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A FRET-based probe for mapping the fluctuation of ONOO− in cisplatin-induced acute kidney injury was constructed. It exhibits ratiometric near infrared fluorescence and a dramatic decrease of its peak absorbance at 719 nm upon addition of ONOO− that is converted into remarkable signal changes in fluorescence and photoacoustic images respectively.

Molecular probes activated by a single enzyme have been extensively used in bioimaging and disease diagnosis; however, imaging and identification in an accurate manner remains a challenge for such probes. Here, based on the specificity of enzyme recognition, we engineered a "double-locked" and enzyme-activated molecular probe (NML) for accurate bioimaging and hepatopathy differentiation. Triggered by the successive reactions with leucine aminopeptidase (LAP, first "key") and monoamine oxidase (MAO, second "key"), the emissive fluorophore (NF) was released. NML can be activated only in the presence of both LAP and MAO and can be silenced when either enzyme is inhibited. Benefiting from the "double-locked" strategy, NML showed higher accuracy for imaging of drug-induced liver injury (DILI) than the "single-locked" probe. With serum testing, NML showed significant differences in mouse models of both CCl4-induced liver cirrhosis and DILI. Significantly, NML can be applied to accurately distinguish serum samples from clinical patients with different hepatopathies. Our smart molecular probe may hold great potential for hepatopathy diagnosis and clinical transformation.

The ability to detect cancer early in an accurate and rapid fashion is of critical importance for cancer diagnosis and accurate resection in surgery. γ-Glutamyltranspeptidase (GGT) is overexpressed in several human cancers, while maintaining a low expression in normal microenvironments, and thus is recognized as an important cancer biomarker. To date, rational design of a zero cross-talk ratiometric near-infrared (NIR) GGT fluorescent probe for efficient cancer diagnosis in various biological samples is still a big challenge. In this work, a zero cross-talk ratiometric NIR GGT fluorescent probe named Cy-GSH is developed. Cy-GSH shows high sensitivity to GGT, which is desired for early cancer diagnosis. Upon additional GGT, a large emission shift from 805 to 640 nm is observed, which is suitable for visualizing deeply located cancer in vivo. In addition, successful monitoring of GGT activity in blood, cells, tissues, and in vivo makes Cy-GSH possess great potential for the clinical cancer early diagnosis. Furthermore, accurately visualizing tumors and metastases in mouse models illuminates that the probe may be a convenient tool for fluorescence-guided cancer surgery. To our knowledge, this is the first report to describe the strategy of a zero cross-talk ratiometric NIR GGT fluorescent probe for early cancer diagnosis and fluorescence-guided surgery.

Abnormal enzymatic activities are directly related to the development of cancers. Identifying the location and expression levels of these enzymes in live cancer cells have considerable importance in early-stage cancer diagnoses and monitoring the efficacy of therapies. Small-molecule fluorescent probes have become a powerful tool for the detection and imaging of enzymatic activities in biological systems by virtue of their higher sensitivity, nondestructive fast analysis, and real-time detection abilities. Moreover, due to their structural tailorability, numerous small-molecule enzymatic fluorescent probes have been developed to meet various demands involving real-time tracking and visualizing different enzymes in live cancer cells or in vivo. In this review, we provide an overview of recent advances in small-molecule enzymatic fluorescent probes mainly during the past decade, including the design strategies and applications for various enzymes in live cancer cells. We also highlight the challenges and opportunities in this rapidly developing field of small-molecule fluorescent probes for interventional surgical imaging, as well as cancer diagnosis and therapy.

Acute organ injury observed during sepsis, caused by an uncontrolled release of inflammatory mediators, such as lipopolysaccharide (LPS), is quite fatal. The development of efficient methods for early diagnosis of sepsis and LPS-induced acute organ injury in living systems is of great biomedical importance. In living systems, cystathionine γ-lyase (CSE) can be overexpressed due to LPS, and H2Sn can be formed by CSE-mediated cysteine metabolism. Thus, acute organ injury during sepsis may be correlated with H2Sn levels, making accurate detection of H2Sn in living systems of great physiological and pathological significance. In this work, our previously reported fluorescent platform was employed to design and synthesize a FRET-based ratiometric two-photon (TP) fluorescent probe TPR-S, producing a large emission shift in the presence of H2Sn. In this work, a naphthalene derivative two-photon fluorophore was chosen as the energy donor; a rhodol derivative fluorophore served as the acceptor. The 2-fluoro-5-nitr...

Drug-induced liver injury (DILI) is a potential complication of any prescribed medication. So far, the diagnosis of DILI is still a clinical challenge due to the lack of efficient diagnosis method. Glutathione S-transferase (GST), with a high concentration in liver cytosol, can reduce toxicity and facilitate urinary excretion by catalyzing the conjugation of glutathione (GSH) with reactive metabolites in liver. When liver is seriously damaged, GST and GSH will be released into plasma from liver cytosol, which caused a lower GST activity in liver cytosol. Therefore, monitoring the level of GST activity in liver tissue may be a potential strategy for diagnosis of DILI. Here, we reported a two-photon probe P-GST for GST activity detection for the first time. In the proposed design, a donor-π-acceptor (D-π-A) structured naphthalimide derivative with efficient two-photon properties was chosen as the fluorescent group, and a 2,4-dinitrobenzenesulfonate group was employed as the GST recognition unit, which also acted as the fluorescence quencher. In the present of GST and GSH, the recognition unit was removed and the fluorophore was released, causing a 40-fold enhancement of fluorescence signal with a detection limit of 35 ng/mL. At last, P-GST was successfully applied in two-photon imaging of GST in cells and DILI samples, which demonstrated its practical application in complex biosystems as a potential method for diagnosis of DILI.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease primarily affecting women. Previous studies have indicated that sex hormone estrogens contribute to the female predilection of SLE. Estrogen regulates gene expression by translocating estrogen receptors (ER) α and β into the nucleus where they induce transcription by binding to estrogen response elements of target genes. We have previously observed that expression of ERα gene and protein in lupus patients is significantly higher than in healthy controls and that estradiol up-regulates calcineurin expression via over-expression of ERα gene in SLE. However, the pathogenesis of over-expression of ERα gene is unknown. Here we report that enhanced expression of ERα mRNA and protein in SLE and rheumatoid arthritis is associated with DNA demethylation within the proximal promoter region located between -232 and +81 base pair relative to transcription start site of human ERα gene (GenBank Accession no. AL356311.6). The frequency of DNA demethylation was comparable between male and female. These findings suggest that estrogen and demethylated ERα promoter associated up-regulated ERα genes are two critical factors in the gender biased development of autoimmune diseases besides genetic factor.

