المؤلفون: Ayaka Yagasaki, Taishi Miyase, Shota Sakai, Kiyofumi Mochizuki, Hirokazu Sakaguchi, Teiji Yagasaki, Naoyuki Ohe, Shiho Yasue, Saori Endo, Michio Ozeki

المصدر: Case Reports in Ophthalmology, Vol 14, Iss 1, Pp 613-619 (2023)

مصطلحات موضوعية: acute acquired comitant esotropia, hess red-green test, magnetic resonance imaging, brainstem tumor, Ophthalmology, RE1-994

الوصف: Introduction: Acute acquired comitant esotropia (AACE) is an acquired strabismus with uncrossed sudden-onset diplopia due to esodeviation, comitant esotropia without accommodation factor, or paretic eye movement. The diagnosis of AACE entails differentiation from incomitant esotropia caused by abnormalities in the central nervous system. We present 2 pediatric patients with AACE as the first symptom of brainstem tumor. Case Presentation: The 2 patients were aware of their diplopia and had no other neurological abnormalities. There were no special findings in the anterior segment, ocular media, or fundus. Esotropia with a difference of no more than 10Δ between distant and near fixations was observed. Eye movements were normal, and Hess red-green test under prism neutralization did not reveal abduction restriction. The presumed cause of AACE in both patients was excessive use of digital displays, and brain magnetic resonance imaging (MRI) was performed to confirm the absence of neurological abnormality. Using MRI, a definitive diagnosis of AACE was made based on comitant esotropia associated with diffuse median glioma and medullary pilocytic astrocytoma without abducens nerve palsy. Conclusion: Although the incidence of AACE caused by brainstem tumors may be low, it is necessary to perform head imaging to confirm etiology. Furthermore, Hess red-green test under prism neutralization is considered important for the differentiation of abducens nerve palsy.

وصف الملف: electronic resource

العلاقة: https://beta.karger.com/Article/FullText/534709Test; https://doaj.org/toc/1663-2699Test

الوصول الحر: https://doaj.org/article/f96efbae2aa641fda56a1aa407b23bf7Test

المؤلفون: Michio Ozeki, Saori Endo, Shiho Yasue, Akifumi Nozawa, Ryuta Asada, Akiko M. Saito, Hiroya Hashimoto, Takumi Fujimura, Yohei Yamada, Tatsuo Kuroda, Shigeru Ueno, Shoji Watanabe, Shunsuke Nosaka, Mikiko Miyasaka, Akihiro Umezawa, Kentaro Matsuoka, Takanobu Maekawa, Satoshi Hirakawa, Taizo Furukawa, Shigehisa Fumino, Tatsuro Tajiri, Junkichi Takemoto, Ryota Souzaki, Yoshiaki Kinoshita, Akihiro Fujino

المصدر: Frontiers in Medicine, Vol 11 (2024)

مصطلحات موضوعية: lymphatic anomalies, lymphatic malformation, generalized lymphatic anomaly, Gorham–stout disease, mammalian target of rapamycin, Medicine (General), R5-920

الوصف: IntroductionIntractable lymphatic anomalies (LAs) include cystic lymphatic malformation (LM; macrocystic, microcystic, or mixed), generalized lymphatic anomaly, and Gorham–Stout disease. LAs can present with severe symptoms and poor prognosis. Thus, prospective studies for treatments are warranted. We conducted a prospective clinical trial of sirolimus for intractable LAs.MethodsThis was an open-label, single-arm, multicenter, prospective trial involving five institutions in Japan. All patients with LAs received oral sirolimus once daily, and the dose was adjusted to ensure that the trough concentration remained within 5–15 ng/mL. We prospectively assessed the drug response (response rate for radiological volumetric change in target lesion), performance state, change in respiratory function, visceral impairment (pleural effusion, ascites, bleeding, pain), laboratory examination data, quality of life (QOL), and safety at 12, 24, and 52 weeks of administration.ResultsEleven patients with LAs (9 generalized lymphatic anomaly, 1 cystic LM, 1 Gorham–Stout disease) were treated with sirolimus, of whom 6 (54.5%; 95% confidence interval: 23.4–83.3%) demonstrated a partial response on radiological examination at 52 weeks of administration. No patients achieved a complete response. At 12 and 24 weeks of administration, 8 patients (72.7%) already showed a partial response. However, patients with stable disease showed minor or no reduction after 12 weeks. Adverse events, such as stomatitis, acneiform dermatitis, diarrhea, and fever, were common with sirolimus. Sirolimus was safe and tolerable.ConclusionSirolimus can reduce the lymphatic tissue volume in LAs and may lead to improvements in clinical symptoms and QOL.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmed.2024.1335469/fullTest; https://doaj.org/toc/2296-858XTest

