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Biomedical subjects

C C Chan

Publications and source records attributed to C C Chan.

At least 253 records · Page 14Linked to original sources
PubMed1997

Predictive pulmonary function of school children in an area of low air pollution in Taiwan.

The objective of this study was to determine the effect of different parameters on a predictive model of pulmonary function for elementary school children in an area of low air pollution in Taiwan. Healthy children aged 7 to 12 years from three elementary schools in low-air-pollution areas (Da-Chen, Mai-Liau and Tai-Si) participated in the study. A total of 836 children (423 boys and 413 girls) were included in the study. During summer vacation, each child underwent a physical examination including a screening spirometry. A questionnaire regarding respiratory symptoms and indoor air pollutants was also completed by the children's parents. Air monitoring showed that the levels of outdoor pollutants were relatively low. Multiple linear regression analysis was performed with FVC (forced vital capacity) and FEV1 (forced expiratory volume in 1 sec) as dependent variables. Gender, age, height, weight, technician and indoor air pollution parameters were the independent variables. The results showed that gender,height, weight and technician were the most significant variables for predicting FVC and FEV1. The various indoor air pollution parameters seemed to have no influence on the pulmonary function of children, except that mildew in bedrooms mildly decreased FEV1. Regression analysis showed that all the pulmonary function parameters measured had a positive correlation with height, whereas weight correlated only with certain parameters. Because both indoor and outdoor air pollution was relatively low, we suggest that this model could be used as a basic predictive model of pulmonary function for elementary school children in Taiwan.

Air Pollution↗
PubMed1997

Twenty-four-hour ambulatory esophageal pH monitoring in patients with symptoms of gastroesophageal reflux.

We investigated the relationship between gastric acid reflux patterns and esophageal mucosal damage in 142 patients with symptoms suggestive of gastroesophageal reflux and esophagitis. Each patient underwent endoscopy of the esophagus and 24-hour ambulatory esophageal pH monitoring. Endoscopy revealed varying degrees of esophagitis in 37 patients and a normal esophagus 105 patients. No significant difference in symptoms was found between patients with and without esophagitis. Sixteen of the 37 patients with esophagitis had a normal composite score on pH monitoring, whereas 24 of the 105 patients without esophagitis had an abnormal composite score (p < 0.001). Comparison of individual pH parameters during the study showed more reflux episodes (pH < 4), a higher percentage of reflux time, and more reflux episodes longer than 5 minutes in the group with esophagitis than in the without (p < 0.05). Both the percentage of reflux time and the number of reflux episodes longer than 5 minutes/hour were significantly higher (p < 0.05) in the group with endoscopically proven esophagitis in the supine period, but not in the upright period. There was a positive correlation between the severity of endoscopic esophagitis and the percentage of reflux time in the supine period (r = 0.64; p < 0.001), and the number of reflux episodes longer than 5 minutes/hour in the supine period (r = 0.56; p < 0.001). In conclusion, our patients with peptic esophagitis had significant gastric acid reflux and impaired acid clearance by the esophagus in the supine position. We advocate that 24-hour ambulatory esophageal pH monitoring should be considered in Chinese patients with normal endoscopy findings but with symptoms suggestive of gastroesophageal reflux disease.

Adult↗
PubMed1996

Dioxabicyclooctanyl naphthalenenitriles as nonredox 5-lipoxygenase inhibitors: structure-activity relationship study directed toward the improvement of metabolic stability.

Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicyclo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).

Animals↗
PubMed1996

Genetic susceptibility to experimental autoimmune uveoretinitis in the rat is associated with an elevated Th1 response.

