Risk Assessment of Early Lung Cancer with LDCT and Health Examinations.

Early detection of lung cancer has a higher likelihood of curative treatment and thus improves survival rate. Low-dose computed tomography (LDCT) screening has been shown to be effective for high-risk individuals in several clinical trials, but has high false positive rates. To evaluate the risk of stage I lung cancer in the general population not limited to smokers, a retrospective study of 133 subjects was conducted in a medical center in Taiwan. Regularized regression was used to build the risk prediction model by using LDCT and health examinations. The proposed model selected seven variables related to nodule morphology, counts and location, and ten variables related to blood tests and medical history, achieving an area under the curve (AUC) value of 0.93. The higher the age, white blood cell count (WBC), blood urea nitrogen (BUN), diabetes, gout, chronic obstructive pulmonary disease (COPD), other cancers, and the presence of spiculation, ground-glass opacity (GGO), and part solid nodules, the higher the risk of lung cancer. Subjects with calcification, solid nodules, nodules in the middle lobes, more nodules, and diseases related to thyroid, liver, and digestive systems were at a lower risk. The selected variables did not indicate causation.

Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study.

Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21-1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15-1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27-2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22-2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D' = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.

Investigation of heavy metal (Cu, Pb, Cd, and Cr) stabilization in river sediment by nano-zero-valent iron/activated carbon composite.

Nano-zero-valent iron/activated carbon (nZVI/AC) composite was evaluated for its effectiveness in the stabilization of Cu, Pb, Cd, and Cr in dredged river sediment. Synthetic precipitation leaching procedure (SPLP) and toxicity characteristic leaching procedure (TCLP) were adopted to compare the effects of nZVI/AC dosage, particle size, time duration, and temperature on heavy metal leachability. The results show that leachability dropped considerably with the addition of nZVI/AC and powdered particles in the size of 0.075-0.18 mm was more effective in stabilization than granular ones. Stabilization effect was stable in long-term and robust against changes in temperature. Tessier sequential extraction revealed that heavy metals were associated with solid particle, inorganic or organic matters in sediment. The addition of nZVI/AC was able to convert relatively weakly bound heavy metals into more strongly bound species and thus reduce the bioavailability and toxicity. Also, the standard potential of heavy metals may decide the mechanism of stabilization process.

High prevalence of fluoroquinolone-nonsusceptible Streptococcus pyogenes emm12 in Taiwan.

Fluoroquinolone-nonsusceptible Streptococcus pyogenes has rapidly emerged in several countries. The aim of this study was to survey the epidemiology and molecular characteristics of fluoroquinolone-nonsusceptible S. pyogenes in Taiwan. A total of 350 consecutive S. pyogenes isolates were collected between January 2005 and December 2012, including 152 (43.4%) invasive and 198 (56.6%) noninvasive isolates. Thirty-nine isolates (11.1%) of S. pyogenes were nonsusceptible to fluoroquinolones, including one emm1/ST28, 4 emm4/ST39, 33 emm12/ST36, and 1 emm87/ST62. Of all the isolates, emm12 (50%) demonstrated the highest prevalence of fluoroquinolone nonsusceptibility. Alterations of Ser79Phe and Ala12Val in ParC were the most frequently mutations in fluoroquinolone-nonsusceptible S. pyogenes isolates. There were no amino acid substitutions in GyrB, and 1 emm87 isolate exhibited 3 nonsynonymous mutations in ParE. Our study reveals the emergence of fluoroquinolone-nonsusceptible S. pyogenes emm12/ST36 in Taiwan. Regular surveillance of fluoroquinolone susceptibility in S. pyogenes is suggested.

Clinical characteristics of Q fever and etiology of community-acquired pneumonia in a tropical region of southern Taiwan: a prospective observational study.

