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Qiang Liu

Publications and source records attributed to Qiang Liu.

At least 73 records · Page 4Linked to original sources

Presynaptic ryanodine receptors are required for normal quantal size at the Caenorhabditis elegans neuromuscular junction.

Analyses of the effect of ryanodine in vertebrate brain slices have led to the conclusion that presynaptic ryanodine receptors (RYRs) may have several functions in synaptic release, including causing large-amplitude miniature postsynaptic currents (mPSCs) by promoting concerted multivesicular release. However, the role of RYRs in synaptic release is controversial. To better understand the role of RYRs in synaptic release, we analyzed the effect of RYR mutation on mPSCs and evoked postsynaptic currents (ePSCs) at the Caenorhabditis elegans neuromuscular junction (NMJ). Amplitudes of mPSCs varied greatly at the C. elegans NMJ. Loss-of-function mutations of the RYR gene unc-68 (uncoordinated 68) essentially abolished large-amplitude mPSCs. The amplitude of ePSCs was also greatly suppressed. These defects were completely rescued by expressing wild-type UNC-68 specifically in neurons but not in muscle cells, suggesting that RYRs acted presynaptically. A combination of removing extracellular Ca2+ and UNC-68 function eliminated mPSCs, suggesting that influx and RYR-mediated release are likely the exclusive sources of Ca2+ for synaptic release. Large-amplitude mPSCs did not appear to be caused by multivesicular release, as has been suggested to occur at vertebrate central synapses, because the rise time of mPSCs was constant regardless of the amplitude but distinctive from that of ePSCs, and because large-amplitude mPSCs persisted under conditions that inhibit synchronized synaptic release, including elimination of extracellular Ca2+, and mutations of syntaxin and SNAP25 (soluble N-ethylmaleimide-sensitive factor attachment protein 25). These observations suggest that RYRs are essential to normal quantal size and are potential regulators of quantal size.

Acetylcholine↗

Redundant localization mechanisms of RIM and ELKS in Caenorhabditis elegans.

Active zone proteins play a fundamental role in regulating neurotransmitter release and defining release sites. The functional roles of active zone components are beginning to be elucidated; however, the mechanisms of active zone protein localization are unknown. Studies have shown that glutamine, leucine, lysine, and serine-rich protein (ELKS), a recently defined member of the active zone complex, acts to localize the active zone protein Rab3a-interacting molecule (RIM) and regulates synaptic transmission in cultured neurons. Here, we test the function of ELKS in vivo. Like mammalian ELKS, Caenorhabditis elegans ELKS is an active zone protein that directly interacts with the postsynaptic density-25/Discs large/zona occludens (PDZ) domain of RIM. However, RIM protein localizes in the absence of ELKS and vice versa. In addition, elks mutants exhibit neither the behavioral nor the physiological defects associated with unc-10 RIM mutants, indicating that ELKS is not a critical component of the C. elegans release machinery. Interestingly, expression of the soluble PDZ domain of RIM disrupts ELKS active zone targeting, suggesting a tight association between the two proteins in vivo. RIM truncations containing only the PDZ and C2A domains target to release sites in an ELKS-dependent manner. Together, these data identify ELKS as a new member of the C. elegans active zone complex, define the role of ELKS in synaptic transmission, and characterize the relationship between ELKS and RIM in vivo. Furthermore, they demonstrate that multiple different protein-protein interactions redundantly anchor both ELKS and RIM to active zones and implicate novel proteins in the formation of the active zone.

Animals↗

[Nonmyleoablative allogeneic stem cell transplantation combined with imatinib in treatment of chronic myeloid leukemia: a clinical study].

