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Biomedical subjects

M Förster

Publications and source records attributed to M Förster.

At least 19 recordsLinked to original sources

Mapping of quantitative trait loci for lactation persistency traits in German Holstein dairy cattle.

A whole genome scan to map quantitative trait loci (QTL) for persistency of milk yield (PMY), persistency of fat yield (PFY), persistency of protein yield (PPY) and persistency of milk energy yield (PEY) was performed in a granddaughter design in the German Holstein dairy cattle population. The analysis included 16 paternal half-sib families with a total of 872 bulls. The analysis was carried out for the first lactation and for the first three lactations combined using univariate weighted multimarker regression. Controlling the false discovery rate across traits and data sets at a level of 0.15 and treating the four persistency traits as different traits revealed 27 significant QTL. A total of 12 chromosomes showed significant QTL effects on a chromosomewise basis. The DGAT1 effect was highly significant for PPY and protein yield. A haplotype analysis using results of previous studies of the same design revealed a co-segregation of various persistency QTL and QTL affecting health traits like dystocia and stillbirth and functional traits like non-return rate 90 and somatic cell score.

Animals↗

[Interferon-alpha treatment of the Churg-Strauss syndrome].

HISTORY: Two patients, 60 (pat. 1; female) and 30 years of age (pat. 2; male), respectively, suffering from a histologically confirmed Churg-Strauss-syndrome and receiving immunosuppressive therapy were treated with Interferon-alpha. INVESTIGATIONS: Clinical complaints, disease activity, blood eosinophil counts, and lung function were monitored. In patient 1 the differential cell counts and immunocytology of bronchoalveolar lavage cells were assessed using flow cytometry. TREATMENT AND COURSE: Both patients were treated with interferon-alpha in dosages of 3 million units of IFN-alpha 2b or an equivalent dosage of interferon-acon thrice weekly subcutaneously. The patients were observed for a period of up to 24 months. Interferon-alpha induced remission of disease and allowed discontinuation of oral glucocorticoid therapy in both patients. Treatment also improved the peripheral polyneuropathia in patient 1 as well as the hemorrhagic cystitis and reduction of the Cushing syndrome (weight reduction of 19 kg) in patient 2. In addition, blood eosinophil counts normalised. After 12 months of treatment, the number of bronchoalveolar eosinophils decreased from 61,5% (5.7 x 106 cells/ml) to 7% (1.1 x 106 cells/ml). In addition, the proportion of CD4+ T-lymphocytes and B-cells increased, while CD8+ T-cells and NK cells decreased (pat. 1). CONCLUSION: Interferon-alpha may represent an effective alternative to the current treatment of Churg-Strauss syndrome consisting of corticosteroids and immunosuppressives.

Administration, Oral↗

Body composition and bone mineralization measurement in calves of different genetic origin by using dual-energy X-ray absorptiometry.

The purpose of this study was to investigate the differences in bone mineralization [bone mineral density (BMD, g/cm(2)), and bone mineral content (BMC, %)] and body composition of F1 and F2 crossbred calves and their purebred controls from the dairy breeds German Holsteins (GH) and German Fleckvieh (FV). In total, 62 male and 64 female calves were analyzed under light sedation with dual-energy X-ray absorptiometry (DXA). The study started when the calves were 4 days old and continued until they were 60 days old. GH calves had a significantly lower BMD than all other lines-with the highest BMD and BMC in the FV male symbol x F1 female symbol line. Since the average BMD of the F1 calves was higher than the average BMD of their parents, a small heterosis effect for this trait seems likely. The absolute differences in soft tissue composition were small with a slightly higher average fat content for F1 calves compared with the parent breeds.

Absorptiometry, Photon↗

Quantitative trait loci mapping of functional traits in the German Holstein cattle population.

