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J P Farrell

Publications and source records attributed to J P Farrell.

At least 37 records · Page 2Linked to original sources
PubMed1994

Site-specific immunity to Leishmania major in SWR mice: the site of infection influences susceptibility and expression of the antileishmanial immune response.

Inbred strains of mice usually develop either of two divergent patterns of infection in response to Leishmania major. Resistant mice, which develop self-limiting infections, respond immunologically with the activation of gamma interferon-secreting Th1 helper T cells, while nonhealing infections in susceptible mice are characterized by the proliferation of interleukin-4-secreting Th2 cells. Development of these divergent responses is dependent primarily on the strain of mouse infected, although factors such as the infective dose, species, and strain of parasite can also influence the degree of resistance. In this study, we show that a single mouse strain, SWR, can develop totally divergent patterns of infection depending on the site of parasite inoculation. Both SWR mice and highly susceptible BALB/c mice developed progressive, ultimately fatal disease when inoculated in the dorsal skin over the base of the tail. However, SWR mice infected in the hind footpad developed far less severe infections, which were for the most part controlled, whereas BALB/c mice infected in this site developed severe, nonhealing lesions. Production of gamma interferon and interleukin-4 and measurement of immunoglobulin E levels in serum were used to assess the degree of Th1 and Th2 cell activation in infected mice. Cytokine profiles early in infection had characteristics of a mixed Th1-Th2 response and were similar in SWR mice infected at either site. These early cytokine responses were not predictive of the ultimate disease outcome, since lymph node cells from healing mice eventually produced higher levels of gamma interferon than did those from nonhealing mice, and healing mice had lower levels of immunoglobulin E in serum, suggesting a functional bias toward Th1 cell activity in these animals. The differential ability of SWR mice to heal infections at different cutaneous sites provides a new model for the study of resistance to cutaneous leishmaniasis. Unlike traditional models of infection in which resistant and susceptible strains of mice are compared, this model allows for the study of factors that contribute to healing and nonhealing infections in a genetically identical strain of mouse.

Animals↗
PubMed1992

Manual therapy: a critical assessment of role in the profession of physical therapy.

Interest in manual therapy appears to continue to grow among physical therapy clinicians and educators throughout the world even though the underlying concepts and techniques have not been justified by a knowledge base. The purposes of this article are to critically assess the role of manual therapy within the physical therapy profession and to provide an introduction to the other articles in this special issue. Eisner's model of explicit, implicit, and null curricula is used as a framework for our analysis and our discussion of manual therapy. The explicit area of manual therapy includes discussions of the definition and the role of manual therapy, the scientific rationale for manual therapy, and manual therapy in education and a comparison of manual therapy evaluative frameworks. The implicit area deals with the role of clinical decision making and critical thinking in manual therapy in education and rehabilitation. In the null (unaddressed) area of manual therapy, we suggest directions for future development and research.

Clinical Competence↗
PubMed1989

A role for Lyt-2+ T cells in resistance to cutaneous leishmaniasis in immunized mice.

The role of Lyt-2+ T cells in immunologic resistance to cutaneous leishmaniasis was analyzed by comparing infection patterns in resistant C57BL/6 mice and susceptible BALB/c mice induced to heal their infections after sub-lethal irradiation or i.v. immunization, with similar mice treated in vivo with anti-Lyt-2 antibodies. Administration of anti-Lyt-2 mAb resulted in a dramatic reduction in the number of lymphoid cells expressing the Lyt-2+ phenotype. Such treatment led to enhanced disease in both resistant C57BL/6 and irradiated BALB/c mice, as assessed by lesion size, but did not affect the capacity of these mice to ultimately resolve their infections. In contrast, anti-Lyt-2 treatment totally blocked the induction of resistance in i.v. immunized mice. These results suggest, that Lyt-2+ T cells may play a role in immunity to a Leishmania major infection and that their relative importance to resistance may depend on how resistance is induced.

Animals↗
PubMed1989

Comparison of T-cell responses in self-limiting versus progressive visceral Leishmania donovani infections in golden hamsters.

