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Biomedical subjects

Y Xue

Publications and source records attributed to Y Xue.

At least 199 records · Page 11Linked to original sources

Effects of the new class III antiarrhythmic drug MS-551 and d-sotalol on canine coronary ligation-reperfusion ventricular arrhythmias.

The antiarrhythmic effects of a new class III antiarrhythmic agent, MS-551 [1,3-dimethyl-6-(2-[N-(2-hydroxyethyl)-3-(4-nitrophenyl) propylamino]ethylamino)-2,4(1H,3H)-pyrimidinedione hydrochloride], were investigated using canine coronary ligation-reperfusion arrhythmia models under slow and fast heart rate conditions and compared with those of d-sotalol. Slow and fast heart rate conditions were produced by using different anesthetics; i.e., halothane anesthesia for the slow heart rate condition and pentobarbital Na anesthesia for the fast heart rate condition. MS-551 prolonged QTc and suppressed the occurrence of fatal ventricular fibrillation (VF) on coronary reperfusion under either halothane or pentobarbital anesthesia. However, it also showed proarrhythmic effects, i.e., induction of torsades de pointes-like arrhythmia in 1 of 6 halothane anesthetized dogs before coronary ligation. d-Sotalol did not suppress the reperfusion VF in halothane anesthetized animals, nor did it show proarrhythmic effects. However, in the pentobarbital anesthetized animals, d-sotalol suppressed reperfusion VF accompanied by proarrhythmic effects in 1 of 7 dogs. d-Sotalol did not show reverse rate dependent QT prolongation. These results indicate that although both these class III drugs have similar electrophysiological properties, such as QTc prolongation, they have different antiarrhythmic effects. Also, antifibrillatory effects of class III drugs on coronary reperfusion apparently can not be explained solely by their QT prolonging effects.

Animals↗

[Preparation of oral berberine bisulfate liposomes].

The co-precipitate has been made from berberine bisulfate and polyvingyl pyrrolidone (PVP) with the ratio of 1 : 5. The liposomes entrapped berberine bisulfate have been prepared with the ration of drug to lipid 1 : 20 and the ratio of cholesterol to soy phosphatide 2 : 7. The percentage of encapsulation is 48.72%. The test in vivo of small intestinal absorption in rats shows that liposomes can increase the absorption by 4-fold odd compared with free ber-berine bisulfate.

Animals↗

Cloning of a gene encoding the precursor of nisin by PCR.

The structural gene for the precursor of nisin was synthesized by polymerase chain reaction and then cloned in pUC18. The nucleotide sequence of the cloned precursor nisin gene was determined by dideoxy termination method. The sequence data obtained agreed with those of precursor nisin genes isolated by other workers from different Lactococcus lactis strains.

Amino Acid Sequence↗

[Production and characterization of specific monoclonal antibody against Porphyromonas endodontalis].

Porphyromonas endodontalis was known to be important microorganisms in the etiology of pulp and apical infection. In this paper, we generated hybridomas secreting monoclonal antibody against Porphyromonas endodontalis ATCC 35406. The specificity of the monoclonal antibody was examined by ELISA against a battery organisms (109 Strains). The results indicated that the monoclonal antibody did not react with any non-Porphy romanas endodontalis (104 Strains). So our monoclonal antibody is specific for Porphyromanas endodontalis and can be used in clinical samples for detection of pulp and apical infections.

Animals↗

Crystal structure of fructose-1,6-bisphosphatase complexed with fructose 2,6-bisphosphate, AMP, and Zn2+ at 2.0-A resolution: aspects of synergism between inhibitors.

The crystal structure of fructose-1,6-bisphosphatase (Fru-1,6-Pase; EC 3.1.3.11) complexed with Zn2+ and two allosteric regulators, AMP and fructose 2,6-bisphosphate (Fru-2,6-P2) has been determined at 2.0-A resolution. In the refined model, the crystallographic R factor is 0.189 with rms deviations of 0.014 A and 2.8 degrees from ideal geometries for bond lengths and bond angles, respectively. A 15 degrees rotation is observed between the upper dimer C1C2 and the lower dimer C3C4 relative to the R-form structure (fructose 6-phosphate complex), consistent with that expected from a T-form structure. The major difference between the structure of the previously determined Fru-2,6-P2 complex (R form) and that of the current quaternary T-form complex lies in the active site domain. A zinc binding site distinct from the three binding sites established earlier was identified within each monomer. Helix H4 (residues 123-127) was found to be better defined than in previously studied ligated Fru-1,6-Pase structures. Interactions between monomers in the active site domain were found involving H4 residues from one monomer and residues Tyr-258 and Arg-243 from the adjacent monomer. Cooperativity between AMP and Fru-2,6-P2 in signal transmission probably involves the following features: an AMP site, the adjacent B3 strand (residues 113-118), the metal site, the immediate active site, the short helix H4 (residues 123-127), and Tyr-258 and Arg-243 from the adjacent monomer within the upper (or lower) dimer. The closest distance between the immediate active site and that on the adjacent monomer is only 5 A. Thus, the involvement of H4 in signal transmission adds another important pathway to the scheme of the allosteric mechanism of Fru-1,6-Pase.

