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Biomedical subjects

D A Fraser

Publications and source records attributed to D A Fraser.

At least 19 recordsLinked to original sources
PubMed2003

Interferon-gamma receptor-1 gene polymorphism in tuberculosis patients from Croatia.

Recent studies have indicated that the interleukin-12/interferon-gamma (IFN-gamma) axis is important in mycobacterial infection susceptibility. Using an intronic (CA)n polymorphic microsatellite marker within the IFN-gamma receptor-1 (IFNGR1) gene, we have compared the allelic frequencies of this marker in hospitalized tuberculosis patients (n = 120) with that of controls (n = 87) from Rijeka, Croatia. We identified 13 (CA)n alleles in the tuberculosis patients, whereas only 10 were found in the controls. A significant difference between one allelic marker and the control group was observed (P = 0.02, 95% confidence interval 0.14-0.94), suggesting a possible protective association. In contrast, several other allelic markers showed a trend towards association with the disease. We also found a trend towards an increased frequency in homozygosity of one allelic marker in patients (11.7%) as compared with controls (4.6%). We conclude that there is no evidence for disease association of the IFNGR1 gene marker in Mendelian-type (single-allele) inheritance. However, our results also suggest that unidentified allelic variations in the IFNGR1 gene might elevate or decrease the risk in this ethnic population, as a part of the multigenic predisposition to tuberculosis.

Adult↗
PubMed2002

Tailoring anti-complement therapeutics.

Complement is a core component of the immune system, which performs vital roles in immune surveillance. However, the active products that enable complement to perform its physiological roles can inappropriately target self tissues and cause pathology. Complement-mediated inflammation and tissue destruction is an important drive to pathology in diseases as diverse as rheumatoid arthritis and dementia. Two decades ago there were no agents that could be used therapeutically to inhibit the activation of complement, but increased understanding of the natural control of complement in vivo has markedly changed this situation. The realization that drugs mimicking the action of the complement regulatory proteins present on self cells, and in plasma, could effectively control pathological activation of complement has opened the door to the use of anticomplement therapy in disease. Here we will review the development of anticomplement therapeutics from the first generation agents, which are unmodified recombinant forms of natural regulators, to recent strategies for making better drugs. We will describe strategies for targeting the anticomplement activity to the site of disease, and for extending the plasma half-life of the agent. Finally, we will illustrate a novel approach to the delivery of anticomplement agents, making prodrugs that are activated only at disease sites thus minimizing the deleterious effects of systemic complement inhibition.

Animals↗
PubMed2001

A preliminary study of circadian serum cortisol concentrations in response to a 72-hour fast in rheumatoid arthritis patients not previously treated with corticosteroids.

The aim of the study was to investigate the effects a 72-h fast upon serum total and free cortisol concentrations in RA patients not previously treated with glucocorticoids. Total serum cortisol and transcortin concentrations were measured in four RA patients with active disease at 4-h intervals during two 24-h periods (1200 h-1200 h), the first while eating a normal diet (fed state) and the second during the last 24 h of a 72-h water fast. Free cortisol concentrations were calculated from the total cortisol and transcortin values. The 3-day fast increased overall 24-h free and total cortisol concentrations by 50% and 35%, respectively. This was due largely to a marked increase in nocturnal serum cortisol concentrations during fasting, particularly at 0400 h, when mean total and free cortisol levels were increased by 170% and 260% compared to the fed state. Between 2000 and 0800 h overall total- and free cortisol concentrations were increased by 72% and 99%, respectively. These results suggest that an increase in nocturnal concentrations of cortisol occurs in response to fasting in RA patients not previously treated with glucocorticoids. These increases may mediate the beneficial clinical response previously found in studies of longer fasting periods in RA patients.

Adult↗
PubMed1999

Decreased CD4+ lymphocyte activation and increased interleukin-4 production in peripheral blood of rheumatoid arthritis patients after acute starvation.

We investigated the effects of acute starvation on mitogen-induced T-cell activation and Th1/Th2 cytokine responses in rheumatoid arthritis (RA) patients. Ten RA patients with active disease underwent a 7-day fast followed by a 2-week refeeding period. Immunological, hormonal, laboratory and clinical evaluations were carried out on days 0, 7 and 21. Using flow cytometry, mitogen-stimulated T-cell activation was assessed in fresh heparinised blood via analysis of CD69 expression. Production of Th1 (interferon-gamma) and Th2 (interleukin-4, IL-4) cytokines was also assessed by ELISA. The 7-day fast significantly decreased the erythrocyte sedimentation rate, C-reactive protein level, joint count, morning stiffness, body weight, CD4+ and CD8+ counts and CD69+ expression on mitogen stimulated CD4+ lymphocytes. A significant increase in mitogen-induced IL-4 production after fasting was found. The fast markedly reduced serum leptin and insulin-like growth factor-1 concentrations. No significant differences occurred in serum cortisol or prolactin before and after fasting. Decreases in CD4+ lymphocyte activation during fasting correlated with decreases in body weight. Our results suggest that the clinical and laboratory improvements in fasting RA patients may be attributed to decreased CD4+ T-cell activation and an increase in the number and/or function of IL-4-producing Th2 cells. Factors associated with loss of body weight during acute starvation appear to have an inhibitory effect on CD4+ lymphocyte activation.

