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Biomedical subjects

J Esdaile

Publications and source records attributed to J Esdaile.

At least 19 recordsLinked to original sources
PubMed1999

Immune responses to cartilage link protein and the G1 domain of proteoglycan aggrecan in patients with osteoarthritis.

OBJECTIVE: To determine whether patients with osteoarthritis (OA) express cellular immunity to cartilage link protein (LP) and the G1 globular domain of proteoglycan (PG) aggrecan, and whether immunity to the G1 domain is influenced by the removal of keratan sulfate (KS). METHODS: LP and the G1 globular domain of PG were isolated from human and/or bovine cartilage and used in proliferation assays with peripheral blood lymphocytes (PBL) from 42 patients with OA and 40 healthy control subjects. RESULTS: Patients with OA expressed a higher prevalence of cellular immunity to human cartilage LP (42.4%) compared with the control group (13.3%). The prevalence of immune reactivity to bovine LP in patients with OA was lower (35.7%) compared with the immunity to human LP, but remained similar in the control group (13.8%). PBL from patients with OA exhibited low reactivity to the native G1 domain of bovine PG. However, removal of KS chains from the G1 globular domain resulted in increased cellular immune responses to the G1 domain in OA patients (45.8%) compared with the control group (7.7%). CONCLUSION: These results indicate the presence of immunity to cartilage-derived LP and the G1 globular domain of PG aggrecan in patients with OA and the inhibitory effect of KS chains on the G1 domain on the expression of this immunity in OA patients. This immune reactivity is commonly observed in patients with inflammatory joint disease and can experimentally induce arthritis. Thus, it may be involved in the pathogenesis of OA.

Aged↗
PubMed1998

Cellular immunity to the G1 domain of cartilage proteoglycan aggrecan is enhanced in patients with rheumatoid arthritis but only after removal of keratan sulfate.

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) express cellular immunity to the purified G1 globular domain of cartilage proteoglycan (PG) aggrecan and whether it is influenced by the removal of keratan sulfate (KS) chains from the molecule. METHODS: The G1 globular domain of PG was purified from mature bovine articular cartilage, digested with keratanase, and used in proliferation assays with peripheral blood lymphocytes (PBL) isolated from 43 patients with RA, 11 patients with nonarticular rheumatism (NAR), including soft tissue rheumatism and mechanical back pain, and 13 healthy age- and sex-matched control subjects. RESULTS: Removal of KS chains from the G1 globular domain resulted in significantly increased prevalence and values of cellular immune responses to G1 in RA patients compared with the control and NAR groups. In the majority of RA patients, KS chains on G1 significantly inhibited its immune recognition by PBL. There was no significant effect of KS removal on the immunity to G1 in patients with NAR and in the healthy control group. CONCLUSION: These results reveal that immune reactivity to the G1 globular domain of the cartilage PG aggrecan is enhanced in patients with RA but only when KS chains are removed. Thus, KS chains inhibit immune responses to this domain of aggrecan. Since immunity to the G1 globular domain of aggrecan induces an erosive polyarthritis in BALB/c mice after removal of KS chains, immunity to the G1 globular domain, cleaved by proteases to remove KS chains, may play a role in the pathogenesis of RA.

Adult↗
PubMed1998

Autoimmunity to cartilage link protein in patients with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) express cellular immunity to cartilage link protein (LP). METHODS: LP was purified from human fetal epiphyseal and bovine adult nasal cartilage. It was used in proliferation assays with the peripheral blood lymphocytes (PBL) isolated from 83 patients with RA, 21 patients with AS, and 30 healthy controls. RESULTS: Patients with RA (34%) and AS (71%) expressed a significantly higher prevalence of cellular immune responses to human LP compared with the healthy control group (13%). Such significant differences were not observed for bovine LP. Half the patients with RA responding to LP exhibited cellular immunity to both human and bovine protein. In the AS group, PBL from a majority of responders to LP recognized only human LP. CONCLUSION: These data suggest that LP is a potential autoantigen in the development of RA and AS and that cellular immune reactivity to common and distinct LP epitopes in patients with RA and AS may play a role in the pathogenesis of these diseases.

