Matsuyama H.,University of Tokyo |
Suzuki H.I.,University of Tokyo |
Nishimori H.,University of Tokyo |
Noguchi M.,Juntendo Urayasu Hospital |
And 6 more authors.
Blood | Year: 2011
Many transformed lymphoma cells show immune-phenotypes resembling the corresponding normal lymphocytes; thus, they provide a guide for proper diagnosis and present promising routes to improve their pathophysiologic understanding and to identify novel therapeutic targets. However, the underlying molecular mechanism( s) of these aberrant immunephenotypes is largely unknown. Here, we report that microRNA-135b (miR-135b) mediates nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-driven oncogenicity and empowers IL-17-producing immunophenotype in anaplastic large cell lymphoma (ALCL). NPM-ALK oncogene strongly promoted the expression of miR-135b and its host gene LEMD1 through activation of signal transducer and activator of transcription (STAT) 3. In turn, elevated miR-135b targeted FOXO1 inALCL cells. miR-135b introduction also decreased chemosensitivity in Jurkat cells, suggesting its contribution to oncogenic activities of NPM-ALK. Interestingly, miR-135b suppressed T-helper (Th) 2 master regulators STAT6 and GATA3, and miR-135b blockade attenuated IL-17 production and paracrine inflammatory response by ALCL cells, indicating that miR-135b-mediated Th2 suppression may lead to the skewing to ALCL immunophenotype overlapping with Th17 cells. Furthermore, antisense-based miR-135b inhibition reduced tumor angiogenesis and growth in vivo, demonstrating significance of this "Th17 mimic" pathway as a therapeutic target. These results collectively illuminated unique contribution of oncogenic kinase-linked microRNA to tumorigenesis through modulation of tumor immune-phenotype and microenvironment. © 2011 by The American Society of Hematology.
Saita Y.,Juntendo University |
Ishijima M.,Juntendo University |
Mogami A.,Juntendo Shizuoka Hospital |
Kubota M.,Juntendo University |
And 16 more authors.
Bone | Year: 2014
Purpose: Atypical femoral fractures (AFFs) are stress-related fractures that are speculated to associate with long-term treatment with bisphosphonates for osteoporosis. A history of AFF is a high risk factor for the development of a subsequent AFF in the same location of the contralateral femur, suggesting that a patient's individual anatomical factor(s) are related to the fracture site of AFFs. In this study, we investigated the radiographs of fourteen AFFs (four bilateral fractures among ten patients) treated at six hospitals associated with our university between 2005 and 2010. The fracture site and standing femorotibial angle (FTA), which reflects the mechanical axis of the lower limb, were measured on weight-bearing lower limb radiographs. The fracture site and FTA of patients with typical femoral fractures (TFF) were compared to those of patients with AFFs. The correlations were examined using Spearman's rank correlation coefficients. The fracture locations in the femora were almost the same in the patients with bilateral AFFs. There was a positive correlation between the fracture site and the standing FTA in the patients with AFFs (r. = 0.82, 95% confidence interval; 0.49 to 0.94), indicating that the larger the standing FTA (varus alignment), the more distal the site of the fracture in the femur. The FTA of the patients with atypical diaphyseal femoral fracture were significantly larger compared to that of those with not only atypical subtrochanteric fractures but also TFFs. In conclusion, the fracture sites of AFFs are associated with the standing lower limb alignment, while those of TFFs are not. © 2014.
Shimizu A.,Juntendo Shizuoka Hospital |
Komuro Y.,Juntendo Urayasu Hospital |
Miyajima M.,Juntendo University |
Arai H.,Juntendo University
Journal of Neurosurgery: Pediatrics | Year: 2012
An otherwise healthy, developmentally normal 3-week-old male infant presented with complex multisuture craniosynostosis involving the metopic suture and bilateral coronal sutures with frontal prominence and hypotelorism. Frontal craniectomy and bilateral frontoorbital advancement remodeling were performed at the age of 5 months. The postoperative course was uneventful. The child's development was normal up to 8 months after the operation. His father and grandfather had similar specific deformities of the cranium, but no anomaly of the extremities was found, and conversation suggested that their intelligence was normal, excluding the possibility of syndromic craniosynostosis. A DNA analysis revealed large-scale copy number polymorphism of chromosome 4 in the patient and his family, which may include the phenotype of the cranium. Neither FGFR mutation nor absence of a TWIST1 mutation in the sequence from 291 to 1087, which includes DNA binding, Helix1, Loop, and Helix2, was identified. The patient apparently had a rare case of familial nonsyndromic craniosynostosis. The authors plan further genomic analysis of this family and long-term observation of the craniofacial deformity of this patient.
