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Biomedical subjects

Y Zou

Publications and source records attributed to Y Zou.

At least 19 recordsLinked to original sources
PubMed2003

Measurement of decay parameters for Xi- --> Lambda pi- decay.

Based on 1.35 x 10(6) polarized Xi(-) events, we measure the parameter phi(Xi) to be -1.61 degrees +/-2.66 degrees +/-0.37 degrees for the Xi(-)-->Lambda pi(-) decay. New results for the parameters beta(Xi) and gamma(Xi) are also presented. Assuming that the CP-violating phase difference is negligible, we deduce the strong phase difference between the P-wave and S-wave amplitudes of the Lambda pi final state to be 3.17 degrees +/-5.28 degrees +/-0.73 degrees, reducing the uncertainty in estimating the level of CP violation in Xi-hyperon decay.

Journal Article↗
PubMed2003

A review of electrical impedance techniques for breast cancer detection.

Some evidence has been found that malignant breast tumors have lower electrical impedance than surrounding normal tissues. Although the separation of malignant tumors from benign lesions based on impedance measurements needs further investigation, electrical impedance could be used as an indicator for breast cancer detection. In this paper, we provide a systematic technical review of the existing electrical impedance techniques proposed for breast cancer detection, with an emphasis on noninvasive impedance imaging techniques. The electrical impedance of human breast tissue is first introduced, with tabulation of previous in vitro impedance measurement results on cancerous and normal breast tissues, and a brief description on the limited in vivo impedance measurements completed with invasive, or noninvasive, non-imaging techniques. A detailed review on noninvasive impedance imaging techniques for breast cancer detection, such as electrical impedance tomography (EIT) and electrical impedance mapping (EIM), is then presented. We suggest that for better breast cancer detection, an invasive impedance technique may be enhanced by combination with other cancer indicators. 3D EIT should be improved through collective efforts. EIM using a pair of electrode arrays is a viable method with great potential. Magnetic induction tomography and other magnetic induction based impedance imaging for breast cancer detection are promising and merit further exploration as well.

Breast↗
PubMed2001

Reactive oxygen species in mechanical stress-induced cardiac hypertrophy.

Mechanical stress induces various hypertrophic responses including activation of mitogen-activated protein kinases (MAPKs) in cardiac myocytes. Here we examined the role of the small GTP-binding proteins of Rho family and reactive oxygen species (ROS) in stretch-induced activation of p38MAPK in cardiomyocytes. Overexpression of dominant-negative mutants of Rac1 (D.N. Rac1), D.N.RhoA and D.N.Cdc42 suppressed stretch-induced activation of p38MAPK. Overexpression of constitutively active mutants of Rac1 (C.A.Rac1) and C.A.Cdc42 increased the p38MAPK activity in the absence of mechanical stress. Pretreatment with N-acetyl-L-cysteine and N-(2-mercaptopropionyl)-glycine (NAC) suppressed stretch-induced activation of p38MAPK. Mechanical stretch increased intracellular ROS generation, which was abrogated by overexpression of D.N.Rac1 and attenuated by overexpression of D.N.RhoA and D.N.Cdc42. An increase in protein synthesis evoked by mechanical stretch was suppressed by overexpression of D.N.Rac1 and pretreatment with NAC. These results suggest that mechanical stress induces cardiac hypertrophy through the Rac1-ROS-p38MAPK pathway in cardiac myocytes.

Animals↗
PubMed2001

Urotensin II induces hypertrophic responses in cultured cardiomyocytes from neonatal rats.

Urotensin II (UII), a cyclic neuropeptide, functions not only in the central nervous system but also in non-neural systems including cardiovascular systems. In the present study we examined whether UII regulates hypertrophy in cardiomyocytes. The exposure of cultured cardiomyocytes from neonatal rats to UII dose-dependently activated extracellular signal-regulated kinases (ERKs), important molecules in the development of cardiac hypertrophy. ERK activation by UII at 100 nM peaked at 8 min after stimulation. UII markedly induced expression of specific genes encoding atrial natriuretic peptide and brain natriuretic peptide, and significantly increased amino acid incorporation into proteins. Incubation of cardiomyocytes with UII increased cell size and myofibril organisation. UII, then, might participate in cardiomyocyte hypertrophy.

