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Biomedical subjects

G Cheng

Publications and source records attributed to G Cheng.

At least 73 records · Page 4Linked to original sources
PubMed2001

[Comparison of stepwise and pulse induced cisplatin-resistant ovarian cancer cell sublines].

OBJECTIVE: To investigate the mechanism responsible for acquired cisplatin resistance induced in human ovarian cancer cell lines by different methods. METHODS: Two resistant cell lines, Skov3/CDDP-P and Skov3/CDDP-50, were established by pulse or stepwise exposures of ovarian cancer cell line Skov3 to cisplatin (CDDP) for 10-12 months with the drug sensitivity monitored by MTT test. The growth rate and cell cycle were compared. The intracellular drug concentration was measured by FACS after 1 hour incubation in 20 mumol/L ADM. The drug-resistance-associated genes: MDR1, MRP, LRP and GST-pi were monitored by RT-PCR and western blotting. RESULTS: The resistance indexes (RI) of Skov3/CDDP-P and Skov3/CDDP-50 were 3.7 and 48.6 to cisplatin, 4.0 and 33.0 to Taxol, 2.2 and 7.3 to adriamycin, 1.5 and 3.4 to VP16, and the intracellular ADM concentration was lowered by 34.6% and 47.2% respectively. Both resistant cell lines grew slowly and exhibited changes in morphology and cell cycle. The expression of the resistance-associated genes MDR1, MRP and LRP was enhanced in both resistant cell lines. However, Skov3/CDDP-50 showed greater increase in MDR1 but Skov3/CDDP-P showed more in MRP. There were no significant changes in GST-pi expression either at mRNA or protein level. The TOPO II activity decreased slightly in both resistant cell lines. CONCLUSION: Stepwise induction of cisplatin resistance in ovarian cancer is more readily acquired in which multiple drug-resistance-associated genes are involved.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

[Landscape change in middle Heihe River Basin].

Using GIS and a landscape structure analysis program FRAGSTATS, this paper dealt with the landscape change in the middle Heihe River Basin during the past 20 years. During the past 20 years, the landscape elements had a complex change of landscape structure and an apparent transition of landscape composition, but the landscape in a whole still displayed a pattern of sharply contrast between oasis landscape and desertification landscape. Human activities significantly changed the distribution and allocation of the limited water resource in the basin, leading to an acute contradiction between desertification and oasisfication. Moreover, the transitional area between desertification and oasisfication was very sensitive to these processes. The decrease of Shannon's diversity index and evenness index manifested the intensive management and reconstruction of landscape by human beings, which improved the socioeconomic benefits of the region on one hand, but decreased the landscape heterogeneity and landscape diversity, leading to the decrease of eco-environmental benefits of some areas in the basin on the other hand. The research method and technology used in this paper were also discussed.

China↗
PubMed2001

[A study on mRNA expression levels of integrin beta 1 during the healing process of mandibular fractures].

OBJECTIVE: The aim of this study was to investigate the spatial and temporal mRNA expression changes of integrin beta 1 during the healing process of mandibular fractures. METHODS: The in situ hybridization was performed using digoxigenin-labeled integrin beta 1 mRNA oligonucleotide probe. During the healing process of mandibular fractures, the staining pattern of beta 1 mRNA was examined both spatially and time-dependently. RESULTS: Integrin beta 1 was widely present in the cells of the fractured bone, especially in osteoblasts. The positive staining was observed in the cytoplasm and nucleolus of osteoblasts. After 7 days of fracture, the expression level of integrin beta 1 increased. The peak appeared between the 14th and the 30th day, and almost recovered to normal between the 60th and 90th day. CONCLUSION: During the healing process of mandibular fracture, the expression level of integrin beta 1 in bone, especially in osteoblasts rose. It is suggested that integrin beta 1 may play an important role in the fracture healing process.

Animals↗
PubMed2001

[Quantum chemistry Ab initio calculation of vibration spectrum of beta-elemene].

In this study, ab initio calculation of vibration spectrum of beta-elemene has been performed at RHF/6-31G* level. Comparison with the experimental results, we succeed in assignment of normal modes of the fundamental frequency of the molecule. We have also discussed the characteristic vibrations, and scaled theoretical frequencies empirically.

Antineoplastic Agents, Phytogenic↗
PubMed2000

CD40 signaling replaces CD4+ lymphocytes and its blocking prevents chronic rejection of heart transplants.

