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M J Chen

Publications and source records attributed to M J Chen.

At least 19 recordsLinked to original sources
PubMed2003

Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant.

Antidepressants and physical exercise have been shown to increase the transcription of hippocampal brain-derived neurotrophic factor (BDNF). Much evidence regarding the initial actions of antidepressant medications as well as exercise leads to the hypothesis that noradrenergic (NE) and/or serotonergic (5-HT) activation is a key element in the BDNF transcriptional elevation common to both interventions. Currently, we used short-term beta-adrenergic, 5-HT(1A), or 5-HT(2A/C) receptor blockade to characterize the influence of NE and 5-HT systems on BDNF transcription during physical exercise and antidepressant treatment. In situ hybridization revealed that beta-adrenergic blockade significantly blunted the BDNF mRNA elevations due to exercise, and also inhibited the modest elevations in the CA3 and dentate gyrus following short-term treatment with tranylcypromine. In contrast, 5-HT(2A/C) blockade only minimally altered exercise-induced BDNF mRNA levels, but inhibited up-regulation of BDNF transcription via tranylcypromine. Finally, 5-HT(1A) blockade did not inhibit exercise-induced BDNF mRNA elevations, but significantly enhanced levels above those achieved with exercise alone in the CA4. These results suggest that NE activation via beta-adrenergic receptors may be essential for both exercise and antidepressant-induced BDNF regulation. 5-HT(1A) and 5-HT(2A/C) activation, on the other hand, appear to be most important for antidepressant-induced BDNF regulation, but may also participate significantly in exercise-induced regulation in the CA4.

Adrenergic Antagonists↗
PubMed2003

The influence of specific noradrenergic and serotonergic lesions on the expression of hippocampal brain-derived neurotrophic factor transcripts following voluntary physical activity.

Previous studies have shown that hippocampal brain-derived neurotrophic factor (BDNF) mRNA levels are significantly increased in rats allowed free access to exercise wheels and/or administered antidepressant medications. Enhancement of BDNF may be crucial for the clinical effect of antidepressant interventions. Since increased function of the noradrenergic and/or serotonergic systems is thought to be an important initial mechanism of antidepressant medications, we sought to test the hypothesis that noradrenergic or serotonergic function is essential for the increased BDNF transcription occurring with exercise. In addition, individual transcript variants of BDNF were examined, as evidence exists they are differentially regulated by discrete interventions, and are expressed in distinct sub-regions of the hippocampus. The neurotransmitter system-specific neurotoxins p-chloroamphetamine (serotonergic) and N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (noradrenergic) were administered to rats prior to commencing voluntary wheel-running activity. In situ hybridization experiments revealed an absence of exercise-induced full-length BDNF mRNA elevations in the hippocampi of noradrenergic-lesioned rats. In addition, the striking elevation of the exon I transcript in the dentate gyrus was removed with this noradrenergic lesion. In contrast, other transcript variants (exons II and III) were elevated in several hippocampal regions as a result of this lesion. In serotonin-lesioned rats, the significant increases in full-length BDNF, exon I and exon II mRNA levels were sustained without alteration (with the exception of exon IV in the cornus ammonis subregion 4, CA4). Overall, these results indicate that an intact noradrenergic system may be crucial for the observed ability of exercise to enhance full-length and exon I hippocampal BDNF mRNA expression. In addition, these results suggest that the promoter linked to exon I may provide a major regulatory point for BDNF mRNA expression in the dentate gyrus. Elevations of other exons, such as II and III, may require the activation of separate neurotransmitter systems and intracellular pathways.

Alternative Splicing↗
PubMed2001

Selection of in vitro produced, transgenic embryos by nested PCR for efficient production of transgenic goats.

