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Biomedical subjects

Z Shao

Publications and source records attributed to Z Shao.

At least 91 records · Page 5Linked to original sources
PubMed1999

[Mechanism of growth inhibition by genistein of human breast carcinoma].

OBJECTIVE: To study the mecnanism of inhibition of breast carcinoma cells by genistein. METHODS: Human breast cancer cell lines were treated in vitro with genistein. Northern blot, Western blot, plasmid transfection and apoptosis assay were used to evaluate the mechanism of cell growth inhibition. RESULTS: Genistein could inhibit proliferation of human breast carcinoma cells with different ER status and p53 status. This inhibition was associated with induction of p21WAF1/CIP1 mRNA and protein expression. Exposure of MCF-7 and MDA-MB-231 cells to genistein resulted in statistically significant increased p21WAF1/CIP1 mRNA stability, accompanied with increased p21WAF1/CIP1 protein expression. This increase in p21WAF1/CIP1 was subsequently followed by the onset of apoptosis. CONCLUSION: The inhibitory effect of genistein on cell proliferation of breast cancer appears to be due to p21WAF1/CIP1 expression and apoptosis through mechanism independent of ER and p53. The results provide evidence for the potential usefulness of genistein in the prevention and treatment of human breast cancer.

Anticarcinogenic Agents↗
PubMed1999

[Prognostic significance of cyclin-dependent kinase inhibitor p27kip1 expression in human breast cancer].

OBJECTIVE: To study the expression of p27kip1 in breast cancer in relation to biological behavior and prognosis. METHODS: p27kip1 expression at protein level was determined by immunohistochemistry technique in 181 patients with breast cancer. In addition, p27WAF1/CIP1, p53 and mdm2 were examined in 106 cases of this series. Data about apoptotic index, bcl-2 and bax protein expression were available in the other 91 patients. RESULTS: Of the 181 patients, p27kip1 expression was low in 121 (66.9%) and high in 60 (33.1%), respectively. p27kip1 expression level was correlated with histological grade, tumor size, axillary lymph node status, post-operative recurrence, invasion and metastasis. It was also correlated with bcl-2, bax, p53, p21WAF1/CIP1, and mdm2 expression levels. Univariate analysis demonstrated better disease-free survival in patients with higher p27kip1 expression than in those with lower expression. However, by Cox multivariate analysis, p27kip1 expression level was not found to be of independent prognostic significance. CONCLUSION: As an inhibitor of cyclin-dependent kinase, p27kip1 favors prognosis of human breast cancer not only by arresting cell cycle in G1 phase but also inducing cancer cell apoptosis.

Adult↗
PubMed1999

[Effects of abalong polysaccharide on the activity of the peritoneal macrophages and delayed-type hypersensitivity in mice bearing S180].

The effect of Abalone polysaccharide(Ap) which extracted from Haliotis discus hannai Ino on phagocytosis activity of the peritoneal macrophages and delayed-type hypersensitivity in mice bearing S180 were studied. The results showd that the ablong polysaccharide promoted the phagocytosis activity of the peritoneal macrophages and delayed-type hypersensitivity in mice bearing S180. It was suggested that the polysaccharide inhibited tumor growth maybe by activating the macrophage and T cells.

Animals↗
PubMed1999

[Synergy and attenuation of cyclophosphamidum (CTX) activities by abalone polysaccharide].

Abalone polysaccharide (AP) was extracted from Haliotis discushannai Ino. The combined effects of AP and CTX against tumor-bearing mice were investigated. The results showed that AP could markedly promote the inhibition effects of CTX on S180 and HepA tumor, enhance protection against leukocytopenia, decrease of spleen and thymus weight and hemolysin in serum, and bone marrow supression induced by CTX.

Animals↗
PubMed1998

Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes.

