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Showing papers by "National Institutes of Health published in 1976"


Journal ArticleDOI
TL;DR: A uniform system of classification and nomenclature of the acute leukaemias should permit more accurate recording of the distribution of cases entered into clinical trials, and could provide a reference standard when newly developed cell‐surface markers believed to characterize specific cell types are applied to cases of acuteLeukaemia.
Abstract: A uniform system of classification and nomenclature of the acute leukaemias, at present lacking, should permit more accurate recording of the distribution of cases entered into clinical trials, and could provide a reference standard when newly developed cell-surface markers believed to characterize specific cell types are applied to cases of acute leukaemia. Proposals based on conventional morphological and cytochemical methods are offered following the study of peripheral blood and bone-marrow films from some 200 cases of acute leukaemia by a group of seven French, American and British haematologists. The slides were examined first independently, and then by the group working together. Two groups of acute leukaemia, 'lymphoblastic' and myeloid are further subdivided into three and six groups. Dysmyelopoietic syndromes that may be confused with acute myeloid leukaemia are also considered. Photomicrographs of each of the named conditions are presented.

5,523 citations


Journal ArticleDOI
TL;DR: This paper reviews the most frequently used and misused reliability measures appearing in the mental health literature and suggests some suitable reliability measures to be used.
Abstract: This paper reviews the most frequently used and misused reliability measures appearing in the mental health literature. We illustrate the various types of data sets on which reliability is assessed (i.e., two raters, more than two raters, and varying numbers of raters with dichotomous, polychotomous, and quantitative data). Reliability statistics appropriate for each data format are presented, and their pros and cons illustrated. Inadequancies of some methods are highlighted. The meaning of different levels of reliability obtained with various statistics is discussed. This critique is intended for the reading professional and the investigator who has an occasional need for reliability assessment. Statistical expertise is not required and theoretical material is referenced for the interested reader. Necessary formulas for computations are presented in the appendices. A summary table of some suitable reliability measures is presented.

1,318 citations


Journal ArticleDOI
TL;DR: The A549 cell line should permit in vitro analysis of human surfactant synthesis and secretion and possibly provide a source of human Surfactant for therapeutic intervention in pulmonary disease states characterized by surfactants deficiency.
Abstract: The A549 tumor-cell line, initiated from a human alveolar cell carcinoma, has been continuously propagated in vitro for more than 3 years (more than 1,000 cell generations). These cells have a human karyotype and appear to have been derived from a single parent cell. All A549 cells examined by electron microscopy at both early and late passage levels contain multilamellar cytoplasmic inclusion bodies typical of those found in type II alveolar epithelial cells of the lung. At early and late passage levels, the cells synthesize lecithin with a high percentage of disaturated fatty acids utilizing the cytidine diphosphocholine pathway; such a pattern of phospholipid synthesis is expected for cells believed to be responsible for pulmonary surfactant synthesis. The A549 cell line should permit in vitro analysis of human surfactant synthesis and secretion and possibly provide a source of human surfactant for therapeutic intervention in pulmonary disease states characterized by surfactant deficiency.

1,217 citations


Book ChapterDOI
01 Jan 1976
TL;DR: In all geographic areas it is now clear that RSV is the major cause of bronchiolitis and pneumonia in infants and young children, and there are many pressing questions concerning the pathogenesis of serious life-threatening disease of the lower respiratory tract produced by this virus during early infancy.
Abstract: Respiratory syncytial virus (RSV) was first isolated from a chimpanzee with common-cold-like illness.(53a) Shortly thereafter, the virus was recovered from young children with severe lower respiratory tract disease in Baltimore. (11,16) Since its initial isolation from infants with respiratory disease almost 20 yr ago, RSV has emerged as the major lower respiratory tract pathogen of infancy and early childhood throughout the world. (3,15,16,69) In all geographic areas it is now clear that RSV is the major cause of bronchiolitis and pneumonia in infants and young children. RSV presents a special challenge to the epidemiologist since this virus exhibits a pattern of infection and disease unlike that of any of the other known respiratory tract viral pathogens. Unanswered are many pressing questions concerning the pathogenesis of serious life-threatening disease of the lower respiratory tract produced by this virus during early infancy.

