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Biomedical subjects

C C Chan

Publications and source records attributed to C C Chan.

At least 307 records · Page 17Linked to original sources

L-745,337: a selective inhibitor of cyclooxygenase-2 elicits antinociception but not gastric ulceration in rats.

L-745,337 [5-methanesulphonamido-6-(2,4-difluorothiophenyl)-1-indan one] a selective cyclooxygenase-2 inhibitor reversed hyperalgesia induced by carrageenan in rats without causing gastric ulceration at doses 100 times those causing antinociception. In contrast, piroxicam and indomethacin produced ulcerations at antinociceptive doses. These findings demonstrate that L-745,337 possesses antinociceptive activity but has a reduced liability for gastric ulceration.

Analgesics↗

Experimental melanin-protein-induced uveitis in the Lewis rat. Immunopathologic processes.

PURPOSE: To study the immunopathology of experimental melanin-protein-induced uveitis in the Lewis rat. METHODS: Rats were immunized with bovine ocular melanin protein. The kinetics of experimental melanin-protein-induced uveitis was studied by clinical examination and immunopathology. Cellular and humoral responses were evaluated by lymphocyte proliferation, delayed-type hypersensitivity, and agglutination. After clinical disease subsided, recurrent experimental uveitis was induced with a low-dose footpad injection of lipopolysaccharide. RESULTS: Experimental melanin-protein-induced uveitis was characterized by bilateral uveal infiltration mainly with lymphocytes and monocytes. Delayed-type hypersensitivity, lymphocyte proliferation, and agglutination to bovine ocular melanin protein were positive. Expressions of major histocompatibility complex class II and intercellular adhesion molecule-1 were observed before ocular infiltration. The predominantly infiltrating cells were CD4+ lymphocytes. Experimental melanin-protein-induced uveitis subsided within 1 month, spontaneously recurred within 1 week in approximately one quarter of the rats, and was inducible in most rats with 5 micrograms of lipopolysaccharide confirmed by histopathology. CONCLUSIONS: Experimental melanin-protein-induced uveitis is a T-cell-mediated autoimmune uveitis, resembling noninfectious recurrent iridocyclitis and choroiditis in humans.

Animals↗

Kinetics of corneal transplant rejection in the rat penetrating keratoplasty model.

Kinetic changes of inflammatory cells and major histocompatibility (MHC) antigenic markers in syngeneic and allogeneic corneal grafts in rats were studied. Syngeneic grafts demonstrated mild inflammation in the first week with macrophages and T-helper/inducer cells found in a 2:1 ratio. By week 2 fewer macrophages were seen, and by week 4 no inflammatory cells were seen in the central graft. Central keratocytes and endothelium were negative for class II MHC expression. Significant inflammation persisted adjacent to the wound with macrophages and T-helper/inducer cells seen surrounding the sutures. Allogeneic grafts in the first week demonstrated mild inflammation with macrophages and T-helper/inducer cells in a 2:1 ratio. The central graft in week 2 had increased numbers of T-helper/inducer cells and T-suppressor/cytotoxic cells. By the third and fourth week, the T-suppressor/cytotoxic cells had become the major infiltrating cell. MHC class II antigens were seen on inflammatory cells, keratocytes, donor, and recipient endothelium.

Animals↗

Clinicopathologic correlation of the multiple recurrent serosanguineous retinal pigment epithelial detachments syndrome.

PURPOSE: Ocular clinicopathologic correlation in a patient with bilateral multiple recurrent hemorrhagic detachments of the sensory retina and retinal pigment epithelium (RPE), which eventually led to rubeosis and loss of useful vision in one eye, is described. The clinical appearance was most consistent with multiple recurrent serosanguineous RPE detachments syndrome (which may be similar to posterior uveal bleeding, or PUB, syndrome). METHODS: Light microscopic examination of 450 serial sections through a 3.7-mm area including the macula, optic nerve head, and superior and inferior peripapillary region of the eye that underwent diagnostic enucleation was performed. One fresh cap was used for immunohistochemical staining. Tissue from the posterior aspect of the other cap was prepared for electron microscopy. RESULTS: Microscopic examination disclosed extensive fibrovascular proliferation in the subretinal space and within Bruch's membrane, and the presence of at least 23 choroidal blood vessels that traversed defects in Bruch's membrane. Immunohistochemical studies of inflammatory infiltrates within the choroid and fibrovascular tissue demonstrated both a B- and T-cell response. CONCLUSION: In this case, recurrent serosanguineous detachments of the sensory retina and RPE were secondary to choroidal neovascularization with extensive fibrovascular proliferation in the subretinal space and within Bruch's membrane. Marked lymphocytic infiltration was present throughout the choroid and the fibrovascular tissue. Clinical improvement in the fellow eye after immunosuppressive therapy suggested that an immunologic component might be a causative factor, although the waxing and waning course in this condition precludes any definitive evaluation for its use in multiple recurrent serosanguineous RPE detachments syndrome.

