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Biomedical subjects

C H Chou

Publications and source records attributed to C H Chou.

At least 19 recordsLinked to original sources

Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-kappaB signal transduction pathway.

This study is to investigate the molecular mechanism of radiation-enhanced cell invasiveness of hepatocellular carcinoma (HCC) correlating with clinical patients undergoing radiotherapy and subsequently developing metastasis. Three HCC cell lines (HepG2, Hep3B and Huh7) and normal hepatocyte cell line (CL-48) were irradiated with different doses. The effect of radiation on cell invasiveness was determined using the Boyden chamber assay. Radiation-enhanced invasion capability was evident in HCC cells but not in normal hepatocytes. Invasion was observed in gelatin-coated but not fibronectin-coated or type I collagen-coated membranes. Radiation upregulated matrix metalloproteinase-9 (MMP-9) mRNA level, MMP-9 protein level and MMP-9 activity. MMP-9 antisense oligonucleotides inhibited radiation-induced MMP-9 expression and thereby significantly inhibited radiation-induced HCC invasion. Furthermore, phosphatidylinositol 3-kinase (PI3K)/Akt chemical inhibitors LY294002 and wortmannin suppressed radiation-induced MMP-9 mRNA expression. Transient transfection with dominant-negative Akt plasmid also showed that the PI3K/Akt-signaling pathway was involved in this radiation-induced MMP-9 expression. Moreover, nuclear factor-kappaB (NF-kappaB) decoy oligodeoxynucleotide suppressed radiation enhanced MMP-9 promoter activity completely. PI3K/Akt chemical inhibitors inhibited radiation-induced NF-kappaB-driven luciferase promoter activity. Taken together, our results indicated that sublethal dose of radiation could enhance HCC cell invasiveness by MMP-9 expression through the PI3K/Akt/NF-kappaB signal transduction pathway.

Carcinoma, Hepatocellular↗

Influences of pH and hydraulic retention time on anaerobes converting beer processing wastes into hydrogen.

To convert high-solids organic wastes (3% w./w.) to high-value hydrogen, a full factorial experimental design was employed in planning the experiments for learning the effects of pH and hydraulic retention time (HRT) on the hydrogen production in a chemostat reactor using waste yeast obtained from beer processing wastes. For determining which experimental variable settings affect hydrogen production, predictive polynomial quadratic equation and response surface methodology were employed to determine and explain the conditions required for high-value hydrogen production. Experimental results indicate that a maximum hydrogen production rate of 460 mL/gVSS/d was obtained at pH = 5.8 and HRT = 32 hours. Moreover, hydrogenase targeted RT-PCR results indicate that Clostridium thermocellum and Klebsiella pneumoniae predominated.

Bacteria, Anaerobic↗

Noninvasive assessment of spontaneous baroreflex sensitivity and heart rate variability in patients with carotid stenosis.

