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Biomedical subjects

Yang Yang

Publications and source records attributed to Yang Yang.

At least 55 records · Page 3Linked to original sources
PubMed2006

ZD6474 induces growth arrest and apoptosis of GIST-T1 cells, which is enhanced by concomitant use of sunitinib.

ZD6474 (Zactima, AstraZeneca, Macclesfield, UK) is an orally available, small-molecule inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases, with additional activity versus rearranged during transfection (RET). This study explored the effect of ZD6474 in gastrointestinal stromal tumor-T1 (GIST-T1) cells that possess a gain of function mutation in exon 11 of the c-KIT gene. ZD6474 induced growth arrest and apoptosis of GIST-T1 cells in association with blockade of c-Kit and its downstream effectors, including Akt and extracellular signal-regulated kinase (ERK). ZD6474 treatment also blocked the mammalian target of rapamycin (mTOR), which lies downstream of Akt and ERK. Interestingly, when ZD6474 was combined with sunitinib (SU11248; Sutent, Pfizer, Kalamazoo, MI, USA), a class III and V receptor tyrosine kinase inhibitor, the ZD6474-mediated growth inhibition was potentiated in association with further down-regulation of the mTOR targets p-p70S6K and p-4E-BP-1. The combination of ZD6474 and sunitinib should be investigated further.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Immunomodulatory therapy of cytomegalovirus pneumonia after liver transplantation.

BACKGROUND: There has been increasing interest in the research into cytomegalovirus (CMV) pneumonia after liver transplantation (LT). This study was undertaken to investigate the immunomodulatory therapy of CMV pneumonia after LT. METHODS: Six patients with CMV pneumonia after LT from October 2003 to November 2005 were analyzed retrospectively. They were diagnosed according to clinical manifestations, chest X-ray findings and pathogenic changes and given comprehensive therapy including mainly immunomodulation therapy and anti-viral medication. At the early stage of CMV pneumonia, the dose of immunosuppressive agents was decreased or ceased, instead replaced by immunoenhancement therapy. During recovery period from CMV pneumonia, the dose of immunosuppressive agents was given again or enhanced, and immunoenhancement therapy was ceased. The liver function of the patients was monitored closely during the treatment. RESULTS: In this series, five patients were survived and one died. The liver function of the six patients remained normal during the treatment, and no episode of acute rejection took place. CONCLUSIONS: Poor immunity is the pathogenic basis of CMV pneumonia after LT. At early stage of CMV pneumonia, the immunity of the patients should be enhanced, and during the recovery period from CMV pneumonia, immunosuppressants should be given again but immunoenhancement therapy ceased. Individualized immunomodulatory therapy is essential to the treatment of CMV pneumonia after LT.

Adjuvants, Immunologic↗
PubMed2006

Comparative proteomic analysis of apoptosis induced by sodium selenite in human acute promyelocytic leukemia NB4 cells.

Selenium (Se) is an essential trace element possessing anticarcinogenic properties. Sodium selenite (Na2SeO3) induced apoptosis in human acute promyelocytic leukemia (APL) cell line NB4 with dose and time dependency. In this study, proteomic techniques were used to study the apoptosis of NB4 cells induced by sodium selenite. Twenty-six downregulated and four upregulated proteins were identified, which exhibited a 1.5-fold change or greater. The identified proteins included key regulators of signal transduction such as Rho GDP dissociation inhibitor (Rho GDI) alpha and beta members of the MAPK family, and proteins involved in the regulation of c-fos or c-myc expression. Importantly, the identified proteins, hnRNP D0B and Rho GDI beta, which were related with the regulation of c-myc, c-fos, and c-jun, were determined by reverse transcription-polymerase chain reaction (RT-PCR) to confirm their downregulation in proteomic study. Western blot analysis and RT-PCR were then performed on three associated proteins: c-Myc, c-Fos, and c-Jun, and their expression were observed to be significantly downregulated. Results showed that certain regulation involved in c-myc, c-fos, and c-jun was present in the apoptosis, and the c-Myc dependent-on and Jun N-terminal kinase (JNK) pathway also play roles.

