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N R Lynch

Publications and source records attributed to N R Lynch.

At least 55 records · Page 3Linked to original sources
PubMed1985

Interrelationships between immediate, intermediate, and delayed cutaneous reactions and their in vitro correlates.

The mutual correlations between immediate, intermediate, and delayed cutaneous reactions, IgE, IgG, or combined IgG, A, and M antibody levels, and antigen- or mitogen-induced lymphocyte transformation were evaluated in a mixed group of allergic or non-allergic individuals. As might be expected, immediate and delayed reactions correlated significantly with IgE antibody levels and lymphocyte transformation, respectively. Intermediate time-course reactions did not correlate with IgG or IgG, A, and M antibody levels, but did so with immediate reactions, thus suggesting their "late phase" nature. Of particular interest was the finding of correlations that do not conform to the classical concept of the mechanisms involved in the generation of the different cutaneous reactions. Significant correlations were found between immediate or intermediate reactions and antigen-induced lymphocyte transformation, and between immediate and delayed reactions. These results are discussed in relation to recent suggestions that factors released from sensitized T cells can mediate early time-course reactions, and that such reactions may contribute to the manifestation of delayed-type hypersensitivity.

Adolescent↗
PubMed1984

Incidence of atopic disease in a tropical environment: partial independence from intestinal helminthiasis.

The reported incidence of atopic disease in the tropical environment, albeit somewhat controversial, has often been very low. This has been postulated to be due to an inhibitory influence of intestinal helminthiasis, although the predominantly rural nature of the populations studied might also be an important factor to consider. We evaluated two tropical groups in Venezuela that were basically comparable, both being highly parasitized but one of which was urban and the other rural. The apparent incidence of allergic conditions in the urban group was, in fact, comparable to that in temperate countries, whereas that of the rural subjects was markedly lower. A similar difference was found in skin test positivity to common inhalant allergens, although reactivity to Ascaris extract was comparably high between the two groups, and total serum IgE and eosinophil levels were uniformly elevated. Our results suggest that the incidence of atopic disease in the topical environment may depend not only on the intensity of helminthiasis suffered but also on factors related to the urban-rural situation.

Adolescent↗
PubMed1984

High allergic reactivity in a tropical environment.

The prevalence of atopic disease in tropical populations is often considered to be low, and this has been attributed to an immunological modulating effect of intestinal helminthiasis. We, however, report that the frequency of positive allergic history and skin-test reactivity to groups of major environmental allergens is extremely high (43 and 63% respectively) in children in Caracas, Venezuela (Lat. 10 degrees N). These values were statistically significantly greater than in a group of children with a similar age and sex distribution studied in parallel, but having limited or no contact with a tropical environment (29 and 37% respectively). The two groups differed with respect to the sporadic and light intestinal helminthic infections (such as ascariasis) experienced by the Venezuelans, compared to rare contact in the 'non-tropical' group. This was probably the cause of the increased total serum IgE levels of the former children (369 vs 68 iu/ml), and possibly, therefore, their higher allergic reactivity.

Adolescent↗
PubMed1983

Allergic reactivity and helminthic infection in Amerindians of the Amazon Basin.

Various aspects of the allergic reactivity of Amerindians in the Venezuelan sector of the Amazon basin were examined. The frequency of positivity in immediate hypersensitivity skin tests with extracts of common local environmental allergens was found to be extremely low (6.7%). As sera from significantly higher proportions of the study group contained specific IgE antibody against the test allergens, and their histamine-induced skin responses were normal, these results support previous suggestions of an inhibited expression of allergic reactivity in such populations. Indeed, the intense helminthic infections detected, and the extremely high total serum IgE levels measured (geometric mean 13,088 IU/ml) indicate the possible occurrence of mast cell saturation by parasite-induced IgE. However, despite a similar lack of agreement between the in vivo and in vitro tests for allergic reactivity against Ascaris lumbricoides in these subjects (43.5 and 97.9% positive, respectively), their extremely high responsiveness to the helminth allergens presents a marked contrast to that against the other environmental materials. Factors other than helminthiasis (e.g. racial, cultural, nutritional) might, therefore, also modulate the expression of allergic reactivity in such populations.