Adult↗
PubMed1999

Changes in plasma free fatty acid concentrations in rheumatoid arthritis patients during fasting and their effects upon T-lymphocyte proliferation.

OBJECTIVE: To measure whether changes in the concentrations of circulating free fatty acids (FFAs) after a 7 day fast in rheumatoid arthritis (RA) patients would inhibit in vitro T-lymphocyte proliferation. METHODS: The concentration and composition of plasma FFAs were measured in nine RA patients at the conclusion of a 7 day fast. A FFA mixture was made up based on these findings (20% linoleic, 43% oleic, 10% stearic, 27% palmitic acid). Mitogen-induced lymphocyte proliferative responses were measured after co-culture of peripheral blood mononuclear cells (PBMC) from healthy individuals in the presence of increasing concentrations of this FFA mixture (from 0 to 2000 microM) and in the presence of FFA mixtures where the relative proportions of fatty acids varied. RESULTS: Both the concentration of the FFA mixture and the ratio between the unsaturated and saturated fatty acids significantly influenced in vitro lymphocyte proliferation (P<0.0001). Unexpectedly, the highest concentrations of the FFA mixture increased lymphocyte proliferation. At equimolar concentrations (600 microM), manipulating the amounts of oleic and linoleic fatty acids relative to stearic and palmitic fatty acids had a potent inhibitory effect upon lymphocyte proliferation. CONCLUSION: Fasting-associated increases in total plasma FFA concentrations do not inhibit, but rather enhance, in vitro lymphocyte proliferation. An inhibitory effect could only be achieved by manipulating the balance between the unsaturated and saturated fatty acids.

Adult↗
PubMed1980

Passive dosimetry using detector tubes.

Detector tubes for toluene were cut to produce a nominal 0.5 cm orifice above the indicator material, and exposed to known vapor concentrations. The time needed to reach a pre-determined stain length by simple diffusion was measured. Calibration charts were prepared for time versus concentration for a 1 mm stain, as well as for various stain lengths. Tests were performed to determine the effect of increasing the orifice length and of diffusion through the glass wool plug. Each of these parameters resulted in less reliable concentration measurements than tubes of relatively shorter orifice length having no glass wool plug. Diffusion theory was used to develop theoretical calibration charts for comparison with experimental results, with the former underestimating necessary for appearance of the experimentally observed stains. The use of detector tubes having an orifice length of 0.5 cm as passive dosimeters is shown to be highly feasible based on experimental results.

Equipment and Supplies↗
PubMed1977

Air sampling and analysis in a rubber vulcanization area.

Results of sampling and analysis of air in a rubber vulcanization area are described. Organic compounds were collected on activated charcoal, desorbed with carbon disulfide and analyzed by gas chromatography. Several previously identified substances were quantitated, including styrene, toluene, ethylbenzene, and several oligomers of 1,3-butadiene. Concentrations ranged from 0.007 to 1.1 ppm.

Air Pollutants↗
PubMed1976

A model for deposition of fibers in the human respiratory system.

A mathematical model for estimating lung deposition of fibers is described. It is based on the aerodynamic behavior of thin straight rods. Predicted deposition values for rods of various equivalent aerodynamic diameters and lengths, for each of three tidal volumes and for each of three respiratory system compartments are reported.

Bronchi↗
PubMed1976

Health aspects of the curing of synthetic rubbers.

A commonly used tread rubber formulation was cured in the laboratory under conditions simulating vulcanization in the Bag-O-Matic press. Volatile emissions were collected on charcoal and analyzed by combined GC-mass spectrometry. The compounds identified were either contaminants present in the raw material or reaction products. Some of these compounds were also identified in charcoal tube samples collected in the atmosphere of the industrial operations. Estimates based on the loss of weight of rubber during curing were used to predict airborne concentrations and compared to the concentrations actually found. The literature of the toxicity of raw materials and effluents was reviewed, and no acute or chronic toxicological effects would be anticipated. Information concerning potential carcinogenicity was not available and could not be evaluated.

Air Pollutants, Occupational↗