10 results on '"Yu Kawakami"'
Search Results
2. Recent advances in mast cell activation and regulation
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Toshiaki Kawakami, Kazumi Kasakura, Hwan Soo Kim, and Yu Kawakami
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0301 basic medicine ,Receptors, Neuropeptide ,Allergy ,FcεRI ,Nerve Tissue Proteins ,mast cells ,Review ,Immunoglobulin E ,General Biochemistry, Genetics and Molecular Biology ,Receptors, G-Protein-Coupled ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,medicine ,Animals ,Humans ,Secretion ,General Pharmacology, Toxicology and Pharmaceutics ,miRNA ,Innate immune system ,General Immunology and Microbiology ,biology ,Pseudoallergy ,General Medicine ,Articles ,Allergens ,medicine.disease ,Acquired immune system ,3. Good health ,Interleukin 33 ,030104 developmental biology ,Immunology ,biology.protein ,IL-33 ,Cytokines ,MRGPRX2 ,IgE ,030215 immunology ,allergen - Abstract
Mast cells are innate immune cells that intersect with the adaptive immunity and play a crucial role in the initiation of allergic reactions and the host defense against certain parasites and venoms. When activated in an allergen- and immunoglobulin E (IgE)-dependent manner, these cells secrete a large variety of allergenic mediators that are pre-stored in secretory granules or de novo–synthesized. Traditionally, studies have predominantly focused on understanding this mechanism of mast cell activation and regulation. Along this line of study, recent studies have shed light on what structural features are required for allergens and how IgE, particularly anaphylactic IgE, is produced. However, the last few years have seen a flurry of new studies on IgE-independent mast cell activation, particularly via Mrgprb2 (mouse) and MRGPRX2 (human). These studies have greatly advanced our understanding of how mast cells exert non-histaminergic itch, pain, and drug-induced pseudoallergy by interacting with sensory neurons. Recent studies have also characterized mast cell activation and regulation by interleukin-33 (IL-33) and other cytokines and by non-coding RNAs. These newly identified mechanisms for mast cell activation and regulation will further stimulate the allergy/immunology community to develop novel therapeutic strategies for treatment of allergic and non-allergic diseases.
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- 2020
3. Histamine-releasing factor enhances food allergy
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Tomoaki Ando, Yuko Kawakami, Naoka Itoh-Nagato, Mizuho Nagao, Takao Fujisawa, Kiyoshi Takeda, Yu Kawakami, Kenji Matsumoto, Hirotaka Yamashita, Naoki Shimojo, Jun-ichi Kashiwakura, Tsutomu Iwata, Minato Baba, Shih Han Tsai, Toshiaki Kawakami, and Naoki Inagaki
- Subjects
Male ,0301 basic medicine ,Allergy ,Inflammation ,Immunoglobulin E ,Proinflammatory cytokine ,03 medical and health sciences ,Th2 Cells ,0302 clinical medicine ,Antigen ,Food allergy ,Biomarkers, Tumor ,medicine ,Animals ,Humans ,Secretion ,Child ,Egg Hypersensitivity ,Mice, Knockout ,Mice, Inbred BALB C ,biology ,business.industry ,Tumor Protein, Translationally-Controlled 1 ,General Medicine ,medicine.disease ,Intestines ,030104 developmental biology ,Child, Preschool ,Egg allergy ,Immunology ,Commentary ,biology.protein ,Female ,medicine.symptom ,business ,030215 immunology - Abstract
Food allergy occurs due to IgE- and mast cell-dependent intestinal inflammation. Previously, we showed that histamine-releasing factor (HRF), a multifunctional protein secreted during allergy, interacts with a subset of IgE molecules and that the HRF dimer activates mast cells in an HRF-reactive IgE-dependent manner. In this study, we investigated whether HRF plays any role in food allergy. Specifically, we determined that prophylactic and therapeutic administration of HRF inhibitors that block HRF-IgE interactions reduces the incidence of diarrhea and mastocytosis in a murine model of food allergy. Food allergy-associated intestinal inflammation was accompanied by increased secretion of the HRF dimer into the intestine in response to proinflammatory, Th2, and epithelial-derived cytokines and HRF-reactive IgE levels at the elicitation phase. Consistent with these data, patients with egg allergy had higher blood levels of HRF-reactive IgE compared with individuals that were not hypersensitive. Successful oral immunotherapy in egg-allergy patients and food-allergic mice reduced HRF-reactive IgE levels, thereby suggesting a pathological role for HRF in food allergy. Together, these results suggest that antigen and HRF dimer amplify intestinal inflammation by synergistically activating mast cells and indicate that HRF has potential as a therapeutic target in food allergy.
