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Biomedical subjects

R Maini

Publications and source records attributed to R Maini.

At least 19 recordsLinked to original sources
PubMed1992

T-cell-targeted immunotherapy.

The pace of T-cell research is matched only by the speed with which fundamental advances are being developed as new therapies. This report from a recent meeting updates developments in a number of immunointervention strategies.

AIDS Vaccines↗
PubMed1990

Detection of transforming growth factor-beta in rheumatoid arthritis synovial tissue: lack of effect on spontaneous cytokine production in joint cell cultures.

The presence of transforming growth factor-beta (TGF-beta) in inflammatory joint disease was investigated. Synovial fluid from patients with rheumatoid arthritis (RA) and patients with other non-autoimmune inflammatory joint diseases contained high levels of both active and latent TGF-beta. Levels of active TGF-beta did not correlate with drug regimen in either patient group or with the recovery period in the individuals with non-RA joint disease. Freshly isolated synovial cells from individuals with RA were shown by Northern blotting to express the mRNA for TGF-beta 1 and to secrete latent TGF-beta protein which could be neutralized by antibodies to TGF-beta 1 and TGF-beta 2. Lipopolysaccharide-stimulated peripheral blood mononuclear cells from normal donors produced interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) which was inhibited by pretreatment of these cells with recombinant TGF-beta. Cytokine production was not inhibited if the addition of TGF-beta was used after the inducing stimulus, suggesting that in activated cells cytokine production cannot be inhibited. This was confirmed by the observation that neither TGF-beta 1 or TGF-beta 2 inhibited spontaneous IL-1 or TNF-alpha production by rheumatoid synovial mononuclear cells in culture. These findings show that despite the presence of active TGF-beta in RA synovial joints and the spontaneous production of latent (potentially active) TGF-beta by RA cells in culture, additional TGF-beta did not inhibit ongoing cytokine synthesis in vitro. This suggests that TGF-beta may not inhibit cytokine production in the rheumatoid joint although it cannot be ruled out that in vivo TGF-beta already has an immunosuppressive effect which cannot be further increased in vitro by exogenous protein.

Arthritis, Rheumatoid↗
PubMed1989

Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis.

The effect of tumour necrosis factor (TNF alpha) antibodies on synovial cell interleukin-1 (IL-1) production was investigated in 7 patients with rheumatoid arthritis and in 7 with osteoarthritis. Synovial cell IL-1 production was significantly reduced by anti-TNF alpha antibody in cultures from patients with rheumatoid arthritis, but antilymphotoxin antibody did not have this effect (except in 1 culture). In cultures from patients with osteoarthritis spontaneous IL-1 production was low, despite high concentrations of TNF alpha, and IL-1 production was not inhibited by anti-TNF alpha antibody. In rheumatoid arthritis, TNF alpha may be the main inducer of IL-1, and anti-TNF alpha agents may be useful in treatment.

Adult↗
PubMed1988

Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis.

High levels of interleukin 6 (IL 6/B cell stimulatory factor-2) were detected in synovial fluids from the joints of patients with active rheumatoid arthritis (RA). The cells found in freshly isolated synovial fluid constitutively expressed IL 6 mRNA. The synovial tissues obtained by joint biopsy were also found to produce IL 6 in vitro. Immunohistochemical analysis demonstrated that CD2+ T cells as well as CD20+ blastoid B cells in the synovial tissues produce IL 6. The data indicate that IL 6 is generated constitutively in RA and its overproduction may explain the local as well as the generalized symptoms of RA, since IL 6 can function as B cell growth and differentiation factor as well as hepatocyte-stimulating factor.

Antigens, CD20↗
PubMed1988

Detection of activated T cell products in the rheumatoid joint using cDNA probes to Interleukin-2 (IL-2) IL-2 receptor and IFN-gamma.

