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Biomedical subjects

C C Chan

Publications and source records attributed to C C Chan.

At least 289 records · Page 16Linked to original sources
PubMed1995

Suramin treatment suppresses induction of experimental autoimmune uveoretinitis (EAU) in rodents.

The experimental drug suramin has been shown to possess several immunosuppressive properties. In this study we investigated the effect of suramin on the development of experimental autoimmune uveoretinitis (EAU) in mice and in rats. EAU was induced either by active immunization with a uveitogenic protein or peptide, or by the adoptive transfer of a uveitogenic T cell line. The development of EAU was assessed by clinical evaluation as well as by histopathology. Immunological responses were measured by delayed type hypersensitivity (DTH), lymphocyte proliferation, and serum antibody levels to the immunizing antigen. Suramin treatment was most effective in suppressing EAU when started concurrently with immunization (afferent). Treatment was less effective in suppressing disease when first administered 7 days after immunization or when given to animals that received an adoptive transfer of uveitogenic T cells (efferent). The effect of suramin on DTH and lymphocyte proliferation roughly paralleled its effect on EAU. Aferent treatment of mice with suramin completely suppressed anti-IRBP antibody titers. Interestingly, animals receiving efferent treatment had unreduced IgM levels but little or no IgG, suggesting prevention of the IgM-to-IgG switch. Depressed in vitro lymphocyte proliferative responses in animals treated with suramin during the afferent stage suggested that the suppressive effect on disease was due at least in part to an inhibition of antigen priming. Our results suggest that suramin merits further investigation as a potential treatment for some types of uveitis.

Animals↗
PubMed1995

Effects of topical FK506 on endotoxin-induced uveitis (EIU) in the Lewis rat.

FK506 is a macrolide antibiotic and a potent immunosuppressant. To investigate the effect of topical FK506 on acute ocular inflammation, we evaluated its action on the development of endotoxin-induced uveitis (EIU). At two different concentrations of 0.05% and 0.3%, topical FK506 was applied to Lewis rats with EIU. In aqueous, the mean number of inflammatory cells per microliter +/- SEM was 2,389 +/- 1,277, 1,571 +/- 1,562, 898 +/- 882, and 69 +/- 152 for rats treated with vehicle alone, 0.05%, 0.3% FK506, and 1% prednisolone acetate. The median of histological grades was 2, 1.5, 0.8, and 0.5 for animals treated with these 4 different regimens respectively. Analysis of aqueous protein showed a small reduction in FK506-treated animals. Mean blood levels of FK506 were low in rats treated with topical FK506 (0.05%, 0.84 ng/ml; 0.3%, 2.0 ng/ml) suggesting that its therapeutic effect was not secondary to the systemic absorption of the drug. Although FK506 is not as effective as prednisolone, 0.3% FK506 produced significant decreases in the mean aqueous inflammatory cell number and histological inflammatory score as compared to control vehicle alone. We conclude that topical FK506 can suppress EIU in a dose-dependent fashion and may be an alternative medication for patients with anterior uveitis and contra-indication to topical steroid.

Administration, Topical↗
PubMed1995

Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745,337: a novel nonsteroidal anti-inflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach.

Recent studies have shown that there are two isoforms of cyclooxygenases. The constitutive form, cyclooxygenase 1 (COX-1), is believed to be involved in the maintenance of physiological functions. A second isoform, cyclooxygenase 2 (COX-2), has been shown to be induced in inflammation. In the present study, the pharmacology of a selective inhibitor of COX-2, L-745,337 (5-methanesulfonamido-6-(2,4-difluorothiophenyl)-1-indano ne), is described. L-745,337 has IC50 values of 23 +/- 8 nM and > 10 microM for the inhibition of prostaglandin E2 production in whole-cell assays for COX-2 and COX-1, respectively. This compound inhibited carrageenan-induced rat paw edema and rat paw hyperalgesia with ID50 values of 2.00 and 0.37 mg/kg, respectively. In an endotoxin-induced pyresis assay in the rat, L-745,337 significantly reversed the pyretic responses (ID50 = 3.75 mg/kg). L-745,337 did not cause visible gastric lesions in rats at up to 30 mg/kg (4 hr after dosing). In a fecal 51chromium (51Cr) excretion assay to detect gastrointestinal integrity in rats and primates, L-745,337 had no effect at doses up to 100 mg/kg (rat) or after chronic dosing at 20 mg/kg per day for 5 days (primates). In contrast, oral administration of indomethacin, diclofenac or flurbiprofen resulted in substantial increase in fecal 51Cr excretion and/or frank gastric ulceration (rats). L-745,337 significantly inhibited the prostaglandin E2 levels in the inflammatory exudates from the rat pleural cavity after injection with carrageenan but did not inhibit prostaglandin E2 levels in the stomach.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Hepatopulmonary syndrome in liver cirrhosis: report of a case.

