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Biomedical subjects

Y N Chen

Publications and source records attributed to Y N Chen.

At least 19 recordsLinked to original sources

Progressive decrease of proinsulin secretion in sulphonylurea-treated type 2 diabetes.

Progressive deterioration of beta-cell function is proposed as a disease-related factor of sulphonylurea (SU) failure in type 2 diabetes. If it gradually worsens over time then disease duration may mirror the progressive beta-cell deterioration. The aim of the present study is to assess whether or not disease duration is influential in remodelling the secretion pattern of insulin-like molecules and in glucose control of SU-treated type 2 diabetes. A research model is used to investigate proinsulin secreting capacity over time, using two groups of patients: i) disease duration <5 years (n=62), comprising SU responders (SUr; n=48) and SU failures (SUf; n=14); and ii) disease duration > or = 5 years (n= 37), comprising an SUr group (n=17) and an SUf group (n=20). Blood samples are taken at 0 h, 0.5 h 1 h, 2 h and 3 h during a standard oral glucose tolerance test and measured for glucose, total proinsulin (TPI), intact proinsulin (IPI) and specific insulin (SI) concentrations. Pairwise comparison of estimated marginal means of blood glucose, SI, IPI and TPI levels at each time point are carried out between groups and subgroups. (SUr vs. SUf). Homa insulin resistance index (IR index) is applied to analyse IR between the groups. It was found that patients with shorter disease duration had higher proinsulin (TPI and IPI) levels at all time points (P<0.05), together with a lower glucose level at 2 h and 3 h (P<0.05). Homa insulin index analysis showed no difference between the two groups (P=0.26). Results also showed that the SUr group had a significantly lower glucose level at Oh and 3h (P<0.05), although no significant difference in insulin and proinsulin levels was found between the SUr and SUf groups. In conclusion, proinsulin may play an important role in glucose control in SU-treated type 2 diabetes, but the effect is reduced in SUf patients.

Adult↗

Congener-specific polychlorinated biphenyls in cetaceans from Taiwan waters.

During 2000 to 2001, a total of 73 blubber samples from 13 species of stranded or accidentally captured cetaceans were collected from Taiwan coastal waters for polychlorinated biphenyl (PCB) analysis. After homogenization, saponification, liquid-liquid extraction, and silica-gel solid-phase extraction, PCB concentrations were determined by gas chromatography/mass spectrometry. Total concentrations of 19 PCB congeners (SigmaPCBs) were between 0.23 microg/g lipid weight of Risso's dolphin to 33.73 microg/g lipid weight of rough-toothed dolphin. Pentachlorobiphenyls, hexachlorobiphenyls and heptachlorobiphenyls were the predominant PCB congeners species. PCB153 was the most abundant congener in all samples. The PCB153/SigmaPCBs consistently comprised between 20% to 30% of all congeners. The toxicity measured as 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs) were from 2.7 pg/g lipid weight of finless porpoise to 2,900 pg/g lipid weight of rough-toothed dolphin. PCB 118, a mono-ortho congener, was the largest contributor to TEQs. PCB concentrations and TEQs were higher in mature male than in immature male animals but were inconsistent in female animals because of a possible transferring of PCBs from maternal cetaceans to their offsprings during gestation and lactation. Stranded cetaceans had significantly higher PCB levels than by-catch cetaceans because of their higher lipid consumption during starvation or illness. From the collected samples, we also found that cetaceans from Taiwan waters had relatively lower PCB concentrations and TEQs than those from high-latitude areas.

Animals↗

Study of a three-stage fluidized bed process treating acrylic synthetic-fiber manufacturing wastewater containing high-strength nitrogenous compounds.

