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Biomedical subjects

W Braun

Publications and source records attributed to W Braun.

At least 145 records · Page 8Linked to original sources
PubMed1988

1H nuclear-magnetic-resonance studies of the three-dimensional structure of the cardiotoxin CTXIIb from Naja mossambica mossambica in aqueous solution and comparison with the crystal structures of homologous toxins.

Using the previously reported sequence-specific 1H-NMR assignments, structural constraints for the cardiotoxin CTXIIb from Naja mossambica mossambica were collected. These include distance constraints from nuclear Overhauser enhancement measurements both in the laboratory and in the rotating frame, dihedral angle constraints derived from spin-spin coupling constants, and constraints from hydrogen bonds and disulfide bridges. Structure calculations with the distance geometry program DISMAN confirmed the presence of the previously identified antiparallel beta-sheets formed by residues 1-5 and 10-14, and by 20-27, 35-39 and 49-55, and established the nature of the connections between the individual beta-strands. These include a right-handed crossover between the two peripheral strands in the triple-stranded beta-sheet, and a type I tight turn immediately preceding the beta-strand 49-55. The spatial arrangement of the polypeptide backbone in the solution structure of CTXIIb is closely similar to that in the crystal structure of the homologous cardiotoxin VII4 from the same species. In an Appendix the origin of the large pH dependence of two amide proton chemical shifts in CTXIIb is explained.

Animals↗
PubMed1988

Rapid (24h) neutralization assay for the detection of antibodies to human cytomegalovirus using a monoclonal antibody to an HCMV early nuclear protein.

Neutralizing antibodies to human cytomegalovirus (HCMV) may play an important role during the course of an HCMV infection but yet detection with conventional methods remains difficult and time consuming. A new neutralization test has been developed basically corresponding to the known microtitre technique. A monoclonal antibody to an HCMV early nuclear protein is utilized to detect HCMV (AD169) infected fibroblasts by biotin/streptavidin-enhanced immunoperoxidase staining. The test procedure was thereby confined to only 24 h. Evaluation of the new neutralization test (24h-NT) was done in comparison to the conventional method (NT). Preselected serum samples (n = 217), of which n = 169 were HCMV-seropositive in ELISA (reciprocal titre greater than or equal to 40), were tested for neutralizing antibodies (NAbs) to HCMV. ELISA titres were measured by a commercially available kit (Behring, F.R.G.). NAbs could be detected in 107 sera by 24h-NT (reciprocal titre greater than or equal to 5) and in 110 sera determined by NT (reciprocal titre greater than or equal to 5). Those sera were exclusively positive in ELISA. ELISA negative sera (n = 48; reciprocal titre less than 40) yielded no detectable neutralizing titres. This specific and rapid test should facilitate HCMV-NAbs detection for a wide variety of applications including routine virology diagnostics, evaluation of HCMV hyperimmunoglobulins and medical research.

Antibodies, Monoclonal↗
PubMed1988

[Doppler flow studies (duplex sonography). Differential diagnostic assessment of intrauterine growth retardation and uncertain gestational age].

In 116 patients referred to Heidelberg University Gynecological Clinic because of a discrepancy between calculated and biologically determined gestational age, the suitability of the Doppler Flow examination method (duplex method) for resolving this question was studied. The signals from the fetal descending aorta, the umbilical artery, and from maternal placental vessels were used. An A/B ratio of over 7 in the fetal aorta, an A/B ratio of over 4 in the umbilical artery, and detection of an early diastolic incisure in the so-called arcuate arteries were considered pathologic. The relatively high accuracy of this examination method is expressed by its sensitivity (91%) and likewise high specificity (86%) for this diagnostic question. In view of the predictive value of 88% thus determined, reliable differential diagnostic distinction between intrauterine growth retardation and uncertainty regarding term appears possible. Doppler sonographic examination can be performed without causing any serious discomfort to the patient and within a short period of time. While the number of false-positive results in this study was in any case relatively low (11%), an in-depth analysis showed that an "acute placental insufficiency" had occurred in the peripartum in more than one-half of the cases.

Aorta, Thoracic↗
PubMed1988

Metabolic differences between AGA- and SGA-infants of very low birthweight. I. Relationship to intrauterine growth retardation.

