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Biomedical subjects

M Albrecht

Publications and source records attributed to M Albrecht.

At least 19 recordsLinked to original sources
PubMed2006

Magnetization reversal in a novel gradient nanomaterial.

The deposition of Co/Pd multilayer films onto self-assembled particle arrays with particle sizes down to 50 nm leads to pronounced curvature-induced physical properties. Unlike in classical nanosystems, the so-formed single caps on top of the spherical particles exhibit a radial symmetric anisotropy orientation across their surface. Its impact on the magnetization reversal process was analyzed experimentally for different particle sizes and compared to micromagnetic simulations, offering new opportunities in the functionalization of magnetic nanostructures.

Journal Article↗
PubMed2006

Cathodoluminescence in transmission electron microscopy.

We describe a cathodoluminescence spectrometer that is attached to an analytical transmission electron microscope. After a brief consideration of the set-up and the peculiarities of recording spectra and of mapping defect distributions in panchromatic and monochromatic cathodoluminescence, we discuss two examples of applications. Emphasis is placed on the potential for obtaining novel information about materials and processes on a microscopic and a nanoscopic scale by combining cathodoluminescence with the structural and chemical information for the same site of the specimen. We select an example concerning the role of In distribution in light emission from InGa/GaN quantum wells and a second one concerning the analysis of the initial electron radiation damage of Cu(In,Ga)Se(2) photovoltaic films.

Journal Article↗
PubMed2006

Update on the pharmacokinetic aspects of antiretroviral agents: implications in therapeutic drug monitoring.

The observed inter-individual variation in antiretroviral pharmacokinetics (PK) that results in a wide range of drug exposures from fixed-dose regimens has led to increasing interest in the clinical use of therapeutic drug monitoring (TDM) to individualize dosing of antiretroviral therapy (ART). The focus of this review is to provide an overview of literature available to support therapeutic drug monitoring among the current classes of antiretrovirals, suggest patient populations that may benefit from TDM and bring forth some of the limitations that may exist for widespread use of TDM in a traditional clinical setting.

Anti-Retroviral Agents↗
PubMed2005

Divergent effects of the major mast cell products histamine, tryptase and TNF-alpha on human fibroblast behaviour.

Fibroblast proliferation is a key process in tissue remodeling and mast cells (MCs) are thought to play a crucial role. Having established that the three major MC products, tryptase, histamine and TNF-alpha (TNF) are normally present in human skin MCs, which are in close proximity to dermal fibroblasts, we studied their individual effects on cell cycle-controlled human dermal fibroblasts (HFFF2). These cells express receptors (H1, PAR2, TNFR1/2) for the major MC mediators, but only tryptase or a PAR2 agonist peptide stimulated proliferation and gene expression. TNF was antimitotic, and histamine, while elevating intracellular Ca2+ levels at high concentrations, did not affect proliferation. We conclude that MC products but also composition and numbers of respective receptors on fibroblasts are crucially responsible for fibroproliferative events.

Cell Cycle↗
PubMed2004

Tryptase inhibits motility of human spermatozoa mainly by activation of the mitogen-activated protein kinase pathway.

BACKGROUND: We previously localized protease-activated receptor 2 (PAR-2) on human spermatozoa and demonstrated that activation of PAR-2 by the mast cell (MC) product tryptase inhibits sperm motility. Importantly, tryptase-secreting MCs are encountered in the male and female genital tract, implying that MC-spermatozoa interactions may be as yet unrecognized factors affecting sperm fertilizing ability. In order to elucidate how tryptase via activation of PAR-2 acts in human spermatozoa, we studied intracellular signal transduction events. METHODS AND RESULTS: Impairment of sperm motility by tryptase was not dependent on the presence of extracellular Ca2+ and tryptase did not alter intracellular Ca2+ levels. Pre-incubation with pertussis toxin (PTX) failed to prevent tryptase effects on sperm motility. Western blot analyses revealed that tryptase increased phosphorylation of the mitogen-activated protein kinases (MAPK) ERK1/2, an effect which was blocked by the MAPK pathway inhibitor PD98059. Pre-treatment of spermatozoa with this inhibitor also blocked the inhibtion of sperm motility evoked by tryptase. CONCLUSIONS: These results indicate that tryptase acts via the ERK1/2 pathway to inhibit motility of human spermatozoa.

