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Biomedical subjects

Lei Yao

Publications and source records attributed to Lei Yao.

At least 19 recordsLinked to original sources
PubMed2006

Mutations induced by carcinogenic doses of aristolochic acid in kidney of Big Blue transgenic rats.

Aristolochic acid (AA) is present in at least 65 different kinds of plants, many of which are used as herbal folk remedies. AA is considered one of the most potent plant carcinogens in humans and animals. It has been associated with the development of urothelial cancers in humans, and kidney and forestomach tumors in rats. In the present study, we used the Big Blue transgenic rat model to evaluate the mutagenicity of AA in kidney of rats and to define the mechanism of action for the tumor induction by AA. Groups of six male Big Blue transgenic rats were gavaged with 0, 0.1, 1.0 and 10.0mgAA/kg body weight 5 times a week for 12 weeks, a treatment protocol that resulted in tumors in kidneys and other tissues. The animals were sacrificed 1 day after the final treatment and the kidneys were isolated for assays to determine the mutant frequencies (MFs) and types of mutations induced by AA in the transgenic cII gene. AA treatment resulted in a strong linear relationship between MF inductions and treatment dose (R(2)=0.998). The cII MFs were 29+/-6x10(-6), 78+/-21x10(-6), 242+/-104x10(-6) and 1319+/-360x10(-6) in the control, low, medium and high dose treatment groups, respectively (p<0.001 for all pair wise comparisons among the four treatment groups). These MFs correlated strongly with tumor incidences induced by the different doses of AA (Mengs et al., 1982). Sequence analysis of the cII mutants revealed that there was a statistically significant difference between the mutational spectra in the AA-treated and control rats (p<0.05). A:T-->T:A transversion was the predominant type of mutation in the AA-treated rats whereas G:C-->A:T transition was the main type of mutations in the control rats. These results suggest that AA induces kidney tumors in rats though a mutagenic mechanism of action.

Amino Acid Substitution↗
PubMed2005

Prostaglandin E2 promotes degranulation-independent release of MCP-1 from mast cells.

Mast cells (MCs) are common components of inflammatory infiltrates and a source of proangiogenic factors. Inflammation is often accompanied by vascular changes. However, little is known about modulation of MC-derived proangiogenic factors during inflammation. In this study, we evaluated the effects of the proinflammatory mediator prostaglandin E2 (PGE2) on MC expression and release of proangiogenic factors. We report that PGE2 dose-dependently induces primary MCs to release the proangiogenic chemokine monocyte chemoattractant protein-1 (MCP-1). This release of MCP-1 is complete by 2 h after PGE2 exposure, reaches levels of MCP-1 at least 15-fold higher than background, and is not accompanied by degranulation or increased MCP-1 gene expression. By immunoelectron microscopy, MCP-1 is detected within MCs at a cytoplasmic location distinct from the secretory granules. Dexamethasone and cyclosporine A inhibit PGE2-induced MCP-1 secretion by approximately 60%. Agonists of PGE2 receptor subtypes revealed that the EP1 and EP3 receptors can independently mediate MCP-1 release from MCs. These observations identify PGE2-induced MCP-1 release from MCs as a pathway underlying inflammation-associated angiogenesis and extend current understanding of the activities of PGE2.

Angiogenesis Inducing Agents↗
PubMed2005

Wnts induce migration and invasion of myeloma plasma cells.

Multiple myeloma is an incurable form of lymphoid cancer characterized by accumulation of neoplastic plasma cells in the bone marrow cavity. Little is known about the mechanisms regulating myeloma cell movement within the bone marrow and metastasis to secondary sites. Herein, we identify multiple members of the wingless/int (Wnt) family as promoters of myeloma cell migration/invasion. Wnt-mediated migration was associated with the Wnt/RhoA pathway and did not necessitate signaling through beta-catenin. Activation of both RhoA and members of the protein kinase C (PKC) family, including PKCalpha, PKCbeta, and PKCmu, were required for induction of migration. Activated RhoA and PKCalpha, PKCbeta, and PKCmu appear to assemble in macromolecular signaling complexes that are associated with the cell membrane. These results suggest that Wnt responsiveness of myeloma plasma cells may be a significant factor in disease progression.

Cell Line, Tumor↗
PubMed2005

[Ultrasonic diagnosis of isolated noncompaction of the ventricular myocardium in adults].