Metabolic response to human milk feeding was studied in 12 appropriate (AGA) and 12 small for gestational age (SGA) infants of very low birthweight (VLBW) on the eighth day of life. Protein intake ranged from 1.98 to 2.47 g/kg/day and caloric intake from 94 to 126 kcal/kg/day with no significant differences between the groups. Alpha-amino-nitrogen, the total bile acid concentration in serum and total- as well as alpha-amino-nitrogen excretion in the urine were estimated. The alpha-amino-nitrogen and the total bile acid concentration in serum increased with increasing degree of intrauterine growth retardation. Also renal total- and alpha-amino-nitrogen excretion increased significantly in relation to the degree of intrauterine growth retardation. Thus, despite a relatively low protein intake in severely growth retarded VLBW-infants, metabolic changes could be found similar to those observed in AGA-infants on high protein intakes. The data suggest that during the first weeks of postnatal life VLBW-infants with intrauterine growth retardation have a decreased capacity to utilize or to metabolize protein when compared to AGA-infants with comparable birthweights. These metabolic differences have to be considered in the nutritional management of VLBW-infants.

Dietary Proteins↗
PubMed1988

[Listeriosis of the central nervous system in children beyond the neonatal period].

Observations on three children with neurolisteriosis (one case of meningitis, two cases of meningoencephalitis, each Serovar 4 b), show that even after the neonatal period, listeriosis must not be ignored in the process of diagnosis and therapy. It is the bacteriological examination of the cerebrospinal fluid, together with the blood culture, and not clinical symptoms and serology that guarantee a timely diagnosis and therapy (ampicillin and gentamicin).

Anti-Bacterial Agents↗
PubMed1988

Phagocytosis of microspheric hydrophile particles (MSHP) by peripheral blood glass-adherent phagocytes of newborns.

The phagocytic activity of glass-adherent peripheral blood leukocytes of 58 healthy term newborns and 19 adult donors was examined using a micromethod employing a new type of synthetic hydrophilic particles based on 2-hydroxyethylmethacrylate. It was found that both the proportion of actively phagocytosing cells and the number of engulfed particles within the cells was significantly lower in neonates as compared with adults.

Cell Adhesion↗
PubMed1987

Protein structures in solution by nuclear magnetic resonance and distance geometry. The polypeptide fold of the basic pancreatic trypsin inhibitor determined using two different algorithms, DISGEO and DISMAN.

A set of conformational restraints derived from nuclear magnetic resonance (n.m.r.) measurements on solutions of the basic pancreatic trypsin inhibitor (BPTI) was used as input for distance geometry calculations with the programs DISGEO and DISMAN. Five structures obtained with each of these algorithms were systematically compared among themselves and with the crystal structure of BPTI. It is clear that the protein architecture observed in single crystals of BPTI is largely preserved in aqueous solution, with local structural differences mainly confined to the protein surface. The results confirm that protein conformations determined in solution by combined use of n.m.r. and distance geometry are a consequence of the experimental data and do not depend significantly on the algorithm used for the structure determination. The data obtained further provide an illustration that long intramolecular distances in proteins, which are comparable with the radius of gyration, are defined with high precision by relatively imprecise nuclear Overhauser enhancement measurements of a large number of much shorter distances.

Algorithms↗
PubMed1987

Improvements of metabolic imbalances after enteral sodium bicarbonate supplementation in infants of very low birth weight (VLBW).

One of the main points of clinical care is the catch-up growth of VLBW infants especially those of small gestational age (SGA). The required high amounts of protein are often not tolerated [1]. Metabolic imbalances due to immaturities of protein metabolism are described [2, 3] also in infants SGA feeding amounts of proteins comparable to mature newborns [4]. Remarkable signs of overloading by proteins are the elevation of amino acid and the bile acid concentrations in the serum [3, 5, 6]. In some of those cases [7] late metabolic acidosis (LMA) is to be seen. There is evidence in the literature that sodium bicarbonate influences nitrogen [8] and ionic balances [9] in newborn animals without any signs of acidosis, besides its simple buffer function. The aim of this study was to control changes of metabolic imbalances after bicarbonate supplementation before development of acidosis in predisposed infants. Therefore we determined parameters, which were significantly changed with LMA [6] during two feeding schedules: firstly, during bolus supplementation in infants feeding (2.0 +/- 0.4) g/kg BW.d protein and secondly during chronic supplementation of bicarbonate to (3.0 +/- 0.4) g/kg BW.d protein. In relation to the improvement of the nitrogen balance in growing lambs [7] we supposed comparable effect of bicarbonate on metabolic imbalances caused by protein overloading.

