Myelofibrosis with a novel translocation, t(1;3)(q31;q23), and response to imatinib mesylate.
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Antigens, CD↗
Biomedical subjects
D Liu
Publications and source records attributed to D Liu.
c-Jun N-terminal kinase is activated in non-small-cell lung cancer and promotes neoplastic transformation in human bronchial epithelial cells.
c-Jun N-terminal kinase (JNK) has been reported to either potentiate or inhibit oncogenesis, depending upon the cellular context, but its role in lung neoplasia is unclear. Here we sought to define the role of JNK in lung neoplasia by examining evidence of JNK phosphorylation in non-small-cell lung cancer (NSCLC) biopsy samples and by using genetic and pharmacologic approaches to modulate JNK expression and activity in cultured cells. Immunohistochemical staining for JNK phosphorylation was detected in 114 (45%) of 252 NSCLC biopsy samples and was predominantly nuclear, providing evidence of JNK activation in a subset of NSCLC cases. Introduction of a doxycycline-inducible, constitutively active, mutant mitogen-activated protein kinase kinase 4 (MKK4) into the human bronchial epithelial cell lines BEAS-2B and HB56B increased the cells' proliferation, migration, invasion and clonogenicity. Depletion of JNK in MKK4 mutant-transformed BEAS-2B cells by introduction of JNK1/2 short hairpin RNA reversed the transformed phenotype, indicating that JNK activation is oncogenic and MKK4 confers neoplastic properties in these cells. The proliferation of NSCLC cell lines HCC827 and H2009, in which JNK and its substrate c-Jun are constitutively phosphorylated, was inhibited by SP600125, a JNK kinase inhibitor. We conclude that JNK is activated in a subset of NSCLC biopsy samples and promotes oncogenesis in the bronchial epithelium, suggesting that strategies to inhibit the JNK pathway should be considered for the prevention and treatment of NSCLC.
Bronchi↗
Structural impact of hydrodynamic injection on mouse liver.
The impact of hydrodynamic injection on liver structure was evaluated in mice using various microscopic techniques. Upon hydrodynamic injection of approximately 9% of body weight by volume, the liver rapidly expanded, reaching maximal size at the end of the injection and returned to its original size in 30 min. Histological analysis revealed a swollen appearance in the peri-central region of the liver where delivery of genes and fluorescence-labeled markers was observed. Scanning and transmission electron microscopy showed enlargement and rupture of endothelium that in about 24-48 h regains its morphology and normal function as a barrier against infection by adenovirus viral particles. At the cellular level in hydrodynamically treated animals, four types of hepatocytes were seen: cells with normal appearance; cells with enriched vesicles in the cytoplasm; cells with lightly stained cytosol; and cells with significant dilution of the cytoplasm. In addition, red blood cells and platelets were observed in the space of Disse and even inside hepatocytes. Vesicle formation is triggered by hydrodynamic injection and resembles the process of macropinocytosis. These results, whereas confirming the physical nature of hydrodynamic delivery, are important for a better understanding of this efficient method for intrahepatic gene and small interfering RNA delivery.
Adenoviridae↗
Impact of different pressures and exposure times of a simulated carbon dioxide pneumoperitoneum environment on proliferation and apoptosis of human ovarian cancer cell lines.
BACKGROUND: This study aimed too evaluate the proliferation and apoptosis of human ovarian cancer cell lines HO8910 and SKOV3 after exposure to a simulated laparoscopic carbon dioxide (CO2) pneumoperitoneum environment at different pressures and lengths of exposure time. METHODS: The effects of the simulated laparoscopic CO2 pneumoperitoneum environment at different CO2 pressures (0-16 mmHg) and exposure times (1-4 h) on tumor cell growth and apoptosis were assessed by 3-[4,5-Dimethylthiazol]-2; 5-diphenyltetrazolium bromide (MTT) chromometry and proliferative index (PI) staining or Annexin V and PI double-staining flow cytometry. Cells cultured in a standard environment were used as the control group. RESULTS: In this study, HO8910 cell growth tended to slow down with the increase in CO2 pressure and exposure time. A significantly lower PI was observed at 72 h of culture after exposure to both 8 and 16 mmHg of pressure, as compared with the control and 0 mmHg pressure group (p < 0.05). The PI of SKOV3 cells tended to decline after exposure. Significantly lower PI was observed in the group with exposure to 16 mmHg for 4 h over a 72-h period, as compared with the control groups exposed to 0 mmHg (p < 0.05). The inhibition of cell growth was associated with an increase in the proportion of cells at stage G1. The apoptotic index and the percentage of apoptotic cells tended to increase with an increase in pressure and a prolonged time of exposure. CONCLUSIONS: The results suggest inhibited cell proliferation and increased cell apoptosis of human ovarian cancer cells were positively related to CO2 pressure and exposure time.
