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Biomedical subjects

H Mayer

Publications and source records attributed to H Mayer.

At least 73 records · Page 4Linked to original sources

Enteroaggregative Escherichia coli as a potential cause of diarrheal disease in adults infected with human immunodeficiency virus.

Stools of 68 human immunodeficiency virus (HIV)-infected adults with diarrhea and 60 without diarrhea were examined for enteroaggregative Escherichia coli (EAggEc) by HeLa cell adherence assay. EAggEc were present in stools of 30 patients with and 18 without diarrhea (P = .05). CD4 cell counts of patients with EAggEc and diarrhea were significantly lower than those of patients with EAggEc without diarrhea (P = .02). There was no difference in the mean duration of diarrheal symptoms or in the number of stools per day between patients with EAggEc and those without. None of the EAggEc strains were positive by polymerase chain reaction for adherence fimbria, but 11 strains were positive for EAggEc heat-stable toxin EAST/1. Of the EAggEc strains, 51% were resistant to trimethoprim-sulfamethoxazole and 65% were resistant to ampicillin. EAggEc may be a pathogen in HIV-infected patients with diarrhea; HIV-infected patients with EAggEc appear to be more symptomatic when HIV disease is more advanced.

AIDS-Related Opportunistic Infections↗

Systematic mutation screening of the pro-opiomelanocortin gene: identification of several genetic variants including three different insertions, one nonsense and two missense point mutations in probands of different weight extremes.

Pro-opiomelanocortin (POMC) is the precursor of melanocortins (adrenocorticotropin: ACTH, beta-endorphin, beta-lipotropin: beta-LPH, corticotropin like intermediate peptide, alpha-, beta- and gamma-melanocyte-stimulating hormone: alpha-, beta- and gamma-MSH) some of which act in the brain to reduce food intake and are potential mediators of leptin action. Recently, three different mutations in the POMC gene (POMC) were identified in two unrelated children that lead to early-onset extreme obesity, adrenal insufficiency, and red hair pigmentation. In the present study we systematically screened the coding region of POMC in 96 extremely obese children and adolescents, 60 healthy underweight individuals and 46 patients with anorexia nervosa (AN) and identified several variants. a) A 9 and an 18 base pair insertion (9bp and 18bp: AGC AGC GGC and AGC AGC GGC AGC AGC GGC, respectively, between codon 73 and 74; 1,2). These in-frame variants lead to the insertion of three or six amino acids (Ser-Ser-Gly; Ser-Ser-Gly-Ser-Ser-Gly) carboxy-terminal to gamma-MSH. Frequencies of the 9bp insertion allele varied between 3 and 5% among the different study groups (Pearson's chi2 P>0.5). b) Both an out-of-frame 6 bp insertion (within codon 176: GGG CCC) leading to the insertion of two amino acids (Arg-Ala) and a premature stop-codon (G-7316-T: Glu-180-Stop) within the gamma-LPH sequence were maternally inherited in an obese female proband. This proband inherited another missense mutation from her father (Glu-188-Gly). c) A missense mutation (G-7016-A; Asp-80-Asn) was observed in a single patient with AN who also harboured the 9bp insertion on a paternally derived haplotype. d) The allelic co-occurence of two silent mutations (C-6982-T and C-7285-T) was detected in two obese subjects. e) Two further silent mutations (C-3832-T; C-7111-G) were detected in an underweight and an obese subject, respectively. We conclude that the POMC gene harbors several different polymorphisms and mutations, none of which can readily be associated with the phenotypes under study.

Adolescent↗

Systematic mutation screening of the estrogen receptor beta gene in probands of different weight extremes: identification of several genetic variants.