Apoptosis↗
PubMed2006

Containing a large bioterrorist smallpox attack: a computer simulation approach.

BACKGROUND: A bioterrorist release of smallpox is a constant threat to the population of the USA and other countries. DESIGN: A stochastic simulation model of the spread of smallpox due to a large bioterrorist attack in a structured population was constructed. Disease natural history parameter estimates, time lines of behavioral activities, and control scenarios were based on the literature and on the consensus opinion of a panel of smallpox experts. RESULTS: The authors found that surveillance and containment, i.e., isolation of known cases and vaccination of their close contacts, would be sufficient to effectively contain a large intentional smallpox release. Given that surveillance and containment measures are in place, preemptive vaccination of hospital workers would further reduce the number of smallpox cases and deaths but would require large numbers of prevaccinations. High levels of reactive mass vaccination after the outbreak begins would further reduce smallpox cases and deaths to a minimum, but would require even larger numbers of vaccinations. Reactive closure of schools would have a minimal effect. CONCLUSION: A rapid and well-organized response to a bioterrorist attack would be necessary for effective surveillance and containment to control spread. Preemptive vaccination of hospital workers and reactive vaccination of the target population would further limit spread, but at a cost of many more vaccinated. This cost in resources and potential harm due to vaccination will have to be weighed against the potential benefits should an attack occur. Prevaccination of the general population is not necessary.

Bioterrorism↗
PubMed2006

The use of coronary stent in hepatic artery stenosis after orthotopic liver transplantation.

PURPOSE: This retrospective study was undertaken to evaluate the effectiveness of coronary stent placement in hepatic artery stenosis after orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Of 430 consecutive adult orthotopic liver transplant recipients between November 2003 and September 2005, 17 had hepatic artery stenosis (HAS). Fourteen of them underwent coronary stent placement in the HAS. The technical results, complications, hepatic artery patency and clinical outcome were reviewed. RESULTS: Technical and immediate success was 100%. After a mean follow-up of 159.4 days (range, 9-375 days), all patients obtained patent hepatic arteries except 2 patients occurred hepatic artery restenoses at 26 and 45 days after stent placement, respectively. Kaplan-Meier curve of patency showed cumulated stent patency at 3, 6, and 12 months of 78%, 58% and 45%, respectively. During the follow-up, 8 patients survived, 5 died of septic multiple-organ failure, 1 received retransplantation because of refractory biliary infection. Hepatic artery dissection induced by a guiding catheter occurred in one patient and was successfully treated with a coronary stent. CONCLUSION: Hepatic artery stenosis after OLT can be successfully treated with coronary stent placement with low complication rate and an acceptable 1-year hepatic artery patency rate.

Adult↗
PubMed2006

[The distribution and pathogen of bacteria infection in patients after liver transplantation].

OBJECTIVE: To find out the epidemiology of bacteria infection after orthotopic liver transplantation (OLT). METHOD: Postoperative bacteria infection of 451 OLT cases were retrospectively analyzed. RESULT: Bacteria infection were detected in 239 OLT cases, and the infection rate was 52.9%. Sum up to 304 bacilli lines were separated from all above cases. Among them, the detectable Gram-positive bacilli (G(+)) accounted for 59.9% (182/304), while Gram-negative bacilli (G(-)) accounted for 40.2% (122/304). The impressionable organ were respiratory tract and bile duct, which occupying 81.5% (248/304) and 15.1% (46/304) among all infective cases respectively. The main infected strain were G(+) bacteria in respiratory tract, account for 65.3%; while G(-) bacteria were mainly in bile duct, account for 60.9%. There was significant difference between each other (P = 0.018). CONCLUSIONS: The bacteria infection rate was high after OLT, and the main infected strain was the G(+) bacteria. Most fo them were the opportunistic pathogenic bacteria and the antibiotic multi-resistant bacteria. The bacteria category was significantly related to the infected tissue, according to which we could adopt corresponding antibacterial approach.

