Biomedical subjects

W Li

Publications and source records attributed to W Li.

At least 19 recordsLinked to original sources

PubMed2007

Effect of placement of calcium sulphate when used for the repair of furcation perforations on the seal produced by a resin-based material.

AIM: To evaluate the sealing ability of calcium sulphate when used under composite resin for the repair of furcation perforations having different diameters. METHODOLOGY: Perforations of different diameter were created in the floors of pulp chambers in 60 extracted human molar teeth with either a number 3 (1 mm diameter) or 5 (1.5 mm diameter) round bur. The specimens of each group were divided into four sub-groups which were repaired with composite resin either alone or in combination with calcium sulphate that created an artificial floor (15 teeth group(-1)). Eight teeth without furcation perforations served as negative controls. In the leakage detection device, 1 mol L(-1) glucose solution was forced under a pressure of 1.5 KPa from the crown towards the pulp chamber floor. The concentration of leaked glucose was measured at 1, 2, 4, 7, 10, 15 and 20 days using a glucose oxidase method and the data evaluated using the rank sum test. RESULTS: The specimens with larger perforations repaired with composite resin alone had significantly more leakage (P < 0.05). Using calcium sulphate as an artificial floor significantly decreased leakage of smaller perforations (P < 0.05). In groups repaired with calcium sulphate under composite resin, leakage in smaller perforations was markedly lower than that in larger ones (P < 0.05). No significant difference was found between the specimens with 1 or 1.5 mm perforations repaired with resin alone (P > 0.05). CONCLUSIONS: Calcium sulphate significantly improved the sealing ability of 1 mm perforations repaired with composite resin but not for 1.5 mm perforations.

Calcium Sulfate↗

PubMed2006

Lysophosphatidic acid downregulates tissue inhibitor of metalloproteinases, which are negatively involved in lysophosphatidic acid-induced cell invasion.

Ovarian cancer is a highly metastatic disease. Lysophosphatidic acid (LPA) levels are elevated in ascites from ovarian cancer patients, but its potential role in ovarian cancer metastasis has just begun to be revealed. In this work, we show that LPA stimulates invasion of primary ovarian cancer cells, but not ovarian epithelial or borderline ovarian tumor cells, although these benign cells indeed respond to LPA in cell migration. We have found that LPA downregulates tissue inhibitor of metalloproteinases (TIMPs). TIMP2 and TIMP3 play functional role in LPA-induced invasion as negative regulators. G(i) protein, phosphatidylinositol-3 kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), cytosolic phospholipase A(2) and urokinase type plasminogen activator (uPA) are required for LPA-induced cells invasion. TIMP3 may affect two independent downstream targets, vascular endothelial growth factor receptor and p38 MAPK. In vivo, LPA stimulates tumor metastasis in an orthotopic ovarian tumor model, which can be inhibited by a PI3K inhibitor, LY294002. In summary, LPA is likely a key component for promoting ovarian metastasis in vivo. LPA downregulates TIMP3, which may have targets other than metalloproteinases. Our in vivo metastasis mouse model is useful for studying the efficacy of therapeutic regimes of ovarian cancer.

Animals↗

PubMed2006

Modelling of fracture behaviour in biomaterials.

One of the most frequent causes of degradation and failure of quasi-brittle biomaterials is fracture. Mechanical breakdown, even when not catastrophic, is of particular importance in the area of biomaterials, as there are many clinical situations where it opens the path for biologically mediated failures. Over the past few decades the materials/biomaterials community has developed a number of numerical models, but only with limited incorporation of brittle failure phenomena. This article investigates the ability of a non-linear elastic fracture mechanics (NLEFM) model to reliably predict failure of biomaterials with a specific focus on the clinical settings of restorative dentistry. The approach enables one to predict fracture initiation and propagation in a complex biomechanical status based on the intrinsic material properties of the components. In this paper, we consider five examples illustrating the versatility of the present approach, which range from the failure of natural biomaterials, namely dentine and enamel, to a restored tooth, a three unit all ceramic bridge structure and contact-induced damage in the restorative layered materials systems. It is anticipated that this approach will have ramifications not only to model fracture events but also for the design and optimisation of the mechanical properties of biomaterials for specific clinically determined requirements.

