Biomedical subjects

Weidong Yang

Publications and source records attributed to Weidong Yang.

27 records · Page 2Linked to original sources

PubMed2003

Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA.

Adenosine deaminases acting on RNA (ADAR) convert adenosine residues into inosines in double-stranded RNA. Three vertebrate ADAR gene family members, ADAR1, ADAR2, and ADAR3, have been identified. The catalytic domain of all three ADAR gene family members is very similar to that of Escherichia coli cytidine deaminase and APOBEC-1. Homodimerization is essential for the enzyme activity of those cytidine deaminases. In this study, we investigated the formation of complexes between differentially epitope-tagged ADAR monomers by sequential affinity chromatography and size exclusion column chromatography. Both ADAR1 and ADAR2 form a stable enzymatically active homodimer complex, whereas ADAR3 remains as a monomeric, enzymatically inactive form. No heterodimer complex formation among different ADAR gene family members was detected. Analysis of HeLa and mouse brain nuclear extracts suggested that endogenous ADAR1 and ADAR2 both form a homodimer complex. Interestingly, endogenous ADAR3 also appears to form a homodimer complex, indicating the presence of a brain-specific mechanism for ADAR3 dimerization. Homodimer formation may be necessary for ADAR to act as active deaminases. Analysis of dimer complexes consisting of one wild-type and one mutant monomer suggests functional interactions between the two subunits during site-selective RNA editing.

Adenosine Deaminase↗

PubMed2003

Inhibition of human mast cell proliferation and survival by tamoxifen in association with ion channel modulation.

BACKGROUND: Human lung mast cells (HLMCs) and the human mast cell line HMC-1 express a strongly outwardly rectifying Cl- current characteristic of that carried by the voltage-dependent Cl- channel ClC-5. A similar but distinct current has been implicated in the control of cell proliferation in astrocytes. OBJECTIVE: In this study, we have examined the effects of the Cl- channel blocker tamoxifen on ion channel activity and cell proliferation in both HMC-1 and HLMCs. METHODS: We used the whole-cell patch-clamp technique to characterize macroscopic ion currents in mast cells before and after addition of tamoxifen. HMC-1 proliferation was assessed by incorporation of tritiated thymidine, HLMC proliferation was determined by counting cells in long-term culture, and cell viability was assessed by annexin V binding and propidium iodide uptake. RESULTS: In HMC-1, tamoxifen reduced the outward Cl- current at +130 mV by 73% +/- 9% at a concentration of 3 micromol/L and simultaneously opened a novel inwardly rectifying nonselective cation current with a mean inward current of 153 +/- 18 pA at -130 mV. Tamoxifen produced a dose-dependent inhibition of HMC-1 proliferation (90.3% +/- 4.0% inhibition at 30 micromol/L) without altering cell viability. Tamoxifen inhibited the outward ClC-5-like current in HLMCs, did not open an inward current, and produced a dose-dependent inhibition of HLMC proliferation in long-term culture. CONCLUSION: Tamoxifen inhibits HMC proliferation, possibly through ion channel modulation. This suggests that tamoxifen might be useful in the treatment of mast-cell-mediated diseases, including mastocytosis, asthma, and pulmonary fibrosis.

Calcium↗

PubMed2003

Timed sequential therapy of acute leukemia with flavopiridol: in vitro model for a phase I clinical trial.

