Biomedical subjects

Dechang Chen

Publications and source records attributed to Dechang Chen.

13 recordsLinked to original sources

PubMed2005

Selecting genes by test statistics.

Gene selection is an important issue in analyzing multiclass microarray data. Among many proposed selection methods, the traditional ANOVA F test statistic has been employed to identify informative genes for both class prediction (classification) and discovery problems. However, the F test statistic assumes an equal variance. This assumption may not be realistic for gene expression data. This paper explores other alternative test statistics which can handle heterogeneity of the variances. We study five such test statistics, which include Brown-Forsythe test statistic and Welch test statistic. Their performance is evaluated and compared with that of F statistic over different classification methods applied to publicly available microarray datasets.

Journal Article↗

PubMed2005

Gene expression data classification with Kernel principal component analysis.

One important feature of the gene expression data is that the number of genes M far exceeds the number of samples N. Standard statistical methods do not work well when N < M. Development of new methodologies or modification of existing methodologies is needed for the analysis of the microarray data. In this paper, we propose a novel analysis procedure for classifying the gene expression data. This procedure involves dimension reduction using kernel principal component analysis (KPCA) and classification with logistic regression (discrimination). KPCA is a generalization and nonlinear version of principal component analysis. The proposed algorithm was applied to five different gene expression datasets involving human tumor samples. Comparison with other popular classification methods such as support vector machines and neural networks shows that our algorithm is very promising in classifying gene expression data.

Journal Article↗

PubMed2005

Induction of the heat shock response in vivo inhibits NF-kappaB activity and protects murine liver from endotoxemia-induced injury.

Liver plays an important role in the pathogenesis of sepsis by releasing various cytokines and producing acute phase proteins. Heat shock preconditioning is reported to be effective in protection of lung and liver from injury in sepsis and in endotoxemia models, but the exact mechanism is still not fully understood. We report here on the effects of the heat shock response (HSR) induced by sodium arsenite on endotoxemia-induced liver injury as well as hepatic NF-kappaB activation and proinflammatory cytokine expression. Prior induction of HSR significantly attenuated endotoxemia-induced histological changes, inhibited hepatic NF-kappaB activation and IkappaBalpha degradation and decreased mortality. Expression of mRNA coding for TNF-alpha and IL-6 in liver was significantly lower in arsenite-pretreated animals. We conclude that attenuation of endotoxin-induced hepatic NF-kappaB activation and subsequent proinflammatory cytokine production may be one of the mechanisms of the beneficial effect of the heat shock response.

Animals↗

PubMed2005

Heat shock response inhibits NF-kappaB activation and cytokine production in murine Kupffer cells.

BACKGROUND: Kupffer cells play a crucial role in the pathogenesis of sepsis through production of proinflammatory mediators and control of systemic endotoxemia. The anti-inflammatory effects of heat shock response (HSP) have been well documented. However, the role of HSP in lipopolysaccharide (LPS) induced Kupffer cell activation has not been fully investigated. In this study, we investigated the effects of HSP on LPS induced Kupffer cell NF-kappaB activation and cytokine production. MATERIALS AND METHODS: Kupffer cells were isolated from mice by collagenase digestion and HSP was induced by culturing Kupffer cells with sodium arsenite. Kupffer cells were stimulated in vitro by LPS. Heat shock protein (HSP)-70 expression and cytoplasmic IkappaBalpha protein was determined by Western blot. Supernatant tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-10 levels were measured by ELISA. NF-kappaB activation was analyzed by electrophoresis mobility shift assay. Cytokine and IkappaBalpha mRNA expression were determined by RT-PCR. Toll-like receptor 4 expression on Kupffer cells was determined by flow cytometry. RESULTS: HSP pre-conditioning significantly inhibited LPS-induced cytokine TNF-alpha and IL-6 production and mRNA expression. NF-kappaB activation and IkappaBalpha degradation induced by LPS were attenuated by HSP. HSP up-regulated expression of IkappaBalpha mRNA. No effect of HSP on cell surface expression of TLR4 was observed. CONCLUSIONS: Increased IkappaBalpha stability and up-regulation of IkappaBalpha gene expression may be one of the mechanisms of the inhibition of LPS induced Kupffer cell activation by HSP. HSP also inhibited expression of the anti-inflammatory cytokine IL-10, and the mechanism and biological significance of this effect merit further investigation.

