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Biomedical subjects

X Gao

Publications and source records attributed to X Gao.

At least 37 records · Page 2Linked to original sources
PubMed2005

VEGF165 and angiopoietin-1 decreased myocardium infarct size through phosphatidylinositol-3 kinase and Bcl-2 pathways.

Angiogenic growth factors, vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang1) could decrease myocardial infarct size, which was assumed to be related with newly formed capillaries. We doubted that these capillaries could do this solely and the potential protective mechanisms of VEGF and Ang1 on myocardium need to be evaluated. Three types of adenoviruses encoding human VEGF(165) (Ad-VEGF(165)), human angiopoietin-1 (Ad-Ang1) and green fluorescent protein (Ad-GFP, as a parallel control) were constructed. Experiments were taken both in vitro and in vivo. As in vitro, the antiapoptosis effect of VEGF(165), Ang1 and VEGF(165)+Ang1 on cardiac myoblasts was observed, which seemed to be related with the activation of phosphatidylinositol-3 kinase and Bcl-2 pathways. As in vivo, adenoviruses were intramyocardially injected immediately after the ligation of the left anterior descending coronay arteries in rats. The results showed positive effect of VEGF(165), Ang1 and VEGF(165)+Ang1 on decreasing the myocardial infarct size at the 7th day. Myocardial PI-3K activity and Bcl-2 expression were elevated relatively at the 3rd day. The protective effect of VEGF(165) and Ang1 on the myocardium may broaden their functional research and contribute to their clinical use in the future.

Adenoviridae↗
PubMed2005

Human leukocyte antigen class I and II haplotypes and risk of cervical cancer.

Human leukocyte antigen (HLA) variations may affect immune response to human papillomavirus infection and subsequent cervical neoplasia risk. We investigated the frequency and relationship between HLA-A-B and HLA-A-B-DR haplotypes among women with cervical cancer/high-grade lesions (n=365) and cytologically normal population controls (n=681) within three cervical neoplasia studies in the US and Costa Rica. Notable differences in haplotype frequencies were observed; the HLA-A*01-B*08 haplotype occurred in >5% of US Caucasians but in <1% of Costa Ricans. The most prevalent HLA-A*24-B*40-DR*04 haplotype in Costa Rica (5%) was found in <1% of US Caucasians. No HLA haplotype was significantly associated with cervical neoplasia, suggesting that individual allele associations reported to date (e.g. HLA-DR*13) are not likely explained by underlying haplotypes.

Costa Rica↗
PubMed2005

Effect of keto-acidosis on seizure occurrence in diabetic patients.

It has been observed anecdotally that diabetics are usually non-ketotic at the time of their seizure presentation. In order to establish some validity on this observation, we reviewed the medical records of patients with diagnoses of diabetes and seizure. Study subjects were diabetics presenting with seizures. Control subjects were random sampling of all diabetics. In 51 diabetics presenting with seizures, 38 were nonketotic and 13 were ketotic. In the control group of 119 diabetics, 63 were non-ketotic and 56 were ketotic. There were no significant differences in the serum levels of glucose, sodium, potassium, chloride, and calcium between the seizure and control groups. Multiple regression analysis showed that non-ketotic patients were at risk for developing seizures with an odds ratio of 4.03 (p=0.001). Male sex and type 1 diabetes were also risk factors while age was not a risk factor. Keto-acidosis may play a role in preventing epileptic seizures from occurring in diabetic patients.

Case-Control Studies↗
PubMed2004

Electro-acupuncture relieves chronic visceral hyperalgesia in rats.

Acupuncture treatment is one of the most desirable choices for the management of pain including chronic visceral pain, but its scientific evidence and laws of action are not very clear at this point. In this study, we examined the immediate and cumulative effects of electro-acupuncture (EA) on chronic visceral pain induced by colorectal distention (CRD) stimuli in rats using an irritable bowel syndrome (IBS) model (a chronic visceral hypersensitivity model). The results demonstrated that EA could significantly depress both abnormally increased abdominal withdrawal reflex (AWR) scores and the magnitude of electromyograms (EMGs) recorded from the rectus abdominis in response to CRD stimulation at strengths of 20, 40, 60, and 80 mmHg. Repeated EA treatment for 14 days showed that the effects of EA on both abnormal AWRs and EMGs appeared 2-4 days after the start of the EA application session, gradually enhanced to its maximum within 8-12 days, and lasted 5 days after EA treatment stopped. These data provide evidence that visceral pain associated with the rat IBS model can be effectively treated by EA and opens up the possibility of clinical treatment of chronic visceral pain with acupuncture.

