Biomedical subjects

Y Zou

Publications and source records attributed to Y Zou.

At least 91 records · Page 5Linked to original sources

PubMed2000

Ca2+/calmodulin-dependent kinase II and calcineurin play critical roles in endothelin-1-induced cardiomyocyte hypertrophy.

Endothelin-1 (ET-1) induces cardiac hypertrophy. Because Ca(2+) is a major second messenger of ET-1, the role of Ca(2+) in ET-1-induced hypertrophic responses in cultured cardiac myocytes of neonatal rats was examined. ET-1 activated the promoter of the beta-type myosin heavy chain gene (beta-MHC) (-354 to +34 base pairs) by about 4-fold. This activation was inhibited by chelation of Ca(2+) and the blocking of protein kinase C activity. Similarly, the beta-MHC promoter was activated by Ca(2+) ionophores and a protein kinase C activator. beta-MHC promoter activation induced by ET-1 was suppressed by pretreatment with the calmodulin inhibitor, W7, the Ca(2+)/calmodulin-dependent kinase II (CaMKII) inhibitor, KN62, and the calcineurin inhibitor, cyclosporin A. beta-MHC promoter activation by ET-1 was also attenuated by overexpression of dominant-negative mutants of CaMKII and calcineurin. ET-1 increased the activity of CaMKII and calcineurin in cardiac myocytes. Pretreatment with KN62 and cyclosporin A strongly suppressed ET-1-induced increases in [(3)H]phenylalanine uptake and in cell size. These results suggest that Ca(2+) plays a critical role in ET-1-induced cardiomyocyte hypertrophy by activating CaMKII- and calcineurin-dependent pathways.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2000

Reduced neointima hyperplasia of vein bypass grafts in intercellular adhesion molecule-1-deficient mice.

Recently, we established a new mouse model of vein graft arteriosclerosis through the grafting of vena cava to carotid arteries. In many respects, the morphological features of this murine vascular graft model resemble those of human venous bypass graft disease. With this model, we studied the role of intercellular adhesion molecule-1 (ICAM-1) in the development of vein graft arteriosclerosis in ICAM-1-deficient mice. Neointimal hyperplasia of vein grafts in ICAM-1 -/- mice was reduced 30% to 50% compared with that of wild-type control animals. Immmunofluorescent analysis revealed that increased ICAM-1 expression was observed on the endothelium and smooth muscle cells (SMCs) of the grafted veins in wild-type, but not ICAM-1 -/-, mice. MAC-1 (CD11b/18)-positive cells that adhered to the surface of vein grafts in ICAM-1 -/- mice were significantly less as identified with en face immunofluorescence, and these positive cells were more abundant in the intimal lesions of vein grafts in wild-type mice. Furthermore, aortic SMCs cultivated from wild-type mice exhibited high ICAM-1 expression in response to tumor necrosis factor-alpha. When tumor necrosis factor-alpha-stimulated SMCs were incubated with mouse spleen leukocytes, the number of cells that adhered to ICAM-1 -/- SMCs was significantly lower than the number that adhered to ICAM-1 +/+ SMCs, which was markedly blocked through pretreatment of leukocytes with the anti-MAC-1 antibody. Taken together, our findings demonstrate that ICAM-1 is critical in the development of venous bypass graft arteriosclerosis, which provides essential information for therapeutic intervention for vein graft disease in patients undergoing bypass surgery.

Animals↗

PubMed2000

Cervical heterotopic arterialized liver transplantation in the mouse.

BACKGROUND: Orthotopic liver transplantation in the mouse is an extremely demanding procedure. Since the mouse, however, would be a good model for the study of various transplantation-related problems, we designed a new surgical technique for cervical heterotopic arterialized reduced-size liver transplantation. METHODS: Eighty percent hepatectomy was performed ex vivo and the remaining liver segment was transplanted to the neck of the recipient. The donor aorta was anastomosed to the right common carotid artery, the portal vein to the distal right external jugular vein, and the donor suprahepatic vena cava to the proximal right external jugular vein using a cuff technique. The bile duct was brought out as a cutaneous stoma. RESULTS: This relatively simple technique was performed in 22 BALB/C mice and associated with a high success rate: three mice died within 5 days due to surgical complications. All grafts in survivors were structurally normal until postoperative day 7 and began to show histological signs of atrophy around day 14. CONCLUSIONS: It is concluded that this technique may be useful for preservation, regeneration and reperfusion studies, and factors responsible for the maintenance of hepatocyte integrity in heterotopic liver transplantation.

