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Biomedical subjects

P Bayer

Publications and source records attributed to P Bayer.

At least 19 recordsLinked to original sources
PubMed2005

Combination of apolipoprotein E2 and lipoprotein lipase heterozygosity causes severe hypertriglyceridemia during pregnancy.

Pregnancy is a physiological condition where plasma triglyceride levels are moderately increased. This results from raised synthesis of very-low-density lipoproteins (VLDL) in response to elevated estrogen levels. The occurrence of marked hypertriglyceridemia (HTG) is rare and may result from combination of heterozygote mutation in the lipoprotein lipase (LPL) gene and apolipoprotein E2 isoform, as reported in this case. This observation illustrates the interaction between genetic and environmental factors, since pregnancy may disclose a silent LPL deficiency. The risk of acute pancreatitis threatens both the mother and fetus lives. Early recognition of severe HTG and appropriate management are essential for a successful pregnancy outcome.

Apolipoprotein E2↗
PubMed2003

[Anaesthesia for caesarean section. Comparison of two general anaesthetic regimens and spinal anaesthesia].

OBJECTIVES: The study was undertaken to compare different anaesthetic techniques for scheduled or urgent caesarean section with respect to maternal circulatory parameters, maternal and fetal endocrine stress response, fetal vitality parameters and further clinical parameters such as recovery and analgesic demand. METHODS: After ethical approval,patients scheduled for general anaesthesia were randomly allocated to the esketamine group ( n=21; induction with 0.5 mg/kg BW esketamine and 1.5 mg/kg BW methohexitone, ventilation until cord cutting with FiO(2) 1.0) and the sevoflurane-group ( n=21; induction with 1.5-2.0 mg/kg BW methohexitone, ventilation until uterotomia with N(2)O/O(2) [FiO(2) 0,5] and endtidal sevoflurane concentrations about 1.0 vol%). After fetal development, all patients received 2.5 microg/kg BW fentanyl and sevoflurane (about 1.0 vol% endtidal) during ventilation with N(2)O/O(2) (FiO(2) 0.33). As a further control, a group with spinal anaesthesia ( n=22; 2.6-3.0 ml isobaric bupivacaine 0.5 %) was investigated. Maternal circulatory and endocrine plasmatic stress parameters were investigated at five time points and fetal parameters once after development.alpha< or =0.05 was considered significant. RESULTS: Biometric data were comparable in all groups. Systolic arterial pressure was higher in the esketamine group ( p=0.008), whereas the heart rate was lower during spinal anaesthesia ( p<0.001). Plasma noradrenaline decreased in all collectives ( p<0.001) and mean group levels of noradrenaline ( p=0.04) and adrenaline ( p<0.001) were lower during spinal anaesthesia. In all groups, antidiuretic hormone (ADH) remained within the normal range or was slightly increased. Adrenocorticotropic hormone (ACTH) initially increased in all groups and decreased in later time course ( p<0.001). Cortisol increased in all groups ( p<0.001) but group levels were lower during spinal anaesthesia ( p<0.001). In the groups with general anaesthesia, no significant differences in recovery times were obvious, and neither recall nor dream reactions were observed. Postoperative hypoxic incidents (psaO(2) <90%) were comparable between the groups. After spinal anaesthesia, first analgesic demand was later than in the controls ( p=0.001), and the total amount of piritramide was lower ( p=0.02). Nausea and vomiting were more frequent during spinal anaesthesia ( p=0.03). All patients were content with their regimen. Apgar scores, pH-values and adrenaline, noradrenaline and cortisol in plasma were comparable in all groups of children (69 children, 5 gemini). The fetal concentration of esketamine (251 ng/ml) was lower than the corresponding maternal values (493 ng/ml). CONCLUSIONS: When compared with methohexitone, sevoflurane and N(2)O for caesarean section, initial total intravenous anaesthesia with esketamine and methohexitone mediated specific antinociception without negative maternal or fetal effects and not taking invasion kinetics or elimination between uterotomia and cord cutting into consideration. Avoidance of N(2)O allows optimal oxygenation of the fetomaternal unit. Stress protection and hemodynamic responses were well balanced, and intraoperative recall or negative dream reactions were lacking. Superior postoperative pain protection was advantageous after spinal anaesthesia, but in contrast, nausea and vomiting were more frequent in this group.

