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Biomedical subjects

D I Grove

Publications and source records attributed to D I Grove.

At least 109 records · Page 6Linked to original sources

Eosinophils and resistance to Trichinella spiralis.

Mice infected with Trichinella spiralis were depleted of eosinophils by repeated administration of rabbit anti-mouse eosinophil serum. There was no effect on the spontaneous expulsion of adult worms from the small intestines, but the numbers of larvae in the muscles were almost doubled. It is concluded that eosinophils contribute to resistance to the systemic phase of trichinosis.

Animals↗

The Schistosoma mansoni egg granuloma: quantitation of cell populations.

Granulomas were induced by the intravenous injection of eggs of Schistosoma mansoni into the lungs of mice which were either unsensitised, sensitised by prior intraperitoneal injection of eggs, or naturally infected with S. mansoni. At various time intervals after egg injection (8, 16 and 32 days in unsensitised mice; 4, 8 and 16 days in sensitised mice; and 8 days in mice infected for 4, 8 16 and 24 wk) the lungs were removed from groups of mice and were placed in a Waring blender at low speed. Complete intact granulomas were isolated, the lesions were dispersed with collagenase and pronase and the cell populations quantified and classified as eosinophils, neutrophils and mononuclear cells less than or equal to 12 or greater than 12 micron in diameter. Small mononuclear cells consisting almost exclusively of lymphocytes were the predominant cells initially, but eosinophils became the most common cell type, reaching a peak of 71% of cells in sensitised animals 16 days after injection. Large mononuclear cells remained relatively constant at about 30% of the total cells. Neutrophils neverreached more than 10% of cells. Sensitisation by a prior intraperitoneal injection of eggs led to an acceleration of granuloma formation. In infected mice, the granulomas with the largest cell counts were seen 8 wk after infection while the smaller granulomas in the mice infected for 16 or 24 wk confirm the previously reported modulation of this immunopathological reaction.

Animals↗

Kinetics of immunological responses, resistance to reinfection, and pathological reactions to infection with Trichinella spiralis.

Changes in immune responses, resistance to reinfection, and pathological reactions were studied serially in mice that had been infected for four to 40 weeks with 150 larvae of Trichinella spiralis. Immediate footpad hypersensitivity reactions to antigens of Trichinella were present throughout the period of observation. Delayed hypersensitivity reactions 48 hr after injection of antigen were first seen in mice infected for 14 weeks and gradually increased in size thereafter. Intestinal adult worm burdens were determined one week after challenge with 5000 larvae. There was resistance to reinfection and accelerated expulsion of worms in animals challenged three weeks after the primary infection; this resistance waned at seven and 13 weeks but reappeared in mice infected for 20 weeks or longer. Counts of larvae in muscle were determined four weeks after challenge with 5000 larvae. Marked resistance was present four weeks after the primary infection and was maintained for the duration of the study.

Animals↗

Suppression of cell-mediated immunity by metronidazole.

Metronidazole administered orally in doses of 20 and 200 mg/kg daily suppressed granuloma formation around Schistosoma mansoni eggs which were injected intravenously and lodged in the pulmonary microvasculature of mice. The same doses did not suppress granuloma formation in animals which had previously been sensitized to the eggs. Nonspecific granulomatous inflammation around divinyl benzene copolymer beads was unaffected by the drug. In a daily dose of 20 mg/kg, metronidazole inhibited delayed footpad reactions to soluble schistosome egg antigen, but 200 mg/kg on alternate days failed to suppress skin allograft rejection. The drug appears to suppress selectively some aspects of cell-mediated immunity.

Animals↗

Sensitivity and specificity of skin reactivity to Brugia malayi and Dirofilaria immitis antigens in Bancroftian and Malayan filariasis in the Philippines.

Saline antigen extracts of microfilariae, adult worms and third-stage larvae of subperiodic Brugia malayi maintained in gerbils were prepared for use as skin test reagents. Patients were studied on three different islands in the Philippines, one endemic for Bancroftian filariasis (Sorsogon, Luzon), another endemic for Malayan filariasis (Palawan) and the third without endemic filariasis (Cebu). A dose-response curve was established initially in patients with Bancroftian filariasis: thereafter 1.0 microng of the B. malayi antigens and 0.05 microng of Dirofilaria immitis FST antigen (obtained from Dr. T. Sawada) were used. Sizes of reactions were measured by recording the diameters of wheals at 20 minutes, 24 and 48 hours. There was a very high correlation in immediate hypersensitivity reactions among the three B. malayi antigens. Reaction sizes followed a normal distribution. When an area of an antigen-induced wheal 3 X that of the saline control was considered a positive reaction, 99% of 150 patients with Bancroftian filariasis and 96% of 45 subjects with Malayan filariasis reacted to B. malayi larval antigen. Only 68% of patients with Bancroftian filariasis but 90% of those with Malayan filariasis reacted to D. immitis FST antigen. There was no relationship between skin reactivity and age, sex, microfilaremia or severity of clinical disease. Approximately half of 50 patients who lived in an endemic area for W. bancrofti but had neither patent infection nor clinical disease reacted to B. malayi antigens. A maximum of 7% of 120 age- and sex-matched controls from Cebu gave false positive reactions with any of the antigens. Only a small proportion of patients gave 24- and 48-hour reactions. It is concluded that the use of antigens prepared from a human parasite, subperiodic B. malayi, which is easily maintained in a laboratory animal host, improves the ability to diagnose filarial infections by immunological means.

