46 results on '"Fan PS"'
Search Results
2. PRS10 INCIDENCE RATE AND MAJOR CAUSES OF PROLONGED MECHANICAL VENTILATION IN TAIWAN: A POPULATION-BASED STUDY DURING 1997-2007
- Author
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Hung, MC, primary, Lu, HM, additional, Chen, L, additional, Chan, SY, additional, Hu, FC, additional, Yan, YH, additional, Fan, PS, additional, Lin, MS, additional, Chen, CR, additional, Kuo, LC, additional, Yu, CJ, additional, and Wang, JD, additional
- Published
- 2010
- Full Text
- View/download PDF
3. PRS33 MEASUREMENT OF QUALITY OF LIFE BY EQ-5D IN PROLONGED MECHANICAL VENTILATION PATIENTS: COMPARISON BETWEEN PATIENTS AND PROXIES
- Author
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Hung, MC, primary, Yan, YH, additional, Fan, PS, additional, Lin, MS, additional, Chen, CR, additional, and Wang, JD, additional
- Published
- 2009
- Full Text
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4. PRS6 ESTIMATION OF QUALITY-ADJUSTED LIFE EXPECTANCY AND LOSS OF UTILITY IN PATIENTS UNDER PROLONGED MECHANICAL VENTILATION
- Author
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Hung, MC, primary, Yan, YH, additional, Fan, PS, additional, Lin, MS, additional, Chen, CR, additional, and Wang, JD, additional
- Published
- 2009
- Full Text
- View/download PDF
5. Skin-like wound dressings with on-demand administration based on in situ peptide self-assembly for skin regeneration.
- Author
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Zhang XY, Liu C, Fan PS, Zhang XH, Hou DY, Wang JQ, Yang H, Wang H, and Qiao ZY
- Subjects
- Anti-Bacterial Agents pharmacology, Bandages, Gelatinases, Peptides, Wound Healing, Epidermal Growth Factor pharmacology, Fibroins
- Abstract
Burn injuries without the normal skin barrier usually cause skin wound infections, and wound dressings are necessary. Although various dressings with antibacterial ability have already been developed, the biosafety and administration mode are still bottleneck problems for further application. Herein, we designed skin-like wound dressings based on silk fibroin (SF), which are modified with the gelatinase-cleavable self-assembled/antibacterial peptide (GPLK) and epidermal growth factor (EGF). When a skin wound is infected, the gelatinase over-secreted by bacteria can cut the GPLK peptides, leading to the in situ self-assembly of peptides and the resultant high-efficiency sterilization. Compared with the commercial antibacterial dressing, the SF-GPLK displayed a faster wound healing rate. When a skin wound is not infected, the GPLK peptides remain in the SF, realizing good biosafety. Generally, the EGF can be released to promote wound healing and skin regeneration in both cases. Therefore, skin-like SF-GPLK wound dressings with on-demand release of antibacterial peptides provide a smart administration mode for clinical wound management and skin regeneration.
- Published
- 2022
- Full Text
- View/download PDF
6. Bridging micro/nano-platform and airway allergy intervention.
- Author
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Sun MJ, Teng Z, Fan PS, Chen XG, and Liu Y
- Subjects
- Administration, Intranasal, Adrenal Cortex Hormones, Humans, Inflammation, Hypersensitivity drug therapy
- Abstract
Allergic airway diseases, with incidence augmenting visibly as industrial development and environmental degradation, are characterized by sneezing, itching, wheezing, chest tightness, airway obstruction, and hyperresponsiveness. Current medical modalities attempt to combat these symptoms mostly by small molecule chemotherapeutants, such as corticosteroids, antihistamines, etc., via intranasal approach which is one of the most noninvasive, rapid-absorbed, and patient-friendly routes. Nevertheless, inherent defects for irritation to respiratory mucosa, drug inactivation and degradation, and rapid drug dispersal to off-target sites are inevitable. Lately, intratracheal micro/nano therapeutic systems are emerging as innovative alternatives for airway allergy interventions. This overview introduces several potential application directions of mic/nano-platform in the treatment of airway allergic diseases, including carriers, therapeutic agents, and immunomodulators. The improvement of the existing drug therapy of respiratory allergy management by micro/nano-platform is described in detail. The challenges of the micro/nano-platform nasal approach in the treatment of airway allergy are summarized and the development of micro/nano-platform is also prospected. Although still a burgeoning area, micro/nano therapeutic systems are gradually turning to be realistic orientations as crucial future alternative therapeutic options in allergic airway inflammation interventions., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2022
- Full Text
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7. In Vivo Self-Assembly Induced Cell Membrane Phase Separation for Improved Peptide Drug Internalization.
- Author
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Guo RC, Zhang XH, Fan PS, Song BL, Li ZX, Duan ZY, Qiao ZY, and Wang H
- Subjects
- Alkaline Phosphatase metabolism, Cell Membrane metabolism, Humans, Peptides chemistry, Peptides metabolism, Protein Conformation, Cell Membrane chemistry, Peptides isolation & purification
- Abstract
Therapeutic peptides have been widely concerned, but their efficacy is limited by the inability to penetrate cell membranes, which is a key bottleneck in peptide drugs delivery. Herein, an in vivo self-assembly strategy is developed to induce phase separation of cell membrane that improves the peptide drugs internalization. A phosphopeptide KYp is synthesized, containing an anticancer peptide [KLAKLAK]
2 (K) and a responsive moiety phosphorylated Y (Yp). After interacting with alkaline phosphatase (ALP), KYp can be dephosphorylated and self-assembles in situ, which induces the aggregation of ALP and the protein-lipid phase separation on cell membrane. Consequently, KYp internalization is 2-fold enhanced compared to non-responsive peptide, and IC50 value of KYp is approximately 5 times lower than that of free peptide. Therefore, the in vivo self-assembly induced phase separation on cell membrane promises a new strategy to improve the drug delivery efficacy in cancer therapy., (© 2021 Wiley-VCH GmbH.)- Published
- 2021
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8. Analysis of persistent organochlorine pesticides in shellfish and their risk assessment from aquafarms in Taiwan.
- Author
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Wang JH, Chang CP, Chang CC, Wang CM, Lin CF, Lin JW, Lin WL, Liao HJ, Kao CY, Fan PS, Yang WC, and Chang GR
- Subjects
- Gas Chromatography-Mass Spectrometry, Risk Assessment, Shellfish, Taiwan, Hydrocarbons, Chlorinated analysis, Pesticides analysis, Water Pollutants, Chemical analysis
- Abstract
In Taiwan, freshwater clams (Corbicula fluminea) and hard clams (Meretrix lusoria) are the most frequently raised shellfish in land-based pond aquaculture, but research on the accumulation of organochlorine pesticides (OCPs) in these shellfish is limited. We detected the levels of 14 OCPs in 62 shellfish from Taiwanese aquafarms by performing gas chromatography-tandem mass spectrometry. OCP residues were detected in 4.84% of the samples including readings of 0.04 mg/kg chlordane (in a freshwater clam), 0.03 mg/g p,p'-DDE (in a freshwater clam), and 0.02 mg/g p,p'-DDE (in a hard clam). However, the associated estimated daily intake values were less than the acceptable daily intake levels of chlordane and p,p'-DDE Therefore, the consumption of these shellfish presents no immediate health risks. Our findings contribute to food safety and serve as a reference for OCP screenings for aquatic shellfish., (Copyright © 2021. Published by Elsevier Ltd.)
- Published
- 2021
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9. The Ameliorative Effects of Fucoidan in Thioacetaide-Induced Liver Injury in Mice.
- Author
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Tsai MY, Yang WC, Lin CF, Wang CM, Liu HY, Lin CS, Lin JW, Lin WL, Lin TC, Fan PS, Hung KH, Lu YW, and Chang GR
- Subjects
- Animals, Cytokines metabolism, Liver pathology, Male, Mice, Mice, Inbred C57BL, Oxidative Stress drug effects, Thioacetamide toxicity, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents pharmacology, Antioxidants administration & dosage, Antioxidants pharmacology, Chemical and Drug Induced Liver Injury, Chronic drug therapy, Liver drug effects, Polysaccharides administration & dosage, Polysaccharides pharmacology
- Abstract
Liver disorders have been recognized as one major health concern. Fucoidan, a sulfated polysaccharide extracted from the brown seaweed Fucus serratus, has previously been reported as an anti-inflammatory and antioxidant. However, the discovery and validation of its hepatoprotective properties and elucidation of its mechanisms of action are still unknown. The objective of the current study was to investigate the effect and possible modes of action of a treatment of fucoidan against thioacetamide (TAA)-induced liver injury in male C57BL/6 mice by serum biochemical and histological analyses. The mouse model for liver damage was developed by the administration of TAA thrice a week for six weeks. The mice with TAA-induced liver injury were orally administered fucoidan once a day for 42 days. The treated mice showed significantly higher body weights; food intakes; hepatic antioxidative enzymes (catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD)); and a lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and C-reactive protein (CRP) levels. Additionally, a reduced hepatic IL-6 level and a decreased expression of inflammatory-related genes, such as cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) mRNA was observed. These results demonstrated that fucoidan had a hepatoprotective effect on liver injury through the suppression of the inflammatory responses and acting as an antioxidant. In addition, here, we validated the use of fucoidan against liver disorders with supporting molecular data.
- Published
- 2021
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10. Doxepin Exacerbates Renal Damage, Glucose Intolerance, Nonalcoholic Fatty Liver Disease, and Urinary Chromium Loss in Obese Mice.
- Author
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Chang GR, Hou PH, Yang WC, Wang CM, Fan PS, Liao HJ, and Chen TP
- Abstract
Doxepin is commonly prescribed for depression and anxiety treatment. Doxepin-related disruptions to metabolism and renal/hepatic adverse effects remain unclear; thus, the underlying mechanism of action warrants further research. Here, we investigated how doxepin affects lipid change, glucose homeostasis, chromium (Cr) distribution, renal impairment, liver damage, and fatty liver scores in C57BL6/J mice subjected to a high-fat diet and 5 mg/kg/day doxepin treatment for eight weeks. We noted that the treated mice had higher body, kidney, liver, retroperitoneal, and epididymal white adipose tissue weights; serum and liver triglyceride, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and creatinine levels; daily food efficiency; and liver lipid regulation marker expression. They also demonstrated exacerbated insulin resistance and glucose intolerance with lower Akt phosphorylation, GLUT4 expression, and renal damage as well as higher reactive oxygen species and interleukin 1 and lower catalase, superoxide dismutase, and glutathione peroxidase levels. The treated mice had a net-negative Cr balance due to increased urinary excretion, leading to Cr mobilization, delaying hyperglycemia recovery. Furthermore, they had considerably increased fatty liver scores, paralleling increases in adiponectin, FASN, PNPLA3, FABP4 mRNA, and SREBP1 mRNA levels. In conclusion, doxepin administration potentially worsens renal injury, nonalcoholic fatty liver disease, and diabetes.
