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Biomedical subjects

B Li

Publications and source records attributed to B Li.

At least 19 recordsLinked to original sources
PubMed2007

Murine dendritic cells modified with CXCL10 gene and tumour cell lysate mediate potent antitumour immune responses in mice.

The aim of our present study was to estimate the effect of a therapeutic vaccine against tumour based on dendritic cells (DC) vaccine modified with tumour cell lysate and chemokine CXCL10 gene. In this study, mouse bone marrow DC were pulsed with tumour cell (RM-1) lysate and then transfected with a plasmid vector expressing CXCL10 cDNA by DOTAP liposome. The protective and therapeutic effects of the DC vaccine in RM-1 tumour model were assessed (divided into CXCL10/Lysate-DC, CXCL10/DC, pcDNA/Lysate-DC, Lysate-DC, pcDNA-DC, DC and PBS). The DC transfected with CXCL10 gene were capable of synthesizing and secreting CXCL10 chemokine. The highest CTL activity against RM-1 cells was induced in mice immunized with DC vaccine that was modified with RM-1 lysate and CXCL10 gene (CXCL10/Lysate-DC) when compared with its counterpart in mice. The CXCL10/Lysate-DC immunized mice also exhibited resistance to tumour challenge most effectively. In the RM-1 tumour model, immunization of CXCL10/Lysate-DC inhibited the tumour growth most significantly when compared with other groups and the survival time of the mice treated with CXCL10/Lysate-DC was greatly extended. These findings provide a potential strategy to improve the efficacy of DC-based tumour vaccine.

Animals↗
PubMed2006

Overload of the heat-shock protein H11/HspB8 triggers melanoma cell apoptosis through activation of transforming growth factor-beta-activated kinase 1.

Molecular therapeutics is a recognized promising approach for melanoma, but relevant target genes remain elusive. We report that overload of the recently cloned H11/HspB8 induces apoptosis in 55% of examined melanoma cultures. Apoptosis was determined by activation of caspases-9 and -3 and terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL), and was not seen in normal melanocytes. It was associated with H11/HspB8 complexation with transforming growth factor-beta-activated kinase (TAK) 1 and activation of TAK1 and p38 mitogen activated protein 3 kinases. TAK1 was not bound, nor activated by the H11/HspB8 mutant W51C, which has dominant antiapoptotic activity. beta-Catenin was phosphorylated by activated TAK1, inhibiting its nuclear accumulation and mictophthalmia-associated transcription factor and cyclin dependent kinase 2 expression. The dominant-negative TAK1 mutant K63W inhibited beta-catenin phosphorylation and caspase activation. The data indicate that H11/HspB8 overload causes melanoma growth arrest and apoptosis through TAK1 activation and suggest that H11/HspB8 is a promising molecular therapy target.

Apoptosis↗
PubMed2006

Prolonged function of macrophage, von Willebrand factor-deficient porcine pulmonary xenografts.

Porcine von Willebrand factor (vWF) activates human and primate platelets. Having determined the importance of pulmonary intravascular macrophages (PIMs) in pulmonary xenotransplantation, we evaluated whether, in the absence of PIMs, vWF might play a role in pulmonary xenograft dysfunction. Utilizing a left single-lung transplant model, baboons depleted of anti-alphaGal antibodies received lungs from either vWF-deficient (n = 2); MCP-expressing (n = 5); MCP PIM-depleted (n = 5); or vWF-deficient PIM-depleted swine (n = 3). Two out of three of the PIM-depleted, pvWF deficient grafts survived longer than any previously reported pulmonary xenografts, including PIM-depleted xenografts expressing human complement regulatory proteins. Depletion of PIM's from vWF-deficient lungs, like depletion of PIM's from hMCP lungs, resulted in abrogation of the coagulopathy associated with pulmonary xenotransplantation. Thus, in terms of pulmonary graft survival, control of adverse reactions involving pvWF appears to be equally or even more important than is complement regulation using hMCP expression. However, based on the rapid failure of PIM-sufficient, pvWF-deficient pulmonary xenografts, pVWF-deficient pulmonary xenografts appear to be particularly sensitive to macrophage-mediated damage. These data provide initial evidence that vWF plays a role in the 'delayed' (24 h) dysfunction observed in pulmonary xenotransplantation using PIM depleted hMCP organs.

