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Biomedical subjects

R D Brown

Publications and source records attributed to R D Brown.

At least 307 records · Page 17Linked to original sources
PubMed1984

Alpha 1-adrenergic receptor activation mobilizes cellular Ca2+ in a muscle cell line.

Regulation of cellular Ca2+ movements by alpha 1-adrenergic receptors has been studied using 45Ca2+ flux techniques in monolayer cultures of intact BC3H-1 cells. Unidirectional 45Ca2+ efflux from BC3H-1 cells reveals multiphasic kinetics, with a major fraction of cellular Ca2+ residing in a slowly exchanging intracellular compartment. Stimulation of alpha 1-adrenergic receptors by the agonist phenylephrine substantially increases 45Ca2+ unidirectional efflux, accompanied by a far smaller increase in 45Ca2+ influx. The selective enhancement of 45Ca2+ unidirectional efflux upon alpha 1-adrenergic receptor activation results in a net 30-40% decline in total cell Ca2+ content, measured either by radioisotopic equilibrium techniques or by atomic absorption spectroscopy. The relatively large pool of Ca2+ responsive to alpha-adrenergic stimulation is not displaced by La3+ but can be depleted with the Ca2+ ionophore A-23187. These results indicate that alpha 1-adrenergic receptor activation predominantly mobilizes Ca2+ from intracellular stores, together with a much smaller increase in transmembrane Ca2+ permeability. This interpretation is supported by comparative 45Ca2+ flux studies using a sister clone of BC3H-1 cells possessing surface nicotinic acetylcholine receptors but no alpha 1-adrenergic receptors. Agonist stimulation of the cholinergic receptor opens a well characterized transmembrane ion permeability gate. Cholinergic receptor activation greatly enhances the observed 45Ca2+ unidirectional influx relative to efflux, leading to net elevation of cellular Ca2+ content as Ca2+ moves down its inwardly directed concentration gradient.

Animals↗
PubMed1984

Scanning electron microscopy of the cochlea in rats with Streptococcus pneumoniae otitis media.

This investigation was performed to determine the morphologic effects of bacterial otitis media on the organ of Corti. The middle ear cavities of rats were inoculated with Streptococcus pneumoniae or saline and the animals were killed on days 1, 4, 7, 10, 14, and 21 after inoculation. Middle ear cultures were obtained and the cochleas were examined using scanning electron microscopy. All animals killed on day 1 had positive cultures, but by day 21, all cultures were negative. Cochlear changes observed were (1) damage to supporting cells (Deiters' cells), (2) morphologic changes of hair cell stereocilia, and (3) loss of inner and outer hair cell stereocilia and cell bodies (to a lesser extent), especially in the lower middle and basal turns. These changes appeared to occur in a definite sequence; ie, damage to the supporting cells, changes in stereocilia, and, finally, hair cell loss. These data show that cochlear damage and hair loss can be associated with bacterial otitis media.

Animals↗
PubMed1984

Fate of stored secretion following ligation of the seminal vesicle-coagulating gland in the rat.

Unilateral ligation of the seminal vesicle-coagulating gland complex in castrated and testes intact sexually mature rats resulted in a significant asymmetry in weight after 14 days, with ligated glands heavier in both groups. Differences in weight between glands resulted from ligation, and the primary route by which stored secretion is eliminated from these glands is by spontaneous ejaculation rather than resorption via the glandular epithelia.

Animals↗
PubMed1984

Determinants of proton relaxation rates in tissue.

