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Biomedical subjects

F C Hay

Publications and source records attributed to F C Hay.

At least 73 records · Page 4Linked to original sources
PubMed1981

Plasma exchange in systemic lupus erythematosus.

Eight out of 10 patients studied longitudinally received benefit from plasmapheresis. The patients were used as their own controls, being treated in a steady state as far as was possible. Levels of circulating complexes did not bear a close relationship with clinical results. On the evidence plasma exchange alone does not appear to represent an important part of the long-term management of patients with systemic lupus erythematosus but may well be of value in combination with other therapy.

Adult↗
PubMed1980

Preparation of a defined immune complex for use in C1q binding assays.

Soluble immune complexes of human beta 2 microglobulin with its IgG antibodies from Macaca irus antisera have been tested for suitability as a reference preparation for immune complex assays in human disease. The defined complex described is stable on storage, behaves reproducibly in a C1q solid phase binding assay and fulfills the criteria required for an international reference standard.

Animals↗
PubMed1980

Affinity, cross-reactivity and biological effectiveness of rabbit antibodies against a synthetic 37 amino acid C-terminal peptide of human chorionic gonadotrophin.

As a part of a programme to develop a fertility regulating vaccine, antibodies specific for human chorionic gonadotrophin were raised by immunizing rabbits with a synthetic 37 amino acid C-terminal peptide of beta hCG conjugated to tetanus toxoid as carrier, and using Bordetella pertussis or Freund's complete adjuvant as adjuvants. Lack of cross-reactivity of the antibodies with human luteinizing hormone was determined by direct binding in a radioimmunoassay and by immunofluorescence on adult human pituitary sections. Not only did the antibodies bind to native hormone in a radioimmunoassay but they also neutralized the biological activity of hCG as measured by an in vivo bioassay. Rabbits which had been injected with the conjugate with B. pertussis as adjuvant made antibodies of comparable affinity to those animals which had been immunized with the antigen in Freund's complete adjuvant, though the latter group did produce more antibodies.

Agglutination Tests↗
PubMed1980

Analysis of immune complexes in synovial effusions of patients with rheumatoid arthritis.

Immune complexes were isolated from the synovial effusions of patients with seropositive definite or classical rheumatoid arthritis by centrifugation over a sucrose-polyethylene glycol gradient. Physiochemical and immunochemical analysis showed IgG and IgM to be the predominant molecular species with lesser amounts of Clq and moderate amounts of IgA and activated C4 and C3. Very low concentrations of Clr, Cls, factor B and beta 2-microglobulin were detected. Trace amounts of four other components totalling less than 4% of the total protein, were seen and their molecular weights established. Reasons were advanced for thinking that fibrinogen, human serum albumin and alpha 2-macroglobulin were only secondarily associated with the complexes. The data are consistent with the hypothesis that IgG is the main, if not the only antigen, responsible for provoking and maintaining the pathological changes in rheumatoid arthritis.

Antigen-Antibody Complex↗
PubMed1979

Characterisation of the immunological response in marmoset monkeys immunised against hCG beta-subunit and its relationship with their subsequent fertility.

Female marmoset monkeys that are actively immunised against hCG beta-subunit remain infertile while antibody titres are high. With declining antibody levels the animals experience recurrent abortions that occur progressively later as the levels continue to wane. After booster immunisations the animals become infertile once more. The affinity and total binding sites of antibodies to beta-hCG were monitored after booster injections in marmosets and the values were correlated with subsequent reproductive events. The relationship between antibody amount and affinity varied considerably and the affinity was the important factor in producing the biological effects, pregnancies being often associated with a fall in antibody affinity. The antisera were also biologically active in inhibiting hCG-induced ovulation and increase in uterine weight in mice. There was no apparent cross-reaction between the antisera and human luteinizing hormone as tested by indirect immunofluorescence on adult human pituitary sections.

Abortion, Incomplete↗
PubMed1979

Intra-articular and circulating immune complexes and antiglobulins (IgG and IgM) in rheumatoid arthritis; correlation with clinical features.

Solid phase radioimmunometric methods have been used to assay immune complexes and IgG and IgM antiglobulins in paired samples of synovial fluid and serum from patients with rheumatoid arthritis (RA) or osteoarthrosis. Over 60% of RA patients had some increase in complexes in their sera, while nearly 90% had synovial fluid complexes. Moreover, the levels of complexes within the joint were much higher than in the serum. Both IgG and IgM antiglobulins were raised in most RA patients. The levels of IgG antiglobulins--and to a less extent IgM antiglobulins--were nearly always higher in synovial fluid than in the corresponding serum sample.A strong correlation was found between the levels of immune complex and IgG antiglobulin. A marked association was seen between the presence of subcutaneous nodules and increased IgG antiglobulins.