الوصول الحر: https://doaj.org/article/75d954cef4394ed4b3e0cce1df803598Test

المؤلفون: Shiho Yasue, Michio Ozeki, Akifumi Nozawa, Saori Endo, Hidenori Ohnishi

المصدر: PLoS ONE, Vol 19, Iss 5, p e0289187 (2024)

مصطلحات موضوعية: Medicine, Science

الوصف: Recently, a low-level somatic mutation in the NRAS gene (c.182 A > G, Q61R) was identified in various specimens from patients with kaposiform lymphangiomatosis. However, it is unknown how these low-frequency mutated cells can affect the characterization and surrounding environment of their lesions. To understand the pathogenesis and association of these gene abnormalities, we established NRASQ61R mutated lymphatic endothelial cells transfected with lentivirus vector and undertook morphological and functional characterization, protein expression profiling, and metabolome analysis. NRASQ61R human dermal lymphatic endothelial cells showed poor tube formation, a low proliferation rate, and high migration ability, with an increase in the ratio of mutated cells. An analysis of signaling pathways showed inactivation of the PIK3/AKT/mTOR pathway and hyperactivation of the RAS/MAPK/ERK pathway, which was improved by MAPK kinase (MEK) inhibitor treatment. This study shows the theoretical circumstances induced in vitro by NRASQ61R-mutated cells in the affected lesions of kaposiform lymphangiomatosis patients.

وصف الملف: electronic resource

العلاقة: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0289187&type=printableTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/d31c1228fc8548449b7d24956c69a887Test

المؤلفون: Azusa Haba, Yuko Imaizumi, Daichi Hayashi, Shiho Yasue, Hiroki Otsuka, Saori Endo, Michio Ozeki, Kazuhiro Kobayashi, Tatsuhiko Miyazaki, Akira Hara, Hidenori Ohnishi

المصدر: Hematology, Vol 28, Iss 1 (2023)

مصطلحات موضوعية: Down syndrome, GATA-binding factor 1, Liver fibrosis, Transient leukemia of Down syndrome, Transient myeloproliferative disorder, Diseases of the blood and blood-forming organs, RC633-647.5

الوصف: ABSTRACTBackground Transient abnormal myelopoiesis (TAM) is characterized by leukocytosis with increased circulating megakaryoblasts that harbor N-terminal truncating mutations in the GATA1 gene. Approximately 10% of affected patients experience early death.Observations A 2-month-old boy with Down syndrome was diagnosed with TAM and followed without treatment. Although the blasts in the peripheral blood disappeared, liver failure progressed. A pathological examination revealed liver fibrosis, and double-immunostaining for full-length GATA1 and CD42b identified megakaryocytes with a GATA1 mutation.Conclusions This simple and cost-effective method can be applied in routine practice to detect TAM blasts during assessment in a TAM crisis.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1607-8454Test

الوصول الحر: https://doaj.org/article/d41750bc1a3346248b64fb0dc059783bTest

المؤلفون: Michio Ozeki, 小関 道夫

المصدر: 脈管学 / The Journal of Japanese College of Angiology. 2023, 63(6):103

المؤلفون: Kazuhiro Yoshida, Michio Ozeki, Shigehisa Fumino, Shigeyoshi Aoi, Shinya Banno, Shohei Takayama, Taizo Furukawa, Takazumi Kato, Tatsuro Tajiri, 加藤 充純, 古川 泰三, 吉田 和弘, 坂野 慎哉, 小関 道夫, 文野 誠久, 田尻 達郎, 青井 重善, 高山 勝平

المصدر: 日本小児外科学会雑誌 / Journal of the Japanese Society of Pediatric Surgeons. 2023, 59(1):51

المؤلفون: Daichi Hayashi, Hidenori Ohnishi, Michio Ozeki, Saori Endo, Shiho Yasue, 大西 秀典, 安江 志保, 小関 道夫, 林 大地, 遠渡 沙緒理

المصدر: 日本小児血液・がん学会雑誌 / The Japanese Journal of Pediatric Hematology / Oncology. 2023, 60(2):161

المؤلفون: Yumiko Hori, Katsutoshi Hirose, Michio Ozeki, Kenji Hata, Daisuke Motooka, Shinichiro Tahara, Takahiro Matsui, Masaharu Kohara, Hiroki Higashihara, Yusuke Ono, Kaishu Tanaka, Satoru Toyosawa, Eiichi Morii

المصدر: Diagnostic Pathology, Vol 17, Iss 1, Pp 1-7 (2022)

مصطلحات موضوعية: Fibro-adipose vascular anomaly, FAVA, PIK3CA, mTOR, Vascular anomaly, Lymphatic malformation, Pathology, RB1-214