Adenosine Monophosphate↗

Drebrin, a development-associated brain protein from rat embryo, causes the dissociation of tropomyosin from actin filaments.

Drebrin is a development-associated neuroprotein whose cDNA into fibroblasts causes the formation of dendrite-like structures (Shirao, T., Kojima, N., and Obata, K. (1992) Neuroreport 3, 109-112). To explore molecular functions of drebrin during brain development, we purified drebrin from brains of rat embryos. Drebrin bound to actin filaments at a stoichiometry of 1:5 with a dissociation constant (Kd) of 1.2 x 10(-7) M. It strongly inhibited the actin binding activity of tropomyosin. Excess amounts of tropomyosin also inhibited the drebrin binding to actin filaments, suggesting that drebrin and tropomyosin competitively bind to actin filaments. Further, drebrin inhibited not only the actin binding activity of alpha-actinin but also the actin cross-linking activity of alpha-actinin. Gene transfection experiments revealed that tropomyosin was dissociated from actin filaments in drebrin-overexpressing fibroblasts. Thus we hypothesize that drebrin may destabilize actin filaments by dissociating tropomyosin and alpha-actinin from actin filaments, resulting in the formation of axon and dendrites during neuronal development.

Actin Cytoskeleton↗

The crystal structure of allosteric chorismate mutase at 2.2-A resolution.

The crystal structure of an allosteric chorismate mutase, the Thr-226-->Ile mutant, from yeast Saccharomyces cerevisiae has been determined to 2.2-A resolution by using the multiple isomorphous replacement method. Solvent-flattening and electron-density modification were applied for phase improvement. The current crystallographic R factor is 0.196. The final model includes 504 of the 512 residues and 97 water molecules. In addition, two tryptophan molecules were identified in the interface between monomers. The overall structure is completely different from the reported structure of chorismate mutase from Bacillus subtilis. This structure showed 71% helices with essentially no beta-sheet structures.

Allosteric Regulation↗

Modification of a metal ligand in carbonic anhydrase: crystal structure of His94-->Glu human isozyme II.

One of the zinc ligands in human carbonic anhydrase II, His94, has been replaced with glutamic acid by site-directed mutagenesis. The mutation leads to a less stable zinc binding site and to significant non-local perturbations of the protein structure. The crystals are composed of a mixture of holo- and apoenzyme, and the side chain of Glu94 has two conformations. In the holoenzyme, Glu94 coordinates to the metal ion and is hydrogen bonded to Gln92. In the apo form, Glu94 is hydrogen bonded to Asn67. The mutation has resulted in a 500-fold decrease of the catalyzed rate of CO2 hydration (kcat/Km).

Apoenzymes↗

The crystallization and preliminary X-ray analysis of allosteric chorismate mutase.

An allosteric chorismate mutase, the Thr226-->Ile mutant, from the yeast Saccharomyces cerevisiae has been crystallized in space group P6(1)(P6(5)) using the hanging drop vapour diffusion method at room temperature. The cell dimensions are a = b = 95.8 A, c = 157.9 A, alpha = beta = 90 degrees, gamma = 120 degrees. It contains a dimer in the crystallographic asymmetric unit. The crystal diffracts to 2.2 A resolution. A native data set has been collected to 82% completeness at this resolution.

Allosteric Regulation↗

Wild-type and E106Q mutant carbonic anhydrase complexed with acetate.

The molecular structures of the acetate complexes of wild-type human carbonic anhydrase II (HCAII) and of E106Q mutant human carbonic anhydrase II were solved with high completeness (89-91%) to 2.1 and 1.9 A resolution, respectively. Both wild-type and mutant enzyme crystallize in space group P2(1) with cell dimensions a = 42.7, b = 41.7, c = 73.0 A and beta = 104.6 degrees. The altered active-site hydrogen-bond network caused by the mutation results in a different binding of the inhibitor in the two complexes. In the mutant, but not in the wild-type complex, a carboxylate O atom is within hydrogen-bond distance of Thr199 Ogamma1. In the wild-type enzyme ligand hydrogen bonding to this atom is normally only found for hydrogen-bond donors. The importance of this discrimination on catalysis by the enzyme is discussed briefly.

