Showing papers by "National Institutes of Health published in 1970"

The congenitally bicuspid aortic valve. A study of 85 autopsy cases.

Abstract: Clinical and necropsy observations are described in 85 autopsy cases in which the subjects had congenially bicuspid aortic valves. Sixty-one subjects had aortic stenosis with or without aortic regurgitation; 11, pure aortic regurgitation; and 13, unexpectedly, had a congenitally bicuspid aortic valve that apparently had functioned normally. The average age at death in patients with stenotic valves was 49 years, and in those with pure regurgitation, 31 years. Aortic valvular calcific deposits occurred in 59 of 61 patients with stenosis but was minimal or absent in the patients with pure regurgitation or normally functioning valves. Infective endocarditis appeared responsible for incompetency in 8 of 11 patients with pure regurgitation. Five of 61 patients with stenosis had had infective endocarditis, but infection occurred on a previously heavily calcified valve in only 1 patient. Sixty-nine of the 72 patients with functionally abnormal valves were observed in a study of 400 autopsy cases; all subjects were over age 14 years, with severe valvular cardiac disease. The 13 functionally normal valves were found during study of 1,440 necropsy cases in which the subjects were free of other valvular or septal defects. The bicuspid aortic valve is the most frequent congenital malformation of the heart or great vessels. It occurs in over 50 percent of patients with anatomically isolated aortic stenosis and in about 25 percent of patients with clinically pure aortic regurgitation. It is not certain why 1 congenitally bicuspid valve becomes severely scarred, calcified and stenotic, another only mildly scarred and incompetent, another the site of infection, and why another remains free of these complications during life.

Indole Metabolism in the Pineal Gland: A Circadian Rhythm in N-Acetyltransferase

Abstract: The activity of N-acetyltransferase in the rat pineal gland is more than 15 times higher at night than during the day. This circadian rhythm persists in complete darkness, or in blinded animals, and is suppressed in constant lighting. The N-acetyltransferase rhythm is 180 degrees out of phase with the serotonin rhythm and is similar to the norepinephrine and melatonin rhythms. Experiments in vitro indicate that norepinephrine, not serotonin, regulates the activity of N-acetyl-transferase through a highly specific receptor.

Size Allometry: Size and Shape Variables with Characterizations of the Lognormal and Generalized Gamma Distributions

Abstract: Size-related shape changes in animals are studied within a general framework of size variables and shape vectors. Isometry, or independence of shape and size, is defined as the independence of some (all) shape vector(s) from a particular size variable. With mild restrictions it is shown that isometry is possible with respect to at most one size variable, or in other words that shape will always be related to a variety of size variables. The choice of a size variable is a hitherto neglected, but important, part of an allometric study. The use of functional relationships in allometry is contrasted with the approach developed here. Also, size and shape variables are used in characterizations of the lognormal, gamma and generalized gamma distributions. The results, given in a biological context, are of interest in size and shape studies generally.

Embryonic vertebrate central nervous system: Revised terminology

Abstract: The layers and cells of the early developing central nervous system lack direct counterparts in the adult and must be designated by a special terminology. The inconsistent and inaccurate language now in use leads to misunderstanding and a revision is proposed in which the four fundamental zones are termed the ventricular, subventricular, intermediate, and marginal zones. Each is defined according to the form, behavior, and fate of its constituent cells. All neurons and macroglia of the central nervous system can be derived from these developmental zones.

Impaired immunologic reactivity and recurrence following cancer surgery

Abstract: One hundred patients were tested for their ability to react to 7 commonly encountered skin test antigens and to develop delayed cutaneous hypersensitivity to 2, 4-dinitrochlorobenzene (DNCB). Following sensitization, more than 95% of normal patients, but only 60% of patients with potentially resectable neoplasms, exhibited delayed cutaneous hypersensitivity to DNCB. A correlation is suggested between the inability to react to DNCB and the incidence of either inoperability, local recurrence, or distant metastases within 6 months post-operatively. Ninety-three percent (27/29) of patients who failed to react to DNCB were inoperable or developed early recurrence, whereas 92% (50/54) of patients who reacted to DNCB were free of disease for 6 months; but many of these patients were nonreactive to all of the common skin test antigens. These studies suggest that there is a significant correlation between cell mediated immunologic reactivity as measured by delayed cutaneous hypersensitivity to DNCB and the course of malignant disease following definitive cancer surgery.

