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Biomedical subjects

N R Lynch

Publications and source records attributed to N R Lynch.

72 records · Page 4Linked to original sources
PubMed1977

Passive cutaneous anaphylaxis and vasoactive amine challenge in nude (nu/nu) mice. A comparison with nu/+, axenic and young normal animals.

Recent suggestions of a thymic origin or thymo-dependent differentiation of tissue mast cells prompted an investigation in the athymic nude (nu/nu) mouse. The outbred nu/nu examined were found to possess mast cells in at least comparable numbers to the phenotypically normal nu/+. These nu/nu were superior to nu/+ as recipient for mast cell-dependent, long latent period (IgE-type), passive cutaneous anaphylactic (PCA) reactions. A variety of studies performed, including competition with nu/+ serum, thymic restoration, quantitation of nu/+ homocytotropic antibody responses, comparison with axenic or young mice and time-course studies of skin sensitization suggested that the higher PCA titres in nu/nu skin were not entirely due to a lack of competitive inhibition of mast-cell sensitization. The nu/+ used in these studies were in fact poor IgE recipients, but were somewhat more sensitive than nu/nu to hypovolaemic shock induced by histamine and serotonin mixtures. Pretreatment with Bordetella pertussis greatly enhanced the sensitivity of nu/+, axenic, holoxenic and young normal mice to the vasoactive effects of histamine and serotonin, but was somewhat less effective in nu/nu and old mice.

Animals↗
PubMed1975

Immunoglobulin classes carrying homocytotropic and passive hemagglutinating antibody activities in the marsupial Setonix brachyurus (the quokka).

On the basis of their physicochemical and antigenic properties, and by analogy with guinea pig immunoglobulins, two antibody classes in the serum of the marsupial Setonix brachyurus have been classified as IgG1 and IgG2 isotypes. The analogy between these marsupial immunoglobulins and those of eutherian (placental) species was extended by an investigation of their biological activities. The electrophoretically slow antibody (IgG2) fixed hemolytic complement, precipitated soluble antigen and predominated early in the response mounted when quokkas were immunized with antigen emulsified in Freund's complete adjuvant (FCA). The more anodic antibody (IgG1) in this marsupial did not fix complement, was inefficient in precipitating antigen and was the predominant antibody synthesized by quokkas immunized with antigen adsorbed to alumina gel. The IgG1 isotype in this marsupial appears to possess both passive hemagglutinating (HA) and homocytotropic antibody (HCA) activities. However, the HCA and IgG1 HA activities did not develop in parallel during the course of the immune response, thus suggesting that only a functional subpopulation of the IgG1 antibodies possess homocytotropic activity.

Absorption↗
PubMed1975

Histamine in the tissues of the marsupial Setonix brachyurus (the quokka).

Passive cutaneous anaphylactic (PCA) reactions in the marsupial Setonix brachyurus (the quokka) were completely inhibited by the histamine antagonist mepyramine maleate, but were unaffected by disodium cromoglycate or the serotonin antagonist, methysergide. Histological examination of quokka skin indicated that mast cell degranulation occurred during the PCA reaction in this marsupial and animals whose skin was relatively deficient in mast cells were poor PCA recipients. In contrast to many eutherian (placental) species, this marsupial was found to lack histamine in blood leukocytes and platelets. Also, while the peritoneal mast cells of rats and mice contain large quantities of histamine, this amine was not detected to quokka peritoneal washings, even after the induction of a peritoneal exudate or the regular intraperitoneal injection of antigen. Immunologic challenge of quokka blood or peritoneal cells did not induce the synthesis of histamine, but histamine release was elicited from sensitized quokka lung by antigenic challenge.

Animals↗
PubMed1975

Influence of IgG antibody and glycopeptide allergens on the correlation between the radioallergosorbent test (RAST) and skin testing or bronchial challenge with alternaria.

The radioallergosorbent test (RAST) for alternaria was compared to skin tests and bronchial challenges in children suffering from chronic intractable asthma. In contrast to when such children were tested with a timothy grass pollen extract, the bronchial challenge and skin test results against alternaria did not correlate significantly. When alternaria allergens were coupled to cyanogen bromide-activated microcrystalline cellulose, the RAST correlated with the results of skin testing but not bronchial challenge. It was demonstrated by column immunabsorption that some allergic sera contained sufficient IgG antibody against alternaria to competitively inhibit the RAST. When Sepharose 2B was substituted for cellulose as the insoluble support, the inhibition by IgG antibody was largely overcome and then the RAST correlated with both skin test and bronchial challenge results. Glycopeptides contribute significantly to the allergenicity of alternaria, and when these materials were coupled to a Sepharose 2B conjugate by mild oxidation, the RAST correlated with bronchial challenge, but not skin test, results. It was concluded that in this group of steroid-dependent asthmatic children, the correlation of the RAST with the in vivo challenges was strongly influenced by the presence of IgG antibody in the allergic sera and the chemical nature of the mould allergens investigated.

