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Biomedical subjects

Hui Xu

Publications and source records attributed to Hui Xu.

At least 127 records · Page 7Linked to original sources
PubMed2004

[Extracorporeal membrane oxygenation treatment with high-volume hemofiltration in patients with multiple organ dysfunction syndrome].

OBJECTIVE: To evaluate whether extracorporeal membrane oxygenation (ECMO) with high-volume hemofiltration (HVHF) improves hypoxemia and renal function in patients with multiple organ dysfunction syndrome (MODS). METHODS: The study was executed in 8 MODS patients with acute respiratory distress syndrome (ARDS) and acute renal failure (ARF). They were randomly assigned to either 8 hours of HVHF combined with ECMO or HVHF alone in random order. The changes in arterial oxygen pressure(PO(2)), pulse oxygen saturation (SpO(2)), arterial carbon dioxide pressure (PCO(2)), serum creatinine (SCr) and blood urea nitrogen (BUN) levels were measured. RESULTS: Compared with that of before the treatment, PO(2) was increased significantly at 1, 4, 8 hours, and SpO(2) was increased significantly at 4, 8 hours after ECMO with HVHF in MODS patients, the changes of PO(2), SpO(2)and PCO(2)were not significantly during HVHF (all P>0.05). The average concentrations of BUN and SCr were decreased significantly after HVHF or HVHF with ECMO therapy in MODS patients. CONCLUSION: HVHF with ECMO, which can improve hypoxemia significantly, may be a better option for the treatment of MODS patients.

Adult↗
PubMed2004

[The role of homeobox B2 gene in vascular endothelial proliferation and the protective effects of VEGF on the endothelia against radiation injury].

OBJECTIVE: To explore the role of HOXB2 gene in the proliferation of primary human umbilical vein endothelial cells (HUVECs) and the protective effects of VEGF on the endothelia against radiation injury. METHODS: HUVECs were isolated, cultured, subcultured and identified. (1) Liposome coated oligodeoxynucleotide (odn) and homeoboxB2 antisense oligodeoxyncleotide (HOXB2asodn) were prepared prepared in the concentrations of 0.25, 0.5, 1.0 and 2.5 mg/L for the stimulation of HUVEC. (3)H-TdR incorporation test and MTT method were employed to determine the proliferation activity of HUVECs after activation. The cell cycle analysis of HUVECs was determined by flow cytometry. The expression level of HOXB2mRNA within HUVECs was detected by RT-PCR (reverse transcription polymerase chain reaction). (2) HUVECs were separately treated with the addition of VEGF in concentration of 50 microg/L, by radiation in the dose of 6 Gy or 12 Gy (60)Co gamma gamma ray, or radiation with 12 Gy (60)Co gamma gamma ray followed by the addition of VEGF in dose of 50 microg/L. The cellular morphology was observed and the cellular proliferation activity was determined by MTT method. RESULTS: (1) The proliferation activity of HUVECs could be markedly inhibited by liposome coated HOXB2asodn in comparison to liposome-odn (P < 0.05 or 0.001), and the inhibition effect was positively correlated with the increase in asodn concentration. The cell ratio in S phase and the expression level of the HOXB2mRNA could be lowered by asodn in dose of 2.5 mg/L (P < 0.05 or 0.001). (2) Radiation by (60)Co gamma ray could lead to the nuclear enlargement, vacuolation in the cytoplasm, multiplicity of nucleus and nuclear swelling. The proliferative activity of HUVECs was increased from 0.365 +/- 0.047 and 0.487 +/- 0.022 without radiation to 0.557 +/- 0.042 and 0.648 +/- 0.021 24 and 48 hours after 6 Gy radiation However it was decreased to 0.263 +/- 0.038 and 0.306 +/- 0.024 (P < 0.01) after 12 Gy (60)Co gamma ray radiation. Nevertheless, the cell morphology was obviously improved and the proliferation was enhanced by the addition of VEGF after 12 Gy radiation. CONCLUSION: HOXB2 gene played important roles in the biological activities of HUVECs. Small dose (6 Gy) gamma-radiation could promote, but large dose (12 Gy) could decrease the mRNA expression of HOXB2 gene in HUVECs. In addition, VEGF could protect HUVECs against radiation injury.

