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Y X Qian

Publications and source records attributed to Y X Qian.

12 recordsLinked to original sources
PubMed1998

Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.

The ligand for osteoprotegerin has been identified, and it is a TNF-related cytokine that replaces the requirement for stromal cells, vitamin D3, and glucocorticoids in the coculture model of in vitro osteoclastogenesis. OPG ligand (OPGL) binds to a unique hematopoeitic progenitor cell that is committed to the osteoclast lineage and stimulates the rapid induction of genes that typify osteoclast development. OPGL directly activates isolated mature osteoclasts in vitro, and short-term administration into normal adult mice results in osteoclast activation associated with systemic hypercalcemia. These data suggest that OPGL is an osteoclast differentiation and activation factor. The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key extracellular regulators of osteoclast development.

Amino Acid Sequence↗
PubMed1995

Biosynthetic processing of neu differentiation factor. Glycosylation trafficking, and regulated cleavage from the cell surface.

new differentiation factor (NDF), also known as heregulin, is structurally related to the epidermal growth factor family of growth factors; it stimulates tyrosine phosphorylation of the neu/HER-2 oncogene and causes differentiation of certain human breast cancer cell lines. Alternative splicing of a single gene gives rise to multiple isoforms of NDF/heregulin, as well as the neuronal homologues, designated ARIA (acetylcholine receptor inducing activity) and GGF (glial growth factor); at least 15 structural variants are known. All but two of the NDF/heregulin cDNAs are predicted to encode transmembrane, glycosylated precursors of soluble NDF. In this report we characterized the biosynthetic processing of different NDF isoforms in stably transfected Chinese hamster ovary cells expressing individual NDF isoforms, and in the native cell line Rat 1-EJ, which expresses at least six different NDF isoforms. We found that the precursors for NDF undergo typical glycosylation and trafficking. A portion of the molecules are proteolytically cleaved intracellularly leading to the constitutive secretion of soluble, mature NDF into the culture media. However, a significant portion of the newly synthesized NDF precursor molecules escape intracellular cleavage and are transported to the cell surface of both transfected and native cells, where they reside as full-length, transmembrane proteins. Finally we show that these full-length, transmembrane NDF molecules can undergo phorbol ester regulated cleavage from the membrane, releasing the soluble growth factor into the medium.

Amino Acid Sequence↗
PubMed1995

The antiproliferative activity of c-myb and c-myc antisense oligonucleotides in smooth muscle cells is caused by a nonantisense mechanism.

Smooth muscle cell (SMC) proliferation is thought to play a major role in vascular restenosis after angioplasty and is a serious complication of the procedure. Developing antisense (AS) oligonucleotides as therapeutics is attractive because of the potentially high specificity of binding to their targets, and several investigators have reported inhibition of SMC proliferation in vitro and in vivo by using AS strategies. We report here the results of our experiments on vascular SMCs using AS oligonucleotides directed toward c-myb and c-myc. We found that significant inhibition of SMC proliferation occurred with these specific AS sequences but that this inhibition was clearly not via a hybridization-dependent AS mechanism. Rather, inhibition was due to the presence of four contiguous guanosine residues in the oligonucleotide sequence. This was demonstrated in vitro in primary cultures of SMCs and in arteries ex vivo. The ex vivo model developed here provides a rapid and effective system in which to screen potential oligonucleotide drugs for restenosis. We have further explored the sequence requirements of this non-AS effect and determined that phosphorothioate oligonucleotides containing at least two sets of three or four consecutive guanosine residues inhibit SMC proliferation in vitro and ex vivo. These results suggest that previous AS data obtained using these and similar, contiguous guanosine-containing AS sequences be reevaluated and that there may be an additional class of nucleic acid compounds that have potential as antirestenosis therapeutics.

Animals↗
PubMed1995

The uptake and distribution of phosphorothioate oligonucleotides into vascular smooth muscle cells in vitro and in rabbit arteries.

Oligonucleotides are a class of compounds with potential as therapeutics for a variety of clinical applications. Local delivery of oligonucleotides to the arterial wall is a challenging aspect of the development of these therapeutics for restenosis, and herein we report experiments characterizing the uptake and distribution of phosphorothiate oligonucleotides into vascular smooth muscle cells in primary cultures and in rabbit arteries. Primary cultures of smooth muscle cells incubated with rhodamine-oligonucleotides showed uptake only into cytoplasmic vesicles. No nuclear or cytosolic localization was detected. In normal arteries there was no visible tissue or cellular uptake of oligonucleotides after intralumenal administration. However, in balloon-injured arteries there was significant oligonucleotide uptake into the tissue with apparent cytoplasmic delivery to the medial smooth muscle cells, as evinced by intense staining of their nuclei with labeled oligonucleotides. Measurement of FITC-oligonucleotide in artery extracts showed significantly greater uptake in injured, compared with normal arteries. Light and electron microscopic studies demonstrated a correlation between the degree of damage and the amount of uptake. These results demonstrate that oligonucleotides penetrate easily into the arterial wall of balloon-injured arteries and accumulate in the medial smooth muscle cells-the target cells for antirestenosis therapeutics following balloon angioplasty.

Animals↗
PubMed1994

Selective expression of potassium channels during mast cell differentiation.

