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Biomedical subjects

C-C Chan

Publications and source records attributed to C-C Chan.

14 recordsLinked to original sources

Interferon-gamma induces regression of epithelial cell carcinoma: critical roles of IRF-1 and ICSBP transcription factors.

We have developed an epithelial cell carcinoma model for studying efficacy of IFNgamma gene therapy and have identified components of IFNgamma-signaling pathway responsible for its direct anti-tumor actions. The tumor results from ectopic expression of SV40 Large T-Antigen (SV40 T-Ag) oncogene in lens of transgenic mouse (alphaT3) and complete regression of the tumor is induced by targeting expression of IFNgamma into malignant lens cells. Inflammatory cells are absent in lens of alphaT3 or DT (co-expressing IFNgamma and SV40-T-Antigen) mice and the transformed lens cells are non-immunogenic, suggesting non-involvement of immunologic cells. We show that IFNgamma has direct growth-inhibitory effects on tumor cells, induces death of tumor cells by apoptosis and that these effects are mediated by two transcription factors, IRF-1 (interferon-regulatory factor-1) and ICSBP (interferon-consensus sequence-binding protein) induced by IFNgamma. Furthermore, stable transfection with ICSBP or IRF-1 construct inhibits lens carcinoma cell growth by upregulating Caspase-1, p21(WAF1) and p27 expression. In contrast, tumor progression in alphaT3 lens correlates with inhibition of IRF-1 and ICSBP expression. Our results suggest that IFNgamma gene therapy maybe effective in malignant diseases for which DNA tumor viruses are etiologic agents and that antitumor actions of IRF-1/ICSBP can be exploited therapeutically to circumvent adverse clinical effects associated with IFN therapy.

Animals↗

Virus-induced chalazion.

PURPOSE: To investigate a viral etiology in certain chalazia. METHODS: A prospective study over 7.5 years of all newly presenting chalazia associated with diffuse follicular conjunctivitis but without any other aetiological factors. Patients were investigated for ocular or systemic infections by history, physical exam, slit-lamp exam, and/or histology of conjunctival biopsy (including transmission electron microscopy). RESULTS: A total of 27 patients developed follicular conjunctivitis without meibomian gland dysfunction, blepharitis, or sexually transmitted diseases. Evidence for a viral aetiology included: recent systemic viral illness (15/27), recent contact with subjects with chalazia or follicular conjunctivitis (5/27), preauricular lymphadenopathy (4/27), viral corneal disease (4/27), or viral particles by ultrastructure (4/4). CONCLUSIONS: Chalazia may be associated with viral conjunctivitis. Intralesional corticosteroids should be considered with great caution for viral-induced chalazia.

Adolescent↗

Detection of CX3CR1 single nucleotide polymorphism and expression on archived eyes with age-related macular degeneration.

There is a significant genetic component in age-related macular degeneration (AMD). CX3CR1, which encodes the fractalkine (chemokine, CX3CL1) receptor, has two single nucleotide polymorphisms (SNPs): V249I and T280M. These SNPs are correlated with other aged-related diseases such as atherosclerosis. We have reported an association of CX3CR1 SNP and AMD. In this study we examined CX3CR1 SNP frequencies and protein expression on archived sections of AMD and normal eyes. We microdissected non-retinal, peripheral retinal and macular cells from archived slides of eyes of AMD patients and normal subjects. CX3CR1 SNP typing was conducted by PCR and restriction fragment length polymorphism analysis. CX3CR1 transcripts from retinal cells were also measured using RT-PCR. CX3CR1 protein expression was evaluated using avidin-biotin complex immunohistochemistry. We successfully extracted DNA from 32/40 AMD cases and 2/2 normal eyes. Among the 32 AMD cases, 18 had neovascular AMD and 14 had non-neovascular AMD. The M280 allele was detected in 19/64 (32 cases x2) with a frequency of 29.7%, which was significantly higher as compared to the frequency in the normal population (11.2%). We detected CX3CR1 expression in the various retinal cells. CX3CR1 transcript and protein levels were diminished in the macular lesions. This study successfully analyzed CX3CR1 SNP and transcript expression in microdissected cells from archived paraffin fixed slides. Our data suggest that the M280 allele, a SNP resulting in aberrant CX3CR1 and CX3CL1 interaction, as well as lowered expression of macular CX3CR1, may contribute to the development of AMD.

Age Factors↗

Lack of detrimental effects of nitric oxide inhibition in bile duct-ligated rats with hepatic encephalopathy.