Animals↗
PubMed2001

Differential regulation of interleukin-12 and interleukin-10 by heat shock response in murine peritoneal macrophages.

Heat shock response is a conserved stress response and has been shown to have anti-inflammatory effects. We investigated the effect of heat shock response on LPS-induced production of IL-12 and IL-10, which are two important cytokines playing contradictory roles in regulation of immune response, by murine peritoneal macrophages. The data showed that induction of heat shock response strongly suppressed LPS-induced production of IL-12 while augmented that of IL-10, suggesting the pleiotropic effects of heat shock response on immune regulatory gene expression. Also, the novel observation on up-regulation of IL-10 by heat shock response adds to the mechanism by which heat shock response exerts its anti-inflammatory effects.

Animals↗
PubMed2001

p202, an interferon-inducible protein, mediates multiple antitumor activities in human pancreatic cancer xenograft models.

p202, an IFN-inducible protein, interacts with certain transcriptional activators leading to transcriptional repression. p202 expression has been associated with inhibition of cancer cell growth in vitro and in vivo. To examine a potential p202-mediated antitumor activity in pancreatic cancer, we used both ectopic and orthotopic xenograft models and demonstrated that p202 expression is associated with multiple antitumor activities that include inhibition of tumor growth, reduced tumorigenicity, prolonged survival, and remarkably, suppression of metastasis and angiogenesis. In vitro invasion assay also showed that p202-expressing pancreatic cancer cells are less invasive than those without p202 expression. That observation was supported by the findings that p202-expressing tumors showed reduced expression of angiogenic markers, such as interleukin 8 and vascular endothelial growth factor, and p202-expressing pancreatic cancer cells have reduced level of matrix metalloproteinase-2 activity, a secreted protease activity important for metastasis. Importantly, we demonstrated a treatment efficacy by using p202/SN2 liposome complex in a nude mice xenograft model, suggesting a feasibility of using the p202/SN2 liposome in future preclinical gene therapy experiments. Together, our results strongly suggest that p202 expression mediates multiple antitumor activities against pancreatic cancer and may provide a scientific basis for developing a p202-based gene therapy in pancreatic cancer treatment.

Animals↗
PubMed2001

Calcineurin plays a critical role in the development of pressure overload-induced cardiac hypertrophy.

BACKGROUND: Although activation of the Ca(2+)-dependent phosphatase calcineurin has been reported to induce cardiomyocyte hypertrophy, whether calcineurin is involved in pressure overload-induced cardiac hypertrophy remains controversial. METHODS AND RESULTS: We examined in the present study the role of calcineurin in pressure overload-induced cardiac hypertrophy using transgenic mice that overexpress the dominant negative mutant of calcineurin specifically in the heart. There were no significant differences in body weight, blood pressure, heart rate, heart weight, and the cardiac calcineurin activity between the transgenic mice and their littermate wild-type mice at basal state. The activity of calcineurin was markedly increased by pressure overload produced by constriction of the abdominal aorta in the heart of wild-type mice but less increased in the heart of the transgenic mice. Pressure overload induced increases in heart weight, wall thickness of the left ventricle, and diameter of cardiomyocytes; reprogramming of expressions of immediate early response genes and fetal-type genes; activation of extracellular signal-regulated protein kinases; and fibrosis. All these hypertrophic responses were more prominent in the wild-type mice than in the transgenic mice. CONCLUSIONS: These results suggest that calcineurin plays a critical role in the development of pressure overload-induced cardiac hypertrophy.

Animals↗
PubMed2001

Isoproterenol activates extracellular signal-regulated protein kinases in cardiomyocytes through calcineurin.