Biocompatible Materials↗

PubMed2006

An optical supernova associated with the X-ray flash XRF 060218.

Long-duration gamma-ray bursts (GRBs) are associated with type Ic supernovae that are more luminous than average and that eject material at very high velocities. Less-luminous supernovae were not hitherto known to be associated with GRBs, and therefore GRB-supernovae were thought to be rare events. Whether X-ray flashes--analogues of GRBs, but with lower luminosities and fewer gamma-rays--can also be associated with supernovae, and whether they are intrinsically 'weak' events or typical GRBs viewed off the axis of the burst, is unclear. Here we report the optical discovery and follow-up observations of the type Ic supernova SN 2006aj associated with X-ray flash XRF 060218. Supernova 2006aj is intrinsically less luminous than the GRB-supernovae, but more luminous than many supernovae not accompanied by a GRB. The ejecta velocities derived from our spectra are intermediate between these two groups, which is consistent with the weakness of both the GRB output and the supernova radio flux. Our data, combined with radio and X-ray observations, suggest that XRF 060218 is an intrinsically weak and soft event, rather than a classical GRB observed off-axis. This extends the GRB-supernova connection to X-ray flashes and fainter supernovae, implying a common origin. Events such as XRF 060218 are probably more numerous than GRB-supernovae.

Journal Article↗

PubMed2006

Microsatellite typing for DRB1 alleles: application to the analysis of HLA associations with rheumatoid arthritis.

The current methods for molecular typing of HLA-DR alleles incur a substantial financial burden when performing large population studies. In the current study, we aimed to provide much less expensive typing approach with high predictability for DRB1 genotype. We have used a panel of three microsatellite markers in the class II region (D6S2666, D6S2665 and D6S2446) for genotyping and haplotype reconstruction in a total of 1687 Caucasian (1313 RA patients and 374 controls) and 1364 Korean individuals (744 RA patients and 620 controls), all of whom were previously genotyped for DRB1. We found that a total of 88.4 and 87.4% of all observed three-marker haplotypes could determine the DR type with a positive predictive value >0.8 with high sensitivity and specificity. There was a high degree of haplotype conservation when comparing Caucasian and Asian populations. Interestingly, we found that the majority of DRB1*09 and DRB1*10 alleles share a common three-marker haplotype in both Caucasian and Asian populations. This is unexpected, since these two alleles are found on very different haplotype families. In addition, these two alleles are both associated with rheumatoid arthritis, making the elucidation of these haplotype relationships potentially important for understanding disease susceptibility.

Alleles↗

PubMed2006

Occupational risk factors for pancreatic cancer among female textile workers in Shanghai, China.

OBJECTIVES: To investigate whether occupational exposures to dusts and chemicals in the Shanghai textile industry are associated with risk of pancreatic cancer. METHODS: A case cohort study nested in a cohort of 267,400 female textile workers in Shanghai, China was conducted among 180 incident pancreatic cancer cases and an age stratified randomly selected comparison subcohort (n = 3188). A complete occupational history of work in the textile industry was obtained for each woman, and was linked to a job exposure matrix developed for the textile industry to estimate exposures to specific dusts and chemicals. Cumulative exposures to cotton dust and endotoxin were reconstructed from historical and contemporaneous measurements. RESULTS: After adjusting for smoking status, a trend of decreasing risk of pancreatic cancer was observed for increasing cumulative exposures to cotton dust and endotoxin with a lag of 20 years. The hazard ratios for women cumulatively exposed to >143.4 mg/m3 x years of cotton dust and >3530.6 EU/m3 x years of endotoxin were 0.6 (95% CI 0.3 to 0.9) and 0.5 (95% CI 0.3 to 0.9), respectively, compared to unexposed women. There was little evidence that exposures to other textile dusts and chemicals were associated with risk of pancreatic cancer. CONCLUSIONS: Occupational exposure to cotton dust and endotoxin in the textile industry may have reduced risks of pancreatic cancer in this cohort. These associations should be replicated by others before making a firm conclusion of their possible effects on pancreatic cancer.

Adult↗

PubMed2006

Arabidopsis thaliana wild type, pho1, and pho2 mutant plants show different responses to exogenous cytokinins.

