Search PubMed⌕ Search

Biomedical subjects

R D Brown

Publications and source records attributed to R D Brown.

At least 343 records · Page 19Linked to original sources
PubMed1983

Experience with the Molteno long tube implant.

Dissatisfaction with other forms of treatment in the neovascular and other 'difficult' glaucomas led the authors to use the Molteno long tube implant. This paper resulted from a review of the results obtained in 30 cases over the past four years. The patients fell naturally into the two groups of neovascular and non-neovascular glaucomas. The eyes with neovascular glaucoma had an implant used early in the disease process, while the eyes with non-neovascular glaucoma tended to have the implant used as a last resort, after the failure of conventional techniques. An overall success rate of 63 per cent was found and this could be subdivided into success rates of 50 per cent for the non-neovascular group and of 75 per cent for the neovascular group. These findings probably reflect the late or early use of the implant in the disease process. The results confirm the authors' clinical impression that the Molteno long tube implant is a useful tool in the management of these glaucomas, and that for optimal results it should be considered early in the condition.

Adolescent↗
PubMed1983

The influence of antibiotics on agonist occupation and functional states of the nicotinic acetylcholine receptor.

Four distinct classes of antibiotics, the aminoglycosides, tetracyclines, lincomycin-clindamycin, and peptides, were examined in intact BC3H-1 cells for their capacity to influence the relationship between agonist binding to the cholinergic receptor and the response elicited. The most potent inhibitors were the peptides of the polymyxin-colistin class, which at submicromolar concentrations noncompetitively blocked agonist-elicited Na+ permeability. These agents at equivalent concentrations also enhanced the apparent affinity of agonists for the receptor. Comparisons of agonist occupation of the receptor and agonist promotion of desensitization showed that the noncompetitive inhibition by peptide antibiotics occurred largely by augmenting the conversion of the receptor to a high-affinity, desensitized state. Rates of receptor desensitization were also substantially enhanced in the presence of these antibiotics. Thus, an analysis of receptor occupation and response suggests that the polymyxin antibiotics act as heterotropic allosteric effectors by promoting the conversion of the cholinergic receptor to its desensitized state. By contrast, the other antibiotics studied inhibited permeability at far higher concentrations. Although a noncompetitive component of inhibition could be identified with certain antibiotics such as neomycin, they did not appear to enhance agonist affinity. Thus, the various antibiotics differ substantially in their potencies and basic mechanisms of inhibition of the acetylcholine receptor.

Animals↗
PubMed1982

Conformational equilibrium of demetalized concanavalin A.

Concanavalin A (Con A) is known to exist in two conformations [Brown, R. D., III, Brewer, C. F., & Koenig, S. H. (1977) Biochemistry 16, 3883-3896] that differ in their metal ion and saccharide binding properties. The conformation that binds metal ions tightly, and which is associated with saccharide binding, has been designated as "locked" and that which binds metal ions only weakly as "unlocked". In the presence of excess metal ions, such as Mn2+ and Ca2+, essentially 100% of the protein is in the locked conformation. The scheme proposed to explain these effects [Koenig, S. H., Brewer, C. F., & Brown, R. D., III (1978) Biochemistry 17, 4251-4260] predicts an equilibrium between these conformations for the apoprotein. By monitoring the solvent proton relaxation dispersion as equimolar concentrations of Mn2+ and Ca2+ are titrated, at 5 degrees C, into an apo-Con A solution that had been equilibrated at 25 degrees C, we find that 12.5% of the apoprotein is in the locked conformation, corresponding to an energy separation of 1.2 kcal mol-1. We also show that these conformations can be separated by column chromatography at 5 degrees C and that the 100% unlocked form prepared in this way returns to the expected equilibrium mixture when kept at 25 degrees C.

Apoproteins↗
PubMed1982

Nuclear magnetic relaxation dispersion in monoclinic lysozyme crystals.

Nuclear magnetic relaxation measurements are reported as a function of field strength corresponding to the frequency range from 0.01 to 20 MHz for water protons in monoclinic lysozyme crystals at 278 and 298 K. Though the instrumentation used selects only a portion of the total magnetization to sample, the data clearly indicate a field dependence of the relaxation rate that signals the presence of slow motions characterized by time constants in the range of tenths of microseconds and slower. The data support, but do not uniquely prove, the hypothesis that this time scale is that appropriate to the isotropic averaging of locally anisotropic water molecule motion at the protein surface.

Animals↗
PubMed1982

The effect of metoclopramide and dopamine on plasma aldosterone concentration in normal man and rhesus monkeys (Macaca mulatta): a new model to study dopamine control of aldosterone secretion.

