Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

ABSTRACT

In paediatric primary Sjögren’s syndrome (SS), the initial symptoms manifest systemically, such as fever, general fatigue, and lymphadenopathy, rather than sicca symptoms. Most children with primary SS have autoantibodies, such as antinuclear, anti-Ro/SS-A, and/or anti-La/SS-B antibodies; however, some patients are seronegative. Similar to paediatric patients with primary SS, those with Takayasu arteritis (TAK) initially only present constitutional symptoms, making it difficult to suspect, unless characteristic features are present. To our knowledge, there have been no reports of the coexistence of both diseases in children. We present a rare case of seronegative SS complicated by TAK in a 9-year-old girl who presented with a persistent low-grade fever, general fatigue, cervical lymphadenopathy, and multiple caries. Although blood examination revealed all autoantibodies to be negative, a lip biopsy revealed lymphocytic sialadenitis, and a sialoscintigraphy indicated hypofunctional salivary glands, leading to the diagnosis of seronegative SS. The patient was treated with low-dose glucocorticoid and immunosuppressant administration to inhibit persistent inflammation and the progression of salivary gland dysfunction; although the symptoms resolved, inflammatory markers remained elevated. When the patient was 14 years old, cervical bruits were incidentally found, and TAK was suspected based on cervical ultrasonography and magnetic resonance angiography findings. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography results demonstrated increased fluorodeoxyglucose accumulation from the ascending to descending aorta. Therefore, she was diagnosed with SS complicated by TAK, which is rare. Aortitis should be suspected when the cause of persistent inflammation cannot be ascertained in patients with SS.

DOI： 10.1093/mrcr/rxac062

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DOI： 10.1111/ped.15654

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DOI： 10.1111/ped.15681

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Trisomy 21 is sometimes complicated by congenital heart disease; however, comorbid type I diabetes mellitus and diseases involving autoantibodies such as Hashimoto's disease and Graves' disease are not uncommon. In contrast, autoinflammatory diseases such as Kawasaki disease and systemic juvenile idiopathic arthritis are rarely observed. We report a rare case of trisomy 21 with systemic juvenile idiopathic arthritis that responded well to the first course of methylprednisolone pulse therapy, but flared up and was complicated by macrophage activation syndrome (MAS). Subsequent methylprednisolone pulse therapy and cyclosporine resolved this condition. Cytokine analyses at several time points during the clinical course revealed that interleukin-18, interleukin-6, and chemokine ligand 9 levels were elevated even MAS onset in the patient with trisomy 21 once the clinical symptoms seemed to have settled down. Thus, in the future, early analysis of cytokine profiles should be performed for risk assessments of MAS and for determining the treatment intensity, even T21 patients.

DOI： 10.1272/jnms.JNMS.2023_90-605

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：(有)科学評論社  

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PURPOSE: Drug resistance is a serious problem in leukemia therapy. A novel purine nucleoside analogue, nelarabine, is available for the treatment of children with T cell acute lymphoblastic leukemia. We investigated the mechanisms of drug resistance to nelarabine. METHODS: Nelarabine-resistant cells were selected by stepwise and continuous exposure to nelarabine using the limiting dilution method in human B and T cell lymphoblastic leukemia cell lines. Expression analysis was performed using real-time polymerase chain reaction, and epigenetic analysis was performed using methylation-specific polymerase chain reaction and chromatin immunoprecipitation. RESULTS: The RNA expression level for deoxycytidine kinase (dCK) was decreased in nelarabine-resistant leukemia cells. There were no differences between the parental and nelarabine-resistant leukemia cells in the methylation status of the promoter region of the dCK gene. In the chromatin immune precipitation assay, decreased acetylation of histones H3 and H4 bound to the dCK promoter was seen in the nelarabine-resistant cells when compared to the parental cells. Furthermore, treatment with a novel histone deacetylase inhibitor, vorinostat, promoted the cytotoxic effect of nelarabine along with increased expression of the dCK gene, and it increased acetylation of both histones H3 and H4 bound to the dCK promoter in nelarabine-resistant leukemia cells. The combination index showed that the effect of nelarabine and vorinostat was synergistic. CONCLUSION: This study reports that nelarabine with vorinostat can promote cytotoxicity in nelarabine-resistant leukemia cells through epigenetic mechanisms.

