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Biomedical subjects

C L Chen

Publications and source records attributed to C L Chen.

At least 37 records · Page 2Linked to original sources

E-cadherin expression is silenced by DNA methylation in cervical cancer cell lines and tumours.

A previous study showed E-cadherin expression was lost in some cervical cancer cell lines and tumours. This study was designed to clarify the significance of DNA methylation in silencing E-cadherin expression. We examined promoter methylation of E-cadherin in five cervical cancer cell lines and 20 cervical cancer tissues using methylation-specific PCR (MSP) and bisulphite DNA sequencing. The correlation of E-cadherin methylation and expression together with methyltransferase (DNMT1) were further studied. We found that hypermethylation of E-cadherin was involved in five cervical cancer cell lines and 40% (8/20) of cervical cancer tissues. E-cadherin protein was lost in 6/8 (75%) samples and 3/5 (60%) cell lines with promoter methylation. E-cadherin methylation was significantly correlated with increased DNMT1. Using an antisense DNMT1 oligo to transfect into SiHa HeLa C33A cell line, E-cadherin protein was re-expressed. We concluded that loss of E-cadherin expression was in part correlated with DNA methylation and DNMT1 expression in cervical cancer.

Antimetabolites, Antineoplastic↗

The detection of small simulated field defects using multifocal VEPs.

INTRODUCTION: The multifocal visual-evoked potential (mfVEP) has been widely investigated in the study of diseases of the visual system. However, the sensitivity of the mfVEP in objective detection of field defects has not been determined. This study investigates the variation of the mfVEP responses whilst simulating field defects by using different sizes of mask on the stimulus pattern. METHODS: Simulated field defects of four different sizes (2, 3, 5, and 7 degrees) at two different eccentricities (10 and 16 degrees) were generated on a standard mfVEP dartboard stimulus using opaque masks. These masks were placed at the centre of each dartboard sector and the modified stimuli were used to elicit mfVEPs from 10 normal subjects. The response densities and latencies of N1, P1 of the mfVEP were compared, without and with small simulated field defects. RESULTS: The minimum size of simulated field defect causing significant response density reduction in P1 and N1 was 5 degrees at both retinal eccentricities. N1 showed similar reduction in response density at both retinal eccentricities, but P1 showed larger reduction at the 10-degree location than at the 16-degree location. There was no change in latencies with simulated field defect at either location. CONCLUSIONS: The mfVEP is only sensitive to a simulated field defect equal to or larger than 5 degrees in diameter, and mfVEP has greater sensitivity at 10-degree eccentricity than at 16-degree eccentricity.

Adult↗

Efficacy of a motilin receptor agonist (ABT-229) for the treatment of gastro-oesophageal reflux disease.

BACKGROUND: ABT-229 is a potent motilin agonist without significant antibiotic activity. It has been shown to improve gastric emptying in humans and to increase lower oesophageal sphincter pressure in cats. AIM: To assess the efficacy of four different doses of ABT-229 (1.25 mg, 2.5 mg, 5 mg, 10 mg b.d.) compared to placebo in the treatment of gastro-oesophageal reflux disease, and to determine its safety in patients with gastro-oesophageal reflux disease. METHODS: In a double-blind, multicentre study, 324 patients with heartburn were randomized to receive four different doses of ABT-229 or placebo for 8 weeks. The efficacy was evaluated by Patient Symptom Questionnaire, daily diary, endoscopy and global evaluation of efficacy. RESULTS: There were no statistically significant improvement scores for any of the ABT-229 treatment groups vs. the placebo group in any of the efficacy parameters. Reflux symptom scores were significantly worse after treatment in the dyspeptic group. ABT-229 appeared to be well tolerated and safe in total daily doses up to 20 mg. CONCLUSION: ABT-229 appears to have limited, if any, clinical utility in the treatment of gastro-oesophageal reflux disease.

Dose-Response Relationship, Drug↗

Aging and neural control of the GI tract: IV. Clinical and physiological aspects of gastrointestinal motility and aging.

The gastrointestinal motility changes that occur as a function of age are reviewed herein. Careful attention must be given in any review of aging phenomena to exclude, or at least be cognizant of, the many comorbid conditions that can alter physiological functioning in older adults. The dramatic increase in life expectancy over the past 10-15 years demands that clinicians be aware of the various physiological and clinically relevant changes that occur with age. Gastrointestinal motility changes associated with age are relatively subtle, and in many instances only conflicting data exist. As the older adult population increases, and as the control of disease is improved, much more work needs to be done to understand the true effects of aging on gastrointestinal functioning.