Polyacrylonitrile (PAN) is one of the major synthetic fibers commonly used in the mass production of clothing. The chemical synthesis of PAN is carried out by polymerization of the acrylonitrile (AN) monomers with co-monomers such as vinyl acetate, methyl acrylate and cyclohexyl acrylate. Using water quality analysis of the PAN wastewater, high concentration of organic nitrogen was found and the TKN/COD ratios achieved were 0.15-0.26, indicating the complicated biodegradation characteristics for the PAN wastewater. In order to enhance biodegradation of nitrogenous compounds in PAN wastewater, a combined three-stage process of thermophilic anaerobic/anoxic denitrification/aerobic nitrification fluidized bed reactors was employed. The results indicated that the concentration of effluent in the three-stage process of OD and organic nitrogen was 175 mg/L and 13 mg/L, respectively. Furthermore, molecular biotechnology was applied to study the microbial population in the thermophilic anaerobic fluidized bed reactor. From the results of denaturing gradient gel electrophoresis, the diversity of PAN-degrading bacteria would change in different volumetric loading. Furthermore, the bacteria communities in the thermophilic anaerobic fluidized bed reactor were also studied by fluorescence in situ hybridization and confocal laser scanning microscopy. Alpha and delta-Proteobacteria were dominant in the bacteria population, and some high G+C content bacteria and Clostridium could be characterized in this system.

Acrylic Resins↗

Current detection of superradiance and induced entanglement of double quantum dot excitons.

We propose to measure the superradiance effect by observing the current through a semiconductor double-dot system. An electron and a hole are injected separately into one of the quantum dots to form an exciton and then recombine radiatively. We find that the stationary current shows oscillatory behavior as one varies the interdot distance. The amplitude of oscillation can be increased by incorporating the system into a microcavity. Furthermore, the current is suppressed if the dot distance is small compared to the wavelength of the emitted photon. This photon trapping phenomenon generates the entangled state and may be used to control the emission of single photons at predetermined times.

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↗

Isolation and identification of Streptomyces sp. and assay of its exocellular water-soluble blue pigments.

A bacterial strain producing a great amount of blue pigment during submerse fermentation was isolated and identified. Based on morphological characteristics, cell-wall chemotype and sequence of 16S rRNA gene, the strain should belong to the genus Streptomyces; it had 99.4% homology of 16S rRNA gene sequence with that of Streptomyces indigocolor. The pigment production by the strain was affected by carbon and nitrogen sources. The main components of the pigment mixture (detected by HPLC and TLC) were tentatively classified as actinorhodin-related compounds. The pigment was relatively stable against light and higher temperature but was sensitive to low pH. The preliminary acute-toxicity determination showed that the pigment was nontoxic (LD50 > 15 mg/g).

Animals↗

Identification of E2F-1/Cyclin A antagonists.

A simple method for the synthesis of a rationally designed (S,S)-[Pro-Leu]-spirolactam scaffold is described. This was expanded to a small biased library of compounds mimicking the 'ZRXL' motif in order to identify E2F-1/Cyclin A antagonists. The synthesized compounds were evaluated in an E2F-1/Cyclin A binding assay and moderately active analogues were identified. In addition, the critical roles of Phe, Leu, Lys, and Arg residues of the identified motif were determined.

Amino Acid Sequence↗

Hepatopancreas is the extraovarian site of vitellogenin synthesis in black tiger shrimp, Penaeus monodon.

The site of yolk protein synthesis in crustaceans has long been a subject of controversy. The vitellogenin gene structure was partially reported only very recently in Macrobrachium rosenbergii, after which the hepatopancreas was confirmed as the extraovarian site of vitellogenin synthesis in that species. Ovaries are the most frequently reported as the site of yolk protein synthesis in penaeid shrimp. Using cDNA reversed-transcribed from mRNA isolated from the hepatopancreas of vitellogenic female shrimp, Penaeus monodon, we found that its deduced amino acid sequence had high identity of 48% with that from M. rosenbergii vitellogenin. A similar location of the intron in the sequenced region of genomic DNA was also found between these two species. We therefore concluded that the hepatopancreas the extraovarian site of vitellogenin synthesis in P. monodon in vivo. The partial structure of vitellogenin gene is presented in this study.