Adult↗
PubMed2003

Reverse cholesterol transport, high density lipoproteins and HDL cholesterol: recent data.

Unlike LDL cholesterol, which is a major cardiovascular risk factor, HDL cholesterol plays an important anti-atherogenic role through reverse cholesterol transport from peripheral cells to the liver. Some recent biochemical and epidemiological data shed light on this key function. In the hereditary Tangier disease with disseminated lipid storage, the main biochemical feature is a dramatically low level of HDL cholesterol. Different mutations in the ATP-binding cassette transporter A1 (ABCA1) gene have been recently described, which interfere with cellular cholesterol efflux. This results in low HDL plasma level, and defective reverse cholesterol transport to the liver. Moreover, selective hepatic uptake of HDL cholesteryl esters by SR-B1, a class B scavenger receptor, also plays a key role. In the follow-up of the PROCAM Study, the relative risk of coronary events is high in a cluster of patients with increased total cholesterol/HDL-cholesterol ratio. In the prospective secondary prevention VA-HIT study, the relative risk of coronary events in patients with low HDL cholesterol levels is decreased of 22% with a treatment by gemfibrozil. If the present available range of drugs targeted at increasing HDL cholesterol levels is rather narrow, future therapies will be encouraging, especially with agonists of PPARs.

Animals↗
PubMed2001

Increased backbone flexibility in threonine45-phosphorylated hirudin upon pH change.

Protein phosphorylation on serine/threonine side chains represents a major regulatory event in the posttranslational control of protein functionality, where it is thought to operate at the level of structural changes in the polypeptide chain. However, key questions about molecular aspects of phosphate ester induced conformational alterations remain open. Among these concerns are the radius of action of the phosphate ester group, its effective ionic state, and its interplay with distinct bonds of the polypeptide chain. Primarily to define short-range effects upon threonine phosphorylation, the native 65 amino acid protein hirudin, conformationally restrained by a proline flanking the pThr(45) site and three intramolecular disulfide bonds, was structurally characterized in both the phosphorylated and the unphosphorylated state in solution. Circular dichroism and hydrogen exchange experiments (MALDI-TOF) showed that structural changes were caused by Thr(45)-Pro(46) phosphorylation only when the phosphate ester group was in its dianionic state. The spatial arrangement of the amino acids, monitored by 1H NMR spectroscopy, appears to be affected within a radius of about 10 A around the pThr(45)-OgammaH, with phosphorylation resulting in a loss of structure and increased flexibility within a segment of at least seven amino acid residues. Thus, the transition from the monoanionic to the dianionic phosphate group over the pH range 5.2-8.5 represents a general phosphorylation-dependent conformational switch operating at physiological pH values.

Amino Acid Sequence↗
PubMed2001

Serum bone sialoprotein as a marker of tumour burden and neoplastic bone involvement and as a prognostic factor in multiple myeloma.

To test the potential of immunoreactive BSP, a non-collagenous bone matrix component, as a clinical guide in patients with plasma cell dyscrasias, serum BSP concentrations were measured in 62 patients with newly diagnosed multiple myeloma (MM) followed over a period of 4 years, in 46 patients with monoclonal gammopathy of undetermined significance (MGUS), in 71 patients with untreated benign vertebral osteoporosis (OPO), and in 139 healthy adults. Results were compared with clinical and laboratory data, including serum osteocalcin (OC), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone turnover. In MM, serum BSP, and urinary PYD and DPD were higher than in healthy controls and in MGUS or OPO (P< 0.001). BSP levels correlated with the bone marrow plasma cell content (r = 0.40, P< 0.001), and serum beta2-microglobulin (r = 0.31, P < 0.01). The differentiation of MM from healthy controls and from MGUS or OPO was highest for BSP. After chemotherapy, BSP reflected the response to treatment and correlated with the change in monoclonal protein (r = 0.55, P< 0.001). MM patients with normal baseline BSP levels survived longer than patients with initially elevated BSP values (P< 0.001, log rank test). Only serum monoclonal protein and BSP were independent predictors of survival. We conclude that in MM, BSP levels are associated with skeletal involvement and tumour cell burden. The quantification of serum BSP may be a non-invasive method for the diagnosis and follow-up, and may improve the prognostic value of conventional staging in MM.

