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Biomedical subjects

W Braun

Publications and source records attributed to W Braun.

At least 37 records · Page 2Linked to original sources
PubMed2000

Homology modeling and characterization of IgE binding epitopes of mountain cedar allergen Jun a 3.

The Jun a 3 protein from mountain cedar (Juniperus ashei) pollen, a member of group 5 of the family of plant pathogenesis-related proteins (PR-proteins), reacts with serum IgE from patients with cedar hypersensitivity. We used the crystal structures of two other proteins of this group, thaumatin and an antifungal protein from tobacco, both approximately 50% identical in sequence to Jun a 3, as templates to build homology models for the allergen. The in-house programs EXDIS and FANTOM were used to extract distance and dihedral angle constraints from the Protein Data Bank files and determine energy-minimized structures. The mean backbone deviations for the energy-refined model structures from either of the templates is <1 A, their conformational energies are low, and their stereochemical properties (determined with PROCHECK) are acceptable. The circular dichroism spectrum of Jun a 3 is consistent with the postulated beta-sheet core. Tryptic fragments of Jun a 3 that reacted with IgE from allergic patients all mapped to one helical/loop surface of the models. The Jun a 3 models have features common to aerosol allergens from completely different protein families, suggesting that tertiary structural elements may mediate the triggering of an allergic response.

Allergens↗
PubMed2000

Eye irritation responses in rabbit and man after single applications of equal volumes of undiluted model liquid detergent products.

A criticism of the use of the rabbit low-volume eye test to determine eye irritation hazard for man is the lack of comparative data in man and rabbit with undiluted products. To address this, such a study has been performed in man and rabbit using undiluted model liquid detergents. The hypothesis tested was that if, under identical test conditions, the effects in the rabbit were the same or greater than the response in man, then it is valid to use the low-volume eye test to assess eye irritation hazard for man. The studies were carried out using 29 human volunteers and 12 rabbits. The effects in the rabbit were unequivocally greater than the effects observed in man, but clearly less than the expected response from these types of product in the Draize test. The results from this study confirm the sensitivity of the rabbit as a test species, and support the use of the low-volume eye test to assess eye irritation hazard for man. Any in vitro/ex vivo alternative to assess eye irritation should be developed against the rabbit low-volume eye test or human data where available.

Animals↗
PubMed2000

Triple therapy for Helicobacter pylori eradication: a comparison of pantoprazole once versus twice daily.

BACKGROUND: Proton pump inhibitor-based triple therapy is recommended as treatment for Helicobacter pylori eradication. The proton pump inhibitor may be given once or twice daily. However, little information is available on how these two treatment strategies compare. METHODS: H. pylori-positive patients (two positive test results) with endoscopy-proven healed duodenal ulcer or non-ulcer dyspesia were randomly allocated to 1 week of double-blind treatment with pantoprazole 40 mg once or twice daily, plus clarithromycin 250 mg and metronidazole 400 mg twice daily. Eradication was defined as a negative 13C-urea breath test (13C-UBT) and histology, 4-5 weeks post-treatment. The follow-up phase comprised 12 months off therapy, with 13C-UBT at 6 and 12 months. RESULTS: Two hundred and four patients received treatment: pantoprazole once daily (x1), n=104; twice daily (x2), n=100. Eradication rates were 84% in both the pantoprazole x1 and pantoprazole x2 groups by modified intention-to-treat analysis and 89% and 87%, respectively, by per protocol analysis. Metronidazole resistance was found in 44% of pre-treatment cultures of H. pylori. Eradication rates were similar in susceptible (72%) and resistant (75%) strains. During follow-up, recrudescence of infection occurred in 3/118 patients. CONCLUSION: When using pantoprazole plus clarithromycin and metronidazole, the proton pump inhibitor can be used once daily without loss of efficacy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

MASIA: recognition of common patterns and properties in multiple aligned protein sequences.

SUMMARY: MASIA is a software tool for pattern recognition in multiple aligned protein sequences. MASIA converts a sequence to a properties matrix that can be scanned in both vertical and horizontal steps. Consistent patterns are recognized based on the statistical significance of their occurrence. Preset macros can be altered on-line to seek any combination of amino acid properties or sequence characteristics. MASIA output can be used directly by our programs to predict the 3D structure of proteins. AVAILABILITY: Access MASIA at http://www.scsb.utmb.edu/masia/ma sia.html.