Animals↗

PubMed2000

Phase I study of liposomal annamycin.

Annamycin is a highly lipophilic anthracycline with the ability to bypass the MDR-1 mechanism of cellular drug resistance. In this phase I study, annamycin entrapped in liposomes was administered by a 1- to 2-h intravenous infusion at 3-week intervals. Thirty-six patients with relapsed solid tumors were treated and 109 courses were administered at doses ranging from 3 to 240 mg/m2. The dose-limiting toxicity was thrombocytopenia. Five patients had a probable allergic reaction, requiring discontinuation of treatment in one. Treatment was well tolerated otherwise. No cardiac toxicity was seen on endomyocardial biopsy of four patients studied. There was limited gastrointestinal toxicity and no alopecia. No objective tumor responses were observed. Pharmacokinetic studies at 24, 120 and 240 mg/m2 showed a biexponential plasma concentration-versus-time profile. There was a linear relationship between the dose and the maximal plasma concentration with relatively constant plasma clearance values. The maximum tolerated dose (MTD) for liposomal annamycin defined in this study is 210 mg/m2. Because of a subsequent change in the formulation of the drug, future studies will use 190 mg/m2 as the MTD.

Adult↗

PubMed2000

Rapid development of vein graft atheroma in ApoE-deficient mice.

Several animal models manifesting lesions resembling neointimal hyperplasia of human vein grafts have been developed, but no spontaneous atheromatous lesions in their vein grafts have been observed. We developed and here characterize a new animal model of vein graft atheroma, a maturated atherosclerotic plaque, in apoE-deficient mice. The lesion displayed classical complex morphological features and heterogeneous cellular compositions and consisted of a fibrous cap, infiltrated mononuclear cells, foam cells, cholesterol crystal structure, necrotic core with calcification, and neovasculature. Cell component analysis revealed smooth muscle cells (SMCs) localized in the cap region, macrophages which made up a large portion of the lesions, and CD4+ T cells scattered under the cap. Importantly, apoptotic/necrotic cells determined by TUNEL assay in vein grafts into apoE-/- mice were significantly higher than wild-type mice, although a similar number of proliferating cell nuclear antigen-positive cells in both types of lesions was found. Interestingly, vascular SMCs cultivated from aortas of apoE-deficient mice showed a high rate of spontaneous apoptosis/necrosis and a higher rate of cell death stimulated by a nitric oxide donor, sodium nitroprusside, H(2)O(2), and oxidized low density lipoprotein (LDL), although no difference in proliferation of both SMCs incubated with platelet-derived growth factor, angiotensin II, LDL, and oxidized LDL was seen. Thus, the pathogenic mechanisms of vein graft atheroma involve increased intimal cell death initiated by biomechanical stress and amplified by hypercholesterolemia, which leads to continuous recruitment of blood mononuclear cells to constitute atheromatous lesions. This mouse model resembling human vein graft disease has many advantages over other animal models.

Animals↗

PubMed2000

Comparison of physical dependence of ohmefentanyl stereoisomers in mice.

Stereo-structural difference of ohmefentanyl stereoisomers on analgesic action and receptor affinity has been studied. To assess the difference of ohmefentanyl stereoisomers in physical dependence, the potency of physical dependence was quantified by estimating the ED50 value of ohmefentanyl stereoisomers in the naloxone-precipitated jumping test in mice. Morphine was used to assess the method and as a drug of comparison. The results indicate that the degree of physical dependence of morphine can been quantified by estimating the ED50 value of morphine withdrawal jumping induced by naloxone. A significant difference was observed in withdrawal jumping ED50 values among ohmefentanyl stereoisomers. Of these isomers, F9202 and F9204 had similarly potent analgesic action, but very significant difference in naloxone precipitated withdrawal response. Dependent potency index of F9204 was 618-fold weaker than that of F9202. It is concluded that a stereo-structural difference in physical dependence is found to exist among ohmefentanyl stereoisomers. Compound F9204 displayed a strong analgesic action and weak physical dependent potency.

