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Joseph J Y Sung

Publications and source records attributed to Joseph J Y Sung.

At least 19 recordsLinked to original sources
PubMed2006

Expression of a cyclo-oxygenase-2 transgene in murine liver causes hepatitis.

BACKGROUND: It has been proved that cyclo-oxygenase-2 (COX-2) is rapidly induced by inflammatory mediators. However, it is not known whether overexpression of COX-2 in the liver is sufficient to promote activation or secretion of inflammatory factors leading to hepatitis. AIM: To investigate the role forced expression of COX-2 in liver by using inducible COX-2 transgenic (TG) mice. METHODS: TG mice that overexpress the human COX-2 gene in the liver using the liver-specific transthyretin promoter and non-TG littermates were derived and fed the normal diet for up to 12 months. Hepatic prostaglandin E(2) (PGE(2)) content was determined using enzyme immunoassay, nuclear factor kappaB (NF-kappaB) activation by electrophoretic mobility shift assays, apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labelling and proliferation by Ki-67 immunohistochemistry. RESULTS: COX-2 TG mice exhibited strongly increased COX-2 and PGE(2), elevated serum alanine aminotransferase level and histological hepatitis. Hepatic COX-2 expression in the TG mice resulted in activation of NF-kappaB and inflammatory cytokine cascade, with a marked expression of the proinflammatory cytokines tumour necrosis factor (TNF)-alpha (9.4-fold), interleukin (IL)-6 (4.4-fold), IL-1beta (3.6-fold), and of the anti-inflammatory cytokine IL-10 (4.4-fold) and chemokine macrophage inflammatory protein-2 (3.2-fold). The inflammatory response of the COX-2 TG mice was associated with infiltration macrophages and lymphocytes, increased cell proliferation and high rates of cell apoptosis. Administration of the COX-2 inhibitor celecoxib in TG mice restored liver histology to normal. CONCLUSION: Enhanced COX-2 expression in hepatocytes is sufficient to induce hepatitis by activating NF-kappaB, stimulating the secretion of proinflammatory cytokines, recruiting macrophage and altering cell kinetics. Inhibition of COX-2 represents a mechanism-based chemopreventive approach to hepatitis.

Animals↗
PubMed2006

Prospective comparison of three predictive rules for assessing severity of community-acquired pneumonia in Hong Kong.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading infectious cause of death throughout the world, including Hong Kong. AIM: To compare the ability of three validated prediction rules for CAP to predict mortality in Hong Kong: the 20 variable Pneumonia Severity Index (PSI), the 6-point CURB65 scale adopted by the British Thoracic Society and the simpler CRB65. METHODS: A prospective observational study of 1016 consecutive inpatients with CAP (583 men, mean (SD) age 72 (17) years) was performed in a university hospital in the New Territories of Hong Kong in 2004. The patients were classified into three risk groups (low, intermediate and high) according to each rule. The ability of the three rules to predict 30 day mortality was compared. RESULTS: The overall mortality and intensive care unit (ICU) admission rates were 8.6% and 4.0%, respectively. PSI, CURB65 and CRB65 performed similarly, and the areas under the receiver operating characteristic (ROC) curve were 0.736 (95% CI 0.687 to 0.736), 0.733 (95% CI 0.679 to 0.787) and 0.694 (95% CI 0.634 to 0.753), respectively. All three rules had high negative predictive values but relatively low positive predictive values at all cut-off points. Larger proportions of patients were identified as low risk by PSI (47.2%) and CURB65 (43.3%) than by CRB65 (12.6%). CONCLUSION: All three predictive rules have a similar performance in predicting the severity of CAP, but CURB65 is more suitable than the other two for use in the emergency department because of its simplicity of application and ability to identify low-risk patients.

Adolescent↗
PubMed2006

Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome.