BACKGROUND: Previous limited observations have suggested that atherosclerosis may affect the distensibility of the carotid sinus and then impair the baroreflex sensitivity (BRS). No studies have been done to compare the BRS and heart rate variability (HRV) in patients with carotid stenosis and normal controls. METHODS: A convenience-consecutive sample of 118 patients with transient ischemic attack or minor stroke 3 months to 1 year before (mean 6 months) who met the study criteria were referred to the neurovascular laboratory of the study hospital. Forty-three age-matched healthy adults were recruited as the normal controls. The inclusion criteria for participation were (1) no diabetes mellitus, (2) no history, symptoms or ECG signs of coronary artery disease or myocardial infarction, and (3) presence of carotid stenosis greater than or equal to 50%. The diagnosis of carotid stenosis was made using color-coded duplex ultrasound with published criteria. We categorized the patients into two groups: group 1 had moderate stenosis (50-75%) and group 2 had high-grade stenosis (75-99%). Instantaneous systolic blood pressure (SBP) and heart rate of all participants were assessed noninvasively using servo-controlled infrared finger plethysmography. The fluctuation in SBP as well as the interpulse interval (IPI) was divided into three components at specific frequency ranges by fast Fourier transform as high frequency (HF; 0.15-0.4 Hz), low frequency (LF; 0.04-0.15 Hz) and very low frequency (VLF; 0.004-0.04 Hz). The BRS was expressed as (1) transfer function with its magnitude in the HF and LF ranges, (2) BRS index alpha, and (3) regression coefficient by sequence analysis. The HRV was expressed as total power and power in the three frequency ranges (HF, LF and VLF). RESULTS: The final analysis included 99 patients (mean age 72 +/- 6 years, 79 male) and 43 healthy controls (mean age 68 +/- 7 years, 30 male). Forty-three patients were classified as group 1 (stenosis 50-75%) and 56 as group 2 (stenosis 75-99%). There was no significant difference in the IPI between patients and controls (p value = 0.8637). We observed a significant decrease in all three HRV components (VLF, LF and HF) in the patients; however, there were no differences between the two patient groups with various degrees of stenosis. All the indices of BRS, including the magnitude of SBP-IPI transfer function at LF and HF, the computed BRS index alpha and the regression coefficient of sequence analysis, revealed similar results. Patients exhibited a significant reduction in the BRS (p < 0.001) compared with controls, and no difference was found between the two groups of patients. CONCLUSIONS: Our study linked significant carotid stenosis to two important autonomic markers (BRS and HRV) that may have prognostic value for patients with cardiovascular events. Further prospective studies are needed to explore whether or not the decreased BRS and HRV can be predictors for poor cardiovascular prognosis, or even for shortened life span in general, in patients with significant carotid stenosis.

Aged↗

Determination of metformin in human plasma by high-performance liquid chromatography with spectrophotometric detection.

A simple, selective, sensitive and precise high-performance liquid chromatographic plasma assay for the hypoglycemic agent metformin is described. Acidified samples of plasma were deproteinated with acetonitrile, washed with dichloromethane and the resulting supernatant injected. Chromatography was performed at 40 degrees C by pumping a mobile phase of acetonitrile (250 ml) in pH 7, 0.03 M diammonium hydrogen phosphate buffer (750 ml) at a flow-rate of 1 ml/min through a silica column. Metformin and the internal standard (atenolol) were detected at 240 nm and were eluted 7.8 and 6.8 min, respectively, after injection. No endogenous substances were found to interfere. Calibration curves were linear (r>0.999) from 10 to 2000 ng/ml. The absolute recovery of both metformin and atenolol was greater than 76%. The detection limit and limit of quantitation were 2.5 and 10 ng/ml, respectively. The intra- and inter-day precision (C.V.) was 12%, or less, and the accuracy was within 6.2% of the nominal concentration. This method is suitable for clinical investigation and monitoring metformin concentration.

Animals↗

The anti-apoptotic role of interleukin-6 in human cervical cancer is mediated by up-regulation of Mcl-1 through a PI 3-K/Akt pathway.