Animals↗
PubMed2004

Effects of sucrose concentration on the developmental potential of human frozen-thawed oocytes at different stages of maturity.

BACKGROUND: Success of human oocyte cryopreservation depends on multiple cryobiological factors that could influence the developmental potential of the oocytes. The objective of this study was to examine the effects of different sucrose concentrations on the developmental potential of human frozen-thawed oocytes at different maturity stages. METHODS: A total of 355 oocytes collected from small follicles were randomly divided into three groups and two groups (B and C) were cryopreserved using slow-freezing method. Group A included 131 oocytes at different maturity stages without freezing. Another 119 oocytes in Group B were cryopreserved with 0.1 M sucrose and 105 oocytes in Group C with 0.2 M sucrose concentration. RESULTS: The post-thaw survival rate of the oocytes and the cleavage rate in Group C were significantly higher than that of Group B (P<0.05). For immature metaphase I (MI) stage oocytes, a significant difference was found in the maturation rate between Group C and Group B (P<0.05). The maturation rate for the GV oocytes in Groups A and C was significantly higher than Group B (P<0.01). CONCLUSIONS: The results suggested that sucrose concentration of 0.2 M in the cryoprotectant solution is more suitable for human oocyte cryopreservation.

Adult↗
PubMed2004

Mechanism of RNA 2'-O-methylation: evidence that the catalytic lysine acts to steer rather than deprotonate the target nucleophile.

The weight of current evidence suggests that RNA 2'-O-MTases employ an S(N)2 mechanism with an in-line attack of the target nucleophile upon the methyl group of the AdoMet cofactor. It has been suggested that, like the phosphohydrolytic enzymes, ribozymes, and nucleic acid polymerases, the RNA 2'-O-MTases initially activate the substrate's attacking hydroxyl oxygen by deprotonation. Here, evidence is presented that the vaccinia virus mRNA cap specific 2'-O-MTase VP39 does not promote RNA 2'-oxyanion formation but that instead it acts by steering a hydroxyl oxygen orbital toward the cofactor methyl center.

Carbon Isotopes↗
PubMed2004

Two-layer simulation model of laser-induced interstitial thermo-therapy.

A two-layer model using different properties for the pathological tissue and the normal tissue was developed to describe the spatial photon, temperature and thermal damage distributions during laser-induced interstitial thermo-therapy (LITT). The photon distribution was simulated using the Monte Carlo method. The optical tissue parameters and the blood perfusion were derived based on the Arrhenius rate process formulation of thermal damage and kinetics of vasodilatation. The corresponding temperature distribution was numerically calculated using the Pennes bio-heat equation. The calculated results showed that the two-layer model predicted different results on the temperature variation and distribution, the thermal damage distribution and the thermal damage volume etc. from the one-layer model. As a more reasonable physical model, the two-layer model can be used to optimize the therapeutic parameters for improved LITT treatments.

Humans↗
PubMed2004

Formation of advanced tokamak plasmas without the use of an ohmic-heating solenoid.

A new operational scenario of advanced tokamak formation was demonstrated in the JT-60U tokamak. This was accomplished by electron cyclotron and lower hybrid waves, neutral beam injection, and the loop voltage supplied by the vertical field and shaping coils. The Ohmic heating (OH) solenoid was not used but a small inboard coil (part of the shaping coil), providing less than 20% of total poloidal flux, was used. The plasma thus obtained had both internal and edge transport barriers, with an energy confinement time of 1.6 times H-mode scaling, a poloidal beta of 3.6, and a normalized beta of 1.6, and a large bootstrap current fraction (>90%). This result opens up a possibility to reduce, and eventually eliminate, the OH solenoid from a tokamak reactor, which will greatly improve its economic competitiveness.

Journal Article↗
PubMed2004

Method for isolating tight-binding inhibitors of rat lens aldose reductase.

