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111.
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Kiminori Terui Tsutomu Toki Takashi Taga Shotaro Iwamoto Takako Miyamura Daisuke Hasegawa Hiroshi Moritake Asahito Hama Kentaro Nakashima Rika Kanezaki Ko Kudo Akiko M. Saito Keizo Horibe Souichi Adachi Daisuke Tomizawa Etsuro Ito 《Genes, chromosomes & cancer》2020,59(3):160-167
Myeloid leukemia associated with Down syndrome (ML‐DS) is characterized by a predominance of acute megakaryoblastic leukemia, the presence of GATA1 mutations and a favorable outcome. Because DS children can also develop conventional acute myeloid leukemia with unfavorable outcome, detection of GATA1 mutations is important for diagnosis of ML‐DS. However, myelofibrosis and the significant frequency of dry taps have hampered practical screening of GATA1 mutations using bone marrow (BM) samples. In response to those problems, 82 patients were enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML‐D11 study. GATA1 mutations were analyzed by Sanger sequencing (SS) using genomic DNA (gDNA) from BM and cDNA from peripheral blood (PB) followed by targeted next‐generation sequencing (NGS) using pooled diagnostic samples. BM and PB samples were obtained from 71 (87%) and 82 (100%) patients, respectively. GATA1 mutations were detected in 46 (56%) and 58 (71%) patients by SS using BM gDNA and PB cDNA, respectively. Collectively, GATA1 mutations were identified in 73/82 (89%) patients by SS. Targeted NGS detected GATA1 mutations in 74/82 (90%) patients. Finally, combining the results of SS with those of targeted NGS, GATA1 mutations were identified in 80/82 (98%) patients. These results indicate that SS using BM gDNA and PB cDNA is a rapid and useful method for screening for GATA1 mutations in ML‐DS patients. Thus, a combination of SS and targeted NGS is a sensitive and useful method to evaluate the actual incidence and clinical significance of GATA1 mutations in ML‐DS patients. 相似文献
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Satoshi Horino Yoji Sasahara Miki Sato Hidetaka Niizuma Satoru Kumaki Daiki Abukawa Atsushi Sato Masue Imaizumi Hirokazu Kanegane Yoshiro Kamachi Shinya Sasaki Kiminori Terui Etsuro Ito Ichiro Kobayashi Tadashi Ariga Shigeru Tsuchiya Shigeo Kure 《Pediatric transplantation》2014,18(1):E25-E30
IPEX syndrome is a rare and fatal disorder caused by absence of regulatory T cells (Tregs) due to congenital mutations in the Forkhead box protein 3 gene. Here, we report a patient with IPEX syndrome treated with RIC followed by allogeneic BMT from an HLA‐matched sibling donor. We could achieve engraftment and regimen‐related toxicity was well tolerated. Although the patient was in mixed chimera and the ratio of donor cells in whole peripheral blood remained relatively low, selective and sustained expansion of Tregs determined as CD4+CD25+Foxp3+ cells was observed. Improvement in clinical symptoms was correlated with expansion of donor‐derived Tregs and disappearance of anti‐villin autoantibody, which was involved in the pathogenesis of gastrointestinal symptoms in IPEX syndrome. This clinical observation suggests that donor‐derived Tregs have selective growth advantage in patients with IPEX syndrome even in mixed chimera after allogeneic BMT and contribute to the control of clinical symptoms caused by the defect of Tregs. 相似文献
116.
