PubMed Health⌕ Search

Biomedical subjects

D M Moran

Publications and source records attributed to D M Moran.

At least 37 records · Page 2Linked to original sources
PubMed1985

In vitro production of IgE and IgG protein by blood mononuclear cells from non-atopic and atopic donors.

The production of IgE and IgG protein by human peripheral blood mononuclear cells in culture has been examined. Cells obtained from 18 grass-sensitive donors during the grass pollen season and from 11 atopic dermatitis patients (total serum IgE levels greater than 960 ng/ml), spontaneously produced significant amounts of IgE but not IgG with time. Similar results were obtained using B-cell enriched preparations from both groups. Cells from 16 non-atopic donors had mean levels of pre-formed IgE similar to those of grass pollen-sensitive donors, but there was no increase in culture IgE with time. Treatment of mononuclear cells with pokeweed mitogen did not influence the production of IgE but markedly increased the amount of IgG synthesized by non-atopic and atopic donor cells. Slight, but significant increases in culture IgE, but not IgG, were seen following a 7-day mixed lymphocyte reaction involving both unrelated non-atopic donor cells and the lymphoblastoid B-cell line, Raji. Treatment of cells with 50 HA units of influenza A/Hong Kong/1/68 (H3N2) virus or with 0.02% v/v (240 IU/ml) of a purified beta-interferon preparation did not alter IgE or IgG produced.

Dermatitis, Atopic↗
PubMed1985

Murine lymphocyte responses to purified components of rye grass pollen extract.

The ability of lymphocytes obtained from mice treated with whole rye grass pollen extract or purified major allergen components (R7--apparent molecular weight 31,000; R14a-apparent molecular weight 11,000) to proliferate in culture on challenge with these allergens has been studied. Whole rye grass pollen extract was found to stimulate responses with lymphocytes from all treated but not non-treated animals, whereas the purified allergens failed to effect proliferation except with cells obtained from animals treated with the homologous allergen. These results accord with previous observations that, of the antigen present in the whole rye grass pollen extract, the components showing greatest immunogenicity in murine systems are not those commonly regarded as being the major allergens in man. The mouse may not thus provide a relevant model of human immune responses to rye grass pollen extracts.

Animals↗
PubMed1985

Suppression of murine IgE responses with amino acid polymer/allergen conjugates. I. Preparation of poly-(N-methylglycine)/grass pollen extract conjugates using 4-(methylmercapto)phenyl-succinimidyl succinate as coupling reagent.

A procedure utilising the latent activating potential of the 4-(methylmercapto)phenyl ester group has been developed for the controlled, reproducible preparation of macromolecular conjugates. This ester, as part of a succinyl-bridging group, was used to couple the water-soluble, amino acid polymer, poly-(N-methylglycine) (polysarcosine), via its N-terminal secondary amine, with the nucleophilic components of the aqueous extract of a mixture of grass pollens. The products exhibit a reproducible, antigen-specific suppressive effect on the in vivo synthesis of IgE in mice.

Allergens↗
PubMed1985

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↗
PubMed1985

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↗
PubMed1984

Assessment of anti-streptokinase antibody levels in human sera using a microradioimmunoassay procedure.

A high capacity, quantitative radioimmunoassay procedure has been developed to measure IgG antibodies to streptokinase (SK) in human serum. Results showed that the use of low concentrations of 125I-SK (100 ng/ml) and ambient temperature incubation conditions minimised degradation of the target labelled antigen and afforded antibody binding values which could be confidently related to the native intact SK protein. SK-complexed to plasminogen was also shown to retain the equivalent antigenic activity of native SK. Comparison of the absolute anti-SK levels with streptokinase resistance titres demonstrated that the two measurements of antibody correlated statistically but afforded quantitatively poor agreements. A survey of IgG levels to SK in sera from 93 normal healthy volunteers showed that all individuals displayed readily measurable anti-SK antibodies, with some 80% having IgG concentration capable of binding in excess of 1 microgram SK per ml serum.

Antibodies↗
PubMed1984

Absorption of ipecac alkaloids in emergency patients.

Syrup of ipecac contains the nauseant alkaloids emetine and cephaeline. Although thousands of doses are given yearly, no data exist on the absorption of these alkaloids in man. We gave 30 mL of USP Syrup to ten adult patients. Blood and urine samples were obtained at approximately one-half and two hours after administration, and the entire volume of vomitus was saved. The samples were then analyzed for cephaeline and emetine by a high-performance liquid chromatographic (HPLC) assay developed in our laboratory. All patients vomited within 30 minutes, but the amounts of alkaloid regurgitated varied from 22 +/- 14% in six patients to 80 +/- 16% in the remaining four. Only six patients had emetine or cephaeline in their blood by two hours (range, 5 to 73 ng/mL), although ten patients had detectable concentrations of the alkaloids in their urine. Measured over two hours, no patient eliminated more than 0.5% of the dose by the urinary route. In our study ipecac was absorbed by all who received it; the extent of absorption varied widely, and elimination by the renal route was small.