This study examines whether genetic susceptibility vs genetic resistance to experimental autoimmune uveoretinitis (EAU) are connected to a predisposition to mount a Th1-dominated (IFN-gamma high, IL-4 low) vs a Th2-dominated (IL-4 high, lFN-gamma low) response. Lewis rats developed disease with high incidence after immunization with the uveitogenic peptide R16, whereas F344 rats were resistant. Primed lymph node cells from both strains proliferated in culture in response to R16. However, while the Lewis cultures transferred EAU to syngeneic recipients, those of F344 did not. The Lewis cultures produced substantially more IFN-gamma mRNA and protein in response to R16, than did those of F344. Both strains made low levels of IL-10 mRNA and IL-4 mRNA. Unlike the primary cultures, long-term (R16-specific) T cell lines derived from each of the strains transferred EAU equally well to their respective recipients, and produced similar, high levels of IFN-gamma mRNA and protein. Treatment of F344 with Bordetella pertussis toxin concurrently with immunization abrogated its resistance, enhanced Ag-specific IFN-gamma production in culture, and yielded a primed cell population capable of transferring EAU. Conversely, immunization of Lewis rats with R16 in IFA induced little or no disease; the primed cells produced minimal amounts of IFN-gamma and did not transfer EAU. However, addition of IL-12 into the culture resulted in a highly pathogenic, IFN-gamma-producing cell population. We conclude that genetic susceptibility to ocular autoimmunity in this model is connected to an elevated Th1 response. Genetic resistance, however, does not seem to involve an elevated Th2 response, but rather an inhibited development of Th1-like effector cells.

Amino Acid Sequence↗
PubMed1996

Contribution of nitric oxide to the host parasite equilibrium in toxoplasmosis.

We studied the effect of nitric oxide (NO) production on the evolution of toxoplasmosis in C57BL/6 mice. Infection was induced by i.p. injection of Toxoplasma gondii strain ME49. NO synthesis was inhibited by treatment with aminoguanidine, a structural analogue of L-arginine. The severity of infection was evaluated by histopathologic examination of the brain. In the infected mice treated for 2 wk with aminoguanidine, we observed an increase in the number of toxoplasma tachyzoites and intracellular cysts accompanied by an exacerbated inflammation of the brain tissue compared with that in controls. When spleen cells from infected mice were stimulated in culture with toxoplasma Ag, there was a marked cytotoxic effect on cells collected during the acute stage of infection and an inhibition of proliferation of the remaining viable lymphocytes. These effects were correlated with high levels of NO and PGE2 production. The suppression of NO synthesis prevented cell death and restored the lymphocyte proliferative response as well as lymphokine production. The neutralization of IFN-gamma or TNF-alpha had no effect on NO production in the cultures of infected mouse spleen cells. Cultures in which purified macrophages and lymphocytes from infected and naive mice were mixed indicated that the production of NO was dependent on lymphocyte activation. In the later stages of infection, when the production of NO was abating, preventing PGE2 secretion with indomethacin also increased the lymphocyte proliferative response. We conclude that the opposing effects of NO in toxoplasmosis, which protects against Toxoplasma gondii and at the same time limits the immune response, probably contribute to the establishment of the characteristic chronic state of host parasite equilibrium.

Animals↗
PubMed1996

Establishment and characterization of a murine CD4+ T cell line and clone that induce experimental autoimmune uveoretinitis in B10.A mice.

B10.A mice develop experimental autoimmune uveoretinitis after active immunization with the interphotoreceptor retinoid-binding protein (IRBP). CD4+ T cells play an important role in the development of the disease. In this study we have isolated and characterized a CD4+ T cell line and a T cell clone that induce experimental autoimmune uveoretinitis when transferred into naive B10.A mice. The cell line was isolated from draining lymph nodes of IRBP-immunized animals by repeated cycles of IRBP stimulation. The line was shown to be pathogenic after 4 rounds of in vitro stimulation with IRBP at 5 x 10(6) cells/mouse. A T cell clone derived from this line by limiting dilution was shown to be pathogenic when the same number of cells was injected; incidence and severity of disease, however, were much lower. After 16 rounds of IRBP-specific stimulation the cell line was pathogenic at 10(5) cells/mouse. Analysis of the V beta repertoire revealed that at this point the line was mostly composed of V beta 8.2- and V beta 6-positive cells (> 80% of the population). The uveitogenic clone expressed V beta 8.2. Both the T cell line and the clone elaborated an unrestricted lymphokine profile in vitro. However, when these cells were adoptively transferred into naive recipients, mRNA isolated from the uveitic retina showed only Th1 type cytokines. These data help to characterize the nature of pathogenic cells involved in ocular autoimmunity.

Animals↗
PubMed1996

Cytokine-dependent modulation of oral tolerance in a murine model of autoimmune uveitis.

