Biomedical subjects

Peter Wiegand

Publications and source records attributed to Peter Wiegand.

8 recordsLinked to original sources

PubMed2006

Application of a quasi-median network analysis for the visualization of character conflicts to a population sample of mitochondrial DNA control region sequences from southern Germany (Ulm).

Entire mtDNA control region sequences from 100 individuals in a west Eurasian population sample from southern Germany (around the city of Ulm) were generated and analyzed. The control region was amplified in one piece and sequenced with ten different sequencing primers. Sequence evaluation was performed independently. Phylogenetic analyses were used for quality assurance purposes and for the determination of the haplogroup affiliation of the samples. The sequences were scrutinized performing a quasi-median network analysis. To visualize character conflicts, frequent mutations were filtered, and the reduced data were represented by the torso of their quasi-median network. Character incompatibilities were found to be based on real biological patterns of homoplasy. The population data will be incorporated in the EMPOP database ( http://www.empop.org ).

DNA, Mitochondrial↗

PubMed2005

The broad-range cyclin-dependent kinase inhibitor UCN-01 induces apoptosis in colon carcinoma cells through transcriptional suppression of the Bcl-x(L) protein.

The broad-range cyclin-dependent kinase inhibitor 7-hydroxystaurosporine (UCN-01) is known to induce both a G1 cell cycle arrest and apoptosis. The mechanism of UCN-01-induced apoptosis is largely unknown. We analysed the mechanism of cytotoxicity of UCN-01 in four established colon carcinoma cell lines. The cell lines SW48 and LS513 responded to UCN-01 treatment by undergoing apoptosis in a concentration-dependent manner while the cell lines HT-29 and WiDr were completely resistant. Apoptosis in LS513 and SW48 cell lines was concomitant with the suppression of Bcl-x(L) on mRNA and protein level. In contrast, in the apoptosis-resistant cell lines, Bcl-x(L) expression was not affected by UCN-01. Stable overexpression of the Bcl-x(L) protein abrogated UCN-01-triggered apoptosis, but only partially restored growth, indicating that both cell cycle arrest and apoptosis exert the anticancer effect in a coordinated manner. The inhibition of Akt phosphorylation did not correlate with the apoptotic phenotype. UCN-01 inhibited the activating STAT3 phosphorylations on Ser727 and, notably, on Tyr705, but STAT3 did not contribute to Bcl-x(L) expression in colon carcinoma cells. Moreover, we show for the first time that UCN-01 induces apoptosis by suppression of Bcl-x(L) expression. The inhibition of this pathway is a new aspect of cytotoxic and modulatory potential of UCN-01.

Antineoplastic Agents↗

PubMed2004

Influence of ischaemia/reperfusion and LFA-1 inhibition on telomere lengths and CDKI genes in ex vivo haemoperfusion of primate kidneys.

The telomere (T) length, p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor (CDKI) genes are the markers of cell senescence and DNA damage. The aim of the study was to determine the influence of renal ischaemia/reperfusion (I/R) and anti-lymphocyte function-associated antigen-1 (LFA-1) monoclonal antibody (mAb) treatment on the value of the above-mentioned markers. Significantly higher levels of p21 and p27 were expressed by the glomeruli (P=0.001 and P=0.0001), tubules (P=0.0065 and P=0.0006), and interstitial cells (P=0.0017 and P=0.0022, respectively) of the xenoperfused kidneys. The mean T length of non-perfused renal specimens (5.56+/-0.60 kbp) was longer than that of the xenoperfused kidneys (5.46+/-0.36 kbp) [P= non-significant (NS)]. Addition of anti-LFA-1 mAb did not significantly influence the gene expression profile in the xenoperfused kidneys. The mean T length was longer in the kidneys with anti-LFA-1 mAb than in those without the medication (5.7+/-0.11 vs 5.13+/-0.31 kbp) (P=0.0661). Kidney I/R is associated with telomere shortening and an over-expression of p21 and p27 CDKIs, which indicates substantial DNA damage and/or accelerated tissue senescence. Although anti-LFA-1 mAb had some protective effect on the telomeres, it did not influence the gene expression profile in this study.

Animals↗

PubMed2003

Cell line DNA typing in forensic genetics--the necessity of reliable standards.

The incorporation of reference DNA is crucial to the validation of any DNA typing protocol. This paper aims to provide a panel of reference DNAs for actual forensic profiling strategies, i.e. autosomal and gonosomal STR typing as well as mtDNA sequencing. We have characterised three human lymphoid cell lines, GM9947, GM9948 and GM3657, and considered 58 autosomal and gonosomal microsatellites as well as the mitochondrial control region sequence. Well-established markers and STRs recently developed for forensic use were involved. K562 DNA samples which we purchased from two different suppliers were also analysed. They revealed conflicting results with regard to the ChrX STR marker genotype. Hence, we suggest that K562 is no longer used for the calibration of profiling techniques. Our investigation establishes a panel of one female and two male DNA samples as an STR allelic ladder calibration tool and offers information on six alleles of each autosome (AS) marker, three alleles of each X chromosome (ChrX) marker and two alleles of each ChrY marker. In addition, sequences of the mitochondrial control region of the three DNAs are communicated in order to provide sequencing quality control.

