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Biomedical subjects

X Qian

Publications and source records attributed to X Qian.

At least 127 records · Page 7Linked to original sources
PubMed1997

Transforming growth factor-beta, transforming growth factor-beta receptor II, and p27Kip1 expression in nontumorous and neoplastic human pituitaries.

Transforming growth factor (TGF)-beta has been implicated in the regulation of normal and neoplastic anterior pituitary cell function. TGF-beta regulates the expression of various proteins, including p27Kip1 (p27), a cell cycle inhibitory protein. We examined TGF-beta, TGF-beta type II receptor (TGF-beta-RII), and p27 expression in normal pituitaries, pituitary adenomas, and carcinomas to analyze the possible roles of these proteins in pituitary tumorigenesis. Normal pituitary, pituitary adenomas, and pituitary carcinomas all expressed TGF-beta and TGF-beta-RII immunoreactivity. Reverse transcription polymerase chain reaction analysis showed TGF-beta 1, -beta 2, and -beta 3 isoforms and TGF-beta-RII in normal pituitaries and pituitary adenomas. Pituitary adenomas cells cultured for 7 days in defined media showed a biphasic response to TGF-beta with significant inhibition of follicle-stimulating hormone secretion at higher concentrations (10(-9) mol/L) and stimulation of follicle-stimulating hormone secretion at lower concentrations (10(-13) mol/L) of TGF-beta 1 in gonadotroph adenomas. Immunohistochemical analysis for p27 protein expression showed the highest levels in nontumorous pituitaries with decreased immunoreactivity in adenomas and carcinomas. When nontumorous pituitaries and various adenomas were analyzed for p27 and specific hormone production, growth hormone, luteinizing hormone, and thyroid-stimulating hormone cells and tumors had the highest percentages of cells expressing p27, whereas adrenocorticotrophic hormone cells and tumors had the lowest percentages. Immunoblotting analysis showed that adrenocorticotrophic hormone adenomas also had the lowest levels of p27 protein. Semiquantitative reverse transcription polymerase chain reaction and Northern hybridization analysis did not show significant differences in p27 mRNA expression in the various types of adenomas or in nontumorous pituitaries. In situ hybridization for p27 mRNA showed similar distributions of the gene product in nontumorous pituitaries, pituitary adenomas, and carcinomas. These results indicate that TGF-beta and TGF-beta-RII are widely expressed in nontumorous pituitaries and in pituitary neoplasms and that TGF-beta 1 regulates pituitary hormone secretion. The levels of the TGF-beta-regulated protein p27 decreases in the progression of normal to neoplastic pituitaries. In contrast, the mRNA levels of p27 remained relatively constant in nontumorous pituitaries, pituitary adenomas, and carcinomas, indicating that p27 protein levels in adenomas and carcinomas are regulated by translational and post-translational mechanisms.

Adenoma↗
PubMed1997

Endogenous regulation of angiogenesis in the rat aorta model. Role of vascular endothelial growth factor.

The purpose of this study was to investigate the role of vascular endothelial growth factor (VEGF) in the rat aorta model of angiogenesis. Freshly cut aortic rings generated microvascular outgrowths in serum-free collagen gel culture. Angiogenesis was reduced to 10% when the explants were embedded in collagen 10 to 14 days after excision from the animal. Immunochemical studies of conditioned medium demonstrated secretion of VEGF by the aortic cultures. Levels of VEGF decreased during the second week of culture when the explants became quiescent and microvessels stopped growing. Treatment of quiescent aortic rings with exogenous VEGF stimulated angiogenesis and restored microvascular growth to values observed in cultures of freshly cut explants. Reverse transcriptase polymerase chain reaction of vasoformative collagen gel cultures of rat aorta demonstrated the expression of the alternatively spliced isoforms VEGF165, VEGF189, and the high affinity VEGF receptor flk-1. Reverse transcriptase-polymerase chain reaction of rat aorta-derived cell strains confirmed the presence of VEGF165 and VEGF189 in endothelial cells, smooth muscle cells, and fibroblasts. The flk-1 receptor was expressed by endothelial cells but not by fibroblasts or smooth muscle cells, which is consistent with the endothelial target specificity of VEGF. The spontaneous angiogenic response of freshly cut aortic rings was inhibited by 70% with a neutralizing antibody against VEGF, whereas nonimmune IgG had no effect (P < 0.001). These findings provide evidence for a VEGF-mediated autocrine/paracrine regulation of angiogenesis in the rat aorta model.

Animals↗
PubMed1997

Percutaneous transluminal coronary angioplasty for acute myocardial infarction: initial experience in 43 cases.