Reactive oxygen species (ROS) have been proposed to participate in the induction of cardiac preconditioning. However, their source and mechanism of induction are unclear. We tested whether brief hypoxia induces preconditioning by augmenting mitochondrial generation of ROS in chick cardiomyocytes. Cells were preconditioned with 10 min of hypoxia, followed by 1 h of simulated ischemia and 3 h of reperfusion. Preconditioning decreased cell death from 47 +/- 3% to 14 +/- 2%. Return of contraction was observed in 3/3 preconditioned versus 0/6 non-preconditioned experiments. During induction, ROS oxidation of the probe dichlorofluorescin (sensitive to H2O2) increased approximately 2.5-fold. As a substitute for hypoxia, the addition of H2O2 (15 micromol/liter) during normoxia also induced preconditioning-like protection. Conversely, the ROS signal during hypoxia was attenuated with the thiol reductant 2-mercaptopropionyl glycine, the cytosolic Cu,Zn-superoxide dismutase inhibitor diethyldithiocarbamic acid, and the anion channel inhibitor 4,4'-diisothiocyanato-stilbene-2,2'-disulfonate, all of which also abrogated protection. ROS generation during hypoxia was attenuated by myxothiazol, but not by diphenyleneiodonium or the nitric-oxide synthase inhibitor L-nitroarginine. We conclude that hypoxia increases mitochondrial superoxide generation which initiates preconditioning protection. Furthermore, mitochondrial anion channels and cytosolic dismutation to H2O2 may be important steps for oxidant induction of hypoxic preconditioning.

Animals↗
PubMed1998

Submolecular resolution of single macromolecules with atomic force microscopy.

The intrinsically high signal-to-noise ratio of atomic force microscopy (AFM) permits structural determination of individual macromolecules to, at times, subnanometer resolution directly from unprocessed images, avoiding the conditions and possible consequences of averaging over an ensemble of molecules. In this article, we will review some of the most recent achievements in imaging single macromolecules with AFM.

Membrane Proteins↗
PubMed1998

Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes.

Cardiomyocytes suppress contraction and O2 consumption during hypoxia. Cytochrome oxidase undergoes a decrease in Vmax during hypoxia, which could alter mitochondrial redox and increase generation of reactive oxygen species (ROS). We therefore tested whether ROS generated by mitochondria act as second messengers in the signaling pathway linking the detection of O2 with the functional response. Contracting cardiomyocytes were superfused under controlled O2 conditions while fluorescence imaging of 2, 7-dichlorofluorescein (DCF) was used to assess ROS generation. Compared with normoxia (PO2 approximately 107 torr, 15% O2), graded increases in DCF fluorescence were seen during hypoxia, with responses at PO2 = 7 torr > 20 torr > 35 torr. The antioxidants 2-mercaptopropionyl glycine and 1,10-phenanthroline attenuated these increases and abolished the inhibition of contraction. Superfusion of normoxic cells with H2O2 (25 microM) for >60 min mimicked the effects of hypoxia by eliciting decreases in contraction that were reversible after washout of H2O2. To test the role of cytochrome oxidase, sodium azide (0.75-2 microM) was added during normoxia to reduce the Vmax of the enzyme. Azide produced graded increases in ROS signaling, accompanied by graded decreases in contraction that were reversible. These results demonstrate that mitochondria respond to graded hypoxia by increasing the generation of ROS and suggest that cytochrome oxidase may contribute to this O2 sensing.

Animals↗
PubMed1998

Staphylococcal alpha-hemolysin can form hexamers in phospholipid bilayers.

Atomic force microscopy (AFM) was used to study the structure of the staphylococcal alpha-hemolysin (alpha HL) oligomer formed in supported phospholipid bilayers. In contrast to the recent X-ray crystallographic demonstration of a heptameric stoichiometry for the oligomer formed in deoxycholate (DOC) micelles, the high-resolution unprocessed AFM images unequivocally revealed a hexamer in these phospholipid bilayers. Independent support of this hexameric stoichiometry was obtained from the measurements of the lattice constant in the AFM images and from gel electrophoresis. Therefore, alpha HL can form two different, energetically stable oligomers, which differ in at least stoichiometry but perhaps subunit structure as well. Furthermore, stable, incomplete oligomers were observed in the AFM images, which may be of relevance to the mechanism by which alpha HL damages the cell.

Bacterial Toxins↗
PubMed1998

Random-priming in vitro recombination: an effective tool for directed evolution.

A simple and efficient method for in vitro mutagenesis and recombination of polynucleotide sequences is reported. The method involves priming template polynucleotide(s) with random-sequence primers and extending to generate a pool of short DNA fragments which contain a controllable level of point mutations. The fragments are reassembled during cycles of denaturation, annealing and further enzyme-catalyzed DNA polymerization to produce a library of full-length sequences. Screening or selecting the expressed gene products leads to new variants with improved functions, as demonstrated by the recombination of genes encoding different thermostable subtilisins in order to obtain enzymes more stable than either parent.

