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L Brown

Publications and source records attributed to L Brown.

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

Digitalis structure-activity relationship analyses. Conclusions from indirect binding studies with cardiac (Na+ + K+)-ATPase.

We have performed direct and indirect binding studies with [3H]ouabain or [3H]digitoxin on beef or guinea pig cardiac (Na+ + K+)-ATPase to measure the potencies of a broad range of cardiotonic steroids for structure-activity relationship (SAR) studies for comparison with previously determined positive inotropic potencies. The positive inotropic potencies of twelve compounds on contracting guinea pig left atria correlated well with the equilibrium dissociation constants (KD values) from the inhibition of [3H]ouabain binding to guinea pig cardiac (Na+ + K+)-ATPase (r = 0.98 for seven 5 beta-compounds, r = 0.95 for five 5 alpha-compounds). Further we calculated KD values from the inhibition of [3H]ouabain binding data for a total of 33 digitalis derivatives on the digitalis-sensitive beef cardiac (Na+ + K+)-ATPase. For the 27 compounds tested on both beef cardiac (Na+ + K+)-ATPase and guinea pig left atria, the potencies showed a significant correlation (r = 0.92 for 22 5 beta-compounds, r = 0.96 for five 5 alpha-compounds. For seven compounds, KD values were measured on beef cardiac (Na+ + K+)-ATPase using inhibition of binding of [3H]digitoxin. These values correlated well (r = 0.99) with the KD values from the [3H]ouabain studies. These results show that: (1) The significant correlation observed between KD values on guinea pig cardiac (Na+ + K+)-ATPase and positive inotropic potency in guinea pig left atria is further evidence that the pharmacological receptor for inotropy is part of the enzyme, (2) Inhibition of the binding of [3H]ouabain or [3H]digitoxin can be used to determine the relative potencies of unlabelled digitalis derivatives. The similar relative potencies on beef and guinea pig cardiac (Na+ + K+)-ATPase of a broad range of digitalis derivatives indicate that the binding site is similar for both species; and (3) SAR studies indicate that functional groups on these steroids have the same influence on potency on either the positive inotropy or cardiac (Na+ + K+)-ATPase studies.

Animals↗
PubMed1983

Utilisation of health services by diabetic patients. 1: The district nursing service.

In 1981 the district nursing service in Christchurch was making 590 home visits, on a weekly basis, to 73 patients for the purposes of drawing up and injecting insulin. This was 13.9% of their total workload. Through a programme of education many were able to manage the injection technique totally. In other cases the provision of pre-loaded syringes permitted less frequent attendance by the district nurse. At survey, one year later, the patient numbers visited had fallen to 46, and the number of weekly visits had been reduced by half. These results show the benefits of research programmes, aimed at evaluation of health delivery, with a view to improving their efficiency and reducing their cost.

Aged↗
PubMed1983

Assay of AHF concentrates and standards: failure to eliminate variability with a monographed assay.

Previous calibration studies have shown a high interlaboratory variability in the potency of the proposed Office of Biologics (National Center for Drugs and Biologics, US-FDA) AHF standard relative to the 2nd International Standard for Factor VIII (Factor VIII:C) (WHO 73/552). This led to the formation of an Industry Collaborative Study group whose objective was to reduce the assay variability. The group, in collaboration with the Office of Biologics and the National Institute for Biological Standards and Control (UK), designed a study based on a monographed one-stage assay protocol, which specified all materials, assay methods, equipment, dilution technique, reagents, assay order, and calculation methodology. All participants received common reagents and samples, with the exception of substrate plasma. It was felt that substrate plasma could not be a common reagent in a monographed assay. However, each laboratory prepared substrate plasma according to the protocol. All data were analyzed by an independent statistical staff. Preparations assayed included two 10-donor plasma pools, the 2nd International Standard for Factor VIII (WHO 73/552), the proposed OoB Lot A internal standard, the participants' own house standards, and commercial AHF concentrate material. The results show a statistically insignificant reduction in the interlaboratory variability, but intralaboratory consistency was generally maintained. The study shows that monographing an assay for Factor VIII.

