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Biomedical subjects

N R Lynch

Publications and source records attributed to N R Lynch.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Housedust mite culture medium: an alternative source for the production of allergenic extracts].

House dust mites are the most important source of allergens in the tropical environment, and aqueous whole body extracts of these organisms have wide use in the diagnosis and treatment of allergic diseases. However, it has been reported that mite excretions have a high allergenic activity. Because of this, we have evaluated spent house-dust mite culture medium as an alternative source of allergens from these organisms. We demonstrated that the extraction of allergens from this material is more efficient in alkaline solutions such as ammonium bicarbonate, and when the extraction process is extended to 48 hours. When the purification process is complemented with dialysis and ammonium sulphate precipitation, the toxicity of the extract decreases and its allergenic activity increases. The electrophoretic pattern of proteins of the spent culture medium extract showed bands that bound specific IgE antibodies, but this extract may be deficient in one of the principle allergens of mites, Der pII. The extract stimulates immediate hypersensitivity skin reactions in house-dust allergic patients, and produces RAST inhibitions with their sera. The allergenic activity of this extract is comparable to that of the 1st. International Standard for house-dust mite extracts. These results demonstrate that spent house-dust mite culture medium is an appropriate source of allergens from these organisms, and because of its low commercial value, may be an economical alternative for the production of allergenic extracts.

Allergens↗
PubMed1994

In vivo biological activity of recombinant Der p II allergen of house-dust mite.

The cDNA coding for one of the major allergens of Dermatophagoides pteronyssinus, Der p II, has been cloned and expressed in Escherichia coli as a fusion protein with glutathione S-transferase. The recombinant material (r Der p II) was tested in the skin of house-dust allergic patients, and was found to be almost as active as the purified native allergen (n Der p II) in stimulating immediate hypersensitivity reactions. The positivity to r Der p II in these patients, who were selected for their skin-test reactivity to house-dust extract (HDE) and whole mite extract (WME), was over 60%, and 80% of their sera contained detectable IgE antibody against the recombinant allergen. The level of specific IgE antibody against r Der p II was a mean of 40% of that against WME in the sera of patients who were skin test positive to both allergen preparations. In contrast to the house-dust allergic patients, none of a group of allergic patients whose clinical history did not implicate house dust, and who were skin test negative to HDE or WME, were positive to r Der p II. Of interest was the observation that only 37% of a group of subjects who were skin test positive to HDE and WME, but who reported no clinical history of allergic disease upon natural exposure to house dust, reacted to r Der p II. These results demonstrate the biological activity of r Der p II, and indicate, in persons skin test positive to house-dust mite extract, an association between reactivity to Der p II and the manifestation of clinical symptoms.

Adolescent↗
PubMed1993

Comparable seropositivity for ascariasis and toxocariasis in tropical slum children.

The seropositivities for infection by Ascaris lumbricoides and Toxocara canis were determined in children (1-15 years old) of a slum area of Caracas, Venezuela, and the levels that indicate the presence of active infection were defined. In children aged from 1 to 3 years, approximately 10% were positive for either parasite, and this figure increased to about 30% in 4- to 6-year-olds. For toxocariasis, the percentage of positivity remained at this level up to the age of 15 years. Whilst the positivity in children 10-15 years of age was comparable for Ascaris and Toxocara, a peak of positivity (50%) was found for Ascaris at 7-9 years of age. These results indicate that for these urban slum children, infection by Toxocara is essentially as common as that by Ascaris and, thus, that toxocariasis represents a potential public health problem in the tropical environment that is largely overlooked.

Adolescent↗
PubMed1993

Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum.

It is well known that helminthic infection can cause a polyclonal stimulation of the synthesis of IgE, which is dependent on interleukin-4 (IL-4) production, and it has been suggested that this can modulate the expression of allergic reactivity in tropical populations. We evaluated the effect of regular anthelmintic treatment, for a period of 22 months, on certain aspects of the allergic reactivity of children in a slum area of Caracas, Venezuela, where helminths are endemic. The treatment (Oxantel-Pyrantel; Quantrel) effectively eliminated intestinal helminthic infection and resulted in a significant decrease in the initially elevated total serum IgE levels. IL-4 was detectable in the serum, and a significant reduction in IL-4 was also observed after treatment. In contrast, both the immediate-hypersensitivity skin-test reactivity and serum levels of specific IgE antibody against environmental allergens were markedly increased in the treated children. In a group of children who were also evaluated in the same slum, but who declined treatment, a substantial increase in helminthic infection occurred, which was related to an acute deterioration of the socioeconomic conditions of Venezuela over the course of our study period. This was paralleled by a considerable increase in total IgE levels in these children and a decrease in the skin-test reactivities and specific IgE levels. The application of Prausnitz-Küstner passive transfer tests and analysis of specific IgE antibody levels indicated that the polyclonal stimulation of IgE synthesis by helminthic parasites results in mast cell Fc epsilon receptor saturation and suppression of specific IgE antibody synthesis. This inhibition of allergic reactivity is reversible by anthelmintic treatment.