BACKGROUND: The pathogenetic mechanisms of hepatic encephalopathy (HE) are not fully understood. Vasodilatation induced by nitric oxide (NO) may be involved in the development of HE. There is no comprehensive data concerning the effects of NO inhibition on HE in chronic liver disease. METHODS: Male Sprague-Dawley rats weighing 240-270 g at the time of surgery were selected for experiments. Secondary biliary cirrhosis was induced by bile duct ligation (BDL). Counts of movements were compared between BDL rats and rats receiving a sham operation. In another series of experiments, BDL rats received either Nomega-nitro-L-arginine methyl ester (L-NAME, 25 mg kg-1 day-1 in tap water) or tap water (control) from the 36th to 42nd days after BDL. Besides motor activities, plasma levels of tumour necrosis factor (TNF)-alpha and nitrate/nitrite, liver biochemistry tests and haemodynamics were determined after treatment. RESULTS: Compared with the sham-operated rats, the total, ambulatory and vertical movements were significantly decreased in the BDL rats (P </= 0.001). The L-NAME group had a significantly higher mean arterial pressure than that of the control group (119.0 +/- 2.5 mmHg vs. 97.3 +/- 2.8 mmHg, P = 0.002). However, the counts of motor activities, plasma levels of TNF-alpha and nitrate/nitrite, and serum biochemistry tests were not significantly different between the L-NAME and control groups. CONCLUSIONS: Bile duct ligation may induce HE evidenced by a decrease in motor activities. However, chronic L-NAME administration did not have significantly detrimental or therapeutic effects on the severity of encephalopathy in BDL rats.

Animals↗

Effects of endothelin-1 on portal-systemic collaterals of common bile duct-ligated cirrhotic rats.

BACKGROUND/AIMS: Endothelin-1 (ET-1) may induce intrahepatic vasoconstriction and consequently increase portal pressure. Endothelin-1 has been shown to exert a direct vasoconstrictive effect on the collateral vessels in partially portal vein-ligated rats with a high degree of portal-systemic shunting. This study investigated the collateral vascular responses to ET-1, the receptors in mediation and the regulation of ET-1 action by nitric oxide and prostaglandin in cirrhotic rats with a relatively low degree of portal-systemic shunting. METHODS: The portal-systemic collaterals of common bile duct-ligated (BDL) cirrhotic rats were tested by in situ perfusion. The concentration-response curves of collaterals to graded concentrations of ET-1 (10(-10)-10(-7) m) with or without BQ-123 (ET(A) receptor antagonist, 2 x 10(-6) m), BQ-788 (ET(B) receptor antagonist, 10(-7) m) or both were recorded. In addition, the collateral responses to ET-1 with preincubation of N(omega)-nitro-L-arginine (NNA, 10(-4) M), indomethacin (INDO, 10(-5) M) or in combination were assessed. RESULTS: Endothelin-1 significantly increased the perfusion pressures of portal-systemic collaterals. The ET-1-induced constrictive effects were inhibited by BQ-123 or BQ-123 plus BQ-788 but not by BQ-788 alone. The inhibitory effect was greater in the combination group. Pretreatment of NNA or NNA plus INDO equivalently enhanced the response of ET-1 while pretreatment of INDO alone exerted no effect. CONCLUSION: Endothelin-1 has a direct vasoconstrictive effect on the collaterals of BDL cirrhotic rats, mainly mediated by ET(A) receptor. Endogenous nitric oxide may play an important role in modulating the effects of ET-1 in the portal-systemic collaterals of BDL cirrhotic rats.

Animals↗

A correlation of pregnancy term, disease activity, serum female hormones, and cytokines in uveitis.

BACKGROUND/AIMS: Pregnancy and the postpartum period are associated with the activity of autoimmune diseases including uveitis. Although the exact mechanism is unknown, hormones are reported to alter inflammatory cytokines and influence disease activity. The authors studied ocular inflammation, female hormones, and serum cytokine levels during and after pregnancy. METHODS: A prospective, observational case study was conducted. Four pregnant women in their first trimester with chronic non-infectious uveitis were followed monthly until 6 months after delivery. Serum female hormones (oestrogen, progesterone, prolactin) and various cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IFN-gamma, and TGF-beta) were measured by ELISA. RESULTS: The four patients had five full term pregnancies. Uveitis activity decreased after the first trimester but flared in the early postpartum period. Serum female hormones, highly elevated during pregnancy, drastically dropped post partum. Cytokine levels except TGF-beta were mostly undetectable. CONCLUSION: Female hormones and TGF-beta may contribute to the activity of uveitis during pregnancy and the postpartum period.

