Showing papers by "National Institutes of Health published in 1977"

The CES-D Scale: A Self-Report Depression Scale for Research in the General Population

Abstract: The CES-D scale is a short self-report scale designed to measure depressive symptomatology in the general population. The items of the scale are symptoms associated with depression which have been used in previously validated longer scales. The new scale was tested in household interview surveys and in psychiatric settings. It was found to have very high internal consistency and adequate test- retest repeatability. Validity was established by pat terns of correlations with other self-report measures, by correlations with clinical ratings of depression, and by relationships with other variables which support its construct validity. Reliability, validity, and factor structure were similar across a wide variety of demographic characteristics in the general population samples tested. The scale should be a useful tool for epidemiologic studies of de pression.

The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat.

Abstract: — A method has been developed for the simultaneous measurement of the rates of glucose consumption in the various structural and functional components of the brain in vivo. The method can be applied to most laboratory animals in the conscious state. It is based on the use of 2-deoxy-D-[14C]glucose ([14C]DG) as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissues. [14C]DG is used because the label in its product, [14C]deoxyglucose-6-phosphate, is essentially trapped in the tissue over the time course of the measurement. A model has been designed based on the assumptions of a steady state for glucose consumption, a first order equilibration of the free [14C]DG pool in the tissue with the plasma level, and relative rates of phosphorylation of [14C]DG and glucose determined by their relative concentrations in the precursor pools and their respective kinetic constants for the hexokinase reaction. An operational equation based on this model has been derived in terms of determinable variables. A pulse of [14C]DG is administered intravenously and the arterial plasma [14C]DG and glucose concentrations monitored for a preset time between 30 and 45min. At the prescribed time, the head is removed and frozen in liquid N2-chilled Freon XII, and the brain sectioned for autoradiography. Local tissue concentrations of [14C]DG are determined by quantitative autoradiography. Local cerebral glucose consumption is calculated by the equation on the basis of these measured values. The method has been applied to normal albino rats in the conscious state and under thiopental anesthesia. The results demonstrate that the local rates of glucose consumption in the brain fall into two distinct distributions, one for gray matter and the other for white matter. In the conscious rat the values in the gray matter vary widely from structure to structure (54-197 μmol/100 g/min) with the highest values in structures related to auditory function, e.g. medial geniculate body, superior olive, inferior colliculus, and auditory cortex. The values in white matter are more uniform (i.e. 33–40 μmo1/100 g/min) at levels approximately one-fourth to one-half those of gray matter. Heterogeneous rates of glucose consumption are frequently seen within specific structures, often revealing a pattern of cytoarchitecture. Thiopental anesthesia markedly depresses the rates of glucose utilization throughout the brain, particularly in gray matter, and metabolic rate throughout gray matter becomes more uniform at a lower level.

Metastasis Results from Preexisting Variant Cells Within a Malignant Tumor

Abstract: Clones derived in vitro from a parent culture of murine malignant melanoma cells varied greatly in their ability to produce metastatic colonies in the lungs upon intravenous inoculation into syngeneic mice. This suggests that the parent tumor is heterogeneous and that highly metastatic tumor cell variants preexist in the parental population.

Preliminary criteria for the classification of the acute arthritis of primary gout

Abstract: The American Rheumatism Association sub-committe on classification criteria for gout analyzed data from more than 700 patients with gout, pseudogout, rheumatoid arthritis, or septic arthritis. Criteria for classifying a patient as having gout were a) the presence of characteristic urate crystals in the joint fluid, and/or b) a topus proved to contain urate crystals by chemical or polarized light microscopic means, and/or c) the presence of six of the twelve clinical, laboratory, and X-ray phenomena listed in Table 5.

Learning and memory

Abstract: How the brain codes, stores, and retrieves memories is among the most important and baffling questions in science. The uniqueness of each human being is due largely to the memory store—the biological residue of memory from a lifetime of experience. The cellular basis of this ability to learn can be traced to simpler organisms. In the past generation, understanding of the biological basis of learning and memory has undergone a revolution. It is clear that various forms and aspects of learning and memory involve particular systems, networks, and circuits in the brain, and it now appears possible to identify these circuits, localize the sites of memory storage, and analyze the cellular and molecular mechanisms of memory.

