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S Shaw

Publications and source records attributed to S Shaw.

At least 271 records · Page 15Linked to original sources
PubMed1991

Activation-independent binding of human memory T cells to adhesion molecule ELAM-1.

The induction of an ensemble of adhesion molecules on endothelial cells by inflammatory cytokines is likely to be crucial to the differential migration of T-lymphocyte subsets into inflammatory sites. Two molecular pathways involving the VLA-4 and LFA-1 integrins are known to mediate T-cell adhesion to activated endothelium. Here we show that a third pathway involving the rapidly inducible endothelial cell-surface adhesion molecule ELAM-1 contributes to the binding of resting CD4+ T cells to IL-1-induced human endothelial cells. All three pathways contribute to the greater adhesion to endothelium of memory T cells than naive T cells. There are two unique features of T-cell adhesion to purified ELAM-1: first, ELAM-1 exclusively mediates adhesion of memory T cells; second, memory T-cell binding to ELAM-1 is independent of acute activation events that regulate integrin-mediated adhesion. Thus, ELAM-1 may be of primary importance in the initial attachment of memory T cells to inflamed endothelium in vivo and to the preferential migration of memory T cells into tissue and inflammatory sites.

CD4 Antigens↗
PubMed1991

Remote T cell co-stimulation via LFA-1/ICAM-1 and CD2/LFA-3: demonstration with immobilized ligand/mAb and implication in monocyte-mediated co-stimulation.

Proliferative response of resting T cells generally requires not only cross-linking of the T cell receptor (TcR) but also co-stimulatory signals from accessory molecules. We here have used a "three-cell" model consisting of: (a) resting human CD4+ T cells as responders; (b) CD3 monoclonal antibody (mAb) OKT3 on latex beads as surrogate stimulators; (c) autologous monocytes as source of co-stimulation. As described by Kawakami et al. (J. Immunol. 1989, 142: 1818), T cell proliferation in this system is observed with paraformaldehyde-fixed monocytes if they have been activated and interleukin (IL) 1 beta/IL 6 is supplied. Since this three-cell system provides TcR cross-linking at a site spatially "remote" from co-stimulation, they help distinguish adhesion from signal transduction but the molecules that mediate co-stimulation in this system have not been identified. Our studies now demonstrate that co-stimulation by the monocytes is dependent on each of two receptor/ligand pathways CD2/LFA-3 and LFA-1/ICAM-1 since it is inhibited by each relevant mAb but not a variety of control mAb. The hypotheses that CD2 and LFA-1 could each mediate co-stimulation was tested in simplified model systems in which the monocyte was replaced with immobilized CD2 mAb or purified ICAM-1 presented on a separate surface from the CD3 mAb. The results in these simplified models demonstrate that on resting T cells either CD2 or LFA-1 molecules alone can mediate "remote" co-stimulation unlike most other T cell surface molecules. Co-stimulation requires IL 1 beta/IL6 both in the weaker LFA-1 ligand-mediated co-stimulation and at lower CD2 mAb concentrations in the stronger CD2 mAb-mediated co-stimulation. Thus: (a) the accessory cell function of stimulated fixed monocytes in T cell proliferation requires both the LFA-1/ICAM-1 and CD2/LFA-3 pathways; and (b) the T cell molecules CD2 and LFA-1 can give co-stimulatory signals that can act in a "remote" fashion.

Antibodies, Monoclonal↗
PubMed1991

Unaltered insulin sensitivity during calcium channel blockade with amlodipine.

The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (SI). To evaluate the effects of calcium channel blokkade on SI, glucose homoeostasis and lipid profiles, studies were made of SI (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal.day-1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P less than 0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol.l-1, respectively) and insulin levels (7.7 vs 7.9 microU.ml-1), SI (10.5 vs 9.6.10(-4) x min-1 pro microU.ml-1), serum total Tg, C and lipoprotein C fractions. The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.

Adult↗
PubMed1991

Reproducibility of insulin sensitivity measured by the minimal model method.

