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Gabriel S. Panayi

Bio: Gabriel S. Panayi is an academic researcher from King's College London. The author has contributed to research in topics: Rheumatoid arthritis & Arthritis. The author has an hindex of 61, co-authored 279 publications receiving 15449 citations. Previous affiliations of Gabriel S. Panayi include University of Cambridge & Guy's Hospital.


Papers
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Journal ArticleDOI
TL;DR: Current slow-acting antirheumatic drugs have limited efficacy and many side effects and do not improve the long-term prognosis of rheumatoid arthritis.
Abstract: Rheumatoid arthritis is a common chronic inflammatory and destructive arthropathy that cannot be cured and that has substantial personal, social, and economic costs. The long-term prognosis is poor: 80 percent of affected patients are disabled after 20 years,1 and life expectancy is reduced by an average of 3 to 18 years.2 The medical cost of rheumatoid arthritis averages $5,919 per case per year in the United States3 and approximately £2,600 per case per year in the United Kingdom.4 Current slow-acting antirheumatic drugs have limited efficacy and many side effects. Moreover, they do not improve the long-term prognosis of rheumatoid arthritis. . . .

2,180 citations

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TL;DR: Highly specific antisera to human Ia-like (HLA-DR) antigens and monoclonal antibodies to various T-lymphocyte subsets were used to analyse both the normal and the rheumatoid synovium and to compare it with normal lymph nodes.

633 citations

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TL;DR: This is the first randomized controlled trial showing that inhibition of IL-6 significantly improved the signs and symptoms of RA and normalized the acute-phase reactants.
Abstract: Objective To investigate the safety and efficacy of MRA, a recombinant human anti–interleukin-6 (anti–IL-6) receptor monoclonal antibody of the IgG1 subclass that inhibits the function of IL-6, in patients with established rheumatoid arthritis (RA). Methods A randomized, double-blind, placebo-controlled, dose-escalation trial was conducted in 45 patients with active RA, as defined by the American College of Rheumatology (ACR) revised criteria. Patients were sequentially allocated to receive a single intravenous dose of either 0.1, 1, 5, or 10 mg/kg of MRA or placebo. The primary efficacy end point was meeting the ACR 20% response criteria at week 2 after treatment. Results Demographic features were similar between treatment groups. At week 2, a significant treatment difference was observed between the 5 mg/kg of MRA and placebo, with 5 patients (55.6%) in the MRA cohort and none in the placebo cohort achieving ACR 20% improvement. There was no statistically significant difference in the ACR 20% response between the other 3 MRA cohorts and placebo at week 2. The mean disease activity score at week 2 in those who received 5 mg/kg and 10 mg/kg of MRA was 4.8 and 4.7 (P < 0.001 and P < 0.001 by analysis of variance), respectively. These mean scores were statistically significantly lower than those in the 0.1- and 1-mg/kg MRA and the placebo cohorts (6.4, 6.2, and 7.0, respectively). The erythrocyte sedimentation rate and C-reactive protein values fell significantly in the 5- and 10-mg/kg MRA cohorts and normalized 2 weeks after treatment. Seventeen patients (5, 4, 6, 2, and 0 patients in the placebo, 0.1-, 1-, 5-, and 10-mg/kg MRA cohorts, respectively) required corticosteroid or disease-modifying antirheumatic drug treatment because of active disease before study end. They were regarded as nonresponders from the time they received these treatments. Diarrhea was the most common adverse event, occurring in 8% of patients. Seven patients (15.6%) reported a severe adverse event (3, 1, 2, and 2 patients in the placebo, 0.1-, 1-, and 10-mg/kg MRA cohorts). There were no serious adverse events that were thought to be related to the study drug. Conclusion This is the first randomized controlled trial showing that inhibition of IL-6 significantly improved the signs and symptoms of RA and normalized the acute-phase reactants. Further research with multiple dosing is necessary to define the most appropriate therapeutic regimen of MRA in RA.

557 citations

Journal ArticleDOI
TL;DR: This short review has produced convincing, although indirect, evidence that in the case of rheumatoid synovitis, the T cell is the conductor of an orchestra playing a tune written by an antigen-presenting cell.
Abstract: We hope that this short review has produced convincing, although indirect, evidence that in the case of rheumatoid synovitis, the T cell is the conductor of an orchestra playing a tune written by an antigen-presenting cell. The tune develops and becomes modified with time, so that it is difficult to discern with clarity much of the original melody. We believe that it may be possible to substitute a new score that will bring this symphony to a harmonious end. We also strongly believe that this is preferable to augmenting the string section or suppressing the percussion section of the orchestra in the vain hope that in the end harmony can be achieved. The final musical analogy must be the hope that the first page of the score can be found, so that we may discover the main theme, the leitmotif, of the rheumatoid-specific antigenic peptide.

