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Showing papers by "Johns Hopkins University School of Medicine published in 1979"


Journal Article
TL;DR: It is proposed that [3H]5-HT and[3H]-spiroperidol label distinct populations of serotonin receptors in rat brain, designated 5-HT1 and 5- HT2 receptors, respectively.
Abstract: [3H]5-Hydroxytryptamine (5-HT), [3H]lysergic acid diethylamide (LSD) and [3H]spiroperidol bind to membranes from the rat frontal cerebral cortex in a manner indicating a selective interaction with serotonin receptors. Differential drug potencies in competing for [3H]5-HT and [3H]spiroperidol binding sites suggest that these two [3H]ligands respectively label two distinct populations of receptors, while [3H]LSD labels both the [3H]5-HT and [3H]spiroperidol sites. After incubation of brain membranes with 30 nM spiroperidol, drug specificity of the residual [3H]LSD binding resembles that of receptors labeled by [3H]5-HT. Conversely, drug effects on [3H]LSD binding in the presence of 300 nM 5-HT resemble effects with [3H]spiroperidol. We propose that [3H]5-HT and [3H]-spiroperidol label distinct populations of serotonin receptors in rat brain, designated 5-HT1 and 5-HT2 receptors, respectively. [3H]LSD appears to bind to both receptors to a similar extent.

1,353 citations


Journal ArticleDOI
TL;DR: The distribution of [3H]diprenorphine binding sites determined by this in vitro method is identical to the distribution found in earlier studies utilizing in vivo labeling of opioid receptors.

780 citations


Journal ArticleDOI
TL;DR: A factor analysis of the 90-item version of the Hopkins Symptom Checklist, performed on the pretreatment self-ratings of nonpsychotic outpatients with symptoms of depression and anxiety, revealed the presence of 8 clinically meaningful factors.

585 citations


Journal ArticleDOI
TL;DR: It was found that the subject was unable to utilize semantic context in the written disambiguation of spoken homophones but could, at the same time, use even minimal syntactic cues as the basis for proper lexical selection, consistent with other lines of evidence pointing to the relative preservation of syntactic operations.

481 citations


Journal ArticleDOI
17 Aug 1979-Science
TL;DR: Following ligation of the right middle cerebral artery, rats were hyperactive for 2 to 3 weeks and did not show any significant change in catecholamines in any of the brain areas studied, suggesting lateralization of behavioral and biochemical response to cerebral infarction may be the consequence of anatomical or physiological asymmetries in the brain.
Abstract: Following ligation of the right middle cerebral artery, rats were hyperactive for 2 to 3 weeks whether activity was measured by running wheel revolutions or open field observations. Assays of brain catecholamines revealed 30 percent reductions of norepinephrine in the injured and uninjured cortex and locus coeruleus and a 20 percent reduction of dopamine in the substantia nigra. In contrast, rats with left middle cerebral artery ligations did not become hyperactive and did not show any significant change in catecholamines in any of the brain areas studied. Right and left hemispheric infarctions were comparable in their locations and extent of tissue damage. This lateralization of behavioral and biochemical response to cerebral infarction may be the consequence of anatomical or physiological asymmetries in the brain.

389 citations


Journal ArticleDOI
TL;DR: Enkephalin immunoreactive perikarya, fibers and nerve terminals, visualized by the indirect immunohistofluorescent method in colchicine-pretreated animals, are localized in many discrete regions of the rat brain stem.

