Biomedical subjects

A C Vickery

Publications and source records attributed to A C Vickery.

31 records · Page 2Linked to original sources

PubMed1987

Brugia pahangi in nude mice: protective immunity to infective larvae is Thy 1.2+ cell dependent and cyclosporin A resistant.

Mechanisms of protective immunity to larvae of Brugia pahangi were studied in congenitally athymic nude C3H/HeN mice and their syngeneic heterozygous littermates. An average 11% of subcutaneous larval inocula was recovered from control nudes 28 days after inoculation. No worms were recovered from nude recipients of viable splenic Thy 1.2+ T lymphocytes from heterozygotes which had killed a priming dose of B. pahangi larvae. Primed T lymphocytes, depleted of either Lyt 1.1+ or Lyt 2.1+ cells or incubated with anti-Thy 1.2 monoclonal antibody and complement, failed to protect nude mice against a larval challenge. Nor were primed B lymphocytes depleted by Thy 1.2+ T cell contaminants protective. Treatment with cyclosporin A (CsA) did not increase the numbers of worms recovered from heterozygotes nor did CsA treatment of heterozygous cell donors abolish the ability of primed Thy 1.2+ T lymphocytes to transfer protection to nude mice. IgG but not IgM antibody titres to B. pahangi antigens were depressed in all CsA-treated mice. CsA treatment of nude mice had no direct effect upon development of B. pahangi larvae. These results show that protective immunity to larvae of B. pahangi in mice depends upon small numbers of Thy 1.2+ T cells which are CsA-resistant.

Animals↗

PubMed1987

Characterization of immunosuppressive proteins of Brugia malayi microfilariae.

Inhibition of Concanavalin A-induced lymphocyte proliferation was used to monitor the partial purification and characterization of suppressor molecules from microfilariae of Brugia malayi. Suppressor activity was present in high molecular weight fractions of microfilarial extracts (Mr greater than 50 kd on SDS-PAGE) and was protease-sensitive but resisted treatment with sodium periodate, indicating that it is associated with parasite proteins. Suppressor activity was released by microfilariae cultured in vitro and could be detected in peritoneal exudates of intraperitoneally-infected jirds and in lymph and sera from athymic C3H/HeN mice with patent B. malayi infections. These findings indicate that immune unresponsiveness during patent filarial infections may result from the in vivo release by microfilariae of high molecular weight proteins that suppress host immune responses.

Animals↗

PubMed1985

Diethylcarbamazine-mediated clearance of Brugia pahangi microfilariae in immunodeficient nude mice.

Congenitally athymic nude C3H/HeN mice, microfilaremic with Brugia pahangi, were treated with diethylcarbamazine citrate (DEC). A single oral dose (100 mg/Kg body weight) of DEC resulted in the rapid reduction of numbers of circulating microfilariae in nude, thymus-grafted nude and complement-depleted nude mice. Antibodies of the IgM and IgG isotypes were not detected in the serum of microfilaremic nudes or on the microfilarial surface. These results suggest that DEC-mediated clearance of microfilariae from the circulation of nude mice is probably independent of thymus-dependent immunological mechanisms.

Animals↗

PubMed1985

Differential pathogenicity of Brugia malayi, B. patei and B. pahangi in immunodeficient nude mice.

Immunodeficient nude mice chronically parasitized by subperiodic Brugia malayi developed an elephantoid appearance with persistent lymphoedema of limbs and massive lymphangiectasis of subcutaneous vessels containing viable adult worms. Removal of worms reversed the process. The syndrome was not caused by B. patei or B. pahangi and was not correlated with the presence or absence of microfilaremia. Histologic examination of elephantoid mice revealed dilated and tortuous lymphatics containing small nonobstructive lymph thrombi composed of small mononuclear cells and multinucleate giant cells. Draining lymph nodes were not enlarged or congested and mast cells in oedematous tissue were not degranulated. Analysis of lymph aspirated from dilated lymphatics showed increased total protein content: bacterial sepsis was not detected. This work suggests that viable adult B. malayi exert direct pathologic effects upon lymphatics and that this parasite is more pathogenic than related Brugia spp.