A whole-genome scan to detect quantitative trait loci (QTL) for functional traits was performed in the German Holstein cattle population. For this purpose, 263 genetic markers across all autosomes and the pseudoautosomal region of the sex chromosomes were genotyped in 16 granddaughter-design families with 872 sons. The traits investigated were deregressed breedingvalues for maternal and direct effects on dystocia (DYSm, DYSd) and stillbirth (STIm, STId) as well as maternal and paternal effects on nonreturn rates of 90 d (NR90m, NR90p). Furthermore, deregressed breeding values for functional herd life (FHL) and daughter yield deviation for somatic cell count (SCC) were investigated. Weighted multimarker regression analyses across families and permutation tests were applied for the detection of QTL and the calculation of statistical significance. A ten percent genomewise significant QTL was localized for DYSm on chromosome 8 and for SCC on chromosome 18. A further 24 putative QTL exceeding the 5% chromosomewise threshold were detected. On chromosomes 7, 8, 10, 18, and X/Yps, coincidence of QTL for several traits was observed. Our results suggest that loci with influence on udder health may also contribute to genetic variance of longevity. Prior to implementation of these QTL in marker assisted selection programs for functional traits, information about direct and correlated effects of these QTL as well as fine mapping of their chromosomal positions is required.

Animals↗

Pesticide residues in biological waste.

The aim of this study was to detect crop protection products (CPP) in single fractions of biological waste and to estimate pesticide concentrations in biological waste, depending on its composition. The composition of biological waste was determined from the literature, which provided information on its local and seasonal variability. The residue analysis included 17 pesticides for the analysis of tropical fruit peels and 48 pesticides for other fractions, e.g. vegetables, other fruits and ornamental flowers. The freeze-dried samples were extracted ultrasonically and purified by means of gel permeation chromatography. The analysis was carried out using gas chromatography with a mass selective detector in the selected ion monitoring mode. All tropical fruit peels contained CPP-residues. Thiabendazole was the most important contaminant with respect to the concentration and frequency of occurrence. The vegetables, other fruits and flowers also contained CPP-residues, such as the fungicides captan and dodemorph and the insecticide endosulfan. Based on import data and the composition of biological waste, the CPP-content of biological waste was estimated for rural and urban areas in summer and winter. Due to the higher percentage of tropical fruit peels, thiabendazole was the main contaminant in winter. The total concentration of CPP, summed up over all substances, ranged between 828 and 1829 microg(kg ww)(-1).

Agriculture↗

Mapping of the bovine blood group systems J, N', R', and Z show evidence for oligo-genetic inheritance.

Genes determining the bovine erythrocyte antigens were mapped by linkage analysis. In total 9591 genotypes of 20 grandsire families with 1074 sires from a grand-daughter design were elucidated for the genes determining the erythrocyte antigens EAA, EAB, EAC, EAF, EAJ, EAL, EAM, EAN', EAR', EAS, EAT', and EAZ according to standard paternity testing procedures in the blood typing laboratories. Linkage analyses were performed with 248 microsatellite markers, eight SSCP markers and four polymorphic proteins and enzymes covering the 29 autosomes and the pseudoautosomal region of the sex chromosomes. The number of informative meioses for the blood group systems ranged from 76 to 947. Blood group systems EAM and EAT' were non-informative. Most of the erythrocyte antigen loci showed significant linkage to a single chromosome and were mapped unequivocally. The genes determining erythrocyte antigen EAA, EAB, EAC, EAL, and EAS were mapped to chromosomes 15, 12, 18, 3, and 21, respectively. Lod-score values ranged from 11.43 to 107.83. Moreover, the EAF system could be mapped to chromosome 17. However, the EAN' system previously known as part of the EAF system could be mapped to chromosome 5. In addition, the blood group systems EAJ, the new EAN', EAR', and EAZ, showed significant linkage to microsatellite markers on various chromosomes and also to other blood groups. The appearance of a single blood group system might be therefore either dependent on the existence of other blood group systems or because of an interaction between different loci on various chromosomes as is known in humans and in pigs.

Animals↗

A whole genome scan for differences in recombination rates among three Bos taurus breeds.

Twenty paternal half-sib families of a granddaughter design were genotyped for 265 genetic markers, most of them microsatellites. These were 16 Holstein families, 3 Simmental families, and 1 Brown Swiss family. The number of sires per breed was 872, 170, and 32, respectively. Two-point recombination rates were estimated both jointly for all breeds and each single breed separately. Of 1168 marker intervals, 865 provided estimates for at least two breeds. Differences between breeds were tested by likelihood ratio tests. Four marker intervals, representing three genomic regions on BTA19, BTA24, and BTA27, show a significant impact of the breed at a false discovery rate of 0.23 and indicate a genetic component of observed heterogeneity of recombination. The variability of recombination rates between cattle breeds might not be a common feature of the whole genome, but rather might be restricted to certain chromosomal segments. Thus, attention should be paid to heterogeneities when pooling data of such regions from different breeds.

