173 research outputs found
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東京理科大学202
ACPA-negative RA consists of two genetically distinct subsets based on RF positivity in Japanese.
HLA-DRB1, especially the shared epitope (SE), is strongly associated with rheumatoid arthritis (RA). However, recent studies have shown that SE is at most weakly associated with RA without anti-citrullinated peptide/protein antibody (ACPA). We have recently reported that ACPA-negative RA is associated with specific HLA-DRB1 alleles and diplotypes. Here, we attempted to detect genetically different subsets of ACPA-negative RA by classifying ACPA-negative RA patients into two groups based on their positivity for rheumatoid factor (RF). HLA-DRB1 genotyping data for totally 954 ACPA-negative RA patients and 2,008 healthy individuals in two independent sets were used. HLA-DRB1 allele and diplotype frequencies were compared among the ACPA-negative RF-positive RA patients, ACPA-negative RF-negative RA patients, and controls in each set. Combined results were also analyzed. A similar analysis was performed in 685 ACPA-positive RA patients classified according to their RF positivity. As a result, HLA-DRB1*04:05 and *09:01 showed strong associations with ACPA-negative RF-positive RA in the combined analysis (p = 8.8×10(-6) and 0.0011, OR: 1.57 (1.28-1.91) and 1.37 (1.13-1.65), respectively). We also found that HLA-DR14 and the HLA-DR8 homozygote were associated with ACPA-negative RF-negative RA (p = 0.00022 and 0.00013, OR: 1.52 (1.21-1.89) and 3.08 (1.68-5.64), respectively). These association tendencies were found in each set. On the contrary, we could not detect any significant differences between ACPA-positive RA subsets. As a conclusion, ACPA-negative RA includes two genetically distinct subsets according to RF positivity in Japan, which display different associations with HLA-DRB1. ACPA-negative RF-positive RA is strongly associated with HLA-DRB1*04:05 and *09:01. ACPA-negative RF-negative RA is associated with DR14 and the HLA-DR8 homozygote
Prognostic impact of complex and/or monosomal karyotypes in post‐transplant poor cytogenetic acute myeloid leukaemia: A quantitative approach
To evaluate the prognostic impact of complex karyotype (CK) and/or monosomal karyotype (MK) in combination with various clinical factors on allogeneic stem cell transplantation (HSCT) outcomes of patients with acute myeloid leukaemia (AML), we analysed the registry database of adult AML patients who underwent allogeneic HSCT between 2000 and 2019 in Japan. Among 16 094 patients, those with poor cytogenetic risk (N = 3345) showed poor overall survival (OS) after HSCT (25.3% at 5 years). Multivariate analyses revealed that CK and/or MK (hazard ratio [HR], 1.31 for CK without MK; 1.27 for MK without CK; and 1.73 for both), age at HSCT ≥50 years (HR, 1.58), male sex (HR, 1.40), performance status ≥2 (HR, 1.89), HCT-CI score ≥3 (HR, 1.23), non-remission status at HSCT (HR, 2.49), and time from diagnosis to HSCT ≥3 months (HR, 1.24) independently reduced post-HSCT OS among patients with poor cytogenetic risk AML. A risk scoring system based on the multivariate analysis successfully stratified patients into five distinct groups for OS. This study confirms the negative effects of CK and MK on post-HSCT outcomes, and offers a powerful risk scoring system for predicting prognoses after HSCT among AML patients with unfavourable cytogenetics
p38 MAPK as a gatekeeper of reprogramming in mouse migratory primordial germ cells
Mammalian germ cells are derived from primordial germ cells (PGCs) and ensure species continuity through generations. Unlike irreversible committed mature germ cells, migratory PGCs exhibit a latent pluripotency characterized by the ability to derive embryonic germ cells (EGCs) and form teratoma. Here, we show that inhibition of p38 mitogen-activated protein kinase (MAPK) by chemical compounds in mouse migratory PGCs enables derivation of chemically induced Embryonic Germ-like Cells (cEGLCs) that do not require conventional growth factors like LIF and FGF2/Activin-A, and possess unique naïve pluripotent-like characteristics with epiblast features and chimera formation potential. Furthermore, cEGLCs are regulated by a unique PI3K-Akt signaling pathway, distinct from conventional naïve pluripotent stem cells described previously. Consistent with this notion, we show by performing ex vivo analysis that inhibition of p38 MAPK in organ culture supports the survival and proliferation of PGCs and also potentially reprograms PGCs to acquire indefinite proliferative capabilities, marking these cells as putative teratoma-producing cells. These findings highlight the utility of our ex vivo model in mimicking in vivo teratoma formation, thereby providing valuable insights into the cellular mechanisms underlying tumorigenesis. Taken together, our research underscores a key role of p38 MAPK in germ cell development, maintaining proper cell fate by preventing unscheduled pluripotency and teratoma formation with a balance between proliferation and differentiation
Advantages of peripheral blood stem cells from unrelated donors versus bone marrow transplants in outcomes of adult acute myeloid leukemia patients