Amino Acid Sequence↗

Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage.

Activation of the stress-activated protein kinase (SAPK/JNK) by genotoxic agents is necessary for induction of apoptosis. We report here that ionizing radiation ionizing radiation exposure induces translocation of SAPK to mitochondria and association of SAPK with the anti-apoptotic Bcl-x(L) protein. SAPK phosphorylates Bcl-x(L) on threonine 47 (Thr-47) and threonine 115 (Thr-115) in vitro and in vivo. In contrast to wild-type Bcl-x(L), a mutant Bcl-x(L) with the two threonines substituted by alanines (Ala-47, Ala-115) is a more potent inhibitor of ionizing radiation-induced apoptosis. These findings indicate that translocation of SAPK to mitochondria is functionally important for interactions with Bcl-x(L) in the apoptotic response to genotoxic stress.

Apoptosis↗

Cardiac troponin I: a marker for post-burn cardiac injury.

Cardiac troponin I (cTnI) was measured by chemiluminescent immunoassay following burn injury. Thirty patients [total body surface area (TBSA) of burn 15-98%] were included in this study and each had four to six blood samples collected at 2-day intervals between the 5th and 14th days post-burn. All patients were found to have increased cTnI on two or more occasions. The mean cTnI concentration was significantly higher in patients with TBSA of burn > 30% (0.34 microg/L compared with 0.09 microg/L, P<0.001) and in those with obvious burn wound exudation (0.32 microg/L compared with 0.12 microg/L, P<0.01). cTnI concentrations peaked at the time when there was obvious burn wound exudation or spontaneous separation of eschar, then decreased after surgical excision. Two patients with persistently high cTnI concentrations developed tachycardia. We conclude that burned patients have varying degrees of non-ischaemic cardiac injury, manifesting as leakage of cTnI from myocytes into the circulation.

Adolescent↗

[The treatment of nasal adhesion after radiotherapy in the patients with nasopharyngeal carcinoma].

OBJECTIVE: In order to find a best way for treating the nasal adhesion after radiotherapy in the patients with nasopharyngeal carcinoma (NPC). METHOD: 4 cases of nasal adhesion after radiotherapy in the patients with NPC were operated by the way through palate. 32 cases were operated under endoscope, in them, 26 cases were set a tube in nasal cavity after operation, and the other 6 cases were not. And the postoperative consequences were analyzed. RESULT: The curative effect of the reconstruction of nasal cavity with a tube through palate are favorable, but the processes are too complex and the trauma are too large for patients. Whereas the way which only sever the nasal adhesion under endoscope is simple, but the disease recur easily. The reconstruction of nasal cavity with a tube under endoscope not only predigest the operation, but also obtain the well effect. CONCLUSION: The reconstruction of nasal cavity with a tube under endoscope is a good way to treat nasal adhesion.

Adult↗

Selective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists.

Recent studies identified a short peptide motif that serves as a docking site for cyclin/cyclin-dependent kinase (cdk) 2 complexes. Peptides containing this motif block the phosphorylation of substrates by cyclin A/cdk2 or cyclin E/cdk2. Here we report that cell membrane-permeable forms of such peptides preferentially induced transformed cells to undergo apoptosis relative to nontransformed cells. Deregulation of E2F family transcription factors is a common event during transformation and was sufficient to sensitize cells to the cyclin/cdk2 inhibitory peptides. These results suggest that deregulation of E2F and inhibition of cdk2 are synthetically lethal and provide a rationale for the development of cdk2 antagonists as antineoplastic agents.

Amino Acid Sequence↗

Site of vitellogenin synthesis determined from a cDNA encoding a vitellogenin fragment in the freshwater giant prawn, Macrobrachium rosenbergii.

