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J A Smit

Publications and source records attributed to J A Smit.

At least 55 records · Page 3Linked to original sources
PubMed1988

Improved technique for the mixed lymphocyte response in the Chacma baboon.

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).

Animals↗
PubMed1988

Growth of Escherichia coli in whole and skim milk from endotoxin-induced mastitic quarters: in vitro effects of deferoxamine, zinc, and iron supplementation.

A marked growth inhibition of Escherichia coli 0101 K99 F41 was observed in whole and skim milk collected from inflamed quarters 18 and 36 h after intramammary administration of .1 mg E. coli lipopolysaccharide. Individual cow variation in the ability of milk from endotoxin-infused quarters to inhibit growth of E. coli was found. Growth inhibition of E. coli was observed in milk from endotoxin-infused quarters and was most pronounced in skim milk sampled at postinfusion h 18, and incubated at 38 degrees C. The mechanism by which bacterial growth was depressed was probably of noncellular origin. Addition of Fe (45.5 micrograms/ml) and Zn (2.7 micrograms/ml) to whole and skim milk sampled from inflamed quarters at 18 h after endotoxin infusion resulted in a growth-promoting effect. Addition of deferoxamine (6 mg/ml) depressed bacterial growth. Effects of Fe, Zn, and deferoxamine on bacterial growth did not differ in whole and skim milk. No clear relationship was observed between reduction in Zn concentrations in skim milk from inflamed quarters at 18 h after endotoxin infusion and growth inhibition of E. coli in the same samples.

Animals↗
PubMed1986

Circulating thyroid hormones in primates with mild or severe hepatitis following liver transplantation.

In order to study the effects of acute immunologically mediated liver disease on circulating thyroid hormones, serum levels of thyroxine (T4, total and free) and triiodothyronine (T3) were measured in 8 baboons before and for 60 days after allogeneic liver transplantation. In 3 animals early rejection and jaundice developed; T4 levels declined as liver function deteriorated. In the 5 tolerant animals liver function was only temporarily deranged without jaundice and there was a consistent early rise in T4 (P less than 0.01) followed by a later fall. T3 concentrations were relatively normal in both groups. The T3 resin uptake test remained virtually unchanged in all animals. Serum T4 and T3 responses to exogenously administered bovine thyrotropin (TSH) were similar in the jaundiced and anicteric animals. We conclude that the early rise in T4 in the tolerant animals was caused by transient increases in thyroid binding globulin in (TBG) while the fall in thyroid hormones in these and in the jaundiced animals was related to a decline in TBG levels. Thyroid responsiveness to TSH is not disturbed by moderately deranged liver function.

Animals↗
PubMed1984

Circulating thyroid hormones in progressive renal failure in the baboon (Papio ursinus).

In order to examine the effects of developing renal failure on circulating thyroid hormones, serum concentrations of thyroxine (T4), free T4 (FT4), triiodothyronine (T3) and reverse T3 (rT3) and TBG capacity were measured in 9 baboons before and during the progress of acute (mean survival 12 days), subacute (32 days) and chronic (120 days) renal failure following allogeneic renal transplantation. Irrespective of the rate of development of renal failure, there were significant, non linear (power functions) negative correlations between serum creatinine or urea concentrations and levels of T4, FT4 and T3; rT3 levels remained unchanged, but the T4: rT3 molar ratio fell from 236.5 +/- 61 (+/- SE) to 121.8 +/- 30.9 (p less than 0.05). T4 and T3 levels were invariably subnormal at creatinine concentrations greater than 250 mumol/l (2.8 mg/dl), but FT4 was subnormal only in chronic renal failure. Thyroxine binding globulin (TBG) capacity did not change significantly; thus the TBG: T4 ratio increased from 3.4 +/- 0.2 (basal) to 10.4 +/- 3.4 before death (p less than 0.05). In animals which survived for greater than 25 days after transplantation, a significant linear correlation between FT4 and T3 was found as uremia progressed. Polyacrylamide gel electrophoresis (pH 7.4) of (125I)-T4 labelled preoperative and uremic serum showed a consistent decline in the proportion of tracer bound to TBG, from 67.0 +/- 0.8% to 58.9 +/- 1.0% (p less than 0.001), with a 48% reduction in TBG saturation (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1984

Total lymphoid irradiation in kidney and liver transplantation in the baboon: prolonged graft survival and alterations in T cell subsets with low cumulative dose regimens.

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.

Animals↗
PubMed1983

The treatment of end-stage renal disease at the Johannesburg Hospital: a 17-year experience. Part II. The role of transplantation.

