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Biomedical subjects

S Y Chen

Publications and source records attributed to S Y Chen.

At least 19 recordsLinked to original sources

Energy and enstrophy transfer in decaying two-dimensional turbulence.

We present experimental data on the direct enstrophy cascade in decaying two-dimensional turbulence. Velocity and vorticity fields are obtained using particle tracking velocimetry. From those fields we directly compute the enstrophy and energy flux by using a filtering technique inspired by large-eddy simulations. This allows considerable insight into the physical processes of turbulence when compared with structure-function or spectral analysis. The direct cascade of enstrophy is weakly forward, with almost as much backscatter as down-scale enstrophy transfer, whereas the inverse energy cascade is strongly upscale with a modest amount of backscatter.

Journal Article↗

Secondary sulphonylurea failure: what pathogenesis is responsible?

Sulphonylurea (SU) stimulates insulin secretion by pancreatic beta-cells and is generally used as a first-line treatment for type 2 diabetes. However, after long-term SU treatment (six months or over), some patients begin to show an increase in blood glucose once again (secondary SU failure). Two theories have been put forward to explain this failure--dysfunction of the proinsulin conversion machinery or insulin resistance. However, the primary pathogenesis behind secondary SU failure still needs to be investigated. Using a reliable technique that specifically identifies intact proinsulin (IPI), total proinsulin (TPI) and specific insulin (SI), this study aims to discover if a defect in the proinsulin converting mechanism plays a role in SU failure. Three groups were recruited for this study: healthy controls (n=8), SU responders (n=38) and secondary SU failures (n= 46). Serum concentrations of insulin-related molecules released in response to a standard glucose challenge test were compared between the groups. It was found that total SI was lower in the patient groups (P<0.05 compared to the control group), while TPI and IPI showed no distinct difference between the three groups (P>0.05). TPI:SI ratio and IPI:SI ratio showed marked increases in the patient groups (P<0.05 compared to control group), with no obvious quantitative difference between SU responders and secondary SU failures (P>0.05). Similar results for the Homa Insulin Resistant Index were found between the two patient groups. Interestingly, blood glucose at 180 mins after glucose challenge was significantly higher in the secondary SU failure group (P<0.05), with no correlation to SI, while the SU responder group showed good correlation between the parameters (P<0.05). We conclude that type 2 diabetes is associated with obvious dysfunction in the proinsulin-converting process and shows severe SI deficiency in responding to glucose challenge. Dysfunction of the proinsulin conversion mechanism was not an extra cause responsible for SU failure.

Adult↗

Case report: diabetic mastopathy.

Diabetic mastopathy is a source of confusion with breast carcinoma. The association between mastopathy and Type I diabetes of long duration has been reported, but this clinical condition is poorly recognized since breast examination is not routinely performed in young diabetic patients. Radiologists' awareness of the constellation of findings in diabetic mastopathy may spare patients from undergoing unwarranted surgical biopsies.

Adult↗

Assessment of sediment toxicity by metal speciation in different particle-size fractions of river sediment.

Mobility and toxicity of metals associated with sediments are generally affected by metal speciation and granular compositions. Due to the various speciation patterns of heavy metals in sediments, it is not reliable to assess the potential toxicity of heavy metals on the aquatic environment with the total concentrations of heavy metals in sediments. The purposes of this study were to investigate the distribution of metal speciation in different particle-size fractions of sediments collected from two rivers (the Ke-Ya River and Ell-Ren River) in Taiwan, and to assess their potential toxicity to the aquatic ecosystem. Metals in the exchangeable, carbonate-bound and Fe/Mn oxide-bound forms obtained by sequential extraction were considered to be mobile and related with anthropogenic pollution. The degree of metal pollution and potential toxicity of sediments were higher in the lower reaches of both rivers. The metal speciation in sediments had a bimodal distribution over particle-size fractions. Heavy metals were subject to accumulation in the silt/clay fraction (< 25 microm) and coarse sand (420-2,000 microm). By normalizing the sum of the exchangeable, carbonate-bound, and Fe/Mn oxide-bound metals, it suggested that the potential toxicity to the aquatic ecosystem was caused by the fine sediments as well as coarse sediments.