Unconventional viruses and the origin and disappearance of kuru.

Abstract: Kuru was the first chronic degenerative disease of man shown to be a slow virus infection, with incubation periods measured in years and with a progressive accumulative pathology always leading to death. This established that virus infections of man could, after long delay, produce chronic degenerative disease and disease with apparent heredofamilial patterns of occurrence, and with none of the inflammatory responses regularly associated with viral infections. Soon thereafter, several other progressive degenerative diseases of the brain were likewise attributed to slow virus infections (see Tables 1 and 2). These include delayed and slow measles encephalitis, now usually called subacute sclerosing panencephalitis (SSPE), progressive multifocal leukoencephalopathy (PML), and transmissible virus dementias usually of the Creutzfeldt-Jakob disease (CJD) type. Thus, slow virus infections, first recognized in animals, became recognized as a real problem in human medicine. Kuru has led us, however, to a more exciting frontier in microbiology than only the demonstration of a new mechanism of pathogenesis of infectious disease, namely the recognition of a new group of viruses possessing unconventional physical and chemical properties and biological behavior far different from those of any other group of microorganisms. However, these viruses still demonstrate sufficiently classical behavior of other infectious microbial agents for us to retain, perhaps with misgivings, the title of “viruses”. It is about these unconventional viruses that I would further elaborate. The group consists of viruses causing four known natural diseases: two of man, kuru and CJD, and two of animals, scrapie in sheep and goats, and transmissible mink encephalopathy (TME) (Table 1). The remarkable unconventional properties of these viruses are summarized in Tables 3 and 4. Because only primate hosts have been available as indicators for the viruses

The framingham eye study i. outline and major prevalence findings

Abstract: During the period 1973--1975, 2675 out of 3977 still-living members of the Framingham, Massachusetts, study population, who have been under investigation for coronary disease risk factors since 1948 and who were in 1973--1975 aged 52 to 85, were given an eye examination stressing cataract, diabetic retinopathy, macular degeneration and glaucoma. Of 2940 subjects who still lived in the local Framingham area, 2477 were examined. Local population prevalence for one or both eyes positive was: 15.5% for senile cataract, 3.1% for diabetic retinopathy, 8.8% for senile macular degeneration and 3.3% for open-angle glaucoma. The proportion of adults with poor "best" visual acuity may be much less than has been estimated by the National Health Survey and the proportion with open-angle glaucoma much more than currently suspected on the basis of foreign studies.

The epsilon-(gamma-glutamyl)lysine crosslink and the catalytic role of transglutaminases.

Abstract: Publisher Summary The production of functional protein units in many cases requires the formation of covalent bonds, and prevalent among these are crosslinks within and between molecules that play a major role in maintaining gross forms of structure and limiting degrees of extensibility. This chapter describes the current knowledge of the distribution, formation, and function of the ɛ-(γ-glutamyl)lysine crosslink, and focuses largely on the crosslink known to be or believed to be formed by the catalytic action of transglutaminases. These enzymes catalyze a calcium-dependent acyl-transfer reaction in which the γ-carboxamide groups of peptide-bound glutamine residues are the acyl donors. Participation of ɛ-amino groups of peptide-bound lysine residues as acyl acceptors yields ɛ-(γ-glutamyl)lysine crosslinks. Although, there is a little doubt that the enzymes described in the chapter are capable of catalyzing crosslink formation, individualities of substrate preference notwithstanding, current data do not prove that this is the biological function of each. The chapter is believed to permit critical evaluation of the information available, suggest areas that hold the greatest opportunity for advances, and will, as a consequence, stimulate further investigations of the synthesis, distribution, and function of the ɛ-(γ-glutamyl)lysine crosslink.