OBJECTIVE: To apply echocardiography in diagnosis of isolated noncompaction of ventricular myocardium (INVM) in adults. METHODS: Six patients with INVM underwent echocardiographic examination using HP5500 ultrasound system with the frequency of 2 approximately equals 4 MHz, and the observation was focused on ventricularmyocardium and endocardium at one-third of the apex. RESULTS: All 6 patients showed typical echocardiographic images characterized by an altered structure of the ventricular myocardium with extremely thickened, hypokinetic segments consisting of two layers: a thin, compacted epicardium and an extremely thickened endocardium, resulting in an extremely thickened ventricular wall. CONCLUSION: Echocardiography should be the first choice to be applied in diagnosis of INVM, which is a distinct entity of specific cardiomyopathy in adults.

Adult↗
PubMed2004

Hyperpolarization-activated, cyclic nucleotide-gated cation channels: roles in the differential electrophysiological properties of rat primary afferent neurons.

The large, medium-sized, and small neurons of the dorsal root ganglion (DRG) have different functions in the processing of various senses. Hyperpolarization-activated, cyclic nucleotide-gated channels (HCN) contribute greatly to neuronal excitability. In the present study, which used whole-cell patch clamp techniques and immunohistochemical staining methods, the electrophysiological properties of DRG neurons were systematically compared, and the roles of HCN-1, -2, and -4 were examined. The main results were as follows. 1) The large neurons had significantly higher V0.5 values (membrane potential at which the HCN channels were half-activated) and shorter time constants (tau) than small or medium-sized DRG neurons. However, large DRG neurons had higher Ih density (HCN neuron current). 2) HCN-1 was found predominantly, but not exclusively, in large and medium-sized DRG neurons; HCN-2 was found in all DRG neurons; and HCN-4 was poorly visualized in all DRG neurons. HCN-1 and HCN-2 were colocalized in large and medium-sized neurons with immunostaining of adjacent sections. In the dorsal horn of the spinal cord, HCN-1, HCN-2, and HCN-4 were all expressed in laminae I-IV, although HCN-1 was not detectable in lamina II. 3) Blockade of Ih current in DRG neurons caused a significant decrease in V0.5, resting membrane potential, and repetitive firing number of action potential and a significant increase in time of rising phase of action potential. These results suggest that the different HCN channels in the three types of DRG neurons might contribute to their differential electrophysiological properties.

Action Potentials↗
PubMed2004

Evidence for the involvement of SDF-1 and CXCR4 in the disruption of endothelial cell-branching morphogenesis and angiogenesis by TNF-alpha and IFN-gamma.

Vigorous inflammatory responses are associated with tissue damage, particularly when toxic levels of inflammatory cytokines are produced. Despite proangiogenic factors being present early at sites of inflammation, vascular repair occurs toward the end of the inflammatory response, suggesting modulation of the proangiogenic response. Endogenous inhibitors of angiogenesis induced during acute inflammation are poorly characterized. Here, we looked for endothelial cell-derived modulators of angiogenesis that may account for delayed neovascularization during inflammation. Gene profiling of endothelial cells showed that the inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) selectively promote expression of the antiangiogenic molecules, IFN-inducible protein-10, monokine induced by IFN-gamma, tryptophanyl-tRNA synthetase, and tissue inhibitor of metalmetalloproteinase-1, and inhibit expression of the proangiogenic molecules, platelet-endothelial cell adhesion molecule-1, vascular endothelial growth factor receptor-2, stromal cell-derived factor-1 (SDF-1), collagen type IV, endothelial cell growth factor-1, and carcinoembryonic antigen-related cell adhesion molecule-1. Reduced endothelial cell expression of SDF-1 protein by TNF-alpha and IFN-gamma disrupts extracellular matrix-dependent endothelial cell tube formation, an in vitro morphogenic process that recapitulates critical steps in angiogenesis. Replacement of SDF-1 onto the endothelial cell surface reconstitutes this morphogenic process. In vivo, TNF-alpha and IFN-gamma inhibit growth factor-induced angiogenesis and SDF-1 expression in endothelial cells. These results demonstrate that SDF-1/CXC chemokine receptor-4 constitutes a TNF-alpha- and IFN-gamma-regulated signaling system that plays a critical role in mediating angiogenesis inhibition by these inflammatory cytokines.

Blotting, Western↗
PubMed2004

Base-promoted reactions of bridged ketones and 1,3- and 1,4-haloalkyl azides: competitive alkylation vs azidation reactions of ketone enolates.