Calcium↗
PubMed2004

Strain induced deep electronic states around threading dislocations in GaN.

Combining through-focus high-resolution transmission electron microscopy and hierarchical multiscale simulations consisting of density-functional theory, analytical empirical potentials, and continuum elastic theory we demonstrate the existence of a new dislocation type in GaN. In contrast with all previously identified or suggested dislocation structures in GaN, all core atoms are fully coordinated; i.e., no broken bonds occur, implying that the dislocation should be electrically inactive. However, as we show, the giant local strain-field around the dislocation core, in combination with the small lattice constant of GaN, causes deep defect states and thus electrically active edge dislocations independent on the specific core structure.

Journal Article↗
PubMed2003

The interleukin-6 promoter polymorphism is associated with elevated leukocyte, lymphocyte, and monocyte counts and reduced physical fitness in young healthy smokers.

Smoking and interleukin-6 are important factors in driving inflammation. This study assessed the relationship between smoking, interleukin-6 genotype, physical fitness, and peripheral blood count in healthy young men. For this interleukin-6 promoter polymorphism -174 genotype-phenotype association study 1,929 healthy German male aviators recruited at the central German Air Force Institute of Aviation Medicine were stratified by smoking habits. Cardiovascular fitness was expressed as maximal physical working capacity (PWCmax) in watts per kilogram body weight as assessed by maximal exercise testing by cycle ergometry up to physical exhaustion. Smokers had higher leukocyte and lymphocyte counts than nonsmokers and lower PWCmax. In the overall study population the C allele of the interleukin-6 polymorphism was weakly associated with elevated leukocytes and lymphocytes; in nonsmokers the interleukin-6 polymorphism was not associated with altered phenotypes, but in smokers the interleukin-6 C allele was associated with higher leukocytes, lymphocytes, and monocytes and with lower PWCmax. Smoking is thus associated with elevated leukocytes and lymphocytes and with reduced physical fitness. Gene carriers with the interleukin-6 C allele may suffer particularly from cigarette smoking.

Adult↗
PubMed2003

Relation of body mass index, physical fitness, and the cardiovascular risk profile in 3127 young normal weight men with an apparently optimal lifestyle.

Obesity is a well-accepted cardiovascular risk factor associated with hypertension and hyperlipidaemia. A body mass index (BMI) within the range of 18.5-25 kg/m(2) is considered normal. To prevent cardiovascular diseases regular physical activity and abstinence from smoking are strongly recommended. Since it is not evident that a lower optimal threshold exists concerning cardiovascular risk factors if other lifestyle conditions are apparently optimised, we studied the relation between BMI and vascular risk factors in 3127 hyperhealthy Caucasian males. They were aged between 18 and 23 y, were nonsmokers, without regular alcohol intake, and had at least 3 h of sports activity per week. Their BMI was below 25 kg/m(2). Low BMI revealed to be significantly associated with high physical fitness, low blood pressure, and low serum lipids. The lower the BMI was, the more favourable these parameters were. Thus, the threshold for an optimal BMI concerning cardiovascular risk factors might be far below 25 kg/m(2) even if other lifestyle conditions are apparently optimal.

Adolescent↗
PubMed2003

Relation between the angiotensinogen (AGT) M235T gene polymorphism and blood pressure in a large, homogeneous study population.

