Showing papers by "National Institutes of Health published in 1968"
1,997 citations
TL;DR: The spectrophotofluorometric determination of hydroxylated benzo[a]pyrene products is sufficiently sensitive to detect 10-12 mole per ml and has great utility in measuring the hydroxymatic activity of cells grown in culture.
1,664 citations
TL;DR: The purpose of this study is to quantify the acute changes in endothelial histology that are associated with an induced increase in blood velocity and to establish the “normal” endothelial cell population density as a function of stress exposure.
Abstract: The purpose of this study is to quantify the acute changes in endothelial histology that are associated with an induced increase in blood velocity A nontraumatic intra-aortic device was designed to produce a rapid convergence of the aortic blood stream into a narrow channel along the ventral aspect of the thoracic aorta in dogs The endothelial surface overlying this channel was exposed to a broad range of surface shearing stress by the accelerated blood flow Techniques were developed to quantify the resulting distribution of shearing stress so that the stress to which the endothelial surface was exposed at every point along the channel could be determined Special histologic techniques were developed using formalin fixation and gelatin embedding of the tissue so that endothelial cytology could be studied and criteria for normal cells established Using these criteria, cell counts were done to establish the "normal" endothelial cell population density as a function of stress exposure The stress corresponding to the mode of these cell density distribution curves was defined as the acute yield stress (τ c ) The acute yield stress for endothelial cells was found to be 379±85 (SD) dynes/cm 2 Exposure to stress in excess of this value for periods as short as one hour resulted in marked deterioration of the endothelial surface consisting of endothelial cytoplasmic swelling, cell deformation, cell disintegration, and finally dissolution and erosion of cell substance The relationship of these events to cellular rheology and interfacial chemistry is discussed
1,249 citations
TL;DR: The liver membrane protein could not be detected in extracts of Morris hepatoma but was found to be present in a highly differentiated second generation hepatoma induced by diacetyl amino fluorene.
822 citations
TL;DR: The clinical courses of 126 patients with hemodynamically documented IHSS, examined repeatedly for up to 12 years, were analyzed, and the patients who were asymptomatic initially tended to remain so, while those who were more disabled generally deteriorated, died, or improved spontaneously.
Abstract: While considerable information concerning the hemodynamic and angiographic features of idiopathic hypertrophic subaortic stenosis (IHSS) is available, data concerning the natural history of the disease are limited. The clinical courses of 126 patients with hemodynamically documented IHSS, examined repeatedly for up to 12 years, were analyzed. The older patients tended to be more severely symptomatic. Although the course was extremely variable, the patients who were asymptomatic initially tended to remain so, while those who were more disabled generally deteriorated, died, or improved spontaneously. Bacterial endocarditis occurred in three patients. Ten patients died as a consequence of the natural history of IHSS; six of these deaths were unexpected. Sudden deaths occurred usually in patients with no or mild obstruction, and in patients with both the familial and sporadic forms of the disease. Atrial fibrillation was observed in 8% of the patients, and abnormalities of atrioventricular conduction, in 30%....
675 citations
TL;DR: Balb/c mouse embryo cultures that are carried under a rigid transfer schedule that minimizes cell‐cell contact evolve into permanent lines that possess properties very similar to 3T3.
Abstract: Balb/c mouse embryo cultures that are carried under a rigid transfer schedule that minimizes cell-cell contact evolve into permanent lines that possess properties very similar to 3T3. From the same embryo cultures, a transfer schedule where cell-cell contact is extensive leads to lines (Balb/3T12) that form multiple cell layers and have saturation densities up to 25-fold higher than the Balb/3T3 lines. All the lines are hypotetraploid.
Comparison of the Balb/3T3 lines with 3T3 reveals similar morphology, ability to grow at high dilution, low saturation density, and high susceptibility to transformation by SV40 virus. The Balb/3T12 lines, which are continually maintained at high cell density, show little improvement in cloning efficiency. Infection with SV40 produces transformants that can be selected by their ability to form colonies at low cell densities. Using the appropriate selective system for each line, it appears that SV40 T antigen induction and transformation in Balb/3T3 and Balb/3T12 are comparable.