Animals↗

PubMed2005

Clustering gene expression data with kernel principal components.

Kernel principal component analysis (KPCA) has been applied to data clustering and graphic cut in the last couple of years. This paper discusses the application of KPCA to microarray data clustering. A new algorithm based on KPCA and fuzzy C-means is proposed. Experiments with microarray data show that the proposed algorithms is in general superior to traditional algorithms.

Algorithms↗

PubMed2005

Nanoparticle delivery by controlled bacteria.

We present a new approach for nano-object directional delivery by bacteria based upon a taxis-controlled mechanism. In this method, a stimulus is used to direct the bacteria's motion. When carrying nano-objects, the bacteria demonstrated the ability to deliver the "loads" to targets where the stimulus is positioned. The scheme of using taxis for targeted delivery may hold a promising future for a new route to bridge nanotechnology and biotechnology.

Chemotaxis↗

PubMed2004

Applications and challenges of DNA microarray technology in military medical research.

This review discusses the challenges and applications of DNA microarray technology as it is being used in each of the four major research areas of the U.S. Army Medical Research and Materiel Command: military infectious diseases, combat casualty care, military operational medicine, and medical chemical and biological defense. The overall objective of this review is two-fold. First, the objective is to increase awareness in senior military leadership of the challenges and opportunities presented by DNA microarray technology and the emerging and rapidly changing field of bioinformatics. Second, the aim is to publicize to the civilian research community the additional challenges associated with the use of microarray technology in military medical research. This discussion contains material that would be useful for making programmatic recommendations that team strategic research investments and emerging technologies with U.S. Army Medical Research and Materiel Command resources.

Biological Warfare↗

PubMed2003

Restriction of third-generation cephalosporin use decreases infection-related mortality.

OBJECTIVE: To determine the effect of restriction of third-generation cephalosporin use on antibiotic resistance and the outcome of patients with infection. DESIGN: A prospective, before-after comparative study. SETTING: A general intensive care unit with 14 beds at a university-affiliated teaching hospital. PATIENTS: All patients admitted to the intensive care unit within 2 yrs. INTERVENTIONS: A new antibiotic treatment strategy was implemented during phase II. All patients with confirmed or suspected Gram-negative bacterial infections were treated mainly with antibiotics other than third-generation cephalosporins. MEASUREMENTS AND MAIN RESULTS: Antibiotic resistance among common Gram-negative bacilli and infection-related hospital mortality during phase I were compared with phase II. A 26.6% reduction in third-generation cephalosporin use (from 168.2 +/- 48.0 to 123.5 +/- 39.3 g/month, p =.021), accompanied by a 277.7% increase in cefepime use (from 10.3 +/- 19.2 to 38.9 +/- 31.7 g/month, p =.014) occurred in phase II compared with phase I. This was accompanied by a significant decrease in reduced susceptibility of Gram-negative bacilli to third-generation cephalosporins (p <.05), mainly because of the improved susceptibility of Escherichia coli and Klebsiella species (p <.05). Infection-related hospital mortality was significantly lower in phase II (19.3% vs. 36.3%, p =.014). Multiple logistic regression analysis demonstrated lower respiratory tract infection, the status of immunocompromise, and continuous veno-venous hemofiltration as independent risk factors for infection-related hospital mortality (p <.05), whereas infection with E. coli or Klebsiella species (p =.039) and restriction of third-generation cephalosporin use (p =.025) were associated with a significantly lower mortality rate. CONCLUSIONS: Restriction of third-generation cephalosporin use may improve the antibiotic susceptibility and reduce infection-related hospital mortality in critically ill patients.

APACHE↗

PubMed2003

Serum procalcitonin and interleukin-6 levels may help to differentiate systemic inflammatory response of infectious and non-infectious origin.

