dizygotic twins brought up together. Finally, we were interested in the degree to which environmental factors affect the characteristics of human brain-wave patterns. Our investigations were based on the empirical data derived from five different populations: (1) 81 healthy subjects, (2) 24 pairs of monozygotic twins brought up together, (3) 25 pairs of dizygotic twins brought up together, (4) 28 pairs of monozygotic twins reared apart, and (5) 21 pairs of dizygotic twins reared apart. Following our similarity conception, repeated measurements on the set of 81 individuals were used as design samples, and new registrations from the same individuals taken 14 days later were referred to as test samples in order to develop the appropriate method and to determine all required calibration parameters. This specific approach allowed us to construct EEG spectral patterns which, with a specificity and reproducibility of greater than 90% each, largely met the requirements of genetic EEG studies. Hence, we were able systematically to investigate the within-pair EEG similarity of our twin samples.(ABSTRACT TRUNCATED AT 400 WORDS)
Electroencephalography↗
The concept of isoreceptors: application to the nicotinic acetylcholine receptor and the gamma-aminobutyric acidA/benzodiazepine receptor complex.
The concept of isoreceptors offers a possible clue to account for pharmacological and biochemical heterogeneity in specific receptor systems. The existence of isozymes has set the foundation for the definition of isoreceptors. The resulting criteria are applied to two central receptor complexes. Accordingly, the nicotinic acetylcholine receptor is defined as an isoreceptor, and research results on the GABA/benzodiazepine receptor are interpreted under the consideration of the possible existence of isoreceptors.
Animals↗
Early ontogeny of the central benzodiazepine receptor in human embryos and fetuses.
The early ontogeny of the central benzodiazepine receptor (BZR) was investigated in human embryos and fetuses between 7 and 26 weeks of gestation. Brain tissue was gained from terminated pregnancies or spontaneous abortions. Binding studies, which were performed with 3H-flunitrazepam (FNZ), revealed that specific benzodiazepine binding is already detectable at an embryonal age of 7 weeks post conceptionem. Binding at this early stage can be displaced potently by clonazepam and the inverse agonist beta-CCE. Additionally, 3H-FNZ binding is enhanced by GABA. Thus, benzodiazepine binding is of the central type. Receptor density increases steeply in whole brain between weeks 8 and 11 of gestation. In frontal cortex receptor density increases gradually between weeks 12 and 26 of gestation. No specific fetal disease entity (including trisomy 21) was consistently associated with exceptionally high or low Bmax-values.
Brain↗
Phylogenetic conservation of the benzodiazepine binding sites: pharmacological evidence.
Phylogenetic research can help to elucidate the structure of the GABA/benzodiazepine receptor complex. In this study the evolution of the beta-carboline binding site was traced to see whether it paralleled that of the benzodiazepine binding site. The ratio of [3H]ethyl-beta-carboline-3-carboxylate (beta-CCE) to [3H]flunitrazepam (FNZ) binding sites was determined in several nonmammalian species. The results further substantiate the tight link between these two binding sites. Photoaffinity labelling of the benzodiazepine receptor (BZR) has revealed phylogenetic variation of the molecular weight of the benzodiazepine binding proteins. The IC50 values for inhibition of [3H]FNZ by various compounds which are active at the central benzodiazepine receptors were determined in three phylogenetically distant species that each showed distinct subunit patterns. In these species, the respective affinities of the compounds were remarkably similar, suggesting that the binding sites for benzodiazepines are conserved in higher bony fishes and tetrapods. The conserved binding sites, in addition to recent immunological results obtained in other research groups, provide further evidence for the existence of the GABA/BZR as an isoreceptor complex.
Affinity Labels↗
Limited tryptic proteolysis of the benzodiazepine binding proteins in different species reveals structural homologies.
Peptide mapping can be used to elucidate further the structural similarities of the benzodiazepine binding proteins in different vertebrate species. Crude synaptic membrane preparations were photoaffinity-labeled with [3H]flunitrazepam and subsequently degraded with various concentrations of trypsin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by fluorography allowed a comparison of the molecular weights of photolabeled peptides in different species. Tryptic degradation led to a common peptide of 40K in all species investigated, a finding indicating that the benzodiazepine binding proteins are structurally homologous in higher bony fishes and tetrapods.
Affinity Labels↗
[Increased birth weight in psoriasis vulgaris--an evolutionary advantage?].
With regard to the frequent alterations of insulin secretion and glucose tolerance in psoriatic patients, the birth weights of children of 100 psoriatic mothers were compared with the birth weights of children of 100 carefully matched control mothers. The mean birth weight in the psoriatic group was 140 g higher than that of the control group. A birth weight of more than 4,000 g was observed in the children of 20.4% of the psoriatic mothers and in only 11.3% in the control group. The frequency of diabetes mellitus independent of insulin (type II) in psoriasis recalls the hypothesis of the "thrifty" genotype, which suggests an explanation for the high incidence of diabetes in modern societies. On the basis of our results, this hypothesis may also be applied to psoriasis. In addition, we studied the influence of pregnancy on the course of psoriasis. Improvement was noted in 27.8% (complete remission in 20%), exacerbation in 14.7%; in 46.6% the disease remained unchanged.