Adolescent↗
PubMed1983

Consequences of specific [3H]ouabain binding to guinea pig left atria and cardiac cell membranes.

An analysis of [3H]ouabain binding to electrically stimulated, contracting guinea pig left atria gave the following results. (1) A non-linear Scatchard plot with at least two binding sites: a high-affinity site (KD 1.1 X 10(-6) M) with about 430 receptors/micron2 related to positive inotropy, and a low-affinity site (KD' 2.1 X 10(-4) M) with about 18,000 receptors/micron2, possibly related to (Na+ + K+)ATPase inhibition. A crude left atrial homogenate gave about 530 receptors/micron2. (2) Half-maximal positive inotropic effects occurred at about 4 X 10(-7) M. (3) 86Rb+-uptake was significantly increased at all inotropic ouabain concentrations (10(-7) - 10(-6) M). Toxic concentrations (above 2 X 10(-6) M) inhibited 86Rb+-uptake (half-maximal inhibition at about 5 X 10(-6) M). [3H]Ouabain binding to partly purified guinea pig cardiac cell membranes showed: (a) linear Scatchard plots for (Mg2+, Pi)- and (Na+, ATP, Mg2+)-supported binding (KD 1.18 X 10(-7) M and 1.49 X 10(-7) M, respectively); (b) non-linear Scatchard plots for (Tyrode + ATP)-supported binding (KD 4.7 X 10(-7) M; KD' 6 X 10(-6) M); and (c) half-maximal [3H]ouabain binding occurred at a lower concentration (about 3.2 X 10(-7) M) than half-maximal inhibition of (Na+ + K+)ATPase activity (about 7.2 X 10(-7) M). Thus, we conclude that there may be more than one type of ouabain binding site in guinea pig left atria, and that measurable inhibition of (Na+ + K+)ATPase is not necessarily related to positive inotropy in the guinea pig.

Animals↗
PubMed1983

A micro sustained release system for epidermal growth factor.

A technique for ensuring the controlled release of microgram and smaller amounts of biologically active epidermal growth factor (EGF) from polymeric delivery systems is described. We show that albumin in milligram quantities can facilitate the sustained release of picogram amounts of EGF for at least 3 wk. The EGF-containing polymer matrix can be placed directly into cell culture and will increase the proliferation rate of serum-starved cells. The method reported here should be suited particularly to the delivery of biologically active growth factors that are obtainable in only microgram or smaller amounts.

Animals↗
PubMed1983

Response to NaCl taste in mixture with sucrose by sodium deficient rats.

Sodium deficient, adrenalectomized rats and nondeficient control rats were offered, for 20 min, either a mixture of 0.15 M sodium chloride and 0.3 M sucrose, or a 0.3 M sucrose solution. The sodium deficient rats drank about 3 times more of the mixture than of the sucrose alone. Nondeficient control animals showed no differential preference for the mixture over the sucrose solution. Subsequent tests indicated that the amount of mixture ingested by the sodium deficient group was comparable to the intake of a much weaker (1/5 as strong) sodium chloride concentration given alone. These results are discussed in the context of taste component analysis of mixtures and suggest that the rodent taste system can specifically respond to sodium chloride in a sodium chloride-sucrose mixture.

Adrenal Glands↗
PubMed1983

The cardiac glycoside-receptor system in the human heart.

