Publications by authors named "Masaki Miura"

15 Publications

  • Page 1 of 1

Efficient detection of copy-number variations using exome data: Batch- and sex-based analyses.

Hum Mutat 2021 Jan 11;42(1):50-65. Epub 2020 Nov 11.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Many algorithms to detect copy number variations (CNVs) using exome sequencing (ES) data have been reported and evaluated on their sensitivity and specificity, reproducibility, and precision. However, operational optimization of such algorithms for a better performance has not been fully addressed. ES of 1199 samples including 763 patients with different disease profiles was performed. ES data were analyzed to detect CNVs by both the eXome Hidden Markov Model (XHMM) and modified Nord's method. To efficiently detect rare CNVs, we aimed to decrease sequencing biases by analyzing, at the same time, the data of all unrelated samples sequenced in the same flow cell as a batch, and to eliminate sex effects of X-linked CNVs by analyzing female and male sequences separately. We also applied several filtering steps for more efficient CNV selection. The average number of CNVs detected in one sample was <5. This optimization together with targeted CNV analysis by Nord's method identified pathogenic/likely pathogenic CNVs in 34 patients (4.5%, 34/763). In particular, among 142 patients with epilepsy, the current protocol detected clinically relevant CNVs in 19 (13.4%) patients, whereas the previous protocol identified them in only 14 (9.9%) patients. Thus, this batch-based XHMM analysis efficiently selected rare pathogenic CNVs in genetic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.24129DOI Listing
January 2021

13q13.3 microdeletion associated with apparently balanced translocation of 46,XX,t(7;13) suggests NBEA involvement.

Brain Dev 2020 Sep 4;42(8):581-586. Epub 2020 Jun 4.

Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, NCNP, Tokyo, Japan.

Background: Deletion of 13q13.3 is an extremely rare event.

Case: We report on a 25-month-old girl with neurodevelopmental disorder and intellectual disability. She had dysmorphic facies characterized by synophrys, long and narrow palpebral fissures; and a large, round face with small organs such as the eyes and mouth positioned near the center. She was hypotonic and had autism-like behaviors. Blood tests and brain MRI revealed no specific findings. However, G-banding chromosome analysis showed an apparently balanced translocation: 46,XX,t(7,13)(q11.23;q12.3). Both parents had normal karyotypes. Furthermore, her abnormal phenotype and chromosomal breakpoint lesion were suspected to be associated. Hence, we conducted array comparative genomic hybridization, which revealed a 3.2 Mb novel pathological microdeletion at 13q13.3 involving 17 genes including neurobeachin (NBEA), a neurodevelopment disorder gene. Furthermore, fluorescence in situ hybridization using probes adjacent to the microdeletion suggested a concomitant occurrence of the deletion and translocation as the structural basis of this rare genomic variant.

Conclusion: NBEA may have roles in her neurodevelopmental phenotypes, whereas other genes within the 13q13.3 microdeletion may contribute to her dysmorphic features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2020.05.006DOI Listing
September 2020

Biphasic changes in β-cell mass around parturition are accompanied by increased serotonin production.

Sci Rep 2020 03 18;10(1):4962. Epub 2020 Mar 18.

Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Pancreatic β-cell mass is known to be considerably altered during pregnancy and after parturition in rodents and humans. While β-cell mass increases during pregnancy and starts to return toward its original level after parturition, the cellular mechanisms by which β-cell mass during this period is regulated remains unclear. To address this issue in mice, we quantified β-cell mass and investigated the mechanisms underlying its regulation throughout the perinatal and postpartum period. The increased β-cell size and proliferation during pregnancy were significantly reduced shortly after parturition, whereas there was no evidence of β-cell reprogramming or increased apoptosis. Direct RNA sequencing of islets from pregnant and postpartum mice demonstrated dynamic changes in gene expression patterns, showing robust downregulation of cell cycle-related genes 1 day after parturition, and the reupregulation of serotonin metabolism-related genes at postpartum day 7. Serotonin synthesis was activated only in lactating females, accompanied by increased β-cell mass. Taken together, these findings demonstrate that β-cell mass is decreased shortly after parturition owing to reduced β-cell size and proliferation, and is subsequently increased, in association with lactation and serotonin biosynthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-61850-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080838PMC
March 2020

Conversion of pancreatic α cells into insulin-producing cells modulated by β-cell insufficiency and supplemental insulin administration.

