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At least 865 records · Page 48Linked to original sources
PubMed1999

A computer-assisted drug prescription system: the model and its implementation in the ATM knowledge base.

Informatisation of drug prescription is an important topic in medical informatics. For several years now, computerized drug databases have been implemented. Usually only a small part of the prescriptions can be stored in prescription systems because of the format of the included information; prescriptions contain essentially free text without any structure and homogeneity of the used vocabulary. In this article a model is presented for knowledge representation in a computerized drug prescription system. The model should be applicable to clinical practice and be didactic for medical students. The problem of standardization of terminology had to be solved. A computer-assisted drug prescription program has been developed. The next step is its validation by clinicians. The program can also be used in a consultation mode.

Database Management Systems↗
PubMed2000

Arsenite induces p53 accumulation through an ATM-dependent pathway in human fibroblasts.

Arsenic compounds are potent human carcinogens. Accumulated evidence has shown that arsenite-induced cytogenetic alterations are associated with the carcinogenicity of arsenic. Because p53 plays a guarding role in maintaining genome integrity and accuracy of chromosome segregation, the mechanistic effects of arsenite on p53 activation were analyzed. In the present study, arsenite-induced DNA strand breaks were confirmed by alkaline single-cell gel electrophoresis (comet assay) in human fibroblast (HFW) cells. Accompanying the appearance of DNA strand breaks was a significant accumulation of p53 in arsenite-treated HFW cells, as demonstrated by immunoblotting and immunofluorescence techniques. p53 downstream proteins, such as p21 and the human homologue of murine double minute-2, were also significantly induced by arsenite treatment. Cell cycle retardation and G2-M arrest were observed in 5-bromo-2'-deoxyuridine pulse-labeled HFW cells by flow cytometry. Wortmannin, an inhibitor of phosphatidylinositol 3-kinases, inhibited arsenite- or X-ray irradiation-induced p53 accumulation but did not alter UV irradiation- or N-acetyl-Leu-Leu-norleucinal-induced p53 accumulation. p53 phosphorylation on serine 15 was also confirmed by immunoblotting technique in arsenite- and X-ray-treated HFW cells but was not observed in UV- or N-acetyl-Leu-Leu-norleucinal-treated HFW cells. These results suggest the involvement of a phosphatidylinositol 3-kinase-related protein kinase in arsenite-induced p53 accumulation. For confirmation, we demonstrated that arsenite treatment, similar to X-ray irradiation, did not induce p53 accumulation in GM3395 fibroblasts derived from a patient with ataxia telangiectasia. In contrast, UV irradiation did cause p53 accumulation in these cells. Together, these findings infer that arsenite-induced DNA strand breaks may lead to p53 phosphorylation and accumulation through an ataxia telangiectasia mutated-dependent pathway in HFW cells.

Arsenites↗