Adult↗
PubMed2001

Structure prediction of protein complexes by an NMR-based protein docking algorithm.

Protein docking algorithms can be used to study the driving forces and reaction mechanisms of docking processes. They are also able to speed up the lengthy process of experimental structure elucidation of protein complexes by proposing potential structures. In this paper, we are discussing a variant of the protein-protein docking problem, where the input consists of the tertiary structures of proteins A and B plus an unassigned one-dimensional 1H-NMR spectrum of the complex AB. We present a new scoring function for evaluating and ranking potential complex structures produced by a docking algorithm. The scoring function computes a 'theoretical' 1H-NMR spectrum for each tentative complex structure and subtracts the calculated spectrum from the experimental one. The absolute areas of the difference spectra are then used to rank the potential complex structures. In contrast to formerly published approaches (e.g. [Morelli et al. (2000) Biochemistry, 39, 2530-2537]) we do not use distance constraints (intermolecular NOE constraints). We have tested the approach with four protein complexes whose three-dimensional structures are stored in the PDB data bank (Bernstein et al., 1977) and whose 1H-NMR shift assignments are available from the BMRB database. The best result was obtained for an example, where all standard scoring functions failed completely. Here, our new scoring function achieved an almost perfect separation between good approximations of the true complex structure and false positives.

Algorithms↗
PubMed2001

[Clinical, epidemiologic, and biochemical findings on the reverse cholesterol transport (cholesterol-HDL)].

Contrary to high plasma levels of low-density lipoprotein cholesterol (LDL-C), closely linked with coronary heart disease (CHD), high-density lipoprotein cholesterol (HDL-C) play an antiatherogenic role, through the reverse cholesterol transport from peripheral cells to the liver. New data in the pathophysiology of a rare genetic dyslipidemia, the Tangier disease, characterized by very low HDL-C levels and premature CHD, have shed light on this complex mechanism. In this disease, cholesterol efflux from peripheral cells is dramatically reduced, and this has been recently shown to be caused by mutations in an ATP-binding cassette transporter, which normally stimulates cholesterol efflux. Reverse cholesterol transport is therefore greatly decreased. Epidemiological data have revealed that 15% to 30% of coronary patients have low HDL-C levels. However, this is often combined with high triglycerides levels, and this association is frequently found in diabetic patients, especially prone to CHD. HDL-C has been repeatedly shown to be an inverse predictor of CHD. This has been enhanced by recent interventional studies (Veterans Affairs HDL Intervention Study, Bezafibrate Infarction Prevention Study) which have provided strong evidence that pharmacological increase of HDL-C, in combination with decrease in triglycerides level, reduces incidence of CHD.

Cholesterol, HDL↗
PubMed2000

NMR solution structure of hPar14 reveals similarity to the peptidyl prolyl cis/trans isomerase domain of the mitotic regulator hPin1 but indicates a different functionality of the protein.