Ecosystem↗

Rates and characteristics of lower limb amputations in Taiwan, 1997.

This study aims to describe the national incidence rate and characteristics of lower limb amputations (LLA) in 1997 from an island-wide database of the national health insurance programme in Taiwan. Some 117,647 discharge records from a sampled database (1 in 20) of the National Health Insurance Research Database were analysed. This study included records (n=171) containing LLA procedures. The LLA procedure rates were obtained by multiplying the number of identified procedures by 20 as the numerator and mid-year total population of Taiwan in 1997 as the denominator. Each procedure was further analysed according to the demographic characteristics of the patients, cause and level of amputation. Summarised gender ratios of LLA procedure rates were obtained by Poisson regression analysis. The crude LLA procedure rate was 18.1 per 100,000 population per year and the crude major LLA procedure rate was 8.8 per 100,000 population per year in Taiwan in 1997. The major cause of LLA procedures was peripheral vascular disease (72%), and the toe was most frequently amputated (48%). The LLA procedure rates, which increased logarithmically with age of patients, were significantly higher in men with a summarised male to female rate ratio of 1.65. The age-standardised LLA procedure rate in Taiwan was lower than that reported in the United States, Finland, the Netherlands, the United Kingdom (Leeds, Middlesborough, and Newcastle), but higher than Spain, Italy, and Japan. The trend of an increasing proportion of PVD-related LLA procedures will prompt the health professionals to develop strategies for LLA prevention.

Adolescent↗

c-Jun potentiates the functional interaction between the amino and carboxyl termini of the androgen receptor.

The transactivation functions of the human androgen receptor (hAR) are regulated by several accessory factors that can be either positive or negative. One factor that has been previously shown to mediate hAR transactivation is the proto-oncoprotein c-Jun. The positive effect is a primary one, can be exerted by both endogenous and exogenous c-Jun, and requires multiple regions of c-Jun. However, the exact mechanism by which c-Jun exerts its enhancing function is unknown. In this study, we have used a mammalian two-hybrid system to ask if c-Jun influences the ligand-dependent amino- to carboxyl-terminal (N-to-C) interaction of hAR, which is thought to be responsible for the homodimerization of this receptor. Our results show that c-Jun enhances both hAR N-to-C terminal interaction and DNA binding in vitro. We have also tested a panel of c-Jun and c-Fos mutants for their activities on the N-to-C interaction, and the data demonstrate that the activities of these mutants parallel their activities on hAR transactivation. A mutation in the hAR activation function-2 (AF-2) abrogates N-to-C interaction, DNA binding, and transactivation, and these activities are not rescued by exogenous c-Jun. Interestingly, the p160 coactivator TIF2 can stimulate hAR N-to-C interaction, a finding consistent with the effect on hAR transactivation. These data strongly suggest that the hAR N-to-C interaction is the target of c-Jun action, and this activity requires a functional receptor AF-2.

Amino Acids↗

p53 represses androgen-induced transactivation of prostate-specific antigen by disrupting hAR amino- to carboxyl-terminal interaction.

