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1.
Bioengineered ; 13(3): 5292-5304, 2022 03.
Article in English | MEDLINE | ID: mdl-35164660

ABSTRACT

Recent studies have demonstrated that zinc-finger protein 677 (ZNF677) acts as a tumor suppressor gene in cancer. However, the expression and function of ZNF677 in clear cell renal cell carcinoma (ccRCC) are still unclear. In this study, we used bioinformatics analysis and in vitro experiments to investigate the expression of ZNF677 in ccRCC tissues and the malignant biological behavior of ZNF677 in 786-0 cells. We demonstrated that ZNF677 is hypermethylated in ccRCC and is associated with clinicopathological features. The results of the functional assays indicate that ZNF677 inhibits tumor cell proliferation and invasion and induces apoptosis. Further prognostic analysis indicated that low expression of ZNF677 is associated with shorter overall survival. Additionally, ZNF677 overexpression suppressed the invasion and epithelial-mesenchymal transition of 786-0 cells by inactivating the PI3K/AKT signaling pathway. This is the first report to evaluate the influence of ZNF677 on ccRCC cells malignant biological behavior. The results indicate that high expression of ZNF677 could be considered as a favorable prognostic indicator for ccRCC.


Subject(s)
Carcinoma, Renal Cell , DNA-Binding Proteins/metabolism , Kidney Neoplasms , Apoptosis/genetics , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Humans , Kidney Neoplasms/metabolism , Phosphatidylinositol 3-Kinases , Zinc
2.
Clin Microbiol Infect ; 27(3): 467.e9-467.e14, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32360207

ABSTRACT

OBJECTIVE: Disease progression is a strong indicator of treatment for Mycobacterium avium complex lung disease (MAC-LD). The impact of MAC subspecies on the risk of disease progression remains uncertain in MAC-LD patients. METHODS: In this cohort study, we included MAC-LD patients from 2013 to 2018 and classified them into M. intracellulare, M. avium, M. chimaera and other subspecies groups by genotype. We observed the disease progression of MAC-LD, indicated by antibiotic initiation and/or radiographic progression. We used Cox regression analysis to assess predictors for disease progression. RESULTS: Of 105 MAC isolates from unique MAC-LD patients, 35 (33%) were M. intracellulare, 41 (39%) M. avium, 16 (15%) M. chimaera and 13 (12%) other subspecies. After a mean follow-up time of 1.3 years, 56 (53%) patients developed disease progression: 71% (25/35), 54% (22/41), 31% (4/13) and 31% (5/16) in patients with M. intracellulare, M. avium, others and M. chimaera, respectively. The independent predictors for disease progression were M. chimaera subspecies (HR 0.356, 95% CI (0.134-0.943)), compared with the reference group of M. intracellulare, body mass index ≤20 kg/m2 (HR 1.788 (1.022-3.130)) and initial fibrocavitary pattern (HR 2.840 (1.190-6.777)) after adjustment for age, sex and sputum smear positivity. Among patients without fibrocavitary lesions (n = 94), the risk of disease progression significantly decreased in patients with other subspecies (HR 0.217 (0.050-0.945)) and remained low in those with M. chimaera (HR 0.352 (0.131-0.947)). CONCLUSIONS: Mycobacterium chimaera was not uncommon in this study; unlike M. intracellulare, it was negatively correlated with disease progression of MAC-LD, suggesting a role of MAC subspecies identification in prioritizing patients.


Subject(s)
Lung Diseases/microbiology , Mycobacterium avium Complex/genetics , Mycobacterium avium-intracellulare Infection/microbiology , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Lung Diseases/pathology , Male , Middle Aged , Retrospective Studies
3.
Epidemiol Infect ; 145(12): 2482-2490, 2017 09.
Article in English | MEDLINE | ID: mdl-28737121

