54 results on '"Yamasaki, N."'
Search Results
2. Associations between electrocardiographic findings and echocardiographic profiles in patients with hypertrophic cardiomyopathy.
- Author
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Matsuo T, Ochi Y, Kubo T, Baba Y, Miyagawa K, Noguchi T, Hirota T, Hamada T, Yamasaki N, and Kitaoka H
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- Male, Humans, Middle Aged, Aged, Echocardiography, Hypertrophy, Left Ventricular diagnostic imaging, Heart Ventricles diagnostic imaging, Electrocardiography, Cardiomyopathy, Hypertrophic
- Abstract
Background: The relationships between electrocardiography (ECG) findings and echocardiographic profiles in patients with hypertrophic cardiomyopathy (HCM) are not fully understood., Methods: One hundred forty patients (mean age: 62.9 ± 15.3 years, 96 men) with HCM were studied. We assessed the associations between ECG findings and echocardiographic findings including maximum left ventricular wall thickness, HCM subtypes and distribution of left ventricular hypertrophy (LVH): the LV was divided into basal, mid, and apical segments by dividing it into thirds along the long axis., Results: In ECG, LVH by voltage criteria, abnormal Q wave, negative T wave, and giant negative T wave (GNT) were observed in 74 (53 %), 30 (21 %), 132 (94 %), and 25 (18 %) of the patients, respectively. In two groups with and without an LVH pattern according to voltage criteria in ECG, there were no significant differences in maximum LV wall thickness, subtype of HCM, and distribution of LVH. Regarding an abnormal Q wave, the proportion of patients with LVH in the basal segment was significantly higher in patients with an abnormal Q wave than in patients without an abnormal Q wave (87 % vs 61 %, p = 0.008). An abnormal Q wave was not observed in patients with LVH confined to the apex. Patients with a GNT included patients with LVH located at only the apex (apical HCM), LVH from the mid segment to apex, and LVH from the base to apex. No GNT was found in patients with hypertrophy located in the upper region from the base to mid segment of the LV., Conclusions: In patients with HCM, there was no significant correlation between the presence of LVH by voltage criteria in ECG and echocardiographic findings. An abnormal Q wave was associated with disproportionate hypertrophy of the basal wall and a GNT reflected the presence of LVH in the apical segment., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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3. Artificial intelligence-assisted ultrasound imaging in hemophilia: research, development, and evaluation of hemarthrosis and synovitis detection.
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Nagao A, Inagaki Y, Nogami K, Yamasaki N, Iwasaki F, Liu Y, Murakami Y, Ito T, and Takedani H
- Abstract
Background: Joint bleeding can lead to synovitis and arthropathy in people with hemophilia, reducing quality of life. Although early diagnosis is associated with improved therapeutic outcomes, diagnostic ultrasonography requires specialist experience. Artificial intelligence (AI) algorithms may support ultrasonography diagnoses., Objectives: This study will research, develop, and evaluate the diagnostic precision of an AI algorithm for detecting the presence or absence of hemarthrosis and synovitis in people with hemophilia., Methods: Elbow, knee, and ankle ultrasound images were obtained from people with hemophilia from January 2010 to March 2022. The images were used to train and test the AI models to estimate the presence/absence of hemarthrosis and synovitis. The primary endpoint was the area under the curve for the diagnostic precision to diagnose hemarthrosis and synovitis. Other endpoints were the rate of accuracy, precision, sensitivity, and specificity., Results: Out of 5649 images collected, 3435 were used for analysis. The area under the curve for hemarthrosis detection for the elbow, knee, and ankle joints was ≥0.87 and for synovitis, it was ≥0.90. The accuracy and precision for hemarthrosis detection were ≥0.74 and ≥0.67, respectively, and those for synovitis were ≥0.83 and ≥0.74, respectively. Analysis across people with hemophilia aged 10 to 60 years showed consistent results., Conclusion: AI models have the potential to aid diagnosis and enable earlier therapeutic interventions, helping people with hemophilia achieve healthy and active lives. Although AI models show potential in diagnosis, evidence is unclear on required control for abnormal findings. Long-term observation is crucial for assessing impact on joint health., (© 2024 The Authors.)
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- 2024
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4. DDX41 expression is associated with tumor necrosis in clear cell renal cell carcinoma and in cooperation with VHL loss leads to worse prognosis.