BACKGROUND: The clinical characteristics of Q fever are poorly identified in the tropics. Fever with pneumonia or hepatitis are the dominant presentations of acute Q fever, which exhibits geographic variability. In southern Taiwan, which is located in a tropical region, the role of Q fever in community-acquired pneumonia (CAP) has never been investigated. METHODOLOGY/PRINCIPAL FINDINGS: During the study period, May 2012 to April 2013, 166 cases of adult CAP and 15 cases of acute Q fever were prospectively investigated. Cultures of clinical specimens, urine antigen tests for Streptococcus pneumoniae and Legionella pneumophila, and paired serologic assessments for Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Q fever (Coxiella burnetii) were used for identifying pathogens associated with CAP. From April 2004 to April 2013 (the pre-study period), 122 cases of acute Q fever were also included retrospectively for analysis. The geographic distribution of Q fever and CAP cases was similar. Q fever cases were identified in warmer seasons and younger ages than CAP. Based on multivariate analysis, male gender, chills, thrombocytopenia, and elevated liver enzymes were independent characteristics associated with Q fever. In patients with Q fever, 95% and 13.5% of cases presented with hepatitis and pneumonia, respectively. Twelve (7.2%) cases of CAP were seropositive for C. burnetii antibodies, but none of them had acute Q fever. Among CAP cases, 22.9% had a CURB-65 score ≧2, and 45.8% had identifiable pathogens. Haemophilus parainfluenzae (14.5%), S. pneumoniae (6.6%), Pseudomonas aeruginosa (4.8%), and Klebsiella pneumoniae (3.0%) were the most common pathogens identified by cultures or urine antigen tests. Moreover, M. pneumoniae, C. pneumoniae, and co-infection with 2 pathogens accounted for 9.0%, 7.8%, and 1.8%, respectively. CONCLUSIONS: In southern Taiwan, Q fever is an endemic disease with hepatitis as the major presentation and is not a common etiology of CAP.

[Effect of extract of radix tetrastigma hemsleyani on apoptosis of human lung carcinoma H1299 cells and its mechanism study].

OBJECTIVE: To study the effect of extract of Radix Tetrastigma hemsleyani on the proliferation and apoptosis of human lung carcinoma H1299 cells, and to explore its mechanisms. METHODS H1299 cells were treated with the extract of Radix Tetrastigma hemsleyani in different concentrations at different time points. Its inhibition on H1299 cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. The morphology of the H1299 cell was observed by inverted microscope. Changes of apoptosis were observed by Hoechst33258 methods. The apoptosis rate was detected by flow cytometry. Expression changes of apoptosis-related proteins pro-caspase-3, pro-caspase-9, cle-caspase-3, cle-caspase-9, and poly-ADP-ribose polymerase (PARP) were detected by Western blot. RESULTS: Compared with the control group, the inhibition rate of H1299 cells increased after acted by 0.5, 1, 5, and 10 mg/mL extract of Radix Tetrastigma hemsleyani (P < 0.05, P < 0.01). The longer the acting time, the higher the inhibition rate (P < 0.01). Under inverted microscope, typical morphological changes could be seen and the number of H1299 cells was reduced. Under fluorescence microscope, dark stained nucleus and formed apoptotic body could be observed. Results of flow cytometry showed that the apoptosis rate was obviously dose-effect correlated with the concentration of extract of Radix Tetrastigma hemsleyani. Results of Western blot indicated that compared with the control. group, the protein expression of pro-caspase-3, pro-caspase-9, and PARP were down-regulated and that of cle-caspase-3, cle-caspase-9, and cle-PARP were up-regulated by 5 and 10 mg/mL extract of Radix Tetrastigma hemsleyani (P < 0.05). CONCLUSIONS: Extract of Radix Tetrastigma hemsleyani had obvious effect in inhibiting the proliferation and inducing apoptosis of human lung carcinoma H1299 cells, which might be achieved by activating the expression of caspase protein.

High seroprevalence of Mycoplasma pneumoniae IgM in acute Q fever by enzyme-linked immunosorbent assay (ELISA).