Apoptosis↗
Evaluations of biomarkers associated with 5-FU sensitivity for non-small-cell lung cancer patients postoperatively treated with UFT.
The sensitivity to 5-fluorouracil (5-FU) has been reported to be associated with target molecule thymidylate synthase (TS), fluoropyrimidine-metabolising enzymes such as orotate phosphoribosyltransferase (OPRT), and dihydropyrimidine dehydrogenase (DPD). We performed an immunohistochemical study on the clinical significance of TS, OPRT, and DPD expression using 151 resected non-small-cell lung cancer (NSCLC) patients postoperatively treated with a combination of tegafur and uracil (UFT). Eighty-two carcinomas were TS-positive, 105 carcinomas were OPRT-positive, 68 carcinomas were DPD-positive. No correlation was observed in the HSCORE between the TS and OPRT expression (r=0.203), between the TS and DPD expression (r=0.098), or between the OPRT and DPD expression (r=0.074). Regarding the survival of NSCLC patients treated with UFT, the 5-year survival rate of patients with TS-negative tumours was significantly higher than that with TS-positive tumours (P=0.0133). The 5-year survival rate of patients with OPRT-positive stage II to III tumours was significantly higher than that with OPRT-negative stage II to III tumours (P=0.0145). In addition, the 5-year survival rate of patients with DPD-negative tumours was also significantly higher than that with DPD-positive tumours (P=0.0004). A Cox multivariate regression analysis revealed the TS status (hazard ratio 2.663; P=0.0003), OPRT status (hazard ratio 2.543; P=0.0005), and DPD status (hazard ratio 2.840; P<0.0001) to all be significant prognostic factors for the survival of resected NSCLC patients postoperatively treated with UFT.
Adult↗
Femoral neck cortical geometry measured with magnetic resonance imaging is associated with proximal femur strength.
INTRODUCTION: Magnetic resonance imaging (MRI) is a promising medical imaging technique that we used to assess femoral neck cortical geometry. OBJECTIVES: Our primary objective was to assess whether cortical bone in the femoral neck assessed by MRI was associated with failure load in a simulated sideways fall, with and without adjustment for total bone size. Our secondary objective was to assess the reliability of the MRI measurements. MATERIALS AND METHODS: We imaged 34 human cadaveric proximal femora using MRI and dual-energy X-ray absorptiometry (DXA). MRI measurements of cross-sectional geometry at the femoral neck were the cortical cross-sectional area (CoCSA(MRI)), second area moment of inertia (x axis; Ix(MRI)), and section modulus (x axis; Zx(MRI)). DXA images were analyzed with the standard Hologic protocol. From DXA, we report the areal bone mineral density (aBMD(DXA)) in the femoral neck and trochanteric subregions of interest. The femora were loaded to failure at 100 mm/s in a sideways fall configuration (15 degrees internal rotation, 10 degrees adduction). RESULTS AND OBSERVATIONS: Failure load (N) was the primary outcome. We observed that the femoral neck CoCSA(MRI) and Ix(MRI) were strongly associated with failure load (r (2)=0.46 and 0.48, respectively). These associations were similar to those between femoral neck aBMD and failure load (r (2)=0.40), but lower than the associations between trochanteric aBMD and failure load (r (2)=0.70). CONCLUSION: We report that MRI holds considerable promise for measuring cortical bone geometry in the femoral neck and for predicting strength at the proximal femur.
