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Yan Xu

Publications and source records attributed to Yan Xu.

232 records · Page 13Linked to original sources

Late reversal of cerebral perfusion and water diffusion after transient focal ischemia in rats.

Region-specific cerebral blood flow (CBF) and the apparent diffusion coefficient (ADC) of tissue water in the rat brain were quantified by high-field magnetic resonance imaging at 9.4 T in the rat suture occlusion model. Cerebral blood flow and ADC were compared during the short- (4.5 hours) and long-term (up to 6 days) reperfusion after 80 minutes of transient middle cerebral artery occlusion, and correlated with the histology analysis. On occlusion, average CBF fell from approximately 100 to less than 50 mL x 100 g(-1) x min(-1) in the cortex, and to less than 20 mL x 100 g(-1) x min(-1) in the caudate putamen (CP). Corresponding ADC values decreased from (6.98 +/- 0.82) x 10(-4) to (5.49 +/- 0.54) x 10(-4) mm2/s in the cortex, and from (7.16 +/- 0.58) x 10(-4) to (4.86 +/- 0.62) x 10(-4) mm2/s in the CP. On average, CBF recovered to approximately 50% of baseline in the first 24 hours of reperfusion. After 2 to 4 days, a strong hyperperfusion in the ipsilateral cortex and CP, up to approximately 300 mL x 100 g(-1) x min(-1), was observed. The ADC ratio in the ipsilateral and contralateral CP was also inverted in the late reperfusion period. Histology revealed more severe tissue damage at the late stage of reperfusion than at 4.5 hours. Significant reversal of CBF and ADC during the late reperfusion period may reflect the impairment of autoregulation in the ischemic regions. Vascular factors may play an important role in the infarct development after 80-minute focal ischemia.

Animals↗

Akt activation induced by lysophosphatidic acid and sphingosine-1-phosphate requires both mitogen-activated protein kinase kinase and p38 mitogen-activated protein kinase and is cell-line specific.

The signaling pathways that lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) use to activate Akt in ovarian cancer cells are investigated here. We show for the first time, with the use of both pharmacological and genetic inhibitors, that the kinase activity and S473 phosphorylation of Akt induced by LPA and S1P requires both mitogen-activated protein (MAP) kinase kinase (MEK) and p38 MAP kinase, and MEK is likely to be upstream of p38, in HEY ovarian cancer cells. The requirement for both MEK and p38 is cell type- and stimulus-specific. Among 12 cell lines that we tested, 11 respond to LPA and S1P and all of the responsive cell lines require p38 but only nine of them require MEK. Among different stimuli tested, platelet-derived growth factor stimulates S473 phosphorylation of Akt in a MEK- and p38-dependent manner. However, epidermal growth factor, thrombin, and endothelin-1-stimulated Akt S473 phosphorylation require p38 but not MEK. Insulin, on the other hand, stimulates Akt S473 phosphorylation independent of both MEK and p38 in HEY cells. T308 phosphorylation stimulated by LPA/S1P requires MEK but not p38 activation. MEK and p38 activation were sufficient for Akt S473 but not T308 phosphorylation in HEY cells. In contrast to S1P and PDGF, LPA requires Rho for Akt S473 phosphorylation, and Rho is upstream of phosphatidylinositol 3-kinase (PI3-K). LPA/S1P-induced Akt activation may be involved in cell survival, because LPA and S1P treatment in HEY ovarian cancer cells results in a decrease in paclitaxel-induced caspase-3 activity in a PI3-K/MEK/p38-dependent manner.

Acute-Phase Proteins↗

Critical role for Env as well as Gag-Pol in control of a simian-human immunodeficiency virus 89.6P challenge by a DNA prime/recombinant modified vaccinia virus Ankara vaccine.

