Biomedical subjects

L Wu

Publications and source records attributed to L Wu.

At least 19 recordsLinked to original sources

PubMed2006

Non-viral ex vivo transduction of human hepatocyte cells to express factor VIII using a human ribosomal DNA-targeting vector.

BACKGROUND: In gene therapy, one of the most important issues is the choice of the vectors. pHrneo is a human-derived vector previously constructed by our group, which can target a foreign gene into a human ribosomal DNA (hrDNA) locus. METHODS AND RESULTS: In this study, we inserted an expression cassette of reconstructive hFVIII (hFVIII-BDDAK39) to pHrneo to construct a targeting vector: pHrneo-BDDAK39. Through electroporation of pHrneo-BDDAK39 into HL7702 cells (human hepatocyte), we identified the homologous recombinants using polymerase chain reaction, and tested the expression of hFVIII-BDDAK39 located at the hrDNA locus. The hFVIII-BDDAK39 was successfully targeted into the hrDNA locus of HL7702 by pHrneo-BDDAK39, and the efficiency of site-specific integration was 1.1 x 10(-5). The hFVIII-BDDAK39 at the hrDNA locus of HL7702 was found to be able to express efficiently (4.3 +/- 0.9 ng 10(-6) cells 24 h(-1)). CONCLUSION: It has been indicated that the targeting vector pHrneo-BDDAK39 can be used in gene therapy for hemophilia A.

Cell Line↗

PubMed2006

Odontogenic tumours: a retrospective study of 1642 cases in a Chinese population.

A total of 1642 odontogenic tumour cases retrieved from the files of the College of Stomatology, Sichuan University, China were retrospectively analyzed for gender, age, tumour site and relative frequency of various types, and the data compared with that of previous reports. The final diagnosis in each case was based on the WHO 2005 histopathological classification of odontogenic tumours. Of these tumours 1592 (97.0%) were benign and 50 (3.0%) were malignant. Ameloblastoma (40.3%) was the most frequent type, followed by keratocystic odontogenic tumour (35.8%), odontoma (4.7%) and odontogenic myxoma (4.6%). The mean age of the patients was 32.1, with a wide range (3-84 years). The male-female ratio and maxilla-mandible ratio were 1.4:1 and 1:4.0, respectively. Ameloblastoma and keratocystic odontogenic tumours, important indications of extensive surgical procedures, are not considered rare in this Chinese population, whereas odontoma is uncommon.

Adolescent↗

PubMed2006

Constitutive nitric oxide acting as a possible intercellular signaling molecule in the initiation of radiation-induced DNA double strand breaks in non-irradiated bystander cells.

The initiation and propagation of the early processes of bystander signaling induced by low-dose alpha-particle irradiation are very important for understanding the underlying mechanism of the bystander process. Our previous investigation showed that the medium collected from cell culture exposed to low-dose alpha-particle rapidly induced phosphorylated form of H2AX protein foci formation among the non-irradiated medium receptor cells in a time-dependent manner. Using N(G)-methyl-L-arginine, 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate and N(omega)-nitro-L-arginine (L-NNA) treatment before exposure to 1 cGy alpha-particle, we showed in the present study that nitric oxide (NO(*)) produced in the irradiated cells was important and necessary for the DNA double strand break inducing activity (DIA) of conditioned medium and the generation of NO(*) in irradiated confluent AG1522 cells is in a time-dependent manner and that almost all NO(*) was generated within 15 min post-irradiation. Concurrently, the kinetics of NO(*) production in the medium of irradiated cells after irradiation was rapid and in a time-dependent manner as well, with a maximum yield observed at 10 min after irradiation with electron spin resonance analysis. Furthermore, our results that 7-Nitroindazole and L-NNA, but not aminoguanidine hemisulfate, treatment before exposure to 1 cGy alpha-particle significantly decrease the DIA of the conditioned medium suggested that constitutive NO(*) from the irradiated cells possibly acted as an intercellular signaling molecule to initiate and activate the early process (<or=30 min) of bystander response after low-dose irradiation.

Alpha Particles↗

PubMed2006

Direct cancer tissue proteomics: a method to identify candidate cancer biomarkers from formalin-fixed paraffin-embedded archival tissues.