Interleukin-6 (IL-6), a multifunctional cytokine, has recently been implicated in human cervical cancer, though the mechanism remains elusive. This study demonstrates that the anti-apoptotic protein Mcl-1 and IL-6 was concomitantly expressed in human cervical cancer tissues and cell lines, but not in normal cervix tissues. Upon IL-6 treatment, Mcl-1, but not other Bcl-2 family members, was rapidly up-regulated peaking at 4-8 h in human cervical cancer C33A cells. Supporting this observation, using anti-IL-6 or anti-IL-6 receptor antibody to interrupt the IL-6 autocrine loop in SiHa cells significantly reduced cellular level of Mcl-1. This study hypothesizes that the expression of Mcl-1 in cervical cancer cells is regulated by IL-6. The matter of which signaling pathways transduced by IL-6 is responsible for the Mcl-1 up-regulation is further investigated herein. Blocking the STAT3 or MAPK pathway with dominant-negative mutant STAT3F or the MEK inhibitor PD98059 failed to inhibit IL-6-mediated Mcl-1 expression. Meanwhile, the IL-6-induced Mcl-1 up-regulation was effectively abolished by treatment with PI 3-K inhibitors, LY294002. Additionally, overexpression of dominant-negative (dn) Akt in C33A cells could inhibit the IL-6-induced increase of Mcl-1. Finally, overexpression of IL-6 in C33A cells caused a markable resistance to apoptosis induced by doxorubicin or cisplatin. Transient transfection of IL-6-overexpressed cells with a mcl-1 antisense vector, leading to the attenuation of their apoptosis-resistant activity. In conclusion, the data herein suggest that IL-6 regulated the mcl-1 expression via a PI 3-K/Akt-dependent pathway that may facilitate the oncogenesis of human cervical cancer by modulating the apoptosis threshold.

Antineoplastic Agents↗

Inhibition of the MEK/ERK signaling pathway blocks a subset of B cell responses to antigen.

Signal transduction initiated by B cell Ag receptor (BCR) cross-linking plays an important role in the development and activation of B cells. Therefore, considerable effort has gone into determining the biochemical signaling events initiated by the BCR and delineating which events participate in specific biological responses to Ag. We used two inhibitors of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) 1 and MEK2, PD98059, and U0126, to assess the role the Ras-mitogen-activated protein kinase pathway plays in several BCR-induced responses. PD98059 or U0126 treatment substantially inhibited the BCR-induced activation of the extracellular signal-regulated kinase (ERK) forms of mitogen-activated protein kinase in the immature B cell line WEHI-231, in immature splenic B cells, and in mature splenic B cells. However, MEK-ERK inhibition did not block BCR-induced growth arrest or apoptosis of WEHI-231 cells or apoptosis of immature splenic B cells, indicating that the MEK-ERK pathway is not required for these events. In contrast, PD98059 and U0126 treatment did inhibit the up-regulation of specific BCR-induced proteins, including the transcription factor Egr-1 in WEHI-231 and mature splenic B cells, and the CD44 adhesion molecule and CD69 activation marker in mature splenic B cells. Moreover, both inhibitors suppressed BCR-induced proliferation of mature splenic B cells, in the absence and in the presence of IL-4. Therefore, activation of the MEK-ERK pathway is necessary for a subset of B cell responses to Ag.

Animals↗

Peripheral tears of triangular fibrocartilage complex: results of primary repair.

In 16 patients with ulnar wrist pain, we performed primary arthroscopic or open repair of the peripheral rim tears of the triangular fibrocartilage complex (TFCC) (14 ulnar, 4 volar, and 3 radial tears). The wrist function was assessed before and 1 year after the repair using the Mayo-modified wrist score. The average pain score improved from 9.1+/-8.0 to 21.2+/-6.5, the average functional score from 5.0+/-8.1 to 20.6+/-6.3, the average motion score from 4.7+/-2.8 to 15.6+/-7.3, and the average grip point from 4.4+/-3.5 to 15.6+/-7.7, all with significant differences (P<0.01). Ten of the 17 cases had instability of the distal radioulnar joint and five had recurrent instability after repair.

Adult↗

Sonographic needle guidance in cholangiography in children.

