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Biomedical subjects

Q Xu

Publications and source records attributed to Q Xu.

At least 361 records · Page 20Linked to original sources
PubMed1996

Diltiazem concentrations in plasma vs PR intervals on electrocardiogram in 8 men.

AIM: To develop an acute tolerant model in describing relationship between diltiazem (Dil) concentrations in plasma and PR intervals on ECG in men. METHOD: Both plasma concentrations of Dil and changes of ECG were simultaneously determined after po Dil 90 mg in 8 men. RESULTS: A two-compartmental pharmacokinetic model with first-order input gave a good fitting for the plasma concentration of Dil. Corresponding pharmacokinetic parameters were estimated: t1/2 beta, 5.9 +/- 1.0 h; MRT, 15.9 +/- 1.0 h; t0, 0.38 +/- 0.07 h; tmax, 2.7 +/- 0.4 h, and Cmax, 161 +/- 60 micrograms.L-1. The good fittings for plasma concentration-effect data were obtained with tolerant model E = S x C/(1 + T/T50). The pharmacodynamic parameters were given as follows: S, 829 +/- 293 s.g-1.L; Kt0, 0.037 +/- 0.024 h-1 and T50, 10 +/- 4 micrograms.L-1. CONCLUSION: Relationship between Dil concentrations in plasma and PR interval changes in men after po 90 mg was described using an acute tolerant model.

Adult↗
PubMed1995

Enhanced affinities and specificities of consolidated ligands for the Src homology (SH) 3 and SH2 domains of Abelson protein-tyrosine kinase.

The possible interrelationships between multiple domains of proteins involved in intracellular signal transduction are complex and not easily investigated. We have synthesized a series of bivalent consolidated ligands, which interact simultaneously with the SH2 and SH3 domain of Abelson kinase in a SH(32) dual domain construct, a portion of native Abelson kinase. Affinities were measured by quenching of intrinsic tryptophan fluorescence. Consolidated ligands have enhanced affinity and specificity compared to monovalent equivalents. Affinity is also dependent on the length of the linker joining the two parts, with an optimum distance similar to that expected from structural models of Abl (SH(32). These results suggest that consolidated ligands may be generally useful reagents for probing structural and functional activities of multidomain proteins.

Abelson murine leukemia virus↗
PubMed1995

Chiral recognition of deoxyoligonucleotides by delta- and lambda-tris(ethylenediamine)cobalt(III).

59Co NMR and CD measurements show for both stereoisomers of Co(en)3(3+) a similar trend in the sequence dependence of DNA recognition, as was reported previously for Co(NH3)6(3+). In particular, specific binding is evident to DNA molecules possessing runs of two or more same-strand guanine residues. The binding of either isomer to such sequences induces structural transitions toward A-DNA characteristics. Such measurements also show significant differences between the two stereoisomers in terms of how they recognize specific duplex DNA sequences. delta-Co(en)3(3+) binds more tightly than lambda-Co(en)3(3+) to right-handed, guanine-rich DNA, whereas lambda-Co(en)3(3+) binds more tightly than delta-Co(en)3(3+) to left-handed DNA. The two stereoisomers bind in an indistinguishable manner to AT-rich DNA.

Base Sequence↗
PubMed1995

Acute hypertension induces heat-shock protein 70 gene expression in rat aorta.

BACKGROUND: Many factors cause acute systemic hypertension, which in turn can result in damage to the vessel wall and lead to vascular disease. In previous studies, we demonstrated that restraint, or immobilization stress, results in the induction of heat-shock protein 70 (hsp70) gene expression in the aorta of adult rat and showed that this response was markedly attenuated with age. METHODS AND RESULTS: Here we provide evidence that restraint-induced hsp70 expression occurs secondary to a rise in systemic blood pressure. Old rats were unable to mount a significant stress-induced hypertensive response, providing an explanation for the reduced hsp70 response in the old rats. A variety of vasoactive agents that induce acute hypertension through distinct signal transduction pathways, including phenylephrine, dopamine, vasopressin, angiotensin II, and endothelin-1, were found to result in hsp70 mRNA induction in the aorta. The magnitude of hsp70 expression achieved with these hypertensive agents was directly correlated with their relative effects on blood pressure. Rats were treated with the vasodilator sodium nitroprusside, which prevented an acute rise in blood pressure from the hypertensive agents tested and abolished induction of hsp70 expression. CONCLUSIONS: These findings support the conclusion that hsp70 induction occurs as a physiological response to acute hypertension and suggest the possibility that hsp70 plays a role in the protecting the vasculature from damage during hemodynamic stress.

Aging↗
PubMed1995

Mutational analysis of photosystem I polypeptides in the cyanobacterium Synechocystis sp. PCC 6803. Targeted inactivation of psaI reveals the function of psaI in the structural organization of psaL.