383 citations


Journal Article
TL;DR: High affinity binding levels vary 14 fold between lowest values in corpus striatum and cerebellum, and highest values in cerebral cortex, and low affinity binding varies less regionally, with highest levels in hypothalamus.
Abstract: [3H]Clonidine (26.7 Ci/mmole) binds with high affinity to sites on rat brain membranes with properties of alpha -noradrenergic receptors. [3H]Clonidine binding shows a biphasic pattern in kinetic and saturation experiments. Fifty percent of the specific binding of 0.4 nM [3H]clonidine is dissociated rapidly in 2 min by excess norepinephrine or clonidine, and the remaining 50% dissociates at a 10-fold slower rate. When slowly-dissociating [3H]clonidine binding is examined in isolation, saturation curves show a single population of high-affinity sites with a KD of 0.5 nM and B max of 1.3-1.6 pmoles/g tissue in cerebral cortex. Rapidly-dissociating [3H]clonidine binding, estimated from the difference between total binding and high-affinity binding, involves a single population of lower affinity sites with a KD of 3.0 nM and B max of 9-10 pmoles/g cerebral cortex tissue. Alpha agonists are in general more potent at the high affinity [3H]clonidine site, while alpha antagonists are more potent at the low affinity site. α-Methylnorepinephrine is less potent than norepinephrine at the high affinity site, but more potent at the low affinity site. Neither [3H]-clonidine binding site resembles the alpha receptor site labeled by [3H]WB-4101. The distribution of high and low affinity [3H]clonidine binding throughout rat central nervous system is different. High affinity binding levels vary 14 fold between lowest values in corpus striatum and cerebellum, and highest values in cerebral cortex. Low affinity binding varies less regionally, with highest levels in hypothalamus. 6-Hydroxydopamine treatment doubles the number of high affinity [3H]clonidine sites in the cortex, but does not alter the number of low affinity sites. 6-Hydroxydopamine increases high affinity binding much more than low affinity binding throughout the brain. 6-Hydroxydopamine also increases by 50% the number of [3H]WB-4101 and [3H]epinephrine alpha receptor sites in the cerebral cortex. ACKNOWLEDGMENTS We thank Mrs. Lynda Hester for excellent technical assistance, and Pam Morgan and Billie Jean Little for manuscript preparation.

378 citations


Journal ArticleDOI
TL;DR: Examination of the retina, optic nervehead, and optic nerves of 21 human eyes from glaucoma patients in whom clinical information was available for comparison confirmed the presumption from visual field testing that arcuate area ganglion cell fibers are selectively more susceptible to damage in chronic glAUcoma.

320 citations


Journal ArticleDOI
TL;DR: An operative technique is presented for the management of the deep dorsal vein and Santorini’s plexus in radical retropubic operations that minimizes blood loss and improves exposure.

311 citations


Journal ArticleDOI
TL;DR: The correspondence of separate binding sites with distinctive patterns of physiological responses indicates the existence of two discrete types of postsynaptic α-receptors, which are proposed to designate sites labeled by WB-4101 as α-1 receptors and those labeled by 3H-clonidine,3H-norepinephrine and 3h-epinephrine asα-2 receptors.

286 citations


Journal ArticleDOI
TL;DR: Neurotensin immunoreactive perikarya, fibers and nerve terminals, visualized by the indirect immunohistofluorescent method in colchicine-pretreated animals, are localized in many discrete regions of the rat brain stem and certain neurotensin localizations suggest an association of the peptide with functional brain systems preferentially involving these regions.

Journal Article
TL;DR: On the basis of the kinetics of binding, differential affinity for competitors and differences in regional distribution in brain, the high and low affinity binding sites represent independent entities.
Abstract: The binding of [3H]kainic acid to washed membranes from rat forebrain was saturable with dissociation constants at 2° of 4-16 nM and 27-66 nM for high and low affinity binding, respectively. The Hill coefficients for binding to high and low affinity sites were 0.99 and 0.85, respectively. At 2° [3H]kainic acid receptor binding reached equilibrium by 60 minutes. Dissociation of the ligand-receptor complex at 2° was biphasic. The kinetically-determined dissociation constant for the high affinity binding site corresponded well with the value obtained in equilibrium studies. Of the substances tested, kainic acid and quisqualic acid were the most potent in competing for [3H]kainic acid binding sites. L-glutamic acid was 40-fold less potent than kainic acid itself but 2500 times more effective than D-glutamic acid; dihydrokainic acid was 200-fold less potent than kainic acid at the low affinity site and 1000-fold less active in competing for binding to the high affinity site. Among the poor displacers of [3H]kainic acid (IC50 > 0.1 mM at 50 nM [3H]kainic acid) were D- and L-aspartic acids as well as several proposed glutamate antagonists. In brain, there was considerable variation in the regional distribution of high affinity binding sites: striatum > frontal cortex = hippocampus > cerebellum > medulla-pons; more than 90% of the total specific binding in the cerebellum and medulla-pons was to low affinity sites. Thus, on the basis of the kinetics of binding, differential affinity for competitors and differences in regional distribution in brain, the high and low affinity binding sites represent independent entities. Negligible specific binding was obtained (< 1 fmole/mg tissue) in liver, lung, kidney and intestine. Ablation of the intrinsic neurons of the caudate nucleus by injecting 10 nmole of kainic acid 28 days before sacrifice was associated with a 57-64% reduction in high and low affinity binding in this region. ACKNOWLEDGMENTS We thank A. Hunter Thompson for providing excellent technical assistance and Victoria Rhodes, Princie Campbell and Carol Kenyon for preparing the manuscript. We are also grateful to Dr. Morley Hollenberg for his helpful comments and Dr. Kathleen Biziere for her contributions.

