Publications by authors named "Yuki Kageyama"

20 Publications

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Sézary Syndrome with CD4/CD8 Double-Negative Neoplastic T Cells in Peripheral Blood.

Case Rep Hematol 2021 1;2021:5527725. Epub 2021 Jun 1.

Department of Hematology, Yokkaichi Municipal Hospital, 2-2-37 Shibata, Yokkaichi 510-8567, Japan.

Sézary syndrome is a rare leukemic type of cutaneous T-cell lymphoma characterized by the presence of neoplastic T cells with cerebriform nuclei (Sézary cells) in the skin, lymph nodes, and peripheral blood. Typical Sézary cells have a CD3CD4CD8 phenotype; however, in cases of the aberrant loss of antigens on Sézary cells, especially the loss of critically important T-cell antigens such as CD4, there is a possibility of misdiagnosing the disease or underestimating the tumor burden of the disease. Here, we report a rare case of Sézary syndrome with CD4/CD8 double-negative Sézary cells in the peripheral blood. Most of the Sézary cells in the peripheral blood had lost CD4 expression, and we diagnosed the disease and evaluated the tumor burden by multicolor flow cytometry. Intriguingly, the Sézary cells showed a typical CD4CD8CD7 phenotype in the skin even though the cells in the peripheral blood lacked CD4. The patient responded well to treatment with bexarotene and narrow-band ultraviolet B therapy. Analysis by multicolor flow cytometry is essential to diagnose this rare type of Sézary syndrome and evaluate the tumor burden.
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http://dx.doi.org/10.1155/2021/5527725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189774PMC
June 2021

Optimizing a Fed-Batch High-Density Fermentation Process for Medium Chain-Length Poly(3-Hydroxyalkanoates) in .

Front Bioeng Biotechnol 2021 26;9:618259. Epub 2021 Feb 26.

Department of Chemistry, State University of New York College of Environmental Science and Forestry, Syracuse, NY, United States.

Production of medium chain-length poly(3-hydroxyalkanoates) [PHA] polymers with tightly defined compositions is an important area of research to expand the application and improve the properties of these promising biobased and biodegradable materials. PHA polymers with homopolymeric or defined compositions exhibit attractive material properties such as increased flexibility and elasticity relative to poly(3-hydroxybutyrate) [PHB]; however, these polymers are difficult to biosynthesize in native PHA-producing organisms, and there is a paucity of research toward developing high-density cultivation methods while retaining compositional control. In this study, we developed and optimized a fed-batch fermentation process in a stirred tank reactor, beginning with the biosynthesis of poly(3-hydroxydecanoate) [PHD] from decanoic acid by β-oxidation deficient recombinant LSBJ using glucose as a co-substrate solely for growth. Bacteria were cultured in two stages, a biomass accumulation stage (37°C, pH 7.0) with glucose as the primary carbon source and a PHA biosynthesis stage (30°C, pH 8.0) with co-feeding of glucose and a fatty acid. Through iterative optimizations of semi-defined media composition and glucose feed rate, 6.0 g of decanoic acid was converted to PHD with an 87.5% molar yield (4.54 g L). Stepwise increases in the amount of decanoic acid fed during the fermentation correlated with an increase in PHD, resulting in a final decanoic acid feed of 25 g converted to PHD at a yield of 89.4% (20.1 g L, 0.42 g L h), at which point foaming became uncontrollable. Hexanoic acid, octanoic acid, 10-undecenoic acid, and 10-bromodecanoic acid were all individually supplemented at 20 g each and successfully polymerized with yields ranging from 66.8 to 99.0% (9.24 to 18.2 g L). Using this bioreactor strategy, co-fatty acid feeds of octanoic acid/decanoic acid and octanoic acid/10-azidodecanoic acid (8:2 mol ratio each) resulted in the production of their respective copolymers at nearly the same ratio and at high yield, demonstrating that these methods can be used to control PHA copolymer composition.
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http://dx.doi.org/10.3389/fbioe.2021.618259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953831PMC
February 2021

Early central nervous system relapse of monomorphic epitheliotropic intestinal T-cell lymphoma after cord blood transplantation.

