Showing papers by "Johns Hopkins University School of Medicine published in 1973"
TL;DR: Tritiated naloxone, a powerful opiate antagonist, specifically binds to an opiate receptor of mammalian brain and guinea pig intestine that closely parallels their pharmacological potency.
Abstract: Tritiated naloxone, a powerful opiate antagonist, specifically binds to an opiate receptor of mammalian brain and guinea pig intestine. Competition for the opiate receptor by various opiates and their antagonists closely parallels their pharmacological potency. The opiate receptor is confined to nervous tissue.
2,319 citations
TL;DR: In mouse somatosensory cortex there are discrete cytoarchitectonic units, called "barrels".
Abstract: In mouse somatosensory cortex there are discrete cytoarchitectonic units, called "barrels." Each barrel is related to one sensory vibrissa on the muzzle. Individual vibrissae were carefully injured at birth; 12 to 43 days later, the corresponding barrels proved to be absent. Evidently the sensory periphery has an important influence on the structure of the somatosensory cortex.
809 citations
TL;DR: The authors describe a relationship between the distribution of opiate receptors and of neurotransmitters that varies dramatically throughout the human and monkey brain.
Abstract: The frequency of opiate receptors varies dramatically throughout the human and monkey brain. The authors describe a relationship between the distribution of opiate receptors and of neurotransmitters.
771 citations
TL;DR: The number of acetylcholine receptors was determined in the neuromuscular junctions of patients with typical myasthenia gravis and in five controls, by means of 1251-labeled α-bungarotoxin binding.
Abstract: The number of acetylcholine receptors was determined in the neuromuscular junctions of eight patients with typical myasthenia gravis and in five controls, by means of (125)1-labeled alpha-bungarotoxin binding. The junctional acetylcholine receptors were reduced in the myasthenic muscles as compared with the controls. This reduction in receptors may account for the defect in neuromuscular transmission in myasthenia gravis.
595 citations
TL;DR: A variety of evidence suggests that the high affinity transport represents a selective accumulation of choline by cholinergic neurons, while the low affinity uptake system has some less specific function.
Abstract: —The accumulation of [3H]choline into synaptosome-enriched homogenates of rat corpus striatum, cerebral cortex and cerebellum was studied at [3H]choline concentrations varying from 0.5 to 100 μm. The accumulation of [3H]choline in these brain regions was saturable. Kinetic analysis of the accumulation of the radiolabel was performed by double-reciprocal plots and by least squares iterative fitting of a substrate-velocity curve to the data. With both of these techniques, the data were best satisfied by two transport components, a high affinity uptake system with Km. values of 1.4 μM (corpus striatum), and 3.1 μM (ceμ(cerebral cortex) and a low affinity uptake system with respective Km. values of 93 and 33 μM for these two brain regions. In the cerebellum choline was accumulated only by the low affinity system. When striatal homogenates were fractionated further into synaptosomes and mitochondria and incubated with varying concentrations of [3H]choline, the high affinity component of choline uptake was localized to the synaptosomal fraction. The high affinity uptake system required sodium, was sensitive to various metabolic inhibitors and was associated with considerable formation of [3H]acetylcholine. The low affinity uptake system was much less dependent on sodium, and was not associated with a marked degree of [3H]acetylcholine formation. Hemicholinium-3 and acetylcholine were potent inhibitors of the high affinity uptake system. A variety of evidence suggests that the high affinity transport represents a selective accumulation of choline by cholinergic neurons, while the low affinity uptake system has some less specific function.
582 citations
TL;DR: Sodium enhances antagonist binding in vitro but decreases agonist binding, a qualitative difference that may be relevant to the divergent pharmacological properties of opiate agonists and antagonists.
Abstract: Receptor binding of opiate agonists and antagonists can be differentiated in vivo and in vitro. Administration of either rapidly elevates stereospecific [(3)H]dihydromorphine binding to mouse brain extracts by 40 to 100 percent, but antagonists are 10 to 1000 times more potent than agonists; as little as 0.02 milligram of naloxone per kilogram of body weight significantly enhances opiate receptor binding. Sodium enhances antagonist binding in vitro but decreases agonist binding, a qualitative difference that may be relevant to the divergent pharmacological properties of opiate agonists and antagonists.
