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Biomedical subjects

M D Lockshin

Publications and source records attributed to M D Lockshin.

At least 19 recordsLinked to original sources

Serologic studies of monozygotic twins with systemic lupus erythematosus.

OBJECTIVE: The goal of these studies was to assess the role of genetic factors and disease expression in the pattern and titer of autoantibodies to several RNA protein antigens in patients with systemic lupus erythematosus (SLE) by studying identical twins concordant and discordant for disease expression. METHODS: Autoantibodies to Ro/SS-A, La/SS-B, U1 RNP, and Sm were measured by quantitative enzyme-linked immunosorbent assay using affinity-purified antigens. RESULTS: Detailed serologic studies were performed in 7 pairs of identical twins, 3 of whom were concordant and 4 of whom were discordant for disease expression. Autoantibody titers were higher in affected than in unaffected twins from discordant pairs, but in 3 of 4 pairs, the profile of anti-RNA proteins (e.g., Ro/SS-A, La/SS-B, U1 RNP, and Sm) was virtually identical. In the SLE pairs concordant for disease expression, the autoantibody titers were very similar, as were the anti-RNA protein profiles. When the identical twins were matched by sex, race, and age to pairs of nontwin SLE patients, the 6 white twins shared an average of 2.5 (+/- 1.05 SD) anti-RNA proteins, while the control SLE pairs shared only 0.33 (+/- 0.82), P less than 0.01 (t = 4.0, P less than 0.01). In addition, in the white SLE twins, all had elevated levels of anti-U1 RNP while in white nontwin SLE patients, the frequency of anti-U1 RNP was 30%. CONCLUSION: These data point to a dominant role for genetic factors in the determination of specific autoantibody profiles.

Antigen-Antibody Reactions

Phospholipid binding of antiphospholipid antibodies and placental anticoagulant protein.

We evaluated the interaction of antiphospholipid antibodies (aPL) with placental anticoagulant protein I (PAP I), a calcium-dependent phospholipid binding protein which may act as a natural anticoagulant. Clotting assays showed additive prolongation of clotting times with aPL and PAP I. ELISA and vesicle phospholipid binding studies showed PAP I inhibition of aPL binding to phospholipid but no inhibition of PAP I-phospholipid binding by aPL. aPL and PAP I interact additively in anticoagulant activity in in vitro clotting systems and compete for phospholipid in ELISA system. These data support the hypotheses that aPL and PAP I may recognize similar phospholipid epitopes and that in vivo interaction may occur.

Annexins

Antiphospholipid antibodies differ in aPL cofactor requirement.

Although autoimmune antiphospholipid antibodies (aPL) may require a serum cofactor, beta 2-glycoprotein I (beta 2GPI), for maximal binding in aPL ELISA, it is not known whether cofactor is absolutely required or is merely an enhancing factor for binding, nor is it clear whether aPL bind to cofactor itself, a cofactor-lipid complex, or a phospholipid modified in some way by cofactor. We therefore isolated and purified beta 2GPI and evaluated its relationship to both IgG and IgM aPL binding. aPL derived from different sera appear to have differing requirements for cofactor; the proportion of total binding attributable to cofactor varies from 46% to 95%. aPL do not bind to beta 2GPI in the absence of phospholipid. Enhanced binding to phospholipid is seen if beta 2GPI is provided either before or with the test antibody. Autoimmune aPL bind phospholipid better with human rather than bovine cofactor. The requirement for cofactor is greater for low-avidity aPL as measured in an IgG-human cofactor system. Cofactor requirement alone does not predict the presence or absence of associated clinical complications.

Antibodies, Antiphospholipid

Fatty acid chain is a critical epitope for antiphospholipid antibody.

To explore the role of phospholipid fatty acids in binding of antiphospholipid antibody (aPL) in ELISA, we tested aPL binding to phospholipids containing fatty acids of varying chain length and degree of saturation using direct ELISA and inhibition methods. Polyclonal IgG and IgM human aPL's bind to C18:1 phosphatidylglycerol (PG) better than to C18:0 PG or C18:2 PG. Binding is greater to C18 than to C14:0 or C16:0 PGs; aPL's do not bind to C12:0 PG. aPL binding is not inhibited by C18:1 diacylglycerol, glycerol-3-phosphate, myoinositol, or myoinositol phosphate. The fatty acid chains are critical determinants for antigen recognition and, by projection, biological activity of aPL.

Autoantibodies

Apparent acute renal failure associated with therapeutic aspirin and ibuprofen administration.

Aspirin and ibuprofen may cause a decrease in renal function which, although statistically significant, is usually small. We report a patient with active systemic lupus erythematosus and apparent acute renal failure associated with the administration of these drugs. Renal biopsy revealed no light microscopic evidence of drug nephrotoxicity although patchy nonspecific ultrastructural changes in the tubular epithelium were seen. The renal failure reversed rapidly when the drugs were withdrawn.

Acute Kidney Injury

Rheumatoid meningitis: a localized immune process.

Rheumatoid pachymeningitis is a rare complication of rheumatoid arthritis. This disease was confined to the dura and pia-arachnoid of the lumbar cord in our patient. Her neurologic deficits responded to surgical decompression and corticosteroid therapy. Radiologic evidence and the differences in cell count, protein, and glucose content between lumbar and cisternal cerebrospinal fluid indicate that rheumatoid pachymeningitis can be localized to a discrete region of the central nervous system. Elevated immunoglobulins, IgM and IgG rheumatoid factors, low molecular weight IgM, and immune complexes were found in the cerebrospinal fluid and implicate an immune reaction in the pathogenesis of this disease, which is probably similar to inflammatory processes involving other organs in rheumatoid arthritis.

Aged

Vasculitis.

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Humans

Education in rheumatology for the primary care physician.

An international workshop considered rheumatological education of the primary care physician. All medical students need exposure to rheumatology. Emphasis should be on the musculoskeletal component and on the better defined diseases. During the postdoctoral years, principles of total health care need to be taught by well trained rheumatologists in tertiary care rheumatic disease units with comprehensive ambulatory care facilities. Continuing education of the generalist needs to be relevant to his professional competence. He needs to acquire and update the knowledge to manage common rheumatic diseases and to learn when to ask for help. General educational objectives are applicable to the field of rheumatology: cognitive skills bring knowledge of the scientific basis and clinical facts; motor skills--the ability to examine competently patients with rheumatic diseases; affective skills--the understanding of and capacity to deal with chronic illness.

Curriculum

Sensitivity to metal as a possible cause of sterile loosening after cobalt-chromium total hip-replacement arthroplasty.

We explored the possibility that wear products of cobalt-chromium alloy might lead to sensitivity to metal wear products and in turn to loosening of a component of the prosthesis after total joint replacement. Twenty patients with sterile, loose McKee-Farrar hip replacements had patch tests for sensitivity to cobalt, nickel, and chromium. All tests were negative in all patients. The histological findings from surrounding tissues in seventeen patients who had reoperation showed no signs of delayed hypersensitivity. In five patients, lymphokine assays for migration inhibition factor and blastogenic factor were done. Only one assay was positive. Our findings do not support the suggestion that hypersensitivity to metal is a cause of component loosening after McKee-Farrar total hip replacement.

Adult