Biomedical subjects
Publications and source records attributed to Y Wu.
We report the first demonstration to our knowledge of an ultrabroad emission laser using InGaAs/GaAs quantum dots by cycled monolayer deposition. The device exhibits a lasing wavelength coverage of approximately 40 nm at an approximately 1160 nm center wavelength at room temperature. The broadband signature results from the superposition of quantized lasing states from highly inhomogeneous dots.
We evaluated the consequences of heterozygous chromosome 22q11 deletion - a significant genetic risk for schizophrenia - for expression levels and patterns of a subset of 22q11 genes implicated in schizophrenia and other phenotypes in mouse models of 22q11 deletion syndrome (22q11DS). In deleted embryos, expression levels of at least nine 22q11 orthologues decline by 40-60% in the frontonasal mass/forebrain and other 22q11DS phenotypic sites (branchial and aortic arches, limb buds); however, coincident expression patterns of 22q11 and Snail genes - diagnostic for neural crest-derived mesenchyme - are unchanged, and Snail1 expression levels do not decline. Subsequently, 22q11 mRNA levels are reduced by 40-60% in the brains of developing, adolescent and adult deleted mice without altered expression patterns, dysmorphology or reduced cell density. Apparently, in deleted individuals, 22q11 gene expression declines across otherwise stable cell populations, perhaps disrupting individual cell function via diminished dosage. Such changes might contribute to schizophrenia vulnerability in 22q11DS.
Crosstalk between T cells and renal tubular epithelial cells (TECs) in the pathogenesis of tubular lesions, the most important sign of progressive renal diseases, has not been clarified. Previous work has shown that TECs harbor co-stimulatory signals that promote T-cell activation, which induces tubular lesions. Nevertheless, the expression and functional role of B7-H4, a recently identified co-stimulatory ligand of the B7 superfamily, in pathologic human kidneys is unclear. We investigated the expression of B7-H4 on cryostat renal biopsies from patients with idiopathic membranous nephropathy (n=20), immunoglobulin A nephropathy (n=19), lupus nephritis (n=16), and acute renal allograft rejection (n=15) using immunohistochemistry. In addition, we also analyzed TEC-associated B7-H4 in the regulation of T-cell activation. Immunohistological staining revealed that B7-H4 antigen is restricted to tubular epithelium and that the protein is prominent in sections with severe tubular lesions, although no correlation was observed between tubular B7-H4 expression and levels of serum creatinine, serum urea nitrogen concentration, and 24-h proteinuria in each type of nephropathy. In vitro, mixed lymphocyte reactions revealed that TEC-related B7-H4 promotes cytokine (interleukin-2 and interferon-gamma) production and proliferation of co-cultured T cells. Interestingly, the secretion of interleukin-2 by C10 T cell hybridomas also increased when C10 cells were co-cultured with the B7-H4-transgenic murine TEC line, 3M-1-secreting tubular epithelial cells (MCT) in the presence of the antigen hen egg lysozyme. Our results clearly show that TEC-associated B7-H4 induces T-cell activation and we propose that B7-H4 is a potential activator that promotes tubular lesion.
Field and laboratory work was carried out to investigate the chemistry and ecotoxicity of stream water affected by acid mine drainage in a tributary catchment of the Pearl River in subtropical China during a major flood that corresponded to a return period of 100 years. The results indicate that stream water was affected by acid mine drainage from the Dabaoshan mine at least to a distance of 25 km downstream of the mine water discharge point. It appears that H(+) generated from sulfide oxidation in the waste rock dumps was readily available for exporting. The amount of H(+) being discharged into the receiving stream depended on the volume of out-flowing waters. However, there was a lag time for the discharges of the metals. This may be attributed to the slower release of metals, relative to H(+), because it might take more time for the dissolution of heavy metal-bearing compounds, particularly the sparsely soluble jarosites. Fe, Zn and Al were the major metals of potential toxicity contained in the AMD-affected stream water, followed by Mn, Cu, Pb, As, Cd and Ni. The concentrations of these metals in the water decreased rapidly down the stream. This corresponds with an increase in the concentrations of reactive heavy metal fractions in benthic mud down the stream, reflecting the precipitation of heavy metal compounds with increasing pH and their subsequent deposition in the streambed. Toxicity tests show that the AMD-affected stream water at 3.5 km downstream of the discharge point was highly toxic to the test organism. At 25 km downstream of the discharge point where stream water pH was as high as 5.75, marked toxic responses of the test organism were still observed.
