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Biomedical subjects

R D Brown

Publications and source records attributed to R D Brown.

At least 289 records · Page 16Linked to original sources
PubMed1985

Interactions of concanavalin A with a trimannosyl oligosaccharide fragment of complex and high mannose type glycopeptides.

It has previously been reported that the binding interactions of concanavalin A with a purified high mannose type glycopeptide from ovalbumin differs from that with simple mono- and oligosaccharides (Brewer, C.F. (1979) Biochem. Biophys. Res. Commun. 90, 117-122). We now report studies with a synthetic analog of complex type glycopeptides, and a synthetic trimannosyl oligosaccharide fragment that is common to both complex and high mannose type glycopeptides. We find that both synthetic oligosacchardes undergo similar interactions with concanavalin A which mimic the effects of binding corresponding larger glycopeptides. Furthermore, the relative affinity of the trimannosyl oligosaccharide is 130-fold greater than the binding of methyl-alpha-D-mannopyranoside. The results indicate that the trimannosyl oligosaccharide is a unique structural element recognized by the lectin.

Concanavalin A↗
PubMed1985

Magnetic field dependence of proton relaxation rates in tissue with added Mn2+: rabbit liver and kidney.

Since contrast in magnetic resonance imaging (MRI) is so sensitive to the magnetic relaxation rates of tissue protons, the use of paramagnetic ions to alter contrast in a tissue-specific fashion is an alluring prospect. The influence of these ions on the proton relaxation rates in homogeneous solutions is known to vary dramatically according to whether the ions are present as hydrated aquoions, in solute chelate, or immobilized in macromolecules. In tissue, there is the additional complication of access of water to the ions. In the present study, Mn2+ ions were introduced into rabbits both orally and intravenously in various chemical complexes. Accumulation of these ions in rabbit liver is demonstrated here, qualitatively, by MRI. The quantitation of the change in relaxation rates is investigated in excised samples of liver and kidney by study of the magnetic field dependence (dispersion) of the relaxation rates of the protons (NMRD profiles) of tissue water. Results are presented for several sets of experiments, including dose-response data for weakly chelated Mn2+ and time-response data for free and complexed Mn2+. The general findings are that, for liver, the response (the increment in the NMRD profile) is relatively rapid (less than 2 m); that it is relatively independent of how, or in what form, the Mn2+ is introduced; that it persists for several hours (at least); and that it saturates with increasing body load of Mn2+. Moreover, from the form of the NMRD profiles of liver, it is clear that the Mn2+ ions are bound irrotationally, perhaps to cell membrane, and, when introduced in chelated form, can become separated even from strongly associated chelate complexes. For kidney, the results are qualitatively similar, though different in detail.

Animals↗
PubMed1985

Magnetic field dependence of solvent proton relaxation in aqueous solutions of Fe3+ complexes.

It might appear that the Fe3+ ion would be particularly useful as an agent for enhancing contrast in NMR images since it has a relatively large magnetic moment and occurs in vivo in a variety of forms. Moreover, the concentration of Fe3+ changes locally in certain disease states (e.g., beta-thalassemia) and in trauma (formation of methemoglobin), and can be altered in the gastrointestinal tract by the ingestion of readily available dietary supplements. However, the Fe3+ ion is insoluble above pH approximately 4, and soluble chelate and protein complexes of Fe3+ tend to sequester the ions from solvent; hence, the efficacy of Fe3+ ions for relaxing water protons ought to be low under typical physiological conditions. We report the magnetic field dependence of the relaxation rate of solvent protons (NMRD profiles) for solutions of a variety of Fe3+ complexes to demonstrate the phenomenology relevant to NMR imaging. From these data we make some estimates to show that, despite the low relaxation rates of solvent protons in solutions of Fe3+ complexes, certain observed changes in image contrast are consistent, quantitatively, with inferences that can be drawn from solution data.

Contrast Media↗
PubMed1985

Link between functional and morphological changes in the inner ear--functional changes produced by ototoxic agents and their interactions.

