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Tomoyuki Endo

Publications and source records attributed to Tomoyuki Endo.

16 recordsLinked to original sources
PubMed2006

BAFF and APRIL support chronic lymphocytic leukemia B-cell survival through activation of the canonical NF-kappaB pathway.

Chronic lymphocytic leukemia (CLL) B cells express BR3, the specific receptor for the B cell-activating factor of tumor necrosis factor family (BAFF). CLL cells also express 2 other receptors for BAFF, namely B-cell maturation antigen (BCMA) and the transmembrane activator and calcium modulator and cyclophilin ligand-interactor (TACI), which also bind a proliferation-inducing ligand (APRIL). We found that signaling through BR3, but not BCMA or TACI, activated the alternative nuclear factor of kappa B (NF-kappaB) pathway in CLL cells, whereas signaling through BCMA/TACI induced activation of the canonical NF-kappaB pathway. Blocking BR3 did not inhibit the capacity of BAFF to support CLL cell survival in vitro. On the other hand, specifically blocking the canonical NF-kappaB pathway with UTC, an inhibitor of IkappaB kinase beta (IKKbeta), or transfection of CLL cells with the IkappaBalpha super-repressor, blocked the capacity of BAFF and APRIL to promote CLL cell survival in vitro. This contrasts what is found with normal blood B cells, which apparently depend on activation of the alternative NF-kappaB pathway for BAFF-enhanced survival. These findings suggest that inhibitors of protein kinase IKKbeta, which is required for activation of the canonical NF-kappaB pathway, might have a therapeutic role in this disease.

B-Cell Activating Factor↗
PubMed2006

Multiple myeloma associated with sialyl salivary-type amylase.

BACKGROUND: There have been several reports describing a notable hyperamylasaemia in patients with multiple myeloma. Such amylase-producing myelomas have been mainly described in the context of concomitant salivary-type hyperamylasaemia, with sialyl salivary-type amylase identified in a portion of those cases. We investigated the incidence of the production of sialyl salivary-type amylase in serum of multiple myeloma patients. METHODS: Eleven patients (6 male and 5 female) who had been diagnosed as having multiple myeloma were enrolled in this study. Sialyl salivary-type amylase was detected by isoamylase electrophoresis and HPLC analysis, and identified by detecting either abnormal neuraminidase-sensitive band through isoamylase electrophoresis or abnormal extra-elution peak of amylase by means of HPLC analysis. RESULTS: Sialyl salivary-type amylase was detected in 7 out of 11 (63.6%) patients. Median total amylase activity was 154 U/l (range 109-43020). Isoamylase electrophoretic patterns of patients' serum were normal in 5 patients (71.4%) out of 7 patients and salivary-dominant in 2 (50.0%) out of 4 patients. CONCLUSIONS: We consider that there is no significant relationship between total serum amylase level and amylase isoenzyme pattern in the incidence of production of sialyl salivary-type amylase with multiple myeloma.

Aged↗
PubMed2006

Hypogammaglobulinemia with a selective delayed recovery in memory B cells and an impaired isotype expression after rituximab administration as an adjuvant to autologous stem cell transplantation for non-Hodgkin lymphoma.

OBJECTIVES: Some studies have indicated patients who received rituximab as adjuvant to stem cell transplantation had an increased risk of developing severe hypogammaglobulinemia. The mechanism of this hypogammaglobulinemia is unknown, although investigators have hypothesized a further delay in the B-cell recovery as one potential etiology. The aim of this study is to clarify the mechanism(s) of this hypogammaglobulinemia. METHODS: A total of 14 patients with high-risk CD20+ lymphoma underwent an autologous peripheral blood stem cell transplantation (APBSCT). After a hematological recovery, rituximab was given weekly for up to four doses as an adjuvant therapy. RESULTS: After a median follow up of 33.5 months, we found six patients (group A) who had hypogammaglobulinemia, while the eight other patients (group B) had normal serum immunoglobulin levels. A phenotypical analysis revealed that group A patients had already achieved B-cell recovery. However, we found a severe delay in the recovery of CD27+ memory B cells, especially in the IgD-/CD27+ switched populations in group A, but CD27 negative naive B-cells reverted to a normal range in both groups. Consistent with this, reverse transcriptase-polymerase chain reaction studies with peripheral blood mononuclear cells revealed that most patients in group A lacked more than two classes of isotype transcripts. CONCLUSIONS: Abnormal repertoires and impaired isotype expression are seen in patients with common variable immunodeficiency, these data suggested that rituximab after APBSCT can affect not only the B-cell quantities, but also the recovery of the B-cell repertoires.

