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Biomedical subjects

David Sacks

Publications and source records attributed to David Sacks.

At least 91 records · Page 5Linked to original sources
PubMed2002

Optimization of DNA vaccination against cutaneous leishmaniasis.

The present studies were designed to examine the requirements of dose, route of inoculation and constituent antigens for the maintenance of complete and long lasting protection against cutaneous leishmaniasis due to Leishmania major conferred by a cocktail DNA vaccine encoding the Leishmania antigens LACK, LmST11 and TSA. Vaccination of C57Bl/6 mice with LACK DNA alone resulted in partial protection, whereas the combination of LmST11 and TSA provided stronger, though still incomplete protection compared to the combination of all three Ag DNAs. When intradermal (i.d), intramuscular (i.m.), and subcutaneous (s.c.) vaccination routes were compared, i.d. immunization reduced by five-fold the dose necessary to maintain complete protection. In vivo depletion of CD4+ or CD8+ T cells provided direct evidence that both populations are necessary to mediate complete protection. These results establish intradermal vaccination using DNA encoding multiple Leishmania antigens as a way to optimize priming of CD4+ and CD8+ T cells necessary for potent and durable protection against cutaneous leishmaniasis.

Animals↗
PubMed2002

CD8+ T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major.

Standard murine models of cutaneous leishmaniasis, involving s.c. inoculation of large numbers of Leishmania major promastigotes, have not supported an essential role for CD8(+) T cells in the control of primary infection. Recently, a L. major model combining two main features of natural transmission, low parasite dose and inoculation into a dermal site, has been established in resistant C57BL/6 mice. In the present studies, C57BL/6 mice with CD8(+) T cell deficiencies, including CD8(-/-) and CD8-depleted mice, failed to control the growth of L. major following inoculation of 100 metacyclic promastigotes into the ear dermis. The resulting dermal pathology was minor and delayed. Lesion formation in wild-type mice was coincident with the killing of parasites in the inoculation site. Both events were associated with the accumulation of CD8(+) T lymphocytes in the skin and with the capacity of CD8(+) T cells recovered from draining lymph nodes or infected dermis to release IFN-gamma following coculture with infected dendritic cells. Reconstitution of resistance to L. major in RAG(-/-) mice using T cells from naive donors was optimal when both CD4(+) and CD8(+) T cells were transferred. Primed CD8(+) T lymphocytes obtained from C57BL/6 mice during the acute stage of infection were able to mediate both pathology and immunity when transferred alone. The low dose, intradermal challenge model reveals that CD8(+) T cells play an essential role in both pathogenesis of and immunity to primary infection with L. major in the skin.

Animals↗
PubMed2002

Guidelines for the reporting of renal artery revascularization in clinical trials.

Although the treatment of atherosclerotic renal artery stenosis with use of percutaneous angioplasty, stent placement, and surgical revascularization has gained widespread use, there exist few prospective randomized controlled trials (RCTs) comparing these techniques to each other or against the standard of medical management alone. To facilitate this process as well as help answer many important questions regarding the appropriate application of renal revascularization, well-designed and rigorously conducted trials are needed. These trials must have clearly defined goals and must be sufficiently sized and performed so as to withstand intensive outcomes assessment. Toward this end, this document provides guidelines and definitions for the design, conduct, evaluation, and reporting of renal artery revascularization RCTs. In addition, areas of critically necessary renal artery revascularization investigation are identified. It is hoped that this information will be valuable to the investigator wishing to conduct research in this important area.

Angioplasty, Balloon↗