Bruch Membrane↗

Comparative evaluation of bipolar atrial electrogram amplitude during everyday activities: atrial active fixation versus two types of single pass VDD/R leads.

Endocardial P wave amplitude (PWA) is an important determinant of the atrial sensing capabilities of an atrial-based pacing system. Although changes in PWA during physical activities are known to occur in DDD/R pacing, there is little information on the P wave stability in single pass lead VDD/R pacemakers using floating P wave sensing. We investigated the variation of PWA during daily life activities using telemetry recorded atrial electrograms in 21 patients with DDDR pacemakers (Relay or Elite) and 29 patients with single lead VDD/R pacemakers (Unity or Thera). Physical activities resulted in marked individual variability of PWA but, as a group, there was no significant difference between PWA during sitting, standing, lying down, and coughing in both DDDR and VDD/R pacing. In the Elite II pacemaker, walking at 2 miles per hour resulted in significant reduction of PWA (11.6% compared with sitting, P < 0.05). The most consistent reduction in PWA occurred in the relaxation phase of the Valsalva maneuver (VM), with all pacemakers showing a reduction in PWA (mean reduction in PWA compared with sitting in DDDR and VDD/R were 16.6% and 12.8%, respectively). Two patients with DDDR pacemakers (Relay) and three patients with VDD/R pacemakers (1 Unity and 2 Thera) had atrial sensing failure during VM or walking. In conclusion, large variation in PWA occurs during daily life activities. The extent of variation is dependent on the patients, types of atrial lead, and the maneuvers performed. A twice sensing threshold may be insufficient to ensure adequate atrial sensing during these activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗

Evaluation of bronchoconstriction induced by neurokinins and its inhibition by selective nonpeptide antagonists in conscious guinea pigs, using a double-chamber plethysmograph technique.

Bronchoconstriction induced by inhaled neurokinins, leukotriene D4 (LTD4), and histamine was examined in conscious guinea pigs, using a double-chamber plethysmography. The reliability of the plethysmograph was established by obtaining stable baseline values of key pulmonary parameters, including specific airway resistance, over a 4-day period. As well, the usefulness of the setup was confirmed using LTD4 and the LTD4 antagonist MK-571. Aerosols of MK-571 inhibited the bronchoconstriction induced by LTD4 (0.3 microM, 3 min aerosol) with an IC50 value of 65 +/- 16 nM. Inhaled neurokinin A (NKA), substance P (SP), [beta Ala8]NKA(4-10), or [Sar9,Met(O2)11]SP at concentrations up to 10 microM had no bronchoconstrictive effect, unless the guinea pigs were pretreated with the neutral endopeptidase inhibitor thiorphan (0.2 mg/mL, 5 min aerosol). The rank order of bronchoconstriction potency was LTD4 > [beta Ala8]NKA(4-10) approximately NKA > [Sar9,Met(O2)11]SP approximately SP >> histamine. Hyperresponsiveness to NKA-induced bronchoconstriction was evident after 1 day and lasted for 4 days. The response to NKA was not inhibited by mepyramine, indomethacin, or MK-571 but was significantly reduced by atropine and hexamethonium, suggesting the involvement of a cholinergic mechanism. Aerosols of SR-48,968 a selective NK2 antagonist, had potent effects on the bronchoconstriction induced by NKA (1 microM, 3 min aerosol), with an IC50 value of 17 +/- 3 nM. SR-48,968 was also active when administered intraperitoneally. The NK1 antagonist CP-99,994 (0.1 microM, 10 min aerosol) inhibited the responses to SP by 70% but had no effect on NKA-induced responses at concentrations up to 10 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Interleukin-2 treatment potentiates induction of oral tolerance in a murine model of autoimmunity.