Adolescent↗
PubMed1993

Ascaris reinfection of slum children: relation with the IgE response.

Total and Ascaris-specific serum IgE levels were measured in a group of 98 Ascaris-infected children from a slum area of Caracas, Venezuela, in whom the infections were eliminated by regular treatment for 22 months with the anthelmint Oxantel/Pyrantel ('Quantrel'). The children were re-evaluated at the end of the treatment programme, and then 8 months later, at which time reinfection was assessed. Total IgE levels at the beginning of the study were significantly higher in the children who became reinfected after treatment, compared with those who did not. The anthelmint treatment caused a significant decrease in the total IgE levels in most of the children, and after a period of 8 months without treatment these continued to decrease in the non-reinfected group, but increased again in the reinfected children. The reverse pattern was found for Ascaris-specific IgE antibody levels, and in fact an inverse correlation was found between total and anti-Ascaris IgE levels. Striking associations were found between reinfection and high pretreatment values of total IgE, but low levels of specific IgE antibody. These data support the concept that specific IgE antibody may participate in the protection against helminthic infection, and suggest that the polyclonal stimulation of IgE synthesis caused by these parasites may reduce the effectiveness of such responses. The results also indicate that different individuals have varying propensities to respond polyclonally to the helminths, and this influences their resistance to infection.

Animals↗
PubMed1993

Modulation of the allergic reactivity of slum children by helminthic infection.

Infection by helminthic parasites can cause the polyclonal stimulation of IgE synthesis, possibly via an enhanced production of interleukin-4 (IL-4), and this has been suggested to influence the allergic reactivity of tropical populations where these parasites are endemic. We evaluated a group of urban slum children in Caracas, Venezuela, with a high prevalence of helminthic infection (70.8%), to establish the relationship between the elevated IgE levels (3696 IU/ml) induced by these parasites and various aspects of the allergic response. Although the absolute levels of IL-4 detected in the sera of these children were low (0.65 +/- 0.20 ng/ml), a strong positive correlation (r = 0.78) was found between these and serum IgE. The cutaneous immediate hypersensitivity reactivity to extracts of common environmental allergens was relatively low (17.5% to house dust), although that to Ascaris extract was moderately high (49.4%). Significant inverse correlations were found between total IgE levels and the different skin test reaction diameters, including Ascaris. The positivity of Prausnitz-Kustner passive transfer tests was low in this group (34%), with a strong inverse correlation (r = -0.75) being found between this and total IgE levels. Significant inverse correlations were also found between total IgE levels and specific IgE antibody to environmental allergens, and to Ascaris antigen. We suggest that the polyclonal production of IgE stimulated by helminthic infection can suppress the allergic response to environmental and parasite allergens via both mast cell saturation and inhibition of specific IgE production.

Allergens↗
PubMed1993

Allergic reactivity of children of different socioeconomic levels in tropical populations.

Widely variable prevalences of allergic diseases have been reported in tropical populations, and this has been suggested to be due to effects of the nonspecific polyclonal stimulation of IgE synthesis caused by the helminthic infections that are endemic in these areas. Since 1980, we have been evaluating the allergic reactivity of different socioeconomic sectors of the population of tropical Venezuela (lat. 2-12 degrees N), and in the present study analyze the overall results obtained in the laboratory evaluation of children (5-15 years of age) belonging to these groups. Children of medium-high socioeconomic level (M-HSEL), who experience occasional helminthic infections, have moderately high total serum IgE levels, and have elevated skin test positivities and specific IgE levels against environmental allergens. Persons of low socioeconomic level, in the urban, and particularly rural situation experience frequent helminthic infection, and have highly elevated total serum IgE levels. In contrast to the M-HSEL, the majority of these children have detectable specific IgE antibody against a variety of inhalant allergens, but relatively few have high levels, and their skin test positivity is also low. In these frequently parasitized persons, evidence of saturation of mast cell Fc epsilon receptors was found by tests of passive sensitization. We propose, therefore, that helminthic parasites have a biphasic effect on allergic reactivity; occasional infections are stimulatory, via their nonspecific potentiation of IgE synthesis against environmental allergens, and frequent infections are suppressive due to the widely polyclonal stimulation that they cause, resulting in both diminished specific antibody production against any given allergen and mast cell Fc epsilon receptor saturation.