Early life stress has been implicated as a risk factor for irritable bowel syndrome (IBS). We studied the effect of neonatal maternal separation on the visceromotor response and the expression of c-fos, 5-HT, and its receptors/transporters along the brain-gut axis in an animal model of IBS. Male neonatal Sprague-Dawley rats were randomly assigned to a 3-h daily maternal separation (MS) or nonhandling (NH) on postnatal days 2-21. Colorectal balloon distention (CRD) was performed for assessment of abdominal withdrawal reflex as a surrogate marker of visceral pain. Tissues from dorsal raphe nucleus in midbrain, lumbar-sacral cord, and distal colon were harvested for semiquantitative analysis of c-fos and 5-HT. The expression of 5-HT expression, 5-HT3 receptors, and 5-HT transporter were analyzed by RT-PCR. Pain threshold was significantly lower in MS than NH rats. The abdominal withdrawal reflex score in response to CRD in MS rats was significantly higher with distension pressures of 40, 60, and 80 mmHg. In MS rats, the number of c-fos-like immunoreactive nuclei at dorsal horn of lumbar-sacral spinal cord increased significantly after CRD. 5-HT content in the spinal cord of MS rats was significant higher. In the colon, both 5-HT-positive cell number and 5-HT content were comparable between MS and NH groups before CRD. Post-CRD only MS rats had significant increase in 5-HT content. Protein and mRNA expression levels of 5-HT3 receptors and 5-HT transporter were similar in MS and NH rats. Neonatal maternal separation stress predisposes rats to exaggerated neurochemical responses and visceral hyperalgesia in colon mimicking IBS.

Animals↗
PubMed2006

The large 386-nt deletion in SARS-associated coronavirus: evidence for quasispecies?

The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is reported to have deletions of various sizes. Recently, the large 386-nucleotide deletion (L386del) comprising nucleotide positions 27719-28104 and spanning open reading frames 9-11 has been reported in the genomes of some human isolates from Hong Kong. In this study, archived specimens from 71 patients with SARS who were admitted to the New Territory East Cluster Hospitals in Hong Kong were analyzed to determine whether the L386del variant of SARS-CoV was present. There was no clear relationship between the presence of the L386del variant and SARS clinical severity as defined either by the need for intensive-care therapy and/or ventilation or by death. One patient had evidence of both the L386del variant and the wild-type variant in the same clinical specimen, supporting the idea that SARS-CoV exists as a quasispecies in some patients, although the clinical significance of these quasispecies remains unclear.

Adolescent↗
PubMed2006

A tumor progression model for hepatocellular carcinoma: bioinformatic analysis of genomic data.

BACKGROUND & AIMS: It is widely recognized that genomic abnormalities underpin the development of human cancers. Aberrant patterns of chromosomal changes may represent useful information that can be used in classifying the complex traits of liver cancer cases for the genetic events involved in tumor carcinogenesis, tumor progression, and prognosis. METHODS: Genome-wide chromosomal aberrations of 158 hepatitis B virus-associated hepatocellular carcinoma (HCC) were studied by comparative genomic hybridization (CGH). By application of a self-organizing tree algorithm, statistically significant CGH events were used to construct an evolutionary tree that could infer patient subgroups with different degrees of tumor progression. The key CGH events in the subgroups were identified. The clinical significance of the groupings and the key CGH events were examined. RESULTS: Based on the patterns of significant chromosomal aberrations derived, 3 HCC subgroups organized in an evolutionary tree were identified. The groupings possessed information reflecting the degrees of tumor progression, including numbers of chromosomal aberrations, tumor stages, tumor sizes, and disease outcome. Gains of 1q21-23 and 8q22-24 were identified as genomic events associated with the early development of HCC. Gain of 3q22-24, however, was identified as 1 of the late genomic events found to be associated with tumor recurrence and poor overall patient survival. CONCLUSIONS: A tumor progression model for HCC was constructed and revealed chromosomal imbalances that were significantly associated with clinical pathologic characteristics of the disease. This model explains a significant part of the variations in clinical outcome among HCC patients.

Adult↗
PubMed2006

Effects of long-term rofecoxib on gastric intestinal metaplasia: results of a randomized controlled trial.

PURPOSE: Gastric cancer and its premalignant gastric lesion, intestinal metaplasia (IM), frequently express cyclooxygenase-2 (COX-2) at high levels. We tested whether long-term use of specific COX-2 inhibitors regress gastric IM. EXPERIMENTAL DESIGN: This is a double-blind, randomized, placebo-controlled trial. Individuals with confirmed IM and Helicobacter pylori clearance were randomized to receive rofecoxib 25 mg daily or placebo. Endoscopy was done at baseline, at the end of year 1, and at the end of year 2, with multiple biopsies taken from the antrum and corpus. The primary end point was the proportion of subjects with regression of IM. Secondary end points were the severity of other histologic variables and the proportion of subjects with complete regression of IM. RESULTS: Two-hundred and thirteen subjects with confirmed IM were randomized. The proportion of subjects with the regression of IM did not differ significantly between rofecoxib and placebo groups (antrum, 24.5% versus 26.9%; P = 0.74; corpus, 4.3% versus 2.2%; P = 0.68). Patients on rofecoxib (19.1%) and on placebo (16.1%) had no IM detected in the stomach (P = 0.59). There was also no significant difference in the severity of IM between the two treatment groups (P >or= 0.3). CONCLUSIONS: There was no trend to suggest that treatment with rofecoxib for 2 years resulted in the regression of gastric IM. Although our findings cast doubt on the reversibility of gastric IM by COX-2 inhibitor, further studies are needed to establish the role of COX-2 inhibitors in different stages of gastric carcinogenesis.