- Published
- 2021
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11. Nanosystems as curative platforms for allergic disorder management.
- Author
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Fan PS, Sun MJ, Qin D, Yuan CS, Chen XG, and Liu Y
- Subjects
- Animals, Humans, Particle Size, Surface Properties, Anti-Allergic Agents therapeutic use, Hypersensitivity drug therapy, Nanotechnology
- Abstract
Allergy, IgE-mediated inflammatory disorders including allergic rhinitis, asthma, and conjunctivitis, affects billions of people worldwide. Conventional means of allergy management include allergen avoidance, pharmacotherapy, and emerging therapies. Among them, chemotherapeutant intake via oral, intravenous, and intranasal routes is always the most common mean. Although current pharmacotherapy exhibit splendid anti-allergic effects, short in situ retention, low bioavailability, and systemic side effects are inevitable. Nowadays, nanoplatforms have provided alternative therapeutic options to obviate the existing weakness via enhancing the solubility of hydrophobic therapeutic agents, achieving in situ drug accumulation, exhibiting controlled and long-time drug release at lesion areas, and providing multi-functional therapeutic strategies. Herein, we highlight the clinical therapeutic strategies and deal with characteristics of the nanoplatform design in allergy interventions via intratracheal, gastrointestinal, intravenous, and ocular paths. The promising therapeutic utilization in a variety of allergic disorders is discussed, and recent perspectives on the feasible advances of nanoplatforms in allergy management are also exploited.
- Published
- 2021
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12. Upregulation of KCNMA1 facilitates the reversal effect of verapamil on the chemoresistance to cisplatin of esophageal squamous cell carcinoma cells.
- Author
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Ge N, Yang GS, Zhang TY, Chang N, Kang YH, Zhou Q, and Fan PS
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Cell Survival drug effects, Cisplatin chemistry, Cisplatin pharmacology, Drug Resistance, Neoplasm drug effects, Esophageal Neoplasms drug therapy, Esophageal Neoplasms pathology, Esophageal Squamous Cell Carcinoma drug therapy, Esophageal Squamous Cell Carcinoma pathology, Female, Humans, Male, Middle Aged, Tumor Cells, Cultured, Verapamil chemistry, Verapamil pharmacology, Young Adult, Esophageal Neoplasms metabolism, Esophageal Squamous Cell Carcinoma metabolism, Large-Conductance Calcium-Activated Potassium Channel alpha Subunits metabolism, Up-Regulation
- Abstract
Objective: This study aimed to investigate the reversal effect of verapamil (VER) on the chemoresistance to cisplatin of esophageal squamous cell carcinoma (ESCC) cells., Patients and Methods: The reversal effect of VER on cisplatin resistance in ESCC cells was evaluated via CCK-8 assay, colony formation assessment, and flow cytometry. The key genes that mediate this effect were screened via high-throughput transcriptome se¬quencing. The mRNA and protein expression levels of potassium calcium-activated channel subfamily M alpha 1 (KCNMA1) in ESCC cells were examined via quantitative real-time PCR and Western blot analysis, respectively. The protein expressions of KCNMA1 in tissue samples from patients with either positive or negative responses to the therapeutic regimen of VER were determined via immunohistochemistry assay. Cell models with KCNMA1 knockdown and overexpression were es¬tablished to examine the role of KCNMA1 in mediating the reversal effect of VER on the chemoresistance to cisplatin of ESCC cells., Results: Results revealed that VER significantly decreased the 50% inhibitory concentration of cisplatin, inhibited colony formation, and induced apoptosis in ESCC cells. The curative effects of VER combined with chemotherapeutic drugs in KCNMA1-positive patients were better than those in KCNMA1-negative patients. KCNMA1 upregulation enhanced the reversal effect of VER on the chemoresistance to cisplatin of ESCC cells., Conclusions: KCNMA1 facilitated the reversal effect of VER on cisplatin resistance in ESCC cells.
- Published
- 2021
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13. Quinolone and Organophosphorus Insecticide Residues in Bivalves and Their Associated Risks in Taiwan.
- Author
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Wu CF, Chen CH, Wu CY, Lin CS, Su YC, Wu CF, Tsai HP, Fan PS, Yeh CH, Yang WC, and Chang GR
- Subjects
- Animals, Aquaculture, Bivalvia metabolism, Chlorpyrifos analysis, Chromatography, High Pressure Liquid, Female, Gas Chromatography-Mass Spectrometry, Humans, Male, Risk Assessment, Seafood analysis, Taiwan, Tandem Mass Spectrometry, Trichlorfon analysis, Bivalvia chemistry, Insecticides analysis, Organophosphorus Compounds analysis, Quinolones analysis
- Abstract
Bivalves, such as freshwater clams ( Corbicula fluminea ) and hard clams ( Meretrix lusoria ), are the most extensive and widely grown shellfish in land-based ponds in Taiwan. However, few studies have examined the contamination of bivalves by quinolone and organophosphorus insecticides. Thus, we adapted an established procedure to analyze 8 quinolones and 12 organophosphorus insecticides using liquid and gas chromatography-tandem mass spectrometry. Surveys in Taiwan have not noted high residual levels of these chemicals in bivalve tissues. A total of 58 samples of freshwater or hard clams were obtained from Taiwanese aquafarms. We identified 0.03 mg/kg of enrofloxacin in one freshwater clam, 0.024 mg/kg of flumequine in one freshwater clam, 0.02 mg/kg of flumequine in one hard clam, 0.05 mg/kg of chlorpyrifos in one freshwater clam, 0.03 mg/kg of chlorpyrifos in one hard clam, and 0.02 mg/kg of trichlorfon in one hard clam. The results indicated that 5.17% of the samples had quinolone insecticide residues and 5.17% had organophosphorus residues. However, the estimated daily intake (EDI)/acceptable daily intake quotient (ADI) indicated no significant risk and no immediate health risk from the consumption of bivalves. These results provide a reference for the food-safety screening of veterinary drugs and pesticides in aquatic animals. Aquatic products should be frequently screened for residues of prohibited chemicals to safeguard human health.
- Published
- 2020
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14. Effect of verapamil in the reversal of doxorubicin chemotherapy resistance in advanced gastric cancer.
- Author
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Wang X, Li Y, Fan GF, Zhang TY, Sun B, and Fan PS
- Subjects
- ATP Binding Cassette Transporter, Subfamily B antagonists & inhibitors, ATP Binding Cassette Transporter, Subfamily B metabolism, Adult, Aged, Carcinoma genetics, Carcinoma metabolism, Carcinoma pathology, Cell Line, Tumor, Dose-Response Relationship, Drug, Female, Glucosyltransferases genetics, Glucosyltransferases metabolism, Humans, Inhibitory Concentration 50, Male, Middle Aged, Stomach Neoplasms genetics, Stomach Neoplasms metabolism, Stomach Neoplasms pathology, Antineoplastic Agents pharmacology, Apoptosis drug effects, Carcinoma drug therapy, Doxorubicin pharmacology, Drug Resistance, Neoplasm drug effects, Stomach Neoplasms drug therapy, Verapamil pharmacology
- Abstract
Objective: Gastric carcinoma is one of the most common malignant tumors and one of the most common cancer-related fatal diseases. Chemotherapy is considered as the major therapy for advanced gastric cancer, and the curative effect of chemotherapy directly affects the treatment of advanced gastric cancer. Drug resistance of tumor cells is one of the important causes that induces failure of chemotherapy. Previous studies have demonstrated that verapamil (VER) can reverse drug resistance by inhibiting the P-glycoprotein (P-gp), which is one of the main targets of VER. The present study aimed at investigating the function of glucosylceramide synthase (GCS) in the VER-induced reversal of doxorubicin (ADM) chemotherapy resistance in gastric carcinoma., Patients and Methods: In the current study, the 4 GC cell line was selected for investigation. The IC50 values of gastric cancer cells were measured using CCK-8 assay. The expression levels of candidate genes in gastric carcinoma cells were measured by RT-qPCR. The expression levels of candidate protein in gastric carcinoma cells were measured by Western blot. The expression of GCS protein in clinical specimens of GC receiving VER+TACE therapy was measured by immunohistochemistry. The test of gastric carcinoma cell apoptosis was measured by Annexin V-FITC/PI double-staining., Results: We found that the expression levels changes of the GCS gene can influence the effects of ADM+VER on cell apoptosis. The role and mechanism of GCS gene in reversing the chemotherapy resistance of gastric carcinoma cells to ADM were explored., Conclusions: In future research, we will explore the mechanism of how GCS affects drug resistance in gastric carcinoma and related signal transduction pathway.
- Published
- 2020
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15. The clinical observation of verapamil in combination with interventional chemotherapy in advanced gastric cancer.
- Author
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Fan GF, Pan JJ, Fan PS, Zhang TY, Liu YB, Huang J, Weng CT, Liu M, Duan QH, Wu Y, Tang LL, Yang GH, Dai HB, and Zhu ZQ
- Subjects
- Adult, Aged, Calcium Channel Blockers administration & dosage, Female, Follow-Up Studies, Humans, Infusions, Intra-Arterial, Liver Neoplasms diagnostic imaging, Liver Neoplasms mortality, Liver Neoplasms secondary, Male, Middle Aged, Stomach Neoplasms mortality, Survival Rate trends, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Stomach Neoplasms diagnostic imaging, Stomach Neoplasms drug therapy, Verapamil administration & dosage
- Abstract
Objective: We analyzed the clinical observations of target arterial infusion of verapamil combined with chemotherapy as therapy for advanced gastric cancer., Patients and Methods: From March 2012 to December 2015, a total of 63 patients with advanced gastric cancer were admitted to our department. The target artery in the control group was perfused with chemotherapy drugs only, and the target artery in the therapy group was injected with verapamil combined with chemotherapy drugs., Results: The therapeutic effect of the therapy group was significantly better than that of the control group in the primary foci of gastric cancer. Liver metastatic lesions: 11 patients in the control group had liver metastases and 25 patients in the therapy group had liver metastases. The effective rate (CR+PR) of the therapy group was significantly better than the control group. Clinical benefit evaluation: in the therapy group of 43 cases, 40 cases presented positive clinical benefit and 38 cases positive clinical weight in KFS scoring system; the clinical benefit of the therapy group was significantly better than control group. Survival analysis: the disease progression-free rate and survival rate of the therapy group were 12 months and 24 months, which were higher than those in the control group. The median PFS and median OS were also significantly longer than those in the control group (p<0.01). In the therapy group, adverse effects of chemotherapy in 43 patients were relieved in a short time., Conclusions: Target arterial infusion of verapamil combined with chemotherapy drugs for advanced gastric cancer can significantly improve the efficacy of chemotherapy drugs and prolong the survival of patients.