Adolescent↗
PubMed1993

Possible relationship between allergic disease and infection by Giardia lamblia.

In order to better understand the possible relationship between allergic reactivity and infection with G. lamblia, specific IgE responses and skin test reactivity were evaluated in allergic or nonallergic Venezuelan children, with or without G. lamblia infection. Two groups of children were studied: one from our Allergy Clinic and the other from a slum area of Caracas. The total serum IgE levels in children from the slum area were significantly higher in those with intestinal helminthic parasites and giardiasis, compared with those with helminthiasis only (P < .001). In atopic children with giardiasis we also found an enhanced IgE antibody response to common environmental allergens (P < .05). As G. lamblia produces intestinal mucosal damage, we also studied the reactivity to cow milk and found that 22% of the children belonging to the low socioeconomic level demonstrated the presence of significant levels of specific IgE against this antigen. Of these milk-positive subjects, 40% were infected by G. lamblia in contrast to only 21% of the milk-negative children (P < .05). These results suggest that children with giardiasis may be exposed to greater amounts of intestinally absorbed antigens. We also studied the specific allergic response to G. lamblia, and found that in an unselected group of children of low socioeconomic level, 25% had positive skin tests, as did 50% of persons with symptomatic giardiasis. The presence of serum anti-Giardia IgE was also demonstrated in 22% of patients with giardiasis.

Animals↗
PubMed1992

Bronchoconstriction in helminthic infection.

In order to determine whether infection by helminthic parasites can be associated with a state of bronchoconstriction, we evaluated the response to the inhalation of a bronchodilator before and after long-term anthelmintic treatment of children in a urban slum of Caracas, Venezuela. In untreated children, a direct association was found between the degree of helminthic infection and the increase in peak expiratory flow rates caused by the bronchodilator. The elimination of the infections was accompanied by a significant decrease in response to the bronchodilator. These results indicate that helminthic infection could contribute to the development of asthmatic conditions in areas where these parasites are endemic.

Albuterol↗
PubMed1991

Determination of phagocytosis of Leishmania spp. by human polymorphonuclear leukocytes using anti-Leishmania monoclonal antibodies.

Phagocytosis of Leishmania is an early event in the capacity of human polymorphonuclear cells to limit the spread of this infectious agent. We compared two methods to assess the phagocytosis of Leishmania by PMN cells; the first using histochemical staining with Wright or Giemsa, and the second using the immunoperoxidase technique with anti-Leishmania monoclonal antibodies. The quantitative results obtained with either of the cytochemical methods were comparable with the immunoperoxidase technique, but the latter offered the advantage of an easier identification of the intracellular parasites. This improvement greatly reduced the time required to quantify phagocytosis compared to the conventional staining techniques.

Adult↗
PubMed1988

Seroprevalence of Toxocara canis infection in tropical Venezuela.

An enzyme-linked immunosorbent assay (ELISA) was used to determine the seroprevalence of Toxocara canis infection in different socio-economic groups of the tropical population of Venezuela. The lack of definitive independent diagnostic criteria for toxocariasis required the establishment of operational upper limits of normality for Toxocara ELISA values, based upon their log-normalized distribution in a presumptive "non-toxocariasis" sub-population. Only 1.8% of urban subjects of medium-high socio-economic level were considered to be clearly positive in Toxocara ELISA, compared to 20.0% of urban slum dwellers, 25.6% rural subsistence farmers and 34.9% Amazon Indians. As the test was performed using excretory-secretory antigen, and under conditions of competitive inhibition by soluble extracts of non-homologous parasites, co-infection by common intestinal helminths, protozoa or other organisms did not give rise to false positive results. However, strong cross-reactivity with Onchocerca volvulus may have influenced the prevalence figure obtained for the Amazon Indians. These results indicate that T. canis is yet another parasite that is widely distributed in economically underprivileged tropical populations.

Adolescent↗
PubMed1988

Specificity of Toxocara ELISA in tropical populations.

