Uraemic rats maintained on either a high or a low phosphate diet for 12 weeks were allocated to one of the following oral vitamin D treatment groups and received: 1,25-dihydroxycholecalciferol [1, 25-(OH)2D3], 24,25-dihydroxycholecalciferol [24,25-(OH)2D3], both 1,25-(OH)2D3 and 24,25-(OH)2D3, or no vitamin D supplements. Mean serum creatinine concentrations were elevated to a similar extent in all groups. Mean serum concentrations of calcium, phosphate and alkaline phosphatase were not significantly different from normal in any of the groups. In the group receiving the high phosphate diet and no vitamin D supplements, calcified bone area measured by quantitative computerized histomorphometry was significantly lower than in the group receiving the low phosphate diet and no vitamin D supplements (0.01 greater than P greater than 0.001), and in the groups receiving high phosphate diet and either 1,25-(OH)2D3 (0.01 greater than P greater than 0.001) or 24,25-(OH)2D3 (0.01 greater than P greater than 0.001). We conclude that uraemic rats maintained on a high phosphate diet for 12 weeks develop skeletal demineralization, this process does not occur in rats on a low phosphate diet, and a decrease in calcified bone area may be prevented by treatment with either 1,25-(OH)2D3 or 24,25-(OH)2D3.

24,25-Dihydroxyvitamin D 3↗

PubMed1986

The effect of cyclosporine on humoral and cellular alloreactivity to allogeneic pregnancy in rats.

We have evaluated the effect of a therapeutic dose (10 mg/kg/day) of the immunosuppressant cyclosporine (CsA) on humoral and cell-mediated immunity in rats during an allogeneic first pregnancy. Virgin female Lewis rats mated with DA males and treated with CsA vehicle produced a humoral response, as measured by both the erythrocyte rosette inhibition (EAI) and indirect hemagglutination assays. The capacity of Lewis splenocytes to mediate a graft-versus-host (GVH) reaction in six-week old F1 (Lewis X DA) hybrid rats was unaffected by either pregnancy or CsA. In mothers treated with CsA, however, no antibody production was detected, and a significant reduction in GVH reactivity was observed using their cells. This reduction was specific for the paternal strain. When compared with vehicle-treated primiparas, suppression of the immune response by CsA had no effect on either the number or viability of fetuses present in utero at day 20. These data suggest that antipaternal antibodies may not be essential to protect the fetus when there is concomitant suppression of the capacity of the mother's T cells to express a cell-mediated antipaternal response.

Animals↗

PubMed1986

Maternal antibodies to paternal B-lymphocytes in normal and abnormal pregnancy.

Sera were obtained prior to conception and during the first trimester of subsequent pregnancies from 22 women over 27 pregnancies; on 15 occasions these pregnancies ended in spontaneous abortion, whereas the remaining 12 achieved live normal babies. In only one pregnancy ending in abortion could antibodies directed to paternal B-lymphocytes determined by the EA rosette inhibition (EAI) assay be detected in the mother's serum, whereas five of the 12 successful pregnancies were associated with such detectable antibodies. Cytotoxic antibodies were also found in all but one of these EAI-positive pregnancies and no antibody activity was present in sera obtained from five primigravidae. These results indicated that normal, but not abnormal, pregnancies were often associated with blocking antibody formation, suggesting that such antibodies may protect the fetus from abortion. However, the failure to detect antibody activity in sera from first trimester primigravidae argues against a central role for blocking antibody, alone, in the maintenance of outbred pregnancy.

Abortion, Spontaneous↗

PubMed1986

Differential expression of trophoblast lymphocyte cross-reactive (TLX) antigens on T and B lymphocytes.