We cloned, characterized, and inactivated the psaI gene encoding a 4-kDa hydrophobic subunit of photosystem I from the cyanobacterium Synechocystis sp. PCC 6803. The psaI gene is located 90 base pairs downstream from psaL, and is transcribed on 0.94- and 0.32-kilobase transcripts. To identify the function of PsaI, we generated a cyanobacterial strain in which psaI has been interrupted by a gene for chloramphenicol resistance. The wild-type and the mutant cells showed comparable rates of photoautotrophic growth at 25 degrees C. However, the mutant cells grew slower and contained less chlorophyll than the wild-type cells, when grown at 40 degrees C. The PsaI-less membranes from cells grown at either temperature showed a small decrease in NADP+ photoreduction rate when compared to the wild-type membranes. Inactivation of psaI led to an 80% decrease in the PsaL level in the photosynthetic membranes and to a complete loss of PsaL in the purified photosystem I preparations, but had little effect on the accumulation of other photosystem I subunits. Upon solubilization with nonionic detergents, photosystem I trimers could be obtained from the wild-type, but not from the PsaI-less membranes. The PsaI-less photosystem I monomers did not contain detectable levels of PsaL. Therefore, a structural interaction between PsaL and PsaI may stabilize the association of PsaL with the photosystem I core. PsaL in the wild-type and PsaI-less membranes showed equal resistance to removal by chaotropic agents. However, PsaL in the PsaI-less strain exhibited an increased susceptibility to proteolysis. From these data, we conclude that PsaI has a crucial role in aiding normal structural organization of PsaL within the photosystem I complex and the absence of PsaI alters PsaL organization, leading to a small, but physiologically significant, defect in photosystem I function.

Amino Acid Sequence↗
PubMed1995

Doppler echocardiographic characteristics of sinus of valsalva aneurysms.

This study evaluated the efficacy of a comprehensive transthoracic Doppler echocardiographic examination for correct detection of SVA and its associated lesions of VSD and aortic insufficiency. A consecutive series of 36 patients was obtained; all had surgical confirmation of the anatomic defects. The location of the SVA was correctly determined in 97% of patients, and the associated presence of a VSD was correctly determined in 79% of the studies. In the cases in which Doppler was available, all 11 patients with associated aortic insufficiency were detected. In this series 32 patients had right SVA, 3 had noncoronary sinus SVA, and 1 had a left SVA. Relative frequency of the rupture site location corresponded closely to that in previous necropsy studies. It is concluded that transthoracic Doppler echocardiography can correctly localize SVAs and most associated lesions.

Adult↗
PubMed1995

Is atherosclerosis an immunologically mediated disease?

In contrast to general beliefs, recent data from different laboratories have provided evidence that the first stages of atherosclerosis are of an inflammatory nature. Here, Georg Wick and colleagues suggest that an autoimmune reaction against heat shock protein 60 (Hsp60), expressed by endothelial cells in areas that are subject to increased haemodynamic stress, is the initiating event in atherogenesis. Humoral and T-cell-mediated immune responses against Hsp60 have both been demonstrated early in disease. This inflammatory stage, which is reversible and has even been found in children, may progress into fully developed atherosclerotic lesions, displaying all the classical pathohistological and functional consequences, if additional risk factors such as high blood cholesterol levels, smoking and obesity, are present.

Animals↗
PubMed1995

Organization of photosystem I polypeptides. Identification of PsaB domains that may interact with PsaD.

PsaA and PsaB are homologous integral membrane-proteins that form the heterodimeric core of photosystem i (PSI). We used subunit-deficient PSI complexes from the mutant strains of the cyanobacterium Synechocystis sp. PCC 6803 to examine interactions between PsaB and other PSI subunits. Incubation of the wild-type PSI with thermolysin yielded 22-kD C-terminal fragments of PsaB that were resistant to further proteolysis. Modification of the wild-type PSI with N-hydroxysuccinimidobiotin and subsequent cleavage by thermolysin showed that the lysyl residues in the 22-kD C-terminal domain were inaccessible to modification by N-hydroxysuccinimidobiotin. The absence of PsaE, PsaF, PsaI, PsaJ, or PsaL facilitated accumulation of 22-kD C-terminal fragments of PsaB but did not alter their resistance to further proteolysis. When the PsaD-less PSI was treated with thermolysin, the 22-kD C-terminal fragments of PsaB were rapidly cleaved, with concomitant accumulation of a 16-kD fragment and then a 3.4-kD one. We mapped the N termini of these fragments by N-terminal amino acid sequencing and the C termini from their positive reaction with an antibody against the C-terminal peptide of PsaB. The cleavage sites were proposed to be in the extramembrane loops on the cytoplasmic side. Western blot analyses showed resistance of PsaC and PsaI to proteolysis prior to cleavage of the 22-kD fragments. Therefore, we propose that PsaD shields two extramembrane loops of PsaB and protects the C-terminal domain of PsaB from in vitro proteolysis.

