Showing papers by "National Institutes of Health published in 1978"

Memory in monkeys severely impaired by combined but not by separate removal of amygdala and hippocampus

Abstract: THE profound anterograde amnesia that has been attributed in the clinical literature to damage of the hippocampal system1,2 has not been observed in animals with such damage. Hippocampal-system lesions in animals do markedly impair some forms of spatial memory3,4, but the effects on other forms of memory have generally seemed minor5,6 compared with the dramatic disorder described in man7,8. This discrepancy between the clinical and animal literature could indicate a true evolutionary shift in the functions of the hippocampus9,10, or, at the other extreme, it could simply reflect the use of incommensurate measures across species11,12. (Strong support for this second interpretation has been provided by Gaffan13.) A third possibility, however, is that the discrepancy points to inaccurate localisation of the neuropathology in man that is responsible for the profound amnesia. Support for this last alternative comes from new evidence in monkeys indicating that a striking impairment in visual memory can be produced by the combined ablation of the hippocampal formation and the amygdaloid body, but not by ablation of either of these structures alone.

The Spectrum of Vasculitis: Clinical, Pathologic, Immunologic, and Therapeutic Considerations

Abstract: Vasculitis is a clinicopathologic process characterized by inflammation and necrosis of blood vessels. Certain disorders have vasculitis as the predominant and most obvious manifestation, whereas others have various degrees of vasculitis in association with other primary disorders. Within the entire spectrum of vasculitis virtually any size or type of blood vessel in any organ system can be involved. Most of the vasculitides can be associated directly or indirectly with immunopathogenic mechanisms. In this regard, immune complex mediation is being increasingly recognized as the underlying mechanism in several of the vasculitides. With clinical, pathologic, and immunologic criteria, certain vasculitic disorders can be clearly recognized and categorized as distinct entities, whereas in others there is an overlap of different diseases within a broader category. In recent years, several of the more serious vasculitides, such as Wegener's granulomatosis and the systemic necrotizing vasculitides of the polyarteritis nodosa group, which formerly had extremely poor prognoses, have been shown to be extraordinarily responsive to chronic low-dose cytotoxic therapy, particularly cyclophosphamide.

Insulin receptors are widely distributed in the central nervous system of the rat.

Abstract: WHILE insulin can affect the function of the central nervous system (CNS) by producing hypoglycaemia, there is substantial evidence suggesting that insulin can also act directly on cells of the CNS to modify their function1–4. In a study of the phylogeny of the insulin receptor, Posner5 reported specific binding of 125I-insulin to membrane preparations from whole brain of rat, monkey and pigeon. Specific receptors for insulin have been detected in the hypothalamus of monkeys but not in the cerebral cortex or thalamus6; other regions of the CNS were not studied. We report here the presence of substantial concentrations of insulin receptors in discrete regions of the CNS of the rat. We detected specific binding of insulin in every area studied, although it differed by as much as five- to 10-fold among regions. The insulin receptor of the cerebral cortex was most extensively characterised, and by all criteria it was indistinguishable from the insulin receptor on classical target tissues (liver, muscle and fat) as well as other cells of humans, rodents7–10, and other mammals and non-mammalian vertebrates.

Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights.

Abstract: More than 20,000 autopsy reports from several general hospitals were surveyed for the purpose of selecting brains without a pathological lesion that had been weighed in the fresh condition. From this number, 2,773 males and 1,963 females were chosen for whom body weight, body height, and cause of death had been recorded. The data were segregated into 23 age groups ranging from birth to 86+ years and subjected to statistical evaluation. Overall, the brain weights in males were greater than in females by 9.8%. The largest increases in brain weights in both sexes occurred during the first 3 years of life, when the value quadruples over that at birth, while during the subsequent 15 years the brain weight barely quintuples over that at birth. Progressive decline in brain weight begins at about 45 to 50 years of age and reaches its lowest values after age 86 years, by which time the mean brain weight has decreased by about 11% relative to the maximum brain weight attained in young adults (about 19 years of age). Computed regression lines for brain weights versus body heights and body weights and for ratios of brain weights to body heights and weights versus age groups show clearly differential rates of change in brain weights which are less affected by sex.