507 citations
TL;DR: These and other properties suggest that in addition to the ∼P storage function usually postulated for it, the phosphocreatine-creatine kinase system serves to smooth out or buffer the rate of respiration of heart mitochondria at a high and constant rate and to channel ∼P to the contractile system via the mitochondrial and sarcoplasmic isoenzymes of creatine kinase.
458 citations
TL;DR: In the proposed nomenclature restriction-modification systems are named according to host organism and strain, different R-M systems in a single host are designated by Roman numerals.
406 citations
TL;DR: It is suggested that the differential association with SCD between ventricular extrasystoles and parasystole in the late postinfarction period may have bearing on the mechanism of ventricular fibrillation and SCD.
Abstract: The role of ventricular dysrhythmias as determinants of sudden coronary death (SCD) was studied prospectively in 160 male survivors of myocardial infarction, all under 65 years of age and in New York Heart Association (NYHA) functional class I or II. Twelve-hour electrocardiographic recordings were taken in all patients at serial intervals and analyzed for frequency and type of ventricular ectopic beat (VEB). Eighty percent showed VEB's on at least one tape recording. There have been 14 SCD's in a follow-up period ranging between 30 and 54 months, 12 in 87 patients (13.8%) with significant VEB's (frequent, unifocal, multifocal, paired or coupled, and ventricular tachycardia), and only two in 66 patients (3%) with absent or infrequent VEB's (P < 0.02). Although the number of patients in this study is small, the results show that all complex VEB forms together were associated with an excess risk of SCD, notwithstanding the absence of SCD in 27 patients with ventricular parasystole. It is suggested that the ...
377 citations
361 citations
TL;DR: A physical map of the Simian virus 40 genome has been constructed on the basis of specific cleavage of Simianirus 40 DNA by bacterial restriction endonucleases and the single site in SV40 DNA cleaved by the Escherichia coli RI restrictions endonuclease has been located.
TL;DR: The sinus wall, reinforced by microfilamentous bands, significantly controlled the circulation of erythrocytes through the spleen, and cells pooled in the cords, macrophages increased in number, and the sequences initiated that resulted in splenomegaly.
TL;DR: The combined evidence suggests that sodium requirement for high affinity uptake is a characteristic of neuroactive substances and may be used as a screening tool to search for other neurotransmitter candidates.
Abstract: —The accumulation by synaptosomal fractions from rat central nervous system tissue of transmitter candidate amino acids and non-candidate amino acids was studied with respect to ionic requirements, metabolic inhibitors, structural analogues, and ontogeny. For l-glutamic and l-aspartic acids in cortex and spinal cord and glycine in spinal cord a stringent sodium requirement for high affinity uptake was demonstrated. Detailed kinetic analysis of the sodium requirement for glutamic acid uptake into cortical synaptosomal fractions suggests that: (1) sodium ion acts both competitively and non-competitively in determining the velocity of high affinity uptake; (2) in the absence of sodium ion only the low affinity uptake can be demonstrated; and (3) inhibition of the Na–K-ATPase enzyme system with ouabain reduces the velocity of uptake to 60% of control values in contrast to alanine whose synaptosomal uptake is less dependent on this enzyme system. No potent inhibitors of l-glutamic acid accumulation were found among several structural analogues or derivatives. The kinetic analysis for glycine accumulation was more complex and suggested allosteric interactions between glycine and sodium ion. Developmental studies revealed GABA and l-glutamic acid to have absolute sodium requirements for cortical synaptosomal accumulation from the 16th gestational day through adulthood, with glycine accumulation showing a decreasing sodium requirement as maturation proceeded over this period. The combined evidence suggests that sodium requirement for high affinity uptake is a characteristic of neuroactive substances and may be used as a screening tool to search for other neurotransmitter candidates.
TL;DR: Sixteen patients were studied prior to and after total hip replacement with an apparatus designed to eliminate all sensory cues to the perception of the position of the joint, except stimuli from the joint capsule and periarticular soft tissues.
Abstract: Sixteen patients were studied prior to and after total hip replacement with an apparatus designed to eliminate all sensory cues to the perception of the position of the joint, except stimuli from the joint capsule and periarticular soft tissues. The detection of passive movement and its extent and t
TL;DR: The reflex controls the total systemic venous capacity to a degree that changes cardiac output potentially by 30–10% per 25-mm Hg change in ISP, which is consistent with quantitative understanding of carotid sinus baroreceptor reflex control of cardiac output.