Insulin resistance is a critical component underlying the altered glucose homeostasis in a variety of metabolic and non-metabolic disorders. Aging, body fat distribution, obesity, diabetes mellitus or hypertension are well recognized conditions associated with an impaired tissue sensitivity to insulin action. Apart from such constant factors, insulin sensitivity can be acutely modified by independent variables such as physical exercise, dietary factors, alcohol intake or harmless drugs. To evaluate the day-to-day intra-individual variation in insulin sensitivity, glucose homeostasis and lipid profiles, we investigated the insulin sensitivity index (S1) (determined by the minimal model method of Bergman), basal and post-glucose-load insulin and glucose levels, serum total triglyceride and lipoprotein cholesterol fractions in 15 healthy young men (24 +/- 1 year, mean +/- SEM), on two different occasions at an interval of 3 weeks (days 1 and 21), after 3 days of a standard dietary regimen and after an overnight fast. Blood pressure, heart rate, body weight and 24 h urinary sodium excretion were almost identical in the two phases. S1(day 1) varied from 4.2 to 15.8 x 10(-4).min-1 pro microU/ml (mean: 10.2 +/- 0.9) and correlated with S1(day 21) (11.2 +/- 1.2 x 10(-4).min-1 pro microU/ml, r = 0.78, p less than 0.0007). The slope of the relationship did not differ from 1 (1.01, p greater than 0.90), the intercept was close to the origin (0.8, p greater than 0.73) and the coefficient of variation was 14.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Altered insulin sensitivity, hyperinsulinemia, and dyslipidemia in individuals with a hypertensive parent.

PURPOSE: Essential hypertension is, in some patients, complicated by impairment of insulin-mediated glucose disposal and hyperinsulinemia. Whether this metabolic disturbance is a consequence of the hypertensive process or whether it may precede, and thus possibly promote, the development of hypertension has been unknown. SUBJECTS AND METHODS: Searching for hereditary or familial defects in hypertension-prone humans, we prospectively investigated insulin sensitivity, plasma insulin and glucose, and serum lipoproteins in normotensive offspring of essential hypertensive as compared with age- and body habitus-matched offspring of normotensive families. RESULTS: Compared with 78 control subjects, 70 offspring of essential hypertensive parents had similar age (mean +/- SEM: 24 +/- 1 versus 24 +/- 1 years, respectively) and body mass index (22.3 +/- 0.2 versus 22.4 +/- 0.2 kg/m2), a blood pressure of 127/77 +/- 1/1 versus 123/76 +/- 1/1 mm Hg (p less than 0.05 for systolic), and significantly elevated (p less than 0.01 to 0.001) fasting plasma insulin levels (9.9 +/- 0.3 versus 8.6 +/- 0.3 microU/mL), serum total triglycerides (1.03 +/- 0.06 versus 0.83 +/- 0.03 mmol/L), total cholesterol (4.37 +/- 0.08 versus 3.93 +/- 0.07 mmol/L), low-density lipoprotein cholesterol (2.45 +/- 0.08 versus 2.14 +/- 0.07 mmol/L), and total/high-density lipoprotein cholesterol ratio (4.3 +/- 0.1 versus 3.7 +/- 0.1). Insulin sensitivity was lower (9.4 +/- 0.7 versus 13.2 +/- 1.1 x 10(-4) x minute-1/microU/mL, p less than 0.001), while post-glucose-load plasma insulin levels were higher (p less than 0.05) in the 41 offspring of essential hypertensive parents than in the 38 offspring of normotensive parents so investigated. CONCLUSION: These findings demonstrate that young normotensive humans in apparently excellent health but with one essential hypertensive parent tend to have an impairment of insulin-mediated glucose disposal, hyperinsulinemia, and dyslipidemia. It follows that a familial trait for essential hypertension seems to coexist commonly with defects in carbohydrate and lipoprotein metabolism that can be detected before or at least at a very early stage of the development of high blood pressure as judged by resting blood pressure measurements.

Adolescent↗
PubMed1991

Roles of multiple accessory molecules in T-cell activation.

Accessory molecules expressed on T cells can mediate adhesion between T cells and other cells, or the extracellular matrix. The same T-cell accessory molecules participate in a dialogue with their ligands (counter-receptors) on the antigen-presenting cells, and elicit signals that determine the specifics of activation and subsequent differentiation of the T cells and antigen-presenting cells.

Animals↗
PubMed1991

Interobserver reliability using the Phonetic Level Evaluation with severely and profoundly hearing-impaired children.

