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Biomedical subjects

J L Day

Publications and source records attributed to J L Day.

At least 55 records · Page 3Linked to original sources
PubMed1980

Regulation of RNA- and DNA-directed actions of 5-fluoropyrimidines in mouse T-lymphoma (S-49) cells.

The mouse T-lymphoma (S-49) cell line is useful for individually studying RNA- and DNA-directed effects of 5-fluoropyrimidines. On the basis of their metabolic activation, biochemical effects on pyrimidine nucleotide metabolism, and biological toxicity, we hve established that incubation of S-49 cells with 5-fluorodeoxyuridine produces only DNA-directed toxicity (thymidylate synthetase inhibition), incubation with 5-fluorouracil (FUra) + thymidine only RNA-directed toxicity, and incubation with FUra alone produces both DNA- and RNA-directed toxicity. The DNA component of 5-fluoropyrimidine toxicity causes immediate growth inhibition of asynchronous S-49 cell cultures, which is self-limited within 12 hr both by the accumulation of intracellular deoxyuridine 5'-monophosphate competing for thymidylate synthetase binding and by the excretion of deoxyuridine into the cell medium which competes with 5-fluorodeoxyuridine uptake. The RNA-directed component causes growth inhibition and cell kill after a delay of 1 doubling time in asynchronous cultures. Studies with cells synchronized by centrifugal elutriation indicate that the RNA-directed FUra effects are expressed only in the G1 phase of the cell cycle and cause rapid cell lysis, while the DNA-directed component is specific to the S phase. Experiments using continuous exposure of synchronized cells to FUra alone demonstrate that the activities of the RNA- and DNA-directed components interact with each other. Specifically, DNA-directed toxicity arrests cells in S phase, preventing them from progressing into G1 where RNA-directed toxicity is expressed, which may account for the augmentation of FUra toxicity by thymidine as reported in other systems.

Animals↗
PubMed1979

Metabolic consequences of atenolol and propranolol in treatment of essential hypertension.

A six-month study of triglyceride, cholesterol, free fatty acid (FFA), glucose, insulin, growth hormone, and glucagon concentrations was carried out in asymptomatic hypertensive normal-weight men randomly allocated to treatment with atenolol or propranolol. A highly significant increase in the basal plasma triglyceride concentration was observed in propranolol-treated patients after three and six months' treatment, with a smaller but significant increase in atenolol-treated subjects after six months' treatment. The changes in triglyceride concentration could not be ascribed to variations in plasma insulin, growth hormone, or glucagon concentrations. Basal FFA concentrations were reduced during the first three months of treatment in both groups but returned to pretreatment levels after six months. Plasma cholesterol concentrations were unchanged by either agent.

Adult↗
PubMed1979

Rapid computation of diagnostic X-ray bremsstrahlung spectra.

A method is described for rapid and accurate computation of diagnostic x-ray spectra. Accuracy limitations of Kramers' equation are overcome by providing intensity correction factors derived from published measured data. Use of a parameter based on the energy of the Kramers spectrum intensity peak permits deriving master factor curves which are remarkably independent of kVp, waveform and filtration. Computed and measured spectra generally agree to better than +/- 1 keV for beams generated at 100 kVp and below. Possible application of the method to higher energy diagnostic beams is discussed.

Mathematics↗
PubMed1979

A study of mammographic exposure and detail visibility using three systems: Xerox 125, Min-R, and Xonics XERG.

A breast phantom of novel design has been used to measure visibility of simulated calcific and soft-tissue fibrillar details in mammography, as well as to determine the roentgen exposure vs. depth. Exposure data were combined with a model of the breast as compressed during mammography to compute the mean exposure to the ductal parenchyma (MDE). Three different imaging systems were compared over a wide range of x-ray beam energies and breast characteristics. "Dosage" criteria other than the MDE are discussed.

Breast↗
PubMed1978

Assay of mercaptopurine in plasma using paired-ion high-performance liquid chromatography.

A sensitive, quantitative, and specific high-performance liquid chromatographic method for mercaptopurine in plasma is described. The analysis, in which mercaptopurine and the internal standard, 6-methylthio-2-hydroxypurine, are chromatographed as ion-pairs with heptane-sulfonic acid, employs a simple and rapid sample preparation based on deproteination using 60% trichloroacetic acid. Quantitation of plasma samples to 0.2 microgram of mercaptopurine/ml is reported. The retention times of the major metabolites do not interfere.

Animals↗
PubMed1978

Factors governing insulin and glucagon responses during normal meals.

An experimental model is described which can be used to study substrate and hormone responses to normal meals administered in very near normal circumstances. After 500, 300 and 125 calorie meals, the relative proportion of fat or protein content did not influence the plasma glucose except for minor differences between the high protein-high fat meals. The insulin response to such meals was correlated positively with the increment in glucose but reduction of protein content below 8 g caused a signficant reduction in the increment in plasma insulin per unit increase in plasma glucose. Alterations in protein content above 8 g made no difference. Fat content of the meal did not significantly alter the insulin response. No evidence was obtained for a major component of insulin release attributable to either bulk or preabsorption phenomena such as sight or smell. It is concluded that a significant accentuation of the insulin response to meals is dependent on a minimum amount of protein and that this is probably mediated by one of the gastro-intestinal hormones. Glucagon release is dependent on protein and carbohydrate content of the meal and is independent of the fat content. There may also be an early stimulation of glucagon release, regardless of content, which may also be hormonally mediated.