Systemic lupus erythematosus (SLE) is an autoimmune disease primarily affecting women (9:1 compared with men). To investigate the influence of female sex hormone estrogen on the development of female-biased lupus, we compared the expression of estrogen receptor alpha (ERα) gene and protein levels as well as expression of T-cell activation gene calcineurin in response to estrogen in peripheral blood lymphocytes (PBLs) from SLE patients and normal controls. PBLs were isolated from 20 female SLE patients and 6 normal female controls. The amount of ERα protein in PBL was measured by flow cytometry. The expression of ERα and calcineurin messenger RNA was measured by semi-quantitative reverse transcription-polymerase chain reaction. Calcineurin phosphatase activity was measured by calcineurin assay kit. The expression of ERα messenger RNA and ERα protein was significantly increased (p = 0.001 and p = 0.023, respectively) in PBL from SLE patients compared with that from normal controls. In addition, the basal calcineurin in PBL from SLE patients was significantly higher (p = 0.000) than that from normal controls, and estrogen-induced expression of calcineurin was increased (p = 0.007) in PBL from SLE patients compared with that from normal controls, a 3.15-fold increase. This increase was inhibited by the ERα antagonism ICI 182,780. The effects of ER antagonism were also found in calcineurin activity. These data suggest that overexpression of ERα gene and enhanced activation of calcineurin in response to estrogen in PBL may contribute to the pathogenesis of female dominant in SLE.

To investigate the associations of DNA methylation levels and mRNA expressions of DNA cytosine-5-methyltransferase 1 (DNMT1) and methyl CpG-binding domain 2 (MBD2) with rheumatoid arthritis (RA).The global methylation status of DNA was measured in 65 patients with RA and 64 healthy controls by the ELISA method. DNMT1 and MBD2 mRNA were also detected in 177 RA patients and 95 controls using the quantitative real-time polymerase chain reaction method.The global methylation of DNA was significantly decreased in the RA patients compared to the controls (p=0.005, 95% CI=0.0835-0.4503). The patients with RA had higher expressions of DNMT1 and MBD2 mRNA than the controls (p0.001, 95% CI=-0.0024 to -0.0053 and p0.001, 95% CI=-0.0079 to -0.0167, respectively). We also found that the MBD2 mRNA level was not related to the disease activity of RA. However, the expression of DNMT1 mRNA tended to be associated with the disease activity of RA (p=0.08). The levels of DNA methylation and DNMT1 mRNA were significantly decreased in the patients with anti-CCP antibody compared with those without (p=0.005, 95% CI=-0.7333 to -0.1373 and p=0.003, 95% CI=-0.0071 to -0.0022, respectively). The differences in the methylation level and expressions of DNMT1 and MBD2 were not significant between the patients treated with and without anti-TNFα biological agents (Enbrel or Humira).This study demonstrated that the RA patients have a significantly lower level of DNA methylation than the controls. Moreover, RA patients have higher expressions of DNMT1 and MBD2 mRNA. The anti-TNFα biological agents do not seem to affect DNA methylation and mRNA expressions of DNMT1 and MBD2 in RA patients.

The objective of this study was to investigate the associations between suppressor of cytokine signaling 1 (SOCS1) mRNA expression and SOCS1 polymorphisms with the development of rheumatoid arthritis (RA). One hundred and eighty-one patients with RA and 96 healthy controls were enrolled in this study. The SOCS1 mRNA level in peripheral blood mononuclear cells (PBMCs) was detected by quantitative real-time polymerase chain reaction. SOCS1 polymorphisms were determined by the polymerase chain reaction/restriction fragment length polymorphism method. We found that the expression of SOCS1 mRNA in PBMCs was significantly greater in patients with RA than in healthy controls. There were no significant differences in the expression of SOCS1 mRNA among patients with different disease activities. The increment in SOCS1 mRNA after stimulation with various cytokines was slightly lower in the patients with RA than in the healthy controls. This study also demonstrated that the SOCS1 polymorphisms were not associated with susceptibility to RA. In conclusion, the expression of SOCS1 mRNA in PBMCs is higher in patients with RA than in healthy controls. The increment in SOCS1 mRNA expression in PBMCs after stimulation with different cytokines seems to be lower in patients with RA than in healthy controls.

To investigate the role ofIκBαpromoter polymorphisms in the development of Behçet’s disease, eighty-six patients with Behçet's disease and 120 healthy controls were enrolled in this study. TheIκBα; -881A/G, -826C/T, -550A/T, -519C/T, and -297C/T polymorphisms were measured by the method of polymerase chain reaction/ restriction fragment length polymorphism. This study demonstrated that the genotype frequencies ofIκBα-826C/T and -826T/T were significantly higher in the patients with Behçet's disease than in the controls. Both in the dominant and in the recessive models, the patients with Behçet's disease have higher frequencies of the IκBα -826T containing genotype than the controls. The allele frequency ofIκBα-826T was significantly increased in the patients with Behçet’s disease. The frequencies of theIκBα-881A -826T -550A -519C -297C andIκBα-881A -826T -550A -519T -297C haplotypes were significantly higher in the patients with Behçet–s disease than in the controls. In contrast, the haplotype frequency ofIκBα-881A -826C -550A -519C -297C in the patients with Behçet’s disease was significantly decreased. This study also revealed that the Behçet’s disease patients with IκBα -826T/T have higher prevalence of skin lesions than those without IκBα -826T/T. In summary, the IκBα -826T allele,IκBα-881A -826T -550A -519C -297C andIκBα-881A -826T -550A -519T -297C haplotypes might be associated with susceptibility to Behçet’s disease. TheIκBα-826T/T genotype was related to the development of skin lesions in the patients with Behçet's disease.

We implemented a nationwide population-based study in Taiwan to compare the physical and biochemical parameters, diet and exercise lifestyles, and prevalences of diabetes, hyperlipidemia, and hypertension between males and females, and to clarify the determinants of diabetes, hyperlipidemia, and hypertension in Taiwan. In this cross-sectional study, 7,578 subjects were selected from the general population by stratified random sampling for the Surveillance of Taiwanese Civil Health in 2002. Blood samples were taken and information on body composition, demographics, exercise and dietary habits, and medical and drug histories were obtained from structured interviews administered by well-trained interviewers. A total of 6,600 subjects (87.1%), aged 15.6–95.0 years old, completed the survey. The overall prevalences of diabetes, hyperlipidemia, and hypertension were 9.9%, 22.8%, and 15.7%, respectively, and hyperlipidemia (27.0%) and hypertension (19.2%) were more prevalent in males. Males were more likely to have high-fat and high-cholesterol diets, compared with females. Although there were differences in the prevalences of hyperlipidemia and hypertension between the sexes, adjusted logistic regression analysis demonstrated little contribution of diet and exercise habits to the risks of diabetes, hyperlipidemia, or hypertension after adjusting for age, sex, waist-to-hip ratio, serum blood sugar levels, cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, creatinine, uric acid, and blood pressure.

