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Biomedical subjects

H Mayer

Publications and source records attributed to H Mayer.

At least 19 recordsLinked to original sources
PubMed2001

Identification of a deletion variant in the gene encoding the human alpha(2A)-adrenergic receptor.

OBJECTIVE: The alpha(2)-adrenergic receptors are involved in the effects of catecholamines on energy metabolism. Of three known subtypes with differential expression, alpha(2A)-adrenergic receptors are also localized in adipose tissue where they counteract the lipolytic activity of beta-adrenergic receptors. This study was undertaken to assess whether variants in the alpha(2A)-adrenergic receptor gene are associated with body weight. DESIGN AND METHODS: Single strand conformation polymorphism (SSCP) screening and subsequent sequencing were applied to determine genetic variants in DNA samples from individuals with obesity, those of normal weight and those underweight. RESULTS: Analysis of the coding region resulted in the identification of an 18 bp deletion, with no other mutation found. Of 429 genotyped subjects, 7 carried the deletion, with no significant differences between lean and obese subjects. A previously identified polymorphism in the promoter of the alpha(2A)-adrenergic receptor gene also did not show an association with any of the tested body weight categories. CONCLUSION: Our data suggest that variants in the alpha(2A)-adrenergic receptor gene are unlikely to contribute to the predisposition for the lean or obese state.

Adolescent↗
PubMed2000

Structure of the O-specific polysaccharide of Mesorhizobium huakuii IFO15243T.

The structure of the O-specific polysaccharide isolated by mild acid hydrolysis of the lipopolysaccharide of Mesorhizobium huakuii IFO15243T was studied using methylation analysis and various one- and two-dimensional 1H and 13C NMR experiments. The O-antigen polysaccharide was found to be linear polymer constituted by a trisaccharide repeating unit of the following structure: --> 2)-alpha-L-6dTalp-(1 --> 3)-alpha-L-6dTalp-(1 --> 2)-alpha-L-Rhap-(1 -->.

Carbohydrate Sequence↗
PubMed2000

Characterization of p40/GPR69A as a peripheral membrane protein related to the lantibiotic synthetase component C.

The 40 kDa erythrocyte membrane protein p40/GPR69A, previously assigned to the G-protein-coupled receptor superfamily, was now identified by peptide-antibodies and characterized as a loosely associated peripheral membrane protein. This result is in striking contrast to the proposed seven-transmembrane protein structure and function and therefore we wish to correct our previous proposal. p40 is located at the cytoplasmic side of the membrane and is neither associated with the cytoskeleton nor lipid rafts. Refined sequence analysis revealed that p40 is related to the LanC family of bacterial membrane-associated proteins which are involved in the biosynthesis of antimicrobial peptides. Therefore, we rename p40 to LanC-like protein 1 (LANCL1) and suggest that it may play a similar role as a peptide-modifying enzyme component in eukaryotic cells.

Amino Acid Sequence↗
PubMed2000

[In vitro manipulation of primary human osteo-progenitor cells for tissue technological bone production].

The aim of the present study was to evaluate the effect of three different techniques for isolation of human bone-marrow-derived mesenchymal stem cells (MSCs) on the in vitro differentiation of these cells. Furthermore, the use of BMP-2 was assessed and the effect of gene transfer of the BMP-2 gene into these cells was evaluated. Reverse transcription polymerase chain reaction showed that isolation of MSCs by outgrowth from cancellous chips resulted in expression of both osteogenic and chondrogenic markers, while cells cultivated from marrow aspirates exhibited only osteogenic markers. Intramuscular reimplantation of BMP-2-transfected cells in poly-(L/DL 70/30) lactic acid fleeces resulted in formation of mineralized tissue after 8 weeks in athymic rats, while control-transfected cells exhibited matrix synthesis without mineralized tissue after intramuscular reimplantation.

Animals↗
PubMed2000

Occurrence and taxonomic significance of oxo-fatty acids in lipopolysaccharides from members of Mesorhizobium.