Adult↗
PubMed1978

Reproducibility and comparative analysis of repeated intravenous and oral glucose tolerance tests.

We have developed a methodology for measuring the reproducibility of the oral glucose tolerance test (OGTT) and the intravenous glucose tolerance test (IVGTT) in normal subjects and in offspring of conjugal diabetic parents. Both groups of subjects revealed more striking correlations of several parameters of blood glucose and insulin secretion between two IVGTTs than between two OGTTs. Employing arbitrary criteria, we calculated a "reproducibility index" as a quantitative measure of blood glucose variability in each subject. No significant difference was found in the reproducibility of OGTT versus IVGTT, nor in normals versus the offspring. Only about 50 per cent of the tests in normals and in the offspring could be considered to be "reproducible." The offspring revealed greater correlations of several parameters, particularly insulin secretion, between the two IVGTTs and between the two OGTTs as compared with the normal group. However, the blood glucose variations tended to be considerably greater in the offspring from one to the other test.

Administration, Oral↗
PubMed1977

Pharmacokinetics of mercaptopurine.

The anatomical distribution of mercaptopurine was investigated in rats at dose levels of 2.5 and 25 mg/kg iv. The plasma and tissues were analyzed by radioisotopic dilution and spectrofluorometric techniques. The tissue-plasma ratios were: liver-plasma, approximately 4.0; kidney-plasma, approximately 2.4; spleen-plasma, approximately 1.7; muscle-plasma, approximately 1.4; gut lumen-plasma, approximately 3; and bone marrow-plasma, approximately 0.35. Physiologically based pharmacokinetic models were developed to simulate concentrations of mercaptopurine in plasma, kidneys, liver, muscle, spleen, bone marrow, and gut lumen. The agreement between experimental and predicted plasma and tissue profiles was good. Human plasma levels of mercapto-purine were predicted and, when compared with clinical data, demonstrated reasonable agreement.

Animals↗
PubMed1975

Glucagon secretion in unaffected monozygotic twins of juvenile diabetics.

Glucagon secretion during a 50-g oral glucose tolerance test has been investigated in 16 nondiabetic monozygotic twins of juvenile diabetics and compared with the results in 10 normal controls and 10 untreated, newly diagnosed, maturity-onset diabetics. Normal subjects showed a significant mean fall in glucagon at 15, 30, and 60 min, with a return to the baseline at 120 min. Maturity-onset diabetics showed a significant mean rise 15 min after oral glucose. The mean of the twin group was intermediate between normals and diabetics, although there was considerable individual variation with some showing suppression and others stimulation of glucagon release. When the twins were divided according to the length of discordance it was found that the mean response in the 8 twins who had been discordant for a mean of 19 years was indistinguishable from that of normal subjects, whereas the mean response of twins discordant for a mean of only 4.5 years was similar to that of the diabetic patients. It is possible, therefore, that hypersecretion of glucagon may occur in some subjects predisposed to develop diabetes mellitus, and the finding of lack of suppression of glucagon in the identical twin of a juvenile diabetic may be of prognostic significance. Identical twins who have been discordant for over 10 years are thought on other grounds to be unlikely to develop diabetes, and the finding of a normal glucagon response is further confirmation of their normal metabolic status and reinforces the suggestion that they are not prediabetic.

Adult↗
PubMed1975

The metabolic consequences of adrenergic blockade: a reveiw.

The effects in man of adrenergic blocking agents on plasma insulin, glucagon, growth hormone, and lipid metabolism are reviewed. Whereas basal insulin may be slightly inhibited by beta- and enhanced by alpha-adrenergic blockade, more marked suppression may be achieved under circumstances of high exogenous or endogenous catecholamine stimulation. The relative effects of beta1 or combined beta 1 and beta2 blockers in man are unknown. Glucagon release is probably provoked by beta- and inhibited by alpha-stimulation in man. Muscle glycogenolysis is inhibited by propranolol, and under situations of hepatic glycogen depletion, clinical hypopglycemia may occur. This may also account for the failure of significant hyperglycemia to be observed in short-term experiments on fasting subjects in whom insulin release may be suppressed and glucagon release enhanced. Growth-hormone release is enhanced by beta-adrenergic blockade. Free fatty acid formation in vivo is inhibited by intravenous beta blockade, but the effects of oral administration on triglyceride production and lipoprotein profiles remain uncertain. The inter-relationships between the effects of adrenergic blockade at different sites of hormone and substrate release are unclear but may have important consequences in alteration in carbohydrate tolerance and lipid metabolism. The relative effects of beta-blocking drugs with differing specificity must be determined.

Adrenergic alpha-Antagonists↗