Attempts to detect immune mediators in RA synovial fluids by bioassay or radioimmunoassay have yielded conflicting results, and so we have begun to analyse the complex immunological reactions occurring within the rheumatoid joint using recombinant DNA technology. High levels of Interleukin-2 (IL-2) and IL-2 receptor transcripts were found in the mononuclear cells of the rheumatoid lesions. Interferon gamma (IFN gamma) mRNA was also detected, although at lower level than IL-2. To investigate the possible relevance of IL-2 and IL-2 receptor mRNA expression to the chronicity of the disease, RA joint cells were cultured in the absence of any stimulus, and the duration of mRNA expression compared to that of blood mononuclear cells (PBM), optimally stimulated. IL-2 mRNA was found to persist in culture for many days, in contrast to its transient (less than 24 h) presence in stimulated PBM. IL-2 receptor expression was also prolonged. In contrast IFN gamma mRNA, present at biopsy in 10/12 RA samples, was found to increase significantly in vitro. These results suggest that persistent T cell activation is of importance in the pathogenesis of RA, and suggests that prolonged mediator production (IL-2 and IFN gamma) may be of importance. The elevation of IFN gamma mRNA in culture and its lower relative expression suggests that there are inhibitory immunoregulatory influences within the RA joint. To determine whether abnormal IL-2 mRNA expression may be due to a genetic defect in the region controlling IL-2 gene expression, Southern blotting analysis of genomic DNA was performed with a 5' flanking probe using normal, RA and systemic lupus erythematosis patients. No abnormalities were detected.

Arthritis, Rheumatoid↗
PubMed1987

Experimental and clinical experience with a gelatin impregnated Dacron prosthesis.

Laboratory and clinical evaluation of a knitted Dacron graft impregnated with gelatin to confer zero porosity is described. Graft performance was tested by standard methods for biodegradation of the sealant and in vitro thrombogenicity. The gelatin sealant was removed after seven to nine days and there was no platelet adhesion to Gelseal compared with unsealed Dacron. Animal experiments revealed normal macroscopic appearances in the graft and histological disappearance of the gelatin impregnate between five and ten days, allowing a cellular response similar to unsealed Dacron. The first 100 patients to have Gelseal aortic bifurcation graft implanted at Glasgow Royal Infirmary are described. The graft did not require preclotting. Blood transfusion was not necessary in 74% of patients. There is 100% patency at 21 months. A knitted Dacron graft sealed with gelatin is a safe, nonporous prosthesis at implantation.

Acute-Phase Proteins↗
PubMed1986

New polyester arterial prostheses from Great Britain: an in vitro and in vivo evaluation.

Two models of knitted velour polyester prostheses have been developed in Great Britain, i.e. the VP1200K and the VP50K Triaxial. The evaluation of these new devices in vitro and in vivo in dogs has demonstrated that, while the first model has similar surgical, mechanical and healing characteristics in the short term to other commercial knitted velour prostheses, the second model has lower water permeability and superior strength and dimensional stability. On the basis of these results, clinical investigations can be undertaken.

Animals↗
PubMed1986

Repeated membrane plasma separation with on-line sorbent treatment of plasma in the conscious rat.

Repeated membrane plasma separation with on-line sorbent treatment of plasma was performed in unrestrained and conscious rats, thus avoiding the possible effects of repeated stress and exposure to anesthetic agents. The procedure was well tolerated, even after four consecutive perfusions. Blood flow was 0.7 ml/min, with a transmembrane pressure of 18.6 mm Hg and plasma filtration rate of 0.21 ml/min. This allowed 12 ml of plasma (greater than 1 plasma volume) to be treated within 1 h. Levels of albumin, immunoglobulin G, and C3 remained constant during each perfusion and were not significantly different from those of animals subjected to control procedures. Results obtained from filtrate were comparable at 15 and 60 min with values obtained from whole blood, with sieving coefficients of approximately 1. Leukocyte, erythrocyte, and thrombocyte counts remained unchanged during each plasma perfusion. A progressive rise in leukocyte counts occurred following successive perfusions, but this was true also of animals subjected to control procedures.

Animals↗
PubMed1978

Studies on sorbents for use in a hepatic support system.

A range of adsorbent and ion exchange materials has been tested for the sorption of fatty acids (hexanoic, octanoic and oleic), bilirubin and bromosulphthalein from human plasma. The importance of sorbent particle size for the kinetics of removal of strongly protein bound substances is shown. A system allowing the use of small particle size bioincompatible sorbents for detoxification is presented.

Adsorption↗