Most researchers believe that the peroxisome proliferative activated receptor gamma (PPARgamma-2) and bone morphogenetic protein receptor type II (BMPR2) play important roles in steroid-induced osteonecrosis (ON). However, the molecular mechanism of this process is still unclear. Recent studies indicate that steroid treatments cause adipocyte formation due to differentiation of mesenchymal stem cells, which then prevents osteoblast formation. This study examined PPARgamma-2, bone morphogenetic protein 2 (BMP2), and BMPR2 in patients with systemic lupus erythromatosus (SLE) who eventually developed ON after prolonged steroid treatment. The subjects of this experiment included 220 SLE patients who had undergone steroid treatment for at least 2 years. Fifty-five of the 220 patients were ON patients, and 165 were non-ON patients. Real-time PCR was performed to analyze the expression of the PPARgamma-2, BMP2, and BMPR2 mRNA in the peripheral blood of these patients. The results indicated that the expression of PPARgamma-2 mRNA increased 37% in the ON patients' peripheral blood, but the expression of BMPR2 mRNA decreased 57%. The average expression of the PPARgamma-2 mRNA in the ON patients was significantly higher than that in the non-ON patients (p = 0.044). Conversely, the expression of BMPR2 mRNA was significantly lower than that in non-ON patients (p = 0.036), but the expression of BMP2 mRNA did not significantly differ. This study demonstrated that the PPARgamma-2 and BMPR2 have important roles in the ON process after prolonged steroid administration in SLE patients; however, the detailed molecular mechanisms of this process require further study.

OBJECTIVES: To test the association between fasting glucose level and left ventricular mass (LVM) and left ventricular hypertrophy (LVH) in people aged 60 and older. DESIGN: Population-based prospective study with 4-year follow-up. SETTING: Department of Internal Medicine and Family Medicine, Kaohsiung Medical University (KMU), Chung-Ho Memorial Hospital, and Graduate Institute of Medicine and Public Health, KMU. PARTICIPANTS: Of 1,500 people screened, 105 without symptoms or signs of diabetes mellitus, hypertension, or cardiovascular disease were recruited from senior activity centers in Kaohsiung city. MEASUREMENTS: All received two-dimensional echocardiography and fasting glucose examination at baseline and at 2- and 4-year follow-up. LVH was defined as a LVM index (LVMI) greater than 122.4 g/m2 or 51 g/m2.7. RESULTS: Age ranged from 60 to 81 (mean 71.7±3.9). Baseline glucose ranged from 83 to 118 mg/dL (mean 99.7±7.9 mg/dL). LVMI was significantly higher at the 4-year follow-up (97.5±24.9 vs 104.5±27.5 g/m2 and 44.2±12.1 vs 47.2±13.4 g/m2.7, both P

To investigate the role of SLC 11A1 polymorphisms in the development of reactive arthritis, 91 patients with reactive arthritis and 163 healthy controls were enrolled in this study. The SLC 11A1 polymorphisms were determined by the method of polymerase chain reaction/restriction fragment length polymorphism. The genotype distributions of SLC 11A1 274, 823, 1703, and 1729+ 55 del 4 were significantly different between the patients with reactive arthritis and controls. The genotype frequency of SLC 11A1 274C/C was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the SLC 11A1 274C/T showed a significant association with reactive arthritis. The patients with reactive arthritis have a significantly higher frequency of SLC 11A1 823C/C than the controls. However, SLC 11A1 823T/T was resistant to the development of reactive arthritis. The allele frequencies of SLC 11A1 274T and 823C were significantly increased in the patients with reactive arthritis in comparison with those of the controls, independent of HLA-B27. On the contrary, the allele frequencies of SLC 11A1 274C and 823T were significantly decreased in the patients with reactive arthritis. The estimated haplotype frequency of SLC 11A1 274C 823T 1703G 1729+55del 4 TGTG+ was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the estimated haplotype frequency of SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ was significantly increased in the patients with reactive arthritis. This study shows that the SLC 11A1 274T and 823C alleles are associated with susceptibility to reactive arthritis independently of HLA-B27 in Taiwan. The SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ haplotype is associated with the development of reactive arthritis in Taiwan. In contrast, the SLC 11A1 274C 823T 1703G 1729+55 del 4 TGTG+ haplotype may be a protective factor.

Our previous studies showed that colorectal tumor has high interleukin-4 receptor α (IL-4Rα) expression, whereas adjacent normal tissue has low or no IL-4Rα expression. We also observed that human atherosclerotic plaque-specific peptide-1 (AP1) can specifically target to IL-4Rα. In this study, we investigated the therapeutic efficacy and systemic toxicity of AP1-conjuagted liposomal doxorubicin. AP1 bound more strongly to and was more efficiently internalized into IL-4Rα-overexpressing CT26 cells than CT26 control cells. Selective cytotoxicity experiment revealed that AP1-conjugated liposomal doxorubicin preferentially killed IL-4Rα-overexpressing CT26 cells. AP1-conjugated liposomal doxorubicin administered intravenously into mice produced significant inhibition of tumor growth and showed decreased cardiotoxicity of doxorubicin. These results indicated that AP1-conjugated liposomal doxorubicin has a potent and selective anticancer potential against IL-4Rα-overexpressing colorectal cancer cells, thus providing a model for targeted anticancer therapy.

To investigate the role of programmed cell death-1 (PD-1) gene polymorphisms in the development of systemic lupus erythematosus (SLE) in Taiwan, 109 patients with SLE and 100 healthy controls were enrolled in this study. The PD-1 gene polymorphisms were determined by the method of polymerase chain reaction/restriction fragment length polymorphism. This study showed that the genotype distributions of PD-1 7209 C/T polymorphisms were significantly different between the patients with SLE and controls (P=0.002, Pc=0.018). The frequencies of the PD-1 7209 C/C genotype and PD-1 7209 C allele were significantly higher in the patients with SLE than those of the controls (P=0.001, OR=2.6, 95% CI=1.5-4.6, and P=0.002, OR=2.1, 95% CI=1.3-3.4, Pc=0.018, respectively). Moreover, the association of PD-1 7209 C with susceptibility to SLE was independent of the PD-1 ligand. This study also showed that the PD-1-536 A 7146 G 7209 C 7499 G haplotype was associated with the development of SLE in Taiwan.