Animals↗

PubMed1984

Immunity to Brugia pahangi in athymic nude and normal mice: eosinophilia, antibody and hypersensitivity responses.

Congenitally athymic nude (nu/nu) mice, immunologically reconstituted by thymus grafting before inoculation with infective larvae, and mice heterozygous for the nu gene (nu/+), mounted potent protective humoral and cellular immune responses to Brugia pahangi. Although responses were not identical, both groups of mice produced IgM, IgG and IgE antibodies specific for adult worm antigen (S-Ag) present in a crude aqueous extract, made immediate and delayed hypersensitivity footpad swelling responses when challenged with S-Ag and eliminated their infection in the early larval stages. Heterozygotes also exhibited a marked eosinophilia which peaked coincident with larval killing. In contrast, thymus grafting of patent nudes had no effect upon microfilaraemias or adult worm burdens and did not completely protect against a challenge larval inoculum although antibodies specific for S-Ag were produced. With the occasional exceptions of moderate immediate footpad swelling and very low titres of IgM specific for S-Ag, no specific immune responses to B. pahangi were found in ungrafted nude mice which allowed full development of adult worms and supported patent infections.

Animals↗

PubMed1984

A survey of filariasis among refugees in south Florida.

Between January 1981 and March 1982, a filariasis survey was conducted among 668 Haitian immigrants and 155 Southeast Asian refugees residing in Florida, U.S.A. Microfilariae were detected only in Haitians, with 6.7% positive for Wuchereria bancrofti and 1.3% positive for Mansonella ozzardi. The majority of individuals with bancroftian filariasis came from five coastal urban areas including Port-au-Prince, Duvalierville, Gonaïves, Leógane and Cap-Haitien. No unequivocal signs of bancroftian filariasis or mansonellosis were seen. Membrane feeding of several species and strains of laboratory-reared mosquitoes on blood from a volunteer microfilaremic with W. bancrofti showed that Aedes aegypti and A. taeniorhynchus, but not Culex quinquefasciatus, were susceptible to infection with the Haitian strain of W. bancrofti. Culicoides furens, a known vector of M. ozzardi in Haiti and present in Florida, was not tested. Further studies are needed to determine the competence of Florida vectors for transmitting W. bancrofti and M. ozzardi to the indigenous human population.

Adolescent↗

PubMed1984

The lymphatic pathology of Brugia pahangi in nude (athymic) and thymic mice C3H/HeN.

The nude (congenitally athymic) mouse, C3H/HeN is highly susceptible to infection with Brugia pahangi (Nematoda: Filarioidea). Normal, hairy mice show a strong thymus-dependent resistance and usually terminate the infection in the larval stages. The present study examined chronological histopathologic changes in the lumbar lymph nodes and adjacent lymphatic vessels of both hosts. In thymic mice, lymphangitis and perilymphangitis reached a maximum 14 to 17 days PI, about the time of disappearance of live worms. The infiltrate showed characteristics of both acute and chronic inflammation: eosinophils, neutrophils, eosinophilic precipitates, and sometimes necrotizing lymphangitis, as well as macrophages and plasma cells. The cellular infiltrate in nude mice was weaker and developed more slowly. Inflammatory responses to identifiable dead worms were seen in both types of hosts but appeared more frequently in thymic mice. Although variable in both models, the granulomas of thymic mice generally showed more tendency to cavitation, greater macrophage or epithelioid cell infiltration, more granulocytes, and appeared to be more destructive than the foreign body responses of nude mice. Whereas lymphangiectasis was generally progressive in nude mice, it was arrested before the end of the third week in thymic mice. In thymic mice, at maximum lumbar lymph node size (17 days), there were large areas of lymphocyte hyperplasia and heavy infiltration of plasma cells. Most nodes returned to normal mean size by the end of the second month. Little or no reactivity was seen in athymic mouse nodes. Our results suggest that some lesions of lymphatic filariasis are potentially thymus-independent: lymphatic fibrosis, lymphangiectasis, accumulations of macrophages and giant cells around disintegrating worms, calcification of worms, intralymphatic thrombosis, and moderate vascular infiltrates including eosinophils.

