18 results on '"Nagamori, Tsunehisa"'
Search Results
2. A 34-year-old Japanese patient exhibiting NBAS deficiency with a novel mutation and extended phenotypic variation
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Suzuki, Shigeru, Kokumai, Takahide, Furuya, Akiko, Nagamori, Tsunehisa, Matsuo, Kumihiro, Ueda, Osamu, Mukai, Tokuo, Ito, Yoshiya, Yano, Koichi, Fujieda, Kenji, Okuno, Akimasa, Tanahashi, Yusuke, and Azuma, Hiroshi
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- 2020
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3. Construction of a scoring system for predicting the risk of severe gastrointestinal involvement in Henoch-Schönlein Purpura
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Nagamori, Tsunehisa, Oka, Hideharu, Koyano, Shin, Takahashi, Hironori, Oki, Junichi, Sato, Yuko, Murono, Koichi, Iseki, Kenichi, Takeguchi, Ryou, Takeda, Takahiro, Sato, Masayuki, Sugai, Rika, Kitamura, Hiroyuki, Kajino, Hiroki, Miura, Yurika, Ishioka, Toru, and Azuma, Hiroshi
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- 2014
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4. Newborn screening of congenital cytomegalovirus infection using saliva can be influenced by breast feeding
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Koyano, Shin, Inoue, Naoki, Nagamori, Tsunehisa, Moriuchi, Hiroyuki, and Azuma, Hiroshi
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- 2013
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5. A novel STAT3 mutation associated with hyper immunoglobulin E syndrome with a paucity of connective tissue signs.
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Yoshida, Yoichiro, Nagamori, Tsunehisa, Takahashi, Hironori, Ishibazawa, Emi, Shimada, Sorachi, Kawai, Toshinao, and Azuma, Hiroshi
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IMMUNOGLOBULINS , *GENETIC mutation , *IMMUNOLOGICAL deficiency syndromes , *GENE expression , *GENES , *ATOPIC dermatitis , *BACTERIAL diseases , *T cells , *CARRIER proteins - Abstract
Background: A heterozygous mutation of STAT3 causes autosomal dominant hyper immunoglobulin E (IgE) syndrome; however, there are still many unclear points regarding the clinical spectrum of this syndrome. Methods: In addition to a clinical description of patients in terms of pedigree, a genetic analysis, quantitation of peripheral blood Th17 and ex vivo IL‐17 production were carried out. Results: The proband, a 2‐year‐old boy (Patient 1) with early onset atopic dermatitis‐like eczema and recurrent bacterial infections, was suspected of autosomal dominant hyper immunoglobulin E syndrome on the basis of his symptoms and family history. His mother (Patient 2) also had skin eczema and recurrent bacterial infections, and his sister (Patient 3) had skin eczema. A novel STAT3 mutation (p.S476F) was detected in all three patients, but not in the father, who had no such symptoms. A significant decrease in peripheral blood Th17 subsets and IL‐17 production was found in all the patients. Curiously, all three patients carrying the p.S476F mutation in STAT3 lacked connective tissue signs such as distinctive facial features, retention of primary teeth, and joint hyperextensibility. Conclusions: Autosomal dominant hyper IgE syndrome should, perhaps, be considered even if patients lack connective tissue signs, as long as hypersensitivity to infection and skin manifestations with hyper IgE are present. [ABSTRACT FROM AUTHOR]
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- 2021
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6. Contribution of long-chain fatty acid to induction of myeloid-derived suppressor cell (MDSC)-like cells – induction of MDSC by lipid vesicles (liposome).