Objectives To investigate the role of inhibitor of kB-like ( IkBL ) gene polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. Methods One hundred and twenty-nine patients with RA and 110 healthy controls were enrolled in this study. Polymerase chain reaction (PCR)/direct sequencing was used to determine the polymorphisms of IkBL −421 8T/9T, −324 C/G, −262 A/G, and −62 A/T. PCR/restriction fragment length polymorphism was used to determine the IkBL +738 T/C polymorphisms. Results The genotype distribution of IkBL −421 was significantly different between DR4 (+) RA patients and DR4 (+) controls ( p = 0.02). The allele frequency of IkBL −421 8T was significantly higher in DR4 (+) RA patients than in DR4 (+) controls ( p = 0.004, OR = 7.2, 95% CI = 1.7–29.2). The allele carriage frequency of IkBL −421 8T also tended to be increased in DR4 (+) RA patients in comparison with DR4(+) controls ( p = 0.07, OR = 14.6, 95% CI = 1.4–147.0). We also found that the allele frequency of IkBL −62 T was significantly higher in RA patients than in controls ( p = 0.04, OR = 1.5, 95% CI = 1.1–2.1). The allele carriage frequency of IkBL −62 T tended to be increased in RA patients ( p = 0.08, OR = 1.7, 95% CI = 1.0–3.0). The estimated haplotype frequency of IkBL −421 8T/−62 T tended to be increased in RA patients compared with controls ( p = 0.07, OR = 1.4, 95% CI = 1.0–2.0). Conclusion The IkBL −62 T may be associated with the development of RA in Taiwan. The IkBL −421 8T may also be related to susceptibility to RA in HLA-DR4 (+) individuals. This study shows that the estimated haplotype IkBL −421 8T/−62 T tends to be associated with susceptibility to RA in Taiwan.

Oxidative stress triggered by septic insult may be the major cause of multiple organ dysfunction syndrome (MODS) in intensive unit care patients. The inducible form of heme oxygenase-1 (HO-1) can be induced by cytokines, lipopolysaccharide, and reactive oxygen species during sepsis. These facts raise the question of whether the expression of HO-1 in leukocytes can indicate the level of oxidative stress of multiple organs in sepsis. Clinical peritonitis was simulated in an animal model by cecal ligation and puncture (CLP). The level of oxidative stress was examined by plasma lipid peroxidation (LPO). Liver function was analyzed by plasma aspartate aminotransferase, alanine aminotransferase, total bilirubin, and direct bilirubin. Lung function was evaluated by severity of edema. Renal function was measured by blood urea nitrogen and creatinine. The correlation between early HO-1 induction and LPO level or organ functional indicators of the same rat at late sepsis was analyzed by linear regression. The results showed that the protein content of HO-1 increased at 9 h after CLP, whereas expression of HO-1 mRNA in leukocytes was significantly increased (P < 0.01) at 6 h after CLP. Plasma level of LPO and the indices of hepatic, pulmonary, and renal function were significantly increased at 18 h after CLP. Moreover, highly negative correlations were observed between HO-1 mRNA expression at 6 h after CLP and level of LPO or severity of hepatic/renal dysfunction at 18 h after CLP. These results suggest that early HO-1 mRNA expression in leukocytes may represent oxidative stress and may predict the severity of liver and renal dysfunction during sepsis.

The aim of this study was to develop a microdialysis-graphite furnace atomic absorption spectroscopy (MD-GFAAS) for monitoring dynamic changes of extracellular magnesium (Mg) and zinc (Zn) in the cortex of gerbils subjected to focal cerebral ischemia, that had been produced in anesthetized gerbils by occlusion of the right middle cerebral artery.Two microdialysis probes were inserted into both sides of the cortex to simultaneously collect dialysates during cerebral ischemia. Dynamic changes in these analytes, on ipsilateral and contralateral sides of the brain, were assayed by MD-GFAAS. Optimal conditions and analytical precision of GFAAS were studied in the present assay.The present study demonstrated significant decreases in Mg (65% of baseline) and zinc (74% of baseline) maintained their levels within 3 h on the ipsilateral side of cortex during cerebral ischemia. Slight changes of Mg and Zn on the contralateral sides were also observed.The derangement of extracellular Mg and Zn could be important in the progression of cell injury and may be associated with cerebral ischemia insult.

The major objective of the present study was to identify biologic and behavioral risk factors of cardiovascular disease (CVD) in the elderly population in Taiwan. It is hypothesized that the selected risk factors are significantly associated with the prevalence of CVD. Data came from a nationwide geriatric survey in 1991. Stratified proportional sampling was used to recruit 2,600 subjects. These were evaluated by family physicians working for the Departments of Family Medicine at four medical centers in four major cities in Taiwan. Univariate and multivariate logistic regression analyses were used to examine the associations between risk factors and the prevalence of CVD. The prevalence of CVD was 38.31%. Patients with CVD consistently had higher values for each selected risk factor except high-density lipoprotein-cholesterol (HDL-C) and glucose concentrations. The findings also indicated that hypertension, hypertriglyceridemia, low HDL-C concentration, ex-drinking status, and overweight were significantly associated with the prevalence of CVD among the elderly in Taiwan. The findings not only confirm the risk factors for CVD, but also invite more attention to be given to the importance of biologic and behavioral risk factors in CVD.

Objective:As there is little understanding of disability processes in Taiwanese elders, the present study aimed to identify medical predictors of the incidence of activities of daily living (ADL) disability. Method:A total of 903 subjects were studied over a 4-year period (1994–1998). The measurement instrument was the Chinese-version Multidimensional Functional Assessment Questionnaire (CMFAQ). Only the subjects free of ADL disability at baseline were included in separate logistic regression models to predict disability in physical and instrumental ADL. Results:The hypothesised associations between chronic conditions and future functional disability were cross-nationally confirmed. Arthritis, diabetes and hypertension were significantly predictive of the onset of physical ADL (PADL) disability; diabetes was the only medical predictor of instrumental ADL (IADL) disability. Age and educational level were significant predictors of PADL and IADL. Conclusions:Prevention programs for chronic disease need to pay more attention not only to the disabled population, but also to secondary prevention among those elders who have higher medical risk of developing disability.

