Decreased secretion of Paneth cell α-defensins in graft-versus-host disease.

Background: Intestinal microbial ecology is actively regulated by Paneth cell-derived antimicrobial peptides, α-defensins. Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT). We previously demonstrated that Paneth cells are targeted by GVHD, and their expression of antimicrobial peptide α-defensins is impaired, leading to a loss of physiological diversity among the microflora and development of bloodstream infection.

Preserved in vivo reconstitution ability of PBSCs cryopreserved for a decade at -80 °C.

PBSC products for auto- and allografting can be cryopreserved in liquid nitrogen with controlled-rate freezing until their use. Alternatively, they can be stored at -80 °C in a mechanical chest freezer, but it remains to be clarified whether PBSCs can be stored for the long term. We evaluated viability and functions of PBSCs cryopreserved for more than 10 years with this simplified method.

Successful treatment of invasive zygomycosis based on a prompt diagnosis using molecular methods in a patient with acute myelogenous leukemia.

Zygomycosis is a lethal and invasive mold infection that is often associated with hematological malignancies. The keys for successful treatment include making a rapid diagnosis and appropriately administering antifungal agents. We herein report the early diagnosis of a case of zygomycosis in a patient with acute myeloid leukemia using a deoxyribonucleic acid sequence analysis.

Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation.

Cellular differentiation is regulated through activation and repression of defined transcription factors. A hallmark of differentiation is a pronounced change in cell shape, which is determined by dynamics of the actin cytoskeleton. Here we show that regulation of the transcriptional coactivator MKL1 (megakaryoblastic leukemia 1) by actin cytoskeleton dynamics drives adipocyte differentiation mediated by peroxisome proliferator-activated receptor γ (PPARγ), a master transcriptional regulator of adipogenesis.

High-dose chemotherapy with autologous stem cell transplantation for elderly patients with relapsed/refractory diffuse large B cell lymphoma: a nationwide retrospective study.

The number of elderly patients with diffuse large B cell lymphoma (DLBCL) continues to increase but the data regarding autologous stem cell transplantation (ASCT) for elderly patients are limited. We analyzed 484 patients, ages 60 years or over, diagnosed with relapsed/refractory DLBCL who received ASCT from 1993 to 2010 in the Japan Society for Hematopoietic Cell Transplantation database. Median age was 64 years (range, 60 to 78).

Radial mycotic aneurysm complicated with infective endocarditis caused by Streptococcus sanguinis.

Peripheral mycotic aneurysm is a rare complication of infective endocarditis. We herein report the case of a 61-year-old man with a mycotic aneurysm in the left brachial artery, that appeared during treatment with antibiotics against infective endocarditis caused by Streptococcus sanguinis. After confirming the collateral blood flow on arteriography, we resected the aneurysm and performed valvuloplasty, annuloplasty and coronary artery bypass grafting.

Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning.

Graft rejection remains a major obstacle in allogeneic hematopoietic SCT following reduced-intensity conditioning (RIC-SCT), particularly after cord blood transplantation (CBT). In a murine MHC-mismatched model of RIC-SCT, primary graft rejection was associated with activation and expansion of donor-reactive host T cells in peripheral blood and BM early after SCT. Donor-derived dendritic cells are at least partly involved in host T-cell activation.

Reduced-intensity conditioning followed by cord blood transplantation in a patient with refractory folliculotropic mycosis fungoides.

Advanced-stage mycosis fungoides (MF) has a generally poor prognosis. Allogeneic hematopoietic stem cell transplantation improves the outcome of advanced-stage MF. Recently, cord blood has been used as an alternative stem cell source; however, there are few reports of MF patients treated using cord blood transplantation.

Reciprocal expression of enteric antimicrobial proteins in intestinal graft-versus-host disease.

We recently demonstrated that expression of α-defensins, the major antimicrobial peptides produced by Paneth cells, was severely suppressed in mice with graft-versus-host disease (GVHD). In this study, we found that antibacterial lectin, regenerating islet-derived IIIγ (RegIIIγ) was upregulated in villous enterocytes, thus demonstrating the reciprocal control of enteric antimicrobial proteins in GVHD. Upregulation of RegIIIγ was mediated by a mechanism independent upon radiation-induced intestinal tract damage.

Combination of high-dose melphalan and bortezomib as conditioning regimen for autologous peripheral blood stem cell transplantation in multiple myeloma.

Bortezomib and melphalan have synergistic effects against multiple myeloma (MM) cells. We conducted a pilot study on the combination of bortezomib and high-dose melphalan (Bor-HDM) as a conditioning regimen followed by autologous stem cell transplant (ASCT) in 17 Japanese patients with newly diagnosed MM, in comparison with a historical control of patients who received high-dose melphalan (HDM) only followed by ASCT. Nine patients received a single dose of bortezomib 1.

Partially silencing brain toll-like receptor 4 prevents in part left ventricular remodeling with sympathoinhibition in rats with myocardial infarction-induced heart failure.

Background: Left ventricular (LV) remodeling and activation of sympathetic nervous system (SNS) are cardinal features of heart failure. We previously demonstrated that enhanced central sympathetic outflow is associated with brain toll-like receptor 4 (TLR4) probably mediated by brain angiotensin II type 1 receptor in mice with myocardial infarction (MI)-induced heart failure. The purpose of the present study was to examine whether silencing brain TLR4 could prevent LV remodeling with sympathoinhibition in MI-induced heart failure.

