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Biomedical subjects

H Mayer

Publications and source records attributed to H Mayer.

At least 91 records · Page 5Linked to original sources
PubMed1997

Further support for linkage of extreme obesity to the obese gene in a study group of obese children and adolescents.

The role of the obese gene in human obesity is presently unclear. Evidence for linkage of markers flanking the gene to obesity has been found in some but not all studies. We investigated transmission disequilibrium between two highly polymorphic microsatellite markers (D7S504 and D7S1875) flanking the human obese gene (OB) and extreme obesity in a study group of German children and adolescents. Due to the early onset and severity of obesity in the ob/ob mouse we hypothesized that especially children and adolescents with extreme obesity are enriched for possible mutations in the human OB. The analysis of 88 trios (index probands and both parents) for transmission disequilibrium of a haplotype which has previously been determined to be linked to extreme obesity (Reed et al., 1996) revealed a one-sided transmission disequilibrium test (TDT) p-value of 0.039. Post hoc analyses revealed one-sided TDT p-values of 0.015 for the 214 bp allele of D7S1875 (corrected p-value = 0.03) and 0.215 for the 145 bp allele of D7S504 (corrected p-value = 0.43). These findings substantiate the evidence for linkage of extreme obesity to OB.

Adolescent↗
PubMed1997

Response of catecholamines to manual teat stimulation or machine-milking of Lacaune and Friesen dairy ewes.

Increased sympathetic activity, including peripheral release of catecholamines, has been hypothesized to inhibit the milk ejection reflex by blocking the release of oxytocin, by blocking the effect of oxytocin at the mammary gland, or both. We attempted to relate differences in milking characteristics of Lacaune and East Friesen ewes to the degree of sympathetic arousal, responses of catecholamines and oxytocin to machine-milking and to manual teat stimulation followed by milking. Peripheral concentrations of epinephrine, 67 +/- 6 pg/ml for Lacaunes and 57 +/- 5 pg/ml for Friesens, were essentially constant. Peripheral concentrations of norepinephrine averaged 682 +/- 68 pg/ml for Lacaunes and 250 +/- 54 pg/ml for Friesens. Elevated norepinephrine concentrations during the pretreatment period were associated with the inhibition of oxytocin responses. When norepinephrine concentrations during the pretreatment period exceeded 300 pg/ml for Friescens, or were rising and exceeded 700 pg/ml at initiation of the experimental period for Lacaunes, oxytocin release was inhibited. Results from this study clearly showed that basal concentrations of norepinephrine vary with breed of ewes and provided the first direct evidence that increased sympathetic activity can result in central inhibition of the milk ejection reflex.

Animals↗
PubMed1997

Characterization of two lipopolysaccharide types isolated from Rhizobium galegae.

Lipopolysaccharides (LPS) of Rhizobium galegae, a symbiotically nitrogen-fixing species of root-nodule bacteria, were isolated by the phenol-water method from strain HAMBI 1461, the LPS of which resembled enterobacterial smooth type LPS, and from strains HAMBI 1174 and HAMBI 1208, the LPSs of which resembled rough type LPS. The results of PAGE analysis of LPSs, Bio-Gel P2 gel filtration of polysaccharide fractions and the presence of deoxysugars and 4-O-methyl-deoxysugar both in the rough and smooth LPSs suggested that rough LPS contained a short O-antigenic polysaccharide for which we propose the name short O-chain LPS. Accordingly, the smooth LPS is called long O-chain LPS. Despite of the differences in the structure of LPS of R. galegae, all strains were equally effective in nodulating their hosts. The short O-chain LPS of R. galegae showed many features similar to those of phylogenetically related agrobacteria.

Carbohydrates↗
PubMed1996

Subtle differences in the mitogenic effects of recombinant human bone morphogenetic proteins -2 to -7 on DNA synthesis on primary bone-forming cells and identification of BMP-2/4 receptor.

The bone morphogenetic proteins (BMPs) are a group of related proteins capable of inducing the formation of new cartilage and bone. We report here a direct comparison of members of the BMP family in their capability to induce DNA synthesis in bone cell cultures. The promotion of DNA synthesis was determined in periosteal cells and epiphyseal and sternal chondrocytes of embryonic chick. We demonstrate that structurally homologous BMP-2 and BMP-4 exhibit the highest specific activity in the three tested cell types, whereas BMP-5, BMP-6 activity is moderately reduced in periosteal cells and highly reduced in epiphyseal and sternal chondrocytes. The specific activity of BMP-7 is the lowest in the three tested cell cultures. Receptor binding characteristics demonstrate a binding of BMP-2 with high affinity (KD = 0.45 nM) on periosteal cells, and excess of TGF-beta 1 does not displace BMP-4 binding. Chemical cross-linking with iodinated BMP-2 generates an affinity complex of 90 kDa. These findings suggest the presence of a BMP-2/BMP-4 receptor that discriminates subtle differences in function among homologous members of the BMP family.