A 52-year-old woman suffered from exertional dyspnea, 5 years after she was diagnosed with cirrhosis of the liver. Hypoxemia was suspected because of persistent exertional dyspnea and was confirmed by contiguous arterial blood gas tests. After excluding other cardiopulmonary factors, a series of studies including lung perfusion scan, echocardiography and cardiopulmonary cineangiography revealed the cause of hypoxemia to be the patient's liver disease. Hepatopulmonary syndrome was diagnosed. Despite supplemental oxygen therapy and oral garlic powder for 6 months, the patient still had exertional dyspnea and platypnea, and arterial blood gas results did not improve. We report this case to call attention to arterial oxygen desaturation in cases of cirrhosis of the liver, and to emphasize that deteriorating oxygenation in patients with chronic liver disease may be an indication for liver transplantation, as such functional microvascular abnormalities could be reversed by liver transplantation.

Female↗
PubMed1995

Identification of a major pathogenic epitope in the human IRBP molecule recognized by mice of the H-2r haplotype.

PURPOSE: Mice of the H-2b, H-2k, and H-2r haplotypes develop experimental autoimmune uveoretinitis (EAU) after immunization with interphotoreceptor retinoid-binding protein (IRBP) of bovine or monkey origin. The purpose of this study was to identify putative pathogenic epitope(s) of IRBP and to establish their immunodominance within the IRBP molecule. METHODS: Overlapping 20-amino acid peptides, spanning the entire human IRBP molecule, were synthesized and used to immunize C57BL/10 (H-2b), B10.BR (H-2k), and B10.RIII (H-2r) mice. Bovine IRBP was used as a positive control. Experimental autoimmune uveoretinitis was examined by histopathology 21 days after immunization. Immunologic responses were assessed by delayed-type hypersensitivity (DH) and lymphocyte proliferation assays. RESULTS: Peptide 161-180, spanning the sequence SGIPYIISYLHPGNTILHVD, was found to be highly pathogenic for B10.RIII mice but not for the other strains. A dose-response curve showed that peptide 161-180 was maximally pathogenic at 50 micrograms, but incidence and scores were reduced at 10 micrograms. The truncated 13-mer 165-177 was also highly pathogenic (100 to 200 micrograms), suggesting that it contained the pathogenic epitope. Mice immunized with the peptide, or with whole IRBP, had positive DH and lymphocyte responses to the immunizing as well as to the reciprocal antigen. A cell line derived to peptide 161-180 was also pathogenic for B10.RIII mice after adoptive transfer and responded (proliferation) to native IRBP. CONCLUSIONS: High incidence and high severity scores, as well as immunologic cross-recognition of peptide 161-180 and native IRBP in vivo and in vitro, suggest that this peptide contains a major epitope recognized as pathogenic by B10.RIII mice.

Amino Acid Sequence↗
PubMed1995

Multimodal approach in the management of 1163 ureteric stone cases.

One thousand one hundred and sixty three patients (male-852, female-311) with ureteric calculi requiring intervention were treated between April 1988 to July 1992. Four hundred and eleven cases were treated by ESWL Monotherapy, 414 by stone manipulation plus ESWL, 301 by retrograde ureteroscopic lithotripsy, 36 by percutaneous antegrade ureteroscopic lithotripsy and 1 case by open ureterolithotomy. There were 25 failures of the initial procedures. Only three cases that failed primary procedures required open surgery. Other complications include minor ureteric mucosal perforation (3%), infection (3%), transient moderate to gross haematuria (20%), loin ache (26.4%), irritative urination (34.4%) and low grade fever (30.1%). Current modalities used in the treatment of ureteric calculi produce good results and there is generally no primary role for any open surgery.