Chronic rejection remains the major obstacle to long term survival in heart transplant recipients. The cellular and molecular mechanisms that underlie chronic rejection are not known, and their discovery can form the basis of clinical intervention. Several investigators have suggested that the development of chronic rejection in solid organ transplants is dependent on help mediated by CD4(+) lymphocytes. Importantly, the mechanism through which help is provided has not been fully delineated in transplant rejection. Using a murine heterotopic heart transplant model without immunosuppression, this study defines the functional role of CD4(+) lymphocytes in chronic rejection. In an MHC class II-mismatched model, we demonstrate that chronic rejection was absolutely contingent on the presence of CD4(+) lymphocytes. Importantly, here we report that signaling through CD40 can replace the requirement of CD4(+) lymphocytes, demonstrated by the development of chronic rejection in CD4 knockout recipients treated with a CD40-activating mAb (FGK45). The return of rejection appears to be a CD8(+) lymphocyte-dependent process, noted by the absence of rejection in FGK45-treated recombinase-activated gene knockout (CD4(+) and CD8(+) lymphocyte-deficient) recipients. The CD40 signaling pathway works independently of B7-CD28 costimulation, as indicated by the development of severe chronic rejection in CD28 knockout recipients. Importantly, this study provides evidence that CD40 ligand-targeted therapies may prevent chronic rejection only in strain combinations where CD4(+) lymphocyte help is absolutely required.

Animals↗
PubMed2000

Conformational transition of DNA in electroreduction studied by in situ UV and CD thin layer spectroelectrochemistry.

Electrochemically induced three conformational transitions of calf thymus DNA from B10.4 to Z10.2-DNA and from B10.2 to B10.4 and to C-DNA in 10 mM phosphate buffer solution (pH 7.21) at glassy carbon electrode are found and studied by in situ circular dichroism (CD) thin layer spectroelectrochemistry with singular value decomposition least square (SVDLS) analysis. It indicates that the so-called B10.2 form and the C-form of DNA may be composed of B10.4 and left-A DNA and of B10.4 and right-A DNA, respectively. The irreversible electrochemical reduction of adenine and cytosine groups in the DNA molecule is studied by UV-Vis spectroelectrochemistry. Some electrochemical parameters alpha n = 0.17, E0' = -0.70 V (vs. Ag/AgCl), and the standard heterogeneous electron transfer rate constant, k0 = 1.8 x 10(-5) cm s(-1), are obtained by double logarithmic analysis and non-linear regression.

Animals↗
PubMed2000

Upregulation of Bcl-x and Bfl-1 as a potential mechanism of chemoresistance, which can be overcome by NF-kappaB inhibition.

In A549 human lung adenocarcinoma cells, we found that TNF-alpha and several commonly used chemotherapeutic agents upregulated the expression of Bcl-x and/or Bfl-1/A1 through an NF-kappaB-dependent pathway. While parental A549 cells were resistant to the cytotoxic effects of both TNF-alpha and chemotherapy agents, NF-kappaB-blocked A549 cells were sensitized to both. Expression of either Bcl-x or Bfl-1/A1 in the NF-kappaB-deficient cells at physiological levels provided differential protection against TNF-alpha and chemotherapeutic treatment. These studies provide a potential mechanism for the phenomenon of chemotherapy-induced chemoresistance, and also reveal a potential strategy by which chemoresistance can be overcome.

Adenocarcinoma↗
PubMed2000

Amperometric quantification of polar organic solvents based on a tyrosinase biosensor.

A novel amperometric biosensor for quantification of the electrochemically inert polar organic solvents based on tyrosinase electrode was preliminarily reported. The biosensor was fabricated by simply syringing an aqueous solution of tyrosinase/PVAVP (PVAVP: copolymer of poly(vinyl alcohol) grafting with 4-vinylpyridine) onto glassy carbon electrode surface followed by drying the modified electrode at +4 degrees C in a refrigerator. The current generated from electrochemical reduction of quinone is a probe signal. The biosensor can be used for quantification of polar organic solvents, and its mechanism was characterized with in situ steady-state amperometry-quartz crystal microbalance experiments. The detection limit, sensitivity, and dynamic range for certain organic solvents are dependent on the kind and concentration of the substrate probe and the hydrophobicity of the immobilization matrix. The response time for all the tested organic solvents is less than 2 min.

Acetonitriles↗
PubMed2000

Vasorelaxant responses to endomorphins, nociceptin, albuterol, and adrenomedullin in isolated rat aorta.

