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Biomedical subjects

D A Power

Publications and source records attributed to D A Power.

At least 19 recordsLinked to original sources
PubMed1992

Elevation of albumin synthesis rates in nephrotic patients measured with [1-13C]leucine.

Eight patients with a nephrotic syndrome and a histologically-proven kidney disease were compared to age- and sex-matched healthy volunteers. Albumin synthesis rates were measured after injection of 13C-labelled leucine (57 mg/kg body wt, 19.4 atoms%). Plasma volume was determined with 125I-albumin. The fractional synthesis rate of albumin was 7.9 +/- 0.4%/day in control subjects in comparison with a marked elevation to 18.4 +/- 2.0%/day (P less than 0.001) in nephrotic patients. The absolute synthesis rate was 145 +/- 9 mg/kg/day in control subjects compared with 213 +/- 17 mg/kg/day (P = 0.005) in the nephrotic patients. There was a statistically significant correlation between ASR and urinary albumin loss (P = 0.035) and serum cholesterol concentration (P = 0.007). The calculated oncotic pressure was significantly lower in the nephrotic group than in the controls (P less than 0.001), but was without correlation with ASR.

Adult↗
PubMed1991

Monoclonal antibodies to cultured human glomerular mesangial cells. I. Reactivity with haematopoietic cells and normal kidney sections.

The aim of this study was to produce monoclonal antibodies to cultured human glomerular mesangial cells in order to obtain specific markers for these cells and to aid the study of their function. Using standard monoclonal antibody techniques, 29 hybridomas producing antibodies directed to cultured mesangial cells were obtained. Most of these antibodies were not reactive with normal or neoplastic haematopoietic cell lines by flow cytometry. Fourteen of the 29 culture supernatants bound to various components of normal human kidney sections stained by the alkaline phosphatase/anti-alkaline phosphatase (APAAP) method. Ten of these supernatants reacted with components within the glomerulus, with six binding to the mesangium. These studies suggest that (1) mesangial cells in culture may show significant de-differentiation, because most supernatants which reacted with mesangial cells in culture did not do so in tissue sections; (2) antibodies reactive with haematopoietic cells may not detect the majority of immunogenic surface antigens on cells in tissues; and (3) some of the antibodies which we have produced may prove to be useful markers for mesangial cells in glomerular disease.

Animals↗
PubMed1991

Cyclosporin A and the humoral response to blood transfusion in the rat: definition of antigens which suppress alloantibody formation.

1. Blood transfusions improve renal allograft survival rates, but may induce antibodies which are directed to class I major histocompatibility complex antigens and mediate hyperacute transplant rejection. A model to study the development of such antibodies was developed in inbred strains of rats. 2. The influence of transplantation antigens shared between an initial course of blood transfusions, given with cyclosporin A, and a subsequent antigenic challenge (blood transfusion), given without cyclosporin A, on alloantibody responses to class I major histocompatibility complex antigens was then investigated. 3. Cyclosporin A administration prevented the development of alloantibodies to class I major histocompatibility complex antigens during the initial transfusion period. 4. After the challenge transfusions, alloantibody responses to class I major histocompatibility complex antigens were suppressed when class I major histocompatibility complex or minor histocompatibility antigens were shared between the initial and final transfusions. 5. This suppression only extended to third party class I antigens when minor histocompatibility complex antigens were shared between the initial and final transfusions. Sharing of class I or class II antigens had no effect on alloantibody responses to third party class I antigens coexpressed on the same cell. 6. These studies suggest that cyclosporin A given with blood transfusions may prevent clinical sensitization while permitting the development of suppressor activity, mediated by shared minor histocompatibility complex determinants, to a broad range of potential donor antigens.

Animals↗
PubMed1991

The effect of cyclosporin administered during a third-party blood transfusion protocol on humoral immune responses.

Antigen pre-treatment in animals undoubtedly prolongs graft survival. In man, however, routine pre-transplantation blood transfusions have recently become controversial, principally because of the adverse effect of transfusion-induced sensitisation on graft survival rates. We have monitored the effect of cyclosporin administered during a planned programme of third-party blood transfusions on the development of both cytotoxic and anti-idiotypic antibodies. A total of 24 patients were recruited to the study; ten received cyclosporin with blood transfusions (BT) (group 1), 14 received BT alone (group 2). Anti-HLA antibodies developed in 3 of 9 patients in group 1 and 8 of 12 patients in group 2 (P less than 0.05). Anti-idiotypic antibody activity was detectable in 9 of 9 patients in group 1 and 7 of 12 patients in group 2 (P less than 0.006). The mechanism by which cyclosporin can prevent an anti-HLA antibody response and promote an anti-idiotypic response is unclear.

Antibodies, Anti-Idiotypic↗
PubMed1991

Immune responses to noninherited maternal RT1A antigens in inbred rats.

