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Biomedical subjects

C C Chan

Publications and source records attributed to C C Chan.

At least 451 records · Page 25Linked to original sources

Expression of class II antigen in endotoxin induced uveitis.

Uveitis can be induced by systemic or intravitreal administration of endotoxin (lipopolysaccharide, LPS). In this study we correlated the expression of class II antigens (la in rat) of the Major Histocompatibility Complex (MHC), with this experimental model of uveitis. Ia antigen was detected by immunohistochemistry using the Avidin-Biotin-Peroxidase Complex (ABC) method and the monoclonal antibody OX6. Ia antigen was not expressed in normal eyes. However, Ia was expressed in the anterior uvea epithelial cells in all eyes with LPS induced uveitis. This study demonstrates that the ocular Ia expression is a localized process in the anterior uvea in response to systemic or intravitreal LPS. This response appears to be distinct from the action of LPS on macrophage Ia expression, where LPS has been shown to inhibit the induction of Ia antigen in macrophages by gamma interferon.

Animals↗

A partially rigid butyrophenone analog with extended conformation.

The synthesis and in vitro dopamine D2 receptor binding of a conformationally restricted analog of 4-piperidinobutyrophenone is described. 2-(2-Piperidinoethyl)-1-tetralone displaces [3H]spiperone from the rat striatal dopamine receptor with an IC50 of 1.2 X 10(-4)mol/l.

Animals↗

Potentiation of the inhibitory effect of a thromboxane A2 antagonist (L-640,035) on arterial thrombosis formation in rabbit by the angiotensin converting enzyme inhibitor enalapril.

The angiotensin converting enzyme inhibitor enalapril (0.5 mg/kg i.v.) potentiated significantly the inhibitory effect of the thromboxane A2 antagonist L-640,035 (1 mg/kg i.v.) on electrically induced platelet accumulation in the rabbit in vivo. Enalapril had no effect upon platelet accumulation when given alone. The hypotensive effects of enalapril did not account for the potentiation because a combination of hexamethonium (5 mg/kg i.v.) and hydralazine (1 mg/kg i.v.), which decreased blood pressure similarly to enalapril, did not augment the effect of L-640,035. Determination by radioimmunoassay of plasma levels of immunoreactive 6-keto-PGF1 alpha, suggested that increases in PGI2 levels after combined administration of enalapril and L-640,035 could explain the observed potentiation.

6-Ketoprostaglandin F1 alpha↗

Granulomas in sympathetic ophthalmia and sarcoidosis. Immunohistochemical study.

Monoclonal antibodies were used to identify cells that form choroidal granulomas and Dalen-Fuchs nodules in sympathetic ophthalmia as well as the granulomas of sarcoid. Immunohistochemical analysis of frozen sections of fresh human tissues obtained after enucleation (sympathetic ophthalmia) and lung biopsy (sarcoid) was performed by the avidin-biotin-peroxidase complex method. The majority of the inflammatory cells within these lesions were identical and were composed mainly of cells originating from bone marrow-derived monocytes (reticuloendothelial system) probably representing immunologically stimulated granulomas. This study suggests possible immune phenomena that may take part in the pathogenesis of sympathetic ophthalmia and provides some insights into the possible mechanism of formation of choroidal granulomas and Dalen-Fuchs nodules in this disease.

Antibodies, Monoclonal↗

Local cyclosporine therapy for experimental autoimmune uveitis in rats.

The use of locally applied cyclosporine was investigated in the retinal S-antigen-induced experimental autoimmune uveitis (EAU) model in Lewis rats. A 2% cyclosporine solution applied topically four times a day for 14 days effectively prevented the expression of EAU. This treatment, however, produced circulating cyclosporine levels in the therapeutic range. Lower concentrations of cyclosporine applied topically did not produce therapeutic levels and were not capable of reliably preventing disease. Intraocular levels of cyclosporine, measured by radioimmunoassay, were extremely low and outside the accepted therapeutic range. Intravitreal cyclosporine therapy appeared to protect eyes from EAU, without producing significant circulating cyclosporine levels. These findings show that, in its present form, cyclosporine in oil is not an efficacious topical therapy. Therefore, a local cyclosporine preparation with enhanced penetration into the globe may be a practical approach to therapy in the future.