Vitellogenesis is an important part of reproductive process in crustaceans, and the process is characterized by the synthesis and accumulation of yolk protein in the developing oocytes. The yolk proteins in crustaceans mainly consist of vitellogenin (Vg) and vitellin (Vn), which are respectively present in extra-oocyte tissues and intra-oocytes. The site and the process of yolk protein synthesis in crustaceans are still controversial. The synthesis site of Vg in a crustacean species, Macrobrachium rosenbergii, is determined by immunological and immunohistochemical techniques, and molecular cloning of a cDNA encoding the primary structure of Vn in this study. The hepatopancrease is clearly shown to be the synthesis site of Vg in this species. The length of Vg mRNA was estimated as about 6 kb from Northern blotting analysis. The partial primary structure of Vg gene is presented, and the post-translational processing are further discussed. For the first time, the partial primary structure of Vg gene and the synthesis site of Vg approached by molecular cloning in crustaceans are presented.

Amino Acid Sequence↗

Effect of panax notoginseng extracts on inferior sperm motility in vitro.

The purpose of this study was to investigate the effects of Panax notoginseng extracts on inferior sperm motility in vitro. Semen samples were collected from 23 patients with sperm motility between 20% and 40%. The sperm count was over 20 x 10(6)/ml in accordance with the World Health Organization standard. 1.0 mg/ml and 2.0 mg/ml of Panax notoginseng extracts including aqueous extract, n-butanol extract, and polysaccharide fraction on sperm motility and progression were evaluated by computer assisted semen analysis. The results demonstrated that sperm motility as well as progression on inferior sperm motility were enhanced at 1 hour and 2 hours after incubation with all three types of extracts.

Adult↗

Monitoring of cardiac troponin I in patients with acute heart failure.

Cardiac troponin I (cTnI) and creatine kinase MB isoenzyme (CK-MB) were measured in the plasma of 37 patients with acute heart failure. Elevated plasma cTnI concentrations were found in 89% of acute heart failure patients (P < 0.001 compared with a normal population), while plasma CK-MB showed no significant difference (P = 0.09). During follow-up, serial measurements of cTnI and CK-MB were performed. In acute heart failure patients, improvement of the clinical profile was associated with declining cTnI concentrations, while deterioration of heart function was closely related to increasing cTnI. Plasma CK-MB activities remained within the normal range throughout the observation period. This preliminary study provides evidence of cardiac damage to functionally overloaded myocytes. cTnI may be a sensitive marker both for early detection of myocyte damage and for monitoring of function in patients with acute heart failure.

Aged↗

Monitoring human chorionic gonadotrophin level: evaluation of urine as an alternative specimen type.

Although urine has been used widely for the qualitative detection of human chorionic gonadotrophin (hCG), serum is chosen conventionally for the serial quantification of the hormone to monitor trophoblastic activity. In response to requests from both clinicians and patients regarding the use of urine as an alternative specimen type, we designed this comparative study to evaluate the possibility, taking into account both laboratory technique and the distribution of hCG within different body fluids. Using the Access Chemiluminescent Immunoassay System, total beta-hCG was measured in serum and urine (n = 30) collected from patients hospitalised for first-trimester abnormal pregnancy. Results obtained with normalised urine (corrected with urinary creatinine) and serum total beta-hCG correlated well (r = 0.98, P < 0.001), and we concluded that urine could be used as an alternative specimen type for the serial quantitation of hCG to monitor trophoblastic activity. However, the assay used must detect the common beta 2 epitope.

Biomarkers↗

Synthesis and potent antifolate activity and cytotoxicity of B-ring deaza analogues of the nonpolyglutamatable dihydrofolate reductase inhibitor Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloyl- L-ornithine (PT523).

