Biomedical subjects

Yong Chen

Publications and source records attributed to Yong Chen.

At least 235 records · Page 13Linked to original sources

PubMed2002

The four-helix bundle of the neuronal target membrane SNARE complex is neither disordered in the middle nor uncoiled at the C-terminal region.

Assembly of the SNARE complex is an essential step for membrane fusion and neurotransmitter release in neurons. The plasma membrane SNAREs syntaxin 1A and SNAP-25 (t-SNAREs) and the delivery-vesicle SNARE VAMP2 (or v-SNARE) contain the "SNARE regions" that essentially mediate SNARE pairing. Using site-directed spin labeling and EPR distance measurement we show that two identical copies of the SNARE region from syntaxin 1A intertwine as a coiled coil near the "ionic layer" region. The structure of the t-SNARE complex appears to be virtually identical to that of the ternary SNARE complex, except that VAMP2 is substituted to the second copy of syntaxin 1A. Furthermore, it appears that the coiled coil structure is maintained up to residue 259 of syntaxin 1A, identical to that of the ternary complex. These results are somewhat contradictory to the previous reports, suggesting that the t-SNARE complex has the disordered midsection (Xiao, W. Z., Poirier, M. A., Bennett, M. K., and Shin, Y. K. (2001) Nat. Struc. Biol. 8, 308-311) and the uncoiled C-terminal region (Margittai, M., Fasshauer, D., Pabst, S., Jahn, R., and Langen, R. (2001) J. Biol. Chem. 276, 13169-13177). The newly refined structure of the t-SNARE complex provides a basis for the better understanding of the SNARE assembly process. It also provides possible structural-functional clues to the membrane fusion in the v-SNARE deleted fusion models.

Amino Acid Sequence↗

PubMed2002

Effects of carnosine on volatile generation from Maillard reaction of ribose and cysteine.

Carnosine occurs naturally in meat and meat products in significant quantity, and it possesses strong antioxidant activity that inhibits lipid oxidation and enhances shelf life. In this study, the effects of carnosine on thermal flavor generation were investigated using the model system of cysteine and ribose, which was heated to the roasting temperature of 180 degrees C for 2 h at pH 5 and pH 8.5. The results indicated that carnosine affected volatile formation in a complex manner. Volatiles identified from the liquid phase of the reaction systems of ribose and cysteine showed that the sulfur-containing compounds such as thiophenes, thiazoles, and polysulfides were the most abundant compounds. The addition of carnosine into the reaction mixtures in general caused a reduction in contents of thiophenes and some important meaty flavor compounds such as 2-methyl-3-furanthiol, 2-furfurylthiol, and their associated dimers. On the other hand, it facilitated the generation of several important nitrogen-containing volatiles such as pyrazine, methylpyrazine, 2,6-dimethylpyrazine, and other alkyl pyrazines and thiazoles, which are known to elicit roasty and nutty flavor notes. The results suggested that carnosine acts as a nitrogenous source to facilitate the formation of nitrogen-containing compounds, possibly by degradation to form ammonia.

Antioxidants↗

PubMed2002

Coupling parameter in synchronization of diluted neural networks.

We study the critical features of a coupling parameter in the synchronization of neural networks with diluted synapses. Based on simulations, an exponential decay form is observed in the extreme case of global coupling among subsystems and full connection in each network: there exists a maximum and a minimum of the critical coupling intensity for synchronization in this spatially extended system. For partial coupling, we present the primary result about the critical coupling fraction for various linking degrees of the networks.

Neural Networks, Computer↗

PubMed2002

Coherent emission of light by thermal sources.

A thermal light-emitting source, such as a black body or the incandescent filament of a light bulb, is often presented as a typical example of an incoherent source and is in marked contrast to a laser. Whereas a laser is highly monochromatic and very directional, a thermal source has a broad spectrum and is usually quasi-isotropic. However, as is the case with many systems, different behaviour can be expected on a microscopic scale. It has been shown recently that the field emitted by a thermal source made of a polar material is enhanced by more than four orders of magnitude and is partially coherent at a distance of the order of 10 to 100nm. Here we demonstrate that by introducing a periodic microstructure into such a polar material (SiC) a thermal infrared source can be fabricated that is coherent over large distances (many wavelengths) and radiates in well defined directions. Narrow angular emission lobes similar to antenna lobes are observed and the emission spectra of the source depends on the observation angle--the so-called Wolf effect. The origin of the coherent emission lies in the diffraction of surface-phonon polaritons by the grating.