Core Conductor Theory and Cable Properties of Neurons

Abstract: The sections in this article are: 1 Introduction 1.1 Core Conductor Concept 1.2 Perspective 1.3 Comment 1.4 Reviews and Monographs 2 Brief Historical Notes 2.1 Early Electrophysiology 2.2 Electrotonus 2.3 Passive Membrane Electrotonus 2.4 Passive Versus Active Membrane 2.5 Cable Theory 2.6 Core Conductor Concept 2.7 Core Conductor Theory 2.8 Estimation of Membrane Capacitance 2.9 Resting Membrane Resistivitiy 2.10 Passive Cable Parameters of Invertebrate Axons 2.11 Importance of Single Axon Preparations 2.12 Estimation of Parameters for Myelinated Axons 2.13 Space and Voltage Clamp 3 Dendritic Aspects of Neurons 3.1 Axon-Dendrite Contrast 3.2 Microelectrodes in Motoneurons 3.3 Theoretical Neuron Models and Parameters 3.4 Class of Trees Equivalent to Cylinders 3.5 Motoneuron Membrane Resistivity and Dendritic Dominance 3.6 Dendritic Electrotonic Length 3.7 Membrane Potential Transients and Time Constants 3.8 Spatiotemporal Effects with Dendritic Synapses 3.9 Excitatory Postsynaptic Potential Shape Index Loci 3.10 Comments on Extracellular Potentials 3.11 Additional Comments and References 4 Cable Equations Defined 4.1 Usual Cable Equation 4.2 Steady-state Cable Equations 4.3 Augmented Cable Equations 4.4 Comment: Cable Versus Wave Equation 4.5 Modified Cable Equation for Tapering Core 4.6 General Solution of Steady-state Cable Equation 4.7 Basic Transient Solutions of Cable Equation 4.8 Solutions Using Separation of Variables 4.9 Fundamental Solution for Instantaneous Point Charge 5 List of Symbols 6 Assumptions and Derivation of Cable Theory 6.1 One Dimensional in Space 6.2 Intracellular Core Resistance 6.3 Ohm's Law for Core Current 6.4 Conservation of Current 6.5 Relation of Membrane Current to Vi 6.6 Effect of Assuming Extracellular Isopotentiality 6.7 Passive Membrane Model 6.8 Resulting Cable Equation for Simple Case 6.9 Physical Meaning of Cable Equation Terms 6.10 Physical Meaning of τ 6.11 Physical Meaning of λ 6.12 Electrotonic Distance, Length, and Decrement 6.13 Effect of Placing Axon in Oil 6.14 Effect of Applied Current 6.15 Comment on Sign Conventions 6.16 Effect of Synaptic Membrane Conductance 6.17 Effect of Active Membrane Properties 7 Input Resistance and Steady Decrement with Distance 7.1 Note on Correspondence with Experiment 7.2 Cable of Semi-infinite Length 7.3 Comments about R∞, G∞, Core Current, and Input Current 7.4 Doubly Infinite Length 7.5 Case of Voltage Clamps at X1 and X2 7.6 Relations Between Axon Parameters 7.7 Finite Length: Effect of Boundary Condition at X= X1 7.8 Sealed End at X= X1: Case of B1 = 0 7.9 Voltage Clamp(V1 = 0) at X = X1: Case of B1 = ∞ 7.10 Semi-infinite Extension at X = X1: Case of B1 = 1 7.11 Input Conductance for Finite Length General Case 7.12 Branches at X = X1 7.13 Comment on Branching Equivalent to a Cylinder 7.14 Comment on Membrane Injury at X = X1 7.15 Comment on Steady Synaptic Input at X= X1 7.16 Case of Input to One Branch of Dendritic Neuron Model 8 Passive Membrane Potential Transients and Time Constants 8.1 Passive Decay Transients 8.2 Time Constant Ratios and Electrotonic Length 8.3 Effect of Large L and Infinite L 8.4 Transient Response to Applied Current Step, for Finite Length 8.5 Applied Current Step with L Large or Infinite 8.6 Voltage Clamp at X = 0, with Infinite L 8.7 Voltage Clamp with Finite Length 8.8 Transient Response to Current Injected at One Branch of Model 9 Relations Between Neuron Model Parameters 9.1 Input Resistance and Membrane Resistivity 9.2 Dendritic Tree Input Resistance and Membrane Resistivity 9.3 Results for Trees Equivalent to Cylinders 9.4 Result for Neuron Equivalent to Cylinder 9.5 Estimation of Motoneuron Parameters