Adolescent↗
PubMed2006

Antimicrobial susceptibility and molecular determinants of quinolone resistance in Neisseria gonorrhoeae isolates from Shanghai.

OBJECTIVES: To determine the antimicrobial susceptibility of Neisseria gonorrhoeae from Shanghai and to type the quinolone resistance-determining regions (QRDRs) of ciprofloxacin-resistant isolates. METHODS: N. gonorrhoeae isolates (n = 159) were consecutively collected from male patients in Shanghai and examined for their antimicrobial susceptibilities to penicillin, tetracycline, ciprofloxacin, spectinomycin and ceftriaxone. The mutation profiles of the QRDRs of gyrA and parC were determined for 103 isolates including one susceptible isolate and one isolate with intermediate levels of susceptibility to ciprofloxacin. RESULTS: High percentages of the 159 isolates were resistant to ciprofloxacin (98.7%), penicillin (93.1%) and tetracycline (56.5%). Penicillinase-producing N. gonorrhoeae (PPNG, 37.8%) or penicillinase-producing/tetracycline-resistant N. gonorrhoeae (PP/TRNG, 13.8%) accounted for 51.6% of the isolates. Chromosomal resistance to penicillin was observed in 41.5% of the isolates. Tetracycline resistance was noted in 56.5% of the isolates with 20.1% carrying plasmid-mediated resistance and 36.4% being chromosomally resistant. All isolates were susceptible to ceftriaxone and spectinomycin, although a trend to decreased susceptibility was noted. QRDR mutations were observed in the 101 ciprofloxacin-resistant isolates and the one ciprofloxacin-intermediate isolate, in contrast to the ciprofloxacin-susceptible isolate tested. Mutations in the QRDRs comprised four predominant (65.0% of the 103 isolates) patterns of a total of 19 patterns. Mutations in parC were significantly associated with higher MICs of ciprofloxacin. CONCLUSIONS: Spectinomycin and ceftriaxone are currently recommended for the treatment of gonorrhoea in Shanghai. Although the present study indicates that these antimicrobials should remain effective, the identification of isolates with decreased susceptibility underscores the importance of ongoing antimicrobial susceptibility surveillance to monitor and respond to the emergence of resistant isolates.

Anti-Infective Agents↗
PubMed2006

Regioregular copolymers of 3-alkoxythiophene and their photovoltaic application.

Low band gap conjugated polymers with proper energy levels for charge transfer are required to achieve high-efficiency polymer solar cells. We report the synthesis and characterization of two new regioregular copolymers that are based on 3-alkoxythiophene monomers: poly(3-octylthiophene-2,5-diyl-co-3-decyloxythiophene-2,5-diyl) (POT-co-DOT) and poly{(9,9-dioctylfluorene)-2,7-diyl-alt-[4,7-bis(3-decyloxythien-2-yl)-2,1,3-benzothiadiazole]-5',5' '-diyl} (PF-co-DTB). Compared to the alkyl substituents, the alkoxy side chains on the thiophene units can effectively lower the band gap of copolymers and enhance the charge transfer to electron acceptors such as (6,6)-phenyl C(61)-butyric acid methyl ester (PCBM). The chemical structure and regioregularity of the copolymers were confirmed by NMR. Both copolymers are readily soluble in organic solvents and form high-quality thin films. Electrochemical and photophysical studies reveal band gaps of 1.64 eV for POT-co-DOT and 1.78 eV for PF-co-DTB. Bulk heterojunction photovoltaic devices were fabricated using blends of these copolymers with PCBM as the active layer, ITO-glass as the anode, and aluminum as the cathode. Power conversion efficiency of 1.6% was obtained under simulated solar light AM 1.5 G (100 mW/cm(2)) from a solar cell with an active layer containing 20 wt % PF-co-DTB and 80 wt % PCBM. Regioregular poly(3-decyloxythiophene-2,5-diyl) (P3DOT) was also studied for comparison purposes.

