Search PubMedSearch

Biomedical subjects

T L Hayes

Publications and source records attributed to T L Hayes.

At least 19 recordsLinked to original sources

Dopamine and the neural circuitry of primate prefrontal cortex: implications for schizophrenia research.

Dopaminergic systems have been implicated in the pathophysiology of schizophrenia; the prefrontal cortex may be a site of dysfunction in this disorder. Until recently, however, relatively little was known about the organization of dopaminergic afferents, or the relationship of those axons to other elements of neural circuitry in the expanded and highly differentiated prefrontal cortex of primates. In this paper we review recent studies demonstrating that monkey prefrontal cortex is innervated by dopaminergic axons in a highly specific regional and laminar fashion. These findings are considered in the context of the organization of other neural systems in monkey prefrontal cortex and with regard to the extent to which they represent the organization of human prefrontal cortex. The resulting model of prefrontal cortical circuitry is then discussed in terms of the ways in which that circuitry might be disrupted in schizophrenia.

Animals

A comparative analysis of the distribution of prosomatostatin-derived peptides in human and monkey neocortex.

Comparative analyses were made of the immunohistochemical and biochemical distributions of three prosomatostatin-derived peptides (PSDP) in human, perfused monkey, and unperfused monkey neocortex. The PSDP we examined were the tetradecapeptide somatostatin 14 (SS14); the N-terminal extension of this peptide, somatostatin 28 (SS28); and somatostatin 28(1-12) (SS28(1-12)). In immunohistochemical experiments, numerous SS28-immunoreactive perikarya were located in both superficial and deep layers of perfused monkey cortex, but none were present in the cerebral cortex from unperfused monkey or autopsied human brains. In contrast, the number of SS28(1-12)-immunoreactive neurons was five times greater in the superficial cortical layers of unperfused monkey than of perfused monkey brain. Moreover, unperfused monkey and human cortex contained notably more SS14-immunoreactive processes than perfused monkey cortex. These data suggested that SS28 may have been converted into SS14 and SS28(1-12) in unperfused tissue during the post-mortem interval. This hypothesis was examined biochemically by measuring the levels of immunoreactivity of SS14, SS28, and SS28(1-12) in samples of unperfused monkey cortex frozen at different time intervals after removal from the brain. Samples frozen 10 minutes or longer after removal contained only 10-20% the level of SS28 immunoreactivity measured in samples frozen immediately or 1 minute after removal. The levels of SS14 and SS28(1-12) immunoreactivity did not demonstrate such reductions, and may instead have increased at early time points. To further characterize post-mortem effects on PSDP and to explore for species differences, we performed a detailed comparison of the regional, laminar, and cellular distribution of SS28(1-12) immunoreactivity under the three conditions. A progressive loss of immunoreactivity, particularly in radial fibers, was found at increasing post-mortem intervals in unperfused monkey neocortex, indicating that differences in density and distribution of immunoreactive fibers between human and perfused monkey may result from post-mortem peptide degradation in unperfused tissue. In contrast, the larger size of SS28(1-12)-immunoreactive white matter neurons in humans as compared to monkeys appeared partially due to a post-mortem effect but also reflected a species difference. In addition, the density of white matter neurons was found to be significantly greater in human than in perfused or unperfused monkey. These data indicate that any study of human autopsy material must be assessed in light of possible post-mortem effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Collared crypts in irradiated small intestine.

Crypts of Lieberkuhn are radiosensitive: the technique of crypt counting is an established method of assessing radiation induced changes in the small intestine. However, there has been little work done on the surface contours of the crypts, as they open into the intervillous cleft. The current paper describes the structure of control mouse crypt mouths as unobtrusive openings approximately 5 microns in diameter. After radiation with heavy ion particles, the crypt mouths are substantially larger (up to 10 microns in diameter) with a marked collar which is similar to that sometimes seen in coeliac disease. The shape and incidence of the collared crypts is described for specimens irradiated with neon, silicon and iron ions, with treatment with iron producing the most marked collars: it is suggested that the size and incidence of the collared crypts may be related to the LET of the beam used. It is of interest that the abnormal crypts are not produced after single doses of X-irradiation. The consideration of the structure of the collared crypts may require a redefinition of the terms crypt and villus with priority being given to the position of subepithelial vessels rather than surface shape. Finally, although the collared crypts can not be directly equated with 'tunnel' or 'channel' lesions, it is pointed out that they do represent localised damage with a specific position and shape.

Animals

Internal structure of the intestinal villus: morphological and morphometric observations at different levels of the mouse villus.

