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Q H Yang

Publications and source records attributed to Q H Yang.

At least 19 recordsLinked to original sources
PubMed2005

Tests of trait-haplotype association when linkage phase is ambiguous, appropriate for matched case-control and cohort studies with competing risks.

The impact of competing risks on tests of association between disease and haplotypes has been largely ignored. We consider situations in which linkage phase is ambiguous and show that tests for disease-haplotype association can lead to rejection of the null hypothesis, even when true, with more than the nominal 5 per cent frequency. This problem tends to occur if a haplotype is associated with overall mortality, even if the haplotype is not associated with disease risk. A small simulation study illustrates the magnitude of bias (high type I error rate) in the context of a cohort study in which a modest number of disease cases (about 350) occur over time. The bias remains even if the score test is based on a logistic model that includes age as a covariate. For cohort studies, we propose a new test based on a modification of the proportional hazards model and for case-control studies, a test based on a conditional likelihood that have the correct size under the null even in the presence of competing risks, and that can be used when haplotype is ambiguous.

Aged↗
PubMed2004

Influence of maturation on constrictive response to stimulation of C-fiber afferents in isolated guinea pig airways.

We investigated whether the airway constrictive response to stimulation of bronchopulmonary C-fiber afferents is altered during the maturation process. Isometric tension was measured in airway rings isolated from three tracheobronchial locations (intrathoracic trachea and main and hilar bronchi) and compared in mature [M, 407 +/- 10 (SE) g body wt, n = 36] and immature (IM, 161 +/- 5 g body wt, n = 35) guinea pigs. Our results showed no difference in the ACh (10(-5) M)- or KCl (40 mM)-induced contraction between M and IM groups, regardless of the airway location. In sharp contrast, the concentration-response curves of 10(-8)-10(-6) M capsaicin were distinctly lower in IM hilar bronchi; for example, response to the same concentration of capsaicin (10(-6) M) was 89.2 +/- 15.3% of the response to 10(-5) M ACh in IM and 284.7 +/- 43.2% in M animals. Similar, but smaller, differences in the bronchoconstrictive response to capsaicin between IM and M groups were also observed in the trachea and main bronchus. Electrical field stimulation induced airway constriction in all three locations in M and IM groups. However, after administration of 10(-6) M atropine and 10(-6) M propranolol, electrical field stimulation-induced contraction was significantly smaller in the hilar bronchus of IM than M animals, and this difference was not prevented by pretreatment with 5 x 10(-5) M indomethacin. Although radioimmunoassay showed no difference in the tissue content of substance P between M and IM airways, the constrictive responses to exogenous substance P and neurokinin A were markedly greater in M airways at all three locations. In conclusion, the constriction of isolated airways evoked by C-fiber stimulation was significantly weaker in the IM guinea pigs, probably because of a less potent effect of tachykinins on the airway smooth muscle.

Aging↗
PubMed2001

Involvement of the chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase sequence His444-Arg-Glu-Arg in modulation of the bisphosphatase activity by its kinase domain.

The bisphosphatase activity of the hepatic bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is repressed by its kinase domain, and regulated by cAMP-dependent protein kinase (PKA)-catalysed phosphorylation. In the present study, the mechanism by which the bisphosphatase activity is repressed by the kinase domain and regulated by phosphorylation was investigated. We found that truncation of the C-terminus of the enzyme by 25, but not 20, amino acids dramatically enhanced the catalytic rate of the bisphosphatase, abrogated the inhibition by the kinase domain, and eliminated the effect of PKA-mediated phosphorylation on activity. In addition, mutation of His444-Arg-Glu-Arg to Ala-Ala-Glu-Ala had similar effects as the deletion. Moreover, the mutations also significantly affected the phosphorylation-mediated regulation of the kinase activity of the enzyme. Furthermore, the mutations altered the pH-dependence of the bisphosphatase, and the mutant bisphosphatases were more sensitive to modification by diethyl pyrocarbonate and guanidine-induced inactivation than the wild-type enzyme. Taken together, these results demonstrate that the sequence His444-Arg-Glu-Arg plays a critical role in repression of the bisphosphatase activity by both the N-terminal kinase domain and the C-terminal tail itself. These results also explain the activation of the bisphosphatase activity by PKA-catalysed phosphorylation, by suggesting that phosphorylation may relieve the inhibitory effect of the kinase domain that is mediated by the three basic residues in this sequence.