Absorptiometry, Photon↗
Past adult lead exposure is linked to neurodegeneration measured by brain MRI.
OBJECTIVE: To determine whether cumulative lead dose in former organolead workers was associated with MRI measures of white matter lesions (WML) and global and structure-specific brain volumes. METHODS: MRIs, tibia lead, and other measures were obtained from 532 former organolead workers with a mean age of 56 years and a mean of 18 years since last occupational exposure to lead. Cumulative lead dose was measured by tibia lead, obtained by X-ray fluorescence, and expressed as microg lead per gram of bone mineral (microg Pb/g). WML were evaluated using the Cardiovascular Health Study grading scale. A total of 21 global and specific brain regions were evaluated. RESULTS: A total of 36% of individuals had WML grade of 1 to 7 (0 to 9 scale). Increasing peak tibia lead was associated with increasing WML grade (p = 0.004). The adjusted OR for a 1 microg Pb/g increase in tibia lead was 1.042 (95% CI = 1.021, 1.063) for a CHS grade of 5+ (> or = 5 vs < 5). In linear regression, the coefficient for tibia lead was negative for associations with all structures. Higher tibia lead was significantly related to smaller total brain volume, frontal and total gray matter volume, and parietal white matter volume. Of nine smaller specific regions of interest, higher tibia lead was associated with smaller volumes for the cingulate gyrus and insula. CONCLUSIONS: These data suggest that cumulative lead dose is associated with persistent brain lesions, and may explain previous findings of a progressive decline in cognitive function.
Adult↗
Functional expression of Candida antarctica lipase B in the Escherichia coli cytoplasm--a screening system for a frequently used biocatalyst.
In this paper, we report for the first time the functional expression of lipase B from the yeast Candida antarctica (CalB) in the Escherichia coli cytoplasm. The enzyme possessing three disulfide bonds was functionally expressed in the strain Origami B. Expression under the control of a lac promoter yielded 2 U mg(-1), whereas expression of a thioredoxin-CalB fusion protein yielded 17 U mg(-1). The native enzyme was most efficiently expressed under control of the cspA promoter (11 U mg(-1)). Coexpression of different chaperones led to a strong increase in active protein formation (up to 61 U mg(-1)). A codon-optimized synthetic variant of calb did not show significant effects on functional protein yield. Functional CalB expression was not only achieved in shake flasks but also in microtiter plate scale. Therefore, this CalB expression system is suitable for high-throughput applications, including the screening of large gene libraries as those derived from directed evolution experiments.
Base Sequence↗
Accuracy of pQCT for evaluating the aged human radius: an ashing, histomorphometry and failure load investigation.
INTRODUCTION: Quantifying the determinants of bone strength is essential to understanding if or how the structure will fail under load. Determining failure requires knowledge of material and geometric properties. However, characterizing the relative contributions of geometric parameters of bone to overall bone strength has been difficult to date because of limitations in imaging technology. Peripheral quantitative computed tomography (pQCT) uses digital images to derive estimates of bone strength in the peripheral skeleton and is a relatively safe technique to differentiate cortical from trabecular bone and assess bone geometry and density. However, in a compromised osteoporotic bone, thin cortices and low scan resolution can limit accurate analysis. METHODS: Therefore, in this two-part investigation we scanned ten pairs (n=20) of fresh-frozen radial specimens [female, mean (SD) age 79(6) years] using pQCT (XCT 2000) at the 4 and 30% sites of the distal radius. We investigated the accuracy of four different acquisition resolutions (200, 300, 400, 500 microm) and several analysis modes and thresholds. We evaluated (1) the accuracy of the Norland/Stratec XCT 2000 pQCT in assessing low-density bones by comparing pQCT outcomes to ashing and histomorphometry and (2) the association of geometric parameters by pQCT and areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) to failure load at the distal radius. RESULTS: Using histomorphometry and ashing as reference standards, we found that pQCT scans varied systematically and underestimated or overestimated total area and mineral content at the radial midshaft depending on the analysis algorithm and selected threshold. Overall, most pQCT analysis modes were accurate. In the mechanical testing studies, bone mineral content and cortical bone content at the midshaft were strongly associated with failure load. The pQCT parameters that best accounted for failure load were total content at the 4% site and cortical thickness at the 30% site and they accounted for up to 81% of the variance. The best DXA predictor of failure load was total density at the distal third site and it explained 75% of the variance. CONCLUSIONS: In summary, analysis mode, resolution and thresholding affected pQCT outputs at the radial midshaft. This study extends our understanding of pQCT analysis and provides important data regarding determinants of bone strength at the distal radius.