Design of liposomes for enhanced local release of drugs by hyperthermia

Abstract: Liposomes can be designed to release an entrapped drug preferentially at temperatures attainable by mild local hyperthermia. In a test system in vitro, protein synthesis by Escherichia coli is inhibited and killing of the cells is enhanced by heating neomycin-containing liposomes to their phase transition temperature to maximize drug release. In the presence of serum the ratio of release at 44 degrees C to that at 37 degrees C can be made greater than 100:1, suggesting possible applications in the treatment of tumors or local infection.

Estimating prevalence from the results of a screening test

Abstract: This paper deals with some basis properties of screening tests. Such tests purport to separate people with disease from people without. Minimal criteria for such a process to be a test are discussed. Various ways of judging the goodness of a test are examined. A common use of tests is to estimate prevalence of disease; frequency of positive tests is shown to be a bad estimate, and the necessary adjustmants are given.

Tumor heterogeneity and the biology of cancer invasion and metastasis.

Abstract: The development of a metastasis is dependent on an interplay between host factors and intrinsic characteristics of malignant tumor cells. The process of metastasis is highly selective, and the metastatic lesion represents the end point of many destructive events that only a few cells can survive. Neoplasms, which are predominantly heterogeneous, contain a variety of subpopulations of cells with differing metastatic potential. Furthermore, metastatic cell variants have been shown to preexist in murine neoplasms of old and recent origin. The possible existence of highly metastatic variant cells within a primary tumor suggests that we no longer should consider a neoplasm to be a uniform entity. Efforts to design effective therapeutic agents and procedures against malignant tumors should be directed toward the few but fatal metastatic subpopulations of cells.

The de facto US mental health services system: a public health perspective.

Abstract: • The President's Commission on Mental Health has highlighted a heretofore unmet need for the linkage of data on the prevalence of mental disorder with national data on the use of mental health services. This study analyzes available epidemiological data and recent mental health services research findings to estimate the percent of the population with a mental disorder and the proportion utilizing various types of specialty mental health and general medical treatment settings. Provisional estimates indicate that at least 15% of the US population is affected by mental disorders in one year. In 1975, only one fifth of these were served in the specialty mental health sector, with about three fifths identified in the general medical (primary care) sector.

Antiepileptic drug development: II. Anticonvulsant drug screening.

Abstract: ummary By means of the maximal electroshock seizure (MES) test, the subcutaneous pentylenetetrazol (PTZ) seizure threshold test, and the Rotorod minimal neurotoxicity test, the Anticonvulsant Screening Project has evaluated the activity of 1,495 experimental compounds accessioned in the first 2 years. A three-screen protocol for appraising these compounds has proved reliable, fast, and inexpensive. Preliminary data show that 430 of these compounds have good anticonvulsant activity. Completed evaluations of 352 identified 16 that have anticonvulsant activity at doses less than 75 mg/kg and protective indices greater than 5.0. RESUME El Proyecto de Seleccion de Anticonvulsivos ha valorado la actividad de 1,495 compuestos que han aparecido en los liltimos 2 anos mediante el test de electroshock maximo, el test de determinacion de umbral epileptico con la inyeccion subcutanea de pentilentetrazol y el test de Rotorod de minima neuro-toxicidad. Un protocolo de tres selecciones para valorar estos compuestos ha demostrado ser fiable, rapido y economico. Los resultados preliminares muestran que 430 de estos compuestos tienen buena actividad anticonvulsiva. Evaluaciones completas de 352 productos identificaron 16 que poseen actividad antiepileptica a dosis menores de 75 mg/kg e indice protectores mayores de 5.0. RESUMEN Le programme de depistage des medicaments anti-epileptiques (anticonvulsant screening project), base sur les deux tests des crises provoqudes chez l'animal par l'electrochoc et l'injection sous-cutanee de pentylenetetrazol et sur le test Rotorod de neurotoxicity minimale, a permis d'evaluer les propriety antiepileptiques de 1,495 produits experimentes pendant les deux premieres annees de son activite. Le protocole operatoire a trois niveaux ainsi utilise s'est avere sur, rapide et economique. Les donnees prdliminaires montrent que 430 de ces produits ont une bonne propridte anticonvulsive. Une Evaluation plus complete de 352 de ces produits a permis d'en identifier 16 qui presentent une propriete anticonvulsive a des doses inferieures a 75 mg/kg et qui possedent un indice de protection supdrieur a 5.0. ZUSAMMENFASSUNG Mit Hilfe des maximalen Elektroshock-Tests, des subkutanen Pentylentetrazol-Krampfschwellentests und des Rotorod minimalen Neurotoxizitats-Test wurden im Antikonvulsiva-Screening-Projekt in den ersten 2 Jahren die Aktivitat von 1,495 eingereichten Substanzen experimentell untersucht. Ein Drei-Raster-Protokoll zur Einschatzung dieser Substanzen wurde als durchfilhrbar, schnell und billig befunden. Die vorlaufigen Ergebnisse zeigen, das 430 dieser Substanzen gute antikonvulsive Wirkung haben. Die endgultige Beurteilung ergab, das 16 von 352 Substanzen eine antikonvulsive Wirkung bei Dosen unter 75 mg/kg und einen Schutzindex tiber 5.0 besitzen.