Int J Hematol 2021 Jul 1;114(1):129-135. Epub 2021 Mar 1.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare subtype of intestinal T-cell lymphoma that occurs mostly in Asia. CHOP-like therapy is usually selected, but the prognosis is very poor. This report concerns a 43-year-old woman with newly diagnosed stage IVA MEITL. The patient obtained a partial response after 4 cycles of GDP (gemcitabine, dexamethasone, cisplatin) and achieved a complete response (CR) after cord blood transplantation (CBT) conditioned with total body irradiation, cyclophosphamide, and cytarabine. Seven months after transplantation, the patient experienced cognitive impairment. Magnetic resonance imaging of the brain showed a high-intensity lesion in the right cerebral peduncle and internal capsule. A cerebrospinal fluid examination confirmed central nervous system (CNS) relapse of MEITL. After 3 cycles of MPV (methotrexate, procarbazine, vincristine) followed by whole-brain radiotherapy, her cognitive impairment improved. Due to disease progression, she died 6 months after CNS relapse. Given the CNS relapse after achieving a CR with GDP and CBT in this patient, CNS prophylaxis during first-line therapy may be beneficial in the treatment of MEITL.
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http://dx.doi.org/10.1007/s12185-021-03107-9DOI Listing
July 2021

Nervonic acid level in cerebrospinal fluid is a candidate biomarker for depressive and manic symptoms: A pilot study.

Brain Behav 2021 04 18;11(4):e02075. Epub 2021 Feb 18.

Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Center for Brain Science, Saitama, Japan.

Objective: Our previous metabolomics study showed that the plasma nervonic acid levels were higher in patients with major depressive disorder (MDD) than those in healthy controls and patients with bipolar disorder (BD). To examine whether the nervonic acid levels differ in the central nervous system, we investigated the levels in the cerebrospinal fluid (CSF) of patients with MDD, BD, and healthy controls.

Methods: Nervonic acid levels in CSF were measured by gas chromatography time-of-flight mass spectrometry. The participants included 30 patients with MDD, 30 patients with BD, and 30 healthy controls.

Results: In contrast to our previous study, no significant differences were found in the nervonic acid level in the CSF among the patients with MDD, BD, and the healthy controls. Though no significant state-dependent changes were found among the three groups, we did observe a significant negative correlation between the nervonic acid levels and depressive symptoms in the depressive state of patients with MDD and BD (r = -0.38, p = .046). Further, a significant positive correlation was found between the nervonic acid levels and manic symptoms in the manic state of patients with BD (r = 0.79, p = .031).

Conclusion: The nervonic acid levels in the CSF did not differ among the patients with MDD, BD, and the healthy controls; however, a significant negative correlation with depressive symptoms and a positive correlation with manic symptoms was observed. Thus, the nervonic acid levels in the CSF may be a candidate biomarker for mood symptoms.
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http://dx.doi.org/10.1002/brb3.2075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035447PMC
April 2021

Ontogeny of human B1 cells.

Int J Hematol 2020 May 12;111(5):628-633. Epub 2019 Nov 12.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, 514-8507, Mie, Japan.

B1 cells, which are distinct from conventional B cells, are a rare B lymphocyte subpopulation that plays a pivotal role in innate immunity. Extensive previous studies have revealed the functions and ontogeny of murine B1 cells, but the properties of human B1 cells have just begun to be uncovered over the past decade. The phenotype of human B1 cells has recently been proposed, facilitating further studies. Here, we review the latest knowledge on human B1 cells, especially their ontogeny. A previous study using xenotransplantation models showed that human hematopoietic stem cells (HSCs) derived from cord blood or adult bone marrow can produce B1 cells in vivo. A recent study by our group reported that human B1 cells in peripheral blood are derived from adult HSCs and persist for approximately 3 years in situ. These findings suggest that adult human HSCs have the ability to produce B1 cells and contribute to maintenance of the adult B1 cell pool in peripheral blood. Further understanding of human B1 cell functions and ontogeny may elucidate the pathogenesis of B cell malignancies and autoimmune diseases.
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http://dx.doi.org/10.1007/s12185-019-02775-yDOI Listing
May 2020

Increased Production and Molecular Weight of Artificial Polyhydroxyalkanoate Poly(2-hydroxybutyrate) Above the Glass Transition Temperature Threshold.

