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J A Featherstone

Publications and source records attributed to J A Featherstone.

3 recordsLinked to original sources

Age and alpha-2 adrenergic regulation of plasma norepinephrine kinetics in humans.

To investigate whether the age-related elevation of plasma norepinephrine (NE) is due to impaired alpha-2 adrenergic inhibition of sympathetic nervous system (SNS) outflow, arterialized plasma NE kinetics were measured before and 120 to 140 min after 1.5 and 5.0 micrograms m/kg oral clonidine in 6 old (57 to 78 years) and 8 young (25 to 39 years) normotensive male volunteers. Baseline plasma NE levels were higher in old compared with young men (M +/- SEM, 355 +/- 58 vs. 197 +/- 22 pg/ml, p less than .02). Clonidine produced significant (p less than .05) dose-related reductions in plasma NE, NE appearance rate, NE clearance, and mean arterial blood pressure (MAP) in both groups. There was no difference between old and young men in response to low dose clonidine. Following the higher dose, both groups had similar suppression of plasma NE (-51 +/- 7% vs. -58 +/- 2%, p greater than .05) and NE appearance (-60 +/- 6% vs. -62 +/- 2%, p greater than .05), but older men had a greater fall in NE clearance (-20 +/- 2% vs. -10 +/- 1%, p less than .003) and MAP (-28 +/- 3% vs. -10 +/- 4%, p less than .006). These findings suggest that sensitivity to alpha-2 receptor-mediated suppression of plasma NE and NE appearance is not diminished in elderly men.

Adult↗

Age differences in plasma norepinephrine kinetics in humans.

To determine if the increased plasma norepinephrine (NE) of older individuals is due to greater plasma NE appearance rate and/or decreased NE clearance, arterialized plasma NE kinetics were measured in 25 healthy young (27 +/- 6 yr, M +/- SD) and 18 healthy older volunteers (68 +/- 5 yr) using a tritium-labeled NE isotope dilution technique. Basal NE levels were 54% greater in the older participants (282 +/- 24 vs. 183 +/- 11 pg/ml, M +/- SEM, p less than .001). The mean plasma NE appearance rate was 32% higher (0.33 +/- 0.03 vs. 0.25 +/- 0.02 microgram/m2/min, p less than .016) and NE clearance was 19% lower (1.21 +/- 0.08 vs. 1.49 +/- 0.06 L/min/m2, p less than .006) in the older participants. There was a close correlation between NE appearance rate and NE levels (r = .76, p less than .001, N = 43), but only modest inverse correlation between NE clearance and NE levels (r = -.37, p less than .01, N = 43). Stepwise multiple linear regression analysis revealed that NE appearance rate and clearance explained 80% of the variance in NE levels and that 57% of the variance was attributable to NE appearance, F (1,41) = 54.8, p less than .001, compared with only 14% by NE clearance, F (1, 41) = 6.5, p = .01. We conclude that the principal factor accounting for the higher plasma NE levels of older individuals is an increase in plasma NE appearance rate.

Adult↗

Characterization of a type VI collagen-related Mr-140 000 protein from cutis-laxa fibroblasts in culture.

The precise biochemical defects in connective-tissue metabolism that are responsible for the laxity of skin seen in the syndrome of cutis laxa are largely unknown. We have studied fibroblasts cultured from skin explants of a 2-year-old male with the syndrome. Electron-microscopic examination of this skin revealed decreased amounts of amorphous elastin and an increase in elastin-associated microfibrils. Although the cultured fibroblasts were similar to control skin fibroblasts in morphology, growth rate and total protein synthesis, there was a 4-6-fold increase in accumulation of a collagenous protein of Mr 140 000 in both the culture medium and in the cell layer. This protein was structurally distinct from collagen types I, III, IV, V and VIII. It was found to be related to a cell-surface-associated glycoprotein, GP140, by both antigenic cross-reactivity and peptide mapping. Our data support observations that GP140 is a precursor of at least one form of pepsin-extracted type VI collagen.

Cells, Cultured↗