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Biomedical subjects

G R Catto

Publications and source records attributed to G R Catto.

At least 55 records · Page 3Linked to original sources
PubMed1989

Renal transplantation: cyclosporin A and antibody development after donor-specific transfusion.

The survival of a one haplotype, mismatched living-related renal allograft is improved by donor specific transfusion (DST) before transplantation although the mechanism is unclear. The major risk of DST is sensitization of the recipient to donor lymphocytes precluding transplantation. Fifty prospective recipients of a living related transplant received either DST with cyclosporin A (group I) or DST alone (group II). Persistent donor sensitization precluding transplantation occurred in no patients in group I but in six in group II (P less than 0.05). Ten of 14 of those who developed donor cytotoxicity had previously been pregnant or received greater than or equal to 10 third party transfusions compared with 11 of 36 without such a history (P less than 0.05). Alloantibodies detected by a cellular ELISA developed following DST in 29% patients and antiidiotypic antibodies detected by the short antiidiotypic assay (SAA) in 36%; antiidiotypic activity occurred more frequently in those given cyclosporin A (P less than 0.02). Potentiating activity in the SAA which occurred in sera from six patients after DST had no influence on transplant outcome. Persistent sensitization, particularly in potential transplant recipients who have been pregnant or received many transfusions, can be prevented by giving cyclosporin A with DST; the mechanisms of this effect may be the induction of antiidiotypic antibodies. Both alloantibodies and antiidiotypic antibodies are induced by DST and may protect a subsequent renal allograft from the specific donor.

Antibodies↗
PubMed1989

Immunological studies of trophoblast antigens: no evidence for human leucocyte antigen (HLA) linkage.

Parental disparity for trophoblast-lymphocyte crossreactive (TLX) antigens may promote successful pregnancy. A TLX antigen system has been defined on peripheral blood lymphocytes by heteroantisera. More recently, we have reported additional activity against antigens on B lymphocytes alone termed trophoblast-B lymphocyte crossreactive (TBX) antigens. In the present study we have investigated ten TLX sera in order to determine if their target antigens are linked to the human leucocyte antigen (HLA) gene complex. The sera showed no selective activity when tested against target B lymphocytes from ten normal donors. Cytotoxic activity of TLX antisera against peripheral blood lymphocytes from six normal donors was not reduced when the class I HLA antigens of the target cells were blocked with a monoclonal antibody (PA 2.6). Similarly the cytotoxic activity of both TBX antisera against B lymphocytes from six normal donors was not decreased when class II HLA antigens were blocked by a monoclonal antibody (FMC 4). Within a family the cytotoxic activity of the TLX antisera was absorbed equally by lymphocytes from siblings who shared neither HLA haplotype. Antibody content in TLX and TBX antisera is not directed toward the classically defined HLA class I or class II antigens and is not linked to the HLA gene complex.

Animals↗
PubMed1989

Fetus as an allograft: noncytotoxic maternal antibodies to HLA-linked paternal antigens.

A cellular enzyme-linked immunospecific assay (CELISA) was used to monitor maternal humoral responses in human pregnancy. Non-cytotoxic IgG antibodies to paternal lymphocytes were detected in sera from 6 of 20 normal first trimester primigravidae and 6 of 13 multiparae. No antibody activity against lymphocytes from their partners was detected in sera from any of the 15 nulliparous women. The differences in antibody response between primigravidae and nulliparae (P = 0.024) and between multiparae and nulliparae (P = 0.005) were statistically significant. Lymphocytotoic antibodies to T- and B-lymphocytes were present in sera from three multiparae, but from none of the women in the other two groups. Family studies indicated that the non-cytotoxic pregnancy-associated maternal antibodies were directed to HLA-linked antigens (P less than 0.001). Evidence obtained using cell panels and platelet absorption suggested, however, that these antibodies were not directed to the currently recognized HLA specificities (HLA-A, -B, -C, or -DR).

Enzyme-Linked Immunosorbent Assay↗
PubMed1989

The effect of nifedipine on graft function in renal allograft recipients treated with cyclosporin A.