Journal Article↗

PubMed2002

A novel locus for autosomal dominant nonsyndromic hearing loss identified at 5q31.1-32 in a Chinese pedigree.

Hearing impairment is an extremely heterogeneous disorder. A total of 35 loci and 17 related genes for autosomal dominant nonsyndromic hearing loss have been identified. In a Chinese pedigree characterized by autosomal dominant inheritance with bilateral, postlingual, progressive, and sensorineural nonsyndromic hearing impairment, the putative disease gene locus was localized to chromosome 5q31.1-32 by a genome-wide scan. Fine mapping indicated that the disease gene was located within an 8.8-cM region between markers D5S2056 and D5S638, with a maximum two-point logarithm of differences (LOD) score of 6.89 (theta = 0) at D5S2017. By the candidate gene approach, mutation screening of the DIAPH1 and POU4F3 genes at 5q31 was performed. No mutation was found, suggesting that this is a novel deafness locus, which has been named DFNA42.

China↗

PubMed2002

Neurologic defects and selective disruption of basement membranes in mice lacking entactin-1/nidogen-1.

Entactin-1 (nidogen-1) is an ubiquitous component of basement membranes. From in vitro experiments, entactin-1 was assigned a role in maintaining the structural integrity of the basement membrane because of its binding affinity to other components, such as type IV collagen and laminin. Entactin-1 also interacts with integrin receptors on the cell surface to mediate cell adhesion, spreading, and motility. Targeted disruption of the entactin-1 gene in the mouse presented in this study revealed a duplication of the entacin-1 locus. Homozygous mutants for the functional locus lacked entactin-1 mRNA and protein and often displayed seizure-like symptoms and loss of muscle control in the hind legs. The behavior patterns suggested the presence of neurologic deficits in the central nervous system, thus providing genetic evidence linking entactin-1 to proper functions of the neuromuscular system. In homozygous mutants, structural alterations in the basement membranes were found only in selected locations including brain capillaries and the lens capsule. The morphology of the basement membranes in other tissues examined superficially appeared to be normal. These observations suggest that the lost functions of entactin-1 result in pathologic changes that are highly tissue specific.

Animals↗

PubMed2002

Use of IMiD3, a thalidomide analog, as an adjunct to therapy for experimental tuberculous meningitis.

Tuberculous meningitis (TBM), the most severe form of Mycobacterium tuberculosis infection in humans, is associated with significant morbidity and mortality despite successful treatment with antituberculous drugs. This is due to the irreversible brain damage subsequent to the local inflammatory response of the host to M. tuberculosis. Corticosteroids have been used in conjunction with antituberculous therapy in an attempt to modulate the inflammatory response, but this strategy has been of limited success. Therefore, we examined whether combining antituberculous drugs with the immunomodulatory drug thalidomide or with a new thalidomide analog, immunomodulatory drug 3 (IMiD3), would be effective in reducing morbidity and mortality in an experimental rabbit model of TBM. Intracisternal inoculation of 5 x 10(4) CFU of Mycobacterium bovis Ravenel in rabbits induced progressive subacute meningitis characterized by high cerebrospinal fluid (CSF) leukocytosis, protein influx, release of tumor necrosis factor (TNF), substantial meningeal inflammation, and mortality by day 28. Treatment with antituberculous drugs or with antituberculous drugs plus thalidomide improved the clinical course of disease somewhat and increased survival to about 50%. In contrast, treatment with antituberculous drugs in combination with IMiD3 limited pathological neurologic changes and resulted in marked improvement (73%) in survival. IMiD3 treatment was also associated with reduced leukocytosis in the CSF and significantly lower levels of TNF in CSF and plasma. Histologically, the meningeal inflammation in animals treated with antituberculous drugs plus IMiD3 was considerably attenuated compared to that of the other treatment groups. These results suggest a potential role for IMiD3 in the management of TBM in patients.

Animals↗

PubMed2002

Isobolographic analysis of the analgesic interactions between ketamine and tramadol.

