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Biomedical subjects

T L Moore

Publications and source records attributed to T L Moore.

At least 109 records · Page 6Linked to original sources

HLA antigens in black and white patients with juvenile arthritis: associations with rheumatoid factor, hidden rheumatoid factor, antinuclear antibodies, and immune complex levels.

HLA typing for -A, -B, -C, -DR, and -MT antigens and simultaneous studies for the presence of 19S IgM rheumatoid factor (RF), hidden 19S IgM RF, antinuclear antibodies (ANA), and immune complexes (IC) were performed on 24 black and 80 white patients with juvenile arthritis (JA) of different onset types. HLA-DRW6 (p less than 0.05) was associated with pauciarticular onset and early onset pauciarticular black patients. HLA-DR4 was found in both blacks and whites with chronic disease (p less than 0.01) and with the presence of RF (p less than 0.05) and hidden RF (p less than 0.05). In the whites, HLA-DR5 (p less than 0.05) and DRW8 (p less than 0.001) were associated with pauciarticular onset and early onset pauciarticular patients. HLA- DRW8 was also associated with white JA patients with iridocyclitis (p less than 0.001) and black (p less than 0.01) and white patients (p less than 0.001) with the presence of ANA. HLA-MT2 was demonstrated in all 24 black patients (p less than 0.001) and in 54/80 white patients (p less than 0.001). HLA-MT2 was associated with black (p less than 0.01) and white (p less than 0.001) patients with early onset pauciarticular disease and the presence of iridocyclitis in white patients (p less than 0.001). The association of HLA antigens in black JA patients has not been reported before.

Antibodies, Antinuclear↗

Precipitation of 19S IgM rheumatoid factor-IgG circulating immune complexes in patients with juvenile arthritis by polyethylene glycol and separation by immobilized protein A.

Immune complexes (IC) in sera and synovial fluid (SF) from patients with juvenile (rheumatoid) arthritis (JA) were isolated by making use of polyethylene glycol (PEG) to precipitate IC and then using staphylococcal protein A to separate the IC. The isolated IC were compared to IC in sera analysed by sucrose density gradients and measured by the C1q solid phase assay (ClqSPA). Isolated IC from sera of 10 of 16 JA patients demonstrated significant 19S IgM rheumatoid factor (RF) titres in their acid elutes utilizing the haemolytic assay. IgM and IgG were detected by low level radial immunodiffusion in the acid eluate of sera in all 10 patients who had significant RF titres. In isolated IC from SF, three of five JA patients had significant 19S IgM RF titres detected in their acid eluates. By sucrose density gradient analysis of these sera, elevated levels of IC detected by ClqSPA were found in the fractions of greater than or equal to 19S comparable to the previous isolated 19S IgM-IgG complexes. This detection of IC like material containing 19S IgM and IgG by the present method further supports the participation of classic and hidden 19S IgM RF in IC formation in JA patients.

Antigen-Antibody Complex↗

Rapid determination of hidden rheumatoid factor.

A method for the determination of hidden 19S IgM rheumatoid factor based on separation by QAE-Sephadex A-50 chromatography followed by hemolytic assay is described. Hidden rheumatoid factor titers and IgM recoveries of sera were comparable to those obtained by the conventional acid gel filtration method. The QAE method saves time, requires only 250 microliters of serum and can be performed with a minimum of specialized equipment.

Arthritis, Juvenile↗

Separation and characterization of immune complexes containing 19S IgM rheumatoid factor-IgG in juvenile arthritis.

Sera from 10 patients with juvenile arthritis (JA), 2 seropositive and 8 with hidden rheumatoid factor (RF), were subjected to affinity chromatography on a rabbit anti-human IgM column. Material retained by the column was eluted sequentially by 1M NH3 and 0.1M glycine-HCl buffer, pH 3.0. The affinity fractions contained both 19S IgM RF and IgG, while corresponding fractions from healthy controls contained neither. Sera from 15 patients with JA, 1 seropositive and 11 with hidden RF, were subjected to 4% polyethylene glycol precipitation followed by acid dissociation of the precipitate. Ten of 15 resultant fractions contained both IgM RF and IgG, while corresponding fractions from healthy controls contained only traces of IgG. Sera from 7 of these JA patients were subjected to sucrose density gradient centrifugation and the resultant fractions analyzed for the presence of immune complexes by the C1q solid-phase assay. Immune complexes were detected at and ahead of the IgM marker, as expected for IgM RF-IgG complexes. These combined data show that the majority of JA patients with classic or hidden 19S IgM RF have immune complexes containing IgM RF and IgG in their sera.