Liposome-Cell Interaction: Transfer and Intracellular Release of a Trapped Fluorescent Marker

Abstract: When small, unilamellar lipid vesicles containing a high concentration of the fluorescent dye 6-carboxyfluorescein are incubated with either frog retinas or human lymphocytes, fluroescence distributes widely throughout each cell. Since "self-quenching" largely prevents the dye from fluorescing as long as it remains sequestered in vesicles, it is clear that a considerable amount of dye is released from the vesicles and diluted into the much larger volume of the cell.

Peripheral suppression of first pain and central summation of second pain evoked by noxious heat pulses

Abstract: Psychophysical experiments were carried out on 6 huma subjects to determine how first and second pain are influenced by peripheral receptor mechanisms and by central nervous system inhibitory and facilitatory mechanisms. For these experiments, brief natural painful stimuli delivered to the hand were a train of 4-8 constant waveform heat pulses generated by a contact thermode (peak temp. = 51-5% C). The magnitude of first and second pain sensations was estimated using cross-modality matching procedures and reaction times were determined. The latter confirmed the relationship between first and second pain and impulse conduction in Adelta and C noxious heat afferents, respectively. The intensity of first pain decreased with each successive heat pulse when the interpulse interval was 80 sec or less. This decrease was most likely the result of heat induced suppression of Adelta heat nociceptors since it did not occur if the probe location changed between successive heat pulses. In contrast, second pain increased in intensity with each successive heat pulse if the interval was 3 sec or less. This summation was most likely due to central nervous system summation mechanisms since it also occurred after blockage of first pain by ulnar nerve compression and when the location of the thermode changed between heat pulses. These observations and their interpretations are supported by our recording of responses of singlt Adelta heat nociceptive afferents, C polymodal nociceptive afferents, and "warm" afferents of rhsus monkeys to similar trains of noxious heat pulses. Their responses to these heat pulses show a progressive suppression. Furthermore, previous studies have shown that wide dynamic range dorsal horn neurons show summated responses to repeated volleys in C fibers (greater than 1/3 sec). These spinal cord summation mechanisms could account for the summation of second pain.

Echocardiographic assessment of a normal adult aging population.

Abstract: Echocardiograms were performed on 105 male participants in the National Institutes on Aging's volunteer Longitudinal Study Program. All subjects (25--84 years of age) were physically active and had no evidence of hypertension or cardiovascular disease. Measurements were made of the initial diastolic (E-F) slope of the anterior mitral valve leaflet, the aortic and left ventricular cavity dimensions, and the thickness of the posterior left ventricular wall. Fractional shortening of the minor semi-axis of the left ventricle and the velocity of circumferential fiber shortening were also determined. It was found that increasing age correlated with a decrease mitral valve E-F slope and increased aortic root diameter and left ventricular wall thickness. Aging did not affect left ventricular cavity dimension, fractional shortening of the minor semi-axis, and velocity of circumferential fiber shortening. These findings suggest that aging in the normal male is associated with altered left ventricular diastolic filling, increased aortic root diameter and left ventricle hypertrophy but little change in contractile ability in the resting state.

Mouse spinal cord in cell culture. I. Morphology and intrinsic neuronal electrophysiologic properties.

Abstract: 1. Reliable methods for establishing fetal mouse spinal cord (SC) and dorsal root ganglion (DRG) cells in long term (greater than 1 mo) dissociated cell cultures are described. These cells have been studied by morphologic and intracellular electrophysiologic techniques. 2. Cells studied electrophysiologically can be relocated after preparation for electron microscopy and examined in thin sections. The electron microscope shows that the surface membranes of these cells were directly accessible to the culture medium. The surfaces of SC cells were studded with synaptic boutons, whereas the DRG cell surfaces generally had none. 3. Current-voltage relationships and linear electrotonic properties of the neurons are described. Delayed and anomalous rectification were seen in both cell types. The length of SC cell dendrites was about one characteristic electrotonic length, while little or no contribution of the relatively sparse DRG cell processes was seen in the transient responses of the DRG cells. 4. Postspike and posttetanic hyperpolarizations in DRG cells were due to a surface membrane conductance increase; this was probably primarily an increase in K+ conductance. Post-activation hyperpolarization in SC cells was primarily due to activation of an electrogenic Na+ pump.