Owing to different mechanisms of analgesia, we hypothesized that the combination of ketamine and tramadol could produce synergistic or additive antinociceptive effects. Swiss albino mice were administered intraperitoneally with ketamine, tramadol, a combination of ketamine and tramadol, or saline, and the resulting antinociceptive effects were tested in the mouse tail-flick and formalin tests. The potencies of the two drugs alone or in combination were obtained by fitting data to the Sigmoid Emax equation. Isobolographic analysis was performed to evaluate the interaction. CNS depression was also monitored. Results showed that tramadol exhibited apparent dose-dependent effects in the tail-flick test, and in phase 1 and phase 2 of the formalin test. Ketamine dose-dependently inhibited the phase 2 responses, but failed to modify the phase 1 and tail-flick responses. Combination of tramadol and ketamine produced significant synergistic interactions only in phase 2 of the formalin test (P < 0.05). The synergistic combinations also displayed less CNS depression than when an equianalgesic dose of ketamine was administered alone. We conclude that in the acute thermal or chemical pain model, ketamine is not effective and the net effect of ketamine and tramadol in combination was simply additive after systemic administration. However, the coadministration produced synergistic antinociception in the chemical-induced persistent pain model.

Analgesics↗

PubMed2002

Polymorphism of structural forms of C-reactive protein.

C-reactive protein (CRP), as a classical member of acute phase reactants, plays a variety of physiological functions in vivo and in vitro. Here we show that CRP exists in different structural forms in solution and on phospholipid membranes. At least three types of CRP structures, i.e., the pentameric ring-like form, the small globulin-like form and the fibril-like structure, were observed by combination of size-exclusion chromatography and electron microscopy. The pentameric ring-like CRPs were discovered mostly on ligand containing membrane in a calcium-dependent manner. The globulin-like monomers found on negatively charged membrane in the absence of calcium exhibited structural stability. The fibril-like structures, that have not been reported before, were formed by face-to-face stacking of pentameric CRP in a number from several to hundreds. The freshly purified CRPs form short single-strand fibrils while those CRPs stored for more than several days form long and bundled fibrils. The different structural forms may convert to each other under certain conditions, which gives some hints as to the structural basis of multiple functions of CRP.

Animals↗

PubMed2002

[DSA manifestation of primary hepatocellular carcinoma complicated by tumor thrombus in the inferior vena cava].

OBJECTIVE: To study the manifestations of the primary hepatocellular carcinoma (PHC) complicated by tumor thrombus (TT) in the inferior vena cava (IVC) in digital subtraction angiography (DSA) and to understand their clinical implications. METHODS: A retrospective study of the hepatic arterial angiography, the inferior vena cavography and the interventional treatment in 8 cases of PHC patients was conducted. RESULTS: Hepatic arterial-venous shunt, tumor thrombus in the hepatic veins and filling defect in the IVC were identified in 6 patients. The IVC TT presented obvious "strip signs" in DSA images. In 4 patients TT in the right atrium (RA) was found in connection with the IVC TT. Scattered lipiodol deposits were observed in the IVC TT, which decreased in volume in 4 patients after hepatic arterial chemoembolization. Five patients with TT in the IVC and blood backflow blockage received IVC stent implantation for alleviation of the symptoms. CONCLUSIONS: The blood supply of TT in IVC is derived from the hepatic artery, and computed tomography, magnetic resonance imaging and DSA all have superior diagnostic value for such TT. Transcatheter hepatic arterial chemoembolization and IVC stent implantation may constitute effective treatment modalities for PHC complicated by TT in the IVC.

Adult↗

PubMed2002

Effect of dosage of anticancer agents during transcatheter arterial chemoembolization on T cell subsets in patients with hepatocellular carcinoma.

