[International expert consensus on gene therapy for hereditary hearing loss: based on clinical trials].
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Journal Article↗
Biomedical subjects
C Cui
Publications and source records attributed to C Cui.
Facile synthesis of cyclopropene analogues of aluminum and an aluminum pinacolate, and the reactivity of LAl[eta(2)-C(2)(SiMe(3))(2)] toward unsaturated molecules (L=HC[(CMe)(NAr)](2), Ar=2,6-i-Pr(2)C(6)H(3)).
Reduction of LAlI(2) (1) (L = HC[(CMe)(NAr)](2), Ar = 2,6-i-Pr(2)C(6)H(3)) with potassium in the presence of alkynes C(2)(SiMe(3))(2), C(2)Ph(2), and C(2)Ph(SiMe(3)) yielded the first neutral cyclopropene analogues of aluminum LAl[eta(2)-C(2)(SiMe(3))(2)] (3), LAl(eta(2)-C(2)Ph(2)) (4), and LAl[eta(2)-C(2)Ph(SiMe(3))] (5), respectively, whereas reduction of 1 in the presence of Ph(2)CO gave an aluminum pinacolate LAl[O(2)(CPh(2))(2)] (6), irrespective of the amount of Ph(2)CO employed. The unsaturated molecules CO(2), Ph(2)CO, and PhCN inserted into one of the Al-C bonds of 3 leading to ring enlargement to give novel aluminum five-membered heterocyclic systems LAl[OC(O)C(2)(SiMe(3))(2)] (7), LAl[OC(Ph)(2)C(2)(SiMe(3))(2)] (8), and LAl[NC(Ph)C(2)(SiMe(3))(2)] (9) in high yields. In contrast, 3 reacted with t-BuCN, 2,6-Trip(2)C(6)H(3)N(3) (Trip = 2,4,6-i-Pr(3)C(6)H(2)), and Ph(3)SiN(3) resulting in the displacement of the alkyne moiety to afford LAl[N(2)(Ct-Bu)(2)] (10) with an unprecedented aluminum-containing imidazole ring, and the first monomeric aluminum imides LAlNC(6)H(3)-2,6-Trip(2) (11) and LAlNSiPh(3) (12). All compounds have been characterized spectroscopically. The variable-temperature (1)H NMR studies of 3 and ESR measurements of 3 and 4 suggest that the Al-C-C three-membered-ring systems can be best described as metallacyclopropenes. The (27)Al NMR resonances of 2 and 3 are reported and compared. Molecular structures of compounds 3, 4, 6.OEt(2), 8.OEt(2), and 9 were determined by single-crystal X-ray structural analysis.
Journal Article↗
A-6G variant of the angiotensinogen gene and essential hypertension in Han, Tibetan, and Yi populations.
To investigate the relationship between the A-6G variant in the promoter of the angiotensinogen gene and essential hypertension in Han, Tibetan, and Yi populations. All patients with essential hypertension were selected by WHO criteria. And the polymorphism of the A-6G variant was determined by PCR/RFLP. The data were analyzed by t test and chi2 test. There was no significant difference in the genotype or allele frequencies between normotensives and hypertensives in the Han, Tibetan, and Yi populations, respectively. However, when the subjects were divided into male and female subgroups, the genotype distributions among hypertensives and normotensives of the Tibetan female group were as follows: AA, 37% vs. 48%; AG, 52% vs. 48%; GG, 11% vs. 4%, respectively and the frequency of the G allele was significantly higher in hypertensives than in normotensives in the Tibetan female group (0.37 vs. 0.28, chi2=4.25, p<0.05). In addition, we observed that there was a significant difference between the Han and Tibetan normotensive groups in the distributions of the allele and genotype frequencies of the A-6G variant. The frequency of the G allele was 0.29 and 0.17 in the Tibetan normotensive and Han groups, respectively (p<0.001). The G allele of the A-6G variant was associated with hypertension in the Tibetan females, but not in the Yi or Han females. And we confirmed that there was a significant difference in the prevalence of the allele frequencies of the A-6G variant between the Han and Tibetan normotensive groups.
Adult↗
[The clinical effect of Tropisetron in the prevention of nausea and vomiting induced by anti-cancer drugs].