Antigen-Antibody Complex↗

The tight-skin mouse: physical and biochemical properties of the skin.

The tight-skin (TSK) mouse has unusual structural skin properties. These include increased thickness of the dermis, increased tensile strength, and increased adherence to subcutaneous tissues. We have investigated several physical and biochemical characteristics of skin from the TSK mouse and compared them to the normal mouse. An increase in thickness, wet weight, and hydroxyproline content was found in the skin of the TSK mouse. In addition, there was an increase in the ratio of soluble to insoluble collagen in the TSK mouse when compared to the normal mouse. These findings in the skin of the TSK mouse are similar to the changes found in the skin of patients with progressive systemic sclerosis.

Animals↗

Frequencies of Epstein-Barr virus-inducible IgM anti-IgG B lymphocytes in normal children and children with juvenile rheumatoid arthritis.

The relative frequencies of IgM antiIgG autoantibody (rheumatoid factor) producing cells induced by the polyclonal B cell activator Epstein-Barr virus were measured in peripheral blood lymphocyte cultures of normal children and patients with juvenile rheumatoid arthritis. The frequencies of rheumatoid factor precursor B cells in normal children were lower than adults, but higher than neonates. The frequency increased with the age of the donor. In seronegative children with the systemic-onset or pauciarticular-onset types of juvenile rheumatoid arthritis, the number of IgM antiIgG inducible B cells was not significantly different (P greater than 0.05) from age-matched controls. Patients with seropositive juvenile rheumatoid arthritis or seropositive adult rheumatoid arthritis had significantly higher IgM antiIgG precursor cell frequencies than age-matched normal subjects (P less than 0.01 and P less than 0.02, respectively). In contrast, the patients with seronegative polyarticular-onset juvenile rheumatoid arthritis had an average precursor frequency significantly lower than normal age-matched controls (P less than 0.05), analogous to results previously noted in adult seronegative rheumatoid arthritis. Thus, both children and adults with seronegative polyarticular rheumatoid arthritis had a deficiency in B cells that produce IgM antiIgG and that are induced by Epstein-Barr virus. This distinguished them from seropositive juvenile rheumatoid arthritis and rheumatoid arthritis patients, normal subjects, and patients with the pauciarticular-onset and systemic-onset types of seronegative juvenile rheumatoid arthritis.

Adolescent↗

Specificity of hidden 19S IgM rheumatoid factor in patients with juvenile rheumatoid arthritis.

Hidden 19S IgM rheumatoid factors (RF)-i.e., RF detected in the IgM-containing fraction after separation of the serum at an acid pH-have been found in 68% of patients with seronegative juvenile rheumatoid arthritis (JRA). Inhibition studies utilizing a hemolytic assay for RF were performed to determine the specificity of hidden 19S IgM RF. Sera from 14 children with JRA were separated by gel filtration at pH 4.05. Two were seropositive for RF and 12 were seronegative; the latter had high titer hidden 19S IgM RF. The IgM-containing fractions were preincubated with monomeric human IgG, rabbit IgG, or bovine IgG, and the complement-dependent hemolytic assay ws performed. The RF in the IgM fraction from the 2 seropositive patients were inhibited most strongly by rabbit IgG, whereas hidden RF in the IgM fraction of 9 seronegative patients were inhibited markedly by human IgG (homologous IgG equal to autologous IgG), poorly by rabbit IgG, and not at all by bovine IgG. Further inhibition studies with the hidden 19S IgM RF demonstrated inhibition by the human IgG1 subclass in all patients and only minimal inhibition by the IgG3 subclass in 3 patients. Inhibition with IgG1 Fc fragments produced by papain and thermolysin digestion demonstrated inhibition by only those fragments that contained the G1m (a) antigenic area which is found in the C gamma 3 homology area of the IgG1 molecule. These data indicate that hidden 19S IgM RF possibly circulate as immune complexes bound to the IgG1 molecule and the binding chiefly occurs in th G1m (a) homology area.

Arthritis, Juvenile↗

Plasma and synovial fluid as solvents for monosodium urate.