In summary, our data suggest that oral tolerance in the mouse EAU model may occur by anergy/deletion or by suppression, depending on the feeding regimen. Tolerance involving putative regulatory cells appears to require the ability to produce both IL-4 and IL-10, whereas induction of tolerance involving anergy may not require the presence of Il-4 and IL-10. We propose that regulatory cells induced by three feedings of IRBP can be selectively enhanced through the use of cytokines. From the point of view of clinical therapy, it would be worthwhile to explore postimmunization feeding regimens involving administration of IL-4 and IL-10.

Administration, Oral↗
PubMed1996

IL-12 inhibits endotoxin-induced inflammation in the eye.

Interleukin-12 (IL-12) is a heterodimeric cytokine that induces interferon (IFN)-gamma production and an increased generation of Th1 cells. Both IL-12 and IL-12 antagonists are being studied for the treatment of allergic reactions, autoimmune disease and malignancy. The goal of the present experiments was to examine the importance of IL-12 in endotoxin-induced ocular inflammation. The number of inflammatory cells infiltrating eyes with endotoxin-induced uveitis (EIU) was significantly increased in animals treated with intraperitoneal anti-IL-12 antibody when compared to control animals, but there was no difference in infiltrating inflammatory cells in the eyes of animals treated with IL-12 when compared to controls. In contrast, intraocular injection of IL-12 significantly inhibited the development of endotoxin-induced intraocular inflammation. The infiltrating inflammatory cells were reduced in the eyes of animals receiving intraocular IL-12 when compared to controls. Cytokine analysis of the aqueous humor obtained from eyes with EIU showed increased levels of IFN-gamma and decreased levels of IL-6 in eyes receiving intraocular IL-12. These data show that IL-12 has an inhibitory effect on endotoxin-induced inflammation in the eye and suggest that IL-12 can have an immunoregulatory function in some forms of inflammatory disease.

Animals↗
PubMed1996

Suppressive effect of transforming growth factor beta1 on the recurrence of experimental melanin protein-induced uveitis: upregulation of ocular interleukin-10.

Uveitis is induced in Lewis rats by immunization with bovine melanin protein (BMP) derived from the uvea and retinal pigment epithelium. Recurrence of this experimental melanin protein-induced uveitis (EMIU) develops after footpad injection of a minimal amount of Salmonella typhimurium endotoxin (LPS) following the remission of EMIU. To investigate the effect of transforming growth factor beta1 (TGFbeta1) on the recurrence of EMIU, 5 micrograms LPS booster was given to Lewis rats by footpad injection on Day 45 after BMP immunization. Daily TGFbeta1 or phosphate-buffered saline was administered either from Day 0 to 7 (group 1) or from Day 7 to 13 (group 2) after LPS booster. Delayed-type hypersensitivity (DTH) ear test was conducted on Day 12 after LPS booster and eye and blood were collected on Day 14. The incidence and severity of recurrent uveitis markedly decreased in both groups of TGFbeta1-treated rats. A lower level of serum BMP antibody was also observed by agglutination in these groups. There was no statistical difference in DTH responses between the treated and control groups. Ocular cytokine mRNA of group 1 and controls was analyzed by RT-PCR. Interleukin (IL)-2 and interferon-gamma were not detectable. IL-4 was identified at a similar level in both groups. A higher level of IL-10 was observed in group 1 rats. We conclude that TGFbeta1 suppresses recurrent EMIU, probably through upregulation of IL-10.

Animals↗
PubMed1996

A human whole blood assay for clinical evaluation of biochemical efficacy of cyclooxygenase inhibitors.

In this study, PGE2 levels in lipopolysaccharide (LPS)-challenged human whole blood and TxB2 levels following blood coagulation were measured as biochemical index for cyclooxygenase (Cox)-2 and Cox-1 activity respectively. Incubation of human mononuclear cells isolated from whole blood with LPS (100 mu g/mL) induced a time-dependent increase in the expression of Cox-2 protein (>100 fold at 24 hr). This is associated with increases in PGE2 production and free arachidonate release in the plasma. Cox-1 protein was detected in the human mononuclear cells at time zero but was not induced by either LPS or PBS. Most non-steroidal anti-inflammatory drugs (NSAIDs) are more potent at inhibiting Cox-1 than Cox-2. Five experimental compounds CGP-28238, Dup-697, NS-398, SC-58125 and L-745,337, have a greater selectivity for Cox-2. Indomethacin at a single oral dose (25 mg) inhibited approximately 90% the whole blood Cox-2 and Cox-1 activities ex vivo in healthy subjects. These results support the use of this assay to assess the biochemical efficacy of selective Cox-2 inhibitors in clinical trials.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

Tumor detachments of the retinal pigment epithelium in ocular/ central nervous system lymphoma.