Metoclopramide, a dopamine receptor antagonist, increases plasma aldosterone concentration in man, suggesting that dopamine regulates the secretion of aldosterone. In the current study, we administered metoclopramide to rhesus monkeys and normal subjects and compared the time-course and dose-response characteristics of plasma aldosterone. We also examined the effect of dopamine on the plasma aldosterone response to metoclopramide in both species. Six male rhesus monkeys and several normal subjects (five women and two men) were studied on diets providing an estimated daily sodium intake of 70 mg/kg. In both species the peak increase in plasma aldosterone occurred 15 min after metoclopramide was injected. The peak plasma aldosterone value was 3-fold higher than control values. There were no significant changes in PRA, cortisol or potassium, whereas plasma PRL increased 7-fold in the monkeys and 11-fold in the normal subjects. After 0.04 mg/kg metoclopramide, there was no change in plasma aldosterone concentration in the monkeys, whereas aldosterone increased significantly (delta = 3.7 +/- 0.68 ng/dl) in the human subjects. The half-maximal dose of metoclopramide was also higher in the monkeys than in the normal subjects. A dopamine infusion at 4.0 to 8.0 micrograms/kg . min partially suppressed the plasma aldosterone response to metoclopramide in both the human subjects and the monkeys. This study demonstrates that metoclopramide produces dose-related increases in plasma aldosterone concentration in the nonhuman primate that are similar to those in normal man and that the increases can be inhibited by dopamine. We conclude that aldosterone secretion may be under dopamine control and that the rhesus monkey should be an excellent model in which to study further the regulation of aldosterone by dopamine.

Adult↗
PubMed1982

A study of the true competitive protein binding of current vitamin B12 radioassays.

The use of purified intrinsic factor in vitamin B12 radioassays has greatly reduced the misdiagnosis of pernicious anaemia in recent years, but anomalies still occur. Observations made on current vitamin B12 radioassays suggest that many methods fail to convert all serum cobalamins to cyanocobalamin and thus are not true competitive protein binding assays. No KCN in the extraction buffer resulted in an average 30% reduction in the vitamin B12 level in normal sera. High concentrations of KCN caused a significant increase in the vitamin B12 level in serum from most vitamin B12 deficient patients. This increase could have caused a misdiagnosis in 7 of 12 patients studied. The specificity of (57Co) cyanocobalamin binding to both transcobalamin II (TCII) in a pool of normal sera and to intrinsic factor in a commercial kit binder reagent was 99%. We conclude that the KCN concentration in the extraction mixture should be between 2 and 5 mg/l.

Anemia, Pernicious↗
PubMed1982

Folate assays--an alternative to microbiological assays and commercial kits.

A simple and reliable folate radioassay technique based on the principles of classic folate radioassays but incorporating several of the recently introduced technical innovations is presented as an alternative to the microbiological assays and commercial kits. Serum and red cell folate values from this method were compared with results from two commercial kits and a Lactobacillus casei (L. casei) assay. There was a good correlation with the L. casei assay for both serum and red cell folate (r = 0.95). The method uses N-methyltetrahydrofolate standards diluted in folate free serum, beta-lactoglobulin as a binder and an alkaline denaturation ('no-boil') of endogenous folate binding proteins. Low hematocrit lysates were best performed at a 1 in 10 rather than 1 in 20 dilution. A comparison of the boil and 'no-boil' kits from Diagnostic Products Corporation revealed that the 'no-boil' kit produced results closer to those obtained from the L. casei assay than the boil kit.

Biological Assay↗
PubMed1982

Gentamicin disposition in children with chronic renal failure.

Gentamicin (G) disposition in six children with stable chronic renal failure (CRF) and in nine children with normal renal function (NRF) was determined by pharmacokinetic analysis of serum G concentration versus time data obtained over an 8-hour period following the administration of an intravenous loading dose. ES-TRIP curve fitting indicated that G disposition was best described by a biexponential function; however, a one-compartment open model also suitably characterized G disposition for an 8-hour period. Peak serum G concentrations were similar between the CRF and NRF groups, but concentrations were significantly different (P less than 0.005) at 8 hours following the loading dose. Also, significant differences (P less than 0.001) were found between the two groups for beta, t1/2 beta, plasma clearance, and k10. The relationship of creatinine clearance (Clcr) versus beta, described by the equation beta = 0.033 + 0.003 X Clcr (P less than 0.005, r = 0.97) permitted the best prediction of the G elimination constant from a parameter of renal function. This relationship remained linear over a broad range of Clcr values in our patients and in other previously reported children with CRF and NRF.

Adolescent↗