Cell Proliferation↗
PubMed2004

[Effect of perindopril on renal interstitial fibrosis of hypertension in rats].

OBJECTIVE: To explore the effect of perindopril on renal interstitial fibrosis of spontaneously hypertensive rats and on the expression of transforming growth factor-beta1. METHODS: Spontaneously hypertensive rats at the age of 9 weeks were randomly assigned to 2 groups: Spontaneously hypertensive rats (SHR, vehicle once daily, n = 10) and Treament-SHR (T-SHR, perindopril, 4 mg/(kg x d), per day PO, n = 10). Wistar-Kyoto rats (WKY, n = 7) were served as controls. After 10 weeks of treatment, the serum concentration of TGF-beta1, collagen type I, III and TGF-beta1 in the renal interstitum and renal mRNA levels of TGF-beta1 were detected. RESULTS: There were no significant differences in the serum TGF-beta1 levels among the 3 groups (P > 0.05). Immunohistochemical studies revealed a significant interstitial accumulation of collagens I, III and TGF-beta1 in SHR compared with those in WKY (P < 0.01 or P < 0.05). These changes in SHR were significantly ameliorated by the administration of perindopril (P < 0.01 or P < 0.05). In SHR, renal TGF-beta1 mRNA expression was increased significantly compared with that in WKY (P < 0.01), but perindopril decreased it to the normal levels of WKY (P > 0.05). The increased expression of TGF-beta1 was blocked by perindopril. The expressions of collagens I and III in renal interstitum significantly correlated with the accumulation of TGF-beta1 in the renal (r = 0. 734, r = 0.762, respectively; P < 0.01). CONCLUSION: The tubulointerstitial fibrosis of spontaneously hypertensive rats is mediated by an increased level of TGF-beta1 in the renal tissue, and perindopril may decrease the expression of TGF-beta1 to ameliorate the tubulointerstitial fibrosis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Neuronal repellent Slit2 inhibits dendritic cell migration and the development of immune responses.

One of the essential functions of dendritic cells is to take up Ags in peripheral tissues and migrate into secondary lymphoid organs to present Ags to lymphocytes for the induction of immune responses. Although many studies have demonstrated that the migration of dendritic cells is closely associated with the development of immune responses, little is known about factors that inhibit dendritic cell migration and control the extent of immune responses to Ag stimulation. We show that Slit2, a neuronal repellent factor, is up-regulated in the skin by allergen sensitization and down-regulates the migration of Langerhans cells. The effect is mediated by direct interaction of Slit2 with cells that express a Slit-specific receptor, Robo1. Slit2-mediated inhibition of Langerhans cell migration results in suppression of contact hypersensitivity responses. These findings provide insights into a novel mechanism by which Slit2 functions as an anti-inflammatory factor for the initiation of immune responses.

Animals↗
PubMed2003

[Long term follow up of patients with knee osteoarthritis after high tibial osteotomy].

OBJECTIVE: To investigate the clinical result of knee osteoarthritis after high tibial osteotomy (HTO) in long term follow-up. METHODS: 107 patients of knee joint osteoarthritis performed with high tibial osteoarthritis between 1983 and 2000 was followed up. Standing anteroposterior radiograph of knee were taken for every patient. RESULTS: The clinical results of 137 knees (88%) were rated as good at 1 to 5 years follow-up. 21 knees were good at 5 to 10 years follow-up. And 5 knees were good at lest 10 years follow-up. Only one patient was done TKA 8 year after HTO. CONCLUSIONS: The patients done HTO show excellent clinical results in short time follow-up. And the results of most patients was maintained in intermediate and long-term follow-up. The internal fixition allow patients early activity and recover quickly.

Adult↗
PubMed2003

Inhibition of alpha-ketoglutarate dehydrogenase complex promotes cytochrome c release from mitochondria, caspase-3 activation, and necrotic cell death.