Lipopolysaccharides (LPSs) isolated from seven strains of Mesorhizobium were studied for the presence of fatty acids with particular attention for 27-oxooctacosanoic acid and 4-oxo fatty acids. The LPSs from all analysed strains contained various amounts of 27-oxo-28:0 and all of them, with the exception of Mesorhizobium tianshanense, contained also 4-oxo fatty acids (4-oxo-20:0, 4-oxo-i-21:0, 4-oxo-22:0). The group of amide-linked fatty acids consisted of a wide range of 3-hydroxylated and 4-oxo fatty acids whereas all the nonpolar as well as the (omega-1) hydroxylated long-chain acids and the 27-oxo-28:0 fatty acids were ester-linked. The characteristic spectrum of 3-hydroxy fatty acids and presence of 27-OH-28:0 as well as 27-oxo-28:0 acid in LPSs of Mesorhizobium showed that these strains were closely related. Therefore the lipid A fatty acid pattern could be a useful chemotaxonomic marker which helps to isolate the Mesorhizobium group from rhizobium bacteria during the classification process.

Amides↗
PubMed2000

Epidemic obesity: are genetic factors involved via increased rates of assortative mating?

OBJECTIVE: Prevalence rates of obesity have been increasing in several countries over the past two decades. Mainly secular changes in energy intake and expenditure have been invoked to underly the increasing rates; genetic factors have not been considered because of the very recency of this phenomenon. We hypothesize that genetic factors might very well be involved via an increased rate of assortative mating between obese individuals. We speculate that the recent upsurge in social stigmatization of obese individuals underlies the hypothesized increase in assortative mating. DESIGN: To accumulate evidence for our hypothesis we analysed deduced rates of assortative mating among parents of extremely obese children and adolescents, who belonged to two different large study groups (n = 201 and n = 270). For this purpose we calculated parental body mass indices (BMIs) based on (a) measured current heights and weights, (b) self-reported current heights and weights, and finally (c) measured current heights and recalled weights at ages 20 and 30, respectively. BMI centiles were determined which in turn were attributed to the respective BMI decile. Deduced rates of assortative mating were evaluated in bivariate histograms of the paternal and maternal BMI deciles. RESULTS: High rates of assortative mating were observed as deduced from the bivariate histograms, which revealed a fairly consistent pattern. Thus, in the first study group almost 35% of the parental pairs had a BMI in the tenth decile; over 50% of the mothers and fathers had a BMI in this top decile. Recalled parental BMIs at ages 20 and 30 also clustered in the upper decile. These results were basically replicated in the second study group. In addition, parental loading on the tenth decile was shown to be higher for the subgroup of children and adolescents who had a BMI equal to or exceeding the highest BMI of the population-based age and gender matched control group. CONCLUSIONS: Our results indicate that assortative mating is common among parents of extremely obese children and adolescents, ascertained between 1995 and 1997. In addition, the parental loading on the tenth decile is most prominent for the most obese children. Whereas we are unable to document an increased rate of assortative mating, we interpret our results as being consistent with the hypothesis that an increased rate of assortative mating has contributed to the recent rise in obesity rates in several countries. Thus, assortative mating warrants further studies to assess its impact on obesity prevalence rates through both genetic and non-genetic mechanisms. Our results suggest that assortative mating might especially increase the rates for extreme obesity.

Adolescent↗
PubMed2000

Cigarette smoke enhances ethanol-induced pancreatic injury.

Alcohol induces pancreatic ischemia, but the mechanisms promoting pancreatic inflammation are unclear. We investigated whether cigarette smoke inhalation is a cofactor in the development of ethanol-induced pancreatic injury. Cigarette smoke was administered to anesthetized rats alone or in combination with intravenous ethanol infusion. Control animals received either saline or ethanol alone. Pancreatic capillary blood flow and leukocyte-endothelium interaction in postcapillary venules were evaluated by intravital microscopy. Leukocyte sequestration was assessed by measurement of myeloperoxidase activity in pancreatic tissue, and pancreatic injury evaluated by histology. Ethanol decreased pancreatic blood flow progressively over 90 minutes (p < 0.001 vs. baseline), but neither leukocyte-endothelium interaction nor leukocyte sequestration was altered. Cigarette smoke alone reduced pancreatic blood flow temporarily (p < 0.01 vs. baseline) and increased leukocyte-endothelium interaction (roller p < 0.001, sticker p < 0.01 vs. baseline). Cigarette smoke potentiated the impairment of pancreatic capillary perfusion caused by ethanol, and both the number of rolling leukocytes and myeloperoxidase activity levels were increased compared to ethanol or nicotine administration alone (p < or = 0.05 and p < or = 0.01, respectively). This study demonstrates that ethanol induces pancreatic ischemia and that cigarette smoke leads to both temporary pancreatic ischemia and minimal leukocyte sequestration. Cigarette smoke potentiates the amount of pancreatic injury generated by ethanol alone. Smoking therefore seems to be a contributing factor in the development of alcohol-induced pancreatitis in the rat model.