OBJECTIVE: To evaluate the efficacy of using procalcitonin (PCT) and interleukin-6 (IL-6) to differentiate sepsis from non-infectious systemic inflammatory response syndrome (SIRS). METHODS: We made a prospective study in a general intensive care unit at Peking Union Medical College Hospital. Twenty patients with sepsis and 31 patients with non-infectious SIRS were enrolled in this study. Serum concentrations of PCT, IL-6 and C-reactive protein (CRP) were determined within 24 h after clinical onset of sepsis or non-infectious SIRS. Leukocyte count, percentage of neutrophils, and absolute neutrophil count, as well as maximal body temperature were also recorded. RESULTS: Serum concentrations of PCT, IL-6, and CRP, as well as maximal body temperature, were significantly higher in septic patients [3.6 (1.8, 27.5) micro g/L, 810 +/- 516 ng/L, 180 +/- 108 g/L, 38.6 +/- 1.2 degrees C] than non-infectious SIRS patients [0.5 (0.2, 1.8) micro g/L, 235 +/- 177 ng/L, 109 +/- 70 g/L, 37.9 +/- 0.9 degrees C]. IL-6 and PCT exhibited the best discriminative power between sepsis and non-infectious SIRS, with sensitivity above 80% and specificity above 70%. A sepsis score with combination of IL-6 and PCT showed the best discriminative power with the area under the receiver operating characteristic curve of 0.923. CONCLUSIONS: Assessing IL-6 and PCT levels are more reliable ways to differentiate sepsis from non-infectious SIRS, compared with conventional inflammatory parameters.

Adult↗

PubMed2002

Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae bloodstream infection: risk factors and clinical outcome.

OBJECTIVES: To study the risk factor for nosocomial bacteremia caused by Escherichia coli or Klebsiella pneumoniae producing extended-spectrum beta-lactamase (ESBL) and the influence on patient outcome. DESIGN: Retrospective, single-center study of consecutive bacteremic patients. SETTINGS: A university-affiliated teaching hospital. PATIENTS: A total of 85 patients with nosocomial bacteremia due to E. coli or K. pneumoniae were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The demographic characteristics and clinical information including treatment were recorded upon review of patients' records. The primary end point was hospital mortality. Twenty-seven percent of isolates produced ESBLs. Previous treatment with 3rd-generation cephalosporins was the only independent risk factor for bacteremia due to ESBL-producing pathogens [odds ratio (OR) 4.146, P=0.008]. Antibiotic treatment was considered appropriate in 71 cases (83%), and failed in 23 patients (27%). Twenty-one patients (25%) died in the hospital. Antibiotic treatment failure was the only independent risk factor for hospital mortality (OR 15.376, P=0.001). Inappropriate antibiotic treatment might lead to significantly higher mortality rate (7/14 vs 14/71, P=0.016). Patients treated with imipenem were more likely to survive while those receiving cephalosporin treatment tended to have a poorer outcome (1/19 vs 14/40, P=0.023). CONCLUSIONS: More judicious use of cephalosporins, especially 3rd-generation cephalosporins, may decrease ESBL-producing E. coli or K. pneumoniae bacteremia, and also improve patient outcome.

APACHE↗

PubMed2002

[Genomic polymorphism within interleukin-1 family cytokines influences the outcome of septic patients].

OBJECTIVE: To determine the allele frequencies and genotype distribution of interleukin (IL)-1 alpha, IL-1 beta and IL-1 receptor antagonist (IL-1ra) gene polymorphism in septic patients. METHODS: A prospective, consecutive entry study was made among 60 patients with the diagnosis of sepsis who were admitted consecutively into the general intensive care unit (ICU), Peking Union Medical College Hospital between 1997 and 1999. APACHE II scoring and MODS scoring were made within 24 hours after admission. The genomic DNA of peripheral blood nucleated cells was extracted. The polymorphic regions within intron 6 of IL-1 alpha gene containing variable numbers of a tandem repeat (VNTR) of 46 bp, and intron 2 of IL-1ra gene containing VNTR of 86 bp were amplified by means of polymerase chain reaction (PCR). Alleles A1-4 and RN1-4 were identified according to the size of amplified DNA product. The region containing the AvaI polymorphic site at position -511 of IL-1 beta gene was amplified by PCR, and subsequently digested with AvaI restriction enzyme. RESULTS: The frequencies of allele IL-1ra RN2 and genotype RN2/2 in the 60 septic patients were significantly higher than those in normal controls (0.34 vs 0.23, P < 0.01, and 0.12 vs 0.05, P < 0.05, respectively). The allele frequencies or genotype distribution of IL-1 alpha VNTR gene polymorphism and IL-1 beta AvaI polymorphism did not differ between the septic patients and normal controls. In addition, genotypes A2/2, B2/2 and RN2/2 were associated with a significantly higher mortality (80%, 81% and 71%, respectively) in septic patients. Patients with any 2 of the three alleles, i.e. A2, B2 and RN2, suffered from a much more severe sepsis (as measured by APACHE II and MODS scores) and higher mortality rate ( 55-65%), while septic patients with genotypes A1/1, B1/1 or RN1/1 showed a much lower mortality (0-13%). CONCLUSION: Allele IL-1RN2 polymorphism, but not IL-1A or IL-1B gene polymorphism, is associated with susceptibility to sepsis. Alleles A2, B2 and RN2 might be important high-risk genetic markers for sepsis.