- Published
- 2018
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16. A phase II study of paclitaxel and nedaplatin as front-line chemotherapy in Chinese patients with metastatic esophageal squamous cell carcinoma.
- Author
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He YF, Ji CS, Hu B, Fan PS, Hu CL, Jiang FS, Chen J, Zhu L, Yao YW, and Wang W
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell secondary, China, Disease Progression, Disease-Free Survival, Drug Administration Schedule, Esophageal Neoplasms mortality, Esophageal Neoplasms pathology, Esophageal Squamous Cell Carcinoma, Female, Humans, Intention to Treat Analysis, Kaplan-Meier Estimate, Male, Middle Aged, Organoplatinum Compounds administration & dosage, Paclitaxel administration & dosage, Time Factors, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Squamous Cell drug therapy, Esophageal Neoplasms drug therapy
- Abstract
Aim: To evaluate the efficacy and safety of paclitaxel-nedaplatin combination as a front-line regimen in Chinese patients with metastatic esophageal squamous cell carcinoma (ESCC)., Methods: A two-center, open-label, single-arm phase II study was designed. Thirty-nine patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. Patients received 175 mg/m² of paclitaxel over a 3 h infusion on 1 d, followed by nedaplatin 80 mg/m² in a 1 h infusion on 2 d every 3 wk until the documented disease progression, unacceptable toxicity or patient's refusal., Results: Of the 36 patients assessable for efficacy, there were 2 patients (5.1%) with complete response and 16 patients (41.0%) with partial response, giving an overall response rate of 46.1%. The median progression-free survival and median overall survival for all patients were 7.1 mo (95%CI: 4.6-9.7) and 12.4 mo (95%CI: 9.5-15.3), respectively. Toxicities were moderate and manageable. Grade 3/4 toxicities included neutropenia (15.4%), nausea (10.3%), anemia (7.7%), thrombocytopenia (5.1%), vomiting (5.1%) and neutropenia fever (2.6%)., Conclusion: The combination of paclitaxel and nedaplatin is active and well tolerated as a first-line therapy for patients with metastatic ESCC.
- Published
- 2013
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17. Improved survival for an integrated system of reduced intensive respiratory care for patients requiring prolonged mechanical ventilation.
- Author
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Lin MS, Yan YH, Wang JD, Lu HM, Chen L, Hung MC, Fan PS, and Chen CR
- Subjects
- APACHE, Aged, Comorbidity, Female, Humans, Life Expectancy, Male, Respiration, Artificial mortality, Retrospective Studies, Survival Rate, Taiwan epidemiology, Time Factors, Respiration, Artificial statistics & numerical data, Respiratory Therapy methods
- Abstract
Background: The introduction of reduced respiratory care may lead to worse long-term outcomes for patients undergoing prolonged mechanical ventilation (PMV) for more than 21 days. The objective of this study was to determine the survival for an integrated system of reduced intensive respiratory care (ISRIRC) by the Taiwan Bureau of National Health Insurance, in patients requiring PMV., Methods: A 10-year retrospective study was performed in a 1,000-bed teaching hospital in Taiwan. A total of 633 consecutive PMV patients transferred from the hospital between 1998 and 2007 were enrolled. Medical records were reviewed to collect the clinical data, which were linked to the National Death Certification Database to ascertain subject survival. Kaplan-Meier estimates were performed, and a Cox proportional hazards model was constructed. We further conducted a corroboration study and retrieved a systematically randomized nationwide sample of PMV subjects with combined septicemia and shock, and compared the survival functions of those who were treated before and after the integrated system, including 228 and 2,677 subjects, respectively., Results: The survival rates at 3 months, 6 months, and 1 year were 60.0%, 44.0%, and 30.0%, respectively. The 1-year survival rates of the subjects before and after ISRIRC were 21.0% and 37.2%, respectively (P = .04). The factors associated with better survival were younger age, absence of cirrhosis, and establishment of the ISRIRC. A comparison of the 4-year survival in the larger random sample of PMV subjects with combined septicemia and shock before and after ISRIRC also showed a significant improvement., Conclusions: With the improvement of PMV technology in the early 2000s, the establishment of ISRIRC seems to be associated with an improved survival rate for subjects under PMV.
- Published
- 2013
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18. A new automatic algorithm to extract craniofacial measurements from fetal three-dimensional volumes.
- Author
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Tsai PY, Chen HC, Huang HH, Chang CH, Fan PS, Huang CI, Cheng YC, Chang FM, and Sun YN
- Subjects
- Face pathology, Female, Gestational Age, Head pathology, Humans, Pattern Recognition, Automated, Pregnancy, Pregnancy Trimester, Second, Reference Values, Reproducibility of Results, Algorithms, Face diagnostic imaging, Head diagnostic imaging, Imaging, Three-Dimensional, Ultrasonography, Prenatal methods
- Abstract
Objectives: Three-dimensional (3D) ultrasound is useful in the prenatal evaluation of fetal craniofacial structures, particularly as it provides a multiplanar view. However, an expert must designate the area of interest and the appropriate view, making measurement of fetal structures using 3D ultrasound both time-consuming and subjective. In this study we propose an image analysis system that measures automatically and precisely the fetal craniofacial structures and evaluate its performance in the second trimester of pregnancy using a new 3D volume analysis algorithm., Methods: A universal facial surface template model containing the geometric shape information of a fetal craniofacial structure was constructed from a fetal phantom. Using the proposed image analysis system we fitted this stored template model using a model deformation approach to individual fetal 3D facial volumes from 11 mid-trimester fetuses, and extracted automatically the following standard measurements: biparietal diameter (BPD), occipitofrontal diameter (OFD), interorbital diameter (IOD), bilateral orbital diameter (BOD) and distance between vertex and nasion (VN). The same five parameters were measured manually by an expert and the results compared., Results: Comparison of the algorithm-based automatic measurements with manual measurements made by an expert gave correlation coefficients of 0.99 for BPD, 0.98 for OFD, 0.80 for BOD, 0.83 for IOD and 0.99 for VN. There were no significant differences between automatic and manual measurements., Conclusion: Our proposed system measures precisely the fetal craniofacial structures using 3D ultrasound, making it potentially useful for clinical service. This system could also be applied to other clinical fields in future testing., (Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.)
- Published
- 2012
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19. Outcomes of prolonged mechanic ventilation: a discrimination model based on longitudinal health insurance and death certificate data.
- Author
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Lu HM, Chen L, Wang JD, Hung MC, Lin MS, Yan YH, Chen CR, Fan PS, Huang LC, and Kuo KN
- Subjects
- Adult, Aged, Aged, 80 and over, Critical Illness epidemiology, Critical Illness therapy, Discriminant Analysis, Female, Humans, Life Expectancy, Logistic Models, Longitudinal Studies, Male, Middle Aged, National Health Programs, Patient Discharge statistics & numerical data, Patient Discharge trends, Retrospective Studies, Taiwan epidemiology, Time Factors, Ventilator Weaning statistics & numerical data, Ventilator Weaning trends, Critical Illness economics, Death Certificates, Insurance Coverage statistics & numerical data, Outcome Assessment, Health Care standards, Outcome Assessment, Health Care statistics & numerical data, Survival Rate trends, Ventilator Weaning economics
- Abstract
Background: This study investigated prognosis among patients under prolonged mechanical ventilation (PMV) through exploring the following issues: (1) post-PMV survival rates, (2) factors associated with survival after PMV, and (3) the number of days alive free of hospital stays requiring mechanical ventilation (MV) care after PMV., Methods: This is a retrospective cohort study based on secondary analysis of prospectively collected data in the national health insurance system and governmental data on death registry in Taiwan. It used data for a nationally representative sample of 25,482 patients becoming under PMV (> = 21 days) during 1998-2003. We calculated survival rates for the 4 years after PMV, and adopted logistic regression to construct prediction models for 3-month, 6-month, 1-year, and 2-year survival, with data of 1998-2002 for model estimation and the 2003 data for examination of model performance. We estimated the number of days alive free of hospital stays requiring MV care in the immediate 4-year period after PMV, and contrasted patients who had low survival probability with all PMV patients., Results: Among these patients, the 3-month survival rate was 51.4%, and the 1-year survival rate was 31.9%. Common health conditions with significant associations with poor survival included neoplasm, acute and unspecific renal failure, chronic renal failure, non-alcoholic liver disease, shock and septicaemia (odd ratio < 0.7, p < 0.05). During a 4-year follow-up period for patients of year 2003, the mean number of days free of hospital stays requiring MV was 66.0 in those with a predicted 6-month survival rate < 10%, and 111.3 in those with a predicted 2-year survival rate < 10%. In contrast, the mean number of days was 256.9 in the whole sample of patients in 2003., Conclusions: Neoplasm, acute and unspecific renal failure, shock, chronic renal failure, septicemia, and non-alcoholic liver disease are significantly associated with lower survival among PMV patients. Patients with anticipated death in a near future tend to spend most of the rest of their life staying in hospital using MV services. This calls for further research into assessing PMV care need among patients at different prognosis stages of diseases listed above.
- Published
- 2012
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20. Estimation of quality-adjusted life expectancy in patients under prolonged mechanical ventilation.
