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Article ; Online: [Development of Novel COX-2 Imaging Agents for the Diagnosis of Brain Lesions].

Yamamoto, Yumi

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan

2023 Volume 143, Issue 12, Page(s) 983–987

Abstract: Cyclooxygenase-2 (COX-2) has attracted attention as a biomarker for neurodegenerative brain diseases. The aim of this study was to develop a COX-2 imaging agent for positron emission tomography (PET) that binds to and emits radiation from COX-2 in the ... ...

Abstract	Cyclooxygenase-2 (COX-2) has attracted attention as a biomarker for neurodegenerative brain diseases. The aim of this study was to develop a COX-2 imaging agent for positron emission tomography (PET) that binds to and emits radiation from COX-2 in the central nervous system to diagnose brain lesions related to COX-2. To this end, the development of PET imaging probes by derivatizing non-steroidal anti-inflammatory drugs that bind to COX-2 was investigated. Herein, we present the findings of a series of studies on indomethacin and nimesulide derivatives. All five
MeSH term(s)	Cyclooxygenase 2/metabolism ; Anti-Inflammatory Agents, Non-Steroidal/metabolism ; Indomethacin ; Brain/diagnostic imaging ; Brain/metabolism ; Cyclooxygenase 2 Inhibitors/metabolism
Chemical Substances	Cyclooxygenase 2 (EC 1.14.99.1) ; nimesulide (V4TKW1454M) ; Anti-Inflammatory Agents, Non-Steroidal ; Indomethacin (XXE1CET956) ; Cyclooxygenase 2 Inhibitors
Language	Japanese
Publishing date	2023-10-31
Publishing country	Japan
Document type	English Abstract ; Journal Article
ZDB-ID	200514-1
ISSN	1347-5231 ; 0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
ISSN (online)	1347-5231
ISSN	0031-6903 ; 0372-7750 ; 0919-2085 ; 0919-2131
DOI	10.1248/yakushi.23-00109
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Article ; Online: Transcriptomic mapping of the human cerebrovasculature.

Ihara, Masafumi / Yamamoto, Yumi

Nature reviews. Neurology

2022 Volume 18, Issue 6, Page(s) 319–320

MeSH term(s)	Cerebrovascular Circulation ; Humans ; Transcriptome/genetics
Language	English
Publishing date	2022-03-24
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2491514-2
ISSN	1759-4766 ; 1759-4758
ISSN (online)	1759-4766
ISSN	1759-4758
DOI	10.1038/s41582-022-00650-9
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Article ; Online: Prevalence of massively diluted bone marrow cell samples aspirated from patients with myelodysplastic syndromes (MDS) or suspected of MDS: A retrospective analysis of nationwide samples in Japan.

Ogata, Kiyoyuki / Mochimaru, Yuto / Kasai, Nana / Sei, Kazuma / Kawahara, Naoya / Ogata, Mika / Yamamoto, Yumi

British journal of haematology

2024

Abstract: Bone marrow (BM) examination is a key element in the diagnosis and prognostic grading of myelodysplastic syndromes (MDSs), and obtaining adequate BM cell samples is critical for accurate test results. Massive haemodilution of aspirated BM samples is a ... ...

Abstract	Bone marrow (BM) examination is a key element in the diagnosis and prognostic grading of myelodysplastic syndromes (MDSs), and obtaining adequate BM cell samples is critical for accurate test results. Massive haemodilution of aspirated BM samples is a well-known problem; however, its incidence in patients with MDS has not been well studied. We report the first study to examine the incidence of massive haemodilution in nationwide BM samples aspirated from patients diagnosed with or suspected of MDS in Japan. Among 283 cases available for analysis, BM smears from 92 cases (32.5%) were hypospicular (massively haemodiluted) and, particularly, no BM particles were observed in 52 cases (18.4%). Regarding hypospicular cases, we examined how the doctors in charge interpreted the BM smears of their patients. In only 19 of 92 cases (20.7%), doctors realised that the BM smears were haemodiluted. Furthermore, the BM biopsy, which can help diagnose hypospicular cases, was oftentimes not performed when the haemodilution was overlooked by doctors (not performed in 50 of 73 such cases). These real-world data highlight that not only researchers who are working to improve diagnostic tests but also clinicians who perform and use diagnostic tests must realise this common and potentially critical problem.
Language	English
Publishing date	2024-04-08
Publishing country	England
Document type	Journal Article
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.19447
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Article ; Online: Phagocytosis of microparticles increases responsiveness of macrophage-like cell lines U937 and THP-1 to bacterial lipopolysaccharide and lipopeptide.