It is well established that the longitudinal magnetic relaxation rate of solvent water protons, 1/T1, increases markedly in homogeneous protein solutions as the magnetic field is reduced well below the traditional NMR range. For a 5% solution of protein of 10(5) Da, for example, 1/T1 increases from about 50% above the pure water rate of 20 MHz to five times the water rate at 0.01 MHz. For tissue, including blood, the behavior is similar. Data for blood show that extracellular water has ready access to the hemoglobin inside red blood cells, which causes the enhanced relaxation. The extent to which cell water can sample the spatial structure of soft tissue, and how this structure influences relaxation rates, is as yet unknown. Nonetheless, the relaxation data for tissue can be accommodated within the conceptual framework developed earlier for analyzing homogeneous solutions of diamagnetic proteins. The variation of 1/T1 with field differs among tissues, and its magnitude at a given field can vary by more than a factor of three, far more than does the water content of the tissues. Solute complexes of paramagnetic ions with macromolecules, which increase the relaxation rates of solvent protons, can be introduced intravenously in tissue. They are known to accumulate in specific organs, and therefore have potential utility as contrast-enhancing agents in NMR imaging. Mn2+ and Gd3+, for example, produce characteristic dependences of 1/T1 on magnetic field that vary with the chemical state of the agent. The possibility exists, therefore, for monitoring the in vivo biochemistry of these agents.

Animals↗
PubMed1984

Relaxation of solvent protons by paramagnetic ions and its dependence on magnetic field and chemical environment: implications for NMR imaging.

Paramagnetic ions have been used to alter the magnetic relaxation rates 1/T1 and 1/T2 of solvent water protons since the first observations of a proton resonance signal almost four decades ago. The earliest theories of relaxation indicated that the influence of solute paramagnetic ions on relaxation rates of solvent protons should depend both on the chemical environment of the solute ions and on the magnetic field strength. Much knowledge, both experimental and theoretical, has since been amassed regarding relaxation effects in solutions of hydrated ions (aquoions) and of complexes of these ions with macromolecules, mainly proteins. The phenomena are well understood at this point, though the understanding is more retrospective than predictive for ion-protein complexes. Nonetheless, from what is now known about homogeneous solutions, and from current reports on the introduction of paramagnetic ions into tissue to alter contrast in NMR images by affecting relaxation rates, it is clear that the solution results are particularly germane, and transferable, to tissue investigations. The main features of relaxation of solvent protons in the presence of solute paramagnetic ions, as hydrated aquoions and complexed with protein, are presented here, with attention to those ions most relevant to in vivo studies, and with emphasis on the influence of the magnetic field and the chemical environment of these ions on solvent proton relaxation rates.

Cobalt↗
PubMed1984

Magnetic field dependence of solvent proton relaxation induced by Gd3+ and Mn2+ complexes.

The effect of solute paramagnetic ions on the longitudinal magnetic relaxation rate 1/T1 of solvent water protons depends on magnetic field strength and on the chemical environment of the ions. The variation of 1/T1 with field has been measured for solutions of Gd3+ and Mn2+ ions in three grossly different environments near physiological pH: the hydrated aquoion; chelated by EDTA (ethylenediaminetetraacetic acid) and DTPA (diethylenetriaminepentaacetic acid); and bound to the protein concanavalin A. It is demonstrated that over the field range at which NMR imaging is currently being done, the chemical environment can alter 1/T1 of solvent protons by more than an order of magnitude. The relevance of these results to the potential utility of these ions as agents for enhancement of contrast in NMR images is discussed.

Concanavalin A↗
PubMed1984

Evaluation of a test using saralasin to differentiate primary aldosteronism due to an aldosterone-producing adenoma from idiopathic hyperaldosteronism.

We evaluated a new method utilizing saralasin to differentiate primary aldosteronism due to an aldosterone-producing adenoma from idiopathic hyperaldosteronism. The test is based on the marked difference in sensitivity to angiotensin II of aldosterone-producing adenomas and hyperplastic adrenal glands and the partial angiotensin II agonist property of saralasin in low-renin states. Saralasin was infused into 14 patients with primary aldosteronism and the plasma aldosterone responses determined. Plasma aldosterone concentration increased in all eight patients with idiopathic hyperaldosteronism, whereas there was no increase in plasma aldosterone in six patients who had a solitary adenoma. We concluded that saralasin may be a clinically useful, noninvasive tool to distinguish patients with an aldosterone-producing adenoma from those who have idiopathic hyperaldosteronism.

Adenoma↗
PubMed1984

Seasonal relationships of thyroid, sexual and adrenocortical hormones to nutritional parameters and climatic factors in white-tailed deer (Odocoileus virginianus) of south Texas.