Numerous animal studies indicate that aldose reductase inhibitors (ARIs) are beneficial for the prevention or amelioration of diabetic complications such as neuropathy, nephropathy and the ocular complications of cataract, retinopathy and keratopathy. To aid in the identification of novel potent ARIs, we have previously developed a screening method that is based on the formation of a non-covalent ternary tight-binding enzyme-inhibitor-nucleotide (AR-ARI-NADPH) complex that can be isolated using YM-10 filter units. Here, we report a modification of this method that permits us to rapidly identify tight binding ARIs that are isolated by denaturation from AR-ARI-NADPH complexes that are free of possible contamination resulting from the reaction of methanol with the YM-10 filter units. For the development of this procedure, nine structurally diverse ARIs were mixed with purified recombinant rat lens aldose reductase (RLAR) bound with NADPH to form tight-binding RLAR-ARI-NADPH complexes. These complexes were purified by high pressure Sephadex 75 size exclusion chromatography using ammonium acetate buffer and the formation of each complex was confirmed by electrospray ionisation mass spectrometry (ESI-MS). Each of the complexes was then denatured with methanol, rechromatographed on the size exclusion column, and the identity of the bound ARIs was confirmed by ESI-MS. The apparent ARI binding with aldose reductase to form a tight binding ARI complex appeared proportional to their IC50 values. This procedure allows for the rapid identification of tight binding ARIs with apparent IC50s<0.1 microm.

Aldehyde Reductase↗
PubMed2004

MICA and recovery from hepatitis C virus and hepatitis B virus infections.

The polymorphic MHC class I chain-related A (MICA) gene encodes a ligand that has different binding affinities for the NKG2D activating receptor of CD8+ T cells and natural killer (NK) cells. We hypothesized that MICA heterogeneity would affect recovery from hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. To test the hypothesis, we initially typed known MICA polymorphisms for 228 persons who cleared HCV infection and 442 persons with persistent hepatitis C matched on other factors affecting viral persistence. Although MICA(*)015 was detected more than two-fold more often in persons with viral clearance (odds ratio 0.36, 95% confidence interval=0.19, 0.80), it occurred in fewer than 5% of the study population. In a similar analysis of 442 persons with chronic hepatitis B and 768 matched controls who recovered, MICA(*)015 was detected in 2.0% of persons with chronic hepatitis B and only 0.9% of controls. No significant associations were detected with other MICA polymorphisms. While further investigation may reveal a structural basis of the MICA(*)015 associations, these data provide little support for the hypothesis that differential distribution of MICA alleles substantially affects recovery from HCV and HBV infections.

Hepacivirus↗
PubMed2004

Hydroporation as the mechanism of hydrodynamic delivery.

We have reported that a rapid tail vein injection of a large volume of plasmid DNA solution into a mouse results in high level of transgene expression in the liver. Gene transfer efficiency of this hydrodynamics-based procedure is determined by the combined effect of a large volume and high injection speed. Here, we show that the hydrodynamic injection induces a transient irregularity of heart function, a sharp increase in venous pressure, an enlargement of liver fenestrae, and enhancement of membrane permeability of the hepatocytes. At the cellular level, our results suggest that hepatic delivery by the hydrodynamic injection is accomplished by the generation of membrane pores in the hepatocytes.

Animals↗
PubMed2004

Simultaneous stimulation of Fas-mediated apoptosis and blockade of costimulation prevent autoimmune diabetes in mice induced by multiple low-dose streptozotocin.

Type I diabetes is the result of a selective destruction of insulin-producing beta cells in pancreatic islets by autoreactive T cells. Depletion of autoreactive T cells through apoptosis may be a potential strategy for the prevention of autoimmune diabetes. Simultaneous stimulation of the Fas-mediated pathway and blockade of costimulation by a CTLA4-Fas ligand (FasL) fusion protein has been reported to lead to enhanced in vitro apoptosis of peripheral lymphocytes. To test the feasibility of CTLA4-FasL-based gene therapy to prevent autoimmune diabetes, we developed a recombinant adenovirus containing the human CTLA4-FasL gene (AdCTLA4-FasL). A single injection of 2 x 10(8) plaque-forming units of AdCTLA4-FasL via the tail vein of mice greatly reduced the incidence of autoimmune diabetes (13%, n=15) induced by multiple low-dose streptozotocin. AdCTLA4-FasL administration abrogated pancreatic insulitis, significantly increased apoptosis of pancreatic T-lymphocytes, and altered splenocyte response to mitogenic and antigenic stimulation. These results indicate the therapeutic potential of simultaneous stimulation of the Fas-mediated pathway and blockade of costimulation by adenovirus-mediated CTLA4-FasL gene transfer in the prevention of autoimmune diabetes.

Adoptive Transfer↗
PubMed2003

Recognition of HLA-A*0248 in a Chinese donor.