1,161 citations


Journal ArticleDOI
TL;DR: The function provides an economic and efficient method of identifying persons at high cardiovascular risk who need preventive treatment and persons at low risk whoneed not be alarmed about one moderately elevated risk characteristic.
Abstract: Persons at high risk of cardiovascular disease can be effectively identified from a measurement of their serum cholesterol and blood pressure, a smoking history, an electrocardiogram and a determination of glucose intolerance. One general function for identifying persons at high risk of cardiovascular disease is also effective in identifying persons at risk for each of the specific diseases, coronary heart disease, atherothrombotic brain infarction, hypertensive heart disease and intermittent claudication, even though the variables used have a different impact on each particular disease. The 10 percent of persons identified with use of this function as at highest risk accounted for about one fifth of the 8 year incidence of coronary heart disease and about one third of the 8 year incidence of atherothrombotic brain infarction, hypertensive heart disease and intermittent claudication. Hence the function provides an economic and efficient method of identifying persons at high cardiovascular risk who need preventive treatment and persons at low risk who need not be alarmed about one moderately elevated risk characteristic.

1,140 citations


Journal ArticleDOI
TL;DR: The decrease in creatinine clearance with age seen in this study represents true renal aging and is not secondary to diseases which become increasingly prevalent in the elderly.
Abstract: Standard true 24-hour creatinine clearance determinations were performed on 884 subjects of the Baltimore Longitudinal Study. On the basis of clinical data, subjects were placed in categories indicating the presence of specific diseases or medications which might alter glomerular filtration rate. Subjects not included in these categories were considered normal (N=548). In the normals, cross-sectional analysis by 10-year age groups showed a progressive linear decline in clearance from 140 ml/min/1.73m2 at age 30 to 97 at age 80. Three or more serial clearances were obtained at 12- to 18-mo. intervals on 293 normal subjects. These longitudinal data showed an acceleration of the rate of decline in creatinine clearance with advancing age. The decrease in creatinine clearance with age seen in this study represents true renal aging and is not secondary to diseases which become increasingly prevalent in the elderly. A nomogram constructed from these data provides normative age-corrected standards for creatinine clearance.

1,064 citations


Journal Article
TL;DR: One of six lines of human breast cancer maintained in long-term tissue culture for at least 1 year and examined for estrogen responsiveness, MCF-7, shows marked stimulation of macromolecular synthesis and cell division with physiological concentrations of estradiol.
Abstract: We have examined five human breast cancer cell lines in continuous tissue culture for androgen responsiveness One of these cell lines shows a 2- to 4-fold stimulation of thymidine incorporation into DNA, apparent as early as 10 hr following androgen addition to cells incubated in serum-free medium This stimulation is accompanied by an acceleration in cell replication Antiandrogens [cyproterone acetate (6-chloro-17alpha-acetate-1,2alpha-methylene-4,6-pregnadiene-3,20-dione) and R2956 (17beta-hydroxy-2,2,17alpha-trimethoxyestra-4,9,11-triene-1-one)] inhibit both protein and DNA synthesis below control levels and block androgen-mediated stimulation Prolonged incubation (greater than 72 hr) in antiandrogen is lethal The MCF- cell line contains high-affinity receptors for androgenic steroids demonstrable by sucrose density gradients and competitive protein binding analysis By cross-competition studies, androgen receptors are distinguishable from estrogen receptors also found in this cell line Concentrations of steroid that saturate androgen receptor sites in vitro are about 1000 times lower than concentrations that maximally stimulate the cells Changes in quantity and affinity of androgen binding to intact cells at 37 degrees as compared with usual binding techniques using cytosol preparation at 0 degrees do not explain this difference between dissociation of binding and effect However, this difference can be explained by conversion of [3H]-5alpha-dihydrotestosterone to 5alpha-androstanediol and more polar metabolites at 37 degrees An examination of incubation media, cytoplasmic extracts and crude nuclear pellets reveals probable conversion of [3H]testosterone to [3H]-5alpha-dihydrotestosterone Our data provide compelling evidence that some human breast cancer, at least in vitro, may be androgen dependent