Front Bioeng Biotechnol 2019 24;7:177. Epub 2019 Jul 24.

Division of Applied Chemistry, Faculty of Engineering, Hokkaido University, Sapporo, Japan.

Poly(2-hydroxybutyrate) [P(2HB)] is an artificial polyhydroxyalkanoate (PHA) synthesized using engineered 2-hydroxyalkanoate-polymerizing PHA synthase. In the present study, the effect of temperature on P(2HB) synthesis was investigated. Recombinant harboring PHA synthetic genes were cultivated with 2HB and 3-hydroxybutyrate (3HB) supplementation at varied temperatures ranging from 24 to 36°C for the synthesis of P(2HB) and natural PHA P(3HB), respectively. P(2HB) production and its molecular weight increased considerably at a threshold temperature of 32-34°C. The trend was not observed during the synthesis of P(3HB). Notably, the threshold temperature was close to the glass transition temperature ( ) of P(2HB) (30°C), while the of P(3HB) (4°C) was much lower than the cultivation temperature. The results suggest that thermal motion of the polymer chains influenced the production and molecular weight of the obtained polymer. According to the results, the production and molecular weight of PHA drastically changes at the threshold temperature, which is linked to the of the polymer. The hypothesis should be applicable to PHAs in general, and potentially explains the inability to biosynthesize high-molecular-weight polylactate homopolymer with a of 60°C.
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http://dx.doi.org/10.3389/fbioe.2019.00177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689969PMC
July 2019

Life-Threatening Tongue and Retropharyngeal Hemorrhage in a Patient with Hemophilia A with Inhibitors.

Am J Case Rep 2019 Jul 15;20:1022-1026. Epub 2019 Jul 15.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

BACKGROUND Massive tongue hemorrhage in patients with hemophilia is a medical emergency because it can lead to airway obstruction. However, managing bleeding in patients with inhibitors is more difficult than in patients without inhibitors. We report a case of life-threatening massive tongue and retropharyngeal hematoma in a patient with hemophilia A who had inhibitors. CASE REPORT The patient was a 71-year-old man with severe hemophilia A with high-responding inhibitors. He was admitted to our hospital with dysarthria and dysphagia secondary to a massive tongue hematoma. Although bypassing therapy was started immediately after admission, he rapidly developed an airway obstruction and cardiopulmonary arrest secondary to suffocation. Cardiopulmonary resuscitation and surgical cricothyrotomy were performed, which restored his pulse and breathing. On day 5 of hospitalization, he underwent tracheotomy under inhibitor-neutralizing therapy, and we began emicizumab on day 19 of hospitalization to prevent further bleeding events. He recovered and was transferred to another hospital for rehabilitation on day 64 of hospitalization. CONCLUSIONS Because tongue hematomas progress dramatically within a few days, prompt airway maintenance by tracheotomy under appropriate hemostatic therapy must be considered. Furthermore, emicizumab induction after primary hemostasis prevents further bleeding. We suggest that initiating emicizumab therapy is a good choice to prevent further bleeding after critical bleeding events if the patient has not received the drug previously.
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http://dx.doi.org/10.12659/AJCR.916151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647615PMC
July 2019

Infiltrating CCR2 monocytes and their progenies, fibrocytes, contribute to colon fibrosis by inhibiting collagen degradation through the production of TIMP-1.

Sci Rep 2019 06 12;9(1):8568. Epub 2019 Jun 12.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.

