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Biomedical subjects

B V Jegasothy

Publications and source records attributed to B V Jegasothy.

At least 19 recordsLinked to original sources
PubMed2000

Blockade of T lymphocyte costimulation with cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (CTLA4Ig) reverses the cellular pathology of psoriatic plaques, including the activation of keratinocytes, dendritic cells, and endothelial cells.

Efficient T cell activation is dependent on the intimate contact between antigen-presenting cells (APCs) and T cells. The engagement of the B7 family of molecules on APCs with CD28 and CD152 (cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) receptors on T cells delivers costimulatory signal(s) important in T cell activation. We investigated the dependence of pathologic cellular activation in psoriatic plaques on B7-mediated T cell costimulation. Patients with psoriasis vulgaris received four intravenous infusions of the soluble chimeric protein CTLA4Ig (BMS-188667) in a 26-wk, phase I, open label dose escalation study. Clinical improvement was associated with reduced cellular activation of lesional T cells, keratinocytes, dendritic cells (DCs), and vascular endothelium. Expression of CD40, CD54, and major histocompatibility complex (MHC) class II HLA-DR antigens by lesional keratinocytes was markedly reduced in serial biopsy specimens. Concurrent reductions in B7-1 (CD80), B7-2 (CD86), CD40, MHC class II, CD83, DC-lysosomal-associated membrane glycoprotein (DC-LAMP), and CD11c expression were detected on lesional DCs, which also decreased in number within lesional biopsies. Skin explant experiments suggested that these alterations in activated or mature DCs were not the result of direct toxicity of CTLA4Ig for DCs. Decreased lesional vascular ectasia and tortuosity were also observed and were accompanied by reduced presence of E-selectin, P-selectin, and CD54 on vascular endothelium. This study highlights the critical and proximal role of T cell activation through the B7-CD28/CD152 costimulatory pathway in maintaining the pathology of psoriasis, including the newly recognized accumulation of mature DCs in the epidermis.

Abatacept↗
PubMed1999

CTLA4Ig-mediated blockade of T-cell costimulation in patients with psoriasis vulgaris.

Engagement of the B7 family of molecules on antigen-presenting cells with their T cell-associated ligands, CD28 and CD152 (cytotoxic T lymphocyte-associated antigen-4 [CTLA-4]), provides a pivotal costimulatory signal in T-cell activation. We investigated the role of the CD28/CD152 pathway in psoriasis in a 26-week, phase I, open-label dose-escalation study. The importance of this pathway in the generation of humoral immune responses to T cell-dependent neoantigens, bacteriophage phiX174 and keyhole limpet hemocyanin, was also evaluated. Forty-three patients with stable psoriasis vulgaris received 4 infusions of the soluble chimeric protein CTLA4Ig (BMS-188667). Forty-six percent of all study patients achieved a 50% or greater sustained improvement in clinical disease activity, with progressively greater effects observed in the highest-dosing cohorts. Improvement in these patients was associated with quantitative reduction in epidermal hyperplasia, which correlated with quantitative reduction in skin-infiltrating T cells. No markedly increased rate of intralesional T-cell apoptosis was identified, suggesting that the decreased number of lesional T cells was probably likely attributable to an inhibition of T-cell proliferation, T-cell recruitment, and/or apoptosis of antigen-specific T cells at extralesional sites. Altered antibody responses to T cell-dependent neoantigens were observed, but immunologic tolerance to these antigens was not demonstrated. This study illustrates the importance of the CD28/CD152 pathway in the pathogenesis of psoriasis and suggests a potential therapeutic use for this novel immunomodulatory approach in an array of T cell-mediated diseases.

Abatacept↗
PubMed1997

Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efficacy, and duration of therapeutic effect.

BACKGROUND: Topical therapy providing initial improvement and maintenance of effect after treatment of the large majority of patients with limited, mild to moderate psoriasis is not presently available. Previous topical retinoids have generally been either ineffective or too irritating for therapy of psoriasis. OBJECTIVE: Our purpose was to evaluate a new topical retinoid, tazarotene, in the treatment of stable plaque psoriasis during treatment and posttreatment periods. METHODS: In a double-blind manner, 324 patients were randomly selected to receive tazarotene 0.1% or 0.05% gel, or vehicle control, once daily for 12 weeks and were then followed up for 12 weeks after treatment. RESULTS: Of the total, 318 patients could be evaluated. Tazarotene gels were superior (p < 0.05) to vehicle, often as early as treatment week 1, in all efficacy measures: plaque elevation, scaling, and erythema; treatment response; percentage treatment success (patients with > or = 50% improvement); and time to initial success. Efficacy was equivalent on target lesion sites (trunk or limbs and knees or elbows) and overall. A sustained therapeutic effect was observed for 12 weeks after treatment. Tazarotene gel was cosmetically acceptable. There was low systemic absorption, limiting toxicity to local irritation. CONCLUSION: Once-daily tazarotene was effective and safe as a topical monotherapy for plaque psoriasis, providing rapid reduction of signs and symptoms.