Animals↗

Genotyping of dinucleotide tandem repeats by MALDI mass spectrometry of ribozyme-cleaved RNA transcripts.

We describe a method for high-throughput typing of short tandem repeat (STR) polymorphisms. Current gel electrophoresis techniques allow only moderate throughput with long hands-on and analysis time, and the output is on a relative scale of electrophoretic mobility, prone to artifacts. Matrix-assisted laser- desorption/ionization mass spectrometry (MALDI-MS) enables an automated high throughput and delivers accurate data directly depicting the molecular nature of the analyte. Analysis of large DNA fragments, however, is limited by adduct formation and fragmentation, which result in peak broadening and low signal intensity. MALDI typing of polymorphic STRs has been reported for tri- and tetranucleotide repeats with sufficient resolution to distinguish alleles. For dinucleotide repeats, essential in animal genome studies, an enhanced resolution is necessary. Increased mass resolution was reported for RNA (ref. 7) and modified DNA (refs 8-10) due to substituents that disfavor intramolecular reactions leading to fragmentation. RNA transcripts can be synthesized enzymatically from PCR products containing a promoter sequence, requiring no specialty reagents or primer labels. Furthermore, RNA transcripts are single-stranded, a prerequisite for high-resolution mass spectrometry of nucleic acids. The 3' heterogeneities produced by viral RNA polymerases, however, impede exact sizing of RNA runoff transcripts. Non-templated multiple-base extensions as well as premature termination have been reported. PCR of dinucleotide repeats tends toward the deletion of repeat units, generating a complex pattern of interleaved extensions (from RNA polymerase) and deletions (from PCR) that obscure the true allele size. We overcome this obstacle by adding a 3' sequence encoding a catalytic RNA sequence, the so-called hammerhead ribozyme, that cleaves itself co-transcriptionally, creating a homogeneous 3' end.

Alleles↗

[Molecular mechanisms of signal transduction in the framework of CD95 and CD65 receptor-induced apoptosis of human eosinophilic granulocytes. Effect on GM-CSF mediated viability and relationship to intracellular bcl-2 expression].

Infiltration of eosinophils into the airways plays a central role in the pathophysiology of asthma. Human blood eosinophils express apoptosis-inducing receptors (e.g. CD95R and CD69R) regulating both viability and survival and, thus, the extent of eosinophil infiltration into the airways. Signal transduction processes induced by occupation of the CD69 receptor expressed by eosinophils are insufficiently known. Purified human peripheral blood eosinophils (MACS, purity > 99%) were pre-incubated with a GM-CSF for 18 h and stimulated with alpha-CD69mAb (clon TP1/55), alpha-CD95mAb (clon CH-11), and as a control alpha-CD11bmAb (clon Bear-1). The specificity of receptor ligation was assessed using a blocking mAb (Klon ZB4). Phenotype, viability, apoptosis and bcl-2-expression were measured employing flow cytometry. alpha-CD95mAb (1 microgram/ml) induced apoptosis both in control and GM-CSF (10 ng/ml) treated eosinophils. Similarly, alpha-CD69mAb (10 micrograms/ml) induced apoptosis of GM-CSF-stimulated CD69+ cells after an incubation period of 114 h which was not affected by a CD95 blocking mAb. Naive eosinophils showed a basale, bcl-2-expression, which decreased to 30% after 66 h. In the presence of GM-CSF, intracellular bcl-2-concentration remained unchanged. Following stimulation with alpha-CD69mAb or alpha-CD95mAb, a dose-dependent decline of the bcl-2-expression was detected, whereas alpha-CD11bmAb (10 micrograms/ml) had no effect. The data suggest that both CD95R- and CD69R-induced apoptosis of human eosinophils involves a bcl-2-dependent signal transduction mechanism.

Antibodies, Monoclonal↗

Complete cDNA sequence and amino acid analysis of a bovine ribonuclease K6 gene.