Objective. The expression of autoimmunity in mice deficient in programmed death 1 (PD-1) suggests that PD-1 is a candidate gene involved in the development of human autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). We therefore tested the potential association between PD-1 and the development of SLE and RA by conducting case–control genetic-association studies. Methods. Ninety-eight SLE patients, 84 RA patients, and sex-matched control subjects for each disease group were recruited and genotyped for a single-nucleotide polymorphism, C+872T, in the human PD-1 gene. The significance of the association of the PD-1 gene with SLE or with RA was analyzed by statistical tests for the difference in genotype distribution between disease and control groups. Results. The human PD-1 gene was found to be significantly associated with disease development in RA patients, but not SLE patients. The risk of RA development appeared to be significantly increased by carriage of the T allele (odds ratio 3.32, P < 0.0001) or the C/T genotype (odds ratio 3.52, P < 0.00005). Conclusion. The PD-1 gene is significantly associated with RA susceptibility, suggesting the possibility that PD-1 may contribute to the pathogenesis of RA.

Objectives: To investigate the association of tumor necrosis factor (TNF) microsatellite alleles with the pathogenesis of rheumatoid arthritis (RA) in Taiwan. Methods: The TNF a, b, c, d, and e microsatellites were determined in 112 patients with RA and 99 healthy controls by using polymerase chain reaction (PCR) and electrophoresis with sequencing gel. All of these patients and controls had known HLA-DR genotypes and TNF-308 polymorphisms. Results: The phenotypic frequency of TNFa9 was significantly higher in DR4(−) RA patients than in DR4(−) controls. However, the phenotypic frequency of TNFb6 was significantly higher in RA patients than in controls in the presence of HLA-DR4. The phenotypic frequency of TNFa3-e1 was significantly lower in DR4(+) RA patients than in DR4(+) controls, while a negative linkage disequilibrium was noted between TNFa3-e1 and HLA-DR4. TNF microsatellite alleles were not related to the prevalences of bone erosion, rheumatoid nodule, sicca syndrome, pulmonary fibrosis, and seropositivity of rheumatoid factor (RF) in patients with RA. Conclusion: The associations of TNF microsatellites with the susceptibility to RA in Taiwan are not completely independent of the HLA-DR associations. The association of TNFb6 with the susceptibility to RA depends on the presence of HLA-DR4, and the correlation of TNFa9 to RA depends on the absence of HLA-DR4. The negative association of TNFa3-e1 with RA may be secondary to the negative linkage disequilibrium between TNFa3-e1 and HLA-DR4. Moreover, TNFb6 and HLA-DR4 have a synergistic effect on the susceptibility to RA. TNFa3-e1 and TNF-308A have a synergistic effect on preventing from RA. The TNF microsatellite alleles are not related to the clinical manifestations and severity of RA patients in Taiwan.

Background In Taiwan, distributions of body composition are usually generated for children, adolescent, and middle-aged groups. This study describes three anthropometric measures (i.e., height, weight, and body mass index [BMI]) of elderly persons in Taiwan. Methods The data was derived from a prospective cross-sectional, population-based geriatric survey funded by the National Department of Health in Taiwan in 1991. A total of 2,600 subjects were successfully evaluated. A descriptive analysis was performed to generate distributions of height, weight, and BMI of elderly persons. Based on these descriptive data, the prevalence of overweight and obesity was estimated, and a cross-national comparison on the prevalence of obesity was made. Results Age-group-specific means and standard deviations for height, weight, and BMI of Taiwanese elderly persons were presented. By gender, the elderly men were taller and heavier than the elderly women: however, the women had a higher mean value of BMI (kg/m2). The prevalence of overweight was 27.3% in men and 34.9% in women; the prevalence of obesity was 3.2% in men and 6.4% in women. The prevalence of obesity for the elderly men and women in Taiwan was lower than in Kuwait, Sweden, the United States, and the Native Americans, but higher than in Japan. Conclusions The comparison indicates cross-cultural differences existing in the prevalence of obesity, which may be due to aging, nutritional status, or environmental factors. For future research, the relationship of anthropometric data to socioeconomic status and behavioral factors will be examined.

Many autoimmune diseases have been reported to be associated with malignancy. Mixed connective tissue disease (MCTD), however, has rarely been associated with malignancy. Thymoma is one of the neoplasms often reported to be related to various immunological disorders. Among the types of thymoma defined by WHO, malignant thymoma (thymoma type C) is the one least reported to be associated with autoimmune disease. Here, we report a case of malignant thymoma with concurrent MCTD, which manifested with acrosclerosis, Raynaud's phenomenon, arthritis (synovitis), and a high titer of anti-ribonucleoprotein antibody.

Cytokines are involved in the pathogenesis of autoimmune diseases. Oncostatin M receptor (OSMR) activates JAK/STAT and MAPK pathways leading to the stimulation of a variety of cytokines and inflammatory substances. Many pro-inflammatory cytokines are involved in the inflammatory process of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this study, we carried out experiments to examine the relationship of OSMR promoter polymorphisms with RA and SLE patients. 241 patients of RA, 143 patients of SLE and 203 healthy controls were enrolled in their recruitment from the Kaohsiung Medical University Hospital. Genomic DNA was extracted from peripheral blood mononuclear cells and gene polymorphism was genotyped by TaqMan real-time polymerase chain reaction. The OMSR promoter region -100 G/T (rs22922016) genotype was in no relation to the susceptibility of RA, but -100 T/T (rs22922016) genotype could prevent the patients with sicca syndrome and the existence of anti-Ro antibodies. In contrast, the -100 G/T+T/T (rs22922016) genotypes were significantly associated with an increased risk of SLE (odds ratio, OR=1.62, 95% confidence interval (CI), 1.01-2.62). 94.38% of SLE patients with arthritis were belonged to the -1687C/C (rs540558) genotype. The T allele of promoter region -100 T/T (rs22922016) has protective effect and could ameliorate the disease condition in RA patients, whereas the same T allele was a risk allele in the susceptibility of SLE. The disease severity of rheumatoid arthritis and systemic lupus erythematosus can be partially affected by the OSMR promoter polymorphisms.

Protein tyrosine phosphatase nonreceptor type 12 (PTPN12) has been recognized as a tumor suppressor gene that may inhibit tumor growth. However, PTPN12 expression in oral squamous carcinoma (OSCC) has not been studied. We showed reduced expression of PTPN12 in OSCC tissues. Decreased PTPN12 expression was significantly associated with clinical stage of the disease (P < 0.01). Moreover, reduction in PTPN12 correlated with the overactivation of STAT3. PTPRD negatively related to STAT3 phosphorylation (R = -0.535). Low expression of PTPN12 and high level of phosphorylation of STAT3 correlated with poor prognosis. Overexpression of PTPN12 inhibited proliferation and migration in OSCC cells. PTPN12 was associated with STAT3 and induced STAT3 dephosphorylation. Moreover, our results suggested that PTPN12 might function through binding and dephosphorylation of STAT3. Therefore, PTPN12 is a potential marker for prognosis of OSCC.

