Proposed immune mechanisms in uveitis and their modulation.
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Animals↗
Biomedical subjects
C C Chan
Publications and source records attributed to C C Chan.
Effects of synthetic leukotrienes on local blood flow and vascular permeability in porcine skin.
The local effects of synthetic leukotrienes (LT) were examined in the skin of the anesthetized pig. Blood flow was measured noninvasively with the use of a laser-Doppler flow meter and changes in vascular permeability were measured using technetium-labeled human serum albumin as a marker for extravasation. LTB4 and the peptidolipid leukotrienes, LTC4, LTD4, LTE4, LTF4, induced vasodilator responses when injected intradermally at a dose of 1 ng. The vasodilator effects of LTB4 and LTF4 were comparable in magnitude to those of prostaglandin E2 (PGE2) and histamine and persisted over a wide dose range. Vascular permeability was induced by histamine, PGE2, and LTB4 but not by the other leukotrienes. The effects of LTB4 were significantly increased in the presence of PGE2. Leukotrienes appear not to produce their effects through the generation of prostaglandins as neither the vasodilator nor the permeability-enhancing effects were affected by treatment with indomethacin. The present investigation demonstrates that the pig is the first animal model to be described which reflects the potent vasodilator actions of leukotrienes in human skin. The porcine skin may thus be a useful model in the study of human skin diseases.
Animals↗
Leukotriene B4 and 12-hydroxyeicosatetraenoic acid stimulate epidermal proliferation in vivo in the guinea pig.
Epidermal proliferation was studied in the guinea-pig ear in vivo using the incorporation of [3H]thymidine into DNA as a measure of cell proliferation. Twenty-four-hour pretreatment of the skin topically with nanomolar amounts of either leukotriene B4 (LTB4), 12-hydroxyeicosatetraenoic acid, ionophore A23187, or the epidermal mitogen 12-O-tetradecanoylphorbol-13-acetate induced dose-dependent increases in epidermal proliferation. The stimulatory effect of LTB4 was stereospecific since a number of biologically inactive LTB4 stereoisomers had no effect.
Animals↗
Pharmacological actions of leukotrienes in the skin.
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Animals↗
Long-term culture of Muller cells from adult rats in the presence of activated lymphocytes/monocytes products.
A method for the culture of retinal Muller cells from adult rats is described. Whereas isolated Muller elements did not grow in a medium composed of MEM + 10% FBS, the addition of supernatant from mitogen activated spleen cells induced a strong proliferative response. The factor(s) responsible for that growth were not species specific, as mouse spleen cells conditioned medium was also an effective stimulant. The highly significant degree of DNA synthesis induced by the supernatant from an S-antigen specific T-helper cell line (reacting to the retinal antigen presented on APC) indicates that the growth promoting activity is not restricted to mitogen driven spleen cells. It is suggested that products of inflammatory cells secreted in the course of intraocular immune processes may contribute to the formation of epiretinal membranes. These products also induced the expression of Ia surface antigens by Muller cells, supporting the hypothesis of a possible involvement in local immune reactions.
Animals↗
Immunopathology of uveitis.
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Autoimmune Diseases↗
Side effects of systemic cyclosporine in patients not undergoing transplantation.
Twenty-six patients with ocular inflammatory disorders of presumed autoimmune origin were treated with oral cyclosporine. Cyclosporine is a potent T cell regulatory agent that has been utilized extensively in organ transplantation. In general, the patients in this study did not have chronic debilitating illnesses that are observed in organ transplant recipients, did not receive corticosteroids in addition to cyclosporine, and did not undergo any surgical procedure during their treatment. This study describes the observed adverse reactions in this group of patients not undergoing transplantation. The reported side effects of cyclosporine in organ transplant recipients have included nephrotoxicity, hepatotoxicity, infections, lymphoma, hirsutism, gingivitis, and central nervous system toxicity. Side effects were observed that were similar to those in previous reports, but the severity of the nephrotoxicity and hepatotoxicity appeared to be less. Nephrotoxicity occurred in eight patients and hepatotoxicity occurred in one patient. No lymphomas were seen. Hypertension and anemia each were observed in six patients. In addition, previously unreported effects of hyperuricemia, elevated sedimentation rate, and hidradenitis were observed. However, the overall severity of the side effects did not seriously affect the usage of cyclosporine in the patients in this study. Cyclosporine may be useful in the treatment of other autoimmune diseases.
Adolescent↗
Improvement of uveitis and optic nerve disease by cyclosporine in a patient with multiple sclerosis.
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Cyclosporins↗
Ophthalmic involvement in acquired immunodeficiency syndrome.