Intestinal fibrosis is a serious complication in inflammatory bowel disease (IBD). Despite the remarkable success of recent anti-inflammatory therapies for IBD, incidence of intestinal fibrosis and need for bowel resection have not significantly changed. To clarify the contribution of haematopoietic-derived cells in intestinal fibrosis, we prepared bone marrow (BM) chimeric mice (chimeras), which were reconstituted with BM cells derived from enhanced green fluorescent protein (EGFP)-transgenic mice or CC chemokine receptor 2 (CCR2)-deficient mice. After 2 months of transplantation, BM chimeras were treated with azoxymethane/dextran sodium sulphate. During chronic inflammation, CCR2 BM-derived monocyte and fibrocyte infiltration into the colon and CC chemokine ligand 2 production increased, leading to colon fibrosis in EGFP BM chimeras. In CCR2-deficient BM chimeras, monocyte and fibrocyte numbers in the colonic lamina propria significantly decreased, and colon fibrosis was attenuated. In colon tissue, mRNA expression of tissue inhibitor of metalloproteinase (TIMP)-1 but not of collagen I, transforming growth factor-β1 or matrix metalloproteinases was significantly different between the two chimeras. CCR2 monocytes and fibrocytes showed high Timp1 mRNA expression. Our results suggest that infiltrating CCR2 monocytes and their progenies, fibrocytes, promote colon fibrosis by inhibiting collagen degradation through TIMP-1 production.
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http://dx.doi.org/10.1038/s41598-019-45012-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562037PMC
June 2019

A population of CD20CD27CD43CD38 B1 cells in PNH are missing GPI-anchored proteins and harbor mutations.

Blood 2019 07 21;134(1):89-92. Epub 2019 May 21.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Japan; and.

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http://dx.doi.org/10.1182/blood.2019001343DOI Listing
July 2019

Expression of CD25 fluctuates in the leukemia-initiating cell population of CD25-positive AML.

PLoS One 2018 14;13(12):e0209295. Epub 2018 Dec 14.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

CD25 is expressed on leukemic cells in 10-20% cases of acute myeloid leukemia (AML), and its expression is associated with poor prognosis. We reevaluated the relationship between CD25 expression and the leukemia-initiating cell (LIC) properties of AML using a patient-derived xenograft model. We divided lineage marker-negative (Lin-) CD34+CD38- or Lin-CD34+ cells from CD25-positive AML into CD25-positive and -negative populations, and then transplanted each population into NOD.Cg-PrkdcscidIl2rgtm1Wjl/Sz mice. Leukemic engraftment was observed with both CD25-positive and -negative populations from three of nine CD25-positive AML patients. In two of those three patients, CD25-positive and -negative Lin-CD34+ cells engrafted at the primary transplantation led to leukemic engraftment at the secondary transplantation, in which engrafted cells contained both CD25-positive and -negative Lin-CD34+ AML cells. In an in vitro culture system, expression of CD25 was considerably induced in the CD25-negative population of Lin-CD34+ cells from two cases of CD25-positive AML. In one case, CD25-positive Lin-CD34+ cells gave rise to CD25-negative as well as -positive CD34+ cells. These observations suggest that there exist CD25-positive and -negative populations that can reconstitute CD25-positive AML in a patient-derived xenograft model, and that CD25 expression fluctuates in the LICs of AML.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209295PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294374PMC
May 2019

Successful treatment of primary bone marrow Hodgkin lymphoma with brentuximab vedotin: a case report and review of the literature.

J Med Case Rep 2018 May 30;12(1):151. Epub 2018 May 30.

Department of Hematology and Oncology, Suzuka General Hospital, Mie, Japan.

Background: Hodgkin lymphoma usually presents with sequential enlargement of peripheral lymph nodes, and bone marrow invasion rarely occurs (approximately 3-5%). However, several cases have been reported as "primary" bone marrow Hodgkin lymphoma, especially among patients with human immunodeficiency virus and the elderly. This type of Hodgkin lymphoma is characterized by no peripheral lymphadenopathies and has been reported to have poorer prognosis.