HLA-A*0248, a rare allele originally found in an individual of Filipino background, was detected in a Chinese donor. We confirmed the novel sequence and analysed its serological reaction pattern. The exon 2 sequence of A*0248 was apparently generated in a gene conversion event with an A2 gene, receiving a sequence segment comprising codons 56 to 74 from an A*24 donor gene. Serological typing showed a clear-cut A2 reaction pattern, indicating that the three amino acid positions 62, 65 and 74, are probably not a critical part of the A2 epitope. Our typing experience also demonstrated that different typing technologies often complement each other in fine HLA typing.

Amino Acid Substitution↗
PubMed2002

Wnt-1 promotes neuronal differentiation and inhibits gliogenesis in P19 cells.

Wnt-1, the vertebrate counterpart of the Drosophila wingless gene, plays an important role in the early morphogenesis of neural tissues. In this report, we have shown that overexpression of Wnt-1 can direct embryonic carcinoma P19 cells to differentiate into neuron-like cells in the absence of retinoic acid. Immunocytochemistry showed that these cells expressed neuronal markers, such as the neurofilament (NF) and microtubule-associated protein 2 (MAP2), but failed to express the glial cell marker, glial fibrillary acidic protein (GFAP). RT-PCR revealed that two basic helix-loop-helix (bHLH) genes, Mash-1 and Ngn-1, were up-regulated during the differentiation stage of Wnt-1-overexpressing P19 cells. These results suggest that the Wnt-1 gene promotes neuronal differentiation and inhibits gliogenesis during the neural differentiation of P19 cells, and that neural bHLH genes might be involved in this process.

Animals↗
PubMed2002

The effect of storage temperatures on the in vitro properties of a polyanhydride implant containing gentamicin.

Septacin is a biodegradable sustained-release implant containing 20% (w/w) gentamicin sulfate. The matrix of the implant is a polyanhydride copolymer composed of erucic acid dimer (EAD) and sebacic acid (SA) in a one-to-one weight ratio. The effect of storage temperatures (-15 degrees C and 25 degrees C) on the stability of Septacin was evaluated with respect to gentamicin potency, copolymer molecular weight, and in vitro drug release. The drug in polymer matrix was stable for at least 12 months when stored at 25 degrees C, but the molecular weight of the copolymer declined rapidly at this temperature. At -15 degrees C, there was no change in the molecular weight of the copolymer. However, the placebo (copolymer without gentamicin) exhibited a significant drop in copolymer molecular weight at both temperatures. The drug release profiles showed no change for samples stored at -15 degrees C for the duration of this study, while the release of drug slowed down significantly for samples stored at 25 degrees C for longer than one month. A pronounced difference in the morphology of the -15 degrees C samples and the 25 degrees C samples was observed during the in vitro dissolution test; cracking of the -15 degrees C samples was evident, but the 25 degrees C samples remained intact.

Anhydrides↗
PubMed2001

Powerful and prolonged protection of human retinal pigment epithelial cells, keratinocytes, and mouse leukemia cells against oxidative damage: the indirect antioxidant effects of sulforaphane.

Mammalian cells are equipped with elaborate systems for protection against the toxicity of reactive oxygen and nitrogen species and electrophiles that are constant dangers to the integrity of their DNA. Phase 2 enzymes (e.g., glutathione transferases, NAD(P)H:quinone reductase) and glutathione synthesis are widely recognized as playing major protective roles against electrophilic carcinogens, but their antioxidant functions have attracted far less attention. The cytotoxicities of four oxidative stressors (menadione, tert-butyl hydroperoxide, 4-hydroxynonenal, and peroxynitrite) for human adult retinal pigment epithelial cells (ARPE-19) were quantified by measuring the concentration dependence of cell death and were expressed as the median effect dose (D(m)) for each oxidant. After treatment of ARPE-19 cells for 24 h with 0-5 microM concentrations of sulforaphane (the powerful Phase 2 enzyme inducer isolated from broccoli), the toxicities of the oxidants were markedly reduced as shown by 1.5- to 3-fold increases in D(m) values. The magnitude of protection was a function of the nature of the oxidants and the concentrations of both the oxidants and sulforaphane. Protection was prolonged and persisted for several days after removal of sulforaphane before returning to control levels. The sulforaphane-dependent increases in specific activities of cytosolic quinone reductase and the glutathione levels were highly significantly correlated with the degree of protection as measured by D(m) values. Antioxidant protection was also demonstrated for human HaCaT keratinocytes and L1210 murine leukemia cells. It is therefore highly likely that the multifaceted and prolonged antioxidant protection provided by sulforaphane is a general phenomenon that is mediated through induction of the Phase 2 enzyme response.

Adult↗