Makoto Hirokawa's research while affiliated with Akita University and other places
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Publications (277)
Acquired chronic pure red cell aplasia (PRCA) develops idiopathically or in association with other medical conditions, including T cell large granular lymphocytic leukemia (T-LGLL) and thymoma. T cell dysregulation is considered a cardinal pathogenesis of PRCA, but genetic-phenotypic associations in T cell abnormalities are largely unclear. We eval...
Objective
Eosinophils are tissue‐dwelling immune cells. Accumulating evidence indicates that a type of cell death termed ETosis is an important cell fate involved in the pathophysiology of inflammatory diseases. Although the critical role of eosinophils in eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg‐Strauss syndrome) is well...
Idiopathic pure red cell aplasia (PRCA) and secondary PRCA associated with thymoma and large granular lymphocyte leukemia are generally considered to be immune-mediated. The PRCA2004/2006 study showed that poor responses to immunosuppression and anemia relapse were associated with death. PRCA may represent the prodrome to MDS. Thus, clonal hematopo...
Hypereosinophilic syndrome, which is characterized by eosinophilia in the peripheral blood, often causes various organ disorders. Charcot-Leyden crystals are recognized features of various diseases, such as parasite infection and asthma, and are known to be classic hallmarks of eosinophilic inflammation. Our recent study revealed the mechanism of C...
Although allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to provide prolonged remission of relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS), its role has not been fully evaluated. Here, the outcomes of allogeneic HSCT for patients with MF/SS were retrospectively evaluated by using the registry database...
The original version of this article incorrectly listed the third author’s name. It should be Yohei Yamamoto, not Yamamoto Yohei.
Purpose of Review
Charcot-Leyden crystals (CLCs), slender bipyramidal hexagonal crystals, were first described by Jean-Martin Charcot in 1853, predating Paul Ehrlich’s “discovery” of eosinophils by 26 years. To date, CLCs are known as a classical hallmark of eosinophilic inflammation. CLC protein expresses palmitate cleaving lysophospholipase activ...
Primary immune thrombocytopenia (ITP) is an acquired form of thrombocytopenia caused by IgG anti-platelet autoantibodies and represents an organ-specific autoimmune disorder. Although the glycoprotein (GP)IIb/IIIa and GPIb/IX have been shown to be targets for autoantibodies, the antigen specificity of autoantibodies is not fully elucidated. To iden...
The choice of alternative donor is a major issue in allogeneic hematopoietic stem cell transplantation (HSCT) for patients with primary myelofibrosis (PMF) without an HLA-matched related donor. We conducted this retrospective study using the Japanese national registry data for 224 PMF patients to compare the outcomes of first allogeneic HSCT from H...
Second allogeneic hematopoietic stem cell transplantation is a curative treatment option for patients with hematologic malignancies. However, it is unclear whether HLA discrepancy between graft and first donor has an impact on the outcome of second transplantation. We retrospectively analyzed 646 patients receiving second transplantation after an i...
Background.
Idiopathic PRCA and secondary PRCA not responding to the treatment of the underlying diseases are generally treated by immunosuppressive therapy. Because of the rarity of this disease, there are few reports regarding the long-term outcome following immunosuppression. We previously conducted the nationwide study for chronic PRCA in Japan...
Background. Idiopathic pure red cell aplasia (PRCA) and secondary PRCA not responding to the treatment of the underlying diseases are generally thought be immune-mediated and treated by immunosuppressive therapy. We previously conducted the PRCA2004/2006 study and reported that poor response to induction therapy and relapse of anemia were associate...
Allogeneic hematopoietic cell transplantation (HCT) is the only treatment modality that can either cure or prolong life of patients with primary myelofibrosis (PMF). However, the issues of the choice of stem cell source, the choice of conditioning regimen, and the timing of HCT are currently under debate. To determine whether a difference in stem c...
Background: Dysregulation of T-cell mediated immunity is responsible for acquired pure red cell aplasia (PRCA). Although STAT3 mutations are frequently detected in patients with T-cell large granular lymphocytic leukemia (T-LGLL), which is often complicated by PRCA and is also reported to be associated with acquired aplastic anemia (AA) and myelody...