Cellular immune responses against epitopes in conserved Gag and Pol sequences of human immunodeficiency virus type 1 have become popular targets for candidate AIDS vaccines. Recently, we used a simian-human immunodeficiency virus model (SHIV 89.6P) with macaques to demonstrate the control of a pathogenic mucosal challenge by priming with Gag-Pol-Env-expressing DNA and boosting with Gag-Pol-Env-expressing recombinant modified vaccinia virus Ankara (rMVA). Here we tested Gag-Pol DNA priming and Gag-Pol rMVA boosting to evaluate the contribution of anti-Env immune responses to viral control. The Gag-Pol vaccine raised frequencies of Gag-specific T cells similar to those raised by the Gag-Pol-Env vaccine. Following challenge, these rapidly expanded to counter the challenge infection. Despite this, the control of the SHIV 89.6P challenge was delayed and inconsistent in the Gag-Pol-vaccinated group and all of the animals underwent severe and, in most cases, sustained loss of CD4(+) cells. Interestingly, most of the CD4(+) cells that were lost in the Gag-Pol-vaccinated group were uninfected cells. We suggest that the rapid appearance of binding antibody for Env in Gag-Pol-Env-vaccinated animals helped protect uninfected CD4(+) cells from Env-induced apoptosis. Our results highlight the importance of immune responses to Env, as well as to Gag-Pol, in the control of immunodeficiency virus challenges and the protection of CD4(+) cells.

AIDS Vaccines↗

Different patterns of immune responses but similar control of a simian-human immunodeficiency virus 89.6P mucosal challenge by modified vaccinia virus Ankara (MVA) and DNA/MVA vaccines.

Recently we demonstrated the control of a mucosal challenge with a pathogenic chimera of simian and human immunodeficiency virus (SHIV-89.6P) by priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env-expressing recombinant modified vaccinia virus Ankara (DNA/MVA) vaccine. Here we evaluate the ability of the MVA component of this vaccine to serve as both a prime and a boost for an AIDS vaccine. The same immunization schedule, MVA dose, and challenge conditions were used as in the prior DNA/MVA vaccine trial. Compared to the DNA/MVA vaccine, the MVA-only vaccine raised less than 1/10 the number of vaccine-specific T cells but 10-fold-higher titers of binding antibody for Env. Postchallenge, the animals vaccinated with MVA alone increased their CD8 cell numbers to levels that were similar to those seen in DNA/MVA-vaccinated animals. However, they underwent a slower emergence and contraction of antiviral CD8 T cells and were slower to generate neutralizing antibodies than the DNA/MVA-vaccinated animals. Despite this, by 5 weeks postchallenge, the MVA-only-vaccinated animals had achieved as good control of the viral infection as the DNA/MVA group, a situation that has held up to the present time in the trial (48 weeks postchallenge). Thus, MVA vaccines, as well as DNA/MVA vaccines, merit further evaluation for their ability to control the current AIDS pandemic.

AIDS Vaccines↗

Activity and conformational changes of horseradish peroxidase in trifluoroethanol.

The effect of trifluoroethanol (TFE) on horseradish peroxidase (HRP) was determined using activity assay and spectral analysis including optical absorption, circular dichroism (CD), and intrinsic fluorescence. The enzyme activity increased nearly twofold after incubation with 5-25% (v/v) concentrations of TFE. At these TFE concentrations, the tertiary structure of the protein changed little, while small changes occurred at the active site. Further increases in the TFE concentration (25-40%) decreased the enzyme activity until at 40% TFE the enzyme was completely inactivated. The alpha-helix content of the protein increased at high TFE concentrations, while near-UV CD, Soret CD, and intrinsic fluorescence indicated that the tertiary structure was destroyed. Polyacrylamide gel electrophoresis results indicated that the surface charge of the enzyme was changed at TFE concentrations greater than 20%, and increasing concentrations of TFE reduced the enzyme molecular compactness. A scheme for the unfolding of HRP in TFE was suggested based on these results. The kinetics of absorption change at 403 nm in 40% TFE followed a two-phase course. Finally, HRP incubated with TFE was more sensitive to urea denaturation, which suggested that the main effect of TFE on HRP was the disruption of hydrophobic interactions.

Binding Sites↗

Dependence of early cerebral reperfusion and long-term outcome on resuscitation efficiency after cardiac arrest in rats.

