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Biomedical subjects

W Braun

Publications and source records attributed to W Braun.

At least 73 records · Page 4Linked to original sources

Pattern recognition and self-correcting distance geometry calculations applied to myohemerythrin.

A topological list, consisting of segments of regular secondary structures and a list of buried and solvent accessible residues, is automatically predicted from multiple aligned sequences in a protein family. This topological list is translated into geometric constraints for distance geometry calculation in torsion angle space. A new self-correcting distance geometry method detects and eliminates false distance constraints. In an application to the four-helix bundle protein, myohem-erythrin, the right-handed global fold was correctly reproduced with a root-mean-square deviation of 2.6 A, when the topological list was derived from the X-ray structure. A predicted topological list, coupled with constraints from the residues in the active site of myohemerythrin, predicted the correct fold with a root-mean-square deviation of 4 A for backbone atoms.

Amino Acid Sequence↗

Determination of the NMR solution structure of the cyclophilin A-cyclosporin A complex.

The three-dimensional NMR solution structure of the cyclophilin A (Cyp)-cyclosporin A (CsA) complex was determined, and here we provide a detailed description of the analysis of the NMR data and the structure calculation. Using 15N- and 13C-resolved three- and four-dimensional [1H,1H]-nuclear Overhauser enhancement (NOE) spectroscopy with uniformly isotope-labeled Cyp in the complex, a final data set of 1810 intra-Cyp, 107 intra-CsA and 63 intermolecular NOE upper distance constraints was collected as input for the structure calculation with the program DIANA. A group of DIANA conformers, selected by a previously described analysis of the dependence of the maximal root-mean-square deviation (rmsd) among the individual conformers on the residual target function value, was subjected to energy refinement with the program FANTOM. The 22 best energy-refined conformers were then used to represent the solution structure. The average rmsd relative to the mean structure of these 22 conformers is 1.1 A for the backbone atoms of all residues of the complex. The molecular architecture of Cyp in the Cyp-CsA complex includes an eight-stranded antiparallel beta-barrel, which is closed on each side by an amphipathic helix. CsA is bound in a cavity formed by part of the barrel surface and four loops with nonregular secondary structure. Comparison of this structure with structures of Cyp-CsA and other Cyp-peptide complexes determined by different approaches shows extensive similarities.

Amino Acid Isomerases↗

Intraosseous leiomyoma of the neck of the femur. A case report.

Intraosseous benign leiomyoma is a rare manifestation of disseminated leiomyomatosis. In a 54 year old housewife presenting with a painful left hip due to a cystic lesion of the femoral neck, histological assessment following resection of the cyst showed a benign intraosseous leiomyoma. Years before a diagnosis of disseminated peritoneal leiomyomatosis had been made.

Biopsy↗

Is the [15N]methacetin liver function test suited to estimate environmental effects on the maturity of neonates?

Clinical and paraclinical data of 91 neonates of the Saxon regions of Leipzig and of Torgau/Elbe were reviewed and correlated to the environmental conditions of the places of residence of their mothers during pregnancy. One of the parameters investigated was the hepatic detoxification capacity of the neonates measured by 15N elimination rates in the [15N]methacetin urine test. Because of heavy air pollution in the places of residence of some of the pregnant women, a distinct reflection of environmental influence in the parameters was expected. While some of the parameters considered, such as birth weight and bilirubin levels, did not correlate with mean exposure data of the residences of the pregnant women, the mean rate of the age-dependent maturation of hepatic 15N elimination did. This maturation was seen to be significantly decreased in heavily polluted districts of the Leipzig region compared to lower polluted places of Leipzig and to the lowly polluted region of Torgau/Elbe.

Acetamides↗

[Can unreamed tibial nailing replace external fixators in management of open tibial fractures?].