Prostate-specific antigen (PSA) is highly overexpressed in prostate cancer. One important regulator of PSA expression is the androgen receptor (AR), the nuclear receptor that mediates the biological actions of androgens. AR is able to up-regulate PSA expression by directly binding and activating the promoter of this gene. We provide evidence here that that this AR activity is repressed by the tumor suppressor protein p53. p53 appears to exert its inhibition of human AR (hAR) by disrupting its amino- to carboxyl-terminal (N-to-C) interaction, which is thought to be responsible for the homodimerization of this receptor. Consistent with this, p53 is also able to block hAR DNA binding in vitro. Our previous data have shown that c-Jun can mediate hAR transactivation, and this appears to result from a positive effect on hAR N-to-C interaction and DNA binding. Interestingly, c-Jun is able to relieve the negative effects of p53 on hAR transactivation, N-to-C interaction, and DNA binding, demonstrating antagonistic activities of these two proteins. Importantly, a p53 mutation found in metastatic prostate cancer severely disrupts the p53 negative activity on hAR, suggesting that the inability of p53 mutants to down-regulate hAR is, in part, responsible for the metastatic phenotype.

Animals↗

Programmed cell death in extraocular muscle tendon/sclera precursors.

PURPOSE: This study was designed to examine the occurrence of natural cell death in the periocular mesenchyme of mouse embryos. METHODS: Vital staining with LysoTracker Red and Nile blue sulfate as well as terminal nick end labeling (TUNEL) were utilized to identify apoptotic cell death in whole and histologicaly sectioned gestational day 10.5 to 14 mouse embryos. Laser scanning confocal microscopy was used to provide a three dimensional representation of the cell death pattern. Immunohistochemical staining for neural crest and myoblast populations was utilized to indicate the cell population undergoing apoptosis. RESULTS: Programmed cell death was evident in the developing rectus muscle tendons/sclera on gestational days 11 through 12.5 (corresponding to the weeks 5-6 of human development). Although each of these peripheral periocular condensations has readily apparent amounts of apoptosis, the pattern of cell death varied among them. Cell death was most apparent in the superior rectus tendon primordium, while that for the lateral rectus had the least evidence of apoptosis. CONCLUSIONS: Although apoptosis was readily evident in the periocular mesenchyme in distinct regions located medial and distal to the developing rectus muscles, programmed cell death in these sites has not previously been reported. New imaging techniques coupled with stains that evidence apoptotic cell death have made it possible to define this tissue as a prominent region of programmed cell death. Although neuronal tissues, including particular regions of the developing eye, are well recognized as sites of programmed cell death, description of this phenomenon in the extraocular tendon/sclera precursors is novel.

Animals↗

Targeting dendritic cells to enhance DNA vaccine potency.

DNA vaccination that can induce both cellular and humoral immune responses has become an attractive immunization strategy against cancer and infection. Dendritic cells (DCs) play a critical role in the induction of immune responses by DNA vaccination. However, a major problem of DNA vaccination is its limited potency, because only a very limited fraction of injected DNA molecules are taken up by DCS: In this study, we describe a novel DNA vaccination strategy to enhance uptake and presentation of antigens by DCS: Specifically, we developed a DNA vaccine based upon expression of a model hepatitis B virus (HBV) e antigen fused to an IgG Fc fragment. After vaccination, the DNA are taken up by cells that produce and secrete the antigen-Fc fusion proteins. The secreted fusion proteins, in addition to inducing B cells, are efficiently captured and processed by DCs via receptor-mediated endocytosis and then presented to the MHC class II and as -I (cross-priming). The results of this study demonstrate that broad enhancement of antigen-specific CD4+ helper, CD8+ cytotoxic T-cell, and B-cell responses can be achieved by this DNA vaccination strategy. Thus, the strategy capable of inducing all arms of the adaptive immunity may provide a novel, generic design for the development of therapeutic and preventive DNA vaccines.

Animals↗

Effect of substrate concentration on bioleaching of metal-contaminated sediment.

The remediation of metal-contaminated sediment was studied using the bioleaching process with a mixed culture of sulfur-oxidizing bacteria. The effects of substrate concentration (elemental sulfur) on sediment acidification, sulfur oxidation and metal solubilization from contaminated sediment during the bioleaching process were investigated with free-cell suspensions. Sulfur concentration greater than 0.5% (w/v) was found to be inhibitory to bacterial activity and metal solubilization from sediment. The sulfate production was well described by a substrate inhibition expression and Haldane's equation. In addition, an empirical equation related to sulfur concentration was also used to describe the metal solubilization in the bioleaching process.

