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Biomedical subjects

L A Price

Publications and source records attributed to L A Price.

89 records · Page 5Linked to original sources

Studies concerned with overcoming resistance to methotrexate: a comparison of the effects of methotrexate and 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine (BW50197) on the colony forming ability of L5178Y cells.

The effects of methotrexate (MTX) and 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine (BW50197) on the colony forming ability of L5178Y cells were compared. Two sub-lines of cells were used, one sensitive to methotrexate and the other resistant. In addition, the inhibitory effects of BW50197 against dihydrofolate reductase (DHFR) extracted from the MTX resistant cells were compared with those of MTX and pyrimethamine. It was found that although BW50197 was a less effective inhibitor of DHFR than MTX, it was superior to MTX at high concentrations in killing MTX resistant cells, and this superiority increased with the time of exposure to the drugs. These findings suggest that (a) when antifolate compounds are screened for antitumour activity it is insufficient simply to assess them on the basis of their ability to inhibit DHFR and (b) BW50197 should be given clinically so as to achieve the highest possible tissue concentration for the longest possible time consistent with the safety of the patient.

Animals↗

Multiple drug therapy for disseminated malignant tumours.

Forty patients with various disseminated malignant tumours were treated with up to six antitumour drugs given for periods not exceeding 24 hours. Complete or partial objective tumour regression was achieved in 20 patients. No regression occurred in the remaining 20. Treatment given in this way seemed to be at least as effective as other multiple drug regimens and had the following advantages: (1) toxicity was reduced to a minimum and no access was needed to sterile rooms or platelet transfusions since severe bone marrow depression did not occur, and (2) the patients spent only a very short time in hospital.

Adult↗

At second glance: employers and employees with learning disabilities in the Americans with Disabilities Act era.

The impact of the Americans with Disabilities Act (ADA) of 1990 on the American workplace is examined. The findings of a previous study (Gerber, 1992) on employer knowledge about learning disabilities are compared to current findings. Important themes and employer beliefs and practices that were consistent in employer responses are described. Although employers are continuing to make efforts to comply with the regulations of the ADA, they still have relatively little knowledge or experience with it in terms of learning disabilities.

Attitude↗

A randomized combination chemotherapy trial, with and without adriamycin, in squamous cell carcinoma of the head and neck.

One hundred seventeen patients with advanced squamous cell carcinoma of the head and neck were treated and placed randomly between two combination protocols, one with adriamycin and the other without. Responses (more than 50% tumor regression) were 67% overall with 63% responding to the combination without adriamycin and 82% responding to the protocol containing it. The increase in the response rate seen with the addition of adriamycin was not statistically significant. The degree of response to chemotherapy was reduced by prior radiotherapy.

Bleomycin↗

Investigation of growth hormone releasing hormone receptor structure and activity using yeast expression technologies.

Growth hormone releasing hormone (GHRH) is the positive regulator of growth hormone synthesis and secretion in the anterior pituitary. The peptide confers activity by binding to a seven transmembrane domain G protein-coupled receptor. Signal transduction proceeds through subsequent G alpha s stimulation of adenylyl cyclase. To investigate ligand/receptor and receptor/G protein associations, the human GHRH receptor was expressed in a modified S. cerevisiae strain which allows for facile measurement of receptor activity by cell prototrophy mediated by a reporter gene coupled to the yeast pheromone response pathway. GHRH-dependent signal activation in this system required the substitution of yeast G alpha protein with proteins containing C-terminal regions of G alpha s. A D60G variant (analogous to the little mouse mutation) of the receptor failed to respond to agonist. In parallel studies, GHRH29 and the N-terminal extracellular region of the receptor were expressed as Gal4 fusion proteins in a 2-hybrid assay. A specific interaction between these proteins was readily observed. The D60G mutation was engineered into the receptor fusion protein. This protein failed to interact with the ligand fusion, confirming the specificity of the association between unmodified proteins. These two yeast expression technologies should prove invaluable in additional structure/activity analyses of this ligand/receptor pair as well as other peptide ligands and receptors.

Animals↗