The recently developed unreamed tibial nail (UTN) offers a new possibility for biological osteosynthesis by intramedullary stabilization for tibial fractures including those with severe closed and open soft tissue damage. In a retrospective study we compared the well established method of external fixation with unreamed intramedullary nailing for open tibial shaft fractures. The data of our first 15 cases treated primarily by UTN (Group 1) and another 15 cases comparable in etiology, severity of trauma, fracture classification, open soft tissue damage and the rate for myocutaneous flaps and skin-grafts, treated initially by external fixation (Group 2) were reviewed. Septic complications were only seen in group 2 and made necessary a lot of following additional operations. One angular deformity was seen in each group. Group 1 showed a mean hospital stay of 26.3 days compared to 75.7 days in group 2. Full weight-bearing was achieved after 1.8 months (group 1) whereas it took 4.5 months in group 2. The first clinical experience using the UTN shows an obvious advantage in comparison to fracture management by external fixation mainly due to a low complication rate and a much shorter over all surgical treatment period.

Adolescent↗

[Is there a classification of pelvic ring injuries, which takes the trauma mechanism, morphology and stability relations into consideration and thereby gives references for subsequent therapy?].

In contrast to earlier classifications, Tile's classification of pelvic ring disruptions considers mechanism of injury, clinical and x-ray evaluations and is therefore almost universally accepted. We propose a more comprehensive classification which gives a guide for treatment of these complex injuries. Moreover it can be used to compare results from different authors. We classify types A-D pelvic injuries according to stability. Type A consists of fractures of the pelvis not involving the ring, type B of stable rotational injuries. Type C and D encompass the unstabile injuries: C is purely rotational and D has a combined rotational and vertical instability. The location of injury is indicated by adding numbers 1-9 (1: rupture of symphysis pubis; 2: transpubic fracture; 3: acetabular fracture; 4: iliac wing fracture; 5: sacroiliac fracture-dislocation; 6: sacroiliac disruption; 7: sacral wing fracture; 8: transforaminal sacral fracture; 9: central sacral fracture). These numbers are arranged in increasing order, one hemipelvis after the other. Thus, in case of a complex pelvic injury with rotational instability on one side and vertical instability on the other each hemipelvis may be classified separately.

Fracture Fixation, Internal↗

Surface area included in energy refinement of proteins. A comparative study on atomic solvation parameters.

With the program FANTOM, we study the effect of a solvation energy term modelled by four atomic solvation parameter sets on energy refinement of proteins. Two parameter sets had previously been derived from measured free energies of transfer of hydrocarbons and amino acid side-chain analogues. Alternatively, the other two parameter sets correspond to the total or apolar accessible surface area of the protein. Twenty-five conformations of BPTI and the alpha-amylase inhibitor tendamistat were refined with respect to empirical energy terms (ECEPP/2) plus a solvation energy term modelled by one of the four atomic solvation parameter sets. These minimizations were compared to minimizations of the ECEPP/2 energy alone with regard to violations of upper distance limits obtained from NMR experiments as well as to root mean square deviations to NMR structures. We find that minimizations of the ECEPP/2 energy plus the total or apolar accessible surface area are superior to minimizations of the ECEPP/2 energy alone. In contrast, minimization of the ECEPP/2 energy plus a solvation energy term based on free energies of transfer perform poorly.

Aprotinin↗

Detection of neutralizing antibodies against human cytomegalovirus: influence of strain variation.

The influence of human cytomegalovirus (HCMV) strain variation on neutralizing antibody titers was investigated in sequential sera obtained from 12 organ transplant recipients (11 renal transplant recipients, 1 liver transplant patient) suffering from primary or secondary HCMV infection. Cross-neutralization assays using either the international HCMV reference strain AD169 or individual clinical isolates from patients showed congruent results. Restriction enzyme analysis of the hypervariable alpha-sequence of the L-S junction of AD169 and HCMV isolates amplified by polymerase chain reaction (PCR) were carried out to confirm the expected strain differences. At least 6 groups of clinical strains were differentiated. The results of this study demonstrated that despite the strain heterogenicity of HCMV, the neutralization assay using AD169 permitted a reliable and quantitative serologic detection of neutralizing antibodies against HCMV.