Estrogens are known to have an inhibitory effect on food intake in rodents and primates. Decreased estrogen levels that are found for instance in menopausal woman and in ovarectomized rodents result in body weight gain. Estrogen can act both in the periphery and in the central nervous system via at least two different estrogen receptors (alpha and beta). We systematically screened the coding region and part of the 5' and 3'regions of the estrogen receptor beta gene (ER beta) in 96 extremely obese children and adolescents, 50 patients with anorexia nervosa (AN), 28 patients with bulimia nervosa (BN), and 25 healthy underweight individuals. We detected five different sequence variants in the ER beta: a) A 21 bp deletion (codons 238 to 244) was detected in two obese probands and an underweight individual. b) An 846G-->A transition leading to a nonconservative amino acid substitution (G-250-S) was found in two obese male probands. Both a) and b) were located within the flexible hinge region between DNA and ligand binding domain. c) For a 1082G-->A polymorphism we found suggestive evidence for an association between the more common 1082G-allele and anorexia nervosa (nominal p=0.04). d) One silent mutation (1421T-->C) was found solely in two obese probands. e) A common variant is located in the 3' nontranslated region at position 1730(A-->G). We did not detect association of this polymorphism to any of the analyzed phenotypes. We conclude that the ER beta harbors several different mutations and polymorphisms, none of which can readily be associated with the phenotypes under study.

Adolescent↗

The diagnostic value of serum homocysteine concentration as a risk factor for coronary artery disease.

Hyperhomocysteinemia is now regarded as an established risk factor for coronary artery disease and is present frequently in the general population. However, the diagnostic value of this risk factor relative to others has only occasionally been investigated. We compared the diagnostic value of classic risk factors and of homocysteine in a retrospective case-control study in 191 cases with angiographically established coronary artery disease and 231 healthy controls. Life style habits were assessed by a detailed questionnaire. Laboratory parameters including lipoproteins and blood lipids, homocysteine, folate, and vitamin B12 were measured and their diagnostic value compared with each other by use of receiver-operator characteristic analysis. Comparison of the receiver-operator characteristic curves revealed that homocysteine significantly discriminated between cases and control subjects. High-density-lipoprotein cholesterol, triglycerides and non-esterified fatty acids also had an area under the curve significantly different from 0.5 (the area under the curve representing no discrimination). Homocysteine was weakly related to folate, vitamin B12, age and serum creatinine concentration. We conclude that hyperhomocysteinemia is at least as important as conventional risk factors for coronary artery disease and that receiver operator characteristic analysis of homocysteine is suitable to determine patients at the highest risk for coronary artery disease. Clinical trials testing the effect of homocysteine lowering by vitamin supplementation in the prevention of coronary artery disease are needed.

Coronary Disease↗

Immunochemical studies on R mutants of Yersinia enterocolitica O:3.

Three mutants of Yersinia enterocolitica O:3, namely: YeO3-R1, YeO3-RfbR7 and YeO3-c-trs8-R were classified on the basis of sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS/PAGE) profile of isolated lipopolysaccharides (LPS) as belonging to the Ra- (the first) and the Rc-type (the other two mutants). Methylation analysis, in addition to 13C and 1H NMR studies of purified core oligosaccharides revealed structures similar to those established previously for the full core of Y. enterocolitica O:3 in the case of the Ra mutant, and identical to that reported for the Rc mutant Ye75R, in the case of the two other mutants. The O-specific sugar, 6d-L-altrose, which forms a homopolymeric O-chain, was present in small amounts in all three LPS preparations, as well as in the core oligosaccha ride preparations along with the Ra and the Rc sugars, characteristic of the Y. enterocolitica O:3 core. This result is in line with genetic data, indicating that it is the inner core region which is the receptor for the O-specific chain in Y. enterocolitica O:3. This region seems likewise to be the anchoring region for the enterobacterial common antigen (ECA), as shown by SDS/PAGE/Western blot analysis with monoclonal antibodies against ECA. In addition, we also demonstrated that the Ye75R mutant Rc and its parental strain Ye75S, both were ECA-immunogenic strains. So far, ECA-immunogenic strains, i.e. those with LPS-linked ECA, were only identified in E. coli mutants of the R1, R4 and K-12 serotype.

Blotting, Western↗

[Decreasing reperfusion damage with N-acetylcysteine in experimental pancreas transplantion].

In this study we investigated the effect of donor and recipient conditioning with N-acetylcysteine on the ischemia/reperfusion injury after experimental pancreas-transplantation. We performed standardized pancreaticoduodenal transplantation in male lewis rats. The pancreas was perfused with UW-solution, harvested and conserved at 4 degrees C. Cold ischemia time was 1.5 hours and 16 hours respectively. The microcirculation in the transplanted organ was quantified by means of intravital microscopy 1.5 hours after implantation and reperfusion in the recipient. After 16 hours of cold ischemia we found a significant reduction in capillary erythrocyte velocity and a significantly enhanced leucocyte/endothelium interaction. The treatment with N-acetylcysteine resulted in a significant improvement of these microcirculatory disorders after prolonged cold ischemia.