For patients with malignant hematological diseases that relapse after allogeneic hematopoietic stem cell transplantation (HSCT), a second HSCT is thought to be a curative option. A second donor is usually searched for due to HLA discrepancy between the graft and the host. However, it is unclear whether HLA discrepancy between the graft and the firs...
There is considerable interest in expanding B cell-targeted therapies in human autoimmune diseases. However, clinical trials in human primary biliary cholangitis (PBC) using a chimeric antibody against human CD20 (hCD20) have showed limited efficacy. Two potential explanations for these disappointing results are the appearance of anti-drug antibodi...
Rituximab treatment did not ameliorate liver pathology. Rituximab was administered using the same protocol as TKM-011 treatment in the mouse model of PBC. (A) Anti-rituximab antibodies were observed in 6 of 7 treated mice. Serum levels of hIgG1 were gradually reduced over the course of treatment. (B) Frequencies of CD19+ and TCR-β+ cells were trans...
Splenic B-cell depletion in human CD20 expressing BALB/c mice in the presence or absence of human FcγR expression. (A,B) Representative flow cytometry dot plots. Splenic mononuclear cells (MNCs) were pre-incubated with mouse FcR blocking reagent and then incubated at 4°C with a combination of fluorochrome-conjugated antibodies (BD Biosciences), inc...
Graphical abstract. Anti-drug antibody against a novel humanized anti-CD20 antibody impair its therapeutic effect on primary biliary cholangitis in human CD20- and FcγR-expressing mice.
Human CD20 and FcγR-expressing B6 mice. Splenic mononuclear cells were pre-incubated with mouse FcR blocking reagent and then incubated at 4°C with a combination of fluorochrome-conjugated antibodies (BD Biosciences), including APC-conjugated anti-mouse CD19 and PE-conjugated anti-human CD20 as well as FITC-conjugated anti-CD49b/DX5 and PE-conjugat...
Dysregulation of T-cell-mediated immunity is responsible for acquired pure red cell aplasia (PRCA). Although STAT3 mutations are frequently detected in patients with T-cell large granular lymphocytic leukemia (T-LGLL), which is often complicated by PRCA and which is also reported to be associated with acquired aplastic anemia (AA) and myelodysplast...
The surface properties and antiplatelet adhesion behavior of terminally functionalized hyperbranched poly(l‐lactide)s (HB PLLAn‐Glu, n = 5, 10, 20) were examined. Contact angle changes and X‐ray photoelectron spectroscopic measurements indicated that the hydrated glutamic acid units in HB PLLAn‐Glu films migrated to the surface during immersing in...
Protein crystallization in human tissue rarely occurs. Charcot-Leyden crystals (CLCs) were described in various eosinophilic diseases over 150 years ago, but our understanding of CLC formation still remains limited. In this study, we demonstrate that CLCs observed in varied inflamed human tissues are closely associated with eosinophil cell-free gra...
Urine xanthine crystals are remarkably rare but can be observed by routine urine microscopy. We report the results of a 67-year-old man with T-cell-prolymphocytic leukemia whose urine contained xanthine crystals after chemotherapy and prophylactic administration of febuxostat. Accumulation of xanthine was due to tumor lysis syndrome causing a massi...
A 77-year-old man presented with fever and back pain. Computed tomography revealed a distal arch aneurysm. Bacteroides fragilis was found in a blood culture, and we diagnosed a thoracic infected aneurysm. Because of the rapid enlargement of the aneurysm and his frailty, a TEVAR procedure was urgently performed. He left the hospital after antibiotic...
POEMS syndrome is a rare plasma cell dyscrasia presenting with polyneuropathy, λ-type M protein, VEGF elevation, and systemic manifestations. The standard treatment has not been established, but autologous stem cell transplantation (ASCT) has exhibited effectiveness in this syndrome. However, the efficacy and long-term outcomes of ASCT have not bee...