We utilized the PCR method to amplify the alpha-thalassemia-1 breakpoint area of the Southeast Asia type and several regions of the alpha-globin gene cluster to diagnose rightward deletion (-alpha 3.7), leftward deletion (-alpha 4.2) or nondeletion forms of the Hb H disease. For the nondeletion form, a natural restriction site of MseI was used to detect the Hb Constant Spring (Hb CS) or other termination codon mutations. Another naturally occurring restriction site of MspI was used to detect the Hb Quong-Sze. For the deletion form of the Hb H disease, the differences among nonhomologous I, II and III of the rightward or leftward deletion were used to distinguish the mutations. For further characterization of the subtype of -alpha 3.7 deletion, the same primers for detecting termination codon mutations were used to amplify part of the alpha-globin gene, then the PCR product was digested by the restriction enzyme ApaI. In the 57 cases which were studied, 19 were deletion forms while 38 were nondeletion forms. In the deletion form cases, 13 were rightward deletion (-alpha 3.7) and the other 6 were leftward deletion (-alpha 4.2). However, all of the nondeletion form cases were alpha-thalassemia-1 with Hb CS. After the subtyping of -alpha 3.7 deletion, 11 out of 13 were type I deletions and the other 2 were type II deletions.

With the aim of investigating the role of suppressor of cytokine signaling 1 (SOCS1) in the pathogenesis of systemic lupus erythematosus, 107 patients with systemic lupus erythematosus, 101 healthy controls, and 151 patients with ankylosing spondylitis were enrolled in this study. SOCS1 mRNA level was measured by the method of quantitative real-time polymerase chain reaction. SOCS1 polymorphisms were detected by the polymerase chain reaction/restriction fragment length polymorphisms method. Systemic lupus erythematosus disease activity was evaluated with the SLEDAI. This study showed that the SOCS1 mRNA expression was significantly higher in the patients with systemic lupus erythematosus than in the healthy controls (p = 0.0014). Patients with active systemic lupus erythematosus had a higher expression of SOCS1 mRNA than the patients with inactive systemic lupus erythematosus (p = 0.035). There was no significant difference in the frequencies of the SOCS1-1478CA/del polymorphisms among the patients with systemic lupus erythematosus, healthy controls, and patients with ankylosing spondylitis. The genotype frequency of the SOCS1-1478 polymorphisms in the dominant model (CA/del+del/del versus CA/CA) was significantly decreased in the patients with thrombocytopenia compared with those without thrombocytopenia (pc = 0.035). Moreover, the allele frequency of SOCS1-1478del was also significantly lower in the patients with thrombocytopenia than in those without thrombocytopenia (p c = 0.02). In conclusion, this study demonstrated that the expression of SOCS1 mRNA was significantly increased in patients with systemic lupus erythematosus. Moreover, SOCS1 mRNA levels in patients with active systemic lupus erythematosus were significantly higher than those in the inactive patients. We also found that the systemic lupus erythematosus patients with thrombocytopenia have a lower frequency of SOCS1-1478del compared with patients without thrombocytopenia. Lupus (2010) 19, 696—702.

We describe a female aborigine from Taiwan with alpha-chain disease associated with multiple polypoid intestinal lymphocytic lymphoma and leukemic manifestation. Initially, the patient experienced intermittent diarrhea, abdominal pain, and leukemic manifestation. No evidence of bone marrow involvement was found. Alpha-chain protein was demonstrated in the serum. Gastroendoscopy and a series of radiographs of the small intestine revealed multiple polypoid tumors involving the entire length of the small intestine. Duodenal biopsy showed diffuse lymphocytic lymphoma. Immunohistochemical staining of tumor samples revealed features typical of alpha-chain disease. Cytogenetic analysis showed the same abnormal karyotypes of neoplastic clones in intestinal tumor cells and in circulating leukemic cells. The data suggest that alpha-chain disease can present initially with intestinal multiple polypoid lymphocytic lymphoma and leukemic manifestation without evidence of bone marrow involvement. The data also support the homing theory of lymphomas from mucosa-associated lymphoid tissue. © 1992 Wiley-Liss, Inc.

The purpose of this study is to investigate the association of IκBα with the development of ankylosing spondylitis (AS) in Taiwan. One hundred and fifty-four patients with AS and 112 unrelated healthy controls were enrolled in this study. The IκBα-881A/G, -826C/T, -550A/T, -519C/T, and -297C/T polymorphisms were determined by the polymerase chain reaction/restriction fragment length polymorphism method. This study demonstrated that the genotype frequencies of IκBα-826C/T and -826T/T, and allele frequencies of IκBα-826T were significantly higher in the patients with AS than in the controls. We also found that the estimated haplotype frequencies of IκBα-881A -826T -550A -519C -297C and IκBα-881A -826C -550A -519T -297C were significantly increased in the patient with AS in comparison with that of the controls. In contrast, the estimated haplotype frequency of IκBα-881A -826C -550A -519C -297C was significantly decreased in the patients with AS. This study demonstrates that IκBα-826T is associated with the development of AS. Furthermore, the IκBα-881A -826T -550A -519C -297C and IκBα-881A -826C -550A -519T -297C haplotypes are related to susceptibility to AS in Taiwan.

To evaluate the significance of natural killer (NK) cell activity in the clinical assessment of patients with hepatocellular carcinoma (HCC), 32 patients combined with liver cirrhosis (LC) and HCC, and 29 LC patients were studied. The NK cell activity was markedly decreased in HCC patients and the LC group as compared with the control group, but there was no statistical difference between the NK cell activity of the HCC group and the LC group. The depression of NK cell activity in HCC patients was inversely correlated with the patient's age, and the HCC patients with venous invasion or with both lobes involved had lower NK cell activity. These results suggest that the decreased NK cell activity in HCC patients might be related to the coexistent liver disease, and marked decrease in NK cell activity might be one of the causes for the early development and invasion of HCC.