The 131-amino acid residue parvulin-like human peptidyl-prolyl cis/trans isomerase (PPIase) hPar14 was shown to exhibit sequence similarity to the regulator enzyme for cell cycle transitions human hPin1, but specificity for catalyzing pSer(Thr)-Pro cis/trans isomerizations was lacking. To determine the solution structure of hPar14 the (1)H, (13)C, and (15)N chemical shifts of this protein have been assigned using heteronuclear two and three-dimensional NMR experiments on unlabeled and uniformly (15)N/(13)C-labeled recombinant protein isolated from Escherichia coli cells that overexpress the protein. The chemical shift assignments were used to interpret the NOE data, which resulted in a total of 1042 NOE restraints. The NOE restraints were used along with 71 dihedral angle restraints and 38 hydrogen bonding restraints to produce 50 low-energy structures. The hPar14 folds into a betaalpha(3)betaalphabeta(2) structure, and contains an unstructured 35-amino acid basic tail N-terminal to the catalytic core that replaces the WW domain of hPin1 homologs. The three-dimensional structures of hPar14 and the PPIase domain of human hPin1 reveal a high degree of conservation. The root-mean-square deviations of the mean atomic coordinates of the heavy atoms of the backbone between residues 38 to 45, 50 to 58, 64 to 70, 81 to 86, 115 to 119 and 122 to 128 of hPar14 were 0.81(+/-0.07) A. The hPar14 model structure provides insight into how this class of PPIases may select preferential secondary catalytic sites, and also allows identification of a putative DNA-binding motif in parvulin-like PPIases.

Amino Acid Sequence↗
PubMed2000

Solution structures of human parathyroid hormone fragments hPTH(1-34) and hPTH(1-39) and bovine parathyroid hormone fragment bPTH(1-37).

Parathyroid hormone (PTH) is involved in regulation of the calcium level in blood and has an influence on bone metabolism, thus playing a role in osteoporosis therapy. In this study, the structures of the human PTH fragments (1-34) and (1-39) as well as bovine PTH(1-37) in aqueous buffer solution under near physiological conditions were determined using two-dimensional nuclear magnetic resonance spectroscopy. The overall structure of the first 34 amino acids of these three peptides is virtually identical, exhibiting a short NH(2)-terminal and a longer COOH-terminal helix as well as a defined loop region from His14 to Ser17, stabilized by hydrophobic interactions. bPTH(1-37), which has a higher biological activity, shows a better-defined NH(2)-terminal part. In contrast to NH(2)-terminal truncations, which cause destabilization of helical structure, neither COOH-terminal truncation nor elongation significantly influences the secondary structure. Furthermore, we investigated the structure of hPTH(1-34) in 20% trifluoroethanol solution. In addition to its helix-stabilizing effect, trifluorethanol causes the loss of tertiary hydrophobic interactions.

Amino Acid Sequence↗
PubMed2000

Comparison of a new method for the direct and simultaneous assessment of LDL- and HDL-cholesterol with ultracentrifugation and established methods.

BACKGROUND: Automated electrophoresis combined with enzymatic cholesterol staining might improve routine assessment of LDL- and HDL-cholesterol (LDLC and HDLC), as an alternative to the Friedewald equation and precipitation. A new method (Hydrasys; SEBIA) that adapts the cholesterol esterase/cholesterol oxidase reaction within urea-free gels was evaluated. METHODS: Fresh sera from 725 subjects (512 dyslipidemics) were analyzed by electrophoresis, in parallel with sequential ultracentrifugation, beta-quantification, calculation, and precipitation. RESULTS: Electrophoresis was linear up to 4 g/L cholesterol, with a detection limit of 0.042 g/L cholesterol/band. Within-run, between-run, between-batch, and between-operator imprecision (CVs) were 1.6%, 2.0%, 1.5%, and 2.7% for LDLC, and 3.9%, 4.3%, 5.5%, and 4.9% for HDLC, and remained unchanged up to 6.3 g/L plasma triglycerides (TGs). Precision decreased with very low HDLC (<0.25 g/L). Serum storage for 3-7 days at +4 or -80 degrees C did not interfere significantly with the assay. Agreement with beta-quantification was stable for LDLC up to 5.07 g/L (r = 0.94), even at TG concentrations >4 g/L (r = 0.91). Bias (2.88% +/- 12%) and total error (7.84%) were unchanged at TG concentrations up to 18.5 g/L. Electrophoresis predicted National Cholesterol Education Program cut-points with <0.04 g/L error, exactly and appropriately classified 79% and 96% of the subjects, and divided by 2.4 (all subjects) and 5.8 (TGs >1.5 g/L) the percentage of subjects underestimated by calculation. One-half of the patients with TGs >4 g/L had LDLC >1.30 g/L. For HDLC, correlation was better with precipitation (r = 0.87) than ultracentrifugation (r = 0.76). Error (-0.10% +/- 26%) increased when HDLC decreased (<0.35 g/L). Direct assessment of the LDLC/HDLC ratio detected 45% more high-risk subjects than the calculation/precipitation combination. CONCLUSIONS: Electrophoresis provides reliable quantification of LDLC, improving precision, accuracy, and concordance over calculation, particularly with increasing plasma TGs. Implementation of methods to detect low cholesterol concentrations could extend the applications for HDLC assessment.