Journal Article↗
PubMed2006

[Effect of human beta defensin 2 on Staphylococcus aureus infection: in vivo study with transgenic mice].

OBJECTIVE: To investigate the effect of human beta defensin 2 (HBD-2) on Staphylococcus aureus infection. METHODS: A minigene of HBD-2 containing pCMV promoter, full length of HBD-2 cDNA, and BGH polyA tail was generated by PCR amplification and introduced into the fertilized oocytes of C57/ICR hybridized mouse by microinjection. After gestation of 3 - 4 weeks, immunohistochemistry was used to detect the expression of HBD-2 peptide in different tissues of the transgenic young mice. Staphylococcus aureus was cultured and injected intraperitoneally to wild type mice and transgenic mice to observe their surviving status. RESULTS: PCR showed that the HBD-2 fragment had been successfully integrated into the chromosome of the mice. A widespread expression of HBD-2 gene was found in many tissues of the transgenic mice: trachea, lung, intestine, esophagus, testis, spleen, skin, endothelium, brain, etc. Four of the 7 transgenic mice survived the Staphylococcus aureus infection, and 10 wild type mice all died within 24 hours. CONCLUSION: HBD-2 may play an important role ion the host defense against Staphylococcus aureus infection.

Animals↗
PubMed2006

[Diagnosis and treatment of invasive aspergillosis infection following orthotopic liver transplantation].

OBJECTIVE: To explore the treatment and appropriate management of invasive aspergillosis infection following orthotopic liver transplantation. METHODS: The clinical data of 576 cases who underwent orthotopic liver transplantation consecutively between January 2000 and January 2005 were analyzed retrospectively. RESULTS: The prevalence of invasive aspergillosis infection was 1.74 (9/576), included 8 cases with pulmonary aspergillosis and 1 case with cerebral aspergillosis. The interval between transplantation and diagnosis were from 10 days to 2 months. Persistent or discontinuous low fever maybe the main clinical presentation after operation. Liposomal amphotericin B (AmBisome) is the mainly treatment for invasive aspergillosis infections, 5 patients were cured and 2 patients developed multi-organ aspergillosis infection died. CONCLUSIONS: The clinical features of invasive aspergillosis infection following orthotopic liver transplantation were un-typical presentations in the early stage and easy to disseminate. Appropriate modification of immunosuppression therapy and early, high dose and long-term application of antifungal treatment is effective and safe to cure the disease.

Adult↗
PubMed2006

[The treatment strategy of early ALI after liver transplantation].

OBJECTIVE: To investigate the treatment strategy of early acute lung injury (ALI) after liver transplantation. METHODS: 18 patients complicated with ALI after liver transplantation were given comprehensive therapies and two minutes of recruitment maneuver (RM) to open previously collapsed lung units and then lung protective ventilatory strategy within 3 hours of hypoxemia. The inspiratory pressure was 25 cm H2O and PEEP 17 cm H2O. Optimal PEEP were maintained after RM to stabilize lung volume. RESULTS: The PaO(2), SaO(2) and PaO(2)/FiO(2) of all 18 patients were improved greatly. RM was effective in 17 patients except one case of severe pulmonary infection, whose PaO(2)/FiO(2) was only improved by 40%. PaO(2), SaO(2) and PaO(2)/FiO(2) were increased by 68 mm Hg, 9.5%, and 104.7% respectively. And the improved oxygenation can be maintained 2 - 24 hours. The effective rate of RM was 94.4%. All 18 patients were weaned and extubated successfully with the survival rate of 100%. RM was well tolerated without complications. CONCLUSION: ALI post liver transplantation should be diagnosed and treated in early stage. RM combined with lung protective ventilatory strategy is a safe and effective treatment for early ALI after liver transplantation.