Administration, Oral↗

Helicobacter pylori (H. pylori) molecular signature in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma.

Conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal marginal zone B-cell lymphoma that is characterized by an exaggerated clonal expansion of B cells, which implicate a pathological proliferative response to antigen(s) including bacteria. Helicobacter pylori (H. pylori) infection is recognized as one of the causative agents of gastric MALT lymphoma; however, it has not been reported in extra gastric MALT lymphoma. We studied 5 patients (4 adults and 1 child) with salmon-colored conjunctival lesions. One patient also had a history of abnormal bone marrow biopsy a year earlier with lymphoid aggregates involving 5% of the overall bone marrow. The conjunctival lesions of the 5 patients were biopsied. Histopathological diagnoses were consistent with conjunctival MALT lymphoma. Lymphoma and normal conjunctival cells were microdissected using laser capture microscopy or manual techniques. DNA was extracted and subjected to PCR amplification using H. pylori gene-specific primers from the urease B and vac/m2 gene. Cells from chronic conjunctivitis (normal lymphocytes), conjunctival human T-cell lymphotropic virus type-1/adult T-cell leukemia/lymphoma (HTLV-1/ATL), and orbital B-cell lymphoma were also microdissected, processed and analyzed. PCR amplification and Southern blot hybridization demonstrated H. pylori DNA in the conjunctival MALT lymphoma cells of 4/5 cases. The negative case was the one with a history of abnormal bone marrow. In contrast, H. pylori gene was not detected in normal conjunctival cells from the cases of MALT lymphoma or the lymphocytes, ATL and orbital B-lymphoma cells from the controls. These data suggest that H. pylori may play a role in conjunctival MALT lymphoma.

Aged↗

A novel inflammatory eye disease induced by lymphocytes from knockout mice sensitized against the deleted ocular antigen.

Lens-associated uveitis (LAU), a severe inflammatory eye disease, is thought to be mediated by autoimmunity against lens crystallins. Previously described animal models for this disease are antibody-mediated, since no cellular response to self crystallins could be induced in experimental animals. Here, we describe a new model for LAU, in which lymphocytes from knockout mice deficient in alphaB-crystallin are sensitized against the deleted protein and induce severe ocular inflammation when adoptively transferred into wild type recipients. Similar to LAU, the experimental disease developed only following rupture of the lens capsule, produced in this study by capsulotomy; no disease was detected in recipient eyes with no capsulotomy, or in those treated with cautery, or in eyes affected by systemic treatment with sodium iodate, lipopolysaccharide or X-irradiation. The ocular changes in affected eyes included heavy cellular infiltration and proteinaceous exudate in both the anterior and posterior segments of the eye, that reached their peak on day 4 following cell transfer and subsided quite rapidly thereafter.

Adoptive Transfer↗

Cyclooxygenase expression in splanchnic hyposensitivity to glypressin of bleeding portal hypertensive rats.

BACKGROUND: Prostacyclin mediates, at least partly, the splanchnic vascular hyporesponsiveness to glypressin in bleeding portal hypertensive rats. This study investigated the relative contribution of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in the splanchnic hyposensitivity to glypressin in rats with portal hypertension induced by partial portal vein ligation (PVL). METHODS: Fourteen days after the operation, the rats were divided into without- and with-bleeding groups. Three series of PVL rats were used to investigate (i). the haemodynamic effects of glypressin (0.07 mg x kg(-1) intravenously), (ii). COX-1/COX-2 mRNA expression over abdominal aorta and superior mesenteric artery and (iii). plasma levels of 6-keto-prostaglandin-F1alpha. In rats with a hypotensive haemorrhage, 4.5 mL of blood was withdrawn and 50% of the withdrawn blood was re-infused before blood and vessel sampling or the administration of glypressin. RESULTS: Splanchnic hyposensitivity to glypressin was demonstrated in the haemorrhage-transfused PVL rats with enhanced COX-1 expression of superior mesenteric artery and increased plasma levels of 6-keto-prostaglandin-F1alpha. There were no differences in the COX-2 expression of superior mesenteric artery and COX-1 and COX-2 expressions of abdominal aorta between without- and with-bleeding groups. CONCLUSION: In portal hypertensive rats with acute haemorrhage, COX-1 over-expression in the superior mesenteric artery plays a role in mediating the splanchnic hyposensitivity to glypressin.

Animals↗

Effects of long-term octreotide treatment on the response of portal-systemic collaterals to vasopressin in portal hypertensive rats.

