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Biomedical subjects

R A Thompson

Publications and source records attributed to R A Thompson.

At least 19 recordsLinked to original sources

Direct liquid chromatographic separation of enantiomers on immobilized protein stationary phases. IX. Influence of the cross-linking reagent on the retentive and enantioselective properties of chiral sorbents based on bovine serum albumin.

Three modifications of silica-bound, cross-linked bovine serum albumin (BSA) were evaluated as chiral sorbents for use in the liquid chromatographic separation of enantiomers. Glutaraldehyde, formaldehyde and di-(N-succinimidyl) carbonate were used as bifunctional reagents for the immobilization of BSA. The sorbents all contain the same loading of BSA (14.4 +/- 0.1%, w/w) and differ only with respect to the cross-linker used for immobilization. Despite their apparent similarity, the sorbents show very different chromatographic properties, not only with respect to retention of analyte enantiomers (k' and alpha), but also with respect to column efficiency (affecting Rs values). The data obtained indicate that the chemical structure of the cross-linking reagent affects to a large extent the accessibility of important chiral binding sites. Although the data obtained are difficult to interpret in any detail, certain generalizations concerning the different behaviour of the sorbents can be made.

Albendazole

Endothelium myeloperoxidase-antimyeloperoxidase interaction in vasculitis.

Antibodies to myeloperoxidase (MPO) are found in the sera of patients with microscopic polyarteritis and idiopathic crescentic glomerulonephritis. Their pathogenicity is unknown. Studies were carried out on the binding of MPO to cultured human umbilical vein endothelial cells and the recognition of endothelium-bound MPO by antibody to MPO. Endothelial cells were cultured from human umbilical veins. The binding of MPO to endothelial cells and its inhibition by poly-D-lysine was detected using a monoclonal antibody to MPO and direct staining with APAAP and also by an enzyme-linked immunoassay (ELISA). The binding of anti-MPO antibody in the sera of patients with microscopic polyarteritis to endothelium-coated MPO was detected by ELISA. MPO bound to endothelial cells both on direct staining and ELISA and this binding was inhibited by the polycation poly-D-lysine, suggesting that it was charge mediated. Binding of anti-MPO antibody in the sera of patients with microscopic polyarteritis to endothelium-coated MPO was significantly higher than the binding of sera from normal subjects (P = 0.04), patients with idiopathic glomerulonephritis (P = 0.0005), and patients with lupus nephritis (P = 0.009). MPO binds to cultured human umbilical vein endothelium probably by a charge mechanism, and can react with anti-MPO antibodies in the sera of patients with microscopic polyarteritis as well as with a mouse monoclonal anti-MPO antibody. This binding of anti-MPO antibody to MPO fixed to the endothelial cell surface provides a mechanism by which endothelial injury and inflammation might occur in microscopic polyarteritis.

Endothelium, Vascular

Lymphokine-activated killer (LAK) cells. V. 8-Mercaptoguanosine as an IL-2-sparing agent in LAK generation.

Guanine ribonucleosides, substituted at the C8 position with either a bromine or a thiol group, have recently been shown to regulate several immunologic responses. We have previously shown that 8-mercaptoguanosine (8MG) can replace the requirement for cytokines in the generation of MHC-restricted CTL. In this paper, we examined the ability of 8MG to induce MHC-nonrestricted killer cells. We found that 8MG did not induce significant lytic activity from normal resting lymphocytes. However, 8MG was able to synergize with minimal amounts of IL-2 in inducing lytic activity similar to lymphokine-activated killers (LAK) in that both NK-sensitive and NK-resistant tumor cells were killed. Both the precursors and effectors of 8MG-LAK activity were similar to NK cells and were CD4- CD8- asialo-GM1+ NK1.1+. Similar to IL-2-induced LAK, 8MG-LAK were B220+. 8MG appeared to "stage" these precursor lymphocytes to become more responsive to IL-2 because optimal induction of 8MG-LAK required preincubation with 8MG before the addition of IL-2. This "staging" appeared to be due to the release of a "second signal" since it was readily inhibited by cyclosporine A. Anti-IFN-alpha beta was as efficient as cyclosporine A in inhibiting 8MG-LAK generation, whereas anti-IFN-gamma and anti-IL-1 did not exhibit significant inhibition. These findings suggest that 8MG can be of possible utility as an IL-2-sparing agent in LAK generation from NK cells.

