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Biomedical subjects

N Xu

Publications and source records attributed to N Xu.

At least 109 records · Page 6Linked to original sources
PubMed1995

The small GTP-binding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway.

c-Jun amino-terminal kinases (JNKs) and mitogen-activated protein kinases (MAPKs) are closely related; however, they are independently regulated by a variety of environmental stimuli. Although molecules linking growth factor receptors to MAPKs have been recently identified, little is known about pathways controlling JNK activation. Here, we show that in COS-7 cells, activated Ras effectively stimulates MAPK but poorly induces JNK activity. In contrast, mutationally activated Rac1 and Cdc42 GTPases potently activate JNK without affecting MAPK, and oncogenic guanine nucleotide exchange factors for these Rho-like proteins selectively stimulate JNK activity. Furthermore, expression of inhibitory molecules for Rho-related GTPases and dominant negative mutants of Rac1 and Cdc42 block JNK activation by oncogenic exchange factors or after induction by inflammatory cytokines and growth factors. Taken together, these findings strongly support a critical role for Rac1 and Cdc42 in controlling the JNK signaling pathway.

Animals↗
PubMed1995

Role of platelet factor Xa in chylomicron-prothrombin complexes induced platelet activation.

The effects of chylomicron-prothrombin complexes on platelet activation, including platelet aggregation, serotonin release, arachidonic acid release and increases of platelet cytosolic [Ca2+]i were examined. Furthermore the role of platelet factor Xa on the conversion of chylomicron bound prothrombin to thrombin was studied by using a synthetic inhibitor of factor Xa, TenStop. The chylomicron-prothrombin complexes could induce platelet aggregation and enhance the platelet serotonin release and arachidonic acid release in contrast to native chyle chylomicrons. An increase of platelet [Ca2+]i was observed during incubation with chylomicron-prothrombin complexes. TenStop inhibited platelet aggregation and serotonin release that were induced by chylomicron-prothrombin complexes in a dose-dependent manner, whereas the TenStop itself did not inhibit the platelet aggregation induced by thrombin and collagen. It is concluded that platelet activation induced by chylomicron-prothrombin complexes is related to the platelet factor Xa that could be the key factor in the conversion of chylomicron bound prothrombin to thrombin.

Animals↗
PubMed1995

Lipid changes in plasma and blood cells following intravenous 10% fat infusion in man.

The effects of a 500 ml 4 hr infusion of 10% fat emulsion (Lipovenös) on the lipid content of plasma lipoproteins and blood cells, and on the platelet aggregation rate, were studied in ten volunteers. The infusion resulted in a significant (P < 0.05) initial increase in plasma total triglycerides (more than 5 times), phospholipids (28.7%) and free cholesterol (43.3%), but a decrease in the free cholesterol content of erythrocytes and mononuclear cells (by 4.4% and by 22.7%, respectively). Plasma cholesteryl ester was reduced by 18.2% after the infusion, most of the reduction being accounted for by the 16.5% reduction in high-density lipoproteins. Our findings suggest more than 35% of the free cholesterol accumulated in plasma to derive from peripheral tissues, in turn suggesting overall reverse cholesterol transport from peripheral tissues to plasma to be enhanced. Post-infusion platelet aggregation in response to adenosine disphophate was significantly reduced, the peak rate by 31% and 1 min. rate by 20.6% (P < 0.05 in both cases). These changes in plasma lipids found in normal volunteers suggest that a short-term intravenous infusion of 10% Lipovenös might also be beneficial in preventing atherosclerosis.

Adolescent↗
PubMed1995

mRNA decay mediated by two distinct AU-rich elements from c-fos and granulocyte-macrophage colony-stimulating factor transcripts: different deadenylation kinetics and uncoupling from translation.

Poly(A) tail removal is a critical first step in the decay pathway for many yeast and mammalian mRNAs. Poly(A) shortening rates can be regulated by cis-acting sequences within the transcribed portion of mRNA, which in turn control mRNA turnover rates. The AU-rich element (ARE), found in the 3' untranslated regions of many highly labile mammalian mRNAs, is a well-established example of this type of control. It represents the most widespread RNA stability determinant among those characterized in mammalian cells. Here, we report that two structurally different AREs, the c-fos ARE and the granulocyte-macrophage colony-stimulating factor (GM-CSF) ARE, both direct rapid deadenylation as the first step in mRNA degradation, but by different kinetics. For c-fos-ARE-mediated decay, the mRNA population undergoes synchronous poly(A) shortening and is deadenylated at the same rate, implying the action of distributive or nonprocessive ribonucleolytic digestion of poly(A) tails. In contrast, the population of granulocyte-macrophage colony-stimulating factor ARE-containing mRNAs is deadenylated asynchronously, with the formation of fully deadenylated intermediates, consistent with the action of processive ribonucleolytic digestion of poly(A) tails. An important general implication of this finding is that different RNA-destabilizing elements direct deadenylation either by modulating the processivity at which a single RNase functions or by recruiting kinetically distinct RNases. We have also employed targeted inhibition of translation initiation to demonstrate that the RNA-destabilizing function of both AREs can be uncoupled from translation by ribosomes. In addition, a blockade of ongoing transcription has been used to further probe the functional similarities and distinctions of these two AREs. Our data suggest that the two AREs are targets of two distinct mRNA decay pathways. A general model for ARE-mediated mRNA degradation involving a potential role for certain heterogeneous nuclear ribonucleoproteins and ARE-binding proteins is proposed.