ABSTRACT

Mycobacterial diseases are prevalent in cancer and rheumatoid arthritis (RA) patients, especially those receiving tumor necrosis factor-α inhibitor (TNFi). However, the impact of cancer development on the risk of mycobacterial diseases among RA patients is unknown. Data from the Taiwan National Health Insurance Research Database were used to conduct a retrospective study to assess the occurrence of mycobacterial diseases in RA patients developing cancer (cancer-positive), those using TNFi (TNFi-exposure), those with cancer and using TNFi (cancer-TNFi-comb), and those without cancer and not using TNFi (cancer-TNFi-free). Cancer and TNFi exposure were time-dependent, and independent risk factors of mycobacterial diseases were assessed by Cox regression. Among 1344 RA patients diagnosed during 2000-2013, 68 (5·1%) developed cancer before their end points. The incidence rates of mycobacterial diseases in the cancer-positive (n = 56), TNFi-exposure (n = 290), cancer-TNFi-comb (n = 12), and cancer-TNFi-free (n = 986) subgroups were 6·7, 2·0, 7·6, and 1·3 per 1000 person-years, respectively. As compared with the cancer-TNFi-free group, the risk for mycobacterial diseases increased for the TNFi-exposure group (adjusted HR = 3·6, 95% confidence interval (95% CI) 1·1-11·5, P = 0·032) and remained high for cancer-positive (adjusted HR = 14·6, 95% CI 3·3-63·7, P < 0·001) after adjustment. This study suggested that cancer development increased the risk of mycobacterial diseases in RA patients, and risk assessment for this subgroup should be considered.


Subject(s)
Arthritis, Rheumatoid/epidemiology , Mycobacterium Infections/epidemiology , Neoplasms/epidemiology , Adult , Arthritis, Rheumatoid/etiology , Female , Humans , Incidence , Male , Middle Aged , Mycobacterium Infections/microbiology , Neoplasms/etiology , Retrospective Studies , Risk Factors , Taiwan/epidemiology
4.
Int J Tuberc Lung Dis ; 21(7): 766-773, 2017 07 01.
Article in English | MEDLINE | ID: mdl-28513421

ABSTRACT

SETTING: The impact of the genetic characteristics of Mycobacterium tuberculosis on the clustering of multidrug-resistant tuberculosis (MDR-TB) has not been analyzed together with clinical and demographic characteristics. OBJECTIVE: To determine factors associated with genotypic clustering of MDR-TB in a community-based study. DESIGN: We measured the proportion of clustered cases among MDR-TB patients and determined the impact of clinical and demographic characteristics and that of three M. tuberculosis genetic characteristics: lineage, drug resistance-associated mutations, and rpoA and rpoC compensatory mutations. RESULTS: Of 174 patients from California and Texas included in the study, the number infected by East-Asian, Euro-American, Indo-Oceanic and East-African-Indian M. tuberculosis lineages were respectively 70 (40.2%), 69 (39.7%), 33 (19.0%) and 2 (1.1%). The most common mutations associated with isoniazid and rifampin resistance were respectively katG S315T and rpoB S531L. Potential compensatory mutations in rpoA and rpoC were found in 35 isolates (20.1%). Hispanic ethnicity (OR 26.50, 95%CI 3.73-386.80), infection with an East-Asian M. tuberculosis lineage (OR 30.00, 95%CI 4.20-462.40) and rpoB mutation S531L (OR 4.03, 95%CI 1.05-23.10) were independent factors associated with genotypic clustering. CONCLUSION: Among the bacterial factors studied, East-Asian lineage and rpoB S531L mutation were independently associated with genotypic clustering, suggesting that bacterial factors have an impact on the ability of M. tuberculosis to cause secondary cases.


Subject(s)
Antitubercular Agents/pharmacology , Bacterial Proteins/genetics , Mycobacterium tuberculosis/isolation & purification , Tuberculosis, Multidrug-Resistant/microbiology , Adult , California , Cluster Analysis , Drug Resistance, Multiple, Bacterial/genetics , Female , Genotype , Humans , Isoniazid/pharmacology , Male , Microbial Sensitivity Tests , Middle Aged , Mutation , Mycobacterium tuberculosis/drug effects , Mycobacterium tuberculosis/genetics , Rifampin/pharmacology , Texas , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Young Adult
5.
Int J Tuberc Lung Dis ; 21(5): 509-516, 2017 05 01.
Article in English | MEDLINE | ID: mdl-28399965

ABSTRACT

BACKGROUND: The impact of demographic, clinical, and bacterial factors on new infection by Euro-American lineage Mycobacterium tuberculosis among contacts of patients with tuberculosis (TB) has not been evaluated. OBJECTIVE: To describe the risk factors for new infection by Euro-American M. tuberculosis sublineages in San Francisco, California. DESIGN: We included contacts of patients with TB due to Euro-American M. tuberculosis. Sublineages were determined by large-sequence polymorphisms. We used tuberculin skin testing or QuantiFERON®-TB Gold In-Tube to identify contacts with new infection. Regression models with generalized estimating equations were used to determine the risk factors for new infection. RESULTS: We included 1488 contacts from 134 patients with TB. There were 79 (5.3%) contacts with new infection. In adjusted analyses, contacts of patients with TB due to region of difference 219 M. tuberculosis sublineage were less likely to have new infection (OR 0.23, 95%CI 0.06-0.84) than those with other sublineages. Other risk factors for new infection were contacts exposed to more than one patient with TB, contacts exposed for 30 days, or contacts with a history of smoking or excessive alcohol consumption. CONCLUSIONS: In addition to well-known exposure and clinical characteristics, bacterial characteristics independently contribute to the transmissibility of TB in San Francisco.


