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Biomedical subjects

Lu Wang

Publications and source records attributed to Lu Wang.

143 records · Page 8Linked to original sources
PubMed2002

Bromite ion catalysis of the disproportionation of chlorine dioxide with nucleophile assistance of electron-transfer reactions between ClO(2) and BrO(2) in basic solution.

The rate of ClO(2) conversion to ClO(2)(-) and ClO(3)(-) is accelerated by BrO(2)(-), repressed by ClO(2)(-), and greatly assisted by many nucleophiles (Br(-) > PO(4)(3-) > HPO(4)(2-) > CO(3)(2-) > Cl(-) approximately OH(-) > CH(3)COO(-) approximately SO(4)(2-) approximately C(5)H(5)N >> H(2)O). The kinetics (at p[H(+)] = 9.3-12.9) show that the first step of the mechanism is an electron transfer between ClO(2) and BrO(2)(-) (k(1) = 36 M(-1) s(-1)) to give ClO(2)(-) and BrO(2). This highly reversible reaction (k(1)/k(-1) = 1 x 10(-6)) accounts for the observed inhibition by ClO(2)(-). The second step is an electron transfer between ClO(2) and BrO(2) to regenerate BrO(2)(-) and form ClO(3)(-). A novel aspect of the second step is the large kinetic contribution from nucleophiles (k(Nu)) that assist the electron transfer between ClO(2) and BrO(2). The k(Nu) (M(-2) s(-1)) values at 25.0 degrees C vary from 2.89 x 10(8) for Br(-) to 2.0 x 10(4) for H(2)O.

Journal Article↗
PubMed2002

Characterization of phycoviolobilin phycoerythrocyanin-alpha 84-cystein-lyase-(isomerizing) from Mastigocladus laminosus.

Cofactor requirements and enzyme kinetics have been studied of the novel, dual-action enzyme, the isomerizing phycoviolobilin phycoerythrocyanin-alpha84-cystein-lyase(PVB-PEC-lyase) from Mastigocladus laminosus, which catalyses both the covalent attachment of phycocyanobilin to PecA, the apo-alpha-subunit of phycoerythrocyanin, and its isomerization to phycoviolobilin. Thiols and the divalent metals, Mg2+ or Mn2+, were required, and the reaction was aided by the detergent, Triton X-100. Phosphate buffer inhibits precipitation of the proteins present in the reconstitution mixture, but at the same time binds the required metal. Kinetic constants were obtained for both substrates, the chromophore (Km = 12-16 micro m, depending on [PecA], kcat approximately 1.2 x 10-4.s-1) and the apoprotein (Km = 2.4 micro m at 14 micro m PCB, kcat = 0.8 x 10-4.s-1). The kinetic analysis indicated that the reconstitution reaction proceeds by a sequential mechanism. By a combination of untagged and His-tagged subunits, evidence was obtained for a complex formation between PecE and PecF (subunits of PVB-PEC-lyase), and by experiments with single subunits for the prevalent function of PecE in binding and PecF in isomerizing the chromophore.

Bacterial Proteins↗
PubMed2002

Monte Carlo evaluation of 6 MV intensity modulated radiotherapy plans for head and neck and lung treatments.

Intensity modulated radiotherapy (IMRT) beams may have strong fluence variations and are advantageous at disease sites such as lung and head and neck (H&N), where neighboring tissues have very different electron densities. We use Monte Carlo (MC) dose calculations to evaluate the dosimetric effects of these inhomogeneities for 10 clinical IMRT treatment plans for five lung patients and four H&N patients. All beams are 6 MV photons. "Standard plans" were first produced on a clinical treatment planning system which optimizes beam intensity distributions to meet dose and dose-volume constraints and calculates dose using a measurement-based pencil-beam algorithm with an equivalent pathlength inhomogeneity correction. Patient anatomy and electron densities were obtained from patient-specific CT images. The dose distribution of each beam was recalculated with the MC method, using the same CT images, beam geometry, beam weighting and optimized fluence intensity distributions as the corresponding standard plan. For the lung cases, the MC calculated dose distributions are characterized by reduced penetrations and increased penumbra due to larger secondary electron range in the low-density media, which is not accurately accounted for in the pencil beam algorithm. For the lung cases, the PTV was underdosed; except for one dose-volume index, underdose was less than 10%. Individual H&N fields are affected to different degrees by tissue inhomogeneities, depending on specific anatomy, especially the size and location of air cavities in relation to the beam orientation and field size. For four H&N plans, PTV coverage changed by less than 2%; for the fifth, there was less than 10% difference between the standard and the MC plans. Critical normal tissue DVHs (cord, lung, brainstem) are changed by <10% at the high dose end and mean lung doses are changed by <6%.