Aged↗

Sialyltransferase family members and cervix squamous cell carcinoma.

Sialic acids including a number of their derivatives are ubiquitous at the terminal positions of the oligosaccharides of glycoproteins. The transfer of sialic acids from cystidine-5-monophospho-N-acetylneuraminic acid (CMP-NeuAc) to the terminal position of the carbohydrate group of glycoproteins and glycolipids is catalyzed by a family of sialyltransferases (STs). There is a large body of evidence to suggest that tumor cells have altered surface properties from their normal counterparts, and that these changes are partially due to altered sialo-glycoconjugates expressed on the plasma membrane and that altered sialylation (change in glycoprotein expression), which occurs during certain pathological processes, such as oncogenic transformation, tumor metastases, and invasion, is associated with enhanced ST activity. In this report we attempt to review the important findings in studing sialyltransferases of cervix squamous cell carcinoma.

Carcinoma, Squamous Cell↗

High-performance liquid chromatographic methods for the determination of topoisomerase II inhibitors.

Various methods for separating eleven different types of topoisomerase II (TOPO-2) inhibitors, including epipodophyllotoxins, anthracyclines, anthracenediones, anthrapyrazoles, anthracenebishydrazones, indole derivatives, aminoacridines, benzisoquinolinediones, isoflavones, bisdioxopiperazines and thiobarbituric acids, are summarized. Proper sample preparation and storage is critical to the successful analysis of some TOPO-2 inhibitors due to difficulties associated with adsorption, instability and complex biological components. Solid-phase and liquid-liquid extractions are widely used to separate TOPO-2 inhibitors from biological samples, although simple deproteinization followed by direct analysis of the supernatant is preferable to extraction based on its speed and simplicity. High-performance liquid chromatography (HPLC) is the favored method for the bioanalysis of TOPO-2 inhibitors. UV or diode array detection is generally employed for early pharmacokinetic studies, while fluorescence or electrochemical detection is used more frequently for analytes with fluorescent or oxidative-reductive properties. For analyses requiring highly sensitive and/or specific detection, electrospray mass spectrometry (ESI-MS or ESI-MS-MS) provides a suitable alternative. A comprehensive compilation of the HPLC techniques currently used to separate TOPO-2 inhibitors will aid the future development of analytical methods for new TOPO-2 inhibitors.

Catalysis↗

Single imaging modality evaluation of living donors in liver transplantation: magnetic resonance imaging.

BACKGROUND: Liver graft size, anatomy of the bile duct and the vascular inflow and outflow are essential for living related liver transplantation (LRLT). Preoperative delineation of those variations that would change the operative procedure to achieve a successful result especially in an emergency condition. PURPOSE: Our aim was to develop a rapid and noninvasive imaging diagnostic method for the detection of anatomical variants that is mandatory for a safe operation when selecting potential liver transplant living donors. We used a different magnetic resonance (MR) imaging technique, which enabled to us to exploit the anatomical landmark of the liver, signal enhancement of blood flow in the abdomen, and the intrahepatic biliary routes inside the liver. Then, with the help of Advantage Window workstation reconstruction, the reconstructed single vascular or biliary systems were displaced in a three-dimensional fashion and the whole examination finished within 30 min. METHODS: Modification of the standard MR technique was performed on a superconductive 1.5T whole body image scanner, MR arteriogaphy, venography, and cholangiography with three-dimensional reconstruction in evaluating the anatomy of the hepatic arteries, hepatic veins, portal venous system, bile ducts, and liver size in potential liver transplant living donors. These anatomical structures were compared with traditional imaging methods. RESULTS: In all 38 cases, as well as delineation of the portal vein detail to the segmental level was satisfactorily obtained in this MR study. The images were well displayed in a three-dimensional fashion, which had good correlation with images from traditional imaging modalities and operative findings. In 86.8% cases, the MR arteriography was well matched with the celiac angiography. Of those 17 operative cases, estimation of liver volume was well correlated with the liver graft within 3.9-12.5% variation. In the major hepatic vein, we obtained 100% accuracy and 88.2% in the minor branches. Of 12 donors received intraoperative cholangiography during liver donation, good correlation of biliary anatomy was achieved. One donor was excluded from graft donation due to the complicated arterial supply to the left liver. According to the anatomical variation, surgical procedures in graft harvesting and anastomosis were readjusted and no major complications were found in those donors and all recipients survived after liver transplantation. CONCLUSION: MR volumetry, venography, angiography, and cholangiography with three-dimensional reconstruction is sufficient for all major imaging evaluation. It may replace the traditional conventional catheter angiography, computed tomography, sonography and endoscopic retrograde cholangiography as a single investigation in the evaluation of the potential liver transplant donors. Angiography is only valuable in suboptimal cases and intraoperative cholangiography is only performed in biliary ductile variants.

