No abstract

The oral administration of CII by gavage to WA/KIR rats before a conventional arthritogenic challenge with bovine CII in FIA reduced the incidence (by 23%) and delayed the onset of collagen-induced arthritis in about 50% of the animals. Selective changes in B cell and T cell responses to CII in animals treated this way are interpreted to indicate a state of tolerance or hyporesponsiveness to CII. Tolerant animals made less serum antibody, to bovine and rat CII, of the IgG2b isotype and more of the IgG1 isotype. Phenotypic and functional analysis of peripheral lymph node cells showed that those from tolerized animals expressed less MHC Class II, proliferated less and secreted less IgG2b anti-CII antibody in response to stimulation in vitro with CII when compared with cells from non-tolerant animals. However, this depression of the immune responses to CII seen in vitro was overcome when the cells were incubated with increasing amounts of CII. Tolerance could be transferred to normal animals. Spleen cells, and nylon wool-filtered splenic T cells (but not mesenteric lymph node cells) adoptively transferred hyporesponsiveness to normal recipients which were then less susceptible to collagen-induced arthritis. Transfer of serum from gavaged animals did not modify the susceptibility of normal recipients to arthritis. Spleen cells from gavaged animals suppressed proliferative and antibody responses in co-cultures in vitro with lymph node cells from animals immunized with CII in FIA. The suppressive spleen cell population contained more cells expressing MHC Class II, in both the CD8+ and CD4+ populations. These studies show that the oral administration of CII alters the subsequent immune response to the arthritogenic challenge and indicate that this oral tolerance of CII is due, not to clonal deletion or anergy, but rather to an antigen-driven active suppression mechanism that affects both T cells and B cells, most likely through the action of regulatory cytokines IL-4, IL-10 and TGF beta.

With 7 figures in the text)The metabolism and pattern of excretion of urinary steroids during oestrus and pregnancy in the Giant panda is described. Three female pandas from the London, Washington and Madrid Zoos were studied over different periods between March 1980 and September 1982. High pressure liquid chromatography and sequential enzyme hydrolysis indicated that oestrone glucuronide was the most abundant urinary oestrogen metabolite during oestrus. Levels of conjugated oestrone in late pregnancy, however, were low and similar to those of conjugated oestradiol-170.There was a rapid increase in the excretion of conjugated oestrone to reach maximum levels during late pro-oestrus; oestrus occurred when levels of conjugated oestrone were declining. The measurement of oestrone-3-glucuronide by direct, non-extraction assay provides a rapid and reliable method for detecting oestrus and ovulation in the Giant panda.Artificial insemination of the London and Madrid pandas was performed in 1981 and 1982, respectively. The Madrid panda gave birth to twin cubs after a gestation period of I59 days. Levels of urinary oestrone conjugate remained low throughout pregnancy. There was no increase in the excretion of pregnanediol-3a-glucuronide (assumed to be an urinary metabolite of progesterone) until approximately day I20 when a rapid. five-fold increase in levels occurred. The levels of pregnanediol-3a-glucuronide remained elevated for approximately three weeks after which there was a gradual decline beginning two-and-ahalf weeks before parturition. Measurement of pregnanediol-3a-glucuronide enables the detection of pregnancy after three to four months and should also be useful in predicting parturition. A delay of implantation during pregnancy in the Giant panda is suggested.There was no consistent elevation in pregnanediol-3a-glucuronide excretion in the five months after artificial insemination of the London panda, despite a marked increase in circulating progesterone of ovarian origin. Pregnancy could not be confirmed from external exam,ination of the uterus at laparotomy; histological examination of biopsy material revealed advanced endometrial h yperplasia.

The function of renal allografts in patients who had received pretransplant immunoadsorption in order to remove cytotoxic anti-HLA antibodies was studied. We reviewed 6 patients who received a graft which functioned beyond 3 months; the mean follow-up period was 76 (range 62-89) months. Two grafts have been lost from chronic rejection, at 12 and 62 months, respectively. The mean plasma creatinine levels at 1 and 5 years were 169 (range 143-211) μmol/l and 155 (range 92-235) μmol/l, respectively (1.91, range 1.62-2.39, mg/dl and 1.75, range 1.04-2.66, mg/dl, respectively). The major source of morbidity during long-term follow-up has been the occurrence of renal artery stenosis in 5 patients and renal vein stenosis in 1. In conclusion, the 5-year graft survival and function was good in patients who received immunoadsorption and whose grafts survived beyond the first 3 months after transplantation.