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Biomedical subjects

D Rodbard

Publications and source records attributed to D Rodbard.

At least 127 records · Page 7Linked to original sources
PubMed1978

Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves.

Physiological and pharmacological studies of hormones, drugs, and neurotransmitters often generate families of sigmoidal dose-response curves. Optimally efficient data analysis should involve simultaneous description of all curves, rather than fitting each one individually. We have developed a general computerized method to describe the dose-response curves in terms of basal and maximal responses, ED50, and curve shape or steepness. This facile method permits rigorous statistical analysis, provides a basis for pooling of information from separate experiments, and allows one to test which characteristics are shared by various curves.

Binding, Competitive↗
PubMed1977

Noninvasive monitoring of beta-adrenergic tone during isoproterenol infusions.

Sphygmo-Recording is a simple, noninvasive technique for analysis of pulse wave contour and timing which has been used to evaluate the change in cardiac dynamics during isoproterenol infusion. The QKd interval, i.e., the time interval between the onset of the QRS complex and the onset of the Korotkoff sound at the brachial artery when the sphygomomanometer cuff is at diastolic pressure, is normally 205 +/- 15 msec. Continuous intravenous infusion of isoproterenol at 0.01, 0.02, and 0.03 microgram/kg/min into 12 euthyroid normotensive adult volunteers for 10-min intervals resulted in decreases of 55, 79, and 89 msec in QKd and increases of heart rate of 14, 27, and 43 beats/min, respectively. The corresponding changes in dP/dt, i.e., slope of the pulse wave upstroke at the brachial artery determined noninvasively from the same records, were 0.65, 1.47, and 2.26 mm Hg/msec. These results confirm previous studies which indicate that the chronotropic response of normal subjects to isoproterenol infusion is comparable to that previously reported in patients with the putative "hyperdynamic beta-adrenergic state."

Adolescent↗
PubMed1977

Can one mix two non-specific antisera and obtain a specific radioimmunoassay?

Sekihara et al. have proposed that it is possible to combine two antisera, each of which is unsatisfactory for a clinical radioimmunoassay due to cross-reactivity problems, and obtain an assay which is of sufficiently good specificity for practical application. The present report provides a theoretical analysis of this problem in a "reduced" case of minimal complexity. We assume infinitesimal concentration of tracer, equilibrium of reactants, perfect separation of bound and free, and that each of the two antisera contain only a single class of antibody sites which can bind to the desired ligand or to a cross-reacting species. Numerical methods are used to generate "ideal" dose response curves. The specificity is evaluated by three criteria: 1) as the ratio of ligand concentrations resulting in 10 or 50% reduction of binding of labeled ligand to antibody, i.e. %B/BO = 90 or 50%; 2) the %B/BO or %B/T at an arbitrary dose level; or 3) the apparent amount of ligand present, for an arbitrary dose of crossreacting ligand. Results indicate that mixing of two nonspecific antisera (each cross-reacting with a different ligand) results in a radioimmunoassay system with a specificity intermediate between that obtained with either of the antisera used alone. Whether this will provide a "satisfactory" assay depends on the purposes for which it is intended, the expected concentrations of cross-reacting ligands, etc. Computer simulation studies may be utilized to select the optimal ratio of the two antisera being used for the assay.

Androstenediols↗
PubMed1977

New method of quantifying ligand binding based on measurement of an induced response.

A new general method is proposed for quantifying ligand-receptor interactions using the biological response induced by the ligand as an index of ligand binding. With this method the binding of human chorionic gonadotropin (hCG), several hCG derivatives, and luteinizing hormone (LH) to rat Leydig cells was measured by analysis of the ability of these materials to stimulate testosterone formation. As applied here, hormone dose-response curves were generated in the presence of increasing numbers of cells incubated in vitro in a successful attempt to alter the concentrations of bound and free hormone in the incubation mixture. Measurements of testosterone synthesis as a function of the total amounts of hormone and numbers of cells enabled us to evaluate the concentrations of both bound and free hormone at any constant fractional response (i.e. quarter-, half-, or three-quarter-maximal). We were thus able to measure hormone binding at the extremely low hormone concentrations (1 pM) within the steroidogenic dose-response range under conditions that would not have been possible using currently available radioiodinated hCG preparations. The results obrained confirmed the presence of spare functional receptors. Specific quantitative results are discussed in the text.