Administration, Topical↗

Effectiveness of cyclosporin therapy for Behçet's disease.

Behcet's disease is a clinical entity with mouth and genital ulcers, skin lesions, and both anterior and posterior uveitis as its major criteria. It has been theorized that Behcet's disease is immune complex mediated, and is characterized by multiple attacks which often lead to severe visual handicap. Behcet's disease patients with severe ocular involvement and cytotoxic and/or systemic corticosteroid agent failures were treated with cyclosporin (CsA). CsA therapy effectively abrogated the acute phase of the ocular attack and either totally prevented, or markedly reduced, the recurrences of these attacks. Generally, patients tolerated the medication well; occasionally however, renal toxicity secondary to cyclosporin therapy prevented prescription of a maximally effective therapeutic dose of the drug. CsA levels in plasma were dose-dependent for each patient, but the dosage per kg of CsA needed to obtain a specific plasma level varied greatly from patient to patient. Circulating immune complex levels were not universally elevated during the acute ocular attack. However, increases in circulating immune complex concentrations were noted after treatment with CsA was begun and the disease became clinically inactive. These data, as well as the effectiveness of CsA, an agent with predominantly anti-T cell effects, raise a question as to whether circulating immune complexes are centrally relevant to the pathogenesis of this disorder, and if T cell mediation of this disease must be contemplated.

Adult↗

Kinetics of T-lymphocyte subsets in the eyes of Lewis rats with experimental autoimmune uveitis.

The kinetic changes of T-lymphocyte subtypes in the eyes of Lewis rats which developed experimental autoimmune uveitis (EAU) were studied. Lymphoid cells were the majority of the ocular inflammatory cells in different stages of the disease. As EAU proceeds, there is an increase in the relative number of OX-8 (suppressor/cytotoxic) T cells, and the decrease of W3/25 (helper/inducer) T cells. These findings were also observed in the animals with EAU and partially treated with corticosteroids or cyclosporine. The kinetics may reflect the role of immunoregulation of the inflammatory response in autoimmune diseases.

Animals↗

T-lymphocyte subsets in experimental autoimmune uveitis.

The dynamic changes of the lymphocyte subsets in the inflamed ocular tissue in Lewis rats with experimental autoimmune uveitis (EAU) were studied by immunohistopathological evaluation at varying intervals after initiation of the disease. Monoclonal antibodies to specific markers of the rat T-helper/inducer lymphocyte (W3/25) and T-suppressor/cytotoxic lymphocyte (OX-8) were used in the avidin-biotin-peroxidase complex (ABC) method. During the early stages of the disease following the acute inflammatory reaction, the T-helper/inducer lymphocytes are found in larger numbers within the infiltrates, the relative number of the T-suppressor/cytotoxic cells is very low during the initial phases, with a ratio as low as 5 to 1. During the later stages, there is a continuous increase in the relative number of suppressor/cytotoxic cells that reaches the ratio of 1 to 1, or even 1 to 2. It is postulated that the observed changes in the ratios between T-helper/inducer and T-suppressor/cytotoxic cells during the different stages of EAU may reflect the kinetics and regulation of the inflammatory response in autoimmune diseases.

Animals↗

The failure of cyclosporin to inhibit granulomatous inflammation in acute Arthus-like panophthalmitis.