Cyclic Adenosine Monophosphate in Bacteria

Abstract: Both cyclic AMP and a specific inducer acting in concert are required for the synthesis of many inducible enzymes in E. coli. Little enzyme is made in the absence of either. In contrast to the specific inducers which stimulate the synthesis only of the proteins required for their metabolism, cyclic AMP controls the synthesis of many proteins. Glucose and certain other carbohydrates decrease the differential rate of synthesis of inducible enzymes by lowering cyclic AMP concentrations. In the lac operon, cyclic AMP acts at the promoter site to facilitate initiation of transcription. This action requires another protein, the cyclic AMP receptor protein. The nucleotide stimulates tryptophanase synthesis at a translational level. The action of cyclic AMP in E. coli may serve as a model to understand its action on transcriptional and translational processes in eukaryotes.

Predicting Measures of Motor Performance from Multiple Cortical Spike Trains

Abstract: Recordings have been obtained simultaneously from several, individually selected neurons in the motor cortex of unanesthetized monkey as the animal performed simple arm movements. With the use of comparatively simple quantitative procedures, the activity of small sets of cells was found to be adequate for rather accurate real-time prediction of the time course of various response measurements. In addition, the results suggest that hypotheses concerning the response variables "controlled" by cortical motor systems may well depend upon whether or not the temporal relations between simultaneously active neurons are taken into account.

Intermittent Claudication: Incidence in the Framingham Study

Abstract: A general population sample of adult men and women was followed biennially over 14 years during which time 79 men and 46 women developed initial symptoms of intermittent claudication. A detailed examination of the incidence of this manifestation of atherothrombosis in comparison to that of coronary heart disease and atherothrombotic brain infarction was undertaken. As for coronary heart disease (CHD), the incidence of intermittent claudication increased with age. Women lagged behind men by 10 years in incidence. Atherothrombotic brain infarction in contrast exhibited no male predominance and after the early sixties the women actually surged ahead. Uncomplicated angina, surprisingly, resembled brain infarction more than intermittent claudication in the age-sex trend. A pronounced increase in risk of intermittent claudication was noted for persons with CHD in general and angina in particular, suggesting a common underlying basis for claudication and coronary disease. The principal hazard for subjects with claudication appeared to derive from an increased propensity to cardiovascular morbidity and mortality rather than from the consequences of impaired circulation to the limb. Risk of death was twofold for those with claudication as compared to those without.

Host-Range Restrictions of Murine Leukemia Viruses in Mouse Embryo Cell Cultures

Abstract: Murine leukemia virus strains fall into three categories with respect to their ability to propagate in cells of National Institutes of Health (NIH) Swiss and BALB/c mouse embryos. Cultures of NIH cells are 100- to 1,000-fold more sensitive to “N-tropic” strains than BALB/c cell cultures, but are 30- to 100-fold less sensitive to “B-tropic” strains. Some virus strains (dually tropic or “NB-tropic”) propagate equally well in both cells. M-MSV pseudotypes show the host-range characteristics of the virus supplying the envelope, both in vitro and in vivo. The host-range characteristics appear to be genetically determined and could not be explained by host-induced modification or virus mixtures. There was no correlation between host range and Gross-AKR or FMR serotype.

Regenerative Calcium Release within Muscle Cells

Abstract: Free calcium appears to trigger the release of stored calcium from the sarcoplasmic reticulum of skinned skeletal muscle fibers immersed in solutions with a low concentration of magnesium ion.

L-Dopa-Induced Release of Cerebral Monoamines

Abstract: L-Dopa markedly increased the efflux of tritiated dopamine and tritiated serotonin from rat brain slices. This action appeared contingent on the decarboxylation of L-dopa to dopamine, since it could be blocked by an inhibitor of L-amino acid decarboxylase. Selective destruction of catecholamine-containing nerve terminals by 6-hydroxydopamine significantly decreased the uptake and release of tritiated dopamine but not that of tritiated serotonin. These observations support the hypothesis that a portion of exogenously administered L-dopa may enter central serotonin terminals and undergo decarboxylation to the amine with resultant displacement of the endogenous indoleamine from vesicular stores.