Adult↗

PubMed2002

[Serum procalcitonin and interleukin-6 help differentiate between severe sepsis and systemic inflammatory response syndrome of non-infectious origin].

OBJECTIVE: To evaluate the efficacy of serun procalcitonin (PCT) and interleukin (IL)-6 in differentiating between severe sepsis and systemic inflammatory response (SIRS) of non-infectious origin. METHOD: The serum PCT, IL-6, C-reactive protein (CRP), white blod cell count, percentage of neutrophils, and absolute neutrophil count were determined, and maximal body temperature was recorded among 21 patients was 3.6 (1.8, 27.5) micro g/L, significantly higher than that in SIRS patients (1.3 micro g/L +/- 1.6 micro g/L, P < 0.05). The IL-6 in sepsis patients was 810 ng/L +/- 516 ng/L, significantly higher than that in SIRS patients (235 ng/L +/- 177 ng/L, P < 0.01). However, the differences of CRP, WBC count, percentage of neutrophil, and absolute neutrophil count between the severe sepsis patients and SIRS patients were not statistically significant. PCT and IL-6 showed sensitivity equal or over 80% and specificity equal to or over 70%. The infection score based on PCT and IL-6 showed the best discriminative power to differentiate between severe sepsis and SIRS with the artea under the receiver operating characteristic curve of 0.923. CONCLUSION: In comparison with the conventional inflammatory markers, PCT and IL-6 are more reliable indicators to differentiate between sepsis and SIRS.

Aged↗

PubMed2002

Genomic polymorphism within interleukin-1 family cytokines influences the outcome of septic patients.

OBJECTIVE: To determine the allele frequencies and genotype distribution of interleukin-1alpha, interleukin-1beta, and interleukin-1 receptor antagonist gene polymorphism in septic patients. DESIGN: Prospective, consecutive entry study of septic patients in a general intensive care unit. SETTING: A 14-bed general intensive care unit of a university hospital. PATIENTS: Sixty patients with diagnosis of sepsis, admitted to the intensive care unit between 1997 and 1999. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: The polymorphic regions within intron 6 of interleukin-1alpha gene containing variable numbers of a tandem repeat (VNTR) of 46 base pairs, and intron 2 of interleukin-1 receptor antagonist gene containing VNTR of 86 base pairs, were amplified by means of polymerase chain reaction. Alleles A1-4 and RN1-4 were identified according to the size of amplified DNA product. The region containing the AvaI polymorphic site at position -511 of interleukin-1beta gene was amplified by polymerase chain reaction and subsequently digested with AvaI restriction enzyme. The allele frequencies of interleukin-1 receptor antagonist RN2 and genotype RN2/2 were increased in 60 septic patients compared with normal controls (p <.01 and.05, respectively). Allele frequencies or genotype distribution of interleukin-1alpha VNTR gene polymorphism and interleukin-1beta AvaI polymorphism did not differ between septic patients and normal controls. In addition, genotypes A2/2, B2/2, and RN2/2 were associated with a significantly higher mortality rate (70% to 80%) in septic patients. Patients with any two of the three alleles (i.e., A2, B2, and RN2) suffered from much more severe sepsis (as measured by the Acute Physiology and Chronic Health Evaluation II and Multiple Organ Dysfunction Syndrome score) and a higher mortality rate (55% to 65%), whereas septic patients with genotypes A1/1, B1/1, or RN1/1 showed a much lower mortality rate (0% to 13%). CONCLUSIONS: Allele interleukin-1RN2, but not interleukin-1A or interleukin-1B gene polymorphism, was associated with susceptibility to sepsis. Alleles A2, B2, and RN2 might be important high-risk genetic markers for sepsis.

Female↗