Acute Arthus-like panophthalmitis (AP) was induced in Lewis rat eyes by lens injury after immunization with whole rabbit lens extract. AP consists of an acute anterior ocular inflammation, followed by a posterior choroidal granulomatous reaction. Neither inflammatory response was inhibited by daily treatment with cyclosporin, 10 mg/kg, beginning on the day of lens injury. Cyclosporin would not be expected to interfere with the lens-induced anterior Arthus-like inflammation. The lack of inhibition of the choroidal inflammation was unexpected. The results are interpreted to indicate that the posterior granulomatous choroidal inflammation is a non-immune reaction initiated by the severe lens-induced Arthus-like reaction.

Animals↗

Laser interferometry and visual prognosis in uveitis.

Forty-six eyes in 26 patients with active, intermediate, and/or posterior uveitis with decreased visual acuity were evaluated with the laser interferometer before treatment with systemic cyclosporine. Pretreatment visual acuity (ETDRS), pretreatment laser interferometric visual acuity, and the best visual acuity obtained while under treatment were compared. Eighty-six percent of patients in whom the laser interferometer predicted an improvement of three or more lines did improve. In contrast, 52% of patients in whom no improvement was predicted improved three or more lines with therapy. There was a moderate correlation (R = 0.59) (P less than 0.001) between the number of lines of improvement predicted and the number of lines of improvement obtained. If the laser visual acuity is three or more lines better than the eye chart acuity, the prognosis for vision improvement after cyclosporine therapy is good, even in those patients with cystoid macula edema.

Humans↗

Anti-retinal auto-antibodies in Vogt-Koyanagi-Harada syndrome, Behcet's disease, and sympathetic ophthalmia.

Sera of patients diagnosed as having the active Vogt-Koyanagi-Harada (VKH) syndrome, Behcet's syndrome or sympathetic ophthalmia as well as normal controls were evaluated by ELISA and by staining of normal human retinal tissue using the avidin-biotin-peroxidase complex (ABC) technique for anti-retinal antibodies. No anti-retinal S-antigen antibodies were detected by ELISA. However, autoimmune antibodies were found against the outer segments of photoreceptors and Müller cells in patients with the VKH syndrome, with lower titers in some patients with Behcet's syndrome, and in a few patients with sympathetic ophthalmia. These results suggested anti-retinal antibodies were present and that retinal autoimmunity may play a role in pathogenesis in varieties of posterior uveitis. In addition, the indirect immunoperoxidase staining technique may facilitate the diagnosis of VKH in uncertain cases.

Autoantibodies↗

Histopathology of the subretinal fibrosis and uveitis syndrome.

A chorioretinal biopsy was obtained from a patient with subretinal fibrosis and chronic uveitis. The biopsy specimen was analyzed by conventional light and electron microscopy and by immunohistochemical methods. These demonstrated a markedly inflamed choroid with a predominance of B cells and plasma cells. Complement and IgG were deposited above Bruch's membrane. The subretinal fibrosis tissue contained islands of cells with retinal pigment epithelial characteristics; however, some of these cells demonstrated surface determinants of Müller cells. There were no circulating antiretinal antibodies detected nor could virus be cultured from the biopsy specimen. The clinical appearance of this entity is distinctive and consists of a chronic posterior uveitis with transient initial yellow-white deep retinal lesions and the later development of large white subretinal fibrotic areas. The EOG is markedly decreased. We hypothesize that the immunologic events involved in this entity include antibody production with immunoglobulin and complement deposition leading to retinal and retinal pigment epithelial destruction and a subretinal fibrous proliferation.

Adolescent↗

Standardization of vitreal inflammatory activity in intermediate and posterior uveitis.

Standardization of observations is recognized as fundamental to clinical research. The methodology for the evaluation of anterior segment inflammatory disease has become well accepted, while the ocular inflammatory standardization of the posterior segment has not been so well described or accepted. A system for the evaluation of vitreal inflammatory activity in patients with intermediate and posterior uveitis is presented. A series of photographs representing various degrees of fundus vitreal haze is depicted. The observer examines the eye with an indirect ophthalmoscope, then chooses the photograph which most closely simulates what is being seen. This technique is rapid and its reproducibility is helpful in standardizing clinical observations.