Animals↗
PubMed1996

How can the bioavailability of timolol be enhanced? A pharmacokinetic pilot study of novel hydrogels.

BACKGROUND: Carbomerbased hydrogels with timolol maleate (T-Gel) were chosen to study the vehicle effect on ocular bioavailability. Pharmacokinetic profiles of T-Gel 0.05% (0.05% timolol), T-Gel 0.025% (0.025% timolol) and commercial timolol ophthalmic solution (TOS 0.1%; 0.1% timolol) were determined and compared. METHODS: A single dose was administered to rabbits' eyes. Timolol was determined by HPLC in aqueous humour, blood samples and washings of the ocular surface (as a measure of residence time). Sampling times were 0.5 h, 1 h and 4 h after instillation. RESULTS: Concentration versus time curves (AUC) of timolol in aqueous humour demonstrate no significant differences between TOS 0.1% and T-Gel 0.025% (P = 0.19), whereas the difference between T-Gel 0.05% and TOS 0.1% is significant (P = 0.006); the AUC ratio of T-Gel 0.05%:TOS 0.1%:T-Gel 0.025% was 2.14:1:0.87. Timolol blood levels were highest with TOS 0.1% at every time point. Peak levels occurred after 0.5 h with all test products; the ratio of peak levels (Cmax) for T-Gel 0.05%:TOS 0.1%:T-Gel 0.025% was 0.55:1:0.17. Timolol was detected in the washings up to 1 h after instillation of test products; the highest levels were observed after T-Gel 0.05%. CONCLUSION: The new vehicle obviously improves the bioavailability of topically applied timolol.

Administration, Topical↗
PubMed1996

Characterization of the lipopolysaccharides from Rhizobium meliloti strain 102F51 and its nonnodulating mutant WL113.

Lipopolysaccharides from the Rhizobium meliloti wild-type strain 102F51, which is effective in symbiosis with alfalfa, and from the nonnodulating mutant WL113, defective in root hair adhesion, derived thereof, were isolated and comparatively analyzed. Both preparations were composed of galactose, glucose, glucuronic acid, galacturonic acid, glucosamine, 3-deoxyheptulosaric acid, and 2-keto-3-deoxyoctonic acid as the major sugar constitutents. After a modified methylation analysis (consisting of the following consecutive steps: methylation, carboxyl reduction, remethylation, mild acid hydrolysis, reduction, and trideuterio-methylation), all of the 3-deoxyheptulosaric and some of the 2-keto-3-deoxyoctonic acid residues were converted into their corresponding 3-deoxyalditol derivatives, which carried trideuteriomethyl groups at positions C-2, C-4, and C-6. Another part of the permethylated 3-deoxyoctitol was also found as 2,5,6- and 2,6,8-tri-O-trideuteriomethyl derivatives. NMR data obtained with the separated oligosaccharides and the results of methylation analysis indicated that the majority of 2-keto-3-deoxyoctonate was present in the fraction of permethylated disaccharide alditols, namely as 6-O-CD3-alpha Glc(1-->5)3-deoxyoctitol, 6-O-CD3-beta GlcNMeAcyl(1-->4)-3-deoxyoctitol, and as the permethylated trisaccharide alditol, alpha GalA(1-->3)-[6-O-CD3]-beta-Glc(1-->5)-[4-O-CD3]-3-deoxyoctitol. The presence of trideuteriomethyl groups at C-4 of both 3-deoxyalditols and at C-6 of the glucosaminyl or glycosyl residues indicated the linkage points of the released acid-labile ketosidic substituents, such as 3-deoxyheptulosarate and 2-keto-3-deoxyoctonate, in these oligosaccharides. The main differences between the preparations from the wild-type 102F51 and its mutant strain WL 113 were found in the higher content (in strain 102F51) of the following oligosaccharides: alpha-glucuronosyl(1-->4)2-keto-3-deoxyoctonate and alpha-galacturonosyl-(1-->3)alpha-glucosyl-(1-->5)2-keto-3-deoxyoc tonate and in the decreased content of beta-glucosaminyl(1-->4)2-keto-3-deoxy-octonate.

Lipopolysaccharides↗
PubMed1996

Structural and immunochemical studies on the lipopolysaccharide of the 'T-antigen'-containing mutant Proteus mirabilis R14/1959.