Combined Modality Therapy↗
PubMed2006

Genome-wide transcriptional analysis of temperature shift in L. interrogans serovar lai strain 56601.

BACKGROUND: Leptospira interrogans is an important mammalian pathogen. Transmission from an environmental source requires adaptation to a range of new environmental conditions in the organs and tissues of the infected host. Several studies have shown that a shift in culture temperature from 28 degrees C to 37 degrees C, similar to that encountered during infection of a host from an environmental source, is associated with differential synthesis of several proteins of the outer membrane, periplasm and cytoplasm. The whole genome of the Leptospira interrogans serogroup Icterohaemorrhagiae serovar lai type strain #56601 was sequenced in 2003 and microarrays were constructed to compare differential transcription of the whole genome at 37 degrees C and 28 degrees C. RESULTS: DNA microarray analyses were used to investigate the influence of temperature on global gene expression in L. interrogans grown to mid-exponential phase at 28 degrees C and 37 degrees C. Expression of 106 genes differed significantly at the two temperatures. The differentially expressed genes belonged to nine functional categories: Cell wall/membrane biogenesis genes, hemolysin genes, heat shock proteins genes, intracellular trafficking and secretion genes, two-component system and transcriptional regulator genes, information storage and processing genes, chemotaxis and flagellar genes, metabolism genes and genes with no known homologue. Real-time reverse transcription-PCR assays confirmed the microarray data. CONCLUSION: Microarray analyses demonstrated that L. interrogans responds globally to temperature alteration. The data delineate the spectrum of temperature-regulated gene expression in an important human pathogen and provide many new insights into its pathogenesis.

Bacterial Proteins↗
PubMed2006

[Prevention and treatment of hepatitis B virus reinfection after liver transplantation].

OBJECTIVE: To investigate the risk factors and treatment of hepatitis B virus (HBV) reinfection after liver transplantation. METHODS: Patients with HBV related end-stage liver disease underwent liver transplantation in our center, and received the combination of intramuscular hepatitis B virus immunoglobulin and oral lamivudine as prophylaxis for HBV reinfection. HBV reinfection cases were monitored after the transplantation. RESULTS: HBsAg disappeared and HBsAb was detectable in 128 of total 130 patients. The median follow-up period was 12.2 months after transplantation. Eight patients developed HBV reinfection. The recurrence rate of HBV was 6.3%. The reinfection risks were 14.3% and 4.0% respectively among patients with serum HBeAg positive and negative before transplantation (P < 0.05). Among patients with serum HBsAg positive and negative at the first day after liver transplantation, the reinfection risks were 21.1% and 3.7% respectively (P < 0.05). CONCLUSIONS: Combination of intramuscular HBIg and Lamivudine as prophylaxis of HBV reinfection is effective. HBeAg positive before liver transplantation and HBsAg positive at the first day after transplantation are risk factors of HBV reinfection.

Antiviral Agents↗
PubMed2006

Spectrins and ankyrinB constitute a specialized paranodal cytoskeleton.

Paranodal junctions of myelinated nerve fibers are important for saltatory conduction and function as paracellular and membrane protein diffusion barriers flanking nodes of Ranvier. The formation of these specialized axoglial contacts depends on the presence of three cell adhesion molecules: neurofascin 155 on the glial membrane and a complex of Caspr and contactin on the axon. We isolated axonal and glial membranes highly enriched in these paranodal proteins and then used mass spectrometry to identify additional proteins associated with the paranodal axoglial junction. This strategy led to the identification of three novel components of the paranodal cytoskeleton: ankyrinB, alphaII spectrin, and betaII spectrin. Biochemical and immunohistochemical analyses revealed that these proteins associate with protein 4.1B in a macromolecular complex that is concentrated at central and peripheral paranodal junctions in the adult and during early myelination. Furthermore, we show that the paranodal localization of ankyrinB is disrupted in Caspr-null mice with aberrant paranodal junctions, demonstrating that paranodal neuron-glia interactions regulate the organization of the underlying cytoskeleton. In contrast, genetic disruption of the juxtaparanodal protein Caspr2 or the nodal cytoskeletal protein betaIV spectrin did not alter the paranodal cytoskeleton. Our results demonstrate that the paranodal junction contains specialized cytoskeletal components that may be important to stabilize axon-glia interactions and contribute to the membrane protein diffusion barrier found at paranodes.

