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A J Vita

Publications and source records attributed to A J Vita.

6 recordsLinked to original sources

Aging, health risks, and cumulative disability.

BACKGROUND: Persons with lower health risks tend to live longer than those with higher health risks, but there has been concern that greater longevity may bring with it greater disability. We performed a longitudinal study to determine whether persons with lower potentially modifiable health risks have more or less cumulative disability. METHODS: We studied 1741 university alumni who were surveyed first in 1962 (average age, 43 years) and then annually starting in 1986. Strata of high, moderate, and low risk were defined on the basis of smoking, body-mass index, and exercise patterns. Cumulative disability was determined with a health-assessment questionnaire and scored on a scale of 0 to 3. Cumulative disability from 1986 to 1994 (average age in 1994, 75 years) or death was the measure of lifetime disability. RESULTS: Persons with high health risks in 1962 or 1986 had twice the cumulative disability of those with low health risks (disability index, 1.02 vs. 0.49; P<0.001). The results were consistent among survivors, subjects who died, men, and women and for both the last year and the last two years of observation. The onset of disability was postponed by more than five years in the low-risk group as compared with the high-risk group. The disability index for the low-risk subjects who died was half that for the high-risk subjects in the last one or two years of observation. CONCLUSIONS: Smoking, body-mass index, and exercise patterns in midlife and late adulthood are predictors of subsequent disability. Not only do persons with better health habits survive longer, but in such persons, disability is postponed and compressed into fewer years at the end of life.

Activities of Daily Living↗

Paradoxical blockade of beta adrenergically mediated inhibition of stimulated eosinophil secretion by salmeterol.

Salmeterol (SALM) is a long-acting beta 2 adrenoceptor agonist that causes prolonged relaxation of airway smooth muscle. To determine whether this agent also causes prolonged inhibition of stimulated eosinophil secretion, we studied interactions between SALM and albuterol (ALB) in inhibiting eosinophil peroxidase (EPO) secretion in human eosinophils in vitro. Peripheral blood eosinophils were isolated from 18 human volunteers by negative immunoselection, and secretion of EPO was elicited with 10(-6) M formyl-met-leu-phe (fMLP) + 5 micrograms/ml cytochalasin B (CytB) in aliquots of 10(5) cells. Eosinophils were pretreated with either 10(-8) M ALB, 10(-8) M SALM or SALM + ALB for 5 min to 18 hr at 37 degrees C. Pretreatment with ALB for 5 min caused inhibition of stimulated secretion of EPO to 783 +/- 210 ng/10(6) cells vs. 1475 +/- 286 ng/10(6) cells for eosinophils not treated with ALB (P < .05; n = 5). Inhibition of EPO secretion caused by ALB was sustained for 30 min (924 +/- 160 ng/10(6) cells; P < .05 vs. fMLP + CytB; n = 5). By contrast, SALM had no inhibitory effect on fMLP-induced secretion after incubation for 5 min to 18 hr. In cells obtained from four separate isolations, pretreatment with 10(-8)M SALM before addition of ALB blocked the inhibition of EPO release caused by 10(-8)M ALB alone (486 +/- 28 ng/10(6) cells for ALB alone vs. 902 +/- 32 ng/10(6) cells for SALM + ALB; P < .01; n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

Contraction of human bronchial smooth muscle caused by activated human eosinophils.

We assessed the effect of activated eosinophils isolated from human peripheral blood in causing contraction of explanted human bronchi in vitro. Sixty-three epithelium-intact fifth generation airway sections were obtained from 16 subjects undergoing lung resection for carcinoma. Eosinophils were isolated by negative immunoselection, and activation with 10(-7) M platelet-activating factor (PAF) was confirmed by measurements of eosinophil peroxidase (EPO) secretion and superoxide (O2-.) generation. EPO secretion increased from 68.6 +/- 13.4 ng/10(6) cells to 420 +/- 125 ng/10(6) cells after activation with PAF (P < 0.05). Similarly, PAF-induced O2-. generation increased from 15.3 +/- 4.64 nmol cytochrome c reduced/10(5) cells to 44.2 +/- 8.50 nmol cytochrome c reduced/10(5) cells (P < 0.05). Cells were instilled into an isolated airway pouch preparation, and, 60 min later, airway contractile responses were determined by optical micrometry as percent decrease in lumenal diameter (%decrease) and percent increase in wall thickness (%increase) using a calibrated magnifying lens. Treatment with either vehicle, PAF alone, or untreated eosinophils had no effect on airway caliber or thickness. PAF-activated cells caused a 30.5 +/- 1.52% decrease in airway caliber (P < 0.001 vs. untreated cells) and a 36.6 +/- 2.54% increase in wall thickness (P < 0.001 vs. untreated cells). Preincubation with A63162, a 5-lipoxygenase inhibitor, caused concentration-dependent inhibition of airway narrowing. After 10(-5) M A63162, decrease in airway diameter caused by PAF was 8.00 +/- 0.10% vs. 30.5 +/- 1.52% for PAF alone (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetamides↗