In DOC-PAGE, lipopolysaccharide (LPS) of Proteus mirabilis R14/1959 (Rb-type) mutant showed a ladder-like migration pattern indicating the presence of a high molecular weight polysaccharide chain. The isolated polysaccharide, called T-antigen because of similarity with the T1 chain of Salmonella friedenau LPS, contained D-glucose, D-galacturonic acid (D-GalA), and D-GlcNAc in molar ratios 2:1:1 and was structurally different from the O-antigen of the parental S-strain P. mirabilis S1959 but identical to the O-antigen of another S-strain Proteus penneri 42. The importance of a D-GalA(L-Lys)-containing epitope, most likely present in the core region of LPS, and of GalA present in the T-antigen chain in manifesting the serological specificity of P. mirabilis R14/1959 were revealed using rabbit polyclonal homologous and heterologous R- and O-specific antisera and the appropriate antigens, including synthetic antigens which represent partial structures of various Proteus LPS.

Animals↗
PubMed1996

Synthesis and biological activities of 26-hydroxy-27-nor-derivatives of 1 alpha, 25-dihydroxyvitamin D3.

Starting with (20S)-20-(p-toluenesulfonyl)oxymethyl-pregna-1, 5-dien-3 alpha-ol (4), we synthesized three vitamin D analogs in 10 to 11 steps: 1 alpha, 26-dihydroxy-27-nor-vitamin D3 (1), its 3-epi analog (2), and 2 beta-methoxy-1 alpha, 26-dihydroxy-27-nor-vitamin D3 (3). We tested the derivatives in the murine mesenchymal cell line C3H1OT1/2. All substances were less potent in inhibition of cell proliferation, inhibition of adipocyte differentiation, and induction of gene activation, and had a lower affinity to the vitamin D receptor than the native vitamin D3 metabolite 1.25(OH)2D3. The affinity of 1 to the vitamin D binding protein was about three times higher than that of 1.25(OH)2D3.

Adipocytes↗
PubMed1996

Differential effects of parathyroid hormone fragments on collagen gene expression in chondrocytes.

The effect of parathyroid hormone (PTH) in vivo after secretion by the parathyroid gland is mediated by bioactive fragments of the molecule. To elucidate their possible role in the regulation of cartilage matrix metabolism, the influence of the amino-terminal (NH2-terminal), the central, and the carboxyl-terminal (COOH-terminal) portion of the PTH on collagen gene expression was studied in a serum free cell culture system of fetal bovine and human chondrocytes. Expression of alpha1 (I), alpha1 (II), alpha1 (III), and alpha1 (X) mRNA was investigated by in situ hybridization and quantified by Northern blot analysis. NH2-terminal and mid-regional fragments containing a core sequence between amino acid residues 28-34 of PTH induced a significant rise in alpha1 (II) mRNA in proliferating chondrocytes. In addition, the COOH-terminal portion (aa 52-84) of the PTH molecule was shown to exert a stimulatory effect on alpha1 (II) and alpha1 (X) mRNA expression in chondrocytes from the hypertrophic zone of bovine epiphyseal cartilage. PTH peptides harboring either the functional domain in the central or COOH-terminal region of PTH can induce cAMP independent Ca2+ signaling in different subsets of chondrocytes as assessed by microfluorometry of Fura-2/AM loaded cells. These results support the hypothesis that different hormonal effects of PTH on cartilage matrix metabolism are exerted by distinct effector domains and depend on the differentiation stage of the target cell.

Animals↗
PubMed1996

Body composition in 5-18-y-old obese children and adolescents before and after weight reduction as assessed by deuterium dilution and bioelectrical impedance analysis.

The aim of the present study was to develop an equation for the prediction of total body water (TBW) from bioelectrical impedance analysis (BIA) in obese children and adolescents before and after weight reduction. In 146 obese subjects with a mean age of 12.7 +/- 3.0 y (5.5-17.8 y), TBW was measured by using deuterium dilution as well as the resistance index (RI; ht2/resistance) using BIA before and after weight loss. Initially, the RI correlated well with measured TBW (r2 = 0.92, P < 0.001). A multiple-regression analysis using forward stepwise selection of the variables RI, sex, age, weight, height, and waist-hip ratio revealed that the equation TBW = 0.35 x RI + 0.27 x age + 0.14 x weight - 0.12 predicts most accurately individual values of TBW before weight loss (adjusted r2 = 0.96, SEE = 1.9 L) with a mean error of predicted TBW of 1.40 +/- 1.38 L. This equation was validated in 1000 random samples (bootstrap-sampling method), giving a mean r2 of 0.95. During the weight-reduction program, which included an energy-restricted diet and an extensive exercise program, the patients lost 7.7 +/- 3.2 kg, leading to a small decrease in TBW of 0.4 +/- 1.5 L. When the developed prediction equation was applied to the data after weight loss, an r2 value of 0.94 between measured and calculated TBW and a mean error of 2.18 +/- 1.89 L was obtained. Validation of the equation in 1000 random samples after weight loss again gave a mean r2 value of 0.95. Individual changes in predicted TBW correlated only weakly with those of measured TBW (r = 0.21, P < 0.05). Thus, individual TBW values before and after weight loss can be predicted by BIA with acceptable accuracy by using the developed equation. However, prediction of small individual changes in TBW during weight loss is not possible by BIA.