Animals↗
PubMed2000

A telemedical approach to the screening of diabetic retinopathy: digital fundus photography.

OBJECTIVE: The importance of screening for diabetic retinopathy has been established, but the best method for screening has not yet been determined. We report on a trial of assessment of digital photographs by telemedicine compared with standard retinal photographs of the same fields and clinical examination by ophthalmologists. RESEARCH DESIGN AND METHODS: A total of 129 diabetic inpatients were screened for diabetic retinopathy by slit-lamp biomicroscopy performed by an ophthalmologist and by two-field 50 degrees non-stereo digital fundus photographs assessed by six screening centers that received the images by electronic mail. Conventional 35-mm transparencies of the same fields as the digital photographs were assessed by a retinal specialist and served as the reference method for detection of diabetic retinopathy. Slit-lamp biomicroscopy was the reference method for the detection of macular edema. RESULTS: The prevalence of any form of diabetic retinopathy was 30% (n = 35); of sight-threatening retinopathy including macular edema, the prevalence was 6% (n = 7). The assessment of digital images by the six screening centers resulted in a median sensitivity of 85% and a median specificity of 90% for the detection of moderate nonproliferative or sight-threatening diabetic retinopathy. Clinically significant macular edema (n = 4) was correctly identified in 15 of the 24 grading reports. An additional seven reports referred the patients for further investigation because of concurrent diabetic retinopathy. CONCLUSIONS: Telescreening for diabetic retinopathy by an assessment of two-field 50 degrees non-stereo digital images is a valid screening method. Although detection of clinically significant macular edema using biomicroscopy is superior to digital or standard non-stereo photographs, only few patients with sight-threatening diabetic retinopathy are missed.

Computer Communication Networks↗
PubMed1999

No evidence for involvement of polymorphisms of the dopamine D4 receptor gene in anorexia nervosa, underweight, and obesity.

Family and twin studies suggest a genetic contribution to the etiology of anorexia nervosa (AN) and obesity. Genes involved in weight regulation can be considered as candidate genes for AN. The dopaminergic system has been implicated in weight regulation; previous results had suggested a possible involvement of the dopamine D4 receptor gene (DRD4). We screened for alleles of two different polymorphisms (13-bp deletion, 48-bp repeat) in the DRD4. For association tests, allele frequencies were compared between 109 inpatients with AN, 82 underweight students, and 327 extremely obese children and adolescents. For application of transmission disequlibrium tests (TDT) we additionally genotyped 57 and 137 trios comprising a patient with AN or an extremely obese child or adolescent, respectively, and both parents. All genotyping was performed with polymerase chain reaction fragment length polymorphism analyses. None of the association tests or TDT rendered nominal P values below 0.1. An influence of alleles of the DRD4 on the development of AN, underweight, or extreme early onset obesity was not detected. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:594-597, 1999.

Adolescent↗
PubMed1999

Hemostatic factors in hypertriglyceridemic men: effects of a fatty meal before and after triglyceride-lowering treatment with etofibrate.

The aims of this double-blind study were to examine whether in hypertriglyceridemic men the ingestion of a standardized fatty meal alters hemostasis negatively and whether triglyceride-lowering treatment with etofibrate for 6 weeks alters fasting and postprandial hemostasis positively, thus reversing the potential negative effects of a fatty meal on postprandial hemostasis. To answer these questions, we measured markers of hemostasis immediately before a standardized fatty meal, and 4, 6, 8, and 10 hours after the meal in 21 hypertriglyceridemic men both before and after treatment with etofibrate. We found that the concentration of plasmin alpha2antiplasmin complex markedly increased for at least 10 hours after the fatty meal, but that the activation of factor XII and the concentration of prothrombin activation fragment1+2 decreased after the fatty meal. These results on factor XII contradict reported in vitro data. Triglyceride-lowering treatment with etofibrate in 10 of these men for 6 weeks increased fasting and postprandial protein C and plasminogen and also slightly decreased the activation of fXII; however, it did not reverse the postprandial increase of PAP or change the decrease of prothrombin activation fragment1+2. Our findings indicate that postprandial lipoproteins alter markers of hemostasis positively in an antithrombotic and profibrinolytic direction. In addition, triglyceride-lowering treatment with etofibrate only slightly improves markers of fasting and postprandial hemostasis in an antithrombotic and profibrinolytic direction.

