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J Hebebrand

Publications and source records attributed to J Hebebrand.

157 records · Page 9Linked to original sources
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↗
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↗
PubMed1986

Genetic studies at the receptor level: investigations in human twins and experimental animals.

In receptors, as in enzymes, quantitative as well as qualitative genetic variation may exist. Studies in inbred strains of mice have shown for various receptors that the receptor density as determined by Bmax values is under genetic control. In healthy adult twins we have shown that the density of alpha-adrenoceptors on platelets is also influenced by genetic factors, since monozygotic twins were much more similar to one another than dizygotic twins. However, Bmax values are up-regulated and down-regulated by endogenous neurotransmitters and pharmacologically active agents. Thus, receptor densities are under considerable regulatory influences. Bmax values therefore reflect regulatory mechanisms rather than innate characteristics of the receptor protein. In another twin study we failed to find evidence for a genetic influence on the density of imipramine-binding sites on platelets. Since qualitative variation (polymorphism) is well known in enzymes, it may also apply to receptors. Qualitative differences in the receptor protein within one species would be of particular interest because of possible functional implications. As a first approach we examined central benzodiazepine receptors by photoaffinity labelling and sodium dodecyl sulphate-polyacrylamide gel electrophoresis. A comparison of fish, frog, chicken, mouse, rat and calf led to the detection of variation between species. Investigations in five inbred mouse and rat strains have not so far revealed genetic variation in benzodiazepine receptors. Nevertheless variation may be detectable by more sensitive methods such as peptide mapping after limited proteolysis or two-dimensional electrophoresis.

Affinity Labels↗
PubMed1986

Benzodiazepine receptor subunits in avian brain.

Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography of the photoaffinity-labeled benzodiazepine receptor in duck brain, two equally intensive bands of relative molecular masses of 53,000 and 54,000 were observed, thus being identical to the subunit pattern previously described for chicken brain. An attempt was made to characterize further the avian subunits. Comparison of the fluorographic subunit pattern in cerebellum and telencephalon revealed a pronounced quantitative heterogeneity. Addition of ethyl beta-carboline-3-carboxylate resulted in the selective inhibition of the 53,000 subunit. These results are compared with the mammalian subunit pattern in the corresponding brain regions. The findings are discussed in view of the apparent contradiction between the existence of regional heterogeneity when photoaffinity labeling is applied and its lack when monoclonal antibodies are used.

Affinity Labels↗
PubMed1984

Influence of sulfur-containing compounds on the acute toxicity of cyclophosphamide in male Sprague-Dawley rats.

The acute toxicity of cyclophosphamide (CP) was investigated following the pretreatment with seven sulfur-containing compounds (SCC): disulfiram (DSF), diethyldithiocarbamate (DDTC), L-cysteine (Cys), N-acetyl-L-cysteine (Ac-Cys), S-carboxymethyl-L-cysteine (Carb-Cys), D-penicillamine (Pen), and cysteamine hydrochloride (1-amino-3-mercaptoethane X HCl, C-NH). The following LD50 values were recorded: CP alone 254, CP + DSF 77, CP + DDTC 260, CP + Cys 345, CP + Ac-Cys 319, CP + Carb-Cys 271, CP + Pen 392, CP + C-NH 299 mg/kg b.wt. Only DSF significantly increased the toxicity of cyclophosphamide. None of the SCC tested seems to be superior to mesna (sodium 2-mercaptoethane sulfonate), a selective protector against cyclophosphamide-induced bladder and kidney toxicity.

Animals↗
PubMedDate not supplied

Prevalence of obesity in adolescent and young adult patients with and without schizophrenia and in relationship to antipsychotic medication.

