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Biomedical subjects

H Klein

Publications and source records attributed to H Klein.

At least 19 recordsLinked to original sources

In situ and real-time probing of quasicrystal solidification dynamics by synchrotron imaging.

Quasicrystal growth remains an unsolved problem in condensed matter. The dynamics of the process is studied by means of synchrotron live imaging all along the solidification of icosahedral AlPdMn quasicrystals. The lateral motion of ledges driving faceted growth at the solid-melt interface is conclusively shown. When the solidification rate is increased, nucleation and free growth of new faceted grains occur in the melt due to the significant interface recoil induced by slow attachment kinetics. The detailed analysis of the evolution of these grains reveals the crucial role of aluminum rejection, both in the poisoning of their growth and driving fluid flow.

Journal Article↗

Transplantation of bone marrow-derived mesenchymal stem cells rescue photoreceptor cells in the dystrophic retina of the rhodopsin knockout mouse.

BACKGROUND: Retinitis pigmentosa belongs to a large group of degenerative diseases of the retina with a hereditary background. It involves loss of retinal photoreceptor cells and consequently peripheral vision. At present there are no satisfactory therapeutic options for this disease. Just recently the use of mesenchymal stem cells has been discussed as one therapeutical option for retinal degeneration, as they have been shown to differentiate into various cell types, including photoreceptor cells. In this article we wanted to investigate the potency of mesenchymal stem cells to induce rescue effects in an animal model for retinitis pigmentosa, the rhodopsin knockout mouse. METHODS: For the experiments, three experimental groups of 10 animals each were formed. The first group consisted of untreated rhodopsin knockout (rho(-/-)) animals used as controls. The second group consisted of rho(-/-) mice that had received an injection of mouse mesenchymal stem cells, which were transduced using an adenoviral vector containing the sequence for the green fluorescent protein (GFP) prior to transplantation. In the third sham group, animals received an injection of medium only. Thirty-five days after transplantation, GFP-expressing cells were detected in whole-mount preparations of the retinas as well as in cryostat sections. For the detection of rescue effects, semi-thin sections of eyes derived from all experimental groups were produced. Furthermore, rescue effects were also analysed ultrastructurally in ultrathin sections. RESULTS: Histological analysis revealed that after transplantation, cells morphologically integrated not only into the retinal pigment epithelium but also into layers of the neuroretina displaying neuronal and glial morphologies. Furthermore, significant rescue effects, as demonstrated by the occurrence of preserved photoreceptor cells, were detected. CONCLUSIONS: Our data indicate that mesenchymal stem cells can prolong photoreceptor survival in the rhodopsin knockout mouse, also providing evidence of a therapeutical benefit in retinitis pigmentosa.

Adenoviridae↗

Multicenter phase-I/II study using a combination of gemcitabine and docetaxel in metastasized and unresectable, locally advanced pancreatic carcinoma.

AIMS: To assess the maximum tolerability of a combined therapy regimen of gemcitabine and docetaxel, and to evaluate tumour response rate, survival time and tolerability in patients receiving these agents for advanced pancreatic carcinoma. PATIENTS AND METHODS: Patients (n=68) with pancreatic carcinoma (advanced and/or unresectable tumour growth or histopathologically diagnosed metastases) were enrolled in a multicenter phase-I (n=25) and phase-II study (n=43). Treatment during phase II of the study was continued until either complete tumour remission (CR), tumour progression, indicated clinically or by means of radiological imaging, or until unacceptable toxicity occurred. RESULTS: Phase I: the tolerability maximum of the combined agents was established at gemcitabine 1000 mg/m(2) and docetaxel 35 mg/m(2) with tolerable adverse events. Phase II: a total of 139 chemotherapy cycles were completed (mean, 3.2; range, 1-10). While CR was achieved in three of 43 patients (7%), in five further cases, partial remission (PR) was documented, amounting to an overall response rate (OR) of 18.6%. Eighteen patients showed stable disease (41.9%), whereas in 17 of 43 subjects (39.5%), primary tumour progression was detected. The median survival time was 9.0 months; the 1-year survival rate was 13.9% (six of 43 patients). These results were associated with a side-effect profile of moderate severity and acceptable quality of life (QOL). CONCLUSION: The combination of gemcitabine and docetaxel for chemotherapy in unresectable pancreatic carcinoma was well tolerated. Survival time and 1-year survival rate proved promising and the regimen appears suitable for further evaluation in a prospective phase-III study setting.

Adult↗

Thin is "in" and stout is out" what animated cartoons tell viewers about body weight.

Relying upon a content analysis of one specific type of medium to which young people are exposed beginning at an early age, on a regular basis, and for many years (i.e., animated cartoons), the present study examines what types of messages are provided about being underweight, overweight and normal weight. This research examines the following issues: (1) How prevalent is weight-related content in animated cartoons? (2) Has this prevalence changed over time? (3) What "types" of characteristics tend to be associated with being thinner-than-normal or heavier-than normal? Results indicate that the prevalence of both underweight and overweight characters has changed dramatically over the course of the past several decades. These relationships are both curvilinear in nature, but in recent decades have demonstrated a significant increase in the proportion of all cartoons showing characters that are underweight and a simultaneous decrease in the prevalence of characters that are overweight. Many variables were found to differ based on cartoon characters' body weight including gender, age, intelligence, physical attractiveness, emotional states experienced, prosocial behaviors, antisocial behaviors, and overall goodness/badness. Whenever differences were found, the overriding tendency was for cartoons to provide positive messages about being thin and negative messages about being overweight.