The endogenous peptides endomorphins 1 and 2 are newly discovered, potent, selective mu-opioid receptor agonists. In the present study, the effects of endomorphins 1 and 2 on vascular smooth muscle tone were investigated on isolated rings from rat aorta with and without endothelium. In rings precontracted with phenylephrine, endomorphins 1 and 2 at concentrations of 0.1 and 1.0 microM, nociceptin at concentrations of 1-100 microM, and adrenomedullin at concentrations of 0.01-1.0 microM induced concentration dependent relaxant responses. The endomorphins and nociceptin were less potent than adrenomedullin. No relaxation was induced by endomorphins 1 and 2 in aortic rings denuded of endothelium and precontracted with phenylephrine. The results of the present studies demonstrate that the endomorphins relax aortic vascular smooth muscle from the rat aorta by an endothelium-dependant mechanism.

Adrenomedullin↗
PubMed2000

Estrogen receptor (ER) beta, a modulator of ERalpha in the uterus.

Many of the effects of estrogens on the uterus are mediated by ERalpha, the predominant ER in the mature organ. Because of the poor reproductive capacity of ERbeta knockout (BERKO) female mice (small litter size, multiple-resorbed fetuses), the role of uterine ERbeta was explored. In the immature uterus, ERalpha and ERbeta are expressed at comparable levels in the epithelium and stroma, and 17beta-estradiol (E(2)) treatment decreases ERbeta in the stroma. The immature uterus of untreated BERKO mice exhibits elevated levels of progesterone receptor (PR) and the proliferation-associated protein, Ki-67. It also exhibits exaggerated responsiveness to E(2), as indicated by enlargement of the lumen, increase in volume and protein content of uterine secretion, induction of the luminal epithelial secretory protein, complement C3, and its regulatory cytokine IL-1beta, and induction of vascular endothelial growth factor and insulin-like growth factor 1 but not its receptor. As expected, E(2) increased PR in the stroma and decreased it in the luminal epithelium of wild-type mice. In the BERKO uterus, E(2) induced PR in the stroma but did not down-regulate it in the epithelium. Increased cell proliferation and exaggerated response to E(2) in BERKO suggest that ERbeta plays a role in modulation of the effects of ERalpha and in addition (or as a consequence of this) has an antiproliferative function in the immature uterus.

Animals↗
PubMed2000

Surfactant protein A exhibits inhibitory effect on eosinophils IL-8 production.

Eosinophils are believed to be one of the important sources of cytokines such as IL-8 at the site of allergic inflammation. It has been demonstrated that pulmonary surfactant protein A (SP-A) plays a potential role in modifying inflammation and the immune function. To verify the regulating effect of SP-A on eosinophil cytokine generation, we studied the effect of SP-A by determining of IL-8 production and expression stimulated with sIgA or PMA. SP-A purified from surfactant recovered from patients with alveolar proteinosis was added to eosinophils isolated by the negative selection method with immunomagnetic beads, and cultured for 24 h. The concentrations of IL-8 in the cell-free supernatants and cell lysates were then measured by ELISA. We also used a semiquantitative reverse transcriptase-polymerase chain reaction assay to detect the effect of SP-A on IL-8 mRNA expression. SP-A inhibited the secretion of IL-8 in a dose-dependent fashion. Suppression of IL-8 production by SP-A was significantly inhibited by SP-A antibody (PE10). SP-A also attenuated expression of IL-8 mRNA in eosinophils. These results indicate that SP-A might have the potential role to modify allergic inflammation by inhibiting IL-8 expression and production from eosinophils.

Antibodies↗
PubMed2000

Membrane localization of TRAF 3 enables JNK activation.

Members of the tumor necrosis factor receptor family as well as other receptors achieve their diverse biological effects through the activation of intracellular signals including the c-Jun N-terminal kinase (JNK) pathway. Such signals are believed to be delivered through mediators known as TNF receptor-associated factors (TRAFs). Although the N-terminal zinc finger region of TRAFs has been shown to be essential for downstream signaling, there is no indication yet as to the nature of its role or of the factors that distinguish the N terminus of TRAF 3, which does not activate JNK in the systems examined thus far, from those of other TRAFs, which do activate this pathway. In the present study, it is shown that, among the known TRAFs, localization to the insoluble cell pellet fraction consistently correlates with JNK activation and that both characteristics map to the TRAF N terminus. Furthermore, it is demonstrated that forced localization of TRAF 3 to the cell membrane is sufficient to convert this molecule into an activator of JNK. This suggests that one of the roles of the TRAF N terminus may be to participate in interactions that promote the recruitment of TRAFs to the membrane and that this localization effect plays an important role in TRAF-mediated JNK activation.

