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Biomedical subjects

V O'Brien

Publications and source records attributed to V O'Brien.

16 recordsLinked to original sources

Signal transduction by cell adhesion receptors.

Over the last few years, it has become clear that cell adhesion receptors function in signal transduction processes leading to the regulation of cell growth and differentiation. Signal transduction by both integrins and CAMs has been shown to involve activation of tyrosine kinases, while CAM signaling in neural cells involves G proteins as well. In the case of integrins, some of the downstream signaling events intersect with the Ras pathway, particularly the activation of MAP kinases. In fibroblasts, integrin mediated anchorage to the substratum regulates cell cycle traverse, while in epithelial cells, loss of anchorage can trigger programmed cell death. In many cell types, but particularly monocytic cells, integrin ligation has a profound impact on gene expression. Preliminary evidence also implicates CAMs and selectins in gene regulation. A consistent theme in signal transduction mediated by adhesion receptors concerns the role of the cytoskeleton. Integrin mediated signaling processes are interrupted by cytoskeletal disassembly. Identification of the APC and neurofibromatosis type 2 tumor suppressors suggest that cytoskeletal complexes also play a key role in signaling by cadherins and CD44, respectively. Thus, signaling by cell adhesion receptors may involve aspects that impinge on previously known signaling pathways including the RTK/Ras pathway and serpentine receptor/G protein pathways. However, novel aspects of signal transduction involving cytoskeletal assemblies may also be critical.

Animals

The development of competence in resting B cells. The induction of cyclic AMP and ornithine decarboxylase activity after direct contact between B and T helper cells.

In the present communication, an experimental approach is utilized that facilitates the study of biochemical processes induced in B cells after their interaction with Th cells. In this approach, Th cell clones are stimulated for 18 h upon anti-CD3-coated plates, fixed with paraformaldehyde, and added at a 2 to 3:1 ratio to small, resting B cells (isolated from Percoll gradients). Th cells not stimulated on anti-CD3-coated plates, but fixed with paraformaldehyde, serve as controls for these experiments. The activated, fixed Th cells induce a transient, sixfold increase in B cell levels of cAMP, as well as an increase in B cell expression of ornithine decarboxylase (ODC) activity. This enzyme initiates the synthesis of polyamines and has been shown to be increased as cells enter the growth phase. In addition, previous studies have shown that the cellular levels of ODC activity are controlled by a multi-tiered regulatory cascade. To examine this aspect, polyclonally stimulated B cells were studied. Such cells demonstrated a gradual increase in ODC mRNA levels that peaked between 6 and 15 h and can be partially explained by a three- to fourfold increase in mRNA stability but not by changes in the enzyme affinity for substrate. The increase in ODC mRNA occurs in the absence of protein synthesis, suggesting that the ODC gene is a member of the immediate/early gene family. Finally, the early increase in ODC mRNA was enhanced in cells in which cAMP levels were artificially elevated, suggesting the possibility that the cAMP-dependent signaling pathway participates during the regulation of this gene expression. The significance of these experimental results concerning the process of B cell activation is discussed.

Animals

The relationship between form and space perception, constructional abilities, and clumsiness in children.

The Sensory Integration and Praxis Tests (SIPT) (Ayres, 1989) were administered to 21 children with learning disabilities and 18 children without learning disabilities, aged 5 to 8 years. The children with learning disabilities were divided into two groups, clumsy and nonclumsy, on the basis of their scores on the Test of Motor Impairment (Stott, Moyes, & Henderson, 1984). It was hypothesized that the learning-disabled children in the clumsy group would score significantly lower than the learning-disabled children in the nonclumsy group on the six SIPT subtests that measure form and space perception and visual construction and that the nonclumsy learning-disabled children, in turn, would score significantly lower than the non-learning-disabled children. It was further hypothesized that there would be a significant correlation between the degree of clumsiness and the degree of visual-perceptual and constructional deficits. An analysis of the data indicated that both groups of learning-disabled children scored lower than the non-learning-disabled children on four of the six SIPT subtests. The clumsy and nonclumsy children with learning disabilities, however, differed from each other on only two subtests. The degree of clumsiness correlated significantly with three of the six subtests. The results are discussed in terms of variations in perceptual and motor skills related to subtypes of learning disabilities.

Child

Estimation of pulsatile ocular blood flow from intraocular pressure.