623 citations
TL;DR: It is concluded that for most practical purposes arteries may be considered incompressible.
Abstract: The assumption of incompressibility has often been applied to the analysis of arterial-wall elasticity; however, the supporting evidence has been incomplete. The present study was designed to explo...
467 citations
TL;DR: Injection into rabbits of radioactive ceruloplasmin from which sialic acid had been removed enzymatically resulted in a rapid disappearance of the asialoceruloplAsmin from the serum and its appearance in parenchymal cells, but not in Kupffer cells, of the liver.
441 citations
TL;DR: The biochemical defect of cultuired skin fibroblasts from Hurler or Hunter patients (faulty degradation of sulfated mucopolysaccharide, resulting in excessive intracellular accumulation) may be corrected if cells of these two genotypes are mixed with each other or with normal cells.
Abstract: The biochemical defect of cultuired skin fibroblasts from Hurler or Hunter patients (faulty degradation of sulfated mucopolysaccharide, resulting in excessive intracellular accumulation) may be corrected if cells of these two genotypes are mixed with each other or with normal cells. The effect is mediated by substances released into the medium.
407 citations
TL;DR: It is indicated that methotrexate transport in the L1210 cell is carrier-mediated and uphill, and the implication of these findings with respect to the development of more effective folic acid antagonists is considered.
398 citations
TL;DR: The membrane-bound protein of erythrocyte ghosts can be solubilized and obtained free of other membrane components by dialysis against adenosine triphosphate and 2-mercaptoethanol.
Abstract: Approximately 20 percent of the membrane-bound protein of erythrocyte ghosts can be solubilized and obtained free of other membrane components by dialysis against adenosine triphosphate and 2-mercaptoethanol. This protein forms one major band on polyacrylamide gels and a single boundary in free-boundary electrophoresis, and it undergoes polymerization in the presence of divalent cations to form coiled filaments visible by electron microscopy. Antibodies to this membrane protein react specifically with red blood cells or their membrane ghosts but do not react with serum, erythrocyte cytoplasm, or other blood cells. The functional role of this protein is unknown, but it appears to be involved in maintaiining the structure of the red cell membrane. We suggest that this protein be called Spectrin since it is obtained from membrane ghosts.
TL;DR: The tissue-culture property that correlates best with tumorigenicity is the loss of contact inhibition of cell division in mouse embryo lines maintained in culture under conditions that minimize cell-cell contact.
Abstract: Balb/c mouse embryo lines maintained in culture for over 200 generations under conditions that minimize cell-cell contact do not become tumorigenic. Lines cultivated under conditions where there is extensive cell contact become tumor-producing within 30 generations. The tissue-culture property that correlates best with tumorigenicity is the loss of contact inhibition of cell division.
TL;DR: Observations on the development of synchrony among Thai fireflies indoors, the results of experiments on phase-shifting in the American Photinus pyralis and comparisons with synchronization between crickets and between human beings are compatible with the suggested Pteroptyx synchrony regulation.
Abstract: In Thailand, male Pteroptyx malaccae fireflies, congregated in trees, flash in rhythmic synchrony with a period of about 560 ± 6 msec (at 28° C). Photometric and cinematographic records indicate that the range of flash coincidence is of the order of ± 20 msec. This interval is considerably shorter than the minimum eye-lantern response latency and suggests that the Pteroptyx synchrony is regulated by central nervous feedback from preceding activity cycles, as in the human "sense of rhythm," rather than by direct contemporaneous response to the flashes of other individuals. Observations on the development of synchrony among Thai fireflies indoors, the results of experiments on phase-shifting in the American Photinus pyralis and comparisons with synchronization between crickets and between human beings are compatible with the suggestion.
TL;DR: The chapter states that the anatomical barriers to the movement of peroxidase from blood to ventricular CSF consist of the structures which are probably tight junctions between the apices of the choroidal epithelial cells and, perhaps, their ventricular surface.