Administration, Topical↗
PubMed1996

Olmsted syndrome. Case report and identification of a keratin abnormality.

BACKGROUND: Olmsted syndrome is a rare disorder characterized by a mutilating palmoplantar keratoderma and periorificial keratotic plaques. It begins in early childhood and is complicated by the development of painful flexion contractures, constrictions, and autoamputations of the digits. Only 11 cases of Olmsted syndrome have been reported to date. However, no biochemical abnormalities in the skin were reported in any of these cases. OBSERVATIONS: We report the 12th case of Olmsted syndrome. In addition, we describe a keratin abnormality found in a skin specimen obtained from our patient. The specimen showed a suprabasilar staining pattern with AE1, an antibody that shows only basilar staining in normal skin. CONCLUSION: We report the 12th case of Olmsted syndrome, review the literature, and describe a keratin abnormality that was found in our patient's skin specimen.

Child↗
PubMed1992

Inocoterone and acne. The effect of a topical antiandrogen: results of a multicenter clinical trial.

BACKGROUND AND METHODS: Because acne is androgen dependent, antiandrogen therapy might improve the condition. Inocoterone acetate (RU 882) is a nonsteroidal antiandrogen that binds to the androgen receptor and has antiandrogenic activity in animal models. To test its topical effect on acne, 126 male subjects with facial acne completed a 16-week, multi-center, double-blind study in which the twice-daily application of a 10% solution of inocoterone was compared with vehicle solution. Baseline and monthly examinations included acne lesion counts and general and endocrine laboratory tests. RESULTS: Inflammatory papules and pustules showed greater reduction in the inocoterone-treated subjects than in the subjects treated with vehicle. This difference achieved statistical significance by week 12 (24% reduction vs 10%) and week 16 (26% reduction vs 13%) and, with longitudinal analysis, throughout the course of the study. Global assessments and changes in comedo counts and sebum excretion rates were not significantly different between the groups. No serious adverse reactions were encountered. CONCLUSIONS: In this double-blind study of 126 male subjects with acne, a topical solution of the antiandrogen inocoterone, compared with vehicle, produced a modest but statistically significant reduction in the number of inflammatory acne lesions.

Acne Vulgaris↗
PubMed1992

Cutaneous T-cell lymphoma: utility of antibodies to the variable regions of the human T-cell antigen receptor.

BACKGROUND: The clonotypic 90 kd Ti heterodimer of the human T-cell antigen receptor is composed of two distinct chains (alpha beta or rarely tau delta) that result from the recombination of variable (V), constant, joining, and, in the case of beta chains, additional diversity regions. OBJECTIVE: The variable region expression of human cutaneous T-cell lymphoma (CTCL) was studied. METHODS: Biopsy specimens from 13 patients with CTCL (7 plaque, 3 tumor stage, 3 Sézary syndrome) were examined immunohistochemically by a panel of seven commercially available monoclonal V-region antibodies. RESULTS: Two patients had significant anti-V-region staining. One patient with Sézary syndrome had two lesions, subjected to biopsy 4 months apart, that reacted with beta V5(a), a specificity previously documented by flow cytometry of leukemic cells. A patient with plaque-stage CTCL, negative for T-cell gene rearrangement by Southern blot, demonstrated reactivity with beta V5(c) largely limited to epidermotropic lymphocytes. CONCLUSION: Panels of V-region antibodies should be useful reagents for diagnosis and follow-up of CTCL.

Adult↗
PubMed1992

Mid-dermal elastolysis with inflammation.

A 71-year-old white woman had finely wrinkled, erythematous patches of skin that met the clinical and histologic criteria for mid-dermal elastolysis. In addition to the loss of mid-dermal elastin described in previous cases, histopathologic examination revealed a superficial and deep perivascular inflammatory infiltrate of lymphocytes and plasma cells and interstitial collections of multinucleated giant cells containing phagocytized elastin. These results support a previously postulated inflammatory pathogenesis for mid-dermal elastolysis.

Aged↗
PubMed1992

Tacrolimus (FK 506)--a new therapeutic agent for severe recalcitrant psoriasis.

BACKGROUND: Psoriasis, a disease of unknown etiology, is in some patients severe, extremely debilitating, and unresponsive to conventional therapies, including UV-B, oral psoralen with long-wave UV radiation in the A range (PUVA), oral retinoids, and methotrexate. We report the results from our study of seven patients with refractory psoriasis who were treated with the new immunosuppressive drug, tacrolimus (FK 506). OBSERVATIONS: All seven patients showed a dramatic resolution of psoriasis that remained in remission as long as they received full-dose therapy. Serial skin biopsy specimens demonstrated a rapid disappearance of the inflammatory infiltrate and a slower resolution of the epidermal changes. Tacrolimus was well tolerated during the 5.5 to 14 months of observation. Side effects, including nephrotoxicity and hypertension, were controlled by appropriate modification of drug dosage. CONCLUSIONS: Tacrolimus, a new immunosuppressive agent, is effective in treating patients with severe recalcitrant psoriasis. The mechanism of its action in psoriasis is unknown, but it may be related to its ability to modulate immune function. Further studies will establish criteria for patient selection and drug dosage, to maximize efficacy of this agent in psoriasis, while minimizing its toxicity.

