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Biomedical subjects

D C Henderson

Publications and source records attributed to D C Henderson.

At least 73 records · Page 4Linked to original sources

Suppression of murine IgE responses with amino acid polymer/allergen conjugates. III. Activity in vitro.

Conjugates of poly-N-methylglycine (polysarcosine) and grass pollen allergen extracts, which have been previously shown to suppress murine IgE responses, were examined for their ability to modify lymphocyte activity in vitro. Allergen-specific T lymphocytes obtained from Balb/c mice gave a reduced response to syngeneic accessory cells pulsed with conjugates of polysarcosine-allergen compared with the response found using equivalent concentrations of native extract. Pretreatment of accessory cells with either polysarcosine or polysarcosine-allergen conjugates did not impair their subsequent ability to present grass pollen extract to immune T cells. Incubation of allergen-specific spleen cells with polysarcosine-allergen conjugates, but not with polysarcosine or allergen alone, resulted in specific cell-mediated suppression which significantly reduced proliferation in vitro. This activity was sensitive to treatment of cells with anti-T-lymphocyte antisera plus complement. Spleen cells obtained from animals immunised with allergen and taken 21 days after intravenous treatment with polysarcosine-allergen conjugates, a regimen that suppressed IgE antibody production, did not proliferate in the presence of grass pollen extract and failed to suppress a secondary lymphoproliferative response in vitro. Spleen cells obtained from similarly treated animals 3 days after the final polysarcosine-allergen injection responded to pollen extract in culture and, additionally, impaired a secondary response. The results suggest that the reduced IgE response found in animals treated with polysarcosine-allergen conjugates may be due, in part, to the generation of a short-lived antigen-specific T cell suppression.

Allergens↗

Suppression of murine IgE responses with amino acid polymer/allergen conjugates. IV. Suppressive activities in established IgE model systems.

Conjugates of poly-N-methylglycine (polysarcosine) and grass pollen extracts, previously found to be capable of suppressing immature IgE antibody responses in mice, were shown to be highly effective at inhibiting the capacity of immune splenocytes to produce a secondary response in sub-lethally irradiated recipient animals. Anamnestic IgE responses in mice primed without adjuvant were also suppressed, but the effects were modest and of short duration. The predictive value of murine models for selecting clinically appropriate specific IgE suppressive agents and treatment schedules that might be successfully employed for clinical use are discussed.

Allergens↗

Suppression of murine IgE responses with amino acid polymer/allergen conjugates. II. Suppressive activities in adjuvant-induced IgE responses.

Treatment with conjugates of polysarcosine and grass pollen allergen extracts efficiently suppressed the induction of IgE responses in mice. The suppressive activity was shown to be allergen-specific and required covalent linking of the polysarcosine. Inhibitory effects could be overcome by booster injections of native allergen when these were given 3-4 weeks after treatment with conjugates. Administration of conjugates had only marginal effects on established IgE responses. The variance of these results with those of other studies on IgE suppression and the suitability of murine models for investigating reaginic antibody suppression are discussed.

Adjuvants, Immunologic↗

Differential suppressive influence of intranasal application of rye grass pollen extract on IgE antibody production in the mouse.

Serum antibody responses to a ubiquitous aero-allergen, rye grass pollen extract, have been monitored in BALB/c and BD1 mice following intranasal and parenteral administration. Parenteral treatments were shown to trigger antibody production while topical administration of low doses of allergen extract preferentially suppressed reaginic antibody production. However, higher doses of extract administered to the respiratory tract were found to induce the formation of IgE antibody. Thus in mice antigen administered intranasally can influence the immune response in a qualitatively different manner to parenteral exposure.

Agglutination Tests↗

Family therapy in the treatment of alcoholism.

The disease of alcoholism has long been known to significantly affect family relationships. Nevertheless, the characteristics and needs of these families are frequently not well understood, and treatment of the alcoholic in isolation continues to remain the norm. Family systems theory can provide a framework for comprehensive diagnosis and treatment which recognizes and addresses alcoholism as a family disease.

Adult↗

Antibody response profiles to components of rye grass pollen extract in various strains of mice.

Using a combination of immunoprecipitation and polyacrylamide gel electrophoresis techniques, patterns of antibody responses to a number of components in rye pollen extract have been studied in hyperimmune mouse sera. Common laboratory strains of mice were investigated, including AKR, C3H/He, SwR, Ist, Asn, Balb/c, C57BL10, DBA2 and BD1:F1 hybrids. All strains responded vigorously to the immunisation protocol used (rye pollen extract/alum followed by a booster dose in aqueous media) when tested with non-discriminating assay procedures such as haemagglutination or passive cutaneous anaphylaxis directed against the whole rye pollen extract. However, markedly variable antibody responses were observed between strains and between murine and human sera when considered in relation to individual rye extract components. Particularly noteworthy was the relatively poor response of all mice to the low molecular weight rye antigen component (11,000 daltons). This material was readily detected by human sera derived from pollenosis patients. Notable also was the fact that no single rye component was detected by all mice sera. These results illustrate the complex serological response induced by heterogeneous antigen mixtures, such as grass pollen extracts.

Animals↗

Evaluation of single and double artificial insemination regimes as methods of shortening calving intervals in dairy cows treated with dinoprost.