BACKGROUND: Extracellular signal-regulated kinases (ERKs) and calcineurin have been reported to play important roles in the development of cardiac hypertrophy. We examined here the relation between calcineurin and ERKs in cardiomyocytes. METHODS AND RESULTS: Isoproterenol activated ERKs in cultured cardiomyocytes of neonatal rats, and the activation was abolished by chelation of extracellular Ca(2+) with EGTA, blockade of L-type Ca(2+) channels with nifedipine, or depletion of intracellular Ca(2+) stores with thapsigargin. Isoproterenol-induced activation of ERKs was also significantly suppressed by calcineurin inhibitors in cultured cardiomyocytes as well as in the hearts of mice. Isoproterenol failed to activate ERKs in either the cultured cardiomyocytes or the hearts of mice that overexpress the dominant negative mutant of calcineurin. Isoproterenol elevated intracellular Ca(2+) levels at both systolic and diastolic phases and dose-dependently activated calcineurin. Inhibition of calcineurin also attenuated isoproterenol-stimulated phosphorylation of Src, Shc, and Raf-1 kinase. The immunocytochemistry revealed that calcineurin was localized in the Z band, and isoproterenol induced translocation of calcineurin and ERKs into the nucleus. CONCLUSIONS: Calcineurin, which is activated by marked elevation of intracellular Ca(2+) levels by the Ca(2+)-induced Ca(2+) release mechanism, regulates isoproterenol-induced activation of ERKs in cardiomyocytes.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Novel alkylpolyamine analogues that possess both antitrypanosomal and antimicrosporidial activity.

A novel series of alkyl- or aralkyl-substituted polyamine analogues was synthesized containing a 3-7-3 polyamine backbone. These analogues were evaluated in vitro, and in one case in vivo, for activity as antitrypanosomal agents, and for activity against opportunistic infection caused by Microsporidia. Compound 21 inhibits trypanosomal growth with an IC(50) as low as 31nM, while compound 24 shows promising activity in vitro against trypanosomes, and against Microsporidia in vitro and in vivo.

Animals↗
PubMed2001

Involvement of the nucleotide excision repair protein UvrA in instability of CAG*CTG repeat sequences in Escherichia coli.

Several human genetic diseases have been associated with the genetic instability, specifically expansion, of trinucleotide repeat sequences such as (CTG)(n).(CAG)(n). Molecular models of repeat instability imply replication slippage and the formation of loops and imperfect hairpins in single strands. Subsequently, these loops or hairpins may be recognized and processed by DNA repair systems. To evaluate the potential role of nucleotide excision repair in repeat instability, we measured the rates of repeat deletion in wild type and excision repair-deficient Escherichia coli strains (using a genetic assay for deletions). The rate of triplet repeat deletion decreased in an E. coli strain deficient in the damage recognition protein UvrA. Moreover, loops containing 23 CTG repeats were less efficiently excised from heteroduplex plasmids after their transformation into the uvrA(-) strain. As a result, an increased proportion of plasmids containing the full-length repeat were recovered after the replication of heteroduplex plasmids containing unrepaired loops. In biochemical experiments, UvrA bound to heteroduplex substrates containing repeat loops of 1, 2, or 17 CAG repeats with a K(d) of about 10-20 nm, which is an affinity about 2 orders of magnitude higher than that of UvrA bound to the control substrates containing (CTG)(n).(CAG)(n) in the linear form. These results suggest that UvrA is involved in triplet repeat instability in cells. Specifically, UvrA may bind to loops formed during replication slippage or in slipped strand DNA and initiate DNA repair events that result in repeat deletion. These results imply a more comprehensive role for UvrA, in addition to the recognition of DNA damage, in maintaining the integrity of the genome.

Adenosine Triphosphatases↗
PubMed2001

Telomere position effect in human cells.

In yeast, telomere position effect (TPE) results in the reversible silencing of genes near telomeres. Here we demonstrate the presence of TPE in human cells. HeLa clones containing a luciferase reporter adjacent to a newly formed telomere express 10 times less luciferase than do control clones generated by random integration. Luciferase expression is restored by trichostatin A, a histone deacetylase inhibitor. Overexpression of a human telomerase reverse transcriptase complementary DNA results in telomere elongation and an additional 2- to 10-fold decrease in expression in telomeric clones but not control clones. The dependence of TPE on telomere length provides a mechanism for the modification of gene expression throughout the replicative life-span of human cells.