The diagnosis of human infection by Toxocara canis relies heavily upon serological tests, the specificity of which can be inadequate in regions of endemic helminthiasis. When different population groups of tropical Venezuela were evaluated using ELISA based upon Toxocara excretory-secretory antigen (TcESA), solid-phase adsorption of the sera with extracts of a wide variety of non-homologous parasites revealed the existence of significant cross-reactivity. This was effectively and conveniently overcome when the test sera were incubated in the presence of the soluble parasite extracts in a competitive inhibition ELISA. The mean reduction of ELISA values caused by pre-adsorption of the sera tested was 32.2%, and that caused by competitive inhibition was 42.3%, the effects of these two procedures being strongly correlated (r = 0.83). The magnitude of the reduction was inversely proportional to the actual ELISA value (r = -0.55), and ranged from a mean of 68.0% in sera from apparently healthy individuals of medium-high socio-economic level, down to 28.1% in heavily parasitized Amazon indians. Ascaris showed the greatest degree of cross-reactivity in these tests, although under conditions of competitive inhibition even sera with high levels of antibody against this parasite could be negative in Toxocara ELISA. Western blotting revealed a major 81,400 D component that was shared between Ascaris and TcESA. Our results indicate that the competitive inhibition of cross-reactivity by soluble non-homologous parasite extracts provides a convenient and economical means of increasing the specificity of ELISA for the determination of the seroprevalence of toxocariasis in tropical populations.

Adsorption↗
PubMed1987

Allergic reactivity and socio-economic level in a tropical environment.

As some factors associated with the tropical environment can modify the expression of atopic disease, various indicators of allergic reactivity were compared between allergic and non-allergic subjects of different socio-economic level in Caracas, Venezuela (Lat. 10 degrees N). The socio-economic levels considered were high (HSEL), medium-high (MSEL) or low (LSEL). As generally found in temperature climates, in the HSEL the total serum IgE levels of allergic patients were significantly greater than those of non-allergic individuals (geometric means of 274 vs 126 IU/ml, respectively), as were also the specific serum IgE antibody levels (55.6 vs 23.8% positive, respectively, for house dust). These results correlated closely with the skin-test reactivity of these subjects (60.3 vs 17.5% positive for house dust). In this group, the degree of intestinal helminthic infection was low (5.6% positive for Ascaris). In contrast, for the MSEL where the degree of parasitic infection was higher (13.0%), the total serum IgE levels were elevated in both allergic and non-allergic subjects (602 vs 363 IU/ml). Similarly, positivity for specific IgE antibody was high, and comparable between allergics and non-allergics of this group (61.5 vs 54.2%), as was also the case for skin-test reactivity (71.9 vs 60.4%). In the LSEL, parasitic infection was prevalent (47.6%), and the total serum IgE levels were markedly elevated, with little difference occurring between allergic and non-allergic individuals (2269 vs 1981 IU/ml). The positivity for specific IgE antibody was high, and effectively independent of the allergic state (75.6 vs 53.7%), but in contrast the skin test reactivity was relatively low (22.0 vs 9.8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

In situ detection of amastigotes in American cutaneous leishmaniasis, using monoclonal antibodies.

Using an immunoperoxidase technique we have applied monoclonal antibodies against American Leishmania for the detection of amastigotes in biopsies from cutaneous leishmaniasis patients. The immunocytochemical procedure was notably superior to conventional histological staining in terms of the visualization and definition of the amastigotes. This technique could eventually prove to be of value in epidemiological studies, and possibly have prognostic importance, by allowing the in situ characterization of the species of infecting organism.

Antibodies, Monoclonal↗
PubMed1986

IgE antibody against surface antigens of Leishmania promastigotes in American cutaneous leishmaniasis.

As IgE-mediated immune mechanisms participate in the host defence against some types of parasites, we evaluated sera from American cutaneous leishmaniasis (ACL) patients for the presence of this antibody against Leishmania. Using monoclonal antibodies against human IgE and an immunoperoxidase staining technique, 48% of the patients sera tested were found to contain IgE antibody that bound strongly to Leishmania promastigotes. A much lower proportion of sera from non-symptomatic subjects from either endemic or non-endemic areas of the disease contained significant levels of anti-Leishmania IgE antibody (6.5% and 0% respectively). The results indicated that the IgE antibody bound predominantly to surface components of the promastigotes, and reactivity against the intracellular amastigote form of the parasite was rarely detected. Somewhat unexpectedly, in a small proportion of the sera, the IgE antibody showed apparent specificity for L. mexicana or L. braziliensis. This study demonstrates that ACL patients can develop anti-Leishmania IgE antibody responses, that seem to be directed preferentially against surface antigens of promastigotes, and that can be strain specific. This raises the question as to the possible contribution of this antibody to the immune defence mechanisms against the parasite.

Animals↗