Yih-Hsin Chang

Elevated circulatory MMP-2 and MMP-9 levels and activities in patients with rheumatoid arthritis and systemic lupus erythematosus

OBJECTIVES Matrix metalloproteinases (MMPs) are suggested to play important roles in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study is to examine the MMPs expressions and activities in Taiwanese RA and SLE patients. DESIGN AND METHODS Levels and activities of plasma MMP-2 and MMP-9 were investigated by enzyme-linked immunosorbent assay and zymography, respectively. RESULTS MMP-2 levels in control subjects, RA and SLE patients were 146.1+/-34.2, 194.0+/-24.2 and 208.9+/-75.9 ng/mL respectively, and for MMP-9 were 51.4+/-57.1, 567.7+/-313.1 and 208.7+/-105.5 ng/mL respectively. Both MMP-2 and MMP-9 levels and activities from all patients were significantly higher than that from control subjects. CONCLUSIONS MMP-2 levels in both patients groups were approximately 1.3-1.4 folds higher than that in control subjects, notably, MMP-9 levels were 11- and 4-folds significantly higher, respectively, in RA and SLE patients. The results which MMP-2 and MMP-9 levels and activities are significantly elevated support the involvement of MMPs proteins in these autoimmune disorders.

Prevalence of antibiotics resistance and OXA carbapenemases genes in multidrug-resistant Acinetobacter baumannii isolates in central Taiwan

This study analyzed the prevalence of antibiotics resistance and the distribution of genes responsible for carbapenems resistance in Acinetobacter baumannii isolates. Clinical A. baumannii isolates were cultured, identified, and collected during the period from May 2007 to February 2009. Antibiotics resistance rates of the clinical isolates were analyzed by antimicrobial susceptibility testing. The distribution of carbapenemase alleles were investigated in the multidrug-resistant (MDR) A. baumannii isolates by multiplex polymerase chain reaction (PCR) techniques. A total of 1,265 independent A. baumannii isolates were identified. Approximately 70% of the clinical isolates were resistant to ampicillin/sulbactam, followed by imipenem, meropenem, cefepime, piperacillin/tazobactam, ceftazidime, and cefoperazone. Overall, 15.18% (192/1,265) of the isolates were characterized as MDR strains. All of the MDR A. baumannii isolates carried the blaOXA51-like allele. The detection rate of the blaOXA23-like and blaOXA24-like alleles was 96.35% (185/192) and 0.52% (1/192), respectively. Most of the isolates (185/192, 96.35%) carried genes which encode more than one carbapenemase. This report demonstrated that approximately 15% of A. baumannii clinical isolates in central Taiwan are MDR strains, with most of them harboring multiple carbapenemases. This study provides updated data regarding the prevalence of β-lactam resistance and genotyping information of carbapenems resistance of A. baumannii in central Taiwan.

Up-regulation of interleukin-17 expression by human papillomavirus type 16 E6 in nonsmall cell lung cancer

Human papillomavirus (HPV) 16/18 infection is associated with nonsmoking lung cancer. In this study, the authors investigated a putative correlation between interleukin (IL)‐17 expression and HPV infection in clinical nonsmall cell lung cancer (NSCLC) tissues and examined the effects of HPV infection on a human NSCLC cell line.

Establishment of a consistent L929 bioassay system for TNF-alpha quantitation to evaluate the effect of lipopolysaccharide, phytomitogens and cytodifferentiation agents on cytotoxicity of TNF-alpha secreted by adherent human mononuclear cells.