Q fever is serologically cross-reactive with other intracellular microorganisms. However, studies of the serological status of Mycoplasma pneumoniae and Chlamydophila pneumoniae during Q fever are rare. We conducted a retrospective serological study of M. pneumoniae and C. pneumoniae by enzyme-linked immunosorbent assay (ELISA), a method widely used in clinical practice, in 102 cases of acute Q fever, 39 cases of scrub typhus, and 14 cases of murine typhus. The seropositive (57.8%, 7.7%, and 0%, p<0.001) and seroconversion rates (50.6%, 8.8%, and 0%, p<0.001) of M. pneumoniae IgM, but not M. pneumoniae IgG and C. pneumoniae IgG/IgM, in acute Q fever were significantly higher than in scrub typhus and murine typhus. Another ELISA kit also revealed a high seropositivity (49.5%) and seroconversion rate (33.3%) of M. pneumoniae IgM in acute Q fever. The temporal and age distributions of patients with positive M. pneumoniae IgM were not typical of M. pneumoniae pneumonia. Comparing acute Q fever patients who were positive for M. pneumoniae IgM (59 cases) with those who were negative (43 cases), the demographic characteristics and underlying diseases were not different. In addition, the clinical manifestations associated with atypical pneumonia, including headache (71.2% vs. 81.4%, p=0.255), sore throat (8.5% vs. 16.3%, p=0.351), cough (35.6% vs. 23.3%, p=0.199), and chest x-ray suggesting pneumonia (19.3% vs. 9.5%, p=0.258), were unchanged between the two groups. Clinicians should be aware of the high seroprevalence of M. pneumoniae IgM in acute Q fever, particularly with ELISA kits, which can lead to misdiagnosis, overestimations of the prevalence of M. pneumoniae pneumonia, and underestimations of the true prevalence of Q fever pneumonia.

High vancomycin minimum inhibitory concentrations with heteroresistant vancomycin-intermediate Staphylococcus aureus in meticillin-resistant S. aureus bacteraemia patients.

Patients with high vancomycin minimum inhibitory concentrations (MICs) and heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) infection are associated with treatment failure and poor outcomes. The main purpose of this study was to investigate the effect of hVISA on patient outcome, considering both the high vancomycin MIC and the existence of heteroresistant phenotypes. From January 2005 to December 2009, consecutive meticillin-resistant S. aureus (MRSA) isolates from 284 cases of MRSA bacteraemia receiving glycopeptide therapy were collected for further MIC and hVISA testing. The demographic distribution, clinical features and outcomes in bacteraemia patients with different vancomycin MICs and hVISA status in MRSA isolates were subsequently compared. Subjects were divided into three groups: low vancomycin MIC (<1.5mg/L) with vancomycin-sensitive S. aureus (VSSA) (n=50); high vancomycin MIC (≥1.5mg/L) with VSSA (n=218); and high vancomycin MIC with hVISA (n=16). Cox regression analysis demonstrated that the high MIC with VSSA group exhibited significantly higher 30-day mortality than the low MIC with VSSA group [odds ratio (OR)=2.349, 95% confidence interval (CI) 1.078-5.118]. The high MIC with hVISA phenotype was not associated with higher mortality but was independently associated with persistent MRSA bacteraemia (OR=5.996, 95% CI 1.438-25.005). To summarise, although hVISA is correlated with persistent bacteraemia, higher mortality in high vancomycin MIC infections could not be explained by the existing hVISA phenotype. Facing persistent bacteraemia under glycopeptide therapy for 7 days, clinicians should consider shifting to an alternative class of antibiotics to treat hVISA infection.

On-substrate fabrication of a bio-conjugated Au nanoring solution for photothermal therapy application.

The on-substrate fabrication of a bio-conjugated Au nanoring (NRI) solution with the localized surface plasmon (LSP) resonance wavelength in the 1200-1300 nm range is demonstrated. Also, the effects of photothermal therapy through LSP resonance-induced absorption enhancement are illustrated by applying the bio-conjugated Au NRIs to human liver cancer cells and illuminating the cells with a laser of 1315 nm in wavelength. The Au NRI fabrication is based on the techniques of nano-imprint lithography and metal secondary sputtering. The procedure for on-substrate surface modification of Au NRIs leads to a high production yield of bio-conjugated NRIs. The threshold levels of the local laser intensity for injuring cancer cells based on the LSP resonances of Au NRIs of two different samples are determined.