Algorithms↗
PubMed2002

Dosimetric advantage of using 6 MV over 15 MV photons in conformal therapy of lung cancer: Monte Carlo studies in patient geometries.

Many lung cancer patients who undergo radiation therapy are treated with higher energy photons (15-18 MV) to obtain deeper penetration and better dose uniformity. However, the longer range of the higher energy recoil electrons in the low-density medium may cause lateral electronic disequilibrium and degrade the target coverage. To compare the dose homogeneity achieved with lower versus higher energy photon beams, we performed a dosimetric study of 6 and 15 MV three-dimensional (3D) conformal treatment plans for lung cancer using an accurate, patient-specific dose-calculation method based on a Monte Carlo technique. A 6 and 15 MV 3D conformal treatment plan was generated for each of two patients with target volumes exceeding 200 cm(3) on an in-house treatment planning system in routine clinical use. Each plan employed four conformally shaped photon beams. Each dose distribution was recalculated with the Monte Carlo method, utilizing the same beam geometry and patient-specific computed tomography (CT) images. Treatment plans using the two energies were compared in terms of their isodose distributions and dose-volume histograms (DVHs). The 15 MV dose distributions and DVHs generated by the clinical treatment planning calculations were as good as, or slightly better than, those generated for 6 MV beams. However, the Monte Carlo dose calculation predicted increased penumbra width with increased photon energy resulting in decreased lateral dose homogeneity for the 15 MV plans. Monte Carlo calculations showed that all target coverage indicators were significantly worse for 15 MV than for 6 MV; particularly the portion of the planning target volume (PTV) receiving at least 95% of the prescription dose (V(95)) dropped dramatically for the 15 MV plan in comparison to the 6 MV. Spinal cord and lung doses were clinically equivalent for the two energies. In treatment planning of tumors that abut lung tissue, lower energy (6 MV) photon beams should be preferred over higher energies (15-18 MV) because of the significant loss of lateral dose equilibrium for high-energy beams in the low-density medium. Any gains in radial dose uniformity across steep density gradients for higher energy beams must be weighed carefully against the lateral beam degradation due to penumbra widening.

Dose-Response Relationship, Radiation↗
PubMed2002

Temporal correlation of measurements of airway hyperresponsiveness in ovalbumin-sensitized mice.

Airway hyperresponsiveness, airway inflammation, and reversible airway obstruction are physiological hallmarks of asthma. These responses are increasingly being studied in murine models of antigen exposure and challenge, using whole body plethysmography to noninvasively assess airway hyperresponsiveness. This approach infrequently has been correlated with indexes of airway hyperresponsiveness measured by invasive means. Furthermore, correlation with quantitative histological data for tissue infiltration by inflammatory and immune cells, particularly in the wall of airways, during daily airway challenge is lacking. To address these uncertainties, we used C57BL/6 mice that were immunized with ovalbumin or vehicle (saline) and sensitized to aerosolized ovalbumin or vehicle 8 days later. The mice were subsequently exposed to aerosolized ovalbumin or vehicle, respectively, on days 14-22. We assessed airway hyperresponsiveness to methacholine noninvasively on days 14, 15, 18, or 22; we studied the same mice 24 h later while they were anesthetized for invasive analyses of airway hyperresponsiveness. Plasma total IgE concentration was significantly higher in the ovalbumin-treated mice compared with the vehicle-treated mice, but this did not correlate with eosinophil number. Peak airway hyperresponsiveness measured by either approach correlated early during daily antigen challenge (days 14 and 15), but this correlation was lost later during subsequent daily antigen challenges (days 18 and 22). On days 14 and 15, peak airway hyperresponsiveness correlated with transmigration of neutrophils and macrophages, but not lymphocytes, in the peribronchovascular connective tissue sheaths. This extravascular accumulation was found to be focal by three-dimensional microscopy. We conclude that, although ovalbumin treatment changed lung function in mice, correlation between noninvasive and invasive measures of peak airway hyperresponsiveness was inconsistent.