The reactions of 1,3- and 1,4-haloalkyl azides with enolates of 2-norbornanone (and a ring-expanded analog) afford polycyclic 1,2,3-triazolines in good yields. The reaction occurs by the initial azidation of the ketone enolate, followed in order by triazoline formation and O-alkylation. An interesting element of this process is the preferential reaction of the alkyl azide with an enolate anion as opposed to the more familiar reaction of the alkyl halide (including Cl and I derivatives). Reactions of acyclic or monocyclic enolates generally lead to 1,2,3-triazoles but none of the alternative C-alkylation product.

Alkylation↗
PubMed2004

Mast cell-derived angiopoietin-1 plays a critical role in the growth of plasma cell tumors.

Multiple myeloma in humans is frequently associated with mast cell infiltration and neovascularization, which correlate directly with disease severity, but the mechanisms underlying this relationship remain unclear. Here, we report that primary murine mast cells express angiopoietin-1 (Ang-1) and low levels of VEGF-A but not Ang-2 and that 2 established murine plasmacytoma cell lines express high levels of VEGF-A but little or no Ang-1 or Ang-2. An in vivo angiogenesis assay using extracellular matrix components shows that mast cells and plasmacytoma cells, together, promote marked neovascularization composed of dilated vessels, which is prevented by neutralization of VEGF-A and Ang-1 but is only partially reduced by neutralization of either VEGF-A or Ang-1. Mast cells within extracellular matrix components express Ang-1, and recombinant Ang-1 together with plasmacytoma cells promotes extracellular matrix neovascularization similar to that induced by mast cells. A transplantation assay shows that primary mast cells accelerate tumor growth by established plasmacytoma cell lines and that neutralization of Ang-1 alone or with VEGF-A reduces significantly the growth of plasmacytomas containing mast cells. These results demonstrate that mast cell-derived Ang-1 promotes the growth of plasmacytomas by stimulating neovascularization and provide further evidence supporting a causal relationship between inflammation and tumor growth.

Angiopoietin-1↗
PubMed2004

Derivation of endothelial cells from CD34- umbilical cord blood.

CD34 is a transmembrane glycoprotein constitutively expressed on endothelial cells and hematopoietic stem cells. Use of CD34-recognizing antibodies has helped in the identification and isolation of CD34+ endothelial precursors from embryonic and adult tissues. However, CD34-null mice display no vascular abnormalities, demonstrating that CD34 antigen expression is not required for normal vascular development. Here we show that a CD34- cell population that includes endothelial cell precursors can be isolated from cord blood. In the presence of angiogenic factors, these cells mature to express the endothelial cell markers vascular endothelial-cadherin, vascular endothelial growth factor receptor-1 and -2, Tie-1 and -2 (tyrosine kinase with immunoglobulin and epidermal growth factor homology domains), von Willebrand factor, and CD31 while maintaining their CD34- status, and can be expanded in vitro for over 20 passages. Moreover, in functional studies, these cells can undergo extracellular matrix-dependent morphogenic changes into capillary-like tubular structures. When transplanted into immunodeficient mice in conjunction with tumor cells or with the proangiogenic factor basic fibroblast growth factor, these cells can form functional microvessels arising along with host blood cells. These studies provide strong evidence for the existence of CD34- endothelial cell precursors in cord blood and suggest the use of ex vivo-expanded cord blood CD34- cells as a unique tool for the investigation of postnatal lineage diversification.

Animals↗
PubMed2003

Insulin-like growth factor I induces migration and invasion of human multiple myeloma cells.

Multiple myeloma (MM) is an incurable form of cancer characterized by accumulation of malignant plasma cells in the bone marrow. During the course of this disease, tumor cells cross endothelial barriers and home to the bone marrow. In latter stages, myeloma cells extravasate through blood vessels and may seed a variety of organs. Insulin-like growth factor I (IGF-I) is one of several growth factors shown to promote the growth of MM cells. In the current study, we have assessed the ability of IGF-I to serve additionally as a chemotactic factor affecting the mobility and invasive properties of these cells. Results indicate that IGF-I promotes transmigration through vascular endothelial cells and bone marrow stromal cell lines. Analysis of endogenous signaling pathways revealed that protein kinase D/protein kinase Cmicro (PKD/PKCmicro) and RhoA were both activated in a phosphatidylinositol 3-kinase (PI-3K)-dependent manner. Inhibition of PI-3K, PKCs, or Rho-associated kinase by pharmacologic inhibitors abrogated migration, whereas mitogen-activated protein kinase (MAPK), Akt, and p70S6 kinase inhibitors had no effect. These results suggest that IGF-I promotes myeloma cell migration by activation of PI-3K/PKCmicro and PI-3K/RhoA pathways independent of Akt. The identification of IGF-I as both a proliferative and migratory factor provides a rational basis for the development of targeted therapeutic strategies directed at IGF-I in the treatment of MM.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2003

Selective expression of stromal-derived factor-1 in the capillary vascular endothelium plays a role in Kaposi sarcoma pathogenesis.