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Kobatake K, Ikeda K, Nakata Y, Yamasaki N, Kanai A, Sekino Y, Takemoto K, Fukushima T, Babasaki T, Kitano H, Goto K, Hayashi T, Sentani K, Teishima J, Kaminuima O, and Hinata N
- Subjects
- Biomarkers, Tumor genetics, DEAD-box RNA Helicases genetics, DEAD-box RNA Helicases metabolism, Gene Expression Regulation, Neoplastic, Humans, Necrosis genetics, Prognosis, RNA, Messenger metabolism, Von Hippel-Lindau Tumor Suppressor Protein genetics, Von Hippel-Lindau Tumor Suppressor Protein metabolism, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology
- Abstract
Background: Histologic tumor necrosis (TN) is a well-established independent prognostic indicator in patients treated surgically for clear cell renal cell carcinoma (ccRCC). However, the precise mechanisms by which TN alters disease progression remain unknown. The DEAD-box protein DDX41, a member of a large family of helicases, has been characterized as a pattern recognition receptor against an array of double-stranded (ds)DNA produced from bacteria, dsDNA viruses, and nearby cells that have released dsDNA fragments through necrosis. We hypothesized that DDX41 expression may be upregulated in ccRCC with TN, leading to worse prognosis., Methods: Relationship between the presence of TN and DDX41 expression were examined using The Cancer Genome Atlas data sets or using ccRCC samples in our institution. Further, the molecular functions of DDX41 were investigated with human ccRCC cells., Results: The presence of TN was significantly associated with the upregulation of mRNA and protein expression of DDX41 in the 2different patient cohorts with ccRCC. In addition, the mRNA and protein expression levels of DDX41 revealed a worse prognosis. In vitro analyses with ccRCC cells revealed that DDX41 expression promotes tumor-promoting activity. Furthermore, VHL loss, 1of the most common features in ccRCC, was shown to play an extremely important role in increasing the expression of the CXCL family in DDX41-expressing ccRCC, leading to the acquisition of a worse malignant phenotype., Conclusions: DDX41 expression is associated with TN in ccRCC and leads to a worse prognosis in cooperation with VHL loss., Competing Interests: Conflict of interest All authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2022
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5. A retrospective investigation to establish new screening approach for the detection of patients at high risk of Fabry disease in male left ventricular hypertrophy patients.
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Kubo T, Amano M, Takashio S, Okumura T, Yamamoto S, Nabeta T, Oikawa M, Kurisu S, Ochi Y, Sugiura K, Baba Y, Kuroiwa H, Hirota T, Yamasaki N, Ishii S, Nochioka K, Takeishi Y, Yasuda S, Tsujita K, Izumi C, and Kitaoka H
- Subjects
- Echocardiography, Humans, Hypertrophy, Left Ventricular diagnostic imaging, Hypertrophy, Left Ventricular epidemiology, Male, Retrospective Studies, alpha-Galactosidase, Fabry Disease complications, Fabry Disease diagnosis, Fabry Disease epidemiology
- Abstract
Background: The prevalence of Fabry disease (FD) in male patients with left ventricular hypertrophy (LVH) is about 1%. From the perspective of performing more efficient screening with measurement of α-galactosidase (α-Gal) activity, it is important to raise the pretest probability., Methods: We retrospectively investigated the prevalence of FD in 701 male patients with LVH who already had been screened by measurement of α-Gal activity in eight hospitals. From the viewpoint of enzymatic screening, we validated previously reported clinical features of FD including the electrocardiographic and echocardiographic characteristics with comparing each clinical determinant between patients with FD and non-FD patients. We finally aimed to establish a new screening approach for the detection of patients at high risk of FD., Results: There were five FD patients (0.7%) in the 701 male patients with LVH. Those five patients with FD all had the cardiac variant type and age at detection of LVH was ≥35 years in all patients. In LVH patients with LV ejection fraction (EF) ≥ 50%, Pend-Q interval < 40 msec, SV1 + RV5 > 4.0 mV, and diffuse LVH were important determinants of FD. In LVH patients with LVEF < 50%, asymmetric septal hypertrophy and posterior wall motion abnormality seemed to be associated with FD., Conclusions: In our retrospective study, the prevalence of FD in male patients with LVH was found to be 0.7%. We established the efficient combinations of clinical determinants using age at detection of LVH, Pend-Q interval, high voltage, and LVH pattern in an echocardiogram., Competing Interests: Declaration of competing interest Dr. Toru Kubo has received remuneration for lectures from Sumitomo Dainippon Pharma Co. The remaining authors have no conflicts of interest to declare. Dr. Yasuchika Takeishi is a chief editor of Journal of Cardiology., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2022
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6. Role of Postoperative Radiotherapy in Patients With Completely Resected pIIIA-N2 Non-Small Cell Lung Cancer.
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Yamasaki N, Kim YH, Iwatsubo S, Nishimura Y, and Funada Y
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- Humans, Neoplasm Staging, Radiotherapy, Adjuvant, Retrospective Studies, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung radiotherapy, Carcinoma, Non-Small-Cell Lung surgery, Lung Neoplasms pathology, Lung Neoplasms radiotherapy, Lung Neoplasms surgery
- Published
- 2022
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7. UTX maintains the functional integrity of the murine hematopoietic system by globally regulating aging-associated genes.