Animals↗
PubMed2002

Changes in force-velocity properties of trachealis due to oscillatory strains.

The physically dynamic environment of the lung constantly modulates the mechanical properties of airway smooth muscle. In vitro experiments have shown that contractility of the muscle is compromised by oscillatory strains, perhaps through disruption of cross-bridge interaction and organization of the contractile filaments. To understand the mechanism by which oscillation affects contractility, functional changes of the muscle in terms of force-velocity relationship were assessed before and after imposition of length oscillation in both relaxed and activated states. The oscillation protocol was designed to reduce isometric force by 15-20%, followed by measurement of force-velocity properties. Maximal velocity and power changed by +8 and -14%, respectively, after oscillation applied in the relaxed state and changed by -15 and -25%, respectively, after oscillation applied during contraction. A simple model of reduced activation could not account for the results; neither could the results be explained satisfactorily by the current cross-bridge theory of contraction. The results, however, could be explained if the possibility of reorganization of the contractile filaments due to oscillatory strains was considered.

Animals↗
PubMed2002

Inhibition of Rho family GTPases by Rho GDP dissociation inhibitor disrupts cardiac morphogenesis and inhibits cardiomyocyte proliferation.

Studies of Rho GTPases in Drosophila and Xenopus suggest that Rho family proteins may play an important role in embryogenesis. A reverse genetic approach was employed to explore the role of Rho GTPases in murine cardiac development. Cardiac-specific inhibition of Rho family protein activities was achieved by expressing Rho GDIalpha, a specific GDP dissociation inhibitor for Rho family proteins, using the alpha-myosin heavy chain promoter, active at embryonic day (E)8.0 during morphogenesis of the linear heart tube. RhoA, Rac1 and Cdc42 activities were significantly inhibited, as shown by decreased membrane translocation of these proteins in the transgenic hearts. Transgenic F1 mice for each of two independent lines expressing the highest levels of the transgene, died around E10.5. Homozygotes of the middle copy-number lines, in which Rho GDIalpha expression was increased four-fold over normal levels, were also embryonic lethal. Cardiac morphogenesis in these embryos was disrupted, with incomplete looping, lack of chamber demarcation, hypocellularity and lack of trabeculation. Cell proliferation was inhibited in the transgenic hearts, as shown by immunostaining with anti-phosphohistone H3, a marker of mitosis. In addition, ventricular hypoplasia was associated with up-regulation of p21, an inhibitor of cyclin-dependent kinases, and with down-regulation of cyclin A, while cell survival was not affected. These results reveal new biological functions for Rho family proteins as essential determinants of cell proliferation signals at looping and chamber maturation stages in mammalian cardiac development.

Animals↗
PubMed2002

P53 immunohistochemical scoring: an independent prognostic marker for patients after hepatocellular carcinoma resection.

AIM: To confirm if p53 mutation could be a routine predictive marker for the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: Two hundreds and forty-four formalin-fixed paraffin-embedded tumor samples of the patients with HCC receiving liver resection were detected for nuclear accumulation of p53. The percent of P53 immunoreactive tumor cells was scored as 0 to 3+ in P53 positive region (<10% -, 10-30% +, 31-50% ++, >50% +++). Proliferating cell nuclear antigen (PCNA) and some clinicopathological characteristics, including patients' sex, preoperative serum AFP level, tumor size, capsule, vascular invasion (both visual and microscopic), and Edmondson grade were also evaluated. RESULTS: In univariate COX harzard regression model analysis, tumor size, capsule status, vascular invasion, and p53 expression were independent factors that were closely related to the overall survival (OS) rates of HCC patients. The survival rates of patients with 3+ for P53 expression were much lower than those with 2+ or + for P53 expression. Only vascular invasion (P<0.05) and capsule (P<0.01) were closely related to the disease-free survival (DFS) of HCC patients. In multivariate analysis, p53 overexpression (RI 0.5456, P<0.01) was the most significant factor associated with the OS rates of patients after HCC resection, while tumor size (RI 0.5209, P<0.01), vascular invasion (RI 0.5271, P<0.01) and capsule (RI-0.8691, P<0.01) were also related to the OS. However, only tumor capsular status was an independent predictive factor (P<0.05) for the DFS. No significant prognostic value was found in PCNA-LI, Edmondson's grade, patients' sex and preoperative serum AFP level. CONCLUSION: Accumulation of p53 expression, as well as tumor size, capsule and vascular invasion, could be valuable markers for predicting the prognosis of HCC patients after resection. The quantitative immunohistochemical scoring for P53 nuclear accumulation might be more valuable for predicting prognosis of patients after HCC resection than the common qualitative analysis.