OBJECTIVE: To study the effect of nonmyeloablative allogeneic peripheral blood stem cell (NST) transplantation combined with imatinib in the treatment of chronic myeloid leukemia (CML). METHODS: Ten CML patients, 5 males and 5 females, aged 21-41, 3 in chronic phase (CP), 4 in accelerated phase (AP) and 3 in blast crisis phase (BP), were treated with imatinib (400-1500 mg/d) before (n = 10) and/or after (n = 6) NST transplantation. The donors were HLA-identical (n = 4), 5/6 antigen-matched (n = 2), 4/6 antigen-matched (n = 2), 3/6 antigen-matched (n = 1) siblings or haplo-identical mothers (n = 2). The preparative regimen included cytoxin (CTX), Ara-C, and fludarabine combined with antithymocyte globulin (ATG) or anti-CD3 monoclonal antibody. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine (CSA) and mycophenolate mofetil (MMF), or with low-dose methotrexate (MTX) or zenapax. RESULTS: All the 10 patients showed donor cell chimerism at different degree: three had full chimerism (> 95%) and seven mixed chimerism (44%-95%). Mixed chimerism in 6 cases had been transformed into full chimerism during 1.5-10 months after NST transplantation through immunosuppressive agent withdrawal, donor peripheral blood stem cell/donor lymphocyte infusion or treatment of imatinib. The time needed for increase of the number of neutrophils to more than 0.5 x 10(9)/L was 16 d days (10-21 days). The time needed for increase of the number of platelets more than 20 x 10(9)/L was 10 days (4-15 days). 6 cases had I-II degrees acute and chronic GVHD of skin. 2 case had III-IV degrees chronic GVHD. 2 cases died of transplantation-related complication 27 and 45 days after transplantation respectively. One patient died of III-IV degrees cGVHD. Seven patients remained alive after a median follow-up of 14.5 months (7-23 months). The time needed for bcr/abl becoming negative was 33-130 days. None case relapsed during the following-up. CONCLUSION: An effective and safer method for CML, especially advanced CML treatment of NST transplantation combined with imatinib before and after transplantation reduces the leukemic cell load before transplantation, inhibits the proliferation of residual leukemic cells, promotes full chimerism change and enhanced the effect of graft versus leukemia.

Adult↗

520-W continuous-wave diode corner-pumped composite Yb:YAG slab laser.

We present a pumping scheme for a quasi-three-level solid-state laser. The scheme uses a slab laser configuration with the pump light incident from the slab corners. A diode-corner-pumped composite Yb:YAG-YAG slab laser operating in high-power cw mode was designed to prove the scheme. As much as 520 W of output power was obtained from a single 1-mm-thick composite slab with 0.5-at. %-doped Yb:YAG. The slope efficiency and the optical-to-optical efficiency with respect to the pump power were 32% and 25%, respectively. This result shows the validity of the corner-pumping concept and its feasibility in the development of high-power solid-state lasers.

Journal Article↗

Mutation rates in the dystrophin gene: a hotspot of mutation at a CpG dinucleotide.

An analysis of mutations was performed in 141 Duchenne muscular dystrophy (DMD) patients previously found to be negative for large deletions by standard multiplex PCR assays. Comprehensive mutation scanning of all coding exons, adjacent intronic splice regions, and promoter sequences was performed by DOVAM-S, a robotically enhanced, high throughput method that detects essentially all point mutations. Samples negative for point mutations were further analyzed for duplications by multiplex amplifiable probe hybridization (MAPH). Presumptive causative mutations were detected in 90% of the patients (70% protein truncating point mutations, 13% duplications, and 7% deletions not detected by the standard multiplex screening method). A total of 40 of the mutations are putatively novel. Most duplications involve multiple exons with an average and median size of about 160 and 153 kb, respectively. This is the first analysis of the absolute and relative rates of point mutations in the dystrophin gene. Relative to microdeletions (0.68 x 10(-9) per bp per generation), transitions at CpG dinucleotides are enhanced 150-fold while complex indels, the least common mutation type, are less frequent than microdeletions by a factor of five. The frequency of microdeletions and microinsertions at mononucleotide repeats increases exponentially with length. When compared to the well-studied human factor IX gene (F9), the results are similar, with two exceptions: a hotspot of mutation in the dystrophin gene (c.8713C>T/p.R2905X) at a CpG dinucleotide and an altered size distribution of microdeletions. The hotspot reflects a difference in the underlying pattern of mutation, while the altered size distribution of microdeletions reflects certain abundant sequence motifs within the dystrophin coding sequence (relative to factor IX).