DOI： 10.1007/s00280-021-04373-4

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: There has been significant progress in reducing perinatal mortality in Japan. However, due to changes in social conditions, the total fertility rate and the number of births are decreasing, whereas the number of low birth weight infants is increasing along with the number of newborn babies that require intensive care. Further, although the number of high-level perinatal medical centers has increased, so has that of infants who need long-term hospitalization. Conversely, the number of regular obstetric facilities has decreased, thus resulting in insufficient beds for neonatal care. To fill this gap, we established a neonatal intensive care unit (NICU) at our hospital. This study aimed to evaluate our new type by comparing the data from ours with that from other facilities. METHODS: The other facilities assessed were two high-level NICU facilities and two regular obstetric facilities. Data, including sex, gestational age, birth weight, Apgar scores at 1 and 5 min, delivery method, and presence of breathing disorders, were extracted from medical records. RESULTS: The birth weight and gestational age distributions were significantly different in the institutions, except in one facility without a NICU. The new NICU saw more infants with low birth weight and respiratory disorders than the regular obstetric facilities. CONCLUSION: The comparison of birth weight and gestational age distributions, cases of respiratory disorders, and delivery methods indicate that our new NICU is positioned as an intermediate facility between a high-level NICU and a regular obstetrics facility.

DOI： 10.1272/jnms.JNMS.2021_88-403

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BACKGROUND: In preparation for the 2021 Tokyo Olympic/Paralympic Games, the Japanese government assessed the risks of infectious disease outbreaks and identified necessary preparations. This present study reviewed efforts made during a previous measles epidemic and describes the roles of hospitals. METHODS: This descriptive study investigated the records of 198 children with measles. All children were treated at a general hospital during the period from January 1997 through February 1998. We also examined the actions of pediatricians during and after a measles outbreak in the community. RESULTS: Of the 198 children, 145 (73%) were hospitalized. The measles vaccination rate in the previous year was approximately 75%. Of the patients examined, 53% were younger than 2 years of age; mean age was 2.75 years. Pneumonia and gastroenteritis accounted for 46% and 30% of the complications, respectively. Issues requiring attention included the number of hospital beds located in a negative pressure room or private room with a window, the need for gamma globulin preparations with high measles antibody titers, the necessity of increasing vaccination opportunities, and extension of physician working hours. CONCLUSIONS: Visitors from other countries could cause measles outbreaks in Japan. Measures that might mitigate an outbreak were maintenance of high vaccination rates, ready availability of information on the location of negative pressure hospital rooms, knowledge of the status of the measle outbreak, and flexible medical staffing. There is a risk of measles outbreaks among infants and among those who do not have a measles antibody titer.

DOI： 10.1272/jnms.JNMS.2021_88-502

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PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19), a respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus), is a pandemic in over 120 countries worldwide. Risk factors for severe COVID-19 include older age, ethnicity, sex, comorbidities, and living conditions. Although asthmatics and those with allergies are susceptible to more severe outcomes to viral infections, interestingly, asthma has not been reported to be a major comorbidity of COVID-19. However, there are some conflicting reports on the impact of asthma on COVID-19. The underlying immunological and molecular mechanisms may explain at least in part these observations. Furthermore, environmental factors like air pollution that have detrimental effects on asthma and respiratory illnesses also have an impact on COVID-19. RECENT FINDINGS: Angiotensin-converting enzyme 2 (ACE2) is the receptor for the attachment and entry of SARS-CoV-2 into the host cells that is upregulated by Th1-mediated responses. In asthmatics, ACE2 gene expression is generally reduced and recent studies have shown a negative correlation between the levels of Th2 cytokines including IL-4, IL-5, and IL-13 in airway epithelial cells and other type 2 biomarkers with ACE2 expression. This may explain in part the potential protective role of asthma on COVID-19. Here, we review the relation of respiratory viral illnesses and asthma, the immune-molecular mechanisms of SARS-CoV-2 infection, the impact of asthma on COVID-19 and that of SARS-CoV-2 on asthma and allergic rhinitis, and the impact of environmental factors like air pollution on COVID-19. SUMMARY: Expression of ACE2 in airway epithelial cells in SARS-COV-2 is influenced by inflammatory profile. Respiratory allergic diseases like asthma appear to have a protective effect against SARS-COV-2 infection. However, the clinical association between asthma and SARS-COV-2 is not fully established and the underlying immune-molecular mechanisms may explain these observations.