Common potentials used to evaluate cochlear function are the ac cochlear potential (ACCP), N1 and the positive dc endocochlear potential (EP). The ACCP is an electrical analogue of the sound stimulus; its source is the electrical activity of the cochlear hair cells. N1 is a volume conductor recorded action potential of the auditory nerve. The EP is the positive polarization of the middle compartment of the cochlea (scala media) with respect to the other compartments (the scalae tympani and vestibuli); the stria vascularis is apparently responsible for the EP. Generally, ototoxic drugs and very intense broad-band noise affect the basal portion of the cochlea first and, because of tonotopic organization, the ACCP responses to high frequency pure tones are affected before those to the low frequencies. However, the correlation between the effect of an ototraumatic agent on the ACCP and its effect on cochlear morphology is not always reliable. The correlations between changes in N1 and EP and in cochlear morphology are even less precise. Also discussed will be the cochlear effects of noise and the ototoxic interactions between drug/drug, noise/drug, and noise/drug/otitis media.

Acetylcysteine↗
PubMed1985

Absence of a pharmacokinetic interaction between chloramphenicol and acetaminophen in children.

The pharmacokinetics of chloramphenicol (CAP; administered intravenously as chloramphenicol succinate, CAPS) was studied in 26 acutely ill febrile children 3 to 58 months of age who either did (n = 18) or did not (n = 8) receive acetaminophen (APAP) for antipyresis. CAP pharmacokinetics were evaluated after the first dose and at steady state. CAP serum levels were quantitated by high-performance liquid chromatography. There were no significant differences between groups (APAP vs non-APAP) or between first dose and steady-state evaluations for the elimination rate constant, serum half-life, apparent volume of distribution, and serum clearance of CAP. Likewise, there were no statistically significant differences when the APAP group was evaluated according to the presence or absence of APAP in serum before the first dose of CAP. Elimination of CAP in subjects with serum CAPS level less than 1 microgram/ml was similar in the first dose and steady-state evaluations and in the APAP and non-APAP groups. The presence or absence of CAPS or APAP did not affect the estimation of CAP elimination. Thus a pharmacokinetic interaction between CAP and APAP was not demonstrated in acutely ill febrile children during concomitant therapy.

Acetaminophen↗
PubMed1985

Lactoferrin in the myeloproliferative disorders: a search for granulopoietic regulator defects.

Evidence of a defect in the negative feedback control of granulopoiesis in the myeloproliferative disorders is presented. Neutrophil release of lactoferrin, plasma lactoferrin concentration, the number of lactoferrin receptor sites on mononuclear cells and granulocyte-monocyte colony stimulating factor (GM-CSF) release from peripheral blood cells were determined in patients with myeloproliferative disorders and compared with normal individuals. There was a significantly (P less than 0.001) decreased release of lactoferrin from the neutrophils of patients with myeloproliferative disorders which could be responsible for a reduced suppression of GM-CSF release from mononuclear cells which in turn may be responsible for the increased myeloid proliferative activity in patients with myeloproliferative disorders.

Colony-Stimulating Factors↗
PubMed1985

The prediction of anatomical morphology of primary aldosteronism using serum 18-hydroxycorticosterone levels.

Serum 18-hydroxycorticosterone, aldosterone, and potassium were measured under basal conditions in 34 patients with documented primary aldosteronism, 10 patients with essential hypertension, and 9 normal subjects. The results revealed that 22 of 23 patients with aldosterone-producing adenomas had 18-hydroxycorticosterone levels greater than 100 ng/dl, and all 9 patients with idiopathic adrenal hyperplasia had plasma levels less than 100 ng/dl. Two patients with unusual macromicronodular hyperplasia of the adrenal glands had levels greater than 100 ng/dl. We found a significant relationship between serum potassium and the ratio of 18-hydroxycorticosterone to aldosterone in patients with idiopathic adrenal hyperplasia, but not in those with an aldosterone-producing adenoma. We conclude that measurement of serum 18-hydroxycorticosterone is a useful predictor of the etiology of primary aldosteronism.

18-Hydroxycorticosterone↗
PubMed1985

Metabolism of calcium and phosphorus during pregnancy and lactation in white-tailed deer.

