Biomedical subjects

S A Youngblood

Publications and source records attributed to S A Youngblood.

4 recordsLinked to original sources

PubMed1998

In vivo gene transfer of nitric oxide synthase enhances vasomotor function in carotid arteries from normal and cholesterol-Fed rabbits.

BACKGROUND: The vascular endothelium is anatomically intact but functionally abnormal in preatherosclerotic states, and an early deficit in the bioavailability of nitric oxide (NO) or related molecules has been described in both humans and animal models. We hypothesized that the targeted gene transfer of NO synthase (NOS) isoforms might ameliorate or reverse the deficit. METHODS AND RESULTS: We constructed a recombinant adenovirus, Ad.nNOS, that expresses the neuronal isoform of NOS (nNOS) and used it for in vivo endovascular gene transfer to carotid arteries (CA) from normal and cholesterol-fed rabbits. Vessels were harvested 3 days after gene transfer. In CA from normal rabbits, Ad.nNOS generated high levels of functional nNOS protein predominantly in endothelial cells and increased vascular NOS activity by 3.4-fold relative to sham-infected control CA. Ad.nNOS gene transfer also significantly enhanced endothelium-dependent vascular relaxation to acetylcholine; at 3 micromol/L acetylcholine, Ad.nNOS-treated arteries showed an 86+/-4% reduction in precontracted tension, whereas control CA showed a 47+/-6% reduction in tension. Contraction in response to phenylephrine and relaxation in response to nitroprusside were unaffected in both control and Ad.nNOS-treated CA. To determine the effect of Ad.nNOS in atherosclerotic arteries, 10 male New Zealand White rabbits maintained on a 1% cholesterol diet for 10 to 12 weeks underwent gene transfer according to the same protocol used in normal rabbits. Ad.nNOS-treated arteries showed a 2-fold increase in NADPH-diaphorase staining intensity relative to sham-infected and Ad. betaGal-treated arteries. The CA from cholesterol-fed rabbits showed impaired acetylcholine-induced relaxation, but this abnormality was almost entirely corrected by Ad.nNOS gene transfer. CONCLUSIONS: In vivo adenovirus-mediated endovascular delivery of nNOS markedly enhances vascular NOS activity and can favorably influence endothelial physiology in the intact and atherosclerotic vessel wall.

Animals↗

PubMed1998

Acute host-mediated endothelial injury after adenoviral gene transfer in normal rabbit arteries: impact on transgene expression and endothelial function.

Acute injury after adenoviral vascular gene transfer remains incompletely characterized. Here, we describe the early response (< or =days) in 52 New Zealand White rabbits undergoing gene transfer (beta-galactosidase or empty vector) or sham procedures to both carotid arteries. After gene transfer, arteries were either left in vivo for 1 hour to 3 days (in vivo arteries) or were excised immediately after gene transfer and cultured (ex vivo arteries). Within 1 hour, in vivo arteries receiving infectious titers of > or = 4X10(9) plaque-forming units (pfu)/mL showed endothelial activation, with an acute inflammatory infiltrate developing by 6 hours. Ex vivo arteries showed endothelial activation but no inflammatory infiltrate. There were also significant differences in transgene expression between in vivo and ex vivo arteries. Ex vivo arteries showed titer-dependent increases in beta-galactosidase expression through 2X10(10) pfu/mL, whereas in in vivo arteries, titers above 4X10(9) pfu/mL merely increased acute inflammatory response, without increasing transgene expression. In vivo arteries showed significant time- and titer-dependent impairment in endothelium-dependent relaxation, with no effect on contraction or nitroprusside-induced relaxation. Interestingly, however, if rabbits were made neutropenic with vinblastine, their arteries maintained full endothelium-dependent relaxation, even after very high titer vascular infection (up to 1X10(11) pfu/mL). These findings show that recombinant adenovirus triggers an early inflammatory response, and it is the inflammatory response that in turn causes functional endothelial injury. This occurs at much lower titers than previously appreciated (though the precise threshold will undoubtedly vary between laboratories). However, titers below the inflammatory threshold produce excellent transgene expression without inflammation or vascular injury.

Adenoviridae↗

PubMed1979

Medically-related absenteeism: random or motivated behavior?

The present study examined alternative measures of absence proneness related to organizationally-defined measures of absenteeism. A typical distinction among various types of absences is to separate medically-related absences from other types, since medically-related absences are believed to reflect random or unsystematic causes of behavior rather than voluntary choice behavior of the employee. The present study defined absence proneness as the degree to which individuals repeat their behavior. Three years of absence data for a sample of employees from one company were examined to discover the degree of absence proneness present in organizationally-defined forms of medically-related and voluntary absenteeism. In addition, a survey was administered to the sample to measure employee perceptions of work and non-work-related factors which were believed to be motivational determinants of absenteeism. A multiple discriminant analysis was developed in an attempt to classify employees to a survey designed to measure motivational determinants of absenteeism. The classification results supported the view that medically-related absenteeism has motivational determinants related to employee work and non-work preferences. Implications for management are discussed.

Absenteeism↗

PubMedDate not supplied

Survival after retirement.

A study of survival rates after retirement was conducted for a large corporation in the petroleum industry. A regression analysis was performed to control for age, sex, job status, and type of work differences that may influence longevity. Examination of the residuals showed a bimodal distribution: one group died (on the average) six and a half years after retirement, while the second group survived (on the average) nineteen years. Implications for health care management are discussed.

Aged↗