Biopolymers↗
PubMed2000

Simultaneous identification of five bifidobacterium species isolated from human beings using multiple PCR primers.

On the basis of 16S rRNA sequences, 5 species-specific forward primers were designed for the identification of 5 Bifidobacterium species isolated from human intestine, namely B. bifidum, B. adolescentis, B. infantis, B. breve and B. longum. As the 5 primers targeted at different sites of 16S rDNA, by using their mixture and a genus-specific reversed primer, the 5 Bifidobacterium species can be simultaneously identified in individual or in mixed culture through PCR amplification. The specificity of the primers was confirmed by the use of genomic DNAs from type strains of all 32 Bifidobacterium species and 6 other relatives. The 5-primer mixture was also applied to the identification of Bifidobacterium strains used commercially. The results turned out to be in accordance with those from conventional identification. This multiple-primer method provides a useful tool for rapid identification of the 5 Bifidobacterium species indicated.

Bifidobacterium↗
PubMed2000

Multi-objective optimization in radiotherapy: applications to stereotactic radiosurgery and prostate brachytherapy.

Treatment planning for radiation therapy is a multi-objective optimization process. Here we present a machine intelligent scheme for treatment planning based on multi-objective decision analysis (MODA) and genetic algorithm (GA) optimization. Multi-objective ranking strategies are represented in the L(p) metric under the displaced ideal model. Goal setting, protocol satisficing and fuzzy ranking of objective importance can be incorporated into the decision scheme to assimilate clinical decision making. For distance measures in the L(p) metric, a dynamic gauge function is defined based on the state energy of the decision system, which is assumed to undergo thermodynamic cooling with iteration time. The MODA scheme interacts with a robust GA engine, which adaptively evolves in the multi-modal landscape that defines the treatment plan quality. A conventionally challenging case of stereotactic radiosurgery of a brain lesion was selected for GA optimization. The resulting dose distributions are compared to human-developed plans, which are commonly regarded as clinically relevant and empirically optimal. The GA-optimized plans achieve substantially better sparing of critical normal neuroanatomy surrounding the brain lesion while respecting the preset constraints on tumor dose uniformity. In addition, machine optimization tends to produce novel treatment strategies which complements expert knowledge. The run time for producing an optimal plan is considerably shorter than the typical planning time for human experts, thus GA can also be used to aid the human treatment planning process. In prostate brachytherapy, MODA-GA was specifically applied to non-ideal conditions in which typical surgical uncertainties in seed implant positioning occur, where noisy objectives were introduced into the optimization scheme. The noisy system is found to be manageable by MODA-GA at uncertainty levels corresponding to reasonably proficient surgery teams. In contrast, noisy objectives would be very difficult to explore by human expert planners. Potential use of noisy optimization with time series analysis is being explored for error-corrective computer guidance in the operating room for prostate seed implantation. In conclusion, the combination of MODA and GA optimization offers both a solution to practical treatment planning tasks and the potential for real time applications in radiotherapy.

Algorithms↗
PubMed2000

Specialized contributions by alpha(1,3)-fucosyltransferase-IV and FucT-VII during leukocyte rolling in dermal microvessels.

Noninflamed skin venules support constitutive leukocyte rolling. P-selectin controls the rolling frequency, whereas E-selectin dictates rolling velocity (Vroll). Fucosylated selectin ligands are essential for all interactions, as rolling was absent in mice doubly deficient in alpha1,3-fucosyltransferase (FucT)-IV and FucT-VII. The rolling fraction was reduced in FucT-VII-/- animals but normal in FucT-IV-/- mice. However, Vroll was markedly increased in both strains. P-selectin ligands generated by FucT-VII are crucial for initial leukocyte tethering, whereas E-selectin ligands that permit maximum slowing of Vroll require simultaneous expression of FucT-IV and FucT-VII. These results demonstrate a role for FucT-IV in selectin-dependent adhesion and suggest that the endothelial selectins and FucTs have distinct but overlapping functions in the immunosurveillance of the skin.

Animals↗
PubMed2000

Identification of paraldol-deoxyguanosine adducts in DNA reacted with crotonaldehyde.