Annual cycles of serum testosterone (T), estradiol 17-beta (E), thyroxine (T4), triiodothyronine (T3) and cortisol (C) and their relationship with dry matter intake (DMI), ambient temperature and daylength (DL) were examined in four male and four female white-tailed deer. Serum T in bucks correlated (P less than 0.05) with DMI during the rut. In does, E correlated (P less than 0.05) with DMI and body wt. Both serum T and E were DL and temperature dependent. Serum T4 in bucks correlated (P less than 0.05) with body wt and increasing temperature while T3 correlated (P less than 0.05) with DMI and body wt. In does, T4 was significantly (P less than 0.05) correlated with DMI and body wt, while T3 was not. Serum C levels were not correlated (P greater than 0.05) with either DMI or body wt. It appears that serum T4 and T3 in bucks and T4 in does offer the best year-round indicators of nutritional stress in deer. Male DMI was temperature and DL dependent. In does, only a short-term effect on DMI was found. After the breeding season in bucks, and throughout the year in does, DL and temperature may control intake via the thyroid hormones.

Adrenal Cortex Hormones↗
PubMed1984

Impairment in cochlear function produced by chloramphenicol and noise.

Ototoxic interaction between chloramphenicol and noise was studied in two separate investigations. In the first study, permanent ototoxicity was demonstrated in a group of rats which were subjected to short-duration, high-intensity noise and were then given chloramphenicol orally. The anatomical damage in this group was consistent with observed changes in cochlear round window recordings of cochlear microphonics at 4 kHz and of the N1 component of the eighth nerve action potential. In the second study, a temporary depression in the function of the cochlea was observed in rats subjected to the noise-chloramphenicol regimen used in the first study. Depressions in recordings of the round window similar to those in the first study were seen only during the first five days of recordings. After the fifth day, the recordings of the round window were normal, indicating recovery from a temporary shift in threshold produced by chloramphenicol and noise. Incidence of purulent otitis media was found in 57 and 0% of the animals in the first and second studies, respectively. The combination of chloramphenicol and noise appears to be responsible for the production of temporary cochlear deficits. The addition of the third variable, otitis media, appears to result in permanent impairment of the cochlea.

Animals↗
PubMed1984

Hepatitis B viral antigenic structure: signature analysis by monoclonal radioimmunoassays.

An approach has been developed for the analysis of hepatitis B viral (HBV) antigenic structure that creates numerical "signatures" of HBV strains. This technique employs high-affinity IgM and IgG monoclonal antibodies (anti-HBsAg) directed toward distinct and separate determinants on hepatitis B surface antigen (HBsAg). Such antibodies have been used to develop sensitive and specific radioimmuno-assays for measurement of HBsAg-associated determinants in serum. In performing "signature" analysis separate binding curves for each monoclonal anti-HBsAg are generated by measuring immunoreactivity in serial dilutions of HBsAg-positive serum. Since the HBsAg concentration in serum is unknown, the binding profiles of groups of samples from the same "classic" HBV subtype are aligned by an iterative maximum likelihood procedure to give the numerical signature of that HBV subtype. By using this approach, HBsAg shows far more antigenic heterogeneity than previously recognized by polyvalent anti-HBsAg antibodies. Indeed, there are subgroups within the classic HBsAg subtypes. In addition, the a domain (common to all known subtypes or strains of HBV) has been shown to be multideterminant. Thus, these studies have demonstrated heretofore unrecognized differences in HBV subtypes. This approach also has broader significance for the study of subtle or major antigenic changes among other viral agents since it is not necessary to know the concentration of virus or viral protein in complex protein mixtures.

Antibodies, Monoclonal↗
PubMed1984

Calcium kinetics in male white-tailed deer.