Conception rates in 535 commercial lactating Friesian dairy cows on two farms were compared between treated animals after two injections of dinoprost at an 11-day interval, and untreated contemporary controls bred by conventional artificial insemination. The conception rate for a single insemination 75 to 80 hours after the second dinoprost injection was 46 per cent, for two inseminations 72 and 96 hours after the second injection was 47 per cent, and for untreated controls was 50 per cent. The differences are not statistically significant. Both dinoprost treated groups had a mean calving interval of 366 days compared with 378 for controls. The time advantage of 12 days in calving interval was principally due to the shorter calving-to-first-service interval of treated cows. This 10-day advantage in calving-to-first-service was increased to a 12-day advantage in calving-to-conception in treated cows, and applied also to cows which failed to conceive to the induced oestrus. The accuracy of pregnancy diagnosis was confirmed by calving data; pregnancy diagnosis by rectal palpation was 94 per cent and by milk progesterone assay 81 per cent accurate, overall. Oestrus occurred in 3.8 per cent of pregnant cows, on the basis of stockmen's observations. The relevance of the information to herd sterility control is discussed.

Animals↗

Dissociation between tumour resistance and delayed-type hypersensitivity to tumour-associated antigens in the mouse.

A comparison was made in mice between resistance to growth of a syngeneic methylcholanthrene-induced fibrosarcoma (Meth A) and specific delayed-type hypersensitivity to this tumour. Resistance could be induced in 90% of mice following a single injection of 10(4) Meth A cells. This resistance could be transferred by spleen cells but not serum. Delayed skin reactivity to ultrasonicated Meth A cells was found in both tumour-resistant and tumour-bearing mice and could be passively transferred by spleen cells and serum. These findings suggest a dissociation between tumour resistance and specific delayed-type hypersensitivity. It would appear that, in this system, delayed skin reactivity to Meth A tumour cells is mediated by humoral antibody despite a mononuclear cell infiltrate at 24 and 48 h and that this could be the reason for its lack of correlation with host resistance to tumour growth which is cell-mediated and not transferable by serum.

Animals↗

Kinetics of the decline phase of the primary response to human serum albumin in the bird.

After the intravenous injection of a wide range of doses of human serum albumin (50 micrograms--10 mg) the biosynthesis of antibody maintained constant kinetics although the peak titre increased with the dose of antigen throughout this range. After the rapid rise to a sharp peak at day 7, the antibody levels in the decline period (7-17 days) manifested exponential decay and a constant half-life of 2.2 days which approximated to that observed with passively administered 131I-labelled 7S chicken Ig. It was concluded that after the antibody peak no further antibody production occurs and the switching-off of this antibody response must begin about 3 days before the time of the peak: counts of antibody-containing plasmacytes in the spleen were maximum at day 4. The rate of antibody catabolism and the timing of switch-off of antibody production appeared to be independent of either the dose of antigen injected or the level of antibody at the peak. The mechanisms of the switch-off are discussed.

Animals↗

Mapping the representation of the visual field by electrical stimulation of human visual cortex.

Electrical stimulation of human visual cortex produces punctuate phosphenes in the visual field. This phenomenon, which is being explored as the basis for a visual prosthesis for the blind, also provides the first electrophysiological information about the retinocortical map in man. Stimulation of points clustered on the surface of the visual cortex produces phosphenes clustered in visual space. However, adjacent surface electrodes located on opposite sides of a sulcus can produce widely separated phosphenes, because the intervening cortex is buried and inaccessible to stimulation. Such electrodes can also produce multiple phosphenes by simultaneously stimulating both banks of the sulcus. Electrodes which are widely spaced on the brain can produce phosphenes close together in visual space providing they stimulate cortex corresponding to overlapping maps in areas 17 and 18. Analysis of the phosphene map indicates that successive stimulation of points further from the tip of the occipital pole produces phosphenes progressively more distant from the fixation point. Successive stimulation of points along the orthogonal dorsoventral dimension produces a progressive change in phosphene bearing. These results confirm the general view of cortical organization derived from field defect studies in man, and from anatomical and electrophysiological studies in monkeys, and provide a new tool for more detailed study of retinotopic projections in man.

Adult↗

Effects of prostaglandins E2 and I2 on human lymphocyte transformation in the presence and absence of inhibitors of prostaglandin biosynthesis.

1 The reactivity of human peripheral blood mononuclear cells to phytohaemagglutinin ([3H]-thymidine incorporation) was enhanced in indomethacin- and eicosatetraynoic acid-treated cells compared with untreated cells, from normal volunteers. This suggests that endogenously synthesized prostaglandins have an inhibitory effect during cell preparation and/or culture. 2 Prostaglandin E2 inhibited [3H]-thymidine incorporation induced by suboptimal phytohaemagglutinin concentrations and had a more potent effect on indomethacin-treated cells than on untreated cells. 3 Prostaglandin I2 also exhibited an inhibitory effect and, under defined conditions, was more potent than prostaglandin E2 or than prostacyclin which had been allowed to decay at pH 7.4 and 37 degrees C. 4 These results indicate that, in attempting to define altered lymphocyte reactivity in disease states, the involvement of prostaglandins should be considered both during cell preparation and culture.

5,8,11,14-Eicosatetraynoic Acid↗