919 citations


Journal ArticleDOI
TL;DR: Bartko and Winer as discussed by the authors presented an analysis of variance (ANOVA) intraclass correlation reliability coefficients that avoid some serious deficiencies not uncommonly found in reliability measures.
Abstract: Bartko (1966, 1974) has presented some analysis of variance (ANOVA) intraclass correlation reliability coefficients that avoid some serious deficiencies not uncommonly found in reliability measures. In his second edition, Winer (1971, pp, 289-296) presented some intraclass correlation results which appear to have deficiencies. His so-called "adjustment for anchor points" approach will produce an intraclass correlation reliability coefficient of unity (as expected) for the case in which the judges (raters) agree perfectly about a group of subjects. However, the method will also yield an intraclass correlation of unity for the case in which the judges display a constant additive bias. In general with Winer's approach, any adjustment of original rating data that leaves the rater's variance-covariance matrix unaltered will produce the same intraclass correlation coefficient, and thus numerous variations (of which additive bias is a subset) of the original data set can and will yield the same intraclass correlation. Bias and Unity Reliability As a first illustration on a more elementary level, the phenomenon discussed above can be observed with the product-moment correlation, which is a sometimes used but not recommended measure of reliability. Consider

791 citations


Journal ArticleDOI
26 Nov 1976-Science
TL;DR: Observations are attempted to unify observations and provide a reasonable interpretation of the role of gangliosides in mediating cell surface phenomena to predict that analyogous phenomena involving gangliosisides will be discovered in brain.
Abstract: Gangliosides are unique acidic glycolipids that are selectively concentrated in the plasma membrane of cells. Surface labeling studies have demonstrated that at least a portion of the oligosaccharde chain of gangliosides extends beyond the hydrophe) is imbedded in the membrane bilayer. It is becoming increasingly apparent that gangliosides participate in the internalization of environmental signals elicited by cholera toxin and glycoprotein hormones such as thyrotropic hormone and chorionic gonadotropin as well as other substances such as interferon and possibly serotonin. The mechanism by which cholera toxin binds to a specific ganglioside receptor on the celraction of trophic agents with gangliosides. We would predict that analyogous phenomena involving gangliosides will be discovered in brain. The biosynthesis of gangliosides proceeds by the ordered sequential addition of sugars to the lipid moiety. These reactions are catalyzed by a cluster of membrane-bound glycosyltransferases. Any alteration in the activity or specificity of one of these enzymes will result in a dramatic change in the ganglioside pattern of an afflicted cell or organ. The drastic consequences that accompany abnormalities of ganglioside synthesis have been documented in a heritable metabolic disorder in vivo and in tumorigenic transformation of cells in vitro. In this article, we have attempted to unify these observations and to provide a reasonable interpretation of the role of gangliosides in mediating cell surface phenomena.

719 citations


Journal ArticleDOI
01 Dec 1976-Pain
TL;DR: The intent of this review is to examine and synthesize the extensive progress that has been made in the last few years describing the anatomical, physiological and neurohumoral substrates of neural systems which modulate pain perception.
Abstract: It has long been recognized that there are central nervous system mechanisms that can strikingly alter the perception of noxious stimuli. Indeed, recent theoretical treatments of pain have often given explicit recognition to this notion although little physiological detail has been available to support it [76,78,83]. The intent of this review is to examine and synthesize the extensive progress that has been made in the last few years describing the anatomical, physiological and neurohumoral substrates of neural systems which modulate pain perception. Particular progress has been made in elucidating a neural system which can be activated by electrical stimulation of certain brain stem structures as well as by the narcotic analgesic drugs. For this reason, considerable emphasis will be placed on explaining its mechanisms. However, we will also review some recent evidence showing that other neural systems as well participate importantly in the modulation of pain.