Abstract: Publisher Summary The entry of radioactively labeled protein from blood into cerebrospinal fluid (CSF) and into cerebral tissue is much slower and less in amount, than that of tritiated water and certain ions. The barrier that impedes the entry of labeled protein into the CSF has been interpreted as being responsible also for the exclusion of intravascularly injected acid dyes which, because of their negative electric charge, bind to serum proteins. The second portion of this paper is concerned with this direction of transfer and offers a brief, preliminary description of the movement of peroxidase from ventricular CSF not only toward the vessels of the choroid plexus but also toward the vessels of the cerebral parenchyma. Some observations on the passage of the protein ferritin in this direction are also included. Movement of peroxidase from choroidal blood to epithelium and also the movement of peroxidase and ferritin from ventricle into choroidal epithelium and cerebral parenchyma are given in detail in the abstract. As a conclusion, the chapter states that the anatomical barriers to the movement of peroxidase from blood to ventricular CSF consist of: (a) the structures (which are probably tight junctions) between the apices of the choroidal epithelial cells and, perhaps, (b) their ventricular surface. This surface has been regarded as the barrier to the movement of fluorescent proflavine dyes out of the choroid plexus, though the only part of the epithelial cells enclosing demonstrable dye was the nuclear membrane rather than any portion of the cell membrane itself.
TL;DR: It is suggested that deamination, reduction, and subsequent conjugation with sulfate is the primary route of metabolism of normetanephrine in rat brain and that norepinephrine is also metabolized to this sulfate conjugate.
TL;DR: An empirical quality control system is utilized in order to obtain estimates of the stability, precision and reproducibility of the radioimmunoassays and CPB assays, and permit the determination of valid estimates of confidence limits on potency estimates.
Abstract: Radioimmunoassay (RIA) and competitive protein binding (CPB) assays provide dose response curves which show severe nonlinearity and the residual (error) variance is non-uniform and not normally distributed. Accordingly, several classic “least squares” statistical procedures commonly used for bioassay data are not directly applicable. Linearization may be obtained by the use of the logit transformation, but this increases non-uniformity of variance. We have utilized an empirical quality control system in order to obtain estimates of the stability, precision and reproducibility of the radioimmunoassays and CPB assays. These methods provide sequential monitoring of the performance of the assays, and permit the determination of valid estimates of confidence limits on potency estimates.
Journal Article•
TL;DR: Cardioactive steroids appear to inhibit (Na+ + K+)-ATPase by reducing the difference between the conformational energies ot the phosphorylated and nonphosphorylated forms of the enzyme.
Abstract: The combination of ouabain with (Na+ + K+)-ATPase is essentially irreversible at physiological temperature and pH. The rate of inhibition of the enzyme by different cardioactive steroids varies widely. The amount of steroid bound parallels the inhibition of enzyme activity. Mg2+, Na+, K+, nucleotides, and orthophosphate markedly influence the rate of interaction. In the presence of nucleotides, the rate is accelerated by Mg2+ and Na+ and retarded by K+. In the presence of orthophosphate, Mg2+ increases, K+ slows, and Na+ markedly decreases the rate of interaction. The ratio of ouabain binding to Na+-dependent phosphorylation is 0.50 for Electrophorus electric organ ATPase. In contrast to the native enzyme, the ouabain-treated enzyme rapidly incorporates orthophosphate. Cardioactive steroids appear to inhibit (Na+ + K+)-ATPase by reducing the difference between the conformational energies ot the phosphorylated and nonphosphorylated forms of the enzyme.
TL;DR: A collagenase, operative at neutral and alkaline pH, has been extracted from the granule fraction of human granulocytic leukocytes and it digests reconstituted collagen fibrils and reduces the viscosity of collagen solutions.
Abstract: A collagenase, operative at neutral and alkaline pH, has been extracted from the granule fraction of human granulocytic leukocytes. It digests reconstituted collagen fibrils and reduces the viscosity of collagen solutions. Cleavage of collagen in solution with purified enzyme produces the discrete products characteristic of other animal collagenases.