Clofibric Acid↗
PubMed1999

Applications of a universal thermal index: physiological equivalent temperature.

The physiological equivalent temperature, PET, is a thermal index derived from the human energy balance. It is well suited to the evaluation of the thermal component of different climates. As well as having a detailed physiological basis, PET is preferable to other thermal indexes like the predicted mean vote because of its unit ( degrees C), which makes results more comprehensible to urban or regional planners, for example, who are not so familiar with modern human-biometeorological terminology. PET results can be presented graphically or as bioclimatic maps. Graphs mostly display the temporal behaviour of PET, whereas spatial distribution is specified in bioclimatic maps. In this article, some applications of PET are discussed. They relate to the evaluation of the urban heat island in cities in both temperate climates and warm climates at high altitude. The thermal component of the microclimate in the trunk space of a deciduous forest is also evaluated by PET. As an example of the spatial distribution of PET, a bioclimatic map for Greece in July (Mediterranean climate) is presented.

Altitude↗
PubMed1999

No evidence for an involvement of alleles of polymorphisms in the serotonin1Dbeta and 7 receptor genes in obesity, underweight or anorexia nervosa.

The serotonergic (5-hydroxytryptamine, 5-HT) system has been implicated in body weight regulation and in the etiology of anorexia nervosa (AN). Here we describe the screening of the known Phe-124-Cys polymorphism in the 5-HT1Dbeta receptor gene and of the known Pro-279-Leu polymorphism in the 5-HT7 receptor gene. For association tests allele frequencies were compared between up to 393 extremely obese children and adolescents, 142 underweight students and 84 patients with AN. None of the association tests revealed nominal P-values below 0.3. We conclude that a major role of the investigated polymorphisms in body weight regulation or AN appears unlikely.

Adolescent↗
PubMed1999

Phenotypes in three pedigrees with autosomal dominant obesity caused by haploinsufficiency mutations in the melanocortin-4 receptor gene.

Recently, haploinsufficiency mutations in the melanocortin-4 receptor gene (MC4-R) were detected which were assumed to lead to the phenotype of extreme obesity. Previously, we detected three obese carriers among 306 index patients. Here we describe the detection of one haploinsufficiency carrier in an additional study group of 186 obese individuals. We subsequently genotyped and phenotyped 43 family members of these four index patients, two of whom were second-degree cousins. A total of 19 carriers were identified. Extreme obesity was the predominating phenotype. However, moderate obesity occurred in three of the carriers. No other specific phenotypic abnormalities were detected. Female haploinsufficiency carriers were heavier than male carriers in the respective families, a finding similar to findings in MC4-R-knockout mice. In conclusion, our data fully support the etiologic role of MC4-R haploinsufficiency mutations in obesity.

Adolescent↗
PubMed1999

An automatic method for the identification and interpretation of clustered microcalcifications in mammograms.

We investigated a method for a fully automatic identification and interpretation process for clustered microcalcifications in mammograms. Mammographic films of 100 patients containing microcalcifications with known histology were digitized and preprocessed using standard techniques. Microcalcifications detected by an artificial neural network (ANN) were clustered and some cluster features served as the input of another ANN trained to differentiate between typical and atypical clusters, while others were fed into an ANN trained on typical clusters to evaluate these lesions. The measured sensitivity for the detection of grouped microcalcifications was 0.98. For the task of differentiation between typical and atypical clusters an Az value of 0.87 was computed, while for the diagnosis an Az value of 0.87 with a sensitivity of 0.97 and a specificity of 0.47 was obtained. The results show that a fully automatic computer system was developed for the identification and interpretation of clustered microcalcitications in mammograms with the ability to differentiate most benign lesions from malignant ones in an automatically selected subset of cases.

Breast Diseases↗
PubMed1999

Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans.