Subject(s)
Alcohol Drinking/epidemiology , Mycobacterium tuberculosis/isolation & purification , Smoking/epidemiology , Tuberculosis/epidemiology , Adult , Contact Tracing , Female , Humans , Interferon-gamma Release Tests , Male , Middle Aged , Mycobacterium tuberculosis/genetics , Regression Analysis , Risk Factors , San Francisco/epidemiology , Time Factors , Tuberculin Test , Tuberculosis/diagnosis , Tuberculosis/microbiology , Young Adult
6.
Osteoporos Int ; 28(5): 1711-1721, 2017 05.
Article in English | MEDLINE | ID: mdl-28331966

ABSTRACT

The occurrence of osteoporosis in tuberculosis, a chronic infection, has rarely been evaluated. In this study, we found significantly higher incidence rates of osteoporosis (Adjusted hazard ratio (AHR) 1.82) and osteoporotic fracture (AHR 2.33) in tuberculosis patients than matched cohorts, which suggest that osteoporosis screening should be considered in tuberculosis patients' follow-up program. The aim of this study is to determine the occurrence of incident osteoporosis in patients who completed anti-tuberculosis (TB) treatment. INTRODUCTION: Chronic inflammatory disorders are associated with an increased risk of osteoporosis. Although TB is an infectious disease characterized by systemic inflammatory responses, the impact of active TB on incident osteoporosis is unclear. We used the Taiwan National Health Insurance Research Database to investigate the association between history of active TB and incident osteoporosis and osteoporotic fracture. METHODS: In this nationwide retrospective cohort study, active TB patients and their age- and sex-matched controls were identified from the National Health Insurance Research Database in Taiwan during 2000-2012. The occurrence of incident osteoporosis, osteoporotic fractures, and risk factors associated with osteoporosis among TB patients and matched controls were analyzed. RESULTS: We observed incident osteoporosis in 2.2% (n = 86) of the TB patients and in 1.1% (n = 162) of the matched controls. The incidence rate of osteoporosis was 4.31 and 1.80 per 1000 person-years, which was significantly higher in TB patients (p < 0.001). In multivariate analysis, TB was an independent risk factor for osteoporosis. The other independent factors associated with osteoporosis were older age, female sex, chronic obstructive pulmonary disease, asthma, and lower income. Moreover, we demonstrated that the occurrence of osteoporotic fracture was significantly higher in TB patients. CONCLUSIONS: Patients with a history of active TB have a higher incidence rate of osteoporosis and osteoporotic fracture.


Subject(s)
Osteoporosis/microbiology , Osteoporotic Fractures/microbiology , Tuberculosis/complications , Adult , Aged , Case-Control Studies , Comorbidity , Databases, Factual , Endemic Diseases , Female , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Osteoporosis/epidemiology , Osteoporotic Fractures/epidemiology , Risk Factors , Socioeconomic Factors , Taiwan/epidemiology , Tuberculosis/epidemiology
7.
Heredity (Edinb) ; 118(6): 517-524, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28295030

ABSTRACT

Multilocus genome-wide association studies (GWAS) have become the state-of-the-art procedure to identify quantitative trait nucleotides (QTNs) associated with complex traits. However, implementation of multilocus model in GWAS is still difficult. In this study, we integrated least angle regression with empirical Bayes to perform multilocus GWAS under polygenic background control. We used an algorithm of model transformation that whitened the covariance matrix of the polygenic matrix K and environmental noise. Markers on one chromosome were included simultaneously in a multilocus model and least angle regression was used to select the most potentially associated single-nucleotide polymorphisms (SNPs), whereas the markers on the other chromosomes were used to calculate kinship matrix as polygenic background control. The selected SNPs in multilocus model were further detected for their association with the trait by empirical Bayes and likelihood ratio test. We herein refer to this method as the pLARmEB (polygenic-background-control-based least angle regression plus empirical Bayes). Results from simulation studies showed that pLARmEB was more powerful in QTN detection and more accurate in QTN effect estimation, had less false positive rate and required less computing time than Bayesian hierarchical generalized linear model, efficient mixed model association (EMMA) and least angle regression plus empirical Bayes. pLARmEB, multilocus random-SNP-effect mixed linear model and fast multilocus random-SNP-effect EMMA methods had almost equal power of QTN detection in simulation experiments. However, only pLARmEB identified 48 previously reported genes for 7 flowering time-related traits in Arabidopsis thaliana.


