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D L Kennedy

Publications and source records attributed to D L Kennedy.

44 records · Page 3Linked to original sources
PubMed1976

Rat high density lipoprotein subfraction (HDL3) uptake and catabolism by isolated rat liver parenchymal cells.

Rat liver parenchymal cell binding, uptake, and proteolytic degradation of rat 125I-labeled high density lipoprotein (HDL) subfraction, HDL3 (1.10 less than d less than 1.210 g/ml), in which apo-A-I is the major polypeptide, were investigated. Structural and metabolic integrity of the isolated cells was verified by trypan blue exclusion, low lactic dehydrogenase leakage, expected morphology, and gluconeogenesis from lactate and pyruvate. 125I-labeled HDL3 was incubated with 10 X 10(6) cells at 37 degrees and 4 degrees in albumin and Krebs-Henseleit bicarbonate buffer, pH 7.4. Binding and uptake were determined by radioactivity in washed cells. Proteolytic degradation was determined by trichloroacetic acid-soluble radioactivity in the incubation medium. At 37 degrees, maximum HDL3 binding (Bmax) and uptake occurred at 30 min with a Bmax of 31 ng/mg dry weight of cells. The apparent dissociation constant of the HDL3 receptor system (Kd) was 60 X 10(-8) M, based on Mr = 28,000 of apo-A-I, the predominant rat HDL3 protein. Proteolytic degradation showed a 15-min lag and then constant proteolysis. After 2 hours 5.8% of incubated 125I-labeled HDL3 was degraded. Sixty per cent of cell radioactivity at 37 degrees was trypsin-releasable. At 37 degrees, 125I-labeled HDL3 was incubated with cells in the presence of varying concentrations of native (cold) HDL3, very low density lipoproteins, and low density lipoproteins. Incubation with native HDL3 resulted in greatest inhibition of 125I-labeled HDL3 binding, uptake, and proteolytic degradation. When 125I-labeled HDL3 was preincubated with increasing amounts of HDL3 antiserum, binding and uptake by cells were decreased to complete inhibition. Cell binding, uptake, and proteolytic degradation of 125I-labeled HDL3 were markedly diminished at 4 degrees. Less than 1 mM chloroquine enhanced 125I-labeled HDL3 proteolysis but at 5 mM or greater, chloroquine inhibited proteolysis with 125I-labeled HDL3 accumulation in cells. L-[U-14C]Lysine-labeled HDL3 was bound, taken up, and degraded by cells as effectively as 125I-labeled HDL3. These data suggest that liver cell binding, uptake, and proteolytic degradation of rat HDL3 are actively performed and linked in the sequence:binding, then uptake, and finally proteolytic degradation. Furthermore, there may be a specific HDL3 (lipoprotein A) receptor of recognition site(s) on the plasma membrane. Finally, our data further support our previous reports of the important role of liver lysosomes in proteolytic degradation of HDL3.

Animals↗
PubMed1976

Behavior of alcoholics and spouses in a simulation game situation.

The interaction of alcoholics and their spouses in a simulation game was systematically observed and compared to the behavior of nonalcoholic couples. Overall, 28 couples played a mixed-motive bargaining game, the "tax game," which is a modification of Kelly's "game of nines." Alcohol couples as a group did not manifest a distinct game "style." They were less uniform in this respect than "normal" couples and a mixed group of "psychiatrically disturbed" couples. Subgroup trends without the alcoholic sample were suggested and discussed. Extreme behavior, rigidity, and lack of communication were common features in the game behavior of alcoholic couples that did not appear to relate to a particular game style, but did distinguish the game play of alcoholic couples from that of nonalcoholic couples.

Adult↗
PubMedDate not supplied

Trends in use of oral hypoglycemic agents 1964-1986.

Oral hypoglycemic (OH) agents have been available in the United States for the treatment of non-insulin-dependent diabetes mellitus (NIDDM) for almost 30 yr. During this time they have been subject to considerable controversy. In this article, we present pharmaceutical marketing research data that provide a review of several facets of OH use. The number of OH prescriptions dispensed peaked in 1973, decreased through 1980, and has been increasing since that year. In 1986, OH agents accounted for 21.5 million prescriptions: 1% of all prescriptions dispensed that year. Chlorpropamide is currently the most frequently ingested OH agent; it is used by 33% of the market. The two OH agents introduced in 1984, glyburide and glipizide, had acquired 41% of the OH market by the end of 1986. The rate of OH use per 1000 diabetes mellitus visits increases with patient's age. Patients aged 60 yr and older received OH prescriptions at a rate of 478 per 1000 diabetes mellitus visits in 1986. Data estimating both the number of patients diagnosed with diabetes and the number of diabetic patients taking OH agents indicate that the percentage receiving OH treatment has increased over the past 5 yr, with approximately 35% of all diabetic patients taking OH agents in 1986.

Diabetes Mellitus, Type 2↗
PubMedDate not supplied

Data sources and methods for ascertaining human exposure to drugs.

Estimates of population exposure based on drug use data are critical elements in the post marketing surveillance of drugs and provide a context for assessing the various risks and benefits associated with drug treatment. Such information is important in predicting morbidity and planning public health protection strategies, indepth studies, and regulatory actions. Knowledge that a population of one thousand instead of one million may potentially be exposed to a drug can help determine how a particular regulatory problem will be handled and would obviously be a major determinant in designing a case-control or cohort study. National estimates of drug use give an overview of the most commonly used drug therapies in current practice. They also furnish valuable comparison data for specific studies of drug use limited to one group of drugs, one geographic region, or one medical care setting. The FDA has access to several different national drug use data bases, each measuring a different point in the drug distribution channels. None covers the entire spectrum of drug exposures. The major "holes" in this patchwork of data bases are the inability to measure OTC drug use with any accuracy and the lack of qualitative information on drug use in hospitals. In addition, there is no patient linkage with the data. The data can only show trends in drug use. They impart no sense of the longitudinal use of drugs for individual patients. There is no direct connection between the different data bases, all of which have their own sampling frames and their own projection methodologies. The market research companies have complete control over these methodologies and they are subject to periodic changes, a situation not entirely satisfactory for epidemiologic research. Sometimes it is a struggle to keep up with these changes. Over the past two years, every one of these data bases has undergone some type of sampling or projection methodology change. One important limitation to the use of all of these data bases is that they are subscription data bases, that is, the FDA purchases the data under contract to the marketing research companies and by doing so assumes certain contract obligations. Anytime the FDA wants to release any data outside of the Agency, it must first notify the company in sufficient time for review and approval. Subscribing to these data bases is costly, but the subscription cost is insignificant, compared to the estimated cost of duplicating these services. In spite of all of the limitations of these systems, there are obvious advantages.(ABSTRACT TRUNCATED AT 400 WORDS)

Computers↗