Mitochondrial dysfunction has been implicated in cell death in many neurodegenerative diseases. Diminished activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a key and arguably rate-limiting enzyme of the Krebs cycle, occurs in these disorders and may underlie decreased brain metabolism. The present studies used alpha-keto-beta-methyl-n-valeric acid (KMV), a structural analogue of alpha-ketoglutarate, to inhibit KGDHC activity to test effects of reduced KGDHC on mitochondrial function and cell death cascades in PC12 cells. KMV decreased in situ KGDHC activity by 52 +/- 7% (1 hr) or 65 +/- 4% (2 hr). Under the same conditions, KMV did not alter the mitochondrial membrane potential (MMP), as assessed with a method that detects changes as small as 5%. KMV also did not alter production of reactive oxygen species (ROS). However, KMV increased lactate dehydrogenase (LDH) release from cells by 100 +/- 4.7%, promoted translocation of mitochondrial cytochrome c to the cytosol, and activated caspase-3. Inhibition of the mitochondrial permeability transition pore (MPTP) by cyclosporin A (CsA) partially blocked this KMV-induced change in cytochrome c (-40%) and LDH (-15%) release, and prevented necrotic cell death. Thus, impairment of this key mitochondrial enzyme in PC12 cells may lead to cytochrome c release and caspase-3 activation by partial opening of the MPTP before the loss of mitochondrial membrane potentials.

Animals↗
PubMed2003

Retinoid receptor-dependent and independent biological activities of novel fenretinide analogues and metabolites.

Fenretinide (4-HPR) is a retinoid analogue with antitumor and chemopreventive activities. In addition to 4-HPR, there are several other new phenylretinamides bearing hydroxyl, carboxyl, or methoxyl residues on carbons 2, 3, and 4 of the terminal phenylamine ring [N-(2-hydroxyphenyl)retinamide (2-HPR), N-(3-hydroxyphenyl)retinamide, N-(2-carboxyphenyl)retinamide, N-(3-carboxyphenyl)retinamide, N-(4-carboxyphenyl)retinamide, and N-(4-methoxyphenyl)retinamide (4-MPR) ]. It is hypothesized that these agents can act independent of the nuclear retinoid receptor pathway. To test this hypothesis directly, we have analyzed the activity of these phenylretinamides in vitro on a panel of F9 murine embryonal carcinoma cell lines, which includes wild-type (F9-WT) and mutant cells that have disrupted genes for both retinoid X receptor alpha and retinoic acid receptor gamma retinoid receptors (F9-KO). The F9-KO cells lack almost all measurable response to all-trans-retinoic acid, the primary biologically active retinoid. Two distinct effects of retinamides were identified. The first is a rapid, dose-dependent induction of cell growth inhibition (reduced cell viability), and the second is a slower induction of differentiation and accumulation of cells in the G(1) phase of the cell cycle that was observed with a concentration of 1 micro M, for only those phenylretinamides bearing charged (hydroxyl or carboxyl) groups on the terminal phenylamine ring. The induction of differentiation and G(1) accumulation was only observed in the F9-WT cells, indicating that this effect is receptor-dependent. 4-MPR, a major metabolite of 4-HPR, lacks a charged group on the terminal phenylamine ring and did not induce retinoid receptor-dependent effects, but did induce cell growth inhibition. Thus, 4-MPR may play a role in the clinical activity of 4-HPR. This study further reveals the mechanism of action of these novel phenylretinamides and supports continued investigation into their development as chemopreventive drugs.

Animals↗
PubMed2003

Quantification of 5-HMF and dextrose in commercial aqueous dextrose solutions.