Animals↗
PubMed2006

Distinct effects of different concentrations of sodium selenite on apoptosis, cell cycle, and gene expression profile in acute promyeloytic leukemia-derived NB4 cells.

Selenium at a low concentration has a chemopreventive role against cancer, while at a high concentration, it exerts a direct antitumor effect. However, the mechanisms remain elusive. In this article, we discovered that Na(2)SeO(3) at 20 micromol/l concentration could significantly inhibit the proliferation of NB4 cells, affect the cell cycle distribution of cell population, and induce cellular changes characteristic of apoptotic cells, while this same compound at 2 micromol/l concentration had no such effects. The mechanisms underlying these overt differences caused by treatment of different concentrations of selenium were further investigated. cDNA microarray analysis showed that after treatment by 20 micromol/l Na(2)SeO(3), 34 genes were changed in expression, while treatment by 2 micromol/l Na(2)SeO(3) resulted in the changes of 29 genes. Nine genes were regulated in both groups, among which three showed opposite changes caused by 2 and 20 micromol/l Na(2)SeO(3). The majority of regulated genes did not coincide between the two experiment groups. In conclusion, 2 and 20 micromol/l Na(2)SeO(3) could have different effects on NB4 cells, and some genes might be involved in the underlying mechanisms. Our findings could provide basis for further uncovering the molecular mechanisms of the chemopreventive and antitumor effects of selenium and, in turn, for probing the rationality of treating leukemia with selenium.

Apoptosis↗
PubMed2006

Phenotypically distinct B cell development pathways map to the three B cell lineages in the mouse.

A recent article by Montecino-Rodriguez et al. [Montecino-Rodriguez, E., Leathers, H. & Dorshkind, K. (2006) Nat. Immunol.7, 293-301] has distinguished the early progenitors for B-1 cells, which principally develop in neonates, from early progenitors for B-2 cells, which principally develop in adult bone marrow. Here we introduce syndecan-1 (CD138) and MHC class II (I-A) as markers of early B cell development [Hardy, R. R., Carmack, C. E., Shinton, S. A., Kemp, J. D. & Hayakawa, K. (1991) J. Exp. Med. 173, 1213-1225; Hardy fractions B-D] and show that the expression of these markers distinguishes the predominant B cell development pathway in neonates from the corresponding predominant pathway in adults (both progenitors are present but differently represented in each case). We show that pre-B cells (Hardy fraction D) in the predominant adult pathway express high levels of CD138 and intermediate levels of I-A, whereas the corresponding pre-B cells in the pathway that predominates in neonates do not express either of these markers. As expected, because most of the pre-B cells in adults express CD138, we find that sorted CD138+ adult pre-B cells differentiate to IgM+ B cells in vitro. Sorted CD138- pre-B cells from neonates, the majority subset at this age, also mature to IgM+ cells (without passing through a CD138+ stage). Importantly, our studies here confirm the differential representation of adult and neonatal progenitor populations and further demonstrate that CD138 expression subdivides the adult CD19+, B220-6B2-/low population shown to contain B-1 progenitors in a way consistent with the predominance of B-1b progenitors in adults. Thus, CD138 expression provides a key route to distinguishing early B cell development pathway for what now are clearly three B cell lineages.

Animals↗