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Sera Y, Nakata Y, Ueda T, Yamasaki N, Koide S, Kobayashi H, Ikeda KI, Kobatake K, Iwasaki M, Oda H, Wolff L, Kanai A, Nagamachi A, Inaba T, Sotomaru Y, Ichinohe T, Koizumi M, Miyakawa Y, Honda ZI, Iwama A, Suda T, Takubo K, and Honda H
- Subjects
- Animals, Cellular Senescence genetics, DNA Breaks, Double-Stranded, DNA Repair, Female, Genetic Predisposition to Disease, Hematopoiesis, Extramedullary, Histone Demethylases deficiency, Histone Demethylases genetics, Immune Reconstitution, Jumonji Domain-Containing Histone Demethylases metabolism, Leukemia, Experimental genetics, Leukemia, Experimental virology, Male, Mice, Mice, Knockout, Moloney murine leukemia virus physiology, Myeloid Cells pathology, Radiation Chimera, Reactive Oxygen Species metabolism, Recombinant Proteins metabolism, Transcription Factors metabolism, Virus Integration, Aging genetics, Gene Expression Regulation genetics, Hematopoiesis genetics, Hematopoietic System physiology, Histone Code genetics, Histone Demethylases physiology
- Abstract
Epigenetic regulation is essential for the maintenance of the hematopoietic system, and its deregulation is implicated in hematopoietic disorders. In this study, UTX, a demethylase for lysine 27 on histone H3 (H3K27) and a component of COMPASS-like and SWI/SNF complexes, played an essential role in the hematopoietic system by globally regulating aging-associated genes. Utx-deficient (UtxΔ/Δ) mice exhibited myeloid skewing with dysplasia, extramedullary hematopoiesis, impaired hematopoietic reconstituting ability, and increased susceptibility to leukemia, which are the hallmarks of hematopoietic aging. RNA-sequencing (RNA-seq) analysis revealed that Utx deficiency converted the gene expression profiles of young hematopoietic stem-progenitor cells (HSPCs) to those of aged HSPCs. Utx expression in hematopoietic stem cells declined with age, and UtxΔ/Δ HSPCs exhibited increased expression of an aging-associated marker, accumulation of reactive oxygen species, and impaired repair of DNA double-strand breaks. Pathway and chromatin immunoprecipitation analyses coupled with RNA-seq data indicated that UTX contributed to hematopoietic homeostasis mainly by maintaining the expression of genes downregulated with aging via demethylase-dependent and -independent epigenetic programming. Of note, comparison of pathway changes in UtxΔ/Δ HSPCs, aged muscle stem cells, aged fibroblasts, and aged induced neurons showed substantial overlap, strongly suggesting common aging mechanisms among different tissue stem cells.
- Published
- 2021
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8. Validation of the Kumamoto criteria for prediction of 99m technetium pyrophosphate scintigraphy positivity as a strategy for diagnosis of transthyretin cardiac amyloidosis: A retrospective cohort study in Kochi.
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Ochi Y, Kubo T, Baba Y, Ueda M, Miyagawa K, Noguchi T, Hirota T, Yamasaki N, and Kitaoka H
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- Aged, Aged, 80 and over, Amyloidosis diagnosis, Female, Heart diagnostic imaging, Heart Ventricles diagnostic imaging, Heart Ventricles pathology, Humans, Male, Predictive Value of Tests, Radionuclide Imaging methods, Reproducibility of Results, Retrospective Studies, Sensitivity and Specificity, Amyloidosis diagnostic imaging, Cardiomyopathies diagnostic imaging, Prealbumin analysis, Radionuclide Imaging statistics & numerical data, Radiopharmaceuticals, Technetium Tc 99m Pyrophosphate
- Abstract
Background: Early diagnosis of transthyretin cardiac amyloidosis (ATTR-CA) is important. The aim of this study was to validate the 'Kumamoto criteria' for prediction of technetium-99m pyrophosphate (
99m Tc-PYP) scintigraphy positivity., Methods: One hundred fifty patients (median age: 79.4 years, 117 males) with the possibility of ATTR-CA who underwent99m Tc-PYP scintigraphy were assessed. We divided the patients into 4 groups (groups with score of 0-3) according to the Kumamoto criteria by total points for the following 3 factors: high-sensitivity cardiac troponin T (hs-cTnT) ≥0.0308 ng/ml, left ventricle posterior wall thickness ≥13.6 mm, and wide QRS (QRS ≥ 120 ms)., Results: Seventy patients (46.7%) were positive for99m Tc-PYP scintigraphy.99m Tc-PYP positivity rates in the groups with score of 0, 1, 2, and 3 were 4%, 39%, 69%, and 89%, respectively. Compared with the original Kumamoto cohort, our patients in the score 1 group showed a relatively high rate of99m Tc-PYP positivity because hs-cTnT as one of the positive factors had high ability to discriminate the disease. The sensitivity and negative predictive value of hs-cTnT ≥0.0308 ng/ml for99m Tc-PYP positivity were 97.1% and 93.9%., Conclusions: In the Kochi validation cohort, the Kumamoto criteria were useful for predicting99m Tc-PYP positivity. However, patients in the score 1 group should be assessed cautiously for the possibility of ATTR-CA if the hs-cTnT value is high., (Copyright © 2020. Published by Elsevier Ltd.)- Published
- 2021
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9. Association of aberrant ASNS imprinting with asparaginase sensitivity and chromosomal abnormality in childhood BCP-ALL.
