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Y Qiu

Publications and source records attributed to Y Qiu.

At least 109 records · Page 6Linked to original sources
PubMed1999

Intragraft CD45 RO gene expression is an early marker to detect small bowel allograft rejection in rats.

Wistar Furth (WF) intestinal allografts were transplanted into Sprague-Dawley (SD) rats. Recipients were randomly allocated into the following groups: (1) no treatment; (2) cyclosporine (CsA) 6 mg/kg/day, daily, subcutaneously (s.c.; full-dose therapy); (3) CsA 3 mg/kg/day, daily, s.c. (half-dose therapy); and (4) CsA 3 mg/kg/day, daily, s.c. + Tripterygium Wilfordii Hook. WF (TW) 3 mg/kg/day, daily, s.c. WF rats with intestinal autografts were used as controls. CD45RO intragraft expression and its index (CD45RO/CD45), measured by reverse transcription polymerase chain reaction (RT-PCR), were significantly elevated in untreated and half-dose CsA-treated allografts as early as postoperative day (POD) 4, when rejection of intestinal allografts was not detected by routine pathology. Intestinal permeability measured by Tc-DTPA radioassay was significantly elevated in untreated allografts on POD 6. Histology showed that there was severe rejection in untreated intestinal allografts and mild rejection in allografts treated with a half dose of CsA on POD 6. There was a normal CD45RO expression, permeability, and histology in intestinal allografts treated with either a full dose of CsA or a half dose of CsA + TW. These data indicate that CD45RO intragraft gene expression is an early marker to detect intestinal allograft rejection in rats.

Animals↗
PubMed1999

Ischemic preconditioning increases iNOS transcript levels in conscious rabbits via a nitric oxide-dependent mechanism.

Recent studies implicate iNOS as the mediator of the late phase of ischemic preconditioning (PC). However, it is unknown whether induction of iNOS activity is mediated by transcriptional, post-transcriptional, translational, or post-translational mechanisms. To address this issue, we isolated and sequenced a partial iNOS cDNA expressed in preconditioned rabbit myocardium. Using a rabbit-specific probe generated from this sequence, we measured the steady state levels of the iNOS transcript after ischemic PC [six cycles of 4-min occlusion/4-min reperfusion (O/R)]. Three hours after ischemic PC, the iNOS mRNA levels in the ischemic/reperfused region were increased approximately three-fold relative to samples from the non-ischemic region and from control rabbits. This increase in mRNA levels was completely abolished by pretreatment with the NOS inhibitor Nomega -nitro- L-arginine. Conversely, administration of the NO donor nitroglycerin induced an increase in iNOS mRNA levels similar to that induced by ischemic PC. We conclude that in the conscious rabbit, ischemic PC induces an increase in iNOS mRNA levels, and that this induction is triggered by increased generation of NO during the PC stimulus. These results provide direct evidence that upregulation of iNOS is a natural response of the heart to a brief ischemic stress and that NO itself, in the absence of ischemia, upregulates myocardial iNOS transcript levels, a finding that may have implications for nitrate therapy. This previously unrecognized NO-dependent upregulation of iNOS mRNA is likely to play an important role in the development of late PC as well as in many other pathophysiological conditions in which NO is implicated.

Amino Acid Sequence↗
PubMed1999

The nuclear orphan receptor COUP-TFI is required for differentiation of subplate neurons and guidance of thalamocortical axons.

Chicken ovalbumin upstream promotor-transcription factor I (COUP-TFI), an orphan member of the nuclear receptor superfamily, is highly expressed in the developing nervous systems. In the cerebral cortex of Coup-tfl mutants, cortical layer IV was absent due to excessive cell death, a consequence of the failure of thalamocortical projections. Moreover, subplate neurons underwent improper differentiation and premature cell death during corticogenesis. Our results indicate that the subplate neuron defects lead to the failure of guidance and innervation of thalamocortical projections. Thus, our findings demonstrate a critical role of the subplate in early corticothalamic connectivity and confirm the importance of afferent innervation for the survival of layer IV neurons. These results also substantiate COUP-TFI as an important regulator of neuronal development and differentiation.

Animals↗
PubMed1999

Enzymatic degradation of leuprolide in rat intestinal mucosal homogenates.