Administration, Oral↗
PubMed1992

Treatment of systemic sclerosis with extracorporeal photochemotherapy. Results of a multicenter trial.

BACKGROUND AND DESIGN: In a pilot study of extracorporeal photochemotherapy, two patients with systemic sclerosis who received this therapy experienced significant clinical improvement. These results prompted the development of a multicenter trial to examine the benefit of extracorporeal photochemotherapy in the treatment of systemic sclerosis. Seventy-nine patients with systemic sclerosis of recent onset (mean symptom duration, 1.83 years) and progressive skin involvement during the preceding 6 months entered a randomized, parallel-group, single-blinded clinical trial comparing extracorporeal photochemotherapy treatments given on 2 consecutive days monthly with treatment with D-penicillamine at a maximum dose of 750 mg/d. Blinded clinical examiners evaluated skin severity score (thickness), percent surface area involvement, oral aperture, and hand closure. Serial skin biopsies and pulmonary function studies were also performed. RESULTS: Following 6 months of treatment, significant improvement in skin severity score occurred in 21 (68%) of 31 patients receiving photochemotherapy and in eight (32%) of 25 receiving D-penicillamine treatment, while significant worsening occurred in three (10%) of 31 receiving photochemotherapy and in eight (32%) of 25 receiving penicillamine treatment, thus indicating a significantly higher response rate for individuals who received photochemotherapy (P = .02). At both the 6- and 10-month evaluation points, the mean skin severity score, mean percent skin involvement, and mean oral aperture measurements were significantly improved from baseline among those who received photochemotherapy. Mean right and left hand closure measurements had also improved significantly by 10 months of therapy. By comparison, among the patients treated with D-penicillamine, none of the parameters of cutaneous disease had improved significantly after 6 months of therapy, although for those individuals in whom treatment was continued, the mean skin severity score and mean percent skin involvement had improved by 10 months. Skin biopsy studies revealed a correlation between clinical improvement and decreased thickness of the dermal layer. Adverse effects of extracorporeal photochemotherapy were minimal and did not require discontinuation of treatment in any of the patients receiving this therapy; six patients permanently discontinued the use of D-penicillamine treatment due to adverse effects. CONCLUSIONS: For patients with systemic sclerosis of recent onset, extracorporeal photochemotherapy is a well-tolerated treatment that may partially reverse the process that results in cutaneous sclerosis.

Adult↗
PubMed1990

Possible role of Epstein-Barr virus infection in cutaneous T-cell lymphomas.

Although cutaneous T-cell lymphoma (CTCL) is a neoplastic helper T-cell disorder of unknown etiology, prolonged antigenic stimulation has been postulated to contribute to the development of this disease. Because Epstein-Barr Virus (EBV) infection has been associated with several different lymphomas, the sera of 21 CTCL patients were examined for antibodies to EBV antigens. By using complement immunofluorescence (CIF) techniques, 13 of 21 CTCL patients had detectable antibodies to Epstein-Barr Nuclear Antigens (EBNA), whereas only five of 20 control psoriatic patients were CIF positive. When immunoblot analysis was employed, all 21 of the CTCL patients had antibodies to the EBV antigens, EBNA, whereas only 12 of the control patients had detectable antibodies to these antigens. In addition, three of 21 CTCL patients had antibodies to the EBV-associated antigen, rheumatoid arthritis nuclear antigen (RANA), as determined by double immunodiffusion, whereas none of the control sera contained anti-RANA antibodies. These results indicate that antibodies against EBV antigens are found with a higher frequency and concentration in patients with CTCL when compared to controls and suggest that EBV products might serve as a possible stimulus for the development of this malignant disease.

Adult↗
PubMed1988

Wound healing of skin incisions produced by ultrasonically vibrating knife, scalpel, electrosurgery, and carbon dioxide laser.

An ultrasonically vibrating knife has been developed for producing surgical incisions with reduced hemorrhage. Tissue injury and wound healing of porcine cutaneous incisions produced by this instrument, conventional scalpel, electrosurgery, and CO2 laser were compared regarding clinical, histopathologic, and tensile strength differences. Scalpel incisions had the least tissue injury and fastest healing, but the ultrasonically vibrating knife produced less tissue injury and faster healing than electrosurgery or CO2 laser.

Animals↗