Active metabolites of vitamin A, retinoic acids (RAs), are known to play critical roles in mucosal immune responses and dramatically inhibit human eosinophil apoptosis, but the detailed mechanisms have not been elucidated. We previously screened for ICAM-1 (CD54) upregulation in RA-stimulated human eosinophils by gene microarray analysis. As ICAM-1...
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for chronic myelomonocytic leukemia (CMML). We retrospectively compared the post-transplant outcomes of 159 CMML patients who received allo-HSCT using 4 types of donor sources: human leukocyte antigen (HLA)-matched related donor grafts, unrelated bone ma...
Purpose
To analyze the quality of infection control activities, bacteriological data relevant to infection control was evaluated through the microbiological data warehouse networking hospitals in two medical regions.
Methods
Data regarding bacterial test results of 19 hospitals were extracted from two microbiological laboratory information data ba...
Purpose of review:
Eosinophilic otitis media (EOM) is a refractory disease characterized by the accumulation of eosinophils in middle ear effusion and mucosa. We summarize current knowledge regarding the clinical characteristics and management of EOM. Although eosinophil activation in inflamed foci is involved in the pathogenesis of EOM, little is...
Clinical efficacy of allogeneic hematopoietic cell transplantation (HCT) using reduced-intensity conditioning (RIC) for younger patients remains unclear. We therefore performed a retrospective registry-based study to evaluate outcomes for patients with AML aged between 16 and 49 years who underwent RIC allogeneic HCT. Patients receiving RIC (N=125)...
Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airw...
The traditional paradigm of eosinophils as end-stage damaging cells has mainly relied on their release of cytotoxic proteins. Cytokine-induced cell survival and secretion of granular contents from tissue-dwelling eosinophil are thought to be important mechanisms for eosinophilic inflammatory disorders, although the occurrence of cytolysis and its p...
An 86-year-old man visited our hospital complaining of persistent epigastric discomfort. This patient had no relevant medical history. The patient's vital signs and the results of physical and laboratory examinations were normal aside from a high white blood cell (WBC) count. The epigastric symptom spontaneously remitted, however, the neutrophilia...
Background:
Tacrolimus is metabolized by cytochrome P450 (CYP) 3A4 and 3A5. We investigated the influence of CYP3A5 polymorphism and concurrent use of azole antifungal agents (AZ) on the pharmacokinetics of a once-daily modified-release tacrolimus formulation (Tac-QD) in patients after hematopoietic stem cell transplantation (HSCT).
Design and me...
Ammonia (NH,) blood test is affcctcd by various conditions including measuring method/condition and methods of sample preservation. We recently experienced a remarkable difference in plasma NH, concentrations between the samples measured at the bedside and those determined by the routine laboratory testing in a patient with acute lymphocytic leukem...
[This corrects the article DOI: 10.1371/journal.pone.0120386.].
The outcomes of allogeneic hematopoietic cell transplantation (HSCT) in patients with biphenotypic acute leukemia (BAL) remain unclear. We retrospectively analyzed the outcomes of HSCT in BAL patients in Japan in comparison to acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) using the registration data from a nationwide database....
With the development of medicine, the field of clinical laboratory medicine evolves rapidly, and it will be more specialized in the near future. Medical technologists are required to hone their skills and knowledge, in order to keep up with the evolution. In recent years, board certifications by several medical societies are considered to indicate...
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic option that may lead to improved outcomes in patients with chronic myelomonocytic leukemia (CMML). However, few studies have examined the impact of the grade of graft-versus-host disease (GVHD) on post-transplant outcomes for CMML. We retrospectively analyzed the outcom...
Hemophagocytic syndrome (HPS) frequently associates with hematopoietic stem cell transplantation (HSCT) and is treated with some benefit being derived from tumor necrosis factor (TNF)-α inhibitors. However, the mechanism how HPS occurs and how TNF-α inhibitor exerts some benefit to HPS management has remained unclear. We evaluated the effect of tol...
Previous studies have repeatedly reported that increasing age is a significant risk factor for worse outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) among patients with acute myeloid leukemia (AML). However, more recent studies reported conflicting results regarding the association between age and outcomes in elderly p...