Leishmania donovani infection in golden hamsters was studied as a model for human kala-azar. After intradermal inoculation of L. donovani amastigotes, hamsters developed positive skin reactions (delayed-type hypersensitivity [DTH]) to parasite antigens and lymphoid cells from these hamsters proliferated to parasite antigens in vitro and transferred DTH reactivity to normal recipients. In contrast, hamsters infected by the intracardial route developed progressive visceral infections and failed to respond to skin test antigens. Spleen cells, lymph node cells, and peripheral blood lymphocytes (PBLs) from these hamsters were unresponsive to parasite antigens in vitro, and spleen cells failed to transfer DTH to normal recipients. Spleen cells, but not PBLs, displayed depressed responses to T-cell mitogens and also suppressed the proliferative response of cells from hamsters inoculated intradermally. Removal of adherent cells restored the capacity of spleen cells, but not PBLs, to respond to parasite antigens. The nonadherent population of these spleen cells also transferred DTH to normal recipients. The adherent suppressor cells, which have the characteristics of macrophages, appear to be localized to the spleen and are apparently not responsible for the failure of peripheral lymphoid cells to respond to antigen. These studies suggest that hamsters with visceral infections develop a population of antigen-reactive cells and that in the absence of suppression these cells may express functional activities, including the capacity to elicit DTH responses.

Animals↗
PubMed1987

Experimental cutaneous leishmaniasis. II. A possible role for prostaglandins in exacerbation of disease in Leishmania major-infected BALB/c mice.

Leishmania major infection in genetically susceptible BALB/c mice is associated with the development of chronic primary lesions as well as multiple metastatic lesions. Spleen cells from these mice were shown to have depressed in vitro responses to concanavalin A (Con A) that coincided with the development of indomethacin-sensitive suppressor cells. Depressed responses to Con A were noted as early as 1 wk after parasite inoculation and correlated with the increased production of prostaglandin E2 (PGE2) by spleen cells from infected mice. Mice induced by prior irradiation (550 rad) to heal infection did not develop indomethacin-reversible depression in responsiveness to Con A. Although macrophages appear to be the major source of PGE2 production, in vitro studies indicate that infection per se is not a sufficient stimulus to initiate prostaglandin (PG) synthesis, suggesting the involvement of other cell types. Mice treated in vivo with indomethacin exhibited significantly fewer metastatic lesions than control mice, suggesting that PG may play a role in the exacerbation of cutaneous disease in these animals.

Animals↗
PubMed1987

Rate of Leishmania-induced skin-lesion development in rodents depends on the site of inoculation.

Regional differences in the response of mice to infection with three strains of dermotropic Leishmania spp. were shown for skin covering the trunk. Lesions tended to appear earlier and to grow more rapidly on sites over the caudal half of the body than the cranial half, and caudal lesions were more likely than cranial ones to result in metastatic disease in susceptible strains of mice. Site-related variations in lesion development were observed in different strains of mice as well as in golden hamsters. The effect of these regional differences on the development of some parasite-specific, immunological reactions was examined, as were parasite thermosensitivity and location-related variations in host skin temperature as possible explanations.

Animals↗
PubMed1987

Experimental infections of the multimammate rat (Mastomys natalensis) with Leishmania donovani and Leishmania major.

The susceptibility of the multimammate rat, Mastomys natalensis, to experimental infections with Leishmania donovani and L. major was examined. Inoculations of L. major promastigotes into the skin resulted in nonulcerating lesions in which parasites could be detected for more than 30 weeks later. Intravenous inoculations of L. donovani promastigotes produced visceral infections characterized by a continuing increase in splenic parasite burdens and liver parasite burdens which peaked during the first few weeks of infection and gradually decreased as the disease became chronic. L. donovani could be isolated from the blood throughout the infection, and promastigotes were cultured from the spleens of rats inoculated intradermally. Thus, the multimammate rat appears to be a good reservoir host for these parasites.

