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Biomedical subjects

L Brown

Publications and source records attributed to L Brown.

At least 289 records · Page 16Linked to original sources
PubMed1986

Additive positive inotropic effects of milrinone, ouabain and calcium in diseased human ventricular myocardium.

The interactions of milrinone, ouabain and calcium on force of contraction in isolated, contracting human papillary muscle strips were measured. Milrinone (EC50, 8 X 10(-5)M) increased force of contraction maximally by 2.8 +/- 0.8 mN at 5 X 10(-4)M; significantly less than either ouabain (1 X 10(-7)M; 4.8 +/- 0.5 mN increase) or calcium (15 mM; 6.2 +/- 0.6 mN increase). A submaximal, but not a maximal, inotropic effect of ouabain could be increased by the addition of milrinone; in contrast, both ouabain and calcium increased the maximal inotropic effect of milrinone by 1.7 +/- 0.2 mN and 2.7 +/- 0.3 mN, respectively. The combined inotropic effect of milrinone with either ouabain of 4.2 +/- 0.3 mN or calcium of 5.6 +/- 0.4 mN was not different from that with calcium or ouabain alone. We conclude that further positive inotropic effects should be expected when digitalis is given to patients with congestive heart failure who are already optimally treated with milrinone.

Adult↗
PubMed1986

Kinetic properties of the purified Ca2+-translocating ATPase from human erythrocyte plasma membrane.

The basic kinetic properties of the solubilized and purified Ca2+-translocating ATPase from human erythrocyte membranes were studied. A complex interaction between the major ligands (i.e., Ca2+, Mg2+, H+, calmodulin and ATP) and the enzyme was found. The apparent affinity of the enzyme for Ca2+ was inversely proportional to the concentration of free Mg2+ and H+, both in the presence or absence of calmodulin. In addition, the apparent affinity of the enzyme for Ca2+ was significantly increased by the presence of calmodulin at high concentrations of MgCl2 (5 mM), while it was hardly affected at low concentrations of MgCl2 (2 mM or less). In addition, the ATPase activity was inhibited by free Mg2+ in the millimolar concentration range. Evidence for a high degree of positive cooperativity for Ca2+ activation of the enzyme (Hill coefficient near to 4) was found in the presence of calmodulin in the slightly alkaline pH range. The degree of cooperativity induced by Ca2+ in the presence of calmodulin was decreased strongly as the pH decreased to acid values (Hill coefficient below 2). In the absence of calmodulin, the Hill coefficient was 2 or slightly below over the whole pH range tested. Two binding affinities of the enzyme for ATP were found. The apparent affinity of the enzyme for calmodulin was around 6 nM and independent of the Mg2+ concentration. The degree of stimulation of the ATPase activity by calmodulin was dependent on the concentrations of both Ca2+ and Mg2+ in the assay system.

Adenosine Triphosphate↗
PubMed1986

Coping behaviors as predictors of the course of clinical depression.

We assessed a large sample of nonmelancholic, depressed subjects, using a self-report measure we developed, to determine behavioral coping dimensions and the predictive validity of the measure. A principal-components analysis of measure scores suggested dimensions of distraction, support seeking, self-consolation, recklessness, affect reduction, and help seeking, largely replicating findings in nonclinical groups. Factor scores on each dimension were calculated for the subsample of depressive subjects consulting a psychiatrist. Those baseline scores were examined against subsequent improvement in depression levels at six and 20 weeks. A significant and consistent predictor of a poor outcome was a higher initial score on the self-consolation dimension. A better outcome was weakly associated at six and 20 weeks with higher scores on affect reduction, whereas higher distraction scores were weakly associated with a poorer outcome at 20 weeks. The study thus confirmed the relevance of coping behaviors in a clinically depressed group and demonstrated the predictive strength of the measure.

Adaptation, Psychological↗
PubMed1986

Molecular detection of a translocation (Y;15) in a 45,X male.

A 45,X male individual was shown to have a translocation of Y-chromosome material to the short arm or proximal long arm of chromosome 15. This translocation was detected by genomic DNA blotting and in situ hybridization with Y-chromosome-specific DNA probes.

Chromosome Banding↗
PubMed1986

Inhibition of human colonic (Na+ + K+)-ATPase by arachidonic and linoleic acid.