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Watanabe A, Miyake K, Nordlund J, Syvänen AC, van der Weyden L, Honda H, Yamasaki N, Nagamachi A, Inaba T, Ikawa T, Urayama KY, Kiyokawa N, Ohara A, Kimura S, Kubota Y, Takita J, Goto H, Sakaguchi K, Minegishi M, Iwamoto S, Shinohara T, Kagami K, Abe M, Akahane K, Goi K, Sugita K, and Inukai T
- Subjects
- Animals, Child, Chromosome Aberrations, DNA Methylation genetics, Genomic Imprinting genetics, Humans, Mice, Asparaginase therapeutic use, Aspartate-Ammonia Ligase genetics, Pharmacogenomic Variants genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
Karyotype is an important prognostic factor in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but the underlying pharmacogenomics remain unknown. Asparaginase is an integral component in current chemotherapy for childhood BCP-ALL. Asparaginase therapy depletes serum asparagine. Normal hematopoietic cells can produce asparagine by asparagine synthetase (ASNS) activity, but ALL cells are unable to synthesize adequate amounts of asparagine. The ASNS gene has a typical CpG island in its promoter. Thus, methylation of the ASNS CpG island could be one of the epigenetic mechanisms for ASNS gene silencing in BCP-ALL. To gain deep insights into the pharmacogenomics of asparaginase therapy, we investigated the association of ASNS methylation status with asparaginase sensitivity. The ASNS CpG island is largely unmethylated in normal hematopoietic cells, but it is allele-specifically methylated in BCP-ALL cells. The ASNS gene is located at 7q21, an evolutionally conserved imprinted gene cluster. ASNS methylation in childhood BCP-ALL is associated with an aberrant methylation of the imprinted gene cluster at 7q21. Aberrant methylation of mouse Asns and a syntenic imprinted gene cluster is also confirmed in leukemic spleen samples from ETV6-RUNX1 knockin mice. In 3 childhood BCP-ALL cohorts, ASNS is highly methylated in BCP-ALL patients with favorable karyotypes but is mostly unmethylated in BCP-ALL patients with poor prognostic karyotypes. Higher ASNS methylation is associated with higher L-asparaginase sensitivity in BCP-ALL through lower ASNS gene and protein expression levels. These observations demonstrate that silencing of the ASNS gene as a result of aberrant imprinting is a pharmacogenetic mechanism for the leukemia-specific activity of asparaginase therapy in BCP-ALL., (© 2020 by The American Society of Hematology.)
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- 2020
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10. Discrepancies in preferences regarding the care of terminal-phase pneumonia in elderly patients among patients, families, and doctors: A multicenter questionnaire survey in nagasaki, Japan.
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Takazono T, Imamura Y, Kawakami K, Yamasaki N, Shimizu H, Usuki K, Kiyohara M, Hirayama T, Tashiro M, Hosogaya N, Saijo T, Yamamoto K, Miyazaki T, Yanagihara K, Izumikawa K, and Mukae H
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- Aged, Humans, Japan epidemiology, Surveys and Questionnaires, Physicians, Pneumonia epidemiology, Pneumonia therapy, Terminal Care
- Abstract
Background: Before advance care planning, it is essential to understand the differences in preferences for medical care of terminal-phase pneumonia in elderly patients among the patients, their families, and their doctors. This study aimed to clarify these differences and investigate the actual care provided to elderly patients with pneumonia in nursing hospitals., Methods: Multicenter questionnaire surveys of 179 patients admitted to nursing homes and long-term care beds in hospitals of three healthcare corporations, their families, and their physicians were conducted between January and August 2018. The questionnaires mainly assessed preferences for life-prolonging medical care procedures, including antibiotic treatments, in terminal-phase pneumonia. A follow-up survey regarding the prognosis and the actual care provided by the physicians was conducted 1 year after the first survey., Results: Only 16.2% of the patients had sufficient prior discussions with their families about their care. More families preferred cardiac massage, intubation, and tracheostomy, while fewer families preferred peripheral intravenous fluids or antibiotics than physicians. A total of 30 patients' families (16.7%) answered to withhold antibiotic treatment, while all physicians supported antibiotic administration. The only significant factor related to withholding antibiotics was high age (P = 0.0057). The follow-up survey administered to the doctors revealed that 49 patients (35.7%) had died within one year. Of the 137 patients, 54 patients (39.4%) had developed pneumonia during this observation period and all were treated with antibiotics., Conclusions: This study revealed large discrepancies between patients/families and physicians regarding preferences for care. Medical staff should make efforts to fill the gap by ensuring advance care planning., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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11. L-type amino acid transporter 1 (LAT1)-specific inhibitor is effective against T cell-mediated nasal hyperresponsiveness.