OBJECTIVE: To investigate the effects of the dosage of anticancer agents during transcatheter arterial chemoembolization (TACE) on the T cell subsets in patients with hepatocellular carcinoma (HCC). METHODS: Thirty-six patients with unresectable HCC were randomly divided into 2 groups to receive superselective TACE. Patients in group A (n=18) received low-dose (2-4 mg) mitomycin C (MMC) as the anticancer drug when the tumor was less than 5 cm in diameter; when the tumor ranged from 5 and 8 cm in diameter, 4-6 mg MMC along with 10 mg epirubicin (EPI) was given, and in cases of even larger tumors, 6-8 mg MMC, 10 mg EPI and 100 mg CBP were prescribed. Conventional chemotherapy regimen constituted by 10 mg MMC, 40 mg PI and 300 mg CBP was adopted in group B (n=18). The peripheral blood T cell subsets including CD3(+), CD4(+), CD8(+), NK, CD4(+)/CD8(+) ratio, CD4(+)CD45(+), CD4(+)CD29(+), CD8(+)CD28(+) and CD8(+)CD28- were measured by flow cytometry in both groups before and one week after treatment. RESULTS: The T cell subsets were comparable in the 2 groups before the treatment. After TACE, no significant changes occurred in CD3(+), CD4(+), CD8(+), NK, CD4(+)/CD8(+), CD4(+)CD29(+) or CD8(+)CD28- cells in group A, while significant decrease in CD4(+)CD45(+) and increase in CD8(+)CD28(+) cells were observed (P<0.05 and P<0.001, respectively). In group B, CD4(+) and CD4(+)CD29(+) levels, together with CD4(+)/CD8(+) ratio, were significantly lower than those before treatment (P<0.05), but CD8(+) and CD8(+)CD28- subsets were significantly higher (P<0.05). CONCLUSIONS: The cellular immune function of HCC patients is significantly impaired by anticancer drugs for TACE at conventional dose, while low-dose of the drugs may enhance the cellular immune function.

Adult↗

PubMed2002

[Clinical analysis of laparoscopic pelvic and paraaortic lymphadenectomy treated patients with gynecological malignancies].

OBJECTIVE: To investigate the possibility and value of laparoscopic radial hysterectomy with lymphadenectomy in patients with gynecology malignancies. METHODS: From July 2000 through June 2002, we performed laparoscopic radial hysterectomy with lymphadenectomy on 56 patients with biopsy-proven endometrial or cervical carcinoma (21 endometrial cancer and 35 cervical cancers). Pelvic, para-aortic, and combinations of both pelvic and para-aortic lymphadenectomies were performed depending on the primary site of the disease and indication for lymph node dissection. RESULTS: Laparoscopic procedure required an average of 3.1 h, with an average blood loss of 198 ml. The average number of nodes was 16. Patients undergoing laparoscopic assisted vaginal radical hysterectomy and lymphadenectomy alone were admitted for 9.6 days on average. There were 5 patients with intraoperative complications. Two patients were bladder injury and other two patients with venous injury. One patient was colon injury and converted to an abdominal procedure. There were no ureteral or intestinal injuries. Postoperative complications occurred in 3% of patients and only one was considered ureteral constriction 1 month after operation. There has been one patient with trocar site recurrences 4 weeks after operation. Three patients have retention of urine. CONCLUSIONS: Laparoscopic assisted vaginal radical hysterectomy and lymphadenectomy was feasible and safe for treatment of cervical or endometrial cancer. Also it was a less invasive, and recovery time was reduced. This was reliable and accurate method for evaluating lymph node metastasis of cervical or endometrial carcinoma.

Adult↗

PubMedDate not supplied

Research on double-probe, double- and triple-tip effects during atomic force microscopy scanning.

Information obtained by atomic force microscopy (AFM) depends strongly on the kind of probe or tip used; therefore, probe and tip effects have to be taken into account when verifying or interpreting the data acquired. In many papers, double-tip effects have been mentioned while other research was done; however, there are only a few special reports on double- or triple-tip effects, especially double-probe effects. In our paper, metaphase chromosomes of Chinese hamster ovary (CHO) cells, aggregates of pectin molecules, membrane surface of mouse embryonic stem cells, and R-phycoerythrin-conjugated immunoglobulin G complexes were imaged by AFM with high-quality probes, double-probe cantilever, and double-tip and triple-tip probes, respectively, in order to determine double-probe, double-tip, and triple-tip effects during AFM scanning. We found that the double-probe, double-tip, and triple-tip effects share the same principle, and that these effects correlate with distance and height differences between probes of double-probe cantilever or tips of double-tip or multiple-tip probes. Since many other factors influence double-probe or double-tip effects, more in-depth studies must be undertaken. However, this initial research will make all users of AFM techniques aware of double-probe and double-tip or triple-tip effects during AFM scanning and aid in verifying or interpreting the data acquired.