The melanocortin-4 receptor gene (MC4-R) has been implicated in weight regulation. Recently, two independent groups reported frameshift mutations associated with a dominant form of obesity (1, 2). We screened the coding region of the MC4-R in 306 extremely obese children and adolescents (mean body mass index: BMI 34.4 +/- 6.6 kg/m2), 25 healthy underweight students (mean BMI 17.1 +/- 0.8 kg/m2), 52 normal weight individuals (mean BMI 22.0 +/- 1.0 kg/m2), 51 inpatients with anorexia nervosa (AN, DSM IV criteria, mean BMI 14.3 +/- 1.5 kg/m2) and 27 patients with bulimia nervosa (BN, DSM IV criteria, mean BMI 21.7 +/- 5.8 kg/m2) by single strand conformation polymorphism analysis (SSCP). Several mutations were identified, including the frameshift mutation described (1). The mutations were as follows: a) The deletion of 4 bp (delta of CTCT at codon 211) results in a frameshift, thus rendering a truncated protein. This mutation has been assumed to be associated with dominantly-inherited morbid obesity in humans (1). Both the index patient (BMI 42.06 kg/m2, height 171 cm, age 19.6 years) and her mother (BMI 37.55 kg/m2, height 164 cm, age 42.5 years) were heterozygous for the deletion. b) A nonsense mutation at position 35 of the MC4-R was detected in two obese probands (BMI 31.29 kg/m2 and BMI 45.91 kg/m2). This mutation leads to a truncated protein that encompasses the N-terminal extracellular domain. Both carriers additionally showed (c) a missense mutation (Asp-37-Val). In both of these cases Tyr-35-Stop and Asp-37-Val were maternally transmitted, thus these variations form a haplotype. d) e) A male obese proband harbored two missense mutations (Ser-30-Phe, Gly-252-Ser). f)-i) Four different missense mutations (Pro-78-Leu, Thr-112-Met, Arg-165-Trp, Ile-317-Thr) were detected in four different male probands, respectively. All of these mutations (a to i) were found solely in extremely obese individuals whose BMIs were all above the 99th percentile. j) A silent mutation (C-579-T, Val-193-Val) was detected in a male underweight individual. k) A previously described polymorphism (Val-103-Ile; 3) was detected with similar frequencies in all different study groups. 1) We identified a novel polymorphism (Ile-251-Leu) with similar allele frequencies in all groups under study. In conclusion, our data indicate that mutations in the MC4-R are not uncommon. Whereas our data support the evidence for dominantly inherited obesity as revealed by the three obese probands with haplo-insufficiency, the functional significance of the missense mutations remains to be determined.

Adolescent↗
PubMed1999

Missense variants in the human peroxisome proliferator-activated receptor-gamma2 gene in lean and obese subjects.

The peroxisome proliferator-activated receptor-gamma2 (PPARgamma2) is almost uniquely expressed in adipose tissue and is of major importance for fat cell differentiation and lipid metabolism. This study was undertaken to assess whether two missense variants in the PPARgamma2 gene are associated with early-onset obesity. A previously described polymorphism encoding for an amino acid exchange in codon 12 (Pro12Ala) was detected with allele frequencies of 0.13 in 296 markedly obese children and adolescents and 0.14 in 130 lean individuals. A Pro115Gln variant, which had been linked to obesity in Germans in a previous association study, was not detected in any of our obese or lean subjects, who are also of German origin. We conclude from our data that these two variants in the PPARgamma2 gene are unlikely to contribute to the high prevalence of early-onset obesity.

Adolescent↗
PubMed1999

Extramedullary relapse despite graft-versus-leukemia effect after bone marrow transplantation in a girl with juvenile myelomonocytic leukemia.

A 12 year-old girl with juvenile myelomonocytic leukemia (JMML) and monosomy 7 underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched brother. To monitor the engraftment and the course of the disease we used fluorescence in situ hybridization (FISH) with probes specific for the centromeres of chromosomes X, Y and 7. Complete hematological remission was achieved and confirmed by the virtually exclusive presence of normal male cells in the bone marrow (BM). Acute graft-versus host disease (GvHD) was treated with prednisone and cyclosporine A (CSA) and female cells with monosomy 7 reoccurred in the peripheral blood (PB) and BM. After discontinuation of the immunosuppressive therapy, the leukemic cells with monosomy 7 disappeared again from these compartments. One year after transplantation, isolated extramedullary relapses occurred in lymph nodes and skin, followed by dissemination of blast cells into the BM, whereas the PB cells remained of donor origin. The fact that the leukemic cells fluctuated with the intensity of the immunosuppressive treatment provides evidence of a graft versus leukemia (GvL) effect in this unusually old girl with JMML with a unique extramedullary disease progression.

Bone Marrow Transplantation↗