PubMed Health⌕ Search

Biomedical subjects

M Hamrell

Publications and source records attributed to M Hamrell.

5 recordsLinked to original sources
PubMed1982

Metabolic inhibition by a new antifolate, 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methyl-pyrido[2,3-d]pyrimidine (BW3O1U), an effective inhibitor of human lymphoid and dihydrofolate reductase-overproducing mouse cell lines.

The human lymphoblastoid cell line, WIL-2, and a mouse cell line, 3T6R400, that overproduces a mutant dihydrofolate reductase (DHFR) having greater than 100-fold increased resistance to methotrexate (MTX) inhibition, were used to compare the inhibitory properties of a novel lipid-soluble antifolate, 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methyl-pyrido[2,3-d]pyrimidine (BW301U), with the 2,4-arylpyrimidine, 2,4-diamino-5-(3,4'-dichlorophenyl)-6-methylpyrimidine (DDMP) and with MTX. These studies demonstrated that, like DDMP, BW301U rapidly entered cells and inhibited the incorporation of dUrd into DNA. Drug association with cells was temperature-independent and apparently did not require active transport. BW301U inhibited cell growth by 50% at 0.025 microM, whereas MTX caused equivalent inhibition at 0.045 microM. Inhibition of DNA synthesis produced by 90 min of exposure to BW301U was completely reversed within 2 hr after washing cells and suspending them in drug-free medium. In contrast, inhibition of DNA synthesis in MTX-treated cells was not reversed by simply removing the antifolate, but required the addition of calcium leukovorin or thymidine to the drug-free medium in order to facilitate complete reversal of DNA synthesis. Finally, like DDMP, BW301U was approximately 1000 times more effective than MTX in inhibiting dUrd incorporation into the DNA of a DHFR gene-amplified cell line of mouse 3T6 cells.

Animals↗
PubMedDate not supplied

Report of the New England Task Force on Reducing Heart Disease and Stroke Risk.

Five years ago, a task force on reducing risk for heart disease and stroke was established by the six New England States. The task force included representatives from State public health departments, academia, the corporate sector, and voluntary organizations. This article is the final report of the task force. Heart disease and cerebrovascular disease are major causes of mortality in the New England region. Heart disease causes nearly 40 percent of all deaths in each of the six States and cerebrovascular disease, 7 percent of the deaths. Major risk factors for ischemic heart disease that have been identified--elevated serum cholesterol, high blood pressure, and cigarette smoking--are caused largely by lifestyle behaviors. Similarly, cerebrovascular disease results largely from uncontrolled high blood pressure, much of which is attributable to unhealthy lifestyle behaviors. In a series of studies evidence has accumulated that the reduction or elimination of these risk factors results in a decline in mortality rates. Many intervention programs have been mounted in the region, but there has been no population-wide effort to attack these risk factors. The task force proposed a broad range of activities for New Englanders at sites in the community and in health facilities. These activities would promote not smoking, exercising regularly, and maintaining desirable levels of serum cholesterol and blood pressure.

Adolescent↗