The IL18 gene and Hashimoto thyroiditis in children.

Interleukin 18 (IL18) stimulates interferon-γ production in Th1 cells which are prominent in the thyroid of Hashimoto thyroiditis (HT). We investigated the association between the IL18 gene and HT. There were 116 children with HT and 1272 controls. rs187238 and rs1946518 in the promoter region of the IL18 gene were genotyped. Differences in genotype, allele, carrier, and haplotype distributions between patients and controls were compared. A Pc value <0.05 was considered significant. The frequency of the C/G genotype of rs187238 was significantly higher in patients and conferred a risk of HT (OR, 1.96; 95% CI, 1.30-2.95; Pc, 0.0021). So did the frequencies of allele C (OR, 1.73; 95% CI, 1.22-2.44; Pc, 0.0035) and carrier C (OR, 1.96; 95% CI, 1.31-2.92; Pc, 0.0017), however the frequency of the G/G genotype was significantly lower in patients than in controls (OR, 0.51; 95% CI, 0.34-0.76; Pc, 0.0034). There was no association between HT and rs1946518. The CT haplotype was significantly more frequent in patients than in controls and conferred a risk of HT (OR, 1.76; 95% CI, 1.24-2.49; Pc, 0.0049). We concluded that the IL18 gene was associated with HT in children. The rs187238C allele and CT haplotype conferred a risk of HT.

Genetic polymorphisms in the ITPKC gene and cervical squamous cell carcinoma risk.

Cervical cancer is caused primarily by infection with oncogenic types of human papillomavirus (HPV). However, HPV infection alone is not sufficient for the progression to cervical cancer. Host immunogenetic factors may involve in the development of this disease. Inositol 1,4,5-trisphosphate 3-kinase C (ITPKC) is recently shown to act as a negative regulator of T-cell activation. We aim to study if polymorphisms in the ITPKC gene are associated with the risk of cervical cancer in Taiwanese women. ITPKC rs28493229 C/G, rs890934 G/T, rs2303723 C/T, and rs10420685 A/G polymorphisms were genotyped in a hospital-based study of 465 women with cervical squamous cell carcinoma (CSCC) and 800 age-matched healthy control women. The presence and genotypes of HPV in CSCC were determined. The frequency of G/G genotype and G allele of the ITPKC rs28493229 polymorphism was significantly higher in patients with CSCC compared with controls (OR = 1.81, 95 % CI 1.20-2.73, P = 0.005, P (c) = 0.02; OR = 1.70, 95 % CI 1.14-2.54, P = 0.008, P (c) = 0.03, respectively). No significant associations were found for other 3 polymorphisms. Haplotype analysis revealed the distribution of haplotype CGTA was significantly reduced in women with CSCC (OR = 0.59, 95 % CI 0.40-0.89, P = 0.01, P (c) = 0.04). In conclusion, we found the G/G genotype and G allele of the ITPKC rs28493229 polymorphism may contribute to the risk of CSCC in Taiwanese women. This finding provides new insights into the mechanisms of immune activation in cervical cancer.

Genetic variability of interleukin4 gene in Taiwanese children with biliary atresia.

Biliary atresia (BA) is a neonatal cholangiopathy of unknown etiology that leads to biliary cirrhosis and is the most common cause of liver transplantation in children. A still undetermined hepatobiliary viral infection may elicit an uncontrollable autoimmune response against the biliary epithelial cells in genetically predisposed children and culminates in atresia of the biliary trees. Interleukin 4 (IL4) is crucial for the differentiation of naive T helper cells into the T helper 2 effector cells that promote humoral immunity. This study aims to investigate whether polymorphisms of the IL4 gene are associated with susceptibility to BA. Genomic DNA was extracted from whole blood samples of 53 Taiwanese children with BA and 904 ethnically-matched healthy controls. The IL4 -590 C/T, -33 C/T, and 8375 A/G polymorphisms were genotyped using the Pre-Developed TaqMan Allelic Discrimination Assay in a real-time polymerase chain reaction system. No significant difference between children with BA and healthy controls were found when comparing genotype, allele, carrier, and haplotype frequencies of these IL4 gene variants. These results suggest that the tested polymorphisms of IL4 gene are unlikely to contribute significantly to BA susceptibility in Taiwanese children.