Environmental Pollution↗

Regulation of acetylcholine release by extracellular matrix proteins at developing motoneurons in Xenopus cell cultures.

Integrins mediate cell-extracellular matrix connections and are particularly important during neuronal development. We here investigated the regulatory role of extracellular matrix (ECM) proteins on the synaptic transmission at developing motoneurons. Synaptic currents were recorded from innervated myocytes of 1-day-old Xenopus cultures by whole-cell recordings. Soluble fibronectin and laminin had no significant effect on the frequency of spontaneous synaptic currents (SSCs) by themselves and markedly increased SSC frequency in the presence of low concentration of protein kinase C (PKC) activators. Pretreatment with Gly-Arg-Gly-Asp-Ser peptide inhibited the SSC increasing action of 12-o-tetradecanoyl-phorbol-13-acetate (TPA, 0.5 microM) plus fibronectin, but not that of TPA plus laminin. Genistein but not cytochalasin D inhibited the SSC increasing action of TPA plus fibronectin or laminin. High concentration of TPA (5 microM) markedly increased the SSC frequency by itself and occluded the SSC increasing action of fibronectin. Very low concentration of TPA (0.05 microM) markedly enhanced the SSC frequency when the cells were plated onto fibronectin- or laminin-coated substratum for 1 day. The SSC frequency increased markedly right after a train stimulation, which was defined as post-train potentiation (PTrP), when the cultures were plated onto fibronectin substratum and chronically treated with brain-derived neurotrophic factor (BDNF). The PTrP phenomenon is not observed upon chronic treatment with neurotrophin-3, glial cell line-derived neurotrophic factor, or ciliary neurotrophic factor. Our results suggest that the activation of PKC and tyrosine kinase but not actin reorganization plays a role in the SSC potentiating action of fibronectin. BDNF exerts synergistic effects in increasing synaptic transmission in neurons grown on fibronectin substratum. ECMs in concert with neurotrophic factor may play a role in regulating synaptic function at developing motoneurons.

Acetylcholine↗

A retrogen strategy for presentation of an intracellular tumor antigen as an exogenous antigen by dendritic cells induces potent antitumor T helper and CTL responses.

Induction of an effective antitumor response requires CD4+ helper T (Th) cells to recognize antigens on the same dendritic cells (DCs) that cross-present CTL antigens. Such cross-presentation is difficult to achieve by current tumor vaccine strategies. Here, we develop a novel "Retrogen" strategy for DCs to efficiently cross-present an intracellular tumor antigen, MAGE-3, to both MHC class I and MHC class II in a cognate manner. Specifically, the MAGE-3 gene was linked to a leader sequence at its NH2 terminus for secretion and to a cell-binding domain at its COOH terminus for receptor-mediated internalization. DCs transduced with the modified MAGE-3 gene produced and secreted MAGE-3 proteins, which were efficiently taken up by DCs via receptor-mediated internalization and presented as exogenous antigens to class I and class II molecules. Immunization of mice with the transduced DCs expressing the MAGE-3 fusion protein, termed "Retrogen" for its retrograde transport/internalization after secretion, efficiently induced all arms of the adaptive antitumor immune responses. Thus, this retrogen strategy of using a unifying mechanism for DCs to cross-present an intracellular tumor antigen in a cognate manner could be generally used to improve the efficacy of tumor vaccines and immunotherapies.

Animals↗

Reinforcement of acrylic denture base resin by incorporation of various fibers.