Adult↗

Effects on murine trichinosis of niridazole, a suppressant of cellular but not humoral immunological responses.

Two groups of mice infected with Trichinella spiralis were treated with niridazole (100 mg/kg), one on alternate days, the other daily. Both regimens failed to influence the numbers of adult worms in the intestines or larvae in the muscles compared with untreated control mice. Mice treated with niridazole daily, but not those treated on alternate days, showed a significant reduction in the inflammatory reaction to larvae in the muscles. Immediate footpad swelling in response to injection of soluble Trichinella larval antigen was not affected by niridazole treatment. Niridazole appears to have a highly selective action on immunological responses suppressing cell-mediated reactions but leaving humoral antibody formation relatively intact. Elimination of worms may require the presence of both cellular and humoral immune mechanisms, while inflammation around larvae in the muscles may be largely a cellular reaction.

Animals↗

Suppression of giardiasis during the intestinal phase of trichinosis in the mouse.

The interaction of the intestinal phases of Giardia muris and Trichinella spiralis was investigated in Swiss albino mice. Intraoesophageal inoculation of G. muris cysts seven days before, or seven days after, similar inoculation of T. spiralis larvae resulted in significant reduction in the numbers of Giardia trophozoites in small bowel and Giardia cysts in stools. This effect was not observed when G. muris cysts were administered after resolution of the intestinal phase of trichinosis. Giardiasis had no effect on trichinosis as assessed by numbers of adult worms in small bowel and larvae in skeletal muscles. Studies of small bowel morphology showed that the intestinal phase of trichinosis was associated with increased numbers of inflammatory cells in the lamina propria, a significant increase in Paneth cells in crypts, and a marked reduction in the villus:crypt ratio of jejunum. These observations suggest that the intestinal phase of trichinosis induced environmental changes in small bowel, perhaps related to inflammation, which resulted in suppression of proliferation of Giardia trophozoites.

Animals↗

Relation of intensity of infection to disease in hamsters with acute schistosomiasis mansoni.

Groups of young hamsters were exposed to 3, 20, 40, 80, or 160 cercariae. A highly significant correlation was observed between the number of cercariae, worm burdens, and liver and fecal egg counts. The most heavily infected animals were the first to lose weight and die. Hamsters exposed to 20 or more cercariae and harboring a mean of 4.2 or more worm pairs developed significant hepatosplenic disease by 10 weeks after infection as assessed by hepatomegaly, splenomegaly and the development of portal hypertension. Lightly infected animals with single worm pairs did not develop significant disease.

Acute Disease↗

Increased resistance to helminth infestation in an atopic population.

Faecal egg counts were compared in three groups in an area of universal hookworm infestation. Egg counts were lower in asthmatic and atopic non-asthmatic subjects than in a non-atopic population. The atopic population was defined by skin testing for immediate hypersensitivity responses. It is suggested that the atopic state may confer increased resistance to helminth infestation.

Adolescent↗

Humoral and cellular immunity in asthma.

Parameters of humoral and cellular immunity have been measured in 91 asthmatic patients. Mean serum levels of IgG and IgE were raised. IgG levels were higher in those with a family history of asthma. IgE levels were higher in those with a past history of atopic eczema, but intrinsic and extrinsic asthma could not be differentiated on the basis of IgE levels. Thirteen of 74 patients failed to respond to tetanus immunization, while only 1 failed to respond to Salmonella typhi H antigen. Tetanus nonresponders had a raised mean serum IgA level, reduced spontaneous lymphocyte tritiated thymidine uptake, and reduced thymidine uptake in fetal calf serum. Eight of 87 patients failed to mount delayed hypersensitivity reactions to a battery of five intradermal antigens. The tritiated thymidine uptake of lymphocytes stimulated with phytohemagglutinin was normal in autologous serum, but reduced in fetal calf serum. The data support the hypothesis that asthma may be associated with immunodeficiency states.

Adolescent↗

Humoral and cellular immunity in atopic eczema.

Parameters of humoral and cellular immunity were measured in thirty-five patients with atopic eczema. The mean serum IgE level was raised but levels of the other major immunoglobulin classes were normal. Ten per cent of patients failed to respond to tetanus immunization. All patients responded to S. typhi H antigen. Fourteen per cent of patients failed to mount delayed hypersensitivity reactions to a battery of three intradermal antigens. The phytohaemagglutinin-stimulated uptake of 3H thymidine by lymphocytes was normal in the presence of autologous or of fetal calf serum, as was the spontaneous lymphocyte uptake. T and B lymphocyte numbers in the peripheral blood were normal. These results are similar to those found in asthmatic patients and support the hypothesis that, in some patients, atopic eczema is associated with an immunodeficiency state.

Adolescent↗