Successful treatment of multiple cancer types requires early detection and identification of reliable biomarkers present in specific cancer tissues. To test the feasibility of identifying proteins from archival cancer tissues, we have developed a methodology, termed direct tissue proteomics (DTP), which can be used to identify proteins directly from formalin-fixed paraffin-embedded prostate cancer tissue samples. Using minute prostate biopsy sections, we demonstrate the identification of 428 prostate-expressed proteins using the shotgun method. Because the DTP method is not quantitative, we employed the absolute quantification method and demonstrate picogram level quantification of prostate-specific antigen. In depth bioinformatics analysis of these expressed proteins affords the categorization of metabolic pathways that may be important for distinct stages of prostate carcinogenesis. Furthermore, we validate Wnt-3 as an upregulated protein in cancerous prostate cells by immunohistochemistry. We propose that this general strategy provides a roadmap for successful identification of critical molecular targets of multiple cancer types.

Amino Acid Sequence↗

PubMed2006

Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer's disease in a sex-dimorphic pattern.

Administration of non-steroidal anti-inflammatory agents reduces the risk of developing Alzheimer's disease in normal aging populations, an effect that may occur from inhibition of the cyclooxygenases, the rate-limiting enzymes in the formation of prostaglandins. In this study, we investigated whether increased activity of cyclooxygenase-2 (COX-2), the inducible isoform of cyclooxygenase, potentiates disease progression in a transgenic mouse model of Alzheimer's disease. To study the functional effects of COX-2 activity, male and female bigenic mice (amyloid precursor protein with Swedish mutation [APPswe]-presenilin-1 protein with deletion of exon 9 [PS1dE9] and trigenic COX-2/APPswe-PS1dE9) were behaviorally tested +/-administration of the selective COX-2 inhibitor celecoxib. Behavioral testing included a three-trial Y maze that measures spatial working and recognition memories and an open field task that tested levels of hyperactivity. Overexpression of COX-2 in APPswe-PS1dE9 mice resulted in specific deficits in spatial working memory in female but not male mice. These sex-specific deficits were abolished by pharmacological inhibition of COX-2 activity. Importantly, COX-2-associated deficits were dependent on co-expression of all three transgenes since COX-2 single transgenic and APPswe-PS1dE9 bigenic mice showed normal memory. Quantification of amyloid plaque load and total Abeta 40 and 42 peptides did not reveal significant differences in trigenic versus bigenic mice treated with either vehicle or celecoxib. Taken together, these data indicate an interaction between the effects of COX-2 and Abeta peptides on cognition that occurs in a sex-specific manner in the absence of significant changes in amyloid burden. These findings suggest that pathological activation of COX-2 may potentiate the toxicity of Abeta peptides, particularly in females, without significantly affecting Abeta accumulation.

Alzheimer Disease↗

PubMed2006

The clinical value of hepatocyte growth factor and its receptor--c-met for liver cancer patients with hepatectomy.