TUMOR necrosis factor-alpha (TNF-alpha) plays an important role in the pathogenesis of rheumatoid arthritis. The present study was to evaluate the effects of lipopolysaccharide (LPS), phytomitogens and cytodifferentiation agents on cytotoxicity of TNF-alpha secreted by adherent human mononuclear cells (AMC). TNF-alpha cytotoxicity in LPS-treated, phytomitogen-treated, and cytodifferentiation agent-treated AMC supernatants were analyzed by the L929 bioassay system. Our results showed that LPS could induce homogeneous TNF-alpha production by AMC whereas, in addition to TNF-alpha, phytomitogens could also induce other TNF-like factors. Neither methotrexate, retinoic acid nor sodium butyrate can inhibit TNF-alpha cytotoxicity, while hexamethylene bisacetamide could not only inhibit TNF-alpha cytotoxicity but also TNF-alpha inducing ability of LPS to AMC.

Association of tumour necrosis factor α promoter polymorphisms with ankylosing spondylitis in Taiwan

Ankylosing spondylitis is a genetic-susceptible inflammatory spondyloarthropathy that mainly affects the sacroiliac joints. Tumour necrosis factor (TNF)α, a potent proinflammatory cytokine and immune modulator of joint destruction, is suggested to be a risk factor for the development of ankylosing spondylitis.1 Evidence of an association between TNFα gene polymorphisms and ankylosing spondylitis showed conflicting results. Most of such studies focused on Caucasian subjects; few in the Taiwanese population were documented except for a recent study that reported the association between the interleukin 1 gene cluster and ankylosing spondylitis.2 Our study examined the distribution of TNFα promoter polymorphisms among Taiwanese patients with ankylosing spondylitis. A total of 143 patients with ankylosing spondylitis (97 men and 46 women, mean (standard deviation (SD)) age 41.7 (11.5) years), defined by the modified …

Association of interleukin-4 promoter polymorphisms in Taiwanese patients with type 2 diabetes mellitus

Many factors have been implicated in the onset of type 2 diabetes mellitus (T2DM). Recently, immune response and inflammation were suggested to play certain roles in the development and complications of T2DM. The aim of this study is to investigate the putative correlation between the promoter polymorphisms of interleukin-4 (IL-4), one of the immune-regulatory type 2 helper T-cell cytokines, and T2DM. Genomic DNA from 425 Taiwanese T2DM patients and 148 nondiabetic control study subjects were extracted, and their IL-4 promoter polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Both of the distribution of IL-4 C-589T (P = .013) and C-34T (P = .05) genotypes were significantly different between T2DM patients and control subjects. Significant association between IL-4 C-589T alleles (P = .002) and T2DM, as well as C-34T alleles and T2DM (P =.024), was also identified. In addition, a statistically significant association between homologous IL-4 -589 C/C genotype and lower circulatory high-density lipoprotein cholesterol levels was observed. Our results suggested that IL-4 promoter polymorphisms are associated with T2DM. A significant association between IL-4 -589 C/C genotype and lower circulatory high-density lipoprotein cholesterol level was observed as well. The above results suggested that IL-4 may participate in lipid metabolism and diabetic susceptibility.

Prevalence of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Taiwanese patients with Type 2 diabetic mellitus.

OBJECTIVES Deficiency and/or decreased activity of methyltetrahydrofolate reductase (MTHFR) resulted from MTHFR variants are associated with hyperhomocysteinemia, an independent risk factor for vasculopathies in diabetic patients. The aim of this study was to examine MTHFR genotypes between healthy and type 2 diabetes mellitus (T2DM) subjects. DESIGN AND METHODS MTHFR C677T and A1298C genotypes were analyzed in 56 T2DM and 62 healthy subjects by PCR-RFLP. Association between MTHFR genotypes and T2DM as well as the lipid/glucose metabolic indexes among T2DM subjects was statistically analyzed. RESULTS No significance in the distribution of MTHFR genotypes between healthy and T2DM subjects is found. Besides, no significant associations between lipid/glucose metabolic indexes with MTHFR genotypes among diabetic patients are observed. CONCLUSIONS These data indicate the previous observation that MTHFR polymorphisms may play some roles in the pathogenesis and complications of T2DM in Caucasians are unlikely to be applied in Taiwanese patients.