Humoral responses to non-inherited maternal class I antigens (class I NIMAs) were assessed in 3 groups of inbred rats expressing the RT1u phenotype. Group 1 consisted of the progeny of (AO X DA)F1 X PVG matings; their haplotype was RT1u/c and their non-inherited maternal haplotype RT1a. Group 2 were the progeny of (AO X LEW)F1 X PVG matings the haplotype of which was also RT1u/c, but their non-inherited maternal haplotype was RT1l. Group 3 comprised 8 (AO X PVG)F1 (RT1u/c) hybrids. All rats received 2 intravenous blood transfusions (0.5 ml) from male DA (RT1Aa) donors on days 0 and 7. They were bled at weekly intervals for 6 weeks and again at 20 weeks after the first transfusion. Alloantibody responses to RT1Aa were assessed by an indirect hemagglutination assay (IHA)* and by a 51Chromium-release complement-dependent red cell cytotoxicity assay. All groups exhibited vigorous anti-class I antibody responses to the DA transfusions. No significant differences were detected, however, in antibody titers between the groups either by IHA or CDC or in the rates of decay of antibody titers up to week 20. In addition no blocking activity was found in sera obtained on day 0 from group 1 animals and tested for antiidiotypic antibody activity to cytotoxic anti-RT1Aa antibodies. In order to assess whether suppressor activity had been activated by the initial transfusions, in the animals in which class I NIMA was RT1Aa, all groups were rechallenged with a DA transfusion at week 20. All animals exhibited vigorous anamnestic responses to this challenge and no significant differences were detected between groups. In order to determine whether cellular tolerance to the noninherited maternal haplotype was present in group 1 animals, proliferative responses were assessed by one-way mixed lymphocyte cultures, using DA lymph node stimulator cells. No significant differences were detected in proliferative or kinetic responses between lymph node cells from rats the noninherited maternal haplotype of which was RT1a or from naive (AO X PVG)F1 hybrids. Peak proliferative responses to DA cells in rats the noninherited maternal haplotype of which was RT1l were similar, but maximal on day 4 as opposed to day 3. Hence in these inbred rat strains no evidence of humoral tolerance to class I NIMAs was detected. In addition there was no evidence of cellular tolerance to the noninherited maternal MHC haplotype.

Animals↗
PubMed1990

The detection of antibodies in pregnancy: a comparison of two assay systems.

In this study we have compared the ability of two assay systems, erythrocyte antibody rosette inhibition (EAI) and cellular enzyme-linked immunospecific assay (CELISA) to detect maternal alloantibody activity during pregnancy. Antibody activity to antigens on paternal lymphocytes was present in nine of 23 primigravid sera tested by EAI and in seven of 23 by CELISA. In multiparous sera, antibodies directed to paternal lymphocytes were detected in 11 of 15 individuals by EAI and in six of 15 by CELISA. The techniques correlated significantly when assaying the humoral response in sera from multiparous women. The lack of correlation when assaying primigravid sera suggests that both assays encounter difficulty in detecting the low titres of antibodies present.

Enzyme-Linked Immunosorbent Assay↗
PubMed1990

Production of human monoclonal antibodies to B lymphocyte cell surface antigens by in vitro immunization and human-human hybridoma technology.

We attempted to produce human monoclonal IgM antibodies to class II HLA antigens by in vitro immunization of human splenocytes with affinity purified HLA or irradiated whole lymphoblastoid B cells using the adjuvant muramyl dipeptide and IL-2. Two fusions where affinity purified HLA was used to stimulate the in vitro immunization produced no hybrids secreting antibodies against the stimulating antigen. However, 13.1% of 381 hybrids from eight fusions were positive by CELISA when whole cells were used to immunize. These antibodies were reactive with a wide range of cell types and were not directed to HLA. It proved difficult to characterize them, possibly because of low affinity. One reacted in Western blots with a 200 kD antigen, but this was exceptional. Most bound to a small percentage of cells in flow cytometry and did not lyse target cells in cytotoxicity assays. Control fusions were performed and similar antibodies were obtained from 2.6% of 235 hybrids. These data suggest that in vitro immunization using the protocol outlined can increase the frequency of some antibodies, but that they may represent a very primitive lineage which does not have the specificity and affinity required to prove useful as diagnostic or therapeutic agents.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1990

Familial incidence of C3 nephritic factor, partial lipodystrophy and membranoproliferative glomerulonephritis.

C3 nephritic factor is an IgG autoantibody that causes complement activation by stabilizing the alternative pathway C3 convertase. It is associated with partial lipodystrophy and membrano-proliferative glomerulonephritis. The occurrence of C3 nephritic factor, partial lipodystrophy and membranoproliferative glomerulonephritis, whether singly or in any combination, is usually sporadic. We describe the coexistence of all three of these conditions in members spanning two generations of a single family. This suggests that the pathogenesis of these conditions may be linked and that genetically determined factors may, in some circumstances, contribute to disease susceptibility.

Biopsy↗
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↗