Biomedical subjects

Hui Sun

Publications and source records attributed to Hui Sun.

At least 109 records · Page 6Linked to original sources

PubMed2003

Low editing efficiency of GluR2 mRNA is associated with a low relative abundance of ADAR2 mRNA in white matter of normal human brain.

The ionotropic glutamate receptor (GluR) subunits GluR2, GluR5 and GluR6 are subject to RNA editing at their Q/R sites, resulting in significant alterations in the channel properties of the receptors. RNA editing at the Q/R site of GluRs is both developmentally and regionally regulated. Here we provide the first quantitative measurements of both mRNAs of the GluR subunits and mRNAs of the RNA editing enzymes ADAR1-ADAR3 in a comparison of the efficiency of editing at the Q/R site with the expression levels of ADAR mRNA in human brain. We demonstrate that the Q/R site of GluRs in white matter is edited significantly less than in grey matter. In addition, by means of quantitative reverse transcription-polymerase chain reaction methods, we demonstrate that the relative abundance of ADAR2 mRNA to GluR2 mRNA is significantly lower in white matter than in grey matter and that the GluR2 Q/R site editing decreased only when the ratio of ADAR2 mRNA (not that of ADAR1 mRNA) to GluR2 mRNA dropped below a threshold (20 x 10(-3)). These results suggest that Q/R site of GluRs editing is regulated in a regional, and hence presumably cell-specific, manner and that the GluR2 Q/R site editing is critically regulated by ADAR2 in human brain.

Adenosine Deaminase↗

PubMed2003

Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS.

AMPA receptor-mediated neurotoxicity is currently the most plausible hypothesis for the etiology of amyotrophic lateral sclerosis (ALS). The mechanism initiating this type of neuronal death is believed to be exaggerated Ca2+-influx through AMPA receptors, which is critically determined by the presence or absence of the glutamate receptor subunit 2 (GluR2) in the assembly. We have provided the first quantitative measurements of the expression profile of AMPA receptor subunits mRNAs in human single neurons by means of quantitative RT-PCR with a laser microdissector. Among the AMPA subunits, GluR2 shared the vast majority throughout the neuronal subsets and tissues examined. Furthermore, both the expression level and the proportion of GluR2 mRNA in motoneurons were the lowest among all neuronal subsets examined, whereas those in motoneurons of ALS did not differ from the control group, implying that selective reduction of the GluR2 subunit cannot be a mechanism of AMPA receptor-mediated neurotoxicity in ALS. However, the low relative abundance of GluR2 might provide spinal motoneurons with conditions that are easily affected by changes of AMPA receptor properties including deficient GluR2 mRNA editing in ALS.

Adult↗

PubMed2003

PAUSED encodes the Arabidopsis exportin-t ortholog.

Los1p/exportin-t (XPOT) mediates the nuclear export of tRNAs in yeast and mammals. The requirements for this transport pathway are unclear, however, because los1 mutations do not affect yeast growth, and the phenotype of XPOT mutations in mammals is unknown. Here, we show that PAUSED (PSD) is the Arabidopsis ortholog of LOS1/XPOT and is capable of rescuing the tRNA export defect of los1 in Brewer's yeast (Saccharomyces cerevisiae), suggesting that its function has been conserved. Putative null alleles of PSD disrupt the initiation of the shoot apical meristem and delay leaf initiation after germination, the emergence of the radicle and lateral roots, and the transition to flowering. Plants doubly mutant for psd and hasty, the Arabidopsis ortholog of exportin 5, are viable but have a more severe phenotype than either single mutant. These results suggest that PSD plays a role in tRNA export in Arabidopsis, but that at least one-and perhaps several-additional tRNA export pathways also exist. The PSD transcript is broadly expressed during development and is alternatively spliced in the 3'-untranslated region. No temporal or spatial difference in the abundance of different splice forms was observed. We propose that the mutant phenotype of psd reflects defects in developmental events and cell/tissue types that require elevated levels of protein synthesis and are therefore acutely sensitive to a reduction in tRNA export.

Amino Acid Sequence↗

PubMed2003

[Expression of nuclear factor-kappaB in bone marrow cells from patients with acute leukemia and its relationship with P21, MMP-2 and MMP-9].