Sequence Alignment↗
PubMed2000

Phase-space structure of a thermoreceptor.

We analyze the phase-space structure of a model for thermoreceptors in fish and mammals. As a function of the temperature we identify a period doubling scenario at low temperatures, a regime where an unstable stationary fixed point collides with the attractor and blocks the thermoreceptor, and a transition from period n+1 to period n as the temperature is further increased. The period reduction phenomenon is due to an autoresonance between fast and slow ion channels and shows the features typical for mode locking.

Action Potentials↗
PubMed1999

Automated 2D NOESY assignment and structure calculation of Crambin(S22/I25) with the self-correcting distance geometry based NOAH/DIAMOD programs.

The NOAH/DIAMOD program suite was used to automatically assign an experimental 2D NOESY spectrum of the 46 residue protein crambin(S22/I25), using feedback filtering and self-correcting distance geometry (SECODG). Automatically picked NOESY cross peaks were combined with 157 manually assigned peaks to start NOAH/DIAMOD calculations. At each cycle, DIAMOD was used to calculate an ensemble of 40 structures from these NOE distance constraints and random starting structures. The 10 structures with smallest target function values were analyzed by the structure-based filter, NOAH, and a new set of possible assignments was automatically generated based on chemical shifts and distance constraints violations. After 60 iterations and final energy minimization, the 10 structures with smallest target functions converged to 1.48 A for backbone atoms. Despite several missing chemical shifts, 426 of 613 NOE peaks were unambiguously assigned; 59 peaks were ambiguously assigned. The remaining 128 peaks picked automatically by FELIX are probably primarily noise peaks, with a few real peaks that were not assigned by NOAH due to the incomplete proton chemical shifts list.

Amino Acids↗
PubMed1999

[Dislocation of the elbow joint--therapy and treatment outcome].

At our hospital, closed dislocations of the elbow without neurovascular or osseous lesion are treated conservatively after successful reduction in the absence of a tendency to redislocation. Indications for surgery are irreducible dislocations and those with a tendency to redislocation as well as open soft tissue injuries, neurovascular and osseous concomitant injuries. During a period of 10 years 113 patients were treated according to this strategy. Of these patients, 46 had simple dislocations of the elbow and 67 suffered from dislocations with osseous lesions. In 95 patients follow-ups could be performed after a mean period of 55 months. In more than 75% of cases good or excellent functional results were documented; unfavourable results were seen only in patients with osseous lesions. Nearly all of the patients had a stable elbow joint at the end of therapy.

Adolescent↗
PubMed1999

[Treatment of acromioclavicular joint separations. Central Kirschner- wire and PDS-augmentation].

Beside the basic question wether a separation of the acromioclavicular joint should be treated operatively or not, the method of operation is discussed in particular. For that reason we investigated our own method of a temporary transfixation of the joint by a centrally drilled K-wire combined with a PDS-augmentation of the coracoclavicular and a suture of the acromioclavicular ligament. Follow up examinations were possible in 57 out of 82 patients which were operated during 5 years. Patients subjective rating and objective follow up and sonographically evaluated joint conditions were scored together. Looking for the range of motion of the shoulder only 5.5% of the patients had a reduction of more than 20 degrees. Out of 12 complications in particular three infections only resulted satisfying by influencing the subjective rating negatively. In 28.1% of patients no durable anatomic reconstruction of the joint was achieved. Score achieved by these patients was significantly lower compared to those with a lasting anatomic reconstruction of the acromioclavicular joint. In conclusion the results confirm our operative regime for separations of the acromioclavicular joint. In literature survey the here described method of operation belongs to the better ones without showing a clear advantage. Nevertheless the method should be modified to decrease the rate of subluxations.

Acromioclavicular Joint↗
PubMed1999

Sequence specificity, statistical potentials, and three-dimensional structure prediction with self-correcting distance geometry calculations of beta-sheet formation in proteins.