Forty patients with acquired immunodeficiency syndrome (AIDS) were examined for ocular abnormalities. Twenty of these patients died and the eyes were obtained for culture and histopathologic examination. These patients have multiple opportunistic infections and neoplasms as the result of a severe depression of cellular immunity. Fifty percent of all patients with AIDS and 75% of the autopsy group have ocular signs attributable to AIDS. Ocular findings were confined to four major categories: cytomegalovirus retinitis (10 patients), retinal cotton wool spots (11 patients), conjunctival Kaposi's sarcoma (2 patients) and neuro-ophthalmic motility abnormalities (3 patients). Cytomegalovirus retinitis was a significant cause of visual loss. Seven of 40 autopsy eyes had hand motion or worse visual acuity prior to the patients' death because of CMV retinitis. This necrotic retinitis showed minimal inflammation and progressed to involve the entire retina in three to six months, resulting in a gliotic retinal membrane. Therapy with antiviral agents was not effective. Recognizing the ocular signs of AIDS may facilitate the diagnosis. The ophthalmologist also has a major role in the observation of progression or regression of these ocular manifestations, and can assist in the evaluation of therapy in patients with AIDS.
Acquired Immunodeficiency Syndrome↗
Plasma catecholamines in rats during rewarming from induced hypothermia.
The present study sought to quantitate the levels of plasma catecholamines [norepinephrine (NE), epinephrine (E), and dopamine (DA)] during induction and rewarming from hypothermia. Male rats (317 +/- 8 g) were made hypothermic by exposure to 0.9% halothane at -10 to -15 degrees C while blood pressure (carotid artery), heart rate, and colonic temperature (Tc) were monitored. Anesthesia was discontinued when Tc reached 28 degrees C. Tc continued to fall but was held at 20-20.5 degrees C for 30 min. Rewarming was then initiated by raising ambient temperature to 22 degrees C. Arterial blood samples were taken 1) before cooling, 2) just before rewarming, 3) when Tc reached 22 degrees C during rewarming, and 4) when Tc reached 27 degrees C during rewarming. Plasma was assayed radioenzymatically for catecholamines using both phenylethanolamine-N-methyltransferase and catechol-O-methyltransferase procedures, and hypothermic induction resulted in significant increases in NE, E, and DA above control levels (P less than 0.01). With rewarming to Tc = 22 degrees C, all catecholamines increased above the level observed during hypothermia (P less than 0.01), and NE and DA increased still further (P less than 0.01) when Tc reached 27 degrees C. The levels of plasma catecholamines observed during hypothermia and during the rewarming phase indicate a role of the sympathoadrenal medullary system in the metabolic adjustments associated with hypothermia and recovery. During rewarming, the levels of E and NE attained exceed those at which both substances may be expected to act as circulating hormones.
Adaptation, Physiological↗
Cellular and humoral immune parameters among patients with retinitis pigmentosa and other retinal disorders.
Patients with retinitis pigmentosa, other retinal degenerations and a group of normal volunteers were included in a masked study designed to examine the existence of autoimmune reactions toward retinal antigens and the possible defect in lymphokine production (IL-1, IL-2 and gamma interferon). The results obtained did not show any specific anamnestic response to the retinal S-Ag nor any outstanding defect in gamma interferon production by the lymphocytes of patients with retinitis pigmentosa. It is suggested that a larger masked study be conducted as soon as possible in order to clarify these aspects of immune aberrations in patients with retinitis pigmentosa.
Antibody Formation↗
Cyclosporine-induced alterations of humoral response in experimental autoimmune uveitis.
Cyclosporine (CsA) has been shown to be effective in preventing S-antigen (S-Ag) induced experimental autoimmune uveitis (EAU) in Lewis rats. Alterations in the humoral immune responses associated with CsA therapy are illustrated by lower peak and delayed production of circulating anti-S-Ag antibodies in a proportional relationship to the dose of CsA in EAU. Circulating immune complexes were not detected in rats with EAU or in rats treated with CsA and without disease. These findings further support the important role of T-cells in EAU and further demonstrate the effect of CsA on helper T-cells. The kinetics of antibody production by S-Ag-immunized rats appears altered by CsA.
Animals↗
An association between susceptibility to experimental autoimmune uveitis and choroidal mast cell numbers.
An association was found in rats of different strains between the susceptibility to EAU and the number of mast cells in the choroid of the eye. High responder rats (Lewis, CAR) had strikingly more choroidal mast cells than the low responder BN animals, whereas intermediate numbers of mast cells were found in the F1 hybrids of Lewis and BN (LBNF), which exhibited an average level of susceptibility to EAU. LeR rats, derived from the Lewis strain, developed EAU only when treated with B. pertussis, and their number of choroidal mast cells was only about 1/5 of that found in the Lewis rats. Unlike the differences in the number of choroidal mast cells, small variations were found in the skin mast cell numbers of the tested rats. It is proposed that the number of local mast cells may be one mechanism by which the susceptibility to an organ-specific autoimmune disease is genetically regulated.