BACKGROUND AND PURPOSE: While it is well known that longer duration of cardiac arrest (CA) is often associated with poorer long-term outcome, the influence of resuscitation efficacy on postischemia recovery is less clear. The objective of the present study is to investigate whether an inadequate and prolonged resuscitation after a shorter CA can lead to worse long-term outcomes than an effective resuscitation after a longer CA, provided that the total time from the onset of CA to the return of spontaneous circulation is comparable. METHODS: Thirty-eight rats were randomized into 2 groups with nominal 9 minutes (group 1) and 15 minutes (group 2) of normothermic asphyxial CA. Each group was further divided into 2 subgroups on the basis of the duration of resuscitation efforts (labeled as S and L for short and long, respectively). Thus, the asphyxia and nominal resuscitation times were 8 and 1 minute, respectively, for group 1S, 5 and 4 minutes for group 1L, 14 and 1 minute for group 2S, and 11 and 4 minutes for group 2L. Cerebral perfusion was measured continuously at the dorsal hippocampus level before, during, and after the CA, with the use of the arterial spin labeling MRI technique. The survival time, histological damage, and neurological deficit were evaluated 5 days after resuscitation. RESULTS: Groups 1S and 1L had nearly the same duration of CA (9.02 +/- 0.17 minutes, n=6 versus 8.58 +/- 0.80 minutes, n=6). The same is true for groups 2S and 2L (15.51 +/- 0.59 minutes, n=11 versus 15.65 +/- 1.25 minutes, n=15). Despite longer asphyxia, shorter and more effective resuscitation was associated with significantly improved long-term outcomes and higher cerebral perfusion at the early stage of reperfusion. CONCLUSIONS: Effective resuscitation increased early reperfusion and improved survival after CA. The clinical implication is that inadequate and prolonged resuscitation may have detrimental effects on the recovery of CA patients.

Animals↗

Gene coding variant in Cas1 between the C57BL/6J and DBA/2J inbred mouse strains: linkage to a QTL for ethanol-induced locomotor activation.

BACKGROUND: Among some (e.g., DBA/2J or D2) but not all (C57BL/6J or B6) inbred strains of mice, ethanol has a marked psychostimulant effect. Intercrosses formed from the D2 and B6 strains have been used to detect quantitative trait loci (QTLs) for this phenotype. The major QTL is found at the mid-region of chromosome 2 (Demarest et al., 1999). This QTL has also been detected in heterogeneous stock mice (Demarest et al., 2001). A potential candidate gene in this region is Cas1, which codes for catalase. The current studies were conducted to determine (a) if there was difference in the open reading frame (ORF) of Cas1 between the D2 and B6 strains; (b) if a difference was found, was it likely that the difference had functional effects; and (c) if it could be established that Cas1 meets the criteria for QTL to gene. METHODS: The open reading frame (ORF) of Cas1 was sequenced in both the D2 and B6 mouse strains. A single polymorphism was found between the strains (see below); the strain distribution pattern for this polymorphism was determined in the 36 strains of the B6XD2 (BXD) recombinant inbred (RI) series. These data were used to map the position of Cas1 as described by Cudmore et al. (1999). RESULTS: The only difference between the D2 and B6 strains in the coding region was found at #349, G->A. This will result in a difference in the amino acid sequence between the strains at amino acid #117-alanine is found in the D2 strain while threonine is found in the B6 strain. The RI strain distribution pattern for this polymorphism was used to determine the relative placement of Cas1. The estimate suggests that Cas1 is flanked by D2Mit12 and D2Mit43 and relative to D2Mit94 (which was set at 47 cM), Cas1 is located at approximately 57 cM, confirming previous estimates (see www.jax.org). CONCLUSIONS: Pharmacological data (Correa et al., 2001) strongly support the idea that Cas1 meets the criteria for QTL to gene. However, based on the mapping data, Cas1 is clearly not included in the QTL for heterogeneous stock mice. Finally, other genetic data suggest that the polymorphism is not sufficient to generate the QTL.

Animals↗

Role of ether-linked lysophosphatidic acids in ovarian cancer cells.