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- 2017
4. DEFENSIVE Stroke Scale: Novel Diagnostic Tool for Predicting Posterior Circulation Infarction in the Emergency Department
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Masahisa Katsuno, Yu Kawakami, Yasuhiro Hasegawa, Shinichiro Yamada, and Keizo Yasui
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Adult ,Brain Infarction ,Male ,medicine.medical_specialty ,Infarction ,Diagnostic accuracy ,Neuroimaging ,Blepharophimosis ,Dizziness ,Decision Support Techniques ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Vertigo ,Internal medicine ,Medicine ,Humans ,In patient ,cardiovascular diseases ,Diagnostic Errors ,Stroke ,Postural Balance ,Aged ,Retrospective Studies ,Aged, 80 and over ,Neurologic Examination ,biology ,business.industry ,Stroke scale ,Rehabilitation ,Reproducibility of Results ,Emergency department ,Middle Aged ,medicine.disease ,biology.organism_classification ,Prognosis ,Anisocoria ,Sensory Thresholds ,Ischemic stroke ,Cardiology ,Surgery ,Ataxia ,Female ,Neurology (clinical) ,Cardiology and Cardiovascular Medicine ,business ,Emergency Service, Hospital ,030217 neurology & neurosurgery - Abstract
Background: Dizziness is the most common posterior circulation symptom; however, diagnosing a posterior circulation infarction is difficult due to a lack of typical symptoms. We aimed to investigate the frequency of misdiagnosis of a posterior circulation infarction in patients who presented with dizziness and to develop a new stroke scale that increased the diagnostic accuracy for stroke among these subjects. Methods: We retrospectively analyzed consecutive data from subjects hospitalized with ischemic stroke who presented with dizziness (the developmental phase). Based on these results, we created a novel stroke scale, which was used as a diagnostic procedure in the prospective validation phase. We compared the rate of misdiagnosis of ischemic stroke between phases. Results: During the development phase, 115 subjects were hospitalized for ischemic stroke accompanied by dizziness. Six ischemic stroke subjects were not properly diagnosed (6/115, 5.2%). We created the new DisEquilibrium, Floating sEnsation, Non-Specific dizziness, Imbalance, and VErtigo (DEFENSIVE) stroke scale to prevent underdiagnosis of a posterior circulation infarction. During the validation phase, 949 subjects with dizziness were examined with the DEFENSIVE stroke scale; among these subjects, 100 were hospitalized for ischemic stroke accompanied by dizziness. No subject with ischemic stroke was overlooked. The new DEFENSIVE stroke scale had a sensitivity of 100% and decreased the rate of improper diagnosis of stroke (5.2% versus 0%; P = .022). Conclusions: Our new stroke recognition instrument for a posterior circulation infarction presenting with dizziness and related symptoms (the DEFENSIVE stroke scale) is easy to administer and has good diagnostic accuracy.
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- 2018
5. Mouse Body Temperature Measurement Using Infrared Thermometer During Passive Systemic Anaphylaxis and Food Allergy Evaluation
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Yu Kawakami, Toshiaki Kawakami, and Rachel Sielski
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0301 basic medicine ,Materials science ,Infrared Rays ,Thermometers ,General Chemical Engineering ,Body temperature measurement ,Temperature measurement ,General Biochemistry, Genetics and Molecular Biology ,Degree (temperature) ,Mice ,03 medical and health sciences ,Systemic anaphylaxis ,Food allergy ,Body surface ,medicine ,Animals ,Humans ,Anaphylaxis ,Immunology and Infection ,General Immunology and Microbiology ,General Neuroscience ,Temperature ,medicine.disease ,030104 developmental biology ,Infrared thermometer ,Female ,Temperature drop ,Food Hypersensitivity ,Biomedical engineering - Abstract
Mouse body temperature measurement is of paramount importance for investigating allergies and anaphylactic symptoms. Rectal probes for temperature readings is common, and they have been proven to be accurate and invaluable in this regard. However, this method of temperature measurement requires the mice to be anesthetized in order to insert the probe without injury to the animal. This limits the ability to observe other phenotypes of the mouse simultaneously. In order to investigate other phenotypes while measuring temperatures, rectal probes are not ideal, and another method is desired. Here, we introduce a noninvasive method of temperature measurement that foregoes the requirement for mouse anesthesia while maintaining equal reliability to rectal probes in measuring body temperature. We use an infrared thermometer that detects body surface temperatures at ranges between 2 and 150 mm. This method of body temperature measurement is successful in reliably replicating temperature change trends during passive system anaphylaxis experiments in mice. We show that body surface temperatures are about 2.0 °C lower than rectal probe measurements, but the degree of temperature drop follows the same trend. Furthermore, we use the same technique to observe mice in a food allergy model to evaluate temperature and activity levels simultaneously.