To investigate the role of ligands for programmed cell death 1 (PD-L) in the pathogenesis of rheumatoid arthritis (RA), 129 patients with RA and 125 unrelated healthy controls were enrolled in this study. The PD-L1 and PD-L2 polymorphisms were determined by the method of polymerase chain reaction (PCR)/direct sequencing or PCR/reaction fragment length polymorphisms. The genotype distributions of PD-L1 6777 C/G were not significantly different between the patients with RA and healthy controls. There was also no significant difference in the allele frequencies of PD-L1 6777 C/G polymorphisms between the patients with RA and controls. Similar findings could also be found in the phenotypes and alleles frequencies of PD-L2 47103 C/T and 47139 T/C polymorphisms between the patients with RA and controls. The patients with PD-L1 6777 G had higher prevalence of rheumatoid nodule in comparison with those without PD-L1 6777 G (p = 0.005, OR = 4.0, 95% CI = 1.5–10.9). In contrast, the PD-L2 47103 C/T and 47139 T/C polymorphisms were not related to the occurrence of rheumatoid nodule. This study demonstrated that the PD-L1 and PD-L2 polymorphisms were not associated with susceptibility to RA in Taiwan. PD-L1 6777 G was associated with the prevalence of rheumatoid nodule.

To search for an effective antiviral agent, this study tested the hypothesis that sho-saiko-to (Xiao-Chai-Hu-Tang) and crude saikosaponins possess the activity directly against HBV and could affect the expressions of viral antigens, HBeAg and HBsAg, in HepG2 2.2.15 cell model. The viral amount and viral antigens in the suspension were estimated by quantitative real time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that sho-saiko-to could inhibit the production of HBV (p < 0.0001), 20 μg/ml sho-saiko-to was efficacious at day-3 of treatment and 10 μg/ml at day-6. The calculated IC50 and CC50 of sho-saiko-to were 55.76 μg/ml and 372 μg/ml, respectively, with a selectivity index of 6.67. Crude saponin of B. chinense could also inhibit the replication of HBV (p < 0.0001). Owing to the anti-neoplastic activity of sho-saiko-to and saikosaponin, their calculated CC50 and selectivity index might be under-estimated. Sho-saiko-to also decreased the expression of HBeAg with the minimal effective concentration of 20 μg/ml. Sho-saiko-to contained too little saikosaponin. Therefore, the anti-HBV activity of sho-saiko-to might not be mediated by saikosaponin. Sho-saiko-to could be supplementary to nucleotide analogues to minimize the recurrence of viremia after its discontinuation.

Rheumatoid arthritis is a systemic disease with manifestations in many organs. In most cases, involvement of the locomotor system dominates the clinical picture. However, extra-articular manifestations can be detected in almost any organ system with varied incidence in different series. Ophthalmic presentations include Sjogren's syndrome, episcleritis, and scleritis. The most severe form of scleritis, scleromalacia perforans, is a very rare ophthalmic manifestation. We present the case of a 60-year-old man who had had rheumatoid arthritis for more than 10 years. He had scleromalacia perforans but no other extra-articular manifestations.

Flame atomic absorption spectrometry (FAAS) and a microdialysis analyzer were employed for dynamic monitoring of magnesium (Mg), glucose and lactate levels in blood samples of gerbils subjected to cerebral ischemia.Focal cerebral ischemia was induced by occlusion of the unilateral common carotid artery and the middle cerebral artery for 60 minutes followed by 180 minutes of reperfusion. Whole blood samples were continuously collected from the jugular vein via an auto-blood sampling system. The dynamic profiles of Mg, glucose and lactate before, during and after ischemia were determined.During cerebral ischemia, blood Mg levels gradually rose to 130% of the baseline and returned to the basal levels within 30 minutes after reperfusion. Lactate concentrations decreased to approximately 50% of the basal levels during cerebral ischemia and returned to basal levels immediately after reperfusion. Glucose levels remained the same during cerebral ischemia and gradually fell to 50% of basal levels at the end of reperfusion. The linearity ranges of glucose, lactate and Mg were 0.1-25 mM, 0.02-2.5 mM and 5-1500 microg/L, respectively. The required volume of each blood sample is less than 30 microL. The intra- and inter-assay variation was less than 3%. Since blood loss is minimal from repeated blood sampling, it is suitable for small animals.Mg may be accumulated in blood cells, which are helpful for reducing glucose utilization. As a result, less lactate was produced during the acute phase of cerebral ischemia. Preservation of glucose is advantageous for brain cells' restoration after ischemia.

Description of use of equipment for on-line microdialysis (MD) coupled with graphite furnace atomic absorption spectrometry (GFAAS) system, for dynamic monitoring of extracellular Mg in gerbils subjected to transient focal cerebral ischemia.Gerbils' right middle cerebral artery (MCA) and common carotid artery (CCA) were occluded for 60 minutes, and then reperfused for 60 minutes with Ringer's solution, after which extracellular fluid samples were collected via a microdialysis probe inserted into the right cortex before, during and after inducing ischemia. Reperfusion was at a rate of 2 microL/min through the microdialysis probe, on-line diluted with measured water injected onto the GFAAS via an autosampler for Mg analysis.The detection limit of the Mg concentrations has ranged from 0.50 to 3.00 microg/L; our detection limit was 0.03 microg/L. We applied this on-line system to monitor extracellular Mg levels in the cortex during focal cerebral ischemia. Mg concentrations significantly decreased to 41% of baseline during cerebral ischemia and gradually returned to 67% of baseline after 60 minutes of reperfusion.We presume that derangement of Mg homeostasis could be important in brain cell injury and is closely associated with cerebral ischemia event. The described analytic system permits autosampling in the brain and allows for continuous determination of Mg and trace minerals in minute sample volumes in a living system.

Hypertrophic osteoarthropathy (HOA) is characterized by clubbed fingers and periosteal new bone formation. Etiologically, it can be divided into primary and secondary HOA, but its pathogenesis is uncertain. We report a 42-year-old male patient who suffered from painful clubbing fingers and toes. Serial examinations revealed periosteal new bone formation in the four limb long bones and a solid mass lesion in the right upper lung field. Pathologic examination of the resected mass lesion showed squamous cell carcinoma. After surgery and chemotherapy, the severity of clubbed fingers decreased and joint pain improved. Follow-up bone scan also suggested regression of the uptake of radioactivity in the four limb bones. We concluded that the HOA in this case was probably caused by lung cancer.

An investigation was conducted to measure the levels of erythrocyte complement receptor type 1 (CR1) in patients with various rheumatic diseases other than systemic lupus erythematosus, and to evaluate the clinical significance of this receptor in patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Erythrocyte CR1 was measured in 37 normal controls and 106 patients with various rheumatic diseases. The levels of erythrocyte CR1 decreased significantly in patients with AS, juvenile rheumatoid arthritis, Sjogren's syndrome, and RA, while there was no statistical difference in levels of erythrocyte CR1 between normal controls and patients with gouty arthritis. This suggests that erythrocyte CR1 deficiency may occur in immune-mediated rheumatic diseases, but not in nonimmune-mediated rheumatic diseases such as crystal-induced arthritis. In this study, we noted that the levels of erythrocyte CR1 were not related to the disease activity and severity of AS. The levels of erythrocyte CR1 were also not correlated with the clinical and laboratory parameters of disease activity in RA patients. However, there was a negative association between the levels of erythrocyte CR1 and titer of rheumtoid factor in RA patients. Further study is needed to determine whether or not the level of erythrocyte CR1 is related to prognosis in patients with RA.