Cell Line, Tumor↗

PubMed2003

Polymerase slippage in relation to the uniformity of tetrameric repeat stretches.

The aim of the study was to test the hypothesis that polymerase slippage correlates to the length of repeat stretches consisting of uniform repeats against the alternative hypothesis that the total number of repeats is most relevant. Two short tetrameric short tandem repeats (STRs) with different repeat structures were investigated: D3S1545 containing only homogeneous (GATA)n repeat stretches and D7S1517 with compound repeat arrays of GAAA and CAAA repeats. Additionally two different polymerases (Herculase and AmpliTaq Gold) were used which gave comparable results. No correlation was found for the hypothesis "total repeat number against percent of stutter"; in contrast, the other hypothesis that the number of uniform repeats is relevant for the degree of stutter gave a strong positive correlation (0.82 for selected D7S1517 alleles) which confirmed the hypothesis that polymerase slippage correlates to the length of repeat stretches consisting of uniform repeats.

Alleles↗

PubMed2003

Effect of ischemia/reperfusion on telomere length and CDKI genes expression in a concordant ex-vivo hemoperfusion model of primate kidneys.

OBJECTIVES: The telomere (T) length, p21(WAF1/CIP1) and p27(Kip1) cyclin dependent kinase inhibitor (CDKI) genes are considered the markers of cell senescence and DNA damage. The aim of the study was to evaluate the influence of renal ischemia/reperfusion (I/R) on the value of above-mentioned markers. METHODS: 13 Macaque cynomolgus monkey kidneys were harvested and placed in Eurocollins solution. 9 kidneys were ex-vivo perfused with human blood and 4 kidneys were not perfused at all (control group). Tissue expression of p21(WAF1/CIP1) and p27(Kip1) was evaluated immunohistochemically and the T lengths were measured by southern blotting technique. RESULTS: Significantly higher levels of p21 and p27 were expressed by the glomeruli (p = 0.001 and 0.0001), tubules (p = 0.0065 and 0.0006) and interstitial cells (p = 0.0017 and 0.0022, respectively) of the xenoperfused kidneys. The mean T length was higher in the control group (5.56 +/- 0.60 kbp) than in the study group kidneys (5.46 +/- 0.36 kbp) (P = NS). CONCLUSION: Renal I/R is associated with telomere shortening and an over-expression of p21 and p27 genes indicating substantial DNA damage and/or accelerated tissue senescence.

Animals↗

PubMed2002

Population genetic data, comparison of the repeat structure and mutation events of two short STRs.

The short tandem repeat (STR) systems D3S1545 and D7S1517, both small size STRs (fragment lengths <160 bp), were investigated in a population sample of German Caucasoids. New primer sequences more closely flanking the repetitive region were designed for D3S1545. For D3S1545, 7 alleles could be found (heterozygosity 0.68) while 11 alleles could be typed for D7S1517 (heterozygosity 0.83). Additionally, sequencing of selected alleles was carried out to establish the allele nomenclature and to clarify the structure of the tandem repeat arrays. D3S1545 showed a uniform GATA repeat structure but, in contrast, the repeat stretch of D7S1517 showed a compound structure characterised by different numbers of GAAA and CAAA repeats. Two isolated cases of a new mutation could be confirmed for D7S1517. The alleles of these two family constellations were characterised by sequencing and the probable mutational events were demonstrated.

Adolescent↗

PubMedDate not supplied

[A hopeless case?].

In a hollow covered with earth, a herb gatherer discovered a severely decomposed corpse mutilated by scavenging animals. Only small areas of the skin had remained intact. A conspicuous tattoo could still be distinguished on the left upper arm. Despite concrete evidence of violence (fracture in the occipital bone, subdural hemorrhage with a volume of 20 ml), the exact cause of death could no longer be established. Police enquiries identified a person in whom such a conspicuous tattoo had been photographed in an earlier criminal case. Eventually, the deceased person could be identified by DNA analysis of a stored blood alcohol specimen. Considered together, the autopsy findings and the results of the investigation of traces of blood on the putative tool used in the crime indicated that the man had been struck dead and the body had afterwards been buried in the wood. Although the prospects of success had been initially slight, it was not only possible to identify the victim, but also to reconstruct the crime.

Adult↗