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Kaminuma O, Nishimura T, Saeki M, Yamasaki N, Ogata S, Fujita T, Endou H, and Hayashi K
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- Activating Transcription Factor 4 metabolism, Animals, Benzoxazoles administration & dosage, Cytokines immunology, Disease Models, Animal, Lymphocyte Activation drug effects, Mice, Rhinitis, Allergic immunology, Signal Transduction drug effects, T-Lymphocytes drug effects, Tyrosine administration & dosage, Tyrosine analogs & derivatives, gamma-Glutamylcyclotransferase metabolism, Large Neutral Amino Acid-Transporter 1 immunology, Rhinitis, Allergic drug therapy, T-Lymphocytes immunology
- Published
- 2020
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12. Integrated diagnostic approach to wild-type transthyretin cardiac amyloidosis with the use of high-sensitivity cardiac troponin T measurement and 99m Tc-pyrophosphate scintigraphy.
- Author
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Ochi Y, Kubo T, Nakashima Y, Baba Y, Hirota T, Yamasaki N, Yamashita T, Ueda M, Ando Y, and Kitaoka H
- Subjects
- Aged, Aged, 80 and over, Amyloid Neuropathies, Familial pathology, Amyloid Neuropathies, Familial physiopathology, Female, Heart Ventricles diagnostic imaging, Heart Ventricles pathology, Humans, Hypertrophy, Left Ventricular blood, Hypertrophy, Left Ventricular diagnostic imaging, Hypertrophy, Left Ventricular pathology, Hypertrophy, Left Ventricular physiopathology, Male, Radionuclide Imaging, Technetium Tc 99m Pyrophosphate, Ventricular Function, Left, Amyloid Neuropathies, Familial blood, Amyloid Neuropathies, Familial diagnostic imaging, Troponin T blood
- Abstract
Background: The diagnosis of wild-type transthyretin cardiac amyloidosis (ATTRwt) is frequently missed or delayed because of the limited specificity of manifestations. We investigated the utility of combined assessment of high-sensitivity cardiac troponin T (hs-cTnT) measurement and
99m Tc-pyrophosphate (99m Tc-PYP) scintigraphy as diagnostic modalities in ATTRwt., Methods: We divided 39 consecutive ATTRwt patients into two groups depending on whether serum hs-cTnT measurement and99m Tc-PYP scintigraphy were adopted as diagnostic tools: group A patients (n=8) who were diagnosed before the introduction of these two tools and group B patients (n=31) who were diagnosed after the introduction of the two tools. We retrospectively evaluated the two groups., Results: Diagnostic yield was higher in group B than in group A (1.2 vs. 5.4 ATTRwt patients per 1000 hospitalized patients, p<0.01). Group B patients presented broad clinical features that were different from group A patients with classical characteristics. Atrial fibrillation was more frequent (12.5% vs. 58.1%, p=0.044) and inter-ventricular septum (IVS) thickness and relative wall thickness (RWT) were smaller in group B patients than in group A patients (IVS thickness: 16.1±2.4mm vs. 13.6±2.8mm, p=0.023; RWT: 0.71±0.11mm vs. 0.58±0.13mm, p=0.014). Furthermore, left ventricular hypertrophy (LVH) (IVS thickness ≥15mm) was more frequent in patients in group A than in patients in group B (87.5% vs. 33.3%, p=0.013). No significant difference was observed in the mean value of left ventricular ejection fraction (LVEF), whereas the dispersion of LVEF was high in group B (interquartile range: 47-58% vs. 39-57%)., Conclusions: An integrated approach consisting of hs-cTnT measurement and99m Tc-PYP scintigraphy significantly increases the diagnostic rate of ATTRwt and has a high potential to identify ATTRwt patients with a variety of clinical phenotypes., (Copyright © 2019. Published by Elsevier Ltd.)- Published
- 2020
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13. Reconsideration of the cut-off value of angiotensin-converting enzyme for screening of sarcoidosis in Japanese patients.
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Baba Y, Kubo T, Yamanaka S, Ochi Y, Hirota T, Yamasaki N, Ohnishi H, Kubota T, Yokoyama A, and Kitaoka H
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- Adult, Biomarkers blood, Female, Humans, Japan, Male, Middle Aged, ROC Curve, Reference Values, Mass Screening statistics & numerical data, Peptidyl-Dipeptidase A blood, Sarcoidosis diagnosis
- Abstract
Background: In clinical practice, we frequently experience patients with sarcoidosis who show relatively high but normal values of angiotensin-converting enzyme (ACE). The objective of this study was to reconsider the cut-off value of ACE., Methods: We studied 79 Japanese patients who were diagnosed as having sarcoidosis at our hospital. We excluded patients who had taken steroids or ACE inhibitors and patients with renal impairment. We respectively evaluated ACE values and performed receiver operating characteristic (ROC) analysis from a comparison with data for 299 normal Japanese subjects who showed ACE values in the current Japanese standard normal range (7.0-25.0IU/L)., Results: Patients with sarcoidosis had higher ACE values than those in normal subjects (ACE: 20.3IU/L [IQR, 16.0-24.4] vs. 15.4IU/L [IQR, 12.8-18.5]; p<0.001). However, 62 patients (78.5%) had normal ACE levels (cut-off value <25.0IU/L), and the sensitivity of ACE level for detecting sarcoidosis was only 21.5%. From ROC analysis, a cut-off value of 17.7IU/L (AUC: 0.727, 95% CI: 0.660-0.794, p<0.001) was the best cut-off value for detecting sarcoidosis and sensitivity increased to 67.0%., Conclusions: The possibility of sarcoidosis cannot be ruled out by using the current Japanese standard value even in patients who have normal ACE levels. Careful interpretation of this biomarker is needed., (Copyright © 2019. Published by Elsevier Ltd.)