Absorption↗
PubMedDate not supplied

Relationship between the degree of poverty and the IgE response to Ascaris infection in slum children.

We examined a group of urban slum children in Caracas, Venezuela, and demonstrated the relationship that exists between poverty, conditions of hygiene and the prevalence of helminth infection. Concordant with the high prevalence of helminth infection in these children, the total serum levels of immunoglobulin E (IgE) and blood eosinophilia were elevated and were directly related to the degree of poverty and lack of sanitary facilities. However, in contrast, the reverse pattern was observed for the specific allergic response to these parasites. Thus, the immediate hypersensitivity skin test reactivity to Ascaris antigens, and the serum levels of specific anti-Ascaris IgE antibody, were lowest in the poorest children, who had the highest prevalence of helminth infection and the highest total IgE levels. As allergic-type reactions may participate in protective mechanisms against helminths, these results suggest that poverty and poor sanitary conditions may, by influencing the IgE response, compromise the resistance of such children to parasitic infections.

Animals↗
PubMedDate not supplied

Nutritional status and the IgE response against Ascaris lumbricoides in children from a tropical slum.

Helminthic infection can stimulate the interleukin-4 (IL-4)-dependent polyclonal synthesis of immunoglobulin E (IgE) in children endemically exposed to these parasites. As such children are also frequently at nutritional risk, in this study we considered the possible influence of malnutrition on serum IL-4 levels and the IgE response in helminthic infection. We evaluated 85 Ascaris-infected children living in an urban slum area of Caracas, Venezuela, and found that the serum levels of IL-4 and total IgE were significantly higher in malnourished children than in their well nourished counterparts. In contrast, the specific anti-Ascaris IgE antibody response was significantly lower in the malnourished group. After anthelmintic treatment of the children, the total serum IgE and IL-4 levels decreased significantly in the well nourished group, while the specific anti-Ascaris IgE antibody response increased. No significant change was detected, however, in the malnourished group. Our results suggested that malnutrition potentiates the polyclonal stimulation of IgE synthesis induced by helminths. As specific IgE antibody has been implicated in the resistance to helminthic infection, and the polyclonal stimulus diminishes this response, these factors may increase the susceptibility of malnourished children to such parasites.

Animals↗
PubMedDate not supplied

Bronchial challenge of tropical asthmatics with Ascaris lumbricoides.

Despite the fact that helminthic parasites can stimulate strong immediate hypersensitivity reactions, it is uncertain whether these are relevant to the development of allergic disease in infected patients. In order to examine this possibility, we tested 20 informed chronic asthmatic patients from an Ascaris-endemic area by bronchial challenge with a partially purified extract of this parasite. Sequential measurements were made of both the forced expiratory volume in the first second (FEV1) and the peak expiratory flow rate (PEFR) up to 6 h postchallenge, then of PEFR from 6 to 14 h and at 24 h. These were compared to the effect of control inhalations of saline. Extremely low doses of Ascaris antigen that did not exceed 10 PNU (6 x 10(-7) g of protein) induced significant reductions (> 20%) in FEV1 within 30 min in 3 (15%) patients, and in PEFR in 5 cases (25%). By 6 h postchallenge, 5 (25%) subjects showed significant alterations in FEV1, and 10 (50%) in PEFR. Significant changes in PEFR were recorded between 6 and 24 h in 12 (60%) patients. The challenge of nonasthmatic subjects from the same Ascaris-endemic area did not produce notable changes in pulmonary function, and although asthmatics with no evidence of prior contact with the parasite showed a certain degree of immediate bronchial reactivity to the parasite extract, the late responses were significantly less frequent than in the infected patients. No correlations were detected between the bronchial responses and skin test reactivities to the Ascaris extract, or serum levels of specific IgE or IgG antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

An unusual case of hyper-production of IgE, treated by plasmapheresis.

A 15-year-old boy with severe inflammatory skin lesions from an early age was found to have extremely elevated serum IgE levels (up to 376.000 IU/ml). His skin showed positive direct immunofluorescence for IgE and he had peripheral and bone marrow eosinophilia. No evidence for atopic disease was found, but he suffered intestinal helminthic infection of moderate intensity. He showed a somewhat depressed cell mediated immune response but a normal polymorphonuclear function. Various treatments that included anti-inflammatory, anti-allergic, anti-parasitic, anti-mycotic and PUVA therapy did not significantly improve his condition A therapeutic test using plasmapheresis produced marked, though short-lived clinical improvement. We believe that this case might result from the superimposition of the stimulatory effects of intestinal helminthiasis on a background of intrinsic hyper-production of IgE.