Acetylcysteine↗

[Lack of stimulation of CD11b/CD18 induced leukocyte adhesioin by platelet activating factor (PAF) and f-MLP in malignant tumor endothelium in experimental pancreas cancer of the rat].

UNLABELLED: The interaction between immunocompetent cells and tumor-endothelium is essential for effective immunologic recognition. In the present study we evaluated resting and CD11b/CD18-mediated leukocyte adhesion on tumor-endothelium of experimental pancreatic carcinoma and in healthy pancreatic venules. METHODS: 22 male Lewis rats (120-140 g) were anesthetized. Duct-like pancreatic carcinoma (DSL6A, Am. J. Pathol. 1993; 143:292) was induced by intrapancreatic implantation of tumor fragments between inert polymethylmetacrylat plates. After 4 wks the tumor-bearing pancreas was exposed and the microcirculation studied. Parameters in tumor vessels (15-40 microns) and healthy pancreatic collecting venules (20-40 microns) included: Erythrocyte velocity, Leukocyte adhesion, Vessel diameter and wall shear rate. Measurements were obtained before and 5 min after adding f-MLP (100 mM) or PAF (50 mM), two CD11b/CD18 agonists of different potency to the immersion chamber. RESULTS: [table: see text] CONCLUSION: In experimental pancreatic carcinoma leukocyte adhesion of low affinity is reduced despite comparable wall shear rates. The CD11b/Cd18-mediated adhesion of high affinity, which is inducible by f-MLP and PAF in healthy pancreatic venules, is absent in tumor vessels. This may be a mechanism by which malignant tumors escape immune control.

Animals↗

Structure of the O-specific polysaccharide of Salmonella enterica ssp. arizonae O50 (Arizona 9a,9b).

On the basis of sugar and methylation analysis, selective removal of 3,6-dideoxy-L-xylohexose (colitose, Col), 1H and 13C NMR spectroscopy, including 1D NOE, 2D COSY, and 2D H-detected 1H, 13C heteronuclear multiple-quantum coherence (HMQC), the following structure of the repeating unit of the O-specific polysaccharide of Salmonella enterica ssp. arizonae O50 (Arizona 9a,9b) was established: [sequence: see text] The O-antigen studied includes a trisaccharide fragment alpha-Co1p-(1-->2)-beta-D-Galp-(1-->3)-beta-D-GlcpNAc, which is a colitose ('3-deoxy-L-fucose') analogue of the Lewis (precursor) blood group antigen.

Carbohydrate Conformation↗

Heat stress in Greece.

For 12 selected synoptic stations of the Greek Weather Service, the daily 12 UTC values of the thermal index Predicted Mean Vote (PMV) were calculated for the years 1980 to 1989. The locally varied occurrence of diverse thermal sensation and particularly of strong heat stress were analysed in relation to the human-biometeorological significance. With the help of a statistical model, PMV values of individual stations were transformed into a high-resolution bioclimatic map. The map presents the average annual number of days with at least strong heat stress (PMV > 3.0).

Climate↗

Individual and combined effects of calciotropic hormones and growth factors on mineral metabolism in embryonic chick tibiae.