The production of valuable pharmaceutical proteins using transgenic animals as bioreactors has become one of the goals of biotechnology. However, the efficiency of producing transgenic animals by means of pronuclear microinjection is low. This may be attributed in part to the low integration rate of foreign DNA. Therefore, a large number of recipients are required to produce transgenic animals. We recently developed a transgenic procedure that combined the techniques of goat oocyte in vitro maturation (IVM), in vitro fertilization (IVF), microinjection, preimplantation selection of the transgenic embryos with nested PCR and transferring the transgenic embryos into the recipient goat uterus to produce transgenic goats. Thirty-seven transgenic embryos determined by nested PCR were transferred to thirty-two recipient goats. In the end, four live-born kids were produced. As predicted, all the live kids were transgenic as identified by PCR as well as Southern blot hybridization, The integration rate was 100% (4/4) which was completely in accordance with the results of embryo preimplantation detection. The results showed a significant decrease in the number of recipients required as only 8 recipients (32/4) were needed to obtain one live transgenic goat. We suggest that the transgenic system described herein may provide an improved way to efficiently produce transgenic goats on a large scale.

Animals↗
PubMed2001

Capillary electrophoresis study on the micellization and critical micelle concentration of sodium dodecyl sulfate. Influence of solubilized solutes.

The influence of solubilized solutes on the micellization and critical micelle concentration (CMC) of sodium dodecyl sulfate (SDS) were investigated by means of capillary electrophoresis (CE). Three different structural types of test solutes, including chloropyridines. chlorophenols and cephalosporins with different binding strength to SDS micelles, were selected in this study. The variations of the effective electrophoretic mobility of these solutes as a function of SDS concentration in the premicellar and micellar regions were analyzed. Interestingly, the results indicate that, in the presence of these solubilized solutes, the micellization of SDS may occur over a range of SDS concentration, with the aggregate size increasing over this range. Depending on the nature of solubilized solutes and the extent of the interactions between solubilized solutes and SDS micelles, the CMC value of SDS may vary significantly. The incorporation of solubilized solutes into SDS micelles to form mixed micelles is proposed to interpret the migration behavior of solubilized solutes in CE.

Cefazolin↗
PubMed2001

Separation and selectivity of benzophenones in micellar electrokinetic chromatography using sodium dodecyl sulfate micelles or sodium cholate modified mixed micelles.

The separation and selectivity of nine benzophenones in micellar electrokinetic chromatography (MEKC) using sodium dodecyl sulfate (SDS) micelles or sodium cholate (SC) modified mixed micelles were investigated in the pH range 6.5-8.0. The results indicate that the combined effects of buffer pH and SC concentration can greatly affect the separation and selectivity of benzophenones, particularly for benzophenones possessing a hydroxyl substituent at the 4-position of the aromatic ring with respect to the carbonyl moiety when using SDS-SC mixed micelles. Better separability can be obtained with SDS-SC mixed micelles than with SDS micelles. Complete separation of nine benzophenones in MEKC can be achieved with an appropriate choice of buffer pH and the concentration of SDS micelles or SC modified mixed micelles. The dependence of the migration order of those benzophenones based on their structures and solute-micelle interactions is discussed.

Benzophenones↗
PubMed2001

Reactive oxygen species and substance P in monocrotaline-induced pulmonary hypertension.

We attempted to evaluate whether the antioxidants 1,3-dimethyl-2-thiourea (DMTU) and hexa(sulfobutyl)fullerenes (FC(4)S) attenuate monocrotaline (MCT)-induced pulmonary hypertension (PH) by lowering lung substance P (SP) in Wistar rats. Sixty-three rats weighing 297 +/- 8 g were divided into six groups: control; MCT; capsaicin + MCT; MCT + DMTU-1; MCT + DMTU-2; and MCT + FC(4)S. Three weeks before the functional study, saline was injected into each control rat, whereas each MCT rat received 60 mg/kg sc MCT. Rats in the third group received capsaicin pretreatment followed by MCT. A 3-day injection of DMTU was performed during the early (DMTU-1) or the late (DMTU-2) post-MCT period. For the last group, each MCT-treated rat received a daily FC(4)S injection until the commencement of the functional study. Compared to the control group, MCT caused significant increases in pulmonary arterial pressure (Ppa), right ventricular hypertropy, pulmonary arterial medial thickness, lung SP level, and luminol-enhanced chemiluminescence counts in bronchoalveolar lavage. Both capsaicin and antioxidants significantly attenuated the above MCT-induced alterations. SP-induced acute increase in Ppa was exaggerated in MCT-treated rats. These results suggest that oxygen radicals play an important role in MCT-induced PH via elevating lung SP level.