Bacteremia caused by extended-spectrum-ß-lactamase-producing Escherichia coli sequence type ST131 and non-ST131 clones: comparison of demographic data, clinical features, and mortality.

Escherichia coli producing the highly virulent, multidrug-resistant, CTX-M-15 extended-spectrum ß-lactamase (ESBL), sequence type 131 (ST131), has emerged on three continents since the late 2000s. We described the molecular epidemiology, clinical features, and outcome of ESBL-producing E. coli bacteremia in Taiwan from 2005 to 2010. This study aims to determine whether the risk factors, clinical features, and outcomes of the ST131 isolate differ from those of non-ST131 isolates. From 2005 to 2010, we collected 122 nonduplicated, consecutive, ESBL-producing E. coli isolates from bloodstream infections in a 1,200-bed hospital in Taiwan. Isolates were characterized using multilocus sequence typing. Demographic data, clinical features, and outcomes were collected from medical chart records. Thirty-six (29.5%) patients with bacteremia with ESBL-producing E. coli ST131 were identified. Patients with clone ST131 were more likely to have secondary bacteremia and noncatheterized urinary tract infections (P < 0.05). Secondary bacteremia (odds ratio [OR], 5.05; 95% confidence interval [CI], 1.08 to 23.56) and urinary catheter nonuse (OR, 3.77; 95% CI, 1.17 to 12.18) were independent risk factors for the ST131 clone after adjustment. Mortality rates at day 28 were similar in ST131 and non-ST131 populations. Independent risk factors predicting mortality at day 28 included malignancy, shock, and hospital-acquired bacteremia. In ESBL-producing E. coli bloodstream infections, the ST131 clone was not associated with health-care-associated risk factors, such as urinary catheter use or antibiotic exposure. Although highly virulent and multidrug resistant, the ST131 clone was not associated with higher mortality than non-ST131 clones.

[Concentrations, sources and ecological risks of polycyclic aromatic hydrocarbons in the topsoils of Quanzhou City, China].

The concentrations of 15 US EPA priority polycyclic aromatic hydrocarbons (PAHs) in 33 soil samples (0-10 cm layer) collected from various functional zones in Quanzhou city were analyzed by UPLC coupled with fluorescence detector. The sources of PAHs in the topsoils were apportioned using isomer ratios, and factor analysis and multiple linear regression. The ecological risks of PAHs in the topsoils were evaluated by using benzo[a]pyrene toxic equivalents (TEQ(BaP)). Results showed that the total concentrations of PAHs in the soils ranged from 28.2 to 1432.3 microg x kg(-1), and 4 to 6 ring PAHs were the dominant compounds. The total concentrations of PAHs in soil samples from different functional zones decreased in the order of industrial areas > residential areas > scenic areas > agricultural fields. The PAHs in soils of Quanzhou city mainly originated from the combustion of coal, biomass fuels (straw), and liquid fossil fuels including gasoline and diesel. The TEQ(BaP) of the 15 PAHs ranged from 1.6 to 131.6 microg x kg(-1), with an average value of 38.9 microg x kg(-1). The total TEQ(BaP) of 10 PAHs in 34.6% of the soil samples exceeded the Dutch target reference value, suggesting that there are potential ecological risks in the topsoils in some areas of Quanzhou city.

Association of polymorphisms in the Interleukin-18 gene with susceptibility to biliary atresia.