The complete cDNA sequence of a ribonuclease k6 gene of Bos Taurus has been determined. It codes for a protein with 154 amino acids and contains the invariant cysteine, histidine and lysine residues as well as the characteristic motifs specific to ribonuclease active sites. The deduced protein sequence is 27 residues longer than other known ribonucleases k6 and shows amino acids exchanges which could reflect a strain specificity or polymorphism within the bovine genome. Based on sequence similarity we have termed the identified gene bovine ribonuclease k6 b (brk6b).

Amino Acid Sequence↗

Complete cDNA sequence and amino acid analysis of a bovine ribonuclease K6 gene.

The complete cDNA sequence of a ribonuclease k6 gene of Bos Taurus has been determined. It codes for a protein with 154 amino acids and contains the invariant cysteine, histidine and lysine residues as well as the characteristic motifs specific to ribonuclease active sites. The deduced protein sequence is 27 residues longer than other known ribonucleases k6 and shows amino acids exchanges which could reflect a strain specificity or polymorphism within the bovine genome. Based on sequence similarity we have termed the identified gene bovine ribonuclease k6 b (brk6b).

Amino Acid Sequence↗

Report of the International Equine Gene Mapping Workshop: male linkage map.

The goal of the First International Equine Gene Mapping Workshop, held in 1995, was the construction of a low density, male linkage map for the horse. For this purpose, the International Horse Reference Family Panel (IHRFP) was established, consisting of 12 paternal half-sib families with 448 half-sib offspring provided by 10 laboratories. Blood samples were collected and DNA extracted in each laboratory and sent to the Lexington laboratory (KY, USA) for dispatch in aliquots to 14 typing laboratories. In total, 161 markers (144 microsatellites, seven blood groups and 10 proteins) were tested for all families for which the sire was heterozygous. Genealogies and typing data were sent for analysis to the INRA laboratory (Jouy-en-Josas, France) according to a specific format and entered into a database with input verification and output processes. Linkage analysis was performed with the CRIMAP program. Significant linkage was detected for 124 loci, of which 95 were unambiguously ordered using a multipoint analysis with an average spacing of 14.2 CM. These loci were distributed among 29 linkage groups. A more comprehensive analysis including synteny group data and FISH data suggested that 26 autosomes out of 31 are covered. The complete map spans 936 CM.

Animals↗

Bovine chromosome 4 workshop: consensus and comprehensive linkage maps.

The report of the bovine chromosome 4 (BTA4) workshop is presented. Six laboratories contributed a total of 30,168 informative meioses from 62 loci. Twenty-two loci were typed by at least two independent laboratories and were used to construct a consensus linkage map of BTA4. The remaining 40 loci were subsequently incorporated into a comprehensive map. The sex-averaged consensus map covered 131.4 cM. The female map was 124.3 cM in length, while the male map was 134.3 cM. The comprehensive sex-averaged map spanned 141.6 cM. The length of the female and male comprehensive maps were 123.1 cM and 156.4 cM, respectively. Average genetic distance between loci was 6 and 2.3 cM for the consensus and comprehensive linkage maps, respectively.

Animals↗

Evidence for eosinophil activation in bronchiectasis unrelated to cystic fibrosis and bronchopulmonary aspergillosis: discrepancy between blood eosinophil counts and serum eosinophil cationic protein levels.

BACKGROUND: Increased serum levels of eosinophil cationic protein (ECP) have been detected in adolescent patients with cystic fibrosis. However, ECP concentrations in adult patients with bronchiectasis unrelated to cystic fibrosis have not been studied. METHODS: Eosinophil numbers and serum concentrations of ECP were determined in 14 patients with known or newly diagnosed bronchiectasis and compared with age and sex matched patients with allergic bronchial asthma, chronic obstructive pulmonary disease (COPD), and controls in whom bronchiectasis or obstructive pulmonary disease could be excluded. RESULTS: Serum ECP levels were significantly raised both in patients with bronchiectasis (median (range) 22.5 micrograms/l (7-85)) and allergic asthma (35.0 micrograms/l (7-128)) compared with the sex and age matched subjects suffering from COPD (6.7 micrograms/l (1.5-28); p < 0.006) and non-obstructive normal controls (7.5 micrograms/l (3.5-19); p < 0.003). In contrast, significantly increased peripheral eosinophil numbers were observed in patients with bronchial asthma (305 x 10(6)/l; p < 0.01) but not in those with bronchiectasis (10(2) x 10(6)/l), COPD (117 x 10(6)/l), and healthy controls (101 x 10(6)/l). CONCLUSIONS: The discrepancy between eosinophil counts and eosinophil numbers in patients with bronchiectasis suggests that serum ECP levels may be more relevant in assessing local eosinophil involvement than blood eosinophil numbers.

