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J A Goodacre

Publications and source records attributed to J A Goodacre.

28 records · Page 2Linked to original sources
PubMed1991

Comparative analysis of murine T lymphocyte responses to cartilage proteoglycans.

Cartilage proteoglycans are large molecules consisting of several sub-regions each of which comprises homologous repeating subunits. Comparisons of murine primed popliteal lymph node responses to human cartilage proteoglycans in BALB and B10 congenic mice showed that the major histocompatibility complex (MHC) influences T cell responsiveness to this antigen. H-2k and H-2d were higher responders than H-2b. Responses were MHC class II-restricted, and human cartilage proteoglycans were cross-reactive with mouse cartilage proteoglycans for a BALB/c T cell line. The proportion of proteoglycan-specific T lymphocytes in BALB/c primed popliteal lymph nodes was about 45% lower in females than males. These results show that in mice both MHC haplotype and sex can determine T lymphocyte responsiveness to cartilage proteoglycans. If the same mechanisms apply in humans they could be important in determining the HLA-DR haplotype associations and the predilection of rheumatoid arthritis for females.

Analysis of Variance↗
PubMed1991

Patients with ankylosing spondylitis show individual patterns of variation in disease activity.

Disease activity was monitored sequentially over 1 year in 22 patients with ankylosing spondylitis (AS) attending regularly the local NASS group. Assessments, using standard methods, were made at monthly intervals by the same observer. There was marked heterogeneity such that each patient's profile of disease activity was virtually unique. All patients experienced at least one exacerbation and most underwent exacerbations and remissions, reminiscent of the experience of many patients with rheumatoid arthritis. In most instances no reason for changes in disease activity could be discerned clinically. These observations raise the possibility that the natural history of disease in AS may be different for each individual patient, which, if true, would have important implications for the design of studies to test the efficacy of therapy and for approaches to investigating pathogenic mechanisms in patients with AS.

Adolescent↗
PubMed1991

Mapping T-cell epitopes in group A streptococcal type 5 M protein.

Group A streptococcal cell surface M proteins elicit highly protective, serotype-specific opsonic antibodies and many serotypes also elicit host cross-reactive antibodies, which may contribute to the pathogenesis of poststreptococcal autoimmune disease. To date, studies aimed at designing safe (non-host-cross-reactive, defined-epitope) M vaccines have focused almost exclusively on antibody epitopes. Here we identify T-cell epitopes recognized by T cells from BALB/c, C57BL/6, and CBA/Ca mice immunized with purified, recombinant serotype 5 M protein (rM5). The responses of rM5-specific, major histocompatibility complex class II-restricted, T-cell clones to synthetic peptides representing most of the M5 sequence identified at least 13 distinct T-cell recognition sites, including sites recognized by more than one major histocompatibility complex haplotype of mice. Although none of these sites appeared to be strongly immunodominant, an N-terminal peptide, sM5[1-35], was recognized by lymph node T cells of rM5-immunized mice and by a larger proportion of rM5-specific T-cell clones than any other individual peptide. The fine specificity of these clones was mapped with subpeptides to a single site at or overlapping the sequence ELENHDL at residues 21 to 27, which is in close proximity to previously mapped protective antibody epitopes. Other T-cell recognition sites are distributed throughout the M protein and include several in the highly conserved C-terminal region of the molecule. One of these C-terminal sites, located within residues 300 to 319, was recognized by a significant proportion of T-cell clones from two strains of mice. Helper T-cell epitopes located in the C-terminal region of M5 are likely to be widely conserved between different M serotypes and could be particularly useful in designing multivalent, defined-epitope M vaccines.

Amino Acid Sequence↗
PubMed1990

The frequency of mouse spleen dendritic cells which present alloantigens or ovalbumin to primed T lymphocytes is equal.