698 citations


Journal ArticleDOI
TL;DR: Biochemical studies suggest that the disease of idiopathic pulmonary fibrosis is probably one of collagen rearrangement rather than collagen increase, and peripheral lymphocytes of these patients recognize collagen as "non-self" and, when exposed to it in vitro, produce lymphokines and cell lysis.
Abstract: Idiopathic pulmonary fibrosis is a fatal disorder that starts as an alveolitis and progresses to interstitial fibrosis. Correlative morphologic, physiologic, and biochemical studies in 29 patients have shown that the inflammatory process in best followed by serial bronchoalveolar lavage and 67 Ga citrate scanning, and the fibrotic process is best followed by quantitation of the exercise-induced drop in arterial oxygen tension per unit of oxygen consumed. Although biopsies in idiopathic pulmonary fibrosis seem to show increased amounts of fibrotic tissue, biochemical studies suggest that the disease is probably one of collagen rearrangement rather than collagen increase. Perhaps becasue of this, peripheral lymphocytes of these patients recognize collagen as "non-self" and, when exposed to it in vitro, produce lymphokines and cell lysis. The fibrotic process is probably irreversible, but the inflammatory and immune processes that cause it may be amenable to therapy if diagnosed early.

Journal ArticleDOI
08 Oct 1976-Science
TL;DR: Comparison of dendritic field diameters and receptive fiedl center sizes of large ganglion cells suggests that neural circuitry in sublamina a conveys "OFF"-center properties and connections insublamina b "ON"- center properties to retinal ganglions.
Abstract: The inner plexiform layer of the mammalian retina has a bisublaminar organization determined by restricted branching of the terminals of cone bipolar cells and dendrites of class I (large) and class II (small) ganglion cells. Comparison of dendritic field diameters and receptive fiedl center sizes of large ganglion cells suggests that neural circuitry in sublamina a conveys "OFF"-center properties and connections in sublamina b "ON"-center properties to retinal ganglion cells.

Journal ArticleDOI
TL;DR: Levels of norepinephrine in human plasma have been determined by a radioenzymatic technique sufficiently sensitive to measure 0.014 ng NE per ml plasma by evaluating sympathetic neuronal function based on the increments in plasma NE produced by postural change and a standard amount of exertion.

Journal ArticleDOI
TL;DR: Hereditary angioedema is manifested by attacks of swelling of the extremities, face, trunk, airway, or abdominal viscera, occurring spontaneously or secondary to trauma.
Abstract: Hereditary angioedema is manifested by attacks of swelling of the extremities, face, trunk, airway, or abdominal viscera, occurring spontaneously or secondary to trauma. It is inherited as an autosomal dominant trait and is due to deficient activity of the inhibitor of the activated first component of complement. The clinical diagnosis can be confirmed by the findings of low levels of C4 or C1 esterase inhibitor activity, or both. Therapy may be divided into three phases: long-term prophylaxis of attacks, short-term prophylaxis of attacks, and treatment of acute attacks. Long-term prophylaxis may be achieved with antifibrinolytic agents and androgens. Short-term prophylaxis with these agents and plasma transfusions has been successful. Specific therapy for acute attacks is not available, but good supportive care, together with a knowledge of the course of the disease, can prevent asphyxiation from airway obstruction. Before the advent of therapy, mortality was reported as high as 30%.

Journal ArticleDOI
TL;DR: In this article, the brain behavior of gerbils subjected to unilateral occlusion of the common carotid artery was studied and it was found that there was a progressive decrease in norepinephrine and dopamine, and an increase in serotonin throughout the duration of an ischemic insult.
Abstract: Behaviour of biogenic amines was studied in the brains of Mongolian gerbils subjected to unilateral occlusion of the common carotid artery. Assays on the hemispheres ipsilateral to occlusion revealed in symptom-positive animals a progressive decrease in norepinephrine and dopamine, and an increase in serotonin throughout the duration of an ischemic insult. In post-ischemic periods following the release of the clip, changes in biogenic amine levels generally conformed to the principles of a previously described “maturation” phenomenon, with delayed reactions occurring after the shorter ischemic insults.