5-Hydroxymethylfurfural (5-HMF) is the major thermal decomposition product formed in aqueous dextrose solutions during sterilization and upon storage. Current compendial tests employ a spectrophotometric assay for 5-HMF and a separate assay based on optical rotation for dextrose. Efforts herein focused on identification of approaches to simultaneously quantify both 5-HMF and dextrose in aqueous solutions. Initial studies employed anion exchange chromatography with pulsed amperometric detection (PAD). These studies showed that the low anion exchange column loading capacity and concentration mismatch of dextrose and 5-HMF in typical commercial solutions makes simultaneous quantitation impractical at a single sample concentration. However, mixed modes of detection for each analyte using refractive index (RI) detection for dextrose and UV detection for 5-HMF proved viable for simultaneous quantitation. The performance of both approaches was evaluated and extremely high sensitivity for 5-HMF demonstrated (30-50 ppb). The formation of 5-HMF upon the forced thermal decomposition of dextrose was monitored and compared with results from the USP spectrophotometric assay.

Chromatography, High Pressure Liquid↗
PubMed2003

A gene-deleted adenoviral vector results in phenotypic correction of canine hemophilia B without liver toxicity or thrombocytopenia.

Many approaches for treating hemophilia via gene transfer have been attempted in large animal models but all have potential drawbacks. Recombinant adenoviral vectors offer high-efficiency transfer of an episomal vector but have been plagued by the cytotoxicity/immunogenicity of early-generation vectors that contain viral genes. In our current study, we have used a nonintegrating helper-dependent (HD) adenoviral vector for liver-directed gene transfer to achieve hemostatic correction in a dog with hemophilia B. We measured plasma canine factor IX (cFIX) concentrations at a therapeutic range for up to 2.5 months and normalization of the whole blood clotting time (WBCT) for about a month. This was followed by a decrease and stabilized partial correction for 4.5 months. Hepatic gene transfer of a slightly lower dose of the HD vector resulted in WBCTs that were close to normal for 2 weeks, suggesting a dose threshold effect in dogs. In sharp contrast to other studies using first- or second-generation adenoviral vectors, we observed no vector-related elevation of liver enzymes, no fall in platelet counts, and normal liver histology. Taken together, this study demonstrates that injection of an adenoviral HD vector results in complete but transient phenotypic correction of FIX deficiency in canine models with no detectable toxicity.

Adenoviridae↗
PubMed2003

Inhibition of hepatitis B virus in mice by RNA interference.

Hepatitis B virus (HBV) infection substantially increases the risk of chronic liver disease and hepatocellular carcinoma in humans. RNA interference (RNAi) of virus-specific genes has emerged as a potential antiviral mechanism. Here we show that RNAi can be applied to inhibit production of HBV replicative intermediates in cell culture and in immunocompetent and immunodeficient mice transfected with an HBV plasmid. Cotransfection with plasmids expressing short hairpin RNAs (shRNAs) homologous to HBV mRNAs induced an RNAi response. Northern and Southern analyses of mouse liver RNA and DNA showed substantially reduced levels of HBV RNAs and replicated HBV genomes upon RNAi treatment. Secreted HBV surface antigen (HBsAg) was reduced by 94.2% in cell culture and 84.5% in mouse serum, whereas immunohistochemical detection of HBV core antigen (HBcAg) revealed >99% reduction in stained hepatocytes upon RNAi treatment. Thus, RNAi effectively inhibited replication initiation in cultured cells and mammalian liver, showing that such an approach could be useful in the treatment of viral diseases.

Animals↗
PubMed2003

A general model for biosorption of Cd2+, Cu2+ and Zn2+ by aerobic granules.

Aerobic granules are microbial aggregates with a strong and compact structure. This study looked into the feasibility of aerobic granules as a novel type of biosorbent for the removal of individual Cd(2+), Cu(2+) and Zn(2+) from aqueous solution. Based on the thermodynamics of biosorption reaction, a general model was developed to describe the equilibrium biosorption of individual Cd(2+), Cu(2+) and Zn(2+) by aerobic granules. This model provides good insights into the thermodynamic mechanisms of biosorption of heavy metals. The model prediction was in good agreement with the experimental data obtained. It was further demonstrated that the Langmuir, Freundlich and Sips or Hill equations were particular cases of the proposed model. The biosorption capacity of individual Cd(2+), Cu(2+) and Zn(2+) on aerobic granules was 172.7, 59.6 and 164.5 mgg(-1), respectively. These values may imply that aerobic granules are effective biosorbent for the removal of Cd(2+), Cu(2+) and Zn(2+) from industrial wastewater.