Adult↗
PubMed2005

Nurselike cells express BAFF and APRIL, which can promote survival of chronic lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF-1alpha.

We examined expression of B cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferation-inducing ligand (APRIL) on chronic lymphocytic leukemia (CLL) B cells and nurselike cells (NLCs), which differentiate from CD14+ cells when cultured with CLL B cells. NLCs expressed significantly higher levels of APRIL than monocytes and significantly higher levels of BAFF and APRIL than CLL B cells. Also, the viability of CLL B cells cultured with NLCs was significantly reduced when CLL B cells were cultured with decoy receptor of B-cell maturation antigen (BCMA), which can bind both BAFF and APRIL, but not with BAFF receptor:Fc (BAFF-R:Fc), which binds only to BAFF. The effect(s) of BAFF or APRIL on leukemia cell survival appeared additive and distinct from that of stromal cell-derived factor-1alpha (SDF-1alpha), which in contrast to BAFF or APRIL induced leukemia cell phosphorylation of p44/42 mitogen-activated protein kinase (extracellular signal-regulated kinase-1/2 [ERK1/2]) and AKT. Conversely, BAFF and APRIL, but not SDF-1alpha, induced CLL-cell activation of the nuclear factor-kappaB1 (NF-kappaB1) and enhanced CLL-cell expression of the antiapoptotic protein Mcl-1. However, BAFF, but not APRIL, also induced CLL-cell activation of NF-kappaB2. We conclude that BAFF and APRIL from NLCs can function in a paracrine manner to support leukemia cell survival via mechanisms that are distinct from those of SDF-1alpha, indicating that NLCs use multiple distinct pathways to support CLL-cell survival.

B-Cell Activation Factor Receptor↗
PubMed2005

Prospective trial of high-dose chemotherapy followed by infusions of peripheral blood stem cells and dose-escalated donor lymphocytes for relapsed leukemia after allogeneic stem cell transplantation.

To determine whether induction of graft-versus-host disease (GVHD) improves the outcome of acute relapsed leukemia after stem cell transplantation (SCT), we used high-dose cytarabine (ara-C) followed by infusions of donor-derived buffy coats containing peripheral blood stem cells to treat 12 patients with relapsed leukemia. Donor lymphocyte infusion (DLI) was repeated at least twice over a 5-week interval for patients in whom grade II to IV acute GVHD did not develop after the first DLI. Grade II to IV acute GVHD developed in 4 (33%) of the patients. Chronic GVHD developed in 3 patients, 2 of whom had not experienced acute GVHD. Four (67%) of the 6 patients who developed grade II to IV acute and/or chronic GVHD after DLI responded, but none of the other 6 patients responded. Four (33%) of the patients (2 with acute myelogenous leukemia [AML] and 2 with acute lymphoblastic leukemia [ALL]) achieved complete remission lasting longer than 4 months after the first DLI, but 3 of them had relapses in bone sites. Of these 4 patients, 1 patient with AML and 2 with ALL were alive 8 to 27 months after DLI. These findings indicate that high-dose ara-C combined with megadose DLI may produce durable remission of acute leukemia that has relapsed after SCT when GVHD is induced. The low induction rate of GVHD and extramedullary relapse after remission is achieved with DLI are problems yet to be solved.

Adult↗
PubMed2004

Correlation of glomerular permeability, endothelial injury, and postoperative multiple organ dysfunction.

PURPOSE: To determine whether the degree of microalbuminuria correlates with the extent of endothelial cell injury, the severity of illness, and the magnitude of multiple organ dysfunction in patients who undergo emergency surgery. METHODS: We measured the urinary albumin : creatinine ratio (ACR) within 24 h after surgery in 31 patients and examined its relationship with various clinical measurements. RESULTS: The ACR increased during the first 24 h postoperatively. The log ACR correlated with the serum thrombomodulin concentration measured on the same day, but not with the level of plasma von Willebrand factor antigen. The increase in the log ACR correlated with the acute physiology and chronic health evaluation score (APACHE III), the simplified acute physiology score, the multiple organ dysfunction score, and the score of sequential organ failure assessment (SOFA) calculated on the same day, and the blood volume lost during the operation. The log ACR did not correlate with the white blood cell count or the serum C-reactive protein measured at the same time. The log ACR correlated with SOFA on postoperative days 3, 7, and 10, and mortality increased in accordance with the increase in log ACR. CONCLUSIONS: The urinary ACR correlated with the extent of endothelial cell injury, the severity of illness, and the magnitude of multiple organ dysfunction.