Amino Acid Sequence↗
PubMed2001

Binding of ATP to the fructose-2,6-bisphosphatase domain of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase leads to activation of its 6-phosphofructo-2-kinase.

To understand the mechanism by which the activity of the 6-phosphofructo-2-kinase (6PF-2K) of chicken liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase is stimulated by its substrate ATP, we studied two mutants of the enzyme. Mutation of either Arg-279, the penultimate basic residue within the Walker A nucleotide-binding fold in the bisphosphatase domain, or Arg-359 to Ala eliminated the activation of the chicken 6PF-2K by ATP. Binding analysis by fluorescence spectroscopy using 2'(3')-O-(N-methylanthraniloyl)-ATP revealed that the kinase domains of these two mutants, unlike that of the wild type enzyme, showed no cooperativity in ATP binding and that the mutant enzymes possess only the high affinity ATP binding site, suggesting that the ATP binding site on the bisphosphatase domain represents the low affinity site. This conclusion was supported by the result that the affinity of ATP for the isolated bisphosphatase domain is similar to that for the low affinity site in the wild type enzyme. In addition, we found that the 6PF-2K of a chimeric enzyme, in which the last 25 residues of chicken enzyme were replaced with those of the rat enzyme, could not be activated by ATP, despite the fact that the ATP-binding properties of this chimeric enzyme were not different from those of the wild type chicken enzyme. These results demonstrate that activation of the chicken 6PF-2K by ATP may result from allosteric binding of ATP to the bisphosphatase domain where residues Arg-279 and Arg-359 are critically involved and require specific C-terminal sequences.

Adenosine Triphosphate↗
PubMed2000

Interaction between the conserved region in the C-terminal domain of GRK2 and rhodopsin is necessary for GRK2 to catalyze receptor phosphorylation.

The C-terminal domain of G protein-coupled receptor kinases (GRKs) consists of a conserved region and a variable region, and the variable region has been shown to direct the membrane translocation of cytosolic enzymes. The present work has revealed that the C-terminal domain may also be involved in kinase-receptor interaction that is primarily mediated by the conserved region. Truncation of the C-terminal domain or deletion of the conserved region in this domain of GRK2 resulted in a complete loss of its ability to phosphorylate rhodopsin and in an obvious decrease in its sensitivity to receptor-mediated phosphorylation of a peptide substrate. On the contrary, deletion of the betagamma subunit binding region in the C-terminal domain of GRK2 did not significantly alter the ability of the enzyme to phosphorylate rhodopsin. In addition, the recombinant proteins that represent the C-terminal domain and the conserved region of GRK2 could inhibit GRK2-mediated phosphorylation of rhodopsin and receptor-mediated activation of GRK2 but not GRK2-mediated phosphorylation of the peptide substrate. Furthermore, the conserved region as well as the C-terminal domain could directly bind rhodopsin in vitro. These results indicate that the C-terminal domain, or more precisely, the conserved region of this domain, is important for enzyme-receptor interaction and that this interaction is required for GRK2 to catalyze receptor phosphorylation.

Adrenergic beta-Antagonists↗
PubMed2000

Transmission/disequilibrium tests for quantitative traits.

The transmission/disequilibrium test (TDT) is a powerful method of locating disease genes. The TDT was originally proposed for use in studies of qualitative traits in families with both parents available. Recently, the TDT has been extended to studies of qualitative traits in sibships without parents available and in families with one parent available. It has also been extended for use in studies of quantitative traits in families with both parents available and in sibships with multiple offspring. In this paper, we first propose a new class of TDT-type tests for linkage in the presence of linkage disequilibrium for use in studies of families with both parents available. The TDT of Spielman et al. (1993) for qualitative traits and the TDT of Rabinowitz (1997) for quantitative traits are special cases of the new tests. Second, we propose a new class of TDT-type tests for linkage for use in studies of families with one parent available. Third, we study the validity and the power of the tests using simulations. Finally, we propose a method of combining data from different types of families. The combined test is valuable and allows researchers full use of the available data in detecting linkage between a marker locus and an unobservable quantitative trait locus. An important feature of the tests proposed in this paper is that no assumptions on the distribution of the quantitative traits are needed.