A statistical analysis of a representative data set of 169 known protein structures was used to analyze the specificity of residue interactions between spatial neighboring strands in beta-sheets. Pairwise potentials were derived from the frequency of residue pairs in nearest contact, second nearest and third nearest contacts across neighboring beta-strands compared to the expected frequency of residue pairs in a random model. A pseudo-energy function based on these statistical pairwise potentials recognized native beta-sheets among possible alternative pairings. The native pairing was found within the three lowest energies in 73% of the cases in the training data set and in 63% of beta-sheets in a test data set of 67 proteins, which were not part of the training set. The energy function was also used to detect tripeptides, which occur frequently in beta-sheets of native proteins. The majority of native partners of tripeptides were distributed in a low energy range. Self-correcting distance geometry (SECODG) calculations using distance constraints sets derived from possible low energy pairing of beta-strands uniquely identified the native pairing of the beta-sheet in pancreatic trypsin inhibitor (BPTI). These results will be useful for predicting the structure of proteins from their amino acid sequence as well as for the design of proteins containing beta-sheets.

Amino Acids↗
PubMed1998

Allostery in rabbit pyruvate kinase: development of a strategy to elucidate the mechanism.

Isozymes of pyruvate kinase (PK) expressed in rabbit muscle and kidney show different allosteric kinetics. The only amino acid changes in the two isozymes, originating from alternative RNA splicing, occur at a stretch of 55 amino acids in the C domain near the subunit interface. The self-correcting distance geometry (SECODG) program DIAMOD was used to calculate a homology model of these interfacial contacts in the four helix bundle of the kidney PK dimer, based on the X-ray structure of the tetrameric rabbit muscle PK [Larsen et al. (1994) Biochemistry 33, 6301-6309]. Energy refinement with the program FANTOM, using the ECEPP/2 force field to assess packing and electrostatic interactions between the two subunits, yielded two groups of energetically favorable conformations. The primary difference in the two groups is the loop conformation of residue Pro 402, which is serine in muscle PK. In one loop conformation, the conserved Lys 421 can form an intersubunit salt bridge as observed in the muscle PK crystal structure. The other loop conformation favors an alternative intrasubunit salt bridge, similar to that found in the Escherichia coli PK structure, which was not used for generating the model. The intersubunit salt bridge leads to an intersubunit hydrogen bonding between Lys 421 of one subunit and Tyr 443 of the other. To provide direct evidence on the roles of these residues, site-directed mutagenesis of the muscle PK gene was conducted. Converting Ser 402 to a proline and Tyr 443 to a phenylalanine changed neither the secondary nor the tetrameric structure, as measured by far UV-CD and sedimentation velocity, respectively. However, the S402P mutant exhibits steady-state kinetics, indicating that the mutant is more reponsive to regulation by effectors, while the mutant Y443F was essentially equivalent to wild-type muscle PK protein except for a lower affinity to phosphoenolpyruvate. These findings suggest a pivotal role for a few key residues in the allosteric regulation in PK.

Allosteric Regulation↗
PubMed1998

Use of dobutamine echocardiography for cardiac risk stratification of patients with chronic renal failure.

OBJECTIVES: This study sought to define the value of dobutamine echocardiography (DbE) for cardiac risk stratification in patients with chronic renal failure (CRF). DESIGN: Outcome study correlating results of DbE with late cardiac events in patients with CRF. SETTING: Academic medical centre. SUBJECTS: All patients with CRF (serum creatinine > 2.5 mg dL-1) undergoing DbE were studied; we analysed 193 consecutive patients (aged 63 +/- 13 years, 73 men). INTERVENTIONS: A standard dobutamine-atropine stress was administered until attainment of peak dose, or the development of severe ischaemia or side-effects. The electrocardiogram (ECG) and echocardiogram were obtained before, during and after stress. Ischaemia was identified by new or worsening wall-motion abnormalities with stress. OUTCOME MEASURES: Patients were followed up after 38 +/- 14 months for cardiac death, myocardial infarction or coronary disease progression requiring revascularization. RESULTS: DbE demonstrated ischaemia in 36 patients (19%), scar in 36 (19%) and a normal study in 121 patients. The heart-rate response to dobutamine was submaximal (< 85% age-predicted heart rate) in the absence of wall-motion abnormalities in 69 patients (36%), 54 of whom completed the protocol. Follow-up data were complete in 191 patients (99%); cardiac events occurred in 33 patients (17%), including 17 with cardiac death, 7 with infarction, and 9 requiring late revascularization. Spontaneous events occurred in 7 patients with ischaemia, 3 with scar (8%), 11 with a nondiagnostic study (16%) and 3 patients with a normal study (6%). Over the entire follow-up, the event-free survival in patients with ischaemia (66%) was markedly lower than those without ischaemia (84%, P = 0.006). However, the event rate in patients with nonischaemic responses increased from 8% to 16% between 24 and 40 months, and whilst ischaemia was an independent predictor of outcome at 24 months, it was not at 40 months. CONCLUSIONS: In patients with CRF, the identification of ischaemia at DbE is associated with a significant risk of adverse cardiac events. Patients with nonischaemic scans have a low frequency of events over short-term follow-up, but this increases at later follow-up. These later events may reflect progressive coronary disease, attributable to the atherogenic milieu of these patients, and imply that repeated testing may be required to maintain cardiac risk stratification in patients with CRF.