Adjuvants, Immunologic

Is faecal alpha 1-antitrypsin excretion a reliable screening test for protein-losing enteropathy?

Estimation of alpha 1-antitrypsin in random faecal samples has been suggested as a reliable index of intestinal protein loss. There was a poor correlation between faecal alpha 1-antitrypsin concentrations and simultaneously measured faecal loss of 51Cr-albumin in twenty adults with suspected protein-losing enteropathy. This indicates that faecal alpha 1-antitrypsin estimation may not be a valid screening test for protein-losing enteropathy.

Adolescent

Long-term parenteral exposure to mercury in patients with hypogammaglobulinaemia.

Patients with hypogammaglobulinaemia commonly receive regular long-term replacement therapy with a concentrate of pooled normal human immunoglobulin G (IgG) containing an organic mercury compound (thiomersal) as a preservative. In 26 such patients the total estimated mercury dosage received ranged from 4 to 734 mg (mean 157 mg) over treatment periods of six months to 17 years (mean 6.5 years). Nineteen patients (73%) had raised urine mercury concentrations, but no correlation was found between urine mercury and the age of the patient, the IgG dose, or the duration of treatment. Urine mercury concentrations are often used to control exposure and evaluate risks in exposed subjects. Hence most patients with hypogammaglobulinaemia are theoretically at risk from mercury exposure, although no clinical evidence of toxicity is yet apparent.

Adolescent

Epidemiologic survey of sylvatic plague by serotesting coyote sentinels with enzyme immunoassay.

The geographic distribution and areas of high sylvatic plague activity in California were verified by using coyotes (Canis latrans) as sentinel animals. Antibody levels against Yersinia pestis were tested using the enzyme-labelled antibody (ELA) test and the microtiter passive hemagglutination and hemagglutination inhibition. A survey using the ELA test indicated that the overall antibody prevalence among 143 coyotes was 21%. By geographic regions, the highest antibody prevalence was 27% among coyotes from mountain areas on the northern and eastern borders of the state. This was followed by 19% in the central coastal area and 12% in the central valley. Areas with a high prevalence of seropositive coyotes or high antibody levels in individual coyotes matched the four areas of human plague exposures reported in 1977 and 1978. These areas included the central Sierra mountains adjacent to Lake Tahoe, southeastern Kern County, the central coastal area and Scott Valley near the Oregon border. The ELA test appears to be a promising tool for future epidemiologic studies of plague.

Animals

Genetic basis of acquired C4 deficiency.

A study of the family of a patient who had an SLE-like syndrome and an extremely low serum C4 revealed an inheritance of C4 types and HLA region markers which indicated that the patient had 60--70% of "normal" C4 level prior to the onset of disease. Thus the extremely low C4 level during her disease may result from a combination of genetically determined low normal C4 and increased consumption/hyposynthesis secondary to her SLE.

Adult

Significance of serum complement levels in patients with gastrointestinal disease.

Levels of the serum complement components, C3 and C4, in patients with Crohn's disease, ulcerative colitis, and miscellaneous gastrointestinal disorders were compared with those of normal blood donors. Significant increases of both components were found in all three patient groups, the highest being in patients with Crohn's disease. Generally, levels of C3 and C4 were lower in patients with inactive rather than active Crohn's disease and ulcerative colitis. These results provide some evidence in support of an immunological basis for inflammatory bowel disease. However, in view of the frequent elevation of C3 and C4 in other gastrointestinal diseases, it is equally possible that the complement components are behaving as acute phase proteins.

Blood Donors

Complement changes during exercise-induced asthma.

Two groups of asthmatic children, one with and one without a history of post-exercise wheezing, and one non-asthmatic adult, were exercised on a treadmill, and their complement levels were measured before and after exercise. The first group of patients had the most obvious fall in FEV 1 and all showed a slight rise in haemolytic complement following exercise. Two of the patients of the second group also had a rise in haemolytic complement. The C4 titre did not change in any of the asthmatic children who did not wheeze after exercise, but there were changes, albeit inconsistent, in the titres of C4 in four of the six patients who exhibited post-exercise wheezing. C3 breakdown products were not detected in any of the sera, following exercise. The role of complement in exercise-induced bronchospasm is not clear, but there does appear to be a greater lability of the complement system in patients who are susceptible to this form of provocation.

Asthma