Calcium kinetic analysis was combined with calcium balance data on two 2-year-old and two 4-year-old male white-tailed deer. There were three 10-day trials. Trial 1, February 3-13, was conducted after velvet shedding. Trial 2, May 26-June 5, was conducted after about a month of slow antler growth. Trial 3, August 18-28, was conducted shortly before velvet shedding, after the peak of antler growth. Significant differences (P less than 0.05) between trials 1 and 2 included increased calcium absorption and fractional calcium absorption from the intestine. Skeletal resorption decreased, resulting in an increased calcium balance. Significant differences (P less than 0.05) between trials 1 and 3 included increased skeletal accretion and total calcium flow into the pool. Nonsignificant differences (P greater than 0.05) between trials 2 and 3 included decreased average intestinal calcium absorption and increased skeletal resorption resulting in a decreased calcium balance. The younger deer had nonsignificantly lower (P greater than 0.1) endogenous fecal and significantly lower (P less than 0.1) urinary calcium excretions. The younger deer also maintained higher fractional absorption rates from the intestine than the older deer. The percent decrease in skeletal resorption and increase in calcium balance was greater in the younger deer between trials 1 and 2 and between trials 1 and 3.

Aging↗
PubMed1984

Ligand exchange at the active site of the carbonic anhydrases: a "ping-ping-pong" view.

We emphasize that the interconversion of CO2 and HCO-3 catalyzed by carbonic anhydrase must be regarded as two-substrate, two-product reactions, involving CO2, H2O and HCO-3, H+. Questions then arise regarding the interactions of substrates and products with enzyme during catalysis. Hydration of CO2 has been described by others as a pair of half reactions in which HCO-3 product is released from enzyme, followed by (usually buffer-catalyzed) release of H+. This "ping-pong" view is extended here to a "ping-ping-pong" sequence; based on analyses of specific models for the several intermediate complexes, we conclude that the second "ping" relates to the rate of ligand exchange of H2O from a pentacoordinate enzyme-H2O-HCO-3 complex, about which little is known at present and that is difficult to investigate. We discuss the types of experiments used to measure enzymatic activity and note that (1) they generally measure the rate of the combined "ping-ping" sequence rather than either independently, and (2) the pathway for exchange of substrate H2O is unrelated to the exchange of H2O measured by proton magnetic relaxation and by loss of isotopically labeled oxygen from the CO2-HCO-3 system. The "ping-ping-pong" view, while giving new insights and raising new questions, is consistent with OH- as the ligand of the high-pH form of isozymes I and II, as well as with the results of magnetic relaxation, isotope mixing and loss, 13C NMR linewidths of CO2 and HCO-3 at equilibrium, and stopped-flow kinetic measurements.

Animals↗
PubMed1984

Seasonal levels of serum parathyroid hormone, calcitonin and alkaline phosphatase in relation to antler cycles in white-tailed deer.

Seasonal levels of serum parathyroid hormone (PTH), calcitonin (CT), and alkaline phosphatase (AP) were studied in relation to antler growth cycles in 8 male (2.5-6 years old) white-tailed deer. Feed consumption was recorded weekly, whereas body weight was recorded biweekly. Antler length was measured from the pedicle to the tip after velvet growth was initiated. Serum samples were obtained biweekly while animals were tranquilized with xylazine hydrochloride. Serum Ca was significantly (P less than 0.05) elevated during the summer. Serum P was significantly (P less than 0.05) elevated only during early fall. There was an increase in serum PTH during velvet initiation in April-May, but not thereafter. CT increased during the rapid antler growth period. Serum PTH levels were significantly (P less than 0.05) elevated (0.628 vs 0.884 ng/ml) during post-velvet shedding and decreased (0.602 vs 0.346 ng/ml, P less than 0.05) during post-antler casting. Serum AP activity was highest during rapid velvet antler growth. Feed intake was lowest in early winter, but a compensatory increase was found in late winter. Feed intake peaked in May, then gradually decreased. Body weight was maximum in November and minimum in March. It is concluded that increased PTH during velvet initiation is responsible for Ca absorption and/or mobilization. Increasing PTH levels are related to final mineralization of antlers post-velvet shedding. Higher levels of serum Ca in June-July inhibit continued increase in PTH. Increased CT during rapid antler growth may have prevented excessive bone resorption.

Alkaline Phosphatase↗
PubMed1984

Effects of xylazine immobilization on biochemical and endocrine values in white-tailed deer.