Body Image↗

Euro heart failure survey. Medical treatment not in line with current guidelines.

UNLABELLED: It was the aim of the Euro Heart Survey on Heart Failure to assess whether patients are being treated according to current guidelines. METHODS: In Germany, patients were screened in 7 medical centers if their discharge diagnoses were myocardial infarction, a new episode of atrial fibrillation, or diabetes mellitus. Patients were enrolled if at least one additional criterion was fulfilled: (1) clinical diagnosis of heart failure, (2) hospital admission due to heart failure within the last 3 years, (3) therapy with loop diuretic, (4) medication for heart failure or ventricular dysfunction documented by echocardiography within the past 24 hours prior to death. RESULTS: 2166 patients were screened of whom 747 were included in the study (478 men, 269 women). 93% of the patients suffered from heart failure. Despite the high number of patients with known heart failure (ischemic heart failure in 71%), only 72% received ACE inhibitors and 62% beta-blockers. Average daily dose met recommendations in only 63% of patients on ACE inhibitors and 54% on beta-blockers. 74% of the patients received diuretics (furosemide 36%, thiazide 34%, spironolactone 17%). CONCLUSION: An inadequately low number of patients with heart failure receives medical therapy according to guidelines, despite all the overwhelming evidence for improved morbidity and mortality. Awareness of physicians needs to be improved.

Adrenergic beta-Antagonists↗

Replacement of a severe chronic post-traumatic aneurysm of the ascending aorta with aortic valve conduit--reconstruction of the anterior mitral valve ring and implantation of A-V sequential/biventricular pacemaker.

We present the case of a 23-year-old African professional footballer who was admitted on April 1, 1999 to the Cardiology Department of the University Hospital in Magdeburg, on an emergency basis, from a regional lung clinic. According to the history, he was involved in a collision with an opposing player during a football match in his country (in Africa). He lost consciousness for a short time, but continued playing to the end of the match. About two months later he was invited by a German football club for a check-up, with the view to ultimately playing for the club. The team did not find him physically fit enough to play professional football, so he decided to go to Paris by bus on March 31, 1999. During the journey he suddenly became cardio-pulmonary decompensated and had to undergo cardio-pulmonary resuscitation (CPR). He was intubated and placed on a respirator and immediately transferred to a nearby lung clinic. From the lung clinic he was transferred to the Intensive Care Unit of the Cardiology Department of the Magdeburg University Hospital, on April 1, 1999 as an emergency case. He was intensively treated with catecholamines, intravenous ACE inhibitors and diuretics. His clinical condition did not improve appreciably. His chest X-ray showed extreme dilatation of the right and left heart as well as extreme pulmonary congestion.

Adult↗

Measurement and Monte Carlo modelling of the JRC 241Am-Li(alpha,n) source spectrum.

The neutron energy spectrum of the JRC 241Am-Li(alpha,n) radionuclide source has been measured at the PTB in Germany using various spectrometry systems, such as Bonner spheres, proton recoil counters and NE213 liquid scintillators. The source photon spectrum has been measured and the neutron contamination due to traces of beryllium through the 9Be(alpha,n)12C reaction has been determined. The effects associated with source encapsulation and the materials it contains have been investigated previously, using Monte Carlo simulations, the various structures seen in the spectra have been explained and the anisotropy of fluence distributions in 4pi have been calculated and compared to measurements. These extensive high resolution spectrometry measurements have been coupled to Monte Carlo calculations to provide a realistic spectrum and new spectrum-averaged fluence-to-dose equivalent conversion coefficients for the actual 241Am-Li source.

Americium↗

Quasi-monoenergetic neutron reference fields in the energy range from thermal to 200 MeV.

Well-characterised neutron fields are a prerequisite for the investigation of neutron detectors. Partly in collaboration with external partners, the PTB neutron metrology group makes available for other users neutron reference fields covering the full energy range from thermal to 200 MeV. The specification of the neutron fluence in these beams is traceable to primary standard cross sections.

Algorithms↗

Contribution of cytosolic cysteine residues to the gating properties of the Kir2.1 inward rectifier.