Heterologous sera raised to human trophoblast (TLX antisera) have been shown to recognize peripheral blood lymphocytes (PBL); in unrelated studies noncytotoxic Fc receptors blocking B lymphocyte antibodies have been found in the sera of women during normal pregnancies. This study aimed to determine whether (a) there was any relation between Fc receptor blocking and cytotoxic anti-TLX activity in ten TLX sera and (b) different reactivity patterns arose when ten TLX antisera were tested in the cytotoxicity assay against separated T and B lymphocytes. Independent factor analysis showed four antisera with T lymphocytotoxicity patterns giving a loading high on one mathematical factor and low on a second. Three sera shared the opposite pattern and three were intermediate. The groups were similar but more discrete than those obtained when PBL were used as targets. Patterns of B lymphocytoxicity were dissimilar from T and both differed from the erythrocyte antibody rosette inhibition activity. Activity did not correlate with the HLA-A, -B, or -DR types carried by the panel cells. These data indicate that TLX antisera contain antibodies directly cytotoxic to antigens differentially expressed on T and B lymphocytes and that noncytotoxic Fc receptor blocking antibodies are not associated with any TLX groupings.

Animals↗

PubMed1986

Identification of HLA-linked antigens by pregnancy-associated non-cytotoxic alloantisera.

Non-cytotoxic sera obtained from post-partum primiparous and multiparous women were examined by a rosette inhibition technique for the presence of antibodies mediating blockade of human B lymphocyte Fc receptors. Selective activity was demonstrated against a panel of normal human B lymphocytes and lymphocytes from patients with chronic lymphocytic leukaemia (CLL). A pattern of specific activity was found in sera and in their IgG fractions, which was not accounted for by antibodies directed to known HLA-A, -B or -DR antigens. Several sera were identified with selective activity in this assay. As the results of testing sera in a direct binding assay correlated with those of the EA inhibition assay, and since EA inhibitory activity occurred in F(ab')2 fractions of sera, it is possible that these non-cytotoxic antibodies bind directly to B cell surface antigens. Sera may therefore have been identified which possess antibodies to hitherto undefined HLA antigens.

Antibodies↗

PubMed1986

The fetus as an allograft: partial definition of the target antigens.

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Animals↗

PubMed1986

The effect of hemodialysis, vitamin D metabolites and renal transplantation on the skeletal demineralization associated with renal osteodystrophy: a computerized histomorphometric analysis.

Twenty-three patients with end-stage renal failure treated by hemodialysis or transplantation were followed for up to 10 years. Sequential full thickness iliac crest bone biopsies were obtained to assess the effects on bone disease of hemodialysis, treatment with 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] and 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] and renal transplantation. The biopsies were analyzed by a computerized histomorphometric technique which allowed accurate measurements of calcified bone and osteoid areas. Serum aluminum and parathyroid hormone concentrations were also monitored. Hemodialysis was associated with a loss of calcified bone and an increase in osteoid areas. The progressive bone loss was arrested but not reversed following treatment with either 1,25-(OH)2D3 or 24,25-(OH)2D3. Osteoid area was unchanged or reduced following treatment with 1,25-(OH)2D3 in all but three patients who had serum aluminum concentrations in excess of 5 mumol/l. 24,25-(OH)2D3 was not effective in reducing osteoid area, and combined treatment with 1,25 and 24,25-(OH)2D3 had no effect beyond that expected with 1,25-(OH)2D3 alone. Bone biopsies showed loss of calcified bone and an increase in osteoid areas one year and more after successful renal transplantation in five patients. Nineteen of the 23 patients developed serum aluminum concentrations greater than 3 mumol/l, probably because of the use of oral aluminum hydroxide as a phosphate binding agent. In these patients serum parathyroid hormone concentrations greater than 600 pg/ml appeared to prevent the development of osteopenia.

24,25-Dihydroxyvitamin D 3↗

PubMed1986

Changing patterns in the management of end stage renal failure in Aberdeen.

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Adolescent↗

PubMed1985

Pregnancy after treatment with paternal lymphocytes.