APACHE↗
PubMed2004

Codevelopment of dendritic cells along with erythroid differentiation from human CD34(+) cells by tumor necrosis factor-alpha.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) inhibits erythropoiesis and enhances nonerythroid colony formation. The present study examines the nature of these nonerythroid cells and investigates their physiologic role in relation to erythroid progenitor cells. MATERIALS AND METHODS: Highly purified human CD34(+) cells underwent erythroid differentiation in the presence of multiple cytokines, including stem cell factor (SCF), interleukin-3 (IL-3), and erythropoietin (EPO), with and without TNF-alpha. We enumerate colony-forming unit-erythroid (CFU-E) and glycophorin A (GPA; a specific marker for erythroid lineage) positive cells in semisolid phase as well as in liquid suspension culture. The character and roles of codeveloping nonerythroid cells in the presence of TNF-alpha were analyzed using fluorescent activating cell sorter, enzyme immunohistochemistry, and confocal microscopy. RESULTS: TNF-alpha inhibited the generation of GPA(+) cells and conversely enhanced the generation of GPA(-) cells. The GPA(-) cells were comprised of cells with excentric cell shape and were positive for HLA class I, HLA class II, CD1a, CD4, CD11c, CD14, CD40, CD80, CD83, and CD86, but not for CD3, CD8, CD19, CD20, and CD56, indicating the codevelopment of dendritic cells (DC) along with erythroid differentiation. Developing DC/DC precursors were detected within 3 days of culture. Only in the presence of TNF-alpha did CD34(+) cells proliferate by forming aggregates where both GPA(+) and CD11c(+) DC/DC precursors were present. During culture period, immature CD11c(+) DC were capable of endocytosing damaged GPA(+) cells. CONCLUSIONS: GPA(-) cells cogenerated from human CD34(+) cells during erythroid differentiation in the presence of IL-3/SCF/EPO and TNF-alpha express DC phenotypes. The CD11c(+) DC subset physically and selectively associates with developing immature erythroid cells and damaged self-GPA(+) cells and then obtains and captures self-substances.

Antigens, CD34↗
PubMed2004

Effective high-dose chemotherapy combined with CD34+-selected peripheral blood stem cell transplantation in a patient with cutaneous involvement of nasal NK/T-cell lymphoma.

The prognosis of nasal natural killer (NK)/T-cell lymphoma with cutaneous involvement especially is morbid despite intensive chemotherapy and radiotherapy. We treated a 52-yr-old Japanese woman with cutaneous dissemination of nasal NK/T-cell lymphoma. Six cycles of chemotherapy, irradiation to skin lesion were administered and complete remission (CR) was attained. High-dose chemotherapy (HDC; etoposide 750 mg/m(2) x 2 d, cyclophosphamide 60 mg/kg x 2 d, total body irradiation 12 Gy two daily fractions x 3 d) followed by CD34(+)-selected autologous peripheral blood stem cell transplantation (CD34(+)-APBSCT) was then prescribed. Complete remission (CR) was obtained and she has been free of disease for 34 months since CD34(+)-APBSCT. We suggest that marrow-ablative chemotherapy facilitated by autologous stem cell transplantation should be considered part of the primary therapy for subjects with a poor prognosis for nasal NK/T-cell lymphoma with cutaneous involvement.

Antigens, CD34↗
PubMed2004

[Correlation between intravascular coagulation/fibrinolysis system and cytokines].

Bacterial factors stimulate the release of tissue factor as well as proinflammatory and antiinflammatory cytokines. TNF augments inflammation, TNF and IFN-gamma induce coagulation, and IL-1beta induces coagulation and fibrinolysis. IL-8 augments synergistic inflammation and coagulation. IL-6 augments coagulation and inhibits fibrinolysis. IL-10 inhibits inflammatory process and inhibits fibrinolysis. IL-4, IL-13, and TGF-beta act for anticoagulation. Administration of IL-2, G-CSF or IFN-gamma has been reported to have side effect of induction of coagulation. IL-12 induces coagulation first and fibrinolysis later. On the other, tissue factor induces proinflammatory (except TNF) and antiinflammatory cytokines, and thrombin enhances inflammation. Patients who died of SIRS/sepsis have been complicated with hypercoagulopathy and impaired fibrinolysis correlated with increased IL-10 production. Inhibition of IL-10 production or administration of fiblynolitic agents may be useful. Recently, activated protein C (APC) which has antiinflammatory effect has been paid attention in the treatment of SIRS/sepsis.

Aged↗
PubMed2003

[Animal models for sepsis].