Analgesics↗

PubMed2000

Identification of MICA as a new polymorphic alloantigen recognized by antibodies in sera of organ transplant recipients.

MHC class I-related chain A (MICA) is an HLA-related, polymorphic gene the product of which may be recognized by a subpopulation of intestinal gamma delta T cells and may play a role in the activation of a subpopulation of natural killer cells. Using anti-MICA specific rabbit sera we previously demonstrated that freshly isolated monocytes, keratinocytes, fibroblasts, and endothelial cells express MICA. To analyze whether MICA may be a target for specific antibodies in sera of transplanted patients, we produced three recombinant MICA proteins consisting of the alpha 1, alpha 2, and alpha 3 domains, and used them in an enzyme-linked immunosorbent assay. We found that several patients had specific antibodies against MICA. Most of them were detected in serum samples collected at different times after organ rejection. Although this finding raises the question of how these patients became immunized, the fact that the polymorphic, HLA-like MICA molecule, expressed at the cell surface of endothelial cells, is recognized by specific antibodies in sera of transplanted patients, suggests the MICA may be a target molecule in allograft rejection.

Amino Acid Sequence↗

PubMed2000

Neuropilin-2 regulates the development of selective cranial and sensory nerves and hippocampal mossy fiber projections.

Neuropilin-1 and neuropilin-2 bind differentially to different class 3 semaphorins and are thought to provide the ligand-binding moieties in receptor complexes mediating repulsive responses to these semaphorins. Here, we have studied the function of neuropilin-2 through analysis of a neuropilin-2 mutant mouse, which is viable and fertile. Repulsive responses of sympathetic and hippocampal neurons to Sema3F but not to Sema3A are abolished in the mutant. Marked defects are observed in the development of several cranial nerves, in the initial central projections of spinal sensory axons, and in the anterior commissure, habenulo-interpeduncular tract, and the projections of hippocampal mossyfiber axons in the infrapyramidal bundle. Our results show that neuropilin-2 is an essential component of the Sema3F receptor and identify key roles for neuropilin-2 in axon guidance in the PNS and CNS.

Animals↗

PubMed2000

Posttranscriptional regulation of smoothened is part of a self-correcting mechanism in the Hedgehog signaling system.

Hedgehog signaling, mediated through its Patched-Smoothened receptor complex, is essential for pattern formation in animal development. Activating mutations within Smoothened have been associated with basal cell carcinoma, suggesting that smoothened is a protooncogene. Thus, regulation of Smoothened levels might be critical for normal development. We show that Smoothened protein levels in Drosophila embryos are regulated posttranscriptionally by a mechanism dependent on Hedgehog signaling but not on its nuclear effector Cubitus interruptus. Hedgehog signaling upregulates Smoothened levels, which are otherwise downregulated by Patched. Demonstrating properties of a self-correcting system, the Hedgehog signaling pathway adjusts the concentrations of Smoothened and Patched to each other and to that of the Hedgehog signal, which ensures that activation of Hedgehog target genes by Smoothened signaling becomes strictly dependent on Hedgehog.

Animals↗

PubMed2000

The ets protein PEA3 suppresses HER-2/neu overexpression and inhibits tumorigenesis.

Because HER-2/neu overexpression is important in cancer development, we looked for a method of suppressing the cell transformation mediated by HER-2/neu overexpression. We have identified that the DNA-binding protein PEA3, which is encoded by a previously isolated gene of the ets family, specifically targeted a DNA sequence on the HER-2/neu promoter and downregulated the promoter activity. Expression of PEA3 resulted in preferential inhibition of cell growth and tumor development of HER-2/neu-overexpressing cancer cells. This is a new approach to targeting HER-2/neu overexpression and also provides a rationale to the design for repressors of diseases caused by overexpression of pathogenic genes.

3T3 Cells↗

PubMed2000

Development of cationic liposome formulations for intratracheal gene therapy of early lung cancer.