Aged↗
MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2.
Motility-related protein-1 (MRP-1/CD9) is involved in cell motility. We studied the change in the actin cytoskeleton, and the expression of actin-related protein (Arp) 2 and Arp3 and the Wiskott-Aldrich syndrome protein (WASP) family according to MRP-1/CD9 gene transduction into HT1080 cells. The frequency of cells with lamellipodia was significantly lower in MRP-1/CD9-transfected HT1080 cells than in control HT1080 cells (P<0.0001). MRP-1/CD9 gene transduction affected the subcellular localization of Arp2 and Arp3 proteins. Furthermore, MRP-1/CD9 gene transduction induced a downregulation of WAVE2 expression (P<0.0001). However, no difference was observed in the expression of Arp2, Arp3 or other WASPs. A neutralizing anti-MRP-1/CD9 monoclonal antibody inhibited downregulation of WAVE2 in MRP-1/CD9-transfected HT1080 cells (P<0.0001), and reversed the morphological effects of MRP-1/CD9 gene transduction. Furthermore, downregulation of WAVE2 by transfection of WAVE2-specific small interfering RNA (siRNA) mimicked the morphological effects of MRP-1/CD9 gene transduction and suppressed cell motility. However, transfection of each siRNA for Wnt1, Wnt2b1 or Wnt5a did not affect WAVE2 expression. Transfection of WAVE2-specific siRNA also did not affect expressions of these Wnts. These results indicate that MRP-1/CD9 regulates the actin cytoskeleton by downregulating of the WAVE2, through the Wnt-independent signal pathway.
Actin-Related Protein 2↗
Significance of the metastasis-inducing protein AGR2 for outcome in hormonally treated breast cancer patients.
The anterior gradient protein-2 (AGR2) is inducible by oestrogen and itself can induce metastasis in a rat model for breast cancer. Here, a rabbit antibody to recombinant human AGR2 was used to assess its prognostic significance in a retrospective cohort of 351 breast cancer patients treated by adjuvant hormonal therapy. The antibody stains 66% of breast carcinomas to varying degrees. The percentage of positive carcinoma cells in tumours directly correlates with the level of AGR2 mRNA (Spearman's rank correlation, P = 0.0007) and protein (linear regression analysis r2 = 0.95, P = 0.0002). There is a significant association of staining of carcinomas for AGR2 with oestrogen receptor alpha (ERalpha) staining and with low histological grade (both Fisher's Exact test P<0.0001). In the ERalpha-positive cases, but not the ERalpha-negative cases, when subdivided into the separate staining classes for AGR2, there is a significantly progressive decrease in patient survival with increased staining (log rank test, P = 0.006). The significant association of staining for AGR2 with patient death over a 10-year period (log rank test P = 0.007, hazard ratio = 3) only becomes significant at 6 years of follow-up. This may be due to the cessation of adjuvant hormonal therapy at an earlier time, resulting in adverse re-expression of the metastasis-inducing protein AGR2.
Adult↗
The HAUSP gene plays an important role in non-small cell lung carcinogenesis through p53-dependent pathways.
