Biomedical subjects

A J Curry

Publications and source records attributed to A J Curry.

4 recordsLinked to original sources

PubMed1992

Recombinant interleukin-1 alpha augments granuloma formation and cytokine production but not parasite clearance in mice infected with Leishmania donovani.

In vivo administration of various doses of recombinant interleukin-1 alpha to B10.D2/n mice chronically infected with Leishmania donovani resulted in enhanced formation of granulomas and in vitro production of gamma interferon. By direct microscopical enumeration, reduction in gross parasite burden in the viscera was not observed, however. These data highlight an important discordance between granuloma formation per se and parasite elimination and suggest that interleukin-1 deficiency alone cannot account for the chronicity of this disease.

Animals↗

PubMed1991

Differential production of Th1- and Th2-derived cytokines does not determine the genetically controlled or vaccine-induced rate of cure in murine visceral leishmaniasis.

Recent studies with models of cutaneous leishmaniasis have provoked much interest in the role of CD4+ T cell subsets in determining the outcome of infectious disease. In Leishmania major infections, cure vs progressive disease correlates with the expansion of Th1-like or Th2-like CD4+ populations, respectively. We have investigated whether similar responses are associated with the differential patterns of infection seen in models of visceral leishmaniasis, caused by L. donovani. Splenic lymphocytes from infected Lsh congenic C57BL/10 (Lshs;H-2b) and B10.L-Lshr (Lshr;H-2b) mice and MHC congenic non-curing B10.D2/n (Lshs;H-2d) mice were examined for the production of cytokines representative of these CD4+ populations (IL-2, IL-3, IL-4, IL-5, and IFN-gamma). In all three strains examined, there was no evidence for the production of Th2-restricted cytokines. In addition, levels of serum IgE were depressed during the early phase of infection, indicative of in vivo IFN-gamma production. In the non-curing B10.D2/n strain, late phase of infection was associated with the decreased ability to produce cytokines in response to Ag and not with the production of IL-4 or IL-5 in response to Ag or mitogen. Serum IgE levels were also not raised above levels seen in uninfected controls. C57BL/10 mice were vaccinated with SDS-PAGE fractionated amastigote Ag bound to nitrocellulose and cytokine levels determined at various times after infection. The protocol used for vaccination was able to induce significant modulation of the course of infection in this strain and it was clear that IFN-gamma production in vitro provided an excellent correlate of rate of cure. Occasional individuals produced low levels of IL-5 in culture in response to parasite Ag, but this did not correlate with disease progression. Together, these data suggest that over-expansion of Th2-type cells and production of their specific cytokines (IL-4 and IL-5) is not a contributing factor to the variable long term course of L. donovani infection in these strains of mice.

Animals↗

PubMed1991

Antigen processing and presentation: modelling with Leishmania.

Most foreign antigens are "processed" by APC into a form in which they can bind MHC molecules and be recognised by the TCR. Functional and immuno-gold labelling studies have been used to determine the putative sites of MHC-Ag interaction following uptake of Leishmania donovani into a phagolysosome. During infection with this parasite in vivo, upregulation of class II occurs. Based on studies using scid mice, NK cells appear to contribute little to this process. During chronic infection, however, APC function is diminished in spite of high class II levels. We propose that a lack of coordinate costimulator expression may lead to subsequent loss of T cell function late in infection, by a mechanism involving the induction of T cell unresponsiveness.

Animals↗

PubMed1987

Incidence of renal artery stenosis in a population having cardiac catheterization.

Patients with renovascular hypertension comprise only a small percentage of those with hypertension. In our study 102 consecutive patients who had cardiac catheterization were screened at the time of the procedure for renal artery stenosis. Only 65 (64%) of the 102 patients were hypertensive, and 14 of the total population (13.7%) had renal artery stenosis. Of these 14 patients, only five had more than 50% narrowing of the arterial lumen. By renal vein renin determination, only four of the five patients with significant renal artery stenosis had lateralizing renins. The frequency of significant renovascular hypertension does not justify the routine search for this problem during catheterization procedures, though it may be worthwhile if the patients are hypertensive. This area deserves further evaluation.

Adult↗