Antibodies, Viral↗

Humoral immune response to human cytomegalovirus infection: diagnostic potential of immunoglobulin class and IgG subclass antibody response to human cytomegalovirus early and late antigens.

For the development of effective prophylaxis (hyperimmune globulins) and improvement of serological testing for human cytomegalovirus (HCMV) infection in immunocompromised patients it is essential to characterize the viral encoded proteins and the humoral immune response in terms of neutralizing antibodies and immunoglobulin class and IgG subclass reactivity to "early" and "late" HCMV proteins. The major neutralizing epitopes have been identified and screening of donor sera for neutralizing antibody by either conventional neutralization assays or enzyme-linked immunosorbent assay using recombinant antigens may help to improve the efficacy of hyperimmune globulin prophylaxis. The humoral response to individual HCMV proteins has been thoroughly investigated in immunocompromised patients. Antibodies against HCMV induced "early" antigens are not exclusively associated with active infection but may indicate an elevated risk for cytomegalic inclusion disease in immunocompromised patients. With a sensitive western blot technique. IgM and IgA antibodies against HCMV "late" proteins can be detected in sera from healthy seropositive individuals. Serum samples from subjects suffering from cytomegalic inclusion disease show significantly larger broader immune responses compared with healthy HCMV antibody carriers. Promising results using recombinant antigens corresponding to immunodominant epitopes for the detection of HCMV specific antibodies have been published.

Antibodies, Viral↗

Extensive distance geometry calculations with different NOE calibrations: new criteria for structure selection applied to Sandostatin and BPTI.

To generate structures efficiently, a version of the distance geometry program DIANA for a parallel computer was developed, new objective criteria for the selection of NMR solution structures are presented, and the influence of using different calibrations of NOE intensities on the final structures are described. The methods are applied to the structure determination of Sandostatin, a disulfide-bridged octapeptide, and to model calculations of BPTI. On an Alliant FX2800 computer using 10 processors in parallel, the calculations were done 9.2 times faster than with a single processor. Up to 7000 Sandostatin structures were calculated with distance and angular constraints. The procedure for selecting acceptable structures is based on the maximum values of pairwise RMSDs between structures. Suitable target function cut-offs are defined independent of the number of starting structures. The method allowed for an objective comparison of three groups of Sandostatin structures that were calculated from different sets of upper distance constraints which were derived from the same NOE intensity data using three empirical calibration curves. The number of converged structures and the target function values differed significantly among the three groups, but the structures were qualitatively and quantitatively very similar. The conformation is well determined in the cyclic region Cys2-Cys7 and adopts a beta-turn centered at D-Trp4-Lys5. The criteria for structure selection were further tested with BPTI. Results obtained from sets of structures calculated with and without using the REDAC strategy are consistent and suggest that the structure selection method is objective and generally applicable.

Amino Acid Sequence↗

Immunoglobulin A and M patterns to human cytomegalovirus during recurrent infection in patients with AIDS using a modified western blot.

Immunoglobulin A and M patterns to human cytomegalovirus (HCMV) were investigated in sera from actively HCMV infected AIDS patients (n = 61) and healthy HCMV seropositive controls (n = 28) by a Western blot method (modi-blotting) and ELISA. The Western blot showed a higher detection rate for both IgA (78.7% vs. 52.5%) and IgM (83.6% vs. 13.1%) than ELISA in the immunocompromised patients suffering from active HCMV infection. Of the healthy seropositive individuals, 35.7% and 21.4% had a weak positive IgA- and IgM-class antibody reactivity respectively with HCMV-specific bands in the immunoblot. Immunoglobulins M and A were not detected by ELISA in the healthy control group. Immunoreactions in this group were restricted to viral polypeptides with M(r) of 68 kDa and 123 kDa. Additional bands were found in the actively infected patients only and were observed more frequently with IgA than IgM (47.5% vs. 29.5%). Results from the present study indicate, that using a sensitive Western blot technique, a higher serologic detection rate of active recurrent infection is achieved in AIDS patients. Nevertheless, immunoglobulin A and M are detected in a certain percentage of HCMV-seropositive healthy individuals not suffering from active HCMV infection. Broader immune reactions of HCMV-IgA as determined by HCMV Western blot assay are associated with an active infection, but were not present in all the actively infected patients.