Journal ArticleDOI
TL;DR: These cell types were incorporated into a hypothetical circuit that generates saccades by rapidly driving the eye to a designated orbital position rather than preprogramming a distance for movement.
Abstract: Eye movements in a patient with saccadic oscillations (ocular flutter) were recorded and analyzed. Findings were related to recent microelectrode studies in the monkey pontine reticular formation which have identified three types of premotor neurons related to saccadic eye movements: burst, tonic, and pause cells. We incorporated these cell types into a hypothetical circuit that generates saccades by rapidly driving the eye to a designated orbital position rather than preprogramming a distance for movement. Physiological measurements suggest that this neural network is unstable and that the burst neurons must be tonically inhibited to prevent saccadic oscillations during periods of fixation. Pause cells, which discharge tonically except during saccades, when they pause, appear to inhibit burst cells and prevent such saccadic oscillations. Analysis of our patient's behavior indicates that many types of saccadic oscillations can be explained and classified by assuming an abnormality of pause cell control over saccadic burst neurons.

Journal ArticleDOI
TL;DR: Jelly coat, a multicomponent extracellular matrix surrounding the sea urchin egg, induces the acrosome reaction in sperm, suggesting that in some species, fertilization appears to involve sperm-egg recognition at the level of the jelly coat as well as at thelevel of sperm- egg receptors.

Journal ArticleDOI
02 Aug 1979-Nature
TL;DR: The light microscopic autoradiographic localisation of BZ receptors in mammalian central nervous system (CNS) and, to the authors' knowledge, the first receptor autorardiography in human brain tissue are reported for the first time.
Abstract: THE benzodiazepine (BZ) drugs are used as anxiolytics, hypnotics, anticonvulsants and muscle relaxants. They are the most widely prescribed of all psychotropic drugs and seem to exert their action by binding to a specific receptor site on brain membranes1–2. This receptor appears to interact with neurotransmission mediated by γ-aminobutyric acid (GABA)3–8. Biochemical studies of BZ receptor distributions in brain reveal large regional variations9,10. An increase in resolution of localisation of BZ receptors would provide greater insight into mechanisms of actions of BZs. In this study, we report for the first time the light microscopic autoradiographic localisation of BZ receptors in mammalian central nervous system (CNS) and, to our knowledge, the first receptor autoradiography in human brain tissue. We observed striking variations in receptor densities in different areas which, in some cases, were species dependent.


Journal ArticleDOI
TL;DR: Isotonic suspensions of erythrocytes exposed to intense electric fields for a duration in microseconds showed time-dependent increase in the conductivity, indicating that the induced membrane conductance is strongly dependent on the membrane potential.

Journal ArticleDOI
TL;DR: Following unilateral 6-hydroxydopamine nigrostriatal lesions in rats, the binding of both 3H-apomorphine and3H-spiroperidol in the striatum is increased and in rats with incomplete lesions or at early time points after lesion, binding is not significantly different from control levels.

Journal ArticleDOI
TL;DR: The tricyclic antidepressant doxepin and the neuroleptic clozapine are the most potent of all drugs examined in competing for [3H]mepyramine binding, exceeding in potency any H1 antihistamines examined.
Abstract: [3H]Mepyramine binds with high affinity to membranes from brain of human, rat, guinea-pig, rabbit and mouse with drug specificity indicating an association with histamine H1receptors. Considerable species differences occur in the affinity of [3H]mepyramine, with guinea-pig and human having 34 times greater affinity than rat, mouse or rabbit. The greater affinity of [3H]mepyramine in guinea-pig than in rat is attributable both to faster association and slower dissociation rates in guinea-pig. Species differences in affinity for H1 receptor sites occur for some antihistamines but not for others. Some tricyclic antidepressant and neuroleptic drugs are extremely potent inhibitors of [3H]mepyramine binding, exceeding in potency any H1 antihistamines examined. The tricyclic antidepressant doxepin and the neuroleptic clozapine are the most potent of all drugs examined in competing for [3H]mepyramine binding. The regional distribution of specific [3H]mepyramine binding differs considerably in the various species examined.

Journal ArticleDOI
01 Sep 1979-Gene
TL;DR: Plasmid pKC7, a derivative of pBR322, specifies resistance to both ampicillin and kanamycin, and contains unique sites for insertion of DNA cleaved with ten different restriction endonucleases.

