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Y Gao

Publications and source records attributed to Y Gao.

At least 523 records · Page 29Linked to original sources

The value of chemical shift parameters in the description of protein solution structures.

An increasing number of protein solution structures, calculated on the basis of nuclear Overhauser enhancement cross-peak intensities observed in two- or higher dimensional NOESY experiments, are becoming available. Among these structures regions of uncertainty are frequently observed particularly with respect to loops and surface side chains. These are commonly ascribed to either a lack of NOE constraints or to some intrinsic mobility within the protein. A powerful method of structural analysis which may resolve this problem is based on the information content of the chemical shift. The value of such an analysis is illustrated here with cytochromes b5 and c, proteins for which high-quality crystallographic and NMR data are available. Comparison of these using a pseudocontact shift-based analysis indicates that NOE data should be combined with the chemical shift data in order to uncover fully the ensemble of protein states and their dynamics in solution.

Amino Acid Sequence↗

R(-)2-fluoro-N-n-propylnorapomorphine: a very potent and D2-selective dopamine agonist.

A series of 2-substituted N-n-propylnorapomorphine (NPA) derivatives were synthesized and compared with other DA agonists for affinity to D1 and D2 dopamine (DA) receptors in rat brain corpus striatum tissue. The 2-substituents tested reduced D1 affinity similarly, but enhanced D2 affinity in the rank order: F greater than OH greater than Br greater than OCH3 greater than H greater than or equal to NH2. The extraordinarily high D2 affinity (Ki = 12 pM) and D2 vs. D1 selectivity (57,500) of 2-F-NPA far-exceeded that of all other DA agonists tested, and it was about 10-times more potent than NPA in vivo.

Animals↗

Renovascular hypertension: information from experiments using conscious dogs.

1. Evidence from experiments in conscious, instrumented dogs shows that hypertension from renal artery stenosis is due to: (i) the stimulus, the mechanical resistance of the stenosis; and (ii) the secondary responses to this, especially angiotensin II (initially) and cardiovascular hypertrophy. 2. The hydraulic resistance of the stenosis is responsible for about 20-25% of the rise in blood pressure. 3. Angiotensin II is initially the most important secondary response to the stenosis. Within days, however, other as yet undetermined factors become dominant in the maintenance of the hypertension. The most important of these factors is probably cardiovascular hypertrophy. 4. These secondary factors are homeostatic, in that they mitigate the effects of stenosis on renal function.

Angiotensin II↗

[Experiment on stability of total flavones in guanshu tablet].

This paper reports the study on the stability of total flavones in guanshu tablet by heating and accelerating method. Taking the total flavone contents of the tablet as the index, the time of validity of guanshu tablet at room temperature 25 degrees C is calculated to be 9.6 years by chemical kinetic analysis.

Drug Stability↗

[The effects of sodium butyrate (NABT) on fibrillar centres and Ag-staining protein of nucleolus of human stomach glandular carcinoma (MGC-803) cells].

The changes in the ultrastructure of fibrillar centres, morphological type of nucleolus, and the content of Ag-nucleolus protein of Sodium Butyrate treated MGC-803 cells have been studied. It was found that the number of fibrillar centres and Ag-staining granules, content of Ag-staining protein of nucleolus were decreased, and nucleolar morphological type was changed from reticulated to ring-shaped in NaBT treated MGC-803 cells. These results indicate that NaBT regulate the proliferation and differentiation of cells by inhibiting rRNA synthesis and rDNA transcriptional activity.

Adenocarcinoma↗

[Studies on deletions on chromosome 13 and their transmission in patients with retinoblastoma].

We analyzed the G-banded high-resolution chromosomes of 10 patients with retinoblastoma and found 3 cases with 13q14.2 deletion. Their fathers showed similar but mosaic deletions. The proportions of abnormal cells were 10%, 14% and 21% in the fathers of cases 4, 8 and 10, respectively. The incidence and extent of deletion are discussed. The results suggest that the incidence of 13q14 deletion in retinoblastoma patients rose. The findings suggest that the three 13q14 deletion carriers who did not develop retinoblastoma transmitted the deletion to their children.