Journal ArticleDOI
19 Feb 1976-Nature
TL;DR: A general method for measuring forces between planar phospho-lipid membranes is devised, and results for the specific case of egg lecithin (phosphatidyl choline) bilayers in water are reported.
Abstract: CELL fusion1 and vesicle-membrane2 or vesicle-synapse3 fusion are currently thought to involve distance-dependent interactions between membranes. We have devised a general method for measuring such forces between planar phospho-lipid membranes, and report here results for the specific case of egg lecithin (phosphatidyl choline) bilayers in water.

Journal ArticleDOI
TL;DR: Autonomic preganglionic, sensory, and lower motoneuron perikarya within the central nervous system, as well as cell bodies with axons projecting to the circumventricular organs, are retrogradely labeled with horseradish peroxidase (HRP) delivered to their axon terminals by cerebral and extracerebral blood.
Abstract: Autonomic preganglionic, sensory, and lower motoneuron perikarya within the central nervous system, as well as cell bodies with axons projecting to the circumventricular organs, are retrogradely labeled with horseradish peroxidase (HRP) delivered to their axon terminals by cerebral and extracerebral blood. Subsequent to vascular injection of HRP into mice, blood-borne peroxidase passes across permeable vessels in muscle, ganglia, and in all circumventricular organs except for the subcommissural organ in which no leak could be discerned. Brain parenchyma adjacent to each of the permeable circumventricular organs quickly becomes inundated with the protein. By four to six hours post-injection, this extracellular HRP reaction product has disappeared, and by eight hours perikarya of specific hypothalamic nuclei contain HRP-positive granules indicative of the intra-axonal retrograde transport of the protein. Hypothalamic neurons so labeled are presumed to send axons to such circumventricular organs as the median eminence or neurohypophysis and include neurons of the magnocellular neurosecretory supraoptic and paraventricular nuclei, the accessory magnocellular nuclei, the parvicellular arcuate nucleus, and a band of periventricular cells extending rostrally into the medial preoptic area. Labeled somata are also adjacent to the organum vasculosum of the lamina terminalis and in the vertical limb of the nucleus of the diagonal band of Broca. No similarly labeled cell bodies were identified near the subfornical organ. At 12 hours post-injection, HRP labeling of specific brain stem and spinal cord somata with axons efferent from the central nervous system indicates that protein from the peripheral blood can be incorporated by neurons of different functional categories for retrograde transport. Thus, blood-borne peroxidase, imbibed presumably from myoneural clefts by motoneuron axon terminals, is transported to perikarya in cranial motor nerve nuclei III, IV, V, VI, VII, XII, the ambiguus nucleus, and in the ventral horn of the spinal cord. Sensory endings afferent to muscle spindles also take up HRP for retrograde transport, as manifested by the labeling of cell bodies in the mesencephalic nucleus of V. Autonomic preganglionic terminals take up HRP for transport back to their cell bodies in the intermediolateral sympathetic cell column in the spinal cord and to parasympathetic cell groups such as the brain stem dorsal motor vagus and salivatory nuclei. Three cell groups in the brain stem that presumably have their efferent projections intrinsic to the central nervous system contain peroxidase-labeled perikarya. These cell groups include a portion of the nucleus of the solitary tract rostral to the area postrema and the noradrenergic A1 and A5 nuclei of Dahlstrom and Fuxe ('64). The area postrema is thought to receive axon collaterals from the nucleus of the solitary tract (Morest, '60). Of the circumventricular organs, only the median eminence is believed to have a prominent noradrenergic innervation originating from somewhere in the brainstem. The peroxidase-labeled A1 and A5 neurons may represent the origin of this innervation. Vascular infusion of peroxidase results in retrograde neuronal labeling of neurosecretory, motor, sensory, and autonomic systems. The inference is made that other substances, such as toxins and neurovirulent viruses, can also enter these neuronal systems, as does peroxidase, from cerebral and extracerebral blood.

