PubMed Health⌕ Search

Biomedical subjects

G W Parker

Publications and source records attributed to G W Parker.

At least 19 recordsLinked to original sources
PubMed2000

Anthrax vaccine: increasing intervals between the first two doses enhances antibody response in humans.

The influence of dosing interval on the human antibody response to anthrax vaccine adsorbed (AVA) was evaluated in two retrospective serological studies. In both studies, the interval between the first two doses was 2, 3 or 4 weeks. In the first study, banked sera were selected from 89 at-risk individuals at a mean time of 13 days after the second dose of vaccine. In the second study, banked sera were selected from 51 at-risk individuals at a mean time of 48 days following the first dose of AVA. In both studies, the geometric mean anti-protective antigen IgG antibody titer increased significantly as the interval between the two doses increased from 2 to 4 weeks (p=0.0005-0.029). In the first study, the seroconversion rate also increased as the interval between the first two doses increased (p=0. 0034). A prospective, randomized study has been completed and is being analyzed to confirm these findings.

Antibodies, Bacterial↗
PubMed1996

Effect of 3,4-diaminopyridine on rat extensor digitorum longus muscle paralyzed by local injection of botulinum neurotoxin.

The actions of the K+ channel blocker, 3,4-diaminopyridine (3,4-DAP), were studied in the rat extensor digitorum longus (EDL) muscle following local inhibition of neuromuscular transmission by botulinum neurotoxin (BoNT). Local paralysis of the EDL muscle was induced by s.c. injections of BoNT serotypes A, B, E or F over the anterior tibialis muscle. One to 14 days later, the rats were anesthetized with urethane, and isometric twitch tensions following stimulation of the peroneal nerve were measured in situ. Muscles were paralyzed within 24 hr of administration of 5 mouse LD50 units (U) of BoNT/A and remained inhibited for the entire 14-day period of observation. Similar levels of inhibition, but of shorter duration, were observed after local injection of 20 U of BoNT/E, 10(4) U of BoNT/B or 20 U of BoNT/F. 3,4-DAP (4 mg/kg, i.v.) potentiated twitch tensions markedly in BoNT/A intoxicated muscle. The increase in tension developed rapidly (halftime = 5.81 +/- 0.6 min), persisted for approximately 1 hr, then decayed slowly with a halftime of 25.2 +/- 4.6 min. Subsequent administration of 3,4-DAP restored tensions to the original maxima, and this procedure could be repeated up to eight times with no decrement. The action of 3,4-DAP was comparable when given 1, 2, 3 or 7 days after BoNT/A and enhanced when administered 14 days after toxin injection. 3,4-DAP was less effective in reversing BoNT/E-induced muscle paralysis and nearly ineffective in antagonizing the paralytic actions of BoNT/B or BoNT/F. The results indicate that 3,4-DAP is of benefit in BoNT/A and BoNT/E intoxication, but is of marginal value after exposure to serotypes B and F.

4-Aminopyridine↗
PubMed1995

Regulation of staphylococcal enterotoxin B-elicited nitric oxide production by endothelial cells.

The effect of staphylococcal enterotoxin B (SEB)-elicited inducible nitric oxide synthase (iNOS) in mouse endothelial cells was investigated. Results showed that SEB stimulated the same level of NO production in gamma interferon (IFN-gamma)-primed cells as did trichloroacetic acid-extracted lipopolysaccharide. The kinetics of induced NO production and expression of mRNA for iNOS differed markedly in endothelial and macrophage cells. Induced endothelial nitrite production was transient and was 15 to 20% of that generated by macrophage cells; mRNA levels peaked by 2 h and then steadily declined, whereas macrophage message levels continually increased. The ability of endothelial cells to produce SEB-induced NO depended on priming with IFN-gamma, although detectable mRNA could be elicited by SEB alone. Induction of endothelial iNOS mRNA was inhibited by cycloheximide, which indicated a requirement for de novo protein synthesis. Niacinamide and interleukin-10 significantly reduced SEB-induced endothelial NO production. Both are reported to affect IFN-gamma-induced class II major histocompatibility complex (MHC) expression on antigen-presenting cells. Niacinamide reduced iNOS mRNA levels and markedly reduced IFN-gamma induction of endothelial class II MHC surface antigen. Interleukin-10 did not consistently reduce iNOS mRNA expression and had no effect on IFN-gamma induction of endothelial class II MHC surface antigen. These results suggest that SEB interacts with IFN-gamma-primed endothelial cells to elicit induced NO and that this induction can be effectively modulated at the receptor or transcriptional level.

Amino Acid Oxidoreductases↗
PubMed1991

Non-specific binding of palytoxin to plastic surfaces.