Animals↗
PubMed1986

Cellular and humoral immune responses of jirds resistant to Dipetalonema viteae infection.

Jirds with prepatent Dipetalonema viteae infections develop an acquired immunity to challenge infections. The objective of the present study was to observe parasite-specific and nonspecific cellular and humoral immune responses in immune jirds. Splenic hyperplasia was observed in infected jirds during the first 5 weeks of infection. Antigen-reactive spleen cells were observed in the lymphocyte transformation assay at 3 weeks postinfection. A depressed response to concanavalin A (ConA) was seen at 1 week postinfection through week 5. Mitomycin C-treated cells from infected jirds were capable of suppressing the response of normal cells to ConA. Sephadex G-10-nonadherent spleen cells from infected jirds showed elevated responses to D. viteae antigen at 1, 3, and 5 weeks and elevated responses to ConA at 3 and 5 weeks. Filaria-specific antibodies were seen at 1 week postinfection, and titers rose through week 5. Plaque-forming cell production to sheep erythrocytes was not depressed in infected jirds. It was concluded that jirds react immunologically with both cellular and humoral responses during the prepatent period of D. viteae infection. A concurrent immune depression was seen. Its effect on resistance and tolerance remains to be determined.

Animals↗
PubMed1986

Protective immune responses of the jird to larval Dipetalonema viteae.

In vivo and in vitro experiments were performed to study immune protective mechanisms against larval Dipetalonema viteae. Jirds infected with 30 third-stage larvae (L3) of D. viteae for 1, 3 or 5 weeks showed significant killing of challenge larvae implanted for 2 weeks in diffusion chambers. A retardation of larval growth was seen 7 days after larval implantation, and larval death was observed beginning at 10 days. When L3 were placed in vitro with peritoneal exudate cells (PEC) from normal jirds, cellular adherence was seen starting on Day 4, and larval death was seen on Day 10. It was concluded that larvae had to undergo some development in vitro, that would allow cellular adherence to larval surface. Larvae, recovered after 7 days in vivo or in vitro, were placed in culture with normal PEC; cell adherence and worm death occurred at equal rates for both groups of worms. Larvae which had been in culture for 7 days were implanted in immunized jirds for 7 days. Significant killing of these worms was observed, whereas larvae recovered from ticks prior to implantation were not killed. In vivo and in vitro results therefore show that larval development is required for generating susceptibility to specific and/or non-specific immune reactions. A hypothesis is suggested for the function of larval retardation.

Animals↗
PubMed1985

Participation of natural killer cells in the recovery of mice from visceral leishmaniasis.

After infection with the protozoan parasite Leishmania donovani, C57BL/6J bg/bg (beige) mice, which are deficient in natural killer (NK) activity, were unable to control splenic parasite loads relative to phenotypically normal C57BL/6J bg/+ and +/+ mice, particularly beyond 21 days of infection. When beige mice were injected intravenously with 2 or 3 X 10(6) syngeneic, cloned NK cells (NKB61B10 cell line), they displayed splenic parasite burdens which did not differ significantly from those of normal controls. In C57BL/6 +/+ mice rendered NK deficient by split-dose irradiation (four weekly, 200-rad doses of gamma irradiation beginning at 4 weeks of age) splenic and hepatic parasite levels were significantly higher than those in nonirradiated controls at 15 days of infection and beyond. In both sets of experiments, relative degrees of hepato- and splenomegaly were not sufficient to account for differences in parasite burdens among NK-deficient and normal mice. Taken together, the results of these experiments suggest that NK cells may contribute to parasite elimination during the acquired-resistance phase of L. donovani infection in mice.

Animals↗
PubMed1985

Inhibition of in vivo and in vitro infectivity of Leishmania donovani by tunicamycin.