Animals↗
PubMed2001

ATM-dependent phosphorylation of human Rad9 is required for ionizing radiation-induced checkpoint activation.

ATM (ataxia-telangiectasia-mutated) is a Ser/Thr kinase involved in cell cycle checkpoints and DNA repair. Human Rad9 (hRad9) is the homologue of Schizosaccharomyces pombe Rad9 protein that plays a critical role in cell cycle checkpoint control. To examine the potential signaling pathway linking ATM and hRad9, we investigated the modification of hRad9 in response to DNA damage. Here we show that hRad9 protein is constitutively phosphorylated in undamaged cells and undergoes hyperphosphorylation upon treatment with ionizing radiation (IR), ultraviolet light (UV), and hydroxyurea (HU). Interestingly, hyperphosphorylation of hRad9 induced by IR is dependent on ATM. Ser(272) of hRad9 is phosphorylated directly by ATM in vitro. Furthermore, hRad9 is phosphorylated on Ser(272) in response to IR in vivo, and this modification is delayed in ATM-deficient cells. Expression of hRad9 S272A mutant protein in human lung fibroblast VA13 cells disturbs IR-induced G(1)/S checkpoint activation and increased cellular sensitivity to IR. Together, our results suggest that the ATM-mediated phosphorylation of hRad9 is required for IR-induced checkpoint activation.

Ataxia Telangiectasia↗
PubMed2001

In vivo gene therapy for colon cancer using adenovirus-mediated, transfer of the fusion gene cytosine deaminase and uracil phosphoribosyltransferase.

Virus-directed enzyme prodrug therapy (VDEPT) utilising cytosine deaminase (CD) converts 5-fluorocytosine (5-FC) into the chemotherapy agent, 5-fluorouracil (5-FU), and has entered into a clinical trial for metastatic colon cancer. To improve this system, a replication-deficient adenovirus, containing a bifunctional fusion gene, CD:uracil phosphoribosyltransferase (UPRT), was constructed (AdCDUPRT). UPRT enhances the conversion of 5-FU into its active metabolites, which inhibit DNA and RNA synthesis. In vitro, AdCDUPRT infection of colon cancer cells resulted in a marked increase in sensitisation to 5-FU, compared with AdCD-infected or uninfected cells. The corollary is a approximately 100-fold and approximately 10 000-fold increase in sensitisation to 5-FC in AdCDUPRT-infected cells, compared to AdCD-infected and uninfected cells, respectively. There was a strong bystander effect in vitro, 70% of tumour cells were killed by 5-FC when only 10% of cells expressed CDUPRT. In vivo, athymic mice with colon cancer xenografts treated with intratumoral AdCDUPRT and intraperitoneal 5-FC, significantly reduced tumour growth rates compared with untreated controls (P = 0.02), whereas AdCD/5-FC treated mice did not. At higher AdCDUPRT virus doses, 5-FC and 5-FU were equally effective at delaying tumour growth compared with controls. In summary, VDEPT for colon cancer utilising AdCDUPRT is more effective than AdCD and the bifunctional CDUPRT gene enables the use of either 5-FC or 5-FU as prodrugs.

Adenoviridae↗
PubMed2001

Granulomatous variant of chronic pigmented purpuric dermatosis: report of two cases.