BACKGROUND: Ocular/central nervous system (CNS) lymphoma is a B-lymphocyte-derived tumor that characteristically involves the retina, optic nerve head, vitreous, and subretinal pigment epithelial areas of the eye. METHOD: A retrospective analysis of clinical history and photography fluorescein angiography, histopathology, and immunocytochemistry of an untreated patient with ocular/CNS lymphoma was performed. RESULTS: Tumor detachments of the retinal pigment epithelium (RPE) evolved into areas of RPE atrophy and depigmentation and disciform scars. Histopathologic studies disclosed foci of tumor cells in the wall of and around blood vessels and between the RPE and Bruch's membrane. Immunocytochemistry identified the malignant cells as B-lymphocytes. CONCLUSIONS: The clinicopathologic features of a patient with ocular/CNS B-cell lymphoma are presented. Retinal pigment epithelium tumor detachments evolved to areas of RPE atrophy and depigmentation and disciform scars.

Aged↗
PubMed1996

Fluorescein angiography in the progressive outer retinal necrosis syndrome.

PURPOSE: Progressive outer retinal necrosis syndrome is a devastating retinopathy seen primarily in patients with acquired immune deficiency syndrome. To provide additional details of the pathogenesis of this disease, the authors describe the evolution of clinical and fluorescein angiographic changes during the course of progressive outer retinal necrosis syndrome. METHODS: The authors performed serial clinical examinations, fundus photography, and fluorescein angiography in a patient with acquired immune deficiency syndrome with progressive outer retinal necrosis syndrome. Clinical and fluorescein angiographic findings were correlated to provide detailed sequential analysis of the pathologic changes occurring during the course of this disorder. RESULTS: The angiographic changes seen during the various stages of the disease consisted of zonal microvascular alterations, retinal pigment epithelium (RPE) destruction, and choroidal leakage. Retinal damage was correlated closely with regions of choroidal leakage and was clinically evident as outer retinal whitening. Disease reactivation occurred as a prominent brush-fire border of intense leakage involving the retina, RPE, and choroid. Extensive damage to the retinal vasculature and RPE was noted in the wake of clinical infection. CONCLUSIONS: The angiographic findings in our patient demonstrate that the progressive outer retinal necrosis syndrome is a retinochoroiditis that involves the full thickness of retina as well as the RPE and choroid. The inflammatory changes seen throughout the course of this disease correlate with the histopathologic patterns reported to date.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Organizational characteristics and information content of an archaeal genome: 156 kb of sequence from Sulfolobus solfataricus P2.

We have initiated a project to sequence the 3 Mbp genome of the thermoacidophilic archaebacterium Sulfolobus solfataricus P2. Cosmids were selected from a provisional set of minimally overlapping clones, subcloned in pUC18, and sequenced using a hybrid (random plus directed) strategy to give two blocks of contiguous unique sequence, respectively, 100,389 and 56,105 bp. These two contigs contain a total of 163 open reading frames (ORFs) in 26-29 putative operons; 56 ORFs could be identified with reasonable certainty. Clusters of ORFs potentially encode proteins of glycogen biosynthesis, oxidative decarboxylation of pyruvate, ATP-dependent transport across membranes, isoprenoid biosynthesis, protein synthesis, and ribosomes. Putative promoters occur upstream of most ORFs. Thirty per cent of the predicted strong and medium-strength promoters can initiate transcription at the start codon or within 10 nucleotides upstream, indicating a process of initial mRNA-ribosome contact unlike that of most eubacterial genes. A novel termination motif is proposed to account for 15 additional terminations. The two contigs differ in densities of ORFs, insertion elements and repeated sequences; together they contain two copies of the previously reported insertion sequence ISC 1217, five additional IS elements representing four novel types, four classes of long non-IS repeated sequences, and numerous short, perfect repeats.