The present study addresses the feasibility of potentiating oral tolerance by immunomanipulation, using the murine model of experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal antigen interphotoreceptor retinoid binding protein (IRBP). Three feedings of 0.2 mg IRBP every other day before immunization did not protect against EAU, whereas a similar regimen of five doses was protective. However, supplementing the nonprotective 3x regimen with as little as one injection of 1,000 U of human recombinant interleukin-2 (IL-2) resulted in disease suppression that was equal to that of the protective 5x regimen. The protective effect was maintained across a range of IL-2 doses and times of administration; none of the IL-2 regimens tested resulted in disease enhancement. Peyer's Patch cells of 3x-fed and IL-2-treated mice showed greatly increased production of TGF-beta, IL-4, and IL-10 compared with animals given the nonprotective 3x regimen and to animals given the protective 5x regimen. We propose that IL-2 treatment enhances protection from EAU at least in part by stimulating production of antiinflammatory cytokines by regulatory cells in Payer's Patches. Moreover, the observed lymphokine production patterns suggest that whereas protection induced by the 3x + IL-2 regimen is likely to involve antiinflammatory cytokines, protection induced by the 5x regimen might involve anergy or deletion of the uveitogenic T cells. These results could have practical implications for use of IL-2 as a safe and effective way of potentiating oral tolerance.

Administration, Oral↗

Ocular inflammation stimulated by the immunomodulator AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate].

The purpose of this study was to investigate the effect of a novel immunomodulator, AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate], in the eye. Lewis rats were injected intravitreally with AS101 at a concentration of 13 micrograms/ml in one eye and BSS in the contralateral eye. Control animals were injected with BSS into the central vitreous of both eyes. Ocular inflammation was evaluated at 20 hours by histology, immunopathology, and by cell count, protein and cytokine measurement in the aqueous humor. At 20 hours, eyes injected with AS101 developed iridocyclitis and mild vitritis versus minimal inflammation and/or protein in contralateral eyes or eyes of control animals (p = 0.0121). The inflammatory infiltrate was mixed in character. Major Histocompatibility Complex (MHC) class II antigens and intercellular adhesion molecules (ICAM-1) were expressed in the anterior segment of eyes injected with AS101. In the aqueous humor of these eyes there were significant quantities of inflammatory cells, protein (mean +/- SEM = 11.2 +/- 2.3 mg/ml) and the cytokine interleukin 6 (IL-6) (450 units/ml) compared with contralateral eyes (p = 0.0005 for inflammatory cells; protein, mean +/- SEM = 1.6 +/- 0.17 mg/ml; IL-6 = 12 units/ml) and both eyes of control animals injected with BSS (p = 0.8955 for inflammatory cells; protein, OD = 1.5 mg/ml, OS = 0.7 mg/ml; IL-6, OD = 8 units/ml, OS = 13 units/ml). AS101 has a local inflammatory effect in the eye. This compound may activate ocular inflammation by releasing cytokines such as IL-6.

Adjuvants, Immunologic↗

Effect of topically administered platelet-derived growth factor on corneal wound strength.

Since the cornea is an avascular tissue, the wound healing process is lengthy, with a need for sutures to stabilize the wound for a long time. Platelet-derived growth factor (PDGF) has been shown to accelerate wound healing in rat dermal models. Accelerated healing, if unaccompanied by side effects may reduce suture related complications such as astigmatism and infectious keratitis. This study evaluated the effect of PDGF on wound strength in corneal laceration and penetrating keratoplasty models using New Zealand white albino rabbits. Twenty-two rabbits were used in the corneal laceration model and sixteen rabbits in the penetrating keratoplasty model. The treated rabbits received 385 picomoles/drop of PDGF-BB dissolved in balanced salt solution six times on day 1 and three times a day for the remainder of the study. The control rabbits received balanced salt solution in the same dosing schedule. The pressure required to rupture the wound was measured using a pressure transducer. In the laceration model the PDGF treated group had mean (+/- standard deviation) average pressures on day 7 of 360 +/- 102 mm Hg for wound rupture compared to 210 +/- 102 mm Hg in the control group. (p = 0.005). The average pressures in the penetrating keratoplasty model on day 17 were 707 +/- 201 mm Hg for the controls and 1042 +/- 292 mm Hg for the PDGF treated group (p = 0.026). Histopathological evaluation of eyes not subjected to bursting showed increased fibroblasts at the wound junction with an increase in types III and type IV collagen production.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

