Showing papers by "Johns Hopkins University School of Medicine published in 1971"
TL;DR: Determinations of ejection fraction in 20 patients using this tracer method were correlated with measurements obtained by contrast cineangiography with the following results: ejections fraction r = +0.92, P < 0.001; end-diastolic volume r = −0.76, P = 0.0005; and end-systolicVolume r = -0.75, P=0.001.
Abstract: A radioactive tracer method for the measurement of left ventricular ejection fraction in man without cardiac catheterization is described. The tracer (99mtechnetium-labeled albumin) is injected intravenously. Images of the heart at end-systole and end-diastole are obtained using a scintillation camera and an electronic gate triggered by the patient's electrocardiogram. Each image is composed of 300,000 counts, representing a summation of 200 to 400 heartbeats at end-systole and end-diastole. An outline of the left ventricular free wall is drawn from each gated image. The position of the aortic and mitral valve planes is determined using a radionuclide angiogram obtained at the time of tracer injection. Left ventricular ejection fraction is calculated from the area and length of the long axis of the ventricular outline at end-systole and end-diastole. Determinations of ejection fraction in 20 patients using this tracer method were correlated with measurements obtained by contrast cineangiography with the following results: ejection fraction r = +0.92, P < 0.001; end-diastolic volume r = −0.76, P < 0.001; and end-systolic volume r = −0.75, P < 0.001.
396 citations
TL;DR: Both nitroglycerin and propranolol failed to cause a significant change in the ratio of circumflex to descendens radioactivity during ischemia, but both caused a significant increase in the ratios of endocardial to epicardial radioactivity in both ischemic and nonischemic areas.
Abstract: Radioactive microspheres were used to estimate the changes in regional myocardial blood flow occurring during acute myocardial ischemia. Carbonized 15-µ spheres were injected into the left atrium of 28 open-chest dogs and the radioactivity of selected areas determined after sacrifice. Acute occlusion of the left circumflex coronary artery produced a significant diminution in the proportion of microspheres reaching the circumflex area. In addition, there was a disproportionate decrease in endocardial radioactivity in the ischemic area (endocardial/epicardial radioactivity ratio falling from 1.17 to 0.76, P < 0.001) but not in the nonischemic area. Both nitroglycerin (0.4 mg) and propranolol (1 mg/kg) failed to cause a significant change in the ratio of circumflex to descendens radioactivity during ischemia. They did, however, cause a significant increase in the ratio of endocardial to epicardial radioactivity in both ischemic and nonischemic areas.
386 citations
Journal Article•
TL;DR: A number of centrally active drugs, including antiparkinsonian agents, antihistamines, tricyclic antidepressants, and phenothiazines, inhibit catecholamine uptake into synaptosomes prepared from various areas of rat brain.
Abstract: A number of centrally active drugs, including antiparkinsonian agents, antihistamines, tricyclic antidepressants, and phenothiazines, inhibit catecholamine uptake into synaptosomes prepared from various areas of rat brain. Many of these drugs have markedly differing affinities for the dopamine neurons of the corpus striatum as compared to the norepinephrine neurons in other brain regions. All drugs examined inhibit catecholamine uptake into hypothalamic synaptosomes competitively, but are noncompetitive inhibitors in the corpus striatum. In both brain areas, uptake inhibition appears to be reversible. In a series of drugs, certain structural features are related to the relative selectivity toward norepinephrine or dopamine neurons. Replacement of an alkylamino side chain by a tropine ring system enhances affinity for the dopamine neurons, as does a relative lack of constraint of the aromatic ring. The antidepressant drugs imipramine and amitriptyline are affected oppositely by N -demethylation. While N -demethylation of imipramine increases its affinity for hypothalamic catecholamine synaptosomes 20-fold, N -demethylation of amitriptyline reduces the inhibition of hypothalamic catecholamine uptake 24-fold. Such structure-activity relationships may facilitate the development of drugs with a high degree of selectivity, respectively, for dopamine and norepinephrine neurons.