Pressure-flow relationships and vascular impedance in man

Abstract: Blood pressure and velocity waveforms were recorded in a series of patients at cardiac catheterization. The changes in shape of the waveforms are interpreted in terms of reflections and are related to computations of vascular input impedance.

Factors related to the occurrence of typical paroxysmal abnormalities in the EEG records of epileptic patients.

Abstract: UMMARY 1The incidence of typical paroxysmal (epileptiform) discharges has been determined in 1824 EEG records from 308 patients with a reasonably certain diagnosis of epilepsy (average 6 records/patient). 1055 records were considered positive (i.e., showing epileptiform discharges) and 769 negative (i.e., either normal or with non-paroxysmal abnormalities). Patients were subsequently subdivided into three main groups: (a) 92 with all + records, (b) 54 with all – records, (c) 162 with mixed, + and – records and various subgroups. 2The purpose of this study was to analyze a number of factors to determine their possible relationship with positivity and negativity of the records within the various patient groups. Such factors included: age at the time of EEG examination and of seizure onset, etiology, clinical-EEG diagnosis and localization and clinical classification, background EEG patterns, presence of generalized convulsions, frequency of seizures, time since last seizure, presence of medication or length of time without medication. 3Positive findings in the first examination were obtained in 55.5% of the patients. About 70% of the patients with mixed tracings had more than half of their records positive. Of 75 patients followed with repeated examinations for at least 1 year, all records remained persistently negative in only less than 8%. 4The patient's age, both at the time of the examination and at the onset of seizures, is suggestively related to presence or absence of epileptiform discharges. The percentage of positive records is very high in the first decade while negative tracings predominate after the age of 40. When seizures started past the age of 30, the number of patients with all their records negative was three times as great as that of patients with all positive records. 5Etiological factors do not seem to play a role on the incidence of epileptiform discharges. 6Seizure patterns, including the occurrence of generalized (grand mal) episodes, and different forms of clinical diagnostic groups were similarly unrelated to positivity or negativity of the records. Only the group of patients with temporal lobe epilepsy would show a significantly larger amount of positive tracings, only 2% of these patients having exclusively negative records. 7Contingent factors such as (a) proximity of a seizure to the EEG examination, (b) frequency of seizures and (c) medication or lack thereof at the time of the examination, all appeared to be suggestively related to presence or absence of epileptiform discharges in the records. The relationship was in the expected direction for (a) and (b): i.e., the closer the examination to a seizure and/or the higher the seizure frequency, the greater the probability that a record would be positive. On the other hand, the results of the present analysis would not seem to support the common assumption that records obtained while the patient is on medication are less likely to be positive. Possible reasons for these somewhat paradoxical findings were discussed. Additional analyses were also performed in a selected group of patients with emphasis on the dynamic aspects of their records (i.e., “positivization” of a previously negative record and vice versa) as well as of some of these contingent factors. RESUME 1On a determine 'incidence des decharges paroxystiques typiques (epileptiformes) dans 1824 traces E.E.G. obtenus chez 308 sujets epileptiques (moyenne de 6 traces par sujet). 1055 traces ont ete consideres comme positifs (c'est-a-dire avec des decharges epileptiformes) et 769 ont ete consideres comme negatifs (c'est-a-dire soit normaux, soit avec des anomalies non paroxystiques). On a distingue 3 groupes de sujets: (a) 92 ayant tous leurs traces positifs, (b) 54 ayant tous leurs traces negatifs, (c) 162 avec des traces mixtes, positifs et negatifs. En outre on a distingue de differents sous-groupes. 2Cette etude se proposait 'analyser un certain nombre de facteurs pour determiner leurs relations possibles avec la positiviste et la negativite des traces dans les differents groupes de sujets. De tels facteurs incluent 'âge au moment des traces E.E.G. et 'âge au moment du debut des crises, 'etiologie, le diagnostic electroclinique, la localisation ainsi que la classification clinique, les types 'activite de fond E.E.G., la presence de crises generalisees, la frequence des crises, 'intervalle de temps depuis la derniere crise, la presence 'un traitement ou la duree de temps sans traitement. 3Lors du premier examen, on a obtenu des donnees positives chez 55.5% des sujets. Environ 70% des sujets avec des traces mixtes avaient plus de la moitie des traces positifs. Parmi les 75 patients suivis avec des traces repetes pendant au moins 1 an, tous les traces ont ete toujours negatifs seulement dans moins de 8% des cas. 4'âge des sujets, soit au moment de 'examen soit au moment du debut des crises est tres probablement en relation avec la presence ou 'absence de decharges epileptiformes. Le pourcentage des traceas positifs est tres eleve dans la premiere decade de la vie tandis que les traces negatifs sont plus nombreux apres 'âge de 40 ans. Lorsque les crises commencaient apres 'âge de 30 ans, les sujets qui avaient leurs traces negatifs etaient trois fois plus nombreux que les sujets ayant tous leurs traces positifs. 5Les facteurs etiologiques ne semblent pas jouer un role important dans 'incidence des decharges epileptiformes. 6Les types de crises, y compris la survenue 'episodes generalises (de type grand mal) et les differentes formes cliniques etaient egalement sans relation avec la positiviste ou la negativite des traces. Seul le groupe de sujets avec une epilepsie du lobe temporal aurait un nombre significativement plus eleve de traces positifs, seulement 2% des patients ayant exclusivement des traces negatifs. 7Les facteurs contingents tels que (a) un trace pres 'une crise, (b) la frequence des crises, (c) la presence ou non de traitement au moment de 'examen, apparaissaient en relation avec la presence ou 'absence de decharges epileptiformes dans les traces. Les relations etaient dans le sens qu'on s'attendait pour (a) et (b), i.e., avec une probabilitye 'avoir un trace positif 'autant plus grande que 'examen etait plus rapproche 'une crise et que la frequence des crises etait plus elevee. 'autre part, les resultats de ce travail ne semblent pas confirmer ce qu'on croit generalement, c'est-a-dire que les traces qu'on obtient lorsque le patient est sous traitement ont moins de chances 'etre positifs. On a discute les raisons possibles de ce resultat un peu paradoxal. On a fait 'autres analyses dans un groupe de patients selectionnes avec une attention toute particuliere pour les aspects dynamiques de leurs traces (c'est-a-dire un changement vers la positiviste 'un trace qui etait precedemment negatif et vice versa) ainsi que pour quelques uns de ces facteurs contingents.