The topological model proposed for the Kir2.1 inward rectifier predicts that seven of the channel 13 cysteine residues are distributed along the N- and C-terminus regions, with some of the residues comprised within highly conserved domains involved in channel gating. To determine if cytosolic cysteine residues contribute to the gating properties of Kir2.1, each of the N- and C-terminus cysteines was mutated into either a polar (S, D, N), an aliphatic (A,V, L), or an aromatic (W) residue. Our patch-clamp measurements show that with the exception of C76 and C311, the mutation of individual cytosolic cysteine to serine (S) did not significantly affect the single-channel conductance nor the channel open probability. However, mutating C76 to a charged or polar residue resulted either in an absence of channel activity or a decrease in open probability. In turn, the mutations C311S (polar), C311R (charged), and to a lesser degree C311A (aliphatic) led to an increase of the channel mean closed time due to the appearance of long closed time intervals (T(c) >or= 500 ms) and to a reduction of the reactivation by ATP of rundown Kir2.1 channels. These changes could be correlated with a weakening of the interaction between Kir2.1 and PIP(2), with C311R and C311S being more potent at modulating the Kir2.1-PIP(2) interaction than C311A. The present work supports, therefore, molecular models whereby the gating properties of Kir2.1 depend on the presence of nonpolar or neutral residues at positions 76 and 311, with C311 modulating the interaction between Kir2.1 and PIP(2).

Animals↗

Internal olefins to linear amines.

The selective synthesis of linear amines from internal olefins or olefin mixtures was achieved through a catalytic one-pot reaction consisting of an initial olefin isomerization followed by hydroformylation and reductive amination. Key to the success is the use of specially designed phosphine ligands in the presence of rhodium catalysts. This reaction constitutes an economically attractive and environmentally favorable synthesis of linear aliphatic amines.

Journal Article↗

X-ray diffraction topography using a diffractometer with a bendable monochromator at a synchrotron radiation source.

The different properties of laboratory- and synchrotron-based double-crystal setups for X-ray topographic applications are discussed as a basis for the realization of a versatile instrument allowing the investigation of all kinds of crystals with high strain sensitivity and without any reduction in image size. It appears that the use of a bendable highly perfect monochromator (silicon) achieves this goal, through the local adaptation of Bragg angles, to compensate either dispersion or a bending of the sample.

Journal Article↗

A specific tryptophan in the I-II linker is a key determinant of beta-subunit binding and modulation in Ca(V)2.3 calcium channels.

The ancillary beta subunits modulate the activation and inactivation properties of high-voltage activated (HVA) Ca(2+) channels in an isoform-specific manner. The beta subunits bind to a high-affinity interaction site, alpha-interaction domain (AID), located in the I-II linker of HVA alpha1 subunits. Nine residues in the AID motif are absolutely conserved in all HVA channels (QQxExxLxGYxxWIxxxE), but their contribution to beta-subunit binding and modulation remains to be established in Ca(V)2.3. Mutations of W386 to either A, G, Q, R, E, F, or Y in Ca(V)2.3 disrupted [(35)S]beta3-subunit overlay binding to glutathione S-transferase fusion proteins containing the mutated I-II linker, whereas mutations (single or multiple) of nonconserved residues did not affect the protein-protein interaction with beta3. The tryptophan residue at position 386 appears to be an essential determinant as substitutions with hydrophobic (A and G), hydrophilic (Q, R, and E), or aromatic (F and Y) residues yielded the same results. beta-Subunit modulation of W386 (A, G, Q, R, E, F, and Y) and Y383 (A and S) mutants was investigated after heterologous expression in Xenopus oocytes. All mutant channels expressed large inward Ba(2+) currents with typical current-voltage properties. Nonetheless, the typical hallmarks of beta-subunit modulation, namely the increase in peak currents, the hyperpolarization of peak voltages, and the modulation of the kinetics and voltage dependence of inactivation, were eliminated in all W386 mutants, although they were preserved in part in Y383 (A and S) mutants. Altogether these results suggest that W386 is critical for beta-subunit binding and modulation of HVA Ca(2+) channels.

Amino Acid Motifs↗

Role of aspartate residues in Ca(2+) affinity and permeation of the distal ECaC1.

The Ca(2+) affinity and permeation of the epithelial Ca(2+) channel (ECaC1) were investigated after expression in Xenopus oocytes. ECaC1 displayed anomalous mole-fraction effects. Extracellular Ca(2+) and Mg(2+) reversibly inhibited ECaC1 whole cell Li(+) currents: IC(50) = 2.2 +/- 0.4 microM (n = 9) and 235 +/- 35 microM (n = 10), respectively. These values compare well with the Ca(2+) affinity of the L-type voltage-gated Ca(2+) (Ca(V)1.2) channel measured under the same conditions, suggesting that high-affinity Ca(2+) binding is a well-conserved feature of epithelial and voltage-gated Ca(2+) channels. Neutralization of D550 and E535 in the pore region had no significant effect on Ca(2+) and Mg(2+) affinities. In contrast, neutralization of D542 significantly decreased Ca(2+) affinity (IC(50) = 1.1 +/- 0.2 mM, n = 6) and Mg(2+) affinity (IC(50) > 25 +/- 3 mM, n = 4). Despite a 1,000-fold decrease in Ca(2+) affinity in D542N, Ca(2+) permeation properties and the Ca(2+)-to-Ba(2+) conductance ratio remained comparable to values for wild-type ECaC1. Together, our observations suggest that D542 plays a critical role in Ca(2+) affinity but not in Ca(2+) permeation in ECaC1.

Amino Acid Sequence↗