Journal ArticleDOI
TL;DR: The clinical spectrum of isoniazid-induced liver injury seems to be clinically, biochemically, and histologically indistinguishable from viral hepatitis, except that the injury occurs primarily in persons older than 35 years, and a possible relation between susceptibility of patients to isoniaZid liver injury and rapid metabolism (acetylation) of the drug has been found.
Abstract: The clinical spectrum of isoniazid-induced liver injury seems to be clinically, biochemically, and histologically indistinguishable from viral hepatitis, except that the injury occurs primarily in persons older than 35 years. A possible relation between susceptibility of patients to isoniazid liver injury and rapid metabolism (acetylation) of the drug has been found. Examination of isoniazid metabolites showed that patients with rapid acetylator phenotype hydrolyze much more isoniazid to isonicotinic acid and the free hydrazine moiety than do slow acetylators. The hydrazine moiety liberated from isoniazid is primarily acetylhydrazine, and studies in animals show this metabolite to be converted to a potent acylating agent that produces liver necrosis. It seems likely that formation of chemically reactive metabolites is also the biochemical event initiating isoniazid liver injury in man. Recognition of the seriousness of isoniazid hepatic injury, not readily accepted at first, has led to revisions in the uses of isoniazid prophylaxis.

Journal ArticleDOI
27 May 1976-Nature
TL;DR: Extending the study to teenage and elderly subjects revealed that basal levels of plasma NA correlate with age and that the increase in plasma NA in response to stress is similarly related to age.
Abstract: WE measured plasma noradrenaline (NA) levels in about 20 individuals who were to serve as normal control subjects and noted that older subjects tended to have higher NA levels. Extending the study to teenage and elderly subjects revealed that basal levels of plasma NA correlate with age and that the increase in plasma NA in response to stress is similarly related to age. There is considerable evidence that sensitivity to NA and NA metabolism change with increasing age. In rabbits and cats the threshold for cardiovascular response to low levels of NA decreases with old age1. In ageing rats uptake of NA into the heart is greater than in young animals2 and there is a diminished inotropic response of aged rat myocardium to a fixed concentration of NA (ref. 3). Cardiac monoamine oxidase activity increases severalfold during the life span of a rat while dopa decarboxylase decreases during the first year2. In man, propranalol, which blocks β-adrenergic receptors, reduces heart rate and cardiac output during exercise, but this effect is considerably smaller in older subjects4. The response of heart rate to hypoxia and hypercapnia is attenuated in older men5.

Journal ArticleDOI
TL;DR: No major innovations are required to identify candidates for coronary disease and to estimate their risk, but there is much to learn about motivating changes in behavior to control risk factors.
Abstract: Epidemiologic investigations have provided a portrait of the potential candidate for coronary heart disease. This is important because studies of the evolution of coronary disease in the general population reveal that it is a common disease that frequently attacks without warning, can be silent in its most dangerous form and can present with sudden death as the first symptom. Progress in identifyin- persons in jeopardy and the factors needing correction makes it theoretically possible to interrupt the chain of factors that eventuate in this disease. Coronary disease does not really begin with crushing chest pain, pulmonary edema, shock, angina or ventricular fibrillation, but rather with more subtle signs like a poor coronary risk profile. The risk factors can be treated quantitatively as ingredients of a cardiovascular risk profile and their joint effect estimated. An efficient practicable set of variables for this purpose is a casual blood test for cholesterol and sugar, a blood pressure determination, an electrocardiogram and a cigarette smoking history. With this set of variables the risk of coronary heart diseases can be estimated over a 30-fold range and 10 percent of the asymptomatic population identified in whom 25 percent of the coronary disease, 40 percent of the occlusive peripheral arterial disease and 50 percent of the strokes and congestive heart failure will evolve. The periodic use of the electrocardiogram at rest and after exercise in persons with a poor risk profile can demonstrate persons with asymptomatic ischemic cardiomyopathy due to advanced coronary artery disease. Most cases of angina pectoris or myocardial infarction represent medical failures; the conditions should have been detected years earlier for preventive management. About 30 percent of patients with infraction will shortly experience new angina, have an annual death rate of 4 percent and a fourfold increased risk of sudden death. Reinfarction will occur at an annual rate of 6 percent, and half the recurrences will be fatal. Congestive heart failure must be expected at 10 times and strokes at 5 times the rate found in the general population. Although no major innovations are required to identify candidates for coronary disease and to estimate their risk, we have much to learn about motivating changes in behavior to control risk factors. Approaches to prevention of coronary heart disease include public health measures to alter the ecology in favor of cardiovascular health, preventive medicine directed at highly vulnerable candidates and hygienic measures initiated by an informed public in its own behalf.