Bacillus subtilis↗
PubMed1998

Treatment of severe aplastic anemia with an immunosuppressive agent plus recombinant human granulocyte-macrophage colony-stimulating factor and erythropoietin.

To evaluate the therapeutic potential of hematopoietic growth factors (HGFs) during immunosuppressive treatment (IST) of severe aplastic anemia (SAA), 38 patients with newly diagnosed SAA received IST alone (group I), or IST plus recombinant human erythropoietin and granulocyte-macrophage colony-stimulating factor (rhEPO + rhGM-CSF) (group II). Eleven patients in each group received antilymphocyte globulin (ALG) for IST, and eight patients in each group received cyclosporine (CSA). Complete remission rates at one year were 26% and 74% for group I and group II patients, respectively. The ALG-treated subgroup showed the greatest differences between treatments. Compared with patients receiving ALG alone, patients treated with ALG plus HGFs had significantly better one-year survival (100% vs. 54.5%, P < 0.05), complete remission rates (91% vs. 36%, P < 0.05), more rapid and complete hematologic recovery, greater reductions in transfusion requirements, and lower infection rates. The data suggest a potential role for rhEPO + rhGM-CSF therapy in SAA patients receiving IST.

Adolescent↗
PubMed1998

Processing of delta-endotoxin of Bacillus thuringiensis subsp. kurstaki HD-1 in Heliothis armigera midgut juice and the effects of protease inhibitors.

Bombyx mori was found to be more sensitive to the protoxins of HD-1 than Heliothis armigera. SDS-PAGE analysis showed that a large amount of activated toxin was yielded from protoxin by B. mori gut juice while little was yielded by H. armigera. Further degradation of activated toxin was observed in H. armigera midgut juice detected by SDS-PAGE. pH influenced the proteolytic activity of the midgut juice significantly, but there was no obvious effect of pH on the degradation of activated toxin. Specific inhibitor study revealed the presence of trypsin, chymotrypsin, and elastase in the midgut juice. TLCK, TPCK, elastatinal and some general serine protease inhibitors successfully prevented the excessive degradation of protoxin in H. armigera midgut juice. Chymotrypsin inhibitors showed strong inhibitory effects against the further degradation of activated toxin, indicating that chymotrypsin played a major role in the process. It was presumed that the excessive degradation of protoxin in H. armigera midgut juice was responsible for the low sensitivity of the insect to Bt. Further study demonstrated that the excessive degradation in vitro was triggered by SDS treatment. However, all of the tested serine protease inhibitors expressed synergism with protoxin against H. armigera larvae, suggesting that the excessive degradation of protoxin may occur in vivo to some extent and may be triggered by receptor binding of activated toxin.

Animals↗
PubMed1998

Hydration force in the atomic force microscope: A computational study.

Using a hard sphere model and numerical calculations, the effect of the hydration force between a conical tip and a flat surface in the atomic force microscope (AFM) is examined. The numerical results show that the hydration force remains oscillatory, even down to a tip apex of a single water molecule, but its lateral extent is limited to a size of a few water molecules. In general, the contribution of the hydration force is relatively small, but, given the small imaging force ( approximately 0.1 nN) typically used for biological specimens, a layer of water molecules is likely to remain "bound" to the specimen surface. This water layer, between the tip and specimen, could act as a "lubricant" to reduce lateral force, and thus could be one of the reasons for the remarkably high resolution achieved with contact-mode AFM. To disrupt this layer, and to have a true tip-sample contact, a probe force of several nanonewtons would be required. The numerical results also show that the ultimate apex of the tip will determine the magnitude of the hydration force, but that the averaged hydration pressure is independent of the radius of curvature. This latter conclusion suggests that there should be no penalty for the use of sharper tips if hydration force is the dominant interaction between the tip and the specimen, which might be realizable under certain conditions. Furthermore, the calculated hydration energy near the specimen surface compares well with experimentally determined values with an atomic force microscope, providing further support to the validity of these calculations.

Calibration↗
PubMed1998

Direct visualization of surface charge in aqueous solution.