Crotonaldehyde (1) is a mutagen and carcinogen, but its reactions with DNA have been only partially characterized. In a previous study, we found that substantial amounts of 2-(2-hydroxypropyl)-4-hydroxy-6-methyl-1,3-dioxane (paraldol, 7), the dimer of 3-hydroxybutanal (8), were released upon enzymatic or neutral thermal hydrolysis of DNA that had been allowed to react with crotonaldehyde. We have now characterized two paraldol-deoxyguanosine adducts in this DNA: N(2)-[2-(2-hydroxypropyl)-6-methyl-1,3-dioxan-4-yl]deoxyguanosine (N(2)-paraldol-dG, 13) and N(2)-[2-(2-hydroxypropyl)-6-methyl-1, 3-dioxan-4-yl]deoxyguanylyl-(5'-3')-thymidine [N(2)-paraldol-dG-(5'-3')-thymidine, 14]. Four diastereomers of N(2)-paraldol-dG (13) were observed. Their overall structures were determined by (1)H NMR, by MS, and by reaction of paraldol with deoxyguanosine and DNA. (1)H NMR data showed that two diastereomers had all equatorial substituents in the dioxane ring, while two others had an axial 6-methyl group. Preparation of paraldol with the (R)- or (S)-configuration at the 6-position of the dioxane ring and the carbinol carbon of the 2-(2-hydroxypropyl) group allowed partial assignment of the absolute configurations of N(2)-paraldol-dG (13). Four diastereomers of N(2)-paraldol-dG-(5'-3')-thymidine (14) were observed. Their overall structure was determined by (1)H NMR, MS, and hydrolysis with snake venom or spleen phosphodiesterase. Reactions of nucleosides and nucleotides with paraldol demonstrated that adducts were formed only from deoxyguanosine and its monophosphates. Experiments with DNA that had been reacted with crotonaldehyde indicated that N(2)-paraldol-dG-containing adducts in DNA are relatively resistant to enzymatic hydrolysis. The results of this study demonstrate that the reaction of crotonaldehyde with DNA is more complex than previously recognized and that stable N(2)-paraldol-dG adducts are among those that should be considered in assessing mechanisms of crotonaldehyde mutagenicity and carcinogenicity.

Aldehydes↗
PubMed2000

Identification of DNA adducts of acetaldehyde.

Acetaldehyde is a mutagen and carcinogen which occurs widely in the human environment, sometimes in considerable amounts, but little is known about its reactions with DNA. In this study, we identified three new types of stable acetaldehyde DNA adducts, including an interstrand cross-link. These were formed in addition to the previously characterized N(2)-ethylidenedeoxyguanosine. Acetaldehyde was allowed to react with calf thymus DNA or deoxyguanosine. The DNA was isolated and hydrolyzed enzymatically; in some cases, the DNA was first treated with NaBH(3)CN. Reaction mixtures were analyzed by HPLC, and adducts were isolated and characterized by UV, (1)H NMR, and MS. The major adduct was N(2)-ethylidenedeoxyguanosine (1), which was identified as N(2)-ethyldeoxyguanosine (7) after treatment of the DNA with NaBH(3)CN. The new acetaldehyde adducts were 3-(2-deoxyribos-1-yl)-5,6,7, 8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2-a]purine-10(3H)one (9), 3-(2-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-(N(2)-deoxyguanosyl+ ++)- 6-methylpyrimido[1,2-a]purine-10(3H)one (12), and N(2)-(2, 6-dimethyl-1,3-dioxan-4-yl)deoxyguanosine (11). Adduct 9 has been previously identified in reactions of crotonaldehyde with DNA. However, the distribution of diastereomers was different in the acetaldehyde and crotonaldehyde reactions, indicating that the formation of 9 from acetaldehyde does not proceed through crotonaldehyde. Adduct 12 is an interstrand cross-link. Although previous evidence indicates the formation of cross-links in DNA reacted with acetaldehyde, this is the first reported structural characterization of such an adduct. This adduct is also found in crotonaldehyde-deoxyguanosine reactions, but in a diastereomeric ratio different than that observed here. A common intermediate, N(2)-(4-oxobut-2-yl)deoxyguanosine (6), is proposed to be involved in formation of adducts 9 and 12. Adduct 11 is produced ultimately from 3-hydroxybutanal, the major aldol condensation product of acetaldehyde. Levels of adducts 9, 11, and 12 were less than 10% of those of N(2)-ethylidenedeoxyguanosine (1) in reactions of acetaldehyde with DNA. As nucleosides, adducts 9, 11, and 12 were stable, whereas N(2)-ethylidenedeoxyguanosine (1) had a half-life of 5 min. These new stable adducts of acetaldehyde may be involved in determination of its mutagenic and carcinogenic properties.

Acetaldehyde↗