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Yoshida, Yoichiro, Nagamori, Tsunehisa, Ishibazawa, Emi, Kobayashi, Hiroya, Kure, Tomoko, Sakai, Hiromi, Takahashi, Daisuke, Fujihara, Mitsuhiro, and Azuma, Hiroshi
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SUPPRESSOR cells , *FATTY acids , *CELL membranes , *INTRAVENOUS injections , *CELLS - Abstract
Effects of liposomal particles on immune function have not been adequately investigated. Earlier reports indicate that intravenous injection of rats with pegylated liposomes comprising chemically defined specific lipids produces myeloid derived suppressor-cell (MDSC)-like cells in the spleen. After liposome injection, we sought a cell surface marker expressed specifically on splenic macrophages. Then we assessed the immunosuppressive activity of macrophages positive for the marker. Furthermore, we investigated whether immunosuppression induction is an immunopharmacological action specific to this pegylated liposome, or not. After using a microarray system to screen genes enhanced by this liposome, we evaluated cell surface expression of gene products using flow cytometry. Liposomes of several kinds, each comprising one type of phospholipid, were prepared and evaluated for their ability to induce T-cell suppression. Microarray analysis indicated enhanced B7-H3 expression. Flow cytometry revealed that the B7-H3 molecule was expressed on splenic macrophages after liposome injection. B7-H3+ macrophages were positive for iNOS. Removing B7-H3+ cells restored T-cell proliferation. Similarly to this liposome, various liposomes with different long chain fatty acids induced T-cell suppression when accumulated in the spleen. Immunosuppressive cells induced by this pegylated liposome closely resemble MDSCs, especially B7-H3+ MDSCs. Immunosuppression induction is not a phenomenon specific to this liposome. Accumulation of long chain fatty acid in macrophages by internalization of liposomal nanoparticles might be related to macrophage acquisition of immunosuppressive activity in vivo. [ABSTRACT FROM AUTHOR]
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- 2020
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7. A case of congenital herpes simplex virus infection diagnosed at 8 months of age.
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Yamamoto, Shiho, Nagamori, Tsunehisa, Komatsu, Shigetsuna, Shirai, Masaru, Suzutani, Tatsuo, and Oki, Junichi
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HERPES simplex virus , *VIRUS diseases , *HERPES genitalis , *MAGNETIC resonance imaging , *BIRTH intervals , *DEVELOPMENTAL delay - Abstract
We present the case of an 8-month-old boy with the repeated recurrence of vesicles from the time of birth and who subsequently manifested psychomotor developmental delay. We retrospectively diagnosed the patient with congenital herpes simplex virus (HSV) infection. Computed tomography showed multiple calcifications in the periventricular white matter and thalami. The bilateral deep white matter showed an abnormally high signal intensity on T2-weighted magnetic resonance imaging. The patient required consecutive, suppressive therapy with valacyclovir to prevent the repeated recurrence of vesicles. This case presented a milder phenotype of congenital HSV infection in comparison to previous reports, and highlights the importance of the careful examination for this disease when neonates present with skin lesions. [ABSTRACT FROM AUTHOR]
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- 2020
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8. Non‐invasive discrimination of acute focal bacterial nephritis with pyelonephritis.