The purpose of this study was to evaluate in vitro enzymatic degradation and protection of leuprolide acetate in the mucosal homogenates of rat small intestine. When leuprolide was incubated at 37 degrees C with the homogenates, it was degraded quickly. The apparent Michaelis-Menten constant, K(m), and the maximal reaction velocity, Vmax, for leuprolide were 898 mM and 3.4 nmol/min/mg protein, respectively. At least four metabolites of leuprolide were observed in HPLC chromatograms, which were related to cleavages by some serine proteases. In the presence of protease inhibitors in the incubation medium, degradation of leuprolide was significantly suppressed by antipain and 3,4-dichloroisocoumarin (DCI), whereas bestatin and p-hydroxymercuribenzoic acid (PCMB) showed weaker protection than antipain and DCI, and alpha 2-macroglobulin (MG) exhibited no protection. When a w/o/w emulsion formulation was used, rapid degradation of the drug in intestinal homogenates was also inhibited. Therefore, the present study with representative protease inhibitors and a w/o/w formulation revealed that the enzymatic degradation of leuprolide is preventable in the rat intestinal mucosal homogenates.

Animals↗
PubMed1999

PrPc glycoform heterogeneity as a function of brain region: implications for selective targeting of neurons by prion strains.

We recently found that deletion of the Asn-linked carbohydrate (CHO) at residue 197 of Syrian hamster (SHa) PrP(C) while retaining the CHO at Asn 181 has a profound effect on which population of neurons are targeted for conversion of SHaPrP(C) to SHaPrP(Sc) in transgenic (Tg) mice inoculated with scrapie prions. We hypothesized that selective targeting of neuronal populations is determined by cell-specific differences in the affinity of an infecting PrP(Sc) (prion) for PrP(C) and that the affinity might be modulated by nerve cell-specific differences in PrP(C) glycosylation. Here we tested this hypothesis by assessing whether or not each brain region in Syrian hamsters synthesizes different PrP(C) glycoforms, as inferred from 2D-gel electrophoresis. Reproducible differences in the number and isoelectric point of PrP(C) charge isomers were found as a function of brain region. The results of this study support the hypothesis that the PrP(Sc) accumulation and the vacuolation pattern phenotypes in the brain are governed by neuron-specific differences in PrP(C) glycoforms.

Animals↗
PubMed1999

The NeuroD1/BETA2 sequences essential for insulin gene transcription colocalize with those necessary for neurogenesis and p300/CREB binding protein binding.

NeuroD1/BETA2 is a key regulator of pancreatic islet morphogenesis and insulin hormone gene transcription in islet beta cells. This factor also appears to be involved in neurogenic differentiation, because NeuroD1/BETA2 is able to induce premature differentiation of neuronal precursors and convert ectoderm into fully differentiated neurons upon ectopic expression in Xenopus embryos. We have identified amino acid sequences in mammalian and Xenopus NeuroD1/BETA2 that are necessary for insulin gene expression and ectopic neurogenesis. Our results indicate that evolutionarily conserved sequences spanning the basic helix-loop-helix (amino acids [aa] 100 to 155) and C-terminal (aa 156 to 355) regions are important for both of these processes. The transactivation domains (AD1, aa 189 to 299; AD2, aa 300 to 355) were within the carboxy-terminal region, as analyzed by using GAL4:NeuroD1/BETA2 chimeras. Selective activation of mammalian insulin gene enhancer-driven expression and ectopic neurogenesis in Xenopus embryos was regulated by two independent and separable domains of NeuroD1/BETA2, located between aa 156 to 251 and aa 252 to 355. GAL4:NeuroD1/BETA2 constructs spanning these sequences demonstrated that only aa 252 to 355 contained activation domain function, although both aa 156 to 251 and 300 to 355 were found to interact with the p300/CREB binding protein (CBP) coactivator. These results implicate p300/CBP in NeuroD1/BETA2 function and further suggest that comparable mechanisms are utilized to direct target gene transcription during differentiation and in adult islet beta cells.

Animals↗
PubMed1999

PKC-dependent activation of p44/p42 MAPKs during myocardial ischemia-reperfusion in conscious rabbits.