ACKNOWLEDGMENTS We wish to thank the following companies for donations of drugs, listed alphabetically: amytriptyline hydrochloride (Merck Sharp & Dohme); benztropine mesylate (Merck Sharp & Dohme); biperiden hydrochloride (Knoll Pharmaceutical Company); BS 6825, 7039, 7042, 7715, and 7723 (Brocades-Stheeman); carbinoxamine maleate (McNeil Laboratories, Inc.); carphenazine dimaleate (Wyeth Laboratories, Inc.); chlorcyclizine hydrochloride (Burroughs Wellcome and Company); chlorpheniramine maleate (Schering Corporation); chlorpromazine hydrochloride (Smith Kline & French Laboratories); cyclizine hydrochloride (Burroughs Wellcome and Company); cycrimine hydrochloride (Eli Lilly and Company); deptropine citrate (Brocades-Stheeman); desipramine hydrochloride (Geigy Chemical Corporation); diethazine hydrochloride (Smith Kline & French Laboratories); diphenhydramine hydrochloride (Parke Davis and Company); diphenylpyraline hydrochloride (Smith Kline & French Laboratories); doxepin hydrochloride (Charles Pfizer and Company); ethopropazine hydrochloride (Warner-Lambert Research Institute); fenazoxine hydrochloride (Riker Laboratories); hyoscine hydrochloride (Smith Kline & French Laboratories); imipramine hydrochloride (Geigy Chemical Corporation); mepazine hydrochloride (Chemische Fabrik Promonta G.m.b.H.); methixene hydrochloride (Dr. A. Wander, Ltd); nortriptyline hydrochloride (Eli Lilly and Company); orphenadrine hydrochloride (Riker Laboratories); phenindamine tartrate (Hoffman-La Roche, Inc.); procyclidine hydrochloride (Burroughs Wellcome and Company); propiomazine hydrochloride (Wyeth Laboratories, Inc.); protriptyline hydrochloride (Merck Sharp & Dohme); pyrathiazine hydrochloride (Upjohn Company); trihexphenidyl hydrochloride (Lederle Laboratories). We would like to thank Dr. Donald Coffey for his advice on some of the kinetic aspects of this work, and also Miss Molly Ruble for her technical assistance.
286 citations
TL;DR: Experiments suggest that several aminoacids, especially glycine and glutamic, aspartic and gamma-aminobutyric acids are neurotransmitters in the central nervous system, but careful subcellular and regional studies have not provided supporting neurochemical evidence.
Abstract: NEUROPHYSIOLOGICAL experiments suggest that several aminoacids, especially glycine and glutamic, aspartic and gamma-aminobutyric (GABA) acids, are neurotransmitters in the central nervous system1–3 But careful subcellular4,5 and regional studies6–8 have not provided supporting neurochemical evidence, because ammo-acids, with the possible exception of GABA, also have general metabolic functions in nervous tissue
284 citations
TL;DR: It is suggested that brain norepinephrine is selectively involved in mediating amphetamine-induced locomotor stimulation while a dopaminergic component may participate in eliciting the compulsive gnawing syndrome.
229 citations
TL;DR: A method has been described that permits the measurement of the integrated concentration of growth hormone or any substance whose concentration in blood fluctuates widely and employs a small portable constant withdrawal pump with heparin-coated plastic cannula and tubing that are inserted intravenously through a disposable needle.
Abstract: A method has been described that permits the measurement of the integrated concentration of growth hormone or any substance whose concentration in blood fluctuates widely. This method employs a small portable constant withdrawal pump with heparin-coated plastic cannula and tubing that are inserted intravenously through a disposable needle. Similar metabolic clearance rates (MCR) of 131I-HGH and nonradioactive HGH were found using a constant infusion technique. Changes in position, except for standing totally immovable, did not significantly alter the MCR, nor did it change the concentration of HGH. The true secretion rate of HGH was calculated in 4 normal female volunteers by multiplying their individual MCR of HGH by their integrated concentration of HGH. The secretion rates of HGH in these subjects ranged from 0.65 to 1.51 mg/24 hr. The secretion rate of HGH in an acromegalic patient was found to be 8.08 mg in 24 hr.