Child↗

[Cell kinetics of oral leukoplakia].

The cell kinetic characteristics of 28 cases of oral leukoplakia were studied by in vitro double labelling with 3H-thymidine and autoradiography. As compared with normal oral mucosa, there were significantly higher LI, shortened Tc and increased labelled basal cells in the leukoplakia with epithelial dysplasia, and similar changes in LI, Tc and labelled basal cells were also found in several cases without epithelial dysplasia which were clinically homogeneous or evidently caused by tobacco use. The expansion of labelled cells was often found in the epithelium with shortened, even disappeared rete pegs. The significances of the findings described above was discussed. The authors consider cell kinetics study may be useful in monitoring the dangerous cases of leukoplakia.

Autoradiography↗

A systematic approach towards the complete assignment of 13C resonances for horse ferrocytochrome c.

The complete 1H-NMR assignments for horse ferrocytochrome c have been reported by Wand and colleagues and by our group at Oxford. Using these 1H assignments, we now report chemical shift assignment for 205 13C resonances arising from horse ferrocytochrome c. This is from a total of 437 13C nuclei with covalently attached protons. These chemical shift assignments have been achieved using 1H-detected two-dimensional heteronuclear 1H-13C correlation techniques. The data have been collected from samples of horse ferrocytochrome c without isotopic enrichment. The complete 13C assignments for all carbons with covalently linked protons are reported for the amino acids Ala, Thr, Val and Gly. Specific assignments are tabulated for all 49 methyl groups, for 52 of 92 alpha-carbon resonances, for 10 resonances associated with the heme group, for all aromatic side-chain 13C resonances which have covalent protons and give rise to observable cross peaks under the experimental conditions used, as well as for a number of other side chains of aliphatic amino acids.

Amino Acids↗

Characterization of 58-kilodalton human neutrophil collagenase: comparison with human fibroblast collagenase.

A series of experiments has been carried out to characterize 58-kDa human neutrophil collagenase (HNC) and compare it with human fibroblast collagenase (HFC). N-Terminal sequencing of latent and spontaneously activated HNC shows that it is a distinct collagenase that is homologous to HFC and other members of the matrix metalloproteinase gene family. Activation occurs autolytically by hydrolysis of an M-L bond at a locus homologous to the Q80-F81-V82-L83 autolytic activation site of HFC. This releases a 16-residue propeptide believed to contain the "cysteine switch" residue required for latency. Polyclonal antibody raised against HNC cross-reacts with HFC but with none of the other major human matrix metalloproteinases examined. Treatment of HNC with endoglycosidase F or N-glycosidase F indicates that it is glycosylated at multiple sites. The deglycosylated latent and spontaneously activated enzymes have molecular weights of approximately 44K and 42K, respectively. Differences in the carbohydrate processing of HFC and HNC may determine why HFC is a secreted protein while HNC is stored in intracellular granules. The kinetic parameters kcat and KM for the hydrolysis of the interstitial collagen types I, II, and III in solution by both collagenases have been determined. The strong preferences of HNC for type I collagen and of HFC for type III collagen found in earlier studies have been confirmed. The preference of HNC for type I over type III collagen is almost abolished when fibrillar collagens are used as substrates, but the preference for HFC for type III over type I collagen is only partially decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Assignment of proton resonances, identification of secondary structural elements, and analysis of backbone chemical shifts for the C102T variant of yeast iso-1-cytochrome c and horse cytochrome c.