Adult↗
PubMed1992

Murine cross-reactive T-cell epitopes of Neisseria meningitidis outer membrane proteins.

Five non-covalent vaccines of outer membrane proteins (OMPs) complexed to capsular polysaccharide were prepared from Neisseria meningitidis serogroup B strains. Each vaccine contained distinct serotype (class 2/3) and subtype (class 1) OMPs. The cross-reactivity of the T-cell response to the meningococcal vaccine-associated proteins was examined in an in vitro T-cell proliferative assay, following antigenic priming of mice with one of these vaccines (MB6:P1.6) or with its purified class 1 (subtype P1.6) and class 2 (serotype 6) proteins. Cross-reactive T-cell epitopes were found in all five vaccine preparations on both the class 1 and class 2/3 OMPs. Priming of mice with the subtype P1.6 N-terminal peptide led to a significant but small increase in T-cell proliferation with the MB6:P1.6 vaccine.

Amino Acid Sequence↗
PubMed1992

Open-label tolerability study of enteric-coated naproxen in the treatment of osteoarthritis and rheumatoid arthritis.

Two hundred and ninety-six patients were enrolled in a 6-month, open-label tolerability study of enteric-coated naproxen in patients with rheumatoid arthritis (n = 174) and osteoarthritis (n = 122). Thirty percent of the patients were greater than 65 years of age. Under standard clinical prescribing conditions, enteric-coated naproxen 500 mg twice daily and 375 mg twice daily demonstrated an acceptable tolerability profile that was not different from what one would expect with standard naproxen.

Adult↗
PubMed1991

Immunogenicity in adult males of a Neisseria meningitidis group B vaccine composed of polysaccharide complexed with outer membrane proteins.

Twenty five adult male volunteers were given a vaccine composed of the capsular B polysaccharide non-covalently complexed to serotype 6 outer membrane proteins (OMP) of Neisseria meningitidis. Subjects were divided into three dose groups receiving 50, 100 or 150 micrograms vaccine in aluminium hydroxide in each of three injections spaced 4 weeks apart. Systemic signs/symptoms considered clinically significant were recorded on 6% (4/70) of occasions and were succeeded by withdrawal of two volunteers from the study. Local injection site reactions, mostly mild to moderate, were reported after all vaccinations with one such reaction leading to a third volunteer withdrawing from the study. Geometric mean anti-B responses before immunization and 1 week after the third immunization (9 weeks) were 3.60 and 7.12 micrograms ml-1 in the 50 micrograms group (p less than 0.05) 2.05 and 12.19 micrograms ml-1 in the 100 micrograms group (p less than 0.001), and 3.68 and 14.20 micrograms ml-1 in the 150 micrograms group (p less than 0.001). The anti-B response was predominantly of the IgM isotype and persistence above prevaccination levels was evident for at least 12 months. Anti-type 6 OMP responses were also evidenced with geometric mean multiplicative increases over prevaccination levels at 9 weeks and 6 months of 7.8 and 4.2 for the 50 micrograms group, 11.6 and 5.6 for the 100 micrograms group and 6.8 and 3.4 for the 150 micrograms group. The bulk of this response was of the IgG isotype. Passive protection of mice was achieved with both pre- and post-vaccination (9 weeks; 100 and 150 micrograms groups) pools of sera.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Specificity of the immune response to the group B polysaccharide of Neisseria meningitidis.