Animals↗

PubMedDate not supplied

Molecular binding behavior of pyridine-2,6-dicarboxamide-bridged bis(beta-cyclodextrin) with oligopeptides: switchable molecular binding mode.

Bridged bis(beta-cyclodextrin) 1 with a pyridine-2,6-dicarboxamide linker was synthesized, and its inclusion complexation behavior with some aliphatic oligopeptides was investigated in aqueous buffer solution of pH 2.0 and 7.2 at 25 degrees C by means of circular dichroism, fluorescence, and 2D NMR techniques. The results show that the resulting inclusion complexes of 1 with oligopeptides adopt a cooperative "cyclodextrin-guest-cyclodextrin" sandwich binding mode in a neutral media, but a "guest-linker-cyclodextrin" coinclusion binding mode in an acidic media. These switchable binding modes consequently rationalize the binding ability of bis(beta-cyclodextrin) 1 at different pH values; that is, 1 shows the stronger association with oligopeptides in a neutral media. Because of the simultaneous contributions of hydrophobic, hydrogen bond, and electrostatic interactions, bis(beta-cyclodextrin) 1 affords length-selectivity up to 4.7 for the Gly-Gly/Gly-Gly-Gly pair at pH 2.0 and sequence-selectivity up to 4.2 for the Gly-Leu/Leu-Gly pair at pH 7.2. These phenomena are discussed from the viewpoint of the size-fit concept and the multipoint recognitions between host and guest.

Binding Sites↗

PubMedDate not supplied

Binding behavior of aliphatic oligopeptides by bridged and metallobridged bis(beta-cyclodextrin)s bearing an oxamido bis(2-benzoic) carboxyl linker.

beta-Cyclodextrin dimers bearing an oxamido bis(2-benzoic) carboxyl linker (1) or its metal complexes (2 and 3) were newly synthesized, and their inclusion complexation behavior with a series of representative aliphatic oligopeptides, i.e., Leu-Gly, Gly-Leu, Gly-Pro, Glu-Glu, Gly-Gly, Gly-Gly-Gly, and Glu(Cys-Gly), was elucidated by means of UV/vis, circular dichroism, fluorescence, and 2D NMR spectroscopy in Tris-HCl buffer solution (pH 7.4) at 25 degrees C. The results obtained indicated that metallobridged bis(beta-cyclodextrin)s 2 or 3 could significantly enhance the original molecular binding abilities of parent bis(beta-cyclodextrin) 1 toward model substrates through the cooperative binding of two cyclodextrin moieties and the additional chelation effect supplied by the coordinated metal centers. It is interesting that hosts 2 and 3 displayed an entirely different fluorescence behavior upon complexation with guest oligopeptides. Among the guest peptides examined, 3 showed the highest complex formation constant of 68 200 M(-)(1) for Glu-Glu, up to 510-fold as compared with 1 (135 M(-)(1)), while 1 gave excellent molecular selectivity for Glu(Cys-Gly)/Glu-Glu pair, up to 51-fold. The molecular binding ability and selectivity were discussed from the viewpoints of the induced-fit and multiple recognition mechanism between host and guest.

Amides↗

PubMedDate not supplied

Small increases in pH enhance retroviral vector transduction efficiency of NIH-3T3 cells.

Increases in pH between 7.1 and 7.7 increase the efficiency of polybrene (Pb)- and protamine sulfate (PS)-aided retroviral transduction of NIH-3T3 cells in a serum-lot-dependent manner. The increase in Pb-aided transduction efficiency at pH 7.7, relative to the value at pH 7.33, ranged from 13% to 49% for three serum lots. For a constant Moloney murine leukemia virus (MMLV) vector dilution at pH 7.33, three different serum lots resulted in absolute transduction efficiencies ranging from 29% to 53% using Pb. At the same vector dilution, PS-aided transduction was less effective on an absolute basis than Pb-aided transduction, but the benefit of elevated pH was more pronounced with PS. There was a similar enhancement with PS at elevated pH for a murine stem cell virus (MSCV) vector as for the MMLV vector. The benefit at pH 7.7 for PS-aided transduction was partially due to greater PS stability at elevated pH. Heat inactivating the serum supplement or adding protease inhibitors helped to stabilize PS. This increased the absolute transduction efficiency but decreased the relative benefit of elevated pH to a level similar to that for Pb-aided transduction. Incubating Pb with the vector at pH 7.1 for 10 min, prior to readjusting to pH 7.7 and transducing the cells, was sufficient to abrogate the beneficial effects of transduction at pH 7.7. In contrast, prior exposure of PS with vector at pH 7.1 did not affect subsequent transduction at pH 7.7. These results indicate that pH is an important variable in retroviral transduction and that the relative benefits of Pb or PS on retroviral vector transduction will vary with the pH, polymer addition method, and serum lot.