In rodents, mast cell progenitors differentiate into distinct mucosal and serosal phenotypes which differ markedly in their functional responses to antigenic and peptidergic stimulation. Although the molecular basis of mast cell differentiation or functional specialization is unknown, it is possible that regulation of calcium entry contributes to one or both processes. The prolonged secretory response of mucosal mast cells (MMC) and the antigen-elicited synthesis of interleukin-3 by immature MMC both require a rise of cytoplasmic calcium sustained by Ca2+ influx across the plasma membrane. This Ca2+ entry is highly sensitive to membrane potential, affording a possible site for regulation of mast cell function by receptor-linked ion channels. We found that rat interleukin-3-dependent bone marrow-derived mast cells of the mucosal phenotype expressed two K+ conductances, neither of which is present in the prototype serosal mast cell from rat peritoneum. An inwardly rectifying K+ conductance was constitutively active and a latent outwardly rectifying K+ conductance was elicited rapidly upon ligation of cell surface adenosine or P2 purinergic receptors linked to G proteins of the Gi family. Stimulation of P2 receptors dramatically potentiated antigen-triggered secretion in a pertussis toxin-sensitive manner, suggesting that activation of the outwardly rectifying K+ channel may regulate antigen-dependent functions of MMC.

Adenosine Diphosphate↗
PubMed1993

Activation of mast cell K+ channels through multiple G protein-linked receptors.

The rat basophilic leukemia (RBL) mast cell line possesses cell surface receptors for adenosine whose ligation markedly potentiates antigen-driven Ca2+ influx and secretion. Here we show that engagement of these receptors and of separate P2 purinergic receptors rapidly activates an outwardly rectifying K+ conductance [GK(OR)] in RBL cells. Activation of GK(OR) by the ligands 5'-(N-ethylcarboxamido)adenosine (NECA), ADP, and ATP was prevented by cytoplasmic guanosine 5'-[beta-thio]diphosphate as well as by pretreatment of the cells with pertussis toxin, implicating mediation by a G protein. Multiple cycles of induction and decay of GK(OR) were produced upon application and removal of ligand. Induction of GK(OR) by either ligand was much faster than the induction caused by guanosine 5'-[gamma-thio]triphosphate (t1/2 < 10 sec vs. 210 sec.). In control cells the maximal whole-cell conductance elicited by ADP (2.25 +/- 0.30 nS) or ATP (2.50 +/- 0.33 nS) was about twice as large as that induced by NECA (1.03 +/- 0.11 nS), and similar to that previously reported for the guanosine 5'-[gamma-thio]triphosphate-elicited GK(OR) in RBL cells (2.58 +/- 1.59 nS). Treatment of RBL cells with dexamethasone upregulated Ca2+ responses to NECA, and it also nearly doubled the maximal conductance elicited by NECA without appreciable effect on responses to ADP or ATP. The failure of water-soluble second messengers to activate GK(OR) and the inability of 11 mM EGTA (< 10 nM Ca2+) to prevent activation by ADP suggest that the relevant pathway is membrane-delimited. Two ion-channel blockers inhibited antigen-stimulated secretion with IC50 values similar to those at which they blocked GK(OR), suggesting that activity of the outwardly rectifying K+ channel may be important for stimulus-response coupling in these cells. Potentiation of the secretory response by NECA may reflect, in part, the activation of GK(OR), which serves to repolarize the membrane more effectively than does the constitutive mechanism, thereby enhancing antigen-driven Ca2+ influx. This channel and its functionally associated receptors may allow neighboring cells of the host to modulate the response of mast cells to exogenous antigen.

Adenine Nucleotides↗
PubMed1989

[Antifertility effects of RU-486 in combination with anordrin in rats].

RU-486 and anordrin suspended or dissolved in tea seed oil, alone or in combination, were given orally to rats on d 6-8 or d 11-13 of pregnancy, respectively. Complete interruption of early pregnancy was obtained after RU-486 at 8 mg/kg alone or 2.5 mg/kg combined with anordrin 2 mg/kg when given on d 6-8 of pregnancy. A complete mid-trimester abortion was obtained after RU-486 10 mg/kg alone or 4 mg/kg combined with anordrin 3 mg/kg when given on d 11-13 of pregnancy. Results obtained from the endometrial transformation test, the uteri cytoplasmic progesterone receptor estimation in immature rabbits, the deciduoma-inhibited test in pseudopregnant rats and the serum progesterone level in pregnant rats showed that RU-486 in combination with anordrin did not possess progestational, but rather marked antiprogestational activities. Since anordrin is relatively easy to obtain in China, RU-486 combined with anordrin may be ready to be used clinically as an effective oral antifertility agent.

Abortifacient Agents, Steroidal↗
PubMed1986

Spermicidal effect in vitro by the active principle of garlic.

The in vitro spermicidal effect of Allitridum, an active principle of garlic, was investigated. The data showed that sperm motility was inhibited with various concentrations of Allitridum at different intervals ranging from 20 seconds-200 minutes as compared to control. An obvious immobilization of spermatozoa occurred at 7.5 mg/ml of Allitridum. The effects on sperm motility appeared to be dose-dependent.

Allyl Compounds↗