We have investigated single and combined effects of calciotropic hormones and growth factors on the regulation of alkaline phosphatase (ALP) activity and calcium metabolism in an optimized serum-free bone organ culture system of embryonic chick tibiae. Parathyroid hormone PTH(1-34) alone mobilized calcium from bone tissue time- and dose-dependently and inhibited ALP activity. Both the bisphosphonate (BM 21.0955) and to a lesser extent salmon calcitonin alone slightly increased calcium uptake and inhibited the stimulation of bone resorption by PTH(1-34). 1,25(OH)2D3 mobilized calcium and inhibited ALP activity in contrast to 24,25(OH)2D3 which inhibited ALP activity but had no significant effect on calcium metabolism. Interestingly the combination of PTH(1-34) with 1,25(OH)2D3 but not 24,25(OH)2D3 reduced calcium mobilization. The combination of the midregional fragment PTH(28-48), which by itself has no effect on calcium metabolism, with 1,25(OH)2D3 reduced calcium mobilization more efficiently. Several PTH-regulated mediators have been assayed in this system. Of the tested growth factors, IGF-I at high concentrations caused bone resorption with no effect on ALP activity. TGF-beta 1 (transforming growth factor beta) and BMP-2 had no significant effect on calcium metabolism; however, ALP activity was inhibited by TGF-beta 1 and induced dose dependently by BMP-2. Of the other factors known to be present in bone, platelet-derived growth factor (PDGFA/B) and epidermal growth factor (EGF) had a small effect on calcium mobilization but had no effect on ALP activity. bFGF reduced ALP activity slightly without an effect on calcium metabolism. Our results show that this in vitro system can mimic some interactions of calciotropic hormones in vivo and allows the assaying of mediators in terms of regulation of ALP activity and of calcium metabolism.

Alkaline Phosphatase↗

Evaluation of a Cys23Ser mutation within the human 5-HT2C receptor gene: no evidence for an association of the mutant allele with obesity or underweight in children, adolescents and young adults.

Serotonin is a neurotransmitter involved in a large number of psychophysiological processes including the regulation of mood, arousal, aggression, sleep, learning, nociceptions, nerve growth and importantly, appetitive functions. Alterations of 5-HT receptor activity have been shown to occur in many psychiatric diseases including depression, anxiety, eating disorders, schizophrenia etc. Hence, genetic variation in genes coding for serotonin receptor proteins might well be involved in the genetic predisposition to these diseases and therefore are of great pharmacogenetic relevance. Knockout mice deficient of a functional 5-HT2C receptor have implicated a potential role of this receptor subtype in the serotonergic control of appetite. A Cys23Ser mutation in the human 5-HT2C receptor gene discovered recently prompted us to investigate this mutation with regard to the development of human obesity. We have evaluated this mutation in 241 obese children and adolescents (mean BMI > or = 97th percentile), 80 normal weight children (BMI 5th-85th percentile) and 92 underweight probands (BMI < or = 15th percentile) for a possible association with obesity. The frequencies of the mutant allele in all three weight groups (obese subjects: 0.1597; normal weight: 0.168; underweight: 0.1575) were very similar. Association as well as linkage studies were negative. Therefore it is unlikely that this receptor mutation plays a direct role in the development of human obesity.

Adolescent↗

Serotonin transporter gene-linked polymorphic region: allele distributions in relationship to body weight and in anorexia nervosa.

Several lines of evidence implicate a role for the serotonergic system in body weight regulation and eating disorders. The magnitude and duration of postsynaptic responses to serotonin (5-HT) is directed by the transport into and release from the presynaptic neuron. Recently, a common polymorphism of a repetitive element in the region of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) was identified that results in a system of two common alleles. The activity of the 5-HTT, as measured in in vitro assays and in human lymphoblastoid cell lines, is dependent on the respective genotype. We thus hypothesized that this polymorphism is relevant for weight regulation in general and is possibly involved in the etiology of anorexia nervosa (AN). Allele frequencies and genotypes were determined in a total of 385 unrelated obese children, adolescents and adults, 112 underweight subjects and 96 patients with AN. Furthermore, both parents of 98 obese children and adolescents and of 55 patients with AN, respectively, were genotyped, thus allowing to test for both association and linkage. The comparison of allele frequencies between obese and underweight probands provided no evidence for a major role of the 5-HTTLPR in weight regulation. Patients with AN had allele frequencies not significantly different to those observed for obese and underweight individuals.

Adolescent↗

Machine milking of Ostfriesian and Lacaune dairy sheep: udder anatomy, milk ejection and milking characteristics.