The prevalence of obesity in inpatients of a German psychiatric rehabilitation center for adolescents and young adults (mean age 19.5 years) is assessed and set into relationship to diagnosis and medication regimen. In a cross-sectional naturalistic study body weights and heights of 151 inpatients, 109 of whom presented with ICD-10 schizophrenia spectrum disorders, were measured for the calculation of body mass indices (BMI, kg/m2); current medication regimen including the duration of treatment was assessed from medical records. BMIs were plotted into gender- and age-specific BMI-percentiles representative for the German population. Among the whole study population, obesity (BMI > or =90th percentile) was apparent in 44/98 (45%) of the male and in 31/53 (59%) of the female inpatients (overall: 50%). With respect to schizophrenia spectrum disorders, 36/70 (51%) males and 25/39 (64%) females (overall: 56%) were obese in contrast to 14/42 (33%) among the individuals without schizophrenia. Set into relationship to the treatment groups, the prevalence rates of obesity were 64% in patients treated with clozapine (n=69), 56% for other atypical antipsychotics (olanzapine, sulpiride, risperidone; n=27), 30% for classic antipsychotics (haloperidol, flupentixol, perazine; n=20) and 28% for the currently drug-free group (n=25). Together with other published findings in adults, these results suggest an increased prevalence of obesity among young patients with schizophrenia and especially among patients chronically treated with atypical antipsychotics.

Adolescent↗
PubMedDate not supplied

The effect of therapeutically induced weight gain on plasma leptin levels in patients with anorexia nervosa.

Previously it was shown that hyperleptinemia ensues from the therapeutically induced weight gain in patients with anorexia nervosa (AN). However, not all studies have been able to confirm this finding. To further investigate leptin secretion during weight gain in AN and potential functional implications serum leptin levels, body mass index (BMI),% body fat, fT3, fT4 and TSH of 18 adolescent AN patients (BMI at admission: 14.4+/-1.2) were examined four times during 11 weeks of re-feeding and compared to 18 weight stable controls. Additionally, serum leptin levels, BMI and % body fat were determined in patients reaching target weight after 11-20 weeks (mean 14.3+/-3) of inpatient re-feeding. At admission patients showed lower lg10 leptin levels (P=0.000) and BMI (P=0.000) than controls. At target weight patients still had significantly lower BMI (P=0.000) and% body fat (P=0.000) than controls but lg10 leptin levels of patients were higher than those of controls when adjusted for BMI and% body fat (ANCOVA, group P=0.038). In patients, correlation coefficients between lg10 leptin levels and BMI increments increased during the 11 weeks of re-feeding. BMI,% body fat and fT3 levels were not significantly correlated to lg10 leptin levels in week 11, however, 53% of the variance of leptin levels (corrected R(2)=0.53, P=0.001) was explained by BMI increments between weeks 7 and 11 (P=0.001) and lg10 leptin level at admission (P=0.002). In conclusion, we confirmed weight gain induced hyperleptinemia in AN. Further research is required to assess if this phenomenon contributes to renewed weight loss.

Adolescent↗
PubMedDate not supplied

Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome.

The aim of this study was to assess rates for tic disorders and obsessive compulsive psychopathology in families of children and adolescents with Gilles de la Tourette syndrome (TS). Diagnoses were based on the DSM III-R criteria. Obsessive compulsive psychopathology, that did not fulfill the criteria for obsessive compulsive disorder (OCD) was additionally assessed and termed obsessive compulsive symptoms (OCS). The authors hypothesized that comorbid OCD or OCS in TS patients predicts a higher familial loading with obsessive compulsive symptomatology. The study cohort included 87 patients with TS who were evaluated clinically and with the use of a structured psychiatric interview. All available parents (152/174; 87%), several sibs (49/93; 53%) and some second degree relatives (27/659; 4.1%) were also interviewed. For other first and second degree relatives the family history method was used. Familial rates for TS were clearly elevated. Rates for chronic tic disorders (CT) were considerably lower than in previous studies. Additionally, tic disorders not otherwise specified (TDNOS) were diagnosed in a substantial number of first degree (15/267; 5.6%) and second degree relatives (36/659; 5.5%). OCD in parents (4/174; 2.3%) did not occur in an above baseline rate. However, both OCD (14/87; 16.1%) and OCS (15/87; 17.2%) were frequently associated with TS in index patients. Interestingly, 10 of 16 fathers with OCS also had a tic disorder. Obsessive compulsive psychopathology clustered in families. It is concluded that genetic studies in TS could profit from adhering to a conservative diagnostic approach to both tic disorders and OCD. The familial clustering of OCS/OCD in conjunction with the elevated paternal rate for the co-occurrence of tic disorders and OCS might indicate heterogeneity of TS.