Subject(s)
Bayes Theorem , Genome-Wide Association Study , Models, Genetic , Polymorphism, Single Nucleotide , Algorithms , Arabidopsis/genetics , Arabidopsis/physiology , Computer Simulation , Flowers/physiology , Likelihood Functions , Linear Models , Monte Carlo Method , Multifactorial Inheritance
8.
Epidemiol Infect ; 145(7): 1374-1381, 2017 05.
Article in English | MEDLINE | ID: mdl-28190404

ABSTRACT

Elderly individuals with tuberculosis (TB) are more likely to have a non-specific clinical presentation of TB and high mortality. However, factors associated with mortality in elderly TB patients have not been extensively studied. This retrospective cohort study aimed to identify factors associated with death among elderly Taiwanese with TB. All elderly patients with TB from 2006 to 2014 in Taipei, Taiwan, were included in a study. Multiple logistic regression was used to identify the factors associated with death in elderly TB patients. The mean age of the 5011 patients was 79·7 years; 74·1% were men; 32·7% had mortality during the study follow-up period. After controlling for potential confounders, age ⩾75 years (reference: 65-74 years), male sex, end-stage renal disease (ESRD), malignancy, acid-fast bacilli-smear positivity, TB-culture positivity, pleural effusion on chest radiograph and notification by an ordinary ward or intensive care unit were associated with a higher risk of all-cause death; while high school, and university or higher education, cavity on chest radiograph and directly observed therapy were associated with a lower risk of all-cause death. This study found that the proportion of death among elderly patients with TB in Taipei, Taiwan, was high. To improve TB treatment outcomes, future control programmes should particularly target individuals with comorbidities (e.g. ESRD and malignancy) and those with a lower socio-economic status (e.g. not educated).


Subject(s)
Tuberculosis/mortality , Age Factors , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Logistic Models , Male , Prognosis , Retrospective Studies , Risk Factors , Sex Factors , Socioeconomic Factors , Taiwan/epidemiology , Tuberculosis/diagnosis , Tuberculosis/microbiology
9.
Int J Tuberc Lung Dis ; 20(2): 265-70, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26792483

ABSTRACT

BACKGROUND: Previous studies have suggested a close correlation between gastroesophageal reflux disease (GERD) and various respiratory disorders. However, the association between GERD and tuberculosis (TB) remains unexplored. METHODS: Using data retrieved from Taiwan's National Health Insurance Research Database from 2000 to 2009, this longitudinal nationwide cohort study included a total of 63,930 patients with GERD and controls matched by age, sex and comorbidities. Risk factors associated with the development of pulmonary TB (PTB) were investigated. RESULTS: Active PTB was documented in 65 (0.20%) patients with GERD and 41 (0.13%) matched cohorts within 1 year of GERD diagnosis. The incidence rate of PTB in the GERD group and the matched cohort was respectively 24.1 and 15.2 cases per 10,000 person-years. In multivariate analysis, GERD was an independent risk factor for PTB (adjusted HR 1.63, 95%CI 1.10-2.40, P = 0.015). Among patients with GERD, independent predictors for PTB included older age, male sex, chronic obstructive pulmonary disease, asthma and exposure to proton pump inhibitors (PPIs). CONCLUSION: Patients with GERD have a significantly increased risk of PTB within 1 year of GERD diagnosis. Exposure to PPIs is an independent predictor for PTB among patients with GERD.


Subject(s)
Gastroesophageal Reflux/epidemiology , Tuberculosis, Pulmonary/epidemiology , Adult , Case-Control Studies , Chi-Square Distribution , Comorbidity , Databases, Factual , Female , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/drug therapy , Histamine H2 Antagonists/therapeutic use , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Proton Pump Inhibitors/therapeutic use , Risk Assessment , Risk Factors , Taiwan/epidemiology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/microbiology
10.
Am J Transplant ; 15(8): 2180-7, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25872600