The aim of this study was to assess the association of the angiotensinogen M235T polymorphism with arterial blood pressure (BP) at rest and under physical stress in a homogeneous large-scale study population. In all, 1903 men who passed routine medical examination for military flying duty were recruited. BP and heart rate were measured at rest, during, and after bicycle ergometry. Genotyping for the AGT M235T polymorphism was carried out by PCR and RFLP technique. The AGT T235 allele was associated with a significantly higher diastolic BP (n=1903; MM 81+/-8, MT 83+/-7, TT 83+/-8; P=0.003). Pulse pressure (PP) at rest differed significantly between AGT genotypes (n=1903; MM 51+/-10 mmHg, MT 49+/-10 mmHg, TT 49+/-10 mmHg; P=0.001). During physical activity, BP values showed no significant difference between genotypes. In healthy young men, the AGT T235 allele is significantly associated with elevated diastolic BP but also reduced PP at rest. During physical activity, the AGT polymorphism had no impact on blood pressure, indicating the existence of other counteracting mechanisms, which might balance the influence of this gene.

Adult↗
PubMed2003

The vitamin D receptor gene variant and physical activity predicts fasting glucose levels in healthy young men.

AIMS: Vitamin D can influence lipolysis and insulin secretion. A common genetic polymorphism of the vitamin D receptor (VDR), which has been found to be associated with bone mineral density, has been reported to be also associated with Type 2 diabetes mellitus (DM). To test the influence of the VDR polymorphism on fasting glucose in healthy young men before the onset of Type 2 DM, we studied a homogeneous population of aircrew members. METHODS: A total of 1539 individuals were recruited during routine medical qualification for flying duty. Physical activity was assessed in all individuals and categorized into low physical activity ( 3 h per week). The BsmI VDR polymorphism was analysed by polymerase chain reaction. On the day of blood testing the individuals were fasting for at least 8 h overnight. Serum glucose was measured within 60 min after sampling venous blood. RESULTS: In young males with low physical activity (n = 752) gene carriers with the VDR genotype BB (n = 137) have significantly (P < 0.001) higher levels of fasting glucose (5.61 +/- 0.49 mmol/l) than gene carriers with the genotype Bb (n = 370; 5.44 +/- 0.44 mmol/l) or bb (n = 245; 5.38 +/- 0.44 mmol/l). Of BB gene carriers, 47% had fasting glucose levels > 5.55 mmol/l compared with 36% of Bb gene carriers and 34% of bb gene carriers (P = 0.018). This effect is absent in gene carriers with high physical activity (n = 787). CONCLUSIONS: The VDR genotype is associated with altered fasting glucose levels in young men with low physical activity. If this association is confirmed in other populations it might be worthwhile studying the particular benefits of an exercise programme in dependents of the VDR genotype.

Adult↗
PubMed2002

Novel sb induced reconstruction of the (113) surface of ge.

Sb induces on Ge(113) a c(2 x 2) reconstruction in which Sb breaks one Ge-Ge bond and occupies an interstitial site, in contrast to Sb adsorption on other Si or Ge surfaces. Sb saturates the three dangling bonds per unit cell of the (113) surface inducing a large strain which is released by occupation of the interstitial site. Two neighboring Sb at interstitial sites form a dimer. The structure has been determined by x-ray diffraction, applying direct methods, and ab initio density-functional-theory calculations. The adsorption geometry and the high binding energy lead one to expect that Sb cannot be used as a surfactant for the growth of Si/Ge layers on the (113) surface.

Journal Article↗
PubMed2002

Application of Nomarski interference contrast microscopy as a thickness monitor in the preparation of transparent, SiC-based, cross-sectional TEM samples.

Reflected light optical microscopy using a Nomarski prism and a differential interference contrast filter have been employed in concert to achieve a technique that provides an accurate color reference for thickness during the dimpling and ion milling of transparent transmission electron microscopy samples of 6H-SiC(000 1) wafers. The samples had thin films of AIN, GaN, and Au deposited on the SiC substrate. A sequence of variously colored primary and secondary interference bands was observed when the SiC was thinner than 20 microm using an optical microscope. The color bands were correlated with the TEM sample thickness as measured via scanning electron microscopy. The interference contrast was used to provide an indication of the dimpling rate, the ion milling rate, and also the most probable location of perforation, which are useful to reduce sample breakage. The application of pressure during the initial cross-sectional preparation reduced the separation of the two halves of the sample sandwich and resulted in increased shielding of the film surface from ion milling damage.