Most deaths from urinary bladder cancer are owing to metastatic disease. A reduction in Rho GDP Dissociation Inhibitor 2 (RhoGDI2) protein has been associated with increased risk of metastasis in patients with locally advanced bladder cancer, whereas in animal models, RhoGDI2 reconstitution in cells without expression results in lung metastasis suppression. Recently, we noted an inverse correlation between tumor RhoGDI2 and Neuromedin U (NMU) expression, suggesting that NMU might be a target of the lung metastasis suppressor effect of RhoGDI2. Here we evaluated whether NMU is regulated by RhoGDI2 and is functionally important in tumor progression. We used small interfering RNA knockdown of endogenous RhoGDI2 in poorly tumorigenic and non-metastatic human bladder cancer T24 cells and observed increased NMU RNA expression. Although NMU overexpression did not increase the monolayer growth of T24 or related T24T poorly metastatic human bladder cancer cells, it did augment anchorage-independent growth for the latter. Overexpression of NMU in T24 and T24T cells significantly promoted tumor formation of both cell lines in nude mice, but did not alter the growth rate of established tumors. Furthermore, NMU-overexpressing xenografts were associated with lower animal body weight than control tumors, indicating a possible role of NMU in cancer cachexia. NMU overexpression in T24T cells significantly enhanced their lung metastatic ability. Bioluminescent in vivo imaging revealed that lung metastases in T24T grew faster than the same tumors in the subcutaneous microenvironment. In conclusion, NMU is a RhoGDI2-regulated gene that appears important for tumorigenicity, lung metastasis and cancer cachexia, and thus a promising therapeutic target in cancer.
In order to verify the relationship between blood pressure and cerebral blood flow velocity in sub-clinical natural population, 1294 middle-aged and old Beijing rural residents were investigated in autumn 2002. For all subjects, systolic blood flow velocities (V(s)) in common carotid artery (CCA), internal carotid artery (ICA) and middle cerebral artery (MCA) were detected with trans-cranial Doppler. Key factors such as anthropometry, medication use, blood pressure and blood biochemical analysis were investigated at the same time. After controlling for age, gender, diabetes, hypercholesterolaemia, smoking and body mass index, multivariate analysis showed that systolic blood pressure (SBP) correlated positively with V(s) at MCA and slight negatively correlated with at CCA. As blood pressure rose by 10 mm Hg, the V(s) at MCA increased by 1.63 cm/s. Duration of hypertension (HD) negatively correlated with V(s) at MCA (P<0.01). The V(s) at MCA in early-stage and chronic hypertensive patients were 92.9+/-1.9 and 84.1+/-2.3 cm/s, respectively. Antihypertensive treatment could modify the V(s) at MCA towards a normal level by lowering blood pressure. In conclusion, the effect of hypertension on cerebral blood flow is complex. V(s) at MCA positively correlated with SBP, but negatively related to HD. Antihypertensive treatment might be helpful to keep cerebral blood flow at a normal level.
Various biomarkers have been suggested as associative or predictive of HIV-associated neurocognitive impairment. Plasma levels of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-alpha), and hematocrit were evaluated for relationships with diffusion tensor imaging measurements of centrum semiovale, caudate, and putamen. MCP-1 levels correlated with tissue status (mean diffusivity) in all examined regions. Plasma markers were also significantly correlated with anisotropy measurements in centrum semiovale (TNF-alpha) and putamen (hematocrit).
Human glutathione S-transferase P1-1 (GSTP1-1) is an ubiquitously expressed protein that plays an important role in the detoxification and xenobiotics metabolism. It has been shown that GSTP1-1 interacts with c-Jun NH(2)-terminal kinase (JNK) and suppresses its activity. Here, we report a novel function of GSTP1-1 in regulating tumor necrosis factor-alpha (TNF-alpha)-triggered signaling. The present experiments showed that GSTP1-1 physically associated with tumor necrosis factor receptor-associated factor 2 (TRAF2) in vivo and in vitro. Overexpression of GSTP1-1 inhibited TRAF2-induced activation of both JNK and p38 but not of nuclear factor-kappaB (NF-kappaB). Glutathione S-transferase P1-1 also attenuated TRAF2-enhanced apoptosis signal-regulating kinase 1 (ASK1) autophosphorylation and inhibited TRAF2-ASK1-induced cell apoptosis by suppressing the interaction of TRAF2 and ASK1. Conversely, silencing of GSTP1-1 expression through RNA interference (RNAi) resulted in increase of TNF-alpha-dependent TRAF2-ASK1 association followed by hyper-activation of ASK1 and JNK. A mutant GSTP1-1 lacking TRAF domain-binding motif exhibited a significant decline of capacity to bind TRAF2 and block TRAF2-ASK1 signaling compared with the wild type of GSTP1-1. Moreover, the glutathione-conjugating activity of GSTP1-1 was not involved in the regulation of TRAF2 signaling. These findings indicate that GSTP1-1 plays an important regulatory role in TNF-alpha-induced signaling by forming ligand-binding interactions with TRAF2, which provides a new insight for analysing the protective effects of GSTP1-1 in tumor cells.