To investigate the expression of NF-kappaB in acute leukemia and its relationship with P21, and matrix metalloproteinases (MMP), the expression of NF-kappaB, P21, MMP-2 and MMP-9 in bone marrow cells from patients with acute leukemia (AL) was detected using immunocytochemical technique. The results showed that the expression ratios of NF-kappaB, P21, MMP-2 and MMP-9 in untreated AL group were significantly higher than those in remission and normal control groups (P < 0.05), and no obvious difference was seen between remission and normal control groups. The expression of NF-kappaB was correlated with that of P21, MMP-2 and MMP-9 (r = 0.767, 0.729 and 0.803, respectively, P < 0.05). This study indicated that P21 protein, encoded by oncogene Ras, and NF-kappaB were super-expressed in leukemia cells. In conclusion, after activation by Ras, NF-kappaB combined with the kappaB sequences of MMP-2 and MMP-9 genes, then upregulated their expression. MMP might enhance the degradative function of leukemic cell, thus to make cells easier to cross through the bone marrow barrier and release into blood.

Acute Disease↗

PubMed2003

[Study on clinical therapeutic effect of composite Salvia injection matched with Western medicine in treating diabetic foot].

OBJECTIVE: To investigate the clinical effects of composite salvia injection (CSI) matched with western medicine (WM) in treating diabetic foot. METHODS: Seventy-two patients, whose diagnosis were confirmed to be diabetic foot, were randomly divided and equally distributed into the comprehensive CSI plus WM treated group and the WM control group, they were treated with the CSI and WM treatment and the conventional WM respectively. The therapeutic effect was evaluated in combining with data of electromyogram and hemorrheologic investigation. RESULTS: All the indexes were improved to various extent after treatment in both groups, but there was more significant in the CSI group than in the WM group, shown as quickening of motor and sensory nerve conduction velocity of median nerve and lowering of blood viscosity, as compared with those before treatment, P < 0.01. CONCLUSION: CSI matched with WM in treating diabetic foot is beneficial for resulting in better effect.

Aged↗

PubMed2003

[Phase II clinical trial on gemcitabine in the treatment of stage IIIB-IV non-small cell lung cancer].

OBJECTIVE: To evaluate the efficacy and safety of domestic Gemcitabine in the treatment of patients with stage IIIB approximately IV non-small cell lung cancer (NSCLC). METHODS: 124 NSCLC patients were randomized into three groups: Group A: single drug group, 40 cases, gemcitabine 1 000 mg/m(2) + NS 100 ml or 200 ml was infused within 30 approximately 60 minutes on D1, 8 and 15, with 28 days taken as one cycle. Group B: combined treatment group, 36 cases, in addition to the above protocol, cisplatin 30 mg/m(2) was infused within 60 approximately 120 min, on D1, 2 and 3. Group C: combined control group: 39 cases, the protocol applied was the same as group B except domestic gemcitabine being replaced by imported gemzar. The efficacy and side effects of treatment were evaluated after 8 weeks of treatment. RESULTS: 115 patients could be evaluated for response rate. PR was observed in 9/40 (22.5%) of group A, 15/36 (41.6%) in group B and 15/39 (38.36%) in group C. There was no significant difference of PR rates between group B and group C (P = 0.552). 117 patients who received the second cycle of treatment were evaluated for toxicity. The incidence of grade III approximately IV nausea, vomiting and loss of appetite was much higher in group B. Hematological toxicity of groups B and C was higher than that of group A. There was no significant difference between groups B and C. CONCLUSION: The efficacy and incidence of side effects between domestic gemcitabine and the imported gemzar are similar.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

[Studies on the method for the processing roots of cultivated Saposhnikovia divaricata].

OBJECTIVE: To establishing a standard processing method for cultivated Saposhnikovia divaricata. METHOD: Crude drug was dried at different temperature, and the contents of prim-O-glucosyl-cimifugin,cimifugin,4'-O-beta-glucosyl-5-O-methylvisamminol, sec-O-glucosyl-hamaudol in the processed crude drug were determined by HPLC. RESULT: Of the contents of the four compounds, the sample that heated by 45 degrees C was at the best level. Prim-O-glucosggl-cinmifugin was 0.636%, cimifugin was 0.043%, 5-O-methtlvsamminol was 0.598%, sec-O-glu-cosyl-hamaudol was 1.85%, and total content was 1.302%. CONCLUSION: The best drying temperature for processing is 45 degrees C.

Apiaceae↗

PubMed2003

[Cloning and prokaryotic expression of yeast GCN5 and RPD3].

The yeast histone acetyltransferase (HAT) gene gcn5 and histone deacetylase (HDAC) gene rpd3 were cloned from yeast genomic DNA by PCR amplification. The two genes,both with additional 6xHis tag,were subcloned into pBV220 vector to construct expression plasmids pBVgcn5 and pBVrpd3,respectively. Both pBVgcn5 and pBVrpd3 were over-expressed in Escherichia coli upon temperature induction,as revealed by SDS-PAGE. The recombinant GCN5 and RPD3 were purified by using a 6xHis affinity column. The purified GCN5 was tested to possess the HAT activity by using a (14)C-labeling assay. This work has laid down the basis for further in vitro studies into roles of histone acetylation/deacetylation in modulating chromatin conformation and transcription activity.