Herpesvirus-associated ubiquitin-specific protease (HAUSP) directly stabilizes the tumour suppressor p53 by de-ubiquitination. Therefore, the HAUSP gene might play an important role in carcinogenesis. In this paper, HAUSP expression and p53 gene status have been studied in relation to the expression of p53 target genes in 131 patients with non-small cell lung cancer (NSCLC). p53 gene status was evaluated by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by sequencing. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was performed to evaluate the gene expression of HAUSP, p21, and bax. Immunohistochemistry was performed to evaluate the protein expression of p53, HAUSP, mdm2, p21, and bax. Fifty-nine carcinomas (45.0%) showed reduced expression of HAUSP, and 58 carcinomas (44.3%) had mutations of p53. Concerning tumour histology, HAUSP mRNA expression was significantly lower in adenocarcinomas than in squamous cell carcinomas (p = 0.0038), while the frequency of p53 mutation was significantly higher in squamous cell carcinomas than in adenocarcinomas (p = 0.0461). There was no significant difference in HAUSP mRNA expression according to p53 gene status. In total, 93 carcinomas (71.0%) showed either mutant p53 or reduced HAUSP expression. The down-regulation of HAUSP was associated with reduced p53 protein expression (p = 0.0593 in tumours with wild-type p53 and p = 0.0004 in tumours with mutant p53). Furthermore, p21 and bax protein expression was significantly lower in tumours with either mutant p53 or reduced HAUSP expression than in tumours with both wild-type p53 and positive HAUSP expression (p = 0.0440 and p = 0.0046, respectively). In addition, the simultaneous evaluation of both HAUSP expression and p53 gene status was a significant indicator of poor prognosis in adenocarcinoma patients (hazard ratio 4.840, p = 0.0357). These results suggest that reduction of HAUSP gene expression may play an important role in NSCLC carcinogenesis, especially in adenocarcinomas, through p53-dependent pathways.
Carcinoma, Non-Small-Cell Lung↗
Protective effects of propofol on lipopolysaccharide-activated endothelial cell barrier dysfunction.
BACKGROUND: Propofol has been widely used in intravenous anesthesia. It possesses antioxidant and immunomodulating effects. This study aimed to investigate whether propofol may attenuate lipopolysaccharide (LPS)-induced endothelial cell barrier dysfunction and the possible mechanisms of such modulation. METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were used to assess the following treatments: (i) no additives (negative control), (ii) LPS alone (1 and 10 microg/ml), (iii) propofol alone (20 microg/ml), (iv) intralipid (a solvent of propofol) alone (20 microg/ml), (v) LPS (10 microg/ml) combination with propofol (4 and 20 microg/ml) and (vi) LPS (10 microg/ml) combination with intralipid (20 microg/ml). Changes of cell permeability and filamentous actin (F-actin) were determined. Expression of nitrotyrosine proteins and activity of nuclear factor kappaB (NF-kappaB) were analyzed by Western blot and immunocytochemistry. Expression of endothelial nitric-oxide synthase (eNOS) and inducible nitric-oxide synthase (iNOS) were analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: LPS markedly increased the permeability of endothelial cells, the formation of peroxynitrite and depolymerization of F-actin in HUVECs. LPS also significantly increased mRNA of iNOS, protein level of NF-kappaB and decreased mRNA of eNOS (P < 0.05). Propofol at both concentrations (4 and 20 microg/ml) significantly inhibited the LPS-induced increase in cell permeability and alteration in F-actin organization. Propofol also reduced the LPS-enhanced iNOS mRNA and NF-kappaB protein levels whilst it increased eNOS mRNA expression (P < 0.05). CONCLUSION: This study demonstrated that propofol, both at therapeutic concentrations and 5 times therapeutic concentrations, inhibited NF-kappaB activation in LPS-stimulated endothelial cells and was found to protect endothelial cells against LPS-induced barrier dysfunction.
Actins↗
Non-myeloablative allogeneic stem cell transplant in a patient with refractory systemic lupus erythematosus.
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Adult↗
Ovipositional preferences, damage thresholds, and detection of the tomato-potato psyllid Bactericera cockerelli (Homoptera: Psyllidae) on selected tomato accessions.