DOI： 10.1097/ACI.0000000000000699

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Language：Japanese   Publisher：(公社)日本化学療法学会  

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In Japan, pneumococcal vaccine has been routinely administered since 2010 to prevent invasive pneumococcal diseases such as Streptococcus pneumoniae meningitis. We describe a case of pneumococcal meningitis in a 7-month-old girl who had received three doses of 13-valent pneumococcal conjugate vaccine. Brain magnetic resonance imaging showed infarcts in the right frontal region, and she was treated with antibiotics, intravenous immunoglobulin, dexamethasone, and edaravone. On day 27, an enhanced brain CT scan showed improvement of abnormal findings in the frontal region, except for slight atrophy. The S. pneumoniae serotype was 12F, which is not included in the 13-valent pneumococcal conjugate vaccine. A future vaccine is expected to use cross-reactivity to target common antigens.

DOI： 10.1272/jnms.JNMS.2020_87-510

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

© 2020, © 2020 Japan College of Rheumatology. Objective: To update and revise the diagnostic criteria for mixed connective tissue disease (MCTD) issued by the Japan Research Committee of the Ministry of Health, Labor, and Welfare (MHLW), a round table discussion by experts from rheumatology, dermatology, and pediatric medicine was conducted in multiple occasions. Methods: The definition of MCTD, and items included in the diagnostic criteria were generated by consensus method and evaluation using clinical data of typical and borderline cases of MCTD, by applying to the diagnostic criteria for MCTD proposed in 1996 and 2004 by the Research Committee of MHLW. Results: To the end, all committee members reached consensus. Then, the criteria were assessed in an independent validation cohort and tested against preexisting criteria. The revised criteria facilitate an understanding of the overall picture of this disease by describing the concept of MCTD, common manifestations, immunological manifestation and characteristic organ involvement. Conditions with characteristic organ involvement include pulmonary arterial hypertension, aseptic meningitis and trigeminal neuropathy. Even if the overlapping manifestations are absent, MCTD can be diagnosed based on the presence of the characteristic organ involvement. Furthermore, the criteria were validated for applicability in actual clinical cases, and public comments were solicited from the Japan College of Rheumatology and other associated societies. Conclusion: After being reviewed through public comments, the revised diagnostic criteria have been finalized.

DOI： 10.1080/14397595.2019.1709944

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Authorship：Lead author,　Corresponding author   Language：English   Publisher：Wiley  

DOI： 10.1111/ped.13575

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOHN WILEY & SONS LTD  

© 2016 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. Effective leukemia treatment is seriously hampered by drug resistance. We previously showed that aberrant methylation of the topoisomerase IIα gene causes altered gene expression and acquired drug resistance in etoposide-resistant leukemia cells. In this study, we analyzed the genome-wide methylation status in resistant leukemia cells. We used MX2, which is a morpholino anthracycline derivative that functions as a topoisomerase IIα inhibitor. We established a human myelogenous leukemia cell line (K562/P) and a related cell line with resistance to MX2 (K562/MX2). Using these cell lines, we investigated the genome-wide methylation status, compared expression profiles with a microarray, and analyzed the data using Gene Ontology and key node analysis. We demonstrate that the MX2-resistant cell line was globally hypermethylated. Gene Ontology analysis identified genes involved in the immunological response and gene silencing that were responsible for methylation-related altered gene expression in drug-resistant cells. Key node analysis showed that p38α mitogen-activated protein kinase was a novel enzyme involved in MX2-related resistance. p38 kinase activity in resistant cells was increased compared to MX2-sensitive parent cells. Blocking p38α activity using inhibitors and p38α knock down with small interfering RNA restored the sensitivity to MX2 in resistant cells with a decrease in p38 kinase activity as well as decreased expression of p38α mRNA and phosphorylated p38α protein. These findings may lead to a new strategy for treatment of drug-resistant leukemia cells.

DOI： 10.1002/prp2.285

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

© The Medical Association of Nippon Medical School. Bacterial infections often cause fatal systemic infections in patients with primary immunodeficiency. To prevent unfortunate results, the selection, dose, and dosage of antibiotics are extremely important. Here, we report a case of Wiskott-Aldrich syndrome in a patient undergoing peritoneal dialysis because of chronic renal failure in whom methicillin-resistant Staphylococcus aureus sepsis developed. Because of the primary disease and complications, teicoplanin was the only chosen anti-S. aureus drug to prevent side effects. We used parameter estimation and dosage adjustment from a therapeutic drug monitoring simulation software program to overcome the challenges with teicoplanin treatment.