Adolescent↗
PubMed2002

[Experimental study of the transferred keratinocytes transplanted on biomembrane].

OBJECTIVE: To search an ideal carrier of transferred keratinocytes for transplantation. METHODS: The transferred keratinocytes were seeded on the surfaces of the artificial dermis and the silicone membrane and cultured in vitro for 2 weeks. The growth of the keratinocytes was observed by microscope and scanning electron microscope. RESULTS: The keratinocytes implanted on the artificial dermis began to rupture and died after 2 to 3 days. While the keratinocytes adhered well on the surface of silicone membrane with pseudopodia formation after 1 week under scanning electron microscope, and the cells kept normal morphological and proliferative properties 2 weeks later. CONCLUSION: The silicone membrane can be applied as an useful carrier for the keratinocytes transplantation.

Cell Culture Techniques↗
PubMed2002

[Quantitation of alpha-fetoprotein messenger RNA in peripheral blood of nude mice and its relationship with tumor recurrence and metastasis after curative resection of hepatocellular carcinoma].

OBJECTIVE: To assess the level of alpha-fetoprotein (AFP) messenger RNA (mRNA) in peripheral blood of nude mice, and to study its relationship with tumor recurrence and metastasis after curative resection of hepatocellular carcinoma (HCC). METHODS: The metastatic model of human HCC in nude mice LCI-D20 was used in this study. Curative resection was performed at 10th day after tumor implantation in 28 nude mice. Interferon alpha-1b (IFN alpha-1b) was administered subcutaneously from the next day after resection, at doses of 3 10(7)U/kg/d (8 nude mice), 1.5 10(7) U/kg/d (8 nude mice) respectively in the treatment groups, and normal saline alone in the controlled group (12 nude mice). Thirty-five days after treatment, one milliliter of peripheral blood was taken and AFP mRNA was quantitatively analyzed using TaqMan real-time quantitative RT-PCR. The mice were sacrificed. The size of recurrent tumor was measured and the presence of lung metastases was observed. RESULTS: The liver recurrent rate, lung metastatic rate and positivity of AFP mRNA in the controlled group were all 100% (12/12), whereas it was 62.5% (5/8), 0% (0/8), 87.5% (7/8) respectively in the IFN alpha-1b 1.5 10(7)U/kg/d treated group. The recurrent tumor in liver of the IFN alpha-1b 1.5 10(7)U/kg/d treated group was much smaller than that of the controlled group (25 mm(3) 2 mm(3) vs 1143 mm(3) 3 mm(3), t =9.27, P<0.01), and the level of AFP mRNA was also lower than that of the controlled group [(85 6)copies/mug vs (955 2) copies/mug, t =4.33, P<0.01]. In the IFN alpha-1b 3 10(7)U/kg/d treated group, there was only one recurrent tumor (0.5 mm(3)), no lung metastasis, and the positivity of AFP mRNA was 0% (?(2)=11.67, P<0.01). CONCLUSIONS: These results suggest that the level of AFP mRNA in peripheral blood may indicate recurrence and/or metastasis after curative resection of HCC. TaqMan real time quantitative RT-PCR is a very sensitive and convenient method for detecting circulating cancer cells.

Animals↗
PubMed2002

[Experimental study on transplantation of acellular xeno-dermis and suspended keratinocytes].