Adolescent↗

Detection of heterozygous deletions and duplications in the MECP2 gene in Rett syndrome by Robust Dosage PCR (RD-PCR).

Fifty to eighty percent of Rett syndrome (RTT) cases have point mutations in the gene encoding methyl-CpG-binding protein-2 (MECP2). A fraction of MECP2 negative classical RTT patients has large heterozygous deletions. Robust Dosage PCR (RD-PCR) assays were developed as a rapid, convenient and accurate method to detect large heterozygous deletions and duplications. A blinded analysis was performed for 65 RTT cases from Portugal by RD-PCR in the coding exons 2-4 of the MECP2 gene. Neither the patients with point mutations nor the non-classical RTT patients without point mutation had a deletion or duplication. One of remaining eight female patients with classical RTT without point mutation had a heterozygous deletion. This is the first report of a deletion spanning the entire MECP2 gene. The deletion was confirmed by Southern blotting analysis and the deletion junction was localized 37 kb upstream from exon 1 and 18 kb downstream from exon 4. No duplications were detected. Our results suggest that RD-PCR is an accurate and convenient molecular diagnostic method.

Blotting, Southern↗

Gene regulation in planta by plant-derived engineered zinc finger protein transcription factors.

The ability to modify plant traits is of great commercial potential in agricultural biotechnology. To this end we have engineered plant-based zinc finger protein transcription factors (ZFP TFs) that minimize the use of non-plant DNA sequences. This novel architecture supports the use of tandem arrays of zinc-finger DNA recognition domains such that the ZFP TF binds a contiguous DNA target site - thus emulating the design of ZFP TFs described previously for mammalian gene regulation. We show that this plant-based ZFP TF architecture supports high affinity DNA binding while allowing the specificity of the DNA-protein interaction to be determined by the amino acid sequences of the recognition helices. This plant-based backbone thus supports the use of previously characterized DNA recognition helices originally identified in a mammalian ZFP context without using mammalian DNA sequences. Moreover, we show that plant-based ZFP TFs employing this new architecture can up-regulate endogenous ADH activity by > 20-fold in transgenic Arabidopsis. Thus plant-based ZFP TFs are shown to be potent regulators of gene expression in vivo.

Alcohol Dehydrogenase↗

Evaluation of two chemiluminescent immunoassays of ADVIA Centaur for hepatitis B serology markers.

BACKGROUND: This study evaluated the performance of 2 Bayer Hepatitis B Chemiluminescent Assays by comparing their performance to the corresponding DPC Immulite 2000 assays. METHODS: 953 samples were tested by both Immulite 2000 and Centaur HBsAg methods; and 75 samples were tested by both Immulite 2000 and Centaur anti-HBc IgM methods. RESULTS: The overall agreement between Immulite 2000 and ADVIA Centaur anti-HBc IgM assays was 100%. The agreement between Immulite 2000 and Centaur HBsAg assays was 100% for Immulite 2000 positive samples. The overall agreement for HBsAg negative samples was 99.9% after confirmation result was included. However, discrepancy between the 2 assays was observed in 53 samples which were tested initially as "weakly reactive"(index 1.0-1.95) but were not confirmed subsequently by the neutralization test on Immulite 2000. All 53 samples tested negative by Centaur HBsAg assay at the initial run. Furthermore, one Immulite 2000 HBsAg negative sample was reactive and confirmed by Centaur assay. CONCLUSIONS: While the performance of Bayer Hepatitis B HBsAg and aHBc IgM assays are in good agreement with corresponding DPC assays, the Bayer HBsAg assay is more efficient than the Immulite 2000 assay with its better separation of signal and background noise, and its complete automation features.

Automation↗

Imaging iron stores in the brain using magnetic resonance imaging.

