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Biomedical subjects

D Rowley

Publications and source records attributed to D Rowley.

At least 55 records · Page 3Linked to original sources

The correlation between serum IgA antibody levels and resistance to infection with Salmonella typhimurium after oral immunization with various salmonellae.

Subsequent to oral feeding of various Salmonella strains to mice, the IgA antibodies directed against the O-somatic antigens of the immunising strain were measured in both serum and intestinal juice, using the ELISA technique. 21 days after oral immunization the IgA antibody levels were relatively high only in those mice which were resistant to challenge with a virulent strain of Salmonella typhimurium. Because there was no correlation between protection and the specificity of the 'O' somatic antigens of the immunising and challenge strains, the IgA antibodies measured were not responsible for protection. Nevertheless, the level of these antibodies affords a good index of the resistance of mice or immune status of mice to Salmonella infection.

Administration, Oral↗

Intestinal absorption of bacterial antigens in normal adult mice. I. Preparation and characterization of the antigens.

The preparation of flagellin (FLA) from Salmonella adelaide and Boivin antigen (BA) from Vibrio cholerae is described. These two antigens differed chemically from each other and showed marked differences in their degradability by mouse intestinal juice in vitro and in their fate in the intact mouse when given intravenously. Unlike BA, FLA was rapidly degraded in intestinal juice and readily sequestered and degraded by the liver. The suitability of these antigens in oral absorption studies is discussed.

Animals↗

Intestinal absorption of bacterial antigens in normal adult mice. II. A comparative study of techniques.

Marked differences were seen in the oral absorption of Boivin antigen (BA) and flagellin (FLA) using antigens labelled by 3H-dinitrophenylation. Thus, after feeding 3H-DNP-FLA, a large proportion of the label was rapidly absorbed, concentrated and degraded by the liver so that no antigenic material could be recovered from the circulation. In contrast, the absorption of 3H-DNP-BA was low and slow; the absorbed material appeared stable and not readily taken up by the liver, so that 8-20% of the non-dialysable radioactivity found in the plasma was precipitable by specific antibodies. Such observations could not be made when 125I-labelled antigens were used: deiodination readily occurred in vivo, and there was re-utilization of the released label. On the other hand, using everted gut sacs, it was possible to recover 125I-labelled antigenic material after transport. A technique of measuring unlabelled antigen absorbed in the intact animal is also described, which detects antigen by combination with radioiodinated antibodies injected intravenously into the animal.

Animals↗

Cerebral and ocular toxicity induced by desferrioxamine.

Seven patients with rheumatoid disease were given the iron-chelating drug desferrioxamine (DFX) to evaluate its possible anti-inflammatory effects. Two of these patients, who also received the anti-emetic prochlorperazine, lost consciousness for 48-72 h and then fully recovered. Electroencephalography showed abnormalities of the type associated with metabolic disturbance. One of these patients showed pyramidal features and subsequently developed an optic neuropathy and pigmentary retinopathy. Analysis of his cerebrospinal fluid showed a decrease in loosely-bound (catalytic) iron and increase in loosely-bound (catalytic) copper, total iron and products of lipid peroxidation, with values approaching normal as the symptoms resolved. Subsequent in vivo/vitro studies clearly demonstrated that the neurological effects were due to a synergistic action of desferrioxamine and prochlorperazine, probably resulting in exceptional fluxes of intra/extra cellular iron/copper disturbing noradrenergic and serotonergic systems. Two other patients who did not receive prochlorperazine, developed retinal problems which later improved, one after only 15 g of desferrioxamine. Our observations suggest a new model for metabolic encephalopathy studies and provide insight into the mechanisms of pigmentary retinopathy.

Adult↗

Lipid peroxidation in rheumatoid arthritis: thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients.

Thiobarbituric acid (TBA)-reactive material is present in serum and knee joint synovial fluid from rheumatoid patients, consistent with lipid peroxidation occurring in vivo. The amount of TBA-reactive material in synovial fluid correlates with the concentration of iron salts present as determined by the bleomycin method, presumably because iron is an important catalyst of radical reactions in vivo. There appear to be significant correlations between the contents of TBA-reactive material and bleomycin-detectable iron in synovial fluid and the activity of rheumatoid arthritis as assessed with a clinical index of local inflammation and with various laboratory parameters.