Elevation of Adrenal Tyrosine Hydroxylase and Phenylethanolamine-N-Methyl Transferase by Repeated Immobilization of Rats

Abstract: Repeated daily immobilizationof rats results in a neuronally dependent elevation of tyrosine hydroxylase in the adrenal medulla. Phenylethanolamine-N-methyl transfera selevels are also increased. After cessation of immobilization intervals, tyrosine hydroxylaselevels decrease toward preimmobilization levels with a half-life of about 3 days. These results are discussed with reference to the changes in adrenal and urinary catecholamine levels found with repeated stress and estimation of the rate of tyrosine hydroxylase synthesis. (Endocrinology 87: 744, 1970)

Biological and Analytic Components of Variation in Long-Term Studies of Serum Constituents in Normal Subjects III. Physiological and Medical Implications

Abstract: Biological components of variation for each of 15 serum constituents have been estimated in 68 normal subjects by weekly measurements over several months, and concurrent measurements on invariant human serum pools. Intra-individual coefficient of variation was smallest, less than 2%, for Na, Cl, Ca, Mg; 3 to 4% for CO 2 , albumin, and total protein; 5 to 7% for K, glucose, cholesterol, and phosphate; and largest, 9 to 12%, for uric acid, urea nitrogen, SGOT, and LDH. Inter-individual variation was larger than intra-individual variation for all 15 tests except Cl, CO 2 , and K. Analytic deviation was as large as or larger than biological (intra- or inter-individual) variability for constituents, such as calcium, which are under precise homeostatic control, thus producing artifactual widening in the observed normal range and obscuring the borderline between normal and abnormal results. Limits of tolerable variability in laboratory procedures are proposed, based on composite intra- and inter-individual variation, that would permit medically significant deviations in results to be detected. Such limits were exceeded by current methodology in at least half the 15 tests.