Ueno, Takayuki / Yamamoto, Yumi / Kawasaki, Kiyoshi

Scientific reports

2021 Volume 11, Issue 1, Page(s) 6782

Abstract: Following bacterial infection, macrophages produce pro-inflammatory cytokines in response to bacterial cell components, including lipopolysaccharide (LPS) and lipopeptide, and simultaneously phagocytize and digest the invading bacteria. To study the ... ...

Abstract	Following bacterial infection, macrophages produce pro-inflammatory cytokines in response to bacterial cell components, including lipopolysaccharide (LPS) and lipopeptide, and simultaneously phagocytize and digest the invading bacteria. To study the effects of phagocytosis on pro-inflammatory responses, we determined if phagocytosis of polystyrene latex beads with ~ 1 µm diameter increases pro-inflammatory cytokine expression by human macrophage-like U937 and THP-1 cells stimulated with LPS. Treating macrophage-like cells with beads coated with IgG to facilitate Fcγ receptor-mediated phagocytosis increased LPS-induced expression of pro-inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6. Treatment with beads coated with poly-L-lysine to facilitate Fcγ receptor-independent phagocytosis also increased LPS-induced cytokine expression. Our results indicate that LPS-induced pro-inflammatory responses are enhanced by bead phagocytosis regardless of the uptake mechanism. Additionally, phagocytosis enhanced LPS-induced NF-κB activation, suggesting that Toll-like receptor (TLR) 4 signaling is enhanced by phagocytosis. Furthermore, bead phagocytosis enhanced pro-inflammatory responses in U937 cells stimulated with lipopeptide, a ligand for the TLR2/TLR6 heterodimeric receptor. In conclusion, microparticle phagocytosis by macrophage-like U937 and THP-1 cells enhances the innate immune response induced by bacterial components.
MeSH term(s)	Animals ; Antigens, Bacterial/immunology ; Cytokines/metabolism ; Host-Pathogen Interactions/immunology ; Humans ; Inflammation Mediators/metabolism ; Lipopeptides/immunology ; Lipopolysaccharides/immunology ; Macrophages/immunology ; Macrophages/metabolism ; NF-kappa B/metabolism ; Phagocytosis/immunology ; Receptors, IgG/metabolism ; THP-1 Cells ; U937 Cells
Chemical Substances	Antigens, Bacterial ; Cytokines ; Inflammation Mediators ; Lipopeptides ; Lipopolysaccharides ; NF-kappa B ; Receptors, IgG
Language	English
Publishing date	2021-03-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-86202-5
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Article: Update on the Epidemiology, Pathogenesis, and Biomarkers of Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

Yamamoto, Yumi / Liao, Yi-Chu / Lee, Yi-Chung / Ihara, Masafumi / Choi, Jay Chol

Journal of clinical neurology (Seoul, Korea)

2023 Volume 19, Issue 1, Page(s) 12–27

Abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disorder of the cerebral small blood vessels. It is caused by mutations in the NOTCH3 gene on chromosome 19, and more than ... ...

Abstract	Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic disorder of the cerebral small blood vessels. It is caused by mutations in the NOTCH3 gene on chromosome 19, and more than 280 distinct pathogenic mutations have been reported to date. CADASIL was once considered a very rare disease with an estimated prevalence of 1.3-4.1 per 100,000 adults. However, recent large-scale genomic studies have revealed a high prevalence of pathogenic
Language	English
Publishing date	2023-01-05
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	2500489-X
ISSN	2005-5013 ; 1738-6586
ISSN (online)	2005-5013
ISSN	1738-6586
DOI	10.3988/jcn.2023.19.1.12
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Article ; Online: Myeloblasts transition to megakaryoblastic immunophenotypes over time in some patients with myelodysplastic syndromes.

Ogata, Kiyoyuki / Mochimaru, Yuto / Sei, Kazuma / Kawahara, Naoya / Ogata, Mika / Yamamoto, Yumi

PloS one

2023 Volume 18, Issue 9, Page(s) e0291662

Abstract: Objectives: In myelodysplastic syndromes (MDS), neoplastic myeloblast (CD34+CD13+CD33+ cells) numbers often increase over time, leading to secondary acute myeloid leukemia (AML). In recent studies, blasts in some MDS patients have been found to express ... ...