OBJECTIVE: To evaluate the initial experience with the use of percutaneous transluminal coronary angioplasty (PTCA) in the set of acute myocardial infarction (AMI). METHODS: Between October 1993 and April 1996, PTCA was performed in 43 patients (34 male, 9 female) with initial onset of AMI. These patients ranged in age from 40 to 74 years (mean +/- SD, 60.3 3 +/- 9.2). Primary PTCA was performed in 16, rescue PTCA in 8, and semi-elective PTCA in 19 patients. RESULTS: The initial success was achieved in 95.3% (41/ 43). Failed angioplasty occurred in 2 patients, with acute reocclusion after rescue PTCA (this patient died of cerebral stroke 3 days later) in one patient, and small local intimal dissection during semi-elective PTCA in another patient. CONCLUSION: PTCA was a safe and effective approach in the treatment of AMI in the present study patients, with a high primary success and low acute complication rate.

Adult↗
PubMed1996

Inhibition of p185neu kinase activity and cellular transformation by co-expression of a truncated neu protein.

The rat neu oncogene product encodes a 185 kDa receptor tyrosine kinase which is constitutively activated as a result of a single amino acid substitution (Val664-->Glu) within the transmembrane region. In this study, we show that the transforming activity of oncogenic p185neu (also termed Tneu) can be inhibited by co-expression of a truncated neu protein with a large cytoplasmic deletion (termed T691stop) which includes the tyrosine kinase domain. In cell lines co-expressing full-length and truncated neu proteins, we observed co-dimerization between full-length p185neu and truncated T691 stop, resulting in the formation of a kinase-inactive heteromeric complex. Phenotypic analysis of several different clones showed that the degree of inhibition of transformation in vitro and tumorigenicity in vivo was related to the ratio of full-length and truncated p185 proteins co-expressed in cells. These results provide evidence that expression of kinase-deficient neu proteins leads to co-dimerization that results in suppression of kinase activation and oncogenicity of associated p185neu-activated receptors. The mutant neu protein mediates inhibition in both transfected fibroblasts expressing oncogenic p185neu and mammalian cancer cells derived from a rat primary neuroglioblastoma expressing oncogenic p185neu. This truncated peptide may be important for the design of future therapies directed against erbB family oncoproteins.

Animals↗
PubMed1996

Thrombospondin-1 (TSP-1) promotes the invasive properties of human breast cancer.

TSP-1 is a matrix-bound adhesive glycoprotein, which plays a role in tumor cell proliferation and tumor angiogenesis. The purpose of this study was to investigate the effect of TSP-1 on breast tumor cell invasion. Tumor cell invasion assays were performed using a modified Boyden chamber apparatus with collagen-coated membranes. Four breast cell lines were studied in serum-free media: the malignant MDA-MB-231, SKBR-3, and MCF-7 cell lines, and the benign MCF-10A cell line. Invasion was measured as the summation of the number of cells in five representative high power fields (400x) traversing the collagen barrier after a 3-hr incubation period. The effect of an anti-TSP-1 antibody (100 microgram/ml) was also evaluated in the malignant cell lines. Statistical analysis was performed by ANOVA and Student's unpaired t test. TSP-1 promoted a dose-dependent increase in invasion as compared to buffer controls in all three malignant cell lines. TSP-1 (100 nM) promoted a greater than five-fold increase over controls in tumor cell invasion for MDA-MB-231, SKBR-3, and MCF-7 cell lines (P < 0.005). TSP-1 had no effect on the invasiveness of the benign cell type MCF-10A. Anti-TSP-1 antibody inhibited TSP-1 promoted invasion in the MDA-MB-231, SKBR-3, and MCF-7 cell lines by 45, 48, and 39%, respectively (P = 0.003, 0.044, 0.047). TSP-1 promotes tumor cell invasion of collagen by breast cancer cells. Therapy designed to inhibit TSP-1 may prevent invasion and metastasis in breast cancer.

Analysis of Variance↗
PubMed1996

Vertebrate neural progenitor cells: subtypes and regulation.

Several advances have been made recently in characterizing neural progenitor cells. In vertebrates, multipotential stem cells have been demonstrated in the developing forebrain both in vitro and in vivo, and a class of stem cells has been identified in the adult CNS. Factors that regulate the proliferation and differentiation of subtypes of neural progenitor cells have also been described. In invertebrates, progress has been made in identifying genes involved in neural progenitor cell specification, cell-fate choices and regulation.

Animals↗
PubMed1996

C2-symmetrical tetrahydroxyazepanes as inhibitors of glycosidases and HIV/FIV proteases.

C2-Symmetrical tetrahydroxyazepanes were synthesized as inhibitors for glycosidases. Tetrahydroxyazepane 1 is a non-specific inhibitor of various glycosidases, while compounds 2, 3 and 4 specifically inhibit beta-N-acetylglucosaminidase, beta-glucosidase, and alpha-fucosidase, respectively, with Ki in the micromolar range. Compound 1 is not an inhibitor of HIV/FIV proteases, but its 3,6-difluorobenzyl derivatives are moderate inhibitors of both enzymes.