Two patients presenting with chronic pigmented purpuric dermatosis (CPPD) on the dorsum of both feet were found to show granulomatous inflammation superimposed on the pathological changes of CPPD. Two similar cases have been reported from Japan. The unique clinicopathological features of this group of patients suggest that they have a rare granulomatous variant of CPPD.

Aged↗
PubMed2001

A prospective randomized study comparing volume-standardized modified and conventional ultrafiltration in pediatric cardiac surgery.

BACKGROUND: Modified ultrafiltration has been touted as superior to conventional ultrafiltration for attenuating the consequences of hemodilution after cardiac surgery with cardiopulmonary bypass in children. We conducted a prospective randomized study to test the hypothesis that modified and conventional ultrafiltration have similar clinical effects when a standardized volume of fluid is removed. METHODS: From October 1998 to September 1999, 110 children weighing 15 kg or less (median weight 6.1 kg, median age 6.3 months) undergoing surgery with cardiopulmonary bypass for functionally biventricular congenital heart disease were randomized to conventional (n = 67) or arteriovenous modified ultrafiltration (n = 43) for hemoconcentration. The volume of fluid removed with both methods was standardized as a percentage of effective fluid balance (the sum of prime volume and volume added during cardiopulmonary bypass minus urine output): in patients weighing less than 10 kg, 50% of effective fluid balance was removed, whereas 60% was removed in patients weighing 10 to 15 kg. Hematocrit, hemodynamics, ventricular function, transfusion of blood products, and postoperative resource use were compared between groups. RESULTS: There were no significant differences between groups in age, weight, or duration of cardiopulmonary bypass. The total volume of fluid added in the prime and during bypass was greater in patients undergoing conventional ultrafiltration than in those receiving modified ultrafiltration (205 +/- 123 vs 162 +/- 74 mL/kg; P =.05), although the difference was due primarily to a greater indexed priming volume in patients having conventional ultrafiltration. There was no difference in the percentage of effective fluid balance that was removed in the 2 groups. Accordingly, the volume of ultrafiltrate was greater in patients receiving conventional than modified ultrafiltration (95 +/- 63 vs 68 +/- 28 mL/kg; P =.01). Preoperative and postoperative hematocrit levels were 35.6% +/- 6.6% and 36.3% +/- 5.6% in patients having conventional ultrafiltration and 34.4% +/- 6.7% and 38.7% +/- 7.5% in those having modified ultrafiltration. By repeated-measures analysis of variance, patients receiving modified and conventional ultrafiltration did not differ with respect to hematocrit value (P =.87), mean arterial pressure (P =.85), heart rate (P =.43), or left ventricular shortening fraction (P =.21) from baseline to the postbypass measurements. There were no differences between groups in duration of mechanical ventilation, stay in the intensive care unit, or hospitalization. CONCLUSIONS: When a standardized volume of fluid is removed, hematocrit, hemodynamics, ventricular function, requirement for blood products, and postoperative resource use do not differ between pediatric patients receiving conventional and modified ultrafiltration for hemoconcentration after cardiac surgery.

Blood Transfusion↗
PubMed2001

Gene therapy for colorectal cancer: therapeutic potential.

Colorectal cancer is a leading cause of cancer mortality in Western countries. Gene therapy has been proposed as a potential novel treatment modality for colorectal cancer, but it is still in an early stage of development. The preclinical data have been promising and numerous clinical trials are underway. This brief review aims to summarise the current status of clinical trials of different gene therapy strategies, including immune stimulation, mutant gene correction, prodrug activation and oncolytic virus therapy, for patients with colorectal cancer. Data from phase I trials have proven the safety of the reagents but have not yet demonstrated significant therapeutic benefit. In order to achieve this and extend the scope of the treatment, continuing efforts should be made to improve the antitumour potency, efficiency of gene delivery and accuracy of gene targeting.

Adenoviridae↗
PubMed2001

Non-penetrating trabeculectomy for open angle glaucoma.