Background:
A number of outbreaks caused by Bacillus species have been reported to date. Outbreaks reported in the last decade have predominantly arisen in Japanese hospitals.
Aim:
To elucidate factors contributing to these real or pseudo outbreaks by Bacillus species, and to evaluate the rate of Bacillus species-positive blood culture samples i...
Hepatic acute GvHD (aGvHD) is associated with high mortality owing to poor response to immunosuppressive therapy. The pathogenesis of hepatic aGvHD differs from that of other lesions, and specific risk factors related to pre-transplant liver conditions should be determined. We conducted a cohort study by using a Japanese transplant registry databas...
Activated human eosinophils, as well as neutrophils, can release extracellular chromatin to form DNA traps through cytolytic extracellular trap cell death (ETosis). Although formations of neutrophil DNA traps are recognized in patients with various inflammatory conditions, neither the presence of ETosis-derived eosinophil DNA traps in human allergi...
Estrogen influences the disease severity and sexual dimorphism in asthma, which is caused by complex mechanisms. Besides classical nuclear estrogen receptors (ERαβ), G-protein-coupled estrogen receptor (GPER) was recently established as an estrogen receptor on the cell membrane. Although GPER is associated with immunoregulatory functions of estroge...
Immunosuppressive therapy has been employed as the initial treatment for acquired chronic pure red cell aplasia (PRCA), such as idiopathic, thymoma-associated, or large granular lymphocyte (LGL) leukaemia-associated PRCA, which is thought to be immune-mediated. To explore the overall long-term outcome following immunosuppression and to identify the...
Recent evidence has shown that eosinophils play an important role in metabolic homeostasis through Th2 cytokine production. GPR120 (FFA4) is a G protein-coupled receptor (GPCR) for long-chain fatty acids that functions as a regulator of physiological energy metabolism. In the present study, we aimed to investigate whether human eosinophils express...
Backgrounds: POEMS syndrome is a rare plasma cell dyscrasia presenting with polyneuropathy, l-type M protein, VEGF elevation and systemic manifestations. The standard treatment of the disease has not been established through clinical trials, but autologous stem cell transplantation (ASCT) has been shown to be effective in patients with the syndrome...
A 62-year-old woman was admitted for nephrotic syndrome and lung tumor. A renal biopsy showed membranous features of the glomeruli.
Immunofluorescence studies revealed granular IgG4-κ deposits along with the glomerular basement membrane. Electron microscopy
revealed granular electron-dense deposits. Further study denied multiple myeloma. Light micr...
The aim of this study was to develop a model able to predict the area under the lenalidomide plasma concentration-time curve (AUC) in multiple myeloma (MM) patients using a limited sampling strategy.
Forty-six hospitalized Japanese MM patients (25 men and 21 women) participated in this study. On days 3-10 of lenalidomide therapy, whole-blood sample...
Networking among regional hospitals recently became required for infection control activities in Japan. In Akita prefecture, we developed a microbiology data warehouse for networking hospital laboratories in 2010. Designated users can easily obtain microbiology data and compare it with other participating hospitals using this system. For example, u...
Introduction
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a therapeutic option for chronic myelomonocytic leukemia (CMML), with the possibility that the graft-versus-CMML (GvL) effect has an important role for survival after allo-HSCT. In a clinical situation, GvL effect was assumed to closely correlate with graft-versus-host d...
Because immune responses simultaneously defend and injure the host, the immune system must be finely regulated to ensure the host’s survival. Here, we have shown that when injected with high Toll-like receptor ligand doses or infected with lymphocytic choriomeningitis virus (LCMV) clone 13, which has a high viral turnover, inflammatory monocyte-der...
Disseminated visceral varicella-zoster virus (VZV) infection rarely occurs in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). To date, only a few cases of isolated VZV-induced fulminant hepatitis following allo-HSCT have been reported. We herein describe the case of a 47-year-old Japanese man with multiple myeloma who...