PURPOSE: The survival of adults with acute leukemias remains unsatisfactory and requires new treatment approaches. Flavopiridol modulates cell cycle progression, inhibits transcription, and induces apoptosis. We designed an in vitro model of timed sequential therapy for acute leukemia to determine whether flavopiridol can: (a). trigger apoptosis in fresh acute leukemia; and (b). recruit surviving leukemic cells to a proliferative state, thereby priming such cells for the S-phase-related cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C). EXPERIMENTAL DESIGN: Bone marrow cells from 20 adults with relapsed and refractory acute leukemias were enriched for blasts by Ficoll Hypaque sedimentation. Blasts were cultured on day 0 in flavopiridol 250 nM for 24 h, removed from flavopiridol for 24 h, and then cultured in ara-C 1 microM for an additional 72 h (F(250)A(1)). Apoptosis and cell cycle phase distribution were estimated from cells stained with propidium iodide. Cell survival was determined after the 72 h ara-C exposure by double cytofluorescence assay with fluorescein diacetate and propidium iodide. RESULTS: Flavopiridol induced a 4.3-fold increase in apoptosis in human leukemia samples within the first 24 h of culture. Subsequent removal of flavopiridol led to a 1.7-fold increase in the proportion of cells in S phase by day 2. Mean survival in F(250)A(1) cultures after 72 h exposure to ara-C was 35.6% compared with flavopiridol alone (F(250)A(0), 56.1%; P = 0.0003) and ara-C alone (F(0)A(1), 65.2%; P < 0.00001). CONCLUSIONS: Flavopiridol induces apoptosis in marrow blasts from patients with refractory acute leukemias. Furthermore, flavopiridol pretreatment increases the proapoptotic and cytotoxic effects of ara-C. The advantage of sequential FP(250)A(1) over either agent alone is seen for both acute myelogenous leukemia and acute lymphoblastic leukemia. These findings support a clinical trial of timed sequential therapy where flavopiridol is given for cytoreduction and subsequent priming of remaining leukemic cells for enhanced cycle-dependent drug cytotoxicity.

Adult↗

PubMed2003

[Effect of Aphanizomenon flos-aquae toxins on some blood physiological parameters in mice].

In order to study the toxic effect of STX on mouse's blood with time lapse, STX from Aphanizomenon flosaquae was collected and the effect of toxins on physiological parameters of blood was measured by analyzing changes in cells and components in blood. Results showed that the blood parameters in mice changed after 0.5, 6, 12 and 24 hours respectively when mice were exposed to 0.5 Mu/ml Saxitoxin (STX). The numbers of red blood cell, Hemoglobin and platelet had little changed, while the number of white cells showed evident change, especially within 30 minutes. The more time extended, the less change of white cells had, namely, the effect of STX on some blood physiological parameters in mice became weaker with time spent. After 24 hours, almost all the blood physiological parameters in mice recovered to the normal level. Therefore, it can be concluded that both of STX and acid had toxic effects on blood of mice. When STX (0.5 Mu/ml, at pH5.3) were injected into blood, STX had the toxic effect within 12 hours, and after that, acid had.

Animals↗

PubMed2003

[Paralytic shellfish toxins in shellfish from the coast of high frequent harmful algae blooms occurrence areas in East China Sea and South China Sea].

The paralytic shellfish poisoning (PSP) toxicity levels of shellfish collected from shellfish growing zones in Zhoushan areas of East China Sea and Shenzhen areas of South China Sea during January-November 2002 were determined with AOAC bioassay method. The results showed that the toxicity levels of shellfish from Zhoushan were very low, and few shellfish samples could be detected the PSP toxicities. The same levels appeared in the shellfish from Shenzhen, but the percentage of shellfish samples contaminated PSP was up to 30%, and the scallop Chalmys nobilis was dominated in the contaminated shellfish species. Analyses on the toxic profiles of digest gland and edible tissue extraction of scallop from Shenzhen showed that a similar suite of toxins presented in the gland and edible tissues. The high potency neoSTX and low potency GTX5 had a high proportions, up to 60.8% and 11.4%, respectively in the tissue, and the high potency GTX1 + 2 and GTX5 were the dominant toxins, up to 38.9% and 20%, respectively in the gland. Most of the toxin were accumulated in ingested gland of scallop, and the toxic content in gland was about 8 folds more than that in the edible tissues.

Animals↗

PubMed2003

[Inhibition and elimination of chlorine dioxide on Phaeocystis globosa].