PubMed | Juntendo University, Juntendo Nerima Hospital and Juntendo Urayasu Hospital
Type: Journal Article | Journal: Journal of orthopaedic surgery (Hong Kong) | Year: 2016
To compare the midterm outcome in 12 women who underwent total hip arthroplasty (THA) for rapidly destructive coxarthrosis (RDC) and in 12 controls who underwent THA for osteoarthritis.Records of 12 women aged 50 to 80 (mean, 72.3) years who underwent THA for RDC after a mean of 9 (range, 4-11) months since symptom onset were reviewed. They were compared with 12 age-and sex-matched controls who underwent THA for primary or secondary osteoarthritis. Acetabular bone deficiency of the 12 RDC patients was classified as type I (n=7), type II (n=4), or type III (n=1). Type I was treated with cementless THA, and types II and III were treated with THA with a cemented acetabular component. The femoral component was cementless. Pre- and post-operative Harris Hip Score was assessed. Radiographs of the hip were evaluated for implant migration, osteolysis, and periprosthetic radiolucency in the acetabulum and proximal femur.The 12 women who underwent THA for RDC and the 12 controls who underwent THA for osteoarthritis were comparable in terms of pre-, intra-, and post-operative parameters. After a mean follow-up of 9.3 years, the mean Harris Hip Score improved from 38.3 to 81.1 in RDC patients and from 43.6 to 84.2 in controls (p=0.13). One RDC patient had dislocation but did not require revision surgery. One RDC patient developed a radiolucent line <2 mm in zones 1 and 7 of the femoral component, but no migration occurred. No patient had progression of bony destruction, loosening, osteolysis, migration, or radiolucency of the acetabular component.Despite the rapid destruction of the acetabulum and femoral head in RDC patients, cemented or cementless THA achieved a good midterm outcome comparable to that for patients with primary or secondary osteoarthritis.
PubMed | Juntendo Urayasu Hospital
Type: Case Reports | Journal: Kyobu geka. The Japanese journal of thoracic surgery | Year: 2014
A 70-year-old man with a history of surgery for colon cancer was found to have multiple enlarging pulmonary nodules( 2 in the left lower lobe and 1 in the right upper lobe), and was suspected of having pulmonary metastases from colon cancer. He underwent left lower lobectomy, and subsequent histopathological examination revealed that one was a pulmonary metastasis from colon cancer, and the other was a pulmonary metastasis from papillary thyroid cancer. There were no abnormalities in the thyroid gland according to computed tomography and ultrasonography findings. Therefore, the patient was diagnosed with synchronous pulmonary metastases of both colon cancer and occult thyroid cancer in the same lobe. This is an exceedingly rare case;to the best of our knowledge, there has been no report thus far regarding multiple pulmonary metastases from different primary sites.
PubMed | Juntendo University and Juntendo Urayasu Hospital
Type: Case Reports | Journal: European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society | Year: 2014
We describe the clinical course and amplitude-integrated EEG findings in three children with non-accidental head injury and discuss on the importance of continuous aEEG monitoring in infants.NCSE was defined as a continuous 30-min seizure or briefer seizures occurring consecutively comprising at least 30 min of any 1-h period. Non-accidental head injury was diagnosed on the basis of neuroimaging findings such as subdural hemorrhage. Antiepileptic treatment was performed with continuous amplitude-integrated EEG monitoring.The age of the patients ranged from 48 days to nine months. All of them had loss of consciousness and seizures on presentation. Nonconvulsive status epilepticus without clinical symptoms were recognized in all patients. Vigorous antiepileptic treatment against nonconvulsive status epilepticus was made in two patients, whereas nonconvulsive status epilepticus disappeared within one hour without additional treatment in one.Our experience indicates that nonconvulsive status epilepticus were not uncommon in children with non-accidental head injury. Continuous amplitude-integrated EEG monitoring will be one of the useful methods in encephalopathic children in order to estimate seizure burden objectively and to treat seizures appropriately.
PubMed | Tama Nanbu Chiiki Hospital, Juntendo University, Juntendo Nerima Hospital, Juntendo Urayasu Hospital and Tokyo Metropolitan Hiroo Hospital
Type: Journal Article | Journal: Journal of neurointerventional surgery | Year: 2015
We report the results of endosaccular coil embolization of asymptomatic unruptured intracranial aneurysms (UIAs) in elderly patients (65years).There were 375 elderly patients with 400 asymptomatic UIAs. Patients were divided into two groups: group A included patients aged 65-74 years and group B patients aged 75years.Endovascular procedures were completed in 97.8% of patients. Immediate anatomical outcomes showed complete occlusion in 53.7%, residual neck in 18.9%, and residual aneurysm in 27.4%. Anatomical follow-ups (mean 36.328.1months) were unchanged in 55.7%, improved in 22.6%, minor recurrence in 11.5%, and major recurrence in 10.2%. Procedure related complications occurred in 31 patients (8.3%). 15 patients had ischemic and 10 hemorrhagic complications. Retreatments were performed in 16 patients (4.3%). Among 366 patients technically completed, 363 (99.2%) showed a favorable clinical outcome (modified Rankin Scale (mRS) score <1) at 30days. The remaining three patients showed a worsening of mRS >0 at 30days. The latest clinical follow-up outcomes showed: mRS score 0 in 362 patients; mRS score 1 in one; mRS score 3 in one; mRS score 4 in one; and mRS score 5 in one patient. Permanent morbidity and mortality rates were 1.1% and 0%, respectively. There were no statistically significant differences in gender, comorbidities, aneurysm size, neck width, dome-to-neck ratio, immediate anatomical outcomes, anatomical follow-up outcomes, or procedure related complications between the groups.Endosaccular coil embolization is safe and feasible for elderly patients with asymptomatic UIAs. Old age itself should not be a contraindication.