Using conscious rabbits, we examined the effect of ischemic preconditioning (PC) on p44 and p42 mitogen-activated protein kinases (MAPKs). We found that both isoforms contribute significantly to total MAPK activity in the heart (in-gel kinase assay: p44, 59 +/- 1%; p42, 41 +/- 1%). Ischemic PC (6 cycles of 4-min occlusion/4-min reperfusion) elicited a pronounced increase in total cellular MAPK activity (+89%). This increase, which occurred exclusively in the nuclear fraction, was contributed by both isoforms (in-gel kinase assay: p44, +97%; p42, +210%) and was accompanied by migration of the two proteins from the cytosolic to the nuclear compartment. In control rabbits, MAPK kinase (MEK)1 and MEK2, direct activators of p44 and p42 MAPKs, were located almost exclusively in the cytosolic fraction. Ischemic PC induced a marked increase in cytosolic MEK activity (+164%), whereas nuclear MEK activity did not change, indicating that MEK-induced activation of MAPKs occurred in the cytosolic compartment. Activation of MAPKs after ischemic PC was completely blocked by the protein kinase C (PKC) inhibitor chelerythrine. Selective overexpression of PKC-epsilon in adult rabbit cardiomyocytes induced activation of both p44 and p42 MAPKs and reduced lactate dehydrogenase release during simulated ischemia-reperfusion, which was abolished by the MEK inhibitor PD-98059. The results demonstrate that 1) ischemic PC induces a rapid activation of p44 and p42 MAPKs in hearts of conscious rabbits; 2) the mechanism of this phenomenon involves activation of p44 and p42 MAPKs in the cytosol and their subsequent translocation to the nucleus; and 3) it occurs via a PKC-mediated signaling pathway. The in vitro data implicate PKC-epsilon as the specific isoform responsible for PKC-induced MAPK activation and suggest that p44/p42 MAPKs contribute to PKC-epsilon-mediated protection against simulated ischemia. The results are compatible with the hypothesis that p44 and p42 MAPKs may play a role in myocardial adaptations to ischemic stress.

Alkaloids↗
PubMed1999

Increased protein synthesis is necessary for the development of late preconditioning against myocardial stunning.

In phase I of this study, the rate of protein synthesis was measured by the incorporation of [(3)H]leucine into the protein pool in the heart of conscious rabbits. At 2 h after ischemic preconditioning (PC) with six 4-min occlusion/4-min reperfusion (O/R) cycles (group II), the [3H]leucine content in the ischemic-reperfused region was increased by 82% compared with that in controls (group I), indicating increased protein synthesis. This increase was completely abrogated by pretreatment with cycloheximide (CH; group III). In phase II, rabbits underwent six O/R cycles for three consecutive days (days 1-3). Controls (group IV) exhibited late PC against myocardial stunning on days 2 and 3. In group V, which received CH 30 min before the 1st O/R cycle on day 1 (same dose as group III), late PC against stunning on day 2 was completely abrogated. In group VI, pretreatment with CH 24 h before the 1st sequence of O/R cycles had no effect on myocardial stunning on day 1, indicating that the absence of late PC on day 2 in group V cannot be ascribed to delayed toxicity of CH. Taken together, these results demonstrate that, in the conscious rabbit, ischemic PC causes a rapid increase in myocardial protein synthesis and that this increased protein synthesis (or at least a fraction of it) is necessary for the development of the protection against myocardial stunning 24 h later. The late phase of ischemic PC is therefore dependent on the formation of new proteins in intact animals.

Animals↗
PubMed1999

PKC-dependent activation of p46/p54 JNKs during ischemic preconditioning in conscious rabbits.