Biochem Biophys Res Commun 2020 01 22;521(1):178-183. Epub 2019 Oct 22.

Department of Metabolism and Endocrinology, Japan; Center for Identification of Diabetic Therapeutic Targets, Japan; Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, Tokyo, Japan.

The emergence of bihormonal (BH) cells expressing insulin and glucagon has been reported under diabetic conditions in humans and mice. Whereas lineage tracing studies demonstrated that glucagon-producing α cells can be reprogrammed into BH cells, the underlying dynamics of the conversion process remain poorly understood. In the present study, we investigated the identities of pancreatic endocrine cells by genetic lineage tracing under diabetic conditions. When β-cell ablation was induced by alloxan (ALX), a time-dependent increase in BH cells was subsequently observed. Lineage tracing experiments demonstrated that BH cells originate from α cells, but not from β cells, in ALX-induced diabetic mice. Notably, supplemental insulin administration into diabetic mice resulted in a significant increase in α-cell-derived insulin-producing cells that did not express glucagon. Furthermore, lineage tracing in Ins2 diabetic mice demonstrated a significant induction of α-to-β conversion. Thus, adult α cells have plasticity, which enables them to be reprogrammed into insulin-producing cells under diabetic conditions, and this can be modulated by supplemental insulin administration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2019.10.100DOI Listing
January 2020

Cellular Autophagy in Cells Plays a Role in the Maintenance of Islet Architecture.

J Endocr Soc 2019 Nov 8;3(11):1979-1992. Epub 2019 Aug 8.

Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Autophagy is known to play a pivotal role in intracellular quality control through the degradation of subcellular damaged organelles and components. Whereas autophagy is essential for maintaining -cell function in pancreatic islets, it remains unclear as to how the cellular autophagy affects the homeostasis and function of glucagon-secreting cells. To investigate the role of autophagy in cells, we generated a mutant mouse model lacking , a key molecule for autophagosome formation, specifically in cells. Histological analysis demonstrated more glucagon-positive cells, with a multilayered structure, in the islets under deficiency, although metabolic profiles, such as body weight, blood glucose, and plasma glucagon levels were comparable between -deficient mice and control littermates. Consistent with our previous findings that deficiency suppressed -cell proliferation, cellular proliferation was suppressed in -deficient cells. These findings suggest that -cell autophagy plays a role in maintaining -cell area and normal islet architecture but appears to be dispensable for metabolic homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/js.2019-00075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786006PMC
November 2019

Suppression of STAT3 signaling promotes cellular reprogramming into insulin-producing cells induced by defined transcription factors.

EBioMedicine 2018 Oct 25;36:358-366. Epub 2018 Sep 25.

Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Center for Identification of Diabetic Therapeutic Targets, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Center for Molecular Diabetology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Background: STAT3 has been demonstrated to play a role in maintaining cellular identities in the pancreas, whereas an activating STAT3 mutation has been linked to impaired β-cell function.

Methods: The role of STAT3 in β-cell neogenesis, induced by the exogenous expression of Pdx1, Neurog3, and Mafa, was analyzed in vitro and in vivo.

Findings: The expression of phosphorylated STAT3 (pSTAT3) was induced in both Pdx1-expressing and Mafa-expressing cells, but most of the induced β cells were negative for pSTAT3. The suppression of STAT3 signaling, together with exogenously expressed Pdx1, Neurog3, and Mafa, significantly increased the number of reprogrammed β cells in vitro and in vivo, enhanced the formation of islet-like clusters in mice, and ameliorated hyperglycemia in diabetic mice.

Interpretation: These findings suggest that STAT3 inhibition promotes cellular reprogramming into β-like cells, orchestrated by defined transcription factors, which may lead to the establishment of cell therapies for curing diabetes. FUND: JSPS, MEXT, Takeda Science Foundation, Suzuken Memorial Foundation, Astellas Foundation for Research on Metabolic Disorders, Novo Nordisk, Eli Lilly, MSD, Life Scan, Novartis, and Takeda.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2018.09.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197741PMC
October 2018

Heterogeneity of autophagic status in pancreatic β cells under metabolic stress.

Biochem Biophys Res Commun 2018 02 11;496(2):328-334. Epub 2018 Jan 11.

Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Center for Identification of Diabetic Therapeutic Targets, Juntendo University Graduate School of Medicine, Tokyo, Japan; Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Autophagy in β cells has been demonstrated to play a pivotal role in cellular homeostasis and the progression of glucose intolerance. Although autophagic activity is affected by metabolic stress both in vivo and in vitro, it remains unclear as to what extent the autophagic status in each β cell is different from its neighboring cells. To address this question, GFP-LC3 reporter mice, which can visualize the autophagic status of each β cell as green-fluorescent puncta, were crossed with obese diabetic db/db mice. Imaging of green-fluorescent puncta in the islets of GFP-LC3 mice revealed that β cells are a heterogeneous population, as the density of GFP-LC3 puncta in each cell was variable. Furthermore, the variability was greater in GFP-LC3; db/db mice than in non-diabetic GFP-LC3; db/+ mice. Furthermore, when GFP-LC3 mice were treated with a low dose of S961, which antagonizes insulin signaling without inducing overt hyperglycemia, the number of β cells with a high density of GFP puncta was increased, suggesting that insulin resistance affects autophagic status independently of glucose profiles. These results suggest that pancreatic β cells under metabolic stress are heterogeneous regarding their autophagic status, which provides insights into the cellular dynamics of each β cell rather than the whole β-cell population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2018.01.070DOI Listing
February 2018

Current Therapeutic Drugs Against Cerebral Vasospasm after Subarachnoid Hemorrhage: A Comprehensive Review of Basic and Clinical Studies.

Curr Drug Deliv 2017 Sep;14(6):843-852

Department of Neurosurgery, Kumamoto Red Cross Hospital, Kumamoto-ken, 8608556, Japan.

Background: Cerebral vasospasm (CVS) is well known as a major complication in subarachnoid hemorrhage (SAH) patients, and research has long been focused on improving morbidity and mortality. As CVS commonly develops from day 4 to day 14 after SAH onset, SAH patients require therapies with drugs for preventing CVS after surgical treatment for the source of hemorrhage, mostly ruptured intracranial aneurysms. It is thought that the pathogenesis of CVS is initiated by prolonged smooth muscle contraction, and the subsequent hypoperfusion and cytotoxic responses induce cerebral ischemia. Although therapeutic investigations have historically focused on morphological improvement, the improvement of outcome is limited by the reversal of arterial narrowing. Therefore, it might be important to look back at evidence from long-lasting studies of CVS and to determine a highroad to effective drugs, including combination therapy.

Objective: In this review, we introduce current candidate beneficial drugs against CVS in clinical SAH, including nimodipine and other Ca2+ channel antagonists, magnesium sulfate, clazosentan, statins, cilostazol, eicosapentaenoic acid, fasudil hydrochloride, milrinone, and edaravone, all of which have been frequently studied in recent years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1567201813666160808100937DOI Listing
September 2017

Bilateral posterior fossa chronic subdural hematoma treated with craniectomy: Case report and review of the literature.

Surg Neurol Int 2016 6;7(Suppl 10):S255-8. Epub 2016 May 6.

Department of Neurosurgery, Kumamoto University, Kumamoto, Japan.

Background: Posterior chronic subdural hematomas (pCSHs) are rare. Their diagnosis and treatment are difficult.

Description: A 69-year-old woman was admitted to our hospital with nausea, headache, and mild consciousness disturbance. Computed tomography and magnetic resonance imaging showed bilateral pCSH. To prevent further neurological deterioration, we performed surgery under general anesthesia by midline suboccipital craniectomy. Unexpected bleeding from a developed circuitous occipital sinus was stopped with hemoclips. After hematoma removal, she recovered and was transferred to a rehabilitation hospital. By the 19(th) postoperative day, she had developed no neurologic deficits.

Conclusion: This experience demonstrates the risk of blind surgical therapy in patients with pCSH. In such patients, posterior fossa craniectomy may be preferable in terms of diagnosis and safe treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/2152-7806.181979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866054PMC
May 2016

A spontaneous superficial temporal artery pseudoaneurysm possibly related to atherosclerosis: Case report and review of literature.

Surg Neurol Int 2016 1;7(Suppl 9):S247-50. Epub 2016 Apr 1.

Department of Neurosurgery, Kumamoto University, Kumamoto, Japan.

Background: Spontaneous superficial temporal artery (STA) pseudoaneurysms are very rare; only four cases, including ours, have been reported to date. Therefore, the cause of them has not been studied.