In-vitro differences in monosodium urate (MSU) crystal dissolution in paired plasma and synovial fluid samples from patients with various arthritides were studied. Plasma was a significantly better solvent for MSU than synovial fluid (overall difference 6.3 mg/dl (0.37 mmol/l); significant at P less than 0.001). Attempts to correlate the solubility differentials with the principal compositional differences between the 2 fluids were only partially successful. (1) A tendency towards higher MSU solubility at higher protein levels was observed, but it was too slight to reach statistical significance. (2) Hyaluronidase treatment of synovial fluid significantly enhanced its ability to dissolve MSU (overall difference 2.2 mg/dl (0.13 mmol/l); significant at P less than 0.01) but not sufficiently to explain wholly the plasma-synovial fluid differential.

Arthritis↗

Immunoprotein deposition in synovial tissue in Reiter's syndrome.

The aetiology of Reiter's syndrome (RS) is unknown. In order to evaluate the role of immunological mechanisms in this disease we performed synovial biopsies on 12 patients with RS looking for deposition of immunoglobulins and complement components in synovial tissue. By immunofluorescent techniques 11 synovia were found to have immunoprotein deposition. IgM deposition was found around vessels in 8 synovia and in the interstitial tissue in 4. C3 was present perivascularly in 11 cases; in 4 of those there was also staining in the interstitial tissue. No immunoproteins were found in infiltrating or synovial lining cells. The finding of immunoproteins in the synovium of the majority of patients with RS suggests that immunological mechanisms are involved in the pathogenesis of this disease.

Adolescent↗

19S IgM Forssman-type heterophile antibodies in juvenile rheumatoid arthritis.

Fifty-four sera from children with juvenile rheumatoid arthritis (JRA) were separated by gel filtration at pH 4.05. The serum and IgM- and IgG-containing fractions were analyzed for heterophile antibodies by subjecting them to a hemolytic assay in tubes with the target cell a 1% washed sheep erythrocyte (SRBC) or beef erythrocyte (BRBC) in suspension. Thirty-three of 54 sera showed hemolytic antibody titers > 1:640 against SRBC alone and 4 of 54 had titers > 1:320 against SRBC and BRBC. All positive titers against SRBC and BRBC were associated with the IgM fraction. Differential absorption with SRBC, BRBC, and tissue sediment of homogenized guinea pig kidney revealed a Forssman specificity in 33 sera and Forssman and Hanganutziu-Deicher specificity in 4. The presence of heterophile antibodies in JRA correlated with the presence of hidden rheumatoid factor. There was also an increased incidence in patients with positive antinuclear antibodies and in teenaged females with polyarticular disease.

Animals↗

Lack of hidden complement fixing IgM rheumatoid factor in adult seronegative rheumatoid arthritis.

IgM rheumatoid factors capable of complement fixation and activation are commonly present in the sera of adults with rheumatoid arthritis. Hidden complement fixing IgM rheumatoid factor has been demonstrated in the majority of patients with juvenile RA and hidden agglutinating IgM rheumatoid factors have been demonstrated in the serum of adults with seronegative rheumatoid arthritis. We studied 27 adults with seronegative rheumatoid arthritis and were unable to demonstrate hidden complement fixing IgM rheumatoid factor in their sera.

Adult↗

Hidden 19S IgM rheumatoid factor in juvenile rheumatoid arthritis.

One-hundred twenty-five serum samples from 82 patients with juvenile rheumatoid arthritis (JRA) were studied for the presence of hidden rheumatoid factor (RF) in an effort to find a better serologic marker to define JRA. Hidden 19S IgM RF was detected by means of a hemolytic assay utilizing the IgM-containing fraction of serum. The IgM fraction was obtained after acid separation of serum on a Sephadex G-200 column. Hidden 19S IgM RF was present in 68% of patients with seronegative JRA with a mean titer of 1:63. The mean titer for the polyarticular JRA group was 1:83, for the pauciarticular JRA group, it was 1:32, and for the systemic type-onset JRA patients, it was 1:32. When disease was active, the mean titer for all JRA patients was 1:108, for the active polyarticular JRA group it was 1:119, for the active pauciarticular JRA, it was 1:97, and for the active systemic JRA patients, it was 1:64. All values were significant at the P less than or equal to 0.001 when compared to disease and normal controls. The hemolytic assay for RF on the IgM-containing fraction of serum thus enhances the serologic capabilities of defining JRA.

Adolescent↗