The effect of occupational therapy education on students' perceived attitudes toward persons with disabilities.

OBJECTIVES: The effect of occupational therapy education on students' perceived attitudes toward persons with disabilities was studied. METHOD: The perceived attitudes of 144 occupational therapy students toward persons with disabilities were measured before (retrospective pretest) and after (posttest) the students attended formal professional education at the University of Alberta. RESULTS: Posttest scores were significantly higher than the retrospective pretest scores, indicating that students' attitudes became more positive after they commenced formal professional education. The posttest scores of students at various levels of education, however, did not show any significant difference. CONCLUSION: On the basis of these observations, a positive but nonlinear relationship between occupational therapy education and attitudes toward persons with disabilities was postulated.

Attitude↗

Case of occupational asthma due to glue containing cyanoacrylate.

Cyanoacrylates are a rare cause of occupational asthma, there being only six cases reported previously. High humidity has been implicated to be protective in the pathogenesis of the asthma. This is a case report of occupational asthma due to cyanoacrylate glue after working three years in a factory manufacturing doors. Diagnosis was made by history, serial peak flow measurements on and off work and specific inhalation challenge which elicited a delayed bronchoconstrictive response. An unusual feature of this case was the positive reaction to cyanoacrylate despite the high ambient humidity in Singapore.

Adhesives↗

A case of occupational asthma due to barley grain dust.

We report a case of occupational asthma due to barley grain dust, species Hordeum Vulgare L, in a 32-year-old storeman of a trading company's department that dealt with packaging of flour, barley and peanuts. He developed immediate symptoms of sneezing, cough and dyspnoea on exposure to barley only. These symptoms showed work relationship. He became asymptomatic after his transfer to another department dealing with sales only. Bronchial provocation testing to the barley confirmed the diagnosis.

Adult↗

A study of bond strength of dentin bonding agents to human dentin.

BACKGROUND: Marginal leakage of restoration induced by polymerization shrinkage of composite resin can be prevented if the dentin bonding agent is strong enough to counteract the force of polymerization shrinkage. METHODS: Fifty molar teeth obtained due to periodontal problem were used in this investigation. Crown portion of the teeth was grounded perpendicular to the long axis of the teeth until a complete layer of dentin surrounded by enamel was created. The teeth were then mounted with dental stone, and divided into five groups randomly. Dentin bonding agent was applied to the dentinal surface and a gelatin capsule mold was used to apply composite resin material. After incubation, the bonded composite specimens were tested with Instron universal testing machine in order to determine the shear strength of the composite bonding result. The fracture patterns were examined with scanning electron microscope. RESULTS: The Universal bond 3 combined with the AP.H composite exhibited the highest shear bond strength (10.76 MPa). The fracture pattern of the Universal Bond 3 combined with AP.H was mainly that of cohesive failure in the composite resin part instead of adhesive failure in the other groups tested. CONCLUSIONS: The shear bond strength of these five dentin bonding agents ranged from 2.89MPa to 10.76MPa. The fracture pattern of the tested groups was mainly that of adhesive failure at the interface between dentin bonding agent and its corresponding composite resin instead of cohesive failure disclosed in the composite resin part of Universal Bond 3 combined with AP.H group.

Biomechanical Phenomena↗

Leukotriene D4-induced increases in cytosolic calcium in THP-1 cells: dependence on extracellular calcium and inhibition with selective leukotriene D4 receptor antagonists.