BACKGROUND: Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations. AIM: To analyse the value of family history, microsatellite instability (MSI) analysis and MMR protein staining in the tumour to predict the presence of an MMR gene mutation in such patients. METHODS: In 281 patients diagnosed with CRC before the age of 50 years or with CRC and at least one additional HNPCC-associated cancer, germline mutation analysis in MLH1, MSH2 and MSH6 was carried out with denaturing gradient gel electrophoresis and multiplex ligation-dependent probe amplification. MSI analysis with five consensus markers and MMR protein staining for MLH1, MSH2 and MSH6 were carried out in the tumours. RESULTS: 25 pathogenic mutations (8 in MLH1, 9 in MSH2 and 8 in MSH6) were found. MSI analysis missed three and immunohistochemistry (IHC) missed two mutation carriers. Sensitivities of family history, MSI analysis and IHC for the presence of a mutation were 76%, 82% and 88%, specificities were 64%, 70% and 84%, and positive predictive values were 19%, 23% and 38%, respectively. Multivariate analysis showed the highest odds ratio for IHC (38.3, 95% confidence interval 9.0 to 184). Prevalence of pathogenic germline MMR gene mutations in patients with CRC before the age of 50 years was 6% and in those with > or =2 HNPCC-associated tumours was 22%. In the second group, no mutation carriers were found among the 29 patients who were diagnosed with their first tumour after the age of 60 years. CONCLUSION: Family history, MSI analysis and IHC are indicative parameters to select patients with CRC for MMR gene mutation analysis. The data show that IHC is the best single selection criterion.
Surfactant deficiency is an important contributor to the acute respiratory distress syndrome, a disorder that commonly occurs after bacterial sepsis. CTP:phosphocholine cytidylyltransferase (CCTalpha) is the rate-limiting enzyme required for the biosynthesis of dipalmitoylphosphatidylcholine (DPPC), the major phospholipid of surfactant. In this study, a cDNA encoding a novel, calpain-resistant mutant CCTalpha enzyme was delivered intratracheally in mice using a replication-deficient adenovirus 5 CTP:phosphocholine cytidylyltransferase construct (Ad5-CCT(Penta)) in models of bacterial sepsis. Ad5-CCT(Penta) gene transfer produced high-level CCTalpha gene expression, increased alveolar surfactant (DPPC) levels and improved lung surface tension and pressure-volume relationships relative to control mice. Pseudomonas aeruginosa (PA103) decreased DPPC synthesis, in part, via calpain-mediated degradation of CCTalpha. Deleterious effects of Pseudomonas on surfactant were lessened after infection with a mutant strain lacking the type III exotoxin, Exo U. Replication-deficient adenovirus 5 CTP:phosphocholine cytidylyltransferase gene delivery improved lung biophysical properties by optimizing surface activity in this Pseudomonas model of proteinase-mediated lung injury. The studies are the first demonstration of in vivo gene transfer of a lipogenic enzyme resulting in improved lung mechanics. The studies suggest that augmentation of DPPC synthesis via gene delivery of CCTalpha can attenuate impaired lung function in surfactant-deficient states such as bacterial sepsis.
