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Biomedical subjects

F Y Liew

Publications and source records attributed to F Y Liew.

242 records · Page 14Linked to original sources
PubMedDate not supplied

Leishmania infecting man and wild animals in Saudi Arabia. 8. The influence of prior infection with Leishmania arabica on challenge with L. major in man.

A clinical trial is described of an attempt to protect against Leishmania major by prior vaccination with live L. arabica. After a single, previously leishmanin-negative, adult male volunteer was bitten by 8 Phlebotomus papatasi infected with L. arabica, no infected lesions were observed. He remained leishmanin-negative and his lymphocytes reacted weakly to antigens of L. arabica or L. major. Subsequently he and 3 other leishmanin-negative adult male volunteers were vaccinated with cultures containing 4 x 10(6) promastigotes of L. arabica. All remained leishmanin-negative but their lymphocytes showed some response to both L. arabica and L. major antigens. 96 d after vaccination these 4, and another, non-vaccinated, volunteer were challenged with 2 x 10(6) promastigotes of L. major. Active cutaneous, ulcerated lesions developed in all 5 volunteers. The lesions in 3 vaccinated volunteers were associated with marked lymphadenitis and beading, but the lesions started to heal spontaneously within 120-250 d after challenge. The lesion in the fourth vaccinated volunteer was less severe and lymphadenitis was not observed. The lesion in the unvaccinated subject developed more slowly and was smaller, but more chronic, than those in the vaccinated individuals. Marked cross-reactivity in terms of lymphocyte proliferation and interferon-gamma production was observed between L. major and L. arabica in both directions in subjects exposed first to one or the other organism. Although the procedure followed in this trial failed to give protection against L. major, further studies in volunteers should be considered.

Adolescent↗
PubMedDate not supplied

Immunoregulatory properties of novel specific inhibitors of 5-lipoxygenase.

The immunoregulatory properties of novel specific inhibitors of 5-lipoxygenase (5-LO) were investigated in vitro. These novel acetohydroxamic acids were found to inhibit the proliferation of lymphocytes in response to Interleukin-1 (IL-1) and Interleukin-2 (IL-2). Mitogen- and antigen-induced lymphoproliferation were likewise inhibited and so too was the spontaneous proliferation of transformed cells of myeloid and lymphoid origin. In this respect the compounds were one-tenth as potent as azathioprine on a molar basis. The production of IL-1 and IL-2 remained unaffected. Inhibition of lymphocyte proliferation was not related to inhibition of 5-LO. The latter occurred at 40-fold lower concentrations of 5-LO inhibitor. Moreover, inhibition of lymphoproliferation was not reversible in the presence of excess arachidonic acid. IL-1-induced collagenase production by chondrocytes was unaffected by 5-LO inhibitors. Contrary to a number of published reports, products of 5-LO do not appear to be obligatory mediators in IL-1 and IL-2 signal transduction. The immunosuppressive action of the 5-LO inhibitors described here seems to be a novel secondary property of the compounds.

Animals↗
PubMedDate not supplied

Inhibition of pathogenic effect of effector T cells by specific suppressor T cells during influenza virus infection in mice.

Mice infected with an aerosol of influenza type A virus, or immunized with purified UV-inactivated whole virus or with viral subunits, develop a transient delayed-type hypersensitivity (DTH) which peaks 5-7 days after immunization. The intensity of DTH is greatly enhanced and sustained when mice are pretreated with cyclophosphamide. The reaction is maximal 24 h after elicitation, has classical tuberculin-type histology and is transferable by immune H-21 region restricted Lyt-1+2- T cells (Td) but not by immune serum. These Td cells not only fail to protect mice against influenza virus infection, but increase the mortality rate due to influenzal pneumonia following challenge with homologous lethal virus. On the other hand, antigen-specific suppressor T (Ts) cells which inhibit DTH are readily generated during influenza virus infection, and are detectable for at least 40 days thereafter. The ease with which they are induced and maintained during the infection may be of evolutionary advantage. In support of this, we now report that these Ts cells can reverse the pathogenic effect of Td cells thereby demonstrating a beneficial influence of Ts cells in a viral disease.

Animals↗
PubMedDate not supplied

Specific suppression of responses to Leishmania tropica by a cloned T-cell line.

Most clinical cases of cutaneous leishmaniasis caused by Leishmania tropica major consist of self-healing lesions that are associated with the development of strong specific cell-mediated immunity (CMI) detected by delayed-type hypersensitivity (DTH). At the other extreme are susceptible individuals who develop persistent or diffuse forms of the disease. This spectrum of cutaneous leishmaniasis can be reproduced in in-bred mouse strains according to their genetic constitution. BALB/c mice are exceptionally susceptible: the disease can be induced with minimum infecting doses and is inexorably progressive, terminating in cutaneous and fatal visceral metastasis. In this case, potentially curative CMI is abrogated by the generation of a specific Lyt-1$2-, I-J- population of suppressor T (Ts) cells, whose induction is probably secondary to a primary macrophage defect controlled by a single major non-H-2-linked autosomal gene. The generation of the Ts cells can be prevented and infection cured by prior sublethal (550 rad) irradiation. The potency of the Ts cells is such that as few as 10(6) cells transferred adoptively can completely reverse this prophylactic effect. In view of their potency and potential relevance to clinical leishmaniasis, I have now studied Ts cells at the clonal level to delineate further their functional characteristics and interaction with the effector mechanism. I report here a cloned T-cell line expressing specific suppression against in vitro lymphocyte proliferation and in vitro induction of DTH to L. tropica antigens.

Animals↗