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Biomedical subjects

A Knoll

Publications and source records attributed to A Knoll.

At least 19 recordsLinked to original sources
PubMed2006

Clinical benefit of enzyme replacement therapy in Fabry disease.

Enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A (r-halphaGalA) enhances microvascular globotriaosylceramide clearance and improves clinical symptoms in patients with Fabry disease. We evaluated whether these effects are translated into a long-term benefit of kidney and heart function. We did a single center, prospective, open label study in 26 patients with Fabry disease (one early death, follow-up in 25 patients). r-Alpha-GalA was administered in a dosage of 1 mg/kg body weight every second week. The effect of therapy on clinical end points (death, cardiac and cerebrovascular event, renal failure), cardiac and renal function monitored by Doppler echocardiography, 99Tc-GFR, and proteinuria was investigated. After a mean treatment time of 23 +/- 8 months, nine patients experienced 12 end points, including two deaths. All end points occurred in patients with impaired renal function (n = 16; GFR 71 +/- 17 ml/min/1.73 m2). Despite ERT, renal function deteriorated to 60 +/- 23 ml/min/1.73 m2 (P = 0.04) and left ventricular posterior wall thickness (PWT) did not change (14.0 +/- 2.1 vs 13.4 +/- 2.3 mm). In contrast, patients without impairment of renal function (n = 9) had a more favorable outcome (no clinical events; GFR 115 +/- 18 vs 102 +/- 14 ml/min/1.73 m2, NS; PWT 11.7 +/- 1 and 10.7+/-0.7 mm, P = 0.04). Proteinuria remained unchanged (1.34 +/- 0.94 vs 1.01 +/- 0.97 g/day, n = 10). Patients with impaired renal function have a less favorable outcome and may develop cardiovascular and renal end points despite ERT.

Adult↗
PubMed2006

Porcine OGN and ASPN: mapping, polymorphisms and use for quantitative trait loci identification for growth and carcass traits in a Meishan x Piétrain intercross.

The porcine orthologues of human chromosome HSA9q22.31 genes osteoglycin (OGN) and asporin (ASPN) were mapped to porcine chromosome SSC3 using linkage analysis and a somatic cell hybrid panel. This mapping was refined to SSC3q11 using fluorescence in situ hybridization. These results confirm the existence of a small conserved synteny group between SSC3 and HSA9. Polymorphisms were revealed in both genes, including a pentanucleotide microsatellite (SCZ003) in OGN and two single nucleotide polymorphisms (AM181682.1:g.780G>T and AM181682.1:g.825T>C) in ASPN. The two genes were included in a set of markers for quantitative trait loci (QTL) mapping on SSC3 in the Hohenheim Meishan x Piétrain F2 family. Major QTL for growth and carcass traits were centred in the ASPN-SW902 region.

Animals↗
PubMed2006

New SNPs in the IGF2 gene and association between this gene and backfat thickness and lean meat content in Large White pigs.

IGF2-in3-G3072A is a causative mutation for paternally expressed quantitative trait loci on the p arm of porcine chromosome 2 with substantial effect on muscle growth and backfat thickness. The linkage disequilibrium between IGF2-in3-G3072A and IGF2-in7-G162C (IGF2-NciI) in four breeds and associations between these polymorphisms and growth and meat performance in pigs of the Large White breed were analysed. A significant effect of these polymorphisms on backfat thickness and lean meat content was found. In addition, we identified two new single nucleotide polymorphisms (SNPs) in intron 7 of the gene. The existence of complete linkage disequilibrium between IGF2-in3-G3072A locus in the population under study where the locus segregated and SNPs in intron 7 of the IGF2 gene detectable with simple and reliable polymerase chain reaction-restriction fragment length polymorphism techniques (G162C, C179G and G186T) offer possibilities to use these SNPs for genotyping of quantitative trait nucleotide in Large White and Landrace breeds.

Animals↗
PubMed2005

Cerebral glucose metabolism in patients with AD and different APOE genotypes.

OBJECTIVE: To examine the influence of the APOE epsilon4 allele on cerebral glucose metabolism in a large series of patients with Alzheimer disease (AD). METHODS: Eighty-three patients (41 APOE epsilon4 positive and 42 epsilon4 negative) were selected from a pre-existing databank of patients with AD (n > 1,000). The patients were carefully matched for age, age at onset, approximate disease duration, educational level, and overall degree of cognitive impairment. Cerebral [18F]fluorodeoxyglucose PET imaging was performed in all patients by a standardized protocol. Statistical comparison of patient PET data vs a healthy control population was performed as well as an analysis of differences between groups (SPM99; Wellcome Department of Cognitive Imaging, London, UK). RESULTS: A similar pattern of cerebral hypometabolism was detected in the epsilon4-positive and -negative patient groups vs healthy volunteers in regions typically affected by AD (bilateral temporal, parietal, posterior cingulate, and prefrontal cortical areas). The comparison between epsilon4-positive and -negative patients additionally revealed stronger abnormalities in epsilon4 carriers in parietal, temporal, and posterior cingulate cortical regions. CONCLUSIONS: A generally similar pattern of cerebral hypometabolism was detected in APOE epsilon4-positive and -negative patients with Alzheimer disease. However, in direct comparison of the two matched groups, the abnormalities in the epsilon4-positive group were demonstrated to be more pronounced.