Journal Article↗
PubMed2002

Effects of dexamethasone on proliferation of and fibronectin synthesis by human primary prostatic stromal cells in vitro.

Glucocorticoids are anti inflammatory stress hormones and have been suggested to be involved in a large number of pathological processes. To test the effects of glucocorticoids on stromal prostatic cell growth and proliferation in vitro, the influence of a synthetic glucocorticoid (dexamethasone, dex) on recently established human primary cells from prostatic stroma (hPCPs) was analysed. The localization and distribution of the glucocorticoid receptor (GR) was investigated by immunohistochemistry. In addition, expression of the active isoform of the receptor (alpha-GR) was examined by reverse transcription PCR, and the effect of different doses of dex on proliferation of the stromal cells evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and amido black assays. alpha-GR mRNA was expressed by the hPCPs, and the GR protein was detected in the cytoplasm and nucleus of these cells. Incubating the cells with dex resulted in an enhanced cell proliferation that was mainly restricted to the fibroblasts. Moreover, fibronectin (FN) gene expression and secretion of the protein was increased by high doses of dex (> or = 10(-8) M), whereas low doses of dex (10(-10)M) showed no effect. Human prostatic stromal cells show sensitivity to dex in vitro, resulting in an increase in cell proliferation and FN synthesis. The authors assume that locally accumulating glucocorticoids can also influence the regulation of cell growth and extracellular matrix synthesis in the human prostate in vivo and may play a role in the pathologically altered prostate.

Cell Division↗
PubMed2001

Response-adapted radiotherapy in the treatment of pediatric Hodgkin's disease: an interim report at 5 years of the German GPOH-HD 95 trial.

PURPOSE: A multinational trial on pediatric Hodgkin's disease (HD) with the aim to reduce the risk of long-term toxicity of combined modality treatment by restricting dose and volume of radiation therapy (RT) while maintaining the excellent treatment results of previous German multicenter trials (DAL-HD82-90). METHODS AND MATERIALS: Patients were treated according to stage of disease (CS) and defined risk factors in three treatment groups (TG) with 2, 4, or 6 cycles of combination chemotherapy. When a complete remission (CR) had been achieved, treatment was terminated without RT independent of initial stage or tumor bulk. Patients with a partial remission (PR) of >75% tumor regression were irradiated with 20 Gy using modified involved fields; in the case of PR <75% RT dose was 30 Gy, residual masses >50 mL received 35 Gy. RESULTS: From August 1995 to July 2000 a total of 956 patients have been registered, 830 as trial patients, 39% in TG1, 27% in TG2, 34% in TG3. 827 patients were evaluable by June 2001 with a median follow-up of 38 months. Chemotherapy (CTx) resulted in CR in 22%, PR >75% in 62%, PR <75% in 12%. Event-free survival (EFS) for the entire group is 90% (SD 0.01), for TG1 94%, TG2 91%, and TG3 84%; the overall survival is 97% in Kaplan-Meier-analysis. Relapse-free survival (RFS) is superior for patients with RT after PR (93%) than for those without RT after CR (89%); the difference is significant (p = 0.01) for advanced stages, however not in TG1. Seventy-two events were observed by June 2001: 28 progressions during the initial therapy or within the first 3 months, 38 relapses, 3 second malignancies, three fatal accidents or infections; 18 patients have died. CONCLUSION: Treatment results of the GPOH-HD 95 trial are excellent thus far. The reduction of RT dose and volume in PR has not caused a significant impairment of overall and event-free survival in comparison to the previous German trials; however, failure rates are higher in advanced stages when RT is omitted after achieving a CR. It is too early to tell whether the HD 95 protocol will be successful in reducing late toxicity.

