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Biomedical subjects

A F Kavanaugh

Publications and source records attributed to A F Kavanaugh.

27 records · Page 2Linked to original sources
PubMed1994

Inhibition of the transendothelial migration of human T lymphocytes by prostaglandin E2.

To determine whether part of the anti-inflammatory effects of prostaglandin E2 (PGE2) was related to inhibition of T cell interactions with endothelial cells (EC), the effects of PGE2 and other cAMP-elevating agents on the transendothelial migration of human T cells was examined. Although PGE2 did not effect T cell binding to EC, concentration-dependent inhibition of the transendothelial migration of T cells through unstimulated or IL-1-activated EC was observed. PGE2 inhibited the function of both T cells and EC, with maximal inhibition observed when both T cells and EC were treated with PGE2. However, the inhibitory action of PGE2 could not be ascribed to an effect on the adhesion receptor pair, CD11a/CD18-CD54. The inhibitory effect of PGE2 seemed to relate to its capacity to elevate cellular cAMP levels, because 3-isobutyl-1-methylxanthine enhanced PGE2 activity and dibutyryl cAMP and forskolin also inhibited transendothelial migration. The inhibitory effect of PGE2 and the other cAMP-elevating agents on the function of T cells related in part to suppression of their intrinsic locomotory behavior as random migration in the absence of EC was blocked. In EC, PGE2 and the other cAMP-elevating agents increased the barrier function of EC as evidenced by a decrease in the diffusion of [3H]mannitol through the endothelium. These results indicate that part of the anti-inflammatory action of PGE2 relates to its capacity to suppress the transendothelial migration of T cells by cAMP-mediated alterations in the function of both T cells and EC.

Bucladesine↗
PubMed1994

Treatment of refractory rheumatoid arthritis with a monoclonal antibody to intercellular adhesion molecule 1.

OBJECTIVE: To assess the safety and efficacy of a monoclonal antibody (MAb) to intercellular adhesion molecule 1 (ICAM-1; CD54) in rheumatoid arthritis (RA). METHODS: A phase I/II, open-label, dose-escalation study of 32 patients. RESULTS: During treatment, a peripheral CD3+/CD4+ lymphocytosis was noted, and several patients demonstrated transient cutaneous anergy, which suggests that therapy modified T cell recirculation. Thirteen of the 23 patients who received 5 days of treatment demonstrated clinical improvement through day 29, and 9 of 23 through day 60. Adverse effects were minor and transient. CONCLUSION: Anti-ICAM-1 MAb therapy was well tolerated, resulted in a transient alteration in T lymphocyte recirculation, and effected clinical improvement in some RA patients.

Adult↗
PubMed1991

Role of CD11/CD18 in adhesion and transendothelial migration of T cells. Analysis utilizing CD18-deficient T cell clones.

The role of leukocyte function-associated Ag-1 (LFA-1) (CD11a/CD18) in T cell-endothelial cell (EC) interactions was assessed by utilizing CD11a/CD18-deficient T cell clones generated from a patient with leukocyte adhesion deficiency (LAD). The ability of these clones to bind to and migrate through monolayers of EC in vitro was compared with that of clones generated in a similar manner from normal controls. The LAD clones bound to EC to a similar extent as the controls. The contribution of other cell surface adhesion molecules was assessed with mAb blocking experiments. It was found that part of the EC binding by these CD11a/CD18-deficient clones was mediated by an interaction of very late Ag-4 (VLA-4) with vascular cell adhesion molecule-1 (VCAM-1) on the EC. In contrast to their normal ability to bind to EC, the capacity of the LAD clones to migrate through EC monolayers was significantly less than that of the control clones. This impairment in migration was not related to decreased intrinsic motility. Moreover, neither phorbol ester stimulation of the LAD clones nor IL-1 stimulation of the EC increased the capacity of the clones to migrate through EC monolayers, although binding to EC was augmented by both treatments. Only a minimal percentage of the migration of either control or LAD clones was inhibited by mAb to VLA-4 or VCAM-1. These data demonstrate that LFA-1 plays a central role in the transendothelial migration of T cells. In the absence of LFA-1, T cells retain the ability to bind to EC because of the activity of other receptor/ligand pairs, including VLA-4/VCAM-1. Finally, it is likely that, during both binding and transendothelial migration of T cells, additional cell surface molecules play a role.

Antibodies, Monoclonal↗
PubMed1990

Variable expression of IgG2 deficiency.

Sustained and significant reversal of antibody deficiencies is uncommon, although it has been noted in some cases during childhood and after viral infections. We report a case of reversal of IgG2 deficiency after splenectomy. A 46-year-old man who suffered recurrent sinusitis despite antibiotic therapy was noted to have IgG2 deficiency and cutaneous anergy. Replacement therapy with intravenous immunoglobulin ameliorated his symptoms. After 13 months of therapy, the patient had a diagnostic laparotomy and splenectomy because of portal hypertension, hypersplenism, and consideration of underlying malignancy. No evidence of malignancy or infection, including human immunodeficiency virus, active cytomegalovirus, or Epstein-Barr virus infection, was found. After splenectomy, the patient's serum IgG2 level normalized without replacement therapy. Subsequently, it fell, then normalized once more, and remains normal. The patient also demonstrated positive reactions to delayed hypersensitivity testing after splenectomy, but, subsequently, became anergic and remains anergic at the present time. Since the splenectomy he has remained clinically well without antibiotics or immunoglobulin replacement. In vitro analysis of his lymphocyte function demonstrated impaired T cell proliferation as well as an intrinsic B cell differentiation defect. This case demonstrates the potentially dynamic nature of IgG subclass deficiencies.

Combined Modality Therapy↗