Adolescent↗
PubMed1995

Evaluation of the efficacy of sequential intravenous-oral administration of pefloxacin in community-acquired lower respiratory tract infections in patients with underlying conditions.

We studied the efficacy of sequential intravenous-oral pefloxacin therapy in community-acquired lower respiratory tract infection in 24 patients with one or more underlying conditions. Twenty-eight patients were enrolled into the study but only 24 patients were evaluated. There were 16 males and 8 females with a mean age of 66.9 +/- 11.2 years (mean +/- SD, range 46 to 87 years). The underlying conditions present were bronchiectasis, chronic obstructive lung disease and diabetes mellitus. Patients who were older than 70 years but without any underlying condition were also enrolled. All received 4 days of intravenous pefloxacin 400 mg twice a day followed by oral pefloxacin 400 mg twice a day for another 10 days. Assessment of success was based on clinical, microbiological and radiological improvement. Pefloxacin produced 79.2% clinical cure rate. Another 8.3% showed improvement. Pefloxacin was well tolerated. There were few adverse effects and none of the patients required a change of antibiotic. Pefloxacin was an effective and well tolerated treatment for respiratory tract infection and had the advantage of broad in-vitro antibacterial activity, twice daily dosing and sequential availability in an intravenous and oral formulation.

Administration, Oral↗
PubMed1994

Clinical biochemical and pathologic correlations in Bietti's crystalline dystrophy.

We examined three affected members of a Chinese-American family with Bietti's crystalline retinopathy. The clinical characteristics of a 24-year-old proband are contrasted to the clinical findings of her grandmother, for whom we have 26 years of follow-up data. Lymphocytes and fibroblasts from a skin biopsy of the grandmother contained crystalline lysosomal material, which supports the diagnosis. Biochemical studies of the crystalline lysosomal material failed to identify the stored compounds but did not show them to be cholesterol or cholesterol ester. Finally, histopathologic studies performed for this condition demonstrated advanced panchorioretinal atrophy, with crystals and complex lipid inclusions seen in choroidal fibroblasts.

Adult↗
PubMed1994

Diagnosis of reactive lymphoid hyperplasia by chorioretinal biopsy.

We treated a patient with reactive lymphoid hyperplasia in whom the diagnosis was made by chorioretinal biopsy. Histopathologic examination and culture of the biopsied specimen allowed us to rule out a neoplastic or infectious process. The biopsy result allowed us to treat him with systemic corticosteroid alone, thus avoiding the potential harmful side effects of other medications, including antituberculous drugs. There were no surgical or postoperative complications. This study confirms the usefulness of chorioretinal biopsy for establishing a diagnosis and formulating a rational treatment plan.

Antigens, CD↗
PubMed1994

Naphthalenic lignan lactones as selective, nonredox 5-lipoxygenase inhibitors. Synthesis and biological activity of (methoxyalkyl)thiazole and methoxytetrahydropyran hybrids.

Combinations of structural elements found in (methoxyalkyl)thiazole 1a and methoxytetrahydropyran 2a with a naphthalenic lignan lactone produce the potent 5-lipoxygenase (5-LO) inhibitors 3 and 4. While the nature of link Y-Z has a major effect on the in vitro activity of compounds 1 and 2, inhibitors 3 and 4 retain their potencies with either an oxymethylene (Y = O, Z = CH2) or a methyleneoxy (Y = CH2, Z = O) link. Compound 4b inhibits the oxidation of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid by 5-LO (IC50 = 14 nM) and the formation of leukotriene B4 in human polymorphonuclear leukocytes (IC50 = 1.5 nM) as well as in human whole blood (IC50 = 50 nM). Compound 4b is a selective 5-LO inhibitor showing no significant inhibition of human 15-lipoxygenase or porcine 12-lipoxygenase or binding to human 5-lipoxygenase-activating protein up to 10 microM and inhibits leukotriene biosynthesis by a direct, nonredox interaction with 5-LO. Compound 15, the open form of lactone 4b, is well absorbed in the rat and is transformed into the active species 4b. In addition, 15 is orally active in the rat pleurisy model (ED50 = 0.6 mg/kg) and in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.3 mg/kg).

Animals↗
PubMed1994

Endogenous systemic IFN-gamma has a protective role against ocular autoimmunity in mice.