Case Presentation: A 38-year-old Japanese man was admitted to our hospital because of fever of unknown origin and pancytopenia without lymphadenopathies. Bone marrow examination revealed Hodgkin cells mimicking abnormal cells. These were positive for CD30, EBER-1, CD15, PAX-5, and Bob-1 and negative for Oct-2, CD3, CD20, surface immunoglobulin, CD56. On the basis of systemic evaluation and bone marrow examination, he was diagnosed with primary bone marrow Hodgkin lymphoma. We initiated therapy with DeVIC (dexamethasone, etoposide, ifosfamide, and carboplatin) therapy, but remission was not achieved. Then, the patient was treated with brentuximab vedotin combined with systemic chemotherapy (Adriamycin, vinblastine and dacarbazine), which was effective.

Conclusions: There is no established treatment strategy for Hodgkin lymphoma, and therapeutic outcomes using ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine)-like or CHOP (cyclophosphamide, Adriamycin, vincristine, and prednisone)-like regimens are reportedly poor. Only a few patients have been reported to achieve long-term remission. Through this case report, we suggest an alternative therapeutic option for primary bone marrow Hodgkin lymphoma.
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http://dx.doi.org/10.1186/s13256-018-1693-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975584PMC
May 2018

Renal papillary tip extract stimulates BNP production and excretion from cardiomyocytes.

PLoS One 2018 7;13(5):e0197078. Epub 2018 May 7.

Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

Background: Brain natriuretic peptide (BNP) is an important biomarker for patients with cardiovascular diseases, including heart failure, hypertension and cardiac hypertrophy. It is also known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease; however, the mechanism remains unclear.

Methods And Results: We developed a BNP reporter mouse and occasionally found that this promoter was activated specifically in the papillary tip of the kidneys, and its activation was not accompanied by BNP mRNA expression. No evidence was found to support the existence of BNP isoforms or other nucleotide expression apart from BNP and tdTomato. The pBNP-tdTomato-positive cells were interstitial cells and were not proliferative. Unexpectedly, both the expression and secretion of BNP increased in primary cultured neonatal cardiomyocytes after their treatment with an extract of the renal papillary tip. Intraperitoneal injection of the extract of the papillary tips reduced blood pressure from 210 mmHg to 165 mmHg, the decrease being accompanied by an increase in serum BNP and urinary cGMP production in stroke-prone spontaneously hypertensive (SHR-SP) rats. Furthermore the induction of BNP by the papillary extract from rats with heart failure due to myocardial infarction was increased in cardiomyocytes.

Conclusions: These results suggested that the papillary tip express a substance that can stimulate BNP production and secretion from cardiomyocytes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197078PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937764PMC
August 2018

Plasma Nervonic Acid Is a Potential Biomarker for Major Depressive Disorder: A Pilot Study.

Int J Neuropsychopharmacol 2018 03;21(3):207-215

Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan.

Background: Diagnostic biomarkers of major depressive disorder, bipolar disorder, and schizophrenia are urgently needed, because none are currently available.

Methods: We performed a comprehensive metabolome analysis of plasma samples from drug-free patients with major depressive disorder (n=9), bipolar disorder (n=6), schizophrenia (n=17), and matched healthy controls (n=19) (cohort 1) using liquid chromatography time-of-flight mass spectrometry. A significant effect of diagnosis was found for 2 metabolites: nervonic acid and cortisone, with nervonic acid being the most significantly altered. The reproducibility of the results and effects of psychotropic medication on nervonic acid were verified in cohort 2, an independent sample set of medicated patients [major depressive disorder (n=45), bipolar disorder (n=71), schizophrenia (n=115)], and controls (n=90) using gas chromatography time-of-flight mass spectrometry.

Results: The increased levels of nervonic acid in patients with major depressive disorder compared with controls and patients with bipolar disorder in cohort 1 were replicated in the independent sample set (cohort 2). In cohort 2, plasma nervonic acid levels were also increased in the patients with major depressive disorder compared with the patients with schizophrenia. In cohort 2, nervonic acid levels were increased in the depressive state in patients with major depressive disorder compared with the levels in the remission state in patients with major depressive disorder and the depressive state in patients with bipolar disorder.

