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Biomedical subjects

D Rowley

Publications and source records attributed to D Rowley.

At least 37 records · Page 2Linked to original sources

Decreasing trends in Reye syndrome and aspirin use in Michigan, 1979 to 1984.

The incidence of Reye syndrome has been decreasing in Michigan, perhaps as a result of decreased aspirin use among children. To evaluate possible changes in the frequency of aspirin use, 199 families in Tecumseh, MI, with children younger than 18 years of age were interviewed by telephone in February 1981 and again in February 1983. Based on the reported use of medications for colds or influenza between 1981 and 1983, fewer parents gave aspirin (56% v 25%), but acetaminophen use did not change (59% v 55%). Younger parents and parents who had heard of the association between aspirin and Reye syndrome were more likely to stop giving aspirin. More parents chose to use either no medication or medications containing neither aspirin nor acetaminophen (6% v 32%) for the treatment of colds or influenza. Approximately 90% of parents who chose not to give aspirin for fever also gave medications for colds or influenza that did not contain aspirin. These results suggest that fewer children are receiving aspirin during illnesses that may precede Reye syndrome. The associated decrease in the incidence of Reye syndrome tends to support the hypothesis that the use of aspirin increases the risk for the development of Reye syndrome.

Acetaminophen

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

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

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

The suppressive effect of circulating specific antibody on the response to oral immunisation with Vibrio cholerae.

Species IgG antibody given intravenously 3-4 hours prior to oral immunisation with Vibrio cholerae led to a specific depression of both the systemic and loca limmune response. One vibriocidal unit of IgG antibody, which itself would given undetectable levels of circulating specific antibody, was significantly immunosuppressive. The suppression is considered to be due to central repression of the antigen-reactive lymphocyte, rather than to antigen exclusion at the gut mucosal surface. The repression appeared less pronounced in some immunoglobulin classes than in others.

Administration, Oral

Clearance of bacteria from lungs of mice after opsonising with IgG or IgA.

The clearance of organisms from the lungs of mice was followed after aerosol administration. Preopsonisation of the organisms with immune serum, as a source of specific antibody, enhanced the rate of pulmonary clearance while s.IgA delayed clearance. In the peritoneal cavity, bacteria pre-treated with immune serum were cleared more rapidly than unopsonised bacteria, but s.IgA had little effect. The presence of Fc receptors for IgG and not s.IgA on alveolar macrophages suggests that, in secretions, IgG is the predominant antibody promoting phagocytosis by alveolar macrophages and that any protective effect of s.IgA is not mediated by these cells.

Animals

Local immune response in mice to Vibrio cholerae.

Cholera immunization schedules were investigated in mice, with emphasis placed on obtaining an immune response in the intestine. The most effective schedule for producing a good local response was found to be several orally-given priming doses of the organism followed after 14 days by an intravenous boosting dose. Major differences between the immune responses in the spleen and the intestine were noted.

Animals

Persistence in the mouse gut as an important factor in oral immunogenicity of strains of V. cholerae.

The immune responses of mice following oral vaccination with two strains of live V. cholerae have been examined. A strain which persisted in the small intestine was a superior local immunogen by comparison with another non-persisting strain. Local persistence and the ability to induce a local immune response appeared to be correlated, since the two vibrio strains elicited identical responses when given parenterally.

Administration, Oral

Intestinal antibody to Vibrio cholerae in immunised mice.

The immune response of the mouse to priming and booster doses of V. cholerae was studied to establish whether serum antibody could be used as a correlate of local immunity. Serum antibody titres following oral boosting of orally-primed animals were shown to reflect the state of local intestinal immunity. This was not the case when the same oral booster dose was given to parenterally-primed animals. These results were discussed in relation to the human endemic situation. The highest titres of intestinal protective antibodies were found following combination of the oral and parenteral routes of immunisation. Various killed or extracted preparations of V. cholerae were used as oral vaccines to test their ability to induce protective antibodies in the gut. Only Boivin antigen was capable of inducing as good an intestinal antibody response as would the living organism.

Administration, Oral

Intestinal and serum antibody responses in mice after oral immunization with Salmonella, Escherichia coli, and Salmonella-Escherichia coli hybrid strains.

After oral feeding of mice with avirulent Salmonella, Escherichia coli, or hybrid strains, only certain bacterial strains were able to multiply and persist within the small intestinal Peyer's patches. After oral vaccination alone, or oral priming and subsequent parenteral boosting, antibody class and titers were detected, using a radioimmunoassay on serum and intestinal fluid or a plaque-forming cell assay on spleens. Only those strains that persisted in the Peyer's patches stimulated the production of serum and intestinal immunoglobulin A antibodies against their respective O antigens. Nonpersistent strains were weakly immunogenic, and antibodies, when present, were largely non-immunoglobulin A and confined to the serum.

Animals

Modifications of the local immune response to Vibrio cholerate attributed to the intestinal microbial flora of the mouse.

Oral immunisation studies in germfree, specific pathogen-free (SPF) and conventionalised mice illustrated that the autochthonous gut flora can have a suppressive effect on the induction of a local intestinal immune response to Vibrio cholerae. Temporary colonisation of the small bowel by viable vibrios occurred only in the germfree animal. The lack of colonisation in SPF and conventionalised mice was presumably a cause of their lower coproantibody responses. Prevention of colonisation was probably due to bacterial antagonism rather than to cross-reaction antibodies. This conclusion was reinforced by studies involving oral immunisation of SPF mice maintained on streptomycin, and of conventionalised ex germfree mice. In addition to the increased protective coporantibody response of animals with reduced gut flora, there were increased levels of non-complement-fixing protective antibodies in their serum, which were probably derived from the guy lamina propria.

Animals

In vitro degradation of mouse, rabbit and dog antibodies to Vibrio cholerae by succus entericus.

Purified antibodies to Vibrio cholerae from mouse, rabbit and dog were digested in vitro by homologous intestinal secretions. When assessed with regard to their complement-dependent vibriocidal activity, IgG antibodies were generally more susceptible to degradation than IgM antibodies, High levels of tryptic inhibitors were required to inhibit this digestion. Rabbit IgG was unusual in being quite resistant to digestion. Gel filtration studies demonstrated that secretory IgA, isolated from mouse intestinal secretions, was resistant to proteolysis. Similar studies on dog IgG and mouse IgM demonstrated production of F(ab') 2-like fragments. Digestss of these antibodies, while devoid of Fc-mediated vibriocidal activity, retained significant protective activity for baby mice.

Animals