OBJECTIVE: To compare the efficacy and adverse effects of Tropisetron with Kytril in the prevention of nausea and vomiting induced by anti-cancer drugs. METHODS: In a clinical randomized controlled cross-over trial, 34 patients (19 among them treated with regimens containing cisplatin) were randomized into A and B group. In group A, Tropisetron was given in the first cycle and Kytril in the second cycle, while in group B Kytril was given in the first and Tropisetron in the second cycle of the same chemotherapy. RESULTS: In the Tropisetron treated group, the response rate was 97.1% with 4.5 episodes of vomiting on the first day of chemotherapy, while that in the Kytril treated patients was 94.1% with 3 episodes of vomiting. There was no statistical difference between the 2 groups. Control of delayed emesis and other adverse reactions were comparable in both arms and there was no notable difference between Tropisetron and Kytril. CONCLUSION: Tropisetron is an effective anti-emetic drug to prevent nausea and vomiting caused by anti-tumor agents, and its adverse reactions are mild.
Adolescent↗
[FTIR studies on two compounds containing cyanide].
Two compounds containing cyanide [Ni(1,10-phen)2O2MoS2(CuCN)]n and [ZnCu4 (CN)6(dmf)4]n have been synthesized. The FTIR spectra and the crystal structure of those clusters have also been deal with. The stretching frequency of cyanide is alterable with the different coordinated environments.
Crystallization↗
The First Structurally Characterized Metal-SeH Compounds:
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Journal Article↗
An optimal condition of bronchial cell proliferation stimulated by insulin-like growth factor-I.
BACKGROUND: It is known that growth hormones such as insulin-like growth factor-I (IGF-I) and several kinds of cytokines are involved in the regeneration process of injured epithelial cells in chronic respiratory inflammatory diseases such as bronchial asthma. Repetitive degeneration/regeneration processes of the airway epithelial layer is supposed to be responsible for the remodeling and irreversible organic changes of the airway in bronchial asthma. The purpose of this study is to establish a simple and reliable in vitro method for studying airway epithelial cell growth and proliferation using IGF-I. METHOD: By altering the number of cultured epithelial cells (strain NCI-H(292)), culture duration before stimulation with IGF-I, concentration of IGF-I, and duration of IGF-I stimulation, the optimum conditions for epithelial cell growth was determined. The epithelial cell growth was evaluated using [methyl-(3)H]thymidine uptake. RESULT: Among various culture conditions, the epithelial cells cultured at 1 x 10(3) cells/well for 24 h followed by 24 h of stimulation by 10(-8) M of IGF-I showed the highest growth. CONCLUSION: The method for the evaluation of epithelial cell growth established in this study requires a small number of cells and has no complicated procedure. This simple model enables us to investigate the effect of various substances on bronchial epithelial cell growth in the presence of IGF-I.
Bronchi↗
Association analysis of variants in the core promoter region of angiotensinogen gene with essential hypertension in Tibetan population.
OBJECTIVE: To detect the variants in the core promoter region of angiotensinogen(AGT) gene, and to analyse the relationship between the AGT gene polymorphisms and essential hypertension in Tibetan population. METHODS: This is a case-control study consisting of 103 essential hypertensive subjects and 82 normotensive controls matched by age and sex. The variants in the AGT gene core promoter region were screened by polymerase chain reaction/single strand conformation polymorphism(PCR/SSCP) and further identified by automated sequencing. The A(-6)G polymorphism was determined in DNA extracted from leucocytes by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). RESULTS: (1) There were two different electrophoresis band patterns in PCR/SSCP analysis. PCR product direct sequencing showed that the two band patterns represented the AA, AC genotypes in the (-20) site of AGT gene respectively. The distribution of A(-20)C genotype was almost identical in essential hypertensive and normotensive groups (P>0.8). The A allele frequency was very high in both groups (control: 0.9175, hypertensive: 0.9124). (2)Distribution of genotype in the (-6) site of AGT gene was much different between the patient group and control group (P<0.005). The frequency of G allele was statistically higher in the patient group than in controls (0.374 vs 0.220, P<0.025). CONCLUSION: Both Tibetan hypertensives and normotensives have higher frequency of A allele in AGT gene (-20) site. The higher frequency of G allele in the AGT gene (-6) site in Tibetan hypertension patients suggests that this allele may be the genetic susceptibility factor in the proceeding of essential hypertension in the Tibetan population.
Angiotensinogen↗
[Analyses on the association of CA-repeat polymorphism and A1166-->C variant in the 3'-flanking region of AT(1)R gene with essential hypertension in Tibetans].