Leishmania donovani 2S strain promastigotes were rendered non-infectious to mice and mouse peritoneal macrophages by treatment with tunicamycin, an inhibitor of N-linked protein glycosylation. Concentrations of tunicamycin (1-10 micrograms ml-1) that reduced promastigote infectivity to 2% or less of control levels had little or no measurable effect on the in vitro growth of the promastigotes. Tunicamycin has no apparent effect on the entry of promastigotes into macrophages. These results indicate that the sugar residues of glycoproteins are important to the promastigote during the early stages of macrophage infection.

Animals↗
PubMed1984

Splenic natural killer-cell activity in mice infected with Leishmania donovani.

Several strains of inbred mice were infected with the protozoan parasite Leishmania donovani, and, at several points during the infection, spleens of groups of these mice were tested for natural killer (NK)-cell activity vs lymphoma target cells in vitro and were evaluated for parasite burdens. Generally, elevated followed by normal (compared to uninfected control mice) or subnormal NK responses occurred as the result of infection. Elevated NK responses were not accompanied by high circulating levels of interferon, yet infected mice responded to an injection of an interferon inducer with interferon production as great as control mice. No consistent correlations among susceptibility phenotype to L. donovani infection, spontaneous NK activity phenotype, and infection-induced NK activation/depression patterns were detected among the various strains of mice.

Animals↗
PubMed1984

Mechanisms of depression of splenic natural killer cell function in C57BL/6 mice infected with Leishmania donovani.

C57BL/6 mice chronically infected with the protozoan parasite Leishmania donovani exhibit profoundly depressed splenic natural killer (NK) cell activity as measured by in vitro cytolysis of lymphoma target cells. Injection of infected mice with an interferon (IFN) inducer or in vitro treatment of infected splenocytes with IFN, a phorbol ester, or indomethacin failed to restore their NK activity to the degree shown by age-matched, uninfected mice. Fractionation of infected splenocytes by nylon wool, Sephadex G-10, or carbonyl iron and magnetism treatments was also unable to effect an increase in NK activity. Addition of infected splenocytes to uninfected ones in in vitro NK assays suppressed the NK activity of the latter, and the suppression could be partially or wholly abrogated by prior fractionation of infected splenocytes by the methods noted above. In vitro treatment of infected splenocytes with concanavalin A revealed the presence of NK activity in these cell populations. The results indicate that splenocytes in L. donovani-infected mice become insensitive to IFN stimulation; and the impairment of another, possibly IFN-independent pathway of NK-cell activation may also contribute to the observed L. donovani-induced depression in splenic NK activity in C57BL/6 mice.

Animals↗
PubMed1984

Leishmania chagasi and L. donovani: experimental infections in domestic cats.

The susceptibility of domestic cats to visceral leishmaniasis was examined by inoculating cats with amastigotes of Leishmania donovani and L. chagasi by the intravenous route, and with promastigotes of L. chagasi by the intradermal route. Parasites were recovered from intravenously inoculated cats as long as 16 weeks after inoculation, but parasites apparently did not locate in the viscera in cats inoculated intradermally. Parasites were not detected in intravenously inoculated cats killed at 24 weeks of infection. All cats developed significantly elevated serum antibody titers to Leishmania spp., but none developed the symptoms usually associated with visceral leishmaniasis in humans.

Animals↗
PubMed1984

Feline giardiasis: observations on natural and induced infections.

The excretion of Giardia sp cysts in the feces of naturally and artificially infected cats fluctuated sporadically, and cysts were undetectable several times during 7 weeks of observation. The mean prepatent period for Giardia infection in 7 cats was 9.6 days (range, 5 to 16 days). The amount of the cyst inoculum did not appear to affect the length of the prepatent period. Six of 11 cats had clinical signs consistent with those of giardiasis. Clinical signs and cyst excretion were eliminated after treatment with metronidazole or furazolidone. Moderate oral or parenteral doses of corticosteroids produced little, if any, alteration in the infection. Postmortem examination of 1 inoculated cat revealed Giardia trophozoites in the jejunum and upper portion of the ileum but not in the duodenum, lower portion of the ileum, cecum, or colon. Giardia cysts isolated from cat feces produced infection in Mongolian gerbils but not in C57BL/6J mice.

Animals↗