Fundus Oculi↗

Immunohistochemistry and electron microscopy of choroidal infiltrates and Dalen-Fuchs nodules in sympathetic ophthalmia.

An immunohistological study using monoclonal antibodies directed at specific membrane antigens of various inflammatory cells was carried out in order to evaluate the identity and topographic localization of the immuno-competent cells in an enucleated eye from a 6-year-old black patient with a three-month history of sympathetic ophthalmia. Correlative light and transmission electron microscopic examination of serial sections was also performed. The data demonstrated that the predominant cells within the choroidal infiltrate were T-lymphocytes (Leu 1+). T-cell subset analysis disclosed that most of these cells harbored specific antigenic determinants of the helper phenotype (Leu 3a+). A smaller proportion of the T cells demonstrated the specific determinants of the suppressor subtype (Leu 2a+). The helper/suppressor ratio varied slightly and ranged in most areas of the choroid between 3:1 and 4:1. Additionally, approximately 15% of the infiltrating lymphocytes harbored the Leu 14+ determinant specific for B cells. The latter were located in the outer choroid adjacent to the sclera. Very few natural killer (NK) cells (Leu 7+) were identified throughout the choroid. The granulomatous foci in the choroid were composed mainly of epithelioid cells and histiocytes expressing the OKM1+ and M221+ antigenic determinants on their membranes and demonstrating a high cytoplasmic nonspecific esterase activity (ANAE+). Within the Dalen-Fuchs nodules, similar to the choroidal nodules, there was a predominance of histiocytes and epithelioid cells (OKM1+, M221+, ANAE+), a few T-helper cells (Leu 1+, Leu3a+) and some OKM1-, M221- cells whose origin could not be determined. These findings were corroborated by electron microscopic observations of serial sections. Careful light and electron microscopic studies disclosed breaks in Bruch's membrane underlying some of Dalen-Fuchs nodules. In our opinion, these observations may be interpreted as the demonstration that Dalen-Fuchs' nodules and the choroidal granulomatous foci could be formed by identical cells of similar function and origin.

Child↗

Cyclosporine therapy for uveitis: long-term followup.

Long term followup in 52 uveitis patients treated with Cyclosporine (CsA) is presented here. The patients included in this study all had intermediate or posterior uveitis of noninfectious etiology; and all were considered therapeutic failures to systemic corticosteroids and/or cytotoxic agents. Patients were considered a therapeutic success if the visual acuity in either eye improved two lines or more and/or the vitreal haze improved more than two grading levels. While five patients stopped therapy before the three month interval, 41 of 52 patients or 79% were therapeutic successes at three months after the initiation of CsA as the sole systemic immunosuppressive agent for their disease. Twenty-five of a potential 35 patients (71%) remained on CsA after one year's time, with 63% (22/35) of these individuals receiving the medication considered a therapeutic success. The patients who appeared to respond particularly well to CsA therapy were those with pars planitis, intermediate uveitis of the non-pars planitis type, VKH, and Behcet's disease. In vitro S-antigen (S-Ag) testing did not appear to have a predictive value in determining which patients would be therapeutic successes (improvement in visual acuity), however the S-Ag responder group did appear to have a statistically greater improvement in vitreal haze. Renal toxicity was by far the most common adverse effect, which we have found to be reversible with our approach to therapy. However, adverse reactions required a reduction in CsA dosage in some patients, making it not feasible to maintain therapeutically effective CsA levels. In those patients, low dose prednisone was added to these patients' CsA regimens with generally good results. We did not observe opportunistic infections nor CsA associated neoplasms in our patients. This long term study demonstrates the potential efficacy of CsA in the treatment of severe intra-ocular inflammatory disorders. However, we firmly believe that only in the context of a randomized clinical trial that a definitive evaluation as to the true effectiveness of CsA will be reached.

Adult↗