- Published
- 2019
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14. Development of a Tailored Thyroid Gland Phantom for Fine-Needle Aspiration Cytology by Three-Dimensional Printing.
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Baba M, Matsumoto K, Yamasaki N, Shindo H, Yano H, Matsumoto M, Otsubo R, John Lawn M, Matsuo N, Yamamoto I, Hidaka S, and Nagayasu T
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- Biopsy, Fine-Needle, Education, Medical methods, Health Personnel statistics & numerical data, Humans, Imaging, Three-Dimensional methods, Models, Educational, Clinical Competence, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Phantoms, Imaging, Printing, Three-Dimensional, Thyroid Gland diagnostic imaging, Thyroid Gland pathology
- Abstract
Background: Fine-needle aspiration cytology (FNAC) is a challenging and risky procedure for inexperienced clinicians to perform because of the proximity of the thyroid to the jugular veins, carotid arteries, and trachea. A phantom model for transfixion practice would help train clinicians in FNAC., Objective: To fabricate a tailored phantom with consideration for authenticity of size, touch, feel, and ultrasonographic (US) characteristics., Methods: A three-dimensional (3D) digital model of the human neck was reconstructed from computed tomography data of a subject. This model was used to create 3D-printed templates for various organs that require US visualization. The templates were injected with polymers that provided similar degrees of ultrasound permeability as the corresponding organs. For fabrication of each organ, the respective molds of organs, blood vessels, thyroid gland, and tumor were injected with the material. The fabricated components were then removed from the templates and colored. Individual components were then positioned in the neck mold, and agar gel was poured in. The complete phantom was then removed from the mold. Thereafter, 45 medical doctors and students performed ultrasound-guided FNAC using the phantom, following which they were queried regarding the value of the phantom., Results: The structure, US characteristics, and elasticity of the phantom were similar to those of the human subject. In the survey, all 45 participants replied that they found the phantom useful for FNAC training, and 30 medical students professed increased interest in thyroid diseases after using the phantom., Conclusions: We successfully fabricated a tailored thyroid gland phantom for transfixion practice. As most of the phantom parts are injected in molds fabricated using a 3D printer, they can be easily reproduced once the molds are fabricated. This phantom is expected to serve as an effective and fully tailored training model for practicing thyroid gland transfixion., (Copyright © 2017. Published by Elsevier Inc.)
- Published
- 2017
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15. Acquired expression of Cbl Q367P in mice induces dysplastic myelopoiesis mimicking chronic myelomonocytic leukemia.
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Nakata Y, Ueda T, Nagamachi A, Yamasaki N, Ikeda KI, Sera Y, Takubo K, Kanai A, Oda H, Sanada M, Ogawa S, Tsuji K, Ebihara Y, Wolff L, Honda ZI, Suda T, Inaba T, and Honda H
- Subjects
- Amino Acid Substitution, Animals, Gene Expression Regulation, Enzymologic, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute pathology, Mice, Mice, Transgenic, Monocytes metabolism, Monocytes pathology, Monomeric GTP-Binding Proteins biosynthesis, Monomeric GTP-Binding Proteins genetics, Phosphatidylinositol 3-Kinases genetics, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction, Cell Cycle, Hematopoietic Stem Cells metabolism, Hematopoietic Stem Cells pathology, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Mutation, Missense, Myelopoiesis, Proto-Oncogene Proteins c-cbl biosynthesis, Proto-Oncogene Proteins c-cbl genetics, Up-Regulation
- Abstract
Chronic myelomonocytic leukemia (CMML) is a hematological malignancy characterized by uncontrolled proliferation of dysplastic myelomonocytes and frequent progression to acute myeloid leukemia (AML). We identified mutations in the Cbl gene, which encodes a negative regulator of cytokine signaling, in a subset of CMML patients. To investigate the contribution of mutant Cbl in CMML pathogenesis, we generated conditional knockin mice for Cbl that express wild-type Cbl in a steady state and inducibly express Cbl
Q367P , a CMML-associated Cbl mutant. CblQ367P mice exhibited sustained proliferation of myelomonocytes, multilineage dysplasia, and splenomegaly, which are the hallmarks of CMML. The phosphatidylinositol 3-kinase (PI3K)-AKT and JAK-STAT pathways were constitutively activated in CblQ367P hematopoietic stem cells, which promoted cell cycle progression and enhanced chemokine-chemokine receptor activity. Gem , a gene encoding a GTPase that is upregulated by CblQ367P , enhanced hematopoietic stem cell activity and induced myeloid cell proliferation. In addition, Evi1 , a gene encoding a transcription factor, was found to cooperate with CblQ367P and progress CMML to AML. Furthermore, targeted inhibition for the PI3K-AKT and JAK-STAT pathways efficiently suppressed the proliferative activity of CblQ367P -bearing CMML cells. Our findings provide insights into the molecular mechanisms underlying mutant Cbl -induced CMML and propose a possible molecular targeting therapy for mutant Cbl -carrying CMML patients.- Published
- 2017
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16. Prevalence and clinical features of Fabry disease in Japanese male patients with diagnosis of hypertrophic cardiomyopathy.