The sodium pump, (Na+ + K+)-ATPase, which is involved in the transport of cations and water movement by the colonic mucosa, may be decreased in various diarrhoeal states. In this study, we have measured 3H-ouabain binding and (Na+ + K+)-ATPase activity in human colonic biopsy homogenates and the influence of various inflammatory and antiinflammatory compounds on these parameters. 3H-ouabain binds to one site of high affinity (KD 1.9 +/- 0.2 X 10(-9) mol/l) with a maximal binding capacity of 7.5 +/- 0.8 X 10(14) binding sites/g protein. Both arachidonic and linoleic acid inhibited (Na+ + K+)-ATPase activity (IC50 arachidonic acid: 7.5 X 10(-5) mol/l, linoleic acid: 6.5 X 10(-5) mol/l) and Mg2+-ATPase activity (IC50 arachidonic acid: 9 X 10(-5) mol/l, linoleic acid: 4 X 10(-5) mol/l). Arachidonic acid inhibited 3H-ouabain binding, (IC50 3.2 X 10(-5) mol/l). The following antiinflammatory compounds, at concentrations up to 1 X 10(-3) mol/l, did not influence ATPase activity directly nor reverse the arachidonic acid-induced inhibition: indomethacin (cyclooxygenase inhibitor), nordihydroguaiaretic acid (lipoxygenase inhibitor), sulphasalazine and its metabolites: 5-aminosalicylic acid, N-acetylaminosalicylic acid and sulphapyridine. These results indicate that human colonic (Na+ + K+)-ATPase is inhibited by the prostanoid precursors, arachidonic and linoleic acid. From a therapeutic point of view (effect on colonic (Na+ + K+)-ATPase and perhaps diarrhoea), the suppression of the production of these prostanoid precursors by drugs may, therefore, be beneficial in the treatment of inflammatory bowel disease.

Anti-Inflammatory Agents↗
PubMed1986

The positive inotropic response to milrinone in isolated human and guinea pig myocardium.

The bipyridine derivative, milrinone, produced positive inotropic effects in isolated, contracting right ventricular papillary muscles and left atria from guinea pigs as well as in human papillary muscle strips. The inotropic effect was biphasic in guinea pig papillary muscles (EC50, high affinity, 1.5 X 10(-6) mol/l, about 35% of maximal effect; apparent EC50, 3 X 10(-5) mol/l with a maximal effect at 2 X 10(-4) mol/l) but monophasic in guinea pig left atria (EC50, 6 X 10(-5) mol/l) and in human papillary muscle strips (EC50, 5.8 X 10(-5) mol/l). In guinea pig papillary muscles, reserpine pretreatment or l-practolol preincubation reduced the low concentration effect only. In the presence of l-practolol, carbachol reduced the low concentration effect only. In the presence of l-practolol, carbachol reduced but not abolished the inotropic effects of milrinone (3 X 10(-6) mol/l, 1 X 10(-4) mol/l) in both guinea pig and human myocardium. This antagonism was prevented by atropine preincubation. The maximum inotropic effect of milrinone was similar to that of ouabain and calcium in guinea pig myocardium but markedly less than either calcium or ouabain in human myocardium. Milrinone inhibited crude guinea pig and human cardiac phosphodiesterase activity in vitro but did not inhibit 3H-ouabain binding to partially purified human cardiac (Na+ + K+)-ATPase-containing membranes. We conclude that the primary mode of action of milrinone in both guinea pig and human myocardium is through inhibition of phosphodiesterase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Cardiac glycosides with non-rotating steroid to sugar linkages: tools for the study of digitalis structure-activity relationships.

The 5 alpha H-cardenolide, gomphoside, is one of a small group of naturally occurring cardiac glycosides in which the sugar residue is bilinked to the steroid ring system. This arrangement prevents the sugar moiety from rotating and this makes gomphoside and related compounds potentially useful for structure-activity relationship (SAR) studies. When gomphoside was tested for inotropic activity using guinea pig left atria, the compound was found to have very high potency comparable to the most active 5 beta H-cardenolides. Removal of the sugar moiety reduced inotropic activity almost 500-fold indicating that it was the presence of the sugar moiety that was mainly responsible for the drug's high potency. Modification of the steroid or sugar residue of gomphoside reduced activity in all cases. It would thus appear that gomphoside with its high potency and non-rotatable glycosidic linkage is an excellent tool for SAR studies.

Animals↗
PubMed1986

Adult and embryonic frontal cortex transplants after frontal cortex ablation enhance recovery on a reinforced alternation task.

Damage to the medial frontal cortex in rats results in a learning deficit on a reinforced alternation task. The rate of recovery from this deficit was accelerated by transplantation of either adult or embryonic frontal cortex, provided that a delay was introduced between injury and transplantation. The rates of recovery for both delayed embryonic and adult transplants did not differ from the undamaged group. In contrast, transplants of embryonic frontal cortex immediately after ablation did not accelerate the rate of recovery. The accelerated rate of behavioral recovery on the reinforced alternation task appeared to correlate with transplant survival.

