[Cardiovascular events in people participating in jogging - results over 27 years]. / Herz-Kreislauf-Risiko bei der Teilnahme am LAUF-TREFF - Ergebnisse über 27 Jahre.

The regulary participation in a jogging-group is a one possibility to do sports under professional surveillance with positive effects of the cardiovascular system. On the other side, the implications of doing sports on the risk of sudden death are debatable. The first jogging-groups were formed twenty-seven years ago in Darmstadt. There were only four serious cardiovascular events ( three deadly) in twenty-seven years. There are several groups for different trained persons, so it's possible to start at all stages of fitness. In addition there are no fees.

Alterations of DNA repair in melanoma cell lines resistant to cisplatin, fotemustine, or etoposide.

Resistance to chemotherapy is a common phenomenon in malignant melanoma. In order to assess the role of altered DNA repair in chemoresistant melanoma, we investigated different DNA repair pathways in one parental human melanoma line (MeWo) and in sublines of MeWo selected in vitro for drug resistance against four commonly used drugs (cisplatin, fotemustine, etoposide, and vindesine). Host cell reactivation assays with the plasmid pRSVcat were used to assess processing of different DNA lesions. With ultraviolet-irradiated plasmids, no significant differences were found, indicating a normal (nucleotide excision) repair of DNA photoproducts. With singlet oxygen-treated plasmid, the fotemustine- and cisplatin-resistant lines exhibited a significantly increased (base excision) repair of oxidative DNA damage. With fotemustine-treated plasmid, the fotemustine-resistant subline did not exhibit an increased repair of directly fotemustine-induced DNA damage. Similar results were obtained with cisplatin-induced DNA crosslinks in the cisplatin-resistant line. The fotemustine- and etoposide-resistant sublines have been shown to exhibit a reduced expression of genes involved in DNA mismatch repair. We used a "host cell microsatellite stability assay" with the plasmid pZCA29 and found a 2.0-fold to 2.5-fold increase of microsatellite frameshift mutations (p < or = 0.002) in the two resistant sublines. This indicates microsatellite instability, the hallmark of an impaired DNA mismatch repair. The increased repair of oxidative DNA damage might mediate an increased chemoresistance through an improved repair of drug-induced DNA damage. In contrast, a reduced DNA mismatch repair might confer resistance by preventing futile degradation of newly synthesized DNA opposite alkylation damage, or by an inability to detect such damage and subsequent inability to undergo DNA-damage-induced apoptosis.

A novel plasmid shuttle vector for the detection and analysis of microsatellite instability in cell lines.

Microsatellite instability is an important feature of tumors from hereditary nonpolyposis colorectal carcinoma (HNPCC) patients as well as a variety of sporadic tumors. Here, we present a novel plasmid shuttle vector for the detection of this replication error (RER+) phenotype in human cell lines. The episomely replicated plasmid pZCA29 harbours the bacterial beta-galactosidase gene interrupted by two palindromically arranged poly-(CA)-repeat tracts. The resulting + 1-frameshift leads to white colonies of Escherichia coli DH10B on X-Gal/IPTG1 agar plates. Mutations in the repeats characteristic of the RER+-phenotype may result in the loss or gain of CA-repeats leading to blue bacterial colonies. We transiently transfected the colorectal cancer cell lines SW480 and HCT116 with the plasmid pZCA29, isolated replicated plasmid DNA after several days and used it to transform E. coli DH10B. We found 1.0 to 1.7% blue colonies after passage of the plasmid through the RER+-cell line SW480 in contrast to 3.5 to 8.1% blue colonies after transfection of the RER+-cell line HCT116, the mutation frequencies increasing with incubation time. Sequence analysis of mutated plasmids revealed mostly 2-bp deletions which occurred especially in one of the repeat tracts. We conclude that pZCA29 appears to be a suitable shuttle vector for the detection and analysis of a RER+-phenotype in cell lines.

Assessment of microsatellite instability in a cell line from a patient with xeroderma pigmentosum variant.

