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Biomedical subjects

D A Levy

Publications and source records attributed to D A Levy.

At least 73 records · Page 4Linked to original sources
PubMed1984

Homologous and distinctive antigens of Onchocerca volvulus and Dirofilaria immitis: detection by an enzyme-linked immuno-inhibition assay.

The limited accessibility of specimens of Onchocerca volvulus has hampered investigations of factors that determine the clinical course of infection of man by this filarial nematode. Parasites antigenically related to O. volvulus have been variously proposed as alternative sources of test antigens. The present study has utilized serologic methods to probe the degree of identity of the antigenic constituents of O. volvulus and Dirofilaria immitis, the dog heartworm. 35S-methionine-labeled proteins of dog heartworm microfilariae (mf) were analyzed in immunoprecipitation assays by using a panel of sera drawn from humans diagnosed for onchocerciasis and from canines infected with D. immitis. Unique and common antigens detected by these sera were resolved in polyacrylamide gels. The majority of high-titered human and infected dog sera reacted with antigenic molecules estimated at 15, 16, 28, 42, 54, 66, and 100 kilodaltons. In addition, a subset of these sera detected large amounts of a 75 kilodalton antigen. Human anti-O. volvulus antibodies were found to bind to intact glutaraldehyde-fixed mf of D. immitis in immunoperoxidase assays. In enzyme-linked immunosorbent assays, the same sera reacted with extracts of three distinct developmental stages of the canine pathogen--namely, the mf, embryonated eggs, and adult worms. Preincubation of dirofilarial antigens with human anti-O. volvulus sera inhibited the binding of dog anti-heartworm serum by as much as 70%. Sera of guinea pigs hyperimmunized with mf of O. volvulus inhibited the binding of the immune dog serum to the same extent. These results represent evidence for extensive homology in the antigenic composition of O. volvulus and D. immitis.

Animals↗
PubMed1983

Dirofilaria immitis: performance and standardization of specific antibody immunoassays for filariasis.

The factors associated with the development, optimization, and validation of immunoassays for the detection of parasite-specific antibody in filariasis infections were investigated using the dog heartworm, Dirofilaria immitis as a model. We examined two assays, the Protein A solid-phase radioimmunoassay (SPRIA) and enzyme-linked immunosorbent assay (ELISA), for quantitation of specific antibody to the parasite in canine serum. Precision, reproducibility, and parallelism were examined using response-error relationships and precision profile analyses. A staphylococcal Protein A saturation analysis was applied to the standardization of IgG anti-parasite antibody reference sera in weight per volume units (microgram/ml). Using the mean minimal detectable dose + 3 SD and an intraassay precision profile less than 10% coefficient of variation (CV) as criteria for assay sensitivity, the SPRIA and ELISA displayed comparable positive thresholds of 1 microgram/ml IgG anti-parasite antibody/ml of serum. Both assays demonstrated good reproducibility (less than 15% interassay CV) and parallelism (less than 20% interdilutional CV) over their working ranges (SPRIA: 1-40 micrograms/ml; ELISA: 1-5 micrograms/ml). Specificity of each assay was enhanced by preadsorption of cross-reacting antibodies in canine serum (i.e., specific for Toxocara canis antigens) with solid-phase antigen prior to assay. Methods for comparing different immunoassay designs are considered in relation to the variables that influence the assays' performance characteristics.

Adsorption↗
PubMed1983

Immunity to intestinal parasites: role of mast cells and goblet cells.

Nippostrongylus brasiliensis infection of rats and mice is a model for studying immunity at mucosal surfaces. Adult worms are spontaneously expelled from the intestine at the end of the second week of infection. Expulsion from the jejunum requires the presence of immune T lymphocytes and IgG antibodies. Mucosal mast cells (MMCs) are a prominent part of the jejunal inflammatory response. They are derived from a hematopoietic stem cell, possibly the same precursor as basophils. Their differentiation is not absolutely T dependent but their accumulation at the site of infection is. The possible involvement of IgE antibodies and intestinal MMCs through a "leak lesion" is still uncertain. Increased mucus secretion from epithelial goblet cells is also a prominent feature of the inflammatory reaction at the site of infection. Goblet cell numbers increase two to four times at the onset of worm expulsion; this increase is regulated by T lymphocytes and possibly immune serum. The mechanism of mucus secretion in these infections is not clear; it may be a response to mast cell mediators. Together with antiworm antibodies, intestinal mucus may trap worms and prevent them from surviving in the intervillous spaces of the jejunum. Thus, expulsion of this intestinal parasite may occur through a nonspecific process that is induced by specific immune mechanisms.

Animals↗
PubMed1980

Expulsion of Nippostrongylus brasiliensis by mice deficient in mast cells.

Expulsion of the intestinal helminth, Nippostrongylus brasiliensis, occurs spontaneously about 2 weeks after a primary infection of rats and mice. Cellular changes in the small intestine coincident with the period of expulsion have suggested several mechanisms by which this 'self-cure' may be effected. Local anaphylaxis was proposed as a possible means of parasite clearance; this hypothesis has been supported by the demonstration of specific reaginic antibody production and jejunal mast cell accumulation in infected animals. In addition, increased mucus secretion and more recently, goblet cell proliferation in the jejunal mucosa of rats have been noted and considered as potentially important in mediating the self-cure reaction. The data presented below indicate that in the absence of demonstrable mast cells, the course of a primary infection with this parasite is unchanged; however, they are supportive of a role for globlet cells in the self-cure reaction.