PURPOSE: To evaluate feasibility and benefits of sonographic guidance of percutaneous transhepatic cholangiography (PTC) in children with liver transplants. MATERIALS AND METHODS: The authors prospectively followed 24 PTC procedures in 19 pediatric patients (11 females, 8 males; age 3 months to 17 years) randomized to fluoroscopic or sonographic guidance. The number of needle passes, the contrast material dose, fluoroscopy time, and procedure time for each procedure were recorded. All patients were transplant recipients-six whole and 13 reduced-size grafts. Cases were randomly assigned to two groups: group I, fluoroscopically guided PTC (12 procedures); group II, sonographically guided PTC (12 procedures). RESULTS: The technical success rate was 92% (11 of 12) for each group. In group I, there were two procedure-related complications: postprocedural fever caused by biliary to portal vein fistula, and peritoneal bleeding requiring surgery. In group II, there were no procedure-related complications. A mean of 8.2 +/- 3.7 needle passes were required in group I compared to only 2.0 +/- 1.3 in group II (P < .0001). A mean contrast material dose of 19.5 mL +/- 13.4 was required in group I compared to only 2.5 mL +/- 1.9 in group II (P < .001). A mean procedure time of 15.7 minutes +/- 7.4 was required in group I compared to only 6.1 minutes +/- 4.5 in group II (P < .001). A mean fluoroscopy time of 10.4 minutes +/- 5.0 was required in group I compared to only 1.0 minutes +/- 0.7 in group II (P < .0001). CONCLUSION: In pediatric patients who have undergone liver transplantation, sonographic guidance significantly decreases the number of needle passes, contrast material dose, and fluoroscopy time required for PTC.

Child, Preschool↗

Monoterpene glycosides and triterpene acids from Eriobotrya deflexa.

A phytochemical study on a methanolic extract of leaves of Eriobotrya deflexa led to the isolation and characterization of nine terpenoid compounds. Four of these are new chemical entities, including two monoterpene glycosides, (3S)-O-alpha-L-rhamnopyranosyl-(1-->3)-[4-O-(E)-coumaroyl]-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranosyl-linalool (1) and (3S)-O-alpha-L-rhamnopyranosyl-(1-->3)-[4-O-(Z)-coumaroyl]-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranosyl-linalool (2), and two triterpene acids, 1beta,2alpha,19alpha-trihydroxy-3-oxo-12-ursen-28-oic acid (3) and 2alpha,3alpha,19alpha-trihydroxy-12-oleanen-28-oic acid (4). Their structures were elucidated on the basis of spectroscopic analysis. The activities of these isolates in an in vitro antiproliferation test were also determined.

Acyclic Monoterpenes↗

Allelopathic prenylflavanones from the fallen leaves of Macaranga tanarius.

Two new prenylflavanones, tanariflavanones A (1), and B (2), and one known compound, (-)-nymphaeol-C (3), were isolated from the fallen leaves of Macaranga tanarius. Compounds 1 and 2 showed inhibition of radical growth of lettuce seedlings at 200 ppm. Their structures were elucidated primarily by NMR, circular dichroism, and mass spectroscopic methods.

Circular Dichroism↗

Organelle DNA phylogeography of Cycas taitungensis, a relict species in Taiwan.

The phylogegraphic pattern of Cycas taitungensis, an endemic species with two remaining populations in Taiwan, was investigated based on genetic variability and phylogeny of the atpB-rbcL noncoding spacer of chloroplast DNA (cpDNA) and the ribosomal DNA (rDNA) internal transcribed spacer (ITS) of mitochondrial DNA (mtDNA). High levels of genetic variation at both organelle loci, due to frequent intramolecular recombination, and low levels of genetic differentiation were detected in the relict gymnosperm. The apportionment of genetic variation within and between populations agreed with a migrant-pool model, which describes a migratory pattern with colonists recruited from a random sample of earlier existing populations. Phylogenies obtained from cpDNA and mtDNA were discordant according to neighbour-joining analyses. In total four chlorotypes (clades I-IV) and five mitotypes (clades A-E) were identified based on minimum spanning networks of each locus. Significant linkage disequilibrium in mitotype-chlorotype associations excluded the possibility of the recurrent homoplasious mutations as the major force causing phylogenetic inconsistency. The most abundant chlorotype I was associated with all mitotypes and the most abundant mitotype C with all chlorotypes; no combinations of rare mitotypes with rare chlorotypes were found. According to nested clade analyses, such nonrandom associations may be ascribed to relative ages among alleles associated with the geological history through which cycads evolved. Nested in networks as interior nodes coupled with wide geographical distribution, the most dominant cytotypes of CI and EI may represent ancestral haplotypes of C. taitungensis with a possible long existence prior to the Pleistocene glacial maximum. In contrast, rare chlorotypes and mitotypes with restricted and patchy distribution may have relatively recent origins. Newly evolved genetic elements of mtDNA, with a low frequency, were likely to be associated with the dominant chlorotype, and vice versa, resulting in the nonrandom mitotype-chlorotype associations. Paraphyly of CI and EI cytotypes, leading to the low level of genetic differentiation between cycad populations, indicated a short period for isolation, which allowed low possibilities of the attainment of coalescence at polymorphic ancestral alleles.