Computer Simulation↗
PubMed2000

The difference in the carboxy-terminal sequence is responsible for the difference in the activity of chicken and rat liver fructose-2,6-bisphosphatase.

The fructose-2,6-bisphosphatase domain of the bifunctional chicken liver enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase shares approximately 95% amino acid sequence homology with that of the rat enzyme. However, these two enzymes are significantly different in their phosphatase activities. In this report, we show that the COOH-terminal 25 amino acids of the two enzymes are responsible for the different enzymatic activities. Although these 25 amino acids are not required for the phosphatase activity, their removal diminishes the differences in the activities between the two enzymes. In addition, two chimeric molecules (one consisting of the catalytic core of the chicken bisphosphatase domain and the rat COOH-terminal 25 amino acids, and the other consisting of most of the intact chicken enzyme and the rat COOH-terminal 25 amino acids) showed the same kinetic properties as the rat enzyme. Furthermore, substitution of the residues Pro456Pro457Ala458 of the chicken enzyme with GluAlaGlu, the corresponding sequence in the rat liver enzyme, yields a chicken enzyme that behaves like the rat enzyme. These results demonstrate that the different bisphosphatase activities of the chicken and rat liver bifunctional enzymes can be attributed to the differences in their COOH-terminal amino acid sequences, particularly the three residues.

Amino Acid Sequence↗
PubMed2000

[Transmission and genetic effect of ting chromosome in cross progenies from octoploid Tritileymus with 4D nullisomic].

A pair of ting chromosomes (ti) added to 72180 4D nullisomic was subcentral centromere chromosome and was about 1/3-1/4 the size of a chromosome on the average length. It's chromosome configuration was 19.59" (18-20) + 0.46' (0-4) + 0.99" (0-1) + 0.96ti" (0-1) + 0.08ti' (0-2) at PMC MI. The cells with ring ti" account for 96.19%, of which 82.38% were free on each side of the equatorial plane. ti chromosome paired in advance, defered segregation and had no synapsis with a chromosome. When the cross progenies from 72180 4D nullisomic with octoploid Trilileymus were backcrossed to the 4D nullisomic used as the male, the transmitting rate of 2ti chromosome was six times higher than that where the nullisomic was used as the female. The transmitting and loss rates of ti chromosome were 50.38% and 18.34% respectively, and averagely each plant has 0.72 ti chromosome in the cross generations. The appearing rate of ti chromosome was 43.18% in root tip cell and 8.16% in PMC MI of the plants without ti chromosome. When the number of a chromosome was less than 42, the genetic effect of ti chromosome on the quantitative character was significant, while the number of a chromosome was 42, the genetic effect was not apparent.

Chromosomes↗
PubMed2000

Nociceptin inhibits electric field stimulation-induced cholinergic constrictions in rat airways.

AIM: To study the effect of nociceptin (orphanin FQ), a newly discovered heptadecapeptide, on cholinergic constrictions in isolated trachea and bronchus of rat. METHODS: The electric field stimulation (EFS) induced a monophasic constriction, which was due to an activation of the cholinergic nerves. RESULTS: Nociceptin 0.001-0.1 mumol/L inhibited cholinergic constriction in a concentration-dependent manner. IC50 (95% of confidence limits) were 0.06 (0.04-0.08) mumol/L and 0.07 (0.05-0.1) mumol/L in tracheae and bronchi respectively. The constrictions inhibited by nociceptin 0.01 mumol/L in traheae and bronchi were (58 +/- 32)% and (60 +/- 26)% respectively compared with the control, in which nociceptin was not applied. After pretreatment with naloxone 0.1 mumol/L, the constrictions were (60 +/- 19)% and (54 +/- 20)% (P > 0.05 vs the above figures). However, the constrictions induced by exogenous acetylcholine were unaffected by nociceptin 0.01 mumol/L. kappa-Opioid receptor agonist, U-50488H (0.01-1 mumol/L) did not affect the EFS-induced cholinergic constrictions in rat airways. CONCLUSION: Nociceptin inhibits EFS-induced cholinergic constriction, which is not affected by naloxone in rat airways.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1999

Bronchodilating effects of bambuterol on bronchoconstriction in guinea pigs.

