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Biomedical subjects

C C Chan

Publications and source records attributed to C C Chan.

At least 379 records · Page 21Linked to original sources

Commuter exposures to VOCs in Boston, Massachusetts.

This study examines the commuter's exposure to six gasoline-related volatile organic compounds (VOCs): benzene, toluene, ethylbenzene, m-/p-xylene, o-xylene, and formaldehyde. The VOC concentrations to which commuters were exposed in four different commuting modes (driving, subway, walking, and biking) in Boston, Massachusetts, are compared. The VOC concentrations in participants' homes and offices were also measured. Factors that could influence in-vehicle VOC concentrations, such as different traffic patterns, car model and vehicle ventilation conditions, were also evaluated. Driving a private car was associated with higher VOC concentrations and commuting on urban roadways resulted in the highest VOC concentrations. The use of car heaters resulted in higher in-vehicle VOC concentrations. The longer the subway commuters stayed underground, the higher their VOC exposures. The home-to-work car or subway commute represented about 10 to 20 percent of an individual's total VOC exposure for these compounds.

Air Pollutants↗

Clinical and immunohistologic studies of corneal rejection in the rat penetrating keratoplasty model.

We used immunohistologic techniques with a penetrating keratoplasty model in the rat to study the mechanisms of corneal transplant rejection. Thirteen of 14 syngeneic grafts remained clear in contrast to 24 of 26 allogeneic grafts, which had a rejection reaction. Immunohistochemical studies of syngeneic grafts showed only rare inflammatory cells in the central grafts; however, a focal inflammatory reaction made up of macrophages and T-helper/inducer lymphocytes was seen surrounding the sutures and in the wound. In contrast, immunohistochemical studies of allogeneic grafts showed diffuse inflammation throughout the donor and recipient corneas with T-suppressor/cytotoxic cells, T-helper/inducer cells, and macrophages, resulting in destruction of the donor endothelium, neovascularization, and graft failure. Class II antigen expression was seen extensively on Langerhans cells, donor keratocytes, and both the donor and recipient endothelial cells. These findings emphasize the role of early nonspecific inflammation in the wound and around the sutures, and delineate the cellular immune response and class II antigen expression in corneal allograft rejection.

Animals↗

Peptide leukotriene involvement in pulmonary eosinophil migration upon antigen challenge in the actively sensitized guinea pig.

Male Dunkin Hartley guinea pigs, actively sensitized to ovalbumin (OA) and pretreated with mepyramine (1 mg/kg i.p.), were challenged with OA as an aerosol. Histological analysis of the lung for eosinophils (EOs) showed significant accumulations in the submucosa of the airways (8 h: 1.477.3 +/- 43 EOs/mm2 airway, n = 3, p less than 0.01), after antigen challenge compared to saline control (478.6 +/- 104 EOs/mm2 airway, n = 4). Pretreatment with both mepyramine and cimetidine (10 mg/kg i.p.) did not affect this response. Aerosolization of OA to unsensitized guinea pigs resulted in no significant accumulation of EOs (360.2 +/- 49 EOs/mm2 airway, n = 4) when compared with the saline-challenged sensitized control group. Pretreatment with the leukotriene (LT)D4 receptor antagonist MK-571 (1 mg/kg p.o.) significantly inhibited the OA-induced EO migration (95 +/- 5% inhibition, n = 5, p less than 0.01) compared to vehicle in the presence of mepyramine and cimetidine, while indomethacin (3 mg/kg p.o., n = 4) had no effect. Aerosolization of synthetic LTC4 (0.3-30 micrograms/ml) resulted in a dose-dependent migration of EOs into the submucosal layer over 8 h, reaching significance at the 10-micrograms/ml dose, with comparable results obtained with LTD4. Pretreatment of animals with MK-571 (1 mg/kg p.o.) before LTC4 and LTD4 aerosol results in inhibition of the response in both cases, suggesting that this effect may be mediated through the LTD4 receptor. We conclude that peptide LTs produce eosinophilia in the airways of the guinea pig.

Animals↗

FK506 treatment of S-antigen induced uveitis in primates.

FK506 is a new immunosuppressive agent which has been found more potent than cyclosporine based on the dosage. FK506 was examined here for its effect on the development of uveitis in primates immunized with S-antigen. FK506 successfully inhibited uveitis in monkeys, even when administered three weeks after the first immunization, at the time when the immunopathogenic mechanism of uveitis is assumed to be developed. All four monkeys injected with 0.5 mg/kg/day of FK506 did not develop uveitis, 2 out of 4 treated with the 0.25 mg and 3 out of 4 of those receiving the 0.125 mg also did not develop disease. FK506 suppressed to some extent the cellular and humoral immune responses to S-antigen. The main side effect of FK506 was weight loss. We consider that this drug may be considered as a new potential therapeutic agent for immune-mediated ocular disease in humans.