Mammary cistern anatomy derived from ultrasound measurement, milk ejection in response to exogenous oxytocin and oxytocin release and milking characteristics with and without manual prestimulation in early (months 2-4) and late (months 5-8) lactation were investigated in Lacaune and Ostfriesian dairy ewes. Vertical ultrasound cisternal cross sections of the cisternal cavities did not differ in the two breeds, whereas the cisternal area fraction located lower than the exit into the teat channel was larger in Ostfriesian than in Lacaune sheep. The cisternal area enlarged within 1 min in response to i.v. oxytocin injection, indicating milk ejection. During milking, oxytocin concentrations in Lacaune generally increased dramatically within 0.5 min from the start of prestimulation or milking, whereas only slight or no oxytocin release was detected during milking without prestimulation in Ostfriesian ewes. Prestimulation induced oxytocin release in Ostfriesian sheep within 1-2 min after the start of milking, indicating delayed response to stimulation. Two peaked milk flow curves were observed when oxytocin release and milk ejection occurred only after removal of cisternal milk. This type of milk flow was more frequent in Ostfriesian than in Lacaune ewes and was reduced in both breeds by prestimulation, while the frequency of one peaked milk flow curves increased. During the course of lactation, milk yield, main milk fraction and milk flow rates decreased, while stripping yield was almost unchanged. Although milk yield was similar in both breeds, milk flow was lower and stripping yield was higher in Ostfriesian than in Lacaune ewes. We conclude that milk ejection in ewes occurred in response to elevated oxytocin concentrations. In Ostfriesian ewes reduced and delayed oxytocin response to teat stimulation resulted in milk ejection only during stripping. Therefore, and probably because a larger volume of the cistern was located below the teat exit in the Ostfriesian breed, stripping yield was higher in Ostfriesian than in Lacaune sheep.

Animals↗

Significant weight gains in a clinical sample of obese children and adolescents between 1985 and 1995.

OBJECTIVE: Within the past decades prevalence rates for obesity among children and adolescents have increased in different populations. The hypothesis of this study is that the degree of adiposity in clinical study cohorts of extremely obese children and adolescents increased within the past decade. DESIGN: In six different study cohorts of the time period from 1985-1995 body mass indices (BMIs) of obese children and adolescents who were treated as inpatients at a specialized children's hospital were evaluated. For this purpose body heights, body weights, ages and sex of all inpatients of three referring agencies were retrospectively assessed biannually. RESULTS: In these six cohorts a significant BMI-increase from 1985-1995 of 1.9 kg/m2 (P < 0.0001) for constant sex, age and referring agencies was found: Comparisons of the quartiles and the ninth decline in both sexes did not show any systematic increase at the first quartile. In contrast, BMI-increases at the ninth decile were approximately 5 kg/m2 for males and 2.5 kg/m2 for females. CONCLUSION: Within the decade studied a significant BMI-increase was detectable in this clinical population. This effect is especially discernible in the most extreme weight groups and in males.

Adolescent↗

Beta 3-adrenergic-receptor allele distributions in children, adolescents and young adults with obesity, underweight or anorexia nervosa.

OBJECTIVE: The missense mutation (64Trp to 64Arg) in the beta 3-adrenergic-receptor has previously been described to confer a genetic predisposition to the development of obesity. DESIGN: To test the hypothesis we evaluated allele frequencies in children, adolescents and young adults who belonged to different weight groups that were delineated with percentiles for the body mass index (BMI; kg/m2). SUBJECTS: 99 underweight probands (BMI < or = 15th percentile). 80 normal weight probands (BMI: 5th-85th percentile). 238 obese children and adolescents (BMI > or = 97th percentile). 84 patients with anorexia nervosa (AN). MEASUREMENTS: The cohorts were screened by polymerase chain reaction with subsequent restriction fragment length polymorphism (PCR-RFLP) analysis. Data were statistically analysed for association. In addition to these case control studies, the transmission disequilibrium test (TDT) was applied to 80 families of obese probands and to 52 families of patients with AN. RESULTS: Both the tests for association and linkage were negative. The Trp64Arg allele frequencies in the three weight groups (obesity: 0.071; normal weight: 0.081; underweight: 0.056) and the AN patients (0.054) were similar. Extremely obese individuals showed no excess of the Trp64Arg allele. No homozygotes for the Trp64Arg allele were detected. CONCLUSION: Heterozygosity for the Trp64Arg allele is not of major importance in regulation of body weight in individuals younger than 35 y. Additionally, the extreme obese subgroup is not enriched for the polymorphism.

Adolescent↗