Despite the involvement of cytokinins in phosphate (Pi) signaling being highlighted, the physiological processes involved remain unclear. In this study, we have evaluated the effect of cytokinins on different physiological responses using wild type (wt) and two Arabidopsis mutants with altered shoot Pi content (pho1 and pho2). Physiological studies were related with those previously described as cytokinin-regulated: including hypocotyl elongation, root growth, anthocyanin accumulation, senescence and relative gene expression. Generally, pho1 mutants showed decreased sensitivity to cytokinin, whereas pho2 mutants showed increased sensitivity to the hormone. This observation applies to inhibition of hypocotyls and root growth and anthocyanin accumulation. However, this effect was not shown during senescence or in the expression of ARR6 (Arabidopsis response regulator, ARR). Interestingly, Pi content in shoot of pho1 mutants increased to wt levels after treatment with cytokinins. These results suggest that the interaction between phosphate signaling and cytokinin signaling may be bidirectional while the differential behavior in response to cytokinin is discussed further.

Anthocyanins↗

PubMed2006

System size and centrality dependence of charged hadron transverse momentum spectra in Au + Au and Cu + Cu collisions at square root of SNN = 62.4 and 200 GeV.

We present transverse momentum distributions of charged hadrons produced in Cu + Cu collisions at square root of SNN = 62.4 and 200 GeV. The spectra are measured for transverse momenta of 0.25 < pT < 5.0 GeV/c at square root of SNN = 62.4 GeV and 0.25 < pT < 7.0 GeV/c at square root of SNN = 200 GeV, in a pseudorapidity range of 0.2 < eta < 1.4. The nuclear modification factor R(AA) is calculated relative to p + p data at both collision energies as a function of collision centrality. At a given collision energy and fractional cross section, R(AA) is observed to be systematically larger in Cu + Cu collisions compared to Au + Au. However, for the same number of participating nucleons, R(AA) is essentially the same in both systems over the measured range of pT, in spite of the significantly different geometries of the Cu + Cu and Au + Au systems.

Journal Article↗

PubMed2006

Acetylcholinesterase expression mediated by c-Jun-NH2-terminal kinase pathway during anticancer drug-induced apoptosis.

It has been shown that acetylcholinesterase (AChE) expression was induced during apoptosis and the anti-sense oligonucleotides and siRNA of AChE may prevent apoptosis in various cell types. However, the mechanisms underlying AChE upregulation remain elusive. We demonstrated here that c-Jun NH2-terminal kinase (JNK) could mediate AChE expression. In this study, both etoposide and excisanin A, two anticancer agents, induced apoptosis in colon cancer cell line SW620 as determined by Annexin V staining, the cleavage of caspase-3 and the proteolytic degradation of poly (ADP-ribose) polymerase (PARP). The results showed that both the agents upregulated AChE in SW620 cells. In the meantime, JNK was also activated and the expression and phosphorylation of c-Jun increased in SW620 cells exposed to the two agents. The induced AChE mRNA and protein expression could be blocked by SP600125, a specific inhibitor of SAPK/JNK, and small interfering RNA directed against JNK1/2. Transfection with adenovirus-mediated dominant negative c-Jun also blocked the upregulation of AChE expression. Together, these results suggest that AChE expression may be mediated by the activation of JNK pathway during apoptosis through a c-Jun-dependent mechanism.

Acetylcholinesterase↗

PubMed2006

High-density SNP analysis of 642 Caucasian families with rheumatoid arthritis identifies two new linkage regions on 11p12 and 2q33.

We have completed a genome wide linkage scan using >5700 informative single-nucleotide polymorphism (SNP) markers (Illumina IV SNP linkage panel) in 642 Caucasian families containing affected sibling pairs with rheumatoid arthritis (RA), ascertained by the North American Rheumatoid Arthritis Consortium. The results show striking new evidence of linkage at chromosomes 2q33 and 11p12 with logarithm of odds (LOD) scores of 3.52 and 3.09, respectively. In addition to a strong and broad linkage interval surrounding the major histocompatibility complex (LOD>16), regions with LOD>2.5 were observed on chromosomes 5 and 10. Additional linkage evidence (LOD scores between 1.46 and 2.35) was also observed on chromosomes 4, 7, 12, 16 and 18. This new evidence for multiple regions of genetic linkage is partly explained by the significantly increased information content of the Illumina IV SNP linkage panel (75.6%) compared with a standard microsatellite linkage panel utilized previously (mean 52.6%). Stratified analyses according to whether or not the sibling pair members showed elevated anticyclic citrullinated peptide titers indicates significant variation in evidence for linkage among strata on chromosomes 4, 5, 6 and 7. Overall, these new linkage data should reinvigorate efforts to utilize positional information to identify susceptibility genes for RA.