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Cytotoxicity, Immunologic↗

PubMed1985

Prolonged survival of rat renal allografts after multiple allogeneic pregnancies: strain specificity and role of erythrocyte antibody rosette inhibiting antibodies.

The influence of allogeneic pregnancies on the survival of subsequent rat renal allografts was investigated in three rat strain combinations. Multiple but not single pregnancies produced significantly more long-term surviving kidney grafts than were found in virgin animals; the effect was specific for paternal antigens, as multiple pregnancies by an unrelated strain did not prolong kidney graft survival. In the multiparous groups, those animals with long-surviving grafts had significantly higher levels of non-cytotoxic antibodies against paternal strain B-lymphocytes (detected by the erythrocyte antibody rosette inhibition assay) than did animals which rejected their grafts. The results show that multiple pregnancies may produce a state of specific unresponsiveness to paternal antigens, similar to enhancement, which is marked by the presence of non-cytotoxic antibodies against paternal B-lymphocytes. It is suggested, therefore, that enhancement may be one of the protective mechanisms which prevent rejection of the fetus during pregnancy.

Animals↗

PubMed1985

Evidence that protective Fc-receptor-blocking antibodies in renal transplantation are alloantibodies not autoantibodies.

We have previously shown that the presence in pretransplant recipient sera of Fc receptor blocking antibodies detected by the EA inhibition assay is correlated with improved allograft survival. Twenty-four such sera were assessed for the presence of autoantibodies by the EA inhibition and lymphocytotoxicity assays. No autolymphocytotoxic antibodies were found, and autologous EA inhibition was noted in only one case. EA-inhibiting alloantibodies did occur, and their presence was correlated with improved allograft survival. Sera from 37 dialysis patients were also studied, and neither autologous EA inhibiting nor autologous lymphocytotoxic antibodies were present. Thus Fc receptor blocking alloantibodies that were correlated with improved renal transplant survival were not autoantibodies.

Autoantibodies↗

PubMed1985

Pharmacokinetics of intraperitoneal cefotaxime treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis.

The pharmacokinetics of intraperitoneal cefotaxime as the sole therapy in patients on continuous ambulatory peritoneal dialysis with peritonitis have been examined. The mean plasma concentrations achieved following 1 h of peritoneal instillation of 500 mg of cefotaxime were 5.0 +/- 1.6 micrograms ml-1. The average plasma concentration over 24 h was 6.9 +/- 0.4 micrograms ml-1 and was no different from that found following a further 9-11 days of successful treatment of the peritonitis. However, the mean dialysate effluent concentration of cefotaxime was increased following the resolution of the peritonitis, 165 +/- 22.7 mg per cycle on day 10 or 12 compared with 50.4 +/- 7.3 mg per cycle on day 1, suggesting enhanced peritoneal cefotaxime absorption during acute peritonitis. Nevertheless, during both periods, adequate concentrations of cefotaxime were achieved in dialysate to treat local complications, but plasma levels may be inadequate to treat systemic complications due to Staphylococcus albus.

Adult↗

PubMed1985

IgA nephropathy is not a rare disease in the United Kingdom.

A retrospective analysis of all renal biopsies performed in the Grampian Region of Scotland during 1977-1980 revealed that IgA nephropathy was the most frequently encountered glomerular lesion. The commonest indications for renal biopsy were the presence of asymptomatic urinary abnormalities (90/184; 48.9%) especially asymptomatic haematuria (42/184; 22.8%). A histological diagnosis was made in 36 of the 42 patients presenting with asymptomatic haematuria (85.7%); 16 of the 26 cases of IgA nephropathy presented in this way. Overall, IgA nephropathy was detected in 14.1% of all biopsies and accounted for 21.8% of primary glomerular diseases. This study indicates that IgA nephropathy is apparently more common in Grampian than elsewhere in the United Kingdom. However, it is suggested that this does not represent a true variation in the prevalence of the condition; IgA nephropathy is probably a common cause of haematuria in the United Kingdom.

Adolescent↗