Evaluating the association between histological manifestations of cord colitis syndrome with GVHD.

Cord colitis syndrome (CCS) is a recently proposed clinical entity characterized by a persistent diarrheal illness after cord blood transplantation (CBT), which is not caused by GVHD or CMV colitis. CCS is histologically characterized by chronic active colitis with granulomatous inflammation and Paneth cell metaplasia suggesting chronicity. However, the specificity of these pathological features to CCS remains to be validated.

Contribution of bone marrow-derived hematopoietic stem/progenitor cells to the generation of donor-marker⁺ cardiomyocytes in vivo.

Background: Definite identification of the cell types and the mechanism relevant to cardiomyogenesis is essential for effective cardiac regenerative medicine. We aimed to identify the cell populations that can generate cardiomyocytes and to clarify whether generation of donor-marker(+) cardiomyocytes requires cell fusion between BM-derived cells and recipient cardiomyocytes.

Methodology/principal Findings: Purified BM stem/progenitor cells from green fluorescence protein (GFP) mice were transplanted into C57BL/6 mice or cyan fluorescence protein (CFP)-transgenic mice.

Diffuse panbronchiolitis after humanized anti-CCR4 monoclonal antibody therapy for relapsed adult T-cell leukemia/lymphoma.

We present the case of a 62-year-old Japanese woman with relapsed adult T-cell leukemia/lymphoma (ATLL) who was treated with humanized anti-CCR4 monoclonal antibody (KW-0761). Although this antibody was highly effective against refractory ATLL, 6 months after the final KW-0761 infusion, the patient complained of hypoxia due to diffuse panbronchiolitis. Physicians should remain vigilant to the possibility of such previously unreported late-onset adverse effects associated with KW-0761 therapy.

A novel filtration method for cord blood processing using a polyester fabric filter.

Introduction: Cord blood (CB) is being increasingly used as a source of hematopoietic stem cells for transplantation to treat diseases of the blood and immune systems, and there is an urgent need to expand CB banking worldwide. CB processing requires costly machinery or a clean room that hampers wider application of CBT particularly in the developing countries.

Methods: We developed a novel filtration system using a nonchemical-coated and nonwoven polyester fabric filter, which traps cells through affinity and does not require centrifugation or potentially toxic chemicals.

Inhibition of oxidative stress in rostral ventrolateral medulla improves impaired baroreflex sensitivity in stroke-prone spontaneously hypertensive rats.

Reactive oxygen species (ROS) in rostral ventrolateral medulla (RVLM) of brainstem contribute to sympathoexcitation and are critically involved in the pathogenesis of hypertension. Baroreflex sensitivity (BRS) is a valuable prognostic parameter of the autonomic nervous system, and is impaired in hypertension. The aim of the present study was to determine whether or not a chronic reduction of ROS in the RVLM improves impaired BRS in hypertensive rats.

Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of α-defensins.

Allogeneic hematopoietic stem cell transplantation (SCT) is a curative therapy for various hematologic disorders. Graft-versus-host disease (GVHD) and infections are the major complications of SCT, and their close relationship has been suggested. In this study, we evaluated a link between 2 complications in mouse models.

The Wnt agonist R-spondin1 regulates systemic graft-versus-host disease by protecting intestinal stem cells.

Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (BMT), and damage to the gastrointestinal (GI) tract plays a critical role in amplifying systemic disease. Intestinal stem cells (ISCs) play a pivotal role not only in physiological tissue renewal but also in regeneration of the intestinal epithelium after injury. In this study, we have discovered that pretransplant conditioning regimen damaged ISCs; however, the ISCs rapidly recovered and restored the normal architecture of the intestine.

Phase I/II study of tandem high-dose chemotherapy with autologous peripheral blood stem cell transplantation for advanced multiple myeloma.

The efficacy and safety of high-dose chemotherapy with tandem autologous peripheral blood stem cell transplantation (auto-PBSCT) were evaluated in a multicenter clinical study of patients with advanced multiple myeloma. Eligible patients (n = 40) were consecutively enrolled in the phase I/II study and received 2-4 cycles of vincristine-adriamycin-dexamethasone regimen. The responding patients underwent PBSC harvesting following high-dose cyclophosphamide and filgrastim administration.

Concurrent infection with Heligmosomoides polygyrus suppresses anti-Plasmodium yoelii protection partially by induction of CD4(+)CD25(+)Foxp3(+) Treg in mice.

Malaria and intestinal nematode infection are widespread and co-infection frequently occurs. We investigated whether co-infected intestinal nematodes modulate immunity against co-existing malaria parasites. Infection of C57BL/6 mice with Plasmodium yoelii 17XNL (Py) was transient and self-limiting, but preceding infection with Heligmosomoides polygyrus (Hp), a mouse intestinal nematode, exacerbated malaria resulting in higher parasite burdens and poor survival of the mice.

Rituximab for the treatment of corticosteroid-refractory chronic graft-versus-host disease.

We prospectively evaluated the safety and efficacy of the anti-CD20 chimeric monoclonal antibody rituximab for the treatment of corticosteroid-refractory chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. Seven patients were treated with 375 mg/m(2) rituximab weekly for 4 consecutive weeks. Rituximab was well tolerated with no severe toxicity observed during treatment.