Specific binding sites have been demonstrated to exist in the heart for several drugs and hormones such as beta-blocking agents, cardiac glycosides, catecholamines, insulin, glucagon and acetylcholine. The specific binding sites for cardiac glycosides in the human heart have certain properties which make it likely that they are the pharmacological receptors for the therapeutic and toxic actions of digitalis glycosides: they are located in the cell membrane and bind cardioactive steroids reversibly with high affinity: half-maximal receptor binding occurs at approximately 2 nM (approximately 1.5 ng/ml) for digoxin; potassium decreases receptor affinity, calcium increases it; specific binding of ouabain, digoxin or digitoxin is related to inhibition of (Na+ + K+)-ATPase activity--which is supposed to be the receptor enzyme for cardiac glycosides. Human left ventricle contains approximately 1.5 x 10(14) binding sites/g wet weight, right ventricle approximately 0.9 x 10(14). In disease the number of receptors may decrease (hypothyroid states, myocardial infarction) or increase (hyperthyroidism, chronic hypokalaemia). Certain drugs (such as phenytoin) or different temperatures or pH changes cause a change in digitalis-receptor affinity. Thus, the number of receptors and possibly their properties are subject to regulation in clinically relevant situations. Further investigations will probably reveal those pathophysiological states, which allow the explanation of toxicity or digitalis refractoriness.

Animals↗
PubMed1983

Regulation of cobalamin and folate metabolism by methionine in human bone marrow cultures.

In cobalamin deficiency folate metabolism is disturbed. In the liver this deranged metabolism can be overcome by methionine, however, methionine failed to overcome this abnormality in bone marrow cultures from cobalamin deficient patients. In cobalamin deficient E. coli mutant bacteria, methionine under different conditions could either inhibit or potentiate the growth of the organism. This study was therefore initiated to test the effect of methionine, under different conditions, on bone marrow cultures. The defective DNA synthesis in megaloblastic bone marrow due to cobalamin deficiency could be corrected by the in vitro addition of low 0.27 mumol (40 micrograms) but not high 6.7 mumol (1 mg) amounts of methionine. This was measured by the ability of deoxyuridine to suppress the 3H-thymidine incorporation into DNA. The effect of methionine in facilitating de novo DNA synthesis is probably due to the catalytic action of SAM which activates cobalamin dependent methyltransferase enzyme thus potentiating the effect of cobalamin. In contrast high concentrations of methionine may inhibit this enzyme.

Bone Marrow Cells↗
PubMed1983

Differentiation of Clostridium difficile toxin from Clostridium botulinum toxin by the mouse lethality test.

The mouse lethality test is the most sensitive method for confirming the diagnosis of infant botulism. Both Clostridium difficile and Clostridium botulinum produce heat-labile toxins which are lethal for mice and can be found in the feces of infants. These two toxins can be distinguished from one another in this assay when both are present in the same fecal specimen because they appear to be immunologically distinct toxins.

Animals↗
PubMed1983

Combination chemotherapy of metastatic thyroid cancer. Phase II study.

Eleven patients with metastatic thyroid cancer received combination chemotherapy with doxorubicin, bleomycin, vincristine, and melphalan. Six of 11 patients responded, two with a minor response, three a partial, and one with a complete response. Most responses were brief (2-3 months), but the patient with a complete response is alive and free of disease at 60+ months. Toxicity was moderate and predominantly hematologic. Thyroid carcinoma is a moderately sensitive neoplasm with occasional prolonged responses to chemotherapy.

Adult↗
PubMed1983

Comparison of the inotropic potencies of some synthetic and naturally occurring cardiac glycosides using isolated left atrium of guinea pig.

The inotropic activity of 19 cardioactive steroids was determined using the electrically driven left atrium of the guinea pig. The compounds tested included five alpha-L-rhamnosides and four alpha-L-thevetosides. These were compared with their related genins and with representative examples of beta-D-glycosides. The study showed that rhamnosides and thevetosides were amongst the most active of all cardiac glycosides. The high activity of these compounds was probably related to the alpha-L-glycoside linkage and the configuration of the 4'-hydroxyl group and the 5'-methyl group. There was a stepwise loss of activity when the hydroxyl groups of the sugars were acetylated. The extent to which rhamnose enhanced the potency of different genins varied with the nature of the genin and ranged from 6- to 35-fold. The great variation in the published values for some of the glycosides tested demonstrates the need to standardize methods for testing cardiac glycosides.

Animals↗