Showing papers by "National Institutes of Health published in 1969"

Junctions between intimately apposed cell membranes in the vertebrate brain

Abstract: Certain junctions between ependymal cells, between astrocytes, and between some electrically coupled neurons have heretofore been regarded as tight, pentalaminar occlusions of the intercellular cleft. These junctions are now redefined in terms of their configuration after treatment of brain tissue in uranyl acetate before dehydration. Instead of a median dense lamina, they are bisected by a median gap 20–30 A wide which is continuous with the rest of the interspace. The patency of these "gap junctions" is further demonstrated by the penetration of horseradish peroxidase or lanthanum into the median gap, the latter tracer delineating there a polygonal substructure. However, either tracer can circumvent gap junctions because they are plaque-shaped rather than complete, circumferential belts. Tight junctions, which retain a pentalaminar appearance after uranyl acetate block treatment, are restricted primarily to the endothelium of parenchymal capillaries and the epithelium of the choroid plexus. They form rows of extensive, overlapping occlusions of the interspace and are neither circumvented nor penetrated by peroxidase and lanthanum. These junctions are morphologically distinguishable from the "labile" pentalaminar appositions which appear or disappear according to the preparative method and which do not interfere with the intercellular movement of tracers. Therefore, the interspaces of the brain are generally patent, allowing intercellular movement of colloidal materials. Endothelial and epithelial tight junctions occlude the interspaces between blood and parenchyma or cerebral ventricles, thereby constituting a structural basis for the blood-brain and blood-cerebrospinal fluid barriers.

Fiber Orientation in the Canine Left Ventricle during Diastole and Systole

Abstract: Fiber orientation across the left ventricular myocardial wall has been studied. Specimens were obtained from 18 dog hearts rapidly fixed in situ in systole, in diastole, and in dilated diastole. Fiber orientation was determined across the free wall at eight sites from a T-shaped specimen by measurements with light microscopy in serial paraffin sections. Results indicate: (1) The wall has a well-ordered distribution of fiber angles varying from about 60° (from the circumferential direction) at the inner surface to about -60° on the outer surface. The greatest change in angle with respect to wall thickness occurs at the two surfaces (endocardial and epicardial). (2) Fiber angles did not change significantly during the transition from diastole to systole, despite a 28% increase in wall thickness (except in the papillary muscle root region). (3) The proportion of fibers lying in the sector of fiber angles oriented circumferentially (0±22.5°) to those oriented longitudinally (67.5 to 90° and -67.5 to -90°) is approximately 10:1. This ratio increases toward the base and diminishes toward the apex of the left ventricle. (4) All fiber angles in the lateral wall of hearts in systole increased through the wall by approximately 7° near the base and 19° near the apex relative to their counterparts in diastole, indicating bending or torsion of the left ventricle during contraction.

Energy of an ion crossing a low dielectric membrane: solutions to four relevant electrostatic problems.

Abstract: The influences on ion energy of membrane thickness, ion-pair formation, “pores” and “carriers” have been estimated. Only “pores” and “carriers” lower the energy barrier significantly.

Murine Sarcoma and Leukemia Viruses: Assay Using Clonal Lines of Contact-Inhibited Mouse Cells

Abstract: A continuous cell line of highly contact-inhibited cells (NIH/3T3) has been developed from NIH Swiss mouse embryo cultures. Its growth properties are similar to those of 3T3 and BALB/3T3. Although 3T3 is relatively insensitive to focus formation by murine sarcoma viruses, cloned lines of both NIH/3T3 and BALB/3T3 have been isolated that are highly sensitive to sarcoma virus focus formation and leukemia virus growth. The sensitivity and specificity are comparable to those found with primary embryo cells. MSV-transformed lines of NIH/3T3 have been obtained.

Cell selection by antigen in the immune response.