For the last century, there has been great physiological interest in brain iron and its role in brain function and disease. It is well known that iron accumulates in the brain for people with Huntington's disease, Parkinson's disease, Alzheimer's disease, multiple sclerosis, chronic hemorrhage, cerebral infarction, anemia, thalassemia, hemochromatosis, Hallervorden-Spatz, Down syndrome, AIDS and in the eye for people with macular degeneration. Measuring the amount of nonheme iron in the body may well lead to not only a better understanding of the disease progression but an ability to predict outcome. As there are many forms of iron in the brain, separating them and quantifying each type have been a major challenge. In this review, we present our understanding of attempts to measure brain iron and the potential of doing so with magnetic resonance imaging. Specifically, we examine the response of the magnetic resonance visible iron in tissue that produces signal changes in both magnitude and phase images. These images seem to correlate with brain iron content, perhaps ferritin specifically, but still have not been successfully exploited to accurately and precisely quantify brain iron. For future quantitative studies of iron content we propose four methods: correlating R2' and phase to iron content; applying a special filter to the phase to obtain a susceptibility map; using complex analysis to extract the product of susceptibility and volume content of the susceptibility source; and using early and late echo information to separately predict susceptibility and volume content.

Brain↗

Retrospective study of adjunctive diode laser therapy for pain attenuation in 662 patients: detailed analysis by questionnaire.

OBJECTIVE: The aim of this study was to assess the long-term effects of low-level laser therapy (LLLT) through a retrospective survey using questionnaires. BACKGROUND DATA: The use of LLLT for chronic pain attenuation has been reported in the international literature for over 20 years. METHODS: We used a series of diode laser systems in which the most effective wavelength was consistently found to be 830 nm with an output power in continuous-wave of 60 mW. Subjects were 1,087 patients treated by LLLT at the Shiroto Clinic from April 1992 to August 1995. Questionnaires were sent to subjects in September and October 1996. RESULTS: The reply rate was 60.9%, comprising 662 questionnaires (265 males, 397 females, mean age of 53.4 years). The total efficacy rating (excellent plus good) immediately after LLLT was 46.8% in men and 47% in women. At the time of the survey, this rose to 73.3% in men and 76.8% in women, with positive effects also recorded on psychosomatic factors such as well-being, physical energy, general fatigue, mental vigor, and emotional stability. LLLT effects continued for 1-3 days. No statistically significant difference in efficacy was seen between males and females. LLLT as used in the study is therefore considered safe, effective, and side-effect-free, making it an ideal adjunctive therapeutic modality for intractable chronic and other pain. CONCLUSION: Infrared diode LLLT is therefore considered safe, effective, and side-effect-free, making it an ideal adjunctive therapeutic modality for intractable chronic pain.

Adult↗

Akt/protein kinase B activation by adenovirus vectors contributes to NFkappaB-dependent CXCL10 expression.

In gene therapy, the innate immune system is a significant barrier to the effective application of adenovirus (Ad) vectors. In kidney epithelium-derived (REC) cells, serotype 5 Ad vectors induce the expression of the chemokine CXCL10 (IP-10), a response that is dependent on NFkappaB. Compared to the parental vector AdLuc, transduction with the RGD-deleted vector AdL.PB resulted in reduced CXCL10 activation despite increasing titers, implying that RGD-alpha(V) integrin interactions contribute to adenovirus induction of inflammatory genes. Akt, a downstream effector of integrin signaling, was activated within 10 min of transduction with Ad vectors in a dose-dependent manner. Akt activation was not present following transduction with AdL.PB, confirming the importance of capsid-alpha(V) integrin interactions in Ad vector Akt activation. Inhibition of the phosphoinositide-3-OH kinase/Akt pathway by Wortmannin or Ly294002 compounds decreased Ad vector induction of CXCL10 mRNA. Similarly, adenovirus-mediated overexpression of the dominant negative AktAAA decreased CXCL10 mRNA expression compared to the reporter vector AdLacZ alone. The effect of Akt on CXCL10 mRNA expression occurred via NFkappaB-dependent transcriptional activation, since AktAAA overexpression and Ly294002 both inhibited CXCL10 and NFkappaB promoter activation in luciferase reporter experiments. These results show that Akt plays a role in the Ad vector activation of NFkappaB and CXCL10 expression. Understanding the mechanism underlying the regulation of host immunomodulatory genes by adenovirus vectors will lead to strategies that will improve the efficacy and safety of these agents for clinical use.

