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Biomedical subjects

E Schröder

Publications and source records attributed to E Schröder.

At least 19 recordsLinked to original sources

Dilatation of the entire thoracic aorta in patients with bicuspid aortic valve: a magnetic resonance angiography study.

BACKGROUND: The presence of a bicuspid aortic valve (BAV) might be associated with a progressive dilatation of the aortic root and ascending aorta. However, involvement of the aortic arch and descending aorta has not yet been elucidated. PATIENTS AND METHODS: Magnetic resonance angiography (MRA) was used to assess the diameter of the ascending aorta, aortic arch, and descending aorta in 28 patients with bicuspid aortic valves (mean age 30 +/- 9 years). RESULTS: Patients with BAV, but without significant aortic stenosis or regurgitation (n = 10, mean age 27 +/- 8 years, n.s. versus control) were compared with controls (n = 13, mean age 33 +/- 10 years). In the BAV-patients, aortic root diameter was 35.1 +/- 4.9 mm versus 28.9 +/- 4.8 mm in the control group (p < 0.01). The diameter of the ascending aorta was also significantly increased at the level of the pulmonary artery (35.5 +/-5.6 mm versus 27.0 +/- 4.8 mm, p < 0.001). BAV-patients with moderate or severe aortic regurgitation (n = 18, mean age 32 +/- 9 years, n.s. versus control) had a significant dilatation of the aortic root, ascending aorta at the level of the pulmonary artery (41.7 +/- 4.8 mm versus 27.0 +/- 4.8 mm in control patients, p < 0.001) and, furthermore, significantly increased diameters of the aortic arch (27.1 +/- 5.6 mm versus 21.5 +/- 1.8 mm, p < 0.01) and descending aorta (21.8 +/- 5.6 mm versus 17.0 +/- 5.6 mm, p < 0.01). CONCLUSIONS: The whole thoracic aorta is abnormally dilated in patients with BAV, particularly in patients with moderate/severe aortic regurgitation. The maximum dilatation occurs in the ascending aorta at the level of the pulmonary artery. Thus, we suggest evaluation of the entire thoracic aorta in patients with BAV.

Adult↗

van der Waals density functional for general geometries.

A scheme within density functional theory is proposed that provides a practical way to generalize to unrestricted geometries the method applied with some success to layered geometries [Phys. Rev. Lett. 91, 126402 (2003)]]. It includes van der Waals forces in a seamless fashion. By expansion to second order in a carefully chosen quantity contained in the long-range part of the correlation functional, the nonlocal correlations are expressed in terms of a density-density interaction formula. It contains a relatively simple parametrized kernel, with parameters determined by the local density and its gradient. The proposed functional is applied to rare gas and benzene dimers, where it is shown to give a realistic description.

Journal Article↗

Van der Waals density functional for layered structures.

To understand sparse systems, we must account for both strong local atom bonds and weak nonlocal van der Waals forces between atoms separated by empty space. A fully nonlocal functional form [Phys. Rev. B 62, 6997 (2000)]] of density-functional theory (DFT) is applied here to the layered systems graphite, boron nitride, and molybdenum sulfide to compute bond lengths, binding energies, and compressibilities. These key examples show that the DFT with the generalized-gradient approximation does not apply for calculating properties of sparse matter, while use of the fully nonlocal version appears to be one way to proceed.

Journal Article↗

Comparison of the decameric structure of peroxiredoxin-II by transmission electron microscopy and X-ray crystallography.

The decameric human erythrocyte protein torin is identical to the thiol-specific antioxidant protein-II (TSA-II), also termed peroxiredoxin-II (Prx-II). Single particle analysis from electron micrographs of Prx-II molecules homogeneously orientated across holes in the presence of a thin film of ammonium molybdate and trehalose has facilitated the production of a >/=20 A 3-D reconstruction by angular reconstitution that emphasises the D5 symmetry of the ring-like decamer. The X-ray structure for Prx-II was fitted into the transmission electron microscopic reconstruction by molecular replacement. The surface-rendered transmission electron microscopy (TEM) reconstruction correlates well with the solvent-excluded surface of the X-ray structure of the Prx-II molecule. This provides confirmation that transmission electron microscopy of negatively stained specimens, despite limited resolution, has the potential to reveal a valid representation of surface features of protein molecules. 2-D crystallisation of the Prx-II protein on mica as part of a TEM study resulted in the formation of a p2 crystal form with parallel linear arrays of stacked rings. This latter 2-D form correlates well with that observed from the 2.7 A X-ray structure of Prx-II solved from a new orthorhombic 3-D crystal form.