This study was designed to evaluate improvements in the mechanical properties of acrylic resin following reinforcement with three types of fiber. Polyester fiber (PE), Kevlar fiber (KF), and glass fiber (GF) were cut into 2, 4, and 6 mm lengths and incorporated at concentrations of 1, 2, and 3% (w/w). The mixtures of resin and fiber were cured at 70 degrees C in a water bath for 13 h, then at 90 degrees C for 1 h, in 70 x 25 x 15 mm stone molds, which were enclosed by dental flasks. The cured resin blocks were cut to an appropriate size and tested for impact strength and bending strength following the methods of ASTM Specification No. 256 and ISO Specification No. 1567, respectively. Specimens used in the impact strength test were reused for the Knoop hardness test. The results showed that the impact strength tended to be enhanced with fiber length and concentration, particularly PE at 3% and 6 mm length, which was significantly stronger than other formulations. Bending strength did not change significantly with the various formulations when compared to a control without fiber. The assessment of Knoop hardness revealed a complex pattern for the various formulations. The Knoop hardness of 3%, 6 mm PE-reinforced resin was comparable to that of the other formulations except for the control without fiber, but for clinical usage this did not adversely affect the merit of acrylic denture base resin. It is concluded that, for improved strength the optimum formulation to reinforce acrylic resin is by incorporation of 3%, 6 mm length PE fibers.

Acrylic Resins↗

Reactive oxygen species mediate cyclic strain-induced endothelin-1 gene expression via Ras/Raf/extracellular signal-regulated kinase pathway in endothelial cells.

Endothelin-1 (Et-1) is a peptide synthesized by endothelial cells (ECs) both in culture and in vivo. Cyclic strain induces gene expression of Et-1, however, the molecular mechanisms remain unclear. Since cyclic strain induces a sustained increase in intracellular reactive oxygen species (ROS), we hypothesized that the ROS could be a modulator in strain-induced Et-1 gene expression. Human umbilical vein ECs (HUVECs) subjected to cyclic strain had increased Et-1 secretion. Pretreatment of HUVECs with antioxidants, catalase (300 U/ml) or 1,3-dimethyl-2-thiourea (DMTU, 0.1 mm), abolished the strain-induced Et-1 release. ECs strained for 6 h had elevated Et-1 mRNA levels. In contrast, ECs treated with catalase or DMTU did not have increase Et-1 mRNA levels stimulated by cyclic strain. Bovine aortic ECs (BAECs) transfected with fusion plasmid containing Et-1 5'-flanking sequence (4.4 kb) and chloramphenicol acetyltransferase reporter gene produced a maximal Et-1 promoter activity after undergoing strain for 6 h, whereas pretreatment with catalase decreased this activity. BAECs cotransfected with a dominant negative mutant of Ras (RasN17), Raf-1 (Raf301), or catalytically inactive mutant of extracellular signal-regulated kinase (mERK2) had inhibited strain-induced Et-1 promoter activity, indicating the Ras/Raf/ERK pathway was involved; moreover, ERK phosphorylation was induced in ECs which were strained. This strain-activated ERK phosphorylation was attenuated in the presence of catalase. Functional analysis of the Et-1 promoter with site-directed mutagenesis indicates that the activator protein-1 (AP-1) binding site had to be within 143 base-pairs upstream of transcription initiation site for strain-induced promoter activity. Pretreatment of ECs with catalase also decreased the strain-induced promoter activity in the minimal construct (-143 bp). Our data demonstrate that strain-induced Et-1 gene expression is modulated by ROS via Ras/Raf/ERK signaling pathway, and indicate the responsiveness of the AP-1 binding site for strain-induced Et-1 expression.

Animals↗

Bioleaching of heavy metals from sediment: significance of pH.

Bioleaching process, which causes acidification and solubilization of heavy metals, is one of the promising methods for removing heavy metals from contaminated sediments. The solubilization of heavy metals from contaminated sediments is governed by the sediment pH. In the present study, the significance of pH in bioleaching of heavy metals from contaminated sediment was evaluated at different solid contents of sediments in a bench-scale reactor. Results showed that a temporal change of pH in the bioleaching process was effected by the buffering capacity of the sediment particulates. The variations of pH in this bioleaching process were calculated by a modified logistic model. It was observed that solubilization of heavy metals from sediments is highly pH-dependent. In addition, a non-linear equation for metal solubilization relating pH value in the bioleaching process was established. This allows an easier and faster estimate of metal solubilization by measuring pH in the bioleaching process.