Peroxisome proliferator-activated receptors (PPARs) are transcription factors that strongly influence molecular events in normal and cancer cells. PPAR-beta/delta (PPAR-b/d) overexpression suppresses the activity of PPAR-gamma (PPAR-g) and PPAR-alpha. This interaction has been questioned, however, by studies with synthetic ligands of PPARs in PPAR-b/d-null cells, and it is not known whether an interaction between PPAR-b/d and PPAR-g exists, especially in relation to the signaling by natural PPAR ligands. Oxidative metabolites of linoleic and arachidonic acids are natural ligands of PPARs. 13-S-hydroxyoctadecadienoic acid (13-S-HODE), the main product of 15-lipoxygenase-1 (15-LOX-1) metabolism of linoleic acid, downregulates PPAR-b/d. We tested (a) whether PPAR-b/d expression modulates PPAR-g activity in experimental models of the loss and gain of PPAR-b/d function in colon cancer cells and (b) whether 15-LOX-1 formation of 13-S-HODE influences the interaction between PPAR-b/d and PPAR-g. We found that (a) 15-LOX-1 formation of 13-S-HODE promoted PPAR-g activity, (b) PPAR-b/d expression suppressed PPAR-g activity in models of both loss and gain of PPAR-b/d function, (c) 15-LOX-1 activated PPAR-g by downregulating PPAR-b/d, and (d) 15-LOX-1 expression induced apoptosis in colon cancer cells via modulating PPAR-b/d suppression of PPAR-g. These findings elucidate a novel mechanism of the signaling by natural ligands of PPARs, which involves modulating the interaction between PPAR-b/d and PPAR-g.
We present a 35-year-old male who, 9 years ago, had his right orbit and face injured in a gun blast accident resulting in severe cicatrical ectropion of the right lower lid. A large advancement facial flap with incision at the naso-labial fold was designed to repair the skin defect, and a strip of autologous fascia lata was grafted in the lower lid to serve as a static sling. The facial flap was dissected and elevated at the subcutaneous fat layer. With adequate separation of the flap and suspension sutures at the undersurface of the flap, tension free closure of the wound was obtained and the ectropion completely corrected. The postoperative course was uneventful and the patient very satisfied with the results.
BACKGROUND: Rapid, sensitive, specific, and cost-effective screening of donated blood to prevent transmission of infectious agents remains challenging. In recent years, incorporation of nucleic acid testing for HIV-1 and HCV RNA improved blood safety by reducing the window period between infection and serologic detection. For HBV infection, this window period with most serologic assays is 50-60 days. Adding a nucleic acid test (NAT) for HBV DNA with existing NATs for HIV-1 and HCV RNA would further improve blood safety and blood screening efficiency. OBJECTIVE: To evaluate the Procleix Ultrio Assay for simultaneous detection of HIV-1 and HCV RNA and HBV DNA and corresponding discriminatory assays. STUDY DESIGN: The performance of these assays, which utilize the same technology and assay format as the Procleix HIV-1/HCV assay, was determined using relevant clinical specimens and analytical sensitivity and specificity panels. RESULTS: The Procleix Ultrio Assay demonstrated specificity of > or =99.5% in healthy donor blood specimens and in plasma containing potentially interfering substances or other blood-borne pathogens. Assay sensitivity demonstrated >95% detection of 100copies/mL, 30IU/mL, and 15IU/mL for HIV-1 and HCV RNA, and HBV DNA, respectively. The assay detects all known HIV-1 subtypes and HCV and HBV genotypes and is highly reproducible. Statistical analysis using receiver operating characteristic plots demonstrated wide analyte cutoff values for each assay associated with assay specificity and sensitivity of > or =99.5%. CONCLUSIONS: In this investigational study, the Procleix Ultrio Assay sensitivity and specificity were similar to existing NATs used in blood-bank settings to detect HIV-1 and HCV RNA and provided equivalent sensitivity and specificity for detection of HBV DNA. Using this combination assay, blood safety may be improved and the multiplex format enhances blood screening efficiency. The throughput capability of this assay is compatible with large volume processing and the chemistry is adaptable to full automation.