The internal structure of the mouse jejunal villus was examined from apex to base in transverse serial sections. The villi were arbitrarily divided into apical (1-160 microns), middle (161-320 microns) and basal (321-480 microns) thirds. Histological and ultrastructural morphometry was performed on villous epithelium, stroma, blood vessels and lacteals at the three levels. The cross sectional area and the number of cells/section increased apico-basally in both the villous epithelium and the stroma, but the increase was greater in the latter. The enterocytes in the villous basal third were narrow and had oblong nuclei. The enterocytes gradually became wider and their nuclei attained a more round or oval shape towards the villous apex. The microvilli of these cells also increased in length from the villous base to apex. Although the number of capillaries/section was approximately the same at the three levels examined, it appeared that the apical third was relatively more vascular if the overall apico-basal increase in the villous size was taken into consideration. The villi had a single lacteal, whose cross sectional area generally increased towards the villous base. The results of this study indicate that the internal structure of the intestinal villus is not uniform along its length. Therefore, it is important that when studying normal and abnormal villi, like should be compared with like so as to ensure that the normally occurring variations in the villous morphology are not confused with those induced by disease or experimental processes.

Animals

The pulmonary effects and clearance of intratracheally instilled Ni3S2 and TiO2 in mice.

The effects and clearance of intratracheally instilled nickel subsulfide (Ni3S2) and titanium dioxide (TiO2) were compared. Instilled Ni3S2 was acutely toxic to mice. Blood was recovered from the lungs during lavage, pulmonary polymorphonuclear leukocyte cell levels were increased, body weights decreased, and mice appeared clinically sick. These effects were in contrast to TiO2-instilled animals, which appeared similar to phosphate-buffered saline-instilled controls. The clearance of instilled particles from the lungs was examined for both Ni3S2- and TiO2-exposed mice. Particles were rapidly cleared to the gastrointestinal (GI) tract within 15 min; this clearance was nonspecific for Ni or Ti and appeared to be due to the coughing reflex. Significantly less Ni was present compared with TiO2 in mouse lungs at 3 and 7 days postexposure (P less than 0.05), with halflifes for the later clearance phase of 119 and 462 hr, respectively. Much of the early Ni lung burden was cleared to the GI tract, and Ni levels in the kidney and blood peaked at 1 hr. Longer-term Ni clearance rate constants were similar for lung, kidney, and blood and were consistent with the hypothesis that 63Ni was first solubilized in the lung then transported through the blood.

Animals

In vitro interactions between pulmonary macrophages and respirable particles.

Pulmonary alveolar macrophage cells (PAM) are an important component of the pulmonary response to particles deposited in the deep lung. To more fully characterize the interactions between macrophages and particulate materials, a correlative light and electron microscopic technique was developed that allowed light microscopic identification of individual cell viability after in vitro particle exposure, followed by scanning and transmission electron microscopic analyses of specific PAM, including surface morphology, X-ray microanalytic evaluation of particle content, and internal cellular structure. Individual cell viability, particle content, and morphologic alterations were evaluated for three particle types: Ni3S2, TiO2, and glass beads. Cell death and stages of cell disruption including bleb cluster formation, loss of surface features, formation of membrane tears and holes, and cell degranulation correlated with Ni3S2 and TiO2 content. Glass beads were not associated with cell disruption or viability reduction. Correlative microscopic techniques were essential in describing particle-dependent effects on an individual cell basis.

Animals

Low-temperature scanning electron microscopy of particle-exposed mouse lung.

Inflated frozen mouse lungs were examined using low-temperature scanning electron microscopy (LTSEM) following bulk fracture under vacuum. Various aspects of pulmonary architecture were identified and correlated with structures revealed by SEM following conventional fixation and preparation techniques. Surface etching of selected samples was performed by radiant heating, revealing characteristic cytoplasmic, nuclear and extracellular lattice patterns resulting from ice crystal formation during freezing. These patterns aided in distinguishing between intra- and extracellular spaces. Pulmonary fluids such as mucus and surfactant were identified. Iron oxide particles were introduced into the lungs of some animals by intratracheal instillation and were subsequently identified in frozen-hydrated lung tissue using characteristic X-ray identification and mapping techniques. Particles were observed both intra-and extracellularly and were commonly found in large deposits. These observations confirm the utility of LTSEM techniques for examination of particles within pulmonary tissue. Particle exposure by intratracheal instillation was found to result in a non-uniform distributional pattern.

Air Pollution

Morphological criteria for comparing effects of X-rays and neon ions on mouse small intestine.

Several techniques have been used to assess changes in different parts of mouse small intestine three days after a single dose of either 16.5 Gy X-rays or 11 Gy neon beam. The doses were chosen to be approximately equivalent in terms of their effect on the number of microcolonies present. In qualitative terms, villous damage was seen after both types of radiation exposure: collared crypts, similar to those seen in biopsies taken from patients suffering from coeliac disease, were conspicuous after neon irradiation. In semi quantitative terms the doses used, although estimated from previous work to give biologically equivalent damage, produced a greater drop in microcolony numbers after X-irradiation. This makes all the more important the fact that significantly greater changes were seen after neon irradiation-a greater drop was seen in the number of villous profiles and the number of goblet cells per villus. There was also greater breakdown in the integrity of the villous basement membrane. Different responses after the two types of irradiation are therefore seen in the cryptal and villous compartment. Progress is being made towards identifying and quantitating radiation induced changes in different populations of cells or tissues in the small intestine.