OBJECTIVE: To investigate the outcome and histological changes of transplantation of acellular xeno-dermis combined with suspended keratinocytes. METHODS: Forty-two nude mice with full-thickness skin defect on the back were randomly divided into 2 groups, then acellular xeno-dermisand and suspended keratinocytes were adopted to cover the skin defect in the experimental group, pure suspended keratinocytes in the control group. The area of wound healing was calculated 2, 3 and 5 weeks after transplantation, and the rates of wound contraction were also calculated, and biopsy for histological examination was performed 3, 6 and 12 weeks after transplantation. RESULTS: Compared with the experimental group, the control group showed delayed wound healing (P < 0.05), intensive wound contraction (P < 0.05), poor durability, elasticity, and cosmetic appearances as well as disordered collagen fibers. In contrast, it was observed that the proliferation of collagen fibers was regularly organized, with no obvious acute immuno-rejection responses in the experimental group. CONCLUSION: The composite transplantation of acellular xenodermis and suspended keratinocytes could promote the wound healing with a satisfactory outcome.

Animals↗
PubMed2002

[Establishment and application of multiplex FISH in detection of the complex chromosome abnormalities in leukemia].

OBJECTIVE: To set up the technical system of multiplex fluorescence in situ hybridization M-FISH and to explore its application in detection of the complex chromosome abnormalities in leukemia. METHODS: The complex chromosome abnormalities of two leukemia patients were analyzed by the combination use of classical cytogenetics, chromosome painting (CP), FISH and M-FISH. RESULTS: In a case of acute lymphoblastic leukemia-L2, the complex karyotype: 46,XY,der(2)t(2;9),der(9)t(9;12;22) was identified by M-FISH, which was detected as 46,XY,der(9)t(9;12) by classical cytogenetics; In a case of acute monocytic leukemia-M5, the complex chromosome abnormalities: 46,XY,der(2)t(2;17), der(10)t(10;11;17), der(11)t(11;?) was revealed by M-FISH, which was confirmed by CP and FISH, and mixed lineage leukemia (MLL) gene was also found involved in this complex chromosome translocation. CONCLUSION: M-FISH was proved to be a powerful tool to examine the complicated karyotypes and hopefully to elucidate nearly all chromosomal aberrations in leukemia and other cancers.

Chromosome Aberrations↗
PubMed2002

[Application of high resolution mass spectra to the analysis of alpha-thiocarbonylthioformamides].

Acetophenone and its derivatives reacted on thionyl chloride to form an intermediate, which can react on the secondary aminnes to form alpha-carbonylthioformamides (1a-1f), followed by sulfurization with lawesson reagent to give target compounds alpha-thiocarbonylthioformamides (2a-2f). Compounds 2a-2f are the deep-red or deep-green crystals because there are two thiocarbonyl groups in the molecule, and they can be used as far-infraed adsorbent dyes, laser-Q switch and organic conductors. Moreover, they are very important intermediates, can react on reagents with amino or diamino groups to produce a variety of acyclic or heterocyclic compounds, which can be used as pesticides and medicines. Therefore, it is necessary to develop a new method for the analysis of alpha-thiocarbonylthioformamides (2a-2f). OA-TOF high resolution mass spectrometer is suitable to do this because of its small volume, high speed and giving elemental composition of ions. In this paper, the mass fragmentation pattern of alpha-thiocarbonylthioformamides was studied in detail using OA-TOF high resolution mass spectrometer of Micromass. The results showed that the molecular ions appeared, then, a neutral molecule S2 was lost easily from the molecular ion of alpha-thiocarbonylthioformamides, forming a particular ion M-S2 (base peak). This provides an effective method for the analysis of these compounds.

English Abstract↗
PubMed2000

Cloning, Expression and Biological Activity of VEGI(151), a Novel Vascular Endothelial Cell Growth Inhibitor.