The effect of xylazine hydrochloride on biochemical and endocrine parameters in plasma was examined in adult white-tailed deer (Odocoileus virginianus (Zimmermann]. In the first experiment, seven animals were injected intramuscularly via a blowgun dart with 0.65 mg/kg xylazine (100 mg/ml) and were bled 10, 20, 30, and 60 min post-injection. In the second experiment, eight animals were manually restrained for the first blood sampling and then injected manually and bled as before. Plasma calcium (Ca), inorganic phosphorus (P), and alkaline phosphatase (AP) were measured spectrophotometrically. Plasma parathyroid hormone (PTH), calcitonin (CT), thyroxine (T4), triiodothyronine (T3), and cortisol were measured by radioimmunoassay. Plasma PTH, CT, T4, T3, and AP activity did not differ (P greater than 0.05) during the 1 hr period studied in either experiment. Plasma Ca and P decreased significantly (P less than 0.05) in the second experiment, whereas cortisol levels increased significantly (P less than 0.05) 10 min post-injection in both experiments. The results may have been due to a drug effect or a combined drug and stress effect. It is suggested that xylazine may be safely used as an anesthetic in measuring PTH, CT, T4 and T3, and plasma AP up to 60 min post-injection in deer. Caution should be taken in using xylazine as an anesthetic to study adrenocortical function.

Animals↗
PubMed1984

The relationship between phosphatidylinositol metabolism and mobilization of intracellular calcium elicited by alpha1-adrenergic receptor stimulation in BC3H-1 muscle cells.

The BC3H-1 cell is a stable cell line of probable smooth muscle origin which expresses nicotinic acetylcholine, alpha1- and beta2-adrenergic receptors on its cell surface. Stimulation of the alpha1 receptor mobilizes 70% of the intracellular Ca2+ within a 2-3 minute interval. To delineate further the linkage between alpha1-receptor occupation and response, we have examined the quantitative relationship between fractional occupation of the receptor, the turnover of inositol-containing phospholipids, and the Ca2+ efflux. Alpha1-receptor activation stimulates the incorporation of [3H]inositol into phosphatidylinositol and the enhanced incorporation is linear over a 60-min interval. In contrast, agonist-elicited increases in hydrolysis of phosphatidylinositol and phosphatidylinositol mono- and bisphosphate develop more slowly, and a 5-min lag in enhanced formation of inositol trisphosphate, inositol bisphosphate, and inositol monophosphate is evident. The increased rate of Ca2+ efflux and enhanced rate of inositol incorporation into phosphatidylinositol elicited by phenylephrine exhibit virtually identical dependencies on agonist concentrations. Moreover, fractional inactivation of receptors with phenoxybenzamine shows equivalent increments in the reduction of the two intracellular responses. Both responses are linearly related to the residual receptor sites remaining after fractional inactivation. These findings indicate an absence of a receptor reserve in activating these intracellular events. Moreover, although alpha receptor occupation stimulates phosphatidylinositol hydrolysis, no evidence is provided that this event would precede Ca2+ release. Should inositol trisphosphate mediate intracellular Ca2+ mobilization in these cells, it would be active in extremely low concentrations or occur as a tightly coupled event in a microscopic environment.

Animals↗
PubMed1984

Studies of selective and reversible monoamine oxidase inhibitors.

Several selective and reversible monoamine oxidase inhibitors (MAOIs) have recently become available. Preliminary studies suggest that these compounds have antidepressant effects and may offer significant safety and side effect advantages over classical MAOIs. Pilot studies with 1-deprenyl, a selective MAO-B inhibitor, indicate that it may be most effective for patients with nonendogenous depression and for those (endogenous or nonendogenous) who present with certain reverse vegetative signs. The drug appears ineffective in depressed patients with associated panic attacks and phobic symptoms. An alternative approach in the development of safer, effective MAOIs is the use of rapidly reversible MAO-A inhibitors, such as moclobemide, that carry less risk of a hypertensive reaction and yet appear to be effective antidepressants. As selective MAO-A and MAO-B inhibition may be effective in different depressive subtypes and may have different side effects, these drugs are valuable pharmacologic probes for studying the biochemical bases of depressive disorders.

Animals↗