OBJECTIVE: To investigate whether CA-repeat polymorphism and A1166 --> C variant in the 3n-flanking region of AT(1)R gene are in association with the genetic susceptibily to essential hypertension (EH) in Tibetans. METHODS: A case-control study was carried out. Sibpair analysis and family linkage analysis were conducted. The CA-repeat polymorphism of AT &(1) R gene was identified by polymerase chain reaction(PCR) with fluorescence labeled dCTP as substrate and by semi-automatic sequence technology. The A1166 -->C variant was detected by PCR-RFLP. RESULTS: Association of AT&(1)R gene locus with EH was confirmed through the case-control study in well-characterized group of 113 Tibetan EH patients and 131 normotensives(chi(2)=26.44, P<0.001). A closer examination of this gene locus found 11 alleles from Tibetan population; allele A7 (138 bp) was more frequent in both the patients and the controls. Allele A8(140 bp) was in strong positive association with genetic susceptibility to EH in Tibetans. Frequency of allele A8 was 20.5% in EH and 7.3% in normotensives. The difference of allele frequencies between the groups was significant (chi(2)=9.64, P=0.002, OR=3.46, 95% CI 1.44-8.51). Affected sibpair analysis showed chi(2)=3.85, P=0.025; family linkage analysis gave Lod score of 0.80. No association between A1166 --> C variant in AT(1)R gene and EH in Tibetans was observed (P>0.05). CONCLUSION: The result suggests that CA-repeat polymorphism of AT(1)R gene be in association with EH in Tibetans, which implicates that AT(1)R gene may be in linkage disequilibrium with the causative genes of EH.
Adult↗
[Effect of 2/100 Hz transcutaneous electrical nerve stimulation on sexual dysfunction and serum sex hormone of heroin addicts].
OBJECTIVE: To evaluate the effect of 2/100 Hz electrical stimulation produced by Han's acupoint nerve stimulator (HANS) in treating heroin induced sex dysfunction. METHODS: Thirty-three heroin addicts were randomly divided into 2 groups to receive either buprenorphine (BPN group, n = 16) or HANS plus small dose of BPN (HANS group, n = 17) for 14 days. The doses of BPN were tailored according to individual requirement that could totally abolish withdrawal syndrome. The frequency of HANS was 2 Hz and 100 Hz shifting automatically, each lasting for 3 seconds. The stimulation was applied to 8 acupoints, the Hegu and Laogong of one upper limb, Neiguan and Waiguan of another limb, Sanyinjiao and Xingjian of both lower limbs, for 30 min. The therapy was carried out 3-4 times per day in the initial two weeks of treatment, and reduced to 1-2 times per day in the following 2 weeks. RESULTS: (1) The urine analysis for morphine in both groups turned to negative 14 days after treatment. (2) After 2 weeks of treatment, the composite score (Visual Analog Scale, VAS) of sexual function in HANS group showed a 102% increase (P < 0.01) compared with before treatment and was 107% of that in the BPN group (P < 0.01). (3) After 4 weeks treatment the serum concentration of luteinizing hormone (LH) and testosterone (T) in the HANS group showed a 137% and 118% increase respectively compared with those before treatment (P < 0.05), and the level of LH was 79.6% of that in the BPN group (P < 0.05). CONCLUSION: The 2/100 Hz transcutaneous electrical stimulation produced by Han's acupoint nerve stimulator could improve the recovery of sexual function and raise the serum concentration of LH and T in heroin addicts.
Adult↗
[Tachycardia ameliorated by electroacupuncture in morphine withdrawal rats].
OBJECTIVE: To establish morphine withdrawal tachycardia model of rat and to observe the effect of electroacupuncture (EA) with different frequency on its heart rate. METHODS: Morphine dependence was induced in Wistar rats by injection of morphine for 8 days successively, and EA 1 mA in strength was given after withdrawal of morphine with different frequencies of 2 Hz, 15 Hz and 100 Hz, the heart rate and blood pressure were recorded in the awaked rats. RESULTS: Morphine abstinent rats showed a 24% increase of heart rate as compared with that of the normal control group, but no significant change was observed in blood pressure. The 100 Hz and 15 Hz EA produced a 13.4% and 13.1% decrease of heart rate respectively, whereas 2 Hz EA produced insignificant change. CONCLUSION: The reducing effect of percutaneous electric stimulation on tachycardia in heroin addicts revealed clinically can be replicated in the rat model.
Animals↗
Functional characterization of a potassium-selective prokaryotic glutamate receptor.