Adenoviridae↗

[Acellular porcine dermal matrix produced with different methods and an experimental study on its transplantation to skin wound].

OBJECTIVE: To observed the effect of healing quality of composite skin grafting consisting of acellular porcine dermal matrix combined with autologous split-thickness skin graft. METHODS: Porcine skin was treated with dispase II/triton X-100 or hyperosmotic saline/sodium-dodecyl-sulfate (SDS) respectively, and acellular porcine dermal matrix I (APDMI) and APDM II were obtained. Sixty-three Sprague-Dawley rats with full-thickness skin defects on the back were separately covered with APDMT + split-thickness autologous skin, or APDM II + split-thickness autologous skin. The quality of wound healing was observed, the rates of survival and contraction of the grafts were calculated, the tissue samples were harvested for histological examination, and compared with that of autologous split-thickness skin graft. RESULTS: The wound healing quality of composite skin I, and II was good. There was no significant difference in the rate of survival and contraction of the grafts between the two composite skin grafting groups. It was indicated by histological examination intact basal membrane. There was no significant difference in the survival rate between composite skin grafting groups and autologous split-thickness skin at the 6 th week after operation, but the contraction rates of the grafts in the composite skin groups were lower. CONCLUSION: Full-thickness skin defect can be healed by covering with acellular porcine dermal matrix produced by two methods combined with split-thickness autograft, and it can help improve the quality of wound healing.

Animals↗

Amplification and functional characterization of MUC1 promoter and gene-virotherapy via a targeting adenoviral vector expressing hSSTR2 gene in MUC1-positive Panc-1 pancreatic cancer cells in vitro.

Mucin1 (MUC1) promoter has been cloned from the 5' flanking region of the MUC1 gene in breast carcinoma, functionally characterized and applied in gene therapy of breast and esophageal carcinoma. In the present study, we amplified a 786 base pair (bp) MUC1 promoter by two-step nest PCR, and identified the activity and tumor-specificity using an enhanced green fluorescent protein (EGFP) gene as a reporter gene by fluorescence microscopy and flow cytometry analysis in Panc-1, primary normal pancreatic (PNPC), and cervical cancer HeLa cell lines. Subsequently, the human somatostatin receptor subtype 2 (hSSTR2) gene driven by MUC1 promoter was cloned into the pAdTrack to produce recombinant adenovirus AdMUC1-hSSTR2. The anticancer effect of AdMUC1-hSSTR2 was determined in Panc-1. The results demonstrated that there was no AdMUC1-hSSTR2-induced apoptosis, but a significant cell proliferation inhibition even without somatostatin (SST) analogue Octreotide, involved in the up-regulation of the cyclin-dependent kinase (CDK) inhibitors p21 and p27. Moreover, the anticancer effect could not be augmented by the addition of Octreotide, revealing a mechanism that was independent from induction of Octreotide. Therefore, this adenovirus system can be used as a novel, potent and specific tool for gene-targeting therapy in the MUC1 positive pancreatic carcinoma as shown in Panc-1.

Adenoviridae↗

[Clinical and angiographic follow-up study of sirolimus-eluting stent for treatment of in-stent restenosis].