482 citations

Journal Article
TL;DR: MAb 1.4C3 adds to the understanding of the kinetics of the EC response to different cytokines and will be useful in studying the regulation of EC activation and may have an important role in leukocyte-EC interactions.
Abstract: The alteration in the surface of endothelial cells (EC) in response to cytokines is likely to be of great importance to the regulation of cell migration and thereby to the evolution of inflammatory processes. We have generated three mAb against cytokine inducible Ag on EC. Whereas mAb 1.2B6 and 6.5B5 were found to react with ELAM-1 and ICAM-1, respectively, mAb 1.4C3 reacted with a novel molecule that showed a different pattern of expression from ELAM-1 or ICAM-1 after stimulation of EC by TNF, IL-1, or LPS. Like ELAM-1, the 1.4C3 Ag was minimally expressed on resting EC, whereas ICAM-1 was moderately expressed. After stimulation with IL-1, TNF, or LPS, ELAM-1 expression was maximal after 4 to 6 h, 1.4C3 Ag after 6 to 10 h, and ICAM-1 after 10 to 24 h. The duration of 1.4C3 expression was intermediate between ELAM-1 and ICAM-1, and was more prolonged in response to TNF than IL-1 or LPS. Whereas the expression of the three Ag showed a similar dose response to varying concentrations of IL-1 or LPS, EC required a 10-fold higher concentration of TNF for half maximal expression of ELAM-1 than for half maximal expression of 1.4C3 Ag or ICAM-1 (5 ng/ml compared to 0.5 ng/ml). Of the three Ag, only ICAM-1 was enhanced by IFN-gamma. SDS-PAGE under reducing conditions showed the 1.4C3 Ag to migrate as a single band with a relative molecular mass of approximately 95 kDa. mAb 1.4C3 adds to our understanding of the kinetics of the EC response to different cytokines and will be useful in studying the regulation of EC activation. Furthermore, the 1.4C3 molecule may have an important role in leukocyte-EC interactions.

365 citations


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Journal ArticleDOI
TL;DR: This review considers recent findings regarding GC action and generates criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stress-response or, as an additional category, is preparative for a subsequent stressor.
Abstract: The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

6,707 citations

Journal ArticleDOI
TL;DR: The increased understanding of the immune mechanisms of rheumatoid arthritis has led to the development of a considerable number of new therapeutic agents that alter the natural history of the disease and reduce mortality.
Abstract: The increased understanding of the immune mechanisms of rheumatoid arthritis has led to the development of a considerable number of new therapeutic agents that alter the natural history of the disease and reduce mortality.

3,975 citations

Journal ArticleDOI
TL;DR: Infliximab is a humanized antibody against tumor necrosis factor α (TNF-α) that is used in the treatment of Crohn's disease and rheumatoid arthritis but there is no direct evidence of a protective role of TNF- α in patients with tuberculosis.
Abstract: Background Infliximab is a humanized antibody against tumor necrosis factor α (TNF-α) that is used in the treatment of Crohn's disease and rheumatoid arthritis. Approximately 147,000 patients throughout the world have received infliximab. Excess TNF-α in association with tuberculosis may cause weight loss and night sweats, yet in animal models it has a protective role in the host response to tuberculosis. There is no direct evidence of a protective role of TNF-α in patients with tuberculosis. Methods We analyzed all reports of tuberculosis after infliximab therapy that had been received as of May 29, 2001, through the MedWatch spontaneous reporting system of the Food and Drug Administration. Results There were 70 reported cases of tuberculosis after treatment with infliximab for a median of 12 weeks. In 48 patients, tuberculosis developed after three or fewer infusions. Forty of the patients had extrapulmonary disease (17 had disseminated disease, 11 lymph-node disease, 4 peritoneal disease, 2 pleural dis...

3,405 citations

Journal ArticleDOI
TL;DR: A single acquired mutation of JAK2 was noted in more than half of patients with a myeloproliferative disorder and its presence in all erythropoietin-independent erythroid colonies demonstrates a link with growth factor hypersensitivity, a key biological feature of these disorders.

3,326 citations

Journal ArticleDOI
TL;DR: CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above.

2,542 citations