Antibody Formation↗
PubMed1983

Humoral and cellular immune responses of atopic individuals in a tropical environment.

In this study we compared immediate, intermediate and delayed skin test reactivity, total and specific serum IgE, IgG, A, M antibody and lymphocyte proliferative responses, between atopic and normal individuals in the tropical environment of Caracas, Venezuela (Lat. 10 degrees N). The allergenic extracts tested were prepared from house dust, mixed moulds and Aspergillus fumigatus. In lymphocyte stimulation the mitogen Concanavalin A was also employed, the cultures being supplemented with either autologous plasma, or a gamma globulin-depleted pool. The results revealed the association of immediate skin reactions with IgE antibody against house dust, and intermediate reactions with IgG, A, M antibody against moulds. No relation was, however, detected between delayed skin reactivity and in vitro lymphocyte transformation; skin reactions occurred at the highest frequency with moulds, while house dust provoked the strongest in vitro stimulation. Also, although the areas of positive delayed reactions were greatest in the atopic individuals, the lymphocyte proliferative responses were clearly highest in the normal subjects. The significance of the positivity of lymphocyte transformation tests in all of the study group, but lower reactivity in the atopics, is considered.

Adolescent↗
PubMed1983

Diagnosis of atopic conditions in the tropics.

Controversy surrounds studies of the incidence and clinical importance of atopic disease in tropical populations. This could be due in part to the methods of evaluation employed. The value of some of the tests commonly used in the diagnosis of atopic disease was therefore examined in a tropical situation. Extracts of environmental allergens are usually obtained from suppliers located in more temperate regions of the world, and skin tests, the radio-allergosorbant test (RAST) and RAST-inhibition demonstrate that these can lack important tropical allergens. In addition, although some local extracts are used in clinical practice, these have great variability in their protein content, allergenicity and toxicity. In the tropical environment serum IgE levels can have a greater relation to intestinal helminthic infestation than to atopic disease, even after anti-parasitic treatment, and thus the definition of "normal" IgE values must take into account the socio-economic status of the groups examined. The helminth-induced elevation of total serum IgE levels can also cause false-positive RAST results.

Dust↗
PubMed1983

IgE in leprosy; effect of a Mycobacterium leprae-BCG vaccine.

Since some previous studies have reported elevated total serum IgE levels in leprosy, that may be associated with the existence of a state of generalized T cell anergy, we undertook a carefully controlled study of this immunoglobulin in such patients before and after treatment with a Mycobacterium leprae-BCG vaccine. We found, firstly, that lepromatous leprosy patients suffering active disease had only a moderate elevation of IgE levels that was not statistically significant when compared to appropriate controls. In addition, multiple injections of the vaccine did not cause alterations in the concentration of this immunoglobulin. We were, therefore, unable to confirm the possible existence of a generalized immunodeficiency in lepromatous leprosy that could cause hyper-production of IgE.

BCG Vaccine↗
PubMed1983

IgE in leprosy.

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Humans↗
PubMed1982

Delayed-type hypersensitivity and immunoglobulin E in American cutaneous leishmaniasis.

Delayed-type hypersensitivity (DTH) and both total and specific immunoglobulin E (IgE) antibody levels were studied during an outbreak of American cutaneous leishmaniasis. Direct correlations were detected between DTH reactivity and either age or the period of evolution of the infection, and a clear association with sex (strongest response in females) was observed. Extremely high, age-dependent, total serum IgE levels were measured in the study group, probably due to concurrent intestinal helminthiasis. A low proportion of the group also had detectable levels of specific anti-Leishmania IgE antibody. Total and specific IgE levels were also sex dependent (lowest in females), and an inverse correlation was found between these levels and DTH responsiveness, possibly reflecting the intervention of regulatory influences of T-lymphocyte activity.