No standard of care for PRCA following major ABO-incompatible HSCT has been established. We conducted a retrospective cohort study to learn the efficacy and outcome of treatment for PRCA. One-hundred forty-five recipients who showed delayed recovery of erythropoiesis and survived >100 days after transplant without early disease progression were sel...
Purpose:
The purpose of this study was to investigate the interactions of itraconazole (ITCZ) with orally administered calcineurin inhibitors (CNIs) in Japanese allogeneic hematopoietic stem cell transplant (HSCT) recipients.
Methods:
Sixteen HSCT patients (8 patients each receiving tacrolimus or cyclosporine) were enrolled. An ITCZ oral solutio...
Human herpesvirus 6 (HHV-6) causes life-threatening limbic encephalitis encephalitis following allogeneic haematopoietic transplantation (HSCT). We describe two patients with post-transplant HHV-6 encephalitis who were treated with corticosteroid pulse therapy. Underlying diseases were myelodysplastic syndrome and relapsing acute myeloid leukemia....
Although there exist case reports describing the association of clonal expansion of γδ T cells with chronic acquired pure red cell aplasia (PRCA), there is no consensus regarding whether clonal expansion of γδ T cells are generally found in chronic PRCA. We examined the γδ T cell receptor repertoire in 19 PRCA patients and found that there was a di...
A 63-year-old woman was admitted to our hospital with high-grade fever, liver dysfunction, and pancytopenia. Computed tomography of the whole body revealed hepatosplenomegaly but no lymphoadenopaties. Bone marrow aspiration showed infiltrations of CD20-positive large atypical B-lymphocytes with severe hemophagocytosis. Although she was a human T-ce...
1918
Background
Reduced-intensity allogeneic stem cell transplantation (RIST) has become more common in elderly patients with acute myeloid leukemia (AML). To clarify the clinical significance of RIST from an HLA-identical donor in elderly patients and identify prognostic factors, we retrospectively surveyed AML patients receiving RIST who were re...
4921
Introduction
Lenalidomide, a novel therapeutic agent, has been found to be effective for the treatment of relapsed or refractory myeloma. However, the ideal lenalidomide dose to obtain sufficient therapeutic efficacy without causing hematologic toxicity is yet to be determined. Although Dimopoulos et al. reported that the initial lenalidomide...
Background:
Liposomal amphotericin B (L-AmB) is recommended as an empirical antifungal treatment for patients at increased risk of fungal infections although renal toxicity remains a clinical problem. We therefore conducted a pilot study to evaluate the safety and efficacy of low-dose L-AmB as an empirical antifungal therapy for patients with prol...
High-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) is widely used as a salvage therapy in the treatment of refractory malignant lymphoma. To investigate the safety and feasibility of a high-dose MCNU, carboplatin, etoposide and cyclophosphamide (MCVC) regimen, we conducted a prospective multicenter trial. Thirty pati...
Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I, and melanoma differentiation-associated antigen 5 (RIG-I/MDA-5) helicases are known to sense double-stranded RNA (dsRNA) virus and initiate antiviral responses, such as production of type-I interferons (IFNs). Recognition of dsRNA by TLR3 or RIG-I/MDA-5 is cell-type-dependent and recent s...
3429
Background
Idiopathic PRCA and secondary PRCA associated with thymoma and large granular lymphocyte leukemia are major subtypes of adult-onset chronic PRCA. We have previously shown that these types of PRCA are responsive to immunosuppressive therapy but most patients require long-term maintenance immunosuppressive treatment. These results su...
Mammalian erythroblasts undergo enucleation, a process thought to be similar to cytokinesis. Although an assemblage of actin, non-muscle myosin II, and several other proteins is crucial for proper cytokinesis, the role of non-muscle myosin II in enucleation remains unclear. In this study, we investigated the effect of various cell-division inhibito...
A 44-year-old woman was admitted with generalized lymphadenopathy, which was diagnosed as angioimmunoblastic T-cell lymphoma (AITL). The patient showed autoimmune hemolytic anemia (AIHA), polyclonal hypergammaglobulinemia and a high antinuclear antibody titer. Moreover, a human immunodeficiency virus (HIV)-1/2 screening test using the particle aggl...