Adult↗
PubMed1979

Behaviour of effector cells, synovial fluids, and sera from rheumatoid arthritis patients in antibody-dependent cell-mediated cytotoxicity.

Antibody-dependent cell-mediated cytotoxicity (ADCC) was examined in patients with rheumatoid arthritis (RA). The cytotoxicity of peripheral blood leucocytes from patients with RA was similar to that found in normal persons, whereas ADCC was less effective in RA synovial fluid cells. It is possible that the activity in these cells is lower because of immune complexes and other factors being absorbed from the synovial fluid itself. Although patients' sera had little effect on normal peripheral blood leucocytes, synovial fluid from RA patients was markedly inhibitory in ADCC. The degree of inhibition correlated significantly with the clinical status of the patients.

Adult↗
PubMed1979

Characteristics of complexes for arming and inhibiting effector cells for antibody-dependent cell-mediated cytotoxicity.

The size of IgG aggregate effective in the inhibition or arming of human effector cells for antibody-dependent cell-mediated cytotoxicity (ADCC) was investigated using heat- and alkalipolymerized rabbit IgG or purified antibody fractionated by gel filtration. In contrast to the inhibition of ADCC against chicken erythrocytes, which was marked when effector cell were pre-incubated with high molecular weight aggregates (19S or greater), small polymers were most effective in arming for cytotoxicity against antigen-coated chicken red cells. Our data also demonstrate that while the cytotoxic potential of armed cells is short-lived and rapidly lost during culture at 37 degrees C but not 4 degrees C, the reduced capacity of these cells to kill antibody-coated targets is not altered by similar incubation at 37 degrees C. The differences in the size of aggregate active in arming and inhibition, and the stability of the two phenomena are compatible with the hypothesis that large aggregates may cause more cross-linking and redistribution of effector cell Fc receptors than small polymers of IgG.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

Immune complexes in ovarian cancer.

Immune complexes have been assayed in ovarian cancer with a polyethylene-glycol (P.E.G.) precipitation assay and a Clq solid-phase assay. Significantly higher levels of immune complexes were detected in patients in relapse compared with those in remission. Remission values were within the range obtained for a control group. Evidence was produced that immune-complex levels rise before the clinical detection of relapse, and it is suggested that the P.E.G. assay could be a useful marker of disease progress.

Antibodies, Neoplasm↗
PubMed1978

Modification of the Farr assay using ethanol-ammonium acetate precipitation and its application to the measurement of affinity of anti-HCG produced in several species.

A double isotope modified Farr assay was used to determine the total binding sites and affinity of antibodies to human chorionic gonadotrophin. Precipitation of the antigen--antibody complex at equilibrium with ammonium sulphate gave very high levels of nonspecific binding. Good discrimination over background was observed using a specific anti-immunoglobulin serum. However since we were interested in measuring the affinity of antibodies raised in several animal species it was more appropriate to use a single nonspecies precipitating reagent. We found that the use of a mixture of ethanol-ammonium acetate gave very low levels of non-specific binding in baboons, marmosets, rabbits and mice.

Animals↗
PubMed1978

Immunological control of fertility: measurement of affinity of antibodies to human chorionic gonadotrophin.

Four baboons were primed with diazotized beta human chorionic gonadotrophin and boosted with diazotized C-terminal beta human chorionic gonadotrophin peptide, and the changes in antibody amount and affinity determined using a double isotope modified Farr assay, using labelled human chorionic gonadotrophin as the antigen. The degree of cross-reaction with human luteinizing hormone was also determined. Although appreciable reactivity with luteinizing hormone was observed soon after immunization, this declined rapidly during the response. At the time intervals studied, there was a progressive increase in affinity of antibodies to human chorionic gonadotrophin until day 248 after priming. At day 313, in two of the animals, there was a decrease in affinity from 1.04 X 10(11) to 6.80 X 10(10) and 1.05 X 10(11) to 4.93 X 10(10) l/mol, whereas in the other two baboons there was a further increase in antibody affinity. At corresponding time intervals, there was a steady decrease in values of total antibody binding sites. To determine the overall effect of the maturation of affinity with a decrease in antibody amount on biological efficacy, the theoretical amount of chorionic gonadotrophin that would be neutralized was calculated. We computed that in all instances, over 99% of a peak concentration of chorionic gonadotrophin that could be in circulation in a pregnant baboon would be neutralized. This was in excellent agreement with results of mating experiments in these baboons. In over forty cycles studied, none of the matings resulted in a sustained pregnancy.