Aged↗
PubMed2005

Morbus Fabry of the heart. Why should cardiologists care?

Fabry Disease is an X-linked lysosomal storage disorder leading to the accumulation of glycosphingolipids, mainly globotriaosylceramides in all tissues and solid organs of the body. The disease was described by Johannes Fabry and William Anderson coevally in 1898. Beside the involvement of the central nervous system, peripheral nerves, kidneys, skin and endovascular endothelium, the heart plays a major role in the disease. Left ventricular hypertrophy is one hallmark initially presenting with preserved ventricular function. However, with progression of the disease patients die due to heart failure. Though angina is often reported, the incidence of epicardial coronary stenosis is not a dominant feature, if at all small vessel disease can occur. In respect of arrhythmias a broad spectrum can be seen including shortened or prolonged PR-intervals, AV blocks of different degrees and sometimes malignant ventricular arrhythmias. In the past, women were considered to be carriers of the disease but hardly to develop clinical symptoms. In recent years there is evidence that female carriers may more often be affected with severe symptoms. In addition, a group of Fabry patients displaying mainly cardiac involvement were described as having a cardiac variant of the disease. This implied the hypothesis that some of those patients with unexplained myocardial hypertrophy do suffer from Fabry disease. Since 2002 enzyme replacement therapy is available and there is first evidence for its efficacy to reduce hypertrophy and increase myocardial function. If this is associated with a prognostic improvement has to be determined in future studies.

Cardiology↗
PubMed2004

Direct imaging and mesoscale modelling of phase transitions in a nanostructured fluid.

The kinetics of phase transitions is essential for understanding pattern formation in structured fluids. These fluids play a key role in the morphogenesis of biological cells, and they are very common in pharmaceutical products and plastic materials. Until now, it has not been possible to follow phase transitions in structured fluids experimentally in real time and with high spatial resolution. Previous work has relied on static images and indirect experimental evidence from spatially averaging scattering experiments. Simulating the processes with computer models is a further challenge because of the multiple time and length scales involved. Our movies based on in situ scanning force microscopy show the time sequence of the elementary steps of a phase transition in a fluid film of block copolymer from the cylinder to the perforated lamella phase. The movies validate a versatile simulation model that gives physical insight into the nature of the process. Our approach provides a means of improving the study and understanding of pattern formation processes in nanostructured fluids. We expect a significant impact on nanotechnology where block copolymers serve as self-organized templates for the synthesis of inorganic nanostructured materials.

Computer Simulation↗
PubMed2004

The Spirit Rover's Athena science investigation at Gusev Crater, Mars.

The Mars Exploration Rover Spirit and its Athena science payload have been used to investigate a landing site in Gusev crater. Gusev is hypothesized to be the site of a former lake, but no clear evidence for lacustrine sedimentation has been found to date. Instead, the dominant lithology is basalt, and the dominant geologic processes are impact events and eolian transport. Many rocks exhibit coatings and other characteristics that may be evidence for minor aqueous alteration. Any lacustrine sediments that may exist at this location within Gusev apparently have been buried by lavas that have undergone subsequent impact disruption.

Atmosphere↗
PubMed2002

Microscopic mechanisms of electric-field-induced alignment of block copolymer microdomains.

We investigate the microscopic mechanisms responsible for microdomain alignment in block copolymer solutions exposed to an electric field. Using time-resolved synchrotron small-angle x-ray scattering, we reveal two distinct processes, i.e., grain boundary migration and rotation of entire grains, as the two dominant microscopic mechanisms. The former dominates in weakly segregating systems, while the latter is predominant in strongly segregated systems. The kinetics of the processes are followed as a function of polymer concentration and temperature and are correlated to the solution viscosity.

Journal Article↗
PubMed2002

Phase behavior in thin films of cylinder-forming block copolymers.

We have experimentally determined a phase diagram for cylinder-forming polystyrene-block-polybutadien-block-polystyrene triblock copolymer in thin films. The phase behavior can be modeled in great detail by dynamic density functional theory. Deviations from the bulk structure, such as wetting layer, perforated lamella, and lamella, are identified as surface reconstructions. Their stability regions are determined by an interplay between surface fields and confinement effects.

Journal Article↗
PubMed2002

UV light-damaged DNA and its interaction with human replication protein A: an atomic force microscopy study.

We have imaged a non-damaged and UV-damaged DNA fragment and its complexes with human replication protein A (RPA) using tapping mode atomic force microscopy (AFM). For imaging, molecules were immobilized under nearly physiological conditions on mica surfaces. Quantitative sizing of the 538 bp DNA before and after UV light treatment shows a reduction in the contour and persistence lengths and mean square end-to-end distance as a consequence of UV irradiation. Complexes of the UV-damaged DNA with RPA, an essential component of the initial steps of nucleotide excision repair, can be detected at high resolution with AFM and reveal conformational changes of the DNA related to complex formation. By phase image analysis we are able to discriminate between protein and DNA in the complexes. The DNA molecules are found to 'wrap' around the RPA, which in turn results in a considerable reduction in its apparent contour length.

DNA↗