Naturally occurring alkyl- and alkenyl-lysophosphatidic acids (al-LPAs) are detected and elevated in ovarian cancer ascites compared with ascites from non-malignant diseases. Here we describe the biological functions and signaling properties of these ether-linked LPAs in ovarian cancer cells. They are elevated and stable in ovarian cancer ascites, which represents an in vivo environment for ovarian cancer cells. They stimulated DNA synthesis and proliferation of ovarian cancer cells. In addition, they induced cell migration and the secretion of a pro-angiogenic factor, interleukin-8 (IL-8), in ovarian cancer cells. The latter two processes are potentially related to tumor metastasis and angiogenesis, respectively. Al-LPAs induced diverse signaling pathways in ovarian cancer cells. Their mitogenic activity depended on the activation of the G(i/o) protein, phosphatidylinositol-3 kinase (PI3K), and mitogen-activated protein (MAP) kinase kinase (MEK), but not p38 mitogen activated protein kinase (MAP kinase). S473 phosphorylation of protein kinase B (Akt) by these lipids required activation of the G(i/o) protein, PI3K, MEK, p38 MAP kinase, and Rho. However, T308 phosphorylation of Akt stimulated by al-LPAs did not require activation of p38 MAP kinase. On the other hand, cell migration induced by al-LPAs depended on activities of the G(i/o) protein, PI3K, and Rho, but not MEK. These data suggest that ether-linked LPAs may play an important role in ovarian cancer development.

Ascites↗

[A study of experimental carbomer glaucoma and other experimental glaucoma in rabbits].

OBJECTIVE: To establish models of experimental glaucoma in rabbits to investigate the treatment of glaucoma. METHODS: Twenty-one normal albino rabbits weighing 2.5 - 3.0 kg were studied. The rabbits were divided randomly into 4 groups: I, II, III and IV. Anterior chamber injection of 0.1 ml of 0.3% carbomer (I), 0.2 ml of methylcellulose (II), 0.2 ml of compound methylcellulose (III) and subconjunctival injection of 5 mg of dexamethasone (IV) were performed respectively on them to induce glaucoma. The intraocular pressure (IOP) was monitored with a Tono-pen XL tonometer several times prior to injection and 2 times per week after injection. The basic IOP in every group served as control. RESULTS: Experimental glaucoma occurred in eleven of twelve eyes in group I and IOP lasted from 20 to 50 days. The mean IOP levels were 29 - 35 mmHg (1 mm Hg = 0.133 kPa) and the peak IOP levels were 37 - 45 mm Hg. The IOP in 2 out of 10 eyes in group II increased to 22 - 50 mm Hg and lasted for 3 days. The IOP of 1 out of 10 eyes in group III increased to 25 - 40 mm Hg and lasted for 4 days. The IOP in eyes of group IV increased only 3 mmHg in the mean and lasted for one week. According to the standard, IOP above 22 mmHg for one week as the successful experimental glaucoma, group II and III were not the ideal ones and group IV was a failure. CONCLUSION: Experimental glaucoma model induced by carbomer has the advantages of producing moderate and sustained IOP elevation. The model is easy to be carried out. It is simple, reliable, and useful for investigating optic nerve and retinal damage in glaucoma and testing the toxicity and efficacy of various therapies.

Acrylic Resins↗

[+Gz protection of the on board oxygen generating system (OBOGS) and anti-G equipment].

OBJECTIVE: To investigate the +Gz protection of the on board oxygen generating system (OBOGS) and anti-G equipment. METHOD: Physical and physiological tests of the OBOGS and anti-G equipment were accomplished using human centrifuge. +Gz tolerance of ten male subjects with or without the anti-G suit, pressure breathing for G (PBG) and OBOGS were determined. RESULT: The performance of the OBOGS and anti-G equipment fulfilled the requirements. The +Gz protections of the anti-G suit, PBG, and anti-G system were 2.08 G, 1.92 G, and 3.92 G, respectively. CONCLUSION: The +Gz protection of the OBOGS and anti-G equipment satisfy the performance requirements of high performance aircraft.

Acceleration↗

[Effects of pilocarpine in new ophthalmic formulations on intraocular pressure in rabbits with ocular hypertension].