Kaposi sarcoma (KS), the most common neoplasm in patients with AIDS, typically presents with multiple skin lesions characterized by "spindle cells," the vast majority of which are infected with KSHV (Kaposi sarcoma herpes virus, also named HHV-8). In patients with AIDS, the presence of cell-associated KSHV DNA in blood is predictive of subsequent KS development, but the mechanisms by which circulating KSHV-infected cells contribute to AIDS-KS pathogenesis are unclear. Here, we show that the chemokine stromal-derived factor-1 (SDF-1), which is constitutively expressed by skin capillary endothelium and displayed on the endothelial cell surface in association with heparan sulfate, can trigger specific arrest of KSHV-infected cells under physiologic shear flow conditions. Moreover, in the presence of soluble SDF-1 gradients, SDF-1 expressed on the endothelial barrier can promote transendothelial migration of KSHV-infected cells. By triggering specific adhesion of circulating KSHV-infected cells and favoring their entry into the extravascular cutaneous space, endothelial cell-associated SDF-1 in cutaneous capillaries may dictate the preferential occurrence of KS in the skin.

AIDS-Related Opportunistic Infections↗
PubMed2003

[Antimicrobial resistance of Escherichia coli isolates collected from inpatients and outpatients].

OBJECTIVE: To investigate the antimicrobial resistance of Escherichia coli (E. coli) isolates collected from the inpatients in the departments of medicine, surgery, and pediatrics, and intensive care unit (ICU), and from the outpatients. METHODS: Disc diffusion test was used to study the antimicrobial resistance of 3909 strains of E. coli collected from the inpatients in the departments of medicine, surgery, and pediatrics, and Intensive care unit (ICU), and from the outpatients, mostly isolated from urine, sputum, blood, and different secreta in the year 2001. WHONET 5 software was used for analysis of the antimicrobial resistance; and significant differences were tested by chi(2) to compare the resistance rates to antibiotics. RESULTS: The incidences of extended-spectrum beta-lactamases producing strains were 11.2% (195/1737), 14.3% (141/983), 17.7% (28/158), 19.7% (24/122) and 8.4% (76/909) in the strains of E. coli isolated from the inpatients in the departments of medicine, surgery, and pediatrics, and ICU and from the outpatients respectively, with a detectable rate among the outpatients significantly lower than that among the inpatients (P < 0.005), and a detectable rate among the inpatients in the department of medicine significantly lower than those among the inpatients in the department of pediatrics and ICU (both P < 0.05). The resistance rates to cefazolin, cefotaxime, gentamicin and aztreonam of the isolates from the outpatients were significantly lower than those of the inpatients (all P < 0.05). The resistance rates to amoxicillin/clavulanic acid, ceftazidime, cefepime and amikacin of the isolates from the outpatients were significantly lower than those of the inpatients in the department of surgery and ICU (all P < 0.05); The resistance rates to ciprofloxacin and trimethoprim/sulfamethoxazole of the isolates from the outpatients were significantly lower than those from the ICU patients (both P < 0.05). The resistance rates to cefazolin and cefotaxime of E. coli isolates collected from the inpatients in the department of medicine were significantly lower than those of the isolates from the department of surgery and ICU (all P < 0.01); the resistance rates to gentamicin of the isolates from the department was significantly lower than that of the isolates from the department of surgery (P < 0.05). The resistance rates to amoxicillin/clavulanic acid and aztreonam of the isolates from the department of medicine were significantly lower than those of the isolates from the ICU (both P < 0.05). The resistance rate to ciprofloxacin of isolates from the inpatients in the department of pediatrics was significantly lower than that of the other isolates (all P < 0.01). CONCLUSIONS: It is of guiding significance for empirical use of antimicrobial agents in clinic to study on the resistant rates of the strains of E. coli isolated from different departments in hospital.