Adsorption↗
PubMed2003

Pig cells that lack the gene for alpha1-3 galactosyltransferase express low levels of the gal antigen.

BACKGROUND: The major antigen recognized on pig tissue by primate antibodies is a terminal galalpha1-3gal carbohydrate structure (gal antigen) present on glycolipids and glycoproteins. The production of animals from somatic cells allows for the inactivation of specific genes. It is anticipated that the complete inactivation of the gene encoding alpha1-3 galactosyltransferase, the enzyme that synthesizes the galalpha1-3gal linkage, will result in loss of that antigen from pig organs and tissue and will provide a survival benefit in pig-to-primate xenotransplants. METHODS: Positive-negative selection was used to produce fetal-pig fibroblasts that were a heterozygous knockout (+/-) of the alpha1-3 galactosyltransferase gene. Nuclear transfer of these cells generated pig embryos and live born pigs with the appropriate genotype. Using a novel selection method with cells from (+/-) embryos, we produced homozygous (-/-) fetal-pig fibroblast cells. RESULTS: Southern blot analysis of the alpha1-3 galactosyltransferase gene showed that we had produced (+/-) pig embryos, (+/-) live born pigs, and (-/-) pig-fetal fibroblast cells. Fluorescence-activated cell sorter (FACS) analysis with some, but not all, mouse anti-gal monoclonal antibodies and sensitized human serum showed that (-/-) cells still synthesized the gal antigen at 1 to 2% of the level of control heterozygous cells. CONCLUSIONS: Fetal-pig fibroblasts homozygous for the knockout of the alpha1-3 galactosyltransferase gene appear to express low but detectable levels of the gal antigen.

Animals↗
PubMed2003

Gene array and protein expression profiles suggest post-transcriptional regulation during CD8+ T cell differentiation.

Peripheral CD8(+) T cells circulate in a quiescent naive state until they are primed by specific antigen and differentiate into effector cells. In the effector state, CD8(+) T cells acquire cytolytic activity and produce increased levels of cytokines such as interferon-gamma. They also exhibit increased T cell receptor sensitivity, decreased CD28 dependence, and become inhibitable by CTLA-4 and other negative regulatory pathways. We hypothesized that one mechanism by which these two states are regulated is via differential expression of specific genes. To this end, basal gene expression profiles of naive and effector 2C TCR transgenic x RAG2(-/-) CD8(+) T cells were analyzed using Affymetrix arrays representing 11,000 genes. Of the 177 differentially expressed known genes, 68 were expressed at higher levels in effector cells, but 109 were more abundant in naive cells, supporting the notion that the naive state is not passive. Expression of genes related to metabolism, actin cytoskeletal dynamics, and effector function increased with priming, whereas expression of putative anti-proliferative genes decreased. Semiquantitative reverse transcription-PCR was utilized as a secondary validation for selected transcripts, and Western blot analysis was used to examine protein expression for molecules of interest. Surprisingly, for 24 genes examined, 12 showed discordant protein versus mRNA expression. In summary, our study indicates that: 1) not only does the expression of some genes in naive CD8(+) T cells become up-regulated upon priming, but the expression of other genes is down-regulated as well and 2) the complexities of T cell differentiation include regulation at the post-transcriptional level.

Animals↗
PubMed2003

Optimization of cis-acting elements for gene expression from nonviral vectors in vivo.