Animals↗
PubMed1977

Automated computer analysis for enzyme-multiplied immunological techniques.

The dose/response curve in enzyme-multiplied immunoassays (EMIT) and related techniques may be described by the same "four-parameter logistic function" as has proven useful in radioimmunoassays, immunoradiometric assays (IRMA), and two-site immunoradiometric ("sandwhich") assays. This function provides an empirical description of the dose/response curve by use of an objective least-squares regression analysis, with the advantages of computerization and automation. This facilitates further statistical analyses, quality control, estimation of precision for an unknown, and improved, objective estimation of the sensitivity or minimal detectable dose.

Computers↗
PubMed1976

Sex differences in binding of human growth hormone to isolated rat hepatocytes.

Since liver is a target for growth hormone action, binding of 125I-labeled human growth hormone to enzymatically isolated rat hepatocytes was studied. Specific binding was shown with hepatocytes from both male and female animals. There was a single class of receptors for human growth hormone on cells from males (affinity constant, Ka = 1.16 x 10(9) liters/mole; sites per cell, q = 6200). In males, bovine growth hormone was almost as potent as human growth hormone in displacing bound 125I-labeled human growth hormone, while ovine prolactin was about 1000 times less potent. Cells from female rats bound more 125I-labeled human growth hormone than cells from males. The cells from females contained at least two classes of receptors for human growth hormone. The receptor of highest affinity had the same affinity for human growth hormone as the single receptor found in males (Ka = 0.96 x 10(9) liters/mole). However, there were three to four times as many of these receptors per cell in females (q = 21,000). In females, bovine growth hormone and ovine prolactin were both about 20 times less potent than human growth hormone. Treatment of male rats with estrone produced cells that show the same binding characteristics as females. These results indicate that human growth hormone binds to a somatogenic receptor in hepatocytes from male rats. In females and estrogen-treated males, the receptors that bind human growth hormone recognize lactogenic as well as somatogenic properties. This suggests that the lactogenic and growth-promoting effects of human growth hormone in the rat are mediated by different receptors.

Animals↗
PubMed1976

Characterization of somatogenic and lactogenic binding sites in isolated rat hepatocytes.

Suspensions of rat hepatocytes isolated enzymatically by the method of Berry and Friend were used to study the binding of 125I-labeled human (hGH) and bovine (bGH) growth hormones and ovine prolactin (oPRL). Displacement of these labeled hormones by their unlabeled analogues was analyzed by means of Scatchard plots and affinity constants (K) and the number of binding sites per cell (q) were calculated. Specificity of binding was studied using hGH, bGH oPRL and rat growth hormone (rGH) and rat prolactin (rPRL). Rat hepatocytes contained two types of binding sites which bound hGH. The first, somatogenic, was specific for the growth-promoting hormones bGH and rGH. The second, lactogenic, was specific for lactogenic hormones, oPRL and rPRL. Human GH, which has both lactogenic and growth-promoting properties in rodents, bound to both sites. The somatogenic binding sites were present in both males and females, and the number of sites was similar in females and in males and was not affected by hypophysectomy. The lactogenic binding sites were present only in females, and the number of lactogenic and somatogenic sites was similar (40,000/cell). The affinity of hGH for the lactogenic binding sites was less than for the somatogenic (0.37 X 10(9) vs. 1 X 10(9)M-1). The lactogenic binding sites were lost when female rats were hypophysectomized and could not be restored by estrogen treatment.

Animals↗
PubMed1976

Improved diagnosis and management of hyper- and hypothyroidism by timing the arterial sounds.

"Sphygmo-Recording," a non-invasive method for timing the arterial pulse wave contour provides an objective measure of responses to medication in patients with hyper- and hypothyroidism. The QKd interval, i.e., the interval from the onset of the QRS complex (Q) to the onset of the Korotkoff sounds (K) at the brachial artery when the sphygmomanometer cuff is at diastolic pressure (d) is the QKd interval. QKd is normally 205 +/- 12 msec. In the hyperthyroidism the QKd interval may be shortened to 110 msec. In hypothyroidism the QKd interval may be prolonged to 320 msec. Changes in QKd parallel changes in clinical status and serum total T4 and T3, measured by radioimmunoassay. QKd can be used as an objective guide to antithyroid therapy in hyperthyroidism and replacement therapy with thyroid hormone in hypothyroid individuals.

Adult↗