TL;DR: Results indicate that cortical neurons have patterns of discharge distinctly related either to saccadic or to pursuit movements, in line with the view that these two different types of eye movement are generated by distinct neuronal mechanisms.
Abstract: The cortical mechanism of eye-movement control was investigated by recording single cell activity from the frontal eye field (FEF) in unanesthetized monkeys seated in a primate chair with head restrained. Two types of cells (I and II) were found. Type I neurons fired during voluntary saccades occurring in a given direction and during the fast phase of nystagmus. Cells of this type were silent during slow pursuit movement. Type II cells showed steady discharge when the eyes were oriented in a specific direction. These cells discharged also during smooth pursuit movements and the slow phase of nystagmus, provided that the eyes were moving across positions which would have been associated with neuronal activity had the eyes come to rest there. All of Type II and a few of Type I neurons were identified by antidromic response to stimulation of the cerebral peduncle. These results indicate that cortical neurons have patterns of discharge distinctly related either to saccadic or to pursuit movements, in line with the view that these two different types of eye movement are generated by distinct neuronal mechanisms.
TL;DR: 5-H.A.T., noradrenaline, and 5-hydroxyindoleacetic acid levels were not significantly different, but 5- H.I.A.'s levels was significantly lower in the hindbrains of the suicides.
TL;DR: The authors showed that epsilon-(gamma-glutamyl)lysine cross-links form in human fibrin during polymerization catalyzed by factor XIII, and showed that the cross-link formation was not observed in non-cross-linked fibrins with ethylenediaminetetraacetic acid.
Abstract: (epsilon)-((gamma)-Glutamyl)lysine has been isolated from enzymatic hydrolyzates of cross-linked human fibrin. This compound was not detected in "non-cross-linked" fibrin prepared with ethylenediaminetetraacetic acid, which inhibits factor XIII; intermediate amounts were observed when the fibrin was prepared with glycine ethyl ester, which inhibits factor XIII competitively. These and ancillary experiments furnish conclusive evidence that epsilon-(gamma-glutamyl)lysine cross-links form in human fibrin during polymerization catalyzed by factor XIII.
TL;DR: The results support the hypothesis that EDTA causes the permeability change by binding a metal, probably Mg++, and that the cell surface then undergoes a steric or chemical change that requires energy metabolism for its reversal.
TL;DR: The incidence of dyspnea, chest pain, effusions into body cavities, precordial murmurs, ventricular gallops, edema and electrocardiographic disturbances was similar in patients with and without cardiac lymphoma, and these clinical findings most often were the result of mediastinal, pleural or pulmonary lymphomas, anemia, hypoalbuminemia, or an underlying cardiac condition.
Abstract: Of 196 patients with malignant lymphoma studied at autopsy, 48 (24 per cent) had lymphoma involving the heart. In 27 subjects the cardiac lymphoma was observed on gross examination, and in the other 21 it was found only on study of histologic sections. Lymphoma in the heart occurred most frequently in mycosis fungoides (33 per cent) and least frequently in Hodgkin's disease (16 per cent). Cardiac lymphoma was found in approximately 25 per cent of patients with lymphosarcoma, reticulum cell sarcoma and undifferentiated or mixed cell malignant lymphoma. The cardiac metastases when observed grossly were usually firm white focal nodules located most frequently in the pericardium but also often in the walls of the chambers. In 9 patients the cardiac lymphoma extended through the wall of a cardiac chamber or septum. The incidence of dyspnea, chest pain, effusions into body cavities, precordial murmurs, ventricular gallops, edema and electrocardiographic disturbances was similar in patients with and without cardiac lymphoma, and these clinical findings most often were the result of mediastinal, pleural or pulmonary lymphoma, anemia, hypoalbuminemia, or an underlying cardiac condition. Signs or symptoms of cardiac dysfunction could be attributed to lymphomatous involvement of the heart in only 5 of the 48 patients with cardiac lymphoma. Three of them had mycosis fungoides, and 2, Hodgkin's disease.
