Visualization of Laterally Spreading Colorectal Tumors by Using Image-Enhanced Endoscopy

Laterally spreading tumors may sometimes evade detection by colonoscopy. This study aimed to evaluate the use of image-enhanced endoscopy for visualizing laterally spreading tumors of the nongranular type. We reviewed consecutive patients with 47 non-granular-type laterally spreading tumors that had been examined using white-light imaging, autofluorescence imaging, narrow-band imaging, and chromoendoscopy with indigo carmine. The quality of visualization was evaluated using a 5-point scale by less- and more-experienced endoscopists. Autofluorescence imaging provided significantly better visualization than white-light imaging for both less-experienced and experienced endoscopists. On the other hand, no significant differences were observed between the quality of visualization provided by white-light imaging and narrow-band imaging for less-experienced endoscopists. Autofluorescence imaging provides high-quality visualization of non-granular-type laterally spreading tumors on still images. Multicenter trials should be conducted to confirm the usefulness of autofluorescence imaging in detecting laterally spreading colorectal tumors

Cost-Effectiveness of Total Colonoscopy in Screening of Colorectal Cancer in Japan

Introduction. In Japan, the cost-effectiveness of total colonoscopy (TCS) for primary screening of colorectal cancer (CRC) is unclear. We compared the cost of identifying a patient with CRC using two primary screening strategies: TCS (strategy 1) and the immunochemical fecal test (FIT) (strategy 2). Materials and Methods. We retrospectively analyzed the TCS screening database at our institution from February 2004 to August 2010 (strategy 1, n = 15,348) and the Japanese nationwide survey of CRC screening in 2008 (strategy 2, n = 5,267,443). Results. 112 and 6,838 CRC cases were detected in strategies 1 and 2, costing 2,124,000 JPY and 1,629,000 JPY, respectively. The rate of earlier-stage CRC was higher in strategy 1. Conclusions. The cost was higher using TCS as a primary screening procedure. However, the difference was not excessive, and considering the increased rate of detecting earlier CRC, the use of TCS as a primary screening tool may be cost-effective

Coordination of Cell Polarity during Xenopus Gastrulation

Cell polarity is an essential feature of animal cells contributing to morphogenesis. During Xenopus gastrulation, it is known that chordamesoderm cells are polarized and intercalate each other allowing anterior-posterior elongation of the embryo proper by convergent extension (CE). Although it is well known that the cellular protrusions at both ends of polarized cells exert tractive force for intercalation and that PCP pathway is known to be essential for the cell polarity, little is known about what triggers the cell polarization and what the polarization causes to control intracellular events enabling the intercalation that leads to the CE. In our research, we used EB3 (end-binding 3), a member of +TIPs that bind to the plus end of microtubule (MT), to visualize the intracellular polarity of chordamesoderm cells during CE to investigate the trigger of the establishment of cell polarity. We found that EB3 movement is polarized in chordamesoderm cells and that the notochord-somite tissue boundary plays an essential role in generating the cell polarity. This polarity was generated before the change of cell morphology and the polarized movement of EB3 in chordamesoderm cells was also observed near the boundary between the chordamesoderm tissue and naïve ectoderm tissue or lateral mesoderm tissues induced by a low concentration of nodal mRNA. These suggest that definitive tissue separation established by the distinct levels of nodal signaling is essential for the chordamesodermal cells to acquire mediolateral cell polarity

Development of a Multi-Step Leukemogenesis Model of MLL-Rearranged Leukemia Using Humanized Mice

Mixed-lineage-leukemia (MLL) fusion oncogenes are intimately involved in acute leukemia and secondary therapy-related acute leukemia. To understand MLL-rearranged leukemia, several murine models for this disease have been established. However, the mouse leukemia derived from mouse hematopoietic stem cells (HSCs) may not be fully comparable with human leukemia. Here we developed a humanized mouse model for human leukemia by transplanting human cord blood-derived HSCs transduced with an MLL-AF10 oncogene into a supra-immunodeficient mouse strain, NOD/Shi-scid, IL-2Rγ−/− (NOG) mice. Injection of the MLL-AF10-transduced HSCs into the liver of NOG mice enhanced multilineage hematopoiesis, but did not induce leukemia. Because active mutations in ras genes are often found in MLL-related leukemia, we next transduced the gene for a constitutively active form of K-ras along with the MLL-AF10 oncogene. Eight weeks after transplantation, all the recipient mice had developed acute monoblastic leukemia (the M5 phenotype in French-American-British classification). We thus successfully established a human MLL-rearranged leukemia that was derived in vivo from human HSCs. In addition, since the enforced expression of the mutant K-ras alone was insufficient to induce leukemia, the present model may also be a useful experimental platform for the multi-step leukemogenesis model of human leukemia

The AAA-ATPase VPS4 Regulates Extracellular Secretion and Lysosomal Targeting of α-Synuclein

Many neurodegenerative diseases share a common pathological feature: the deposition of amyloid-like fibrils composed of misfolded proteins. Emerging evidence suggests that these proteins may spread from cell-to-cell and encourage the propagation of neurodegeneration in a prion-like manner. Here, we demonstrated that α-synuclein (αSYN), a principal culprit for Lewy pathology in Parkinson's disease (PD), was present in endosomal compartments and detectably secreted into the extracellular milieu. Unlike prion protein, extracellular αSYN was mainly recovered in the supernatant fraction rather than in exosome-containing pellets from the neuronal culture medium and cerebrospinal fluid. Surprisingly, impaired biogenesis of multivesicular body (MVB), an organelle from which exosomes are derived, by dominant-negative mutant vacuolar protein sorting 4 (VPS4) not only interfered with lysosomal targeting of αSYN but facilitated αSYN secretion. The hypersecretion of αSYN in VPS4-defective cells was efficiently restored by the functional disruption of recycling endosome regulator Rab11a. Furthermore, both brainstem and cortical Lewy bodies in PD were found to be immunoreactive for VPS4. Thus, VPS4, a master regulator of MVB sorting, may serve as a determinant of lysosomal targeting or extracellular secretion of αSYN and thereby contribute to the intercellular propagation of Lewy pathology in PD

Luminescence enhancement of water soluble CdTe quantum dots by proper surface modification with ethylene diamine

Thioglycolic acid (TGA) capped CdTe quantum dots (QDs) have been synthesized in aqueous media. The effect of diamine on luminescence property of TGA capped CdTe QDs has been investigated and it has been found that the diamine significantly affects the optical properties of CdTe QDs. Luminescence efficiency as well as lifetime of CdTe QDs have seen to be enhanced notably up to certain concentration of the ethylene diamine added and the observation is much more pronounced in case of smaller size QDs. The results indicate that the local surface-trap states of CdTe QDs reduced effectively by the EDA treatment. (C) 2011 Elsevier B.V. All rights reserved