Cycas↗

Phylogeography of Kandelia candel in East Asiatic mangroves based on nucleotide variation of chloroplast and mitochondrial DNAs.

Vivipary with precocious seedlings in mangrove plants was thought to be a hindrance to long-range dispersal. To examine the extent of seedling dispersal across oceans, we investigated the phylogeny and genetic structure among East Asiatic populations of Kandelia candel based on organelle DNAs. In total, three, 28 and seven haplotypes of the chloroplast DNA (cpDNA) atpB-rbcL spacer, cpDNA trnL-trnF spacer, and mitochondrial DNA (mtDNA) internal transcribed spacer (ITS) were identified, respectively, from 202 individuals. Three data sets suggested consistent phylogenies recovering two differentiated lineages corresponding to geographical regions, i.e. northern South-China-Sea + East-China-Sea region and southern South-China-Sea region (Sarawak). Phylogenetically, the Sarawak population was closely related to the Ranong population of western Peninsula Malaysia instead of other South-China-Sea populations, indicating its possible origin from the Indian Ocean Rim. No geographical subdivision was detected within the northern geographical region. An analysis of molecular variance (AMOVA) revealed low levels of genetic differentiation between and within mainland and island populations (phiCT = 0.015, phiSC = 0.037), indicating conspicuous long-distance seedling dispersal across oceans. Significant linkage disequilibrium excluded the possibility of recurrent homoplasious mutations as the major force causing phylogenetic discrepancy between mtDNA and the trnL-trnF spacer within the northern region. Instead, relative ages of alleles contributed to non-random chlorotype-mitotype associations and tree inconsistency. Widespread distribution and random associations (chi2 = 0.822, P = 0.189) of eight hypothetical ancestral cytotypes indicated the panmixis of populations of the northern geographical region as a whole. In contrast, rare and recently evolved alleles were restricted to marginal populations, revealing some preferential directional migration.

Alleles↗

Apoptosis induced by the antigen receptor and Fas in a variant of the immature B cell line WEHI-231 and in splenic immature B cells.

Signaling by the BCR causes proliferation and resistance to Fas-induced apoptosis in mature B cells, but growth arrest and apoptosis in immature B cells. We have identified a variant of the immature B cell line WEHI 231 that retains the apoptotic response to the BCR but has acquired susceptibility to Fas-induced apoptosis. The Fas susceptibility was associated with increased Fas expression on the cell surface and down-regulated IgD expression. These cells exhibited a distinctive functional relationship in response to signals from the BCR, Fas and CD40: BCR stimulation markedly promoted Fas-mediated apoptosis (and vice versa) and Fas-induced apoptosis was not subject to modulation by CD40 signaling. While BCR-induced apoptosis was effectively rescued by CD40, it was not affected by the expression of a dominant-negative FADD. The mechanistic distinctions between BCR- and Fas-induced apoptosis were further characterized by the differential effects of different caspase inhibitors on these two processes which imply the involvement of different subsets of caspases. For BCR-induced apoptosis, we provide evidence that the final apoptotic destruction phase can be inhibited by the pan-caspase inhibitor BOC-Asp-FMK (BD) and that, in the presence of BD, the BCR only induces growth arrest which is reversible. The striking enhancing effects of Fas on BCR-induced apoptosis seen in the variant cells prompted us to examine if a similar cooperation in induction of apoptosis occurs in the highly tolerizable immature B cells of the spleen. We found that the splenic immature B population contains a significant number of Fas-expressing cells, but neither Fas-induced apoptosis nor an enhancing effect of Fas on BCR-induced apoptosis of these cells was detected in vitro.