Animals↗
PubMed2006

Potent antitumor efficacy of XAF1 delivered by conditionally replicative adenovirus vector via caspase-independent apoptosis.

XAF1 is a newly identified tumor-suppressor gene that can antagonize XIAP and sensitize cells to other cell death triggers. In this study, we utilized ZD55, a conditionally replicative adenovirus (CRAd) similar to ONYX-015 as the vector to transfer XAF1 into the tumor cells to evaluate its antitumor efficacy in vitro and in vivo. Potent and specific cytopathic effect (CPE) was observed upon infection with ZD55-XAF1 in tumor cell lines. Importantly, ZD55-XAF1 exhibited a superior suppression of tumor growth in an animal model of colorectal carcinoma in nude mice compared with Ad-XAF1 (E1-deleted replication-defective viral) and ONYX-015. Complete eradication of the established tumors was observed in four of eight mice. Our data also showed that infection with ZD55-XAF1 resulted in caspase-independent apoptosis. Although caspase-3, poly(ADP-ribose) polymerase were mildly activated in response to ZD55-XAF1 infection, pretreatment with pan-caspase inhibitor hardly influence its apoptosis-inducing activity. In summary, our study strongly suggested that ZD55-XAF1 could serve as an effective gene-virotherapy strategy and has highly potential against human cancers.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Magnetic field effects on spatial relaxation of swarm particles in the idealized steady-state Townsend experiment.

The effect of a magnetic field at right angles to an electric field on spatial relaxation of a swarm of charged particles emitted by a plane source into a gas-the idealized steady-state Townsend experiment-is examined. The Boltzmann equation is solved using an adaptation of the "two-temperature" moment method, involving a Burnett function representation of the velocity distribution function, a technique which is valid for charged particles of arbitrary mass and is intrinsically of a "multiterm" nature. Results are presented for electrons in model and real gases, and are benchmarked against an exact analytical solution of the Boltzmann equation for a particular collision model. The application of a magnetic field significantly alters the relaxation profiles: in general, it can both enhance or retard spatial relaxation of transport properties. For methane gas, a multiterm analysis is essential to correctly account for the relaxation near the source, even though a two-term approximation may be sufficient when the magnetic field is sufficiently strong and hydrodynamic conditions dominate.

Journal Article↗
PubMed2006

Improved reversed-phase liquid chromatographic method combined with pulsed electrochemical detection for the analysis of amikacin.

A two-step gradient liquid chromatographic method combined with pulsed electrochemical detection is described for the determination of amikacin and its impurities. The mobile phase is composed of an aqueous solution containing 1.8 g/l sodium 1-octanesulphonate, 14 ml/l tetrahydrofuran, 50 ml/l of phosphate buffer pH 3.0 and sodium sulphate, which was 20 g/l in mobile phase A and 28 g/l in mobile phase B. 0.5 M sodium hydroxide was added post-column to enhance the detection. An investigation of different reversed-phase columns indicated that the Discovery (C18, 5 microm, 250 mm x 4.6 mm i.d.) column was the most suitable. Compared to previously published investigations, the proposed method showed higher sensitivity and efficiency, allowing the separation of the main component amikacin from 16 impurities, 7 of which were of unknown identity. A central composite experimental design was used to assess the robustness. The method showed good repeatability and linearity in the assay range. The method was further applied to analyze some commercial samples.

Algorithms↗
PubMed2006

Applications of noise theory to plasma fluctuations.

Noise theory is used to study the temporal correlations of stationary random fluctuations that are homogeneous in space. Statistical properties of the fluctuations, such as the power spectrum and the correlation function, are computed. The results are compared with the observed plasma density fluctuations from tokamak experiments.

Journal Article↗
PubMed2006

Centrosomal proteins Nde1 and Su48 form a complex regulated by phosphorylation.