Conclusion: These results suggested that plasma nervonic acid is a good candidate biomarker for the depressive state of major depressive disorder.
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http://dx.doi.org/10.1093/ijnp/pyx089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838832PMC
March 2018

CXCL12-CXCR4 Axis Is Required for Contact-Mediated Human B Lymphoid and Plasmacytoid Dendritic Cell Differentiation but Not T Lymphoid Generation.

J Immunol 2017 10 25;199(7):2343-2355. Epub 2017 Aug 25.

Department of Hematology and Oncology, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.

We investigated the involvement of CXCL12-CXCR4 interactions in human lymphohematopoiesis by coculture with telomerized human stromal cells. CXCR4 expression was low in CD34CD38CD45RACD10CD7CD19 immature hematopoietic stem/precursor cells (HSPCs) but higher in CD34CD38CD45RACD10CD7CD19 early lymphoid precursors and even higher in CD34CD38CD45RACD10CD7CD19 pro-B cells. Inhibition of the effect of stromal cell-produced CXCL12 by an anti-CXCR4-blocking Ab suppressed the generation of CD45RACD10CD7CD19 early T lymphoid precursors (ETPs) and CD45RACD10CD7CD19 B lymphoid precursors on stromal cells, but it did not affect the generation of ETPs in conditioned medium of stromal cell cultures. Replating assays showed that contact with stromal cells was critical for HSPC-derived CD45RACD10CD7CD19 B lineage-biased precursors to differentiate into CD19 pro-B cells, which was suppressed by the anti-CXCR4 Ab. Conversely, HSPC-derived ETPs possessed T and B lymphoid and monocytic differentiation potential; stromal cell contact was not required for their growth but rather promoted B lymphoid differentiation. The anti-CXCR4 Ab did not affect the growth of ETPs in conditioned medium, but it suppressed their B lymphoid differentiation on stromal cells. CD14CD11cHLA-DRCD123CD303 plasmacytoid dendritic cells developed from HSPCs and ETPs exclusively in contact with stromal cells, which was suppressed by the anti-CXCR4 Ab. These data indicate that CXCL12 plays an essential role in stromal cell contact-mediated B lymphoid and plasmacytoid dendritic cell differentiation from immature hematopoietic and early T lymphoid precursors with a multilineage differentiation potential, but it does not participate in contact-independent generation of early T lymphoid precursors.
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http://dx.doi.org/10.4049/jimmunol.1700054DOI Listing
October 2017

The relationship between circulating mitochondrial DNA and inflammatory cytokines in patients with major depression.

J Affect Disord 2018 06 6;233:15-20. Epub 2017 Jun 6.

Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan. Electronic address:

Background: Although inflammatory cytokines are established biomarkers of mood disorders, their molecular mechanism is not known. We hypothesized that circulating mitochondrial DNA (mtDNA) contributes to inflammation and could be used as biomarkers. We investigated if circulating mtDNA level is associated with inflammatory cytokines and can be used as a biomarker of mood disorders.

Methods: Plasma mtDNA concentration was measured with real-time quantitative PCR targeting two regions of the mtDNA and plasma levels of four cytokines (GM-CSF, IL-2, IL-4, and IL-6) were measured with a multiplex immunoassay method in 109 patients with major depressive disorder (MDD). The most significantly correlated cytokine was verified with an enzyme-linked immunosorbent assay (ELISA). The data from 28 patients with bipolar disorder (BD), 17 patients with schizophrenia (SZ), and 29 healthy controls were compared.

Results: MtDNA levels showed a nominal positive correlation with GM-CSF, IL-2 and IL-4 in patients with MDD. The most significant correlation with IL-4 (ρ = 0.38, P < 0.00005) was verified with an ELISA (ρ = 0.19, P = 0.049). Unexpectedly, patients with MDD and BD showed significantly lower plasma mtDNA levels than controls. MtDNA levels were lower in the depressive state than in the euthymic state in patients with MDD. Patients with depression, bipolar disorder, and schizophrenia did not show significantly higher levels of these four cytokines than controls.