The effects of pregnancy and early lactation on blood parameters were studied in 4 white-tailed does in 1981-82 and 8 in 1982-83. No year or fecundity effects (P less than 0.05) were found on plasma calcium (Ca), inorganic phosphorus (P), calcitonin (CT), parathyroid hormone (PTH), or oestradiol -17 beta (E2). An increase (P less than 0.05) in dry matter and metabolic feed intake occurred during pregnancy and lactation. Plasma Ca tended to increase during pregnancy and peaked 5-7 weeks pre-partum, while hypocalcaemia was observed 1-2 weeks pre-partum. Elevated concentrations of plasma Ca and P were found during lactation. During the last trimester of pregnancy, plasma concentrations of alkaline phosphatase (AP), PTH, and E2 but not of CT were higher (P less than 0.05) than in the other trimesters. The results indicate a physiological hyperparathyroidism in pregnant deer. Plasma concentrations of CT were higher (P less than 0.05) during lactation and post-weaning than during pregnancy. Increased AP and PTH during late pregnancy may be responsible for Ca absorption and mobilization, whereas elevated plasma concentrations of E2 may function to block excessive bone resorption. After parturition, lowered E2 may allow bone resorption to proceed, relatively high PTH may enhance Ca absorption and mobilization, and elevated CT may protect the skeleton against excessive bone resorption.

Animals↗
PubMed1984

Preparation and characterization of Ca2+-Zn2+-derivatives of lentil and pea lectins and comparison with the native forms.

Ca2+-Zn2+-derivatives of lentil and pea lectins were prepared for the first time by a unique method involving dialysis of the native Ca2+-Mn2+-lectins against large excesses of metal ions in pH 4.0 buffer. Each derivative contained about 1.5 g atoms of Ca2+ and about 1 g atom of Zn2+ per monomer. The derivatives were found to be identical to their respective native forms, both in molecular weight and carbohydrate binding activities. Solvent proton relaxation dispersion measurements were used to characterize both the Ca2+-Zn2+- and Ca2+-Mn2+-complexes of the lentil lectin.

Calcium↗
PubMed1984

The relationship between alpha 1-adrenergic receptor occupation and the mobilization of intracellular calcium.

We have simultaneously quantitated alpha 1-adrenergic receptor occupation and agonist-elicited Ca2+ mobilization monitored as unidirectional 45Ca2+ efflux from intact BC3H-1 muscle cells in order to examine the relationship between the number of surface receptors occupied and the functional response. [3H]Prazosin has been used to measure receptor number as well as the binding kinetics with surface receptors, and the observed equilibrium and kinetic constants are in close accord with values obtained previously in cellular homogenates. Since alpha 1-agonist-elicited 45Ca2+ efflux can be monitored over intervals of 3 min or less and prazosin dissociation from its receptor has a t 1/2 of 44 min, prazosin can be employed to produce a pseudoirreversible inactivation of receptors. A comparison of the remaining receptors and residual response reveals an inverse linear relationship between receptors inactivated by prazosin and 45Ca2+ efflux. A similar result is obtained following fractional receptor inactivation with the irreversible alkylating agent phenoxybenzamine. Parameters of receptor occupation and response also correlate well for the agonist phenylephrine and for the competitive antagonist phentolamine. The unitary relationship between sites available for occupation and response indicates that the alpha 1 receptor does not function as an oligomer where fewer bound antagonist molecules are required to block the receptor than sites of agonist occupation necessary for activation. Moreover, substantial evidence has accrued in intact smooth muscle for a receptor reserve or nonlinear coupling between alpha 1 receptor occupation and contraction in smooth muscle. Our findings demonstrate that such behavior does not exist for alpha 1 receptor-elicited mobilization of Ca2+ in the BC3H-1 muscle cell.

Animals↗
PubMed1984

A new interstellar molecule: tricarbon monoxide.

The cold dark interstellar Taurus Molecular Cloud One (TMC-1) is a rich source of acetylenic and polyacetylenic molecular species. As well as linear closed-shell molecules (H(C triple bond C)nCN) and symmetric rotors (CH3C triple bond CH, CH3C triple bond CCN), several radicals (C triple bond CH, C triple bond CCN, (C triple bond C2H) have also been identified, many of which had not been studied previously in the laboratory. Whether the observed abundances can be understood in terms of purely gas-phase ion-molecule chemical schemes, which produce reasonable agreement for the simplest polyatomic species, is unclear; alternative models involving the particulate interstellar grains as catalysts or sources have also been suggested. We now report the detection in TMC-1 of a new molecule, tricarbon monoxide (C3O), whose pure rotational spectrum has only very recently been studied in the laboratory. As C3O is the first known interstellar carbon chain molecule to contain oxygen, its existence places an important new constraint on chemical schemes for cold interstellar clouds. In fact, the observed abundance of tricarbon monoxide fits quite well into our model of galactochemistry.

Astronomical Phenomena↗