Case Description: A 57-year-old woman was admitted to our hospital with a pulsatile mass in the left preauricular region. Her medical history included hypertension, dyslipidemia, and angina pectoris. She denied a history of head injury or minor head trauma. Three-dimensional computed tomography angiography showed a well-enhanced saccular aneurysm on the main trunk of the STA. To prevent rupture it was removed surgically. The histological diagnosis was pseudoaneurysm with atherosclerosis. By the 2(nd) postoperative day, she had completely recovered and was discharged home. There has been no relapse.

Conclusions: As all four documented patients were at high risk for atherosclerosis, we posit that a causal factor was weakening of the arterial wall due to atherosclerosis and chronic pressure on the STA from anatomical structures. Here, we present histological evidence to support this hypothesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/2152-7806.179586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828951PMC
April 2016

Sequential changes in Rotterdam CT scores related to outcomes for patients with traumatic brain injury who undergo decompressive craniectomy.

J Neurosurg 2016 Jun 23;124(6):1640-5. Epub 2015 Oct 23.

Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University School of Medicine, Chuo-ku, Kumamoto, Japan.

OBJECT Rotterdam CT scoring is a CT classification system for grouping patients with traumatic brain injury (TBI) based on multiple CT characteristics. This retrospective study aimed to determine the relationship between initial or preoperative Rotterdam CT scores and TBI prognosis after decompressive craniectomy (DC). METHODS The authors retrospectively reviewed the medical records of all consecutive patients who underwent DC for nonpenetrating TBI in 2 hospitals from January 2006 through December 2013. Univariate and multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used to determine the relationship between initial or preoperative Rotterdam CT scores and mortality at 30 days or Glasgow Outcome Scale (GOS) scores at least 3 months after the time of injury. Unfavorable outcomes were GOS Scores 1-3 and favorable outcomes were GOS Scores 4 and 5. RESULTS A total of 48 cases involving patients who underwent DC for TBI were included in this study. Univariate analyses showed that initial Rotterdam CT scores were significantly associated with mortality and both initial and preoperative Rotterdam CT scores were significantly associated with unfavorable outcomes. Multivariable logistic regression analysis adjusted for established predictors of TBI outcomes showed that initial Rotterdam CT scores were significantly associated with mortality (OR 4.98, 95% CI 1.40-17.78, p = 0.01) and unfavorable outcomes (OR 3.66, 95% CI 1.29-10.39, p = 0.02) and preoperative Rotterdam CT scores were significantly associated with unfavorable outcomes (OR 15.29, 95% CI 2.50-93.53, p = 0.003). ROC curve analyses showed cutoff values for the initial Rotterdam CT score of 5.5 (area under the curve [AUC] 0.74, 95% CI 0.59-0.90, p = 0.009, sensitivity 50.0%, and specificity 88.2%) for mortality and 4.5 (AUC 0.71, 95% CI 0.56-0.86, p = 0.02, sensitivity 62.5%, and specificity 75.0%) for an unfavorable outcome and a cutoff value for the preoperative Rotterdam CT score of 4.5 (AUC 0.81, 95% CI 0.69-0.94, p < 0.001, sensitivity 90.6%, and specificity 56.2%) for an unfavorable outcome. CONCLUSIONS Assessment of changes in Rotterdam CT scores over time may serve as a prognostic indicator in TBI and can help determine which patients require DC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2015.4.JNS142760DOI Listing
June 2016

[A case of advanced gastric cancer with disseminated carcinomatosis of bone marrow treated by S-1 and CDDP].

Gan To Kagaku Ryoho 2009 Dec;36(13):2653-5

Dept. of Internal Medicine, Nishiwaki Hospital.

A 33-year-old man was admitted to our hospital due to DIC and multiple bone metastasis after distal gastrectomy for gastric cancer (Stage IIIB). We diagnosed disseminated carcinomatosis of bone marrow by gastric cancer. The patient was treated with combination chemotherapy of S-1 and CDDP (S-1 80 mg/m (2), po, day 1-21 and CDDP 60 mg/m(2), iv, day 8). After one course of the treatment, DIC was resolved and severe pain in his back and legs which had been poorly controlled was dramatically improved. He could thus be discharged from our hospital and survived for about six months. S-1 and CDDP therapy are considered to be effective for disseminated carcinomatosis of bone marrow due to gastric cancer, even if complicated by DIC.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2009

Contribution of angiotensin-converting enzyme and angiotensin II to ischemic stroke: their role in the formation of stable and unstable carotid atherosclerotic plaques.

Surg Neurol 2004 Oct;62(4):292-301; discussion 301-3

Departments of Neurosurgery, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan.