Adolescent↗
PubMed1981

Possible role of macrophage-like suppressor cells in the anti-tumour activity of BCG.

The i.v. injection of high doses (3 mg) of BCG into C3H mice bearing a transplantable 3-methylcholanthrene-induced fibrosarcoma caused the regression of a significant proportion. This effect was most evident when the BCG was injected on the day of the graft, or 7 days later. The injection of this agent either 14 days before the graft, or in low doses (0.1 or 0.5 mg), or directly into the tumour (i.t.) only prolonged the survival of the animals. Spleen cells from systemic high-dose BCG-treated mice were found to exert a strong nonspecific cytostatic effect in vitro that was not an artefact of the test conditions, and was not expressed by cells from low-dose animals. The cytostatic effect was shown to be caused by cells with the characteristics of macrophages, i.e. they were strongly adherent, unaffected by treatment with anti-Thy 1.2 + C', radioresistant but heat-sensitive, and were detected in BCG-treated "B" mice. The spleens of high-dose BCG-treated mice also contained suppressor cells that were capable of inhibiting the in vitro reactivity of normal T cells to PHA. Like the cytostatic effect, this suppressor activity was not detected in low-dose mice, and the cells responsible had the properties of macrophages; the effect was lost after the removal of adherent cells by sequential exposure to plastic and colloidal iron, but was conserved after treatment with anti-Thy 1.2 + C'. T-cell-deprived animals, such as "B" or nude mice, also developed suppressor-cell activity when treated with systemic high-dose BCG. Close parallels became evident between the in vivo anti-tumour activity of BCG, the in vitro cytostatic effect, and the suppressor-cell activity. We here discuss the possible role of suppressor cells in the mechanism of action of this agent.

Animals↗
PubMed1979

Tumor growth inhibition and potentiation of immunotherapy by indomethacin in mice.

Indomethacin was continuously administered in the drinking water of inbred C3H mice given grafts of syngeneic 3-methylcholanthrene-induced fibrosarcomas. A minor proportion of these animals died at the same time as the untreated controls, and others completely rejected their tumors; however, in most cases, the tumor growth rate was significantly slowed, and growth recommenced rapidly after drug withdrawal. This was the pattern for tumors either in their 10th to 14th transplant generation or only their third in vivo passage. Indomethacin exerted little prophylactic effect, in that it neither increased the minimal cell number required to initiate tumor growth nor significantly decreased the proportion of tumors established in drug-treated animals recieving tumor grafts. The injection of killed Corynebacterium parvum organisms into small, growing McC3-I tumors [intratumor (IT) route] caused the regression of most of these. In contrast, IT injection of BCG, ip injection of C. parvum, or IT injection of C. parvum into larger tumors had no effect. Oral administration of indomethacin enhanced BCG treatment and augmented the activity of C. parvum injected either systemically into animals with small tumors or IT into those with substantial tumor burdens. The duration of these effects was, however, often dependent on the continued administration of the drug.

Animals↗
PubMed1978

Mechanism of inhibition of tumour growth by aspirin and indomethacin.

The growth of a 3-methylcholanthrene-induced fibrosarcoma of C3H mice was inhibited by aspirin and indomethacin. While the tumour contained relatively high concentrations of PGE2-like material, that were markedly diminished by indomethacin treatment, our results did not confirm the recently proposed hypothesis that the anti-tumour effect arises from a restoration of depressed immune function. For example, mice that had completely eliminated their tumours under indomethacin administration were not immune to rechallenge. The tumour-bearing animals were not non-specifically immunodepressed, as their splenic PFC responses against SRBC were enhanced. However, while indomethacin augmented the PFC response in normal mice, this adjuvant effect was depressed in tumour-bearing animals. The spleen-cell PHA responses of tumour bearers were severely depressed, and such cells suppressed the PHA response of normal cells. Only after prolonged indomethacin treatment did animals (with comparable tumour burdens) show weak PHA responses and somewhat diminished suppressive activity. Possible alternative mechanisms, such as direct cytotoxicity, or inhibition of inflammation, phosphodiesterase activity, blood coagulation or calcium availability were not implicated (nor definitively excluded) in the anti-tumour effect.