OBJECTIVE: To assess the effects of pilocarpine (PC) incorporated into an in situ gelling vehicle, submicron emulsion vehicle, polyvinyl alcohol vehicle and PC solution on intraocular pressure (IOP) in rabbits with carbomer-induced elevation of IOP. METHODS: Forty-three rabbit eyes with carbomer-induced elevation of IOP were randomly divided into 5 groups. Each eye in every group received topical application of PC from one of the ophthalmic formulations. IOP was measured before and 1, 2, 3, 4, 5, 7, 10, 12, 22 and 24 hours (h) after topical ocular administration of the ophthalmic formulations. RESULTS: The reduction in IOP lasted for 7 h and the maximum decrease was (12.25 +/- 5.28) mm Hg in the hypertensive eyes treated by 2% PC solution. The reduction in IOP lasted for 12 h and the maximum decrease was (13.67 +/- 4.61) mm Hg in the hypertensive eyes treated by 2% PC gel. The reduction in IOP lasted for 24 h and the maximum decrease was (13.63 +/- 3.58) mm Hg in the hypertensive eyes treated by 4% PC gel. The reduction in IOP lasted for 12 h and the maximum decrease was (13.55 +/- 3.90) mm Hg in the hypertensive eyes treated by 2% PC submicron emulsion. The reduction in IOP lasted for 10 h and the maximum decrease was (10.89 +/- 4.04) mm Hg in the hypertensive eyes treated by 2% PC polyvinyl alcohol. The duration of action for lowering IOP lasted longer following administration with new ophthalmic formulations as compared to 2% PC solution. The series of prolongation is as follows: 4% PC gel > 2% PC gel = 2% PC submicron emulsion > 2% PC polyvinyl alcohol > 2% PC solution. The maximum reduction in IOP was not significantly different among the groups. No clinical evidence of ocular toxicity occurred in all groups except mild conjunctival injection. CONCLUSION: These results indicate that the duration of action for lowering IOP is longer in PC gel, PC submicron emulsion and PC polyvinyl alcohol as compared to PC solution. The duration of action with 4% PC gel lasts the longest among all the groups. A single dose of 4% PC gel applied once daily can reduce IOP for 24 h.

Animals↗

[Relationship of changes in sleep architecture and cognitive function in patients with obstructive sleep apnea syndrome].

OBJECTIVES: To explore the relationship between sleep architecture changes and cognitive impairment in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Thirty-six patients with OSAS and 18 controls were administered polysomnography and neuropsychological tests of visual regeneration, digital symbol, comprehensive memory and digital span. RESULTS: Performances on the visual regeneration test and digital symbol test in patients with OSAS were impaired significantly compared with the control group (P < 0.01). Patients' performance on the visual regeneration test was significantly associated with slow wave sleep duration (r = 0.423, P < 0.05) and that on the digital symbol test was significantly associated with REM sleep duration (r = 0.378, P < 0.05). CONCLUSIONS: Slow wave sleep and REM sleep derivation may play a role in the cognitive impairment in patients with OSAS.

Adult↗

Expression of cyclooxygenase isoforms in developing rat placenta, human term placenta, and BeWo human trophoblast model.

Cyclooxygenase (COX) catalyzes the rate-limiting step in the conversion of essential fatty acids (EFAs) to bioactive molecules such as prostaglandins (PGs), which play critical roles in many aspects of female reproduction and in fetal development. There are two primary related COX isoforms, the constitutively expressed COX-1 and the inducible COX-2. Although the expression of COX-1 and COX-2 has been demonstrated in the amnion, chorion, and decidua, relatively little information exists with regard to their expression and physiological function in the placenta during gestation. In this study, we have elucidated the spatial and temporal patterns of COX-1 and COX-2 expression in the labyrinthine and junctional zones of the developing rat placenta, in the human term placenta, and in the BeWo human trophoblast model using semiquantitative RT-PCR, Western blot, and immunohistochemical analyses. The mRNA and protein expression of COX-1 and COX-2 were demonstrated in the developing rat placenta with increasing expression observed toward parturition. COX-2 exhibited greater expression than COX-1 after mid-gestation and had a corresponding shift in spatial expression from the labyrinthine to the junctional zone at term. COX-1 and -2 were also expressed in human term placenta, while BeWo cells exhibited moderate expression of COX-1 and weak expression of COX-2. The results demonstrate that COX-1 and COX-2 are expressed in the rat and human placentas. The differential expression patterns in the rat placenta, especially of COX-2, imply that there may be gestational changes in the biosynthesis of PGs and other potential bioactive EFA metabolites. Establishing the expression of the COX isoforms provides a framework for future investigations into the functional and physiological significance of COX-1 and COX-2 in the placenta, particularly with respect to influencing normal pregnancy and fetal development, and to provide insights into therapeutic utilization of COX inhibitors in pregnancy.

Animals↗