Experience with 525 kidney transplants performed at the Johannesburg Hospital from 1966 to 1982 is reviewed. The 1-year graft survival rates for HLA-identical related living donor (RLD) transplants, haplo-identical RLD transplants, and first and subsequent transplants from cadaver donors (CDs) are 95%, 72%, 59% and 52% respectively. One-year patient survival figures for all RLD and all CD transplants are 93% and 78% respectively. There is a slower but steady attrition in both graft and patient survival over the next 10-15 years which is the same for all patients irrespective of donor source. Infection and myocardial infarction remain the major causes of mortality and morbidity. Mortality in the 1st year after transplantation has been reduced dramatically in the last 5 years of the programme. This has coincided with the introduction of a policy of routine pretransplant blood transfusion and a less aggressive approach to the treatment of severe and recurrent rejection episodes. However, the incidence of irreversible graft rejection in the 1st year has remained the same. These results, although gratifying in a broad context, leave no room for complacency. The induction of a state of specific tolerance towards the grafted organ remains the ultimate goal in clinical transplantation.

Actuarial Analysis↗
PubMed1983

Renal allograft survival in the baboon using a pretreatment protocol with cyclosporine.

Cyclosporine extends kidney allograft survival in the chacma baboon, and this study explores various administration protocols to generate optimal serum concentrations of the drug, assessed by radioimmunoassay and by inhibition of lymphocyte transformation by phytohemagglutinin and allogeneic lymphocytes in culture. Serum levels commensurate with concentrations that have been shown to be immunosuppressive in humans (150-400 ng/ml) are reached after 14 days of pretreatment with 10 mg cyclosporine/kg, and after 7 days with 20 and 30 mg cyclosporine/kg. The 10-mg dose prolongs median graft survival from 11 to 21 days, which is the same as that obtained with 20 mg/kg administered after transplantation. Further increases in the pretreatment dose to 20 or 30 mg/kg result in survivals of 27 and 31 days, respectively. All the animals died from rejection during therapy and the T-cell-binding avidity, and absorptive or degradative processes may necessitate doses far in excess of those currently used in transplantation.

Absorption↗
PubMed1980

Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. II. Renal allografts.

A modified regimen of fractionated total lymphoid irradiation and allogeneic bone marrow (BM) injection in chacma baboons produced transplantation tolerance for allografted kidneys from the BM donors, and substantial chimerism without evidence of graft-versus-host disease. Increasing the dose of nucleated BM cells injected 4-fold over that used in liver transplantation resulted consistently in normal graft function in the early weeks after transplantation. Bone marrow injection and challenge with renal allografts could be delayed for at least 3 weeks after completion of irradiation. If it can be shown that this period can be extended even further, the protocols will be relevant to the circumstances of clinical cadaveric renal transplantation.

Animals↗
PubMed1980

Transplantation tolerance in primates after total lymphoid irradiation and allogeneic bone marrow injection. III. Lymphocyte responsiveness and suppressor cell activity.

After total lymphoid irradiation (TLI), allogeneic bone marrow (BM) injection, and organ transplantation in baboons, there is a prolonged period of reduced lymphocyte proliferative responsiveness to polyclonal mitogens and allogeneic lymphocytes. The effect observed is greater with the use of fractionated TLI than after single doses of irradiation. Suppressor cell activity can be demonstrated in vitro in most animals by inhibition of mixed lymphocyte reactivity (MLR) by mitomycin-treated recipient lymphocytes harvested after TLI, with or without allogeneic BM injection, and organ transplantation. Preliminary data suggest the presence of both donor-specific and nondonor-specific suppression, although other interpretations are possible, and suppressor phenomena may not be responsible for the transplantation tolerance observed.

Animals↗
PubMed1979

The effect of blood transfusion on the immune response and renal graft survival in the Chacma baboon.

There is uncertainty about the role of blood transfusion of potential kidney graft recipients. In this study baboons were transfused under conditions mimicking the clinical situation and then callenged with kidney allografts. Eleven baboons were transfused 10 times with blood from different donors. Lymphocytotoxic antibodies induced against the separated B and T cells of a panel of 12 normal baboons were as follows: B-T- 30%; B+T- 3%; B-T+ 1% and B+T+ 66%. Kidney transplantations were done from donors against which the recipients had negative B-T- cross-matches. Median allograft survival time (MST) of 12 days in this group, which was immunosuppressed with azathioprine and prednisolone, was not prolonged when compared with non-transfused, immunosuppressed animals (MST 12 days). A second group of 14 animals was screened for cytotoxins after each transfusion against a panel of five to six normal baboons. The antibody profile of 80 combinations tested after three transfusions was as follows: B-T- 65%; B+T- 16%, B-T+ 0% and B+T+ 19%. Transplantation was with donors against which the transfused recipient had formed B+T- antibodies. Kidney allograft survival was again not prolonged (MST 13 days) but the mean serum creatinine level 8 days after transplantation was significantly lower than that observed in the first group.

Animals↗