ABSTRACT

Morbidity and mortality from tuberculosis (TB) are high in Taiwan. We conducted a nationwide population-based matched cohort study using data retrieved from the Taiwan's National Health Insurance Research Database to determine the impact of TB after liver transplantation (LT). During 2000-2011, we identified 3202 liver transplant recipients and selected subjects from the general population matched for age, sex, and comorbidities on the same index date of recognition of LT with a 1:10 ratio. The data were analyzed using Cox proportional hazards models. Compared to the matched cohort, liver transplant patients had a higher risk for TB (adjusted HR 2.25, 95% CI 1.65-3.05, p < 0.001), and those with TB showed higher mortality (HR 2.27, 95% CI 1.30-3.97, p = 0.004). Old age (HR 2.64, 95% CI 1.25-5.54, p = 0.011) and mammalian target of rapamycin inhibitors (mTORis) (HR 3.09, 95% CI 1.68-5.69, p < 0.001) were significant risk factors for TB in LT; mTORis were also associated with mortality after adjusting for confounders (HR 2.13, 95% CI 1.73-2.62, p < 0.001). Therefore, regular surveillance of TB and treatment of latent TB infection in high-risk patients after LT are important, especially in TB-endemic areas.


Subject(s)
Liver Transplantation , Tuberculosis/epidemiology , Adult , Endemic Diseases , Female , Humans , Incidence , Male , Retrospective Studies , Risk Factors , Taiwan/epidemiology
11.
Braz. j. med. biol. res ; 48(2): 186-190, 02/2015. tab
Article in English | LILACS | ID: lil-735855

ABSTRACT

Myoclonus induced by etomidate during induction of general anesthesia is undesirable. This study evaluated the effect of dexmedetomidine (DEX) pretreatment on the incidence and severity of etomidate-induced myoclonus. Ninety patients undergoing elective surgical procedures were randomly allocated to three groups (n=30 each) for intravenous administration of 10 mL isotonic saline (group I), 0.5 µg/kg DEX in 10 mL isotonic saline (group II), or 1.0 µg/kg DEX in 10 mL isotonic saline (group III) over 10 min. All groups subsequently received 0.3 mg/kg etomidate by intravenous push injection. The incidence and severity of myoclonus were recorded for 1 min after etomidate administration and the incidence of cardiovascular adverse events that occurred between the administration of the DEX infusion and 1 min after tracheal intubation was recorded. The incidence of myoclonus was significantly reduced in groups II and III (30.0 and 36.7%), compared with group I (63.3%). The incidence of severe sinus bradycardia was significantly increased in group III compared with group I (P<0.05), but there was no significant difference in heart rate in groups I and II. There were no significant differences in the incidence of low blood pressure among the 3 groups. Pretreatment with 0.5 and 1.0 µg/kg DEX significantly reduced the incidence of etomidate-induced myoclonus during anesthetic induction; however, 0.5 µg/kg DEX is recommended because it had fewer side effects.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Anesthetics, General/adverse effects , Bradycardia/epidemiology , Dexmedetomidine/administration & dosage , Etomidate/adverse effects , Hypnotics and Sedatives/administration & dosage , Myoclonus/chemically induced , Myoclonus/prevention & control , Blood Pressure/drug effects , Elective Surgical Procedures , Heart Rate/drug effects , Incidence , Myoclonus/epidemiology , Severity of Illness Index , Treatment Outcome
12.
Int J Tuberc Lung Dis ; 19(1): 58-64, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25519791

ABSTRACT

BACKGROUND: Tuberculosis (TB) is a serious problem for patients undergoing haematopoietic stem cell transplantation (HSCT) in TB-endemic areas; however, data on these patients are limited. METHODS: We obtained data on 2040 HSCT recipients from the Registry of Catastrophic Illness in Taiwan from 1997 to 2006. We also obtained data on age-, sex- and enrolment date-matched controls from the Longitudinal Health Insurance Database. The cumulative incidence of active TB in HSCT recipients and controls and risk factors for TB were analysed. RESULTS: Among 2040 HSCT recipients identified, 39 (1.9%) had newly diagnosed TB. The incidence rate was 688 per 100 000 person-years. The 10-year cumulative TB incidence was respectively 3.52% and 0.38% in HSCT recipients and controls (P < 0.001). HSCT was an independent risk factor for TB compared with matched controls. Among post-HSCT patients, independent risk factors for TB included age ⩾18 years and allogeneic recipients with graft-versus-host disease (GVHD). Post-HSCT patients with subsequent TB had a higher mortality rate than those without TB (P < 0.001). CONCLUSION: HSCT is associated with an increased risk of TB in endemic regions. Older age and development of chronic GVHD are independent predictors of late onset active TB in HSCT recipients.