Aspartic Acid Endopeptidases↗
PubMed1996

Association of signaling proteins with a nonmitogenic heterodimeric complex composed of epidermal growth factor receptor and kinase-inactive p185c-neu.

The functional consequences of heterodimer formation between the epidermal growth factor receptor (EGFr) and the p185c-neu receptor tyrosine kinase include increased mitogenic and transformation potencies. To determine the possible alteration of signal transduction pathways resulting from this heteromeric complex, the capacity of several signaling proteins to associate with the heterodimeric receptors has been assayed. The in vivo interaction with the EGFr/p185c-neu heterodimer of several signal transduction proteins, including phospholipase C-gamma 1 (PLC-gamma 1), the p85 subunit of phosphotidylinositol 3-kinase, the ras GTPase activating protein, SHC, NCK, p72RAF, and the tyrosine phosphatase SHPTP2, was measured by coimmunoprecipitation. The binding of these signaling proteins to a complex composed of EGFr and a kinase-inactive form of p185 (p185K757M) was not impaired, even though the mitogenic and transformation activity of this complex had been abrogated. In addition, the EGF-induced phosphorylation of GAP, p85, and PLC-gamma 1 did not correlate with the dominant-negative action of p185K757M on EGFr function. Thus, substrate association and phosphorylation do not correlate stringently with the mitogenic and transforming activity of this receptor complex, suggesting additional pathways or mechanisms vital to EGFr/p185c-neu heterodimeric signaling.

Animals↗
PubMed1996

Transforming growth factor-beta and p27 expression in pituitary cells.

Transforming growth factor-beta (TGF beta) is a member of a family of growth factors that regulates differentiation and cellular proliferation in a wide variety of tissues, including the anterior pituitary gland. TGF beta regulates the expression of various proteins, including p27Kipl (p27), a cell cycle inhibitory protein. The cell types in normal rat anterior pituitary producing TGF beta1, one of the principal isoforms of TGF beta, and p27 were examined by in situ methods. The regulation of p27 messenger RNA (mRNA) and protein by TGF beta1 was also examined in cultured anterior pituitary cells. In situ hybridization, in situ reverse transcriptase PCR, and immunocytochemical staining for pituitary hormones showed that PRL, TSH, and gonadotroph cells all had a higher percentage of cells expressing TGF beta1 mRNA and p27 protein than did GH and ACTH cells. After treatment with 10(-9) M TGF beta1 in vitro for 3 days, there were significant decreases in p27 mRNA and protein levels (P < 0.05) in normal pituitary cells. The GH3 and GHRH-CL1 cell lines, which secrete PRL and GH, had undetectable p27 protein by immunocytochemical staining and immunoblotting, although the GH3 cell line had p27 mRNA detected by reverse transcriptase PCR. Analysis of [3H]thymidine uptake in cultured dissociated pituitary cells by double staining for hormones showed that only PRL cells had significant proliferative activity during a 3-day cell culture period. There was a biphasic effect of TGF beta1 on PRL cell proliferation, with marked inhibition by 10(-9) M and a slight stimulation by 10(-13) M. These results indicate that there is a differential distribution of both TGF beta1 and p27 in various anterior pituitary cell types and that TGF beta1 directly down-regulates p27 in cultured anterior pituitary cells.

Animals↗
PubMed1996

Expression of thrombospondin-1 in cancer: a role in tumor progression.

Thrombospondin-1 (TSP-1), a trimeric high molecular weight glycoprotein, is one of the major secreted proteins of human platelets and an extracellular matrix component of a variety of cells including vascular endothelial cells and tumor cells. TSP-1 has been shown to be highly expressed in human malignant tissues and present in higher than normal levels in the plasma of cancer patients. TSP-1 has also been shown to promote hematogenous tumor spread, tumor cell adhesion and invasion, and angiogenesis. Overall these studies provide compelling evidence for the conclusion that TSP-1 plays an important role in tumor progression.

Blood Platelets↗
PubMed1996

Detection of PML-RAR alpha in patients with APL during follow-up period.

OBJECTIVE: To evaluate the significance of PML-RAR alpha transcripts in patients with acute promyelocytic leukemia (APL) during remission period and to follow up the patients through monitoring aberrant gene expression. PATIENTS AND METHODS: This study included 17 patients with APL (5 females and 12 males). Another 19 APL patients during relapse served as control. RNA extraction was obtained through the single-step method. By means of reverse transcriptase polymerase chain reaction (PCR), the PML-RAR alpha was detected in the sample mRNA. RESULTS: Nine out of 10 patients with complete remission (CR) duration shorter than 3 years were positive. Four cases became negative and three remained positive among 7 cases in a long remission of over 3 years. The difference of the positive rate of PML-RAR alpha transcripts between the 2 groups was significant (P < 0.05). Four among 12 positive cases relapsed. No evidence of relapse was present in the 5 negative patients after 9.6 +/- 3.9-month follow-up. Further treatment was therefore given to the 4 positive patients whose treatment was already ceased at that time. By this management they were all in CR during the following 10-month observation. CONCLUSIONS: RT-PCR detection for PML-RAR alpha transcripts was useful in monitoring MRD and guiding further treatment to obtain a long remission. Persistently positive transcripts were closely associated with the relapse.