DOI： 10.1272/jnms.84.177

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

© 2015 Japan Pediatric Society. Although thrombotic thrombocytopenic purpura (TTP) is rare, early diagnosis and treatment are important for decreasing the mortality rate. Acquired vitamin B12 deficiency is frequently overlooked because of its rarity in developed countries, particularly in children and adolescents. The hematological changes in vitamin B12 deficiency present as megaloblastic anemia, increased lactate dehydrogenase, vasoconstriction, increased platelet aggregation, and abnormal activation of the coagulation followed by microangiopathy as well as neutropenia and thrombocytopenia. We report herein the case of a 15-year-old girl who had been neglected, which might have caused pseudo-TTP through malnutrition, particularly vitamin B12 deficiency. When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect.

DOI： 10.1111/ped.12718

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Language：English   Publisher：WILEY-BLACKWELL  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

© 2015 ISEH - International Society for Experimental Hematology. Drug resistance remains a serious problem in leukemia therapy. Among newly developed nucleoside antimetabolites, clofarabine has broad cytotoxic activity showing therapeutic promise and is currently approved for relapsed acute lymphoblastic leukemia. To investigate the mechanisms responsible for clofarabine resistance, we established two clofarabine-resistant lymphoblastic leukemia cell lines from parental lines. To elucidate the mechanisms against clofarabine resistance in two newly established clofarabine-resistant cell lines, we measured the expression of export pumps multidrug resistance protein 1, multidrug resistance-associated protein 1, and ATP-binding cassette subfamily G member 2. There were no differences in the expression between clofarabine-sensitive and -resistant cell lines. Next, we determined expression of deoxycytidine kinase (dCK), which phosphorylates clofarabine to exert cytotoxicity, in clofarabine-sensitive and -resistant cells. Clofarabine-resistant cells showed significantly decreased expression of dCK RNA when compared with sensitive cells. To elucidate the mechanisms of decreased dCK expression in clofarabine-resistant cells, we analyzed the methylation status of CpG islands of the dCK promoter and found no differences in methylation status between clofarabine-sensitive and -resistant cells. Next, we measured the acetylation status of histone and found that total histone acetylation, and histone H3 and H4 acetylation on chromatin immunoprecipitation assay were significantly decreased in resistant cells. Melatonin is an indolamine that functions in the regulation of chronobiological rhythms to exert cytotoxic effects. We examined the effects of melatonin in clofarabine-resistant cells and found that melatonin treatment led to significantly increased cytotoxicity with clofarabine in resistant cells via increased acetylation. Melatonin may be a useful candidate for overcoming clofarabine resistance in two newly established clofarabine resistant leukemia cell lines.

DOI： 10.1016/j.exphem.2014.11.001

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Language：English   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

DOI： 10.1272/jnms.82.74

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

© 2015, Medical Association of Nippon Medical School. All rights reserved. Antiphospholipid syndrome (APS) is an autoimmune disease caused by antiphospholipid antibodies. At our institution, APS is diagnosed on the basis of the Sapporo criteria, which consist of thrombosis and recurrent pregnancy-related complications and the following laboratory findings: the presence of lupus anticoagulant, anticardiolipin antibody, or anti-β2 glycoprotein 1 antibody. However, we sometimes treat patients we strongly suspect of having APS but who do not satisfy the laboratory criteria. To accommodate such suspected cases, a subtype of APS termed seronegative APS has been proposed. Here, we report on a man with chronic thromobocytopenic purpura since the age of 3 years and multiple cerebral infarctions since the age of 14 years who finally received a diagnosis of seronegative APS with positive antiphosphatidylethanolamine antibodies.