Animals↗

Determination of 14 elements in Taiwanese bones.

The objective of this study was to measure the concentration of 14 elements in human bone and investigate the affecting factors. This study aims to establish a database of elements in Taiwanese bone. Seventy-seven bone samples were taken from 70 subjects who were undertaking various bone surgeries from a medical center in central Taiwan. Bone samples were pretreated using microwave digestion and then, after determining the optimal conditions for analysis, fourteen elements were analyzed using Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES). Results showed that Ca had the highest concentration, followed by Mg and Zn. The lowest concentrations were of Mn, followed by Cd and Co. There was a positive correlation between the frequency of seafood intake and presence of all the 14 elements in human bone. There were several elements that had positive inter-correlation: As with Co; Al, Ag and Ca; Ni with Co, Mn and Al; Co with Al, Ag and Ca; Mn with Cr and Cu; Cr with Cu; Mg with Ca; Al with Ag and Ca; Ag with Ca; and also Zn with Mg. There were no significant differences found between concentrations of elements and etiology of bone disease and age. The authors suggest that further studies be conducted to establish a normal value of elements in human bone in Taiwan. This will greatly benefit the understanding of the relationship between disease pattern and elements in human bone.

Adult↗

Three new flavonol galloylglycosides from leaves of Acacia confusa.

Myricetin 3-O-(2"-O-galloyl)-alpha-rhamnopyranoside 7-methyl ether (1), myricetin 3-O-(3"-galloyl)-alpha-rhamnopyranoside 7-methyl ether (2), and myricetin 3-O-(2",3" -di-O-galloyl)-alpha-rhamnopyranoside (3), three new flavonol galloylglycosides, were isolated from leaves of Acacia confusa sampled from Chaoushi in the north of Taiwan. Their structures were established by analysis of spectroscopic data, and the compounds were evaluated for anti-hatch activity against brine shrimp.

Acacia↗

Uptake and dispersion of metformin in the isolated perfused rat liver.

Although metformin is a widely used oral antihyperglycaemic, the exact mechanisms of its cellular uptake and action remain obscure. In this study the hepatic extraction and disposition kinetics of metformin were investigated by use of an isolated in-situ rat liver preparation. The liver was perfused in single-pass mode with protein-free Krebs bicarbonate medium at a flow rate of 20 mL min(-1). During constant infusion with 1 mg L(-1) metformin hydrochloride the hepatic uptake of metformin approached equilibrium within 10 min. The steady-state availability, F, determined from the ratio of outflow concentration to input concentration, was 0.99+/-0.02 (mean +/- s.d., n = 4). The outflow profile of metformin resulting from a bolus injection of 25 microg into the portal vein, had a sharp peak then a slower declining terminal phase. The mean transit time (MTT; 49.5+/-14.5, n = 6) and normalized variance (CV2; 4.13+/-0.05) of the hepatic transit times of metformin were estimated by numerical integration from the statistical moments of the outflow data. The volume of distribution of metformin in the liver (1.58+/-0.28 mL (g liver)(-1)) was estimated from its MTT. The volume of distribution is greater than the water space of liver, indicating that metformin enters the hepatic aqueous space and becomes distributed among cellular components. The magnitude of CV2 for metformin is greater than for the vascular marker sucrose, suggesting that distribution of metformin into hepatic tissue is not instantaneous. In conclusion, hepatic uptake of metformin is rate-limited by a permeability barrier. Although metformin is accumulated in the liver, the organ does not extract it.

Animals↗