Arthritis, Rheumatoid↗

PubMed2006

Cia27 is a novel non-MHC arthritis severity locus on rat chromosome 10 syntenic to the rheumatoid arthritis 17q22-q25 locus.

Cia27 on rat chromosome 10 is a collagen-induced arthritis (CIA) severity quantitative trait locus originally identified in a study of (DA x ACI) F2. As an initial step towards the positional cloning of the Cia27 gene, a 17 cM (21 Mb) interval from the DA strain (arthritis-susceptible) containing the two-logarithm of odds support interval comprising Cia27 was introgressed into the ACI (arthritis-resistant) background through genotype-guided congenic breeding. ACI.DA(Cia27) congenics developed a significantly more severe form of arthritis (CIA), with a 5.9-fold increase in median arthritis severity index, a parameter known to correlate with synovial inflammation, and cartilage and bone erosions, compared with ACI (P< or =0.001). The arthritis severity enhancing effect could be detected from day 21 onwards. Rats heterozygous at the congenic interval developed a disease similar to ACI rats, suggesting that DA alleles operate in a recessive manner. Levels of autoantibodies anti-rat type II collagen did not correlate with arthritis severity. Synovial tissue mRNA levels of interleukin-1beta (IL-1beta) were significantly increased in ACI.DA(Cia27) congenics compared with ACI. These results demonstrate that Cia27 harbors a novel arthritis severity regulatory gene. The identification of this gene should facilitate the identification of the rheumatoid arthritis gene mapped to the human syntenic region on chromosome 17q22-q25.

Alleles↗

PubMed2006

Defects in articular cartilage metabolism and early arthritis in fibroblast growth factor receptor 3 deficient mice.

Fibroblast growth factor (FGF) receptor 3 has been identified as a key regulator of endochondral bone development and of post-natal bone metabolism through its action on growth plate chondrocytes and osteoblasts, respectively. It has also been shown to promote chondrogenesis and cartilage production by cultured pre-chondrogenic cells in response to FGF18. In the current studies, we show that the absence of signaling through Fgfr3 in the joints of Fgfr3(-/-) mice leads to premature cartilage degeneration and early arthritis. Degenerative changes in cartilage matrix included excessive proteolysis of aggrecan core protein and type II collagen, as measured by neo-epitope immunoreactivity. These changes were accompanied by increased expression of metalloproteinase MMP13, type X collagen, cellular hypertrophy and loss of proteoglycan at the articular surface. Using a novel micro-mechanical indentation protocol, it was shown that articular cartilage in the humeral head of 4-month-old Fgfr3(-/-) mice was less resistant to compressive force and less stiff than that of littermate controls. These results identify Fgfr3 signaling as a potential target for intervention in degenerative disorders of cartilage metabolism.

Aggrecans↗

PubMed2006

Interferon-gamma induces regression of epithelial cell carcinoma: critical roles of IRF-1 and ICSBP transcription factors.

We have developed an epithelial cell carcinoma model for studying efficacy of IFNgamma gene therapy and have identified components of IFNgamma-signaling pathway responsible for its direct anti-tumor actions. The tumor results from ectopic expression of SV40 Large T-Antigen (SV40 T-Ag) oncogene in lens of transgenic mouse (alphaT3) and complete regression of the tumor is induced by targeting expression of IFNgamma into malignant lens cells. Inflammatory cells are absent in lens of alphaT3 or DT (co-expressing IFNgamma and SV40-T-Antigen) mice and the transformed lens cells are non-immunogenic, suggesting non-involvement of immunologic cells. We show that IFNgamma has direct growth-inhibitory effects on tumor cells, induces death of tumor cells by apoptosis and that these effects are mediated by two transcription factors, IRF-1 (interferon-regulatory factor-1) and ICSBP (interferon-consensus sequence-binding protein) induced by IFNgamma. Furthermore, stable transfection with ICSBP or IRF-1 construct inhibits lens carcinoma cell growth by upregulating Caspase-1, p21(WAF1) and p27 expression. In contrast, tumor progression in alphaT3 lens correlates with inhibition of IRF-1 and ICSBP expression. Our results suggest that IFNgamma gene therapy maybe effective in malignant diseases for which DNA tumor viruses are etiologic agents and that antitumor actions of IRF-1/ICSBP can be exploited therapeutically to circumvent adverse clinical effects associated with IFN therapy.