Background: The angiotensin-converting enzyme/angiotensin II (ACE/Ang II) system is a strong contributor to intimal hyperplasia in atherosclerotic lesions. To illuminate its role in ischemic stroke, we examined the expression of ACE/Ang II in stable and unstable carotid atherosclerotic plaques from symptomatic and asymptomatic patients.

Methods: Using immunohistochemical methods, we studied differences between carotid atherosclerotic lesions obtained at carotid endarterectomy (CEA) from symptomatic (n = 36) and asymptomatic (n = 28) patients. The specimens were classified as stable (n = 30) and unstable (n = 34) plaques, and their fibrous cap, lipid core, and shoulder lesion were examined. We used antibodies against smooth muscle cells (SMC), macrophages, endothelial cells (EC), ACE, and Ang II.

Results: Of 28 lesions from asymptomatic patients, 20 (71.4%) manifested features characteristic of stable plaques: the expression of ACE/Ang II co-localized with SMC, EC, and macrophages in the shoulder lesion. In contrast, 26 of 36 symptomatic lesions (72.2%) exhibited the typical features of unstable plaques: dense accumulations of macrophages near the luminal surface in the shoulder lesion and weak immunoreactivity for ACE/Ang II, EC, and SMC. Furthermore, most of the lesions were accompanied by early stage atherosclerotic lesions (satellite lesions) that were strongly immunoreactive with macrophages, EC, and ACE/Ang II.

Conclusions: ACE/Ang II expression may induce the proliferation of SMC and EC and result in the formation of carotid atherosclerotic plaques with a thick fibrous cap. Notably, the shoulder lesion of unstable plaques exhibited a thin fibrous cap and faintly expressed ACE/Ang II. Lack of the ACE/Ang II system may contribute to the final step in plaque rupture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.surneu.2004.02.027DOI Listing
October 2004

Brain metastases from asymptomatic adenocarcinoma of the pancreas: an autopsy case report.

Surg Neurol 2002 Nov;58(5):332-6; discussion 336-7

Department of Neurosurgery, Kumamoto University Medical School, Kumamoto City Hospital, Japan.

Background: Brain metastasis from pancreatic cancer is extremely rare. Because pancreatic cancer usually has a rapidly progressive nature, the majority of affected patients die from primary lesions before exhibiting clinical signs suggestive of brain metastases.

Case Description: The patient was a 62-year-old man who developed generalized convulsion followed by right hemiparesis accompanied by decreased consciousness level. Computed tomography (CT) scan revealed multiple brain tumors with ring-like contrast enhancement. Stereotactic biopsy disclosed mucinous adenocarcinoma. A marked increase in the serum CA19-9 level was noted, but the patient did not exhibit any other signs of pancreatic disease. Repeated whole body CT scan and ultrasonography demonstrated no primary lesions. The patient died of multi-organ failure during chemotherapy combined with radiation for metastatic brain tumors. Autopsy revealed well-differentiated papillary adenocarcinoma in the pancreatic head and systemic metastases associated with tumor emboli were widely distributed in various organs.

Conclusion: This patient initially presented only with symptoms of neurologic disorder and no pancreatic symptoms. Moreover, repeated radiologic examinations did not reveal the primary lesion. We considered that the unusual clinical course in our patient may be partly explained by the autopsy findings: diffuse sclerotic changes of the pancreas without swelling. The present report suggests that undetected pancreatic cancer may have been the primary lesion classified as "unknown origin" in some cases of metastatic brain tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0090-3019(02)00805-4DOI Listing
November 2002

Recovery from marked altered consciousness in a patient with adult-onset type II citrullinemia diagnosed by DNA analysis and treated with a living related partial liver transplantation.

Intern Med 2002 Jul;41(7):555-60

Department of Internal Medicine, Nishiwaki City General Hospital, Hyogo.

A 21-year-old woman was admitted with altered consciousness and hyperammonemia. She was diagnosed as having adult-onset type II citrullinemia (CTLN2) by DNA analysis. The patient had mutations of the SLC25A13 gene, which were compound heterozygotes of 851 del 4 and IVS11+1G>A. CTLN2 has a poor prognosis, in spite of various intensive medications, and we performed a living related partial liver transplantation (LRLT). Over a 2-year follow-up, the patient has been well. CTLN2 can be diagnosed by the DNA analysis and can be treated by LRLT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.41.555DOI Listing
July 2002