Biological Evolution↗
Human erythrocyte transketolase: no evidence for variants.
Using isoelectric focusing of human erythrocyte transketolase, the isoenzyme pattern described recently (Kaczmarek and Nixon, 1983) was reexamined. Seven bands having pI values of 7.4-8.4 were common to the central part of the transketolase isoenzyme pattern in 63 healthy subjects investigated and were definitely reproduced, whereas four additional marginal bands (pI values of 7.2, 7.3, 8.6 and 8.8) were found with varying intensities in part of the samples and could not always be reproduced. We conclude that the method used does not permit the distinction of transketolase variants, that would allow to postulate a genetic polymorphism, based only on variation of the marginal bands of the pattern.
Chromatography, Ion Exchange↗
Genetic aspects of the EEG: an investigation into the within-pair similarity of monozygotic and dizygotic twins with a new method of analysis.
A considerable number of previous studies emphasized the importance of genetic factors in the spontaneous EEG. In this context MZ twins were found to resemble their co-twins as much as they resemble themselves over time, whereas investigations into the within-pair similarity of DZ twins yielded very inconsistent findings. To test these conclusions, we re-analysed the EEGs of an earlier twin study (24 MZ pairs/25 DZ pairs) by means of a new method of analysis. In our study, MZ twins proved to be less like one another than each person is to himself over time. However, this result might be because the EEG data were not optimal for the applied method of analysis, but the existence of true within-pair differences cannot be excluded. Contrary to earlier findings in the literature, the analysis of the EEG of DZ twins showed that, for a sufficiently representative sample, the within-pair similarity is significantly above the inter-individual similarity between unrelated persons.
Adult↗
Studying biological vulnerability and heterogeneity--a long way ahead.
Common diseases are usually the consequence of a variety of etiologies. This rule applies, for example, to mental retardation and epilepsy. There is evidence that genetic factors influence the propensity to utilize alcohol on an addictive basis at two levels of interaction between the drug and the body. It is doubtful that psychiatric symptoms are specific for defined etiologies. Individuals who are heterozygous for autosomal-recessive alleles may show slight deviations toward the homozygous genotype. These findings are applied to a polygenic concept of psychiatric disorders. Data are presented that would be compatible with a slightly increased incidence of heterozygotes for Wilson's disease and metachromatic leucodystrophy in psychiatric patients.
Brain Diseases, Metabolic↗
Further characterization of the avian benzodiazepine receptor subunits including phylo- and ontogenetic aspects.
The two avian benzodiazepine binding proteins offer an opportunity for further studies concerning their regional variation and their phylo- and ontogenetic development. Accordingly, regional variation of the benzodiazepine binding proteins is investigated further in two reptiles and chicken using photoaffinity labeling with [3H]flunitrazepam followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Whereas regional heterogeneity is pronounced in chicken, it is not readily apparent in the two reptiles. The ontogeny of the benzodiazepine binding proteins in chicken forebrain and cerebellum is remarkably similar to that previously reported in rodents. The results are discussed in light of the possible existence of the gamma-aminobutyric acid/benzodiazepine receptor as an isoreceptor complex.
Animals↗
Phylogenetic comparison of the photoaffinity-labeled benzodiazepine receptor subunits.
The late evolutionary appearance of the benzodiazepine receptor (BZR) allows an experimental approach for evaluation of the qualitative development of its subunits. Photoaffinity labeling of brain membranes with [3H]flunitrazepam followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography offers a suitable method for tracing the qualitative evolution of the BZR. A systematic comparison of the subunit patterns in fishes, amphibians, reptiles, birds, and mammals revealed that the subunit of 53K is phylogenetically the oldest photoaffinity labeled subunit; whereas it is the only band present in the lungfish and most amphibians, additional bands are apparent in higher tetrapods. In fishes, the evolution of the BZR subunits leads to the loss of the 53K subunit. KD values are discussed in relation to specific subunit patterns. Possible explanations for the observed variation of the subunits are discussed, with special emphasis placed on the possible evolution by gene duplication and subsequent divergence.
Amphibians↗
Autosomal dominant polycystic kidney disease in children.
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Child↗
Genetic influences on CNS diseases secondary to alcoholism.
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Alcohol Amnestic Disorder↗
Prenatal diagnosis of autosomal dominant polycystic kidney disease with a DNA probe.
A highly polymorphic DNA probe genetically linked to the locus of autosomal dominant polycystic kidney disease was used in linkage studies for prenatal diagnosis in a nine-week fetus at risk for the disease. The fetus was judged to have inherited the polycystic kidney disease mutation, and this was confirmed by microscopic examination of the fetal kidneys at necropsy.
Abortion, Therapeutic↗