The tomato-potato psyllid Bactericera [Paratrioza] cockerelli (Sulc) has recently caused losses exceeding 50% on fresh market tomatoes in California and Baja, Mexico by injecting a toxin that results in a condition known as 'psyllid yellows'. The objectives of this study were to: (i) document oviposition preferences on a range of tomato cultivars; (ii) determine threshold levels for psyllid densities that would cause psyllid yellows on tomatoes within the first three weeks following transplanting; and (iii) identify the most important 'psyllid yellows' symptoms that might be used in surveying and monitoring for this pest. Plant lines tested included the commonly-planted commercial cultivars 'Shady Lady' and 'QualiT 21', an older, previously commercial cultivar '7718 VFN', a common cultivar planted by consumers 'Yellow Pear', and a wild type plant accession, PI 134417. When given a choice, psyllids significantly preferred 'Yellow Pear' and avoided PI 134417 for oviposition. Under no-choice conditions psyllids laid significantly fewer eggs on PI 134417, but all the other plant lines were equally good substrates for laying eggs. Thus, oviposition preference is not likely to provide a functional management strategy in large plantings. On 'Shady Lady', psyllids preferred to oviposit on plants already infested with adults. On both 'Shady Lady' and '7718 VFN' oviposition was significantly greater on plants previously infested by nymphs as compared to uninfested control plants. This suggests that, at least for some cultivars, there is a physiological change in plant attractiveness following psyllid feeding. 'Yellow Pear' and 'QualiT 21' were relatively tolerant of psyllids, requiring 18 nymphs per plant to produce the disease symptoms. Only eight nymphs per plant were needed on 'Shady Lady' and '7718 VFN'. For all cultivars, the pest density showed strong correlations with measurements such as the number of yellowing leaves and leaflets and distorted leaves, which were as good as or better than the first factor extracted from principal component analysis. Therefore, such measurements have the potential to simplify field surveys.
Analysis of Variance↗
Use of a putative transcriptional regulator gene as target for specific identification of Staphylococcus epidermidis.
AIMS: To investigate the use of a Staphylococcus epidermidis transcriptional regulator gene as target for species-specific determination. METHODS AND RESULTS: Staph. epidermidis genes encoding putative transcriptional regulators were retrieved from GenBank and those showing no homology with other bacterial sequences were selected. Of the four PCR primer sets analysed, the primers Serp0107F/R from serp0107 amplified a specific product of 581 bp from Staph. epidermidis DNA only, and they did not cross-react in PCR with nonepidermidis staphylococci and other common bacteria. CONCLUSION: Being uniquely present in Staph. epidermidis, putative transcriptional regulator gene serp0107 offers a valuable target for specific identification of Staph. epidermidis. SIGNIFICANCE AND IMPACT OF THE STUDY: As a member of a specialized gene group, putative transcriptional regulator gene serp0107 may be important to Staph. epidermidis adaptation to its niche environment. Further analysis of serp0107 and its related protein may help reveal new insights on the molecular regulation of Staph. epidermidis survival and virulence.
Bacterial Typing Techniques↗
[Combined large cell neuroendocrine carcinoma and squamous cell carcinoma of the lung; report of a case].
An 80-year-old man was admitted to our hospital because a routine chest X-ray had revealed a nodular shadow in the right lower lung field. Transbronchial lung biopsy (TBLB) failed to give at definitive diagnosis, therefore open lung biopsy was performed because of suspected lung cancer. Rapid intraoperative pathological examination diagnosed the tumor as large cell carcinoma. However, bloody pleural effusion was classified as class V. It was judged difficult to perform a curative operation, so the operation was interrupted. Pathological diagnosis was combined large cell neuroendocrine carcinoma and squamous cell carcinoma. Pleurodesis was done, and the patient is under observation at 7 months after the operation.
Aged, 80 and over↗
Thermally switchable and discretely tunable comb filter with a linearly chirped fiber Bragg grating.
We propose and experimentally demonstrate a novel switchable and discretely tunable comb filter based on a thermally induced linearly chirped fiber Bragg grating. Experimentally we achieved a thermally induced optical bandpass filter that has eight switchable passband peaks with peak separations of 1.6 and 3.2 nm, a very narrow bandwidth (as small as 10 pm) of each peak, a tunable range of 16.5 nm, and a greater than 25 dB rejection ratio. Two spectral peaks separated by only 0.8 nm were also obtained with this comb filter. This filter provides the unique advantages of an all-fiber structure, switchable spectral peaks, independent tuning of the center wavelength and wavelength spacing of the spectral peaks, low polarization sensitivity, simple structure, ease of fabrication, and low cost.
Journal Article↗