BACKGROUND: To study the dynamic change of hepatocyte growth factor after hepatectomy in patients with primary liver cancer, and to analyse the prognostic value of hepatocyte growth factor and c-met for these patients. METHODS: Thirty-one consecutive patients undergoing partial hepatectomy for liver cancer were studied. Serum hepatocyte growth factor level was determined by using enzyme-linked immunosorbent assay kit before and after operation, respectively. C-met protein and MRNA expressions in cancerous and paracancerous tissues were examined by immunohistochemical and RT-PCR methods, respectively. The correlations between clinical-pathologic parameters and the expressions of hepatocyte growth factor in serum and c-met in cancerous tissues were analysed, respectively. RESULTS: Liver cancer patients had a significantly higher level of serum hepatocyte growth factor than normal controls (1.0424+/-0.498 ng/ml versus 0.685+/-0.115 ng/ml, p=0.008). Serum hepatocyte growth factor level was positively affected by tumour size, node cirrhosis, portal vein tumour thrombi, cholangiocarcinoma (including combined hepatocellular carcinoma), poorly differentiated hepatocellular carcinoma and tumour recurrence or metastases. After hepatectomy, serum hepatocyte growth factor level peaked on the third postoperative day, and then declined, but did not return to normal level on the postoperative day 10. From the preoperative day to postoperative day 10, the level of serum hepatocyte growth factor had a decrease of percent (85.33+/-10.2%) in the group with large tumours (>5 cm), but an elevation of percent (121.9+/-10.3%) in the group with small tumours (<or=5 cm). From the preoperative day to postoperative day 3, the level of serum hepatocyte growth factor had a higher elevation in the group with major resection than in the group with local resection (p=0.016). Moderately or strongly positive expression of c-met protein was observed in 27 cancerous regions (27/31), and only in 5 paracancerous regions. The intensive expression of c-met MRNA was 100% (31/31) detectable in the cancerous tissues, but only 22.6% (7/31) in the paracancerous tissues. C-met protein expression in cancerous tissues was correlated with portal vein tumour thrombi, cholangiocarcinoma and tumour recurrence or metastases, and the expression in paracancerous tissues was correlated with node cirrhosis. No significant correlation was observed between the hepatocyte growth factor in serum and c-met in cancerous tissues. CONCLUSION: The over-expressions of the hepatocyte growth factor and c-met indicates an adverse prognosis for patients with liver cancer. The sustained high level of serum hepatocyte growth factor after hepatectomy may be a factor related to early tumour recurrence and metastasis. Liver regeneration may be a main factor leading to high level of serum hepatocyte growth factor in early postoperative stage.

Adult↗

PubMed2006

Structure determination and relative properties of novel noncentrosymmetric borates MM'4(BO3)3 (M = Na, M' = Ca and M = K, M' = Ca, Sr).

A series of novel noncentrosymmetric borates, MM'4(BO3)3 (M = Na, M' = Ca; M = K, M' = Ca, Sr), have been successfully synthesized via a standard solid-state reaction. The crystal structures have been determined by the SDPD (structure determination from powder diffraction) method. They crystallize in the noncentrosymmetric space group Ama2 with the following lattice parameters: a = 10.68004(11) A, b = 11.28574(11) A, c = 6.48521(6) A for NaCa4(BO3)3; a = 10.63455(10) A, b = 11.51705(11) A, c = 6.51942(6) A for KCa4(BO3)3; and a = 11.03843(8) A, b = 11.98974(9) A, c = 6.88446(5) A for KSr4(BO3)3. The fundamental building units are isolated BO3 anionic groups. Their second harmonic generation (SHG) coefficients were one-half (NaCa4(BO3)3), one-third (KCa4(BO3)3), and two-thirds (KSr4(BO3)3) as large as that of KH2PO4 (KDP). The infrared and UV-vis spectra of the three compounds are discussed. Moreover, a comparison of the structures of these novel compounds and three other novel cubic compounds with the same formula, MM'4(BO3)3 (M = Li, M' = Sr; M = Na, M' = Sr, Ba), is presented here.

Journal Article↗

PubMed2006

Gene expression profiles in hepatitis C virus (HCV) and HIV coinfection: class prediction analyses before treatment predict the outcome of anti-HCV therapy among HIV-coinfected persons.

Therapy for hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients results in modest cure rates. Gene expression patterns in peripheral blood mononuclear cells from 29 patients coinfected with HIV and HCV were used to predict virological response to therapy for HCV infection. Prediction analysis using pretherapy samples identified 79 genes that correctly classified all 10 patients who did not respond to therapy, 8 of 10 patients with a response at the end of treatment, and 7 of 9 patients with sustained virological response (86% overall). Analysis of 17 posttreatment samples identified 105 genes that correctly classified all 9 patients with response at the end of treatment and 7 of 8 patients with sustained virological response (94% overall). Failure of anti-HCV therapy was associated with elevated expression of interferon-stimulated genes. Gene expression patterns may provide a tool to predict anti-HCV therapeutic response.