Adult↗

Prospective study of Helicobacter pylori eradication therapy in stage I(E) high-grade mucosa-associated lymphoid tissue lymphoma of the stomach.

PURPOSE: High-grade mucosa-associated lymphoid tissue (MALT) lymphomas of the stomach are generally believed to be Helicobacter pylori-independent, autonomously growing tumors. However, anecdotal cases of regression of high-grade lymphomas after the cure of H pylori infection had been described. The present prospective study was conducted to evaluate the effect of anti-H pylori therapy in stage I(E) high-grade gastric MALT lymphomas. PATIENTS AND METHODS: Sixteen patients with H pylori infection and stage I(E) gastric high-grade MALT lymphoma consented to a brief antibiotic therapy as first-line treatment from June 1995 through April 2000. Then, patients underwent intensive endoscopic follow-up examinations (+/- endoscopic ultrasonography) with biopsy to evaluate tumor response. Patients with significant improvement of gross lesions that accompanied regression of large cells were followed up without additional treatment. Patients without significant improvement were immediately referred to systemic chemotherapy. RESULTS: Eradication of H pylori was achieved in 15 patients and was accompanied by rapid gross tumor regression and disappearance of large cells in 10. All 10 of these patients with early response had subsequent complete histologic remission of lymphoma. The complete remission rate was 62.5% (95% confidence interval, 35.8% to 89.1%). The response rate was not affected by the tumor grading (proportion of large blast cells within the tumor) but was adversely affected by the depth of tumor invasion. At a median follow-up of 43.5 months (range, 21.1 to 67.4 months), all 10 of these patients remained lymphoma-free. The median duration of complete response was 31.2 months (range, 14.4 to 49.1 months). CONCLUSION: These results suggest that high-grade transformation is not necessarily associated with the loss of H pylori dependence in early-stage MALT lymphomas of the stomach.

Adult↗

Formation of brainstem (nor)adrenergic centers and first-order relay visceral sensory neurons is dependent on homeodomain protein Rnx/Tlx3.

Brainstem visceral sensory and (nor)adrenergic neurons play crucial roles in modulating cardiovascular and respiratory functions. The origins and formation of these neurons are poorly understood. Here we show that these two classes of neurons are derived from Mash1-positive precursor cells, and can be prospectively identified by combinatorial expression of two homeobox genes, Rnx and Phox2 (Phox2a or Phox2b). It was previously shown that Rnx-deficient mice die from respiratory failure. Here we show that Rnx function is required for formation of first-order relay visceral sensory neurons in the brainstem. In addition, as in Phox2b-deficient mice, the development of most (nor)adrenergic centers is compromised in Rnx mutants. We also provide genetic evidence to show that Rnx and Phox2 proteins may function independently to specify the (nor)adrenergic phenotype. Our studies reveal a surprising ontogenetic relationship between relay visceral sensory and (nor)adrenergic neurons, and suggest that it may be a common theme in the developing nervous system that the same set of transcriptional regulators is associated with formation of multiple components within a neuronal network.

Animals↗

NF-kappaB mediates FGF signal regulation of msx-1 expression.

The nuclear factor-kappaB (NF-kappaB) family of transcription factors is involved in proliferation, differentiation, and apoptosis in a stage- and cell-dependent manner. Recent evidence has shown that NF-kappaB activity is necessary for both chicken and mouse limb development. We report here that the NF-kappaB family member c-rel and the homeodomain gene msx-1 have partially overlapping expression patterns in the developing chick limb. In addition, inhibition of NF-kappaB activity resulted in a decrease in msx-1 mRNA expression. Sequence analysis of the msx-1 promoter revealed three potential kappaB-binding sites similar to the interferon-gamma (IFN-gamma) kappaB-binding site. These sites bound to c-Rel, as shown by electrophoretic mobility shift assay (EMSA). Furthermore, inhibition of NF-kappaB activity significantly reduced transactivation of the msx-1 promoter in response to FGF-2/-4, known stimulators of msx-1 expression. These results suggest that NF-kappaB mediates the FGF-2/-4 signal regulation of msx-1 gene expression.

Animals↗

Genomic structure and transcriptional regulation of the early B cell gene chB1.