- Author
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Hung MC, Yan YH, Fan PS, Lin MS, Chen CR, Kuo LC, Yu CJ, and Wang JD
- Subjects
- Aged, Comorbidity, Cost-Benefit Analysis, Female, Follow-Up Studies, Humans, Life Expectancy, Life Tables, Male, Monte Carlo Method, National Health Programs, Quality-Adjusted Life Years, Respiration, Artificial economics, Survival Analysis, Taiwan, Time Factors, Respiration, Artificial adverse effects, Respiration, Artificial psychology
- Abstract
Objectives: The purpose of this study was to estimate the quality-adjusted life expectancy (QALE) and the expected lifetime utility loss of patients with prolonged mechanical ventilation (PMV)., Methods: PMV was defined as more than 21 days of mechanical ventilation. A total of 633 patients fulfilled this definition and were followed for 9 years (1998-2007) to obtain their survival status. Quality of life of 142 patients was measured with the EuroQol five-dimensional (EQ-5D) questionnaire during the period 2008 to 2009. The survival probabilities for each time point were adjusted with a utility measurement of quality of life and then extrapolated to 300 months to obtain the QALE. We compared the age-, gender-matched reference populations to calculate the expected lifetime utility loss., Results: The average age of subjects was 76 years old. The life expectancy and loss of life expectancy were 1.95 years and 8.48 years, respectively. The QALE of 55 patients with partial cognitive ability and the ability to respond was 0.58 quality-adjusted life years (QALY), whereas the QALEs of 87 patients with poor consciousness were 0.28 and 0.29 QALY for the EQ-5D measured by family caregivers and nurses, respectively. The loss of QALE for PMV patients was 9.87 to 10.17 QALY, corresponding to a health gap of 94% to 97%., Conclusions: Theses results of poor prognosis would provide stakeholders evidence for communication to facilitate clinical decisions. The estimation may be used in future studies to facilitate the cost-effectiveness and reduction of the health gap., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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21. Life expectancies and incidence rates of patients under prolonged mechanical ventilation: a population-based study during 1998 to 2007 in Taiwan.
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Hung MC, Lu HM, Chen L, Hu FC, Chan SY, Yan YH, Fan PS, Lin MS, Chen CR, Kuo LC, Yu CJ, and Wang JD
- Subjects
- Aged, Aged, 80 and over, Databases, Factual, Female, Humans, Incidence, Male, Middle Aged, Respiration, Artificial mortality, Survival Analysis, Taiwan epidemiology, Time Factors, Treatment Outcome, Life Expectancy trends, Respiration, Artificial statistics & numerical data
- Abstract
Introduction: The present study examined the median survival, life expectancies, and cumulative incidence rate (CIR) of patients undergoing prolonged mechanical ventilation (PMV) stratified by different underlying diseases., Methods: According to the National Health Insurance Research Database of Taiwan, there were 8,906,406 individuals who obtained respiratory care during the period from 1997 to 2007. A random sample of this population was performed, and subjects who had continuously undergone mechanical ventilation for longer than 21 days were enrolled in the current study. Annual incidence rates and the CIR were calculated. After stratifying the patients according to their specific diagnoses, latent class analysis was performed to categorise PMV patients with multiple co-morbidities into several groups. The life expectancies of different groups were estimated using a semiparametric method with a hazard function based on the vital statistics of Taiwan., Results: The analysis of 50,481 PMV patients revealed that incidence rates increased as patients grew older and that the CIR (17 to 85 years old) increased from 0.103 in 1998 to 0.183 in 2004 before stabilising thereafter. The life expectancies of PMV patients suffering from degenerative neurological diseases, stroke, or injuries tended to be longer than those with chronic renal failure or cancer. Patients with chronic obstructive pulmonary disease survived longer than did those co-morbid with other underlying diseases, especially septicaemia/shock., Conclusions: PMV provides a direct means to treat respiratory tract diseases and to sustain respiration in individuals suffering from degenerative neurological diseases, and individuals with either of these types of conditions respond better to PMV than do those with other co-morbidities. Future research is required to determine the cost-effectiveness of this treatment paradigm.
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- 2011
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22. Measurement of quality of life using EQ-5D in patients on prolonged mechanical ventilation: comparison of patients, family caregivers, and nurses.
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Hung MC, Yan YH, Fan PS, Lin MS, Chen CR, Kuo LC, Yu CJ, Yao G, Hsieh CL, and Wang JD
- Subjects
- Activities of Daily Living, Adaptation, Psychological, Adult, Aged, Cognition, Cognition Disorders, Cross-Sectional Studies, Female, Glasgow Coma Scale, Humans, Male, Middle Aged, Patient Satisfaction, Professional-Family Relations, Quality of Health Care, Respiratory Tract Diseases nursing, Respiratory Tract Diseases therapy, Stress, Psychological, Surveys and Questionnaires, Taiwan, Time Factors, Treatment Outcome, Caregivers, Nurses, Psychometrics, Quality of Life psychology, Respiration, Artificial, Respiratory Tract Diseases psychology
- Abstract
Purpose: This study reports how QOL (quality of life) assessments differ between patients on prolonged mechanical ventilation (PMV) and their proxies (family caregivers and nurses)., Methods: We enrolled consecutive subjects on PMV for more than 21 days from five institutions. We conducted QOL assessments using the Taiwanese version of the EQ-5D in face-to-face interviews. Direct caregivers (family members and nurses) also completed the EQ-5D from the patient's point of view., Results: For 55 of the 142 enrolled patients who were able to assess their QOL, we recruited 44 patient-family caregiver pairs, 53 patient-nurse pairs, and 42 family caregiver-nurse pairs. There were 81 family caregiver-nurse pairs out of 87 patients with poor cognition. The agreement between patient-family caregiver pairs was generally higher than that of patient-nurse pairs. As the proportions of exact agreement between family caregivers and nurses for patients with poor cognition were 98-99% for observable dimensions of mobility, self-care, and usual activities, they lead to a minimal difference in the final values., Conclusions: QOL assessments from family caregivers agreed more closely with patients than did those from nurses using EQ-5D evaluations for patients with clear cognition, but either proxy was acceptable for rating PMV patients with poor cognition.
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- 2010
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23. Oral administration of Yokukansan inhibits the development of atopic dermatitis-like lesions in isolated NC/Nga mice.
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Jiang J, Yamaguchi T, Funakushi N, Kuhara T, Fan PS, Ueki R, Suto H, Kase Y, Ikeda S, and Ogawa H
- Subjects
- Administration, Oral, Animals, Corticosterone blood, Dermatitis, Atopic pathology, Immunoglobulin E blood, Male, Mice, Nerve Growth Factor blood, Skin immunology, Skin pathology, Social Isolation psychology, Dermatitis, Atopic drug therapy, Dermatitis, Atopic psychology, Drugs, Chinese Herbal administration & dosage, Pruritus drug therapy, Pruritus psychology
- Abstract
Background: Increasing evidence suggests that stress can trigger and exacerbate atopic dermatitis (AD). Psychotherapy is becoming more important in the treatment of AD patients. Yokukansan (YKS, Yi-Gan San in Chinese), a traditional Japanese medicine, has been widely utilized in the treatment of neurosis, insomnia and anxiety especially in Asian countries. Furthermore, it was reported that YKS inhibited skin lesions in socially isolated mice but not in group-housed mice. Therefore, in the present study it was investigated whether or not YKS was effective in the treatment of AD using socially isolated NC/Nga mice., Objective: The present study was designed to assess the effect of YKS on the development of AD-like lesions in socially isolated NC/Nga mice to obtain information about its usefulness in the treatment of AD., Methods: Ten-week-old male NC/Nga mice were socially isolated under conventional conditions. YKS was administered orally to mice at the dose of 0.5% or 1.0% together with diet. The efficacy of YKS was evaluated by assessing skin lesion severity, scratching behaviors, skin hydration, and infiltration of inflammatory cells in the skin. Grooming behaviors evoked by social isolation stress and serum corticosterone levels were also measured., Results: Oral administration of YKS to socially isolated NC/Nga mice resulted in the inhibition of exacerbation of AD-like skin lesions. It seemed that the inhibition of exacerbation of AD-like skin lesions observed in NC/Nga mice might be due to suppression of the scratching and grooming behaviors, inhibition of the infiltration of mast cells and eosinophils, and retention of humidity in the skin. Serum corticosterone levels were also significantly inhibited in the 1%-YKS-treated mice as compared with those of the control mice. There were no significant differences in the levels of serum total IgE and nerve growth factor (NGF) between the YKS-treated mice and the non-treated control mice., Conclusion: YKS inhibited the development of AD-like skin lesions in socially isolated NC/Nga mice by suppressing scratching and infiltration of inflammatory cells in the skin. These results indicate that YKS possesses an anti-itching property, and its anti-itching may be partly through attenuation on social isolation stress. It is expected that YKS might provide an effective alternative therapy for AD in human patients.
- Published
- 2009
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24. Effect of carbendazim resistance on trichothecene production and aggressiveness of Fusarium graminearum.
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Zhang YJ, Yu JJ, Zhang YN, Zhang X, Cheng CJ, Wang JX, Hollomon DW, Fan PS, and Zhou MG
- Subjects
- Benzimidazoles metabolism, Blotting, Southern, Carbamates metabolism, Fusarium genetics, Gene Expression Regulation, Fungal drug effects, Genes, Fungal, Microbial Sensitivity Tests, Mutagenesis, Site-Directed, Reproducibility of Results, Time Factors, Triticum microbiology, Antifungal Agents pharmacology, Benzimidazoles pharmacology, Carbamates pharmacology, Drug Resistance, Fungal drug effects, Fusarium drug effects, Fusarium pathogenicity, Trichothecenes biosynthesis
- Abstract
Fusarium graminearum (teleomorph, Gibberella zeae) causes head blight of cereals and contaminates grains with trichothecene mycotoxins that are harmful to humans and domesticated animals. Control of Fusarium head blight relies on carbendazim (MBC) in China, but resistance to MBC in F. graminearum is now widespread. Sixty-seven strains were evaluated for trichothecene production in shake culture or in the field. The strains included 60 wild-type strains (30 MBC-resistant and 30 MBC-sensitive), three MBC-resistant site-directed mutants at codon 167 in beta(2)-tubulin, three MBC-sensitive site-directed mutants at codon 240 in beta(2)-tubulin, and their MBC-sensitive wild-type progenitor strain ZF21. The incidence of infected spikelets and the amount of F. graminearum DNA in field grain (AFgDNA) also were evaluated for all strains. MBC resistance increased trichothecene production in shake culture or in the field. Although MBC resistance did not change the incidence of infected spikelets, it did increase AFgDNA. Tri5 gene expression increased in MBC-resistant strains grown in shake culture. We found a significant exponential relationship between trichothecene production and Tri5 gene expression in shake culture and a linear relationship between the incidence of infected spikelets or AFgDNA and trichothecene production in field grain.