Six new B-ring analogues of the nonpolyglutamatable antifolate Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloy l-L-ornithine (PT523, 3) were synthesized with a view to determining the effect of modifications at the 5- and/or 8-position on dihydrofolate reductase (DHFR) binding and tumor cell growth inhibition. The 5- and 8-deaza analogues were prepared from methyl 2-L-amino-5-phthalimidopentanoate and 4-amino-4-deoxy-N10-formyl-5-deaza- and -8-deazapteroic acid, respectively. The 5,8-dideaza analogues were prepared from methyl 2-L-[(4-aminobenzoyl)amino]-5-phthalimidopentanoate and 2, 4-diaminoquinazoline-6-carbonitriles. The Ki for inhibition of human DHFR by the 5-deaza and 5-methyl-5-deaza analogues was about the same as that of 3 (0.35 pM), 11-fold lower than that of aminopterin (AMT, 1), and 15-fold lower than that of methotrexate (MTX, 2). However the Ki of the 8-deaza analogue was 27-fold lower than that of 1, and that of the 5,8-dideaza, 5-methyl-5,8-dideaza, and 5-chloro-5,8-dideaza analogues was approximately 50-fold lower. This trend was consistent with the published literature on the corresponding DHFR inhibitors with a glutamate side chain. In colony formation assays against the human head and neck squamous carcinoma cell line SCC25 after 72 h of treatment, the 5- and 8-deaza analogues were approximately as potent as 3, whereas the 5,8-dideaza analogue was 3 times more potent. 5-Methyl and 5-chloro substitution was also favorable, with the 5-methyl-5-deaza analogue being 2. 5-fold more potent than the 5-deaza analogue. However the effect of 5-methyl substitution was less pronounced in the 5,8-dideaza analogues than in the 5-deaza analogues. The 5-chloro-5,8-dideaza analogue of 3 was the most active member of the series, with an IC50 = 0.33 nM versus 1.8 nM for 3 and 15 nM for MTX. The 5-methyl-5-deaza analogue of 3 was also tested at the National Cancer Institute against a panel of 50 human tumor cell lines in culture and was consistently more potent than 3, with IC50 values in the low-nanomolar to subnanomolar range against most of the tumors. Leukemia and colorectal carcinoma cell lines were generally most sensitive, though good activity was also observed against CNS tumors and carcinomas of the breast and prostate. The results of this study demonstrate that B-ring analogues of 3 inhibit DHFR activity and tumor cell colony formation as well as, or better than, the parent compound. In view of the fact that 3 and its B-ring analogues cannot form polyglutamates, their high cytotoxicity relative to the corresponding B-ring analogues of AMT is noteworthy.

Antineoplastic Agents↗

Interaction of tomudex with radiation in vitro and in vivo.

The potential of the thymidylate synthase inhibitor, Tomudex to interact with ionizing radiation was assessed in vitro and in vivo in comparison with 5-fluorouracil. A concentration of 1 microM Tomudex decreased the shoulder of the radiation survival curves for normally oxygenated and hypoxic human HT-29 colon carcinoma cells and human SCC-25 head and neck squamous carcinoma cells, resulting in enhancement ratios of 10 and 2.8 for normally oxygenated and hypoxic HT-29 cells at 5 Gray, respectively, and enhancement ratios of 19.5 and 2.7 for normally oxygenated and hypoxic SCC-25 cell at 5 Gray, respectively. Two schedules of Tomudex administered to animals bearing the Lewis lung carcinoma resulted in additive tumor growth delay with the fractionated radiation therapy. In nude mice bearing the HT-29 colon carcinoma grown as a xenograft, administration of Tomudex daily for 5 days on a 1 or 2-week schedule resulted in increased tumor growth delay along with fractionated radiation therapy on the same schedules. However, administration of Tomudex intermittently on a 2-week schedule appeared to be more interactive with daily fractionated radiation therapy on the 2-week schedule. In each assay, the results obtained with Tomudex were equal to or exceeded those obtained with 5-fluorouracil. These findings indicate that clinical trial of Tomudex along with fractionated radiation therapy is warranted.

Animals↗