3T3 Cells↗
PubMed1995

Vascular effects and mechanism of action of endothelin-1 in isolated perfused pig skin.

We investigated the vascular effects and mechanism of action of endothelin-1 (ET-1) in the skin by intra-arterial infusion of ET-1 and its precursor Big ET-1 via a direct cutaneous artery in isolated perfused pig skin flaps (6 x 16 cm). The vascular contractivity was studied by monitoring the perfusion pressure in the skin flap. There was evidence to indicate local conversion of Big ET-1 to ET-1 in the pig skin. It was also observed that ET-1 was a potent long-lasting vasoconstrictor with a potency of approximately 10- and 300-fold higher than those of Big ET-1 and norepinephrine, respectively. The vasoconstrictor action of ET-1 was blocked (P < 0.01) by a selective ETA-receptor antagonist (BQ-123 or BQ-610; 10(-7) M) and enhanced (P < 0.05) by a nitric oxide synthase inhibitor (NG-monomethyl-L-arginine or N omega-nitro-L-arginine methyl ester; 10(-5) M). ET-1-induced increase in perfusion pressure was attenuated (P < 0.05) by an L-type Ca(2+)-channel antagonist (nitrendipine, verapamil, or nifedipine; 10(-5) M) and by removal of Ca2+ from the perfusate. ET-1-induced increase in perfusion pressure was also attenuated (P < 0.05) by a phospholipase C inhibitor (neomycin; 10(-2) M), a protein kinase C (PKC) inhibitor (chelerythrine or H-7; 10(-5) M), and an intracellular Ca2+ chelator [1,2-bis(2-aminophenoxy)]ethane-N,N,N',N'-tetraacetic acid (BAPTA); 10(-5) M]. Furthermore, it was observed that the concentration-dependent (5 x 10(-8) to 10(-5) M) increase in perfusion pressure induced by phorbol 12,13-dibutyrate, a PKC activator, was not affected by verapamil (10(-5) M) or removal of Ca2+ from the perfusate. Taken together, these observations suggest that the vasoconstrictor mechanism of ET-1 in the pig skin involved activation of ETA receptors, L-type Ca2+ channels, phospholipase C, and PKC and that the vasoconstrictor effect caused by activation of PKC was independent of L-type Ca2+ channels.

Animals↗
PubMed1995

Uptake of radiolabeled and colloidal gold-labeled chyle chylomicrons and chylomicron remnants by rat platelets in vitro.

This study examined the uptake of chyle chylomicrons (CMs) and chylomicron remnants (CMRs) by rat platelets in vitro. CMs and CMRs were doubly labeled with [3H]arachidonate ([3H]-20:4) and [14C]cholesterol and were incubated with platelets for up to 4 hours. A significant uptake (binding and/or internalization) of CMs by the platelets occurred, as indicated by the parallel increase of [3H]20:4 and [14C]cholesterol in platelets with incubation time. Addition of unlabeled CMs, VLDLs, LDLs, and HDLs decreased the uptake of labeled CMs. The competition experiments suggested that there is both a saturable binding and a nonspecific uptake of CMs. During incubation with CMs, the proportion of [3H]20:4 in phospholipids decreased and that in 1,2-x-diacylglycerol increased. The data indicated that a phospholipase C-mediated degradation of phosphatidylcholine and phosphatidylethanolamine occurred, whereas [3H]20:4 in triglyceride and 14C in cholesterol ester did not change. Electron microscopic studies after incubation with colloidal gold-labeled CMs (CM-Au's) demonstrated an accumulation of CM-Au particles in the open canalicular system of the platelets. Some CM-Au particles were localized in cytoplasmic vacuoles that were not stained by ruthenium red. Some CM-Au's or free gold particles were in vacuoles that showed acid phosphatase activity, indicating that some true endocytosis of CM occurred. The uptake of [3H]-20:4- and [14C]cholesterol-labeled CMRs was low compared with the uptake of CMs. After incubation with colloidal gold-labeled CMRs (CMR-Au's), only a few platelets contained CMR-Au in their open canalicular systems, and no CMR-Au particles were seen in the cytoplasm or in acid phosphatase-positive vacuoles. Rat platelets can thus interact with CMs by a process that leads to a sequestration in the open canalicular system and endocytosis and a net degradation of CM phospholipids. The conversion of CMs to CMRs counteracts this interaction.

Animals↗
PubMed1995

Acute ischaemic preconditioning protects against skeletal muscle infarction in the pig.