Subject(s)
Graft vs Host Disease/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effects , Transplant Recipients , Tuberculosis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Comorbidity , Female , Follow-Up Studies , Graft vs Host Disease/drug therapy , Graft vs Host Disease/microbiology , Humans , Immunosuppressive Agents/therapeutic use , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Risk Factors , Taiwan/epidemiology , Young Adult
13.
Heredity (Edinb) ; 112(5): 479-88, 2014 May.
Article in English | MEDLINE | ID: mdl-24595363

ABSTRACT

Epistasis has been frequently observed in all types of mapping populations. However, relatively little is known about the effect of epistatic distorted markers on linkage group construction. In this study, a new approach was proposed to correct the recombination fraction between epistatic distorted markers in backcross and F2 populations under the framework of fitness and liability models. The information for three or four markers flanking with an epistatic segregation distortion locus was used to estimate the recombination fraction by the maximum likelihood method, implemented via an expectation-maximisation algorithm. A set of Monte Carlo simulation experiments along with a real data analysis in rice was performed to validate the new method. The results showed that the estimates from the new method are unbiased. In addition, five statistical properties for the new method in a backcross were summarised and confirmed by theoretical, simulated and real data analyses.


Subject(s)
Algorithms , Chromosome Mapping/methods , Epistasis, Genetic , Models, Genetic , Oryza/genetics , Chromosomes, Plant/genetics , Computer Simulation , Crosses, Genetic , Gene Frequency , Genetic Fitness , Genetic Linkage , Genetic Markers/genetics , Genotype , Monte Carlo Method , Reproducibility of Results , Selection, Genetic
14.
Eur Rev Med Pharmacol Sci ; 17(22): 2994-3001, 2013 Nov.
Article in English | MEDLINE | ID: mdl-24302177

ABSTRACT

AIM: To investigate the underlying molecular mechanisms of renal cell carcinoma (RCC) by using the microarray expression profiles of normal kidney and RCC tissue for early diagnosis and treatment of RCC. MATERIALS AND METHODS: The gene expression profile of GES781 was downloaded from Gene Expression Omnibus database, including including nine tissue samples of RCC tissues removed from nine patients and eight adjacent normal renal tissue samples. We identified the differentially expressed genes (DEGs) by Multtest package in R software. The screened DEGs were further analyzed by bioinformatics methods. Firstly, the comparison of the DEGs expression degree was performed by cluster analysis. Secondly, DAVID was used to perform functional analysis of up- and down- regulated genes and the protein-protein interaction (PPI) networks were constructed by prePPI. Finally, the pathways of genes in PPI networks were discovered by WebGestalt. RESULTS: Compared with the control, we screened 648 down-regulated and 681 up-regulated DEGs. And the down- and up-regulated DEGs with maximum expression degree were UMOD (uromodulin) and FABP7 (fatty acid binding protein 7), respectively. There was significant difference in the gene expression between the normal kidney and RCC tissue. The up-regulated DEGs in RCC tissue were significantly related to the immune responses and the down-regulated DEGs were significantly related to the oxidation reduction. The most significant pathway in the PPI network of UMOD was cytokine-cytokine receptor interaction. CONCLUSIONS: The screened DEGs have the potential to become candidate target molecules to monitor, diagnose and treat the RCC, and might be beneficial for the early diagnosis and medication control of RCC.


Subject(s)
Carcinoma, Renal Cell/genetics , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/genetics , Oligonucleotide Array Sequence Analysis/methods , Gene Expression Profiling , Humans , Kidney/metabolism , Protein Interaction Maps
15.
Clin Microbiol Infect ; 18(9): E331-7, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22734962

ABSTRACT

Gender disparities in tuberculosis (TB) cases are reported worldwide, and socio-cultural factors have been proposed as possible causes. To date, gender differences in treatment outcomes of TB patients remain controversial. In this prospective observational study, newly diagnosed, culture-proven TB patients from six hospitals in Taiwan were enrolled for analysis. Gender differences in demographic characteristics and treatment outcomes, including sputum conversion and on-treatment mortality, were analysed accordingly. From January 2007 through to December 2009, a total of 1059 patients were enrolled, including 819 (77.3%) males and 240 (22.7%) females. The ratio of male gender was around 50 ~ 60% in TB patients below 35 years and >80% for those older than 65 years. When compared with the female patients, the male patients were older, more likely to have the habit of smoking, chronic obstructive pulmonary disorder, malignancy and liver cirrhosis, and more likely to present with haemoptysis, body weight loss and pleural effusion. Regarding treatment outcomes, male gender is associated with a lower 2-month sputum culture conversion rate (78.8% vs. 89.3%, p 0.002) and higher on-treatment mortality (21.1% vs. 12.1%, p 0.002). Kaplan-Meier survival analysis demonstrated significantly higher mortality in the men (p 0.005). In multivariate analysis, male gender was an independent risk factor for 2-month sputum culture un-conversion (OR, 1.96; 95% CI, 1.12-3.41). Our findings suggest that male gender is associated with older age, more co-morbidities and worse treatment outcomes. Gender-specific strategies, including active case finding in elderly women and smoking cessation in male patients, are warranted to optimize TB management.