Resonance assignments for the main-chain, side-chain, exchangeable side chain, and heme protons of the C102T variant of Saccharomyces cerevisiae iso-1-cytochrome c in both oxidation states (with the exception of Gly-83) are reported. (We have also independently assigned horse cytochrome c.) Some additional assignments for the horse protein extend those of Wand and co-workers [Wand, A. J., Di Stefano, D. L., Feng, Y., Roder, H., & Englander, S. W. (1989) Biochemistry 28, 186-194; Feng, Y., Roder, H., Englander, S. W., Wand, A. J., & Di Stefano, D. L. (1989) Biochemistry 28, 195-203]. Qualitative interpretation of nuclear Overhauser enhancement data allows the secondary structure of these two proteins to be described relative to crystal structures. Comparison of the chemical shift of the backbone protons of the C102T variant and horse protein reveals significant differences resulting from amino acid substitution at positions 56 and 57 and further substitutions between residue 60 and residue 69. Although the overall folding of yeast iso-1-cytochrome c and horse cytochrome c is very similar, there can be large differences in chemical shift for structurally equivalent residues. Chemical shift differences of amide protons (and to a lesser extent alpha protons) represent minute changes in hydrogen bonding. Therefore, great care must be taken in the use of differences in chemical shift as evidence for structural changes even between highly homologous proteins.

Amino Acid Sequence↗

R(-) and S(+) stereoisomers of 11-hydroxy- and 11-methoxy-N-n-propylnoraporphine: central dopaminergic behavioral activity in the rat.

R(-)11-Hydroxy-N-n-propylnoraporphine (11-OH-NPa) induced stereotyped behavior in the rat as potently (ED50 = 0.80 mg/kg, i.p.) as R(-)apomorphine (APO) and this effect was blocked by haloperidol; the 11-methoxy congener, R(-)11-MeO-NPa, had a weak effect (ED50 greater than 10 mg/kg) and the S(+) isomers had none. The isomer R(-)11-OH-NPa potentiated locomotion stimulated by apomorphine; S(+)11-OH-NPa inhibited it and the isomers of 11-MeO-NPa were inactive. Catecholaporphines usually are inactive orally, but both R(-) and S(+)11-OH-NPa were similarly potent after oral or parenteral administration. The isomer S(+)11-OH-NPa inhibited spontaneous and apomorphine-induced locomotion (ID50 = 1.8-2.7 mg/kg, p.o. and i.p.) and stereotyped behavior (ID50 = 3 mg/kg, p.o. or i.p.), all without inducing catalepsy. While apomorphine was short-acting (1-2 hr), the effects of R(-)11-OH-NPa persisted up to 6-7 hr and those of the S(+) isomer for at least 2.5 hr; moreover, the efficacy of R(-)11-OH-NPa increased markedly up to 3-4 hr, although its ED50 was independent of time (ED50 = 1.7-1.9 mg/kg, i.p. from 1-3 hr). The total effect of R(-)11-OH-NPa (p.o. or i.p.) over time was more than 10-times greater than that of injected apomorphine. These observations accord with the reported high (nM) affinity of 11-OH-NPa at cerebral DA receptor sites (D2 greater than D1) and weak interactions of the 11-methoxy congener. They support the conclusion that the R(-) and S(+) stereoisomers are neuropharmacologically active, respectively, as DA agonist and apparent antagonist, as was found with the enantiomers of N-n-propylnorapomorphine, perhaps due to the low intrinsic postsynaptic agonist activity of the S(+) isomers. Moreover, 11-OH-NPa was highly bioavailable orally and unusually long-acting; it may be absorbed slowly or have active metabolites. Hydroxy-substitution of aporphines at the 11-position, homologous to the 3-OH of DA, evidently is critical for affinity and activity at the DA receptor. These or other monohydroxyaporphines may represent leads to potentially useful DA agonist or antagonist drugs.

Animals↗

Epithelial modulation of airway smooth muscle.

The responsiveness of airway smooth muscle is influenced by the functional integrity of the respiratory epithelium. The nature of this regulatory action by the epithelium remains largely unresolved. Several explanations may account for the epithelium-dependent responses induced by numerous stimuli. This review will present and discuss the evidence suggesting that the epithelium generates an inhibitory signal or signals that function to modulate the responsiveness of the underlying smooth muscle. In addition, the possible candidates for the identity of this epithelium-derived relaxing factor or factors will be assessed. Finally, the mechanisms by which the epithelium-derived relaxing factors may act to modulate bronchomotor tone will be discussed.

Animals↗