Beta adrenergic modulation of formyl-methionine-leucine-phenylalanine-stimulated secretion of eosinophil peroxidase and leukotriene C4.

The inhibitory effect of beta-2 adrenergic receptor stimulation on leukotriene C4 (LTC4) secretion and eosinophil peroxidase (EPO) release caused by exogenous activation with 10(-8) to 10(-6) M formyl-met-leu-phe (fMLP) + 5 micrograms/ml of cytochalasin B (Cyto B) in purified human peripheral blood eosinophils was studied. Cells from normal subjects were isolated by negative immunoselection and remained > or = 98% viable as determined by trypan blue exclusion. Duplicate aliquots of eosinophils (10(5) cells/intervention) were activated with 1) fMLP + Cyto B alone, 2) fMLP + Cyto B after pretreatment with 10(-8) M albuterol, 3) 10(-8) M albuterol + fMLP + Cyto B after pretreatment with 10(-8) M propranolol or 4) vehicle control. After incubation, the supernatants were tested for concentration of LTC4 and EPO. Concentration-related release of EPO was demonstrated for 10(-8) M fMLP + 5 micrograms/ml of Cyto B to 10(-6) M fMLP + 5 micrograms/ml of Cyto B, and the greatest concentration of fMLP was used in all subsequent studies. FMLP + Cyto B caused substantial LTC4 secretion in eosinophils (300 +/- 83.0 pg/ml) as compared to sham-activated eosinophils (3.3 +/- 1.9 pg/ml; P < .02). Similarly, maximum EPO release increased from 277 +/- 17.8 to 3956 +/- 1230 ng/10(6) cells (P < .02) after activation with fMLP + Cyto B. Treatment with albuterol decreased markedly both LTC4 secretion to 144 +/- 54.0 pg/ml (P < .05 vs. fMLP + Cyto B-activated eosinophils) and EPO release to 1993 +/- 368 ng/10(6) cells (P < .05 vs. fMLP + Cyto B-activated eosinophils).(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗

Physiologic significance of epithelial removal on guinea pig tracheal smooth muscle response to acetylcholine and serotonin.

We studied the modulatory effect of airway epithelium on guinea pig tracheal smooth muscle (TSM) contraction. Isometric force was measured in vivo before and after removal of the tracheal epithelium. In parallel studies, TSM contraction was also measured isometrically in epithelium-intact and epithelium-denuded TSM strips in vitro. Epithelial removal in vivo did not alter the contractile response of TSM to acetylcholine (ACh) or serotonin. In nine guinea pigs, active tension (AT) caused by 3 x 10(-7) mol/kg of intravenous ACh was 0.74 +/- 0.14 g force per longitudinal length of the segment (g/cm) in the presence of epithelium versus 0.89 +/- 0.16 g/cm after removal of airway epithelium (confirmed histologically) (p NS). The threshold response to ACh was also unchanged (-8.0 +/- 0.3 log mol/kg control versus -8.3 +/- 0.3 log mol/kg after epithelial removal, p NS). In six guinea pigs, the AT caused by 3 x 10(-8) mol/kg of intravenous serotonin was 1.92 +/- 0.63 g/cm with an intact epithelium versus 2.15 +/- 0.70 g/cm after epithelial removal in vivo (p NS). Epithelial removal in vitro increased the sensitivity of TSM contraction to ACh when the data were expressed as the percentage maximal response to ACh. The concentration of ACh causing 50% of the maximal response (EC50) was -5.74 +/- 0.25 log M in eight epithelium-intact TSM strips versus -6.37 +/- 0.16 log M after epithelial removal in controls (n = 8) (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