Analysis of cellular and protein content of broncho-alveolar lavage fluid from patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis.

Abstract: To evaluate cellular and protein components in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (CHP), limited broncho-alveolar lavage was done in 58 patients (19 IPF, 7 CHP, and 32 controls). Analysis of the cells and protein in the lavage fluids from patients with IPF revealed an inflammatory and eosinophilic response and a significant elevation of IgG in the lungs. With corticosteroid therapy, inflammation diminished but eosinophils remained. Lavage fluid from patients with CHP also had eosinophils and elevated levels of IgG. However, in contrast to IPF, lavage fluid from CHP patients contained IgM, fewer inflammatory cells, and a strikingly increased number (38-74%) of lymphocytes. Identification of lavage lymphocytes in CHP showed that T lymphocytes were significantly elevated and B lymphocytes were decreased compared to peripheral blood. These studies suggest nthat the lung in IPF and CHP may function as a relatively independent immune organ, and that analysis of cells and proteins in broncho-alveolar lavage fluid may be of diagnostic, therapeutic, and investigative value in evaluating patients with fibrotic lung disease.

An intricately patterned prefronto-caudate projection in the rhesus monkey

Abstract: The distribution of prefronto-caudate fibers in the caudate nucleus was studied autoradiographically in monkeys of various ages in which tritiated amino acids had been injected into the middle one-third of the length of the dorsal bank of the principal sulcus. The results indicate that, contrary to previous reports which had suggested a projection to only the head of the caudate nucleus, area 9 of Brodmann projects to the entire length of the nucleus. In the head of the caudate nucleus the cortico-caudate fibers are distributed in a pattern which is remarkable in two respects. First, the grains are not uniformly distributed but rather are segregated into clusters separated from one another by territories in which grain density does not exceed background. Second, individual clusters of grains, circular or elliptical in shape, surround grain free cores. These patterns of fiber distribution within the head of the nucleus are more sharply defined in newborn than in older monkeys. Our findings suggest that the caudate nucleus is organized more as an anatomic and functional mosaic than as the homogeneously organized structure that it is commonly considered to be.

Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts

Abstract: Two types of host reactivities not requiring immunization in the mouse and not mediated by T lymphocytes were compared: resistance of irradiated and nonirradiated F1 hybrids to accept parental grafts of normal or malignant hemopoietic cells (Hh system), and the natural killer cell activity against mouse lymphomas (NK system). The effects of six independent variables known to influence resistance to marrow grafts were investigated in the NK system using YAC-1 lymphoma cells as targets. The following properties were shared: (a) maturation during the fourth week of life; (b) low sensitivity to acute total body irradiation; (c) dependence on the integrity of bone marrow as demonstrated by reduced reactivity in 89Sr-treated mice; (d) suppression by a single injection of rabbit anti-mouse bone marrow serum; (e) suppression by a single injection of the anti-macrophage agents silica and i-carrageenan; and (f) suppression by multiple injections of parental spleen cells into F1 mice. These positive correlations are particularly significant because most of the variables have either opposing or no effect on conventional immunity. F1 mice rendered specifically unresponsive to parental marrow grafts, could retain NK cell activity, and genetically susceptible mice could be rendered hyporeactive in terms of NK cells, indicating that the specificities of YAC-1 and Hh-1 incompatible targets were different. It is extremely unlikely that this remarkable parallelism is fortuitous. These results indicate that either a very similar, or more likely a common mechanism is operative in the two cell-mediated natural reactivities: effector cells in the NK and Hh systems do not bear B or T lymphocyte markers but are nevertheless endowed with “specificity”. They are dependent for generation in vivo (presumably by maturation or by recruitment) on the interaction with nonlymphoid accessory cells not endowed with specificity, capable of also interacting in vitro with Thy-1-positive F1 hybrid prekiller cells specific for parental targets. Because of thymus independence in vivo and apparent restriction to target cells of the hemopoietic system, these reactivities should be effective in the regulation of hemopoiesis and surveillance over leukemogenesis.