Itraconazole is a potent inhibitor of CYP3A4 and P-glycoprotein, but not CYP2C9. Herein, we report a case study in which the plasma concentration of the CYP2C9 substrate (S)-warfarin, and not the CYP3A4 substrate (R)-warfarin, increased with itraconazole coadministration.
A 67-y-old man received an allogenic bone marrow transplant for acute lymphoi...
We report a 47-year-old man with acute leukemia who survived a severe case of necrotizing fasciitis caused by Clostridium perfringens involving his right upper extremity. On day 5 after stem cell transplantation, progressive local tissue necrosis led to septicemia and disseminated intravascular coagulation. Early diagnosis and prompt initiation of...
It has been suggested that γδ T cells are involved in certain autoimmune disorders. To establish reference data for clinical studies to explore the role of γδ T cells in autoimmune bone marrow failure syndrome, we examined the γδ T-cell repertoire in 120 healthy Japanese individuals by flow cytometry. The average numbers of T lymphocytes in blood w...
Stenotrophomonas maltophilia is increasingly emerging as a multiresistant pathogen in the hospital environment. In immunosuppressed patients, this bacterium may cause severe infections associated with sepsis and multiple organ dysfunction. We report on a 57-year-old woman treated with intensive chemotherapy for non-Hodgkin lymphoma who developed se...
1807
Dasatinib (DA) is approved for use in imatinib-resistant or intolerant chronic myeloid leukemia (CML)/Philadelphia-positive acute lymphoid leukemia (Ph+ALL) and may also be useful for central nervous system (CNS) leukemia accompanied with CML/Ph+ALL; however, little is known about the relationship between DA pharmacokinetics and its ability to...
4588
Background
High-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (auto-HSCT) has been shown to be appropriate approach compared with standard salvage therapy in patients with chemo-sensitive relapsed/refractory malignant lymphoma. Although a regimen consisting of high dose ranimustine (MCNU), carboplatin...
Imatinib mesylate (IM) trough concentration varies among IM-treated chronic myeloid leukemia (CML) patients. Although IM pharmacokinetics is influenced by several enzymes and transporters, little is known about the role of pharmacogenetic variation in IM metabolism. In this study, associations between IM trough concentration, clinical response and...
Cell dose is one of the major factors that can be manipulated in unrelated BMT. However, regarding disease-stage-stratified effects of cell dose, data are limited. We analyzed the registry data from 3559 patients with acute leukemia, CML and myelodysplastic syndrome who received T-cell replete unrelated BMT through the Japan Marrow Donor Program. A...
Recent studies have shown that anemia is commonly observed after exposure to pathogens or pathogen-derived products, which are recognized via Toll-like receptor 9 (TLR9). In the current study, we demonstrate that CpG oligodeoxynucleotide-2006, a TLR9 ligand with phosphodiester (PO; 2006-PO) but not with the phosphorothioate backbone, selectively in...
We have developed a method that cells exhibiting typical dendritic cell (DC) characteristics are generated from human CD34(+) cells and phagocytose cogenerating erythroid progenitor cells in the presence of tumor necrosis factor-alpha (TNF-alpha), interleukin-3, stem cell factor and erythropoietin. Using this system, we titrated the effects of TNF...
How human erythroblasts enucleate remains obscure, and some investigators suspect the effect of mechanical forces on enucleation in vitro. We determined the dynamics of the enucleation process of highly purified human erythroblasts and whether enucleation can occur without external mechanical forces. Highly purified human CD34(+) cells were culture...
Citations
... Because mutation of clonal hematopoiesis-related genes including TET2, DNMT3A, and BCOR often occurs in BMFS such as PRCA and aplastic anemia 17,18 and a subset of T-LGL occurs concomitantly with BMFS 6, 12,19,20 , the mutational patterns of T-LGL may differ according to the concomitant disorders. The signi cant variation in frequency of STAT3 mutation in PRCA reported in the literature, ranging from 0-63%, appears to depend on concomitant T-LGL 21,22 . ...