The avian B cell differentiation Ag chB1 is a membrane glycoprotein relative of the mammalian B cell differentiation Ag CD72. Unlike CD72, this C-type lectin is expressed in relatively high levels on immature B cells in the bursa of Fabricius and is down-regulated on mature B cells in the periphery. An immunoreceptor tyrosine-based inhibitory motif in the chB1 cytoplasmic tail suggests a potential regulatory role in intrabursal B cell development. To gain further insight into the selective expression and function of chB1, we determined the genomic organization of chB1 and examined the mechanism of its transcriptional regulation. The 8-exon chB1 gene proved to have very similar organization to that of mouse CD72, further supporting the idea that chB1 is a CD72 relative. As for mouse CD72, the chB1 promoter region lacks a TATA box but contains a conserved initiator element. The 131-bp region (-161 to -30) proximal to the transcriptional start site, which contains a potential early B cell factor binding site, is essential for the B lineage stage-specific transcription of chB1, whereas PU.1 and B cell-specific activator protein/Pax5 have been shown to play important roles in CD72 promoter activity and cell-type specificity. This analysis suggests that differences in transcriptional regulation of these phylogenetically related genes may determine the differences in expression pattern and, therefore, the function of avian chB1 and mammalian CD72 during B cell development.

5' Untranslated Regions↗

Assessment of donor fatty livers for liver transplantation.

AIM: The effect of fatty liver on graft survival, especially with reference to macrovesicular and microvesicular steatosis, is still uncertain. This preliminarily study was designed to create a noninvasive method for the quantification of the hepatic fat content in vivo and to establish provisional criteria for the assessment of fatty donor livers before liver transplantation among transplant surgeons, radiologists, and pathologists. METHODS AND MATERIALS: Different degrees of rat fatty liver model were established by feeding rats a diet deficient in choline and methionine for different periods of time. Computed tomography (CT) with test tubes containing variable percentages of fat equivalent substance were used to assess the severity of fatty change of the rat liver. This was then correlated with the histological classification, level of hepatic enzymes, and graft survival. RESULTS: Linear correlation between the fat volume fraction added to the test tubes and CT density were found. The process of producing a fatty liver via diet alteration peaked at week 3. At this time hepatic enzymes, radiological fat content, and posttransplantation survival were worse (P=0.013), compared with other time points. Radiological assessment of fatty liver correlated well with survival and serum glutamic oxaloacetic transaminase and glutamic pyruvate transaminase levels. CONCLUSION: Severe microvesicular steatosis does not influence recipient survival, however, macrovesicular steatosis affects graft survival. Caliber CT is a practical and simple method that allows an accurate noninvasive quantitative assessment of hepatic fatty infiltration. It has potential to be a useful parameter for the assessment of donor livers for clinical liver transplantation.

Animals↗

Comparison of MALT and non-MALT primary large cell lymphoma of the stomach: does histologic evidence of MALT affect chemotherapy response?

BACKGROUND: Although the clinicopathologic features of low grade gastric MALToma (lymphoma of mucosa-associated lymphoid tissue) recently have been well delineated, the significance of identifying histologic evidence of MALT origin in a primary high grade gastric lymphoma is less clear. The authors sought to address this issue and, in particular, to clarify if MALT and non-MALT primary large cell gastric lymphoma might have a different response to systemic chemotherapy. METHODS: The authors reviewed the pathologic specimens of all patients who had a diagnosis of primary large cell lymphoma of the stomach and who had been treated primarily by systemic chemotherapy in our institutions January 1, 1988-December 31, 1998. The patients were divided into two groups by experienced hematopathologists, based on the presence or absence of histologic features suggestive of MALToma, including typical lymphoepithelial lesions and infiltration of characteristic centrocyte-like cells. Disease staging was done according to the AJCC/UICC system with Musshoff modification. The median number of gastric biopsies for each patient was 7 (range, 1-21). RESULTS: Seventeen patients with and 26 patients without histologic evidence of MALToma were identified. Clinical features were similar between the two groups except that a greater proportion of patients without evidence of MALToma had elevated levels of serum lactate dehydrogenase (50% vs. 12%, P = 0.01). The median duration of follow-up for the 43 patients was 46.5 months (range, 17-124 mos). All patients received standard systemic chemotherapy including anthracyclines or anthracenedione. The response rate was 88.2% for patients with evidence of MALToma and 57.7% for those without (P = 0.03). The 5-year overall survival rate was 80.5% for patients with evidence of MALToma and 48.9% for those without (P = 0.02). Multivariate analysis indicated that response to chemotherapy, disease stage (Stage I and II-1 vs. Stage II-2, III, and IV), and the presence of MALToma features were independent prognostic factors for overall survival. CONCLUSION: The results of this relatively small study series suggested that the presence of histologic features of MALToma in patients with primary large cell gastric lymphoma might have been associated with a better response to systemic chemotherapy and a better prognosis. Further studies to consolidate this conclusion are necessary.