Virus-Induced Diabetes Mellitus

Abstract: Insulin-dependent diabetes mellitus (IDDM), also known as juvenile diabetes, results from destruction of the insulin-producing beta cells in the pancreas [1]. Both viruses and autoimmunity have been suggested as possible causes. The evidence for viruses comes largely from experiments in animals, but several studies in humans point to viruses as an occasional trigger of this disease.

Electrically gated ionic channels in lipid bilayers.

Abstract: The generation of action potentials in nerve and muscle requires cell membranes with steeply voltage-dependent ionic permeabilities. The voltage-dependent, ion-selective pathways responsible for excitation have been characterized for numerous excitable tissues such as nerve axon, muscle, electric organ, algae and epithelia (Aidley, 1971; Hodgkin, 1964; Cole, 1968). The process of activating ionic pathways by some stimulus, such as a change in membrane potential, is called gating.

Suprachiasmatic nucleus: use of 14C-labeled deoxyglucose uptake as a functional marker.

Abstract: Glucose consumption of the rat suprachiasmatic nuclei (SCN) was studied under various experimental conditions by means of the [14C]deoxyglucose (DG) technique. The results show that glucose consumption of the SCN, in contrast to other brain structures, is a function of both the time of day and environmental lighting conditions. These data are consistent with the hypothesis that the SCN have an essential role in circadian rhythm regulation and indicate that the DG technique may provide a novel approach for the study of the central neural mechanisms underlying circadian rhythm regulation.

Use of Plasma Pharmacokinetics to Predict and Prevent Methotrexate Toxicity

Abstract: To correlate the pharmacokinetics and toxicity of methotrexate, we measured the drug's clearance from plasma after 395 high-dose, six-hour infusions given to 78 patients. After 375 infusions, 48 hour methotrexate levels fell within 2 standard deviations of the mean for nontoxic infusions, and myelosuppression did not occur. Methotrexate concentrations exceeded the range for nontoxic patients (mean +/- 2 standard deviations) after 20 infusions. Serious myelosuppression occurred after six of these 20 infusions, including five of 12 infusions associated with 48-hour drug concentrations above 9 X 10(-7) M. In seven patients with 48-hour concentrations above 9 X 10(-7) M, the absence of toxicity could be attributed to subsequent rapid clearance of the drug; four of these patients also received large doses of supplemental leucovorin (50 to 100 mg per square meter every six hours). Determination of methotrexate concentration in plasma thus identified patients at high risk of toxicity, a group that may benefit from supplemental leucovorin rescue.

Characterization of a new human diploid cell strain, IMR-90.

Abstract: A new human diploid fibroblast-like cell line has been established from lung tissue of a female fetus. This has been frozen away in large quantity and characterized for use in research and related purposes. This is the first of a planned series of human cell lines to be established, characterized, and banked in large quantity in support of the National Institute on Aging research and general cell biology.

Dimeric immunoglobulin E serves as a unit signal for mast cell degranulation.

Abstract: Rat immunoglobulin E (IgE) was treated with a crosslinking reagent, dimethyl suberimidate, and fractionated by gel filtration into monomers, dimers, trimers, and higher polymers The fractions retained substantial ability to bind specifically to mast cells About one-third of the cell-bound dimers appeared to bind bivalently The fractions were assayed in vivo by passive cutaneous anaphylaxis in rats, and for histamine or serotonin release in vitro using normal or tumor mouse mast cells The monomers showed no activity, while the dimers and higher polymers gave excellent and approximately equivalent responses We conclude that IgE that has been crosslinked to form dimers prior to the addition to mast cells can serve as a unit signal for triggering IgE-mediated exocytosis