... CLCs have been identified in several diseases linked to eosinophilic inflammation such as celiac disease [87], hypereosinophilic syndrome [88] and Aspergillus diseases [89]. CLCs are also highly expressed in EGPA and closely related to disease severity, vascular damage and IL-5 serum concentrations [90]. Gal-10 also appears to have a role in the development of seasonal allergic rhinitis in pediatric patients, especially considering its relationship with IL-5 production and Th2 inflammation [48]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/1095642805997568-1638233009149_Q64/Masami-Taniguchi-2.jpg)
... Fujishima et al also proposed that CH might have associations with the pathophysiology or treatment outcomes in specific aPRCA patients. [54] These studies collectively suggest that aPRCA constitutes a heterogeneous hematopoietic disease with a complex cytogenetic landscape. Nevertheless, it is essential to note that the sample sizes were relatively small, and more data are required to definitively establish the connection between CH and aPRCA. ...
... CLCs have been identified in several diseases linked to eosinophilic inflammation such as celiac disease [87], hypereosinophilic syndrome [88] and Aspergillus diseases [89]. CLCs are also highly expressed in EGPA and closely related to disease severity, vascular damage and IL-5 serum concentrations [90]. ...
... There is an increase in eosinophil in OM patients in the present study compared to patients without OM. This agreement with Ohta et al. [31] reported that the number of blood eosinophils and the level of IgE increase in otitis media. ...
... Data on the role of allo-HSCT in CTCL are also limited, and no prospective trials have been performed to date. Retrospective registry analyses on allo-HSCT in CTCL include the 2010 and 2021 European Society for Blood and Marrow Transplantation (EBMT) studies, the 2014 CIBMTR study, and the 2020 Japanese Society for Hematopoietic Cell Transplantation study [19][20][21][22][23]. These retrospective registry studies of CTCL report rates of acute GVHD at 35% to 87% and chronic GVHD at 32% to 48% [19][20][21][22][23]. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/276944483569667-1443040118748_Q64/Ritsuro-Suzuki.jpg)
... [28,131,132] Kawakami et al detected that STAT3 mutations in 8 out of the 27 aPRCA patients without T-LGLL (30%) and 10 of the 13 aPRCA patients with T-LGLL (77%). [133] These studies implied that STAT3 mutations may be linked to all aPRCA, not just aPRCA associated with LGLL. Furthermore, Jerez et al revealed that clonal expansion of STAT3-mutated CTLs, similar to LGL-like cells, can be detected in the context of AA and MDS. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/289197853298698-1445961549958_Q64/Nodoka-Sekiguchi.jpg)
... [28,29] The depletion of V 2 T-cells and increased cytotoxicity are unique features in AA, consistent with acquired chronic pure red cell aplasia. [30] FASLG expression is upregulated in CD8 + T-cells during cell activation. [31] FASLG inhibits normal hematopoiesis in myelodysplastic syndrome marrow. ...
... On a molecular level, while the role of CLC26 and its receptor CCR3 is well-known in the pathogenesis of EoE, 21 the mechanistic role of the ion channels KCNJ2, ANO1, the classical hallmark of eosinophilic inflammation CLC, 22 immune modulating CD200R1 23 and of cell attachment inducing POSTN 24 is still unknown and requires further investigation. We also found that CDH26 is upregulated in patients with histologically active EoE and can discriminate conventional EoE from the EoE variants. ...
![[object Object]](https://i1.rgstatic.net/ii/profile.image/430930071429121-1479753143379_Q64/Peter-Weller-2.jpg)
... CLCs, a hallmark of eosinophilic inflammation, have been reported in several Th2 inflammatory disorders, including asthma, CRS, and other eosinophil-associated diseases [17] CLCs have been shown to induce the release of the proinflammatory cytokine IL-1β, which plays a role in eosinophilic immune functions [18]. Several studies have shown that CLCs expression is upregulated in eosinophilic CRSwNP, and it can serve as a potential marker for identifying patients who may respond to glucocorticoid treatment and have a higher risk of recurrence [19,20]. ...