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- 2009
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25. Repeated pneumonia severity index measurement after admission increases its predictive value for mortality in severe community-acquired pneumonia.
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Chen CZ, Fan PS, Lin CC, Lee CH, and Hsiue TR
- Subjects
- Community-Acquired Infections diagnosis, Female, Follow-Up Studies, Hospital Mortality trends, Humans, Male, Middle Aged, Pneumonia diagnosis, Prognosis, Prospective Studies, Survival Rate trends, Taiwan epidemiology, Time Factors, Community-Acquired Infections mortality, Patient Admission, Pneumonia mortality, Severity of Illness Index
- Abstract
Background/purpose: Severe community-acquired pneumonia (CAP) is associated with high hospital mortality, and accurate assessment of patients is important for supporting clinical decision making. The Pneumonia Severity Index (PSI) is a good tool for predicting disease severity, especially in the low-risk group of patients with CAP. We investigated whether the change in PSI measurement after admission could identify patients at high risk of mortality from CAP., Methods: We prospectively studied 250 inpatients with CAP. PSI was measured at admission and 72 hours later at a tertiary referral medical center from May 2005 to February 2006. The initial and repeated PSI results were compared. Hospital mortality was used as the outcome measure., Results: Initial PSI in high-risk patients (PSI class > IV) had a low specificity (37%), and a low positive predictive value (PPV) (17%). Increased repeated PSI score, as compared with initial score, was associated with an increased mortality rate (from 7.8% to 33.3% in class IV, and 25.3% to 53.3% in class V; p < 0.0001), and improved the predictive value, with 94% specificity and a PPV of 46% for mortality in high-risk patients., Conclusion: Increased PSI score, 72 hours after admission, for patients with CAP improved the predictive value of PSI score and more accurately identified patients with a high risk of mortality.
- Published
- 2009
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26. Quantification of Fusarium graminearum in harvested grain by real-time polymerase chain reaction to assess efficacies of fungicides on fusarium head blight, deoxynivalenol contamination, and yield of winter wheat.
- Author
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Zhang YJ, Fan PS, Zhang X, Chen CJ, and Zhou MG
- Subjects
- DNA, Fungal isolation & purification, Food Contamination, Polymerase Chain Reaction, Fungicides, Industrial pharmacology, Fusarium drug effects, Fusarium isolation & purification, Trichothecenes chemistry, Triticum microbiology
- Abstract
We used a real time polymerase chain reaction-based assay and visual disease assessment to evaluate the efficacies of Js399-19, tebuconazole, a mixture of tebuconazole and thiram, azoxystrobin, carbendazim, and thiram on the development of Fusarium head blight (FHB) and deoxynivalenol (DON) contamination and on the yield of winter wheat (cv. Nannong no. 9918) after artificial inoculation under field conditions with Fusarium graminearum. The incidence of infected spikelets (IIS), amount of F. graminearum DNA (Tri5 DNA), total DON (containing DON, 3-acetyl-deoxynivalenol, and 15-acetyl-deoxynivalenol) concentration, and 1,000-grain weight (TGW) were quantified in 2006 and 2007. A strong positive correlation was found between IIS or Log10Tri5 DNA and total DON concentration in the harvested grain. The Js399-19, tebuconazole, and the mixture of tebuconazole and thiram significantly reduced IIS of FHB, amount of Tri5 DNA, and total DON within the grain and increased TGW. Although azoxystrobin, carbendazim, and thiram can increase TGW, they had no effect on the occurrence of F. graminearum compared with those of the untreated controls. Surprisingly, azoxystrobin and carbendazim significantly increased the total DON content in the harvested grain because they might have stimulated the amount of total DON production per Tri5 DNA. The fungicides Js399-19, tebuconazole, and the mixture of tebuconazole and thiram were the most effective in controlling FHB and reducing DON contamination of the wheat.
- Published
- 2009
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27. Identification of poly-reactive natural IgM antibody that recognizes late apoptotic cells and promotes phagocytosis of the cells.
- Author
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Fu M, Fan PS, Li W, Li CX, Xing Y, An JG, Wang G, Fan XL, Gao TW, Liu YF, and Ikeda S
- Subjects
- Actins metabolism, Amino Acid Sequence, Animals, Antigens metabolism, Base Sequence, Germ Cells immunology, Immunoglobulin Fc Fragments immunology, Immunoglobulin Variable Region chemistry, Immunoglobulin Variable Region genetics, Kinetics, Ligands, Mice, Mice, Inbred BALB C, Phospholipids metabolism, Protein Binding, Apoptosis immunology, Immunoglobulin M immunology, Macrophages cytology, Phagocytosis immunology, Thymus Gland cytology
- Abstract
Unlabelled: Natural IgM can recognize apoptotic cells, but the molecular structure and the role in macrophage phagocytosis of apoptotic cells remain unclear., Objectives: (1) To examine the binding of previously isolated natural IgM (3B4) to apoptotic cells and its effects on phagocytosis of apoptotic cells. (2) To characterize the molecular structure of 3B4., Methods: 3B4 binding to apoptotic thymocytes was examined by flow cytometry. Polyreactivity of 3B4 was assayed by ELISA. PKH26-labeled Macrophages were incubated with PKH67-stained apoptotic cells in the presence of 3B4. Macrophages phagocytosis of apoptotic cell was evaluated by flow cytometry. The DNA segments of 3B V(H) and V(K) were sequenced and analyzed., Results: 3B4 IgM recognized late apoptotic cells. Polyreactive-recognitions of lysophosphatidylcholine (LPC) as well as some autoantigens were observed in 3B4. Phagocytosis of late apoptotic cells was increased in the presence of 3B4. The V(H) and V(K) genes of 3B4 showed a germline gene context, while N-sequences and nucleotide loss were observed in CDR3., Conclusion: 3B4 promotes macrophage phagocytosis of late apoptotic cells in a complement-independent process. 3B4 has a germline configuration and is possibly ligand-selected. Out experiments suggest an independent role of natural IgM as opsonin in clearance of late apoptotic cells.
- Published
- 2007
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28. Association between enhanced type I collagen expression and epigenetic repression of the FLI1 gene in scleroderma fibroblasts.
- Author
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Wang Y, Fan PS, and Kahaleh B
- Subjects
- Azacitidine pharmacology, Cells, Cultured, Collagen Type I metabolism, CpG Islands genetics, CpG Islands physiology, DNA Methylation, DNA Modification Methylases antagonists & inhibitors, DNA Modification Methylases physiology, Epigenesis, Genetic physiology, Fibroblasts drug effects, Fibroblasts pathology, Gene Expression Regulation drug effects, Gene Expression Regulation physiology, Genes, Suppressor physiology, Histone Deacetylase Inhibitors, Histone Deacetylases physiology, Humans, Hydroxamic Acids pharmacology, Phenotype, Promoter Regions, Genetic physiology, Proto-Oncogene Protein c-fli-1 metabolism, Scleroderma, Systemic metabolism, Scleroderma, Systemic pathology, Signal Transduction genetics, Signal Transduction physiology, Skin drug effects, Skin metabolism, Skin pathology, Transfection, Collagen Type I genetics, Epigenesis, Genetic genetics, Fibroblasts metabolism, Proto-Oncogene Protein c-fli-1 genetics, Scleroderma, Systemic genetics
- Abstract
Objective: Scleroderma (systemic sclerosis; SSc) is an autoimmune disease characterized by vasculopathy and widespread organ fibrosis. Altered fibroblast function, both in vivo and in vitro, is well documented and illustrated by augmented synthesis and deposition of extracellular matrix proteins. We undertook this study to investigate the possibility that epigenetic mechanisms mediate the emergence and persistence of the altered SSc fibroblast phenotype., Methods: The effects of DNA methyltransferase and histone deacetylase inhibitors on collagen expression and the level of epigenetic mediators in fibroblasts were examined. The effects of transient transfection of SSc fibroblasts with FLI1 gene and normal cells with FLI1 antisense construct on collagen expression were determined. The methylation status of the FLI1 promoter was tested in cultured cells and in SSc and normal skin biopsy specimens., Results: Increased levels of epigenetic mediators in SSc fibroblasts were noted. The addition of epigenetic inhibitors to cell cultures normalized collagen expression in SSc fibroblasts. The augmented collagen synthesis by SSc fibroblasts was linked to epigenetic repression of the collagen suppressor gene FLI1. Heavy methylation of the CpG islands in the FLI1 promoter region was demonstrated in SSc fibroblasts and skin biopsy specimens., Conclusion: The results of this study indicate that epigenetic mechanisms may mediate the fibrotic manifestations of SSc. The signal transduction leading to the SSc fibrotic phenotype appears to converge on DNA methylation and histone deacetylation at the FLI1 gene.
- Published
- 2006
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29. Altered keratin 17 peptide ligands inhibit in vitro proliferation of keratinocytes and T cells isolated from patients with psoriasis.