Adolescent↗
PubMed2001

Dinuclear titanium(IV) complexes from amino acid bridged dicatechol ligands: formation, structure, and conformational analysis.

Amino acid bridged dicatechol ligands 3a-e-H4 form dinuclear double-stranded coordination compounds [(3a-e)2Ti2(OCH3)2]2- with titanium(IV) ions. Due to the directionality of the ligands, the chirality of the strand, and the chiral complex units, up to seven isomers, I-VII, can be obtained for the double-stranded complexes of ligands 3a-e-H4. The composition of the mixture of isomeric compounds in solution is strongly dependent on the conditions of complex formation. Under thermodynamic control, only a few isomers are obtained, one of which is the major component of the mixture. X-ray structure analyses were performed for K2[(3b)2Ti2(OH)2] and K2[(3d)2Ti2(OH)2] (type I), and for the meso complex Na2[(3e)(3e')Ti2(OCH3)2]. A conformational analysis that uses Ramachandrans method revealed that the conformation of the amino acids in the ligand strands can be compared with those found for amino acids in helical peptide structures. The most favored isomer of [(3)2Ti2(OCH3)2]2- appears to be of type I, with the catecholamide unit located at the N terminus of the ligand strand that binds to a lambda-configurated titanium(IV) complex unit and the dihydroxybenzyl group at the C terminus that coordinates to a delta-configurated titanium(IV) complex unit. The lambda configuration at the N terminus induces the conformation of a right-handed helix in the amino acid residue, while the delta configuration induces the less favored left-handed helix.

Amino Acids↗
PubMed2001

C(arenium)-C(alkyl) bond making and breaking: key process in the platinum-mediated C(aryl)-C(alkyl) bond formation. Analogies to organic electrophilic aromatic substitution.

The reaction of cationic platinum aqua complexes 2 [Pt(C(6)H(2)[CH(2)NMe(2)](2)-E-4)(OH(2))](X') (X' = SO(3)CF(3), BF(4)) with alkyl halides RX gave various air-stable arenium complexes 3-5 containing a new C-C bond (R = Me, 3; Et, 4; Bn, 5). Electron-releasing oxo-substituents on the aromatic ligand (E = e.g., OH, b; OMe, c) enhance the reactivity of the aqua complex 2 and were essential for arenium formation from alkyl halides different from MeX. This process is initiated by oxidative addition of alkyl halides to the platinum(II) center of 2, which affords (alkyl)(aryl) platinum(IV) complexes (e.g., 9, alkyl = benzyl) as intermediates. Spectroscopic analyses provided direct evidence for a subsequent reversible 1,2-sigmatropic shift of the alkyl group along the Pt-C(aryl) bond, which is identical to repetitive C(arenium)-C(alkyl) bond making and breaking and concerted metal reduction and oxidation. Temperature-dependent NMR spectroscopy revealed DeltaH degrees = -1.3 (+/- 0.1) kJ mol(-1), DeltaS degrees = +3.8 (+/- 0.2) J mol(-1) K(-1), and DeltaG degrees (298) = -2.4 (+/- 0.1) kJ mol(-1) for the formation of the arenium complex 5b from 9 involving the migration of a benzyl group. The arenium complexes were transformed to cyclohexadiene-type addition products 7 or to demetalated alkyl-substituted arenes, 8, thus completing the platinum-mediated formation of a sp(2)-sp(3) C-C bond which is analogous to the aromatic substitution of a [PtX](+) unit by an alkyl cation R(+). The formation of related trimethylsilyl arenium complexes 6 suggests arenium complexes as key intermediates, not only in (metal-mediated) sp(2)-sp(3) C-C bond making and breaking but also in silyl-directed cyclometalation.

Journal Article↗