English Abstract↗

PubMed2002

Histone acetylation is involved in hsp70 gene transcription regulation in Drosophila melanogaster.

The acetylation/deacetylation modifications of N-terminal tails of core histones play critical roles in activation/repression of many eukaryotic genes. However, the role of acetylation in transcription regulation of heat shock protein genes (hsp) is still a disputed issue. In this study, we investigated the influences of histone acetylation modification on changes in structure of polytene chromosomes and in expression of hsp70 gene in Drosophila melanogaster, by using histone deacetylase (HDAC) inhibitors Trichostatin A (TSA) and sodium butyrate (BuA), and the heat shock treatment of larvae of the flies. The results presented in this paper demonstrate that both TSA and BuA were able to affect the chromatin structure at the site where hsp70 gene is located along the polytene chromosome. Furthermore, the HDAC inhibitors significantly promoted the hsp70 gene transcription, at an extent similar to that induced by heat shock. The immunofluorescence in situ localization study further confirmed that the hsp70 gene locus was hyperacetylated after the heat induction. We therefore conclude that histone acetylation can significantly enhance both the basal and the inducible expression of hsp70 gene in D. melanogaster and hence plays important roles in hsp gene regulation. This study has provided a basis and a framework for further investigations aimed at the establishment of the correlation between acetylation modification and hsp gene regulation.

Acetylation↗

PubMed2002

Distinct molecular basis for differential sensitivity of the serotonin type 3A receptor to ethanol in the absence and presence of agonist.

Ethanol can potentiate serotonin type 3 (5-HT(3)) receptor-mediated responses in various neurons and in cells expressing 5-HT(3A) receptors. However, the molecular basis for alcohol modulation of 5-HT(3) receptor function has not been determined. Here we report that point mutations of the arginine at amino acid 222 in the N-terminal domain of the 5-HT(3A) receptor can alter the EC(50) value of the 5-HT concentration-response curve. Some point mutations at amino acid 222 resulted in spontaneous opening of the 5-HT(3A) receptor channel and an inward current activated by ethanol in the absence of agonist. Among these mutant receptors, the amplitude of the current activated by ethanol in the absence of agonist was correlated with the amplitude of the current resulting from spontaneous channel openings, suggesting that the sensitivity of the receptor to ethanol in the absence of agonist is, at least in part, dependent on the preexisting conformational equilibrium of the receptor protein. On the other hand, point mutations that conferred greater sensitivity to ethanol potentiation of agonist-activated responses were less sensitive or insensitive to ethanol in the absence of agonist. For these receptors, the magnitude of the potentiation of agonist-activated responses by ethanol was inversely correlated with the EC(50) values of the 5-HT concentration-response curves, suggesting that these mutations may modulate ethanol sensitivity of the receptor by altering the EC(50) value of the receptor. Thus, distinct molecular processes may determine the sensitivity of 5-HT(3A) receptors to ethanol in the absence and presence of agonist.

Amino Acid Sequence↗

PubMed2002

Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways.

The PTEN/PI3K signaling pathway regulates a vast array of fundamental cellular responses. We show that cardiomyocyte-specific inactivation of tumor suppressor PTEN results in hypertrophy, and unexpectedly, a dramatic decrease in cardiac contractility. Analysis of double-mutant mice revealed that the cardiac hypertrophy and the contractility defects could be genetically uncoupled. PI3Kalpha mediates the alteration in cell size while PI3Kgamma acts as a negative regulator of cardiac contractility. Mechanistically, PI3Kgamma inhibits cAMP production and hypercontractility can be reverted by blocking cAMP function. These data show that PTEN has an important in vivo role in cardiomyocyte hypertrophy and GPCR signaling and identify a function for the PTEN-PI3Kgamma pathway in the modulation of heart muscle contractility.

Adrenergic beta-Agonists↗

PubMed2002

Immunotherapy with interleukin-10 depends on the CXC chemokines inducible protein-10 and monokine induced by IFN-gamma.