AIM: To study the effects of bambuterol (Bam) on bronchoconstriction in guinea pigs. METHODS: Bronchospasm induced by histamine aerosol, lung resistance (RL) and dynamic lung compliance (Cdyn) changes induced by ovalbumin aerosol in vivo, isolated resting lung parenchyma strips, and carbamylcholine-induced tracheal constriction in vitro in guinea pig were investigated. RESULTS: Bam dose-dependently prolonged the time to histamine-induced collapse, ED50 values (95% confidence limits) of Bam intragastric gavage (i.g.) after 1 h, 4 h, and 24 h were 0.74 (0.60-0.91), 0.75 (0.61-0.91) and 1.00 (0.77-1.30) mg.kg-1, respectively. Bam 2 or 10 mg.kg-1 i.g. 2 h before ovalbumin aerosol partly or almost completely inhibited bronchial challenge of ovalbumin-induced change of RL and Cdyn. Bam 0.1-1.0 mumol.L-1 gave a weak relaxation on isolated tracheal strips induced by carbamylcholine and failed to relax the isolated resting lung parenchyma strips in guinea pig. CONCLUSION: Bam showed a long-acting bronchodilation by its slow metabolism in vivo.

Animals↗
PubMed1997

Low concentration of inducer favors production of active form of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in Escherichia coli.

Expression of chicken and rat liver bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, in Escherichia coli encountered two common problems: the chicken enzyme was liable to proteolysis and the rat enzyme was prone to form inclusion bodies. Reducing the rate of protein synthesis by lowering either growth temperature or isopropyl-beta-D-thiogalactopyranoside (IPTG) concentration alleviated these two problems. Growth at 22 degrees C was optimum for expression of both enzymes. The optimum range of IPTG concentration for expression was 0.1-1 microM for the chicken liver bifunctional enzyme and 10 microM for rat liver enzyme. The components of growth medium also influenced the production. Compared with Luria-Bertani medium, an enriched medium-tryptone-phosphate medium-tripled the production of the active enzymes. Addition of glucose (0.2%) doubled the expression level of active chicken liver enzyme, but reduced the production of active rat liver enzyme to half the maximal level, while the phosphate in tryptone-phosphate medium had no effect on the production of the two enzymes.

Animals↗
PubMed1997

A preliminary analysis of antineoplastic activity of parvovirus MVMp NS-1 proteins.

Human gastric cancer MKN-45 cells were transfected with pULB 3238, a plasmid carrying MVMp NS-1 gene with its original P4 promoter replaced by the glucocorticoid inducible promoter MMTV-LTR. After the integration and expression of NS-1 gene, some of the transfectants died, while others remained alive, but the growth features of survived cells were changed. For further study on the antineoplastic function of parvoviral NS-1 protein in vivo, transgenic mice carrying NS-1 genes were established by conventional method. Among 4 founders, one of them was found to be able to transmit the transgene to around 50% of their offsprings. RT-PCR was performed to indicate the expression of NS-1 gene in transgenic mice and its mRNA appeared in a variety of tissues. The expression of integrated NS-1 gene may correlate with the decreased incidence of tumor induced in vivo by chemical carcinogens.

Animals↗
PubMed1996

Linkage of replication to start by the Cdk inhibitor Sic1.

In Saccharomyces cerevisiae, three G1 cyclins (Clns) are important for Start, the event committing cells to division. Sic1, an inhibitor of C1b-Cdc28 kinases, became phosphorylated at Start, and this phosphorylation depended on the activity of Clns. Sic1 was subsequently lost, which depended on the activity of Clns and the ubiquitin-conjugating enzyme Cdc34. Inactivation of Sic1 was the only nonredundant essential function of Clns, because a sic1 deletion rescued the inviability of the cln1 cln2 cln3 triple mutant. In sic1 mutants, DNA replication became uncoupled from budding. Thus, Sic1 may be a substrate of Cln-Cdc28 complexes, and phosphorylation and proteolysis of Sic1 may regulate commitment to replication at Start.

Anaphase-Promoting Complex-Cyclosome↗
PubMed1995

Use of polymerase chain reaction epitope tagging for protein tagging in Saccharomyces cerevisiae.