Limitations: There is a possibility that the patients in this study are different from previous studies in which increased cytokine levels were reported. MtDNA levels should be measured in patients showing elevated plasma cytokine levels. A larger sample is required to generalize the results.

Conclusions: The present findings coincide with our hypothesis that circulating mtDNA contributes to the inflammation in MDD. Further studies are needed to conclude whether plasma mtDNA would be a biomarker of mood disorders.
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http://dx.doi.org/10.1016/j.jad.2017.06.001DOI Listing
June 2018

[Valacyclovir Maintenance Therapy for a Case of Unilateral Acute Retinal Necrosis during Chemotherapy].

Kansenshogaku Zasshi 2017 Mar;91(2):159-62

Acute retinal necrosis (ARN) is an infectious retinitis caused by varicella zoster virus (VZV), herpes simplex or cytomegalovirus. Without systemic therapy, ARN may progress bilaterally in seventy percent of unilateral patients. A 38-year-old-man was admitted to our hospital with Hodgkin's lymphoma and hemophagocytic lymphohistiocytosis. During the chemotherapy, left facial herpes zoster developed. He received valacyclovir for 14 days. After improvement of the blisters, he continued acyclovir as secondary prophylaxis. Three weeks after the facial zoster, sudden visual loss in the left eye occurred. ARN induced by VZV was diagnosed with ophthalmoscopy and the polymerase chain reaction test of the anterior chamber. Because continuous chemotherapy for Hodgkin's lymphoma was needed, he continued valacyclovir as secondary prophylaxis for 6 months and he accomplished the chemotherapy without contralateral progression. Our case suggested the utility of valacyclovir for secondary prophylaxis. Further experiments would be required to establish secondary prophylaxis in immunocompromised patients.
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March 2017

Search for plasma biomarkers in drug-free patients with bipolar disorder and schizophrenia using metabolome analysis.

Psychiatry Clin Neurosci 2017 Feb 16;71(2):115-123. Epub 2016 Nov 16.

Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan.

Aim: There is an urgent need for diagnostic biomarkers of bipolar disorder (BD) and schizophrenia (SZ); however, confounding effects of medication hamper biomarker discovery. In this study, we conducted metabolome analyses to identify novel plasma biomarkers in drug-free patients with BD and SZ.

Methods: We comprehensively analyzed plasma metabolites using capillary electrophoresis time-of-flight mass spectrometry in patients with SZ (n = 17), BD (n = 6), and major depressive disorder (n = 9) who had not received psychotropics for at least 2 weeks, and in matched healthy controls (n = 19). The results were compared with previous reports, or verified in an independent sample set using an alternative analytical approach.

Results: Lower creatine level and higher 2-hydroxybutyric acid level were observed in SZ than in controls (uncorrected P = 0.016 and 0.043, respectively), whereas they were unaltered in a previously reported dataset. Citrulline was nominally significantly decreased in BD compared to controls (uncorrected P = 0.043); however, this finding was not replicated in an independent sample set of medicated patients with BD. N-methyl-norsalsolinol, a metabolite of dopamine, was suggested as a candidate biomarker of BD; however, it was not detected by the other analytical method. Levels of betaine, a previously reported candidate biomarker of schizophrenia, were unchanged in the current dataset.

Conclusion: Our preliminary findings suggest that the effect of confounding factors, such as duration of illness and medication, should be carefully controlled when searching for plasma biomarkers. Further studies are required to establish robust biomarkers for these disorders.
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http://dx.doi.org/10.1111/pcn.12461DOI Listing
February 2017

Solitary pulmonary MALT lymphoma presenting crystal-storing histiocytosis.

Rinsho Ketsueki 2016 08;57(8):1032-7

Department of Hematology and Oncology, Suzuka General Hospital.