This study examines whether observers reliably categorize selected speech production behaviors in hearing-impaired children. A group of experienced speech-language pathologists was trained to score the elicited imitations of 5 profoundly and 5 severely hearing-impaired subjects using the Phonetic Level Evaluation (Ling, 1976). Interrater reliability was calculated using intraclass correlation coefficients. Overall, the magnitude of the coefficients was found to be considerably below what would be accepted in published behavioral research. Failure to obtain acceptably high levels of reliability suggests that the Phonetic Level Evaluation may not yet be an accurate and objective speech assessment measure for hearing-impaired children.

Analysis of Variance↗
PubMed1991

Four molecular pathways of T cell adhesion to endothelial cells: roles of LFA-1, VCAM-1, and ELAM-1 and changes in pathway hierarchy under different activation conditions.

T cell adhesion to endothelium is critical to lymphocyte recirculation and influx into sites of inflammation. We have systematically analyzed the role of four receptor/ligand interactions that mediate adhesion of peripheral human CD4+ T cells to cultured human umbilical vein endothelial cells (HUVEC): T cell LFA-1 binding to ICAM-1 and an alternative ligand ("ICAM-X"), T cell VLA-4 binding to VCAM-1, and T cell binding to ELAM-1. Contributions of these four pathways depend on the activation state of both the T cell and HUVEC, and the differentiation state of the T cell. ELAM-1 plays a significant role in mediating adhesion of resting CD4+ T cells to activated HUVEC. LFA-1 adhesion dominates with PMA-activated T cells but the strength and predominant LFA-1 ligand is determined by the activation state of the HUVEC; while ICAM-1 is the dominant ligand on IL-1-induced HUVEC, "ICAM-X" dominates binding to uninduced HUVEC. Adhesion via VLA-4 depends on induction of its ligand VCAM-1 on activated HUVEC; PMA activation of T cells augments VLA-4-mediated adhesion, both in the model of T/HUVEC binding and in a simplified model of T cell adhesion to VCAM-1-transfected L cells. Unlike LFA-1 and VLA-4, ELAM-1-mediated adhesion is not increased by T cell activation. Differential expression of adhesion molecules on CD4+ T cell subsets understood to be naive and memory cells also regulates T/HUVEC adhesion. Naive T cell adhesion to HUVEC is mediated predominantly by LFA-1 with little or no involvement of the VLA-4 and ELAM-1 pathways. In contrast, memory T cells bind better to HUVEC and utilize all four pathways. These studies demonstrate that there are at least four molecular pathways mediating T/HUVEC adhesion and that the dominance/hierarchy of these pathways varies dramatically with the activation state of the interacting cells and the differentiation state of the T cell.

Animals↗
PubMed1991

Cardiovascular pressor reactivity after chronic converting enzyme inhibition.

In addition to inhibiting the formation of angiotensin II, chronic converting enzyme inhibition may affect other blood pressure modulating factors. The influence of an 8 week treatment phase with cilazapril on the activity of the renin-angiotensin-aldosterone and sympathetic nervous systems, the pressor reactivity to infused angiotensin II or norepinephrine, the chronotropic response to isoproterenol, and body sodium and plasma atrial natriuretic peptide concentrations was assessed in 11 normal subjects and 12 patients with essential hypertension. As compared to a 4 week placebo phase, cilazapril decreased arterial pressure in both study groups (from 124/83 +/- 9/6 to 114/77 +/- 9/5 mm Hg and from 143/102 +/- 13/7 to 137/96 +/- 10/10 mm Hg; P less than .025); exchangeable sodium (-158 mmol and, respectively, -104 mmol) and upright plasma aldosterone (-24% and -15%) also tended to fall. Heart rate, the chronotropic response to posture or isoproterenol, plasma norepinephrine levels, the concentration/pressor response curve to norepinephrine, plasma atrial natriuretic peptide concentration, plasma angiotensin II and the responses of blood pressure or plasma aldosterone to angiotensin II were unchanged after 8 weeks of cilazapril. Plasma renin activity increased (+175% to +650%). These findings indicate that the blood pressure lowering effect of cilazapril in the stable phase of pharmacological intervention is not associated with modifications of sympathetic-dependent pressor reactivity or beta-adrenergic sensitivity. Plasma angiotensin II concentration and angiotensin II-dependent pathways including the pressor and aldosterone responsiveness to angiotensin II are also unchanged.

