Search PubMed⌕ Search

Biomedical subjects

P Wright

Publications and source records attributed to P Wright.

330 records · Page 19Linked to original sources

Prolonged isometric exercise. Part 1: Effect on circulation and on renal excretion of sodium and potassium in mild essential hypertension.

The effect of stress, in the form of prolonged isometric exercise, on the circulation and on the renal excretion of sodium and potassium was studied in 18 patients with mild essential hypertension. Thirteen men and five women, aged 20 to 50 years with basal diastolic blood pressure (BP) between 90 and 110 mm Hg were matched by age, sex, and race with 18 controls who had basal diastolic BPs less than 85 mm Hg. After the subjects rested for 90 minutes, basal measurements of pulse rate, BP, and rates of sodium and potassium excretion were made. The subjects then underwent a 1-hour period of isometric exercise involving all four limbs in rotation, followed by 5 hours of rest during which the measurements were repeated at half-hourly intervals for the first 2 hours and at hourly intervals for the last 3 hours. On another day, the subjects were again studied after 1 hour of resting instead of exercise. Responses of each subject were then expressed as ratios of changes from the basal values observed on the exercise and rest days. Changes in systolic and diastolic BP and hart rate were not significantly different in the hypertensive and control groups. In hypertensive subjects, the rate of sodium and potassium excretion was decreased after isometric exercise compared with the rest day, whereas in normal subjects this response was reversed. For the first 3 hours after exercise, the cation excretion rate of the hypertensive group was significantly less than that of the control group. These results indicate that isometric exercise in mild hypertension induces prolonged renal retention of both sodium and potassium.

Adult↗

Prolonged isometric exercise. Part 2: Effect on circulation and on renal excretion of sodium and potassium in young males genetically predisposed to hypertension.

The effect of stress, in the form of prolonged isometric exercise, on the circulation and on the renal excretion of sodium and potassium was studied in 16 male medical students whose parental blood pressure (BP) was less than 140/85 mm Hg, and in 17 male students with one or two parents who had BPs greater than 150/95 mm Hg. After the subjects rested initially for 90 minutes, basal measurements were made of heart rate, BP, and the rates of sodium and potassium excretion. The subjects then underwent a 1-hour period of intermittent isometric exercise involving all four limbs in rotation, during which BP and heart rate were measured. A 5-hour period of rest followed, during which BP, heart rate, and the rate of electrolyte excretion were measured at half-hourly intervals for the first 2 hours and at hourly intervals for the last 3 hours. The precise protocol was repeated on another day in the absence of the period of isometric exercise. The electrolyte excretion responses of each subject were then expressed as the ratio of the changes from basal values observed on exercise and rest days. At no time was there any difference in systolic and diastolic BP, heart rate, and rate of sodium and potassium excretion following exercise when sons of normotensive parents were compared to the sons of hypertensive parent(s). These results indicate that the retention of sodium and potassium following isometric exercise seen in patients with hypertension does not occur in subjects genetically predisposed to hypertension and suggest that the effect is a consequence of, rather than a predisposing factor to, hypertension.

Adult↗

Intratumoral vaccination of adenoviruses expressing fusion protein RM4/tumor necrosis factor (TNF)-alpha induces significant tumor regression.

Recombinant adenovirus (AdV) vectors are highly efficient at in vitro and in vivo gene delivery. VKCK is a murine myeloma cell line expressing the light chain of the fusion protein RM4/tumor necrosis factor (TNF)-alpha. The in vitro transfection of VKCK cells with the AdV AdV5LacZ, which contains the marker gene beta-galactosidase, can reach a maximal 75% at a multiplicity of infection of 1000. Intratumoral injections of AdV5LacZ (2 x 10(9) plaque-forming units) resulted in substantial gene transfer in nearly 50% of VKCK tumors. The AdV pLpA/M4-TNF-alpha, which contains a fused gene M4-TNF-alpha that codes for the heavy chain of fusion protein RM4/TNF-alpha, was constructed. After the in vitro transfection of pLpA/M4-TNF-alpha at a multiplicity of infection of 1000, transfected VKCK cells showed significant secretion of RM4/TNF-alpha (36 ng/mL/10(6) cells) containing the functional TNF-alpha moiety in tissue culture. The secretion peaks at day 3 and is diminished at day 6 following the viral infection. These transfected VKCK cells also became more immunogenic with enhanced expression of major histocompatibility complex class I antigen. Intratumoral injections of 2 x 10(9) plaque-forming units of pLpA/M4-TNF-alpha virus with a repeated booster resulted in significant VKCK tumor regression in immune-competent mice, but not in athymic nude mice with a mean tumor weight of 0.07 g that were compared with 1.58 g and 1.70 g for tumors injected with AdV5LacZ and phosphate-buffered saline, respectively (P < .01). The tumor regression also results in protective immunity against a second challenge with parental tumor cells, which is mainly mediated by VKCK tumor-specific CD8+ T cells. These results indicate that AdV-mediated cytokine gene therapy may be a useful approach in the clinical management of solid human tumors.

Adenoviridae↗