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Oka, Hideharu, Nagamori, Tsunehisa, Yamamoto, Shiho, Manabe, Hiromi, Taketazu, Genya, Mukai, Tokuo, Sakata, Hiroshi, and Oki, Junichi
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ANTI-infective agents , *DIAGNOSIS of bacterial diseases , *URINARY tract infection diagnosis , *BIOMARKERS , *CLINICAL pathology , *FEVER , *NEPHRITIS , *PYELONEPHRITIS , *SUPPURATION , *URINE , *SYMPTOMS , *RETROSPECTIVE studies , *ACUTE diseases , *DISEASE duration , *CHILDREN - Abstract
Background: The appropriate antimicrobial treatment period for febrile urinary tract infection (UTI) can be changed, depending on whether the patient has acute focal bacterial nephritis (AFBN). The aim of this study was to clarify the characteristics of AFBN compared with those of acute pyelonephritis (APN) and establish a strategy to detect AFBN. Methods: A total of 77 patients diagnosed with febrile UTI were enrolled. They were divided into APN (n = 64) and AFBN groups (n = 13). The clinical data and other laboratory biomarkers were retrospectively analyzed. Results: The time required for fever resolution after antimicrobial treatment was significantly longer in the AFBN group than in the APN group (2.77 days vs 1.11 days, respectively, P < 0.001). Also, the time to disappearance of pyuria after antimicrobial treatment was longer in the AFBN group than in the APN group (6.22 days vs 2.32 days, respectively, P = 0.001). Fever lasting >1.75 days after antimicrobial treatment had a sensitivity of 92% and specificity of 79% for the detection of AFBN, while pyuria disappearance after 4 days had a sensitivity of 88% and specificity of 85%. When patients fulfilled both cut‐offs, the sensitivity and specificity were 89% and 97%. Conclusion: Acute focal bacterial nephritis was associated with fever of significantly longer duration after antimicrobial treatment, and it took a longer time for pyuria to disappear. Children with febrile UTI should be evaluated for AFBN if the fever persists ≥48 h after the initiation of antimicrobial treatment and if pyuria lasts for 4 days. [ABSTRACT FROM AUTHOR]
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- 2019
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9. A Marked Response to Immunosuppressive Intervention for Abruptly Occurring Cardiac Complications in a Case of Juvenile Systemic Sclerosis Overlapped with Dermatomyositis.
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Nagamori, Tsunehisa, Yoshida, Yoichiro, Takahashi, Hironori, Oka, Hideharu, Kajihama, Aya, Nakau, Koichi, Sugimoto, Masaya, Minami-Hori, Masako, and Azuma, Hiroshi
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SYSTEMIC scleroderma , *DERMATOMYOSITIS , *IMMUNOSUPPRESSION , *IMMUNE response , *DISEASE complications , *JUVENILE diseases - Abstract
Juvenile-onset systemic sclerosis (jSSc) is a rare condition, having unique characteristic features compared to adult-onset SSc. Although cardiac involvement (CI) is known as a leading cause of mortality overall in SSc, the importance of CI in jSSc has not been emphasized. Here we present a 13-year-old female with jSSc overlapped with dermatomyositis (DM) complicated CI. She developed skin thickness and induration, Raynaud’s phenomenon, digital pitting scars in fingertips, and skeletal myositis. Oral prednisolone and pulse methotrexate treatment led to the improvement of skin findings; however two weeks after the initiation she suddenly presented with muscle pain and dyspnea within a few days. Cardiac investigations then showed pericardiac effusion and diastolic dysfunction due to significant biventricular hypertrophy causing heart failure. As pericardiac effusion and exacerbation of skeletal myositis were evident, steroid pulse therapy was initiated. Unexpectedly, not only the myositis but also the CI including diastolic dysfunction was improved. She thereafter followed a favorable clinical course without reactivation of the CI or cardiac fibrosis. As a conclusion, close attention to CI must be paid in jSSc patients, especially when skeletal muscle involvement is evident and immunosuppressive therapy may be effective for CI in jSSc in cases where it occurs abruptly. [ABSTRACT FROM AUTHOR]
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- 2017
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10. Severe gastrointestinal involvement predictive score in IgA vasculitis is also a risk factor for nephritis being varied depending on their ages of onset.
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Nagamori, Tsunehisa, Yoshida, Yoichiro, Azuma, Hiroshi, Takahashi, Hironori, Oka, Hideharu, Yamamoto, Shiho, Manabe, Hiromi, Taketazu, Genya, Mukai, Tokuo, Sakata, Hiroshi, and Oki, Junichi
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NEPHRITIS , *AGE of onset , *DISEASE risk factors , *SCHOENLEIN-Henoch purpura , *VASCULITIS - Abstract
The article focuses on the severe gastrointestinal (GI) involvement as a risk factor for Immunoglobulin A (IgA) vasculitis. It discusses the definition of nephritis due to the presence of microscopic hematuria, showing positive faecal haemoglobin, logistic regression models for nephritis development and calculated likelihood.