Adenocarcinoma↗
PubMed2006

Effects of Helicobacter pylori eradication on methylation status of E-cadherin gene in noncancerous stomach.

PURPOSE: Promoter hypermethylation of E-cadherin plays an important role on gastric cancer development. Whereas E-cadherin methylation was frequently detected in the stomach of Helicobacter pylori-infected individuals, we tested whether eradication of H. pylori alters the methylation status of the noncancerous gastric epithelium. EXPERIMENTAL DESIGN: Endoscopic biopsies were taken from the antrum and corpus of H. pylori-infected subjects without gastric cancer. Presence of methylated E-cadherin sequences in the gastric specimens was detected by methylation-specific PCR. Bisulfite DNA sequencing was done to determine the topographical distribution and changes in methylation profiles with H. pylori eradication. RESULTS: Among the 28 H. pylori-infected subjects (median age, 44.5 years), 15 (53.6%) had E-cadherin methylation detected in stomach at baseline. Discordant methylation patterns between the antrum and corpus were noted in six patients. One year after successful H. pylori eradication, there was a significant reduction in the methylation density of the promoter region and exon 1 of the E-cadherin gene as detected by bisulfite DNA sequencing (P < 0.001). CONCLUSION: Promoter methylation in E-cadherin was frequently detected in the stomach of H. pylori-infected individuals. Eradication of H. pylori might possibly reduce the methylation density in E-cadherin gene and the chance of subsequent neoplastic transformation.

Adult↗
PubMed2006

Kinetics and synergistic effects of siRNAs targeting structural and replicase genes of SARS-associated coronavirus.

SARS-associated coronavirus was identified as the etiological agent of severe acute respiratory syndrome and a large virus pool was identified in wild animals. Virus generates drug resistance through fast mutagenesis and escapes antiviral treatment. siRNAs targeting different genes would be an alternative for overcoming drug resistance. Here, we report effective siRNAs targeting structural genes (i.e., spike, envelope, membrane, and nucleocapsid) and their antiviral kinetics. We also showed the synergistic effects of two siRNAs targeting different functional genes at a very low dose. Our findings may pave a way to develop cost effective siRNA agents for antiviral therapy in the future.

Animals↗
PubMed2006

Anti-severe acute respiratory syndrome coronavirus immune responses: the role played by V gamma 9V delta 2 T cells.

Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus (SARS-CoV) strain. Analyses of T cell repertoires in health care workers who survived SARS-CoV infection during the 2003 outbreak revealed that their effector memory V gamma 9V delta 2 T cell populations were selectively expanded ~3 months after the onset of disease. No such expansion of their alpha beta T cell pools was detected. The expansion of the V gamma 9V delta 2 T cell population was associated with higher anti-SARS-CoV immunoglobulin G titers. In addition, in vitro experiments demonstrated that stimulated V gamma 9V delta 2 T cells display an interferon- gamma -dependent anti-SARS-CoV activity and are able to directly kill SARS-CoV-infected target cells. These findings are compatible with the possibility that V gamma 9V delta 2 T cells play a protective role during SARS.

Adult↗
PubMed2006

Sapovirus detection by quantitative real-time RT-PCR in clinical stool specimens.

Sapovirus (SV) is one of the major causative agents of viral gastroenteritis affecting all age groups worldwide. A new method for the quantitative detection of SV from clinical stool specimens by real-time reverse transcription-polymerase chain reaction (RT-PCR) based on TaqMan MGB technology was described. Primers and probe were designed to target the RNA-dependent RNA polymerase/capsid genes junction. Performance of the newly developed assay was validated against a panel of 244 clinical stool specimens collected for patients with gastroenteritis. SV was detected in eight (3.3%) specimens. Phylogenetic analysis of the positive isolates suggested that the assay could detect at least SV genogroups I, II and IV. In addition, the assay had an increased detection rate compared with a widely used conventional RT-PCR assay. Quantitative analysis showed that the assay could detect as low as 10 copies of viral cDNA per reaction. No cross-reactivity with norovirus and rotavirus was observed. In conclusion, the assay is a sensitive and specific method for the detection of SV from clinical stool specimens.

Adolescent↗
PubMed2006

Serum proteomic fingerprints of adult patients with severe acute respiratory syndrome.