A panel of monoclonal antibodies (mAb) and polyclonal sera of murine, human and equine origin, of IgM isotype and with specificity for Neisseria meningitidis group B polysaccharide, an alpha(2----8)-linked homopolymer of sialic acid, were examined for their antigenic and biological specificities. The nature of the antigenic determinants on B polysaccharide was investigated using a series of N-acyl derivatives of B polysaccharide, two sialic acid polymers containing alpha(2----9)-linkages and a series of polynucleotides. The panel of antibodies recognized an array of unrelated antigenic determinants on the B polysaccharide, despite its structural simplicity, and all but one were highly effective in an in vitro bactericidal assay and/or in an in vivo murine passive protection model. There was no evidence that B polysaccharide induced antibody capable of blocking biological activity (blocking antibody).

Animals↗
PubMed1989

Passive transfer of meningococcal group B polysaccharide antibodies to the offspring of pregnant rabbits and their protective role against infection with Escherichia coli K1.

Pregnant rabbits vaccinated with meningococcal group B polysaccharide complexed to outer membrane proteins (serotype 6) responded to produce IgG, IgM and IgA anti-B polysaccharide antibodies, which were passively transferred to the offspring (IgG preferentially) and could be detected in their sera immediately after birth. These antibody levels were sustained in the mothers but diminished in the offspring to background levels at day 22 after birth. In a subsequent experiment, rabbits immunized with the group B vaccine had offspring that proved considerably more resistant to infection with Escherichia coli K1 than the control litters from non-immune mothers. Although not complete, protection was statistically of high significance and correlated well with the anti-B polysaccharide titres obtained in the mothers.

Animals↗
PubMed1987

Reticuloendothelial system Fc receptor function in systemic lupus erythematosus: effect of decreased sensitization on clearance of autologous erythrocytes.

Recent reports of reticuloendothelial system Fc receptor function using anti-Rh(D) coated red blood cells (RBC) provide conflicting data regarding the degree of abnormality in systemic lupus erythematosus (SLE). The effect of different sensitizing doses of anti-Rh(D) on Fc receptor function was evaluated in 10 controls and 9 patients with SLE (5 with renal disease, 4 without) using 1 microgram anti-Rh(D) (6,700 molecules anti-Rh(D)/RBC by saturation analysis) and 0.125 microgram anti-Rh(D) (1,100 molecules/RBC). At the lower sensitizing dose the sensitivity of the assay was significantly increased. To correctly interpret the significance of studies of Fc receptor function from different centers, it is necessary to know the exact sensitizing doses used for each study.

Adult↗
PubMed1986

Thymic-dependence and immune memory in mice vaccinated with meningococcal polysaccharide group B complexed to outer membrane protein.

Athymic mice were capable of producing IgM antibodies to B polysaccharide of N. meningitidis when immunized with the polysaccharide complexed to outer membrane proteins, whereas no immunogenicity could be demonstrated with the purified polysaccharide. Transfer of T cells to athymic cells demonstrated that the primary anti-B response was truly thymus-independent but the bulk of the secondary response was thymus-dependent. Transfer of T and B cells purified from spleens of immune mice into irradiated recipients showed the presence of memory T cells, but no memory B cells could be found.

Animals↗
PubMed1985

Immunity and protection of mice against Neisseria meningitidis group B by vaccination, using polysaccharide complexed with outer membrane proteins: a comparison with purified B polysaccharide.

A methodology for preparing outer membrane proteins (type specific) complexed to group B polysaccharide of Neisseria meningitidis is described. These complexes, low in nucleic acid and lipopolysaccharide content, were immunogenic in mice with induction of humoral antigroup B and antiprotein responses. Immunized mice were also protected against challenge with N. meningitidis group B strains of the same or a different type from that used for vaccination. Both immunity and protection were enhanced when the mice received a secondary immunization with the protein-polysaccharide complex. Additional data have shown the capacity of purified B polysaccharide to induce immunological memory, even though it is incapable of inducing a humoral response when given alone.

Animals↗
PubMed1985

Effect of aluminum ions on chemical and immunological properties of meningococcal group B polysaccharide.