The centrosome modulates spindle formation and plays a critical role in guiding proper segregation of chromosomes during cell division. Centrosome aberrations, frequently seen in human tumors, may cause abnormal chromosome segregation and contribute to malignant transformation. To explore the components of the centrosomes, we previously identified a novel centrosomal protein called Su48. To further characterize the Su48-containing protein ensemble in the centrosome, we performed yeast two-hybrid screens and isolated a number of Su48-interacting molecules, including the centrosomal protein Nde1. Here, we demonstrate that Su48 can associate with Nde1. Moreover, we found that Nde1 is subjected to phosphorylation in vivo. In particular, we identified six putative Cdc2 phosphorylation sites in Nde1 and found that alteration of these sites diminishes phosphorylation by Cdc2 in vitro and affects the stability of Su48-Nde1 interactions and the centrosomal localization of Nde1. Ablation of Nde1 by gene specific small interfering RNA causes mitotic delay and cell death, coupled with a modest decrease in the incidence of the cells that harbor excessive centrosomes. Collectively, our findings indicate that Nde1 can form a protein complex with Su48 in the centrosome and plays an important role for successful mitosis.

Carrier Proteins↗
PubMed2006

Numerical simulations of type-III solar radio bursts.

The first numerical simulations are presented for type-III solar radio bursts in the inhomogeneous solar corona and interplanetary space, that include microscale quasilinear and nonlinear processes, intermediate-scale driven ambient density fluctuations, and large scale evolution of electron beams, Langmuir and ion sound waves, and fundamental and harmonic electromagnetic emission. Bidirectional coronal emission is asymmetric between the upward and downward directions, and harmonic emission dominates fundamental emission. In interplanetary space, fundamental and/or harmonic emission can be important. Langmuir and ion sound waves are bursty and the statistics of Langmuir wave energy agree well with the predictions of stochastic growth theory.

Journal Article↗
PubMed2006

The decline of the photopic negative response (PhNR) in the rat after optic nerve transection.

PURPOSE: To investigate the contribution to the photopic negative response (PhNR) of the electroretinogram (ERG) by retinal ganglion cells (RGCs). The PhNR was assessed longitudinally following optic nerve transection (ONTx). METHODS: Photopic ERGs were recorded from each eye of an anesthetized (ketamine/xylazine, 60 mg/kg and 5 mg/kg) Brown Norway rat using custom made electrodes (PT-IR Tef., A-M System Inc). ERGs were elicited using green Ganzfeld flashes (11.38 scd/m(2), 22.76 cds/m(2)) and a rod suppressing green-background (40 cd/m(2)). PhNRs were compared before and after optic nerves were transected. Cresyl violet stained retinal flatmounts were used to estimate cell loss in the ganglion cell layer 3 and 15 weeks after optic nerve transection. The pharmacological effect of 1.3 microM intravitreal TTX on the PhNR was also evaluated. RESULTS: There was a significant loss (p <0.05) in the PhNR of 20, 36, 34, 35, 48, 48 and 56% for ONTx eye versus the contralateral eye, at post ONTx times of 24 h, 1, 2, 3, 4, 8 and 15 weeks. B-wave amplitudes of ONTx eyes were not significantly different from the control eyes. In ONTx eyes, mean cell loss in the retinal ganglion cell layer was 27 and 55% at the 3 week and 15 week time periods. In the eyes with ONTx, the decline of PhNR amplitudes was correlated positively with RGC loss (r = 0.98; p < 0.01). Thirty minutes after intravitreal TTX injection, the PhNR was significantly reduced (57%, p<0.01). CONCLUSIONS: There was a time-dependent decline in the PhNR after ONTx, as exemplified by a 35% reduction from 1-3 weeks, a 48% decline for 4-8 weeks and a 56% decline after 15 weeks. The correlation between the decline in the PhNR and retinal ganglion cell loss suggests that the PhNR depends on inner retina integrity and the PhNR may be important biological signal or detecting glaucomatous damage and the monitoring of RGC function changes in early glaucoma.