Acquired Immunodeficiency Syndrome↗

[The viral and allergic origin of nasal polyposis].

In spite of recent advances in basic science, the etiology and pathogenesis of nasal and paranasal polyps have still not been clarified. Well-defined causal factors are hereditary diseases such as cystic fibrosis and primary ciliary dyskinesia. Allergic and non-allergic processes of the airways, particularly intrinsic asthma and intolerance to non-steroidal antiinflammatory drugs, are implicated in the development of nasal polyposis. In the 1930s nasal polyps were strongly considered to be a manifestation of allergy. The theory was challenged in the 1970s. Many patients with nasal polyps have no identifiable allergic disease. The cause of nasal polyps is speculative. 221 patients were included in this study, 154 suffering from chronic rhinosinusitis and another 46 from nasal polyps. The incidences of aspirin intolerance and of allergy were of no statistic relevance. The data indicate that preoperative cortisone application does improve the disease-free interval.

Aspirin↗

Detection of IgM antibodies against coxsackie B viruses by a western blot technique.

We report the application of a modified Western blot (WB) micromethod basically relying on a diffusion-blotting technique (Modi-blot) combined with an immunological detection system using monoclonal antibodies and a biotinavidin amplification step for the detection of IgM antibodies against coxsackieviruses B1 (CBV1), CBV2 and CBV4. Fifty-one adult patients with clinical signs of coxsackievirus B infection (e.g. myocarditis and meningitis) were investigated. The test revealed a total of 31 (60%) IgM positives. The majority of IgM antibodies were group reactive (22/31). Type-specific antibodies could be recognized in 9 cases (3 with CBV1, 5 with CBV2 and 1 with CBV4). The highest rate of antibody prevalence was found in sera from patients with acute meningitis (12/14). Controls [healthy adults (n = 13) and individuals with other infections (n = 13)] were all negative for specific IgM against coxsackievirus B1, B2 and B4. Further WB tests of 8 IgM positive specimens with coxsackievirus B4 revealed specific IgA responses in all cases, reinforcing the evidence for a recent infection. In addition, the patterns of IgG antibody subclasses, also investigated in this group, showed a clear predominance of specific IgG1 and IgG3 antibodies.

Acute Disease↗

[Primary intracerebral non-Hodgkin's lymphoma--a clinicopathologic study].

Primary cerebral lymphomas (PCL) were diagnosed with increasing frequency also in our retrospective study of 44 patients. Clinically these tumors presented with signs of a rapidly growing brain neoplasm. The analysis of CCT data showed that the tumors were of varying density before and showed mostly (60%) homogeneous enhancement after contrast medium application. MR imaging was more sensitive, but could not aid in distinguishing PCL from other brain tumors. The lesions lay mainly (82%) in the supratentorial space and involved the frontal lobe in 42% of cases. Only 16% were located in the periventricular region including corpus callosum and basal ganglia. 20% of cases showed multiple lesions. Suspected diagnoses were therefore mainly meningeoma, glioma and metastases. Morphological diagnosis was easily possible with the aid of immunohistological methods: there were 41 B-cell lymphomas (93%), two T-cell lymphomas and one large cell anaplastic lymphoma of the non-B non-T phenotype. An unequivocal correlation between morphology and radiological picture existed in the way that tumors with a dense cellular infiltrate appeared mainly as hyperdense lesions with homogeneous contrast enhancement. The clinical course was characterized by CNS-relapses frequently with multiple cerebral lesions and a spinal recurrence in one case. 7% of cases showed evidence of extracerebral disease in a bone marrow biopsy specimen or at autopsy. The average survival of the patients was 15 months, one year survival was 36%, two year survival 12% and 5% of patients lived for more than 5 years.

Adult↗