Adult↗

PubMed2006

Functional variants of antioxidant genes in smokers with COPD and in those with normal lung function.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is predominantly the consequence of chronic smoking exposure, but its development may be influenced by genetic variants that affect lung remodelling, inflammation, and defence from oxidant stress. A study was undertaken to determine whether genetic variants within genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase may be associated with the development of impaired lung function. METHODS: In a case-control study, the allele and genotype frequencies of functional polymorphisms from SOD1 (CuZnSOD), SOD2 (MnSOD), SOD3 (extracellular SOD), and catalase (CAT) were compared in chronic smokers with normal lung function (resistant smokers) and in those with COPD. RESULTS: Significantly higher frequencies of the G allele and CG/GG genotype of the 213 SOD3 polymorphism were found in resistant smokers (odds ratios (ORs) 4.3 (95% CI 1.5 to 13.3) and 4.2, 95% CI 1.4 to 13.3), Bonferroni corrected p = 0.02 and p = 0.02, respectively) than in those with COPD. There were no differences between the COPD and resistant smokers for the SOD1, SOD2, or CAT polymorphisms tested. CONCLUSIONS: The 213Gly variant of the SOD3 gene may, through antioxidant or anti-inflammatory effects, confer a degree of resistance in some smokers to the development of COPD.

Adult↗

PubMed2006

Gender-related differences in advanced glycation endproducts, oxidative stress markers and nitric oxide synthases in rats.

An age- and blood pressure-associated increase in methylglyoxal (MG) and MG-induced advanced glycation endproducts (AGEs), including N(epsilon)-carboxyethyl-lysine (CEL) and N(epsilon)-carboxymethyl-lysine (CML), in the kidney of spontaneously hypertensive rats (SHR) has been shown. In the present study, gender-related changes in AGEs and nitric oxide synthase were investigated in Sprague-Dawley (SD) and stroke-prone SHR (SHRsp) rats. Immunohistochemical analyses were conducted on kidneys from 24-week-old male and female SD rats as well as SHRsp. The systolic blood pressure of SHRsp was significantly higher than that of SD rats. Male SD rats had more intense kidney staining for CEL than female SD rats. Both male and female SHRsp had more marked CEL and CML staining localized to kidney tubules, as opposed to SD rats. Female rats showed more staining in glomerular vessels than male rats in both SD and SHRsp. Nuclei containing nuclear factor-kappaB (NF-kappaB) p65 and activated macrophages were seen in the kidney from SHRsp, not so much in SD rats, localized to renal tubules in male and glomerular vessels in female SHRsp. A higher protein level of NF-kappaB p65 was found in SHRsp than in SD rats. SD rats had more intense kidney neuronal nitric oxide synthase staining than SHRsp. The intensity of inducible nitric oxide synthase staining was significantly higher in SHRsp than in SD rats, with no gender differences in either strain. SHRsp and male rats exhibited higher AGEs and oxidative stress than SD and female rats, respectively. These differences might partly account for the development of hypertension in SHRsp and the higher vulnerability of male animals to renal pathology.

Animals↗

PubMed2006

Increased HO-1 expression and decreased iNOS expression in the hippocampus from adult spontaneously hypertensive rats.

Brain expression of heme oxygenase (HO) and nitric oxide synthase (NOS) in hypertension may participate in the pathogenesis of hypertension-related neuronal disorders, such as vascular dementia. In the present study, expression levels of HO and NOS in spontaneously hypertensive rats (SHR) were investigated using Western immunoblotting assay. Expression level of inducible HO-1 in hippocampus of 4-wk prehypertensive SHR was about twofold of that in age-matched Sprague-Dawley (SD) rats (p < 0.01). In 23-wk SHR with fully developed hypertension, hippocampal HO-1 level was significantly greater than that of age-matched SD rats (p < 0.05), but not different from 4-wk SHR. There was no difference in expression levels of hippocampal HO-2 between SHR and SD rats at different ages. Total enzymatic activity of hippocampal HO was significantly greater in 23-wk SHR than in age-matched SD rats or 4-wk SD/SHR (p < 0.01). Although hippocampal expression of nNOS protein was relatively unchanged, iNOS expression in 23-wk SHR was about fourfold lower than that in age-matched SD rats and 4-wk SD/SHR (p < 0.01). Total enzymatic activity of hippocampal NOS was significantly lower in 23-wk SHR than in age-matched SD rats or 4-wk SD/SHR (p < 0.01). Significantly suppressed Morris water maze performance was found in 23-wk SHR in comparison with age-matched SD rats. Because SHR has been used as a model of vascular dementia and hippocampus is essential for spatial learning and memory, understanding of altered HO/CO and NOS/NO systems in the hippocampus of adult SHR may shed light on the pathogenic development of memory deficits associated with vascular dementia.