TL;DR: Kinetic studies indicate that while platelets and plasma MAO are distinct from that of liver mitochondria, the platelet and liver enzymes are quite similar, particularly in the characteristics of their response to inhibitors.
TL;DR: When Escherichia coli O111:B4 is exposed briefly to ethylenediaminetetraacetate (EDTA) it releases 30 to 50% of its lipopolysaccharide, determined not only by measuring percentage release of colitose, a sugar unique to this polymer, but also by measuring the amount of phenol-extractable lipopoly Saccharide remaining with the cell.
TL;DR: The contractile state of the left ventricle in man was analyzed by correlating left ventricular dimensional changes during contraction determined from cineangiograms, with simultaneous measurements of LV pressure and the time course of LV wall tension (stress).
Abstract: The contractile state of the left ventricle in man was analyzed by correlating left ventricular (LV) dimensional changes during contraction determined from cineangiograms, with simultaneous measurements of LV pressure. The mechanical characteristics of ventricular contraction were expressed quantitatively by deriving the extent and velocity of circumferential fiber shortening at the midwall and the time course of LV wall tension (stress); the instantaneous relations between tension, velocity, and length were then examined. In 6 patients without LV disease, wall tension became maximal soon after the onset of ejection, then declined rapidly; in 9 patients with LV disease, tension fell only slightly with continued ejection. The extent of shortening of the minor LV circumference was consistently less in patients with LV disease than in those without such disease. Velocity of circumferential fiber shortening throughout contraction ranged from 0.22 to 1.11 circumferences/sec in patients with LV disease and from 1.66 to 2.71 circumferences/sec in patients without LV disease, at comparable levels of wall tension (137 to 467 g/cm 2 , and 175 to 409 g/cm 2 , respectively). The initial rate of change of velocity of the circumferential fibers at the onset of ejection also was less than in the group without LV disease. The velocity of shortening of the contractile elements at maximum wall tension was 0.11 to 0.87 circumferences/sec in patients with LV disease and 1.46 to 2.04 circumferences/sec in patients without LV disease.
TL;DR: The fifth component of guinea pig complement, with a sedimentation coefficient 7.8S, is cleaved by sensitized sheep erythrocytes treated with the first four components of complement into two fragments with sedimentation coefficients of 7.4S and 1.5S, which possesses chemotactic activity for rabbit polymorphonuclear leukocytes, as well as anaphylatoxic activity for Guinea pig ileum.
Abstract: The fifth component of guinea pig complement, with a sedimentation coefficient 7.8S, is cleaved by sensitized sheep erythrocytes treated with the first four components of complement into two fragments with sedimentation coefficients of 7.4S and 1.5S. The smaller fragment, with a molecular weight of about 15,000, possesses chemotactic activity for rabbit polymorphonuclear leukocytes, as well as anaphylatoxic activity for guinea pig ileum.
TL;DR: The technique allows stereotaxic orientation of micro-electrodes for single unit recording in the intact monkey and provides for vertical penetrations and for minimum loss of time between completion of one penetration and reorientation of the electrode for the subsequent penetration.
TL;DR: Double-stranded ribonucleic acid extracted from purified reoviruses of all three serotypes and from type 3 virus-infected cells was analyzed by polyacrylamide gel electrophoresis and calculated that each RNA includes 10 segments.
Abstract: Double-stranded ribonucleic acid (RNA) extracted from purified reoviruses of all three serotypes and from type 3 virus-infected cells was analyzed by polyacrylamide gel electrophoresis. It was calculated that each RNA includes 10 segments: 3 large, 3 intermediate, and 4 small fragments corresponding to molecular weights of about 2.5, 1.4, and 0.8 × 106 daltons, respectively, or a total of 15 × 106 daltons.
TL;DR: These studies suggest that the induction of aryl hydroxylase activity involves an activation of specific genes and changes in their transcription into messenger RNA.