OBJECTIVE: To evaluate the effectiveness and safety of sirolimus-eluting stents (SESs) for treatment of in-stent restenosis (ISR). METHODS: All 27 patients with ISR and clinical evidence of ischemia had been treated with SESs. Among them, 23 patients had diffuse and complex lesions, and 5 of them received 2 SESs. Clinical and angiographic follow-up were performed for all patients and the results were analyzed. RESULTS: All stents were implanted successfully. There were no remained stenosis and major in-hospital complications. Average follow-up time was 8.9 +/- 2.1 (5-14) months, with a clinical follow-up rate of 96.3% and angiographic follow-up rate of 92.6%. During the follow-up, there was none of death. One patient had recurrent angina with an angiographic evidence of the proximal edge restenosis of the stent. Mild neointimal hyperplasia in the proximal edge was found in 2 patients, but the stenosis was less than 25%. No late lumen loss was found in other 24 patients. The late lumen loss of the in-stent averaged 0.09 +/- 0.02 mm, and of the distal edge vessel averaged 0.10 +/- 0.03 mm, and of the proximal edge vessel averaged 0.20 +/- 0.06 mm. The rate of target vessel revascularization was 3.8%. CONCLUSION: The SES implantation is safe and feasible for the treatment of in-stent restenosis, which could effectively prevent neointimal hyperplasia and recurrent restenosis of the lesion.

Adult↗

[Surgical treatment of 475 patients with periampullary carcinoma].

OBJECTIVE: To compare of the outcome of all patients who received surgical treatment in one institute for periampullary carcinoma during different intervals over the past 40 years. METHODS: Retrospective review of 475 patients suffering from periampullary carcinoma in intervals 1958 approximately 1976, 1977 approximately 1987, 1988 approximately 1998 and 1999 approximately 2003 is presented. RESULTS: In interval 1958 approximately 1976, for 128 patients, the tumor resection rate was: pancreatic carcinoma (PC) 26.6% (21/79), ampullary carcinoma (AC) 86.2% (25/29), distal bile duct cancer (DBDC) 38.5% (5/13), and duodenal cancer (DC) 57.1% (4/7). In interval 1977 approximately 1987, for 70 patients, the tumor resection rate was: PC 26.7% (16/60), AC 66.7% (4/6), DBDC 100% (1/1), and DC 66.7% (2/3). In interval 1988 approximately 1998, for 147 patients, the tumor resection rate was: PC 20.2% (22/109), AC 75.0% (12/16), DBDC 50.0% (2/4), and DC 66.7% (12/18). In interval 1999 approximately 2003, for 130 patients, the tumor resection rate was: PC 20.4% (20/98), AC 100% (4/4), DBDC 75.0% (12/16), and DB 83.3% (10/12). Cumulatively, from 1958 to 2003, the incidence of DBDC has become significantly higher, and the average of total bilirubin level (TBIL) has gradually been going downward, the average of blood transfusion during operation and the diameter of resected tumor has been becoming smaller. From 1999 to 2003, none of the 130 periampullary carcinoma patients had received biliary drainage before operation. CONCLUSION: Mortality and complication have become significantly lower because of effective improvement in the perioperative preparation and the care after surgery of periampullary cancer in the recent years. Even though the accurate diagnosis has become increasing earlier than before, the resection rate and prognosis of periampullary carcinoma remain poor.

Ampulla of Vater↗

[Effects of 2,5-hexanedione on NGF expression in motor and sensory neuronal cells of rats].

OBJECTIVE: To investigate the effects of 2,5-Hexanedione (2,5-HD), a metabolite of n-hexane,on nerve growth factor (NGF) expression in motor and sensory neuronal cells of peripheral nervous system of rats. METHODS: Primary cultured dorsal root ganglion (DRG) neurons were obtained from new born rats on day 4. The cell line VSC4.1 were cultured. The growth condition of cells were observed with a phase contrast microscope. Immunohistochemistry technology was used to analyze the NGF expression in both VSC4.1 cells and primary cultured DRG cells treated with 4 different dosages of 2, 5-HD (2.5, 5.0, 10.0, 20.0 mmol/L) respectively for 24 hours. RESULTS: The NGF expression decreased significantly in both DRG neurons and VSC4.1 cells dosed respectively with 5.0,10.0,20.0 mmol/L 2,5-HD in comparison with the control group (P < 0.05), with a tendency of dose-effect correlation. CONCLUSION: The results suggested that 2,5-HD can decrease the endogenous NGF levels in both cultured DRG sensory neurons and VSC4.1 motor neuron cells of rats.

Animals↗