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Biomedical subjects

L Beckmann

Publications and source records attributed to L Beckmann.

9 recordsLinked to original sources
PubMed2006

Gene polymorphisms in Toll-like receptors, interleukin-10, and interleukin-10 receptor alpha and lymphoma risk.

Interactions between environment and immune system play an essential role in the aetiology of immunopathologies, including lymphomas. Toll-like receptors (TLR) belong to a group of pattern recognition receptors, with importance for innate immune response and inflammatory processes. Interleukin-10 (IL-10) is a key regulatory cytokine and has been implicated in lymphomagenesis. Functional polymorphisms in these inflammation-associated genes may affect the susceptibility towards lymphoma. To test this hypothesis, we have genotyped DNA of 710 lymphoma cases and 710 controls within the context of a population-based epidemiological study for 11 functionally important single-nucleotide polymorphisms in TLR1, -2, -4, -5, -9, IL10 and IL10 receptor (IL10RA). The IL10RA Ser138Gly variant was underrepresented among lymphoma cases (odds ratio (OR)=0.81, 95 per cent confidence interval (95% CI)=0.65-1.02), mainly owing to an inverse association with Hodgkin's lymphoma (HL). The TLR2 -16933T>A variant was associated with a 2.8-fold increased risk of follicular lymphoma (95% CI=1.43-5.59) and a decreased risk of chronic lymphocytic leukaemia (OR=0.61, 95% CI=0.38-0.95). Furthermore, the TLR4 Asp299Gly variant was positively associated with the risk of mucosa-associated lymphoid tissue lymphoma (OR=2.76, 95% CI=1.12-6.81) and HL (OR=1.80, 95% CI=0.99-3.26). In conclusion, this study suggests an effect of polymorphisms in factors of the innate immune response in the aetiology of some lymphoma subtypes.

Adult↗
PubMed2005

The in vitro stabilising effect of polyetheretherketone cages versus a titanium cage of similar design for anterior lumbar interbody fusion.

UNLABELLED: This biomechanical study was performed to test the primary segmental in vitro stabilising effect of a standard and large footprint radiolucent poly-ether-ether-ketone (PEEK) box cage versus a titanium box cage for anterior lumbar interbody fusion. Eighteen L2-L3 and sixteen L4-L5 cadaveric motion segments were divided into three groups and received a titanium cage or a radiolucent PEEK cage with standard or large footprint. All specimens were tested in three testing conditions: intact, stand-alone anterior cage and finally with supplemental translaminar screw fixation. Full range of motion and neutral zone measurements were determined and anterior cage pull out force was tested. The titanium design was significantly more effective in reducing the range of motion only in axial rotation. The larger footprint radiolucent cage did not increase stability as compared to the standard footprint. The titanium cage pull out force was significantly (P=0.0002) higher compared to both radiolucent cage constructs. CLINICAL RELEVANCE: Supplemental posterior fixation is strongly recommended to increase initial stability of any anterior interbody fusion cage construct. Although the biomechanical stability necessary to achieve spinal fusion is not defined, the radiolucent designs tested in this study, with a standard footprint as well as with a larger footprint, may be insufficiently stabilised with translaminar screws as compared to the titanium implant. Supplemental pedicle screw fixation may be required to obtain adequate stabilisation in the clinical setting.

Benzophenones↗
PubMed2005

SDMinP: a program to control the family wise error rate using step-down minP adjusted P-values.

SDMinP is an easy-to-use program for fast calculation of empirical and adjusted P-values for correlated and uncorrelated hypotheses in multiple testing experiments. It is based on the Free Step-Down Resampling Method for controlling the family wise error rate, and implements a variation of an efficient algorithm, which reduces the originally required re-sampling effort considerably and makes the method computationally feasible. The program is independent of the underlying test statistic and works with provided observed and permutation test statistics.

Algorithms↗
PubMed2005

Haplotype sharing analysis using mantel statistics.