Adolescent↗
PubMed1991

Molecular basis of sequestration in severe and uncomplicated Plasmodium falciparum malaria: differential adhesion of infected erythrocytes to CD36 and ICAM-1.

The CD36 and ICAM-1 glycoproteins on vascular endothelial cells have been implicated as cytoadherence receptors for Plasmodium falciparum-infected erythrocytes (IRBC). Adhesion of IRBC from Thai patients with uncomplicated and severe falciparum malaria to purified CD36 or ICAM-1 and to C32 melanoma cells was compared. All malaria isolates bound to solid phase-adsorbed CD36 and to fluid-phase 125I-labeled CD36. IRBC adhesion to purified ICAM-1 varied widely, and no correlation with clinical severity of disease was observed. The cytoadherent phenotype of IRBC was modulated by selective panning on plates coated with purified CD36 or ICAM-1. IRBC selected by panning on CD36+, ICAM-1+ melanoma cells bound to cells that express surface CD36 but not to CD36-deficient cells, indicating that CD36 exerts a strong selective pressure on the IRBC cytoadherent phenotype. IRBC adhesion to CD36 and ICAM-1 suggests that P. falciparum parasites may use these receptors in vivo to promote parasite survival and immune evasion.

Animals↗
PubMed1991

Lymphocyte interactions with extracellular matrix.

To mediate an immune response, lymphocytes must be able to interact with and respond to the surrounding extracellular environment. In addition to cell surface molecules that facilitate adhesion of lymphocytes to other cells, recent studies have demonstrated that lymphocytes interact with glycoproteins and glycosaminoglycans that are major components of the extracellular matrix (ECM). Although many receptors mediating the effects of ECM components on lymphocyte function remain poorly defined, a number of lymphocyte ECM receptors have recently been identified; these include members of the integrin family of adhesion molecules as well as structurally unrelated molecules such as CD44 and CD26. Furthermore, as lymphocytes must be able to move between various microenvironments in vivo, they have proved to be an excellent cell type in which to identify and analyze various modes of regulation of cell-ECM interactions. As with other cell types, the ECM has been shown to have multiple effects on lymphocytes; functional analysis reveals effects of the ECM on lymphocyte migration, recognition/activation, and differentiation. These studies emphasize: 1) the importance of lymphocytes as a model system for identifying and analyzing ECM receptor expression and function, and 2) the multiple roles that the ECM plays in the function of the immune system in vivo.

Animals↗
PubMed1991

Atrial natriuretic factor after cardiac surgery with cardiopulmonary bypass in children.

OBJECTIVE: To determine circulating atrial natriuretic factor (ANF) concentrations in the postoperative state and to define potential hemodynamic determinants of regional plasma ANF concentrations. DESIGN: Cohort study. SETTING: Pediatric ICU in a university hospital. PATIENTS: Twenty-two children, mean age 4.2 yrs (range 0.9 to 13.5), were studied 18 hrs after corrective surgery on cardiopulmonary bypass. The underlying cardiac malformations were ventricular septum defect (n = 5), transposition of great arteries (n = 5), tetralogy of Fallot (n = 4), pulmonary stenosis (n = 3), and miscellaneous (n = 5). INTERVENTIONS: In addition to the commonly monitored variables in postoperative cardiac patients, blood volume was estimated by the 125I albumin method, and plasma samples for radioimmunoassay determination of ANF concentrations were taken simultaneously from indwelling catheters. MEASUREMENTS AND MAIN RESULTS: Compared with normal age-matched values, plasma ANF concentrations were increased in all patients, with values tending to be highest in the left atrium, followed by systemic artery, superior vena cava, and pulmonary artery (345 +/- 158, 333 +/- 169, 311 +/- 154, and 272 +/- 160 pg/mL, respectively [mean +/- SD; NS]). Simple regression analysis demonstrated a moderate correlation between blood volume and the concentration of ANF in the superior vena cava (p less than .05). Stepwise multivariate analysis showed no significant independent predictor of plasma ANF concentrations. CONCLUSIONS: Plasma ANF concentrations are increased after open-heart surgery in children, with moderate direct correlation to blood volume. The wide scatter of increased hormone concentrations may be explained by the many factors known to influence circulating ANF concentrations, such as age, underlying disease, cardiovascular state, and drugs.