The biology of cancer invasion and metastasis.

Abstract: Publisher Summary This chapter summarizes the findings and hypotheses of cancer metastasis and elucidates the complex mechanisms involved in the pathogenesis of metastasis. The development of a metastasis is dependent on the interplay of host and tumor cell properties. The process is complex, highly selective, and represents the end stage of several destructive events from which few tumor cells survive. Malignant neoplasms may consist of a variety of subpopulations of cells with differing capabilities for invasion and metastasis. Only a few tumor cells within a primary neoplasm may actually invade blood vessels, and of those, even fewer survive in the circulation. The unique characteristics of tumor cells, including modifications in cell surface properties, adhesive capacities, cell motility, and enzyme secretion, are of paramount importance in determining the eventual outcome of the metastasis. Such acquired properties of malignant cells allow for interaction with host tissues and cells, which leads to tumor cell survival and growth. Three mechanisms are invoked to explain tumor cell invasion—(1) the rapid multiplication of malignant cells leading to growth and infiltration by mechanical pressure, (2) the destruction of host tissue by the products of the tumor cell, and (3) the lack of tumor cell adhesiveness accompanied by an increase in the cell motility.

Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells

Abstract: NEURONE-SPECIFIC ENOLASE (NSE) is the most acidic brain isoenzyme of the glycolytic enzyme enolase (EC4.2.1.11) and has been shown to be homologous to the 14-3-2 protein isolated from bovine brain by Moore1–3. Whereas NSE is exclusively localised in neurones in mammalian nervous tissue4,5, another brain enolase isoenzyme termed non-neuronal enolase (NNE) is localised in glial elements5. As NSE and NNE are structurally, functionally and immunologically distinct isoenzymes that represent separate gene products6,7, they are useful markers for cell classes in the nervous system. Although NNE is probably identical to liver enolase, NSE has to date been considered to be localised in neurones. We now report that NSE is also present in peripheral and central neuroendocrine cells, also termed amine precursor uptake and decarboxylation (APUD) cells8–10. Immunocytochemistry using the unlabelled antibody enzyme method of Sternberger11 demonstrates that APUD cells in both laboratory rat and rhesus monkey (Macacca mulatta) stain positively with NSE antiserum. Using a sensitive radioimmunoassay (RIA) for NSE, it is possible to confirm their localisation in adrenal gland and to support the finding in other APUD-cell-containing tissues in rat, monkey and man. The results in human tissues suggest that the immunocytochemical localisation in rat and monkey will be valid for man and prove useful in the study of human diseases involving the APUD cell class.