Abstract	Objectives: In myelodysplastic syndromes (MDS), neoplastic myeloblast (CD34+CD13+CD33+ cells) numbers often increase over time, leading to secondary acute myeloid leukemia (AML). In recent studies, blasts in some MDS patients have been found to express a megakaryocyte-lineage molecule, CD41, and such patients show extremely poor prognosis. This is the first study to evaluate whether myeloblasts transition to CD41+ blasts over time and to investigate the detailed immunophenotypic features of CD41+ blasts in MDS. Methods: We performed a retrospective cohort study, in which time-dependent changes in blast immunophenotypes were analyzed using multidimensional flow cytometry (MDF) in 74 patients with MDS and AML (which progressed from MDS). Results: CD41+ blasts (at least 20% of CD34+ blasts expressing CD41) were detected in 12 patients. In five of these 12 patients, blasts were CD41+ from the first MDF analysis. In the other seven patients, myeloblasts (CD34+CD33+CD41- cells) transitioned to megakaryoblasts (CD34+CD41+ cells) over time, which was often accompanied by disease progression (including leukemic transformation). These CD41+ patients were more frequently observed among patients with monosomal and complex karyotypes. CD41+ blasts were negative for the erythroid antigen, CD235a, and positive for CD33 in all cases, but CD33 expression levels were lower in three cases when compared with CD34+CD41- blasts. Among the five CD41+ patients who underwent extensive immunophenotyping, CD41+ blasts all expressed CD61, but two cases had reduced CD42b expression, three had reduced/absent CD13 expression, and three also expressed CD7. Conclusions: Myeloblasts become megakaryoblastic over time in some MDS patients, and examining the megakaryocyte lineage (not only as a diagnostic work-up but also as follow-up) is needed to detect CD41+ MDS. The immunophenotypic features revealed in this study may have diagnostic relevance for CD41+ MDS patients.
MeSH term(s)	Humans ; Granulocyte Precursor Cells ; Immunophenotyping ; Megakaryocyte Progenitor Cells ; Retrospective Studies ; Antigens, CD34 ; Myelodysplastic Syndromes
Chemical Substances	Antigens, CD34
Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0291662
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Article ; Online: Clinical significance of CD41-positive blasts in association with a monosomal karyotype in patients with myelodysplastic syndrome treated with azacitidine.

Ogata, Kiyoyuki / Sei, Kazuma / Kawahara, Naoya / Yamamoto, Yumi

British journal of haematology

2020 Volume 189, Issue 4, Page(s) e144–e147

MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic/pharmacology ; Antimetabolites, Antineoplastic/therapeutic use ; Azacitidine/pharmacology ; Azacitidine/therapeutic use ; Female ; Humans ; Karyotype ; Male ; Middle Aged ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/immunology ; Platelet Membrane Glycoprotein IIb/immunology ; Young Adult
Chemical Substances	Antimetabolites, Antineoplastic ; Platelet Membrane Glycoprotein IIb ; Azacitidine (M801H13NRU)
Language	English
Publishing date	2020-03-04
Publishing country	England
Document type	Letter
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.16565
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Article ; Online: Radiosynthesis and in Vivo and ex Vivo Evaluation of Isomeric [

Yamamoto, Yumi / Tago, Tetsuro / Toyohara, Jun / Saito, Yohei / Yamamoto, Fumihiko

Biological & pharmaceutical bulletin

2021 Volume 45, Issue 1, Page(s) 94–103

Abstract: Our previous studies identified that nimesulide analogs which bear a methoxy substituent at the para-position of the phenyl ring could be potential radiotracer candidates for detecting disorders related to cyclooxygenase-2 (COX-2) expression and activity ...

Abstract	Our previous studies identified that nimesulide analogs which bear a methoxy substituent at the para-position of the phenyl ring could be potential radiotracer candidates for detecting disorders related to cyclooxygenase-2 (COX-2) expression and activity in vivo using positron emission tomography (PET) in the brain. The present study was conducted to evaluate the in vivo characteristics of
MeSH term(s)	Animals ; Brain/diagnostic imaging ; Brain/metabolism ; Carbon Radioisotopes/metabolism ; Cyclooxygenase 2/metabolism ; Mice ; Positron-Emission Tomography/methods ; Sulfonamides ; Tissue Distribution
Chemical Substances	Carbon Radioisotopes ; Sulfonamides ; Cyclooxygenase 2 (EC 1.14.99.1) ; nimesulide (V4TKW1454M)
Language	English
Publishing date	2021-12-01
Publishing country	Japan
Document type	Journal Article
ZDB-ID	1150271-x
ISSN	1347-5215 ; 0918-6158
ISSN (online)	1347-5215
ISSN	0918-6158
DOI	10.1248/bpb.b21-00608
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Article ; Online: Clinical, immunophenotypic, and cytogenetic characteristics of high-grade myelodysplastic syndromes with CD41-positive progenitor cells.