DOI： 10.1272/jnms.82.117

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Authorship：Lead author,　Corresponding author  

DOI： 10.3978/j.issn.2224-4336.2013.04.06

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Authorship：Lead author,　Last author,　Corresponding author   Publishing type：Research paper (scientific journal)  

DOI： 10.1272/jnms.79.95

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

L-asparaginase (L-Asp) is an important reagent for acute lymphoblastic leukemia because asparagine is required for the malignant growth of tumor cells, especially lymphoblastic leukemia cells. An allergic response to L-Asp is not unusual because L-Asp is derived from Escherichia coli and is often recognized as a foreign protein. The hypersensitivity induced by LAsp is of the immediate type in most cases. We report on a 5-year-old girl who was hospitalized for precursor T-cell lymphoblastic leukemia. She was treated according to a Tokyo Children's Cancer Study Group protocol (TCCSG ALL L09-1603 HEX/BFM). During the intensification phase, blisters with erythema developed on the arm proximal to the catheter insertion site owing to a delayed-type hypersensitivity reaction caused by intravenous L-Asp administration. She was treated with additional methylprednisolone, tapered dexamethasone, and an antihistamine for the allergic reaction. No asparaginases other than E. coli L-Asp have been approved for use in Japan. Other asparaginases, such as polyethylene glycol L-Asp and Erwinia L-Asp should be quickly approved for use as alternative chemotherapy reagents in Japan.

DOI： 10.1272/jnms.79.489

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Language：Japanese  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MEDICAL ASSOC NIPPON MEDICAL SCH  

DOI： 10.1272/jnms.78.2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC HEMATOLOGY  

T-cell tolerance is the central program that prevents harmful immune responses against self-antigens, in which inhibitory PD-1 signal given by B7-H1 interaction plays an important role. Recent studies demonstrated that B7-H1 binds CD80 besides PD-1, and B7-H1/CD80 interaction also delivers inhibitory signals in T cells. However, a role of B7-H1/CD80 signals in regulation of T-cell tolerance has yet to be explored. We report here that attenuation of B7-H1/CD80 signals by treatment with anti-B7-H1 monoclonal antibody, which specifically blocks B7-H1/CD80 but not B7-H1/PD-1, enhanced T-cell expansion and prevented T-cell anergy induction. In addition, B7-H1/CD80 blockade restored Ag responsiveness in the previously anergized T cells. Experiments using B7-H1 or CD80-deficient T cells indicated that an inhibitory signal through CD80, but not B7-H1, on T cells is responsible in part for these effects. Consistently, CD80 expression was detected on anergic T cells and further up-regulated when they were reexposed to the antigen (Ag). Finally, blockade of B7-H1/CD80 interaction prevented oral tolerance induction and restored T-cell responsiveness to Ag previously tolerized by oral administration. Taken together, our findings demonstrate that the B7-H1/CD80 pathway is a crucial regulator in the induction and maintenance of T-cell tolerance. © 2010 by The American Society of Hematology.

DOI： 10.1182/blood-2010-01-265975

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC HEMATOLOGY  

Antigen-specific memory T cells (Tms) are essential in the immune surveillance of residual and metastatic tumors. Activation of Tms requires designing vaccines based on tumor rejection antigens, which are often not available to cancer patients. Therefore, it is desirable to have a general applicable approach to activate Tms without extensive knowledge of tumor antigens. Here, we report that activation of antigen-specific Tms could be achieved by the administration of agonistic anti-CD137 monoclonal antibody without additional tumor vaccination, leading to the prevention of recurrence and metastases after surgical resection of primary tumors in mouse models. By reconstitution with CD137-deficient Tms, we demonstrate that expression of CD137 on antigen-specific Tms is only partially required for the effect of anti-CD137 antibody. Other host cells, including those from hematopoietic and nonhematopoietic origins, are also important because ablation of CD137 from these cells partially but significantly eliminates antitumor effect of anti-CD137 antibody. Our findings implicate a potential new approach to prevent recurrence and metastases in cancer patients. © 2010 by The American Society of Hematology.

DOI： 10.1182/blood-2008-12-192591

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Leucocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a membrane receptor of the immunoglobulin (Ig) superfamily that is expressed on most types of haematopoietic cells, and delivers inhibitory signals through interacting with collagens. In order to elucidate the immunological functions of LAIR-1 in vivo, we established transgenic mice expressing a chimeric protein composed of the extracellular domain of LAIR-1 fused with an Ig tag (LAIR-1-Ig), which acts as a decoy by competing with endogenous LAIR-1. The transgenic mice showed an increased susceptibility for development of contact hypersensitivity (CHS), an experimental model of allergic contact dermatitis, in association with enhanced hapten-specific T-cell responses. When T cells from the hapten-sensitized donor mice were transferred into non-sensitized recipients, treatment of either donor mice or recipient mice with LAIR-1-Ig protein accelerated CHS, suggesting a potentially negative role of LAIR-1 in both the sensitization and the elicitation of hapten-reactive T cells. In vitro assays revealed that LAIR-1 decreased the production of interleukin-6 and interleukin-12 in dendritic cells, and inhibited the proliferation and cytokine production of naïve and memory T cells along with G0-G1 cell cycle arrest. Collectively, our findings suggest that LAIR-1 plays a crucial inhibitory role in CHS by regulating antigen-presenting cell and T-cell functions. © 2009 Blackwell Publishing Ltd.