Abstract: Publisher Summary This chapter discusses the essential features of the antibody with respect to the interaction of antigen with preformed, cell-bound, antibody-like receptors. The effect of this interaction on individual cells is determined by the affinity of the antigen cell-bound antibody combination and results in the recruitment or selection of cells and their activation. The chapter also describes certain basic phenomena that are characteristic of the immune response and analyzes their mechanism at both the cellular and the molecular levels. These phenomena are an attempt to formulate a unified concept of the immune response as an antigen-driven proliferation and selection of specific cells that are committed to the synthesis of specific immunoglobulin molecules prior to the contact with antigen. This process, describable in thermodynamic terms, is the central biological event that can explain or predict such features of the antibody response as the progressive increase in average binding affinity of antibody produced, the effect of antigen dose on amount and affinity of antibody, the mechanism of action of adjuvants, the essential role of specific cell proliferation stimulated by antigen, the interference of humoral antibody with antigenic selection of cells, the phenomenon of “original antigenic sin,” and the induction of tolerance.

A radioisotopic method for measuring the formation of adenosine 3',5'-cyclic monophosphate in incubated slices of brain.

Abstract: — A simple and sensitive method for measuring the effect of neurohormones and other chemical agents on the formation of adenosine 3′,5′-cyclic monophosphate (cyclic 3′,5′-AMP) in incubated slices of brain was developed. The principle of the method depends on pulse-labelling of adenosine-5′-triphosphate in slices of brain with [8-14C]adenine, followed by incubation in a medium containing the test substance, separation by thin-layer chromatography of the cyclic nucleotide formed in the slices, and radioassay. The purity of the cyclic nucleotide was confirmed by chromatography in a variety of systems and by hydrolysis with a specific, bovine-heart phosphodiesterase. The method was used to study the effect of histamine, norepinephrine, and adenosine on the accumulation of adenosine 3′,5′-cyclic monophosphate in incubated slices of brain.

Concepts of Independence for Proportions with a Generalization of the Dirichlet Distribution

Abstract: Concepts of independence for nonnegative continuous random variables, X 1, …, Xk , subject to the constraint ΣXi = 1 are developed. These concepts provide a means of modeling random vectors of proportions which is useful in analyzing certain kinds of data; and which may be of interest in quantifying prior opinions about multinomial parameters. A generalization of the Dirichlet distribution is given, and its relation to the Dirichlet is simply indicated by means of the concepts. The concepts are used to obtain conclusions of biological interest for data on bone composition in rats and scute growth in turtles.

Rhabdomyosarcoma in children: epidemiologic study and identification of a familial cancer syndrome.

Abstract: To study the origins of childhood rhabdomyosarcoma, an examination was made of the 418 death certificates of U.S. children who died of this neoplasm, 1960-64, and of 280 medical charts from 17 hospital centers. Of exceptional interest was the presence in 5 Families of a second child with a soft-tissue sarcoma, 3 sibs (vs. 0.06 expeded by chance), and 2 cousins. The parents, grandparents, and other relatives of children in these families had a high Frequency of carcinoma ofthe breastand diverse neoplasms (e.g., acute leukemia and carcinomas of the lung, pancreas, and skin) at relatively young ages, suggesting a new Familial syndrome of multiple primary cancers. Additional components of the syndrome were implicated by the occurrence of adrenocortical carcinoma and brain tumor in the ~rst­ degree relatives of 2 other children with rhabdomyosarcoma. While suggesting the role of inheritance, the familial patterns seen with rhabdomyosarcoma may result from an interaction of genetic and environmental (?viral) fadors. The oncogenic agents and mechanisms in human cancer may be identified by the use of such family aggregations For laboratory studies and Further epidemiologic studies. Like most childhood neoplasms, rhabdomyosarcoma showed a peak mortality beFore 4 years of age and occurred slightly more often in males. This neoplasm was diagnosed in 29 children in the hospital series beFore 1 year of age and in 9 within 1 month of birth; this indicates that rhabdomyosarcoma may arise in utero. Unlike most neoplasms of

Initial events in interactions of blood with a foreign surface.