Crystal-storing histiocytosis (CSH) is characterized by the accumulation of large histiocytes with intracytoplasmic crystallized immunoglobulin and is typically associated with hematological malignancies. A 69-year-old man, who had a history of left nephrectomy and chemotherapy for renal pelvic cancer six years earlier, had received a CT scan every year thereafter and a small nodule was found in the left lower lobe of his lungs two years prior to the current presentation. Because of progression of this pulmonary nodule, he underwent pulmonary lobectomy on suspicion of lung cancer. He was ultimately diagnosed as having CSH accompanied by mucosa-associated lymphoid tissue lymphoma stage IAE. In the absence of further treatment, he has been well with no recurrence of the disease for 10 months postoperatively. Because CSH could reportedly be an initial presentation of hematological malignancies, careful observation and evaluation for the presence of these blood disorders is essential.
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http://dx.doi.org/10.11406/rinketsu.57.1032DOI Listing
August 2016

[Superior sagittal sinus thrombosis after intrathecal chemotherapy and intravenous high-dose cytarabine in an acute myeloid leukemia case with t(8;21)(q22;q22)].

Rinsho Ketsueki 2016 Apr;57(4):477-82

Division of Hematology and Oncology, Suzuka General Hospital.

Superior sagittal sinus thrombosis (SSST) is a very rare but life-threatening complication in leukemia patients. SSST is very rare in acute myeloid leukemia (AML). In leukemia patients, several risk factors for SSST have been reported such as administration of L-asparaginase, disseminated intravascular coagulation, congenital thrombophilia, meningeal leukemia, and intrathecal chemotherapy (IT). Lumbar puncture itself and corticosteroid administration have also been acknowledged as risk factors. We describe herein our clinical experience with SSST in a 29-year-old Japanese man suffering from AML with t(8;21)(q22;q22), who presented with abrupt onset of loss of consciousness, left hemiplegia, and seizure soon after IT and high-dose cytarabine (HD-AraC) with dexamethasone for post remission consolidation. Despite the presence of intracranial hemorrhage (ICH) due to SSST rupture, we conducted anticoagulant therapy with heparin. Although ICH worsened temporarily, his clinical condition gradually improved with resolution of the SSST, and he eventually became fully ambulatory. There were no deficiencies of natural anticoagulants. Three additional cycles of HD-AraC without IT therapy were conducted, but no neurological complications recurred with the concomitant use of warfarin. He was discharged free of neurological deficits. In our case, there is a possibility that IT and the administration of corticosteroids along with HD-AraC triggered SSST.
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http://dx.doi.org/10.11406/rinketsu.57.477DOI Listing
April 2016

[Development of syndrome of inappropriate secretion of ADH and reversible posterior leukoencephalopathy during initial rituximab-CHOP therapy in a patient with diffuse large B-cell lymphoma].

Rinsho Ketsueki 2013 Mar;54(3):269-72

Department of Internal Medicine, Matsusaka Chuo General Hospital, Japan.

A 61-year-old woman presented with a right mandibular tumor and was diagnosed with DLBCL clinical stage IIIA from the biopsy results of the tumor and CT examination. An initial rituximab was administrated a week after the first CHOP treatment. During the infusion of rituximab, she exhibited disorientation, seizure, and consciousness disturbance. Hyponatremia due to SIADH and hypertension were coincidentally observed. MRI revealed T2 and FLAIR hyperintense signals involving the bilateral occipital, parietal, frontal lobes and the cerebellum that were consistent with reversible posterior leukoencephalopathy syndrome (RPLS). Her consciousness level recovered in parallel with corrections in serum sodium levels and blood pressure. Although she presented with transient cortical blindness, all neurological abnormalities disappeared 40 hours after the occurrence of seizure. She received a further 7 cycles of CHOP followed by 7 cycles of rituximab treatment with no relapse of RPLS. After irradiation for a residual abdominal tumor, she has maintained complete remission for 2 years. Although RPLS is a rare complication of rituximab-CHOP chemotherapy, it should be considered in patients with DLBCL who present with acute neurological deterioration.
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March 2013
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