Subject(s)
Antitubercular Agents/therapeutic use , Tuberculosis/drug therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prospective Studies , Sex Factors , Sputum/microbiology , Taiwan/epidemiology , Treatment Outcome , Tuberculosis/mortality
16.
Neurogastroenterol Motil ; 23(9): 862-e342, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21726355

ABSTRACT

BACKGROUND: This study was to investigate the effects of the novel cannabinoid receptor - G protein-coupled receptor 55 (GPR55) - and its ligands O-1602 and cannabidiol (CBD) on gastrointestinal (GI) motility in rodents. METHODS: Lipopolysaccharide (LPS) was used in vivo to produce the model of septic ileus. The intestinal motility was measured by recording myoelectrical activity of jejunum in rats, and by measuring GI transit with a charcoal marker in mice, in presence of O-1602 or CBD. Inflammatory response was assessed serologically and histologically. The expression and distribution of GPR55 in the different parts of rat intestine were investigated by real-time PCR and immunohistochemistry. In vitro, the effects of the drugs on the GI movement were investigated by measuring the contraction of the intestinal muscle strips in organ bath, and the intracellular responses of the muscle cells with microelectrode technique. KEY RESULTS: G protein-coupled receptor 55 was expressed in different parts of rat intestine. Lipopolysaccharide significantly inhibited the intestinal motility, increased inflammatory cytokines and GPR55 expression. Pretreatment with CBD normalized LPS-induced hypomotility and improved the inflammatory responses serologically and histologically. Both O-1602 and CBD counteracted LPS-induced disturbances of the gut contraction, but had no effect on the membrane potential of the muscle cells, while cannabinoid type 1 receptor antagonist AM251 and cannabinoid type 2 receptor antagonist AM630 increased the potential. CONCLUSIONS & INFERENCES: G protein-coupled receptor 55 existed throughout the whole intestine of rats. O-1602 or CBD selectively normalized the motility disturbances. Possible mechanisms involved systemic anti-inflammation and the regulation of myoelectrical activity of the intestine.


Subject(s)
Cannabidiol/analogs & derivatives , Cannabidiol/metabolism , Gastrointestinal Motility/physiology , Ligands , Receptors, Cannabinoid/metabolism , Receptors, G-Protein-Coupled/metabolism , Animals , Electromyography , Gastrointestinal Motility/drug effects , Gastrointestinal Transit/drug effects , Gastrointestinal Transit/physiology , Indoles/metabolism , Inflammation/chemically induced , Inflammation/metabolism , Interleukin-6/blood , Intestines/cytology , Intestines/drug effects , Intestines/pathology , Intestines/physiology , Lipopolysaccharides/pharmacology , Membrane Potentials/physiology , Mice , Mice, Inbred C57BL , Myocytes, Smooth Muscle/physiology , Piperidines/metabolism , Pyrazoles/metabolism , Random Allocation , Rats , Rats, Sprague-Dawley , Receptors, Cannabinoid/genetics , Tumor Necrosis Factor-alpha/blood
17.
Eur Respir J ; 37(2): 376-83, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20516049

ABSTRACT

Sputum smears and culture conversion are frequently used to evaluate treatment response in pulmonary tuberculosis patients. Limited data are available on the evaluation of the correlation between under-treatment sputum smear results and culture conversion. This prospective study included sputum culture-proven pulmonary tuberculosis patients at six hospitals in Taiwan. At least two sets of sputum were collected at the completion of 8 weeks of TB treatment. The sensitivities and specificities of 2-month sputum smears were estimated based on culture conversion status. A total of 371 patients were enrolled for analysis. Factors associated with culture conversion included having a smear positive before treatment, presence of a cavity on radiography, rifampicin resistance and usage of the DOTS (directly observed therapy, short course) strategy. The sensitivities of 2-month sputum smears for culture conversion among all patients, initially smear-positive patients and initially smear-negative patients were 64.3, 71.4 and 38%, respectively, and the specificities were 81.6, 69.9 and 92.8%, respectively. In patients who were 2-month sputum smear-positive, the 2-month culture conversion rate was 80% if the patients were under DOTS and without cavitary lesions in radiograms. The predictive value of 2-month sputum smears in culture conversion was limited and highly influenced by clinical factors in pulmonary tuberculosis patients.