Abstract: The nature of the events occurring immediately after exposing foreign surfaces to fresh flowing blood was assessed using a combination of MAIR infrared spectroscopy, ellipsometry, and contact angle measurements. Within the first 5 sec after contact with blood issuing from the jugular veins of lightly anesthesized dogs, germanium prisms were uniformly coated with strongly adherent proteinaceous filsm having an average optical thickness equivalent to 2 layers of stearic acid (approx. 50 A) and having critical surface tensions of about 36 dyne/cm. A contact time of 60 sec led to a less uniform coating of average optical thickness equivalent to 5 layers of stearic acid (approx. 125 A), but with similar MAIR spectrum and wettability. The internal refelection spectra were consistent with the presence of either alpha-helical or random-chain configurations, but not with the extended chain beta-structure for proteins. Films cast from purified fibrinogen on platinum foils gave similar spectra and exhibited similar wetting properties; these observations are consistent with the hypotehsis that initial adsorptive events are dominated by fibrinogen deposition. The involvement of small amounts of lipid or other protein remains a distinct possibility, however.

The Elastic Symmetry of Arterial Segments in Dogs

Abstract: Elastic symmetry was studied in the middle descending thoracic aorta, abdominal aorta, and left common carotid artery under physiologic ranges of loading in ten dogs. A segment of the blood vessel was isolated and hung vertically. As the segment was pressurized, the radius, length, and the rotation of the lower end of the vessel were measured with respect to the fixed upper end. In addition, the angular displacement of a glass whisker initially placed perpendicularly through the wall was measured. From these data it was possible to calculate the values of shearing strains and elongating strains associated with pressurization and various imposed longitudinal stresses. The values of shearing strain varied from 0.003 to 0.115 over pressure ranges of 3 to 270 cm H2O. In all instances the values of shearing strain were much smaller than the corresponding elongating strains. It was concluded that the vessel has elastic properties that are nearly symmetrical about the planes perpendicular to principal stresses under physiologic loading, i.e., the vessel may be treated as a cylindrically orthotropic tube.

Certain Histological and Chemical Responses of the Vascular Interface to Acutely Induced Mechanical Stress in the Aorta of the Dog

Abstract: The purpose of this study is to quantify certain histologic and chemical responses of the intimal tissues in vivo to acutely induced mechanical stresses. Evans blue dye was given to tag serum albumin and an artificial fat emulsion was infused so that altered fluxes of either serum proteins or the artificial chylomicrons across the vascular interface into the intimal region could be detected. Special histologic and photodensimetric techniques were developed to estimate these fluxes as well as the architectural changes in the endothelial cell population. Architectural changes were quantified by doing endothelial cell counts to quantify the "normal" and "abnormal" endothelial cell population density as a function of stress exposure. The stress corresponding to the greatest rate of change of normal to abnormal cell forms is defined as the acute critical yield stress (τc) and was found to average < 420 dynes/cm2. Similarly the stress at which the greatest number of cells are being eroded is defined as the erosion stress (τe). The flux of Evans blue dye into the intima increased with pressure or wall strain, with shearing stress, and with increased turbulence. The flux of artificial chylomicrons into the intimal region never occurred in the presence of a normal endothelial cell population and was found to be most heavy in areas of total cellular erosion.

On the theory of screening for chronic diseases

Abstract: SIUMMARY It is assumed that a chronic disease progresses from a pre-clinical state to a clinical state. If an individual, having pre-clinical disease, participates in an early detection programme, the disease may be detected in the pre-clinical state. The potential benefit of a screening programme is related to the lead time gained by early diagnosis. A stochastic model is developed for early detection programmes which leads to an estimate of the mean lead time as a function of observable variables. An investigation is also made of a non-progressive disease model in which individuals in a pre-clinical state may not necessarily advance to the clinical state. At the present time special diagnostic procedures are available for early detection of some chronic diseases. For example, chest X-rays have long been used to detect tuberculosis. Currently, there are many public health programmes to detect women having cancer of the uterine cervix by using Papanicolaou smears; other programmes designed to test for glaucoma and diabetes are in wide use. An especially interesting programme for early detection of breast cancer using soft tissue X-rays, mammography, is now being conducted by the Health Insurance Plan of Greater New York; see Shapiro, Strax & Venet (1967). The aim of all such programmes is to detect the disease earlier than it normally would be detected, the motivation being that earlier detection may result in a cure or better prognosis. Unfortunately, with only a few exceptions we know of no chronic disease in which unambiguous evidence has been coLlected showing that early detection has resulted in significantly improved prognosis. Even in cancer of the uterine cervix, the results are not without question, because the survival rate had been increasing before the widespread introduction of the Papanicolaou smear. It is the purpose of this paper to discuss statistical considerations associated with the evaluation of such early detection programmes. Attention is confined to screening programmes where an individual is examined only once. In a future paper, we shall examine problems associated with screening programmes where an individual is examined periodically. It will be assumed that a person having a particular chronic disease can be regarded as