Aging↗

PubMed2005

An investigation of job satisfaction, organizational commitment and role conflict and ambiguity in a sample of Chinese undergraduate nursing students.

This study aimed to explore the relationships between job satisfaction and organizational commitment, role conflict and ambiguity, and demographic variables associated with retention of nurses within the Chinese healthcare workforce. A hypothetical model derived from a review of research studies investigating relationships between these variables was tested in a cross-sectional questionnaire survey of all the final year nursing students in a medical university in China. Seventy-one out of the total sample of 75 final year nursing students completed the questionnaire, producing a response rate of 95%. Descriptive and inferential statistical analysis of the data revealed a positive relationship between job satisfaction and organizational commitment, and a negative relationship between job satisfaction and role conflict and ambiguity. These results largely support the hypothesised associations between variables found in research studies derived mainly from samples of Western qualified nurses. However, contrary to previous studies, the findings suggest that aspirations to work in a clinical post are associated with high job satisfaction, and degree level student nurses have relatively high job satisfaction. The main implications for nursing education and practice are that educators and clinical mentors should work collaboratively to reduce the gap between theory and practice, specifically to improve the quality of student nurses' clinical experience in China and elsewhere. Positive clinical placement experience is related to high job satisfaction, and so, potentially, to improved retention. Future studies are needed which investigate changes in job satisfaction and other related variables over time, which have student nurse samples that are sufficient to enable the predictive value of these variables on retention in the healthcare workforce to be investigated.

Adult↗

PubMed2005

Inhaled corticosteroids and mortality in chronic obstructive pulmonary disease.

BACKGROUND: Clinical studies suggest that inhaled corticosteroids reduce exacerbations and improve health status in chronic obstructive pulmonary disease (COPD). However, their effect on mortality is unknown. METHODS: A pooled analysis, based on intention to treat, of individual patient data from seven randomised trials (involving 5085 patients) was performed in which the effects of inhaled corticosteroids and placebo were compared over at least 12 months in patients with stable COPD. The end point was all-cause mortality. RESULTS: Overall, 4% of the participants died during a mean follow up period of 26 months. Inhaled corticosteroids reduced all-cause mortality by about 25% relative to placebo. Stratification by individual trials and adjustments for age, sex, baseline post-bronchodilator percentage predicted forced expiratory volume in 1 second, smoking status, and body mass index did not materially change the results (adjusted hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.55 to 0.96). Although there was considerable overlap between subgroups in terms of effect sizes, the beneficial effect was especially noticeable in women (adjusted HR 0.46; 95% CI 0.24 to 0.91) and former smokers (adjusted HR 0.60; 95% CI 0.39 to 0.93). CONCLUSIONS: Inhaled corticosteroids reduce all-cause mortality in COPD. Further studies are required to determine whether the survival benefits persist beyond 2-3 years.

Administration, Inhalation↗

PubMed2005

Structure determination and relative properties of novel cubic borates MM'4(BO3)3 (M = Li, M' = Sr; M = Na, M' = Sr, Ba).

A series of novel borates, MM'4(BO3)3 (M = Li, M' = Sr; M = Na, M' = Sr, Ba), have been successfully synthesized by standard solid-state reaction. The crystal structures have been determined from powder X-ray diffraction data. They crystallize in the cubic space group Iad with large lattice parameters: a = 14.95066(5) A for LiSr4(BO3)3, a = 15.14629(6) A for NaSr4(BO3)3, and a = 15.80719(8) A for NaBa4(BO3)3. The structure was built up from 64 small cubic grids, in which the M' atoms took up the corner angle and the BO3 triangles or MO6 cubic octahedra filled in the interspaces. The isolated [BO3]3- anionic groups are perpendicular to each other, distributed along three 100 directions. The anisotropic polarizations were counteracting, forming an isotropic crystal. Sr and Ba atoms were found to be completely soluble in the solid solution NaSr(4-)xBax(BO3)3 (0 < or = x < or = 4). The photoluminescence of samples doped with the ions Eu2+ and Eu3+ was studied, and effective yellow and red emission was detected, respectively. The results are consistent with the crystallographic study. The DTA and TGA curves of them show that they are chemically stable and congruent melting compounds.