Adrenergic beta-Agonists↗
PubMed1997

Mapping of the primary binding site of measles virus to its receptor CD46.

The measles virus (MV) hemagglutinin binds to the complement control protein (CCP) CD46 primarily through the two external modules, CCP-I and -II. To define the residues involved in binding, 40 amino acids predicted to be solvent-exposed on the CCP-I-II module surface were changed to either alanine or serine. Altered proteins were expressed on the cell surface, and their abilities to bind purified MV particles, a soluble form of hemagglutinin (sH) and nine CD46-specific antibodies competing to different levels with sH attachment, were measured. All proteins retained, at least in part, MV and sH binding, but some completely lost binding to certain antibodies. Amino acids essential for binding of antibodies weakly or moderately competing with sH attachment are situated in the membrane-distal tip of CCP-I, whereas residues involved in binding of strongly sH competing antibodies cluster in the center of CCP-I (Arg-25, Asp-27) or in CCP-II (Arg-69, Asp-70). Both clusters face the same side of CCP-I-II and map close to amino acid exchanges impairing sH binding (E11A, R29A, P39A, and D70A) or MV binding (D70A and E84A) and to a six-amino acid loop, previously shown to be necessary for sH binding.

Amino Acid Sequence↗
PubMed1997

A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies.

The two terminal complement control protein (CCP) modules of the CD46 glycoprotein mediate measles virus binding. Three-dimensional models for these two domains were derived based on the NMR structures of two CCP modules of factor H. Both CD46 modules are about 35 A long, and form a five-stranded antiparallel beta-barrel structure. Monte Carlo simulations, sampling the backbone torsion angles of the linker peptide and selecting possible orientations on the basis of minimal solvent-exposed hydrophobic area, were used to predict the orientation of CCP-I relative to CCP-II. We tested this procedure successfully for factor H. For CD46, three clusters of structures differing in the tilt angle of the two domains were obtained. To test these models, we mutagenized the CCP modules. Four proteins, two without an oligosaccharide chain and two with mutated short amino acid segments, reached the cell surface efficiently. Only the protein without the CCP-I oligosaccharide chain maintained binding to the viral attachment protein hemagglutinin. These results are consistent with one of our models and suggest that the viral hemagglutinin does not bind at the membrane-distal tip of CD46, but near the concave CCP-II interface region.

Amino Acid Sequence↗
PubMed1997

[Reconstruction of complex acetabular fractures using the extensile kocher-langenbeck approach (modified maryland approach).].

GOAL OF SURGERY: Approach to the essential bony parts of the pelvis which can be adapted to the fracture pattern and which causes minimal soft tissue damage. It allows exposure of the posterior and anterior columns and the roof of the acetabulum. INDICATIONS: Complex acetabular fractures such as 2-column fractures, T-fractures, displaced transverse fractures with posterior rim fragment, fractures of 1 column. CONTRAINDICATIONS: Fractures which can be approached through smaller incisions, preexisting lesions of the superior gluteal artery, arterial occlusive diseases, particularly of the pelvis. PREOPERATIVE WORK UP: Radiographs of the pelvis in anterior-posterior and two oblique news. Special radiographs and CT. POSITIONING AND ANAESTHESIA: Lateral decubitus with free draping of the leg. Endotracheal anaesthesia. Cell saver optional. SURGICAL TECHNIQUE: T-shaped skin incision and gradual extension of the Kocher-Langenbeck approach depending on the fracture pattern. First extensile step: Transverse division of the fascia lata and osteotomy of the greater trochanter. Second extensile step: Osteotomy of part of the iliac crest and exposure of the outer and inner cortex of the iliac wing. POSTOPERATIVE MANAGEMENT: Operated leg rests in a foam padded splint. Careful wound drainage, routine low dose radiation or indomethacin to prevent heterotopic ossification. CPM starting the 2nd postoperative day, mobilization starting the 2nd or 3rd day with partial weight bearing of 15 kg. Full weight bearing depends on fracture type and consolidation. POSSIBLE COMPLICATIONS: Delayed wound healing with risk of infection. Injury to the superior gluteal artery with danger of necrosis of the abductor muscles. Injury through stretching of the sciatic nerve. Injury of the lateral femorocutaneous nerve. RESULTS: Seven patients with complex acetabular fractures were operated between June 1993 and January 1994. Use of the 1st extensile step was sufficient in 3 patients and 3 times all 4 steps were used. Postoperative necrosis of fatty tissue necessitated 2 revisions. All fractures consolidated. During the follow-up examination 1 case of heterotopic ossification was seen (Brooker grade II). Using the classification of Merle D'Aubigné we had 1 excellent, very good, 2 good and 1 satisfactory result.