The cytokine interleukin (IL)-10 has potent antitumor activity in many model systems when expressed locally at very high levels from the time of tumor transplantation. We now demonstrate that systemic administration of recombinant human IL-10 to animals bearing established highly malignant mammary tumors also leads to significant growth inhibition. We had shown previously that expression of the CXC chemokines Mig (monokine induced by IFN-gamma) and IP-10 (inducible protein 10) is observed in IL-10 transduced but not neo-vector control tumors. We now demonstrate that treatment of IL-10-tumor-bearing mice with antibodies to either chemokine partially reverses the therapeutic effect of IL-10. Tumor growth in animals treated with both antibodies is comparable with that of vector control tumors. Direct transduction of Mig cDNA into the parental tumor cell line before transplantation also results in smaller tumors. This tumor growth inhibition is associated with increased numbers of CD4+ cells, consistent with a T-cell chemoattractant activity for Mig. No change in vascularization, as indicated by CD31+ cells, was observed in either Mig or IL-10-transfected tumors. Thus, an antiangiogenic activity for either cytokine could not be confirmed. Mig and IP-10 are critical to the therapeutic response resulting from high levels of IL-10, and, furthermore, Mig as a single agent also has tumor-inhibitory activity in a model of breast cancer.

Adenocarcinoma↗

PubMed2002

The vitelliform macular dystrophy protein defines a new family of chloride channels.

Vitelliform macular dystrophy (VMD/Best disease; MIM*153700) is an early-onset autosomal dominant disorder in which accumulation of lipofuscin-like material within and beneath the retinal pigment epithelium is associated with a progressive loss of central vision. Bestrophin, the protein product of the VMD gene, has four predicted transmembrane domains. There are multiple bestrophin homologues in the human, Drosophila, and Caenorhabditis elegans genomes, but no function has previously been ascribed to these proteins, and they show no detectable homology to other proteins of known function. Using heterologous expression, we show here that human, Drosophila, and C. elegans bestrophins form oligomeric chloride channels, and that human bestrophin is sensitive to intracellular calcium. Each of 15 missense mutations asscociated with VMD greatly reduces or abolishes the membrane current. Four of these mutant bestrophins were coexpressed with the wild type and each dominantly inhibited the wild-type membrane current, consistent with the dominant nature of the disease. These experiments establish the existence of a new chloride channel family and VMD as a channelopathy.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed2002

Diversification of olfactory receptor genes in the Japanese medaka fish, Oryzias latipes.

Vertebrate olfactory receptors (OR) exists as the largest multigene family, scattered throughout the genome in clusters. Studies have shown that different animals possess remarkably diverse set of OR genes to recognize diverse odor molecules. In order to examine the evolutionary process of OR diversification, we examined three OR gene subfamilies from Japanese medaka fish (seven lines sampled from four populations). For each subfamily, the sequences of ancestral genes were inferred based on distance method. Examination of d(N)/d(S) ratios for each branch of phylogenetic trees suggested that purifying selection is the major force of evolution in medaka OR genes. However, for the mfOR1 and mfOR2 paralogous gene pairs, a nonrandom distribution of fixed amino acid changes and the d(N)>d(S) in a branch suggested that diversifying selection occurred after gene duplication. The fixed amino acid changes were observed in the third, fifth and sixth transmembrane domains, which has been predicted to serve as a ligand-binding pocket in a structural model. Compatibility test suggested that interlocus recombinations involving the fourth transmembrane domain occurred between the mfOR1 and mfOR2 gene pairs. The pattern of nucleotide substitutions in other OR genes agrees with the hypothesis that a limited number of amino acid residues are involved in odorant binding. Such comparative analyses of paralogous OR genes should provide bases for understanding the evolution, the structure, and the functional specificity of OR genes.

Amino Acid Sequence↗

PubMed2002

Remodeling of Ca(2+)-handling by atrial tachycardia: evidence for a role in loss of rate-adaptation.

BACKGROUND: Loss of rate-dependent action potential (AP) duration (APD) adaptation is a characteristic feature of atrial tachycardia-induced remodeling (ATR). ATR causes sarcolemmal ion-channel remodeling (ICR) and changes in Ca(2+)-handling. The present studies were designed to quantify Ca(2+)-handling changes and then to apply a mathematical AP model to assess the contributions of Ca(2+)-handling abnormalities and ICR to loss of APD rate-adaptation. METHODS: Indo-1 fluorescence was used to measure intracellular Ca(2)-transients and whole-cell patch-clamp to record APs in atrial myocytes from control dogs and dogs subjected to atrial pacing at 400/min for 6 weeks. A previously developed ionic model of the canine atrial AP was modified to reproduce measured Ca(2+)-transients of control and ATR myocytes. RESULTS: In control, APD to 95% repolarization (APD(95)) decreased by 91 ms experimentally and by 88 ms in the model over the 1-6 Hz range. In ATR myocytes, APD(95) failed to decrease over the 1-6 Hz range. Ca(2+)-handling abnormalities in ATR myocytes included slowed upstroke, decreased amplitude and strong single-beat post-rest potentiation. Unaltered Ca(2+)-handling properties included caffeine-releasable Ca(2+)-stores and Ca(2+)-transient relaxation before and after exposure to the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor cyclopiazonic acid (CPA). Including ICR alone in the model accounted for loss of APD(50) rate-adaptation; however, KR alone reduced APD(95) rate-adaptation by only 19% to 71 ms. When both ICR and Ca(2+)-handling changes were incorporated, APD(95) rate-adaptation decreased to 6 ms, accounting for experimental observations. CONCLUSION: ICR alone does not fully account for loss of APD rate-adaptation with atrial remodeling: Ca(2+)-handling changes appear to contribute to this clinically significant phenomenon.