Ion channels are molecular pores that facilitate the passage of ions across cell membranes and participate in a range of biological processes, from excitatory signal transmission in the mammalian nervous system to the modulation of swimming behaviour in the protozoan Paramecium. Two particularly important families of ion channels are ionotropic glutamate receptors (GluRs) and potassium channels. GluRs are permeable to Na+, K+ and Ca2+, are gated by glutamate, and have previously been found only in eukaryotes. In contrast, potassium channels are selective for K+, are gated by a range of stimuli, and are found in both prokaryotes and eukaryotes. Here we report the discovery and functional characterization of GluR0 from Synechocystis PCC 6803, which is the first GluR found in a prokaryote. GluR0 binds glutamate, forms potassium-selective channels and is related in amino-acid sequence to both eukaryotic GluRs and potassium channels. On the basis of amino-acid sequence and functional relationships between GluR0 and eukaryotic GluRs, we propose that a prokaryotic GluR was the precursor to eukaryotic GluRs. GluR0 provides evidence for the missing link between potassium channels and GluRs, and we suggest that their ion channels have a similar architecture, that GluRs are tetramers and that the gating mechanisms of GluRs and potassium channels have some essential features in common.
Amino Acid Sequence↗
Heteromeric kainate receptors formed by the coassembly of GluR5, GluR6, and GluR7.
In the CNS kainate subtype glutamate receptors (GluRs) are likely to be heteromeric assemblies containing multiple gene products. However, although recombinant kainate receptors from the GluR5-GluR7 gene family have been studied extensively in their homomeric forms, there have been no tests to determine whether these subunits can coassemble with each other. We used the GluR5 selective agonists (RS)-2-amino-3-(3-hydroxy-5-tertbutylisoxazol-4-yl)propanoic acid (ATPA) and (S)-5-iodowillardiine (I-will) to test for the coassembly of GluR5 with GluR6 and GluR7 by measuring changes in rectification that occur for heteromeric receptors containing both edited and unedited Q/R site subunits. Birectifying ATPA and I-will responses resulting from polyamine block for homomeric GluR5(Q) became outwardly rectifying when GluR6(R) was coexpressed with GluR5(Q), although GluR6 was not activated by ATPA or I-will, indicating the formation of heteromeric receptors. Similar approaches showed the coassembly of GluR7 with GluR6 and GluR5. Heteromeric kainate receptors containing both GluR5 and GluR6 subunits exhibited novel functional properties, including reduced desensitization and faster recovery from desensitization than those recorded for homomeric GluR5. Coexpression of GluR6 with GluR5 also enhanced the magnitude of responses to GluR5 selective agonists. In contrast, the coassembly of GluR7 with GluR6 markedly decreased the amplitude of agonist responses. Our results indicate that, similar to AMPA receptors, the kainate receptor subunits GluR5-GluR7 exhibit promiscuous coassembly. The formation of heteromeric kainate receptors may help to explain why the functional properties of native kainate receptors differ from those that have been reported for recombinant kainate receptors.
Alanine↗
Conformation of the diphtheria toxin T domain in membranes: a site-directed spin-labeling study of the TH8 helix and TL5 loop.
The isolated T domain of diphtheria toxin was mutated by cysteine-scanning mutagenesis at 28 consecutive sites (residues 328-355) that comprise the TH8 helix and the TL5 interhelical loop in the native toxin. After derivatizing the mutant proteins with a sulfhydryl-selective nitroxide reagent, we examined the mobility of each nitroxide and its accessibility to polar and nonpolar paramagnetic reagents, before and after insertion into phospholipid bilayers. The data obtained with the proteins in solution at pH 8 are generally consistent with predictions from the crystal structure of the toxin. Upon membrane binding at pH 4.6, a major structural reorganization of the domain was seen, which dramatically reduced the accessibility of most residues in this region to the polar reagent nickel(II)-ethylenediaminediacetate complex (NiEDDA). Many of these residues also showed reduced accessibility to the nonpolar reagent O(2). Periodic accessibility of the nitroxide side chains along the sequence to these reagents shows that TH8 remains largely helical in the membrane-bound state, with one surface associated with protein and the other facing the hydrophobic interior of the bilayer. In addition, the TL5 loop also appears to become alpha-helical in the membrane, with one surface in contact with protein and the other in contact with the bilayer interior. These findings provide a structural framework for understanding how the T domain forms a transmembrane channel and mediates translocation of diphtheria toxin's enzymic moiety across a membrane.