Adolescent↗
PubMedDate not supplied

Reduced body fat in long-term followed-up female patients with anorexia nervosa.

We aimed to evaluate both body composition and serum leptin levels in females with a past history of anorexia nervosa (AN) adjusted for their current body mass index (BMI). Twenty-three females with a past history of AN were followed-up 10 years after inpatient treatment and compared to 23 female controls of a similar age range matched for BMI on a one to one basis. Serum leptin levels were assessed and percent body fat (%BF) was determined via bioelectric impedance analysis. Differences of both %BF and leptin levels between cases and controls were tested under the hypothesis that cases have lower %BF and lower serum leptin levels than the controls. %BF was indeed lower in the cases compared to the controls (p < 0.05). However, differences in leptin levels between both groups just failed significance (p = 0.051). We conclude that body composition differs between long-term followed-up patients with AN and BMI- and gender-matched controls. Based on the finding that the former patients reported being more physically active, we assume that the higher physical activity levels in recovered patients with AN underlie the lower %BF.

Adipose Tissue↗
PubMedDate not supplied

[Prevalence of melanocortin 4 receptor (MC4R) mutations and polymorphismsin consecutively ascertained obese children and adolescents from a pediatric health care utilization population].

BACKGROUND: The prevalence of childhood obesity is steadily increasing. Weight regulation and food intake are subject to complex regulatory mechanisms. The leptinergic-melanocortinergic system is known to be of major importance. AIM OF THE STUDY: Identification of mutations in the melanocortin 4 receptor gene (MC4R) and of phenotypic effects of detected mutations in German obese children and adolescents. Family specific and cardiovascular risk factors were also analysed. PATIENTS: Consecutive ascertainment of 90 obese children and adolescents with a medium BMI SDS of + 2.6, age range 3 to 16 years. METHODS: Mutation screen within the MC4R was carried out by denaturing high performance liquid chromatography (dHPLC) and re-sequencing of samples with aberrant dHPLC patterns. Eating behaviour and obesity-associated diseases within the families were evaluated by semi-structured interviews. Metabolic evaluation included: oral glucose tolerance test (OGTT, WHO criteria) for calculation of insulin resistance (Homeostasis Model Assessment, HOMA) and insulin sensitivity index (ISI), lipid panel for lipid status, blood pressure measurement and abdominal ultrasound. RESULTS: Three patients were heterozygous MC4R mutation carriers (Thr112Met, Ala175Thr and Gly181Asp). Gly181Asp leads to a complete loss of function; whereas Thr112Met and Ala175Thr lead to a reduced receptor function. The patients with heterozygous MC4R mutations had BMIs, cholesterol levels and waist to hip ratios (W/H) that did not differ from the rest of our study group. The overall occurrence of hypertriglyceridemia (34 %) and hypercholesterinemia (22 %) was correlated with the W/H-ratio. The overall incidence of impaired glucose tolerance was 12 %. In those with a normal glucose tolerance 68 % already had an increased HOMA (mean 3.12; reference value < 1.9) and decreased ISI (mean 4.3; reference value > 7.2). The patients with MC4R mutations had a normal glucose tolerance with similar HOMA and ISI values compared to the rest of the patients. Hypertension was found in 24 % of all cases and blood pressure was correlated with BMI (r+ 0.8). None of the patients with MC4R mutations were hypertensive. Leptin levels did not discriminate between patients with MC4R mutations and the other patients. Five patients harboured one of the MC4R polymorphisms (Val103Ile, Ile251Leu). These were phenotypically indistinguishable from the individuals without MC4R variants. CONCLUSION: We detected MC4R mutations (Thr112Met, Ala175Thr and Gly181Asp) in 3.3 % and MC4R polymorphisms (Val103Ile, Ile251Leu) in 5.5 % of the analysed obese children and adolescents, respectively. The patients with MC4R mutations did not show a higher metabolic risk compared to obese children and adolescents without mutations. However the total study group is prone to an increased risk for developing metabolic and cardiovascular diseases.

Adolescent↗