BACKGROUND AND OBJECTIVE: Biliary atresia (BA) is a destructive inflammatory obliterative cholangiopathy of neonates that affects both intrahepatic and extrahepatic bile ducts. Although the etiology is unknown, immunologically mediated injury of the bile ducts triggered by as yet unidentified infectious agents is likely to play a critical role. Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in immune, infectious, and inflammatory diseases because of its induction of interferon-gamma. In this study, we investigated whether polymorphisms of the IL18 gene were associated with susceptibility to BA. PATIENTS AND METHODS: Genomic DNA was extracted from whole-blood samples of 50 Taiwanese children with BA and 1117 ethnically matched healthy controls. The IL18 -1297 T/C, -607 C/A, -137 G/C, and +105 A/C polymorphisms were genotyped using the TaqMan assay. RESULTS: No statistically significant differences of genotype, allele, carrier, and haplotype frequencies of these IL18 gene variants were found between children with BA and healthy controls. CONCLUSIONS: Our data suggest that the IL18 gene does not play a major role in BA predisposition in Taiwanese children.

Association of an IL-4 gene haplotype with Graves disease in children: experimental study and meta-analysis.

Investigations of an association between Graves disease (GD) and the IL-4 gene have yielded conflicting results. We performed a case-control study of IL-4 gene polymorphisms possibly associated with GD, as well as a meta-analysis of other such studies. We genotyped IL-4 single nucleotide polymorphisms (SNPs) rs2243250 and rs2243289 in 220 unrelated children with GD and 904 healthy controls. No significant differences between patients and controls were observed in the genotype, allele, or carrier frequencies of the 2 SNPs. The levels of autoantibodies did not differ significantly between the genotypes of each SNP. Linkage disequilibrium between the 2 SNPs was strong in the controls (D', 0.916; r(2), 0.824). Haplotype TA conferred a significant risk of GD (odds ratio = 2.47, 95% confidence interval 1.24-4.95, corrected p value = 0.033). The T allele frequency of rs2243250 was 80.0% in Asians, significantly higher than the 12.6% in Caucasians (p = 1.4 × 10(-269)). Meta-analysis of data from 8 published reports and our own study did not reveal any significant association between these SNPs and GD. Our study showed an association between the IL-4 gene and GD in children, but only using a haplotype-based method, suggesting that this might be a better approach than evaluating individual SNPs.

Sphingomonas paucimobilis bacteremia in humans: 16 case reports and a literature review.

BACKGROUND/PURPOSE: Sphingomonas paucimobilis is a glucose-nonfermenting Gram-negative bacillus that is widely distributed in both natural environment and hospitals. Various infections in humans have been reported, but most have been limited to sporadic case reports. The aim of this study was to describe the clinical characteristics and manifestations of S. paucimobilis bacteremia. We also reviewed the literature on S. paucimobilis bacteremia. METHODS: Cases of S. paucimobilis bacteremia were identified retrospectively at a university-affiliated hospital in Taiwan. In addition, relevant case reports were identified through PubMed and reviewed. RESULTS: From April 2004 to April 2008, 42 cases of S. paucimobilis bacteremia were identified in this study. Among them, 16 cases were identified from E-Da hospital, Kaohsiung, Taiwan and 26 cases from the literature review. The median age of patients was 48.5 years and 57.1% were male. The most common comorbidities included malignancy (57.1%), immunosuppressant use (40.5%), and diabetic mellitus (11.9%). Hospital-acquired bacteremia accounted for 69.0% of infections. Primary bacteremia and catheter-related bloodstream infection were found in 35.7% and 33.3% respectively. The most effective antibiotics were fluoroquinolones, carbapenems, and beta-lactam/beta-lactamase inhibitor combinations. All 42 patients survived the S. paucimobilis bacteremic episodes, but three patients experienced septic shock. CONCLUSION: S. paucimobilis can cause infections in healthy as well as immunocompromised individuals. Although it is an organism of low clinical virulence, infection caused by S. paucimobilis can lead to septic shock. Further clinical research is required to characterize this infection.