Crystallography, X-Ray↗

Crystal structure of decameric 2-Cys peroxiredoxin from human erythrocytes at 1.7 A resolution.

BACKGROUND: The peroxiredoxins (Prxs) are an emerging family of multifunctional enzymes that exhibit peroxidase activity in vitro, and in vivo participate in a range of cellular processes known to be sensitive to reactive oxygen species. Thioredoxin peroxidase B (TPx-B), a 2-Cys type II Prx from erythrocytes, promotes potassium efflux and down-regulates apoptosis and the recruitment of monocytes by endothelial tissue. RESULTS: The crystal structure of human decameric TPx-B purified from erythrocytes has been determined to 1.7 [corrected)] A resolution. The structure is a toroid comprising five dimers linked end-on through predominantly hydrophobic interactions, and is proposed to represent an intermediate in the in vivo reaction cycle. In the crystal structure, Cys51, the site of peroxide reduction, is oxidised to cysteine sulphinic acid. The residue Cys172, lies approximately 10 A away from Cys51 [corrected]. CONCLUSIONS: The oxidation of Cys51 appears to have trapped the structure into a stable decamer, as confirmed by sedimentation analysis. A comparison with two previously reported dimeric Prx structures reveals that the catalytic cycle of 2-Cys Prx requires significant conformational changes that include the unwinding of the active-site helix and the movement of four loops. It is proposed that the stable decamer forms in vivo under conditions of oxidative stress. Similar decameric structures of TPx-B have been observed by electron microscopy, which show the protein associated with the erythrocyte membrane.

Catalytic Domain↗

The size of the CAG repeat in exon 1 of the androgen receptor gene shows no significant relationship to impaired spermatogenesis in an infertile Caucasoid sample of German origin.

The androgen receptor (AR) gene, located on the X-chromosome at Xq11-12, contains in exon 1 a polymorphic CAG repeat which codes for a polyglutamine tract. Contractions of the CAG repeat are said to be related to prostate cancer. In contrast, sizeable expansion of the CAG repeat can cause spinal and bulbar muscular atrophy (SBMA). In infertile patients of Chinese origin and in a Melbourne multinational population impaired sperm production has been postulated to be related to moderate expansions of the polyglutamine tract. In a study of a Swedish population of infertile patients these findings could not be corroborated. The aim of our investigation was to examine the correlation between the length of the CAG repeat and impaired sperm production in an infertile Caucasoid patient sample of German ethnic origin. We found no statistically significant relationship between the size of the CAG repeat or polyglutamine tract and idiopathic impaired sperm production in the population studied. The variability of the results by various investigators may be attributed to different ethnic origins and hence different genetic modifiers of the populations studied and/or to the high probability that these infertile males may represent a heterogeneous group with respect to the causes of defective spermatogenesis.

Adult↗

Upregulation of MAP1B and MAP2 in the rat brain after middle cerebral artery occlusion: effect of age.

Although stroke in humans usually afflicts the elderly, most experimental studies on the nature of cerebral ischemia have used young animals. This is especially important when studying restorative processes that are age dependent. To explore the potential of older animals to initiate regenerative processes after cerebral ischemia, the authors studied the expression of the juvenile-specific cytoskeletal protein, microtubule-associated protein (MAP) 1B, and the adult-specific protein, MAP2, in male Sprague-Dawley rats at 3 months and 20 months of age. The levels of MAP1B and MAP2 transcripts and the corresponding proteins declined with increasing age in the hippocampus. In the cortex, the levels of the transcripts did not change significantly with age, but the morphologic features of immunostained fibers were clearly affected by age; that is, cortical MAP1B fibers became thicker, and MAP2 fibers, more diffuse, in aged rats. Focal cerebral ischemia, produced by reversible occlusion of the right middle cerebral artery, resulted in a large decrease in the expression of both MAP1B and MAP2 in the infarct core at the messenger ribonucleic acid and protein levels. However, at 1 week after the stroke, there was vigorous expression of MAP1B and its messenger ribonucleic acid, as well as MAP2 protein, in the border zone adjacent to the infarct of 3-month-old and 20 month-old male Sprague-Dawley rats. The upregulation of these key cytologic elements generally was diminished in aged rats compared with young animals, although the morphologic features of fibers in the infarct border zone were similar in both age groups. These results suggest that the regenerative potential of the aged rat brain appears to be competent, although attenuated, at least with respect to MAP1B and MAP2 expression up to 20 months of age.