Adolescent↗
PubMedDate not supplied

Measurement of anti-Ascaris IgE antibody levels in tropical allergic patients, using modified ELISA.

The two most common situations in which the determination of serum immunoglobulin E (IgE) levels is of interest are allergic disease and helminthic infection. This is of particular importance in the tropical environment, as helminthiasis possibly influences the expression of allergic reactivity. Because of the low absolute serum levels of IgE, solid-phase radioimmunoassay (RIA) is conventionally used for its measurement. The radioactive and toxic volatile reagents required restricted application of such assays in the tropical situation. We evaluated a nitrocellulose-based, avidin biotin-amplified enzyme-linked immunosorbent assay (ELISA) for IgE, in which monoclonal anti-IgE antibodies were employed. Excellent correlations were obtained between ELISA and RIA for both total and allergen-specific IgE measurement. The ELISA was then applied to determine the levels of anti-Ascaris antibodies in selected allergic patients, in whom no cutaneous immediate hypersensitivity reactions were demonstrated against common environmental allergens such as house dust, but who had positive skin reactions to Ascaris extract. When compared with non-allergic subjects who had equivalent cutaneous reactivity, no significant differences were found in total IgE levels, house-dust specific IgE levels or non-reaginic anti-Ascaris antibody levels. However, higher levels of IgE antibody against the parasite were detected in the allergic subjects. This observation raises the question of the possible role of Ascaris infection in the stimulation of allergic reactions in such patients. We describe an immunoenzymatic assay for total and specific IgE antibody that is better adapted to the tropical situation than the commonly used radioimmunoassays.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascaris↗
PubMedDate not supplied

Nonspecific changes in immunotherapy with house dust extract.

Despite the possible complications and inadequacies of the immunotherapy of allergic patients with house dust extracts (HDE), this is widely applied in Latin America and is commonly considered to be a cost-effective treatment for allergic diseases. Doubts about its efficacy and mechanism of action prompted us to evaluate the immunological changes that occurred in a group of 99 patients selected for their confirmed allergic sensitivity to house dust, and who showed significant clinical improvement after a minimum of 12 months of immunotherapy with HDE. The favorable clinical response of these patients was associated with some of the mechanisms reported for immunotherapy with pollen or venom allergens, such as increased levels of IgG or IgG4 "blocking" antibodies, and the increased affinity of these antibodies for house dust antigens, or diminished basophil sensitivity to HDE. However, the magnitude of these changes was relatively small, and their biological significance questionable. In contrast, particularly evident was a reduction in the cutaneous reactivity not only to the specific allergen, but also to the nonspecific mast cell degranulator codeine and to histamine. These results suggest that as yet unidentified "nonspecific" mechanisms might contribute to the effect of immunotherapy with extracts as heterogeneous and complex as HDE.

Adolescent↗
PubMedDate not supplied

Effect of age and helminthic infection on IgE levels in slum children.

Helminthic infections can cause an IL-4-dependent polyclonal synthesis of IgE, which is the major cause of the elevated serum levels of this immunoglobulin in tropical populations. In the present study, we measured the IgE levels in the serum of children of different ages in slum areas of Caracas, Venezuela, where intestinal helminths are endemic. As would be expected, in children over 5 years of age, the IgE levels were highly elevated, and in addition, the cord blood serum levels were higher than those reported for populations where parasitic infections are uncommon. However, the IgE levels measured in the sera of children under 5 years of age were relatively low, and within the generally accepted normal ranges. This was surprising because the latter children were infected by parasites and had high IgG antibody levels against helminths. We found, however, that whereas older children had detectable IL-4 levels in their sera, the younger children did not. These results suggest that, despite infection of these slum children by common intestinal helminths, a polyclonal stimulation of IgE synthesis did not occur, possibly due to a lack of IL-4 production by an immature immune system.

Adolescent↗
PubMedDate not supplied

[Host-tumour relationships and immediate hypersensitivity reactions].

When radiolabelled lymphoid cells and the extracellular dye Lissamine green were injected IV into C3H mice carrying non-necrotic methylcholanthrene-induced tumours, the tumour content of these agents was significantly lower than in other organs. The tumour content of these circulating blood components was significantly increased by the intratumoral (IT) induction of local passive anaphylactic reactions, and such reactions exerted an anti-tumour effect, and enhanced the therapeutic activity of IT BCG. No anti-tumour IgE antibody was detected in this model, but the tumour inhibited passive and active anaphylactic reactions in its host.

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