Regional (intratracheal or aerosol) delivery of cationic liposome-DNA complexes for gene therapy of lung disease offers distinct advantages over systemic (intravenous) administration. However, optimal formulations for early lung cancer treatment have not been established. Therefore, we investigated >50 different liposome and micelle formulations for factors that may affect their transcription efficiency and tested the ideal formulations in an in vivo mouse model. Our data showed that cationic liposomes were generally more effective at transfecting genes than were micelles of the same lipid composition, thus suggesting a role for the bilayer structure in facilitating transfection. In addition, the transfection efficiency of liposome-delivered genes was highly dependent upon the lipid composition, lipid/DNA ratio, particle size of the liposome-DNA complex, and cell lines used. By optimizing these factors in vitro and in vivo, we developed a novel liposome formulation (DP3) suitable for intratracheal administration. Using G67 liposome as control, we found that DP3 was more effective than G67 in vitro and as effective as G67 at both preventing lung tumor growth and prolonging survival in our lung cancer mouse model. We observed a positive correlation between the in vitro p53 function and the in vivo antitumoral activities of liposome-p53 formulations, which had not been reported previously in studies of an intravenous liposome gene delivery system. This correlation may facilitate the development and optimization of a liposome-p53 formulation for aerosol use in lung cancer patients.

Aerosols↗

PubMed2000

Biomechanical stress-induced apoptosis in vein grafts involves p38 mitogen-activated protein kinases.

The present study was designed to investigate whether apoptosis occurs in early-stage vein grafts and to determine the mechanisms by which mechanical stress contributes to apoptosis in vascular smooth muscle cells (SMCs). Apoptosis in vessel walls of mouse vein grafts was confirmed by morphological changes and by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). TUNEL(+) cells in vein grafts 1, 4, and 8 wk postoperatively was 13%, 29%, and 21%, respectively, and apoptosis occurred mainly in veins grafted to arteries, remaining unchanged in vein-to-vein grafts. When mouse, rat, and human arterial SMCs were cultured on a flexible membrane and subjected to cyclic strain stress, apoptosis was observed in a time- and strength-dependent manner. All three types of SMCs showed apoptotic death as confirmed by TUNEL, propidium iodide, and annexin V staining. To further study the signal pathways leading to apoptosis, activities of p38, a subfamily of mitogen-activated protein kinases (MAPKs), were determined. Mechanical stress resulted in p38 MAPK activation, reaching high levels within 8 min. SB 202190, a specific inhibitor for p38 MAPKs, prevented SMC apoptosis in response to mechanical stress. SMC lines stably transfected with a dominant negative rac, an upstream signal transducer, or overexpressing MAPK phosphatase-1, a negative regulator for MAPKs, completely inhibited mechanical stress stimulated p38 activation and abolished mechanical stress-induced apoptosis. Thus, we provide solid evidence that one of the earliest events in venous bypass grafts is apoptosis, in which mechanical stress-induced p38-MAPK activation is responsible for transducing signals leading to apoptosis.-Mayr, M., Li, C., Zou, Y., Huemer, U., Hu, Y., Xu, Q. Biomechanical stress-induced apoptosis in vein grafts involves p38 mitogen-activated protein kinases.

Animals↗

PubMed2000

Mouse model of transplant arteriosclerosis: role of intercellular adhesion molecule-1.

Transplant-accelerated arteriosclerosis in coronary arteries is the major limitation to long-term survival of patients with heart transplantation. The pathogenesis of this disease is not fully understood. Herein, we describe a simplified model of artery allografts in the mouse that allows us to take advantage of transgenic, knockout, or mutant animals. Common carotid arteries or aortic vessels were end-to-end allografted into carotid arteries between C57BL/6J and BALB/c mice. Neointimal lesions were observed as early as 2 weeks after surgery and had progressed at 4 and 6 weeks postoperatively. The lumen of grafted arteries was significantly narrowed due to neointima hyperplasia 4 weeks after transplantation. Using this model, we studied the role of intercellular adhesion molecule-1 (ICAM-1) in the development of transplant arteriosclerosis in ICAM-1-deficient mice. Neointimal lesions of artery grafts from ICAM-1 -/- C57BL/6J to BALB/c mice were reduced up to 60% compared with wild-type controls. MAC-1 (CD11b/18)-positive cells adhering to the surface of ICAM-1 -/- artery grafts were significantly less as identified by en face immunofluorescence, and these positive cells were more abundant in intimal lesions of artery grafts in wild-type mice. Furthermore, the major cell component of neointimal lesions 4 weeks after surgery was found to be alpha-actin-positive smooth muscle cells, which were significantly reduced in lesions of ICAM-1 -/- artery grafts. Thus, this model has been proven to be useful for understanding the mechanism of transplant arteriosclerosis. Our findings demonstrate that ICAM-1 is critical in the development of allograft arteriosclerosis via mediation of leukocyte adhesion to, and infiltration into, the vessel wall.