Agonist-induced changes in intracellular calcium ion concentration ([Ca++]i) were examined in human monocytic leukemia THP-1 cells loaded with fura 2/acetoxymethyl ester (fura 2/AM). Leukotriene (LT)D4 induced a concentration-dependent biphasic response consisting of a transient phase (up to 5-fold peak increase) followed by a sustained phase, showing characteristics of a receptor-operated calcium channel. Homologous desensitization to LTD4 was observed. The responses to LTD4 were reduced by 80 to 90% in calcium-free buffer. The responses to LTD4 in a calcium-free buffer were dependent upon the duration of prior exposure of the cells to a calcium-free environment. The response at 30 or 60 min after exposure to calcium-free buffer was greater than that at earlier time points (time-dependent sensitization). Similar responses were obtained with THP-1 cells exposed to EDTA-containing buffer. It is speculated that such time-dependent sensitization is a result of changes at the receptor level. The responses to LTD4 were blocked by two specific LTD4 antagonists, MK-0571 and ICI-204,219, in a concentration-dependent manner. When given after addition of LTD4, MK-0571 or ICI-204,219 reversed the sustained phase of the LTD4-induced response, suggesting that maintenance of the response requires persistent activation of the LTD4 receptor. ICI-204,219 was 5 to 10 times more potent than MK-0571 (IC50 values of 1.1 and 9.3 nM, respectively), in agreement with results from radioligand binding studies reported separately.

Calcium↗

Ocular toxoplasmosis in the fetus. Immunohistochemistry analysis and DNA amplification.

PURPOSE: Ocular toxoplasmosis is often the result of a congenital infection. However, the earlier stages of the ocular lesions in the fetus have not been well studied. The purpose of the present study is to analyze the ocular findings in four aborted fetuses that were infected congenitally with Toxoplasma gondii. METHODS: Eight eyes from four fetuses of 22 to 27.5 weeks with T. gondii infection were studied by routine and immunohistochemical techniques. Two of the four were also examined by polymerase chain reaction (PCR). RESULTS: In two cases, the results of gross and histopathologic of the eyes were normal; marked retinal necrosis was present in the other two cases. Although no toxoplasmic cysts were identified by routine histopathologic examination, antigens of the tachyzoite were detected by immunohistochemistry analysis in the areas of retinal necrosis. In one of the cases with ocular lesions, the presence of T. gondii was confirmed by PCR. The presence of ocular lesions correlated with the severity of pathologic changes in the central nervous system. Large numbers of T cells were observed in the retinal lesions and in the choroid. CONCLUSION: Retinal necrosis, neovascularization, and marked chorioretinal inflammations despite the absence of bradyzoites are characteristic findings in the fetal eyes infected with T. gondii, and infiltrating T lymphocytes play a role in early recognition of the toxoplasma organism.

Adult↗

Ectopic expression of gamma interferon in the eyes of transgenic mice induces ocular pathology and MHC class II gene expression.

PURPOSE: To direct the expression of gamma IFN to the eyes of transgenic mice as a means of investigating the possible role of this lymphokine in ocular pathogenesis. METHODS: Transgenic mouse strains were generated by injection of a DNA fragment containing the murine alpha A-crystallin promoter fused to the coding sequence of murine gamma IFN gene. PCR and RT-PCR were used to screen for the presence of the transgene and mRNA analyses, respectively. Methacrylate-embedded eye sections were analyzed for morphology and cryosections for immunoperoxidase antibody staining. RESULTS: The most notable effects of gamma IFN in these transgenic mice include cataract, microphthalmia, blepharophimosis, microphakia, impairment of lens fiber formation, arrest of retinal differentiation, serous retinal detachment with presence of macrophages in the subretinal space, persistent hyperplastic primary vitreous, and corneal vascularization. MHC class II mRNA levels were significantly increased in the transgenic eyes and MHC class II proteins were expressed in their cornea, iris, ciliary body, choroid, lens and RPE. CONCLUSIONS: Ectopic expression of gamma IFN in the lens affected the growth of the whole eye, resulting in microphthalmia and microphakia. The author's data suggest that alpha ACry-gamma IFN transgenic mouse ocular cells express functional gamma IFN receptors and that interaction of gamma IFN with its receptor induced biochemical and morphologic changes in the transgenic eyes. These mice provide an animal model for the study of the linkage between aberrant MHC expression and predisposition to autoimmune diseases.

Animals↗