Animals↗
PubMed1978

Selective blocking of T cell-mediated in vitro cytotoxicity to a xenogeneic tumour by anti-immunoglobulin sera.

Rejection of a xenograft by BALB/c mice results in a highly potent immune peritoneal population. When these immune cells are analysed by using two in vitro assays in parallel, at least two active cytotoxic mechanisms can be demonstrated. Target cells can be labelled with [125I]iododeoxyuridine (IUdR) before the effector cells are added and the detachment of the DNA from plastic can be used to detect cell-mediated immunity. This is referred to as the direct cytotoxicity test. This assay is largely dependent on T-cell function and evidence is presented here that it can be inhibited by anti-immunoglobulin (anti-Ig) antisera. The second test, which reflects the inhibition of incorporation of IUdR by previously mixed effector and target cells, is called the cytostatic assay. This test, although presumably affected by cytotoxic T cells, also reflects a T-independent mechanism which is not inhibited by anti-Ig sera.

Animals↗
PubMed1977

The binding constants of IgM rheumatoid factors and their univalent fragments for native and aggregated human IgG;.

IgM rheumatoid factors (RF) were isolated from the sera of patients with rheumatoid arthritis and a serologically active Fabmicron RF fragment prepared by papain digestion. A radioimmunoassay was developed for the determination of interaction of 19S IgM RF and Fabmicron RF with human 7S IgG, heat-aggregated IgG, rabbit 7S IgG, and human pFc'. RF isolated under neutral conditions had a very low binding constant for human 7S IgG (of the order of 10(2) to 10(3) 1 mole-1) and a considerably higher value (ca. 10(5)) for the aggregated protein and monomeric rabbit IgG. RF obtained under acid conditions which dissociate the complexes with endogenous Ig, had a higher avidity for human IgG monomer as expected and also a comparable reactivity with rabbit IgG. Monovalent Fabmicron fragments of 'acid' RF had closely similar affinities for 7S and aggregated IgG suggesting that the enhanced binding with the aggregated protein is essentially dependent on its multivalency rather than the exposure of a new determinant lacking in the native molecule.

Antibody Specificity↗
PubMed1976

Laboratory diagnosis of rheumatoid arthritis: a solid phase radioassay for IgG and IgM antiglobulins.

A technique suitable for the routine estimation of IgM and IgG antiglobulins has been devised. The assay involves the binding of antiglobulins to plastic tubes coated with rabbit immunoglobulin: the amount of antiglobulin bound is then determined by adding radiolabelled antihuman IgG or IgM. The conditions for the assay have been examined and optimal incubation times and amounts of reagents established. Verification of the antibody nature of antiglobulin activity has been obtained. Both IgG and IgM antiglobulins were raised in virtually all seropositive rheumatoid arthritics, and most seronegative patients gave elevated values for either IgM or IgG rheumatoid factors. The use of an anti-light chain reagent as a screening test for total antiglobulins was investigated. These tests should prove valuable in diagnosis and permit quantitative evaluation of research studies.

Antibodies, Anti-Idiotypic↗
PubMed1976

A solid-phase radioassay for the detection of anti-thyroglobulin antibodies in different immunoglobulin classes.

A convenient technique suitable for the routine estimation of IgG and IgA anti-thyroglobulin antibodies has been devised. The assay involves the binding of anti-thyroglobulin to human thyroglobulin linked to the surface of plastic tubes; the amount of antibody bound is then determined by adding radiolabelled anti-human IgG or IgA. IgG antibody was raised in virtually all patients and significantly elevated levels of IgA antibody were also found in some patients. The test should prove helpful in diagnosis and provide quantitative evaluation of research studies.

Antibodies↗
PubMed1976

Hidden' IgG antiglobulins in normal human serum.

Hidden antiglobulins reacting with whole rabbit immunoglobulin were found by radioassay or indirect haemagglutination after gel filtration or ultracentrifugation of normal serum. Suprisingly, both the IgM and IgG antiglobulins were present in the same macroglobulin fractions. The IgG antiglobulins could be dissociated into 7S components by separating the serum under acid conditions. Antiglobulin activity was a function of the Fab region.

Antibodies, Anti-Idiotypic↗