BACKGROUND: Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a new coronavirus strain, SARS-CoV. Specific proteomic patterns might be present in serum in response to the infection and could be useful for early detection of the disease. METHODS: Using surface-enhanced laser desorption/ionization (SELDI) ProteinChip technology, we profiled and compared serum proteins of 39 patients with early-stage SARS infection and 39 non-SARS patients who were suspected cases during the SARS outbreak period. Proteomic patterns associated with SARS were identified by bioinformatic and biostatistical analyses. Features of interest were then purified and identified by tandem mass spectrometry. RESULTS: Twenty proteomic features were significantly different between the 2 groups. Fifteen were increased in the SARS group, and 5 were decreased. Their concentrations were correlated with 2 or more clinical and/or biochemical variables. Two were correlated with the SARS-CoV viral load. Hierarchical clustering analysis showed that a majority of the SARS patients (95%) had similar serum proteomic profiles and identified 2 subgroups with poor prognosis. ROC curve analysis identified individual features as potential biomarkers for SARS diagnosis (areas under ROC curves, 0.733-0.995). ROC curve areas were largest for an N-terminal fragment of complement C3c alpha chain (m/z 28 119) and an internal fragment of fibrinogen alpha-E chain (m/z 5908). Immunoglobulin kappa light chain (m/z 24 505) positively correlated with viral load. CONCLUSIONS: Specific proteomic fingerprints in the sera of adult SARS patients could be used to identify SARS cases early during onset with high specificity and sensitivity.

Adult↗
PubMed2006

Inhibition of gastric cancer cells associated angiogenesis by 15d-prostaglandin J2 through the downregulation of angiopoietin-1.

Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have been shown to inhibit angiogenesis. We showed that treatment with 15d-PGJ(2), a PPARgamma ligand, downregulate the expressions of angiopoietin-1 (Ang-1) in gastric cancer cells MKN45. The medium of MKN45 cells treated with 15d-PGJ(2) significantly inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Moreover, Matrigel plug assay revealed that 15d-PGJ(2) reduced in vivo angiogenesis induced by MKN45 cells. These modulations were restored by the addition of recombinant Ang-1. Our findings supported that 15d-PGJ(2) suppressed angiogenesis of gastric cancer cells by downregulation of Ang-1.

Angiogenesis Inhibitors↗
PubMed2006

Endoscopic plication of massively bleeding peptic ulcer by using the Eagle Claw VII device: a feasibility study in a porcine model.

BACKGROUND AND OBJECTIVE: We examined the efficacy of endoscopic plication when using Eagle Claw VII in a porcine bleeding ulcer model. ANIMAL MODEL PREPARATION: The right gastroepiploic artery (diameter 1.5-2 mm) was isolated and was tunneled to small gastrotomies at either the lesser or greater curvature of the stomach. INTERVENTIONS: We applied the Eagle Claw VII to achieve hemostasis. MAIN OUTCOME MEASUREMENTS: The survival of the pigs after endoscopic plication for hemostasis, time to achieve hemostasis with Eagle Claw VII, recurrent bleeding, number of successful plication, and number of suture remained. RESULTS: Endoscopic plication was performed on bleeding gastric ulcers in 6 pigs. The time to achieve hemostasis was 6 minutes 56 seconds +/- 3 minutes 50 seconds. There was no complication. A total of 14 plications were performed. All animals survived for 1 week without recurrent bleeding. At the postmortem, 10 of the plication sutures remained. LIMITATION: Our model cannot simulate the chronicity of peptic ulcer. CONCLUSIONS: In this porcine model, the Eagle Claw VII effectively stopped bleeding from arteries 2 mm in size.

Animals↗
PubMed2006

Colorectal neoplasia in Asia: a multicenter colonoscopy survey in symptomatic patients.

