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Biomedical subjects

T Meinhardt

Publications and source records attributed to T Meinhardt.

7 recordsLinked to original sources

TRANSFAC: an integrated system for gene expression regulation.

TRANSFAC is a database on transcription factors, their genomic binding sites and DNA-binding profiles (http://transfac.gbf.de/TRANSFAC/). Its content has been enhanced, in particular by information about training sequences used for the construction of nucleotide matrices as well as by data on plant sites and factors. Moreover, TRANSFAC has been extended by two new modules: PathoDB provides data on pathologically relevant mutations in regulatory regions and transcription factor genes, whereas S/MARt DB compiles features of scaffold/matrix attached regions (S/MARs) and the proteins binding to them. Additionally, the databases TRANSPATH, about signal transduction, and CYTOMER, about organs and cell types, have been extended and are increasingly integrated with the TRANSFAC data sources.

Database Management Systems↗

Expanding the TRANSFAC database towards an expert system of regulatory molecular mechanisms.

TRANSFAC is a database on transcription factors, their genomic binding sites and DNA-binding profiles. In addition to being updated and extended by new features, it has been complemented now by a series of additional database modules. Among them, modules which provide data about signal transduction pathways (TRANSPATH) or about cell types/organs/developmental stages (CYTOMER) are available as well as an updated version of the previously described COMPEL database. The databases are available on the WWW at http://transfac.gbf.de/

Animals↗

Resistance of young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions.

Regulated expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) plays a role in various physiological processes. To determine in vivo how unbalanced expression of these factors can promote or affect the course of pathologies, we knocked out the mouse gelatinase B gene by replacing the catalytic and zinc-binding domains with an antisense-oriented neomycin resistance gene. Adult gelatinase B-deficient mice and wild-type controls could be induced to develop experimental autoimmune encephalomyelitis (EAE) with similar scores for neurologic disease, blood-brain barrier permeability, and central nervous system histopathology. However, whereas diseased control animals showed necrotizing tail lesions with hyperplasia of osteocartilaginous tissue, adult gelatinase B-deficient mice were resistant to this tail pathology. Gelatinase B-deficient mice younger than 4 weeks of age were significantly less susceptible to the development of EAE than were age matched controls and, even as they aged, they remained resistant to tail lesions. These data illustrate that gelatinase B expression plays a role in the development of the immune system and that, in ontogenesis, the propensity to develop autoimmunity is altered by the absence of this MMP.

Age Factors↗

A cytogenetic study of papaya workers exposed to ethylene dibromide.

Ethylene dibromide (EDB) has been shown to be carcinogenic in animal studies and mutagenic in vitro. One cytogenetic study of workers exposed to low levels of EDB for short durations was negative. To test whether exposure to low levels of EDB over long periods caused cytogenetic changes, we have assessed the frequencies of sister-chromatid exchanges (SCE) and chromosomal aberrations (CA) in the peripheral blood lymphocytes of 60 men occupationally exposed to EDB. These men worked in papaya-packing plants where EDB was used to fumigate the fruit after harvest to kill fruit-fly larvae. 42 other men who worked at a nearby sugar mill served as controls. The average duration of exposure of the papaya workers was 5 years. 82 full shift personal breathing-zone air samples indicated that the papaya workers were exposed to a geometric mean of 88 ppb of EDB, as an 8-h time weighted average (TWA). Peaks up to 262 ppb were measured. The proposed OSHA 8-h TWA for EDB is 100 ppb, while NIOSH recommends 45 ppb. No differences in SCE levels were found between exposed and nonexposed workers. No differences were found in the total CA frequency between exposed and nonexposed workers. SCE levels were significantly increased in men who smoked cigarettes (p = 0.0001) and in men who smoked marijuana (p = 0.01). CA levels showed a significant increasing trend with age (p = 0.03).

Adult↗

Cytogenetic studies in humans after short-term exposure to ethylene dibromide.

Ethylene dibromide (EDB) has been shown to increase sister chromatid exchange in animal cells in vitro, but its cytogenetic effects in humans have not been previously studied. A solution containing EDB is used in the summer months in Colorado to spray felled pine trees to kill pine beetles. We have assessed the frequencies of sister chromatid exchanges and chromosomal aberrations in the peripheral blood lymphocytes of 14 sprayers both before and after exposure. Six nonexposed individuals also were tested. Full-shift personal breathing-zone air samples indicated that the sprayers were exposed to an average of 60 ppb of EDB, as an eight-hour time weighted average. The range of exposure was from 5 to 281 ppb. Workers sprayed EDB for only five to 26 days during the summer, with an average of 14 days. After adjusting for smoking and the use of prescription medicine, there was no statistically significant difference between the frequencies of either sister chromatid exchange or chromosomal aberrations before and after spraying.

Adult↗

A retrospective cohort mortality study of a phosphate fertilizer production facility.

A retrospective cohort mortality study of phosphate fertilizer production workers was undertaken to determine whether this group is at increased risk of dying from any cause, particularly from lung cancer. A total of 3,199 workers who had ever been employed at one facility were included in this investigation. These workers were followed for vital status ascertainment from their first date of employment up to December 1, 1977, or the date of death, whichever occurred first. Overall, no statistically significant elevations in cause-specific mortality were observed for the entire study population. However, when the analysis was stratified by duration of employment, and length of follow-up, a statistically significant (P less than .05) excess in lung cancer mortality was observed among workers with more than 10 yr of employment and follow-up (standardized mortality ratio = 411). Because of the small number of deaths involved, and because we had prior knowledge of a lung cancer cluster at this plant, we believe that these findings should be viewed as suggestive, and that other investigations in plants with similar exposures are needed to clarify whether an occupationally related lung cancer excess truly exists.

Adolescent↗