Journal ArticleDOI
20 Jul 1979-Science
TL;DR: The trajectory of the intracortical noradrenergic fibers has been characterized by histochemical analysis following the production of cortical lesions in the rate to show a medial to lateral topographic relationship between deep longitudinally running fibers and overlying cortex.
Abstract: The trajectory of the intracortical noradrenergic fibers has been characterized by histochemical analysis following the production of cortical lesions in the rate. A large group of noradrenergic fibers enters the cortex at the frontal pole and proceeds caudally through the deep layers of dorsolateral cortex. Branches arise from these longitudinally directed fibers and form a uniform pattern of innervation throughout lateral cortex. Because these fibers travel long distances rostrocaudally within the gray matter, a large area of cortex can be deprived of noradrenergic innervation by a relatively small lesion of frontal cortex. The medial and lateral cortex can be selectively and differentially denervated of noradrenergic fibers, and there is a medial to lateral topographic relationship between deep longitudinally running fibers and overlying cortex.


Journal ArticleDOI
TL;DR: The effectiveness of this biofeedback conditioning demonstrates for the first time that manometric techniques can play a direct therapeutic role in the treatment of gastrointestinal disorders.

Journal ArticleDOI
TL;DR: Recommendations are derived from experience with the evaluation of over 500 patients and the therapy of over 300 adults and children, and a degree of controversy persists in this field, and additional data must be gathered before a fully defined position can be established.
Abstract: There has been significant recent progress in the diagnosis and treatment of patients with Hymenoptera sensitivity.‘-” Many problems remain, and, indeed, the introduction of new information has raised additional questions. Treatment is highly efficacious but expensive, of long duration, and has an unknown degree of long-term side effects. The question of whom to treat, therefore, becomes critical. With the commercial availability of venoms for immunotherapy, the practicing allergist will need to make a series of difficult decisions. With this in mind, it seems appropriate to present our clinical and laboratory experience during the last five years and to summarize our suggestions concerning the management of patients with an allergy to insect stings. Our recommendations are derived from experience with the evaluation of over 500 patients and the therapy, including inhospital sting, of over 300 adults and children. A degree of controversy persists in this field, and additional data must be gathered before a fully defined position can be established. We have tried to make what follows as precise a statement of what is and is not known as is currently possible. Whole body extract therapy In the first volume of the

Journal ArticleDOI
TL;DR: MAM treatment at 15 DG severely reduces intrinsic neuronal populations including GABAergic and glutamatergic neurons, and produces a shrunken cortex relatively hyperinnervated by noradrenergic and cholinergic neurons.

Journal ArticleDOI
TL;DR: An underlying disorder of dopamine and serotonin metabolism in Tourette syndrome is suggested, as both baseline and accumulated levels of HVA after probenecid were decreased.
Abstract: Biogenic amine metabolism in the central nervous system of 9 children with Tourette syndrome was evaluated by quantitation of their metabolites in cerebrospinal fluid by a gas chromatographic/mass spectrometric method. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) were measured in CSF before and after oral administration of probenecid. Dopamine metabolism appeared defective, as both baseline and accumulated levels of HVA after probenecid were decreased. Serotonin metabolism also appeared defective in some patients with low baseline and low accumulated levels of 5-HIAA after probenecid. Taken together with other clinical features of this disease, the results suggest an underlying disorder of dopamine and serotonin metabolism in Tourette syndrome.

Journal ArticleDOI
TL;DR: The urea cycle may serve as a model for the development of excretion pathways of toxic precursors which accumulate in inborn errors of metabolism.

Journal ArticleDOI
TL;DR: The potencies of various opiates in displacing several 3H-opiate ligands' binding to rat membranes vary depending on the nature of the ligand, and these agonists differ from the other opiate classes by possessing a relatively hydrophilic component in their C-ring moieties.

Journal ArticleDOI
TL;DR: Enkephalinase A activity can be completely resolved by DEAE column chromatography from angiotensin converting enzyme activity, demonstrating that they are distinct enzymes.

Journal ArticleDOI
TL;DR: Herpes simplex virus encephalitis tends to localize to the temporal and orbitofrontal lobes, giving characteristic clinical and pathological findings, and it is postulate that this localization may be explained by reactivated virus spreading along the fifth nerve fibers, which innervate basal meninges of the anterior and middle fossae.
Abstract: Herpes simplex virus encephalitis tends to localize to the temporal and orbitofrontal lobes, giving characteristic clinical and pathological findings. Since the virus remains latent in the trigeminal ganglia, we postulate that this localization may be explained by reactivated virus spreading along the fifth nerve fibers, which innervate basal meninges of the anterior and middle fossae.