BACKGROUND: Non-penetrating trabeculectomy is used as the surgical intervention for open angle glaucoma. It has advantage of creating gradual filtration through the thin trabeculo-Descemet membrane to reduce markedly the postoperative complications typical for penetrating operation. We described our experience of the non-penetrating trabeculectomy for open angle glaucoma. METHODS: This is a retrospective study of 28 eyes of 28 patients with primary open glaucoma (POAG). Non-penetrating trabeculectomy was performed by one surgeon from July 1998 to March 2000. Examinations were performed preoperatively and postoperatively in 1 and 7 days and 1, 3, 6, 12 and 21 months. RESULTS: The mean follow-up was 12.5 +/- 6.3 months (S.D.). The mean preoperative intraocular pressure (IOP) was 27.8 +/- 6.7 mmHg. The mean postoperative IOP was 11.5 +/- 6.2 mmHg in 1 day and 15.7 +/- 5.8 mmHg in 1 week, and it remained stable in the following 12 months. IOP of 71.3% (20/28) of the eyes could be controlled below or equal to 21 mmHg with no or only topical antiglaucoma medication. There were only few postoperative complications. CONCLUSIONS: Non-penetrating trabeculectomy is efficient in controlling intraocular pressure of open angle glaucoma. No entering the anterior chamber diminishes the postoperative complications typical of the penetrating trabeculectomy.

Aged↗
PubMed2001

Color Doppler imaging of retrobulbar hemodynamics after topical carteolol in normal tension glaucoma.

BACKGROUND: Carteolol is a nonselective adrenergic blocking agent. The aim of this study was to evaluate the effect of topical carteolol on retrobulbar hemodynamics in patients with normal tension glaucoma (NTG). METHODS: Twelve NTG patients received twelve-week topical treatment of 2% carteolol. Color Doppler imaging (CDI) was used to evaluate the hemodynamic effects before and after drug therapy. Measurements were obtained from the central retinal artery (CRA), the lateral posterior ciliary artery (LPCA) and the medial posterior ciliary artery (MPCA). From each vessel, peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI) and Gosling's pulsatility index (PI) were collected and analyzed. RESULTS: After topical carteolol treatment for twelve weeks, mean resistance index reduced significantly from 0.83 to 0.74 in the CRA (p = 0.03), from 0.74 to 0.68 in the LPCA (p = 0.09). Moreover, mean pulsatility index of the LPCA decreased from 1.45 to 1.26 (p = 0.08). CONCLUSIONS: Twelve weeks of 2% carteoiol treatment may decrease the vascular resistance in NTG patients possibly due to the intrinsic sympathomimetic activity (ISA) of carteolol.

Administration, Topical↗
PubMed2001

PCR Based Cloning and Sequence Analysis of the Pichia pastoris Cystathionine beta-Synthase Gene.

The cystathionine beta-Synthase (CBS) gene of Pichia pastoris has been cloned by homology to the CBS gene of Saccharomyces cerevisiae. First, based on the homology alignment of CBS genes from different sources, a pair of degenerate PCR primers were designed to amplify a conservative fragment of Pichia pastoris CBS gene. After the sequence was revealed, 5' RACE and 3' RACE were performed separately. The whole sequence of Pichia pasotris CBS gene was assembled. This gene encodes a polypeptide of 501 residues. Comparison of deduced amino acid sequence of this new gene with that of S. cerevisiae CBS showed 54% identity. Disruption of CBS gene resulted in a Cys(-) auxotrophy in Pichia pastoris. Thesequence was submitted to GenBank/EMBL/DDBJ under Accession No.AF367364.

Journal Article↗
PubMed2000

Total synthesis of (+)-blastmycinone, (-)-litsenolide C1, and related natural trisubstituted lactones via alkynyltungsten compounds.