The effect of the calcium channel antagonist nifedipine on renal allograft function was assessed in two groups of renal transplant recipients at least one year after transplantation. Group 1 comprised 10 patients receiving low-dose prednisolone and cyclosporin A, and Group 2 comprised 9 patients receiving low-dose prednisolone and azathioprine. Before commencing nifedipine, creatinine and sodium clearance rates and the fractional excretion of sodium were similar in both two groups. Lithium clearance rates and the fractional excretion of lithium were, however, significantly lower (p less than 0.01) in Group 1 than in Group 2. The absolute reabsorption of sodium from the distal nephron (p less than 0.01), the absolute reabsorption of water from the distal nephron segment (p less than 0.01) and the fractional reabsorption of sodium from the distal tubule relative to the delivery of sodium from the proximal tubule (p less than 0.05) were also lower in Group 1. After seven days of nifedipine treatment (10 mg/8 h) there was a significant fall in sodium clearance (p less than 0.01) and fractional sodium excretion (p less than 0.05), and an increase in the fractional distal reabsorption of sodium relative to the delivery of sodium from the proximal tubule (p less than 0.01), and the fractional distal reabsorption of water relative to the delivery of water from the proximal tubule (p less than 0.02), in Group 1 but not Group 2. The only alterations observed in Group 2 were an increase in fractional lithium excretion (p less than 0.05), and a significant fall in the absolute proximal tubular reabsorption of iso-osmotic fluids (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Characterisation of the humoral immune response during murine pregnancy.

Blood samples from female C57BL/10 mice mated with CBA/Ca males were obtained before, during and after both first and second pregnancies. A cellular enzyme-linked immunospecific assay (CELISA) was used to detect maternal antibodies against antigens on paternal splenocytes. Alloantibodies were detected in 48% of mice during or 9 days after a first pregnancy and in 82% of mice by the ninth day after the second pregnancy; these antibodies were first observed on day 10 of the first pregnancy. In two of four active multigravid sera tested, an increase in IgG1 concentration was detected; the level of all other isotypes remained within normal limits. Weak binding of alloantibody to an antigen of approximate molecular weight 44,000 was detected on CBA/Ca splenocytes by immunoblotting sera from multiparous animals. These sera also recognised an antigen of similar molecular weight on H-2b identical 129J splenocytes but not on splenocytes from the maternal strain. These results provide further information on the maternal humoral immune response during murine pregnancy.

Animals↗
PubMed1988

Drug hypersensitivity causing granulomatous interstitial nephritis.

In association with treatment for pharyngitis, a 47-year-old white man developed a systemic illness with fever, myalgia, episcleritis, hemoptysis, pleurisy, eosinophilia, and renal impairment. Renal biopsy revealed granulomatous interstitial nephritis, which resolved due to no specific treatment other than withdrawing all medication. Both the severe systemic manifestations and spontaneous recovery are unusual in association with drug-induced granulomatous nephritis. The drugs that may have caused the reaction included dihydrocodeine, phenylpropanolamine, erythromycin, and amoxycillin. Although the latter three drugs have been previously implicated in the development of interstitial nephritis, there have been no previous reports of granulomatous interstitial nephritis with any of these drugs.

Amoxicillin↗
PubMed1988

Renal transplantation: HLA-linked, non-cytotoxic antibodies develop after blood transfusion.

1. A previously untransfused dialysis patient was given blood from a single donor on three occasions and sera were obtained from the recipient before and after transfusion. 2. The sera were tested against B-lymphocytes from the blood donor and his family in the erythrocyte-antibody rosette inhibition assay to determine whether any Fc-receptor-blocking activity which developed was HLA linked. 3. Antibody activity was noted after the second transfusion and was directed toward B-lymphocytes from the blood donor and his family members sharing the haplotype HLA A11, B12 with him. 4. These antibodies were removed by the absorption of active sera with lymphocytes from the blood donor but not from (a) his sibling who shared no HLA antigens with him or (b) the transfusion recipient. Absorption of the active sera with platelets from the blood donor did not remove activity. 5. These results indicate that Fc-receptor-blocking antibodies developing after blood transfusion are directed to HLA-linked antigens on donor lymphocytes.

Absorption↗
PubMed1988

Cyclosporin A prevents sensitization after blood transfusion in multiparous rats.

1. Humoral immune responses to allogeneic blood transfusions and semi-allogeneic pregnancies were monitored by the indirect haemagglutination assay in strains of inbred rats. 2. Similar titres and ranges of cross-reactive alloantibodies were induced by blood transfusions and pregnancy; the maternal alloantibody response to paternal antigens was not increased by an unrelated antigenic stimulus. 3. Immunosuppression with cyclosporin A was effective in preventing the primary humoral immune response produced by blood transfusion but not in abrogating the established immune response to previous pregnancy. 4. These studies have established an animal model of sensitization that both stimulates the clinical situation of many potential renal transplant recipients and permits analyses of the different antigenic stimuli involved.

Animals↗