AIMS/HYPOTHESIS: This study aimed to identify the expression of angiotensin II receptors in isolated human islets and beta cells and to examine the functional consequences of their activation. MATERIALS AND METHODS: Single-cell RT-PCR was used to identify whether human islet cells express mRNA for type 1 angiotensin II receptors (AT(1)), and western blotting was used to determine AT(1) protein expression by human islets and MIN6 beta cells. We measured changes in intracellular calcium by microfluorimetry using Fura 2-loaded MIN6 cells and human islet cells. Dynamic insulin secretory responses were determined by RIA following perifusion of human islets and MIN6 cells. RESULTS: Human islets expressed mRNAs for both the angiotensin precursor, angiotensinogen, and for angiotensin-converting enzyme. In addition, human and mouse beta cells expressed AT(1). These were functionally coupled to increases in intracellular calcium, which occurred at least in part through phospholipase-C-sensitive mechanisms and calcium influx through voltage-operated calcium channels. Short-term exposure of human islets and MIN6 cells to angiotensin II caused a rapid, short-lived initiation of insulin secretion at 2 mmol/l glucose and potentiation of insulin secretion induced by glucose (at 8 and 16.7 mmol/l). CONCLUSIONS/INTERPRETATION: These data demonstrate that the AT(1) is expressed by beta cells and that angiotensin II effects a short-lived and direct stimulation of human and mouse beta cells to promote insulin secretion, most probably through elevations in intracellular calcium. Locally produced angiotensin II may be important in regulating a coordinated insulin secretory response from beta cells.
Sodium tanshinone IIA sulfonate (STS), a hydrophilic ionic substance, is used as a cardiovascular drug. An ion-pair reversed-phase high-performance liquid chromatography (IP-RP-HPLC) method for the determination of STS in mouse plasma was initially developed. The assay involved a rapid and simple extraction process and subsequent detection at 271 nm. The retention time for STS was 7.5 min. Based on extracted STS standard mouse plasma at 1.5,10 and 50 microg/ml, the assay precision were 2.7, 2.1 and 1.7% with a mean accuracy of 96.7, 98.5 and 99.4%, respectively. At plasma concentration of 1.5, 50 and 75 microg/ml, the mean recovery of STS were 93.1, 96.3 and 97.5%. The limit of detection (LOD) and limit of quantification (LOQ) for STS was 0.1 microg/ml and 0.5 microg/ml, respectively. Linear responses were observed over a wide concentration range (0.5-100 microg/ml) for STS in mouse plasma. STS can be detected after intravenous administration. This method was performed for the first time in pharmacokinetic studies of STS in the mouse.
Recent work in k-t BLAST and undersampled projection angiography has emphasized the value of using training data sets obtained during the acquisition of a series of images. These techniques have used iterative algorithms guided by the training set information to reconstruct time frames sampled at well below the Nyquist limit. We present here a simple non-iterative unfiltered backprojection algorithm that incorporates the idea of a composite image consisting of portions or all of the acquired data to constrain the backprojection process. This significantly reduces streak artifacts and increases the overall SNR, permitting decreased numbers of projections to be used when acquiring each image in the image time series. For undersampled 2D projection imaging applications, such as cine phase contrast (PC) angiography, our results suggest that the angular undersampling factor, relative to Nyquist requirements, can be increased from the present factor of 4 to about 100 while increasing SNR per individual time frame. Results are presented for a contrast-enhanced PR HYPR TRICKS acquisition in a volunteer using an angular undersampling factor of 75 and a TRICKS temporal undersampling factor of 3 for an overall undersampling factor of 225.
OBJECTIVE: To investigate protective effect of glutathione (GSH) against lipopolysaccharide (LPS)-induced inflammation and mortality in rats. METHODS: Male Sprague-Dawley rats were injected intraperitoneally (i. p.) with GSH (40 mg/kg) 30 min prior to LPS injection (20 mg/kg). Animal survival rate and the production of nitric oxide in serum were measured. Morphology of lung was observed using hematoxylin and eosin staining. Western blotting was used to assess the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and the phosphorylation of p38 in rat peritoneal macrophages. RESULTS: GSH significantly decreased LPS-induced mortality, inhibited serum NO production and eliminated lung histological injury. Furthermore, GSH inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and the phosphorylation of p38 in LPS-stimulated rat peritoneal macrophages. CONCLUSIONS: These results indicated that GSH suppressed LPS-induced systemic inflammatory response in rats and p38 MAPK signal pathway was involved in this process.
The precision of patient position set-up is important in radiotherapy. A simple and effective scheme is proposed to calibrate the binocular cameras into the treatment machine co-ordinate system to accomplish the patient's first set-up using the video-based positioning system. We also introduce the marking of points on the surface of the body, which can be clearly imaged by computed tomography and are easily recognised from the photograph by the charge coupled device (CCD) camera. By comparing the real-time co-ordinates of the marked points with those obtained from the computed tomography, and with subsequent adjustment, the patient's first set-up in radiotherapy is realised with the video-based positioning system.