Aging↗

Crystallization and preliminary X-ray analysis of human thioredoxin peroxidase-B from red blood cells.

Two different crystal forms of human thioredoxin peroxidase-B have been grown by vapour diffusion using polyethylene glycol 400 as a precipitant. Monoclinic P21 crystals were grown from freshly purified protein, whilst orthorhombic P212121 crystals were grown from purified protein that had been stored in ammonium sulfate, but otherwise under the same conditions. The diffraction from both crystal forms was observed to extend to beyond 2.0 A resolution using synchrotron radiation. Complete native data sets to 1.8 and 3. 7 A have been collected from the monoclinic and orthorhombic crystals, respectively.

Crystallization↗

Crystallization and preliminary X-ray diffraction studies of the oxygenating subunit of 3,6-diketocamphane monooxygenase from Pseudomonas putida.

The oxygenating constituent of the 3,6-diketocamphane monooxygenase isozyme from Pseudomonas putida NCIMB 10007 has been crystallized under two different conditions. Crystals were initially grown from polyethylene glycol (PEG) 8000 and sodium acetate using the vapour-phase diffusion method. The crystals were of orthorhombic P212121 space group, with cell dimensions a = 55.8, b = 94.5 and c = 163.7 A and diffracted to 2.8 A resolution. More recently, improved crystals, which diffracted beyond 2 A, have been grown from ammonium sulfate. These crystals also belong to the orthorhombic P212121 space group, with cell dimensions of a = 54.6, b = 93.2 and c = 154. 1 A. A full native data set to 2.5 A resolution has been collected from the ammonium sulfate grown crystals.

Bacterial Proteins↗

Porcine natural-killer-enhancing factor-B: oligomerisation and identification as a calpain substrate in vitro.

Natural-killer-enhancing factor-B (NKEF-B) (monomeric mass = 21.82 kDa) was purified from the cytosol of porcine red blood cells and its identity was established by microsequencing. NKEF-B oligomerisation was investigated by gel filtration and small-angle X-ray scattering (SAXS). Native NKEF-B readily forms disulphide-linked dimers, but when fully reduced, the protein forms discrete oligomers containing 16 +/- 1 monomers. A total of 40% of the purified enzyme was deduced to be cysteinylated, which is consistent with the modification of one or both of two putative active site cysteine residues. In vitro, NKEF-B was found to be a specific substrate of mu- and m-calpains, the calcium-dependent cysteine proteases. The cleavage events were followed by SDS-PAGE and the cleavage sites pinpointed by N-terminally sequencing the resulting digestion fragments. This in vitro cleavage data provides support to the hypothesis that calpromotin (NKEF-B), an erythron peroxiredoxin involved in the regulation of calcium-dependent potassium transport across the plasma membrane, is cleaved by calpain in vivo.

Amino Acid Sequence↗

Evidence that peroxiredoxins are novel members of the thioredoxin fold superfamily.

Peroxiredoxins catalyze reduction of hydrogen peroxide or alkyl peroxide, to water or the corresponding alcohol. Detailed analysis of their sequences indicates that these enzymes possess a thioredoxin (Trx)-like fold and consequently are homologues of both thioredoxin and glutathione peroxidase (GPx). Sequence- and structure-based multiple sequence alignments indicate that the peroxiredoxin active site cysteine and GPx active site selenocysteine are structurally equivalent. Homologous peroxiredoxin and GPx enzymes are predicted to catalyze equivalent reactions via similar reaction intermediates.

Amino Acid Sequence↗

beta-Amyloid precursor protein and ss-amyloid peptide immunoreactivity in the rat brain after middle cerebral artery occlusion: effect of age.