A conscious rabbit model was used to study the effect of ischemic preconditioning (PC) on stress-activated kinases [c-Jun NH(2)-terminal kinases (JNKs) and p38 mitogen-activated protein kinase (MAPK)] in an environment free of surgical trauma and attending external stress. Ischemic PC (6 cycles of 4-min ischemia/4-min reperfusion) induced significant activation of protein kinase C (PKC)-epsilon in the particulate fraction, which was associated with activation of p46 JNK in the nuclear fraction and p54 JNK in the cytosolic fraction; all of these changes were completely abolised by the PKC inhibitor chelerythrine. Selective enhancement of PKC-epsilon activity in adult rabbit cardiac myocytes resulted in enhanced activity of p46/p54 JNKs, providing direct in vitro evidence that PKC-epsilon is coupled to both kinases. Studies in rabbits showed that the activation of p46 JNK occurred during ischemia, whereas that of p54 JNK occurred after reperfusion. A single 4-min period of ischemia induced a robust activation of the p38 MAPK cascade, which, however, was attenuated after 5 min of reperfusion and disappeared after six cycles of 4-min ischemia/reperfusion. Overexpression of PKC-epsilon in cardiac myocytes failed to increase the p38 MAPK activity. These results demonstrate that ischemic PC activates p46 and p54 JNKs via a PKC-epsilon-dependent signaling pathway and that there are important differences between p46 and p54 JNKs with respect to the subcellular compartment (cytosolic vs. nuclear) and the mechanism (ischemia vs. reperfusion) of their activation after ischemic PC.

Alkaloids↗
PubMed1999

Nitroglycerin induces late preconditioning against myocardial stunning via a PKC-dependent pathway.

Previous studies have shown that administration of nitric oxide (NO) donors induces a delayed cardioprotective effect indistinguishable from the late phase of ischemic preconditioning (PC). However, the ability of clinically relevant NO donors to elicit this phenomenon has not been evaluated. In this study we tested whether an NO-releasing agent that is nitroglycerin (NTG), which is widely used clinically, can mimic the late phase of ischemic PC. Four groups of conscious rabbits underwent six cycles of 4-min occlusion (O)/4-min reperfusion (R) for 3 consecutive days (days 1, 2, and 3). The severity of myocardial stunning was assessed as the total deficit of systolic wall thickening (WTh) after the last O/R cycle. In the control group (group I, n = 6), the total deficit of WTh was reduced by 50% and 51% on days 2 and 3 vs. day 1, respectively, indicating late PC against stunning. Pretreatment with NTG (2 microg. kg(-1). min(-1) iv over 1 h) on day 0 (group II, n = 6) was as effective as ischemic PC in mitigating myocardial stunning 24 h later (day 1); on days 2 and 3, no further reduction of stunning was seen. Coadministration of the PKC inhibitor chelerythrine (5 mg/kg) with NTG (group III, n = 6) completely abrogated the NTG-induced protection. Pretreatment with chelerythrine alone (group IV, n = 5) did not alter stunning. These results demonstrate that a relatively brief infusion of NTG induces a robust protective effect against stunning 24 h later via a protein kinase C (PKC)-dependent signaling mechanism. The magnitude of NTG-induced protection is equivalent to that observed during the late phase of ischemic PC. Late PC induced by brief treatment with NTG could be a useful therapeutic strategy for myocardial protection in patients with ischemic heart disease.

Alkaloids↗
PubMed1999

Application of an in situ PCR hybridization method to detection of human T-lymphotropic virus type I-infected cells in the lung.

We applied an in situ polymerase chain reaction (PCR) hybridization method in order to detect human T-lymphotropic virus type I-infected cells in routinely-processed paraffin sections of the lung from 13 autopsied patients with adult T-cell leukemia (ATL). Previously reported protocol resulted in somewhat non-specific staining in our sections. Therefore, we used a hot start PCR method using specialized commercially-available polymerase in order to increase the specificity. Of 6 patients with ATL cell invasion into the lungs, 4 exhibited strong positive staining of almost all invading ATL cells. In contrast, 7 patients without ATL cell invasion into the lungs did not demonstrate any significant reactivity. Since the method described here is a relatively simple hot start method and does not yield false-positives, it may allow us to determine whether human T-lymphotropic virus type I (HTLV-I) associated disorders are related to lymphocytes integrating the HTLV-I genome.

Adult↗
PubMed1999

Inducible nitric oxide synthase (iNOS) gene deficiency increases the mortality of sepsis in mice.