OBJECTIVE: The aims were to investigate the efficacy of acute ischaemic preconditioning for protection of skeletal muscles against infarction and its effect on muscle blood flow and ischaemic muscle metabolism. METHODS: The efficacy of preconditioning was tested by subjecting pig latissimus dorsi and gracilis muscles to different numbers and durations of ischaemia/reperfusion cycles before 4 h of global ischaemia. Infarction was assessed at 48 h of reperfusion, using nitroblue tetrazolium dye. Blood flow in the latissimus dorsi was measured at the end of preconditioning and 1.5 and 3.0 h of reperfusion, using the radioactive microsphere (15 microns) technique. Muscle biopsies were taken from the latissimus dorsi before ischaemia, at the end of 2 and 4 h of ischaemia, and 1.5 h of reperfusion. RESULTS: At least three cycles of 10 min ischaemia and 10 min reperfusion were required for preconditioning of latissimus dorsi and gracilis muscles for protection against infarction. Preconditioning reduced the total infarct size by 44% and 62% in latissimus dorsi and gracilis muscles, respectively. Preconditioning did not affect preischaemia muscle blood flow but it reduced the muscle content (preischaemia reserve) of phosphocreatine and ATP and the muscle energy charge potential (ECP) by 13.5%*, 27.5%*, and 8%* (*P < 0.05), respectively. In spite of a lower preischaemia reserve of phosphocreatine and ATP, the muscle contents of phosphocreatine and ATP and muscle ECP were maintained higher and the lactate lower (*P < or = 0.05) in the preconditioned than in the non-preconditioned (control) muscles at the end of 4 h of ischaemia [phosphocreatine 8.0(SEM 0.4) v 3.2(0.3)*; ATP 9.8(0.7) v 7.8(0.3); ECP 0.72(0.02) v 0.66(0.01)*; lactate 115.4(8.6) v 160.5(11.8)* mumol.g-1 dry muscle]. The level of ATP and ECP also remained significantly higher and the level of lactate significantly lower in the preconditioned than in the non-preconditioned latissimus dorsi muscles at 1.5 h of reperfusion. Hyperaemia was seen in the preconditioned latissimus dorsi muscles at 1.5 h of reperfusion and it subsided by the end of 3h of reperfusion. CONCLUSIONS: The protective effect of preconditioning can be induced in pig skeletal muscle but at a higher threshold than reported previously in pig cardiac muscle (one cycle). Preconditioning of pig skeletal muscle is associated with a lower energy metabolism during sustained ischaemia. At the present time, it is not known if this energy sparing effect is a major mechanism of ischaemic preconditioning against infarction in skeletal muscles.

Acute Disease↗
PubMed1995

[Pharmacokinetics of ciprofloxacin injection in healthy volunteers].

The results of pharmacokinetic study of intravenous infusion ciprofloxacin in normal male volunteers were presented. Serum and urine concentrations of ciprofloxacin were determined by high performance liquid chromatography. The single dose 200 mg iv concentration-time curve fitted to two-compartment open model in eight volunteers. Its main pharmacokinetic parameters were: C0 4.61 +/- 1.64 mg/L, t1/2 beta 3.86 +/- 0.67 h and AUC 7.06 +/- 1.21 mg/L.h. The urinary recovery rate of ciprofloxacin over 12 h after dosing was 60.85%.

Adult↗
PubMed1995

[Effect of electroacupuncture at "shenshu" point on renal blood flow in rabbits].

The purpose of this study is to observe the effect of electroacupuncture at "Shenshu" point (U.B.-23) on the renal blood flow (RBF) under the conditions of normal, glycerol-induced renal ischemia and renal neurotomy. The RBF, which is measured by hydrogen gas clearance method, was chosen as index. The results are as follows: 1. RBF is decreased by electroacupuncturing "Shenshu" point under both conditions of normal and glycerol-induced renal ischemia. 2. After renal neurotomy, RBF is increased by electroacupuncturing "Shenshu" point. These facts suggest that the effects of electroacupuncture at "Shenshu" point relate to the renal nerve and body fluid.

Acupuncture Points↗
PubMed1995

[A multiple center clinical trial on fluconazole for deep-seated fungal infections].

A multiple center clinical trial was conducted to evaluate the efficacy and safety of domestic fluconazole in treating 913 cases of deep-seated fungal infections. Fluconazole was given 100-200 mg daily for 3 days to 8 months. The results showed that the cure rate and the total efficacy rate were 69.26% and 94.29% respectively. The fungal clearance rate was 93.83%. The main side-effects were nausea, vomiting, diarrhea and abdominal pain, but most of the patients could endure. The side-effect rate was 9.20%. This clinical trial indicated that domestic fluconazole was effective and safe in treating deep-seated fungal infections.

Adolescent↗
PubMed1994

Identification of metabolic intermediates in microbial degradation of phenol using laser desorption time-of-flight mass spectrometry.

Laser desorption time-of-flight (LD-TOF) mass spectrometry was utilized to determine the metabolic intermediates in microbial degradation of phenol. The identified components were in good agreement with the well-documented pathway. This technique also demonstrated excellent precision. Analytical merits, instrumentation and methodology are discussed.

Environmental Monitoring↗