BACKGROUND AND PURPOSE: Previous studies have shown that the ss-amyloid precursor protein (ssAPP) is upregulated after cerebral ischemia and that the ss-amyloid (Ass) fragment may be toxic to brain cells. Although stroke in humans usually afflicts the elderly, most experimental studies on the nature of cerebral ischemia have used young animals. To test the hypothesis that the upregulation and/or persistence of amyloidogenic proteins is exacerbated in aged rats after cerebral ischemic stroke, we studied the expression of ssAPP and its proteolytic product Ass in the brains of young and old rats 7 days after temporary cerebral ischemia. METHODS: Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. After 1 week, brains were removed and immunostaining was performed for ssAPP, Ass, and ED1 for macrophages and glial fibrillary acidic protein (GFAP). RESULTS: Histological staining revealed that the degree of necrotic cavitation in the infarct core was relatively less in aged rats than in young rats, suggesting a slower pace of degenerative change and/or tissue removal in older animals. ssAPP immunoreactivity was robustly increased, primarily in macrophage-like, ED1-positive cells in the infarct core and in the penumbra of both young and aged animals. Ass immunoreactivity was evident in GFAP-positive astrocytic somata and processes, and also in clusters of small spherical structures in the penumbra. These Ass-immunoreactive minispheres were more numerous in aged rats than in young rats. CONCLUSIONS: The presence of ssAPP and Ass immunoreactivity in the infarct core and penumbra indicates that cerebral ischemia promotes conditions that are favorable to the focal accumulation of ssAPP and its proteolytic fragments, especially in the aged brain.

Aging↗

Excimer laser photorefractive keratectomy for hyperopia.

PURPOSE: To achieve less variation in the refractive outcome of hyperopic photorefractive keratectomy (PRK) by enlarging the treatment zone to 9.0 mm. SETTING: Marienhospital, Amberg, Germany, and Klinika Ocni A Esteticke Chirurgie, Zlin, Czech Republic. METHODS: This prospective clinical study was based on the results of PRK in 68 hyperopic eyes (62 patients) using an MEL 60 excimer laser. Mean attempted correction was +4.85 diopters (D) +/- 1.45 (SD) (range +2.00 to +8.25 D). Maximum follow-up was 12 months (68 eyes). RESULTS: One year after PRK, 55 eyes (81%) were within 1.00 D and 40 eyes (59%) were within 0.50 D of the intended correction (predictability). Best corrected visual acuity was unchanged or improved in 62 eyes (92%) (safety). Four eyes (6%) lost one line, 1 eye (1%), two lines, and 1 eye (1%), three lines. Sixty-six eyes (97%) had an uncorrected visual acuity of 20/40 or better (efficacy) and 27 (40%), 20/20 or better. CONCLUSION: Photorefractive keratectomy with a 9.0 mm treatment zone was an efficient and relatively safe procedure for correcting hyperopia of up to 8.25 D. The predictability was good. Great care must be taken to improve the centration of the optical zone.

Adult↗

Geographic distribution and origin of CFTR mutations in Germany.

The geographic distribution and origin of CFTR mutations in Germany was evaluated in 658 three-generation families with cystic fibrosis (CF). Fifty different mutations were detected on 1305 parental CF chromosomes from 22 European countries and overseas. The major mutation. delta F508 was identified on 71.5% of all CF chromosomes, followed by R553X (1.8%), N1303K (1.3%), G542X (1.1%), G551D (0.8%) and R347P (0.8%). According to the grandparents' birthplace, 74% of CF chromosomes had their origin in Germany; the delta F508 percentage was 77%, 75%, 70% and 62% in northern, southern, western and eastern Germany, respectively. Ten or more mutant alleles in the investigated CF gene pool originated from Austria, the Czech Republic, Poland, Russia, Turkey and the Ukraine. This widespread geographic origin of CFTR mutations in today's Germany reflects the many demographic changes and migrations in Central Europe during the 20th century.

Cystic Fibrosis↗

Excimer laser correction of high astigmatism after keratoplasty.

PURPOSE: To assess the effectiveness of excimer laser correction of high astigmatism after keratoplasty. SETTING: Kiel University Eye Hospital, Kiel, Germany. METHODS: In a prospective study, we treated high astigmatism in 16 patients using a 193 nm excimer laser with a rotating mask system to make a toric ablation. Thirteen patients had postkeratoplasty astigmatism, 3, idiopathic natural astigmatism. Preoperative refractive cylinder ranged from 3.0 to 9.0 diopters (D). Minimum follow-up was 6 months. RESULTS: Mean uncorrected visual acuity increased by 3.3 lines in 13 patients. Best corrected visual acuity decreased by no more than two lines in 6 patients and improved by at least one line in 6 patients. Mean cylindrical reduction was 2.8 D. Haze was classified from 0.5 to 2.0. CONCLUSIONS: In this study, the excimer laser technique effectively reduced high corneal astigmatism. The main problems incurred were development of a hyperopic shift and, in some patients, an uncertain refractive outcome. Reasons for inadequate correction of postkeratoplasty astigmatism included a slightly decentered mask and irregular astigmatism from the circular scar.

Adolescent↗