Locally produced IFN-gamma has been implicated in enhancing inflammation and in promoting organ-specific autoimmunity. In the present study, we investigated the influence of systemically available IFN-gamma on the expression of experimental autoimmune uveoretinitis (EAU) induced in mice with the retinal Ag, interphotoreceptor retinoid binding protein (IRBP). EAU-susceptible B10.A mice treated with a mAb to IFN-gamma developed much more severe EAU than did the controls and had increased delayed hypersensitivity (DH) responses to IRBP. There was an increase in the proportion of macrophage/monocytes vs lymphocytes in the ocular lesions of treated animals. The anti-IFN-gamma treatment did not prevent expression of MHC class II within the ocular tissues. Conversely, treatment with rIFN-gamma ameliorated EAU expression and lowered DH responses. This occurred despite widespread induction of MHC class II Ag in the ocular tissues and other organs. In contrast to EAU and DH, serum antibody titers and lymphocyte proliferation to IRBP were not significantly affected by either treatment. Experiments in several genetically resistant strains of mice showed that treatment with anti-IFN-gamma was able to up-regulate disease expression also in some EAU-resistant strains. In the case of one such strain, resistance to EAU induction was completely abrogated by the treatment. We conclude that endogenously produced IFN-gamma at the systemic level acts to down-regulate EAU in the mouse and that IFN-gamma-related mechanisms may be involved in conferring resistance to EAU in some mouse genotypes.

Animals↗
PubMed1994

The role of nitric oxide in uveitis.

OBJECTIVE: To evaluate the possible role played by nitric oxide in the pathogenesis of uveitis. METHODS: Uveitis was induced in rats with subcutaneous lipopolysaccharide. Lipopolysaccharide stimulates nitric oxide production from L-arginine. The animals were treated with NG-nitro-L-arginine methyl ester, an L-arginine analogue acting as a specific inhibitor of nitric oxide synthesis. Ocular inflammation was evaluated by measuring protein concentration and leukocyte number in the aqueous humor of one eye, and by histopathologic examination of the contralateral eye. RESULTS: Aqueous humor protein levels were reduced 73% to 82% and cellular infiltration was almost abrogated in NG-nitro-L-arginine methyl ester-treated rats compared with controls. The histopathologic examination also showed a similar inhibition of uveal tissue inflammation in treated rats. CONCLUSION: By inhibiting nitric oxide synthesis, NG-nitro-L-arginine methyl ester inhibits the induction of endotoxin-induced uveitis in the rat. This observation demonstrates that nitric oxide is an important mediator of anterior uveitis in this model system and suggests that nitric oxide may also be implicated in human uveitis.

Animals↗
PubMed1994

A clinicopathologic report of the retinal lesions associated with didanosine.

Didanosine, a purine analogue with antiretroviral activity, is used in the treatment of human immunodeficiency virus disease. Associated toxic effects of didanosine include pancreatitis, peripheral neuropathy, and retinopathy. The retinal lesions associated with didanosine therapy were studied in a 6-year-old girl with acquired immunodeficiency syndrome. Gross examination disclosed multiple well-circumscribed depigmented lesions in the midperipheral retina. Microscopic examination of these lesions showed multiple areas of retinal pigment epithelial (RPE) loss, some surrounded by areas of hypertrophy or hypopigmentation of the RPE. Partial loss of the choriocapillaris and neurosensory retina were also noted in areas of diseased RPE. Transmission electron microscopy showed numerous membranous lamellar inclusions and cytoplasmic bodies in the RPE cells. These data show that didanosine primarily affects the RPE and that the choriocapillaris and overlying neurosensory retina are also dystrophic in areas of RPE loss.

Child, Preschool↗
PubMed1994

Nasal septum lesions caused by chromium exposure among chromium electroplating workers.