BACKGROUND: The incidence of colorectal cancer is rising rapidly in some Asian countries. OBJECTIVE: To determine the prevalence and the distribution of colorectal neoplasm in Asian populations. DESIGN: A multicenter colonoscopy survey. PATIENTS: Between July 2004 and April 2005, consecutive symptomatic patients undergoing colonoscopic examinations in 10 different Asian countries. SETTING: The location and the histologic features of all colonic neoplasms were recorded. Advanced neoplasm was defined as adenoma larger than 10 mm in size, with >25% villous features or with high-grade dysplasia or invasive carcinoma. MAIN OUTCOME MEASUREMENTS: The prevalence and the distribution of colorectal neoplasm and advanced neoplasm. RESULTS: A total of 5464 eligible patients underwent colonoscopy. Advanced neoplasm was found in 512 patients (9.4%). Factors associated with the presence of advanced neoplasm in this symptomatic Asian population included male sex (relative risk [RR] 1.52, 95% confidence interval [CI] 1.26-1.84), older age (RR 1.05, 95% CI 1.04-1.06), and ethnicity (P = .001). Advanced proximal neoplasm was detected in 136 patients (2.5%); 83 (61.0%) of the patients had normal distal colon. The RR of proximal advanced neoplasm was 2.5, 95% CI 1.7-3.7 in those with any adenoma in the distal colon compared with those with normal distal colon. LIMITATIONS: Possible underrepresentation of some ethnic groups because of uneven ethnic group distribution and the lack of population-based registry. CONCLUSIONS: This was the first multicenter colonoscopy survey that examined the characteristics of colorectal neoplasm in Asia. The results will have important implications on the planning for future colorectal cancer screening in this region.

Adenoma↗
PubMed2006

Study of serum haptoglobin and its glycoforms in the diagnosis of hepatocellular carcinoma: a glycoproteomic approach.

Increased serum haptoglobin concentration and changes in its glycosylation have been reported in certain cancer types. Information for hepatocellular carcinoma (HCC) has not yet been available. In this study, we aimed to carry out a systematic analysis of serum concentrations of haptoglobin (Hp) and its glycoforms in the patients with HCC and noncancer patients only with chronic liver diseases (CLD) and to examine their clinical values. This study was divided into two major parts, (1) measurement of serum Hp concentration, and investigation of its value in the diagnosis of HCC, and (2) quantitative analysis of Hp glycoforms with alpha-2,6-sialylation and/or alpha-1,6-fucosylation by using lectin affinity purification and 2D gel electrophoresis and investigation of their relationships with tumor stage. The concentrations of serum Hp in HCC patients were significantly higher than those in noncancer patients with CLD. With the use of serum concentrations of Hp and alpha-fetoprotein, a logistic regression (LR) model was developed from the training data set and used to classify the validation cases. At a specificity of 95%, the sensitivity for HCC detection was 79%. Comparing serum concentrations of alpha-2,6-sialylated Hp (S-Hp) and alpha-1,6-fucosylated Hp (F-Hp) between HCC and CLD patients suggests that purification of S-Hp and F-Hp could enrich the glycosylation variants associated with HCC. 2D gel analysis of S-Hp and F-Hp identified a total of 18 glycoforms. A unique pattern of Hp glycoforms comprising both hypersialylated fucosylated and hyposialylated fucosylated species was found in the HCC patients. Serum concentrations of these glycoproteins were significantly higher in the patients with advanced tumors, suggesting their tumor-specific nature. We have shown that serum Hp is a potential biomarker in the diagnosis of HCC. The combined use of Hp and AFP could greatly improve the diagnostic accuracy. A unique pattern of Hp glycoforms with altered sialylation and fucosylation is specific to HCC and associated tumor progression.

Adult↗
PubMed2006

Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients.

BACKGROUND & AIMS: In patients with stones in their bile ducts and gallbladders, cholecystectomy is generally recommended after endoscopic sphincterotomy and clearance of bile duct stones. However, only approximately 10% of patients with gallbladders left in situ will return with further biliary complications. Expectant management is alternately advocated. In this study, we compared the treatment strategies of laparoscopic cholecystectomy and gallbladders left in situ. METHODS: We randomized patients (>60 years of age) after endoscopic sphincterotomy and clearance of their bile duct stones to receive early laparoscopic cholecystectomy or expectant management. The primary outcome was further biliary complications. Other outcome measures included adverse events after cholecystectomy and late deaths from all causes. RESULTS: One hundred seventy-eight patients entered into the trial (89 in each group); 82 of 89 patients who were randomized to receive laparoscopic cholecystectomy underwent the procedure. Conversion to open surgery was needed in 16 of 82 patients (20%). Postoperative complications occurred in 8 patients (9%). Analysis was by intention to treat. With a median follow-up of approximately 5 years, 6 patients (7%) in the cholecystectomy group returned with further biliary events (cholangitis, n = 5; biliary pain, n = 1). Among those with gallbladders in situ, 21 (24%) returned with further biliary events (cholangitis, n = 13; acute cholecystitis, n = 5; biliary pain, n = 2; and jaundice, n = 1; log rank, P = .001). Late deaths were similar between groups (cholecystectomy, n = 19; gallbladder in situ, n = 11; P = .12). CONCLUSIONS: In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.

Aged↗