Anesthetics, Local↗
PubMed2006

cisRED: a database system for genome-scale computational discovery of regulatory elements.

We describe cisRED, a database for conserved regulatory elements that are identified and ranked by a genome-scale computational system (www.cisred.org). The database and high-throughput predictive pipeline are designed to address diverse target genomes in the context of rapidly evolving data resources and tools. Motifs are predicted in promoter regions using multiple discovery methods applied to sequence sets that include corresponding sequence regions from vertebrates. We estimate motif significance by applying discovery and post-processing methods to randomized sequence sets that are adaptively derived from target sequence sets, retain motifs with p-values below a threshold and identify groups of similar motifs and co-occurring motif patterns. The database offers information on atomic motifs, motif groups and patterns. It is web-accessible, and can be queried directly, downloaded or installed locally.

Animals↗
PubMed2006

Factors related to post-liver transplantation acute renal failure.

Acute renal failure (ARF) after liver transplantation (OLT) is a common complication with severe impact on early and late prognosis of recipients. Factors predicting its incidence have not been fully identified due to the lack of a universal standard as well as the variance of data between transplant centers. To identify factors related to post-OLT ARF, we retrospectively collected materials on 89 patients, who underwent OLT from 1999 to 2001 in our center. Factors associated with post-OLT ARF were identified using univariate logistic regression. Significant factors were then entered into a multivariate logistic regression to identify factors independently associated with post-OLT ARF. Upon univariate analysis, intraoperative volume of blood transfusion (P = .041) and duration of operation (P = .005) were significant. ARF was associated with a poor prognosis (P < .001). Only duration of operation (P = .026) was an independent factor predicting the development of ARF. In conclusion, intraoperative volume of blood transfusion and duration of operation were factors contributing to post-OLT ARF in which the duration of the operation was an independent risk factor. The incidence of post-OLT ARF greatly increased recipient mortality in the early postoperative period.

Acute Kidney Injury↗
PubMed2006

Postoperative severe pneumonia in adult liver transplant recipients.

Severe pneumonia in adult liver transplantation (OLT) recipients is a dangerous condition with significant morbidity and mortality. To analyze the risk factors for postoperative severe pneumonia in OLT patients, we collected data from 132 consecutive adult patients who underwent OLT between February 1999 and April 2004. According to the American Thoracic Society consensus statement, episodes of severe pneumonia were observed in 24 patients (18.2%). We retrospectively reviewed the etiology diagnosis, treatment, and prognosis of the 24 recipients. Bacteria were responsible for 95.8% of these episodes (23 of 24), fungi for 16.7% (4 of 24) and viruses for 4.4% (1 of 24). Twenty-six percent of the bacterial pneumonias were due to Streptococcus alpha hemolyticus. The mortality rate was 37.5% (9 of 24) for patients with severe pneumonia versus 7.4% (8 of 108, P = .004) for patients without pneumonia. Two cases with hepatorenal syndrome died, and three patients with coinfection by bacteria and fungi died. Acute rejection episodes occurred in 15 patients, four of whom died. Mechanical ventilation and tracheotomy were required in 13 cases (54%). Six who experienced prolonged intubation died. Sputum and pleural fluid cultures helped to establish a diagnosis in 91.7% (22 of 24) of cases. Twenty cases (83%) underwent reduction in the immunosuppressive regimen. Patient age, intraoperative transfusion requirements, extubation time, and hospital stay were fatal predictors of prognoses. We concluded that early detection of the responsible pathogen; timely and specific diagnosis; reduction in the immunosuppressive regimen; appropriate treatment with reliable, effective techniques; and implementation of sensitive culture-based antibiotics was an effective strategy to treat severe adult pneumonia in liver transplantation recipients.

Adult↗
PubMed2006

Bone marrow cell infusion ameliorates progressive glomerulosclerosis in an experimental rat model.