Animals↗

PubMed2006

Inhibition of tumor growth and metastasis in vitro and in vivo by targeting macrophage migration inhibitory factor in human neuroblastoma.

Macrophage migration inhibitory factor (MIF) has been defined as a novel oncogene. Our previous results have shown that MIF may contribute to the progression of neuroblastoma by (a) inducing N-Myc expression and (b) upregulating the expression of angiogenic factors. The aim of this study was to test whether tumor growth could be inhibited by reduction of endogenous MIF expression in neuroblastoma and clarify the molecular mechanisms underlying MIF reduction on the control of neuroblastoma growth. We established human neuroblastoma cell lines stably expressing antisense MIF (AS-MIF) cDNA. These stable transfectants were characterized by cell proliferation, gene expression profile, tumorigenicity and metastasis in vitro and in vivo. Decreased MIF expression was observed after transfection with AS-MIF in neuroblastoma cells and downregulation of MIF expression significantly correlated with decreased expression of N-Myc, Ras, c-Met and TrkB at protein level. Affymetrix microarray analysis revealed that expression of IL-8 and c-met was inhibited and neuroblastoma-favorable genes such as EPHB6 and BLU were upregulated in MIF reduced cells. Neuroblastoma cell growth exhibited a nearly 80% reduction in AS-MIF transfectants in vitro. Furthermore, mice in which tumors formed after subcutaneous injection of AS-MIF transfectants showed a 90% reduction in tumor growth compared to control. Metastasis in mice was also suppressed dramatically. Our data demonstrate that targeting MIF expression is a promising therapeutic strategy in human neuroblastoma therapy, and also identifies the MIF target genes for further study.

Animals↗

PubMed2006

Transhemispheric functional reorganization of the motor cortex induced by the peripheral contralateral nerve transfer to the injured arm.

Peripheral nerve injury in a limb usually causes functional reorganization of the contralateral motor cortex. However, a dynamic process of the novel transhemispheric functional reorganization in the motor cortex was found in adult rats after transferring the seventh cervical nerve root from the contralateral healthy side to the injured limb. Initially the ipsilateral motor cortex activated the injured forepaw for 5 months after the operation. Then, both hemispheres of the cortex activated the injured forepaw, and finally the contralateral cortex exclusively controlled the injured forepaw. It is concluded an extensive functional shift occurred between two hemispheres based on neural plasticity in the CNS. The experimental results of the later lesions of the ipsilateral cortex suggest that maintaining transhemispheric functional reorganization does not depend on the corpus callosum, but depends on mechanisms involving central axonal sprouting. Possible mechanisms underlying the alternative changes in cortical functions were discussed in rats and in patients having similar operations.

Animals↗

PubMed2006

Umbilical cord blood cell transplantation for myocardial regeneration.

Bone marrow remains the most frequently used source of adult stem cells, but its angiogenic and possibly also myogenic potentials are likely to regress with increasing donor age and morbidity. Recently, cord blood has been suggested as a readily available source for non-embryonic stem cells with high regenerative capacity. We first tested the capacity of mononuclear cells obtained from human umbilical cord blood (UCB(mn)) to migrate to the heart on IV delivery in NOD/Scid mice. As evidenced by the presence of human DNA by PCR analysis, UCB(mn) cells migrated to the heart in 50% of the mice with myocardial infarctions, but in none of the sham-operated control mice. In UCB(mn) cell-positive injured hearts, the infarct size was smaller and capillary density higher in the ischemic myocardium. By immunohistology, we observed endothelial cell differentiation of UCB(mn) cells in the heart but there was no colocalization of UCB cell-specific antibodies with markers of myocyte-type cells. In a second series of experiments, we injected 5 x 10(5) UCB cells enriched for CD133 directly into the necrotic myocardium of NOD/Scid mice. Comparisons were performed with an equivalent number of CD133+ bone marrow (BM) cells or a sham injection in the respective control groups. Both BMCD133+ and UCBCD133+ cells abolished postoperative mortality and improved capillary density in the injured myocardium, but only BMCD133+ cells led to a detectable improvement in myocardial contractility in vivo. We conclude that human UCB cells facilitated neovascularization of ischemic myocardium, but their capacity for formation of contractile neotissue needs further investigation.