Animals↗

PubMed1983

Brugia pahangi: antibodies and microfilaremias in Lewis rats.

Male and female Lewis rats were inoculated subcutaneously in the left groin with 75 infective larvae of Brugia pahangi and microfilaremias were followed for as long as 420 days postinoculation. Patent infections developed in 64% of the female rats and 95% of the male rats. Mean prepatent periods were similar (65.9 and 63.9 days, respectively), but mean microfilaremias in males rose much higher, to a mean of 218 mf/0.25 ml blood at 270 days postinoculation. IgG titers, as measured by enzyme-linked immunosorbent assay (ELISA), to adult worm somatic antigen were higher than those to microfilariae in almost all rats. For both sexes, the most consistently microfilaremia rats had highest titers to these antigens. Granulomas with degenerating microfilaria were present in the spleen of male rats with high microfilaremias (greater than 100-300 mf/0.25 ml blood). Ouchterlony precipitin reactions suggested that most rats with spleen granulomas responded to microfilarial antigen components to which most rats without granulomas did not. Neither spleen granulomas nor antibody responses measured in this study appeared to have protective (microfi8laremia-lowering) value. As measured by microfilaremias, the male Lewis rat is not as susceptible as some conventional hosts of B. pahangi, but it does consistently become infected and remains microfilaremic for more than a year. Preferential male susceptibility indicates that this model may be useful for studying this aspect of human lymphatic filariasis.

Animals↗

PubMed1983

Effect of immune reconstitution on resistance to Brugia pahangi in congenitally athymic nude mice.

The dichotomy of resistance to Brugia pahangi (Nematoda: Filarioidea) between nonsusceptible, euthymic C3H/HeN mice, heterozygotic for the "nu" gene (+/nu), and susceptible, congenitally-athymic "nude" (nu/nu) C3H/HeN mice, suggests that resistance is thymus-dependent. To test this hypothesis, the effect of syngeneic neonatal thymus grafts and neonatal thymus cell suspensions on recovery of worms at day 40 PI, and responses to Concanavalin A (Con A) were examined in reconstituted nudes. Nude recipients of a thymus graft 7 or 14 wk before subcutaneous inoculation with 50 infective larvae (L3) yielded no worms and responded strongly to Con A. Serum from these mice reacted in two lines of identity with serum from similarly-infected heterozygotes by double radial immunodiffusion against an adult worm saline extract. Nude recipients of a thymus 2 days or 3 wk before inoculation harbored an average of three or two worms, respectively. Intravenous injection of nude recipients with 10(7) or 10(8) neonatal thymus cells seven weeks before inoculation was less effective in conferring resistance to B. pahangi and responsiveness to Con A. Complete resistance to B. pahangi could be adoptively transferred to nude mice by 10(8) spleen cells obtained from infection-primed heterozygotes and injected intravenously on the day of larval inoculation. The same numbers of worms were significantly reduced. less effective when injected 3 wk before inoculation, although numbers of worms were significantly reduced. Passive transfer of primed heterozygote serum, containing high titers of antibodies to adult worm and larval antigens, failed to protect nude recipients against a larval inoculum in the absence of cellular reconstitution.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1982

Nondevelopment of Wuchereria bancrofti in nude (congenitally athymic) mice.