Animals↗

Isolation of dengue virus with a human promonocyte cell line.

In October-November, 1988 there was an outbreak of dengue fever in the Kaoshiung area of southern Taiwan. We collected 100 serum samples from 96 patients at the onset of their fever for virus cultures and identification. A human promonocyte cell line (HL-CZ) established in our laboratory was used and proved to be susceptible for dengue virus propagation. Type 1 dengue virus in the HL-CZ cell culture was identified by immunofluorescence tests using monoclonal antibodies, and also by hemagglutination tests with goose red blood cells. The density of the virus particles, as measured by sucrose gradient ultracentrifugation, ranged from 1.186 to 1.224 g/ml. The virus yield from this cell culture is comparable with that from the C6/36 mosquito cell line. There was a significant correlation between the antibody responses tested with Western dot blots and hemagglutination inhibition techniques.

Adolescent↗

Assessment of microleakage of cervical restorations.

Cervical lesions restored with composite resin seem to be more susceptible to marginal leakage, because the gingival margin is usually placed in cementum and/or dentin. The purpose of this study was to evaluate the effectiveness of five dentinal bonding agents, four composite resins and a glass ionomer cement in eliminating marginal gaps in an extraoral model. This study was accomplished using extracted human teeth and dye penetration method. The results indicated that none of the available dentinal bonding agents was able to eliminate marginal gaps completely. The cavities restored with the two component type dentinal adhesives leaked less than the negative control, glass ionomer cement.

Dental Cements↗

[Immunologic suppression of experimental autoimmune uveitis].

Experimental autoimmune uveitis (EAU) is induced in rats by active immunization with retinal S-Antigen (S-Ag) in complete Freund's adjuvant. In contrast, oral administration of an antigen induces specific suppression. We investigated the potential of oral administration of S-Ag for the treatment of EAU. Prior to active immunization rats received 3 x 1 mg S-Ag orally. In contrast to untreated controls, the treated rats were significantly protected from EAU, as determined by clinical and histological examination. Lymphocytes from treated rats showed no proliferative response to S-Ag in vitro, but had a normal proliferative response to other antigens. CD8-positive T cells from S-Ag-fed rats inhibited the proliferation of an antigen-specific uveitogenic T-cell line in vitro. Moreover, the intensity of the inflammatory reaction to active immunization could be suppressed when feeding was started after the active immunization. These data show, that oral administration induced suppression, which provided significant protection from the development of uveitis.

Administration, Oral↗

Ocular inflammation stimulated by intravitreal interleukin-8 and interleukin-1.

Interleukin-8 (IL-8), a cytokine with neutrophil chemotactic and activating properties, is known to be stimulated by IL-1. Fischer rats are more resistant to inflammation than Lewis rats probably due to a higher corticosteroid stress response. To determine the role of IL-8 in ocular inflammation, the effect of intravitreal injection of IL-8 was compared with that of IL-1 in both Lewis and Fischer rats. The IL-8, IL-1 alpha, or sterile balanced salt solution (control) was injected into one eye of each animal. Both IL-8 and IL-1 alpha caused inflammation in the eye of both strains, as detected by leukocyte counts of the anterior chamber and histopathologic examination. The eyes of animals injected with a cytokine had significantly higher numbers of leukocytes compared with eyes of control animals. Histopathologic examination confirmed these findings. The IL-1 alpha induced inflammation more consistently and more severely than the most effective dose of IL-8. This finding agreed with the concept of IL-1 initiating a cascade of inflammatory mediators including IL-8, which acts more specifically on a smaller population of leukocytes. A contralateral response was observed in the uninjected eye of experimental and control animals. The contralateral response in animals receiving the cytokines was significantly greater than that in controls. Lewis rats show a higher inflammatory response to the injections than do the Fischer rats. These data suggest that IL-8 may be active as one component in neutrophil-mediated ocular inflammation.

Animals↗

Eosinophil-eicosanoid interactions: inhibition of eosinophil chemotaxis in vivo by a LTD4-receptor antagonist.