- Author
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Shen Z, Chen L, Liu YF, Gao TW, Wang G, Fan XL, Fan JY, Fan PS, Li CY, Liu B, Dang YP, and Li CX
- Subjects
- Cell Proliferation, Cells, Cultured, Humans, Ligands, Peptides, Receptors, Antigen, T-Cell physiology, Keratinocytes cytology, Keratins physiology, Psoriasis pathology, T-Lymphocytes cytology
- Abstract
Background: Identification of critical autoantigenic T-cell epitopes is key to developing antigen-based therapies for autoimmune diseases, including psoriasis. Our previous work demonstrated that 3 peptides on keratin 17 are able to stimulate peripheral blood lymphocytes of HLA-DRB1*07-positive patients with psoriasis and to serve as immunodominant T-cell epitopes., Objective: We sought to determine antagonistic altered peptide ligands to psoriatic T cells with a down-modulatory effect in inhibiting keratinocyte proliferation., Methods: Psoriatic altered peptide ligands were generated by single alanine residue substitutions at a critical T-cell receptor contact residue position. Antagonistic altered peptide ligands were identified by suppression screening of psoriatic T-cell activation and keratinocyte proliferation., Results: Altered peptide ligands 119R and 355L can inhibit psoriatic T-cell activation more effectively than other altered peptide ligands, especially 355L, with inhibition of T-cell proliferation and the secretion of interferon gamma and interleukin 2 in parallel with the up-regulation of interleukins 4 and 10 as well as transforming growth factor-beta. In coincubation assay, altered peptide ligands 119R and 355L can down-regulate the function of psoriatic T cells more effectively than wild-type epitopes solely, but less effectively than altered peptide ligands solely. In prepulse assay altered peptide ligand 119R can down-regulate the activation of psoriatic T cells more effectively than in coincubation but less effectively as compared with altered peptide ligand 119R only. Altered peptide ligand 355L was also shown to have a similar presentation. T-cell culture supernatants (1:100) from the concentrations (10 microg.mL(-1) and 100 microg.mL(-1) with 119R, 100 microg.mL(-1) with 355L) were more effective than the other ratios in inhibiting keratinocyte proliferation., Limitations: This study had a relatively small sample size (52 patients and 48 healthy controls)., Conclusion: Our findings show that the altered peptide ligands 119R (VAALEEANTELEVKI) and 355L (ENRYCVQASQIQGLI) are capable of inhibiting proliferative responses of psoriatic T cells and keratinocyte proliferation in vitro, at least, with enhanced helper T cell type 2 polarization. Thus, to our knowledge, this article is the first report of the demonstration of therapeutic activity of altered peptide ligands derived from keratin 17.
- Published
- 2006
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30. Clinicopathological and ultrastructural study of multiple lobular capillary hemangioma after scalding.
- Author
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Liao WJ, Fan PS, Fu M, Gao TW, Liu YF, and Ikeda S
- Subjects
- Adult, Humans, Male, Burns complications, Granuloma, Pyogenic pathology, Granuloma, Pyogenic physiopathology
- Abstract
We herein report 2 cases of multiple lobular capillary hemangiomas after scalding. The patients exhibited papules and nodules on the scalded areas after healing. Histopathological examination of the lesions showed capillary proliferation in the upper dermis with edematous stroma containing inflammatory infiltrates predominantly composed of neutrophils. Biopsy tissue and secretion specimens from lesions of case 1 were cultured for bacteria, and both grew Enterobacter cloacae. Ultrastructural examination revealed features typical of a lobular capillary hemangioma and viral inclusion bodies in the epidermis of case 1. Multiple lobular capillary hemangiomas after scalding are rarely reported. Trauma may play an important role in the development of this rare condition. Accumulation of similar cases and its precise observation is needed to confirm the associations and to establish an etiological link between the disease and the pathogens.
- Published
- 2006
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31. Increased expression of 70 kD heat shock protein in cultured primary human keratinocytes induced by human papillomavirus 16 E6/E7 gene.
- Author
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Liao WJ, Fan PS, Fu M, Fan XL, and Liu YF
- Subjects
- Cells, Cultured, Humans, Papillomavirus E7 Proteins, Transfection, HSP72 Heat-Shock Proteins biosynthesis, Keratinocytes metabolism, Oncogene Proteins, Viral genetics, Repressor Proteins genetics
- Abstract
Background: Heat shock protein 70 (HSP70) is expressed highly in epithelial tumours associated closely with human papillomavirus 16 (HPV16) infections. However, evidence about the direct relationship between HSP70 expression and HPVs infections are still lacking. In the present study, we examined the expression of HSP70 in keratinocytes introduced with HPV16 E6/E7 oncogenes., Methods: Stable transfected cells were established by transfection of the plasmids pLXSN16E6/E7 into cultured primary keratinocytes and subsequently selected by plasmid specific selection antibiotic (G418) at the required concentration. The expression of HSP70 in pLXSN16E6/E7 transfected keratinocytes was determined by Western blot. The correlation of HSP70 expression and E6/E7 transfection was further confirmed by doubly labelled immunofluorescent staining., Results: Compared to non-transfected keratinocytes, there was a significant trend for higher levels of HSP70 in pLXSN16E6/E7 transfected keratinocytes. Doubly labelled immunofluorescent staining experiment showed that the co-localization of HPV16 E6/E7 and HSP70 in transfected keratinocytes was observed and increased expression of HSP70 was strongly associated with the transfection of HPV16 E6/E7., Conclusions: Our studies demonstrated increased levels of HSP70 proteins in keratinocytes stably transfected by HPV16 E6/E7 oncogenes. It suggests that the expression of HSP70 is modulated by HPV16 E6/E7 proteins, which may be involved in HPV16 E6/E7 induced immortalization.
- Published
- 2005
32. Effects of ultraviolet B irradiation, proinflammatory cytokines and raised extracellular calcium concentration on the expression of ATP2A2 and ATP2C1.
- Author
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Mayuzumi N, Ikeda S, Kawada H, Fan PS, and Ogawa H
- Subjects
- Cell Differentiation genetics, Cell Differentiation physiology, Cell Differentiation radiation effects, Cells, Cultured, Darier Disease genetics, Gene Expression Regulation drug effects, Gene Expression Regulation genetics, Gene Expression Regulation radiation effects, Humans, Infant, Newborn, Interleukin-1 pharmacology, Interleukin-6 pharmacology, Interleukin-8 pharmacology, Keratinocytes drug effects, Keratinocytes radiation effects, Pemphigus, Benign Familial genetics, RNA, Messenger analysis, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Tumor Necrosis Factor-alpha pharmacology, Calcium metabolism, Calcium-Transporting ATPases genetics, Cytokines pharmacology, Keratinocytes physiology, Ultraviolet Rays adverse effects
- Abstract
Background: Darier disease (DD) and Hailey-Hailey disease (HHD) are autosomal dominantly inherited skin disorders that histologically share the characteristics of suprabasal separation and acantholysis of epidermal keratinocytes. Various mutations in the DD gene (ATP2A2) and the HHD gene (ATP2C1) (respectively encoding the calcium pumps of the sarco/endoplasmic reticulum and the Golgi apparatus) have recently been described in multiple families with DD and HHD. Mutations in ATP2A2 or ATP2C1 have been suggested as causing the conditions via the mechanism of haploinsufficiency. Ultraviolet (UV) B irradiation is thought to be an aggravating factor in both diseases., Objectives: To examine the effects of various stimuli on ATP2A2 and ATP2C1 mRNA expression, and to examine the role of calcium pumps during keratinocyte differentiation., Methods: The effects of UVB irradiation, of UVB-inducible inflammatory cytokines produced by keratinocytes and of high-calcium medium (1.8 mmol L(-1) as opposed to 0.08 mmol L(-1) Ca2+) on ATP2A2 and ATP2C1 mRNA expression were quantified in cultured normal human keratinocytes using reverse transcription-polymerase chain reaction., Results: Expression of ATP2A2 and ATP2C1 mRNA was suppressed immediately after exposure to UVB irradiation, and modulation of mRNA expression was achieved in keratinocytes cultured with proinflammatory cytokines. The mRNA expression of both genes was increased significantly after the shift to high extracellular Ca2+ concentration., Conclusions: The results suggest that modulation of ATP2A2 and ATP2C1 mRNA expression by UV or cytokines might contribute to the clinical presentations unique to DD and HHD, and that the controlled expression of these genes plays an important role in keratinocyte homeostasis, function and differentiation.
- Published
- 2005
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33. Inhibitory effect of quercetin on proliferation of human microvascular endothelial cells in vitro.
- Author
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Fan PS, Gu ZL, Sheng R, Liang ZQ, Wang XX, and Zhu Y
- Subjects
- Cell Division drug effects, Cells, Cultured, Endothelial Cells cytology, Humans, Skin cytology, Endothelial Cells drug effects, Quercetin pharmacology
- Abstract
Aim: To investigate the role of quercetin (Que) in the proliferation of cultured human skin microvascular endothelial cells (MVEC)., Methods: Cell count and [methyl-3H]thymidine ([3H]TdR) uptake assay were used to measure the effect of Que in the proliferation of cultured MVEC. Cytotoxicity of Que on MVEC was also evaluated by 51Cr release assay., Results: When MVEC were treated with Que, the proliferation was significantly inhibited in a time-course and dose-dependent manner. Que 5 micromol/L did not inhibit the proliferation of MVEC. When the concentration of Que increased to 20, 40, 80, and 160 micromol/L, the cell numbers per well were decreased and the inhibition rate was 12.2 %, 23.5 %, 35.3 %, and 54.1 % respectively with IC50 of 138 micromol/L. The inhibitory rate of [3H]-TdR uptake was 18.7 %, 34.4 %, 48.9 %, and 62.5 % respectively (IC(50)=87.5 micromol/L). (51)Cr release assay showed that Que 160 micromol/L incubated with MVEC from 1 to 16 h had no clear cytotoxicity compared with control group., Conclusion: Que greatly inhibited the proliferation of cultured human MVEC in vitro. This effect may not be related to the cytotoxicity of Que on MVEC.
- Published
- 2003
34. [Effects of quercetin on platelet-endothelial cell adhesion and their expression of adhesion molecules].
- Author
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Liang ZQ, Zhu Y, Gu ZL, Lu Q, and Fan PS
- Subjects
- Blood Platelets metabolism, Cells, Cultured, Endothelium, Vascular metabolism, Humans, Intercellular Adhesion Molecule-1 metabolism, P-Selectin metabolism, Umbilical Veins cytology, Blood Platelets drug effects, Cell Adhesion drug effects, Endothelium, Vascular drug effects, Gene Expression drug effects, Quercetin pharmacology
- Abstract
Aim: To observe the effect of quercetin (Que) on the adhesion of platelets to cultured endothelial cells and adhesion molecule expression by human umbilical vein endothelial cells (HUVEC) and platelets., Methods: [3H]-Adenine labeled platelets were incubated with HUVEC to investigate the effect of Que on adhesion of platelets to HUVEC. The number of platelets adhering to the HUVEC monolayer was determined by liquid scintillation spectroscopy. TNF-alpha induced HUVEC expression ICAM-1 and thrombin induced platelets expression of P-selectin were measured by flow cytometry., Results: Que (0.3-2.4 mumol.L-1) was shown to inhibit the increase of P-selectin expression of thrombin activated platelets. Pretreatment of HUVEC with tumor necrosis factor (TNF-alpha) significantly increased platelets adhesion to HUVEC and the expression ICAM-1. Que (0.6-2.4 mumol.L-1) inhibited this effect of TNF-alpha in a concentration-dependent manner., Conclusion: Que can inhibit the adhesion of platelets to HUVEC and the expression of adhesion molecules (P-selectin and ICAM-1).