BACKGROUND: Nitric oxide (NO) produced by the inducible isoform of NO synthase (iNOS or NOS2) has been implicated in the hypotension, organ failure, and death that complicate sepsis. To avoid the confounding effects and limitations of iNOS inhibitors, we used iNOS gene "knockout" mice to examine the effect of inducible NO production in a model of polymicrobial abdominal sepsis treated with antibiotics. We hypothesized that iNOS gene deficiency would significantly alter outcome. METHODS: C57BL6 wild-type (control) and congenic iNOS knockout mice were studied concurrently. Under halothane anesthesia, the ceca were ligated with 4-0 silk suture and punctured twice with a 26-gauge needle (cecal ligation and puncture, CLP). Survival was followed for 7 days, after which necropsies were performed in surviving animals. In an accompanying study examining the acute effects of sepsis, organ injury at 18 hours after CLP as determined by histology and the degree of cell death by apoptosis were examined with the use of hematoxylin and eosin (H&E) and TUNEL staining and two-channel fluorescence-activated cell sorter (FACS) analysis. RESULTS: Sham laparotomy produced no lethality in either knockout (n = 3) or wild-type (n = 3) animals. Compared with survival in controls (n = 20), survival after CLP in iNOS knockout mice (n = 21) was significantly decreased (P < .01 at 2 days, P = .080 at 7 days, Mantel-Haenszel log-rank test). CLP-induced apoptotic cell death was significantly less in the thymus of iNOS knockout mice compared with wild-type mice. CONCLUSIONS: We conclude that iNOS gene function provides a survival benefit in septic mice and is associated with increased sepsis-induced thymocyte apoptosis. To our knowledge, this is the first survival study examining the effect of iNOS gene deficiency in a clinically relevant model of sepsis.

Animals↗
PubMed1999

Vascular effects of arachidonic acid in the rat perfused heart. Role of the endothelium, cyclooxygenase, cytochrome P450, and K(+) channels.

The vascular effects of arachidonic acid (AA) were addressed in the rat perfused heart in terms of metabolic pathways and effector mechanisms. Under basal perfusion pressure, AA elicited dilator responses. However, in hearts treated with nitroarginine to eliminate nitric oxide and to elevate perfusion pressure, the predominant effect of AA was vasoconstriction which was converted to a vasodilator effect by inhibition of cyclooxygenase or antagonism of TP receptors. The vasodilator effect of AA in nitroarginine- and indomethacin-treated hearts was greatly attenuated by clotrimazole, an inhibitor of cytochrome P450, and by inhibition of K(+) channels with tetraethylammonium; in the absence of indomethacin, clotrimazole enhanced the vasoconstrictor effect of AA. When endothelin was used to constrict the coronary vasculature, AA also produced cyclooxygenase-dependent vasoconstriction. In hearts constricted with the endoperoxide analogue, U46619, only endothelium-dependent vasodilator effects of AA were observed that were reduced by indomethacin or clotrimazole. These results indicate that the coronary vasoconstrictor effect of AA which is expressed with elevated tone, results from its conversion by cyclooxygenase to a product(s) that activates TP receptors. The vasodilator effect exhibits two endothelium-dependent components, one mediated by cyclooxygenase products and the other by a cytochrome P450-derived product that activates K(+) channels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

[Study on the relationship between first ovulation and infant feeding in lactating postpartum women].

OBJECTIVE: To determine the first ovulation after delivery and to provide scientific data for contraception in lactating postpartum women. METHODS: From January 1996 to December 1998, 101 lactating women were continuously monitored of their ovulation by ultrasound, basal body temperature (BBT) measurement and cervical mucus examination. RESULTS: The evidences of first ovulation (follicle > 1.8 cm in diameter) were found by ultrasound in 53 (52.5%) women during 154 days after delivery on the average and there were 11 (10.9%, 11/101) subjects who had first ovulation during 4 months after delivery and 42 (41.6%, 42/101) subjects had, after 4 months. Significant positive correlation was found between the time of supplementary feeding and the time of the first menses (n = 100, r = 0.4764, P < 0.01) and first ovulation (n = 53, r = 0.5554, P < 0.01). CONCLUSION: For postpartum mother it is suitable to begin with birth control method at the 4th month after delivery and to prolong the breast feeding is also a good method for birth control.

Adult↗
PubMed1999

[Function of B7/CD28 in anti-myeloma immunoreaction through activating T cells].