Adult↗

Description and physical localization of the bovine survival of motor neuron gene (SMN).

Proximal spinal muscular atrophy (SMA) is an autosomal recessive disease in humans and other mammals, characterized by degeneration of anterior horn cells of the spinal cord. In humans, the survival of motor neuron gene (SMN) has been recognized as the SMA-determining gene and has been mapped to 5q13. In cattle, SMA is a recurrent, inherited disease that plays an important economic role in breeding programs of Brown Swiss stock. Now we have identified the full- length cDNA sequence of the bovine SMN gene. Molecular analysis and characterization of the sequence documents 85% identity to its human counterpart and three evolutionarily conserved domains in different species. Physical mapping data reveals that bovine SMN is localized to chromosome region 20q12-->q13, supporting the conserved synteny of this chromosomal region between humans and cattle.

Animals↗

Immobilization of invertase by encapsulation in polyelectrolyte complexes.

Free and polystyrene-bound invertase from Saccharomyces cerevisiae were encapsulated within symplex membranes which were composed of cellulose sulfate as the polymeric anion and poly(dimethyldiallylammonium chloride) as the polymeric cation. The kinetics and the performance of the encapsulated enzyme preparations have been compared to the free enzyme employing the hydrolysis of sucrose. The pH and temperature optima were only slightly affected by the encapsulation. The kinetic constants, however, were changed by the encapsulation as a result of diffusional limitation. Encapsulated invertase showed a high storage stability and a high operational stability if low substrate concentrations were applied. The coimmobilization of invertase with living cells, which are not capable of utilizing sucrose, in the described capsules, opens many possibilities in fermentation technology.

Enzyme Stability↗

New and recurrent tumor foci following local treatment as well as external beam radiation in eyes of patients with hereditary retinoblastoma.

The study is based on a retrospective analysis of data from 200 patients with hereditary retinoblastoma. Apart from four unilateral cases with a positive family history all patients had bilateral disease; 229 appeared suitable for conservative treatment while 167 eyes had to be enucleated. Primary local treatment was performed in 102 eyes, while 127 eyes received primary external beam radiation using a linear accelerator. Follow-up was adjusted by life tables, with 75% of the patients being observed longer than 2 years. Using life-table statistics new and recurrent tumors were found in 41% of all patients and in 95% of these cases they were noted within 26 months after initiation of therapy. Among eyes treated with primary external beam radiation new and recurrent tumors were observed significantly less frequently when 50 Gy (22% compared with 49% after 40 Gy) and a highly accurate beam alignment technique (22% compared with 48% after alignment to the outer bony canthus) were applied. The incidence of recurrent tumors following primary local treatment did not differ significantly with regard to the application of either photo- or cryocoagulation (28% vs 33%), while no recurrence was observed among tumors that were suitable for primary treatment using ruthenium or cobalt plaques.

Brachytherapy↗

Further evidence for direct interaction of pyruvate dehydrogenase multienzyme complex with citric acid cycle based on nonlinearity of hill plots in presence of C2 and C4 substrate analogues.

1. Mammalian pyruvate dehydrogenase multienzyme complex (PDC) is measured with two different optical assays: (i) formation of p-nitro-acetanilid with arylamine-acetyltransferase and (ii) NAD reduction. 2. It is found that in contrast to the NAD assay system (ii) the coupled system (i) exhibits cooperativity with a Hill coefficient n = 3 over the whole range of substrate concentration. 3. The cooperative behaviour can be modified by presence of dichloroacetate (n = 2) and acetoin (n = 1----3). From additional measurements of PDC activity with toluene permeabilized mitochondria of fed and starved rats it is concluded that PDC activity in vivo is modified by changes in enzyme enzyme aggregation and interaction beside the known phosphorylation dephosphorylation mechanism.

Animals↗