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- 2018
6. Histamine-Releasing Factor, a New Therapeutic Target in Allergic Diseases
- Author
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Yu Kawakami, Toshiaki Kawakami, and Kazumi Kasakura
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Models, Molecular ,0301 basic medicine ,Allergy ,Protein Conformation ,FcεRI ,mast cells ,Inflammation ,Review ,Immunoglobulin E ,Allergic inflammation ,Structure-Activity Relationship ,03 medical and health sciences ,0302 clinical medicine ,Food allergy ,In vivo ,Biomarkers, Tumor ,Hypersensitivity ,medicine ,Animals ,Humans ,Anti-Asthmatic Agents ,Molecular Targeted Therapy ,biology ,business.industry ,Tumor Protein, Translationally-Controlled 1 ,General Medicine ,Allergens ,allergy ,medicine.disease ,In vitro ,3. Good health ,030104 developmental biology ,030220 oncology & carcinogenesis ,Immunology ,HRF ,biology.protein ,translationally controlled tumor protein (TCTP) ,Disease Susceptibility ,IgE ,Protein Multimerization ,medicine.symptom ,Antibody ,business ,basophils ,Biomarkers ,Protein Binding - Abstract
Histamine-releasing activities on human basophils have been studied as potential allergy-causing agents for four decades. An IgE-dependent histamine-releasing factor (HRF) was recently shown to interact with a subset of immunoglobulins. Peptides or recombinant proteins that block the interactions between HRF and IgE have emerged as promising anti-allergic therapeutics, as administration of them prevented or ameliorated type 2 inflammation in animal models of allergic diseases such as asthma and food allergy. Basic and clinical studies support the notion that HRF amplifies IgE-mediated activation of mast cells and basophils. We discuss how secreted HRF promotes allergic inflammation in vitro and in vivo complex disease settings.
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- 2019
7. Specific binding of collagen Q to the neuromuscular junction is exploited to cure congenital myasthenia and to explore bases of myasthenia gravis
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Eric Krejci, Andrew G. Engel, Yu Kawakami, Mikako Ito, and Kinji Ohno
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medicine.medical_specialty ,animal structures ,Neuromuscular Junction ,Muscle Proteins ,Perlecan ,GPI-Linked Proteins ,Toxicology ,Injections, Intramuscular ,Synaptic Transmission ,Article ,Neuromuscular junction ,Mice ,chemistry.chemical_compound ,Internal medicine ,COLQ ,medicine ,Animals ,Humans ,Cholinesterase ,Acetylcholine receptor ,Mice, Knockout ,Myasthenic Syndromes, Congenital ,biology ,fungi ,Receptor Protein-Tyrosine Kinases ,Colocalization ,Genetic Therapy ,General Medicine ,Dependovirus ,medicine.disease ,Acetylcholinesterase ,Recombinant Proteins ,Myasthenia gravis ,Myasthenia Gravis, Autoimmune, Experimental ,Cell biology ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Immunoglobulin G ,biology.protein ,Female ,Collagen - Abstract
Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ) in the form of asymmetric AChE (AChE/ColQ). The C-terminal domain of ColQ binds to MuSK, the muscle-specific receptor tyrosine kinase, that mediates a signal for acetylcholine receptor (AChR) clustering at the NMJ. ColQ also binds to heparan sulfate proteoglycans including perlecan. Congenital defects of ColQ cause endplate AChE deficiency. A single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq-/- mice rescued motor functions, synaptic transmission, and the ultrastructure of NMJ. We