Cells from patients with xeroderma pigmentosum (XP) variant are thought to be defective in postreplication repair. This DNA repair pathway is not well defined in human cells and the exact genetic defect of XP variant is unknown. In another cancer-prone hereditary disorder, hereditary nonpolyposis colon cancer, tumors are characterized by a DNA mismatch repair defect with microsatellite instability. Since there are some similarities between postreplication repair and mismatch repair, we investigated microsatellite instability, the hallmark of a DNA mismatch repair defect, in a lymphoblastoid cell line from a patient with XP variant. Two normal lines and one nucleotide excision repair-defective XP group A line were used as controls. In a host cell microsatellite instability assay, the recently developed shuttle vector pZCA29 was transfected into these cells and replicated plasmid recovered after 3 days. The plasmid contains two CA repeat tracts that interrupt the reading frame of the lacZ gene. Reversion to active beta-galactosidase, detectable by a color reaction of bacterial transformants, represents the frequency of frameshift mutations in the CA repeat tracts during replication of the plasmid, and thereby the host cells' microsatellite instability. We did not find any significant differences in the mutation frequencies of the plasmids after passage through either cell line. This indicates that there is no microsatellite instability in the examined XP variant cell line.

Processing of three different types of DNA damage in cell lines of a cutaneous squamous cell carcinoma progression model.

In order to study the role of DNA damage processing in the development of cutaneous squamous cell carcinoma (SCC), we assessed the ability of six keratinocyte cell lines from a multistage-tumor progression model to repair three types of DNA damage: pyrimidine dimers, oxidative DNA lesions and DNA double strand breaks (DSB). The model comprised the spontaneously immortalized, non-tumorigenic human keratinocyte cell line HaCaT, four different c-Ha-ras transfectants of HaCaT (non-, benign- and two malignant-tumorigenic) and a SCC-derived cell line. Host cell reactivation assays with UVB-treated plasmid vectors pRSVcat showed no significantly altered repair of UVB-induced pyrimidine dimers in the tumorigenic cell lines, compared with the non-tumorigenic lines. Using the singlet oxygen-treated plasmids pRSVcat the Ha-ras-HaCaT-clones and the SCC-cells, exerted a DNA repair efficiency that was not significantly different from HaCaT cells. In order to assess the ability of the cells to ligate free DNA ends (repair of DSB), we used a plasmid shuttle vector assay with linearized plasmid pZ189. We found a significant increase of DNA end joining ability in the non-tumorigenic, the benign and in one of the malignant HaCaT-clones II-4. The malignant HaCaT-clone II-3, however, exerted a significantly lower rate of rejoining the linearized plasmid. This cell line also showed a highly and significantly elevated rate of micronuclei, which reflects a pronounced chromosomal instability. The SCC-cells exhibited a more efficient repair of DNA DSB than the HaCaT cells. We conclude that in the examined model, progression of human keratinocytes from the non-tumorigenic to the highly tumorigenic phenotype, is not accompanied by a decrease in the cell's capacity to repair UVB- and singlet oxygen-induced DNA lesions. However, an acquired deficiency in repairing DNA double strand breaks can be one mechanism promoting progression towards malignancy, possibly through impairing chromosomal stability.

[Criteria for running (jogging) shoe tests]. / Testkriterien für Lauf-(Jogging-)schuhe.

Shoes for jogging are presently being tested by a great many institutes using widely divergent criteria and according to a plethora of different interests, and hence the assessments and test results may be poles apart and even contradictory. Most of the tests are based on much too short stress periods and either disregard biomechanical properties entirely or determine them via methods that must be classified as questionable. Today no manufacturer offers models one could definitely classify as excellent or deficient. A shoe for jogging may be optimal for one jogger and fatal for another. The following article sets criteria yielding two important kinds of information: on the one hand, an analysis of weak points that will help the manufacturer by telling him where he must improve his product, and on the other hand target-group oriented usage recommendations for the benefit of the consumer (jogger) that help him to find the shoe that suits him best among a never-ending conglomerate of sports shoes.