الوصف: Abstract Background Fibro-adipose vascular anomaly (FAVA) is a rare and new entity of vascular anomaly. Activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene were identified at a frequency of 62.5% in FAVA cases. The PIK3CA mutations excessively activate mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis, implying that PIK3CA mutations may act as drivers of FAVAs. This study investigated the correlations between PIK3CA mutational status, clinicopathological features and immunohistochemical expression of the mTOR pathway in a series of FAVA. Methods We retrospectively evaluated the clinical and pathological findings of four FAVA cases. We performed next-generation sequencing (NGS) with a custom panel of genes associated with the mTOR pathway and genes responsible for other vascular anomalies; followed by direct sequencing and immunohistochemical analysis of the mTOR pathway. Results Two PIK3CA-mutation cases and two PIK3CA-wild-type (wt) cases exhibited similar typical clinical features of FAVA. Histological analysis revealed venous malformation, lymphatic malformation, nerves containing enlarged abnormal vessels and fibrofatty tissue were observed regardless of PIK3CA mutational status. In contrast to clinical and histological findings, the immunohistochemical expression of activated AKT and mTOR that are upstream of the mTOR pathway was detected in abnormal vessels of PIK3CA-mutation cases but not in those of PIK3CA-wt cases. However, activated eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1), both of which are downstream effectors of the mTOR pathway, were expressed in abnormal vessels of both PIK3CA-mutation and PIK3CA-wt cases. Furthermore, targeting NGS did not find any common genetic mutations involved in the mTOR pathway among PIK3CA-wt cases. Conclusions There was no significant association between the presence of PIK3CA mutations and the clinicopathological features of FAVA, suggesting that the PIK3CA gene is not necessarily involved in the onset of FAVA. FAVAs lacking PIK3CA mutations may be caused by other gene mutations that activate 4EBP1 and S6K1.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1746-1596Test

الوصول الحر: https://doaj.org/article/b3aeca8a4e6c408cb4fa27d6fd3e1461Test

المؤلفون: Michio Ozeki, 小関 道夫

المصدر: 小児耳鼻咽喉科 / Pediatric Otorhinolaryngology Japan. 2022, 43(1):29

المؤلفون: Michio Ozeki, Yoko Aoki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Yumiko Hori, Kentaro Matsuoka, Tetsuya Niihori, Ryo Funayama, Matsuyuki Shirota, Keiko Nakayama, Toshiyuki Fukao

المصدر: Orphanet Journal of Rare Diseases, Vol 14, Iss 1, Pp 1-9 (2019)

مصطلحات موضوعية: Vascular anomaly, Kaposiform lymphangiomatosis, Neuroblastoma RAS viral oncogene homolog, Cell-free DNA, Liquid biopsy, Medicine

الوصف: Abstract Background Kaposiform lymphangiomatosis (KLA) has recently been distinguished as a novel subtype of generalized lymphatic anomaly (GLA) with foci of spindle endothelial cells. All cases of KLA involve multiple organs and have an unfavorable prognosis. However, the molecular pathogenesis is unknown, and there are no useful biomarkers. In the present study, we performed genetic analysis to elucidate the cause of this disease and detect biomarkers for it. Methods We performed whole-exome sequencing of DNA samples from leukocytes and a biopsy specimen and analyzed cell-free DNA (cfDNA) from plasma and pleural effusion of patients to identify the NRAS c.182A > G (p.Q61R) mutation using the droplet digital polymerase chain reaction (ddPCR). Results All KLA patients (patients 1–5) had invasive and aggressive features (hemorrhagic pleural effusions, coagulation disorder, and thrombocytopenia) and characteristic findings of KLA in their pathological examinations. In whole exome sequencing for patient 1, c.182A > G missense variant (p.Q61R) in NRAS was identified in fresh frozen samples of a mass on the left chest wall at a frequency of 5% of total alleles but not in his blood leukocytes. Furthermore, the same mutation was detected in cfDNA isolated from plasma and pleural effusion by using ddPCR. ddPCR analysis of plasma/pleural effusion samples from an additional four KLA patients showed that the same mutation was detected in isolated cfDNA in three of the four, as well as in a tissue sample from one of the three plasma/effusion-positive patients that had been obtained to confirm the mutation. Conclusion These results provide the first evidence that NRAS oncogenic variant was identified in DNA samples from KLA patients from not only two affected lesions but also plasma and pleural effusion.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s13023-019-1191-5Test; https://doaj.org/toc/1750-1172Test

الوصول الحر: https://doaj.org/article/b6246cfbeb3548eaa352aee6bbce0d20Test