The chromosomal translocation t(7; 11)(p15;p15), observed in human myeloid leukemia, results in a NUP98 and HOXA9 gene fusion. We generated a transgenic mouse line that specifically expressed the ...chimeric NUP98-HOXA9 gene in the myeloid lineage. While only 20% of the transgenic mice progressed to leukemia after a latency period, myeloid progenitor cells from nonleukemic transgenic mice still exhibited increased proliferative potential. This suggested that the NUP98-HOXA9 fusion induced a preleukemic phase, and other factors were required for complete leukemogenesis. NUP98-HOXA9 expression promoted the onset of retrovirus-induced BXH2 myeloid leukemia. This phenomenon was used to identify cooperative disease genes as common integration sites (CISs). Meis1, a known HOX cofactor, was identified as a CIS with a higher integration frequency in transgenic than in wild-type BXH2 mice. By the same means we identified further 4 candidate cooperative genes, Dnalc4, Fcgr2b, Fcrl, and Con1. These genes cooperated with NUP98-HOXA9 in transforming NIH 3T3 cells. The system described here is a powerful tool to identify cooperative oncogenes and will assist in the clarification of the multistep process of carcinogenesis.
The SIDDHARTA experiment aims at a precise measurement of K -series kaonic hydrogen x-rays and the first-ever measurement of the kaonic deuterium x-rays to determine the strong-interaction ...energy-level shift and width of the lowest lying atomic states. These measurements offer a unique possibility to precisely determine the isospin-dependent -nucleon scattering lengths.
Abstract We report the first measurement of the exclusive cross sections e + e − → B B ¯ $$ B\overline{B} $$ , e + e − → B B ¯ ∗ $$ B{\overline{B}}^{\ast } $$ , and e + e − → B ∗ B ¯ ∗ $$ {B}^{\ast ...}{\overline{B}}^{\ast } $$ in the energy range from 10.63 GeV to 11.02 GeV. The B mesons are fully reconstructed in a large number of hadronic final states and the three channels are identified using a beam-constrained-mass variable. The shapes of the exclusive cross sections show oscillatory behavior with several maxima and minima. The results are obtained using data collected by the Belle experiment at the KEKB asymmetric-energy e + e − collider.
We report the first observation of the Ξc(2930)0 charmed-strange baryon with a significance greater than 5σ. The Ξc(2930)0 is found in its decay to K-Λc+ in B-→K-Λc+Λ¯c- decays. The measured mass and ...width are 2928.9±3.0(stat.)-12.0+0.9(syst.) MeV/c2 and 19.5±8.4(stat.)-7.9+5.9(syst.) MeV, respectively, and the product branching fraction is B(B-→Ξc(2930)0Λ¯c-)B(Ξc(2930)0→K-Λc+)=1.73±0.45(stat.)±0.21(syst.)×10-4. We also measure B(B-→K-Λc+Λ¯c-)=4.80±0.43(stat.)±0.60(syst.)×10-4 with improved precision, and search for the charmonium-like state Y(4660) and its spin partner, Yη, in the Λc+Λ¯c- invariant mass spectrum. No clear signals of the Y(4660) nor its spin partner are observed and the 90% credibility level (C.L.) upper limits on their production rates are determined. These measurements are obtained from a sample of (772±11)×106BB¯ pairs collected at the Υ(4S) resonance by the Belle detector at the KEKB asymmetric energy electron–positron collider.
For clinicians, the orthodox histological investigation of patients with invasive ductal carcinoma (IDC) remains important for predicting prognoses. The purpose of the present study was to determine ...the most important of the known prognostic histological parameters (including fibrotic focus and tumor necrosis), enabling the outcomes of 101 patients with IDC of the pancreas to be predicted accurately. Furthermore, we established a scoring classification consisting of important prognostic histological parameters examined in this study. Multivariate survival analyses showed that invasive tumor size of more than 3 cm, the presence of tumor necrosis, the presence of nerve plexus invasion and lymph vessel invasion scores of 2 or 3 were important prognostic factors. Our scoring classification, consisting of the above four parameters, accurately classified the outcome of patients independent of the invasive tumor size of IDC. We concluded that invasive tumor size of 3 cm or more, the presence of tumor necrosis, the presence of nerve plexus invasion and lymph vessel invasion scores of 2 or 3 are important histological prognostic parameters for patients with IDC of the pancreas. Furthermore, the scoring system consisting of the above four histological parameters is probably a very useful prognostic histological classification for patients with IDC of the pancreas. (Cancer Sci 2005; 96: 858–865)
Background: Allergic rhinitis is an inflammation involving TH2-type cytokine production, with pathologic eosinophil infiltration in the nasal mucosa. Although TNF-α is thought to be a ...pro-inflammatory cytokine, the relationship between TNF-α and allergic rhinitis has not been clarified. Objectives: The role of TNF-α in a murine model of ovalbumin (OVA)-sensitized allergic rhinitis was investigated by using mice deficient in the gene encoding TNF-α (TNF-α–/– mice). Methods: Both wild-type (TNF-α+/+) and TNF-α–/– mice were sensitized with OVA by means of intraperitoneal injection. They were then challenged with intranasal OVA, and various allergic responses were assessed. Results: The production of OVA-specific IgE in the serum (P < .05) and the frequency of sneezes (P < .05) and nasal rubs (P < .05) decreased significantly in TNF-α–/– mice after OVA sensitization compared with that in TNF-α+/+ mice (P < .05). The mRNA expression of IL-4, IL-10, and eotaxin in nasal mucosa in TNF-α–/– mice was also significantly suppressed compared with that in TNF-α+/+ mice after OVA sensitization (P < .05). Furthermore, the expression of both endothelial-leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1 mRNA in the nasal mucosa was significantly suppressed (P < .05), although intercellular adhesion molecule 1 mRNA expression did not decrease significantly in TNF-α–/– mice compared with that in TNF-α+/+ mice after OVA sensitization. In addition, the effect of TNF-α on endothelial-leukocyte adhesion molecule 1 and vascular cell adhesion molecule 1 expression by means of Western blot analysis was compatible with the mRNA results. Pathologically, eosinophil infiltration in nasal mucosa was significantly restricted in TNF-α–/– mice compared with in TNF-α+/+ mice after OVA sensitization (P < .05). Conclusion: TNF-α is necessary for antigen-specific IgE production and for the induction of TH2-type cytokines and chemokines. Furthermore, TNF-α might be important for the expression of adhesion molecules to recruit eosinophils to the allergic inflammatory site. We conclude that the lack of TNF-α inhibited the development of allergic rhinitis. (J Allergy Clin Immunol 2003;112:134-40.)