Prognosis in Children With Febrile Seizures

Abstract: Febrile seizures occurred in 3.5% of white and 4.2% of black children who were followed up in a large prospectively defined cohort. The frequency of adverse outcomes was examined in this population and risk factors were identified. Among 1,706 children with febrile seizures, no deaths or persistent motor deficits occurred as sequelae of seizures. Todd9s paresis occurred in 0.4%. Risk factors identified for epilepsy after febrile seizures were family history of afebrile seizures, preexisting neurological abnormality, and complicated initial seizure. Of the 60% of children with febrile seizures who had none of these factors, 1% developed epilepsy by age 7 years. A single risk factor was present in 34%, of whom 2% developed epilepsy. Of the 6% with two or more of these factors, 10% developed epilepsy. After an initial brief febrile seizure, 1.4% experienced a subsequent attack which lasted 30 minutes or longer; none of these children had an afebrile seizure by the age of 7 years. Febrile seizures were associated with an increased risk of intellectual deficit only among children with preexisting neurological or developmental abnormality, and in those who developed subsequent afebrile seizures. A third of the children with febrile seizures had a recurrence, and 9% had three or more recurrences. The major predictor of recurrence was early age at onset.

Ratio scales of sensory and affective verbal pain descriptors

Abstract: The results of two experiments show that ratio scales of sensory and affective verbal pain descriptors are valid, reliable and objective. In the first experiment, 16 subjects rated 15 sensory and 15 affective verbal pain descriptors by numerical magnitude estimation and by cross-modality matching to handgrip force. Ratio scales of sensory and affective verbal pain descriptors computed for two separate groups were highly correlated between the groups (sensory, r = 0.97; affective, r = 0.98), as well as over session (r = 0.99, 0.98). Scales based on an individual's data correlated equally with either another set of scales from the same individual (r = 0.96, 0.98) or a mean scale from a similar group (r = 0.96, 0.89). Sensory and affective verbal descriptor scales from the first experiment correlated highly (r = 0.99, 0.99) with those from the second experiment in which 40 subjects rated verbal pain descriptors by cross-modality matching to time duration and to handgrip force. The ratio responses to the verbal descriptors in both experiments demonstrated specific functional relationships found for measurable psychophysical stimuli. This result supports the validity of cross-modality matched ratio scales of verbal stimuli. The reliability of these scales is shown by the high between-session, between-group and between-experiment correlations. The objectivity is shown by the similarity of within-subject and between-subject correlations for both group and individual descriptor scales.

The Reciprocal Effects of the Substantive Complexity of Work and Intellectual Flexibility: A Longitudinal Assessment

Abstract: Our previous research, based on cross-sectional data, provided prima facie evidence of a reciprocal relationship between the substantive complexity of men's work and their intellectual flexibility. The present study employs longitudinal data to make a more definitive assessment. Using maximum-likelihood confirmatory factor analysis to separate measurement error from real change, it develops measurement models for both substantive complexity and intellectual flexibility. These models show that, over a 10-year time span, the "stability" of both variables, shorn of measurement error, is high, that of intellectual flexibility especially so. Nevertheless, a structural equation causal analysis demonstrates that the effect of the substantive complexity of work on intellectual flexibility is real and remarkably strong-on the order of one-fourth as great as the effect of men's earlier levels of intellectual flexibility on their present intellectual flexibility. The reciprocal effect of intellectual flexibility on substantive complexity is even more pronounced. This effect, however, is not contemporaneous but, rather, a lagged effect occurring more gradually over time.

Brain endolases as specific markers of neuronal and glial cells

Abstract: There are three distinct enolase isoenzymes in brain; neuron-specific enolase (NSE), formerly referred to as neuron-specific protein, which is specifically localized in neurons, a nonneuronal enolase (NNE), and a third hybrid form. Light microscopy with immunocytochemical techniques has permitted localization of non-neuronal enolase. The NNE is located in glial cells with no staining of endothelial cells or neurons. Thus, NSE and NNE can be used as specific metabolic markers for neurons and glial cells, respectively.

Right ventricular infarction complicating left ventricular infarction secondary to coronary heart disease. Frequency, location, associated findings and significance from analysis of 236 necropsy patients with acute or healed myocardial infarction.