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- 2019
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11. Sequential changes in pathophysiology of systemic inflammatory response in a disseminated neonatal herpes simplex virus (HSV) infection
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Nagamori, Tsunehisa, Koyano, Shin, Asai, Yoko, Nohara, Fumikatsu, Okamoto, Toshio, Nagaya, Ken, Hayashi, Tokitsugi, Miura, Yurika, Tsuda, Naoya, Iseki, Kenichi, and Azuma, Hiroshi
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HERPES simplex virus , *PATHOLOGICAL physiology , *NEONATAL diseases , *ANTI-inflammatory agents , *CYTOCHROME c , *BIOMARKERS , *APOPTOSIS - Abstract
Abstract: Background: Disseminated neonatal herpes simplex virus (HSV) infection causes a typical systemic inflammatory response syndrome and has a high mortality rate. However, the validity of anti-inflammatory intervention against this condition remains unknown. Objectives: We sought to demonstrate the sequential changes in the pathophysiology of disseminated neonatal HSV infections. Study design: The HSV serum copy number as well as high-mobility group box 1 (HMGB1) and cytochrome c concentrations, which predict the severity and mortality rate of sepsis, were sequentially evaluated in a patient with disseminated neonatal HSV infection caused by HSV-2. Results: As the patient presented with evidence of hyper-inflammation and severe illness, we empirically undertook anti-inflammatory intervention that included the administration of prednisolone, high-dose immunoglobulin, and blood exchange therapy in addition to high-dose acyclovir (ACV) therapy. The patient survived without significant neurological sequela. We found that (1) the serum concentrations of both HMGB1 and cytochrome c were extremely high, (2) temporal increases in these biomarkers were observed after admission, and (3) interestingly, the increase in HMGB1 level preceded that of cytochrome c. These results suggested that the pathophysiology of this condition changed sequentially in a dramatic manner, and the timing of our anti-inflammatory intervention was prior to the transition of pathological status from hyper-inflammation to massive apoptosis. Conclusions: Anti-inflammatory intervention may only be effective if it is undertaken during the early phase of disseminated neonatal HSV infections. [Copyright &y& Elsevier]
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- 2012
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12. Single cytomegalovirus strain associated with fetal loss and then congenital infection of a subsequent child born to the same mother
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Nagamori, Tsunehisa, Koyano, Shin, Inoue, Naoki, Yamada, Hideto, Oshima, Miho, Minematsu, Toshio, and Fujieda, Kenji
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VERTICAL transmission (Communicable diseases) , *CYTOMEGALOVIRUS diseases , *GENETIC disorders in children , *HIV-positive persons , *DEAFNESS in children , *NYSTAGMUS , *INFECTIOUS disease transmission ,DIAGNOSIS of neonatal diseases - Abstract
Abstract: Background: Intrauterine transmission of cytomegalovirus (CMV) can occur even in CMV-seropositive mothers. Previous studies demonstrated re-infection with a newly acquired CMV strain during pregnancy had a major role in such transmission. Although reactivation of latently infected CMV is another plausible cause, no direct evidence has been documented. Objectives: We sought to identify the route(s) and maternal risk factor of CMV infection that occurred in consecutive pregnancies and resulted in symptomatic congenital infections. Study design: A newborn identified with congenital CMV infection in our newborn screening program developed hearing loss and subsequent nystagmus. The mother had a history of an elective abortion due to a severe fetal CMV infection 32 months prior to delivery of this newborn. We analyzed maternal serological changes and compared CMV genomic sequences in specimens obtained from the aborted fetus and the present case. We also analyzed immunological functions of the mother. Results: Our major findings were as follows: (1) the aborted fetus and the present case were infected with the same strain. (2) The congenital infection that resulted in the abortion was due to a primary infection. (3) CMV DNA was undetectable in the mother''s blood from 3 months after the abortion. These results strongly suggested that maternal viral reactivation caused the congenital infection in the present case. However, we could not find impairment of immunological functions in the mother. Conclusions: Viral reactivation in an apparently immunocompetent mother can cause symptomatic congenital CMV infection. [Copyright &y& Elsevier]
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- 2010
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13. Dried Umbilical Cords in the Retrospective Diagnosis of Congenital Cytomegalovirus Infection as a Cause of Developmental Delays.