215 citations
TL;DR: Modification of the membranes with several protein reagents suggests that tyrosyl and possibly histidyl residues may be important in the binding interaction, and no evidence is present for the involvement of sulfhydryl, tryptophanyl, or carboxyl groups of the membrane.
211 citations
TL;DR: The amino acid composition of the purified ATPase from rat liver mitochondria is strikingly similar to amino acid compositions reported for ATPases from such diverse sources as bovine heart mitochondria, spinach chloroplasts, and bacteria.
208 citations
TL;DR: The data suggest that the functional defect is caused by poor nutrition rather than a toxic effect of ethanol on the jejunum, and confirms that the absorption of folic acid is decreased in malnourished, actively drinking alcoholics.
Abstract: The jejunal uptake of labeled folic acid (3H-PGA) was measured in chronic alcoholic patients without definite liver disease. The intestine was perfused through a triple lumen tube with a solution containing 3H-PGA in a concentration of 25 ng per milliliter. Uptake was low in eight patients who gave a history of poor diet during the alcoholic binge that preceded admission (20.4 per cent ± 4.16 S.D.). A significantly greater value was obtained in nine abstinent subjects fed a hospital diet for two weeks (36.5 per cent ± 5.75). The subsequent administration of ethanol for two weeks to seven patients did not change the mean uptake of 3H-PGA (34.8 per cent ± 9.87). This study confirms that the absorption of folic acid is decreased in malnourished, actively drinking alcoholics. The data suggest that the functional defect is caused by poor nutrition rather than a toxic effect of ethanol on the jejunum.
196 citations
TL;DR: The present studies indicate that displacement of phospholipids from liver and fat cell membranes can result in the unmasking of substantial quantities of insulin receptor which is probably identical with that normally exposed to the solvent in these cells.
178 citations
TL;DR: Extracellular histamine stimulates accumulation of adenosine 3',5'-monophosphate in human leukocytes and prevents antigenic release of histamine from cells of allergic donors and both effects occur at histamine concentrations that can be achieved by antigenicrelease of the amine in vitro.
Abstract: Extracellular histamine stimulates accumulation of adenosine 3',5'-monophosphate in human leukocytes and prevents antigenic release of histamine from cells of allergic donors. Both effects occur at histamine concentrations that can be achieved by antigenic release of the amine in vitro.
TL;DR: A 3.7% T polyacrylamide gel allowed for isoelectric focusing of hemoglobin and cyanogen bromide fragments of both collagen and hemoglobin in the absence of significant molecular sieving and provided satisfactory mechanical stability.
TL;DR: There is strong evidence that the effects of tryptic digestion result exclusively from perturbations of superficial structures of the cell membrane, and there is no evidence that this specific and well characterized effect oftryptic digestion is subject to facile and spontaneous repair.
TL;DR: The data presented reveal that an orthodox → condensed ultrastructural transformation is linked to induced oxidative phosphorylation in mitochondria in the intact ascites tumor cell.