Journal Article↗

PubMed2005

Structural analysis of a set of proteins resulting from a bacterial genomics project.

The targets of the Structural GenomiX (SGX) bacterial genomics project were proteins conserved in multiple prokaryotic organisms with no obvious sequence homolog in the Protein Data Bank of known structures. The outcome of this work was 80 structures, covering 60 unique sequences and 49 different genes. Experimental phase determination from proteins incorporating Se-Met was carried out for 45 structures with most of the remainder solved by molecular replacement using members of the experimentally phased set as search models. An automated tool was developed to deposit these structures in the Protein Data Bank, along with the associated X-ray diffraction data (including refined experimental phases) and experimentally confirmed sequences. BLAST comparisons of the SGX structures with structures that had appeared in the Protein Data Bank over the intervening 3.5 years since the SGX target list had been compiled identified homologs for 49 of the 60 unique sequences represented by the SGX structures. This result indicates that, for bacterial structures that are relatively easy to express, purify, and crystallize, the structural coverage of gene space is proceeding rapidly. More distant sequence-structure relationships between the SGX and PDB structures were investigated using PDB-BLAST and Combinatorial Extension (CE). Only one structure, SufD, has a truly unique topology compared to all folds in the PDB.

Databases, Protein↗

PubMed2005

Synthesis and ab initio X-ray powder diffraction structure of the new alkali and alkali earth metal borate NaCa(BO3).

A sodium calcium borate, NaCaBO3, has been synthesized by the solid-state reaction method and the structure solved from X-ray powder diffraction data. The compound crystallizes in space group Pmmn and has a desired structure type containing isolated planar BO3(3-) anions. Mixed occupancy is found to exist in the Ca site, with partial replacement by Na. One Ca/Na mixed atom and one Na atom are at sites with mm2 symmetry, and a second Ca/Na mixed atom, an Na atom, two B and two O atoms are on mirror planes.

Journal Article↗

PubMed2005

Excision of a selectable marker in transgenic rice (Oryza sativa L.) using a chemically regulated Cre/loxP system.

Removal of a selectable marker gene from genetically modified (GM) crops alleviates the risk of its release into the environment and hastens the public acceptance of GM crops. Here we report the production of marker-free transgenic rice by using a chemically regulated, Cre/loxP-mediated site-specific DNA recombination in a single transformation. Among 86 independent transgenic lines, ten were found to be marker-free in the T0 generation and an additional 17 lines segregated marker-free transgenic plants in the T1 generation. Molecular and genetic analyses indicated that the DNA recombination and excision in transgenic rice were precise and the marker-free recombinant T-DNA was stable and heritable.

Base Sequence↗

PubMed2005

Role of activated astrocytes in neuronal damage: potential links to HIV-1-associated dementia.

HIV-1-associated dementia (HAD) is an important complication of HIV-1 infection. Reactive astrogliosis is a key pathological feature in HAD brains and in other central nervous system (CNS) diseases. Activated astroglia may play a critical role in CNS inflammatory diseases such as HAD. In order to test the hypothesis that activated astrocytes cause neuronal injury, we stimulated primary human fetal astrocytes with HAD-relevant pro-inflammatory cytokine IL-1beta. IL-1beta-activated astrocytes induced apoptosis and significant changes in metabolic activity in primary human neurons. An FITC-conjugated pan-caspase inhibitor peptide FITC-VAD-FMK was used for confirming caspase activation in neurons. IL-1beta activation enhanced the expression of death protein FasL in astrocytes, suggesting that FasL is one of the potential factors responsible for neurotoxicity observed in HAD and other CNS diseases involving glial inflammation. Our data presented here add to the developing picture of role of activated glia in HAD pathogenesis.

Analysis of Variance↗