Absorption↗
PubMed1984

Rebound following hemodialysis of cimetidine and its metabolites.

The effect of hemodialysis on the pharmacokinetics of cimetidine and its metabolites was studied after the intravenous administration of a 300-mg dose of cimetidine. Serum concentrations were monitored before, during, and after hemodialysis. Cimetidine pharmacokinetics were similar to those in patients with end-stage renal failure, with a total body clearance of 3.3 +/- 1.0 mL/min/kg and a half-life of 4.1 hours. Dialysis caused an initial decrease in serum concentrations for cimetidine, hydroxymethyl cimetidine, and cimetidine sulfoxide, followed by a rebound in serum concentrations immediately after treatment. Dialysis clearances, as calculated from extraction ratios, were 83 +/- 15, 90 +/- 16, 93 +/- 24, and 126 +/- 23 mL/min for cimetidine, hydroxymethyl, sulfoxide, and creatinine, respectively. After four hours of dialysis, 10% +/- 3.2% of the cimetidine dose was recovered in the dialysate. The sulfoxide and hydroxymethyl metabolites demonstrated relatively constant serum concentrations for up to 24 hours postdosing, and therefore, estimates of their terminal half-lives were not possible. In one patient, accumulation of both metabolites occurred during multiple dosing. Hemodialysis is an ineffective means of decreasing the total body load of cimetidine and its metabolites. Presumably, sequestration of the drug in body tissues decreases the amount of drug present in the blood available for dialysis removal, with rebound occurring due to postdialysis re-equilibriation between blood and extravascular fluids.

Adult↗
PubMed1984

An evaluation of naloxone as a gastric cytoprotective agent during hemorrhagic shock.

Administration of naloxone, an opiate antagonist, is known to improve survival from hemorrhagic shock and to reverse the effects of septicemia on gastric mucosal O2 tension and potential difference (PD). We tested these potentially cytoprotective actions in the ex-vivo canine gastric chamber model with acid, bile, and hemorrhagic hypotension. Naloxone (2 mg/kg IV bolus, then 2 mg/kg/hr IV) was given before or during shock. Naloxone did not affect oxygen consumption, the bile-induced drop in PD, or the transmucosal oxygen consumption, the bile-induced drop in PD, or the transmucosal movements of H+, Na+, K+, and fluid. The reduction in average mucosal lesion formation with naloxone pretreatment (5.4 +/- 1.2 vs. 2.8 +/- 0.5%) was not statistically significant (p = 0.07). Similarly, administration of naloxone after the onset of shock also failed to protect the mucosa from stress ulceration. We conclude: 1) naloxone does not inhibit the effects of topical bile on the gastric mucosal barrier; 2) naloxone has no apparent effect on local gastric vascular resistance during hemorrhagic shock; and 3) the therapeutic potential of naloxone as an anti-ulcer drug is questionable. 24GM 23095

Acute Disease↗
PubMed1984

Accessory cell response to rye grass pollen extract in mice, guinea pigs and man.

The ability of murine, guinea-pig and human accessory cells to function in antigen presentation has been assayed by a T-cell proliferative response to adherent cells pulsed with rye grass pollen extract. A population of phagocytic, esterase-positive, plastic-adherent splenocytes from non-immune Balb/c mice briefly incubated with solubilized rye antigen were capable of stimulating syngeneic T lymphocytes from immune mice in an antigen-specific manner. Accessory cell function was H-2 restricted and required Ia-positive cells. Treatment with a monoclonal anti-Ia antibody impaired proliferation, whereas the presence of polyclonal rabbit anti-rye antibody increased activity. Guinea-pig peritoneal and alveolar adherent cells pulsed with up to 1 mg/ml antigen increased the response of rye-immune lymph node T cells in vitro. Proliferation was dose-dependent, despite less than 0.1% of the available antigen being cell-associated, and could be inhibited by treating the accessory cells with trypsin, sodium iodoacetate and chloroquine. Adherent human peripheral blood cells treated with rye antigen supported the proliferation of non-adherent and nylon wool-enriched mononuclear cells obtained from both grass pollen-sensitive donors and from individuals lacking either detectable serum IgE antibody or a positive skin test to rye antigen.

Adult↗
PubMed1984

Proliferation of mouse lymphocytes to rye grass pollen extract: effect of inflammatory exudate cells.