Abstract: We have examined the ultrastructure of mitochondria as it relates to energy metabolism in the intact cell Oxidative phosphorylation was induced in ultrastructurally intact Ehrlich ascites tumor cells by rapidly generating intracellular adenosine diphosphate from endogenous adenosine triphosphate by the addition of 2-deoxyglucose The occurrence of oxidative phosphorylation was ascertained indirectly by continuous and synchronous monitoring of respiratory rate, fluorescence of pyridine nucleotide, and 90° light-scattering Oxidative phosphorylation was confirmed by direct enzymatic analysis of intracellular adenine nucleotides and by determination of intracellular inorganic orthophosphate Microsamples of cells rapidly fixed for electron microscopy revealed that, in addition to oxidative phosphorylation, an orthodox → condensed ultrastructural transformation occurred in the mitochondria of all cells in less than 6 sec after the generation of adenosine diphosphate by 2-deoxyglucose A 90° light-scattering increase, which also occurs at this time, showed a t ½ of only 25 sec which agreed temporally with a slower orthodox → maximally condensed mitochondrial transformation Neither oxidative phosphorylation nor ultrastructural transformation could be initiated in mitochondria in intact cells by the intracellular generation of adenosine diphosphate in the presence of uncouplers of oxidative phosphorylation Partial and complete inhibition of oxidative phosphorylation by oligomycin resulted in a positive relationship to partial and complete inhibition of 2-deoxyglucose-induced ultrastructural transformation in the mitochondria in these cells The data presented reveal that an orthodox → condensed ultrastructural transformation is linked to induced oxidative phosphorylation in mitochondria in the intact ascites tumor cell
TL;DR: It appears that visual adaptation in the skate retina occurs before the S-unit is reached, i.e., at the receptors themselves, as indicated by the recorded S-potentials.
Abstract: The S-potentials recorded intracellularly from the all-rod retina of the skate probably arise from the large horizontal cells situated directly below the layer of receptors. These cells hyperpolarize in response to light, irrespective of stimulus wavelength, and the responses in photopic as well as scotopic conditions were found to be subserved by a single photopigment with λmax = 500 nm. The process of adaptation was studied by recording simultaneously the threshold responses and membrane potentials of S-units during both light and dark adaptation. The findings indicate that the sensitivity of S-units, whether measured upon steady background fields or in the course of dark adaptation, exhibits changes similar to those demonstrated previously for the ERG b-wave and ganglion cell discharge. However, the membrane potential level of the S-unit and its sensitivity to photic stimulation varied independently for all the adapting conditions tested. It appears, therefore, that visual adaptation in the skate retina occurs before the S-unit is reached, i.e., at the receptors themselves.
TL;DR: The effects of digesting fat cells with various combinations of C. perfringens neuraminidase and trypsin on glucose oxidation and the patterns of release of sialic acid and sialyl peptides suggest that the biological effects resulting from digesting cells with these enzymes are a consequence of cleavage of similar portions of the same or closely related membrane structures.
TL;DR: The findings suggest that the mechanism of induction by ethanol is different from that of other known inducers, and that in vivo factors beside the absolute increase in microsomal enzyme activity must account for the observed changes in the rates of ethanol degradation.
TL;DR: The kinetic properties, and the effects of enzymic perturbations of the membrane, suggest that the insulin receptors of liver and of adipose tissue cells may be very similar structures.
TL;DR: The biosynthesis of the intermediate oligosaccharide was shown to be initiated by the incorporation of galactose into an endogenous phospholipid, and restored the polysaccharide-synthesizing capacity of enzyme preparations which had been depleted of endogenous lipid by treatment with organic solvents.
TL;DR: A selective adsorbent for neuraminidase was prepared by attaching through azo linkage an inhibitor of this enzyme, N-(p-aminophenyl) oxamic acid, to agarose beads containing the tripeptide, glycyl-glycyl-tyrosine, demonstrating the feasibility of using functional purification procedures for resolving complex and particulate biological structures.
TL;DR: Lactose-induced diarrhea in lactase-deficient subjects results, in large part, from the combination of net fluid secretion by the small intestine in response to an osmotic load and interference with net fluid absorption in the small bowel and colon.
TL;DR: The distribution of adenosyltransferase enzyme, in normal and malignant tissues, appears to be ubiquitous although the enzyme is most active in liver and moderately active in kidney and pancreas, and a number of regulatory roles including feedback inhibitions and allosteric modifiers have been recently recognized.