DOI： 10.1111/j.1365-2567.2009.03140.x

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Publishing type：Research paper (scientific journal)   Publisher：6  

The prognosis and clinical and biological characteristics of infant leukemia differ from those of leukemia in children 1 year or older. We reviewed the charts of patients younger than 1 year in whom leukemia was diagnosed from January 1981 through December 2003 at our institution. Fourteen infants had leukemia, 6 had acute lymphoblastic leukemia (ALL), and 8 had acute myeloid leukemia (AML). The age of patients at diagnosis ranged from 2 to 11 months. Five of 8 AML patients presented with cutaneous manifestations, such as erythema and nodules, at diagnosis. Central nervous system (CNS) involvement was seen in 1 AML patient at diagnosis. Hyperleukocytosis of more than 50 × 10 9/L was seen in 4 of 6 ALL patients and in 4 of 8 AML patients at diagnosis. All ALL patients showed a morphological diagnosis of L1 using the French-America-British classification system. For patients with AML, the morphological diagnoses were M0 for 1 patient, M2 for 1 patient, M4 for 2 patients (1 with eosinophilia), M5b for 2 patients, and M7 for 2 patients. One patient showing M7 morphology had Down syndrome. Surface markers were examined in 5 of 6 ALL patients and all AML patients. Five ALL patients showed a B-cell precursor immunophenotype. Two of 5 patients with ALL had CD10-positive leukemic cells and 3 of 5 patients with ALL had CD10-negative leukemic cells. All AML patients were positive for CD13 or CD33 or both. Three of 5 patients with ALL showed abnormal chromosomes related to 11q. Six of 7 patients with AML showed abnormal karyotypes. MLL gene rearrangements were seen in 3 (2 ALL, 1 AML) of 5 (2 ALL, 3 AML) patients. Serum immunoglobulin M levels were increased in 9 of 14 patients. Complete remission (CR) was achieved in all infants with ALL. Three patients relapsed and then died of the original disease. One of these 3 patients died after cord blood transplantation. Three ALL patients are alive without leukemia. CR was achieved in 6 of 8 AML patients. Four of 6 patients are alive without leukemia. Infant leukemia patients in our institution had some special features. CNS involvement at diagnosis was seen in only 1 patient and serum IgM levels were higher than those in children whose leukemia was diagnosed at 1 to 10 years of age.

DOI： 10.1272/jnms.72.355

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC IMMUNOLOGISTS  

MHC class I-restricted CD8+ T cells are a crucial component of the host defense against mycobacterial infection in mice, but it has often proved very difficult to identify the CD8 T cell response in humans. Human group 1 CD1 molecules (CD1a, -b, -c) mediate MHC-independent presentation of mycobacteria-derived lipid and glycolipid Ags to CD8+ T cells, and their intracellular localization to the endocytic system may favor efficient monitoring of phagosome-resident mycobacteria. Here, we show that bacillus Calmette-Guérin (BCG)-immunized subjects contain a significant circulating pool of CD8+ T cells that recognize BCG-infected DCs in a CD1-dependent, but MHC-independent, manner. These CD1-restricted T cells efficiently detected live, rather than dead, BCG and produced IFN-γ, an important cytokine for protection against mycobacterial infection. These results emphasize that lipid-reactive CD8+ T cells may contribute to host defense against mycobacterial infection.

