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Biomedical subjects

W Friedl

Publications and source records attributed to W Friedl.

At least 145 records · Page 8Linked to original sources
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

Genetic variation in the apolipoprotein AI-CIII-AIV gene cluster and coronary heart disease.

Six RFLPs in the apolipoprotein (apo) AI-CIII-AIV gene region detected with the restriction enzymes XmnI, MspI, PstI, SstI and PvuII were used to study the role of genetic variation at this locus in the development of coronary heart disease and in the regulation of serum levels of various lipid and lipoprotein parameters in the Austrian population. 106 male patients with coronary heart disease and 118 matched controls were investigated. None of the alleles defined by these RFLPs was associated with increased coronary risk. In the patients, but not in the control group individuals with the genotype P1P2 for the PstI polymorphism in the 3' flanking region of the apo AI gene had significantly lower serum levels of high density lipoprotein (HDL)-cholesterol and apo AI levels than those with the genotype P1P1. The S2 allele of the SstI polymorphism at the 3' end of the apo CIII gene was significantly associated with elevated serum levels of triglycerides in the patient, but not in the control group. Controls with the genotype V2V2 for the PvuII(A) polymorphism at the 5' end of the apo CIII gene had significantly higher serum levels of apo B than those with V1V1 or V1V2. This association did not exist among the patients. These findings suggest that variation associated with some of these RFLPs is contributing to the determination of lipid levels in patients and controls, but that the RFLPs themselves cannot be used as markers for increased coronary risk in the Austrian population.

Adult↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

[The value of clinical aspects, laboratory and circulatory parameters in blunt abdominal trauma].

Within seven years 506 patients with blunt abdominal trauma were included into a prospective trial. The aim of the study was checking of the validity of clinical parameters, routinely performed laboratory examinations and of the initial circulatory situation in relation to an abdominal organ lesion. Three groups were separated out of the total collective: Group 1: Patients without abdominal lesion (N = 274). Group 2: Patients with abdominal lesion, verified by operation, sonography or CAT scan (N = 232). Group 3: Patients with rupture of the spleen (N = 107) (subgroup of 2). Among the clinical parameters: spontaneous abdominal pain, contusions marks, abdominal tenderness, shoulder pain, and abdominal palpation, the latter does have a high validity (92%). However, in group 1, more than half of the cases also had palpation pain. Shoulder pain has a high sensitivity. Of the laboratory parameters: hemoglobin, hematocrit and leucocytes, only the leucocyte count provided a certain importance: 83% of group 2 had values above 10,000. The circulatory parameters blood pressure and pulse as initial spot picture are of minor validity. Continuous registration of these values at clinical observation has much higher relevance indicating trends towards improvement or deterioration.

Abdominal Injuries↗
PubMed1987

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↗
PubMed1987

[Load capacity and deformation of unstable pertrochanteric osteotomies following 145 degree angle plate osteosynthesis and Ender nailing].

In 24 femora an unstable intertrochanteric osteotomy was performed. In twelve an endernail osteosynthesis and in the other twelve a 145 degree-plate osteosynthesis was performed. Eight femora were tested as control. The loading capacity was 500 N higher in the endernail group. In four cases after 145 degrees-plate osteosynthesis but only in one case after endernailing the osteosynthesis becomes unstable under an alternating load of 2000 N. In femora with pronounced osteoporosis the maximal loading capacity is higher in the endernail osteosynthesis group. The loading capacity increase with the CCD-angle. The deformation after alternating load of 500 N is significantly lower in the 145 degree-plate osteosynthesis group. At higher alternating load the deformation of the 145 degree-plate osteosynthesis exceeds that of the endernail osteosynthesis.

Biomechanical Phenomena↗
PubMed1987

[Study of the correlation between early and late changes in the roentgenologic and functional status following conservative and surgical treatment of the head of the tibia].