OBJECTIVE: The potential value of haplotypes has attracted widespread interest in the mapping of complex traits. Haplotype sharing methods take the linkage disequilibrium information between multiple markers into account, and may have good power to detect predisposing genes. We present a new approach based on Mantel statistics for spacetime clustering, which is developed in order to improve the power of haplotype sharing analysis for gene mapping in complex disease. METHODS: The new statistic correlates genetic similarity and phenotypic similarity across pairs of haplotypes for case-only and case-control studies. The genetic similarity is measured as the shared length between haplotypes around a putative disease locus. The phenotypic similarity is measured as the mean-corrected cross-product based on the respective phenotypes. We analyzed two tests for statistical significance with respect to type I error: (1) assuming asymptotic normality, and (2) using a Monte Carlo permutation procedure. The results were compared to the chi(2) test for association based on 3-marker haplotypes. RESULTS: The results of the type I error rates for the Mantel statistics using the permutational procedure yielded pointwise valid tests. The approach based on the assumption of asymptotic normality was seriously liberal. CONCLUSION: Power comparisons showed that the Mantel statistics were better than or equal to the chi(2) test for all simulated disease models.

Case-Control Studies↗
PubMed2004

Analysis of gyrA mutations in quinolone-resistant and -susceptible Campylobacter jejuni isolates from retail poultry and human clinical isolates by non-radioactive single-strand conformation polymorphism analysis and DNA sequencing.

AIMS: The aims of this study were to characterize the molecular variations in the quinolone resistance-determining region (QRDR) of gyrA among quinolone-resistant and -susceptible Campylobacter jejuni isolates originating from foods of animal origin and human infections and to evaluate the suitability of the single-strand conformation polymorphism (SSCP) method as a screening method for molecular characterization of fluoroquinolone resistance. METHODS AND RESULTS: Alterations in QRDR of gyrA from 182 C. jejuni isolates were determined by nonradioisotopic SSCP analysis and direct sequencing. A total of 13 types of nucleic acid sequence combinations within the QRDR of the gyrA gene resulted in 11 different SSCP patterns. All nalidixic acid resistant strains possessed nucleotide substitution at either codon Thr-86 or Asp-90. Silent mutations were detected additionally. Thr-86 to Ile mutation was detected in all 139 ciprofloxacin resistant strains, which showed cross-resistance to nalidixic acid. CONCLUSIONS: The SSCP method is suitable for a molecular screening of quinolone resistant C. jejuni isolates and in combination with DNA sequencing suitable to detect genetic variations of the QRDR of gyrA. SIGNIFICANCE AND IMPACT OF STUDY: This study provides data of the genetic variations of the QRDR of gyrA from C. jejuni isolates of foods and human beings.

Animals↗
PubMed2001

Exploring haplotype sharing methods in general and isolated populations to detect gene(s) of a complex genetic trait.

We applied a new haplotype sharing method to the simulated Genetic Analysis Workshop 12 data for both isolated and general populations without knowledge of the disease model, using affection status as phenotype and three different sample sizes. The highest peak for the mean sharing of the haplotypes was found in the isolated population for the markers D06G034 and D06G035, which flank the candidate genes located on chromosome 6, with -log10(p) values of 2.9 and 7.0 in the moderate and large study samples, respectively. The whole genome screen detected three further loci with -log10(p) values of 3.0, which turned out to be false positives. None of the true gene loci were detected in the general population even in the largest sample. The test of linkage disequilibrium based on excess haplotype sharing over the linkage equilibrium expectation revealed z-values one order of magnitude higher in the isolated than in the general population. This approach appears to be promising for mapping genes of complex diseases depending on population characteristics.

Chromosome Mapping↗
PubMed2000

Isolation of an 1,3-1,4-beta-glucan degrading Enterococcus faecium strain from the intestinal tract of chicken and partial characterization of its novel 1,3-1,4-beta-glucanase.

An Enterococcus faecium strain with a novel endo 1,3-1,4-endo-beta-glucanase (lichenase, E.C. 3.2.1.73) was isolated from the intestinal tract of broiler chicken. The enzyme was secreted into the culture medium and acted exclusively on mixed linked 1,3-1,4-beta-glucans as determined with a reducing sugar assay. The purified enzyme has its isoelectric point at pI 4.8, maximum activity was determined at pH 6.5 and 40 degrees C. Thermal stability of the enzyme was low, but high pH stability and high residual activity was observed after incubation in digesta samples from the chicken intestine. Multiple lichenase activities were obtained from culture supernatants on SDS/PAGE and native zymograms, but it is concluded that the lichenase consists of one active protein at 30.5 kD and additional polypeptides of unknown function.

Animals↗