- Published
- 2003
35. Expression of recombinant human ICOS and in vitro characterization of its bioactivity on B lymphocytes.
- Author
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Deng ZB, Lu CM, Huang WD, Shen LQ, Zhu W, Ma HB, Fan PS, and Zhang XG
- Subjects
- Antigens, Differentiation, T-Lymphocyte isolation & purification, Antigens, Differentiation, T-Lymphocyte pharmacology, Cloning, Molecular, Escherichia coli genetics, Genetic Vectors, Humans, Immunoglobulin G biosynthesis, Inducible T-Cell Co-Stimulator Protein, Lymphocyte Activation drug effects, Recombinant Proteins isolation & purification, Recombinant Proteins pharmacology, Antigens, Differentiation, T-Lymphocyte biosynthesis, B-Lymphocytes drug effects, Recombinant Proteins biosynthesis
- Abstract
Inducible costimulator (ICOS) is a novel costimulatory molecule expressed in activated T cell and has critical regulation effect on special immune response. In this study, the cDNA encoding human ICOS was cloned from activated tonsil cells via RT-PCR, and was expressed in E. coli on pET28 expression vector. The recombinant ICOS protein expressed from E. coli showed a molecular weight of 14 kD on SDS-polyacrylamide gel electrophoresis and was further confirmed by Western blot. In presence of IL-10, the purified rhICOS significantly increased in vitro B cell growth stimulated by pokeweed mitogen (PWM), and enhanced the secretion of IgG from B cells.
- Published
- 2003
36. Inhibitory effects of prostaglandin A1 on apoptosis of rat cardiac microvascular endothelial cells was mediated by NF-kappaB.
- Author
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He JK, Gu ZL, and Fan PS
- Subjects
- Animals, Capillaries cytology, Cell Hypoxia, Cells, Cultured, Coronary Vessels cytology, Endothelium, Vascular cytology, Proto-Oncogene Proteins biosynthesis, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins c-bcl-2 biosynthesis, Proto-Oncogene Proteins c-bcl-2 genetics, RNA, Messenger biosynthesis, RNA, Messenger genetics, Rats, Rats, Wistar, bcl-2-Associated X Protein, Apoptosis, Endothelium, Vascular drug effects, NF-kappa B metabolism, Prostaglandins A pharmacology
- Abstract
Aim: To study the effects of prostaglandin A1 (PGA1) on rat cardiac microvascular endothelial cells. METH-ODS: Isolated rat cardiac microvascular endothelial cells were cultured in hypoxia and reoxygen conditions, respectively. Endothelial cell apoptosis was detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling staining. The activity of NF-kappaB was detected by electrophoretic mobility shift assay. Bcl-2 and Bax protein expression were examined by Western blot and bcl-2 mRNA expression was examined by Northern blot., Results: PGA1 reduced endothelial cell apoptosis markedly, inhibited activity of NF-kappaB, and increased expression of Bcl-2 protein and bcl-2 mRNA. However, PGA1 did not alter Bax protein expression resulting in an increase in the ratio of Bcl-2 to Bax., Conclusion: PGA1 can inhibit rat cardiac microvascular endothelial cell apoptosis by inhibiting activity of NF-kappaB.
- Published
- 2002
37. Reproducible gene expression measurement among multiple laboratories obtained in a blinded study using standardized RT (StaRT)-PCR.
- Author
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Crawford EL, Peters GJ, Noordhuis P, Rots MG, Vondracek M, Grafström RC, Lieuallen K, Lennon G, Zahorchak RJ, Georgeson MJ, Wali A, Lechner JF, Fan PS, Kahaleh MB, Khuder SA, Warner KA, Weaver DA, and Willey JC
- Subjects
- Binding, Competitive genetics, Cell Line, DNA, Complementary genetics, Databases, Genetic, Double-Blind Method, Gene Expression, Gene Expression Profiling classification, Gene Expression Profiling statistics & numerical data, Humans, Lung chemistry, Lung cytology, Lung metabolism, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction statistics & numerical data, Templates, Genetic, Terminology as Topic, Gene Expression Profiling standards, Reverse Transcriptase Polymerase Chain Reaction standards
- Abstract
Background: A method that provides standardized data and is relatively inexpensive and capable of high throughput is a prerequisite to the development of a meaningful gene expression database suitable for conducting multi-institutional clinical studies based on expression measurement. Standardized RT (StaRT)-PCR has all these characteristics. In addition, the method must be reproducible. StaRT-PCR has high intralaboratory reproducibility. The purpose of this study is to determine whether StaRT-PCR provides similar interlaboratory reproducibility., Methods and Results: In a blinded interlaboratory study, expression of ten genes was measured by StaRT-PCR in a complementary DNA sample provided to each of four laboratories. The average coefficient of variation for interlaboratory comparison of the nine quantifiable genes was 0.48. In all laboratories, expression of one of the genes was too low to be measured., Conclusion: Because StaRT-PCR data are standardized and numerical and the method is reproducible among multiple laboratories, it will allow development of a meaningful gene expression database.
- Published
- 2001
- Full Text
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38. Initial evidence of endothelial cell apoptosis as a mechanism of systemic capillary leak syndrome.
- Author
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Assaly R, Olson D, Hammersley J, Fan PS, Liu J, Shapiro JI, and Kahaleh MB
- Subjects
- Humans, Microcirculation pathology, Pancreatitis pathology, Reactive Oxygen Species metabolism, Systemic Inflammatory Response Syndrome pathology, Apoptosis physiology, Capillary Leak Syndrome pathology, Endothelium, Vascular pathology
- Abstract
Background: Systemic capillary leak syndrome (SCLS) is a rare disorder of unknown etiology that is characterized by acute recurrent attacks of hypovolemic shock commonly following an inflammatory stimulus such as a viral illness. Prophylactic therapy is generally ineffective, and the outcome is frequently fatal., Methods: In order to investigate the cellular mechanisms leading to SCLS, we examined the effects of sera from two patients with active SCLS on microvascular endothelial cell apoptosis in vitro. Apoptosis was determined by morphologic criteria, DNA fragmentation, annexin V stain, and by a quantitative photometric assay. The apoptotic pathway was investigated by Western blot of endothelial cells lysate after exposure to SCLS sera., Results: The sera from patients with active SCLS mediated profound apoptosis of microvascular endothelial cells shortly after exposure. The exposed microvascular endothelial cells underwent immediate apoptosis as evidenced by morphologic changes, plasma membrane phosphatidylserine exposure, and by DNA fragmentation. Increased Bax/Bcl-2 ratio in endothelial cells exposed to SCLS sera was observed and suggested an oxidation injury as the possible mechanism for endothelial apoptosis. This potential mechanism was further explored by measuring intracellular reactive oxygen species (ROS) following SCLS serum exposure. Sera from both patients caused marked increases in ROS, initially detectable at 1 h and persisted for at least 12 h, with control serum from healthy subjects showing no effect on basal endothelial cell ROS concentrations., Conclusion: Components from the sera of patients with active systemic capillary leak syndrome in contrast to healthy subject sera mediate early and extensive endothelial apoptosis in vitro that is associated with oxidation injury. These data represent compelling initial evidence for oxidation-induced apoptosis as a likely mechanism for endothelial injury leading to SCLS.
- Published
- 2001
- Full Text
- View/download PDF
39. Effect of quercetin on adhesion of platelets to microvascular endothelial cells in vitro.
- Author
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Fan PS, Gu ZL, and Liang ZQ
- Subjects
- Capillaries cytology, Cell Adhesion drug effects, Cell Separation, Humans, Blood Proteins pharmacology, Endothelium, Vascular cytology, Platelet Adhesiveness drug effects, Quercetin pharmacology
- Abstract
Aim: To study the effect of quercetin(Que) on the adhesion of platelets to microvascular endothelial cells (MVEC) isolated from human skin., Methods: [3H]-adenine-labeled platelets were incubated with MVEC. Effect of Que on platelet endothelial cell adhesion molecular (PECAM) expression on MVEC was also evaluated using enzyme-linked immunosorbent assay (ELISA)., Results: Adhesion of platelet to MVEC reached to maximum at about 30 min. Que inhibited the adhesion of platelets to MVEC in a concentration-dependent manner. Que 5 micromol/L did not show any significant inhibition. When the concentration of Que increased to 10, 20, and 40 micromol/L, the inhibition rate increased to 10.5 %, 20.0 %, and 42.2 %, respectively. Pre-incubation of Que (10 - 40 micromol/L) with labeled platelets for 30 min also inhibited the adhesion but Que 5 micromol/L did not. The inhibition rate of Que 10, 20, and 40 micromol/L was 18.2 %, 29.8 %, and 65.3 % respectively. Expression of PECAM on the endothelial cells was decreased in a concentration-dependent manner when MVEC were treated with Que (10 - 40 micromol/L) for 12 h but Que 5 micromol/L did not significantly affect the expression., Conclusion: Que could inhibit the adhesion of platelets to MVEC. This effect may be related to decreased expression of PECAM on MVEC.