Animals

Etched surfaces of plastic embedded and frozen hydrated gastrointestinal tissue.

Scanning electron microscopy (SEM) is most often used to describe the structure of natural surfaces, but it can also be used to examine surfaces created artificially by sectioning or cryofracture. When plasma etched resin sections are studied, the SEM combines some of the functions of a light microscope and a transmission electron microscope. When etched frozen hydrated tissue is examined the groundwork is laid for the use of X-ray microanalysis for the study of elemental concentrations in tissue unexposed to chemical agents of any kind. Examples are given of the study of jejunum and stomach with these two techniques. The results are integrated with data from conventional SEM images to produce composite diagrams which assist with the interpretation of function and topographical morphology.

Animals

Cold-stage scanning electron microscope measurement of ice morphology in apple tissue as a function of freezing rate.

A cold-stage SEM was used to document the morphology of ice in apple tissue and a sucrose solution frozen at rates ranging from 450 to 0.03 degrees K/min. Freezing rates of 3-mm-thick apple discs were measured with a differential thermocouple technique, which gave measurement of the growth velocity and the temperature gradient through the solidified specimen as well as the cooling rate during solidification. Cold-stage SEM micrographs were used to measure the dendritic spacing of the ice structures, and these data were found to correlate linearly with the square root of the cooling rate during solidification as would be predicted by a theoretical analysis of mass transfer in the formation of dendrites. Comparison of freeze-substituted and freeze-dried apple-tissue micrographs with those from a cold-stage SEM showed that the cold-stage SEM technique was the only one which correctly represented ice morphology in apple tissue.

Food Preservation

Low temperature scanning electron microscope studies of mouse small intestine.

Etched frozen hydrated specimens of mouse small intestine have been examined with low temperature scanning electron microscopy as a preliminary to X-ray microanalysis. Recognizable images have been obtained of most of the known histological features of the gut. Nuclear and cytoplasmic details were often seen. Ice crystal damage was evident, although the degree of artefact depended on the cell type being examined and also varied from cell to cell or within cells. The same specimens were later examined with resin light microscopy and transmission electron microscopy. These two techniques confirmed that preservation was adequate for identification of cells and tissues, although cavities were seen, representing ice crystal damage. These preliminary results indicate that SEM of etched, frozen, hydrated specimens provides adequate identification of cellular detail to allow further work using X-ray microanalysis to be carried out.

Animals

Lung structure as revealed by microdissection. Positional morphology of human lung.

A technique of lung structure analysis is presented that allows visualization of the airway in its conceptual form. The lung is dissected such that the bronchial tree appears as a branching, continuous surface whose fine structure varies as a function of position along the airway. In these preparations, single loci of interest can be studied sequentially with any optical or electron microscope. This provides precise correlation of surface morphology and intracellular structure. Microstructural information can be indexed by either branch order or linear distance along the air path. Morphometry can be performed on surface features of the airway imaged with the scanning electron microscope using this indexing system. The anatomy of a human airway is presented.

Aged

Surface morphology and functional studies of human alveolar macrophages from cigarette smokers and nonsmokers.

The surface of macrophages inhabiting the peritoneal and alveolar spaces is pleomorphic in structure. The internal structure of these cells has been widely described and is not discussed here. Although external cell morphology has been well characterized by many researchers, this subject has not been reviewed. This review, therefore, describes in detail the surface features of macrophages as well as factors affecting macrophage morphology. Morphological studies of human cells are emphasized. Functional studies are presented and, when possible, morphological parameters are correlated with cell function. Because cigarette smoking has been well studied, the effects of this pulmonary insult are described in detail.

Anesthetics, Local

Endogenous and exogenous ocular and systemic silver deposition.

The ocular distribution of particulate silver after prolonged ingestion and the topical application of an organic silver compound (argyrol) are described and compared with the distribution after long-term occupational contact with refined silver. The deposits appear to be inert and to cause no functional visual deficit.

Aged

Survival of cultured mammalian cells exposed to ultrasound.

The colony-forming ability of cultured mammalian cells exposed to monochromatic ultrasonic vibrations of different frequencies (0.1, 0.5, 1.0, 2.0, 3.3 MHz) was studied. The combined effect of x rays and 1.0-MHz ultrasonic waves on the survival of M3-1 cells was also investigated. Split-dose experiments showed that cells exposed to ultrasound are "sensitized" to a subsequent exposure. Almost twice as many cells survive a given ultrasonic dose when exposed in the M phase as when exposed in the S phase. A small amount of synergism between ultrasound and x rays has been observed. The extent of synergism depends on the experimental factors, and may be due to an interaction between nuclear damage caused by x rays and the damage to the cell membrane caused by ultrasound.

Cell Survival