Bone marrow (BM) cells contribute to the maintenance and repair of several compartments of the kidney, including the endothelium, interstitium, epithelium, and the mesangium. The aim of this study was to explore the therapeutic use of bone marrow-derived cells (BMDC) that can differentiate into endothelial and mesangial cells in a model of progressive glomerulosclerosis. To investigate the involvement of BMDC in glomerular repair, progressive glomerulosclerosis was induced in enhanced green fluorescent protein BM chimeric rats by a one-shot injection of anti-Thy-1.1 monoclonal antibody, followed by unilateral nephrectomy. Subsequently, these rats were treated with either a BM cell infusion or phosphate-buffered saline. Renal function, intravital glomerular hemodynamics, and histological alterations were examined 12 weeks after anti-Thy-1.1 monoclonal antibody injection. Inflammatory infiltration of macrophages in the kidneys was evaluated by immunofluorescence of ED-1. We also determined whether BMDC contributed to repair and regeneration of endothelial and mesangial cells by immunofluorescence monitoring. As a result, BM cell infusion improved renal function and glomerular hemodynamics, and histological alterations with reduced glomerular infiltration of macrophages, leading to dramatically reduced mortality in this model of progressive glomerulosclerosis. We also demonstrated that, in the BM cell infusion group, more BMDC contributed to repair and regeneration of endothelial and mesangial cells than in the untreated group. The present study provides us with a conceptual basis for the development of therapeutic stem cell strategies aimed at enhancing recovery from progressive glomerulosclerosis.

Animals↗
PubMed2006

Turbulence of glomerular hemodynamics involved in progressive glomerulosclerosis.

There is increasing evidence that changes of glomerular hemodynamics or glomerular growth responses may promote the development of glomerulosclerosis. Major problems retarding research progress include lack of suitable experimental animal models, with the exception of the ablation model, and the need for in vivo real-time analysis of glomerular hemodynamics. This study examined the sequence of pathological changes from the viewpoints of microcirculation and histopathology, from the acute stage to the chronic course and the final stage of glomerulosclerosis, using the confocal laser scanning microscope system. There is a marked difference in prognosis between sham-operated (two-kidney) and nephrectomized (one-kidney) rats after injection with anti-Thy-1 antibody. The former reversibly returns to normal and the latter irreversibly go to progressive sclerosis, respectively. The turning point determining the progression of glomerulosclerosis in both groups seemed to be the period from 7 to 14 days after disease induction, when disturbance of local intraglomerular blood flow continued in the one-kidney groups. In conclusion, this study provides the first hemodynamic-based evidence showing that disturbance of intraglomerular microcirculation is a critical marker for progressive glomerulosclerosis.

Albumins↗
PubMed2006

Inhibition of human leukemia xenograft in nude mice by adenovirus-mediated tissue inhibitor of metalloproteinase-3.

Considerable studies have demonstrated the pivotal roles of matrix metalloproteinases (MMPs) in leukemia dissemination and extramedullary infiltration. Tissue inhibitors of matrix metalloproteinases (TIMPs) are multifunctional proteins with MMPs inhibitory effects. However, little is known about the application of TIMPs in the treatment of leukemia. Here, we investigated the effects of TIMP-3 overexpression via adenoviral gene delivery on the in vitro growth and invasiveness of leukemic cells and the in vivo progress of K562-derived xenografts in nude mice. The in vitro invasiveness of K562 cells was markedly impaired by AdTIMP-3 infection. Moreover, TIMP-3 significantly inhibited K562-derived angiogenic factors-induced proliferation, migration and bFGF-induced tube formation of endothelial cells (ECs) in vitro, and reduced VEGF-induced gelatinases expression and activation in ECs. Although TIMP-3 overexpression had no direct effect on the growth of K562 cells in vitro, repeated intratumoral injection of AdTIMP-3 significantly inhibited the growth of K562 xenografts in nude mice. Furthermore, lower microvessel density, less vessel maturity and increased apoptosis were observed in AdTIMP-3-treated K562 xenografts, suggesting the importance of antiangiogenic action of TIMP-3. These data demonstrated the potential of applying AdTIMP-3 as an effective antiangiogenic adjuvant in the treatment of leukemia progression.

Adenoviridae↗