BACKGROUND: Chronic portal hypertension is associated with the development of portal-systemic collaterals. Long-term octreotide treatment has been shown to enhance the constrictive response to vasopressin in the mesenteric arteries of portal hypertensive rats. This study investigated the effects of long-term octreotide treatment on the response of portal-systemic collaterals to vasopressin in portal hypertensive rats. METHODS: Partially portal vein-ligated rats were divided into two groups to receive subcutaneous injection of either placebo (5% dextrose in water) or octreotide (30 microg kg(-1)) twice daily for 7 days. Two series of experiments were performed to measure: (a) the systemic and portal hemodynamics and cumulative concentration-response curves of collateral vessels to vasopressin (10(-10) to 10(-7 )M) and (b) the slopes of the flow-pressure curves of collaterals (an index of portal-systemic shunting). The cumulative concentration-response curves and flow pressure curves were determined by the in situ collateral perfusion. RESULTS: Long-term octreotide treatment significantly lowered the portal pressure without changes in the mean arterial pressure. Vasopressin significantly and similarly increased the perfusion pressure of collateral vessels in both the placebo- and octreotide-treated groups. In addition, long-term octreotide treatment exerted no effect on the EC(50) of vasopressin (-8.25 +/- 0.19 vs. -8.20 +/- 0.10, P > 0.05) and the slopes of flow-pressure curves (0.97 +/- 0.02 vs. 0.94 +/- 0.04, P > 0.05) in the collaterals. CONCLUSION: Despite lowering the portal pressure, long-term octreotide treatment did not enhance the vasoconstrictive effect of vasopressin in the collateral vessels of portal hypertensive rats and ameliorate the degree of portal-systemic shunting.

Animals↗

Increased morbidity from nasopharyngeal carcinoma and chronic pharyngitis or sinusitis among workers at a newspaper printing company.

OBJECTIVES: To determine the association between printing works and nasopharygeal carcinoma as well as other diseases. METHODS: Demographic data were obtained for those who had worked in a particular newspaper company since its establishment in 1950. Through access to the data bank of the hospital records of the Labor Insurance Bureau for 1985-94, all workers were identified who had been admitted to hospital during their employment in the newspaper company. Multiple logistic regressions were performed to estimate the adjusted morbidity odds ratio (OR) for various diseases among the printing workers with cardiovascular diseases as the reference diseases. Biopsy specimens from patients with nasopharyngeal carcinoma were all subjected to in situ hybridisation of Epstein-Barr virus (EBV), and colocalisation of EBV and secretor component protein. RESULTS: Of the 1564 people who had worked in this company, 579 of them were admitted to hospital at least once. Five out of 144 printing workers admitted to hospital were diagnosed with nasopharyngeal carcinoma compared with none of the other 435 non-printing workers admitted to hospital. The morbidity OR for nasopharyngeal carcinoma in printing workers was 57.0 (95% confidence interval (95% CI) 2.8 to 1155.3). The morbidity OR for benign skin tumours was 28.0 (95% CI 2.7 to 293.1). Chronic pharyngitis or sinusitis also showed significant relations with printing works with a morbidity OR 29.4 (95% CI 1.7 to 514.7). Using all other diseases as the reference diseases for calculation of morbidity ORs still showed a similar trend. In situ hybridisation of EBV encoded small nuclear RNA-1 (EBER-1) showed tumour cells free of the EBV in each biopsy specimen. Colocalisation of EBER-1 and secretor component showed that some tumour cells contained both secretor component and EBV signal in each case. CONCLUSION: Printing works are associated with an increased risk of nasopharyngeal carcinoma, benign skin tumours, chronic pharyngitis or sinusitis, chronic liver diseases, and mechanical injuries. Induction of the development of nasopharyngeal carcinoma is probably not related to EBV infection in these patients.

Adult↗

Comparison of nitric oxide production motion characteristics of sperm after cryopreserved in three different preparations.

Three ml of semen collected from 20 volunteers were divided into three aliquots: a) semen cryopreserved for 48 hr then swim-up method; b) using swim-up method then cryopreserving for 48 h; and c) using 45%-90% two layers PureSperm to prepare sperm then cryopreserved for 48 h. Motility characteristics were evaluated before cryopreservation and after thawing. NO was measured using the chemiluminescence method after centrifugation. The recovery rate and motion parameters were the highest in the swim-up group. NO produced in the swim-up group was significantly lower than the PureSperm group, and the PureSperm group was lower than the semen treated with cryoprotectant group. Best semen quality was achieved due to the decreased NO production.

Cryopreservation↗