- Published
- 2001
40. Nerve growth factor and neuropeptides circulating levels in systemic sclerosis (scleroderma).
- Author
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Matucci-Cerinic M, Giacomelli R, Pignone A, Cagnoni ML, Generini S, Casale R, Cipriani P, Del Rosso A, Tirassa P, Konttinen YT, Kahaleh BM, Fan PS, Paoletti M, Marchesi C, Cagnoni M, and Aloe L
- Subjects
- Biomarkers blood, Case-Control Studies, Data Interpretation, Statistical, Female, Humans, Lung physiopathology, Male, Middle Aged, Neuropeptide Y blood, Scleroderma, Systemic pathology, Scleroderma, Systemic physiopathology, Skin pathology, Statistics, Nonparametric, Vasoactive Intestinal Peptide blood, Nerve Growth Factor blood, Neuropeptides blood, Scleroderma, Systemic blood
- Abstract
Objective: To determine the circulating levels of nerve growth factor (NGF), neuropeptide Y (NPY), and vasoactive intestinal peptide (VIP) in systemic sclerosis (SSc), and to correlate these levels with clinical and laboratory features., Methods: Forty four patients with SSc were evaluated for circulating NGF (immunoenzymatic assay), NPY and VIP (radioimmunoassay), anticentromere and antitopoisomerase I autoantibodies, lung disease (pulmonary function tests with carbon monoxide transfer factor (TLCO), ventilation scintiscan with 99mTc DTPA radioaerosol, high resolution computed tomography (HRCT), pulmonary pressure (echo colour Doppler)), heart disease (standard and 24 ECG, echocardiography), cutaneous involvement (skin score), joint involvement (evidence of tender or swollen joints, or both), peripheral nervous system (PNS) involvement (electromyography), rheumatoid factor, angiotensin converting enzyme (fluorimetric method), von Willebrand factor (ELISA), and erythrocyte sedimentation rate (ESR) (Westergren)., Results: Circulating NGF levels in SSc were significantly increased compared with controls (p<0.00001) and significantly higher in the diffuse than in the limited subset of patients (p<0.01). Patients with articular disease had significantly higher levels of NGF. A significant indirect correlation between NGF levels and TLCO was detected (p<0.01), but no correlation was found between NGF and HRCT, DTPA, skin score, PNS involvement and angiotensin converting enzyme and von Willebrand factor levels, antitopoisomerase or anticentromere antibodies, and ESR. NGF levels increased progressively as the disease worsened. Similarly, VIP circulating levels were significantly increased in patients with SSc (p<0.001), whereas the increase of NPY levels did not reach statistical significance. However, both neuropeptides, following the same trend as NGF, increased as the disease worsened (skin score and lung disease)., Conclusions: The increase of NGF and VIP in patients with SSc, the former in the diffuse subset of the disease, and in patients with prominent articular disease, may suggest a link between neurotransmitters and the disease pathogenesis. Neuropeptide circulating levels seem to increase only in patients with the most severe disease.
- Published
- 2001
- Full Text
- View/download PDF
41. Gammadelta receptor bearing T cells in scleroderma: enhanced interaction with vascular endothelial cells in vitro.
- Author
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Kahaleh MB, Fan PS, and Otsuka T
- Subjects
- Cell Division, Cells, Cultured, Cytotoxicity, Immunologic, Endothelium, Vascular cytology, Granzymes, Humans, RNA, Messenger, Scleroderma, Systemic immunology, Serine Endopeptidases genetics, Receptors, Antigen, T-Cell, gamma-delta immunology, T-Lymphocytes immunology
- Abstract
In view of the documented perivascular mononuclear cell infiltration in the involved organs in scleroderma (SSc) and the reported accumulation of gammadelta-T cells in SSc skin and lung, we evaluated gammadelta-T cell interaction with endothelial cells (EC) in vitro. gammadelta- and alphabeta-T cells were isolated from BPMN of SSc patients with early diffuse disease and of matched control subjects by an immunomagnetic method after stimulation with mycobacterium lysate and interleukin-2 for 2 weeks. Lymphocyte adhesion, proliferation, and cytotoxicity to EC were investigated. SSc gammadelta-T cells adhered to cultured EC and proliferated at higher rates than control cells. Furthermore, significant EC cytotoxicity by SSc gammadelta was seen. The cytotoxicity was blocked by addition of anti-gammadelta-TCR antibody and by anti-granzyme A antibody but not by anti-MHC class I and II antibodies. Expression of granzyme A mRNA was seen in five/five SSc gammadelta-T cells and in one/five control cells. alphabeta-T cells from both SSc and control subjects were significantly less interactive with EC than gammadelta-T cells. The data demonstrate EC recognition by SSc gammadelta-T cells and propose gammadelta-T cells as a possible effector cell type in the immune pathogenesis of SSc., (Copyright 1999 Academic Press.)
- Published
- 1999
- Full Text
- View/download PDF
42. Mechanism of serum-mediated endothelial injury in scleroderma: identification of a granular enzyme in scleroderma skin and sera.
- Author
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Kahaleh MB and Fan PS
- Subjects
- Adult, Biopsy, Cell Division drug effects, Cells, Cultured, Cytotoxicity, Immunologic, Endothelium cytology, Female, Fibroblasts cytology, Gene Expression, Granzymes, Growth Inhibitors blood, Humans, Leukocytes, Mononuclear enzymology, Male, Scleroderma, Systemic immunology, Scleroderma, Systemic pathology, Serine Endopeptidases genetics, Serine Endopeptidases isolation & purification, Serine Endopeptidases metabolism, Skin pathology, Tissue Distribution, Endothelium injuries, Scleroderma, Systemic blood
- Abstract
Circulating endothelial cell growth-inhibitory factor with a molecular weight of 40-60 kDa was described in scleroderma (SSc) sera and shown to have a proteolytic action. In view of the recent demonstration of cellular immune activation in SSc, and because of the description of novel serine proteases in the granules of activated cytolytic T cells (granzymes), we hypothesized that granzymes represent the endothelial inhibitory principal in SSc sera. Granular enzymes were isolated from IL-2-activated nonadherent normal lymphocytes, and a 60-kDa granzyme was isolated using benzamidine-affinity column and molecular sieve column. A polyclonal antiserum was generated by immunizing rabbits with the isolated granzyme. Anti-granzyme antibody abolished SSc serum-mediated EC growth inhibition. Furthermore, a circulating protein similar to isolated granzyme was identified as a 60-kDa band on Western blots of benzamidine column-purified SSc sera. Immunofluorescence studies of SSc skin biopsies using anti-granzyme antibody demonstrated the presence of granzyme reactivity, while healthy control tissues were negative. Moreover, granzyme A gene expression was identified in SSc skin biopsies by a PCR method. The data suggest cytolytic mechanism involvement in the pathogenesis of scleroderma.
- Published
- 1997
- Full Text
- View/download PDF
43. Effect of cytokines on the production of endothelin by endothelial cells.
- Author
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Kahaleh MB and Fan PS
- Subjects
- Cells, Cultured, Endothelins metabolism, Endothelium, Vascular metabolism, Humans, Interleukin-1 pharmacology, Interleukin-4 pharmacology, Interleukin-6 pharmacology, Lymphotoxin-alpha pharmacology, Tumor Necrosis Factor-alpha pharmacology, Cytokines physiology, Endothelins biosynthesis, Endothelium, Vascular cytology
- Abstract
Objective: Circulating levels of endothelin (ET), a potent vasoconstrictor peptide and a mitogen for smooth muscle cells and fibroblasts, are reported to be increased in a variety of human diseases characterized by vascular pathology. In view of the probable immune bases for vascular injury in connective tissue disorders, we examined the effect of the cytokines IL-1 alpha, IL-4, IL-6, TNF-alpha and lymphotoxin on the production of ET-1 by cultured vascular endothelial cells., Results: ET levels in endothelial cell conditioned media were measured by radioimmunoassay. IL-4 and lymphotoxin had no effect on ET release by endothelial cells, while IL-6, TNF-alpha and IL-1 alpha stimulated ET mRNA expression and ET release in a dose dependent fashion. IL-6 was the most potent stimulator and IL-1 was the least effective. The addition of neutralizing antibodies to the cytokines inhibited the observed increase in ET release., Conclusions: These results suggest that cytokines may play a significant role in the control of vascular tone. Furthermore, cytokines may indirectly contribute to the development of proliferative vascular lesions by stimulating smooth muscle and interstitial cell proliferation through their effects on endothelin release by the vascular endothelium.
- Published
- 1997
44. Effects of quercetin on Na(+)-K(+)-exchanging ATPase and Ca(2+) Mg(2+)-ATPase in rats.
- Author
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Gu ZL, Xiao D, Jin LQ, Fan PS, and Qian ZN
- Subjects
- Animals, Cell Membrane enzymology, Male, Rats, Rats, Wistar, Brain enzymology, Ca(2+) Mg(2+)-ATPase metabolism, Myocardium enzymology, Quercetin pharmacology, Sarcolemma enzymology, Sodium-Potassium-Exchanging ATPase metabolism
- Abstract
Quercetin (Que) ig 200 mg.kg-1, qd x 14 d decreased activities of the Na(+)-K(+)-exchanging ATPase (I) of rat brain plasma membranes and heart sarcolemmal and Ca(2+) Mg(2+)-ATPase (II) of heart sarcolemmal membrane. Que 100 mg.kg-1 reduced the activity of I from rat heart sarcolemmal preparation, but had no effect on that from rat brain plasma membranes. The result shows that I of myocardium is more sensitive than that of brain in rat. Que also showed a remarkable inhibitory effect in the II of heart sarcolemma.
- Published
- 1994
45. [Effects of total saponins of Panax notoginseng on increasing PGI2 in carotid artery and decreasing TXA2 in blood platelets].
- Author
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Shi L, Fan PS, Wu L, Fang JX, and Han ZX
- Subjects
- Animals, Arteriosclerosis prevention & control, Blood Platelets metabolism, Carotid Arteries metabolism, Male, Rabbits, Rats, Rats, Inbred Strains, Epoprostenol blood, Panax, Plants, Medicinal, Saponins pharmacology, Thromboxane A2 blood
- Abstract
Total saponins of Panax notoginseng (PNS) were given orally 100 mg/(kg.d) to rabbit for 8 wk. Aortic atherosclerotic plaque formation was restrained as compared to the control group. Radioimmunoassay was used to investigate the effects of PNS on the contents of prostacyclin in carotid artery and thromboxane A2 in blood platelets of rat. Oral administration of PNS 25,50,100 mg/(kg.d) for 10 d, the caused an increase of prostacyclin in carotid artery and a decrease of thromboxane A2 in blood platelets as compared to the control group. These results show that the anti-atherosclerotic action of PNS may be a result of the correction of the unbalance between prostacyclin and thromboxane A2.
- Published
- 1990
46. [Inhibitory effects of paeonol on experimental atherosclerosis and platelet aggregation of rabbit].
- Author
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Shi L, Fan PS, Fang JX, and Han ZX
- Subjects
- Acetophenones therapeutic use, Animals, Arteriosclerosis pathology, Cholesterol, HDL blood, Cholesterol, LDL blood, Cyclic AMP metabolism, Female, Male, Rabbits, Rats, Acetophenones pharmacology, Arteriosclerosis drug therapy, Platelet Aggregation drug effects, Platelet Aggregation Inhibitors
- Published
- 1988
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