We have used limiting dilution analysis to compare the frequency of dendritic cells (DC) which present endogenous alloantigens with that which present an exogenous protein antigen to T lymphocytes. Spleen DC present alloantigens or ovalbumin to primed T lymphocytes with equal frequency, showing that DC are equipotent for presenting endogenous and exogenous antigens. Also, antigen-presenting cell (APC) frequencies among DC were compared with other APC populations. DC were enriched about 1000-fold for APC compared to unfractionated spleen cells.

Animals↗
PubMed1989

Hormone-sensitive lipase is responsible for the neutral cholesterol ester hydrolase activity in macrophages.

Anti-hormone-sensitive lipase (HSL) immunoglobulin selectively immunoprecipitates a single 84 kDa 32P-phosphoprotein from macrophage homogenates previously phosphorylated by cyclic AMP-dependent protein kinase in the presence of [gamma-32P]ATP-Mg. This immunoglobulin also completely removes the neutral cholesterol ester hydrolase activity from macrophage homogenates. These data demonstrate that HSL is responsible for the neutral cholesterol ester hydrolase activity in macrophages and hence plays a key role in cholesterol metabolism in these cells.

Adipose Tissue↗
PubMed1987

A limiting dilution assay to determine the frequency of antigen presenting cells.

A limiting dilution assay to measure the functional frequency of antigen presenting cells (APC) has been developed and used to measure the frequency of mouse lymphoid cells which stimulated the mixed leucocyte response. The experiments utilised measurements of proliferation in 20 microliter hanging drop microcultures of activated T lymphocytes. When the data supported a model of single-hit kinetics, the APC frequency in the titrated stimulating cell population was calculated by the method of maximum likelihood. The assay was validated by measuring the frequency of unpurified spleen cells and enriched spleen dendritic cells which presented alloantigens in mixed leucocyte culture. APC frequency in unpurified spleen cells was 1:7254 (SE +/- 2134, 8 experiments) and was increased markedly to 1:15 (SE +/- 7, 7 experiments) when enriched populations consisting 70-95% of dendritic cells were used as stimulators.

Animals↗
PubMed1987

Studies with an enthesis index as a method of clinical assessment in ankylosing spondylitis.

The histopathological characteristic of ankylosing spondylitis (AS) is the presence of chronic enthesitis. Our aim was to develop a clinical measurement of the severity of tenderness over entheses. The scoring system was based on the patients' response to palpation over entheses easily accessible to examination. The enthesis index (EI) correlated with pain (r = 0.67, p less than 0.01) and stiffness (r = 0.46, p less than 0.05) scores. A single, blind, crossover study was conducted to determine the sensitivity of the index to change in clinical state associated with non-steroidal antirheumatic drug therapy and to record the interobserver variability. The index showed significantly lower scores after one week's drug treatment (p less than 0.05). The EI is a convenient, non-invasive measure of disease severity in patients with AS. Potential applications include the assessment of enthesitis in other polyarthritides and a means of distinguishing clinically between severity of enthesitis and synovitis in different types of polyarthritis.

Adolescent↗
PubMed1985

A reinvestigation of the cross-reactivity between Klebsiella and HLA-B27 in the aetiology of ankylosing spondylitis.

The existence of cross-reactivity between Klebsiella antigens and cells from donors who are HLA-B27 positive and exhibit ankylosing spondylitis (AS) has been reinvestigated. Cells and antisera from different laboratories have been tested together using simultaneously microcytoxicity, chromium release and enzyme linked immunosorbent assays (ELISA). No reproducible interaction has been found. Mitogenic stimulation did not induce cross-reactivity and 'transformation' of B27+AS- cells by Klebsiella culture supernatants failed. Two transformed cell lines from B27+ AS+ donors exhibited specific cross reaction with two anti-Klebsiella antisera but only by chromium release. Immunoprecipitation with these cells and antisera showed the absence of any AS+ -specific antigen. It is concluded that the involvement of Klebsiella in ankylosing spondylitis through simple immunological cross-reactivity or through interaction with HLA-B27 is unlikely.

Antigens, Bacterial↗