Ogata, Kiyoyuki / Sei, Kazuma / Kawahara, Naoya / Ogata, Mika / Yamamoto, Yumi

Cytometry. Part B, Clinical cytometry

2021 Volume 104, Issue 1, Page(s) 98–107

Abstract: Background: Patients with myelodysplastic syndromes (MDS) with progenitors expressing CD41 (CD41+ MDS) showed a poor prognosis in a previous study but their detailed characteristics remain unclear.: Methods: One hundred thirty-seven subjects at our ... ...

Abstract	Background: Patients with myelodysplastic syndromes (MDS) with progenitors expressing CD41 (CD41+ MDS) showed a poor prognosis in a previous study but their detailed characteristics remain unclear. Methods: One hundred thirty-seven subjects at our institution were diagnosed with excess blasts (EB)-1, EB-2, and acute myeloid leukemia with a low blast count (20%-30%). The immunophenotypes of progenitor cells in their bone marrow (BM) were determined by CD45-gating flow cytometry. A false-positive reaction to CD41 was eliminated by examining the flow cytometry data of lymphocytes and monocytes in addition to progenitors and by examining CD42b in histological sections. The characteristics were compared between CD41+ and CD41- MDS patients. Results: Forty-three patients (31%) were CD41+. Additionally, 91% of the CD41+ MDS patients were very high-risk defined by the Revised International Prognostic Score System, which was higher than in patients with CD41- MDS (p = 0.015). Approximately 60% of the CD41+ MDS patients had a monosomal karyotype and very poor cytogenetics, which was higher than in CD41- MDS patients (p < 0.001). Normal cytogenetics was less common in CD41+ patients (p = 0.0016). Blasts with bleb formation were more abundant in CD41+ MDS patients (p = 0.026). All CD41+ MDS patients were positive for CD13 and were mostly positive for CD33. The frequency of aberrant expression of other antigens on progenitors was similar between CD41+ and CD41- MDS patients. Conclusions: We determined clinical, immunophenotypic, and cytogenetic characteristics of CD41+ MDS patients. Further studies are needed to improve the survival of these patients.
MeSH term(s)	Humans ; Flow Cytometry ; Myelodysplastic Syndromes/diagnosis ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/pathology ; Bone Marrow/pathology ; Karyotyping ; Stem Cells/pathology
Language	English
Publishing date	2021-12-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2099657-3
ISSN	1552-4957 ; 1552-4949 ; 0196-4763
ISSN (online)	1552-4957
ISSN	1552-4949 ; 0196-4763
DOI	10.1002/cyto.b.22052
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Article ; Online: Disruption of transforming growth factor-β superfamily signaling: A shared mechanism underlying hereditary cerebral small vessel disease.

Yamamoto, Yumi / Ihara, Masafumi

Neurochemistry international

2017 Volume 107, Page(s) 211–218

Abstract: Cerebral small vessel disease (SVD) is not only one of the leading causes of cognitive impairment but also an important contributory factor in Alzheimer's disease. SVD and related white matter changes are common in the elderly, but the underlying ... ...

Abstract	Cerebral small vessel disease (SVD) is not only one of the leading causes of cognitive impairment but also an important contributory factor in Alzheimer's disease. SVD and related white matter changes are common in the elderly, but the underlying pathogenic mechanism remains unclear. The end-stage pathology of SVD often involves replacement of vascular smooth muscle cells with collagenous or other nontensile fibrillary material. Recent studies on hereditary SVD have revealed a close relationship between small vessel pathology and disruption of transforming growth factor-β (TGF-β) superfamily signaling. TGF-β superfamily members, such as TGF-β and bone morphogenetic proteins, are multifunctional proteins that regulate production of extracellular matrix proteins, which in turn control the bioavailability of TGF-β superfamily members and modulate their signaling activities. This article reviews hereditary disorders with small vessel pathology and their relation to TGF-β superfamily signaling.
Language	English
Publishing date	2017-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	283190-9
ISSN	1872-9754 ; 0197-0186
ISSN (online)	1872-9754
ISSN	0197-0186
DOI	10.1016/j.neuint.2016.12.003
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