Chelating Agents↗
Carbon nanotube actuators
Electromechanical actuators based on sheets of single-walled carbon nanotubes were shown to generate higher stresses than natural muscle and higher strains than high-modulus ferroelectrics. Like natural muscles, the macroscopic actuators are assemblies of billions of individual nanoscale actuators. The actuation mechanism (quantum chemical-based expansion due to electrochemical double-layer charging) does not require ion intercalation, which limits the life and rate of faradaic conducting polymer actuators. Unlike conventional ferroelectric actuators, low operating voltages of a few volts generate large actuator strains. Predictions based on measurements suggest that actuators using optimized nanotube sheets may eventually provide substantially higher work densities per cycle than any previously known technology.
Journal Article↗
Discrimination between sialic acid-containing receptors and pseudoreceptors regulates polyomavirus spread in the mouse.
Variations in the polyomavirus major capsid protein VP1 underlie important biological differences between highly pathogenic large-plaque and relatively nonpathogenic small-plaque strains. These polymorphisms constitute major determinants of virus spread in mice and also dictate previously recognized strain differences in sialyloligosaccharide binding. X-ray crystallographic studies have shown that these determinants affect binding to the sialic acids. Here we report results of further experiments designed to test the importance of specific contacts between VP1 and the carbohydrate moieties of the receptor. With minor exceptions, substitutions at positions predicted from crystallography to be important in binding the terminal alpha-2,3-linked sialic acid or the penultimate sugar (galactose) destroyed the ability of the virus to replicate in cell culture. Substitutions that prevented binding to a branched disialyloligosaccharide were found to result in viruses that were both viable in culture and tumorigenic in the mouse. Conversely, substitutions that allowed recognition and binding of the branched carbohydrate chain inhibited spread in the mouse, though the viruses remained viable in culture. Mice of five different inbred strains, all highly susceptible to large-plaque virus, showed resistance to the spread of polyomavirus strains bearing the VP1 type which binds the branched-chain receptor. We suggest that glycoproteins bearing the appropriate O-linked branched sialyloligosaccharide chains are effective pseudoreceptors in the host and that they block the spread of potentially tumorigenic or virulent virus strains.
3T3 Cells↗
Whole-blood flow-cytometric analysis of induction of adhesion molecules expression on eosinophils stimulated by phorbol-12-myristate-13-acetate/ionomycin.
BACKGROUND: Activation of eosinophils is closely associated with the pathology of allergic inflammatory disease, especially bronchial asthma. We recently investigated the activation of eosinophils by applying whole blood to a flow cytometer. We measured here beta1 and beta2 integrin on eosinophils stimulated by phorbol-12-myristate-13-acetate (PMA)/ionomycin to evaluate eosinophil activation in vitro using whole blood. METHODS: Heparinized whole blood was diluted with the same volume of RPMI 1640, then cells were incubated in the presence or absence of PMA and ionomycin for 45 min at 37 degrees C. After hemolyzation with lysing solution, flow-cytometric findings for CR3, LFA1-alpha, LFA1-beta and VLA-4 expression on eosinophils were examined. RESULTS: Mean fluorescent intensity (MFI) of CR3 and LFA1-beta stimulated by PMA and ionomycin was significantly higher than that of the unstimulated control. MFI of LFA1-alpha showed no significant difference from the unstimulated control. On the other hand, MFI of VLA-4 tended to decrease. CONCLUSIONS: Our method to distinguish eosinophils from various cell groups in whole blood is simple and time-saving, similar to conditions in vivo and may allow intensive investigation of eosinophils in clinical laboratories as well as in research laboratories. We are currently investigating the influence of different kinds of stimulations, regulation factors or agents on eosinophils using this method.
Carcinogens↗
CCR3 mRNA expression in bronchial epithelial cells and various cells in allergic inflammation.
BACKGROUND: RANTES and eotaxin are important chemokines involved in the activation and migration of eosinophils and are considered to play a major role in allergic inflammation. METHODS: In this study, we used RT-PCR to investigate the kinds of cells that express mRNA for CCR3, a common receptor of these chemokines, and eotaxin, a ligand for CCR3. RESULTS: CCR3 mRNA was expressed in eosinophils, peripheral mononuclear cells, an eosinophilic cell line (EoL-1), a bronchial epithelial cell line (NCI-H(292)), human endothelial cells and nasal washings from patients with allergic rhinitis. CONCLUSION: These results suggest that the CCR3-eotaxin system plays an important role in generating inflammation, since these substances are expressed not only in cells implicated in activation or migration of eosinophils but also in various other cells involved in allergic inflammation.
Bronchi↗