Adolescent↗
PubMed1991

Postsynaptic alpha 1-blockade with terazosin does not modify insulin sensitivity in nonobese normotensive subjects.

Plasma insulin levels and the sensitivity of peripheral tissue to insulin (SI) have pathophysiological, therapeutic, and possibly also prognostic relevance. To investigate the effects of short-term selective alpha 1-adrenergic receptor blockade in nonobese normotensive humans on glucose and lipoprotein homeostasis, we assessed SI (determined by the minimal model method of Bergman), before and after glucose load plasma, glucose, and insulin levels, serum total triglycerides and lipoprotein cholesterol fractions, and some other variables in 20 healthy young men (26 +/- 1 years old, mean +/- SEM) during placebo and after 5 weeks of terazosin administration at a dose up to 10 mg once daily. Measurements were made after 3 days of standard diet (2,500 kcal/day, 45% carbohydrates, 40% fat, and 15% proteins) and after an overnight fast. Compared to placebo, terazosin decreased the upright systolic blood pressure (placebo vs. terazosin: 125 +/- 2 vs. 117 +/- 2 mm Hg, p less than 0.05) and increased supine (63 +/- 2 vs. 70 +/- 1 beats/min, p less than 0.05) and upright (77 +/- 2 vs. 88 +/- 2 beats/min, p less than 0.01) heart rates, while the body weight was unaltered. Terazosin did not significantly modify fasting plasma glucose (5.08 +/- 0.09 vs. 5.23 +/- 0.08 mmol/L, respectively), or insulin (8.9 +/- 0.5 vs. 8.6 +/- 0.6 microU/ml), SI (14.3 +/- 1.8 vs 11.8 +/- 1.5 x 10(-4)/min/microU/ml), the areas under the insulin or glucose curves, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1991

Enhanced exercise-induced rise of aldosterone and vasopressin preceding mountain sickness.

A possible contribution of exercise to the fluid retention associated with acute mountain sickness (AMS) was investigated in 17 mountaineers who underwent an exercise test for 30 min on a bicycle ergometer with a constant work load of 148 +/- 9 (SE) W at low altitude (LA) and with 103 +/- 6 W 4-7 h after arrival at 4,559 m or high altitude (HA). Mean heart rates during exercise at both altitudes and during active ascent to HA were similar. Exercise-induced changes at LA did not differ significantly between the eight subjects who stayed well and the nine subjects who developed AMS during a 3-day sojourn at 4,559 m. At HA, O2 saturation before (71 +/- 2 vs. 83 +/- 2%, P less than 0.01) and during exercise (67 +/- 2 vs. 72 +/- 1%, P less than 0.025) was lower and exercise-induced increase of plasma aldosterone (617 +/- 116 vs. 233 +/- 42 pmol/l, P less than 0.025) and plasma antidiuretic hormone (23.8 +/- 14.4 vs. 3.4 +/- 1.8 pmol/l, P less than 0.05) was greater in the AMS group, whereas exercise-induced rise of plasma atrial natriuretic factor and changes of hematocrit, potassium, and osmolality in plasma were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗
PubMed1991

Effects of slow ascent to 4559 M on fluid homeostasis.

Since acute mountain sickness (AMS) is associated with rapid ascent and with fluid retention, we assessed clinical status and fluid homeostasis in men slowly ascending on foot over 3 d to 4559 m and remaining at this altitude 5 d. We studied 15 male mountaineers, 6 of whom had previously had repeated, severe AMS or high altitude pulmonary edema (HAPE), at 1170 m, 3611 m, and 4559 m. We found that four of the six subjects with previous AMS or HAPE compared with none of nine with no such history, developed these conditions. Those who remained well had a diuresis that could not be overcome by increasing fluid intake and no change in renin activity, plasma aldosterone, or atrial natriuretic peptide (ANP). Those who became ill showed considerable weight gain independent of fluid intake, and a great increase in ANP which correlated with measurements of right atrial cross section. We conclude that mountaineers who have previously experienced repeated AMS or HAPE get fluid retention despite slow ascent and that this is associated with widening of the atrium and an increase in ANP.

Adult↗