Bicarbonates↗
PubMed1987

Spatial structure of rabbit liver metallothionein-2 in solution by NMR.

Sequence-specific assignments of the proton spin systems of (Cd7) rabbit liver metallothionein-2 were obtained with homonuclear two-dimensional nuclear magnetic resonance techniques. On the basis of the NMR data the amino acid sequence had to be modified in six positions, and it was found that the protein consists of 62 rather than 61 residues. Through-bond connectivities between the metals and sequentially assigned cysteine residues were obtained with two-dimensional heteronuclear 1H-113Cd correlated spectroscopy. This information, and distance constraints obtained from nuclear Overhauser enhancement spectra were used as input for distance geometry calculations of the spatial polypeptide fold. The polypeptide chain forms two domains which enclose a three-metal cluster and a four-metal cluster, respectively. The metal coordination within the clusters is markedly different from that of (Cd5, Zn2)-MT-2 from rat liver as determined by X-ray crystallography (Furey, et al., 1986) i.e. in the two structures different metal-cysteine combinations prevail for 5 of the 12 connectivities in the three-metal cluster and for 14 of the 16 connectivities in the four-metal cluster.

Amino Acid Sequence↗
PubMed1987

Distance geometry and related methods for protein structure determination from NMR data.

Computational tools have been developed in the last few years, to allow a direct determination of protein structures from NMR data. Numerical calculations with simulated and experimental NMR constraints for distances and torsional angles show that data sets available with present NMR techniques carry enough information to determine reliably the global fold of a small protein. The maximum size of a protein for which the direct method can be applied is not limited by the computational tools but rather by the resolution of the two-dimensional spectra. A general estimate of the maximum size would be a molecular weight of about 10,000 (Markley et al. 1984), but parts of larger proteins might be accessible with the method. Effort for improvement of the NMR structures should be concentrated more on the local conformation rather than the global features. The r.m.s. D values for variations of the polypeptide backbone fold are on the order of 1.5-2 A for several of the studied proteins, indicating that the global structure is well determined by the present NMR data and their interpretation. The local structures are sometimes rather poor, with standard deviations for the backbone torsion angles of about 50 degrees. Possible improvements would be stereospecific resonance assignments of individual methylene protons and individual assignments of the methyl groups of the branched side-chains. Accurate estimates of the short-range NOE distance constraints by calibrating the distance constraints, including segmental flexibility effects, and combined use of distance geometry, energy minimization and molecular dynamics calculations, are further tools for improving the structures.

Magnetic Resonance Spectroscopy↗
PubMed1987

Cholestasis in late metabolic acidosis of prematurely born infants.

Serum concentrations of bile acids and tyrosine were determined in 14 premature infants with late metabolic acidosis and in 13 comparable controls without acidosis (protein intake 2 g/kg X d). At the same time the bile acids and the catalytic activity concentrations of lipase and trypsin were estimated in the duodenal juice. The daily faecal excretion and the percentage of fat eliminated were measured. In 8 patients with late metabolic acidosis the duodenal studies were repeated one week after late metabolic acidosis. Infants with late metabolic acidosis showed significantly higher concentrations of bile acids and tyrosine in the serum than the controls (p less than 0.0005). In the duodenal juice the activities of lipase and trypsin and the concentration of bile acids--especially of dihydroxy bile acids--were decreased (p less than 0.001). The faecal excretion during late metabolic acidosis was significantly increased, with high percentage of fat. Eight days after late metabolic acidosis all duodenal parameters equalled the range of the control group. The relations between acidosis, cholestasis, and amino acid transport to the liver are discussed.

Acidosis↗