Amino Acid Sequence↗
PubMed1995

Preliminary structure determination of the capsular polysaccharide of Vibrio cholerae O139 Bengal Al1837.

Vibrio cholerae O139 Bengal has recently been identified as a cause of epidemic cholera in Asia. In contrast to V. cholerae O1, V. cholerae O139 Bengal has a polysaccharide capsule. As determined by high-performance anion-exchange chromatography and 1H nuclear magnetic resonance analysis, the capsular polysaccharide of V. cholerae O139 Bengal strain Al1837 has six residues in the repeating subunit; this includes one residue each of N-acetylglucosamine, N-acetylquinovosamine (QuiNAc), galacturonic acid (GalA), and galactose and two residues of 3,6-dideoxyxylohexose (Xylhex). The proposed structure is [formula: see text]

Bacterial Capsules↗
PubMed1995

Sug1 modulates yeast transcription activation by Cdc68.

The Cdc68 protein is required for the transcription of a variety of genes in the yeast Saccharomyces cerevisiae. In a search for proteins involved in the activity of the Cdc68 protein, we identified four suppressor genes in which mutations reverse the temperature sensitivity caused by the cdc68-1 allele. We report here the molecular characterization of mutations in one suppressor gene, the previously identified SUG1 gene. The Sug1 protein has been implicated in both transcriptional regulation and proteolysis. sug1 suppressor alleles reversed most aspects of the cdc68-1 mutant phenotype but did not suppress the lethality of a cdc68 null allele, indicating that sug1 suppression is by restoration of Cdc68 activity. Our evidence suggests that suppression by sug1 is unlikely to be due to increased stability of mutant Cdc68 protein, despite the observation that Sug1 affected proteolysis of mutant Cdc68. We report here that attenuated Sug1 activity strengthens mutant Cdc68 activity, whereas increased Sug1 activity further inhibits enfeebled Cdc68 activity, suggesting that Sug1 antagonizes the activator function of Cdc68 for transcription. Consistent with this hypothesis, we find that Sug1 represses transcription in vivo.

Adenosine Triphosphatases↗
PubMed1995

Autoantibodies against heat shock protein 60 mediate endothelial cytotoxicity.

Stress or heat shock proteins (hsp) are a family of approximately two dozen proteins with a high degree of amino acid sequence homology between different species, ranging from prokaryotes to humans, and are representative of a generalized response to environmental and metabolic stressors. Our previous studies showed increased expression of human hsp60 on endothelial cells of arterial intima with atherosclerotic lesions, and elevated levels of serum antibodies (Ab) against hsp65/60 in subjects with carotid atherosclerosis. To investigate the possible involvement of anti-hsp65/60 Ab in endothelial injury, specific hsp-Ab were isolated from human high titer sera by affinity chromatography and probed on heat-shock human umbilical vein endothelial cells. Purified human anti-hsp65/60 Ab reacted specifically with mycobacterial hsp65, human hsp60, and a 60-kD protein band of heat-shocked endothelial cells. High levels of hsp60 mRNA expression in endothelial cells were found between 4 and 12 h after 30 min treatment at 42 degrees C. In immunofluorescence tests, positive staining of heat-stressed endothelial cells was observed not only in the cytoplasm but also on the cell surface. Furthermore, only heat-stressed, but not untreated, Cr-labeled endothelial cells were lysed by anti-hsp65/60 Ab in the presence of complement (complement-mediated cytotoxicity) or peripheral blood mononuclear cells (antibody-dependent cellular cytotoxicity). Control Abs, including human anti-hsp65/60 low titer antiserum, human Ig fraction deprived of hsp65/60 Ab, and mAbs to Factor VIII, alpha-actin, hsp70, and CD3 showed no cytotoxic effect. In conclusion, human serum anti-hsp65 antibodies act as autoantibodies reacting with hsp60 on stressed endothelial cells and are able to mediate endothelial cytotoxicity. Thus, a humoral immune reaction to hsp60 may play an important role in the pathogenesis of atherosclerosis.

Aged↗
PubMed1995

Midline signalling is required for Pax gene regulation and patterning of the eyes.