Chromosomes, Bacterial↗
PubMed1996

Transdiaphragmatic pressure in young adult Singaporean subjects--normal values and a comparison between different respiratory manoeuvres.

BACKGROUND: Most published normal values for transdiaphragmatic pressure (Pdi) have been from Caucasian subjects and there is no universal agreement regarding the most appropriate manoeuvre for assessing Pdi. AIMS: The aims of our study were to obtain normal values and to compare the different manoeuvres used to assess Pdi in normal young Singaporean adults. METHODS: Twenty-four normal subjects (23 Chinese, one Indian) were studied by measuring Pdi during maximal sniffs from functional residual capacity (sniff Pdi), maximal inspiration to total lung capacity (Pdi TLC) and maximal static inspiratory efforts from residual volume (Pdi PImax). RESULTS: Mean values +/- SD for sniff Pdi, Pdi TLC and Pdi PImax were 101.8 +/- 31.7, 46.8 +/- 26.4 and 83.5 +/- 35.5 cm H2O respectively. Sniff Pdi was significantly higher than Pdi TLC (p < 0.001) and Pdi PImax (p = 0.005). Pdi PImax was significantly higher than Pdi TLC (p < 0.001). Males had significantly higher values for sniff Pdi (p = 0.026) and Pdi PImax (p = 0.022) than females. There was a significant correlation between the different methods of recording Pdi. Sniff Pdi had the highest values, least between- and within-subject variation and most consistent pattern of respiratory muscle recruitment with the lowest proportion of negative gastric pressure (Pg) values (p < 0.001). CONCLUSIONS: Therefore, sniff Pdi may be better than Pdi TLC and Pdi PImax in assessing diaphragm function. Also, our subjects seemed to have lower sniff Pdi and Pdi PImax, and higher Pdi TLC compared with Caucasian subjects.

Adult↗
PubMed1996

Protective role of nitric oxide in ocular toxoplasmosis.

AIMS: To evaluate the role of nitric oxide (NO) in ocular involvement during systemic toxoplasmosis. METHODS: C57B1/6 mice were infected with Toxoplasma gondii strain ME49. The synthesis of NO was inhibited by an intraperitoneal injection of aminoguanidine every 8 hours, starting on the day of infection. Control infected mice received phosphate buffered saline vehicle alone. After 14 days, the ocular lesions were evaluated by histopathological examination. The expression of NO synthase induced in the spleen by toxoplasma infection was evaluated by immunostaining. The production of NO by the spleen cells of infected mice was measured by the colorimetric assay of Griess in the supernatant of cultures stimulated with toxoplasma antigen or concanavalin A. RESULTS: The inhibition of NO production in T gondii infected mice resulted in a marked increase in the symptoms of ocular inflammation. We observed a strong induction of NO synthase expression in the spleen of infected animals. In culture, the spleen cells from these mice produced high levels of NO in response to T gondii antigens. This elevation of NO synthesis was suppressed in the presence of aminoguanidine. CONCLUSION: This study indicates that NO plays a crucial role in the protection against T gondii infection as reflected by the severity of the ocular involvement.

Animals↗
PubMed1996

Compressibility of perfused passive myocardium.

In most theoretical analyses of the heart, the tissue has been assumed to be incompressible. Because the myocardium is extensively perfused with distensible vessels, increasing the stiffness of the surrounding tissue, as with contraction or passive stretching, should decrease the volume of fluid in these vessels. Using a digital subtraction angiographic method, we quantified the amount of vascular volume extruded from six passive, perfused canine interventricular septa during cyclic biaxial loading from 300 to 900 g force. At pressures from 0 to 120 mmHg the amount of fluid extruded during a loading cycle varied from 2 to 4 ml/100 g tissue at 0 and 120 mmHg, respectively. This volume change increased with perfusion pressure and was significantly greater at 120 than at 0, 30, or 60 mmHg. The amount of fluid extruded was on the same order as that estimated during active contraction or with a 60-mmHg change in perfusion pressure. The finding that perfused myocardium is compressible implies that results from existing analyses of the heart assuming incompressibility are not realistic. Such analyses must account for compressibility with, e.g., mixture theory or other similar approaches.

Angiography, Digital Subtraction↗