also injected AAV1-COLQ-IRES-EGFP to the left tibialis anterior and observed colocalization of AChE/ColQ at all the examined NMJs of the non-injected limbs. Additionally, injection of purified recombinant AChE/ColQ protein complex into gluteus maximus accumulated AChE in non-injected forelimbs. These observations suggest that the tissue-targeting signal of ColQ can be exploited to specifically deliver the transgene product to the target tissue. MuSK antibody-positive myasthenia gravis (MG) accounts for 5-15% of autoimmune MG. As AChR deficiency is typically mild and as cholinesterase inhibitors are generally ineffective or worsen myasthenic symptoms, we asked if the patient's MuSK-IgG interferes with binding of ColQ to MuSK. In vitro overlay of AChE/ColQ to muscle sections of Colq-/- mice revealed that MuSK-IgG blocks binding of ColQ to the NMJ. In vitro plate-binding of MuSK to ColQ disclosed that MuSK-IgG exerts a dose-dependent block of MuSK-ColQ interaction. In addition, passive transfer of MuSK-IgG to mice reduced the size and density of ColQ to ∼10% of controls and had a lesser effect on the sizes and densities of AChR and MuSK. Elucidation of molecular mechanisms of specific binding of ColQ to the NMJ enabled us to ameliorate devastating myasthenic symptoms of Colq-/- mice and to reveal bases of anti-MuSK MG.
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- 2013
8. Collagen Q is a Key Player for Developing Rational Therapy for Congenital Myasthenia and for Dissecting the Mechanisms of Anti-MuSK Myasthenia Gravis
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Kinji Ohno, Kenji Ohtsuka, Yu Kawakami, and Mikako Ito
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medicine.medical_specialty ,Aché ,Neurotransmission ,Motor Endplate ,Antibodies ,Neuromuscular junction ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Internal medicine ,COLQ ,medicine ,Animals ,Humans ,Receptors, Cholinergic ,Myasthenic Syndromes, Congenital ,Chemistry ,Receptor Protein-Tyrosine Kinases ,General Medicine ,Congenital myasthenic syndrome ,medicine.disease ,Acetylcholinesterase ,Myasthenia gravis ,language.human_language ,Myasthenia Gravis, Autoimmune, Experimental ,Cell biology ,medicine.anatomical_structure ,Endocrinology ,language ,Basal lamina ,Collagen - Abstract
Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ) in the form of asymmetric AChE (AChE/ColQ). We exploited the proprietary NMJ-targeting signals of ColQ to treat congenital myasthenia and to explore the mechanisms of autoimmune myasthenia gravis (MG). Mutations in COLQ cause congenital endplate AChE deficiency (CEAD). First, a single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq−/− mice normalized motor functions, synaptic transmission, and partly the NMJ ultrastructure. Additionally, injection of purified recombinant AChE/ColQ protein complex into gluteus maximus accumulated AChE in non-injected forelimbs. Second, MuSK antibody-positive MG accounts for 5–15 % of MG. In vitro overlay of AChE/ColQ to muscle sections of Colq−/− mice, as well as in vitro plate-binding of MuSK to ColQ, revealed that MuSK-IgG blocks binding of ColQ to MuSK in a dose-dependent manner. Passive transfer of MuSK-IgG to wild-type mice markedly reduced the size and intensity of ColQ signals at NMJs. MuSK-IgG thus interferes with binding of ColQ to MuSK. Elucidation of molecular mechanisms of specific binding of ColQ to NMJ enabled us to ameliorate devastating myasthenic symptoms of Colq−/− mice and also to reveal underlying mechanisms of anti-MuSK-MG.