While naked DNA gene transfer in vivo usually results in transient gene expression, in some cases long-term transgene expression can be achieved. Here we demonstrate that cis-acting DNA elements flanking the transgene expression cassette and components in the plasmid backbone can significantly influence expression levels from nonviral vectors. To demonstrate this, we administered our most robust human coagulation factor IX (hFIX) expression cassette placed in two different plasmid backbones, into the livers of mice, by hydrodynamic transfection. We found that placing the expression cassette within a minimal plasmid vector pHM5, a modified version of pUC19, resulted in 10 times higher serum hFIX expression levels (up to 20000 ng/ml, 400% of normal hFIX serum levels), compared to a pBluescript backbone. To optimally increase expression levels from a nonviral vector, we added matrix attachment regions (MARs) as cis-acting DNA elements flanking the hFIX expression cassette. We detected five fold higher hFIX expression levels in vivo for up to 1-year posttransfection from a vector that contained the chicken MAR from the lysozyme locus. Together, the present work demonstrates that in addition to the transgene expression cassette, cis-acting DNA elements within and outside of the plasmid backbone need to be evaluated to achieve optimal expression levels in a nonviral gene therapy approach.

Animals↗
PubMed2003

The in vitro and in vivo effects of anti-galactose antibodies on endothelial cell activation and xenograft rejection.

We have previously produced a series of antigalactose (anti-Gal) hybridomas and characterized their heavy chain gene usage. Here we have quantified the affinity of these Abs for the alpha-Gal epitope and characterized their in vitro effects on endothelial cell activation and apoptosis. We report that anti-Gal mAbs derived from Gal(-/-) mice show a range of affinity for the alpha-Gal epitope, and that affinity was generally increased as the V(H) gene usage transitioned from germline sequences to sequences exhibiting somatic maturation. Despite an 85-fold range in affinity, all the anti-Gal mAbs examined induced alpha-Gal-specific endothelial cell activation, and after prolonged exposure induced endothelial cell apoptosis in a complement-independent manner. Only murine anti-Gal mAbs of the IgM or IgG3 subclass, but not IgG1, were effective at initiating complement-dependent cell lysis. Using a novel rat to mouse xenograft model, we examined the in vivo ability of these mAbs to induce xenograft rejection and characterized the rejection using histology and immunohistochemistry. Infusion of complement-fixing IgG3 mAbs resulted in either hyperacute rejection or acute vascular rejection of the xenograft. Surprisingly, infusion of an equal amount of a high affinity anti-Gal IgG1 mAb, that fixed complement poorly also induced a rapid xenograft rejection, which we have labeled very acute rejection. These studies emphasize the importance of in vivo assays, in addition to in vitro assays, in understanding the role of anti-Gal IgG-mediated tissue injury and xenograft rejection.

Animals↗
PubMed2003

Inhibition of the alpha-ketoglutarate dehydrogenase complex alters mitochondrial function and cellular calcium regulation.

Mitochondrial dysfunction occurs in many neurodegenerative diseases. The alpha-ketoglutarate dehydrogenase complex (KGDHC) catalyzes a key and arguably rate-limiting step of the tricarboxylic acid cycle (TCA). A reduction in the activity of the KGDHC occurs in brains and cells of patients with many of these disorders and may underlie the abnormal mitochondrial function. Abnormalities in calcium homeostasis also occur in fibroblasts from Alzheimer's disease (AD) patients and in cells bearing mutations that lead to AD. Thus, the present studies test whether the reduction of KGDHC activity can lead to the alterations in mitochondrial function and calcium homeostasis. alpha-Keto-beta-methyl-n-valeric acid (KMV) inhibits KGDHC activity in living N2a cells in a dose- and time-dependent manner. Surprisingly, concentration of KMV that inhibit in situ KGDHC by 80% does not alter the mitochondrial membrane potential (MMP). However, similar concentrations of KMV induce the release of cytochrome c from mitochondria into the cytosol, reduce basal [Ca(2+)](i) by 23% (P<0.005), and diminish the bradykinin (BK)-induced calcium release from the endoplasmic reticulum (ER) by 46% (P<0.005). This result suggests that diminished KGDHC activities do not lead to the Ca(2+) abnormalities in fibroblasts from AD patients or cells bearing PS-1 mutations. The increased release of cytochrome c with diminished KGDHC activities will be expected to activate other pathways including cell death cascades. Reductions in this key mitochondrial enzyme will likely make the cells more vulnerable to metabolic insults that promote cell death.

Calcium↗