Acetylcholinesterase↗
PubMed1986

Renal function and (NA+ + K+)-ATPase in chronic unilateral hydronephrosis in dogs.

Recovery of various parameters of kidney function after varying periods of complete unilateral ureteral obstruction was studied in dogs under hydropenic conditions. Changes of PAH and inulin clearance appeared to be parallel. After one week of obstruction, renal clearances of PAH and inulin were decreased to seven per cent of values measured before the obstruction period, after two weeks to four per cent and after three or four weeks to two per cent. Within 10 to 28 days after release of obstruction by cutaneous ureterostomy, PAH and inulin clearance increased to 66 per cent after one week, to 50 per cent after two weeks, to 10 per cent after three weeks with no change after four weeks of obstruction. Na+ content in the hydronephrotic kidney differed from contralateral kidneys only in the inner medulla. The affinity for ouabain (dissociation constant, KD, normal = 3.85 X 10(-9) M; hydronephrotic = 3.05 X 10(-9) M; contralateral = 7.05 X 10(-9) M) was significantly higher only in the outer medulla of contralateral kidneys. Turnover number (normal = 3.6; hydronephrotic = 5.1; contralateral = 3.4 X 10(3) min.-1) in hydronephrotic or contralateral outer medulla was not significantly different from normal. Changes in kinetic constants (association rate constant, k+1, normal = 4.49 X 10(4) M-1 sec.-1; hydronephrotic = 4.13 X 10(4) M-1 sec.-1; contralateral = 5.97 X 10(4) M-1 sec.-1; dissociation rate constant, k-1, normal = 1.03 X 10(-4) sec.-1; hydronephrotic = 1.29 X 10(-4)sec.-1; contralateral = 1.39 X 10(-4) sec.-1) were considered to be too small to be relevant. Similar changes of KD, k+1 and k-1 were observed in the renal cortex. The osmotic concentrating capacity correlated well with (Na+ + K+)-ATPase activity (r = 0.85) and number of 3H-ouabain binding sites (r = 0.89) in renal outer medulla. The results indicate that recovery of osmotic concentrating capacity depends on the length of obstruction, and that a reduction of (Na+ + K+)-ATPase molecules in the thick ascending limb of the loop of Henle is a primary factor in the decrease in the concentrating capacity of chronic unilateral hydronephrotic kidneys.

Animals↗
PubMed1986

Ouabain binding and inotropy in acute potassium depletion in guinea pigs.

In hypokalaemia the incidence of cardiac toxicity with digitalis is increased, possibly through changes in the affinity or capacity of the digitalis receptor in the heart. Previous studies have reported an increased ouabain binding capacity or Na+-K+ ATPase activity after hypokalaemia in human erythrocytes and rabbit and guinea pig hearts and no change or decreases in rabbit or rat skeletal muscles with no changes in ouabain affinity. The present study determined (a) the effect of potassium on 3H-ouabain binding to normokalaemic guinea pig cardiac cell membranes, (b) the effect of acute hypokalaemia induced by a potassium deficient diet for 14-18 days in guinea pigs on 3H-ouabain binding to erythrocytes and cardiac and skeletal muscle homogenates, and (c) ouabain induced inotropy in isolated contracting guinea pig left atria, right ventricular papillary muscles, and soleus muscle strips from normokalaemic and hypokalaemic guinea pigs. 3H-ouabain binds to cardiac cell membranes in the presence of magnesium and inorganic phosphate with an affinity (KD value) of 1.13 X 10(-7) mol X litre-1. Potassium decreased this affinity without changing the binding capacity. Erythrocytes and heart muscle homogenates showed the same affinity as cardiac cell membranes, whereas soleus muscle homogenates had a higher affinity for ouabain (KD 5.1 X 10(-8) mol X litre-1). After hypokalaemia, the ouabain affinity did not change in any tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Reduced positive inotropic effects in diseased human ventricular myocardium.

In isolated contracting human ventricular myocardium taken from patients undergoing mitral valve replacement the positive inotropic effects of calcium, isoprenaline, dobutamine, dopamine, histamine, milrinone, isobutylmethylxanthine, and theophylline were determined. Calcium (15 mmol X litre-1) produced an increase in force of contraction similar to that of a maximal effective concentration of ouabain (1 X 10(-7) mol X litre-1); significantly lower maximal effects were measured with all the other positive inotropic compounds tested. The addition of these positive inotropic substances after a stable maximum effect with ouabain (1 X 10(-7) mol X litre-1) had been reached increased the incidence of toxicity without producing any further inotropic effects. These results suggest that inotropic substances acting through cyclic adenosine monophosphate give less than the maximum inotropic response in isolated muscle from diseased human hearts, which is not additive to the maximal ouabain induced inotropy.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Controlled release of insulin from polymer matrices. In vitro kinetics.