The ability of inflammatory peritoneal exudate cells to modify a murine lymphoproliferative response to rye grass pollen extract was investigated. Popliteal and mesenteric lymph node cells from Balb/c mice immunised with either aqueous rye or rye grass emulsified in complete Freund's adjuvant were co-cultured with 2 X 10(3)-10(5) macrophage or polymorphonuclear neutrophil (PMN)-enriched exudate cells. There was a dose-dependent increase in the response to rye grass antigen with increasing numbers of PMN. A similar enhancement was seen with up to 10(4) macrophages per culture; higher numbers were inhibitory. Lymph node cells from rye grass or ovalbumin-immune mice that had been challenged with a combination of sensitising antigen plus 10(7) PMN gave an increased antigen-specific response in vitro. Neither antigen alone, PMN nor a mixture of PMN plus heterologous antigen was active. Adoptive transfer of a similar number of peritoneal macrophages plus antigen was also without effect. These results are in accord with the suggestion that cells obtained from acute inflammatory lesions can directly influence the activity of immunocompetent lymphocytes.

Animals↗
PubMed1984

Adjuvant properties of hydrophobic derivatives prepared from L-tyrosine.

The capacity of various N-acyl, O-acyl, amide and ester derivatives of L-tyrosine to promote the induction of antibodies to grass pollen extracts has been studied in guinea pigs. Antibody production was generally found to be enhanced when these derivatised materials were used as adsorbate vehicles compared with either L-tyrosine or simple aqueous presentations. Increases in alkyl chain length were found to parallel increased adjuvant activity. Unlike L-tyrosine, however, these hydrophobic materials tended to produce tissue lesions in experimental animals at concentrations which displayed apparent adjuvant advantages.

Adjuvants, Immunologic↗
PubMed1982

The use of an antihistamine-decongestant in conjunction with an anti-infective drug in the treatment of acute otitis media.

We evaluated the efficacy of an antihistamine-decongestant combination as adjunctive therapy in the treatment of acute otitis media with effusion. In a randomized study, 53 children were treated for acute otitis media with antibiotics and either Naldecon or placebo. Subjects were evaluated by tympanometry and pneumotoscopy. Follow-up evaluation was performed at days seven and 14 of therapy. The antihistamine-decongestant prescription was found to influence both the duration of nasal congestion and the course of middle ear effusion: Naldecon-treated subjects were symptomatic with nasal congestion for an average of six days compared to nine days reported by those given placebo, and the risk of persisting middle ear effusion was approximately two times greater in the placebo-treated group when evaluated by tympanometry.

Acoustic Impedance Tests↗
PubMed1982

l-Tyrosine as an immunological adjuvant.

A series of experiments has been carried out to investigate the adjuvant properties of the amino acid L-tyrosine in laboratory animals. Adsorption of various allergenic materials to L-tyrosine was found to enhance the induction of IgG antibodies, but no unusual propensity to stimulate IgE antibody or delayed hypersensitivity was observed. Administration of the amino acid at a site remote from the allergen was found not to augment antibody production. This, together with evidence of reduced bioavailability of the tyrosine-adsorbed allergen, suggested that the adjuvant activity observed resulted from a short-term depot effect.

Adjuvants, Immunologic↗
PubMed1982

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↗
PubMed1980

Further studies on histamine release from rat mast cells in vitro induced by peptides. Characteristics of a synthetic intermediate with potent releasing activity.

Previous studies on histamine release by corticotropin peptides and melittin peptides were extended, leading to the identification of a synthetic peptide intermediate, Lys(Z)-Arg(NO2)-Arg(NO2)OMe, (I) as an active non-cytolytic histamine releaser from rat mast cells. However, significant differences in the releasing capacity of optical isomers of this compound, and of Lys-Lys-Arg-ArgOMe [methyl ester of corticotropin-(15-18)-tetrapeptide; 'basic core'] were observed, with the L-forms being markedly more active. A study of various analogues of the tripeptide compound (I) indicated that the structural basis for mast-cell triggering by such peptidic agents was highly specific. The relevance of these observations to the immunologically induced histamine-release processes is discussed.

Adrenocorticotropic Hormone↗
PubMed1979

Synthetic peptides comprising sequences of the human immunoglobulin E heavy chain capable of releasing histamine.

On the basis of previous studies on the structure-activity relationship of model polypeptide histamine liberators, a site within the Fc region of immunoglobulin E antibody molecules has been proposed as that responsible for the direct triggering of target mast cells after antigen challenge. Peptides comprising this region of the epsilon-chain have now been synthesized and shown to induce histamine release from normal rat peritoneal mast cells in a selective manner essentially similar to that mediated by anaphylactic antibody-antigen interaction.

Animals↗