Signal Transmission along Retinal Rods and the Origin of the Electroretinographic a -Wave

Abstract: WHEN light is absorbed in the outer segment at one end of a vertebrate retinal rod or cone, sensory signals quickly reach its other end where its synapse with the visual system lies. Because rods and cones resemble short neurones in structure, it is thought that these signals travel as membrane polarization induced by light-activated current generators in the outer segments. Indeed, the membrane potentials of some rods and cones do increase in light1–3, but it is not clear whether the effect is primary and not the result of synaptic feedback from deeper retinal neurones. Attempts to show that the outer segments are sources of membrane current by analysing the a-wave and PIII components of the electroretinogram4 with intraretinal microelectrodes have not yielded consistent results, however5–8. We have therefore studied the spatial distribution of membrane current of the rods of the rat retina by an improved method using arrays of extracellular microelectrodes inserted in the receptor layer under direct vision by infrared microscopy.

Subacute sclerosing panencephalitis: isolation of measles virus from a brain biopsy.

Abstract: INDIRECT, evidence has suggested that subacute scleros-ing panencephalitis (SSPE, Dawson's encephalitis, van Bogaert's leukoencephalitis)—hardened inflammation of the brain—is associated with measles virus. This association is supported by: (1) the presence of type A inclusion bodies in brain tissue specimens1; (2) specific immuno-fluoresceiice with measles antibody in brain biopsies2; (3) extremely high measles complement fixing (OF) and haemagglutination inhibition (HI) antibody titres in the sera and spinal fluid2; and (4) electron microscopic evidence of paramyxovirus-like particles and nucleocapsids in brain biopsies3. We describe here the successful isolation of the presumed aetiological agent of SSPE.

Maternal Care and Infant Behavior in Japan and America

Abstract: (1969). Maternal Care and Infant Behavior in Japan and America. Psychiatry: Vol. 32, No. 1, pp. 12-43.

Dextran-induced Agglutination of Streptococcus mutans, and Its Potential Role in the Formation of Microbial Dental Plaques

Abstract: Glucose-grown washed cells of streptococci similar to Streptococcus mutans, which contain cell-bound dextransucrase, have been observed to agglutinate upon the addition of high molecular weight dextran. Low molecular weight dextran or unrelated polysaccharides were ineffective. Agglutination also occurred upon addition of sucrose, which can be converted into dextran, but not with other mono- and disaccharides. Other bacteria, including species capable of synthesizing dextrans, were not observed to exhibit this phenomenon. Cells of S. mutans agglutinated upon addition of dextran over a wide pH range, but maximal sensitivity to dextran occurred at pH 8.5. At this pH, such cells can be used for a simple, specific, and exquisitely sensitive qualitative assay for high molecular weight dextran, for addition of 6 ng of dextran with a molecular weight of 2 x 10(6) (i.e., approximately three molecules per cell) caused detectable agglutination. High concentrations of glucose, levan, and dextran of molecular weight of 2 x 10(4) inhibited the reaction. Fluorescein-labeled cells of S. mutans were observed to adhere to dextran-containing plaques and dextran-treated teeth, suggesting that this phenomenon may be of importance in the formation of streptococcal dental plaques. The mechanism responsible for dextraninduced agglutination appears to involve the affinity of a receptor site, possibly dextransucrase, on the surface of several cells for common dextran molecules.