A biocompatible system was developed that permits continuous release of biologically active insulin from small polymer matrices. Powdered insulin particles were incorporated into an ethylene-vinyl acetate copolymer matrix. The presence of particulate insulin resulted in a matrix composed of tortuous channels and constricted pores through which release occurred. When aqueous release media permeated the matrix, the insulin dissolved and diffused slowly through this tortuous network. The large concentration of insulin within the matrix provided the driving force for release. Release kinetics from these insulin polymer matrices were enhanced by increasing the insulin solubility, the insulin powder particle size, the loading of insulin within the matrix, and the porosity of the matrix. Appropriate geometric design of the polymer matrix resulted in near-constant insulin release rates.

Delayed-Action Preparations↗
PubMed1986

Controlled release of insulin from polymer matrices. Control of diabetes in rats.

The controlled release of insulin from ethylene-vinyl acetate copolymer matrices was demonstrated for over 100 days in vivo. The matrices were designed to release sodium insulin at near-constant rates. These 0.06-cm3 implants were coated completely with an impermeable layer of polymer. An aperture was drilled in the center of one face of the matrix, restricting release through this opening. These devices were implanted into 13 streptozocin-induced diabetic rats. Plasma glucose concentrations fell from 386 +/- 18 to 119 +/- 35 mg/dl (mean +/- SEM), and urinary glucose was eliminated. Thee parameters were controlled for up to 105 days by a single implant. Glycosylated hemoglobin concentrations measured 90 days after implantation were 3.86 +/- 0.11% for the polymer-treated rats, 3.10 +/- 0.18% for the normal controls, and 5.42 +/- 0.33% for the diabetic controls. The average weight gain of the treated rats was similar to that of the controls, whereas the diabetic controls failed to thrive. In addition, all of the diabetic controls developed cataracts 1 mo after diabetes induction, whereas none of the treated rats developed cataracts.

Animals↗
PubMed1986

A deletion map of the human Y chromosome based on DNA hybridization.

The genomes of 27 individuals (19 XX males, two XX hermaphrodites, and six persons with microscopically detectable anomalies of the Y chromosome) were analyzed by hybridization for the presence or absence of 23 Y-specific DNA restriction fragments. Y-specific DNA was detected in 12 of the XX males and in all six individuals with microscopic anomalies. The results are consistent with each of these individuals carrying a single contiguous portion of the Y chromosome; that is, the results suggest a deletion map of the Y chromosome, in which each of the 23 Y-specific restriction fragments tested can be assigned to one of seven intervals. We have established the polarity of this map with respect to the long and short arms of the Y chromosome. On the short arm, there is a large cluster of sequences homologous to the X chromosome. The testis determinant(s) map to one of the intervals on the short arm.

Chromosome Banding↗
PubMed1986

The origin of 45,X males.

Maleness in association with the karyotype 45,X is a very rare and hitherto unexplained condition previously described in only four or five patients. This study was carried out to determine whether such males might actually possess Y-chromosomal material. Of the two 45,X males studied, one was found to be a low-grade mosaic with a 46,XY karyotype in less than 3% of fibroblasts; all lymphocytes karyotyped were 45,X. Fibroblast DNA from this individual was found to contain Y-specific repeated sequences in 1%-3% the amount observed in the father, consistent with mosaicism for a 46,XY cell line. No Y-specific repeated sequences were detected in the other patient, in whom all mitoses were 45,X. In neither patient were there detectable amounts of any of the single-copy Y-specific DNA sequences for which we tested. Studies of Xg blood groups and of X-linked restriction fragment length polymorphisms indicated that the single X chromosome was of maternal origin in both 45,X male probands. In contrast to the situation in XX males, we can exclude paternal X-Y interchange as the etiology in the cases described here. Our findings are compatible with mosaicism being the explanation of at least some "45,X" males.

DNA Restriction Enzymes↗
PubMed1986

Possible efficacy of alprazolam in restless leg syndrome.

Restless leg syndrome is a frequently misdiagnosed and often misunderstood condition contributing to a complaint of insomnia in geriatric patients. Various pharmacologic agents used to treat the condition are often ineffective and have not consistently provided relief for the majority of patients with this condition. Our recent experience with Xanax suggests its possible effectiveness in controlling symptoms of the restless leg syndrome. Further, more controlled double blind studies--especially comparing other benzodiazepines at appropriate dosages--are called for.

Aged↗