Cell Division↗
PubMed2001

Telomerase can inhibit the recombination-based pathway of telomere maintenance in human cells.

Telomere length can be maintained by telomerase or by a recombination-based pathway. Because individual telomeres in cells using the recombination-based pathway of telomere maintenance appear to periodically become extremely short, cells using this pathway to maintain telomeres may be faced with a continuous state of crisis. We expressed telomerase in a human cell line that uses the recombination-based pathway of telomere maintenance to test whether telomerase would prevent telomeres from becoming critically short and examine the effects that this might have on the recombination-based pathway of telomere maintenance. In these cells, telomerase maintains the length of the shortest telomeres. In some cases, the long heterogeneous telomeres are completely lost, and the cells now permanently contain short telomeres after only 40 population doublings. This corresponds to a telomere reduction rate of 500 base pairs/population doubling, a rate that is much faster than expected for normal telomere shortening but is consistent with the rapid telomere deletion events observed in cells using the recombination-based pathway of telomere maintenance (Murnane, J. P., Sabatier, L., Marder, B. A., and Morgan, W. F. (1994) EMBO J. 13, 4953-4962). We also observed reductions in the fraction of cells containing alternative lengthening of telomere-associated promyelocytic leukemia bodies and extrachromosomal telomere repeats; however, no alterations in the rate of sister chromatid exchange were observed. Our results demonstrate that human cells using the recombination-based pathway of telomere maintenance retain factors required for telomerase to maintain telomeres and that once the telomerase-based pathway of telomere length regulation is engaged, recombination-based elongation of telomeres can be functionally inhibited.

Chromosome Aberrations↗
PubMed2001

gp130 plays a critical role in pressure overload-induced cardiac hypertrophy.

gp130, a common receptor for the interleukin 6 family, plays pivotal roles in growth and survival of cardiac myocytes. In the present study, we examined the role of gp130 in pressure overload-induced cardiac hypertrophy using transgenic (TG) mice, which express a dominant negative mutant of gp130 in the heart under the control of alpha myosin heavy chain promoter. TG mice were apparently healthy and fertile. There were no differences in body weight and heart weight between TG mice and littermate wild type (WT) mice. Pressure overload-induced increases in the heart weight/body weight ratio, ventricular wall thickness, and cross-sectional areas of cardiac myocytes were significantly smaller in TG mice than in WT mice. Northern blot analysis revealed that pressure overload-induced up-regulation of brain natriuretic factor gene and down-regulation of sarcoplasmic reticulum Ca(2+) ATPase 2 gene were attenuated in TG mice. Pressure overload activated ERKs and STAT3 in the heart of WT mice, whereas pressure overload-induced activation of STAT3, but not of ERKs, was suppressed in TG mice. These results suggest that gp130 plays a critical role in pressure overload-induced cardiac hypertrophy possibly through the STAT3 pathway.

Animals↗
PubMed2001

Binding of DCC by netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation.

Netrins stimulate and orient axon growth through a mechanism requiring receptors of the DCC family. It has been unclear, however, whether DCC proteins are involved directly in signaling or are mere accessory proteins in a receptor complex. Further, although netrins bind cells expressing DCC, direct binding to DCC has not been demonstrated. Here we show that netrin-1 binds DCC and that the DCC cytoplasmic domain fused to a heterologous receptor ectodomain can mediate guidance through a mechanism involving derepression of cytoplasmic domain multimerization. Activation of the adenosine A2B receptor, proposed to contribute to netrin effects on axons, is not required for rat commissural axon outgrowth or Xenopus spinal axon attraction to netrin-1. Thus, DCC plays a central role in netrin signaling of axon growth and guidance independent of A2B receptor activation.

Animals↗
PubMed2001

Hierarchy of DNA damage recognition in Escherichia coli nucleotide excision repair.