Polymorphisms of cytotoxic T lymphocyte-associated antigen-4 and cytokine genes in Taiwanese patients with ankylosing spondylitis.

Cytokines, costimulatory and counter-regulatory molecules play important roles in the regulation of inflammatory response, and are good candidates involved in the development of ankylosing spondylitis (AS). This study investigated the genotypic distribution of proinflammatory cytokines and T-cell negative regulator cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in healthy subjects and AS patients. Genomic DNA was extracted from 143 AS patients and 166 ethnic-matched healthy subjects. Nine polymorphisms within the genes of interleukin-4 (IL-4) (-34T>C, -81A>G, -285C>T and -589T>C), interleukin-6 (IL-6) (-174G>C), interleukin-10 (IL-10) (-592A>C and -819T>C) and CTLA-4 (-318C>T and +49A>G) were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Significantly less AS patients carried the CTLA-4 high-expressing -318 T allele (P = 0.040). The CTLA-4 +49A>G genotypes were associated with circulatory levels of the inflammatory marker C-reactive protein (CRP) (P = 0.022). Our study documented the most complete genetic information of Taiwanese AS patients. The observations that CTLA-4 +49A>G genotypes are associated with circulatory CRP levels and significantly less AS subjects carrying CTLA-4 higher-secretor -318 T allele suggest the level and regulation of inflammation in AS subjects may be pre-determined by and associated with CTLA-4 genotypes.

Trends of mycobacterial clinical isolates in Taiwan

Non-tuberculous mycobacteria (NTM) can cause chronic pulmonary infection, however, NTM infection is generally overlooked. This retrospective study analyzed the frequencies of Mycobacterium tuberculosis complex (MTBC) and NTM clinical isolates from 99 200 specimens of patients suspected with pulmonary mycobacterial infection in Taiwan from 2002-2007. A total of 8024 mycobacterial isolates, including 5349 MTBC and 2675 NTM, were obtained from the 99 200 specimens in the study period. The overall mycobacterial isolation rate was 8.09% (8024/99 200), and the overall MTBC and NTM isolation rate was 5.39% (5349/99 200) and 2.7% (2675/99 200), respectively. Notably, the prevalence of NTM isolates among the identified mycobacteria strains was increased 2.6 fold from 2002 (17.54%, 147/838) to 2007 (45.80%, 659/1439). The frequencies of MTBC and NTM isolates showed a reciprocal trend: the NTM isolation rates were steadily increasing while the overall mycobacterial isolation rates remained stable over the study period. Our results suggest that the diagnosis, identification and susceptibility tests for NTM should be standardized and integrated in clinical routines, for providing the information of NTM infection and prescribing clinical treatment in a more precise and efficient way to reduce the increasing NTM in the studied area.

Seroepidemiology of hepatitis A virus infection among schoolchildren in Taiwan

Taiwan was a hyperendemic area for hepatitis A virus (HAV) infection before 1980. The aim of this study was to examine the association between seropositivity of antibodies against HAV (anti‐HAV) by a community‐based survey. School children from 10 elementary and 3 junior high schools, as well as staff members who worked at the above schools in central Taiwan were selected at random in this study. Anti‐HAV was tested in sera of 1,954 healthy schoolchildren (aged 7–15 years old) and 254 teachers by enzyme‐linked immunosorbent assay. Schoolchildren had a low prevalence of anti‐HAV (2.3%) in contrast to the high seroprevalence in their teachers (52%). The seropositive rates of HAV antibody among the study subjects were increasing with age. No significant differences of anti‐HAV seroprevalence among the study subjects were observed when they were stratified by gender, geographical area, household members, and parental education. Whereas, the anti‐HAV seroprevalence was significantly higher in schoolchildren who were either aboriginal or living in areas without a supply of drinking tap‐water. The seroprevalence of HAV data among the healthy pediatric population would be helpful to evaluate the need for mass vaccination policies. J. Med. Virol. 83:196–200, 2011.