Animals↗
Monoclonal antibodies to Müller's cells of the retina.
The immunohistologic properties of two monoclonal antibodies produced by hybridomas generated from bovine retinal S-antigen (S-Ag) immunized mice were investigated. These monoclonal antibodies demonstrated a low antibody titer to the original S-Ag preparation by the ELISA method. Immunohistologic studies using avidin-biotin-peroxidase complex (ABC) showed strong specific binding to the retinal Müller cells of all species tested (human, bovine, guinea pig and rat), a weaker binding to cell bodies and proximal component of the outer segments of the photoreceptor, but no apparent binding to the distal component of the outer segments of the photoreceptor cells.
Animals↗
Inhibition of prostanoid-mediated platelet aggregation in vivo and in vitro by 3-hydroxymethyl-dibenzo(b,f)thiepin 5,5-dioxide (L-640,035).
Platelet aggregation was studied in vitro with human platelets and in vivo in guinea pigs and rabbits. L-640,035 and its acetic acid metabolite, L-636,499, significantly inhibited human platelet aggregation induced by arachidonic acid, collagen and a prostaglandin endoperoxide analog (U44069) but not ADP. In guinea pigs, circulating platelets labeled with 111indium were monitored with probes in the lung and abdominal regions. Platelet aggregation was indicated by an increase in the ratio of gamma-radiation of the lung vs. the abdominal region, as aggregates of platelets accumulate in the microvascular network in the lung. L-640,035 (1 and 3 mg/kg i.v.) inhibited platelet aggregation induced in this model by U-44069 but not by ADP. In rabbits acute thrombosis was induced in the carotid artery by local electrical stimulation and platelet accumulation at the stimulus site was quantitated using 111indium-labeled autologous platelets. L-640,035 (1 and 3 mg/kg i.v.) significantly reduced electrically evoked platelet accumulation. It is concluded that L-640,035 is a novel and selective antagonist of platelet aggregation induced by thromboxane A2 or prostaglandin endoperoxides and that it may have utility as an antiplatelet drug.
Adenosine Diphosphate↗
Cyclosporin A therapy in the treatment of intraocular inflammatory disease resistant to systemic corticosteroids and cytotoxic agents.
Sixteen patients (ten women and six men, ranging in age from 20 to 67 years) with active bilateral posterior uveitis of noninfectious origin were treated with cyclosporin A, a specific anti-T-cell medication. All had previously received systemic corticosteroids or cytotoxic agents or both and had responded poorly or had intolerable side effects. Fifteen of 16 patients had positive responses to oral cyclosporin A therapy (initially 10 mg/kg of body weight/day), measured by a decrease in inflammatory activity, with a concomitant improvement in visual acuity in most patients. Fluorescein angiographic findings varied considerably with some patients showing an improvement with continued cystoid macular edema. Renal toxicity occurred in five patients, but renal function reverted toward normal with a decrease in cyclosporin A dosage.
Adult↗
Corneal epithelial iron deposition.
Different patterns of iron deposition in the epithelium in 96 of 120 corneal buttons that had superficial irregularities of different causes, as examined after staining grossly with Prussian blue by Gomori's method were detected. These observations were confirmed by light microscopy in 86 cases. The deposition was either diffuse or it formed a linear pattern within the epithelium adjacent to elevated areas of corneal scarring. The authors believe that the tear film is the source of iron in these cases, and that relative pooling of tears on an irregular surface is the mechanism by which iron lines are formed.
Cornea↗
Multicentric Kaposi's sarcoma of the conjunctiva in a male homosexual with the acquired immunodeficiency syndrome.
A 38-year-old male homosexual with the new Acquired Immunodeficiency Syndrome (AIDS) had biopsy proven Kaposi's sarcoma of the right palpebral conjunctiva, extraocular mucocutaneous areas, and lymph nodes. Histologically, the palpebral tumor was characterized by atypical spindle cell proliferation and multiple slit-like vessels. Staining for Factor VIII-related antigen was positive in the cytoplasm of some tumor cells. Electron microscopy disclosed Weibel-Palade bodies in cells lining scattered slit-like vascular channels. The palpebral tumor mass was relatively nonadherent to its surrounding tissues and thus its simple excision was noteworthy; despite the prominent vascularity of the tumor, minimal bleeding was associated with its surgical resection. Any patient with AIDS should have all mucosal surfaces routinely examined for the presence of Kaposi's sarcoma lesions.
Acquired Immunodeficiency Syndrome↗