PubMed | Juntendo University, Juntendo Nerima Hospital, Koto Hospital, Juntendo Urayasu Hospital and 2 more.
Type: | Journal: Bone | Year: 2014
Atypical femoral fractures (AFFs) are stress-related fractures that are speculated to associate with long-term treatment with bisphosphonates for osteoporosis. A history of AFF is a high risk factor for the development of a subsequent AFF in the same location of the contralateral femur, suggesting that a patients individual anatomical factor(s) are related to the fracture site of AFFs. In this study, we investigated the radiographs of fourteen AFFs (four bilateral fractures among ten patients) treated at six hospitals associated with our university between 2005 and 2010. The fracture site and standing femorotibial angle (FTA), which reflects the mechanical axis of the lower limb, were measured on weight-bearing lower limb radiographs. The fracture site and FTA of patients with typical femoral fractures (TFF) were compared to those of patients with AFFs. The correlations were examined using Spearmans rank correlation coefficients. The fracture locations in the femora were almost the same in the patients with bilateral AFFs. There was a positive correlation between the fracture site and the standing FTA in the patients with AFFs (r=0.82, 95% confidence interval; 0.49 to 0.94), indicating that the larger the standing FTA (varus alignment), the more distal the site of the fracture in the femur. The FTA of the patients with atypical diaphyseal femoral fracture were significantly larger compared to that of those with not only atypical subtrochanteric fractures but also TFFs. In conclusion, the fracture sites of AFFs are associated with the standing lower limb alignment, while those of TFFs are not.
PubMed | Juntendo University, Juntendo Nerima Hospital, Juntendo Urayasu Hospital, Kyorin University and 3 more.
Type: | Journal: EBioMedicine | Year: 2016
Some risk classifications to determine prognosis of patients with non-muscle invasive bladder cancer (NMIBC) have disadvantages in the clinical setting. We investigated whether the EORTC (European Organization for Research and Treatment of Cancer) risk stratification is useful to predict recurrence and progression in Japanese patients with NMIBC. In addition, we developed and validated a novel, and simple risk classification of recurrence.The analysis was based on 1085 patients with NMIBC at six hospitals. Excluding recurrent cases, we included 856 patients with initial NMIBC for the analysis. The Kaplan-Meier method with the log-rank test were used to calculate recurrence-free survival (RFS) rate and progression-free survival (PFS) rate according to the EORTC risk classifications. We developed a novel risk classification system for recurrence in NMIBC patients using the independent recurrence prognostic factors based on Cox proportional hazards regression analysis. External validation was done on an external data set of 641 patients from Kyorin University Hospital.There were no significant differences in RFS and PFS rates between the groups according to EORTC risk classification. We constructed a novel risk model predicting recurrence that classified patients into three groups using four independent prognostic factors to predict tumour recurrence based on Cox proportional hazards regression analysis. According to the novel recurrence risk classification, there was a significant difference in 5-year RFS rate between the low (68.4%), intermediate (45.8%) and high (33.7%) risk groups (P<0.001).As the EORTC risk group stratification may not be applicable to Asian patients with NMIBC, our novel classification model can be a simple and useful prognostic tool to stratify recurrence risk in patients with NMIBC.None.
PubMed | Juntendo University and Juntendo Urayasu Hospital
Type: Comparative Study | Journal: European journal of orthopaedic surgery & traumatology : orthopedie traumatologie | Year: 2016
Clinical outcomes of total hip arthroplasty (THA) to treat rapidly destructive coxarthrosis (RDC) have been reported, but to our knowledge, there have been no studies comparing implants. The aim of this study was to examine the effectiveness of acetabular reconstruction for RDC by comparing the clinical results of THA using a Kerboull-type plate with an uncemented cup.Among 921 primary THAs performed between 2006 and 2014, 27 were performed for the treatment for RDC using a Kerboull-type plate or a conventional uncemented cup. A Kerboull-type plate for acetabular reinforcement device was used in 13 hips and an uncemented cup in 14 hips. The mean follow-up period was 61.2 months.The duration of surgery was 156.8 36.4 min in the Kerboull-type plate group and 103.3 14.4 min in the uncemented cup group, being significantly longer in the former (P = 0.0002). In the Kerboull-type plate group and the uncemented cup group, the 5-year survival rates were 100 and 83.9 %, respectively. Recurrent dislocation was observed in two cases in which the posterior approach had been used.In our study, the loosening of the acetabular components was noted in 14.3 % of uncemented cup-applied cases, but no loosening was noted in any Kerboull-type plate-applied case. Therefore, for RDC, in which objective evaluation of fragile bone quality is difficult, the use of the Kerboull-type plate, which disperses weight-bearing of the acetabular, may be an effective means to achieve early functional recovery as well as a long-term favorable outcome.