3T3 Cells↗

PubMedDate not supplied

Transduction efficiency of pantropic retroviral vectors is controlled by the envelope plasmid to vector plasmid ratio.

Pantropic retroviral vectors pseudotyped with vesicular stomatitis virus envelope G protein (VSV-G) are typically produced by transient transfection of the VSV-G expression plasmid because constitutive expression of VSV-G is cytotoxic. To produce pantropic vectors, the VSV-G expression plasmid and the vector plasmid are cotransfected into a packaging cell line, such as 293-gag-pol. Typically, the ratio of VSV-G plasmid to the vector plasmid ranges from 0.33 to 1.0. However, it is not clear that this range is optimal for vector production. In this study we have systematically examined the effect of the ratio of VSV-G plasmid (pVSV-G) to vector plasmid on vector production. For this, 293-gag-pol stable packaging cells were cotransfected with pVSV-G and an enhanced green fluorescent protein- (EGFP-) expressing retroviral vector plasmid (pLTR-EGFP) by use of lipofectamine. Vector was collected following transfection and used to transduce three target cell lines, namely, 3T3 fibroblasts, telomerase-immortalized human diploid fibroblasts (HDF), and the human hepatoma cell line HuH7. Transduction efficiency was evaluated for vectors produced at different pVSV-G:pLTR-EGFP ratios such that the total amount of plasmid transfected into 293-gag-pol cells was kept constant. Our results indicate that transduction efficiency is greatest when the pVSV-G:pLTR-EGFP ratio is substantially below 1.0. For 3T3 and HDF cells, the maximum transduction efficiency was obtained when a ratio of pVSV-G:pLTR-EGFP ranging from 0.053 to 0.2 was used for transfection. The relative magnitude of this effect was greater for lower transduction efficiencies in control cultures. For HuH7 cells, the beneficial effects were smaller than those observed when HDF or 3T3 cells were used. The difference in transduction efficiency for vector produced under various pVSV-G:pLTR-EGFP ratios was not due to differences in the proliferation of packaging cells or target cells. Further characterization showed that the amount of vector RNA relative to p30gag decreased as the ratio of pVSV-G:pLTR-EGFP increased. These results indicate that transduction efficiency increases with increasing levels of vector RNA as long as a minimally sufficient level of pantropic envelope protein is expressed.

3T3 Cells↗

PubMedDate not supplied

The effects of natural flavonoids on lipoxygenase-mediated oxidation of compounds with a benzene ring structure--a new possible mechanism of flavonoid anti-chemical carcinogenesis and other toxicities.

Numerous studies have strongly suggested that flavonoids exhibit antimutagenic, anticarcinogenic, antiallergic, and anti-inflammatory properties, but the mechanism is still far from clear. In this study, the effect of natural flavonoid compounds, such as green tea polyphenol, epigallocatechin gallate, quercetin, and rutin on lipoxygenase-mediated co-oxidation of guaiacol, benzidine, paraphenylenediamine, and dimethoxybenzidine was investigated. Green tea polyphenol, epigallocatechin gallate, quercetin, and rutin can reduce the co-oxidation reaction speed of tested compounds mediated by soybean lipoxygenase and the production of oxidative products and free radical intermediates. Their median inhibition concentrations on guaiacol oxidation mediated by soybean lipoxygenase were 8.22 mg.L-1, 17.8 micromol.L-1, 41.5 micromol.L-1, and 46.3 micromol.L-1, respectively. These were all significantly lower than glutathione, dithiothreitol, butylated hydroxyanisole and gossypol. The data collected in this study suggest that flavonoids may have an anticarcinogenicity and antitoxicity effect through inhibition of oxidative activation.

Anticarcinogenic Agents↗