Infective larvae of Wuchereria bancrofti (Nematoda: Filarioidea) were harvested from Aedes aegypti mosquitoes fed in vitro on microfilaremic blood of Haitian volunteers. Larvae were inoculated either into the subcutaneous tissue (SC) or peritoneal cavity (IP) of congenitally athymic (nude) mice, C3H/HeN (nu/nu). Initially 15 male and two female mice received larval doses from 38-180, and necropsy was done between 11 and 75 days post-inoculation. No worms were found at necropsy. Four additional male mice given 75 larvae each were also injected daily with 0.3 ml of normal human serum, but again no worms were recovered at necropsy on days 13 through 17. Given the severe nature of the nude immunodeficiency, it seems unlikely that the total failure of W. bancrofti to develop in nude mice results from a T cell-dependent immune response. Perhaps either non-immune mechanisms actively destroy larvae or the mouse lacks a factor(s) essential for parasite development, but not found in human serum. In any case, the thymic independence of resistance to W. bancrofti is clearly unlike that shown to the related filaria, Brugia pahangi.

Animals↗

PubMed1982

Life cycle of Brugia pahangi (Nematoda) in nude mice, C3H/HeN (nu/nu).

The development of Brugia pahangi (Nematoda: Filarioidea) was studied in nude (congenitally athymic) mice C3H/HeN (nu/nu) and in their phenotypically normal littermates (nu/+). Nude mice were highly susceptible to this parasite. As in the natural host (the cat), the nematodes' third molt in nude mice occurred at 7 to 10 days. The final molt occurred at about 24 days for male worms and 33 days for female worms. Adult worms were smaller than those from other hosts, such as the cat. After inoculation of various numbers of infective larvae, recoveries of adult worms averaged about 15% of the inoculum. In long-term infections initiated with 100 larvae, about 75% of the worms localized in the heart or lungs. Patent infections were seen as early as day 50 PI. Microfilaremia developed in most nude mice given 100, 50, or 25 infective larvae, but was less frequent in those given only 10. Mean filaremias generally rose during the first 6 mo, but in individuals usually did not exceed 500-600/20 mm3 of blood. As in the Mongolian jird, intraperitoneal inoculations yielded large quantities of worms and microfilariae. Few worms could be recovered from normal mice after day 40, even when large (1,000 larvae) inocula were used. Microfilaremia was not detected in normal mice. Although recoveries of adult worms from some nude females were not as high as those from nude males, neither nude nor normal mice showed consistent evidence of a differential susceptibility based on sex. Given the strong, consistent dichotomy of response to B. pahangi between nude and normal mice, this system may be useful in studies of protective immune responses in filariasis.

Animals↗

PubMed1981

Modulation of lymphoid cell blastogenic responsiveness to mitogens by Nippostrongylus brasiliensis infection.

Spleen and mesenteric lymph node cell blastogenic responses to the mitogens concanavalin A and lipopolysaccharide and to parasite antigens were examined in vitro following removal from mice undergoing primary or secondary infection with Nippostrongylus brasiliensis. During primary infection spleen cells showed a marked increase in proliferative responsiveness to both mitogens, followed by a marked depression thereafter. During a secondary infection the response of spleen cells to both mitogens remained depressed. In contrast, cells from the mesenteric lymph nodes of infected mice exhibited enhanced responsiveness to Con A and LPS, followed by depression of the response, followed by another cycle of enhancement upon reinfection. Sensitivity of both spleen and especially mesenteric lymph node cells to Nb antigens was greatest at approximately the time of worm expulsion: Day 13 after primary and Day 8 after secondary infection.

Animals↗

PubMed1981

Flubendazole and mebendazole in the treatment of trichuriasis and other helminthiases.

Forty patients were treated with either flubendazole or mebendazole, 100 mg twice a day for three days, in a double-blind, prospective, randomized study. The study concentrated on patients with Trichuris trichiura infections, although the effects of the anthelmintic agents on concomitant Ascaris lumbricoides and hookworm infections were also evaluated. Results from 35 evaluable patients showed complete cure in 17/19 (89%) patients treated with flubendazole and 15/16 (94%) patients treated with mebendazole (P less than 0.05, no significant difference). Significant reduction in Trichuris egg counts was noted in the three other patients. No significant adverse clinical or laboratory reactions were noted. Other roundworms were completely eradicated by both anthelmintic agents. Based on this study, flubendazole appears to be as effective and safe as mebendazole in the treatment of nematode infections.

Antinematodal Agents↗