Abstract: To attain a quantitative understanding of carotid sinus baroreceptor reflex control of cardiac output, we studied the reflex control of total systemic vascular capacity in vagotomized dogs. In experiments measuring blood volume shifts caused by the carotid sinus reflex (series 1), venous return was diverted into a reservoir while cardiac output and central venous pressure were maintained at constant levels. The pressure in the isolated carotid sinuses (ISP) was lowered or raised in 25-mm Hg steps between 75 and 200 mm Hg. This procedure mobilized blood into or out of the reservoir, indicating a decrease or an increase in total vascular capacity, respectively. The mean maximum volume shift, 3.6 ml/kg body weight, occurred in the same ISP region, 135 ± 12.5 mm Hg, where reflex control of total peripheral resistance was strongest. The total volume shift was approximately 7.5 ml/kg for ISP changes from 75 to 200 mm Hg. When mean arterial blood pressure was maintained constant during the ISP step changes, the ...
TL;DR: This chapter describes the neurotransmitter uptake as a tool in identifying neurotransmitter-specific pathways and there is abundant evidence that the sites of NE uptake in brain, under high-affinity conditions are localized to NE-containing neurons.
TL;DR: It is suggested that histamine could “feedback” to control the spread of an allergic response by decreasing the response of other target cells (tissue mast cells, blood basophils) to an allergenic challenge.
Abstract: AGENTS which increase the intracellular level of adenosine 3′-5′-monophosphate (cyclic AMP) in human leukocyte preparations such as the catecholamines, methylxanthines and prostaglandins, inhibit the antigen induced, IgE antibody mediated release of histamine from human leukocytes (basophils)1–3 Not only are the dose response relationships for increased cyclic AMP levels and the inhibition of histamine release similar, but the kinetics of the two events are also parallel and it is accepted as a working hypothesis that changes in the cyclic AMP level of human basophils (and mast cells) modulate the in vitro allergic response4–6 Recently, we showed that exogenous histamine could increase the cyclic AMP level of human leukocyte preparations and stop the release of endogenous histamine This occurred at concentrations of histamine (about 10−6 M) which are present in the cell suspension under study7 For this reason we suggested that histamine could “feedback” to control the spread of an allergic response by decreasing the response of other target cells (tissue mast cells, blood basophils) to an allergenic challenge No clear effect of antihistamines on the inhibition of histamine release by histamine was observed: concentrations up to 10−3 M to 10−4 M of several antihistamines had little effect and higher concentrations of these drugs either caused inhibition of histamine release themselves or were cytotoxic2,7
TL;DR: The driving force for entry of ornithine+ is concluded to be a negative-inside transmembrane potential produced when proton-conducting anions enter mitochondria to relieve the alkaline-inside pH gradient generated by electron transport.
TL;DR: The RAST is a quantitative technique that gives diagnostically useful information in ragweed hay fever, although not significantly different from basophil histamine release or carefully performed skin testing, and the convenience to the patient may, however, offer a noticeable advantage.
Abstract: In 87 patients with both spring and fall hay fever symptoms the radioallergosorbent test (RAST) technique for specific IgE antibodies to ragweed was compared with basophil histamine release and direct intradermal skin testing by the threshold dilution technique. The three techniques gave good agreement except with the leastsensitive patients, some of whom had a positive skin test but undetectable histamine release or IgE antibodies. Twenty-one patients who were highly sensitive to ragweed as measured by all three techniques were followed without specific immunotherapy. There was significant agreement between the level of positivity of all three tests and the symptom index obtained during the ragweed season. In 14 of the 21 patients there was a significant correlation between daily ragweed pollen counts and daily symptom indexes during the season. On the other hand, among the 16 least-sensitive patients (as judged by histamine release) the correlation between daily ragweed pollen counts and symptom indexes was significant in only 3 patients. Other significant allergens could not be identified in the latter group, and the cause of their symptoms is not clearly identified but appears not to be ragweed. The RAST is a quantitative technique that gives diagnostically useful information in ragweed hay fever, although not significantly different from basophil histamine release or carefully performed skin testing. The convenience to the patient may, however, offer a noticeable advantage.