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- 2013
9. Defective natural killer cell activity in a mouse model of eczema herpeticum
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Tomoaki Ando, Tae Nakasaki, Manando Nakasaki, Yuko Kawakami, Gisen Kim, Youn Soo Choi, Jong Rok Lee, Kenji Matsumoto, Toshiaki Kawakami, and Yu Kawakami
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0301 basic medicine ,Adoptive cell transfer ,Pathology ,medicine.medical_specialty ,Immunology ,FOXP3 ,Atopic dermatitis ,Skin infection ,Biology ,medicine.disease ,Natural killer cell ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,medicine ,Eczema herpeticum ,Immunology and Allergy ,Cytotoxic T cell ,030215 immunology - Abstract
Background Patients with atopic dermatitis (AD) are susceptible to several viruses, including herpes simplex virus (HSV). Some patients experience 1 or more episodes of a severe skin infection caused by HSV termed eczema herpeticum (EH). There are numerous mouse models of AD, but no established model exists for EH. Objective We sought to establish and characterize a mouse model of EH. Methods We infected AD-like skin lesions with HSV1 to induce severe skin lesions in a dermatitis-prone mouse strain of NC/Nga. Gene expression was investigated by using a microarray and quantitative PCR; antibody titers were measured by means of ELISA; and natural killer (NK) cell, cytotoxic T-cell, regulatory T-cell, and follicular helper T-cell populations were evaluated by using flow cytometry. The role of NK cells in HSV1-induced development of severe skin lesions was examined by means of depletion and adoptive transfer. Results Inoculation of HSV1 induced severe erosive skin lesions in eczematous mice, which had an impaired skin barrier, but milder lesions in small numbers of normal mice. Eczematous mice exhibited lower NK cell activity but similar cytotoxic T-cell activity and humoral immune responses compared with normal mice. The role of NK cells in controlling HSV1-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. Conclusion A murine model of EH with an impaired skin barrier was established in this study. We demonstrated a critical role of defective NK activities in the development of HSV1-induced severe skin lesions in eczematous mice.
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- 2017
10. Anti-MuSK autoantibodies block binding of collagen Q to MuSK
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Ko Sahashi, Masaaki Hirayama, Akio Masuda, Andrew G. Engel, Kinji Ohno, Yu Kawakami, Mikako Ito, Bisei Ohkawara, Naoki Mabuchi, and Hiroshi Nishida
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medicine.medical_specialty ,Muscle Proteins ,Neuromuscular junction ,Receptor tyrosine kinase ,chemistry.chemical_compound ,Mice ,Internal medicine ,COLQ ,medicine ,Animals ,Receptors, Cholinergic ,Antibodies, Blocking ,Cholinesterase ,Acetylcholine receptor ,Autoantibodies ,Mice, Knockout ,biology ,Receptor Protein-Tyrosine Kinases ,Articles ,medicine.disease ,Acetylcholinesterase ,Molecular biology ,In vitro ,Myasthenia gravis ,Myasthenia Gravis, Autoimmune, Experimental ,Endocrinology ,medicine.anatomical_structure ,chemistry ,biology.protein ,Neurology (clinical) ,Binding Sites, Antibody ,Collagen - Abstract
Objective: Muscle-specific receptor tyrosine kinase (MuSK) antibody-positive myasthenia gravis (MG) accounts for 5%–15% of autoimmune MG. MuSK mediates the agrin-signaling pathway and also anchors the collagenic tail subunit (ColQ) of acetylcholinesterase (AChE). The exact molecular target of MuSK–immunoglobulin G (IgG), however, remains elusive. As acetylcholine receptor (AChR) deficiency is typically mild and as cholinesterase inhibitors are generally ineffective, we asked if MuSK-IgG interferes with binding of ColQ to MuSK. Methods: We used 3 assays: in vitro overlay of the human ColQ-tailed AChE to muscle sections of Colq−/− mice; in vitro plate-binding assay to quantitate binding of MuSK to ColQ and to LRP4; and passive transfer of MuSK-IgG to mice. Results: The in vitro overlay assay revealed that MuSK-IgG blocks binding of ColQ to the neuromuscular junction. The in vitro plate-binding assay showed that MuSK-IgG exerts a dose-dependent block of MuSK binding to ColQ by but not to LRP4. Passive transfer of MuSK-IgG to mice reduced the size and density of ColQ to ∼10% of controls and had a lesser effect on the size and density of AChR and MuSK. Conclusions: As lack of ColQ compromises agrin-mediated AChR clustering in Colq −/− mice, a similar mechanism may lead to AChR deficiency in MuSK-MG patients. Our experiments also predict partial AChE deficiency in MuSK-MG patients, but AChE is not reduced in biopsied NMJs. In humans, binding of ColQ to MuSK may be dispensable for clustering ColQ, but is required for facilitating AChR clustering. Further studies will be required to elucidate the basis of this paradox.
- Published
- 2011
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