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Kubo T, Ochi Y, Baba Y, Hirota T, Tanioka K, Yamasaki N, Yoshimitsu M, Higuchi K, Takenaka T, Nakajima K, Togawa T, Tsukimura T, Sano S, Tei C, Sakuraba H, and Kitaoka H
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cardiomyopathy, Hypertrophic etiology, Cardiomyopathy, Hypertrophic pathology, Echocardiography, Electrocardiography, Fabry Disease diagnostic imaging, Fabry Disease epidemiology, Heart Failure etiology, Heart Failure pathology, Humans, Hypertrophy, Left Ventricular enzymology, Hypertrophy, Left Ventricular etiology, Japan epidemiology, Male, Middle Aged, Mutation, Prevalence, Young Adult, alpha-Galactosidase blood, Fabry Disease complications, Fabry Disease pathology, Hypertrophy, Left Ventricular epidemiology, Hypertrophy, Left Ventricular pathology
- Abstract
Background: The prevalence of Fabry disease (FD) in Japanese patients presenting with unexplained left ventricular hypertrophy (LVH) has remained unclear., Methods: We measured plasma α-galactosidase A activity in 177 men with a diagnosis of hypertrophic cardiomyopathy (HCM) (maximum LV wall thickness ≥15mm)., Results: Two patients (1.1%) showed very low α-galactosidase A activity [0.0 and 0.3nmol/hr/ml (normal range: 3.6-17.6nmol/hr/ml)], and a clinical diagnosis of cardiac variant of FD was finally made. One patient was a 55-year-old man who came to our hospital because of abnormal results of electrocardiography and showed concentric LVH in echocardiography. A missense mutation, R112L, was identified. The other was a 74-year-old man who had been diagnosed with HCM at the age of 60 years in another hospital and was referred for evaluation of repeated hospitalization for heart failure. Although echocardiography revealed asymmetric septal hypertrophy (ASH) with interventricular septal wall thickness of 16mm and posterior wall thickness of 11mm and reduced LV ejection fraction with hypokinetic posterior wall motion, his echocardiographic findings at the initial diagnosis of HCM were not ASH but concentric LVH with normal LV systolic function. A splicing mutation, IVS4+919G>A, was identified., Conclusions: The prevalence of FD in Japanese male patients with a clinical diagnosis of HCM was found to be 1.1%. These patients showed late onset and concentric LVH at initial presentation., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2017
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17. Erythrocyte creatine as a marker of intravascular hemolysis due to left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.
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Kubo T, Okumiya T, Baba Y, Hirota T, Tanioka K, Yamasaki N, Sugiura T, Doi YL, and Kitaoka H
- Subjects
- Adult, Aged, Biomarkers blood, Cardiomyopathy, Hypertrophic complications, Female, Humans, Male, Middle Aged, Rest physiology, Valsalva Maneuver, Ventricular Outflow Obstruction etiology, Ventricular Pressure, Cardiomyopathy, Hypertrophic blood, Creatine blood, Erythrocytes chemistry, Hemolysis physiology, Ventricular Outflow Obstruction blood
- Abstract
Background: Erythrocyte creatine, a marker of erythrocyte age that increases with shortening of erythrocyte survival, has been reported to be a quantitative and reliable marker for intravascular hemolysis. We hypothesized that hemolysis could also occur due to intraventricular obstruction in patients with hypertrophic cardiomyopathy (HCM). The purpose of this study was to examine the presence of subclinical hemolysis and the relation between intravascular hemolysis and intraventricular pressure gradient (IVPG)., Methods and Results: We measured erythrocyte creatine in 92 HCM patients. Twelve patients had left ventricular outflow tract obstruction (LVOTO), 4 had midventricular obstruction (MVO), and the remaining 76 were non-obstructive. Erythrocyte creatine levels ranged from 0.92 to 4.36μmol/g hemoglobin. Higher levels of erythrocyte creatine were associated with higher IVPG (r=0.437, p<0.001). If erythrocyte creatine levels are high (≥1.8μmol/g hemoglobin), subclinical hemolysis is considered to be present. Half of LVOTO patients and no MVO patients showed high erythrocyte creatine levels. Although non-obstructive patients did not show significant intraventricular obstruction at rest, some showed high erythrocyte creatine levels. When LVOT-PG was measured during the strain phase of the Valsalva maneuver in 20 non-obstructive patients, 7 of those 20 patients showed LVOTO. In the 20 patients, there was no relation between erythrocyte creatine levels and LVOT-PG before the Valsalva maneuver (r=0.125, p=0.600), whereas there was a significant correlation between erythrocyte creatine and LVOT-PG provoked by the Valsalva maneuver (r=0.695, p=0.001)., Conclusions: There is biochemical evidence of subclinical hemolysis in patients with HCM, and this hemolysis seems to be associated with LVOTO provoked by daily physical activities., (Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2016
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18. Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia involving metabolic activation and upregulation of Nsg2.