Journal ArticleDOI
TL;DR: Three strains of miniature swine, each homozygous for a different allele of the major histocompatibility locus (MHC), have been developed by a selective breeding scheme based on tissue typing of the offspring of each generation, confirming the homology between the MHC of these miniature Swine and those of man and mouse.
Abstract: Three strains of miniature swine, each homozygous for a different allele of the major histocompatibility locus (MHC), have been developed by a selective breeding scheme based on tissue typing of the offspring of each generation. Prior to breeding, the original parents were reciprocally immunized by skin grafts and lymphocyte injections to produce lymphocytotoxic antisera. These antisera were then used to assess the MHC genotype of the offspring by an analysis based on selective absorption of cytotoxicity. Offspring inheriting the same serologically determined genotype were then bred sequentially. Subsequent mixed lymphocyte cultures showed a pattern of reactivity consistent with the serological genotyping, further confirming the homology between the MHC of these miniature swine and those of man and mouse. In addition to their usefulness as a model for large animal surgical transplantation, these animals provide an abundant homozygous source of histocompatibility antigens and of antihistocompatibility antisera for use in chemical characterization of products of the MHC.

Journal ArticleDOI
22 Apr 1976-Nature
TL;DR: It is reported for the first time that repetitive cocaine administration can be associated with progressively increasing effects on horizontal and vertical hyperactivity as well as stereotypy in the rat.
Abstract: REPORTS of chronic cocaine (and related psychomotor stimulant) administration suggest that tolerance develops to many drug effects1–3. A few studies of high dose cocaine administration have suggested that, on the contrary, repetitive administration may be associated with increasing effects on cocaine-induced convulsions in the rat4,5 and monkey6 and increasing bizarre visual and inhibitory behaviour, as well as dyskinesias, in the monkey6. We now report for the first time that repetitive cocaine administration can be associated with progressively increasing effects on horizontal and vertical hyperactivity as well as stereotypy in the rat.

Journal ArticleDOI
TL;DR: Two heat-stable and trypsin-labile inhibitors of phosphorylase phosphatase, designated inhibitor-1 and inhibitor-2, were partially purified from extracts of rabbit skeletal muscle by heating and coloumn chromatography using DEAE-dellulose and Bio-gel P-60.
Abstract: Two heat-stable and trypsin-labile inhibitors of phosphorylase phosphatase, designated inhibitor-1 and inhibitor-2, were partially purified from extracts of rabbit skeletal muscle by heating and coloumn chromatography using DEAE-dellulose and Bio-gel P-60. Inhibitor-1 exists in an active phosphorylated form and an inactive dephosphorylated form. The interconversion of phosphorylated inhibitor-1 and dephosphorylated inhibitor-1 is mediated by protein kinase dependent on adenosine 3':5'-monophosphate (cyclic AMP) and a Mn2+-stimulated phosphoprotein phosphatase. Inhibitory activity of inhibitor-2 is not influenced by treatment with either the kinase or the Mn2+-stimulated phosphatase. The molecular weights of inhibitor-1 and inhibitor-2 estimated by sodium dodecylsulfate-polyacrylamide gel electrophoresis are 26000 and 33000 respectively. Both inhibitor-1 and inhibitor-2 inhibit phosphorylase phosphatase by a mechanism which appears to be non-competitive with respect to the substrate phosphorylase a. Inhibitor fractions at early stages of purification also inhibit cyclic-AMP-dependent histone phosphorylation, but this kinase inhibitory activity resides with a protein moiety which is separable from inhibitor-1 and inhibitor-2.