Pax6 and Pax2 are members of the Pax family of transcription factors that are both expressed in the developing visual system of zebrafish embryos. Pax6 protein is present in all cells that form the neural retina and pigment epithelium, whereas Pax2 is located primarily in cells that will give rise to the optic stalk. In this study, we have addressed the role of midline signalling in the regulation of Pax2 and Pax6 distributions and in the subsequent morphogenesis of the eyes. Midline signalling is severely perturbed in cyclops mutant embryos resulting in an absence of ventral midline CNS tissue and fusion of the eyes. Mutant embryos ectopically express Pax6 in a bridge of tissue around the anterior pole of the neural keel in the position normally occupied by cells that form the optic stalks. In contrast, Pax2 protein is almost completely absent from this region in mutant embryos. Concommitant with the changes in Pax protein distribution, cells in the position of the optic stalks differentiate as retina. These results suggest that a signal emanating from the midline, which is absent in cyclops mutant embryos, may be required to promote Pax2 and inhibit Pax6 expression in cells destined to form the optic stalks. Sonic hedgehog (Shh also known as Vhh-1 and Hhg-1) is a midline signalling molecule that is absent from the neuroepithelium of cyclops mutant embryos at early developmental stages. To test the possibility that Shh might be able to regulate the spatial expression of Pax6 and Pax2 in the optic primordia, it was overexpressed in the developing CNS. The number of cells containing Pax2 was increased following shh overexpression and embryos developed hypertrophied optic stalk-like structures. Complimentary to the changes in Pax2 distribution, there were fewer Pax6-containing cells and pigment epithelium and neural retina were reduced. Our results suggest that Shh or a closely related signalling molecule emanating from midline tissue in the ventral forebrain either directly or indirectly induces the expression of Pax2 and inhibits the expression of Pax6 and thus may regulate the partitioning of the optic primordia into optic stalks and retinal tissue.

Animals↗
PubMed1995

Expression of truncated Sek-1 receptor tyrosine kinase disrupts the segmental restriction of gene expression in the Xenopus and zebrafish hindbrain.

During development of the vertebrate hindbrain regulatory gene expression is confined to precise segmental domains. Studies of cell lineage and gene expression suggest that establishment of these domains may involve a dynamic regulation of cell identity and restriction of cell movement between segments. We have taken a dominant negative approach to interfere with the function of Sek-1, a member of the Eph-related receptor tyrosine kinase family expressed in rhombomeres r3 and r5. In Xenopus and zebrafish embryos expressing truncated Sek-1, lacking kinase sequences, expression of r3/r5 markers occurs in adjacent even-numbered rhombomeres, in domains contiguous with r3 or r5. This disruption is rescued by full-length Sek-1, indicating a requirement for the kinase domain in the segmental restriction of gene expression. These data suggest that Sek-1, perhaps with other Eph-related receptors, is required for interactions that regulate the segmental identity or movement of cells.

Amino Acid Sequence↗
PubMed1995

Phenopyrrozin, a new radical scavenger produced by Penicillium sp. FO-2047.

A new radical scavenger, named phenopyrrozin, was isolated from the culture broth of Penicillium sp. FO-2047. Phenopyrrozin was purified from whole broth solvent extraction, silica gel chromatography, and HPLC. The structure of phenopyrrozin was elucidated as 5,6,7,7a-tetrahydro-2-hydroxy-1-phenyl-3H-pyrrolizin-3-one. The IC50 of phenopyrrozin against lipid peroxidation induced by Cr2K2O7 was 73 micrograms/ml. Phenopyrrozin also reduced chromosomal aberrations induced by paraquat.

Animals↗
PubMed1995

New glycosidases inhibitors, panosialins D and wD produced by Streptomyces sp. OH-5186.

New panosialin analog, panosialins D and wD have been isolated from the culture broth of Streptomyces sp. OH-5186. Their structures were elucidated as 5-(13-methylpentadecyl)-1,3-benzenediol bis(sodium sulfate) and 5-(13-methylpentadecyl)-1,3-benzenediol 1-(sodium sulfate), respectively. They showed strong inhibitory activity against alpha-mannosidase, alpha-glucosidase, and beta-glucosidase. Panosialins wA-wD mixture also showed weak mitogenic activity but suppressed the mitogen induced activity.

Animals↗
PubMed1995

[Synthesis of S(+)-2-(4-isobutylphenyl) propionic acid by asymmetric hydrolysis of microbial enzyme. II. Reaction conditions and product extraction].

Trichosporon cutaneum 158 exhibited higher sterospecificity to hydrolyze substrate ibuprofen ester. Among the five chosen substrate, asymmetric hydrolysis of methyl ester or isopropyl ester formed S(+)-ibuprofen of 97% ee. While ethyl ester not only gave ee 93% but also showed the highest hydrolytic activity. The optimum pH range for asymmetric hydrolysis was 6.5-7.0. Ability of resolusion was stabler in the range of temperature 28-37 degrees C. This yeast produced intracellular enzyme. Hydrolysis can be carried out by powered cells treated by iced-acetone to improve the specificity of resolution. The product S(+)-ibuprofen can be got with acid-base reaction and organic solvent extraction, unreacted esters can be recovered simultaneously.

Hydrolysis↗