Prostaglandin D2 is known to be the major prostanoid produced by allergen-activated mast cells, but its role in the formation of allergic diseases is not well established because of complexity of its ...receptor system and lack of appropriate inhibitors. We have recently identified a new-type prostaglandin D2 receptor, named CRTH2. Studies with normal subjects have shown that CRTH2 appears to be selectively expressed by T helper 2 cells but not T helper 1 cells among circulating CD4+ lymphocytes. The exact correlation between CRTH2 and T helper 2 cells in various disease settings and the impact of CRTH2-mediated prostaglandin D2 activities on various T helper 2 responses in vivo still remain to be elucidated, however. In this study, we investigated the correlation between CRTH2 and T helper 2 cells among circulating CD4+ lymphocytes in normal adults and patients with atopic dermatitis, a T-helper-2-involving disease. The results showed that virtually all CRTH2+CD4+ lymphocytes had a pure T helper 2 phenotype and formed not all but a large proportion of circulating T helper 2 cells for both normal and atopic dermatitis subjects. In chemotaxis assays, peripheral blood CRTH2+CD4+ lymphocytes were significantly attracted by prostaglandin D2 as well as by a typical T-helper-2-attracting chemokine, thymus and activation regulated chemokine, whereas they showed little chemotactic migration toward typical T-helper-1-attracting chemokines, macrophage inflammatory protein 1β and interferon-γ-inducible protein 10. Furthermore, in atopic dermatitis patients, a preferential increase of CRTH2+ cells was noted within the disease-related cutaneous lymphocyte-associated antigen-positive, but not the cutaneous lymphocyte-associated antigen-negative, CD4+ lymphocyte compartment. Our results suggest the involvement of the prostaglandin D2/CRTH2 system in both normal and pathogenic T helper 2 responses.
Abstract Using a data sample of 980 fb −1 collected with the Belle detector at the KEKB asymmetric-energy e + e − collider, we study for the first time the singly Cabibbo-suppressed decays Ω c 0 → Ξ ...− π + $$ {\Omega}_c^0\to {\Xi}^{-}{\pi}^{+} $$ and Ω − K + and the doubly Cabibbo-suppressed decay Ω c 0 → Ξ − K + $$ {\Omega}_c^0\to {\Xi}^{-}{K}^{+} $$ . Evidence for an Ω c 0 $$ {\Omega}_c^0 $$ signal in the Ω c 0 $$ {\Omega}_c^0 $$ → Ξ − π + mode is reported with a significance of 4.5σ including systematic uncertainties. The ratio of branching fractions to the normalization mode Ω c 0 $$ {\Omega}_c^0 $$ → Ω − π + is measured to be B Ω c 0 → Ξ − π + / B Ω c 0 → Ω − π + = 0.253 ± 0.052 stat . ± 0.030 syst . . $$ \mathcal{B}\left({\Omega}_c^0\to {\Xi}^{-}{\pi}^{+}\right)/\mathcal{B}\left({\Omega}_c^0\to {\Omega}^{-}{\pi}^{+}\right)=0.253\pm 0.052\left(\textrm{stat}.\right)\pm 0.030\left(\textrm{syst}.\right). $$ No significant signals of Ω c 0 → Ξ − K + $$ {\Omega}_c^0\to {\Xi}^{-}{K}^{+} $$ and Ω − K + modes are found. The upper limits at 90% confidence level on ratios of branching fractions are determined to be B Ω c 0 → Ξ − K + / B Ω c 0 → Ω − π + < 0.070 $$ \mathcal{B}\left({\Omega}_c^0\to {\Xi}^{-}{K}^{+}\right)/\mathcal{B}\left({\Omega}_c^0\to {\Omega}^{-}{\pi}^{+}\right)<0.070 $$ and B Ω c 0 → Ω − K + / B Ω c 0 → Ω − π + < 0.29 . $$ \mathcal{B}\left({\Omega}_c^0\to {\Omega}^{-}{K}^{+}\right)/\mathcal{B}\left({\Omega}_c^0\to {\Omega}^{-}{\pi}^{+}\right)<0.29. $$
We will measure the Balmer-series x-rays of kaonic-3He atoms using large-area high-resolution silicon drift x-rays detectors in order to provide the crucial information of K−-nucleus strong ...interaction at the low energy limit. The strong interaction 2p level shift will be determined with a precision of a few eV. At the present status, the construction of all detectors is in progress. In February, 2009, the first tuning of K1.8BR beamline was performed by the secondary beam generated in J-PARC hadron facility. The data taking will be started soon.
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