Different densities of red tide organism, Phaeocystis globosa (ST strain) were exposed to different concentrations of chlorine dioxide. The results showed that chlorine dioxide could effectively kill and control the algae. When the algae, in the density of 2.35 x 10(9) cells.L-1, was exposured to ClO2 above 0.74 x 10(-2) mmol.L-1, it was inhibited, and eliminated under ClO2 concentration above 2.96 x 10(-2) mmol.L-1. When the density of algae was 2.35 x 10(9), 1.18 x 10(9), 4.70 x 10(8) and 1.18 x 10(8) cells.L-1, the concentration of chlorine dioxide which could kill the algae efficiently in 96 h was 2.96 x 10-2, 2.22 x 10-2, 1.48 x 10-2 and 0.59 x 10-2 mmol.L-1, respectively. Under the same rate of inhibition or elimination, the higher the density of algae was, the lower the concentration of chlorine dioxide was to effectively control the growth of algae cell, ClO2 could be considered as a potential algaecide to control red tide.

Chlorine Compounds↗

PubMed2003

[Effect of the long-term intake of yttrium in drinking water on trace elements in F1 generation mice].

The effects of the long-term intake of yttrium on trace elements in tissues and yttrium in brain of F1 generation mice were studied so as to elucidate some physiological function of the rare earths. The mice were fed with Y3+ (0, 23.25 mg/L, 2325.00 mg/L) dissolved water at different levels for seven months. The level of trace elements such as Cu, Cd, Pb and Y in brain and Se in brain, liver, spleen and kidney of F1 generation mice were measured by ICP-MS and atom fluorescent method. The results showed that, compared with control mice, significant changes in content of Se (P < 0.05) in spleen and Y (P < 0.05) in brain were observed, but no changes were found in content of Pb, Cd, and Cu in brain for the high dose group, and an increase was detected in content of Se(P < 0.05) in spleen for the low dose group, suggesting that long-term intake of Y3+ might enhance the absorption of Se in some tissue that might be one of the biological effect of rare earth and, Y3+ might enter young mammalian brain.

Animals↗

PubMed2002

[Experimental study on subcutaneous bone formation by marrow stromal osteoblast-cancellous bone matrix compound artificial bone].

OBJECTIVE: To investigate the feasibility of using marrow stromal osteoblast (MSO) as bone derived cell and using cancellous bone matrix (CBM) as scaffold for bone tissue engineering, the subcutaneous osteogenesis of MSO-CBM compound artificial bone (MCCAB) was observed in the experiment. METHODS: The marrow stromal cells of adult New Zealand rabbits cultivated and induced in vitro were used to form MCCAB by mixing, seeding and solidifying methods assisted by alginate. The MCCABs were auto-transplanted subcutaneously into the rabbits for 4 to 8 weeks. The alginate-cancellous bone matrix composites or the cancellous bone matrix alone were implanted as control. The effectiveness of bone formation was assessed by means of roentgenography, histology and computerized histomorphometry. RESULTS: The osteogenesis of MCCABs was better than that of the alginate-cancellous bone matrix composites and of the cancellous bone matrixes. In the MCCABs, both intramembranous and cartilaginous osteogeneses were seen but the former was obvious. In the control, only slight cartilaginous osteogeneses were seen. CONCLUSIONS: The osteogeneses of the MCCABs constructed by using tissue engineering method were obvious when transplanted subcutaneously. The MSO and CBM can be used as good bone-derived cell and scaffold material respectively for tissue-engineered bone construction.

Animals↗

PubMed2002

[Experimental studies on cranial defect repair with marrow stromal osteoblast-cancellous bone matrix compound artificial bone].

OBJECTIVE: To investigate the feasibility of using marrow stromal osteoblast-cancellous bone matrix compound artificial bone (MCCAB) as tissue-engineered bone, the osteogenesis of MCCAB in the cranial defect was observed in the experiment. METHODS: The in vitro cultivated and induced marrow stromal cells of adult New Zealand rabbits were seeded into the alginate-cancellous bone matrix to form MCCAB. The MCCAB was then implanted into the cranial defect for 4 to 8 weeks. The cancellous bone matrix (CBM) alone or the marrow stromal osteoblasts (MSOs) alone was implanted as the control. The effectiveness of bone formation was assessed by histological and roentgenographic analysis. RESULTS: The osteogenesis of MCCAB was better than CBM or MSOs and superior to the blank group. CONCLUSION: MCCAB can effectively repair cranial defect. It could be used clinically to restore large bone defects.

Animals↗