English Abstract↗
PubMed1997

[The Chopart dislocation. A frequently underestimated injury and its sequelae. A clinical study].

During a 7-year period (between July 1987 and June 1994) 19 patients were treated for Chopart dislocation. Seventeen patients were examined clinically 48 months following trauma. We found 1 excellent, 6 good, 6 mediocre, and 4 poor results. Only 4 patients were able to achieve their pre-accident level of work and no patients could return to sports at the same level. In our patients, Chopart dislocation had a negative social consequence both at the work place and in recreational activities. In long-term follow-up, the Chopart dislocation was the most debilitating injury even for polytrauma patients.

Adult↗
PubMed1997

Automated combined assignment of NOESY spectra and three-dimensional protein structure determination.

A procedure for automated protein structure determination is presented that is based on an iterative procedure during which the NOESY peak list assignment and the structure calculation are performed simultaneously. The input consists of a list of NOESY peak positions and a list of chemical shifts as obtained from sequence-specific resonance assignment. For the present applications of this approach the previously introduced NOAH routine was implemented in the distance geometry program DIANA. As an illustration, experimental 2D and 3D NOESY cross-peak lists of six proteins have been analyzed, for which complete sequence-specific 1H assignments are available for the polypeptide backbone and the amino acid side chains. The automated method assigned 70-90% of all NOESY cross peaks, which is on average 10% less than with the interactive approach, and only between 0.8% and 2.4% of the automatically assigned peaks had a different assignment than in the corresponding manually assigned peak lists. The structures obtained with NOAH/DIANA are in close agreement with those from manually assigned peak lists, and with both approaches the residual constraint violations correspond to high-quality NMR structure determinations. Systematic comparisons of the bundles of conformers that represent corresponding automatically and interactively determined structures document the absence of significant bias in either approach, indicating that an important step has been made towards automation of structure determination from NMR spectra.

Magnetic Resonance Spectroscopy↗
PubMed1997

Maturation of hepatosomal mono-oxygenation and glucuronidation activities in pre- and full-term infants as studied using the [15N]methacetin urine test.

The non-distressing [15N]methacetin liver function test was modified and applied to newborn healthy infants in order to measure both the total [15N]methacetin metabolites excreted in the urine (total elimination capacity) and the proportion of glucuronated metabolite. By studying pre- and full-term normotrophic neonates 3-168 days old, the age-dependent maturation of the two developing liver function processes can be compared on the basis of either postnatal or postmenstrual age. When solely considering postnatal age, no significant differences between the pre- and full-term infants were observed in the development of the total elimination capacity. However, when postmenstrual age was considered, it became apparent that this development starts earlier in pre-term infants and continues at the same rate as their full-term counterparts, up to the postmenstrual age of approximately 280 days. This increase subsequently diminishes in the pre-terms. In the same study group, the proportion of glucuronidation, another indicator of the hepatic detoxification system, appears to develop at a lower rate in pre-term than in full-term infants. When postmenstrual age is taken into consideration, glucuronidation development is also observed to begin earlier in pre-term infants and the slower maturation is more pronounced. Although these results are not generally applicable, they contribute to a better interpretation of the [15N]methacetin liver function test--for instance when estimating effects due to environmental exposure or accurately calculating age-related drug dosage for neonates.

Acetamides↗