Soluble salts of aluminum were examined for their capacity to complex with purified meningococcal group B polysaccharide. The formation of the complexes resulted, first, in a markedly reduced rate of internal esterification at acid pH and, consequently, prolonged stability of the antigen as measured by its reactivity with antibody at pH 4 and, second, in an increased resistance to neuraminidase. Al3+ complexes of B polysaccharides were tested for immunogenicity in mice and found to be no better than the purified polysaccharide in the Na+ or Ca2+ form. However, when Neisseria meningitidis type 6 protein (outer membrane) complexed to B polysaccharide was tested, a substantial increase in anti-B titers was detected, whereas antiprotein titers remained unchanged. The possibility of using combinations of metal-polysaccharide-outer membrane protein complexes as vaccines for humans is discussed.

Aluminum↗
PubMed1985

The randomized clinical trial in orthopaedics: obligation or option?

The classic randomized clinical trial is difficult to apply to the evaluation of surgical procedures. After reviewing the structure and rationale of cohort studies and randomized clinical trials, four types of bias in randomized clinical trials that present difficulties in clinical studies are identified. Other problems that may limit the willingness of orthopaedic surgeons to conduct randomized clinical trials relate to the surgical procedure itself, the outcome of the trial of interest, surgical philosophy, and the ethical implications for a surgeon of a randomized clinical trial. A recently proposed variation of the classic randomized clinical-trial model, the randomized-surgeon design, appears to solve some of these problems.

Clinical Trials as Topic↗
PubMed1984

A controlled two-centre trial of parenteral methotrexate therapy for refractory rheumatoid arthritis.

Forty-eight patients with rheumatoid arthritis refractory to other treatments were studied in a placebo controlled trial of methotrexate (MTX) in 2 institutions. Once weekly for 6 weeks, the patients were injected with placebo (Group 1), MTX 10 mg (Group 2), or MTX 25 mg (Group 3). Then, for the next 6 weeks, Group 1 received MTX, either 10 or 25 mg/wk, and Groups 2 and 3 continued their same dose. Adverse reactions necessitated change from 25 mg to 10 mg in some patients, but no major side effects of MTX were noted. At 6 weeks, the effect of the 2 MTX doses did not differ significantly but patients on MTX had fared significantly better (p less than 0.005 - less than 0.001) than those given placebo. At 12 weeks, all indices showed significant improvement in Group 1 and maintenance or enhancement of the improvement in Groups 2 and 3. We conclude that weekly low dose MTX therapy is efficacious for refractory rheumatoid arthritis.

Adult↗
PubMed1984

An immunogenetic study of older age onset rheumatoid arthritis.

Thirty-two patients with older age onset rheumatoid arthritis (ORA), defined as disease onset after age 60, were selected for HLA typing. The majority (69%) were rheumatoid factor (RF) seronegative. An increase in HLA-DR4, though not statistically significant, was seen in ORA (38% vs 17% normals). This antigen was strongly associated with RF seropositivity (70%, p less than 0.01) and rheumatoid nodules (75%, p less than 0.01) in ORA. We conclude that the immunogenetics of ORA are similar to that described for adult RA in general.

Aged↗
PubMed1983

Wegener's granulomatosis. Clinical features and outcome in 13 patients.

Thirteen patients with Wegener's granulomatosis were seen over 10.5 years. The clinical features resembled those in previously reported series, except for the increased frequency of inflammatory arthritis, which was a prominent early feature in ten patients (77%). Four (31%) of the 13 had fulminant vasculitis and died before receiving an adequate course of cytotoxic drug therapy. Two of these four had a pulmonary-renal syndrome that mimicked Goodpasture's syndrome. All of the remaining nine patients (69%) achieved an initial remission with cytotoxic agents (azathioprine or cyclophosphamide), but four died in less than one year with no evidence of vasculitis at autopsy. The 56% survival rate to one year in these nine patients contrasts with an 86% to 100% survival in other series. Chronic renal failure was a prominent sequela in those who survived one year.

Adolescent↗