Biomedical subjects

M M McKinney

Publications and source records attributed to M M McKinney.

23 records · Page 2Linked to original sources

PubMed1986

Digitoxin metabolism by liver microsomal cytochrome P-450 and UDP-glucuronosyltransferase and its role in the protection of rats from digitoxin toxicity by pregnenolone-16 alpha-carbonitrile.

The aim of the present study was to investigate whether the mechanism by which pregnenolone-16 alpha-carbonitrile (PCN) protects rats from digitoxin toxicity was dependent on the induction of liver microsomal cytochrome P-450p and/or the UDP-glucuronosyltransferase active toward digitoxigenin monodigitoxoside (UDP-GT-dt1). Evidence is presented that suggests troleandomycin is a selective inhibitor of cytochrome P-450p in vivo, based on the pattern of inhibition observed when zoxazolamine paralysis time and hexobarbital sleeping time were measured in rats treated with different cytochrome P-450 inducers. A single dose of troleandomycin completely reversed the ability of PCN to protect rats from digitoxin toxicity, establishing the importance of cytochrome P-450p induction in the protective effect of PCN. The postpubertal decline in constitutive cytochrome P-450p levels in female but not male rats was paralleled by a female-specific, age-dependent decline in the rate of digitoxin sugar cleavage (i.e., digitoxosyl oxidation of digitoxin to 15'-dehydrodigitoxin and digitoxosyl cleavage to digitoxigenin bisdigitoxoside). This resulted in a marked sex difference in the rate of digitoxin sugar cleavage catalyzed by liver microsomes from mature rats (male/female approximately 6). However, no sex difference in digitoxin toxicity was observed in either immature or mature rats. In contrast to cytochrome P-450p, liver microsomal UDP-GT-dt1 activity increased dramatically with age in both male and female rats (mature/immature approximately 10). However, no age differences in digitoxin toxicity were observed in rats of either sex. The results indicate that cytochrome P-450p and UDP-GT-dt1 can be independently regulated in rat liver and that large changes in the constitutive levels of these microsomal enzymes have no effect on digitoxin toxicity. This suggests that the induction of cytochrome P-450p and UDP-GT-dt1 does not fully account for the mechanism by which PCN protects rats from digitoxin toxicity.

Age Factors↗

PubMed1986

Stimulation of arachidonic acid release and eicosanoid biosynthesis in an interleukin 2-dependent T cell line.

Previous studies have provided pharmacologic evidence that T lymphocyte function may be regulated in part by the intracellular production of various arachidonic acid (AA) metabolites in response to cellular stimulation. However, the specific AA metabolic capabilities of homogeneous T cell populations have not been clearly defined. In the present studies, we have employed an accessory cell-free T cell line, HT-2, as a model system for the examination of stimulus-induced eicosanoid biosynthesis in T lymphocytes. HT-2 cells were biosynthetically labeled with [3H]-AA and challenged briefly with various agents that stimulate the hydrolytic release of AA from cellular phospholipids. The bee venom peptide melittin stimulated a profound AA release response in the cells and the concomitant synthesis of both cyclooxygenase (PGF2 alpha, PGE2 and PGD2) and lipoxygenase (5-,12-,15-HETE and possibly 5-,12-diHETE) metabolites of AA. The formation of PGs was blocked by 5 microM indomethacin, demonstrating that this cell line contains cyclooxygenase activity functionally similar to that described in macrophages and other cell types. The high activity of melittin in this system was shown to result largely from a synergy between the peptide itself and a persistent bee venom phospholipase A2 contaminant. However, experiments with melittin freed of detectable phospholipase A2 activity by heating, and with synthetic homopolymers of (L)-lysine and (L)-arginine demonstrated that HT-2 cells contain sufficient endogenous, stimulus-responsive phospholipase A2 to provide both the cyclooxygenase and lipoxygenase pathways of AA metabolism ith substrate. In contrast, Ca++ ionophores, which are known to stimulate AA release and metabolism in certain cell types, stimulated only AA release but no detectable eicosanoid biosynthesis in HT-2 cells. Experiments with exogenous bacterial phospholipase C suggested that this cell line can also generate free AA for eicosanoid biosynthesis from membrane-derived 1,2-diacylglycerol. These results indicate that multiple intracellular pathways of AA metabolism are present HT-2 cells, and that the stimulus-induced release of AA and the production of eicosanoid second messengers may result from activation of either phospholipase A2 or phospholipase C.

Animals↗

PubMedDate not supplied

A time to gain, a time to lose: new directions for western European HIV/AIDS alliances.

The complex and varied needs of people with HIV/AIDS have prompted major changes in the way that health care is organized and delivered. In the USA, the Netherlands and the UK, many HIV service providers have formed alliances to better coordinate policies and programs. These structural reforms have been accompanied by extensive reforms in the financing of health services. Drawing upon case studies of seven HIV/AIDS alliances in the Netherlands and the UK, the article examines how alliances are adapting their missions, organizational structures and functions to be responsive to changing community attitudes and the gradual elimination of earmarked HIV/AIDS funding. The case studies suggest strategies for maintaining interorganizational cooperation around public health issues in unstable and competitive funding environments.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

The newest miracle drug: quality circles in hospitals.

In recent years, a number of hospitals throughout the United States have been exploring the use of Japanese-style quality circles to reduce their operating expenses, improve productivity, and enhance the quality of work life for hospital employees. This article examines the organizational climate necessary for quality circles, methods used to implement quality circles, and management's role in guiding and responding to circle activities. Ideas for building and maintaining staff support are presented along with a cost/benefit analysis of quality circle programs. The author concludes that quality circles are most successful in hospitals where they are part of a larger organizational development effort. When administrators believe in their employees' ability to contribute to the institution and are willing to invest necessary time and resources in employee education and the measurement of quality circle achievements, quality circles can produce creative solutions to perplexing institutional problems.

Management Quality Circles↗

PubMedDate not supplied

States' responses to Title II of the Ryan White CARE Act.

Title II of the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act of 1990 provides formula-based grants to States to help them improve the quality, availability, and organization of health care and support services for people with human immunodeficiency virus (HIV) infection. This article reviews State expenditures during the first year of CARE Act funding (April 1991-March 1992) within the context of Title II guidelines and the federally funded grant programs that preceded and helped shape Title II. The authors also discuss future challenges that require development of resources, the assessment of program impact, and the evaluation of the quality and appropriateness of HIV-related services. Ninety-one percent of the $77.5 million awarded to States during fiscal year 1991 went for the provision of medical and support services through HIV care consortia, drug reimbursement programs, home and community-based care programs, and health insurance initiatives. The remaining monies were used for planning, evaluation, and program administration. Forty States allocated $38.9 million for the establishment of HIV care consortia to assess service needs and to develop comprehensive continuums of health and support services in the areas most affected by HIV disease. Fifty States allocated an additional $28.3 million for the continuation or expansion of FDA-approved drug therapies for low-income people with HIV infection. Twenty-five States allocated $2.2 million for the provision of home- and community-based health services, and 16 States allocated $1.3 million for programs that help low-income people with HIV infection to purchase or maintain health insurance coverage.

Financing, Government↗