[Background aims] In allogeneic stem cell transplantation, unrelated donors are chosen in cases where appropriate related donors are not available. Peripheral blood stem cells (PBSCs) are more often selected as a graft source than bone marrow (BM). However, the prognostic benefits of PBSCs versus BM transplants from unrelated donors have not been carefully examined in patients with acute myeloid leukemia (AML). This study compared outcomes of adult AML patients who underwent unrelated PBSC and BM transplantation, evaluating post-transplant complications, including engraftment, graft-versus-host disease (GVHD) and infections, and determined subgroups of patients who are most likely to benefit from unrelated PBSCs compared with BM transplants. [Methods] The authors analyzed 2962 adult AML patients who underwent unrelated PBSC or BM transplants between 2011 and 2018 (221 PBSC and 2741 BM) using the Japanese nationwide registry database, in which graft source selection is not skewed toward PBSCs. [Results] In 49.7% of patients, disease status at transplantation was first complete remission (CR1). In 57.1% of cases, HLA-matched donors were selected. Myeloablative conditioning was performed in 75.1% of cases, and anti-thymocyte globulin (ATG) was added to conditioning in 10.5%. Multivariate analyses showed a trend toward favorable non-relapse mortality (NRM) in PBSC recipients compared with BM recipients (hazard ratio [HR], 0.731, P = 0.096), whereas overall survival (OS) (HR, 0.959, P = 0.230) and disease-free survival (DFS) (HR, 0.868, P = 0.221) were comparable between PBSC and BM recipients. Although the rate of chronic GVHD (cGVHD) was significantly higher in PBSC patients (HR, 1.367, P = 0.016), NRM was not increased, mainly as a result of significantly reduced risk of bacterial infections (HR, 0.618, P = 0.010), reflecting more prompt engraftments in PBSC recipients. Subgroup analyses revealed that PBSC transplantation was advantageous in patients transplanted at CR1 and in those without ATG use. PBSC recipients experienced significantly better OS and/or DFS compared with BM recipients in this patient group. [Conclusions] The authors' results confirmed the overall safety of unrelated PBSC transplantation for adult AML patients and suggested an advantage of PBSCs, especially for those in CR1. Further optimization of the prophylactic strategy for cGVHD is required to improve the overall outcome in transplantation from unrelated PBSC donors
Measurement of the Branching Fraction for B->eta' K and Search for B->eta'pi+
We report measurements for two-body charmless B decays with an eta' meson in
the final state. Using 11.1X10^6 BBbar pairs collected with the Belle detector,
we find BF(B^+ ->eta'K^+)=(79^+12_-11 +-9)x10^-6 and BF(B^0 ->
eta'K^0)=(55^+19_-16 +-8)x10^-6, where the first and second errors are
statistical and systematic, respectively. No signal is observed in the mode B^+
-> eta' pi^+, and we set a 90% confidence level upper limit of BF(B^+->
eta'pi^+) eta'K^+- decays is
investigated and a limit at 90% confidence level of -0.20<Acp<0.32 is obtained.Comment: Submitted to Physics Letters
Search for Direct CP Violation in B -> K pi Decays
We search for direct CP violation in flavor specific B -> K pi decays by
measuring the rate asymmetry between charge conjugate modes. The search is
performed on a data sample of 11.1 million B B bar events recorded on the
Upsilon(4S) resonance by the Belle experiment at KEKB. We measure 90%
confidence intervals in the partial rate asymmetry A_CP of -0.25 < A_CP(K-/+
pi+/-) < 0.37, -0.40 < A_CP(K-/+ pi^0) < 0.36, and -0.53 < A_CP(K^0 pi-/+) <
0.82. By combining the K-/+ pi+/- and K-/+ pi^0 final states, we conclude that
-0.22 < A_CP[K-/+(pi+/- + pi^0)] < 0.25 at the 90% confidence level.Comment: Submitted to PRD Rapid Communication
A Measurement of the Branching Fraction for the Inclusive B --> X(s) gamma Decays with the Belle Detector
We have measured the branching fraction of the inclusive radiative B meson
decay B --> X(s) gamma to be Br(B->X(s)gamma)=(3.36 +/- 0.53(stat) +/-
0.42(sys) +0.50-0.54(th)) x 10^{-4}.
The result is based on a sample of 6.07 x 10^6 BBbar events collected at the
Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e^+e^-
storage ring.Comment: 14 pages, 6 Postsript figures, uses elsart.cl
Observation of Mixing-induced CP Violation in the Neutral B Meson System
This report describes an observation of mixing-induced CP violation and a
measurement of the CP violation parameter, sin(2phi_1), with the Belle detector
at the KEKB asymmetric e+e- collider. Using a data sample of 29.1 fb-1 recorded
on the Upsilon(4S) resonance that contains 31.3 million BBbar pairs, we
reconstruct decays of neutral B mesons to the following CP eigenstates: J/psi
K_S^0, psi(2S) K_S^0, chi_c1 K_S^0, eta_c K_S^0, J/psi K_L^0 and J/psi K^*0.
The flavor of the accompanying B meson is identified by combining information
from primary and secondary leptons, K+/- mesons, lambda baryons, slow and fast
pions. The proper-time interval between the two B meson decays is determined
from the distance between the two decay vertices measured with a silicon vertex
detector. The result sin(2phi_1) = 0.99 +/- 0.14(stat) +/- 0.06(syst) is
obtained by applying a maximum likelihood fit to the 1137 candidate events. We
conclude that there is large CP violation in the neutral B meson system. A zero
value for sin(2phi_1) is ruled out by more than six standard deviations.Comment: 25 pages, 16 figures, accepted for publication in Physical Review
Observation of Cabibbo suppressed decays at Belle
Cabibbo-suppressed decays using a 10.4 fb data
sample accumulated at the resonance with the Belle detector at
the KEKB storage ring. The high-momentum particle identification
system of Belle is used to isolate signals for , ,
and from the decay processes which
have much larger branching fractions. We report ratios of Cabibbo-suppressed to
Cabibbo-favored branching fractions of: ; ; ; and
. The first error is statistical and the second is systematic.
These are the first reported observations of the , and
decay processes.Comment: LaTeX, 12 pages, 2 figure
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