Between 1976 and 1980 161 patients were admitted to our department with condylar fractures of the tibia. 60% of the patients were treated conservatively, 40% underwent surgery. The patients follow-up was analysed three to seven years after therapy and an examination of a representative group of patients was performed 1983. A direct comparison of therapeutic results between the conservative and operative treatment groups is not possible, since fractures with a particularly poor prognoses including depression and impression fractures of the articular surface were more frequent in the operative treatment group. It is noteworthy, however, that the patients' activity at work and in their leisure time was increased in the operative group. Additionally in this group the remaining complaints were less and the final results more favourable according to the patients' self-judgment. Unchanged irregularities of the joint surface following initial therapy were found in 40.5% of conservatively treated patients and in 6.9% of operated patients respectively. At the time of reassessment, however, differences of radiological findings could not be seen between the two treatment groups. Whereas in the conservative treatment group a difference in length of the two legs of 2 cm or more were observed in 16% of cases, not a single case was found in the operative treatment group. There was a correlation of the functional and the result of the radiological examination, although considerable exceptions from this correlation were also seen. Therefore it is not possible from the individual X-ray findings to predict the functional results of the patient.

Arthritis↗
PubMed1987

Phylogenetic receptor research: implications in studying psychiatric and neurological disease.

Phylogenetic studies will help to evaluate the structure and function of receptors. We were able to show that the regional heterogeneity of the central benzodiazepine receptor previously described in mammals also applies to avians. In addition, a systematic species comparison of the subunit patterns revealed a certain phylogenetic relationship suggesting evolution by gene duplication and subsequent divergence. In analogy to isozyme systems, these results possibly indicate that the GABA/benzodiazepine receptor is an isoreceptor complex. The implications for neuropsychiatric genetics are discussed.

Animals↗
PubMed1987

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↗
PubMed1987

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↗
PubMed1987

Lipoprotein binding to cultured human hepatoma cells.

Binding of various 125I-lipoproteins to hepatic receptors was studied on cultured human hepatoma cells (Hep G2). Chylomicrons, isolated from a chylothorax, chylomicron remnants, hypertriglyceridemic very low-density lipoproteins, normotriglyceridemic very low-density lipoproteins (NTG-VLDL), their remnants, low-density lipoproteins (LDL), and HDL-E (an Apo E-rich high-density lipoprotein isolated from the plasma of a patient with primary biliary cirrhosis) were bound by high-affinity receptors. Chylomicron remnants and HDL-E were bound with the highest affinity. The results, obtained from competitive binding experiments, are consistent with the existence of two distinct receptors on Hep G2 cells: (a) a remnant receptor capable of high-affinity binding of triglyceride-rich lipoproteins and HDL-E, but not of Apo E free LDL, and (b) a LDL receptor capable of high-affinity binding of LDL, NTG-VLDL, and HDL-E. Specific binding of Apo E-free LDL was completely abolished in the presence of 3 mM EDTA, indicating that binding to the LDL receptor is calcium dependent. Specific binding of chylomicron remnants was not inhibited by the presence of even 10 mM EDTA. Preincubation of the Hep G2 cells in lipoprotein-containing medium resulted in complete suppression of LDL receptors but did not affect the remnant receptors. Hep G2 cells seem to be a suitable model for the study of hepatic receptors for lipoprotein in man.

Apolipoproteins E↗
PubMed1987

[Experimental studies of the effectiveness of the sliding principle in dynamic hip screw osteosynthesis and its value in managing unstable pertrochanteric femoral fractures].

54 human corpse femora were tested. In 18 unstable pertrochanteric osteotomies were performed, in other 18 femora valgisation osteotomies were performed. 18 femora served as control. In the unstable pertrochanteric osteotomy-group 135 degrees-DHS-osteosynthesis was performed. In the valgisation-osteotomy-group a 150 degrees-DHS-osteosynthesis was performed. Half of the femora were tested under physiological load, the other femora were tested with the load acting from cranial-lateral (50 degrees difference to the physiological load direction). Under physiological condition the load capacity was 5769 N in the 135 degrees-DHS-group and 7261 N in the 150 degrees-DHS-group, and so 8 to 10 times higher as the body weight. In the groups with the false loading direction the mean stability of the osteosynthesis was 2937 N in the 135 degrees-DHS-osteosynthesis-group and 3942 N in the 150 degrees-DHS-osteosynthesis-group. The load capacity of the control femora was 7451 N. The deformation under physiological load was similar in both groups. Under unphysiological load the deformation was 2-3 times higher in the 135 degrees-DHS-group because of the higher bending compared with the 150 degrees-DHS and because of the medical cortical defect. The results demonstrate the effectivity of the sliding osteosynthesis technique of the DHS. After DHS-osteosynthesis of unstable pertrochanteric fractures with limited medial defect in all cases full weight bearing after operation is possible. Valgisation osteotomy is not necessary in this type of fracture.

Biomechanical Phenomena↗