Tapping mode atomic force microscopy operated in the phase shift mode is used to directly visualize the surface charge on biological macromolecules under solution. A simple theory is presented which is qualitatively consistent with experimental observations, although a more complicated theoretical analysis is required for a quantitative comparison.

Lipid Bilayers↗
PubMed1998

Molecular evolution by staggered extension process (StEP) in vitro recombination.

We have developed a simple and efficient method for in vitro mutagenesis and recombination of polynucleotide sequences. The staggered extension process (StEP) consists of priming the template sequence(s) followed by repeated cycles of denaturation and extremely abbreviated annealing/polymerase-catalyzed extension. In each cycle the growing fragments anneal to different templates based on sequence complementarity and extend further. This is repeated until full-length sequences form. Due to template switching, most of the polynucleotides contain sequence information from different parental sequences. The method is demonstrated by the recombination of two genes encoding thermostable subtilisins carrying two phenotypic markers separated by 113 base pairs and eight other point mutation markers. To demonstrate its utility for directed evolution, we have used StEP to recombine a set of five thermostabilized subtilisin E variants identified during a single round of error-prone PCR mutagenesis and screening. Screening the StEP-recombined library yielded an enzyme whose half-life at 65 degrees C is 50 times that of wild-type subtilisin E.

Bacillus subtilis↗
PubMed1998

Immunophenotype of myeloid cells in myelodysplastic syndromes and its clinical implications.

OBJECTIVE: To explore the immunophenotype of myeloid cells in myelodysplastic syndyomes (MDS) and its clinical implications. METHODS: A panel of monoclonal antibody was used to detect CD13+, CD33+, CD15+ and CD14+ antigens on the membrane surfaces of myeloid cells in the bone marrow from 51 MDS, 21 aplastic anemia (AA), 21 paroxysmal nocturnal hemoglobinuria (PNH) patients. 10 acute myeloblastic leukemia (AML) patients and 15 normal subjects by immunoenzymatic assay. The morphology and chromosome karyotype of bone marrow cells of MDS patients were also examined. RESULTS: CD14+, CD13+ and CD33+ cells in the bone marrow were more in MDS patients than in normal controls, AA patients and PNH patients. CD15+ cells in the bone marrow were less in MDS patients than in normal controls. CONCLUSIONS: The percentages of CD14+, CD13+ and CD33+ positive cells in the bone marrow of MDS patients were related to the percentage of myeloblasts, the chromosomal aberrations and the response to treatment. It indicated that there is immunophenotypic misexpression of myeloid cells in MDS patients. Immunophenotype analysis of myeloid cells might be useful for the diagnosis and treatment of MDS patients.

Adolescent↗
PubMed1998

[WAF1/CIP1/p21 gene in wild type p53 and mutant p53 human breast cancer cell lines in relation to its cytobiological features].

OBJECTIVE: To study the WAF1/CIP1 gene DNA status, mRNA and protein expressions in human breast cancer cell line and its significance. METHODS: Using cell culture, molecular biological techniques such as Southern blot, Northern blot and immunocytochemical methods, the WAF1/CIP1 gene DNA status, mRNA and protein expression levels in MCF-7 expressing wild type p53(wtp53) and MDA-MB-231 expressing mutant p53 (mtp53) human breast cancer cell lines were detected respectively. The p53 and mdm-2 protein expression levels and cytobiological features of the 2 cell lines were compared and correlated to their WAF1/CIP1 gene expression levels. RESULTS: (1) There was no difference in WAF1/CIP1 gene DNA status in the two breast cancer cell lines. Neither of them showed gene amplificatian or deletion. However, the WAF1/CIP1 mRNA and p21WAF1/CIP1 protein expression levels of MCF-7 cells were higer than those of MDA-MB-231 cells (P < 0.05). (2) The character and cellular distribution of p53 protein in the two cell lines were clearly different. The expression level of mdm-2 proteion was significantly higher in MCE-7 than in MDA-MB-231 cells (P < 0.05). (3) Compered to the other breast cancer cell line, MCF-7 cells were better differentiated, grew more slowly and adhered more closely with each other. CONCLUSION: The WAF1/CIP1 gene expression at mRNA and protein levels is associated with p53 phenotype and some cytobiological features of human breast cancer.

Breast Neoplasms↗