TL;DR: Histamine content of rat brain was lowered quickly by inhibitors of histidine decarboxylase, suggesting that a portion of brain histamine turns over rapidly and markedly augmented its formation in the hypothalamus.
Abstract: Histamine content of rat brain was lowered quickly by inhibitors of histidine decarboxylase, suggesting that a portion of brain histamine turns over rapidly. Restraint and exposure to cold also reduced brain histamine levels and markedly augmented its formation in the hypothalamus.
TL;DR: The distribution of the enzymes of phospholipid synthesis in cell wall and membrane subfractions of the cell envelope of Escherichia coli, isolated by a procedure involving particle electrophoresis and sucrose gradient density centrifugation, has been studied.
TL;DR: It is suggested that both ethanol and retinol are oxidized by the same enzyme in the liver, but not in the retina.
TL;DR: Observations suggest that increases in the activity of the NADPH-dependent ethanol-oxidizing system may contribute to, but do not fully explain, the enhanced rates of ethanol clearance in actively imbibing chronic alcoholics.
TL;DR: Using 15μ spheres, it was found that the ratio of endocardial to epicardial radioactivity in the left ventricular wall was increased by propranolol, decreased by isoprenaline, and unchanged by nitroglycerin.
Abstract: Regional myocardial blood flow was studied in the anaesthetized dog by determining the distribution of 15 and 50μ radioactive microspheres after left atrial injection Doses of the 15μ spheres below 4 × 106 did not significantly alter coronary or systemic haemodynamics Larger doses produced a significant increase in mean aortic pressure Less than 1% of the 15μ spheres delivered to the heart passed into the coronary sinus The myocardial distribution of 15 and 50μ spheres was not significantly different except for the ratio of left ventricular endocardium to epicardium (1·12 for 15μ and 1·45 for 50μ, P<0001) Using 15μ spheres, it was found that the ratio of endocardial to epicardial radioactivity in the left ventricular wall was increased by propranolol, decreased by isoprenaline, and unchanged by nitroglycerin
TL;DR: An increase of the H-ion concentration apparently confined to the lesion occurred within the first 24 hr of inflammation and persisted during wound healing and a correlation between the histology of the inflammatory reaction and the pH of the exudate was not apparent.
Abstract: SummaryInflammatory exudates were collected at various times in small chambers adhered over skin wounds of normal rabbits. The exudate pH was compared with the blood pH. At termination of each experiment the lesions were excised for histologic study. The blood pH remained unchanged. The pH of the exudate decreased with time showing a definite fall at 24 hr and reaching the lowest value at 72 hr without appreciable further change at 96 hr. The inflammatory cell response in the lesions was slight. Exudation of cells had subsided at 24 hr and thereafter only reparative processes were present. An increase of the H-ion concentration apparently confined to the lesion occurred within the first 24 hr of inflammation and persisted during wound healing. A correlation between the histology of the inflammatory reaction and the pH of the exudate was not apparent.
TL;DR: A demonstration of abstinence and controlled drinking in 4 alcoholics indicates that excessive drinking can be moderated by reinforcement contingencies and suggests that controlled drinking might be maintained if the reinforcers dispensed to the alcoholic were made contingent on moderate drinking.
Abstract: A demonstration of abstinence and controlled drinking in 4 alcoholics indicates that excessive drinking can be moderated by reinforcement contingencies. Ss could earn money each time that they abstained or stopped drinking after a priming dose for one day. The magnitude of reinforcement required for maintaining abstinence or moderation was a function of the priming dose of alcohol and the delay of reinforcement. This result suggests that controlled drinking might be maintained if the reinforcers dispensed to the alcoholic were made contingent on moderate drinking.
TL;DR: Adult albino rabbits (2-3 kg) were killed with an overdose of sodium pentobarbital and the corneas removed and transferred immediately to a Petri dish containing Krebs-bicarbonate Ringer's solu tion (pH 7.2) at 23-24° C.