Journal Article↗

Regulation of primary erythropoiesis in the ventral mesoderm of Xenopus gastrula embryo: evidence for the expression of a stimulatory factor(s) in animal pole tissue.

We have previously shown that the animal pole tissue from a st.10+ early gastrula Xenopus embryo stimulates the primary differentiation of erythrocytes in the ventral mesoderm in combination culture. To characterize the nature of this stimulation, various sizes and different portions of animal pole tissue were combined with the ventral mesoderm explants. The erythrocyte differentiation in terms of globin expression depended on the size of the animal pole tissue that was combined with the ventral mesoderm. No difference was observed in the potency of stimulation between the ventral and dorsal halves of animal pole tissue. We also found that animal pole tissue from as late as st.7 failed to stimulate both mRNA and protein levels of globin in the explant. Histological studies of the combination explant with st.7 animal pole tissue showed that epidermis, vesicle structure, and blood-cell-like cells developed in the explant, but very few blood cells expressed globin molecules. However, the stimulation of erythroid differentiation was restored if total (20 ng) or poly(A)+ (0.2 ng) RNA from st.10+ animal pole tissue was previously injected at the 2-cell stage and the resulting animal pole tissue at st.7 was combined with st.10+ ventral mesoderm. Erythroid differentiation was also restored by injection with 1 ng of Xenopus bone morphogenetic protein-4 (XBMP-4) RNA. The effect of an extremely small dose of poly(A)+ RNA on erythroid differentiation suggests that in addition to XBMP-4 there exist substances, expressed later than st.7 in the animal pole region, which can stimulate erythrocyte differentiation in the ventral mesoderm.

Animals↗

Differential screening of mitochondrial cDNA libraries from male-fertile and cytoplasmic male-sterile sugar-beet reveals genome rearrangements at atp6 and atpA loci.

As part of a strategy to define differences in genome organization and expression between cytoplasmic male-sterile (CMS) and male-fertile (MF) sugar-beet mitochondria, cDNA libraries from both mitochondrial genotypes were constructed. Preliminary screening with ribosomal RNA gene probes identified candidate cDNA clones corresponding to structural genes. In addition, reciprocal hybridization experiments were performed using labelled first-strand cDNA to identify uniquely transcribed sequences. One cDNA clone (pYC700) is unique to CMS mitochondria and is located upstream of the F0F1-ATPase subunit 6 gene (atp6). Another cDNA clone (pYC130), when used as a probe in northern hybridization analysis, revealed novel transcript profiles in CMS sugar-beet mitochondria. Sequence analysis of this cDNA showed strong homology with the F0F1-ATPase subunit alpha (atpA) coding sequences from several higher plants. The atp6 and atpA loci from each genotype were cloned and the genomic organization, DNA sequence and transcription of each locus was studied. Differences in the transcript profiles of each gene are a consequence of genomic rearrangements 5' to the coding sequence.

Amino Acid Sequence↗

Heparin potentiation of the effect of acidic fibroblast growth factor on astrocytes and neurons.

Acidic fibroblast growth factor (aFGF) could stimulate the proliferation of astrocytes and promote the survival of neurons from newborn rat brain in vitro. The effects of aFGF on both astrocytes and neurons were significantly potentiated by heparin. The effect of aFGF (2 ng/ml) with heparin (10 mu g/ml) on the survival of neurons was a hundredfold more potent than that of aFGF (200 ng/ml) without heparin.

Animals↗

Translocation (8;21) in oligoblastic leukemia: is this a true myelodysplastic syndrome?

An 8;21 translocation with trisomy 4 is described in a 36-year-old Chinese woman who presented with an oligoblastic leukemia with myelodysplastic (MDS) features. Progression to acute myeloblastic leukemia (AML) occurred 3 months after presentation. She died of septicemia without remission. Through a review of the data in 10 cases of oligoblastic leukemia with t(8;21) in the literature, we make the following comments. (i) Oligoblastic leukemia with t(8;21) represents 2-3% of cases with this karyotype. (ii) Such cases behave in a similar manner to de novo AML. (iii) The presence of features of MDS has no affect on the behaviour of the disease. (iv) Such cases should be treated without delay with intensive chemotherapy.

Adult↗