Journal ArticleDOI
TL;DR: Using a sensitive radioimmunoassay, the level of substance P is higher in the mesencephalon, hypothalamus and preoptic area than in other regions of the brain and is found in especially high concentrations in the reticular part of the substantia nigra and the interpeduncular nucleus.

Journal Article
TL;DR: It is proposed that two distinct signals are required to activate this T lymphocyte subpopulation, one signal is delivered by the interaction of the mitogen with the T cell surface, and the second signal is delivery by a soluble factor(s) produced by macrophages.
Abstract: A T lymphocyte subpopulation that contains only 0.3% macropages and less than 2% B lymphocytes has been prepared from guinea pig lymph node cells by the use of two different types of adherence columns. This subpopulation does not proliferate in response to the mitogens Con A or PHA unless additional macrophages are added. The means by which macrophages restore T cell responsiveness to PHA has been investigated. Macrophages appear to function via two distinct mechanisms in this experimental situation. The first mechanism involves the binding of PHA to the macrophage followed by the “presentation” of the mitogen to the T lymphocyte in a manner that induces cell activation. This presentation function requires that the macrophage be viable and metabolicially active. The second mechanism by which macrophages function is by the elaboration of a soluble factor or factors. The presence of these factors has been reliably and reproducibly demonstrated by using a double-chambered, Marbrook-type tissue culture vessel. This soluble factor can induce activation of T lymphocytes with surface bound PHA in the apparent absence of any form of macrophage presentation. In contrast, the function of this factor is clearly distinct from that of the reducing agent, 2-mercaptoethanol, (2-ME) since 2-ME does not enable this T cell subpopulation to be activated by mitogens. On the basis of these observations, we propose that two distinct signals are required to activate this T lymphocyte subpopulation. One signal is delivered by the interaction of the mitogen with the T cell surface, and the second singal is delivered by a soluble factor(s) produced by macrophages. Whether all types of T lymphocytes require two signals to be activated, remains to be established.

Journal ArticleDOI
TL;DR: Women being treated with hydantoin anticonvulsants should be told of the nature and magnitude of risks to the developing fetus before considering a pregnancy.

Journal ArticleDOI
TL;DR: Isometric responses of individual gastrocnemius muscle units of both fast (F) and slow (S) twitch type were studied during repetitive intracellular stimulation of the innervating motoneurons in anesthetized cats to represent a disenhancement process intrinsic to muscle unit fibers activated in unfused tetani.

Journal ArticleDOI
TL;DR: Turbidometric measurements of the kinetics of filament assembly revealed a biphasic mechanism, involving the initial rate-limiting formation of a hexamer nuclear particle followed by a more rapid rate of polymerization to filaments.

Journal ArticleDOI
04 Nov 1976-Nature
TL;DR: The results suggest that a produce of the Sarcoma virus genome specifically changes cell EGF receptors; the sarcoma gene product may, then, be functionally related to EGF.
Abstract: Normal cells in culture have membrane receptors for epidermal growth factor (EGF); EGF stimulates cells to divide by binding to these receptors. Cells transformed by murine and feline sarcoma viruses rapidly lose the ability to bind EGF, whereas cells transformed by the DNA tumour viruses, polyoma and SV40, or infected with non-transforming RNA tumour viruses have normal levels of functional EGF receptors. The results suggest that a produce of the sarcoma virus genome specifically changes cell EGF receptors; the sarcoma gene product may, then, be functionally related to EGF.

Journal ArticleDOI
13 Feb 1976-Science
TL;DR: An array of alternating anion and cation exchange membranes can be used to generate electric power from the free energy of mixing of river and sea waters, and a simple mathematical model is useful in exploring conditions for optimization.
Abstract: An array of alternating anion and cation exchange membranes can be used to generate electric power from the free energy of mixing of river and sea waters. A simple mathematical model, which predicts experimental results well, is useful in exploring conditions for optimization of the process. Major, but not impossible, improvements in technology would be required to bring the cost of power from the dialytic battery into line with foreseeable energy prices.