Drug Resistance, Bacterial↗
PubMed2003

[Changes in long-term synaptic plasticity in the spinal dorsal horn of neuropathic pain rats].

OBJECTIVE: To observe the change in induction of long-term potentiation (LTP) of C-fiberevoked potentials in the spinal dorsal horn of neuropathic pain rats, examine the changes in plasticity of synaptic transmission, and explore the effects and mechanisms of central sensitization and neuropathic pain following noxious stimulation or nerve injury. METHODS: Neuropathic pain model was produced by tight ligation of the L5/L6 spinal nerve in Sprague-Dawley rats and the control group rats were received sham operation. The C-fiber-evoked field potentials in rat spinal dorsal horn were recorded by extracellular recording techniques. The differences in induction of LTP of C-fiber dorsal horn field potentials in sham-operated and neuropathic pain rats were compared. RESULTS: (1) In neuropathic pain rats, the LTP in the dorsal horn was induced by high-frequency, low-intensity conditioning stimulation (100 Hz, 10 V, 0.5 ms, given in 4 trains of 1 s duration at 10 s intervals) of the sciatic nerve, while the same stimulation couldn't induce LTP in sham-operated rats. The LTP could only be induced by high-frequency, high-intensity conditioning stimulation (100 Hz, 30-40 V, 0.5 ms, given in 4 trains of 1 s duration at 10 s intervals) of the sciatic nerve in these control rats. (2) The thresholds for evoking C-fiber dorsal horn field potentials were significantly lower and the amplitudes tended to be higher in neuropathic pain rats as compared to controls. CONCLUSION: These data suggest that the nerve injury itself is likely to induce a state of hyperexcitability at the spinal nociceptive synapses, and further support the notion that the long-term synaptic plasticity and the central sensitization may contribute to the development of neuropathic pain.

Animals↗
PubMed2003

[Antimicrobial resistance of Staphylococcus aureus isolates from inpatients of departments of internal medicine, surgery, and pediatrics and intensive care unit].

OBJECTIVE: To investigate the antimicrobial resistance of Staphylococcus aureus isolates obtained from inpatients of departments of internal medicine, surgery, and pediatrics and intensive care unit (ICU), and study on the differences of resistant rates among the clinical isolates. METHODS: The strains of Staphylococcus aureus were cultured and their antimicrobial resistance was assayed by disc diffusion test (K-B method) and the data was analyzed by WHO NET 5 software. chi(2) test was made to identify the significance of difference. RESULTS: 2 625 strains of Staphylococcus aureus were obtained from the clinical departments of 60 hospitals all over China, among which 1 669 strains (63.3%) were obtained from the inpatients of departments of internal medicine, surgery, and pediatrics and ICU from 1 January to 31 December 2001. Most of the strains were isolated from sputum (34.3%, 572/1 669), secretion (13.2%, 221/1 669), pus (11.7%, 195/1 669), blood (10.2%, 171/1 669), and wound (5.6%, 94/1 669). The resistant rates of Staphylococcus aureus isolates from the inpatients in department pediatrics of to oxacillin, gentamicin, clindamycin, ciprofloxacin, levofloxacin, and chloramphenicol were 23.3%, 16.1%, 29.3%, 11.2%, 4.0% and 14.4% respectively, all significantly lower than those of the isolates from the inpatients of the departments of internal medicine and surgery, and ICU (all P < 0.001). The resistant rates of Staphylococcus aureus isolates from the inpatients of departments of internal medicine and surgery to oxacillin, gentamicin, clindamycin, ciprofloxacin, and levofloxacin were significantly lower than those of isolates from the patients of ICU (all P < 0.001). CONCLUSION: A high isolation rate of multi-drug resistant Staphylococcus aureus among the inpatients of departments of internal medicine, surgery, and pediatrics and ICU. It is important to select appropriate antimicrobial agents based on the origin of bacterial strains and avoid blindness before the results of drug sensitivity are obtained.

Anti-Bacterial Agents↗
PubMed2003

Aplidin PharmaMar.

Aplidin is a cell cycle inhibitor being developed by PharmaMar SA for the potential treatment of a variety of cancers, including non-Hodgkin's lymphoma (NHL), non-small-cell lung cancer (NSCLC), acute lymphoblastic leukemia (ALL), neuroendocrine, prostate, gastric and colorectal cancers [390131], [464778].

Animals↗