Epitope tagging is the insertion of a short stretch of amino acids constituting an epitope into another protein. Tagged proteins can be identified by Western, immunoprecipitation and immunofluorescence assays using pre-existing antibodies. We have designed vectors containing the URA3 gene flanked by direct repeats of epitope tags. We use the polymerase chain reaction (PCR) to amplify the tag-URA3-tag cassette such that the ends of the PCR fragments possess homology to the gene of interest. In vivo recombination is then used to direct integration of the fragment to the location of interest, and transformants are selected by their Ura+ phenotype. Finally, selection for Ura- cells on 5-fluoro-orotic acid plates yields cells where recombination between the repeated epitopes has 'popped out' the URA3 gene, leaving a single copy of the epitope at the desired location. PCR epitope tagging (PET) provides a rapid and direct technique for tagging that does not require any cloning steps. We have used PET to tag three Saccharomyces cerevisiae proteins, Cln1, Sic1 and Est1.

Amino Acid Sequence↗
PubMed1995

Inhibitory effect of tetrandrine on C fiber activation-induced contractions in trachea and bronchus of guinea pig.

AIM: To study the inhibitory effects of tetrandrine (Tet) on an activation of the sensory nervous C fibers in isolated trachea and bronchus of guinea pig. METHOD: The electric field stimulation induced a phase II contraction of the preparations, which was due to an activation of the C fifers. The effects of Tet on phase II contraction were analyzed. RESULTS: Tet 0.3-30 mumol.L(-1) inhibited phase II contractions in a concentration-dependent manner. That phase II contractions inhibited by Tet 1 mumol.L(-1) were 40 +/- 38% and 75 +/- 22% of control in tracheae and bronchi respectively. After pretreatment with chlorphenamine or atropine phase II contraction were still reduced by Tet 1 mumol.L(-1), inhibitory rates being 70 +/- 16% and 64 +/- 16% of control, respectively. The contractile responses of the preparations to exogenous substance P, however, were unaffected by treatment with Tet 1 mumol.L(-1). CONCLUSION: Tet 1 mumol.L(-1) inhibits phase II contraction, related to the inhibition of local release of neuropeptides from C fibers of guinea pig airway.

Alkaloids↗
PubMed1994

Mediator difference in contractions between trachea and bronchus of guinea pig induced by stimulation of C-fibers in vitro.

In trachea and bronchus of guinea pig in vitro, electric field stimulation (EFS) induced a rapid contraction (phase I) followed by a long-lasting contraction (phase II). The pretreatments of chlorphenamine (Chl) 1 mumol.L-1 and disodium cromoglycate (Cro) 10 mumol.L-1 reduced the tracheal contraction of phase II from 49 +/- 23 mg and 34 +/- 18 mg to 27 +/- 21 and 18 +/- 12 mg, respectively. The contractile responses of the tracheae to increasing concentrations of substance P (SP) 0.1-3.0 mumol.L-1 were reduced by the pretreatment of Cro 10 mumol.L-1 (P < 0.01). On the contrary, the contractile responses of the bronchi were not inhibited by Cro or Chl but were inhibited by pretreatment of atropine 1 mumol.L-1 from 61 +/- 36 mg to 36 +/- 15 mg. These results show that there are different mechanisms in the EFS-induced contractions between the trachea and bronchus; that different mediators amplify the phase II contractions.

Acetylcholine↗
PubMed1992

[Acute side effect of postoperative radiotherapy in malignant head and neck neoplasm]

From August 1989 to May 1991,160 patients with malignancies of the head and neck region were treated by surgery and postoperative radiotherapy.Seventy seven patiens underwent resection of the primary lesion combined with neck dissection and 83 patients had resecton of the primary lesion only before radiotherapy.After irradiation 33.8% (54/160) patients developed edema in face and neck,13.1%(21/160) patients developed headache.The style of neck dissection (unilateral,bilateral or no neck dessection) did significantly influence the rates of the acute side effect(P<0.01).The interval between surgery and radiotherapy and radiation dose were not important influential factors(P>0.05).The clinical manifestations,possible mechanism and prevention of the acuter side effect is presented.

Journal Article↗