A sensitive double-isotope derivative assay for norepinephrine and epinephrine. Normal resting human plasma levels.

Abstract: A sensitive and specific double-isotope dilution method for assaying norepinephrine and epinephrine separately is described. The method is based on enzymatic conversion of these two catecholamines to their respective metanephrines and was applied successfully to measurement of resting plasma concentrations of norepinephrine and epinephrine in normal subjects with the finding that norepinephrine (0.20 ± 0.08 µg/liter) normally constitutes approximately 80% of the plasma catecholamine content and epinephrine (0.05 ± 0.03 µg/liter) 20%.

Catch Property in Single Mammalian Motor Units

Abstract: The tension output of single motor units in the cat triceps surae muscle was studied during patterned stimulation of the innervating motoneurons. With repetitive stimulation within a rather narrow frequency range, the tension output of slow-twitch (type S) motor units may be quite sensitive to the pattern of stimulus intervals in the train. The presence of only one stimulus interval that is much shorter than the others in the train can cause marked, long-lasting tension enhancement, provided that the stimulus repetition rate in the basic train is within certain limits.

Blood fibrinolytic activity in man. Diurnal variation and the response to varying intensities of exercise.

Abstract: This investigation was undertaken in normal subjects to define the relationship between the intensity of exercise and magnitude of fibrinolytic response and to examine the effect of diurnal variations on the exercise response. Fibrinolytic activity was measured on fibrin plates and expressed as mm2. Diurnal variations occurred with lowest activity at 8:00 AM (mean, 66 mm2), and peak activity between 5:00 and 8:00 PM (mean, 266 mm2, P<0.001). Five minutes of maximal treadmill exercise caused a marked increase in mean activity from 90 to 658 mm2 (P<0.001). Five minutes of 70% maximal exercise produced no significant increase, but 30 minutes increased activity to 626 mm2 (P<0.005). In contrast, 30 minutes of 40% maximal exercise produced a small elevation from 80 to 173 mm2 (P<0.005). Maximal and 40% maximal exercise evoked greater responses at 4:00 PM than 8:00 AM. Exercise produces increases in fibrinolytic activity which are related to the relative intensity of exercise, its duration, and the time of day ...

Carrier function in anti-hapten immune responses. I. Enhancement of primary and secondary anti-hapten antibody responses by carrier preimmunization.

Abstract: Preimmunization of either guinea pigs or rabbits to bovine gamma globulin (BGG) prepares the animals for markedly enhanced antibody responses to 2,4-dinitrophenyl-BGG (DNP-BGG). This phenomenon is observed both in the primary anti-DNP antibody response to DNP-BGG and in the secondary anti-DNP antibody response to DNP-BGG in animals primed with DNP-ovalbumin (DNP-OVA). The BGG preimmunization is most effective if the antigen is administered as a complete Freund's adjuvant emulsion; in rabbits, a dose of 1 µg of BGG is more effective than a dose of 50 µg, whereas the reverse is true in guinea pigs. Transfusion of homologous anti-BGG sera fails to replace active immunization with BGG in the preparation of animals for these enhanced anti-DNP antibody responses. Both the immunoglobulin class and the average association constant for ϵ-DNP-L-lysine of the anti-DNP antibody produced in these enhanced responses is determined by the mode and time of immunization with haptenic conjugates and is not appreciably influenced by the nature of the carrier preimmunization. These studies indicate that the carrier specificity of hapten-specific anamnestic antibody responses is largely due to the interaction of two independent cell associated recognition units, one specialized for carrier and the other specific for haptenic determinants.

RNA Dependent DNA Polymerase of Human Acute Leukaemic Cells

Abstract: An RNA dependent DNA polymerase analogous to that of RNA tumour viruses has been found in lymphoblasts of leukaemic patients but not of normal donors. The enzyme can use an RNA template from mammalian cells to synthesize DNA.