Animals↗
PubMed1980

Is ABH nonsecretor status a risk factor for obstructive lung disease?

In a multidisciplinary study of risk factors for chronic obstructive pulmonary disease (COPD), a significantly more impairment of forced expiration was observed in ABH nonsecretors than in ABH secretors among 1017 white adults. (ABH refers to the "A" and "B" antigens of the ABO blood group system and "H", the heterogenetic substance which is found in persons of all ABO types including type "O".) Nonsecretors had significantly lower mean values of forced expiratory volume in one second as a percentage of forced vital capacity (FEV1/FVC%) and a significantly larger proportion of them had aberrant values, defined as FEV1/FVC% less than 68. These differences remained when mean values or rates of aberrancy were adjusted for other factors reported to alter risk of airway obstruction. In view of the known COPD-peptic ulcer and nonsecretor-duodenal ulcer associations, these findings suggest that the ability to secrete ABH antigens into secretions of the respiratory and gastrointestinal tract may have a protective effect on epithelialized organs in general, or on the lung and portions of the gut specifically.

ABO Blood-Group System↗
PubMed1980

Alcohol consumption and airway obstruction.

To clarify the basis of the reported association between alcohol and pulmonary disease, the relationship between intake of alcohol and pulmonary function was examined in 2,539 community-dwelling adult participants in an ongoing longitudinal study of risk factors for airway obstruction. Forced expiratory volume in 1 s, expressed as a percentage of forced vital capacity, was used as the indicator of airway obstruction, and forced vital capacity expressed as a percentage of the predicted value was used as an index of restriction. Although crude (unadjusted) mean values of the ratio of forced expiratory volume in 1 s to forced vital capacity were significantly lower for heavy than for light drinkers, the difference disappeared when adjustment was made for numerous confounding factors (including such recognized risk factors for pulmonary disease as cigarette smoking, low socioeconomic status, male sex, and age). There was also no evidence of an association between consumption of alcohol and airway restriction. Although these findings do not rule out a possible effect of alcohol on pulmonary disease, its impact, if any, is probably the result of interaction with other factors associated with alcoholism, if not derived primarily from those other factors.

Adult↗
PubMed1980

Patterns of forced expiratory flows in groups at risk for chronic obstructive pulmonary disease.

In a modified case-control study of obstructive pulmonary disease (COPD), airways obstruction has been found to be associated with age, sex, protease inhibitor type, socioeconomic status (SES) and smoking. In this paper patterns of forced expiratory flows are examined in persons demonstrating various risk factors. Two broad patterns of flow limitation emerge. The first pattern, characterized by lower flows at high lung volumes, is found in first-degree relatives of patients with COPD and subjects with a low SES. This pattern, consistent dysfunction of large airways, may reflect reversible decreases of airway caliber. The second pattern, characterized by lower flows at low lung volumes, is found in older subjects. This pattern, consistent with nonhomogeneously emptying lungs or dysfunction of small airways, may reflect more chronic irreversible changes. Smokers and male subjects exhibit both patterns of flow limitation when compared with subjects who had never smoked and female subjects. It is possible that the combination of the patterns reflects a particularly high risk for the development of COPD in male smokers.

Adult↗
PubMed1979

Early effects of corticosteroids on basophils, leukocyte histamine, and tissue histamine.

The comparative effect in 11 atopic subjects of a single intravenous injection of methylprednisolone on sequential studies of blood eosinophils, basophils, leukocyte sensitivity to antigen for histamine release, leukocyte histamine content, and skin histamine was examined. No significant changes occurred in any parameter after placebo treatment. In contrast, 4 hr after intravenous treatment with steroid there were significant decreases in mean eosinophil counts (-95%), basophil counts (-72%), and histamine content of 1 X 10(7) leukocyte samples (-62%). Temporal changes in the latter paralleled alterations in circulating basophil levels. No significant changes occured in the antigen histamine release sensitivity, or the total skin histamine. Studies over a longer period after steroids in 4 subjects showed eosinophil and basophil levels at a nadir at 8 hr, remaining suppressed for 24 hr, and returned to pretreatment levels by 72 hr. Results suggest that corticosteroids induce a prominent decrease in leukocyte histamine due to a depletion of basophils without a decrease in histamine content per basophil, and that skin tissue histamine stores remain unchanged by such treatment.

Basophils↗
PubMed1977

A common familial component in lung cancer and chronic obstructive pulmonary disease.

First-degree relatives of lung-cancer patients and of patients with chronic obstructive pulmonary disease had significantly higher age-sex-race-smoking-adjusted rates of impaired forced expiration than first-degree relatives of patients with non-pulmonary disease or community-derived comparison series (neighbourhood controls and teachers). Subclassification of the data and multiple adjustment for smoking, race, sex, and other confounding factors emphasised the consistency of the pattern. These findings strongly suggest that lung cancer and chronic obstructive pulmonary disease share a common familial component other than smoking. The clinical manifestation may depend on the presence of one or more other cofactors as yet undefined.

Adult↗
PubMed1977

Risk factors in chronic obstructive pulmonary disease (COPD).

In a genetic-epidemiologic study of chronic obstructive pulmonary disease (COPD) observations adjusted for age, sex, race, and smoking indicate certain factors to be associated with increased pulmonary function aberrancy, and suggest that they are risk factors for COPD. These presumptive "risk factors" include not only cigarette smoking, but also alpha1-antitrypsin (Pi system) variation, one or more other familial components, low socioeconomic status (SES), and, in whites, ABO blood type (either absence of "B" or presence of "A").

ABO Blood-Group System↗