Adolescent↗
PubMed2000

[Analysis of the needs for diagnosis and therapy of tobacco dependence in Austria].

In Austria we find 2.3 Mio. tobacco users (29% of the population). 1.3 Mio. are dissonant smokers, they want to stop (18%) or reduce (37%) tobacco consumption. The assumption that 10% of dissonant smokers (130,000 tobacco users) need a diagnosis and therapy leads to a bottleneck: 130,000 patients versus 20 therapists. Demanded consequences of this disproportion are training for health-care workers, implementation of diagnosis and treatment, financing and refunding. Diagnosis and therapy of tobacco dependence should be offered in highly specialised organisations such as the prototypical Nicotine Institute in Vienna, in hospitals and in primary health care.

Adolescent↗
PubMed1999

Effects of low density and high density lipoproteins isolated from non-insulin dependent diabetic patients on prostaglandin secretion by mouse macrophage cell line P388D1.

We have previously shown that low-density (LDL) and high-density (HDL) lipoprotein from healthy subjects can promote in vitro prostaglandin (PG) release by murine macrophages. In this pilot study, we have measured PG production induced by lipoproteins of six diabetic patients with poor metabolic control, compared to five healthy controls. Plasma lipoprotein levels were similar in both groups. Lipoprotein fractions were purified by sequential ultracentrifugation. After lipoprotein incubation with cells, supernatants were extracted and PG quantified by HPLC. In presence of LDL, in control subjects, there was an increase in total PG production, mainly due to thromboxane B2 (TxB2). In diabetic patients, the secretion pattern was similar. In presence of HDL, in control subjects, total PG secretion was also increased, but it was balanced between TxB2 and prostacyclin. In diabetic patients, at low HDL concentration (10 mg/l) the secretion was mainly due to TxB2, while at higher HDL concentrations (100 mg/l). the secretion was balanced between TxB2 and prostacyclin. Comparison of means of areas under curve for the two groups studied showed that LDL increased all PG secretion in diabetic patients compared to controls (P < 0.05 for PGF2alpha), while HDL increased all PG secretion in controls compared to diabetic patients, except PGF2alpha. Our work suggests a key role of LDL in TxB2 secretion in diabetic patients, which is a major proaggregant and vasoconstrictive agent. There was also an increased secretion of all PG in diabetic patients.

Animals↗
PubMed1999

Refinement of the structure of protein-RNA complexes by residual dipolar coupling analysis.

The main limitation in NMR-determined structures of nucleic acids and their complexes with proteins derives from the elongated, non-globular nature of physiologically important DNA and RNA molecules. Since it is generally not possible to obtain long-range distance constraints between distinct regions of the structure, long-range properties such as bending or kinking at sites of protein recognition cannot be determined accurately nor precisely. Here we show that use of residual dipolar couplings in the refinement of the structure of a protein-RNA complex improves the definition of the long-range properties of the RNA. These features are often an important aspect of molecular recognition and biological function; therefore, their improved definition is of significant value in RNA structural biology.

Cloning, Molecular↗