Action Potentials↗

PubMed2002

Separation of ephedrine stereoisomers by molecularly imprinted polymers--influence of synthetic conditions and mobile phase compositions on the chromatographic performance.

Separation of ephedrine stereoisomers by molecularly imprinted polymers was performed to study the factors that affect the selectivity and column efficiency. The polymer synthesized with pentaerythritol triacrylate as the cross-linker and chloroform as the porogen was found to have the best overall separation performance. Investigation of the recognition mechanism by NMR and chromatographic analysis revealed that the major binding forces between the polymer stationary phase and ephedrine are the ionic and hydrogen bonding interactions. Studies of the influence of mobile phase compositions on the HPLC analysis have shown that a methanol-aqueous buffer was the suitable mobile phase for the separation in which pH, ionic strength and water content can be adjusted to optimize the chromatographic analysis.

Adrenergic Agents↗

PubMed2002

[Molecular typing of Shiga-toxin producing Escherichia coli O157:H7 isolated in China with pulsed field gel electrophresis].

OBJECTIVE: To type and group the Shiga-toxin producing Escherichia coli O157:H7 strains isolated recent years in China to understand the epidemiological features caused by the pathogen. METHODS: Pulsed field gel electrophoresis of large restriction fragments of bacterial chromosomal DNA was used. RESULTS: The 51 isolates of E. coli O157:H7 collected in recent years in China could be divided into 8 Pulsed Field Gel Electrophoresis (PFGE) types based on the size and number of restriction fragments and patterns, that were digested by XbaI. Strains isolated from Ningxia province showed only two types- PFGE1 and PFGE2. Strains isolated in Xuzhou of Jiangsu province had 6 PFGE types. Isolates identified between 1986 - 1988 belonged to PFGE7. Strains isolated from patients in 1999 - 2000 were PFGE5 and PFGE3. Strains isolated from stool samples of domestic animal, food and vegetable were PFGE3 - 6, of which the predominant type was PFGE5. All of the 5 strains isolated from patients with diarrhea and hemolytic uremic syndrome (HUS) belonged to PFGE type 5, which was the dominant type of the isolates from stool samples of domestic animal and samples of food and vegetable contaminated. CONCLUSION: Data suggested that the cluster patients with diarrhea and HUS might have been related to the pathogens from domestic animas and contaminated food or vegetables. The distribution of PFGE types also varied in different provinces of China.

Electrophoresis, Gel, Pulsed-Field↗

PubMed2002

[The selecting experiment of resistance to Marek's disease of chicken].

The Marek's Disease is an acute infectious disease in poultry production. The selecting experiment through blood-group gene inspection of adult parents and attack-test by using of Marek's Disease virus (MDV) for offspring chicks was carried out. The results showed as follows: (1) The rates of positive reaction by No. 614 blood-group gene inspection of adult parents in four generations were increased due to generation increase, as F0-68.8%, F1-77.3%, F2-81.8% and F3-90.5%. (2) In the attack-test by using of MDV at 10 days of age of chicks the mortalities of the experimental group at 60 days of age of chicks whose parents have positive reaction by No. 614 blood-group reagent detect in F2-F4 generations were 25.8%, 69.2% and 29.4% respectively, while the mortalities of the control group at same age of chicks whose parents have negative reaction were 30.6%, 81.0% and 52.9% respectively. These differences of mortality were significant (P < 0.01 or P < 0.05). (3) The rates of pathological change of 9 viscera tumor of the experimental group chicks in F2-F4 generations were 87.6%, 83.3% and 58.8% respectively, while chicks in the control group were 88.1%, 84.5% and 70.6% respectively. Except individual generation and viscera, these differences between the experimental group and the control group were almost not significant (P > 0.05). The experimental results and genetic control of resistance to Marek's Disease are discussed in this paper. The new strain of chicken resistant to Marek's Disease will be bred.

Animals↗