Arthritis, Rheumatoid↗

Modulation of antibody responses to Vibrio cholerae in mice by adoptive transfer of Peyer's patch lymphocytes from orally immunised donors.

Peyer's patch lymphocytes from mice orally primed with V. cholerae injected into recipient mice together with V. cholerae led to a considerable suppression of IgM antibody-forming cells in the spleen by comparison with control mice receiving the same schedule but with Peyer's patch lymphocytes from unprimed mice. The effect on the splenic IgA responses of recipients was variable. Incomplete separation of the Peyer's patch cells showed that both T and B cell enriched fractions were active in this suppressive effect.

Animals↗

The role of antibody in the interaction of Salmonella and listeria with peritoneal macrophages.

That in vitro killing by normal and activated macrophages of S. typhimurium and other gram-negative organisms is dependent on the presence of antibody has been confirmed. It has been shown that antibody is required for the binding of S. typhimurium to the surfaces of macrophages. This binding can be inhibited by the Fc portion of immunoglobulin, indicating that the Fc receptors on macrophages are used for binding S. typhimurium. It has also been confirmed that antibody does not appear to be necessary for killing of L. monocytogenes to occur. The organisms bind to the surface of macrophages by different receptors. Binding of L. monocytogenes occurs in the absence of added antibody and Fc fragments of immunoglobulin do not affect the binding. Attachment can be inhibited, however, by removal of divalent cations, a treatment that has no effect on antibody-mediated binding as, under these conditions, the binding of L. monocytogenes to macrophages can be enhanced by antibody. The significance of these findings is discussed.

Animals↗

Local immunity to klebsiella pneumoniae in the lungs of mice.

The development of local immunity to Klebsiella pneumoniae in the lower respiratory tract is described. Immunity to intranasal infection is produced by systemic immunization resulting in high titers of circulating antibody. Protection also follows intranasal immunization with glutaraldehyde-killed organisms. Low levels of antibodies develop in serum after intranasal immunization. IgA antibody can be detected in the serum of these mice whereas little IgA antibody is detected in the serum of mice immunized systemically. Both IgA and IgG antibodies can be found in the pulmonary secretions of locally immunized mice. IgA and IgG from these secretions may be used to passively transfer protection when used to opsonize the infecting dose of K. pneumoniae. Protection mediated by IgA is not due to any interaction of IgA with cells present in the lower respiratory tract during infection, but exerts its protective effect in the upper respiratory tract, thereby preventing the spread of bacterial infection to the lower respiratory tract.

Administration, Intranasal↗

The role of the flagellum in the adherence of Vibrio cholerae.

The role of the flagellar structure in the in vitro adherence and in vivo colonization of Vibrio cholerae was studied by comparing the behavior of pairs of related motility variants. Although the presence of the flagellum seemed essential for in vitro attachment, the property of motility was neither necessary nor sufficient. Since it was possible to demonstrate independently both motility and binding capacities associated with this structure, it was concluded that the flagellum functions as the carrier of the moieties that promote adherence. Studies using the infant mouse cholera model unequivocally demonstrated the in vivo significance of a functional flagellum and suggested that this structure enhances virulence by facilitating the initial colonization of the small bowel.

Adhesiveness↗

The specificity of Vibrio cholerae adherence and the significance of the slime agglutinin as a second mediator of in vitro attachment.

The aim of the present studies was to clarify Vibrio cholerae adherence by elucidating the basis for the apparently variable nature of in vitro attachment. An examination of the purported specificity of vibrio adherence did not support the concept of host receptor structures; organisms selected for their capacity to adhere to inert substrates simultaneously acquired the capacity to bind to intestinal tissue in vitro. Further investigation of the bacterial factors involved in adherence confirmed the in vitro significance of the slime agglutinin, although this moiety appeared to have no pathogenic relevance. The conflicting descriptions of V. cholerae attachment are discussed in terms of the nature of the factor responsible for binding in each system.