Adult↗

Roles of an endogenous serum lectin in the immune protection of blue gourami, Trichogaster trichopterus (Pallus) against Aeromonas hydrophila.

The serum of blue gourami, Trichogaster trichopterus (Pallus), contains a calcium-dependent, N-acetyl-galactosamine-binding lectin (BGL) which efficiently activates and enhances the non-specific immune response of fish towards a virulent strain of Aeromonas hydrophila. In the in vitro studies, a lectin concentration range of 0.05-1.0 ng ml(-1) was found to significantly promote phagocytic uptake of the bacteria by macrophages. This effect was further augmented when purified lectin was combined with laminarin (beta-1,3-D-glucan). Supernatants obtained from these lectin-stimulated macrophage cultures also exhibited significant bacteria-killing activities. In addition, complement from naive fish serum, in the presence of purified BGL, was able to kill A. hydrophila. Finally, challenge experiments demonstrated that BGL could confer effective immune protection to naive blue gourami against an Aeromonas infection.

Aeromonas hydrophila↗

Identification of two down-regulated genes in rat liver allografts by mRNA differential display.

Total RNA differential display (DD) using random primers was performed for rat orthotopic liver transplantation (OLT) models. DA (RT1a) donor livers were transplanted into DA, PVG (RT1c), and LEW (RT1l) recipients: (1) syngeneic OLT (DA-DA): no rejection occurs; (2) allogeneic OLT (DA-PVG): rejection occurs, but is naturally overcome without immunosuppression; (3) allogeneic OLT (DA-LEW): animals die of acute rejection within 14 days. cDNA was isolated from selected bands, re-amplified for sequencing, and confirmed by Northern blots. Two down-regulated genes were observed in day-7 allogeneic OLT livers (DA-PVG, DA-LEW), while they were consistently expressed in day-7 syngeneic OLT (DA-DA) livers. These two genes were identified as alpha-glutathione sulfotransferase (alpha-GST) Ya gene and estrogen sulfotransferase (EST), respectively. Northern blots confirmed that their expression was down-regulated in OLT (DA-PVG) livers on days 7-26 and gradually restored. The mRNA expression of GST and EST may be good markers to predict rejection or induction of tolerance.

Animals↗

Interventional radiologic procedures in liver transplantation.

Postoperative biliary and vascular complications contribute significantly to morbidity and mortality in liver transplantation. Interventional radiologists are an integral part of the multidisciplinary team necessary for optimizing the management of these complications. During a 15-year period, 39 cadaveric and 25 living related liver transplantations were performed at the Chang Gung Memorial hospital, Taiwan. Of 64 liver transplant recipients, 9 (3 adult and 6 pediatric) underwent 13 interventional radiological procedures for the treatment of biliary sludge-casts (n = 2), bile duct occlusion or stenosis (n = 2), hepatic veins thrombosis (n = 1), hepatic veins stenosis (n = 1), portal vein stenosis with splenorenal shunting (n = 1), biloma (n = 1), and infected fluid collection or ascites (n = 4). Antegrade or retrograde interventional approach was used to successfully treat all biliary complications, and all percutaneous drainage procedures were effective in the control of intra-abdominal fluid collections. Portal vein stenosis was treated by balloon dilatation, and the associated splenorenal shunt was closed by metallic coil embolization via transhepatic catheterization of the portal vein. Hepatic vein stenosis was effectively treated by balloon dilatation and expandable metallic stent deployment via transfemoral and jugular venous approaches, respectively. Hepatic vein thrombosis was only partially lysed by transvenous streptokinase administration, and surgical thrombectomy was needed to achieve complete recanalization. The total success rate of the interventional procedures was 92 % with no procedure-related complications. The overall survival rate in this series is 89 %, and all patients who underwent living related liver transplantation maintain to date a 100 % survival rate. We can conclude that interventional radiological procedures are very useful for managing biliary and vascular complications after liver transplantation. These techniques provide a cure in most situations, thus obviating the need for further surgical intervention or re-transplantation.

Adolescent↗