A general method for total synthesis of natural trisubstituted gamma-lactones is developed on the basis of the chemistry of alkynyltungsten compounds. The key step in this approach involves the cycloalkenation of tungsten-eta1-(3R,4S)-pent-1-yne-3,4-diol with aldehydes to give tungsten-oxacarbenium salts, further leading to 3-alkylidene-4-hydroxy-5-methyl-gamma-lactones upon demetalation. This synthetic sequence proceeds well for alkynylaldehydes and the MOM derivative of tungsten-eta1-(3R,4S)-pent-1-yne-3,4-diol. The resulting butyrolactone products are transformed into natural trisubstituted butyrolactones including (+)-blastmycinone, (+)-blastmycinolactol, (+)-antimycinone, NFX-2, and (+)-isodihydromahubanolide A. By using the same approach based on (R)-ethyl lactate, the natural (-)-litsenolide C1 can be prepared in a few steps.

4-Butyrolactone↗
PubMed2000

A potent dimeric peptide antagonist of interleukin-5 that binds two interleukin-5 receptor alpha chains.

Two series of peptides that specifically bind to the extracellular domain of the alpha chain of the human interleukin-5 receptor (IL-5Ralpha), but share no primary sequence homology to IL-5, were identified from libraries of random recombinant peptides. Affinity maturation procedures generated a 19-aa peptide that binds to the IL-5 receptor alpha/beta heterodimer complex with an affinity equal to that of IL-5 and is a potent and specific antagonist of IL-5 activity in a human eosinophil adhesion assay. The active form of the peptide is a disulfide-crosslinked dimer that forms spontaneously in solution. Gel filtration analysis, receptor-binding studies, and analytical ultracentrifugation reveal that the dimeric peptide binds simultaneously to two receptor alpha chains in solution. Furthermore, the dimer peptide, but not IL-5, can activate a chimeric receptor consisting of the IL-5Ralpha extracellular domain fused to the intracellular domain of the epidermal growth factor receptor, thus demonstrating that the peptide also promotes receptor dimerization in a cellular context. The functional antagonism produced by the bivalent interaction of the dimeric peptide with two IL-5R alpha chains represents a distinctive mechanism for the antagonism of cytokines that use heteromeric receptors.

Amino Acid Sequence↗
PubMed2000

Lifestyle habits and gastric cancer in a hospital-based case-control study in Taiwan.

OBJECTIVES: The aim of this study was to evaluate the effect of lifestyle habits on the risk of primary gastric cancer. METHODS: A hospital-based case-control study of matched pairs was conducted in Kaohsiung, Taiwan, from 1992 to 1996. The study included 649 subjects (152 cases and 497 controls). All subjects were personally interviewed face-to-face by a trained interviewer using a structured questionnaire to collect data about lifestyle. An average of approximately three controls were matched to each case based on age (+/-3 yr), sex, and time of hospitalization (+/-2 wk). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to evaluate results, and a multivariate analysis of the data was performed using a conditional logistic regression model. RESULTS: A significantly elevated risk of contracting gastric cancer was observed in cigarette smokers (OR: 2.7, 95% CI: 1.5-4.3), but not in drinkers of alcoholic beverages (OR: 1.5, 95% CI: 0.9-3.2). A synergistically augmented relationship (multiplication effect) was found between smoking and drinking alcohol for controlling the major confounders. The combined adjusted ORs for all subjects with gastric cancer were 3.0 (95% CI: 1.4-7.1) for current smokers and 1.7 (95% CI: 1.2-4.4) for ex-smokers. Furthermore, a statistically significant positive dose-response trend in gastric cancer was demonstrated based on the age at which smoking was initiated, the duration of the habit, the number of cigarettes smoked per day, and the degree of smoke inhalation. We did not find any association between the other risk factors and gastric carcinogenesis. CONCLUSIONS: Our findings provide further evidence that in Taiwan, cigarette smoking may play the most harmful role in the initial development of gastric cancer, and that drinking alcohol may promote the process.

Alcohol Drinking↗