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Koyano, Shin, Inoue, Naoki, Nagamori, Tsunehisa, Hainian Yan, Asanuma, Hideomi, Yagyu, Kazuyori, Osaki, Masaya, Seiwa, Chizuru, and Fujieda, Kenji
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CYTOMEGALOVIRUS diseases ,UMBILICAL cord abnormalities ,DEVELOPMENTAL disabilities ,HERPESVIRUS diseases ,PEOPLE with developmental disabilities ,MEDICAL research ,RETROSPECTIVE diagnosis - Abstract
To clarify the impact of congenital cytomegalovirus (CMV) infection on developmental disabilities, 20 children with disabilities of unknown cause were analyzed. Five children were CMV positive and had no clinical manifestations at birth. Intracranial calcification was observed in 4 cases. Thus, congenital CMV infection is a significant cause of developmental disabilities. [ABSTRACT FROM AUTHOR]
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- 2009
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14. A Rare Mutation in Cystic Fibrosis Transmembrane Conductance Regulator Gene in a Recurrent Pancreatitis Patient Without Respiratory Symptoms.
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Koyano, Shin, Hirano, Yoshiki, Nagamori, Tsunehisa, Tanno, Satoshi, Murono, Koichi, and Fujieda, Kenji
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- 2010
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15. Demonstration of equivocal anti-glomerular basement membrane antibody positivity as a non-specific reaction through multiple immunologic assays in a case of pediatric asymptomatic hematuria.
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Sato, Masayuki, Nishibata, Yuka, Masuda, Sakiko, Nagamori, Tsunehisa, Ishibazawa, Emi, Yoshida, Yoichiro, Takahashi, Hironori, Ishizu, Akihiro, and Takahashi, Satoru
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IMMUNOASSAY , *IMMUNOGLOBULINS , *BASAL lamina , *ENZYME-linked immunosorbent assay , *ANTI-glomerular basement membrane disease , *HEMATURIA - Abstract
• There are few reports of patients false-positive for anti-GBM antibody. • An 8-year-old boy had a high anti-GBM antibody titer measured by a commercial assay. • We performed additional assays of anti-GBM antibody, which were all negative. • The positivity of commercial assay in our patient is believed to be non-specific. • Multiple serological assays could be helpful in detecting false-positive results. Anti-glomerular basement membrane (anti-GBM) antibody is essential for the diagnosis of anti-GBM disease. The major epitope consists of the α3 subunits of type IV collagen non-collagenous domain (α 3(IV)NC1). There have been only a few reports of patients false-positive for anti-GBM antibody. We experienced an 8-year-old boy who presented with asymptomatic hematuria followed by positivity for anti-GBM antibody as evaluated by a commercially available chemiluminescent enzyme immunoassay (CLEIA). While his condition remained stable other than continuing hematuria, his anti-GBM antibody titer increased. Further examination of another anti-GBM antibody assay (fluoroenzyme immunoassay) showed negative results. Thus, evaluation of the accuracy of his positivity for anti-GBM antibody was required. We conducted the following examinations: A) enzyme-linked immunosorbent assay, B) immunoblotting for recombinant α 1–5(IV)NC1, and C) immunohistochemical analysis of normal kidney tissue sections. Specimens used for the analysis were sera in A and IgG from the patient in B and C, respectively. As a result, no anti-GBM antibody was detected in A. In B, no band specific to α 1–5(IV)NC1 was observed. In C, the kidney tissue was not stained. Taken together, these results led us to judge the positive anti-GBM result in CLEIA of our patient to be a non-specific reaction. The commercial assays for anti-GBM antibody can lead to false-positive results. We recommend confirmation of anti-GBM antibody positivity through the use of multiple assays in patients demonstrating an atypical clinical course for anti-GBM disease. [ABSTRACT FROM AUTHOR]
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- 2023
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16. A Continuous Increase in CXC-Motif Chemokine Ligand 10 in a Case of Anti-Nuclear Matrix Protein-2-Positive Juvenile Dermatomyositis.