Chemotaxis of guinea-pig eosinophils in vivo has been studied in the guinea-pig conjunctiva. Guinea-pig eosinophils were labelled with 111In oxine and injected i.v. into recipient animals. Circulating radioactivity remained constant over a period of 4 h but dropped transiently in response to a bolus injection (1 nmol) of platelet activating factor (PAF), suggesting that the 111In-labelled eosinophils had retained their responsiveness to PAF. Leukotriene D4 (LTD4, 1 nmol/eye) and PAF (10 nmol/eye), but not histamine (5 nmol/eye), induced a significant 2.5-fold increase in conjunctival radioactivity, a measure of eosinophil chemotaxis in vivo, after 17 h. Antigen challenge (250 micrograms/eye) in ovalbumin-sensitized animals produced larger responses (8-fold increases) at the same time point. A specific LTD4 receptor antagonist MK-571 (10 micrograms/eye) completely inhibited in vivo chemotactic responses to LTD4, and partially inhibited (54%) the responses to ovalbumin (observations subsequently confirmed by histological studies). As eosinophils may play an important role in allergic diseases, the results with MK-571 indicate that selective and potent LTD4 receptor antagonists may provide a novel therapy for allergic conjunctivitis, rhinitis and asthma.

Animals↗

Histopathologic study of the Molteno glaucoma implant in three patients.

Three eyes with the Molteno glaucoma implant (one eye with epithelial downgrowth, one eye with iridocorneal endothelial syndrome, and one eye with aphakia and glaucoma) were enucleated two to six years after implantation. Histopathologic examinations disclosed no evidence of erosion of sclera or conjunctiva of the eye by the glaucoma implant device. In the outer layers of the bleb wall, few and mostly degenerated inflammatory cells were present, which represented a minimal inflammatory reaction. Scanning electron microscopy of the tubes in these three patients showed that the tube was intact, patent, and without signs of degradation. The tube entering into the anterior chamber caused no appreciable inflammation and maintained its patency even when downgrowth epithelial cells lined the anterior chamber. The Molteno plate induced little or no inflammatory reaction. Therefore, the Molteno glaucoma implant is a useful device for patients with high risk for failure after surgery for glaucoma.

Aged↗

Inhibition of S-antigen induced experimental autoimmune uveoretinitis by oral induction of tolerance with S-antigen.

The ability to prevent the expression of retinal SAg induced experimental autoimmune uveitis (EAU) in Lewis rats by oral administration of the SAg and SAg fragments was investigated. Oral administration of the SAg molecule prevented or markedly diminished the clinical appearance of SAg-induced disease as measured by ocular inflammation. Furthermore, oral administration of the SAg also markedly diminished uveitis induced by the uveitogenic M and N fragments of the SAg. M and N fragments were not effective in preventing SAg-induced EAU, although feeding the M fragment prevented disease induced by the M fragment. Oral administration of the SAg did not prevent myelin basic protein induced experimental autoimmune encephalomyelitis, whereas feeding myelin basic protein did. In vitro studies demonstrated a significant decrease in proliferative responses to the SAg in lymph node cells draining the site of immunization from fed vs nonfed animals. Furthermore, the addition of splenocytes from SAg-fed animals to cultures of a CD4+ SAg-specific cell line profoundly suppressed the cell line's response to the SAg, whereas these splenocytes had no effect on a purified protein derivative-specific cell line. The Ag-specific in vitro suppression was blocked by anti-CD8 antibody (OX-8) demonstrating that this suppression is dependent on CD8+ T-cells. These experiments demonstrate that Ag-specific immunomanipulation can be achieved in the EAU model by oral administration of the SAg and raise the possibility that such an approach may have practical clinical implications in uveitis as well as other human autoimmune diseases.

Administration, Oral↗

Thrombin stimulates the proliferation of human retinal glial cells.

Retinal glial cells may play a role in most of the proliferative retinopathies. Although glial cell proliferation is a frequent event in retinal pathobiology, no specific mitogens for human retinal glial cells are known. Using cultured retinal glial cells obtained from postmortem adult human eyes, we found that thrombin stimulates glial cell proliferation in a dose-dependent manner with a half-maximal concentration of 100 ng/ml (0.4 U/ml). Thus, thrombin may be a plasma-derived mitogen capable of stimulating retinal glial cells to proliferate when there is a breakdown of the blood-retinal barrier. We also observed that this proliferative response of retinal glia requires more than 6 h of continuous exposure to thrombin. This finding suggests that a thorough wash-out of a thrombin-containing infusate and/or the rapid inactivation of this molecule would prevent thrombin form exacerbating a proliferative disorder of the retina.

