Search PubMed⌕ Search

Biomedical subjects

J A Edwards

Publications and source records attributed to J A Edwards.

120 records · Page 7Linked to original sources
PubMedDate not supplied

Antigenic structure of bovine growth hormone: location of a growth enhancing region.

Site-directed antisera generated by peptide immunization have been used to study the antigenicity of bovine growth hormone (bGH). Prediction of sequential antigenic sites has been performed using secondary structure information derived from the 'Protean' prediction routine. The structures predicted by this programme agree closely with the corresponding structure of GH recently derived from crystallographic studies. We have previously shown that the binding of monoclonal antibodies of particular epitope specificity to human or bovine GH results in significant enhancement of hormonal activity in vivo; however, the sites recognized by these antibodies were not known. Here we identify a sequence region, corresponding to a loop structure joining helices 3 and 4, which, is associated with the growth enhancement phenomenon. Antisera raised to either of two overlapping peptides (residues 120-140 and 134-154) significantly increase the biological activity of GH in vivo. Antisera directed to other regions on the GH molecule failed to demonstrate this property. Coincidentally, the sites recognized by the growth-enhancing anti-peptide antisera overlap with the site on GH which is highly susceptible to proteolytic cleavage; such cleavage has been shown in some cases to result in hormone enhancement.

Amino Acid Sequence↗
PubMedDate not supplied

O6-methylguanine-DNA methyltransferase in lymphocytes of the elderly with and without Alzheimer's disease.

Deficiency in DNA repair has been linked to aging, mutagenesis, carcinogenesis and several types of primary neuronal degeneration. O6-Methylguanine-DNA methyltransferase is a key enzyme in the repair of DNA alkylation damage that removes a methyl group from the O6 position of methylguanine. This study was carried out to determine whether there were any changes in the activity of this enzyme in lymphocytes of patients with Alzheimer's disease (AD) as compared to lymphocytes of age-matched non-demented elderly. The transferase activity in lymphocytes from 19 elderly patients with AD (mean 87.7 fmole/100 micrograms protein +/- SD 44.7) was not statistically different from that in 19 age/sex-matched controls (mean 91.3 fmole/100 micrograms protein +/- SD 40.0). There was no significant trend with age in transferase activity and the activity levels in the elderly subjects studied were the same as those reported previously for younger individuals by this laboratory. It is concluded that a reduction in O6-methylguanine-DNA methyltransferase activity is unlikely to be involved in the etiology or the pathogenesis of AD.

Age Factors↗
PubMedDate not supplied

Design and evaluation of a breath-analysis system for biological monitoring of volatile compound.

To ensure the health and safety of workers, integrated industrial hygiene methodologies often include biological monitoring of the workers to help understand their exposure to chemicals. To this end, a field-portable breath-analysis system was developed and tested to measure selected solvents in exhaled air. The exhaled breath data were evaluated using a physiologically based pharmacokinetic (PBPK) model to relate exposure to tissue dose. The system was designed to monitor workers every time they entered or left a work environment--a vast improvement over current 8-hour integrated monitoring strategies. The system combines (1) chemical dosimeters to measure airborne contaminant levels (analyzed in the field/ workplace); (2) real-time breath analysis to quantitate exposure; and 3) PBPK models to estimate internal target tissue dose. To evaluate the system, field tests were conducted at two locations: (1) at an incinerator in Tennessee monitoring benzene and toluene exposures; and (2) a waste repackaging facility in Washington State where hexane, trimethylbenzene, and methylene chloride was monitored. Exhaled breath was sampled and analyzed before and after each specific job task, which ranged from 15 min to 8 hours in duration. In both field studies several volunteers had posttask breath levels higher than pretask levels. The greatest increase corresponded to 573 ppb for methylene chloride and 60 ppb for toluene. Compared with breath analysis, the chemical dosimeters underpredicted the dosimetry, particularly for longer sampling intervals when the volume of air sampled may have diluted exposures. The results of the field studies illustrate the utility of monitoring workers for exposures throughout the day, particularly when job-specific tasks may indicate a potential for exposure.

Air Pollutants, Occupational↗
PubMedDate not supplied

A real-time in-vivo method for studying the percutaneous absorption of volatile chemicals.

Realistic estimates of percutaneous absorption following exposures to solvents in the workplace, or through contaminated soil and water, are critical to understanding human health risks. A method was developed to determine dermal uptake of solvents under non-steady-state conditions using real-time breath analysis in rats, monkeys, and humans. The exhaled breath was analyzed using an ion-trap mass spectrometer, which can quantitate chemicals in the exhaled breath stream in the 1-5 ppb range. The resulting data were evaluated using physiologically-based pharmacokinetic (PBPK) models to estimate dermal permeability constants (Kp) under various exposure conditions. The effects of exposure matrix (soil versus water), occlusion versus non-occlusion, and species differences on the absorption of methyl chloroform, trichloroethylene, and benzene were compared. Exposure concentrations were analyzed before and at 0.5-hour intervals throughout the exposures. The percentage of each chemical absorbed and the corresponding Kp were estimated by optimization of the PBPK model to the medium concentration and the exhaled-breath data. The method was found to be sufficiently sensitive for animal and human dermal studies at low exposure concentrations over small body surface areas, for short periods, using non-steady-state exposure conditions.

Animals↗
PubMedDate not supplied

Neural-immune interrelationship: effect of optic, sympathetic, temporofacial, or sensory denervation on the secretory immune system of the lacrimal gland.

Previous research has demonstrated that the nervous system may exert a significant impact on lymphocyte distribution and function in certain mucosal tissues. Given this neural-immune interaction, the present study was designed to evaluate whether ocular nerves might influence the distribution, density, and output of IgA-containing cells in the lacrimal gland. Male Sprague-Dawley rats were subjected to one of the following surgical protocols: denervation of the temporofacial, optic, or trigeminal nerves or ablation of the superior cervical ganglion. Denervations were performed on one side and sham-operations on the contralateral side. Additional groups of rats were exposed to bilateral sham or complete optic nerve disruption. Two to four weeks after surgery, tears were collected from individual eyes for the measurement of IgA and protein levels and lacrimal glands were processed for the immunofluorescent identification of IgA-containing cells. Our results showed that a marked heterogeneity is present in the frequency distribution of IgA-containing cells in lacrimal tissue sections of sham-operated rats. Statistical analysis of this distribution showed that the topographical location of IgA-containing cells per section or through the gland was not random. This heterogeneity did not appear to be modified by interrupting various nerves to the eye. Moreover, severance of the temporofacial, optic, or trigeminal nerve supplies or extirpation of the superior cervical ganglion did not significantly alter either the density or total number of IgA-containing cells in the lacrimal gland, as compared to values in contralateral "sham-operated" tissues. In addition, these neural disruptions had no apparent influence on the IgA content or the IgA/protein ratio in tears.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