Actins↗

PubMed2000

[Exclusive mapping on polydactyly with markers on chromosome 7 and 2 in a Chinese kindred].

OBJECTIVE: This study was aimed at mapping polydactyly related genes in a Chinese kindred. METHODS: Linkage analysis was performed using 7 markers on chromosome 7 and 1 marker on chromosome 2. RESULTS: Pairwise linkage analysis showed no linkage between the markers and polydactyly related gene in the kindred. CONCLUSION: The polydactyly related gene in this kindred may be located on a new locus.

Chromosome Mapping↗

PubMed2000

[Genetic polymorphism of 5 STR loci on chromosome 14 in Chinese Han].

OBJECTIVE: To understand the distribution of genes and genotypes of 5 STR loci on chromosome 14 in Chinese Han. METHODS: PCR and polyacrylamide gel electrophoresis were used to analyze the polymorphism of 5 STR loci (D14S742, D14S306, D14S606, D14S617, D14S611) on chromosome 14 in Chinese Han. RESULTS: 5 alleles and 13 genotypes, 5 alleles and 13 genotypes, 6 alleles and 13 genotypes, 9 alleles and 21 genotypes, and 6 alleles and 13 genotypes were observed at D14S742, D14S306, D14S606, D14S617 and D14S611, respectively. The frequencies of the most common allele at these five loci were 0.31, 0.31, 0.47, 0.35 and 0.29 respectively. CONCLUSION: These five loci are highly polymorphic in Chinese Han and their allele distribution is in good agreement with Hardy-Weinberg equilibrium.

China↗

PubMed2000

Genetic polymorphism of 4 STR loci on chromosome 17 in Chinese Han.

OBJECTIVE: To analyze genetic polymorphism of D17S1290, D17S1293, D17S1303 and D17S1308 in Chinese Hans. METHODS: Fifty unrelated individuals were analyzed by PCR amplification fragment length polymorphism analysis method. RESULTS: 9, 7, 5, 5 alleles were observed at these 4 STR loci respectively, the genotypes distributions in Chinese Hans were in accordance with Hardy-Weinberg equilibrium, the expected heterozygosities for these loci were 0.770, 0.828, 0.608, 0.669 respectively, the polymorphism information contents(PIC) were 0.763, 0.820, 0.602, 0.662 respectively. CONCLUSION: The results demonstrate these 4 STR loci can be used for genetic analysis.

China↗

PubMed2000

[Predation on Myzus persicae by Propylaea japonica adults with different extents of starvation].

The study showed that the functional response of predation on M. persicae by the female and male adults of P. japonica with different extents of starvation belonged to the type of Holling II. Female adults had a larger attacking rate than male adults, but the predacious amount of M. persicae by female and male adult predators of different extent of starvation within 24 hrs had no significant difference. The predacious amount by female adult was larger than that of male. The significant difference of predacious amount between female and male adults increased with the time of their starvation and the prey density. The predation by unstarved female and male adult predators on M. persicae in 24 hours was concentrated at 6:00-18:00 and the predation rate (V) between female and male adults had no significant difference. The predation by starved female and male adults for 48 h on the prey in 24 hours was at 0-4 hours after the experiment started, and the predation rate(V) between female and male starved adults had no significant difference either.

Animals↗

PubMed2000

[Impact of starvation on predation by male adult Chrysopa septempunctata].

The predation on Schizaphis graminum by male adult Chrysopa septempunctatata at various levels of starvation was examined in this paper. Th results showed that the functional reactive types of predator were not altered by its starvation duration, and the amount(Na) of catched S. graminum by C. septempunctata within 24 hrs varied with duration time(t), which could be expressed by the model: Na = 100/(1 + e-0.3088 - 0.0996t). The relationship between predation rate(v) and time(x) could be described as v = 6.7117 x-0.7928. The male adult predators preferred feeding on the young preys.

Animals↗