Geologic Sediments↗

Retroesophageal aortic arch: diagnostic and therapeutic implications of a rare vascular ring.

Retroesophageal aortic arch (REAA) can be further divided to right or left retroesophageal aortic arch. The right REAA has right ascending and left descending aorta with retroesophageal segment, whereas the left REAA has left ascending and right descending aorta. The REAA with retroesophageal segment may cause tracheoesophageal compression by the formation of a vascular ring. A total of eight patients were identified from the database from 1996 to 1999. Among them, five were right REAA and three were left REAA. The age at diagnosis varied from 4 days to 16 years (median 8 years). The clinical findings and initial diagnostic investigations, including the chest X-ray, echocardiography and esophagogram, suspected the presence of this anomaly. The diagnosis can be confirmed by ultrafast computed tomography with or without three-dimensional reconstruction. Half of the total patients, two of right and two of left REAA were symptomatic and needed operation. The symptoms related to the retroesophageal aortic arch appeared during infancy and early childhood (six cases), and only rarely in late childhood and adults (two cases). Half of the patients were associated with congenital heart disease, but no specific patterns of congenital heart disease were identified. The sensitivity of the early diagnosis of REAA by chest roentgenogram, echocardiography, esophagogram and angiography was 37% (3/8), 0% (0/7), 100% (1/1) and 60% (3/5), respectively. The sensitivity of ultrafast CT was 100% (8) in delineating both retroesophageal segment and complete vascular ring. Operation to relieve the vascular compression was performed in two cases with right REAA and two with left REAA. Only one died after the operation, due to pulmonary arterial sling and tracheal stenosis. The surviving patients had been asymptomatic during follow up. In conclusion, REAA can be best diagnosed by ultrafast computed tomography with or without three-dimensional reconstruction. If symptomatic, surgery to relieve the compression is effective and safe.

Adolescent↗

Activation of noradrenergic mechanism attenuates glutamate-induced vasopressor responses in the pons and medulla of cats in vivo.

1. Using anesthetized cats, the authors examined the noradrenergic modulation of the glutamate induced pressor and depressor responses in various brainstem areas, including pontine gigantocellular tegmental field (FTG), dorsomedial medulla (DM), rostral ventrolateral medulla (RVLM), and caudal ventrolateral medulla (CVLM). 2. Unilateral microinjection of L-glutamate (Glu, 3 nmol in 30 nL saline) into FTG, DM and RVLM produced an increase in systemic arterial pressure (SAP) and a decrease in heart rate (HR), while into CVLM produced decreases of SAP and HR. 3. Application of norepinephrine (NE) into the pressor areas (0.05 to 5 nmol) did not alter the resting SAP and HR, but significantly attenuated the Glu-induced pressor response with an order of potency: FTG > DM > RVLM. In the depressor CVLM, NE alone produced a dose-dependent decrease of resting SAP and HR, but did not affect the Glu-induced depressor responses. 4. The involvement of different adrenoceptor subtypes was further investigated by application of selective adrenoceptor agonists including phenylephrine (alpha1), clonidine (alpha2), and isoproterenol (beta). Responses to these agonists are similar to those elicited by NE, except that only alpha-adrenoceptor agonists could antagonize the Glu-induced pressor responses of the RVLM. 5. Our observations indicate that NE not only inhibits the pressor mechanisms in various brainstem areas but also elicits a direct depressor response in CVLM. These findings also suggest that NE acts more likely a neurotransmitter, rather than a modulator, in the CVLM.

Adrenergic alpha-Agonists↗