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Nagamori T, Ishibazawa E, Yoshida Y, Izumi K, Sato M, Ichimura Y, Okiyama N, Nishino I, and Azuma H
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Anti-nuclear matrix protein-2 (NXP2) antibody is associated with the severe, chronic myositis phenotype in juvenile dermatomyositis (JDM). Although hyperproduction of type I interferon is considered to play an important role in JDM, sequential changes in biomarkers associated with this pathophysiology have not yet been described in detail. An 8-year-old boy who presented with muscle weakness, heliotrope rash, and Gottron's papules was diagnosed with JDM. With regard to myositis-specific autoantibodies, anti-NXP2 was detected. Although the increase of serum myogenic enzymes was modest at onset, two courses of methyl-prednisolone (mPSL) pulse therapy followed by oral prednisolone and methotrexate were insufficient to initiate remission. Therefore, additional treatment, with intravenous cyclophosphamide (IVCY) and intravenous immunoglobulin (IVIG) was required to obtain a favorable outcome. We also retrospectively evaluated serum concentration of several cytokines: interleukin (IL)-6, soluble tumor necrotizing factor receptor (sTNFR)-1, sTNFR-2, IL-18, and CXC-motif chemokine ligand (CXCL)-10. The cytokine profile of this patient at onset showed a CXCL-10-dominant pattern. Additionally, sequential evaluation of CXCL-10 revealed an aberrantly high level of CXCL-10 persistent despite two courses of mPSL pulse therapy, and the level of this cytokine only gradually decreased after initiation of IVCY and IVIG. The hyperproduction of CXCL-10, presumably reflecting the hyperproduction of type I interferon in the affected tissue, may persist for a certain period, even after the initiation of multiple courses of mPSL pulse therapy. With regard to the fact that anti-NXP2 is associated with subcutaneous calcification, our data suggest the importance of aggressive intervention in cases of anti-NXP2-positive JDM as well as the need for the development of a more pathophysiologically specific treatment., Competing Interests: None to declare., (Copyright 2022, Nagamori et al.)
- Published
- 2022
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17. Variations in the pathophysiology of respiratory syncytial virus infection depend on the age at onset.
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Nagamori T, Yoshida Y, Ishibazawa E, Oka H, Takahashi H, Manabe H, Taketazu G, Shirai M, Sakata H, Oki J, and Azuma H
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- Age of Onset, Child, Hospitalization, Humans, Infant, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus, Human, Respiratory Tract Infections
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Background: Lower respiratory tract infections due to respiratory syncytial virus are associated with morbidity and mortality in infants and children. Thus precise elucidation of respiratory syncytial virus lower respiratory tract infection pathophysiology is important., Methods: Medical records of hospitalized patients were reviewed. Patients were divided into three groups. Group I: patients who improved without oxygen supply. Group II: patients who received oxygen supply, but not nasal high-flow cannula therapy. Group III: patients who received nasal high-flow cannula. Patients were also divided by age group into the <6 months and ≥6 months groups. Parameters for differentiating the severity among groups were then evaluated. Further, serum concentration of high-mobility group box-1 and several cytokines (Inerleukin-6, soluble tumor necrosis factor receptor-1/2, Interleukin-18, Interferon-gamma responsive protein-100) were evaluated., Results: One hundred eighty-nine were enrolled. An analysis of variance for those <6 months showed overall differences including younger age, lower pH, and increased partial pressure of carbon dioxide (pCO2), bicarbonate (HCO3-), and base excess at the time of admission. On the other hand, analysis of variance for ≥6 months revealed that, in addition to a lower pH and increased pCO2, patients showed differences including decreased serum total protein and albumin, and increased aspartate aminotransferase (AST), alanin aminotransferase (ALT), lactate dehydrogenase (LDH), Ferritin and C-reactive protein (CRP) levels. Further, evaluation of serum cytokines showed that IL-6, s tumor necrotizing factor receptor-1/2, and high-mobility group box-1 were higher in Group II/III among the ≥6 months age group, but not for those in the <6 months group., Conclusions: The pathophysiology of severe respiratory syncytial virus lower respiratory tract infection varies according to the age at onset. In late infancy and childhood, a certain proportion of patients show a hyperinflammatory status., (© 2021 Japan Pediatric Society.)