DNA damage recognition plays a central role in nucleotide excision repair (NER). Here we present evidence that in Escherichia coli NER, DNA damage is recognized through at least two separate but successive steps, with the first focused on distortions from the normal structure of the DNA double helix (initial recognition) and the second specifically recognizing the type of DNA base modifications (second recognition), after an initial local separation of the DNA strands. DNA substrates containing stereoisomeric (+)- or (-)-trans- or (+)- or (-)-cis-BPDE-N(2)-dG lesions in DNA duplexes of known conformations were incised by UvrABC nuclease with efficiencies varying by up to 3-fold. However, these stereoisomeric adducts, when positioned in an opened, single-stranded DNA region, were all incised with similar efficiencies and with enhanced rates (by factors of 1.4-6). These bubble substrates were also equally and efficiently incised by UvrBC nuclease without UvrA. Furthermore, removal of the Watson-Crick partner cytosine residue (leaving an abasic site) in the complementary strand opposite a (+)-cis-BPDE-N(2)-dG lesion led to a significant reduction in both the binding of UvrA and the incision efficiency of UvrABC by a factor of 5. These data suggest that E. coli NER features a dynamic two-stage recognition mechanism.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2001

Inhibitory effects of tumor necrosis factor-alpha on cationic lipid-mediated gene delivery to airway cells in vitro.

Cationic liposomes have been used successfully for DNA delivery to airway cells in vitro and are being tested in human clinical trials for their efficacy in cystic fibrosis transmembrane conductance regulator (CFTR) gene delivery in cystic fibrosis patients. While cationic liposomes are effective for transfection of airway cells in culture, they have not been effectively used for gene delivery to human airway cells in vivo. Several barriers in cystic fibrosis lungs, including increased amounts of mucus, phagocytic cell activity and cytokine-rich milieu caused by inflammation, may cause inhibition of gene transfection. As presented in this paper, we examined the effects of inflammatory cytokines on cationic lipid-mediated transfection of model airway cells. The results of these experiments indicate that tumor necrosis factor (TNF)-alpha dramatically inhibits Lipofectin-mediated transfection efficiency of H441 cells. Addition of anti-TNF-alpha neutralizing antibody results in recovery of efficiency. Results of temporal studies are consistent with the concept that TNF-alpha reduces transfection efficiency by a mechanism(s) other than or in addition to gene expression. These results are corroborated by fluorescence microscopic experiments which demonstrate that endocytosis of lipoplex is altered in the presence of TNF-alpha.

Cells, Cultured↗
PubMed2001

High-yield purification of lung surfactant proteins sp-b and sp-c and the effects on surface activity.

Several protocols for purification of milligram quantities of lung surfactant proteins (SP)-B and SP-C were studied for separation efficiency and surface activity of the isolated proteins recombined with synthetic phospholipids (SPL). SP-B and SP-C were obtained from calf lung surfactant extract by C8 chromatography with isocratic elution by either of three solvent systems: 7:1:0.4 MeOH/CHCl(3)/5% 0.1 M HCl (solvent A), 7:1 MeOH/CHCl(3)+ 0.1% TFA (solvent B), and 7:1:0.4 MeOH/CHCl(3)/H(2)O + 0.1% TFA (solvent C). Solvents A and C yielded pure apoprotein in a single pass, with estimated total protein recoveries of >85 and >90%, respectively. Solvent B was less effective in purifying SP-B and SP-C, had a lower recovery efficiency, and gave isolates with less surface activity. Mixtures of SPL plus SP-B eluted with solvents A and C adsorbed to equilibrium surface tensions of 21-22 mN/m and reached minimum surface tensions <1 mN/m during dynamic cycling. Mixtures of SPL with SP-C obtained with solvents A and C had equilibrium surface tensions of 26-27 mN/m and minimum dynamic values of 2-7 mN/m. The ability to obtain milligrams of virtually lipid-free SP-B and SP-C in a single column pass will facilitate research on their biological, structural, and biophysical properties.

Adsorption↗