Adolescent↗
PubMed1996

Identification of a transthyretin enhancer site that selectively binds the hepatocyte nuclear factor-3 beta isoform.

The upstream proximal region of the transthyretin (TTR) promoter and a distal enhancer are sufficient to drive liver-specific expression of the TTR gene, as demonstrated by experiments in transgenic mice. Previous analyses have characterized the binding of a number of liver-enriched transcription factors of the TTR promoter including hepatocyte nuclear factors one (HNF-1), HNF-4, and three distinct HNF-3 proteins (alpha, beta, and gamma), which are members of the winged helix (fork head) family. The TTR enhancer was shown to bind members of the CCAAT/enhancer binding protein (C/EBP) family at two distinct sites (TTR-2 and TTR-3), and an oligonucleotide containing the activation protein one (AP-1) binding sequence competed for recognition to a third enhancer site (TTR-1). In this study, we have carried out a detailed analysis of the transcription factors that recognize the TTR enhancer elements (TTR-1, TTR-2, and TTR-3 oligonucleotide sequences). Analysis of the TTR-1 site demonstrates that the putative AP-1 site in the TTR enhancer binds a ubiquitously expressed factor that is distinct from the AP-1 family of proteins. Next we demonstrate, via gel shift analysis, that the TTR-3 site is recognized by the C/EBP family in liver nuclear extracts. We also show that whereas the TTR-2 enhancer site is capable of binding recombinant C/EBP proteins, it does not bind C/EBP proteins from liver nuclear extracts. The TTR-2 site does, however, contain a variant HNF-3 recognition sequence that exclusively binds the HNF-3 beta isoform. Mutation of this HNF-3 beta-specific recognition sequence caused reductions in TTR enhancer activity. We had previously observed a 95% decrease in HNF-3 alpha expression and a 20% reduction in HNF-3 beta expression in acute phase livers, which correlated with a 60% decrease in TTR gene transcription. We propose that the HNF-3 beta-specific binding site in the TTR enhancer may play a role in maintaining TTR gene expression during the acute phase response in spite of the dramatic reduction in HNF-3 alpha protein levels.

Animals↗
PubMed1996

A security mediator for health care information.

The TIHI (Trusted Interoperation of Healthcare Information) project addresses a security issue that arises when some information is being shared among collaborating enterprises, although not all enterprise information is sharable. It assumes that protection exists to prevent intrusion by adversaries through secure transmission and firewalls. The TIHI system design provides a gateway, owned by the enterprise security officer, to mediate queries and responses. The latter are typically transmitted via the Internet. The enterprise policy is determined by rules provided to the mediator. We show examples of typical rules. The problem and our solution, although developed in a healthcare context, is equally valid among collaborating enterprises.

Computer Communication Networks↗
PubMed1996

Long-term oral administration of L-arginine enhances endothelium-dependent vasorelaxation and inhibits neointimal thickening after endothelial denudation in rats.

OBJECTIVE: To further prove the hypothesis that local decrease of nitric oxide (NO) synthesis and/or its activity might be critically important in the disturbance of vascular homeostasis after vascular injuries. METHODS: Intimal thickening model induced by air-drying denudation of rat right common carotid artery was performed to evaluate the effects of long-term oral administration of L-arginine on neointimal thickening and acetylcholine-induced endothelium-dependent vasorelaxation (EDR) by histomorphometric and functional studies. RESULTS: Reductions in EDR function persisted and simultaneously developed prominent neointimal thickening by 14 days after denudation. Long-term oral supplementation of L-arginine (1 g/kg/day) significantly enhanced EDR from 43.5% +/- 12.35% to 68.8% +/- 9.0% (n = 10, P < 0.001) and reduced neointimal thickening from 62.45 microns +/- 11.26 microns to 21.45 microns +/- 6.34 microns (n = 10, P < 0.001) as compared with each control animals. CONCLUSIONS: This study shows that oral administration of L-arginine significantly inhibits neointimal thickening and preserves NO-mediated EDR in experimental endothelial denudation, suggesting an important role for L-arginine, NO pathway in the regulation of vascular homeostasis after endothelial injury which might be salutary in prevention restenosis after coronary angioplasty.

Administration, Oral↗