Background and Purpose We investigated the influence of alcohol consumption and cigarette smoking on all types of stroke and cerebral infarction, in particular among a representative sample of elderly residents in Taiwan. Methods This study was a component of a nationwide survey of health and living status of residents aged 65 years or older in Taiwan in which subjects received detailed physical, neurological, and laboratory examinations. Inquiries were made about medical history, and information on the amount and duration of drinking and smoking was obtained. Diagnoses of stroke were made according to the results of brain computed tomography at the onset of disease or were based on criteria established by the World Health Organization. Results Of the 2600 subjects, there were 155 elderly persons with stroke (prevalence, 6%). Excessive drinking of more than 367.6 g/wk of alcohol was associated with a high prevalence of cerebral infarction. Consumption of ≤367.5 g/wk of alcohol did not have an influence on stroke prevalence. The relationship between duration of alcohol drinking and stroke was equivocal. More than 30 pack-years of cigarette smoking was a significant risk factor for all types of stroke and cerebral infarction in particular. Using multiple logistic regression to control for possible confounders, it was found that smoking was an independent risk factors for all stroke and was of borderline significance for cerebral infarction. Although excessive drinking was a significant risk factor for cerebral infarction in univariate analysis, this effect was lost after adjustment for other confounders. Conclusions Cigarette smoking was a more important risk factor for stroke and cerebral infarction than excessive drinking of alcohol.

Excessive lead exposure in indoor firing ranges workers is a documented hazard (1-3), but the incidence has not previously been reported in Taiwan. Eight indoor range workers with elevated blood lead levels employed by an arsenal were discovered during routine medical examination. Two of the cases show mild anemia and two of the cases show early mild peripheral neuropathy.

Systemic lupus erythematosus (SLE) is an important autoimmune disease with multiple organ system involvement. From preliminary studies, we have found that six Chinese herbs: Atractylodes ovata, Anqelica sinensis, Cordyceps sinensis, Liqustrum lucidum, Codonopsis pilosula and Homo sapiens can improve defective in vitro interleukin-2 (IL-2) production in patients with SLE. In order to investigate the in vivo effects of these herbs, we used NZB/NZW F1 mice, a typical lupus animal model used to test these herbs. It was found that C. pilosula, H. sapiens and C. sinensis could prolong the life span of female NZB/NZW F1 mice and inhibited anti-ds DNA production. Although A. sinensis could prolong the life span of experimental mice, it did not inhibit the production of anti-ds DNA antibody. These herbs may have great potential for the management of human SLE in the future.

To evaluate the role of severe liver damage on natural killer cell activity, 29 patients with liver cirrhosis were examined. The natural killer cell activity was measured with a 4-hr chromium release assay, and the K562 cell line was employed as target cells. The natural killer cell activity was significantly decreased in cirrhotic patients compared with normal controls and patients with chronic active hepatitis. Cirrhotic patients with Pugh's C grade of severity of liver disease had lower natural killer cell activity. The depression of natural killer cell activity in cirrhotic patients was inversely correlated with prothrombin time ratios, and the natural killer cell activity in cirrhotic patients with hepatic encephalopathy was lower than in patients without hepatic encephalopathy. Thus, the diminished natural killer cell activity in cirrhotic patients might be related to the severity of liver damage.

The National Health Insurance (NHI) and social welfare agencies have implemented the Elderly Health Examination Program (EHEP) for years. No study has ever attempted to evaluate whether this program is cost-effective. The purposes of this study were, firstly, to understand the prevalence and incidence rates of hypertension and, secondly, to estimate the cost and effectiveness of the EHEP, focusing on hypertension screening. The data sources were: (1) hypertension and clinical information derived from the 1996 and 1997 EHEP, which was used to generate prevalence and incidence rates of hypertension; and (2) claim data of the NHI that included treatment costs of stroke patients (in- and outpatients). Hypothetical models were used to evaluate the cost-effectiveness of the hypertension screening program in various conditions. Sensitivity analysis was also employed to evaluate the effect of each estimation indicator on the cost and effectiveness of the hypertension screening program. A total of 28.3% of the elderly population in Kaohsiung (25,174 of 88,812) participated in the 1996 EHEP; 14,915 of them participated in the following 1997 EHEP, with a retention rate of 59.3%. Criteria from the Sixth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) (systolic blood pressure/diastolic blood pressure>or=160/95 mmHg or taking antihypertensive drugs) were used; we found that prevalence and incidence rates of hypertension were 24.6% and 6.6%, respectively. Hypertension rates are increasing in the aging process as shown in both prevalence and incidence models. In comparison with non-participants, the prevalence model indicates that each hypertension patient who had attended the EHEP not only saved NT$34,570-34,890 in medical and associated costs, but also increased their lifespan by 128 days. The present findings suggest that the EHEP is a cost-effective program with health and social welfare policy implications. With the relatively low participation rate of the EHEP, health and social agencies need to put more effort into the promotion of this free health examination program to attract potential participants. In doing so, the population at risk for hypertension would be identified for early treatment, and the probability of having stroke could be decreased. Consequently, health care expenditures for treatment and caregiving of stroke patients would be minimized. Finally, it should be noted that the sensitivity and values of selected parameters can modify the results of cost-effectiveness analysis. Interpretations of the effects of prevention services on costs and effectiveness need to be treated with caution.

Antiphospholipid syndrome (APS) is an antibody-mediated hypercoagulable state characterized by recurrent venous and arterial thromboembolic events. The presence of serum antibodies are collectively termed as antiphospholipid antibodies (aPL) and is the hallmark of the disease. Interest in the pathogenesis has mostly been focused on the blood coagulation factor. However, endothelial cells might play an important role. When stimulated, cell membrane would flip to expose negatively charged phospholipids and activation markers such as adhesive molecules may appear. We consider that these changes may play an important role in the initiation of the thrombotic process when endothelial cells encounter a PL. In this study, we incubated human umbilical vein endothelial cells (HUVECs) with IgG isolated from patients with APS and found that the HUVECs were activated by the expression of negatively charged phospholipids, as shown by high annexin V binding and negative propidium iodide staining and by an increase in the level of intracellular cell adhesion molecule-1 on the cell surface. The above findings indicate that endothelial cells can be activated on exposure to aPL and trigger the thrombotic event.