Anastassios C. Koumbourlis Etsuro K. Motoyama Rebecca L. Mutich George B. Mallory Stephen A. Walczak Kathleen Fertal 《Pediatric pulmonology》1996,21(1):28-34
We investigated whether early lung function abnormalities in prematurely born children with a history of chronic lung disease improve in late childhood and adolescence. We performed a prospective, longitudinal evaluations of pulmonary function over an 8 year period. In seventeen patients from the age (mean ± SD) of 8.2 ± 1.2 years to the age of 15.1 ± 1.6 years. They had been born at 29.1 ± 1.9 weeks of gestation, with a birthweight of 1120 ± 190 g, and they had received supplemental oxygen, with or without mechanical ventilation, for 40.4 ± 23.8 days during the neonatal period. They all had radiographic evidence of chronic lung disease at 4 weeks of age. Annual measurements of lung volumes using the helium dilution technique, and of airway function with spirometry and maximal expiratory flow-volume curves over a 5 to 8 year period, were obtained. The results indicated that total lung capacity (TLC) and vital capacity (VC) were within the predicted normal range in all patients and increased over time. In contrast, the initially abnormal residual volume (RV) and RV/TLC ratio decreased over time, suggesting gradual resolution of air-trapping. The peak expiratory flow rate (PEFR), forced expiratory volume in 1 second (FEV1), and the ratio FEV1/FVC remained at or above the predicted normal range in all patients. FEF25–75, FEF50, and FEF75 were within normal limits in eight patients and abnormally low (more than 2 SD below the predicted normal value) in the remaining nine patients, indicating small airway obstruction. Eight of the nine patients with lower airway obstruction showed significant response to inhaled bronchodilator, and four responded to a histamine challenge. None of the eight patients with normal airway function responded to histamine, but four responded to bronchodilators. The perinatal history, family history of asthma, and exposure to smoking were similar in patients with and without airway obstruction. The height and weight were and remained within the normal range. We conclude that gradual normalization of air-trapping continues well into adolescence in virtually all patients with a history of prematurity and chronic lung disease. In contrast, airflow obstruction may persist but does not get worse later in life. Although chronic airflow obstruction probably is the consequence of injury to the small airways during the neonatal period, it is present in only some of the children, and it does not appear to be directly related to the perinatal history. Finally, there is evidence that airway hyperresponsiveness may be a contributing factor to the development and/or persistence of airflow obstruction in chronic lung disease of prematurity. Pediatr Pulmonol. 1996; 21:28–34 . © 1996 Wiley-Liss, Inc. 相似文献
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Christina Andica Koji Kamagata Taku Hatano Yuya Saito Wataru Uchida Takashi Ogawa Haruka Takeshige-Amano Akifumi Hagiwara Syo Murata Genko Oyama Yashushi Shimo Atsushi Umemura Toshiaki Akashi Akihiko Wada Kanako K. Kumamaru Masaaki Hori Nobutaka Hattori Shigeki Aoki 《Journal of neuroscience research》2020,98(5):936-949
Neurocognitive and psychiatric disorders have significant consequences for quality of life in patients with Parkinson's disease (PD). In the current study, we evaluated microstructural white matter (WM) alterations associated with neurocognitive and psychiatric disorders in PD using neurite orientation dispersion and density imaging (NODDI) and linked independent component analysis (LICA). The indices of NODDI were compared between 20 and 19 patients with PD with and without neurocognitive and psychiatric disorders, respectively, and 25 healthy controls using tract-based spatial statistics and tract-of-interest analyses. LICA was applied to model inter-subject variability across measures. A widespread reduction in axonal density (indexed by intracellular volume fraction [ICVF]) was demonstrated in PD patients with and without neurocognitive and psychiatric disorders, as compared with healthy controls. Compared with patients without neurocognitive and psychiatric disorders, patients with neurocognitive and psychiatric disorders exhibited more extensive (posterior predominant) decreases in axonal density. Using LICA, ICVF demonstrated the highest contribution (59% weight) to the main effects of diagnosis that reflected widespread decreases in axonal density. These findings suggest that axonal loss is a major factor underlying WM pathology related to neurocognitive and psychiatric disorders in PD, whereas patients with neurocognitive and psychiatric disorders had broader axonal pathology, as compared with those without. LICA suggested that the ICVF can be used as a useful biomarker of microstructural changes in the WM related to neurocognitive and psychiatric disorders in PD. 相似文献
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Differences in cerebral metabolic impairment between early and late onset types of Alzheimer's disease 总被引:19,自引:0,他引:19
Sakamoto S Ishii K Sasaki M Hosaka K Mori T Matsui M Hirono N Mori E 《Journal of the neurological sciences》2002,200(1-2):27-32
Hypercortisolemia is thought to be a marker of the stress response following stroke. The aim of this study was to investigate the prevalence and prognostic significance of hypercortisolemia. The circadian variation of cortisol level and the relationship between serum cortisol levels and other stress, inflammatory, and haemostatic markers were also investigated. Seventy consecutive patients with their first ischemic stroke and 24 age- and sex-matched controls were included in the study. Serum cortisol levels (at 6:00 AM, 10:00 AM, 6:00 PM, and 10:00 PM), 24-h urine catecholamine excretion, beta-thromboglobulin levels, and other standard biochemical and haematological parameters were measured on the first day of hospitalisation and in control subjects. Outcome measures used the Barthel Index at Day 30, as well as 30- and 90-day mortality rates. Hypercortisolemia, defined as at least two of the four measurements above the normal range of serum cortisol levels (i.e. >618 nmol/l from the morning samples and >460 nmol/l from the evening samples) was found in 25 (35.7%) of the acute stroke patients and in 3 (12.5%) of the controls (p<0.05). Hypercortisolemia was associated with older age, greater severity of neurological deficit, larger ischemic lesions on CT, and worse prognoses (p<0.05). The study did not find a correlation between serum cortisol levels and other markers of the stress response such as catecholamines excretion and glucose levels. A significant correlation between serum cortisol levels and some markers of the inflammatory response, such as fever, fibrinogen level, white blood cell (WBC) count, and beta-thromboglobulin level, was established in stroke patients. Prognostic significance of hypercortisolemia in acute stroke patients seems to be related to the inflammatory response rather than to the stress response. 相似文献