Adhesiveness↗

Prophylactic significance of the nonlipopolysaccharide antigens of Vibrio cholerae.

The infant-mouse cholera model was used for evaluation of the immunoprophylactic significance of the nonlipopolysaccharide antigens of Vibrio cholerae. The protective efficiency of antibodies to the nonlipopolysaccharide components of the 569B strain was much greater than that of antibodies to the lipopolysaccharide. Protective nonlipopolysaccharide antigens were not detected in two other strains, however; the possible basis for this restricted distribution was considered in light of studies from other laboratories. An investigation of the mechanism by which antibodies mediate protection in this model suggested that the critical property of protective antibodies is their capacity to block vibrio attachment directly.

Animals↗

Resistance to Klebsiella pneumoniae and the importance of two bacterial antigens.

The resistance of mice to a lethal infection with Klebsiella pneumoniae, type I, was investigated. Antibody of both IgG and IgM class produced good protection when given with an intra-nasal inoculum of the organism. While antibody directed against capsular antigens was highly protective, so too was antibody directed against a second, non-capsular and heat-labile antigen. This antigen does not appear to be related to either the K or O antigens of Klebsiella and is present in several strains of Klebsiella. It is suggested that this antigen may play a role in determining resistance to this organism by humans.

Absorption↗

The effect of antibody on the intestinal absorption of macromolecules and on intestinal permeability in adult mice.

Oral immunization was shown to reduce the passage of bacterial antigen (BA) through the intestinal wall. The extent of the reduction found was dependent on the technique used for antigen assay, but with 125I-BA in an everted gut sac system, the amount of transported antigen was less than 60% of the amount in a control non-immune system. The inhibitory effect was due to coproantibodies which probably function by complexing and trapping the antigen in the mucous layer. This inhibition of antigen transport seems a prerogative of IgA antibodies since serum-derived antibodies caused concomitant adverse effects.

Aging↗

Processing of orally absorbed immunogen.

The absorption of immunogen from the adult mouse intestine was demonstrated. This was shown indirectly by the ability of oral doses of a bacterial antigen to prime an animal for an anamnestic, systemic response, and directly by the ability of absorbed material from the plasma in vivo or everted gut sacs in vitro to prime normal mice when injected intravenously. In all cases, the resultant, systemic response in the recipient animals was qualitatively different (presumably due to IgA production) from that obtained in mice primed intravenously with the native antigen.

Administration, Oral↗

Antibodies in serum and secretions 1 year after salmonella gastroenteritis.

The antibody response in serum and intestinal fluid in eight patients 1 year after their recovery from salmonella gastroenteritis was measured by solid phase radioimmunoassay and compared to the immune response within a few weeks of infection, reported previously in these and other patients. High concentrations of intestinal antibody were found in six patients compared to the concentrations found in 10 control subjects. By contrast the serum antibody concentration in the patients was only marginally higher than in the controls. The use of IgA and IgG specific antisera in the assay confirmed the presence of IgA antibody in the absence of IgG antibody in the gastrointestinal secretions, and the predominance of IgG antibody in the serum. The prolonged immune response in the gut after acute bacterial gastroenteritis supports the possibility of effective immunization against diseases entering via the gut.

Adult↗

Local cell-associated immunity in the Peyer's patches of mouse intestines.

After oral infection of mice with a Salmonella strain, low numbers of organisms could be found in the Peyer's patches of the small intestine. In the course of a few days the organism in the Peyer's patches multiplied to about 10(5) and then were steadily eliminated so that by 10 days, very few organisms could be found in the lymphoid follicles. Because no organisms could be found in the spleen or other organs during this period, it is probable that the decline in numbers was due to killing of the organisms in situ. This development of antibacterial ability was not inhibited by treatment with cyclophosphamide, in contrast to the rapid growth of organisms which occurred in the spleen after intravenous injection in the presence of cyclophosphamide. The difference in behavior between Peyer's patches and the spleen upon treatment with cyclophosphamide is explained in terms of the extent of natural priming of Peyer's patches due to continual contact of the intestine with gram-negative enteric organisms. Once the spleen was primed, cyclophosphamide did not interfere with the elimination of a second challenge with the same organism.

Animals↗