Subject(s)
Antitubercular Agents/therapeutic use , Mycobacterium tuberculosis/isolation & purification , Sputum/microbiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiology , Adult , Aged , Aged, 80 and over , Ethambutol/therapeutic use , Female , Humans , Isoniazid/therapeutic use , Male , Middle Aged , Mycobacterium tuberculosis/drug effects , Pyrazinamide/therapeutic use , Radiography , Rifampin/therapeutic use , Sensitivity and Specificity , Treatment Outcome , Tuberculosis, Pulmonary/diagnostic imaging
18.
J Int Med Res ; 38(6): 2053-62, 2010.
Article in English | MEDLINE | ID: mdl-21227010

ABSTRACT

Thymosin-α(1) (TA(1)) has been shown to be effective treatment for chronic hepatitis B virus (HBV) infection. This study investigated the immune response after TA(1) monotherapy in 25 HBV e antigen (HBeAg)-positive patients randomized to receive either 1.6 mg active TA(1) (group A), 1.6 mg recombinant TA(1) (group B) or 3.2 mg recombinant TA(1) (group C) monotherapy for 52 weeks. The percentages of T-helper 1 (T(h)1) cytokine-producing T-cells (interleukin-2 [IL-2], interferon-γ [IFN-γ], tumour necrosis factor-α) and T(h)2 cytokine-producing T-cells (IL-4) were analysed using flow cytometry. In all patients treated with TA(1), cytokine levels and the proportion of peripheral blood mononuclear cells producing these cytokines were significantly increased, compared with baseline and healthy controls. The proportions of each cytokine-producing cell increased gradually over time and were restored to normal levels, and proportions of IFN-γ and IL-4-producing cells reached higher levels than in normal (healthy) controls. The results showed that treatment with TA(1) increased cytokine production, especially IFN-γ, and higher-dose TA(1) exhibited better efficacy against HBV, compared with other treatments studied.


Subject(s)
Cytokines/biosynthesis , Hepatitis B e Antigens/immunology , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/immunology , Th1 Cells/immunology , Th2 Cells/immunology , Thymosin/analogs & derivatives , Adult , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Case-Control Studies , Demography , Female , Hepatitis B, Chronic/virology , Humans , Male , Middle Aged , Th1 Cells/drug effects , Th2 Cells/drug effects , Thymalfasin , Thymosin/pharmacology , Thymosin/therapeutic use
19.
Int J Tuberc Lung Dis ; 13(11): 1387-92, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19861011

ABSTRACT

SETTING: The W-Beijing strain of Mycobacterium tuberculosis is distributed globally, and is associated with high drug resistance rates in some areas. The effect of the W-Beijing strain on radiological features of pulmonary tuberculosis (PTB) remains unclear. OBJECTIVE: To compare the chest radiological presentation of PTB in patients infected with W-Beijing with that of patients infected with non-W-Beijing strains, and to explore factors affecting radiological patterns. DESIGN: Culture-proven PTB patients without previous anti-tuberculosis treatment were enrolled retrospectively. Chest radiographs were independently reviewed by two qualified chest physicians, and radiological presentation was classified into characteristic and unusual patterns. RESULTS: Of 233 patients studied, 123 (52.8%) were infected with the W-Beijing strain. Characteristic radiological patterns (91.1% vs. 76.4%, P = 0.002) and fibronodular lesions without cavity (57.7% vs. 43.6%, P = 0.032) were more common, while miliary lesions (0.0% vs. 3.8%, P = 0.048) were less frequent, in the W-Beijing group. After stepwise logistic regression analysis, the W-Beijing strain (P = 0.006) was found to be an independent factor for the characteristic radiological pattern for PTB. CONCLUSION: The characteristic radiological pattern for PTB was more common in patients infected with the W-Beijing strain. M. tuberculosis genotyping was an independent factor affecting the radiological presentation of pulmonary TB.


Subject(s)
Mycobacterium tuberculosis/pathogenicity , Tuberculosis, Pulmonary/diagnostic imaging , Aged , Aged, 80 and over , Female , Genotype , Humans , Logistic Models , Male , Middle Aged , Mycobacterium tuberculosis/classification , Mycobacterium tuberculosis/genetics , Predictive Value of Tests , Radiography , Retrospective Studies , Risk Assessment , Risk Factors , Tuberculosis, Pulmonary/microbiology
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