OBJECTIVE: To explore the role of B7/CD28 molecule in priming the anti-myeloma effect of T lymphocyte and the mechanism by which CD28 promoted the immunogenicity of myeloma cells. METHODS: Human B7-1 gene was transducted into XG-s cells. CD28 agonist monoclonal antibody was primed. Primary allogeneic MLR, immunophenotypic analysis and quantitative measurement of IL-2 were performed. RESULTS: XG cells were successfully transfected with B7-1 cDNA. The expressions of CD54, CD58, CD11a/CD18, CD40, CD40L, CD56, B7-2(CD86), HLA-I and HLA-II molecules were not affected by the transfection. The transduction of B7 gene dramatically increased the immunogenicity of tumor cells. In allo-MLR, the B7-1 expressing XG cell could more effectively mediate the activation, proliferation and IL-2 secretion of alloantigenic CD8+ T cells than XG cells did. Like B7-1 molecules, anti-CD28 agonistic McAb could induce the MLR of allo-T cell. CONCLUSION: Human multiple myeloma cells failed to induce antitumor immunoreaction because of the weak expression of B7 molecules. The transfection of B7-1 or CD28 agonist antibody could stimulate and proliferate T lymphocytes and increase the immunogenicity of myeloma cells. CD28 agonist antibody might be promising for clinical application.

Antibodies, Monoclonal↗
PubMed1999

[The role of cytokeratin 13 gene in human nasopharyngeal carcinoma].

OBJECTIVE: To study the significance of cytokeratin 13 (CK13) gene expression and its methylation in human nasopharyngeal carcinoma (NPC). METHODS: The expression of CK13 in 32 cases of NPC and 8 cases of chronic inflammatory diseases of nasopharyngeal epithelia (CIDNE) was studied using Northern blot hybridization. The methylation pattern of CK13 gene was analyzed by Southern blot hybridization using methylation sensitive restriction endonuclease Hpa II and Msp I in NPC cell lines HNE1 and normal human primary cultures of nasopharyngeal epithelial cells. RESULTS: High expression of CK13 gene was found in 8(100%) CIDNE, low-expression of the gene in 12(37.5%) NPC, negative expression in 9(28.1%) and high expression in 11(34.4%). The degree of methylation was increased in NPC cell lines HNE1, compared to that of normal human primary cultures of nasopharyngeal epithelial cells. CONCLUSION: The expression of the CK13 gene in NPC is partly or completely down regulated. It is possibly related to hyper-methylation of CK13 gene.

Gene Expression Regulation, Neoplastic↗
PubMed1998

Gene therapy with extracellular superoxide dismutase attenuates myocardial stunning in conscious rabbits.

BACKGROUND: Administration of Cu/Zn superoxide dismutase (SOD) without catalase fails to alleviate myocardial stunning, but extracellular SOD (Ec-SOD) may be more effective because it binds to heparan sulfate proteoglycans on the cellular glycocalyx. We therefore used in vivo gene transfer to increase systemic levels of Ec-SOD and determined whether this gene therapy protects against myocardial stunning. METHODS AND RESULTS: The cDNA for human Ec-SOD was cloned behind the cytomegalovirus (CMV) promoter and incorporated into a replication-deficient adenovirus (Ad5/CMV/Ec-SOD). Injection of this virus (2x10(8) pfu/kg IV) produced high levels of Ec-SOD in the liver, which could be redistributed to the heart and other organs by injection of heparin. Conscious rabbits underwent a sequence of six 4-minute coronary occlusion/4-minute reperfusion cycles for 3 consecutive days starting 3 days after intravenous injection of Ad5/CMV/Ec-SOD or Ad5/CMV/nls/LacZ (negative control). Both groups were given heparin (2000 U/kg IV) 2 hours before the first sequence of occlusions. The severity of myocardial stunning was measured as the total deficit of LV wall thickening after the last reperfusion. On day 1, the total deficit of wall thickening was markedly decreased in Ad5/CMV/Ec-SOD rabbits versus controls and similar to that seen on days 2 and 3 in controls. CONCLUSIONS: The results demonstrate that in vivo gene transfer of the cDNA encoding Ec-SOD provides the heart with substantial protection against myocardial stunning without the need for concomitant administration of catalase. The present observations provide the basis for controlling gene therapy at the posttranslational level and for simultaneously protecting multiple organs from oxidant stress.

Adenoviruses, Human↗