Animals↗
PubMed1977

Passive local anaphylaxis: demonstration of antitumor activity and complementation of intratumor BCG.

When an extracellular dye, Lissamine green, or 51Cr-labeled spleen cells were injected iv into C3H mice bearing small, partially necrotic 3-methylcholanthrene-induced transplantable fibrosarcomas (McC3), the tumor content of these circulating elements per unit weight was substantially lower than that of other selected organs. The level of these blood-borne materials was, however, significantly augmented by the intratumor induction of passive local anaphylaxis (PLA). The PLA-induced augmentation was inhibited by administration of the histamine and serotonin antagonist cyproheptadine; comparable increases were also induced by the intratumor injection of a histamine and serotonin mixture or BCG. The weekly intratumor induction of PLA in McC3 tumors resulted in the complete regression of a significant number of the tumors, and this therapeutic effect was eliminated by cyproheptadine treatment. The intratumor injection of BCG induced the regression of approximately 50% of injected tumors, and the combination of this immunostimulant treatment with the generation of PLA was more therapeutically effective than either treatment alone. PLA in the vicinity of solid tumors may, by increasing vascular permeability, potentiate antitumor effector mechanisms, particularly when these are BCG-stimulated. Despite this demonstration of a possible role of anaphylactic reactions in tumor immunity, no definitive evidence was found that active reagin-mediated local anaphylaxis occurred in C3H mice bearing the McC3 tumor, whether or not they were treated with immunostimulants.

Anaphylaxis↗
PubMed1977

Sensitivity to intravenous injections of histamine and serotonin in inbred mouse strains.

A large panel of inbred strains of mice and some of their Fl hybrids were tested on their sensitivity to the hemoconcentrating effects of intravenous injections of histamine alone, serotonin alone, or histamine-serotonin mixtures. Major differences in susceptibility were observed. Crosses and backcrosses were made between susceptible (SJL/J) and less susceptible (RF/J, C57BL/6J) strains; it was found that the sensitivity to vasoactive amines is, at least partially, inheritable.

Anaphylaxis↗
PubMed1977

Tumour-associated inhibition of immediate hypersensitivity reactions in mice.

The intensity of anaphylactic shock was lower in C3H mice carrying a methylcholanthrene-induced tumour (McC3) than in their normal counterparts when immunized with ovalbumin and challenged i.v. after 14 days. This tumour-associated inhibitory effect on active systemic anaphylaxis was exerted mainly on events occurring after homocytotropic antibody synthesis because the serum titres of these antibodies were comparable in normal and tumour-bearing animals. In addition, passive systemic anaphylactic reactions were suppressed in animals carrying the tumour and the sensitivity of these animals to challenge with histamine and serotonin mixtures was also reduced. The presence of a growing McC3 tumour did not, however, diminish the amine-sensitizing effect of treatment with Bordetella pertussis vaccine. The McC3 tumour inhibited the generation of passive cutaneous anaphylactic reactions, an effect that was also exerted by a tumour extract, particularly when administered to the recipients shortly before antigen challenge. Thus immediate hypersensitivity reactions, like a variety of other immunological processes, can be inhibited by tumour products which by compromising the immune status of the host might permit tumour growth. The nature of the inhibiting factor is unknown, except that it is probably not the amine-degrading enzyme histaminase. In addition, which it is uncertain whether the inhibitory effect is exerted directly or indirectly, the possible importance of prostaglandins in the phenomenon is discussed.

Amine Oxidase (Copper-Containing)↗