A chromium electroplating worker, suffering from epistaxis during work, was found to have nasal septum perforation. To determine the etiology and prevalence of nasal septum lesions, we conducted a survey of seven chromium electroplating factories and examined 79 workers. Forty workers from three aluminum electroplating factories were also enrolled as the reference group. Subjects were thoroughly examined by an otolaryngologist and each of them provided a blood and urine sample. A questionnaire interview regarding symptoms of the upper respiratory tract, past medical history, life style, and work history was also conducted. Air chromium concentrations were measured by taking area samples for 4-6 hours. Based on field observation and chromium measurements, we divided chromium electroplating into three different exposure zones: workers directly dealing with electroplating tanks (n = 31), other process workers (n = 29), and office workers and drivers (n = 19). Among the 79 chromium electroplating workers, there were 16 cases of nasal septum perforation, and 42 with either scar formation or ulceration; 10 chromium electroplating workers developed skin ulcers after performing chrome plating. No workers from aluminum electroplating factories had any nasal septum or skin abnormalities. There was a consistent trend between the degree of chromium exposure and the signs and symptoms related to the nose, throat, and skin. Immediate improvement of occupational hygiene is warranted.

Adult↗
PubMed1994

gamma Interferon expression disrupts lens and retinal differentiation in transgenic mice.

We previously generated an animal model for the study of autoimmune diseases of the eye by targeting gamma interferon (gamma IFN) expression to the lens of transgenic mice. Here, we have studied the effect of constitutive lens expression of gamma IFN on eye development of these transgenic mice. By Day 18 of embryonic development, lens and retinal differentiation programs are completely disrupted; normal lens epithelia and fibers are replaced by balloon-like cells and retinal differentiation into inner and outer neuroblastic layers is already affected. The mRNA levels of gamma E- and/or gamma F-crystallin and MIP, markers of lens cell differentiation, are drastically reduced, while expression of ICSBP, a gamma IFN-inducible transcriptional factor, is induced in the alpha ACry-gamma IFN transgenic mouse eyes. Taken together, our results suggest that constitutive expression of gamma IFN and its induction and activation of gamma IFN-inducible transcriptional factors in the eye altered the developmental fate of cells destined to become lens fiber cells by altering the pattern of lens gene expression.

Animals↗
PubMed1994

Corticosteroids enhance S-antigen expression in nonretinal ocular tissues of rats with experimental autoimmune uveitis.

S-antigen (S-Ag), a major protein on the retinal photoreceptor cell, can induce experimental autoimmune uveitis (EAU). We have previously detected S-Ag and its mRNA in irises of chronic uveitis patients receiving long-term steroid therapy. To further investigate the effect of steroid therapy on ocular tissue, we compared levels of S-Ag and its mRNA in EAU rats with and without steroid treatment. EAU was induced in 72 Lewis rats by two footpad injections of S-Ag. The rats were then treated with Depo-Medrol or phosphate-buffered saline by intramuscular injection. Eyes were collected at different time points. S-Ag mRNA was detected in the lens epithelium, trabecular meshwork, iris, and ciliary body of 47.2% of the steroid-treated group vs 22.2% of the controls. S-antigen was also detected in 30.6% of the eyes of the treated group vs 16.7% of the controls. S-Ag and its mRNA was found only in the retina of normal rats. These results support the hypothesis that prolonged corticosteroid therapy in uveitic patients might enhance the expression of S-Ag in nonretinal ocular tissues and might contribute to the ocular side effects of corticosteroid.

Animals↗
PubMed1994

Toxoplasma gondii: acquired ocular toxoplasmosis in the murine model, protective role of TNF-alpha and IFN-gamma.

DNA and mRNA amplification by the polymerase chain reaction (PCR), immunohistochemical, and histopathology were performed in the eyes and brains from C57BL/6 mice infected with an avirulent strain of Toxoplasma gondii (ME49). Focal ocular inflammation and retinal pigment epithelial involvement were commonly observed after 15 days of infection. Four weeks after infection a stable number of cysts was observed in the brain but rarely in the eye, and they did not elicit an inflammatory response. In most of the ocular lesions the presence of the parasite could not be demonstrated even with the PCR technique. B1 DNA fragments of T. gondii were detected in only 4 of 11 eyes tested by PCR and Southern blot hybridization. Treatment of mice with mAbs against T cells (CD4 plus CD8) or cytokines (IFN-gamma or TNF-alpha) resulted in a marked increase of ocular lesions, more often associated with the presence of the parasite and the severity of inflammatory response. This model and the techniques utilized here can improve our understanding of the respective roles of parasite proliferation and immune mechanisms involved in the pathogenesis of acquired ocular toxoplasmosis.

Animals↗