ITPKC gene SNP rs28493229 and Kawasaki disease in Taiwanese children.

Kawasaki disease (KD) is a systemic vasculitis caused by unknown infectious agents, host immune dysregulation and genetic susceptibility in children. Coronary artery lesions (CALs) complicate 15-25% of cases of untreated KD. The aim of this study was to investigate if the single-nucleotide polymorphism (SNP) rs28493229 of the ITPKC gene is associated with susceptibility to KD or with CALs in Taiwanese children. A total of 385 unrelated Taiwanese children (222 boys and 163 girls) with KD were included, 140 of whom had CALs. Mean age at diagnosis was 1.9 +/- 1.7 (0.1-10.2) years. Rs28493229 was genotyped in children with KD and 1158 ethnically matched healthy controls using the TaqMan Allelic Discrimination Assay. In 184 families with KD, both biological parents were available, constituting 184 trios with their children. They were assessed in a family-based study by means of a transmission/disequilibrium test (TDT). No significant differences in genotype (P = 0.29 and P = 0.29, respectively), allele (P = 0.14 and P = 0.22, respectively) and carrier (P = 0.22 and P = 0.25, respectively) frequencies of the SNP were found between healthy controls and children with KD or those with CALs. TDT in the 184 family trios and in 69 trios where the child had CALs did not reveal significant overtransmittion of the C allele. In conclusion, we did not find a statistically significant association between the ITPKC gene SNP rs28493229 and KD or CALs in Taiwanese children.

Association of interferon-gamma gene polymorphisms in Taiwanese children with biliary atresia.

BACKGROUND: Biliary atresia (BA) is a devastating neonatal hepatobiliary disease characterized by bile duct inflammation and fibrosis. The pathogenesis remains unclear, but immunologically mediated injury to bile ducts following an infectious insult is likely to play a critical role. Interferon-gamma (IFN-gamma) is a key cytokine that affects immune-mediated inflammatory responses. OBJECTIVE: This study aims to investigate whether polymorphisms of the IFN-gamma (IFNG) gene were associated with susceptibility to BA. METHODS: The IFNG -1615 C/T, -183 G/T, +874 A/T, and +2197 A/G polymorphisms were genotyped using the TaqMan assay, and CA repeat microsatellite was analyzed using capillary electrophoresis in 50 children with BA and 788 ethnically matched healthy controls. RESULTS: The distribution of genotype, allele, and haplotype frequencies of these IFNG gene variants did not differ significantly between children with BA and controls. CONCLUSION: Polymorphisms of the IFNG gene do not appear to play a major role in the genetic predisposition to BA in Taiwanese children.

Genetic variation in the vascular endothelial growth factor gene is associated with biliary atresia.

BACKGROUND AND GOALS: Biliary atresia (BA) is a chronic inflammatory disease of the bile ducts resulting in biliary cirrhosis. Vascular endothelial growth factor (VEGF) has been implicated in cell-mediated inflammatory reactions. We aimed to study the relationship between genetic variations of the VEGF gene and susceptibility to BA using both case-control and family-based methodologies. STUDY: A total of 45 Taiwanese children with BA, 160 ethnically matched healthy controls, and 40 families (consisting of parents, affected children, and unaffected siblings) were studied. Three functional VEGF polymorphisms (-2578 A/C, -634 G/C, and +936 C/T) were assessed by using TaqMan assay. RESULTS: The +936 CC genotype [odds ratio (OR) 3.51, 95% confidence interval 1.54-8.01, P(c)=0.006] and C allele (OR 3.19, 95% confidence interval 1.48-6.90, P(c)=0.004) were significantly associated with increased risk of BA. The association of the +936 C allele with BA was also confirmed in a family-based association study (OR 5.7, chi2=9.8, P(c)=0.005). None of the haplotypes studied significantly influenced the risk to BA in either the case-control or family data sets. CONCLUSIONS: The VEGF +936 C/T polymorphism and particularly the C allele are associated with BA, possibly conferring increased susceptibility to the disease.