DOI： 10.4049/jimmunol.170.11.5345

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

The T-cell subset expressing Vδ2 paired primarily with Vγ2 comprises a majority of γδ T-cells in human adult peripheral blood and expands significantly during a variety of infectious diseases. In contrast, the other subset of γδ T-cells that express Vδ1 is rare among circulating T-cells and its function is poorly understood. Here, we show that a Vγ1Vδ1+ T-cell line, 3-D, established from human peripheral blood by immortalization with Herpesvirus saimiri was able to specifically recognize tumor cells, such as K562 cells, and release cytotoxic granules containing perforin for target cell killing. Some tumor cells, including Daudi cells that are known to be susceptible to killing by Vδ2+ T-cells, were resistant to 3-D killing, implicating distinct pathways for tumor cell control by Vδ1+ and Vδ2+ T-cells. The 3-D T-cell receptor (TCR):CD3 complex reconstituted in TCR-deficient Jurkat cells was capable of transmitting signals, evidenced by activation of the interleukin 2 (IL-2) gene following ligation with anti-CD3 antibody, yet the TCR-reconstituted cells failed to produce IL-2 in response to the target cells. Thus, these results raise the possibility that some Vγ1Vδ1+ T-cells could potentially be stimulated and lyse tumor cells via ligation of TCR/CD3-unassociated molecules. © 2002 Elsevier Science B.V. All rights reserved.

DOI： 10.1016/S0165-2478(02)00292-4

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Authorship：Lead author   Language：Japanese   Publisher：医歯薬出版(株)  

脂質に富む厚い細胞壁は結核菌の生存に必須であり,菌の病原性を規定している.免疫系はこの細胞壁構成脂質を抗原として認識し,結核菌に特異的なT細胞反応を惹起する.非ペプチド抗原である脂質抗原をT細胞に提示するCD1分子の研究の進展を紹介すると共に,結核免疫を脂質に対するT細胞反応という新しい観点から述べた

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00643&link_issn=&doc_id=20180427030063&doc_link_id=%2Fag1snrsd%2F2018%2F007105%2F063%2F1012-1020%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2018%2F007105%2F063%2F1012-1020%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本アレルギー学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：金原出版(株)  

DOI： 10.18888/J00639.2017086357

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：(一社)日本小児リウマチ学会  

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Language：Japanese   Publisher：(一社)日本リウマチ学会  

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Language：Japanese   Publisher：(株)日本小児医事出版社  

CiNii Books

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J00643&link_issn=&doc_id=20150324100064&doc_link_id=%2Fag1snrsd%2F2015%2F006804%2F064%2F0942-0948%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fag1snrsd%2F2015%2F006804%2F064%2F0942-0948%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：金原出版(株)  

A群溶血性連鎖球菌(GAS)の感染後に発症するリウマチ熱(RF)はよく知られているが、GAS感染後に強迫性障害(OCD)やチック障害などを発症または急激に増悪する症状が注目されるようになり、1998年にSwedoらが、小児自己免疫性溶連菌関連性精神神経障害(PANDAS)という疾患概念を提唱した。PANDASの定義と概念、疫学、病態、症状と診断、治療法について解説した。

CiNii Books

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：金原出版(株)  

小児期発症の全身性エリテマトーデス(SLE)は初発時から数年以内にループス腎炎が約9割の症例で認められ、組織所見もWHO分類III〜IV型の重症例が多い。また、他のリウマチ性疾患とのオーバーラップが多く、適切な治療法の選択が重要である。現在SLEの治療に用いられている薬剤(ステロイド薬、アルキル化薬、代謝拮抗薬、シグナル伝達阻害薬、ヒドロキシクロロキン、非ステロイド系消炎鎮痛薬)について概説すると共に、現在治験進行中の新規治療法(抗サイトカイン薬、B細胞療法、免疫調整療法)の動向についても述べた。

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(株)日本臨床社  

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Language：Japanese   Publisher：鳥居薬品(株)  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(株)東京医学社  

＜Key Points＞(1)小児の長引く発熱の鑑別診断として、感染症・悪性腫瘍・自己炎症症候群を含めた小児リウマチ疾患・薬剤性を念頭におく。(2)熱型の記録は、不明熱の鑑別診断に非常に重要である。(3)長引く発熱の鑑別において、発熱以外の症状・情報を細かく収集することがきわめて重要である。(4)自己炎症症候群は疾患概念が発展途上であるが、長引く発熱の鑑別疾患として念頭においておく必要がある。(著者抄録)

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(一社)日本てんかん学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：日本医科大学医学会  

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Language：Japanese   Publisher：日本小児血液学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本小児科学会  

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Language：Japanese   Publisher：(公社)日本小児科学会  

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J-GLOBAL

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Language：Japanese   Publisher：(NPO)日本免疫学会  

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Event date： 2019.10

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Oral presentation (general)  

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Language：Japanese   Presentation type：Symposium, workshop panel (public)  

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Presentation type：Symposium, workshop panel (nominated)  

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Presentation type：Symposium, workshop panel (nominated)  

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