Adolescent↗
PubMed1996

Efficacy of a novel hydrogel formulation in human volunteers.

In a two-period crossover study, 20 subjects without an ocular disease received single doses of either a novel timolol hydrogel (T-Gel 0.1%) or aqueous timolol 0.5% in one eye and placebo in the fellow eye. Diurnal variation curves of intraocular pressure of both eyes were obtained for a 24-hour period. Peak effects up to -30% of the baseline were observed. A statistically significant residual effect was still detectable 24 h after application. The timolol gel had the same efficacy in lowering intraocular pressure as the commercially available aqueous timolol solution with a five times higher strength. Equivalence of treatment effects was statistically proved.

Administration, Topical↗
PubMed1996

Structure of recombinant human parathyroid hormone in solution using multidimensional NMR spectroscopy.

The solution structure of human parathyroid hormone, in the form of recombinant prolyl-hPTH(1-84), has been investigated by multidimensional NMR spectroscopy under conditions (aqueous trifluoroethanol) which favour the structured-state of the protein. Spin systems were identified from 3D 1H DQF (double-quantum filtered)-COSY and TOCSY spectra and sequence-specific assignments were from 2D 1H phase-sensitive NOESY spectra. Signal overlap was resolved in a 3D-NOESY-TOCSY spectrum and assignments were confirmed with 2D NOESY-15N-HMQC (heteronuclear multiple-quantum coherence) spectra taken of a sample universally labeled with 15N. A satisfactory set of final structures was calculated from the quantitative NOE data using restrained molecular dynamics and energy minimization calculations. The N-terminus is dominated by three, well defined helices between Ser-3 to Asn-10, Ser-17 to Lys-27 and Asp-30 to Leu-37, while the most significant structural features in the C-terminus are a short, less-well defined helix between Asn-57 to Ser-62 and a series of loose turns. These two terminal units are joined by an unstructured mid-region. The molecule shows a tendency towards tertiary structure, defined by a number of long-range NOEs. A detailed RMS deviation analysis allowed the final refined structures to be classified into a limited ensemble of stable conformations that reflect the inherent flexibility of the hormone in solution.

Amino Acid Sequence↗
PubMed1996

[General stress response in laparoscopic and conventional cholecystectomy].

To objectify perioperative stress response to laparoscopic (LCE) and conventional cholecystectomy (CCE) a prospective, controlled trial was planned and biochemical stress parameters were measured in the blood of patients, who underwent elective surgery because of symptomatic cholecystolithiasis. Patients with acute cholecystitis, pancreatitis, choledocholithiasis or malignant disease were excluded from the study. Values from 40 patients after LCE and from 18 patients after CCE were compared. Both groups had statistically similar patient characteristics and perioperative care. The LCE group showed a significantly lower stress response with respect to interleukin 1 beta, interleukin 6, epinephrine, norepinephrine and glucose.

Adult↗
PubMed1996

Insulin-like growth factors and their binding proteins before and after weight loss and their associations with hormonal and metabolic parameters in obese adolescent girls.

OBJECTIVE: To investigate serum concentrations of insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) in obese adolescent girls before and after weight reduction and to examine their associations with hormonal and metabolic parameters. PATIENTS AND METHODS: 73 girls (age: 15.0 +/- 1.1 y, BMI: 31.1 +/- 3.8 kg/m2) participated in this 6 w intervention study. RESULTS: (1) Compared to 100 normal-weight girls of same age the obese subjects had increased levels of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 and normal levels of IGF-II. (2) After weight loss (8.1 +/- 2.0 kg) IGF-II and IGFBP-2 increased and IGF-I, IGFBP-1, IGFBP-3 and the ratio IGF-I/IGFBP-3 decreased significantly. (3) Correlation analysis revealed that fasting insulin levels of the patients were positively correlated with IGF-I but inversely with IGFBP-1 and IGFBP-2. IGFBP-2 was associated with several metabolic parameters: it showed an inverse correlation with uric acid and triglyceride levels. The ratio IGFBP-2 to IGFBP-1 was inversely correlated with total cholesterol and LDL-cholesterol. In addition, IGFBP-2 was inversely correlated with the waist-to-hip ratio of the girls. CONCLUSIONS: These studies of a homogeneous group of patients give further insight into possible physiological regulations and roles of IGFs and IGFBPs. The main conclusion is that obesity has to be considered for interpretation of serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3. Furthermore, out results suggest that (i) the decrease in IGF-I/IGFBP-3 after weight loss could be partly responsible for the impaired growth velocity seen in obese children during hypocaloric feeding and (ii) low IGFBP-2 and high IGFBP-1 levels are associated with an unfavorable atherogenic risk factor profile.

Adolescent↗