The changes in blood pressure induced by palytoxin (PTX) administered intravenously through polyethylene (PE) tubing were varied, suggesting either non-specific binding of the toxin to PE or deactivation. By spectrophotometry and HPLC, we found that PTX bound non-specifically to PE tubing and that this binding was attenuated by adding 0.1% rat serum albumin. Furthermore, the chemical stability and activity of PTX were not affected by exposure to room light and/or room temperature. Biological deactivation was excluded as a cause of the observed variability because the hypertensive and lethal effects of infused PTX, delayed with simultaneous administration of sodium nitroprusside (NNP), were in full evidence when the NNP was discontinued 35 min later.

Acrylamides↗
PubMed1990

Central beta-adrenergic mechanisms may modulate ischemic ventricular fibrillation in pigs.

A central noradrenergic process may permit expression of the stress-related increase in cardiac vulnerability to ventricular fibrillation (VF). Thus, the effect of central beta-adrenergic receptor blockade with L-propranolol (0.01 and 0.05 mg/kg) on ischemia-induced VF vulnerability was evaluated in the psychologically stressed pig model and compared with Ringer's solution and D-propranolol (0.05 mg/kg). The ischemia of a maximum 15-minute left anterior descending coronary artery occlusion was used since we previously determined that pigs surviving 15 minutes usually do not fibrillate. Time to the onset of VF was analyzed by time-to-event analysis and ranged from 0.75 to 13.8 minutes in vulnerable pigs. Intracerebroventricular administration of L-propranolol (0.05 mg/kg) prolonged the time to VF compared with Ringer's solution and D-propranolol (p less than 0.05). The high dose of L-propranolol also reduced the incidence of VF (7/15 fibrillated) compared with Ringer's solution (12/12 fibrillated) and D-propranolol (6/7 fibrillated). The lower dose of L-propranolol was without effect on VF vulnerability (7/9) fibrillated). The plasma concentration resulting from central administration of 0.05 mg/kg L-propranolol was found to be 9.05 +/- 3.25 ng/ml, which is significantly below therapeutic antiarrhythmic blood levels. We conclude that the reduced vulnerability to ischemia-induced VF after intracerebroventricular administration of propranolol is due to alteration of a central beta-adrenergic receptor-mediated phenomenon as opposed to an effect on the heart directly or to nonspecific membrane stabilization.

Adaptation, Physiological↗
PubMed1987

An animal model to examine the response to environmental stress as a factor in sudden cardiac death.

Sudden cardiac death is the leading mode of death in adults in the United States. While it appears intimately associated with coronary artery disease, the factors that render some subjects vulnerable to sudden cardiac death, while others with the same coronary disease do not die suddenly, are unknown. An approach is described which considers that sudden cardiac death represents a separate syndrome of coronary artery disease within certain vulnerable subjects. It is suggested that the response to psychosocial stress in vulnerable subjects results in deleterious cerebral cortical influences on the autonomic control of the heart which render it more vulnerable to ischemia-induced ventricular fibrillation. Studies in the pig, an animal known to be susceptible to sudden death resulting from an environmental stress, demonstrate that cerebral cortical influences on autonomic centers play a central role in vulnerability to ventricular fibrillation after coronary artery occlusion. In this model, the incidence of ventricular fibrillation can be reduced by psychologic adaptation of the animal to his environment, cryoblockade of frontal cortical brain stem pathways and by central administration of propranolol. The relative role of adrenergic and cholinergic innervation of the heart is an important consideration.

Animals↗
PubMed1981

17 beta-estradiol stimulation of uterine blood flow in oophorectomized rabbits with complete inhibition of uterine ribonucleic acid synthesis.

The 17 beta-estradiol-induced increase of uterine blood flow (UBF) was studied in 7- to 8-month-old oophorectomized rabbits 6-39 days after operation. Baseline blood flows were determined with 141Ce-labeled microspheres and 2-h flows with 85Sr-labeled microspheres. Mean UBF in control groups ranged from 0.11-0.26 mi/min . g. Mean UBF 2 h after 17 beta-estradiol (10 microgram/kg BW) was 1.51 ml/min . g. Utilizing [3H]uridine (100 microCi/kg 15 min before the 2-h flow study), 3H incorporation into uterine RNA was 2-fold higher than background. Estradiol treatment produced a 4-fold increase in 3H incorporation into uterine RNA. Estradiol-treated animals, pretreated with actinomycin D (4 mg/kg), increased UBF to 1.09 ml/min . g 2 h after estradiol but failed to increase uterine RNA synthesis. 3H incorporation into uterine RNA in this group was suppressed to undetectable (background) levels. These findings indicate that a mechanism other than accelerated transcription, whether induced directly or by translocation of a cytosolic receptor, underlies the increased UBF after estradiol administration to oophorectomized rabbits.

Animals↗