Animals↗

PubMed2006

The role of Foxp3+ regulatory T cells in liver transplant tolerance.

The liver has long been considered a tolerogenic organ that favors the induction of peripheral tolerance. The mechanisms underlying liver tolerogenicity remain largely undefined. In this study, we characterized Foxp3-expressing CD4+ CD25+ regulatory T cells (Treg) in liver allograft recipients and examined the role of Treg in inherent liver tolerogenicity by employing the mouse spontaneous liver transplant tolerance model. Orthotopic liver transplantation was performed from C57BL/10 (H2b) to C3H/HeJ (H2k) mice. The percentage of CD4+ CD25+ Treg was expanded in the liver grafts and recipient spleens from day 5 up to day 100 posttransplantation, associated with high intracellular Foxp3 and CTLA4 expression. Immunohistochemistry further demonstrated significant numbers of Foxp3+ cells in the liver grafts and recipient spleens and increased transforming growth factor beta expression in the recipient spleens throughout the time courses. Adoptive transfer of spleen cells from the long-term liver allograft survivors significantly prolonged donor heart graft survival. Depletion of recipient CD4+ CD25+ Treg using anti-CD25 monoclonal antibody (250 microg/d) induced acute liver allograft rejection, associated with elevated anti-donor T-cell proliferative responses, CTL and natural killer activities, enhanced interleukin (IL)-2, interferon-gamma, IL-10, and decreased IL-4 production, and decreased T-cell apoptotic activity in anti-CD25-treated recipients. Moreover, CTLA4 blockade by anti-CTLA4 monoclonal antibody administration exacerbated liver graft rejection when combined with anti-CD25 monoclonal antibody. Thus, Foxp3+ CD4+ CD25+ Treg appear to underpin spontaneous acceptance of major histocompatability complex- mismatched liver allografts in mice. CTLA4, IL-4, and apoptosis of alloreactive T cells appear to contribute to the function of Treg and regulation of graft outcome.

Animals↗

PubMed2006

Anti-CD25 mAb administration prevents spontaneous liver transplant tolerance.

Liver allografts are accepted spontaneously in all mouse strain combinations without immunosuppressive therapy. The mechanisms underlying this phenomenon remain largely undefined. In this study, we examined the effect of CD4+ CD25+ T regulatory cells (Treg) on the induction of mouse liver transplant tolerance. Orthotopic liver transplantation was performed from B10 (H2b) to C3H (H2k) mice. Depleting rat anti-mouse CD25 mAb (PC61) was given to the donors or recipients (250 microg/d IP) pretransplant or to the recipients postoperatively. At day 5 posttransplantation, both effector T cells (mainly CD8) and CD4+ CD25+ Treg were increased in the liver allografts and host spleens compared to naïve mice. Anti-CD25 mAb administration, either pretransplantation or posttransplantation, reduced the ratio of CD4+ CD25+ Treg to the CD3 T cells of liver grafts and recipient spleens and induced liver allograft acute rejection compared to IgG treatment. Anti-CD25 mAb administration elevated anti-donor T-cell proliferative responses and CTL and NK activities of graft infiltrates and host splenocytes; reduced CTLA4, Foxp3, and IDO mRNA levels; increased IL-10 and IFN-gamma; and decreased IL-4 mRNA levels in the livers or host spleens. The number of apoptotic T cells was reduced significantly in the liver grafts and treated host spleens. Therefore, anti-CD25 mAb administration changed the balance of CD4+ CD25+ Treg to activated T cells of liver graft recipients, preventing liver transplant tolerance. This was associated with enhanced anti-donor immune reactivity, downregulated Treg gene expression, and reduced T cell apoptosis in the grafts and host spleens.

Animals↗