Adult↗

Experimental autoimmune uveoretinitis in mice. Induction by a single eliciting event and dependence on quantitative parameters of immunization.

Experimental autoimmune uveoretinitis (EAU) in the mouse is a recently developed model of ocular autoimmunity. Dependence of disease induction on qualitative and quantitative parameters of immunization was studied in B10.A mice immunized with interphotoreceptor retinoid-binding protein (IRBP). It was found that use of Bordetella pertussis adjuvant as well as its mode of preparation was of critical importance for disease induction; no disease was induced if pertussis adjuvant was omitted. The minimal effective protocol for EAU induction when the vaccine form of B. pertussis adjuvant was used consisted of pretreatment with cyclophosphamide, two divided doses of IRBP in complete Freund's adjuvant (CFA), and two divided doses of B. pertussis vaccine. Any reduction in the immunization schedule resulted in reduced incidence of disease. In contrast, substituting purified B. pertussis toxin (PTX) for the vaccine allowed reduction of the immunization schedule to a single dose of IRBP in CFA and omission of the cyclophosphamide pretreatment. Severity and incidence of disease could be quantitatively controlled by varying the respective doses of IRBP and PTX. In addition, a chronic or an acute clinical course of EAU could be obtained by using either a low-dose or a high-dose immunization, respectively. Establishment of a single dose induction protocol and the quantitation of the immunopathogenic response as a function of the variables of immunization lay the foundation for the further development and utilization of this promising model of ocular autoimmunity.

Adjuvants, Immunologic↗

Pathology of experimental autoimmune uveoretinitis in mice.

The histopathology and immunopathology of murine experimental autoimmune uveoretinitis (EAU) following active immunization with the interphotoreceptor retinoid-binding protein (IRBP) were studied. The methods used included conventional light microscopy and immunoperoxidase staining. Lesions were located mainly in the uvea and the retina and were characteristically focal. The prominent histopathologic findings in the retina were vasculitis, granuloma, retinal fold, focal serous detachment, and loss of photoreceptors. Granulomas, formation of Dalen-Fuchs nodules, inflammatory cellular infiltration and increase in the thickness of the choroid and ciliary body were frequent findings. Subretinal neovascularization occurred in 10% of the experimental animals. Mild to moderate inflammation was also noted in the vitreous. The predominant infiltrating cells in the retinal and uveal granuloma and the Dalen-Fuchs nodules were macrophages. In contrast, the predominant infiltrating cell types in the vitreous were T helper/inducer lymphocytes. T suppressor/cytotoxic cells were rarely seen. Expression of Ia antigens on the ocular cells was confined to the immediate area of the inflammatory sites. The kinetics of histopathology showed two peaks at the 5th and 10th week after immunization, suggesting a relapsing course of the disease.

Animals↗

Immune mechanisms in choroido-retinal inflammation in man.

The immunohistopathological findings of enucleated eyes and immunological abnormalities in several clinical disorders which result in intraocular inflammation are presented. With current immunological techniques, it is possible to define the type and activation status of the cells infiltrating the tissues. In all eyes examined, the predominant cell type was of activated CD4+ T-cells suggesting that the mechanisms involved in the perpetuation of the inflammatory response are similar and it is the initiating events which are likely to determine the site of pathology. The effects of activated CD4+ T-cells and the lymphokines they secrete in the chronic inflammatory process in the ocular tissues are discussed.

Behcet Syndrome↗

Determination of organic contaminants in residential indoor air using an adsorption-thermal desorption technique.

This field study evaluated the ability of a multi-sorbent sampling tube/thermal desorption technique to identify and to provide quantitative data on volatile organic contaminants in indoor air. Air samples, from 12 Canadian homes, were collected on multilayer sorbent cartridges and analyzed using Adsorption/Thermal Desorption coupled with Gas Chromatography/Mass Spectrometry. The study included the identification and quantitation of 23 target compounds. Analysis of sorbent tubes fortified with these target compounds indicated that recoveries were greater than 70 percent and the precision was usually better than 15 percent. These organic compounds were found to be stable on the sorbent tubes for at least seven days. With some exceptions, the target compounds were usually detected at 1 to 10 micrograms/m3 in indoor air samples; other organics identified qualitatively were saturated hydrocarbons, unsaturated hydrocarbons, cyclic hydrocarbons, substituted aromatics, oxygenates, some halogenates and cyclic species such as camphenes/pinenes and carenes.

Adsorption↗