TL;DR: Results indicate that the mannosyl lipid formed in hen oviduct and bovine thyroid catalyze the transfer of mannose from GDP-mannose to endogenous acceptors has the structure of mannosy phosphoryl polyisoprenol; the precise chain length of the poly isoprenyl moiety remains to be established.
TL;DR: The measurement of Pleural fluid pH is useful in the diagnosis and management of pleural effusions and has predictive value for the course of parapneumonic effusions.
TL;DR: A relatively small proportion of individuals highly allergic to ragweed were found to develop marked reaginic (immunoglobulin E-mediated) skin sensitivity to a minor ragweed pollen allergen Ra5, the first evidence of a strong association between a specific immune response and a specific group of closely related HL-A antigens in man.
Abstract: A relatively small proportion (17 percent) of individuals highly allergic to ragweed were found to develop marked reaginic (immunoglobulin E-mediated) skin sensitivity to a minor ragweed pollen allergen Ra5 (molecular weight 5200). Sensitivity to Ra5 was significantly associated with the possession of a major histocompatibility antigen of the HL-A7 cross-reacting group. This appears to be the first evidence of a strong association between a specific immune response and a specific group of closely related HL-A antigens in man.
TL;DR: The effectiveness of low energy intraventricular catheter defibrillation in man provides background for the development of the transvenous automatic defibrillator for protection of selected high-risk patients.
Abstract: The effectiveness of low energy intraventricular catheter defibrillation was evaluated in 11 patients undergoing coronary artery surgery, in whom ventricular fibrillation occurred after anoxic arrest of 21-42 min. A distal electrode catheter was introduced through an atriotomy into the right ventricular apex. In eight patients the proximal electrode was a saline-soaked sponge placed on the superior vena cava, while in three this electrode formed an integral part of the superior vena cava cannula used in cardiopulmonary bypass. Intraventricular catheter defibrillation was accomplished in nine patients using 5-15 w-sec, considerably less energy than required for paddle defibrillation. There were no apparent short or long-term ill effects. Unsuccessful defibrillation in the two remaining patients was ascribed to difficulties in electrode placement. The effectiveness of low energy intraventricular catheter defibrillation in man, in addition to raising basic electrophysiologic questions, provides background fo...
TL;DR: It is demonstrated that chloroquine in concentrations around 1–2 × 10−5 M strongly interferes with mucopolysaccharide degradation in the living cell and electron microscopy shows that a morphological picture resembling a lysosomal storage disease develops in these cells after less than 2 days exposure to the drug.
TL;DR: One of the major difficulties in estimating the genetic hazards of ionising radiation to human populations has been the inability to extrapolate with confidence from mutation rate data in lower organisms to man1,2.
Abstract: ONE of the major difficulties in estimating thegenetic hazards of ionising radiation to human populations has been our inability to extrapolate with confidence from mutation rate data in lower organisms to man1,2. Experimentally observed mutation rates per locus per rad extend over an enormous range of three orders of magnitude. For instance, the forward mutation rate per locus per rad is 1 × 10−9 in Escherichia coli B/r at two loci for phage T1 resistance, 2.7 × 10−9 in Neurospora at the ad3 locus, 1.4 × 10−8 in Drosophila for eight specific loci (averaged), 1.7 × 10−7 in the mouse for twelve specific loci (averaged), and 1 × 10−6 in barley for three loci.
TL;DR: The most effective affinity adsorbents were prepared by attaching 17β-estradiol 17-hemisuccinate to agarose derivatives containing albumin or the branched copolymer of poly(l-lysine) ("backbone") and poly(dl-alanine) "side arms").
TL;DR: The phosphorylation reaction does not appear to have greater specificity for rhodopsin than for other proteins present as minor components in retinal outer segment preparations; however, of a variety of soluble proteins added to the incubation mixture in high concentrations along with outer segment membranes, only calf thymus histone is capable of binding 32P from [γ-32P]ATP.
TL;DR: The results indicate that the changes in the binding of insulin occur by direct binding of the plant lectins to the insulin receptor macromolecule, which are proteins of complex carbohydrate composition which have several chemically distinct sites capable of binding plant Lectins in a manner which perturbs the insulin-receptor interaction.
TL;DR: The preliminary data suggest that the combination of dietary folate deficiency and prolonged ethanol intake results in intestinal malabsorption of several water-soluble substances, which may account in part for the poor nutrition often found in binge drinkers.