Abstract: Right ventricular infarction associated with left ventricular infarction was identified by gross examination at necropsy in 33 (14 percent) of 236 patients with transmural myocardial infarction. Right ventricular infarction occurred exclusively as a complication of posterior left ventricular infarction. Associated right ventricular infarction occurred in none of the 97 patients with isolated anterior wall infarction of the left ventricle, but in 33 (24 percent) of the 139 patients with posterior left ventricular infarction. Transmural infarction of the posterior ventricular septum was an additional prerequisite for right ventricular infarction. Of the 139 patients with infarction of the posterior left ventricular wall, 74 had no transmural infarction of the ventricular septum and none of these 74 had associated right ventricular infarction. In contrast, of the 65 patients with infarction of the posterior left ventricular wall and transmural infarction of the ventricular septum, 33 (50 percent) had associated right ventricular infarction. Among the 33 patients with right ventricular infarction, the infarct was limited to the posterior right ventricular free wall in 27 (82 percent); in the other 6 patients (18 percent) it extended to involve the anterolateral right ventricular free wall. Among patients with a posterior left ventricular infarct, those with a right ventricular infarct had right ventricular dilatation nearly three times (P Hemodynamic data in four patients with a right ventricular infarct disclosed previously reported characteristic hemodynamics of right ventricular infarction in only one patient. Recognition of right ventricular infarction is important because it implies specific therapy, namely, aggressive volume administration. Clinical evidence of posterior left ventricular infarction and right ventricular dilatation should arouse strong suspicion of associated right ventricular infarction.

Kindling as a model for alcohol withdrawal syndromes.

Abstract: Periodic brain stimulation, particularly in the limbic system, at stimulus intensities initially too low to produce any behavioural or EEG effects, progressively produces EEG changes, motor automatisms, and eventually convulsions, an effect called kindling. Data are presented and reviewed that suggest that the severity of alcohol withdrawal symptoms progressively increases over years of alcohol abuse in a stepwise fashion similar to the kindling process. The model is presented that the limbic system hyperirritability which accompanies each alcohol withdrawal serves over time to kindle increasingly widespread subcortical structures. These long-term changes in neuronal excitability might relate to the progression of alcohol withdrawal symptoms from tremor to seizures and delirium tremens, as well as the alcoholic personality changes between episodes of withdrawal.

Establishment and Characterization of Three New Continuous Cell Lines Derived from Human Breast Carcinomas

Abstract: Three continuous lines of mammary tumor cells (ZR-75-1, ZR-75-27, and ZR-75-30) have been established from malignant effusions of two women with breast cancer. Differentiated properties expressed by each cell line include: (a) epithelial morphology (by light and electron microscopy) resembling that of the parental tumors; (b) presence of receptors for estrogen and other steroid hormones; and (c) growth responsiveness to estrogen and/or progesterone. All three cell lines possess human karyotypes that differ from one another in modal chromosome number as well as in characteristic marker chromosomes. Two of the cultures (ZR-75-27 and ZR-75-30), although derived from the same patient, have stable differences in their karyotypes.

Characterization of lymphocyte-activating factor (LAF) produced by the macrophage cell line, P388D1. I. Enhancement of LAF production by activated T lymphocytes.

Abstract: Based on the results of these studies, it appears that P388D1 cells are an excellent source of LAF for both biologic and biochemical studies

Bronchoalveolar lavage in interstitial lung disease.

Abstract: Cellular and immunoglobulin components of bronchoalveolar fluid recovered by bronchoscopic lavage were evaluated in 32 control patients, 10 normal volunteers, and 60 patients with the following interstitial lung diseases: idiopathic pulmonary fibrosis, pulmonary fibrosis associated with collagen-vascular disease, eosinophilic granuloma, sarcoidosis, and hypersensitivity pneumonitis. The percentage of lymphocytes distinguished two general disease categories: those with increased lymphocytes (sarcoidosis and hypersensitivity pneumonitis); and those with normal lymphocytes (idiopathic pulmonary fibrosis, pulmonary fibrosis associated with collagen-vascular disease, and eosinophilic granuloma). Patients in all five disease categories had elevated IgG levels and percentages of neutrophils compared with control patients, with the highest proportion of neutrophils found in idiopathic pulmonary fibrosis. Immunoglobulin levels also helped distinguish among patient groups, in that patients with hypersensitivity pneumonitis had lavage IgG/albumin ratios greater than 1, whereas patients with sarcoidosis had ratios less than 1; and with infrequent exceptions, the finding of IgM in lavage fluid was limited to patients with hypersensitivity pneumonitis.