The effect of total lymphoid irradiation (TLI) on interleukin-2 (IL-2) and its receptor in the chacma baboon.
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Biomedical subjects
Publications and source records attributed to J H Stark.
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In order to decide on a suitable sampling depth for grassland soil treated with sewage sludge and to assess implications for grazing animals, a field trial on two soils was designed to estimate the distribution of metals in grassland soil profiles following surface applications of sludge. Thus the sites represented permanent grassland where no form of cultivation had taken place. Soil cores were taken using specialised equipment to 30 cm depth and divided into seven sections. Movement from the soil surface to a depth of 10 cm was observed for all of the seven metals, Cd, Cr, Cu, Mo, Ni, Pb and Zn, but most of the metal (60%-100%, mean 87%) remained in the upper 5 cm of soil. It was concluded that sampling to a depth of 5 or 7.5 cm would be most suitable for monitoring long-term grassland treated with surface applications of sludge.
Lymphocyte responsiveness in cells collected from baboons (Papio ursinus orientalis) has consistently been 1/10 of that obtained using human cells. Animals that vigorously rejected organ allografts demonstrated that this lack of responsiveness was not due to genetic identity. This paper defines the kinetics of the baboon mixed lymphocyte response (MLR) and suggests several modifications to improve the sensitivity of the technique. Optimal response was obtained using nylon wool purified T-cell responders, 20% fresh autologous plasma to supplement culture medium, an incubation period of 6 days and exposure to 3H-thymidine (2 Ci/mmol) for 24 h prior to harvesting. These modifications enhanced the MLR response from a stimulation index +/- standard error of 2.5 +/- 0.3 (n = 79) to 25.2 +/- 5.4 (n = 38).
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Prolonged kidney and liver allograft survival was produced in baboons by low cumulative doses (500 to 1200 rad) of total lymphoid irradiation (TLI). Continuing normal graft function for more than 1 yr after transplantation was seen in 10 animals in this series. The longest survivor (greater than 4 years) rejected a third party kidney allograft in typically acute fashion 1 yr after the original transplantation. The dose-response effect was parabolic, with a cumulative dose of 800 rad given as twice weekly fractions of 100 rad each being the most effective. With smaller cumulative doses (500 or 600 rad) results were improved if TLI was administered as a larger number of smaller fractions. These regimens are free of the radiation related mortality observed in earlier studies with larger cumulative doses. As in previous studies, the injection of donor bone marrow was not essential for prolonged and continuing graft survival. The field irradiated was extensive, and included a substantial part of the of the hemopoietic bone. Restricting the field irradiated to that approximating what is used clinically in patients with Hodgkin's disease resulted in markedly poorer graft survival. Alterations in T cell subpopulations were studied in these baboons with the use of the anti-human monoclonal antibodies OKT11 (anti-total T cells), OKT4 (anti-T helper cells; Th), and OKT8 (anti-T suppressor/cytotoxic cells, Tsc), which cross-react with baboon lymphocytes. After completion of TLI but before transplantation, the relative percentage of Tsc cells fell and the percentage of Th and the Th/Tsc ratio rose. Transplantation was followed by an inversion of this ratio due to reciprocal changes in the percentages of Th and Tsc cells. This pattern persisted and increased until 6 mo after transplantation, when it reverted to that seen in untreated control animals. This was maintained in long surviving animals up to 17 mo after transplantation. Transplantation was also followed by a marked early increase in the percentage of Ia+ (OKIa1 anti-human monoclonal antibody) total T, T4+, and T8+ cells. If findings in the human, in which activated suppressor but no cytotoxic T cells are Ia+, can be extrapolated to the baboon, a possible explanation for the serial changes observed in the present studies may be that transplantation after TLI results in a polyclonal expansion of nonspecific suppressor T cells. These disappear with time leaving specific suppressor T cells that may be responsible for continuing graft acceptance. Formal proof of this hypothesis will require appropriate functional studies.
A 125I-DNA preparation for the detection of human anti-DNA antibodies (ADA) was evaluated as a diagnostic test for systemic lupus erythematosus (SLE). A normal range of 0-25 U/ml was established. Serum ADA level greater than 110 U/ml were diagnostic in clinically active SLE and levels greater than 45 U/ml were found in 75% of patients with inactive disease. This value was significantly greater than that found in rheumatoid arthritis, renal disease caused by non-immune mechanisms, post-streptococcal glomerulonephritis and a miscellaneous group of disorders comprising connective tissue diseases, auto-immune disorders and chronic active hepatitis. Anti-nuclear factor (ANF) titres greater than 1/160 and LE cells were found in 85% of these patients. In inactive disease the ADA levels ranged between 25 and 98 U/ml, ANF titres varied from 1/40 to 1/640, and LE cells were detected in only 20% of the cases. In 3 patients investigated during the course of the disease, the ADA levels correlated best with clinical improvement. Two patients with apparent active lupus nephritis showed intermediate ADA levels, which were probably caused by antigen-antibody formation and immune complex deposition in the kidneys.