VEGI(vascular endothelial cell growth inhibitor) is a novel cytokine which belongs to the TNF super-family. In this study, the VEGI gene from ECV304 cells was cloned. A truncated form of VEGI, where 23 amino acids from N-terminal were deleted and named VEGI(151), was expressed in E.coli with 25.5% of expression rate. The purity of VEGI(151) reached 92.5% after purification. VEGI(151) showed significant inhibitory effect on endothelial cells. IC(50) of VEGI151 was 10 mg/L at 24 h. At the concentration of 0.613 mg/L, VEGI(151) induced apoptosis of endothelial cells within 36 h. However, neither stimulatory effect nor inhibitory effect of VEGI(151) was detected on tumor cells(A549 HepG2 Hela)cultured in vitro. These results suggest that endothelial cells was the main target cells of VEGI(151). Our findings indicate that VEGI(151) is a potential therapeutic drug on angiogenic disease and cancer.

Journal Article↗
PubMedDate not supplied

Mechanism of interferon alpha on inhibition of metastasis and angiogenesis of hepatocellular carcinoma after curative resection in nude mice.

The aim of this study was to examine the mechanism of interferon alpha (IFN-alpha) on inhibition of metastasis and recurrence of hepatocellular carcinoma (HCC). Nude mice bearing human HCC xenografts with high metastatic potential (LCI-D20) underwent curative resection of tumors on postimplant day 11. IFN-alpha was begun the next day at different dosages given subcutaneously for 35 consecutive days; normal saline solution was injected into the control mice. The mice were killed 48 hours after the final treatment, and the parameters were evaluated. The HCC intrahepatic recurrence rate, the size of the recurrent lesions, the rate of lung metastasis, the serum vascular endothelial growth factor level, and the microvessel density (immunohistochemistry) were as follows: 100%, 2136+/-794 mm(3)(mean+/-standard deviation), 100%, 265.7+/-154.7 pg/ml, and 144+/-37/HP, respectively, in the control mice, whereas these same values were 62.5%, 89+/-45 mm(3), 12.5%, 53.3+/-9.9 pg/ml, and 86+/-25/HP, respectively, in the IFN-alpha 1.5 x 10(7)U/kg treatment group (P<0.05) and 26.7%, 46+/-21 mm(3), 0%, 65.2+/-17.9 pg/ml, and 39+/-14/HP in the IFN-alpha 3 x 10(7)U/kg treatment group, respectively (P<0.05). However, a significant difference was not found in the serum levels of basic fibroblast growth factor among the control and IFN-alpha treatment groups. IFN-alpha inhibits metastasis and recurrence of human HCC after curative resection in nude mice mediated by antiangiogenesis through downregulating expression of vascular endothelial growth factor but not basic fibroblast growth factor.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced prostate specific antigen gene expression and prostate tumor cell growth by estrogens.

Androgens via the androgen receptor (AR) play crucial roles in prostate physiology and pathophysiology. These androgen actions can be either inhibited or potentiated by estrogens. The mechanisms of these seemingly opposing estrogen effects are unclear. We studied the effects of estrogens on the modulation of androgen induction of prostate specific antigen (PSA) gene expression and prostate tumor cell growth. Cotransfection analyses in CV-1, DU-145, and PC-3 cells showed that dihydrotestosterone (DHT)-induced PSA transcription activity was inhibited by 17beta-estradiol, diethylstilbestrol, ICI182780, and 17alpha-estradiol, but not by tamoxifen via estrogen receptor alpha (ERalpha). In the presence of ERbeta, 17beta-estradiol and diethylstilbestrol had no significant effect, while 17alpha-estradiol inhibited and ICI182780 and tamoxifen potentiated DHT action. When both ERalpha and ERbeta were present, all ER-ligands except tamoxifen inhibited DHT action. The inhibition of DHT action by 17beta-estradiol via ERalpha was mainly dependent on the DNA binding domain, while the 17alpha-estradiol effect was mainly dependent on the ERalpha carboxyl terminus. Treatment with DHT in LAPC-4 prostate tumor cells that express a wild-type AR and both ERbeta and ERalpha greatly increased the PSA gene expression and cell growth. These DHT effects were significantly attenuated by the addition of 17alpha-estradiol, 17beta-estradiol, or cyproterone acetate in a dose-dependent manner. These results indicate that estrogens produce an ER-isoform- and ER-ligand-specific modulation of DHT induction of PSA gene expression and prostate tumor cell growth, providing a molecular basis for designing favorable agents for the prevention and control of prostate cancer.

Animals↗