A relationship has been derived between intraocular pressure and pulsatile blood flow in the eye. Measurements of intraocular pressure show a time variation that is associated with the pulsatile component of arterial pressure. Experimental results provide a means of transforming intraocular pressure changes into ocular volume changes. The eye is represented by a chamber with elastic walls, a pulsatile incoming flow of incompressible fluid (blood), and a steady outgoing flow of blood. Under these conditions, the rate of pulsatile blood flow through the eye can be approximated from the instantaneous intraocular pressure measurements. Data from a healthy human eye are used to illustrate the analysis.

Blood Flow Velocity

Malnutrition in aboriginal children at Yalata, South Australia.

Comparative studies of body weight, height, intracellular water representing cell mass, and age, and plasma concentrations of albumin, vitamins, trace elements and iron stores in Aboriginal children aged 6 to 13.5 years, from two rural Aboriginal settlements and one rural Caucasian school (Hawker) provided evidence of significant deficits in one of the Aboriginal settlements (Yalata). Yalata Aboriginal children had lower body weights and heights for age and lower intracellular water values. Plasma albumin, zinc, iron, alpha-tocopherol, beta-carotene and retinol concentrations were lower relative to the normally grown Aboriginal children at Nepabunna. The latter children did not differ from rural Caucasian children for the parameters studied. The reasons for this poorer growth at Yalata may reside in poor nutrition, or repeated bowel infection in postnatal life leading to malabsorption, or both. Limited observational evidence suggests that Giardiasis has a high prevalence at Yalata, and it has been shown elsewhere that Giardiasis is capable of inducing malabsorption with resulting nutritional deficiencies.

Adolescent

The relationship between visual-perceptual motor abilities and clumsiness in children with and without learning disabilities.

One visual-perceptual test, four visual-motor tests, and a test of motor impairment were administered to 22 children with learning disabilities and 22 children without learning disabilities, aged 5 to 8 years. The children with learning disabilities were divided into two groups--"clumsy" and "nonclumsy"--based on their scores on the motor impairment test. It was hypothesized that the clumsy children with learning disabilities would score significantly lower on visual-perceptual and visual-motor tests than the nonclumsy children with learning disabilities who, in turn, would score significantly lower than the children without learning disabilities. It was further hypothesized that there would be a significant correlation between the degree of clumsiness and the degree of visual-perceptual and visual-motor deficit. Analysis of the data indicated that, as expected, the clumsy children with learning disabilities scored significantly lower than the children without learning disabilities (the control group). There was no significant difference between the clumsy and nonclumsy children with learning disabilities or between the nonclumsy children with learning disabilities and the control group. Degree of clumsiness significantly correlated with scores on four of five tests. Results are discussed in terms of subtypes of learning disabilities and sample size.

Analysis of Variance

Simple pulsatile flow in an artery with a constriction.

A smooth isolated, axisymmetric occlusion in a straight vascular tube is a tractable problem for pulsatile flow calculations via finite-difference approximations to the Navier-Stokes equation. Steady flow depends on the Reynolds number and two geometric parameters which describe the stenosis. The mere addition of a simple harmonic to the mean flow adds two more parameters. One is the reduced frequency, or Strokes number, and the other epsilon, the ratio of unsteady to steady flux. After describing steady stenosis flow examples, the dynamic patterns of pulsatile flow are illustrated indicating the inadequacy of basing hypotheses of atherosclerosis on mean (steady) flow.

Arterial Occlusive Diseases

Calculations of pulsatile flow through a branch: implications for the hemodynamics of atherogenesis.

Numerical simulations of pulsatile blood flow through a symmetrical branch modeling the aortic bifurcation were carried out to assess several hemodynamic theories of atherogenesis by comparing the distribution of hemodynamic variables with that of early lesions in arterial branches. Considerable spatial and temporal variations in wall shear were found when the flow was pulsatile; the highest values occurred at the convex corner on the outer wall of the branch and in the neighborhood of the flow divider tip, and the lowest shears were experienced by the outer wall of the daughter vessel a short distance distal to the corner. Transient flow reversal occurred almost everywhere in the branch, and a transient separated region was found corresponding to the low-shear region in the daughter vessel. The shear profiles and the calculated separated region were influenced to some degree by the extent of flow development at the branch inlet and markedly by the branch area ratio. All of the proposed hemodynamic promoters of atherosclerosis that were examined--high shear, low shear, and separation--were found at sites in the branch where lesions commonly develop. Comparisons with a steady-flow calculation at the same mean flow rate showed that the severity of all of these proposed hemodynamic determinants was increased by pulsatility.

Arteries

Nursing and computers.

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British Columbia