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- 2022
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18. ABIN2 Function Is Required To Suppress DSS-Induced Colitis by a Tpl2-Independent Mechanism.
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Nanda SK, Nagamori T, Windheim M, Amu S, Aviello G, Patterson-Kane J, Arthur JSC, Ley SC, Fallon P, and Cohen P
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- Adaptor Proteins, Signal Transducing genetics, Animals, Cells, Cultured, Colitis chemically induced, Cyclooxygenase 2 genetics, Cyclooxygenase 2 metabolism, Dextran Sulfate, Dinoprostone metabolism, Gene Knock-In Techniques, Interleukin-1beta metabolism, MAP Kinase Kinase Kinases genetics, Mice, Mice, Knockout, Mice, Transgenic, Mutation genetics, Protein Binding genetics, Proto-Oncogene Proteins genetics, Ribonuclease, Pancreatic metabolism, Signal Transduction, Ubiquitins metabolism, Adaptor Proteins, Signal Transducing metabolism, Colitis immunology, MAP Kinase Kinase Kinases metabolism, Macrophages immunology, Myofibroblasts immunology, Proto-Oncogene Proteins metabolism
- Abstract
The A20-binding inhibitor of NF-κB 2 (ABIN2) interacts with Met1-linked ubiquitin chains and is an integral component of the tumor progression locus 2 (Tpl2) kinase complex. We generated a knock-in mouse expressing the ubiquitin-binding-defective mutant ABIN2[D310N]. The expression of Tpl2 and its activation by TLR agonists in macrophages or by IL-1β in fibroblasts from these mice was unimpaired, indicating that the interaction of ABIN2 with ubiquitin oligomers is not required for the stability or activation of Tpl2. The ABIN2[D310N] mice displayed intestinal inflammation and hypersensitivity to dextran sodium sulfate-induced colitis, an effect that was mediated by radiation-resistant cells rather than by hematopioetic cells. The IL-1β-dependent induction of cyclooxygenase 2 (COX2) and the secretion of PGE
2 was reduced in mouse embryonic fibroblasts and intestinal myofibroblasts (IMFs) from ABIN2[D310N] mice. These observations are similar to those reported for the Tpl2 knockout (KO) mice (Roulis et al. 2014. Proc. Natl. Acad. Sci. USA 111: E4658-E4667), but the IL-1β-dependent production of COX2 and PGE2 in mouse embryonic fibroblasts or IMFs was unaffected by pharmacological inhibition of Tpl2 in wild-type mice. The expression of ABIN2 is decreased drastically in Tpl2 KO mice. These and other lines of evidence suggest that the hypersensitivity of Tpl2 KO mice to dextran sodium sulfate-induced colitis is not caused by the loss of Tpl2 catalytic activity but by the loss of ABIN2, which impairs COX2 and PGE2 production in IMFs by a Tpl2 kinase-independent pathway., (Copyright © 2018 by The American Association of Immunologists, Inc.)- Published
- 2018
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