When new immunomodulatory agents are developed for the treatment of sepsis, the efficacy is usually tested in animal models before going to clinical trials. However, despite promising preclinical evidence, dozens of new agents have failed to demonstrate clinical efficacy. One of the reasons may be that the preclinical trials were conducted using animal models that did not adequately reflect clinical realities. Various kinds of experiments utilized for the development of new agents were carried where bolus or short term continuous infusions of large doses of bacteria or endotoxin were administered intravenously. Massive i.v. bolus models using bacteria or endotoxin generally produce a rapid hypodynamic cardiovascular response with the animals dying within hours. The serum cytokine response is transient and is much greater in magnitude than that observed in septic patients. For the preclinical testing of agents, 1) i.v. bacteria and endotoxin models in which the total challenge dose of adequate bacteria or endotoxin is reduced and/or the length of administration time is increased, and 2) peritonitis models, e.g., cecal ligation and puncture and peritoneal implantation of bacteria or endotoxin, will become reasonable choices. The animals are also required to receive volume resuscitation and adjuvant antibiotic therapy.

Animals↗
PubMed2002

Tumor necrosis factor-alpha inhibits generation of glycophorin A+ cells by CD34+ cells.

OBJECTIVE: The inhibitory effects of tumor necrosis factor-alpha (TNF-alpha) on cytokine-induced proliferation and differentiation of normal human erythroid progenitors have been characterized extensively, yet little is known about the maturation level of erythroid progenitors that are sensitive to TNF-alpha or of the expression of TNF receptors (TNFRs) in erythroid lineage. The aim of this study was to determine the extent to which human erythroid progenitor cells are sensitive to TNF-alpha, and to relate this to the expression of TNFRs in the erythroid lineage. MATERIALS AND METHODS: Highly purified human CD34+ cells underwent erythroid differentiation, with or without TNF-alpha. We used colony assay as well as a method by which colony-forming unit-erythroid (CFU-E) and glycophorin A (GPA; a specific marker for erythroid lineage) positive cells can be generated in liquid phase from purified human CD34+ cells in the presence of multiple cytokines, including stem cell factor (SCF), interleukin-3 (IL-3), and erythropoietin (EPO). During erythroid differentiation of CD34+ cells, TNFRs expression were monitored. RESULTS: TNF-alpha inhibited the generation of GPA+ cells by CD34+ cells as well as the proliferative capacity of GPA+ cells supported by EPO, IL-3, and SCF. Erythroid progenitors became resistant to the inhibitory effect of TNF-alpha as they matured. The detectable expression of TNFR-I was transient in the early phase of erythroid differentiation, whereas TNFR-II was expressed through the entire course of erythroid differentiation of CD34+ cells. CONCLUSIONS: TNF-alpha suppresses erythropoiesis by inhibiting the generation of GPA+ cells derived from CD34+ cells as well as by inhibiting the proliferative capacity of GPA+ cells. Although the presence of TNFRs does not directly indicate that the receptor(s) mediates death signaling, altered expression of TNFRs depending on the level of maturation may imply altered sensitivities to TNF-alpha in various stage of erythroid progenitors.

Adult↗
PubMed2002

Recombinant human interleukin-1alpha increases serum albumin, Gc-globulin, and alpha1-antitrypsin levels in burned mice.

The response to thermal injury is a complex physiologic process requiring communication between sites of injury and distant target organs. The liver, one of these target organs, synthesizes a family of secretory proteins, the acute phase proteins, that carries out specific immunoprotective functions. In this study we investigated the effects of daily recombinant human interleukin-1alpha (rhIL-1alpha) administration on the serum levels of negatively regulated, i.e., albumin and Gc-globulin and positively regulated, i.e., alpha1-antitrypsin, acute phase proteins in a murine model of thermal injury. Adult CF-1 female mice underwent a 6.5-seconds, 20% total burn surface area, full thickness steam injury, and received either intraperitoneal rhIL-1alpha (20 microg x kg(-1) x day(-1)) or diluent for 10 days. Seven and 14 days after injury, mice were sacrificed, and serum albumin, Gc-globulin and alpha1-antitrypsin levels were measured by crossed immunoelectrophoresis technique. Thermal injury significantly lowered serum albumin levels, tended to decrease Gc-globulin levels, and increased serum alpha1-antitrypsin levels. Daily rhIL-1alpha administration after burn injury prevented hypoalbuminemia, and increased serum levels of Gc-globulin and alpha1-antitrypsin. IL-1 therapy might be helpful to maintain the homeostasis and immunity of the host after thermal injury.

Animals↗