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Ueda T, Nagamachi A, Takubo K, Yamasaki N, Matsui H, Kanai A, Nakata Y, Ikeda K, Konuma T, Oda H, Wolff L, Honda Z, Wu X, Helin K, Iwama A, Suda T, Inaba T, and Honda H
- Subjects
- Animals, B-Lymphocytes pathology, Carrier Proteins genetics, Cell Differentiation genetics, Cell Proliferation genetics, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic metabolism, F-Box Proteins metabolism, Jumonji Domain-Containing Histone Demethylases metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Myeloid Cells pathology, Nerve Tissue Proteins genetics, Oncogenes, Up-Regulation genetics, Carrier Proteins metabolism, F-Box Proteins genetics, Hematopoietic Stem Cells metabolism, Jumonji Domain-Containing Histone Demethylases genetics, Leukemia genetics, Leukemia metabolism, Nerve Tissue Proteins metabolism
- Abstract
We previously reported that deficiency for Samd9L, which was cloned as a candidate gene for -7/7q- syndrome, accelerated leukemia cooperatively with enhanced expression of a histone demethylase: F-box and leucine-rich repeat protein 10 (Fbxl10, also known as Jhdm1b, Kdm2b, and Ndy1). To further investigate the role of Fbxl10 in leukemogenesis, we generated transgenic (Tg) mice that overexpress Fbxl10 in hematopoietic stem cells (HSCs). Interestingly, Fbxl10 Tg mice developed myeloid or B-lymphoid leukemia with complete penetrance. HSCs from the Tg mice exhibited an accelerated G0/G1-to-S transition with a normal G0 to G1 entry, resulting in pleiotropic progenitor cell expansion. Fbxl10 Tg HSCs displayed enhanced expression of neuron-specific gene family member 2 (Nsg2), and forced expression of Nsg2 in primary bone marrow cells resulted in expansion of immature cells. In addition, the genes involved in mitochondrial oxidative phosphorylation were markedly enriched in Fbxl10 Tg HSCs, coupled with increased cellular adenosine 5'-triphosphate levels. Moreover, chromatin immunoprecipitation followed by sequencing analysis demonstrated that Fbxl10 directly binds to the regulatory regions of Nsg2 and oxidative phosphorylation genes. These findings define Fbxl10 as a bona fide oncogene, whose deregulated expression contributes to the development of leukemia involving metabolic proliferative advantage and Nsg2-mediated impaired differentiation.
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- 2015
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19. Gender differences in the clinical features of hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations.
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Terauchi Y, Kubo T, Baba Y, Hirota T, Tanioka K, Yamasaki N, Furuno T, and Kitaoka H
- Subjects
- Adult, Age Factors, Aged, Cardiomyopathy, Hypertrophic mortality, Cardiomyopathy, Hypertrophic pathology, Female, Genotype, Heart Failure epidemiology, Humans, Incidence, Kaplan-Meier Estimate, Male, Middle Aged, Retrospective Studies, Risk Factors, Cardiomyopathy, Hypertrophic genetics, Carrier Proteins genetics, Mutation genetics, Phenotype, Sex Factors
- Abstract
Background: Although gender may be one of the important factors modifying phenotypic expression in hypertrophic cardiomyopathy (HCM), there has been little information on it., Methods and Results: We investigated gender differences in the clinical features of HCM caused by cardiac myosin-binding protein C gene (MYBPC3) mutations. Sixty-one subjects (28 families) carrying MYBPC3 mutations were studied. Of the 61 subjects with MYBPC3 mutations, 50 patients including 23 female patients were phenotype-positive by echocardiography. Disease penetrance in subjects aged ≤40 years old was 92% in males and 67% in females. Females showed delayed onset of left ventricular hypertrophy compared with males in subjects who were genotype-positive. Female patients were more symptomatic at diagnosis than were males (mean New York Heart Association class: 1.7±0.8 versus 1.2±0.4, p=0.012). From a longitudinal point of view by age, no significant gender difference in cardiovascular deaths or cardiovascular events was found. During the follow-up period after diagnosis of HCM (13±8 years), female patients who were phenotype-positive had significantly more frequent heart failure events than did phenotypically affected male patients (p=0.028)., Conclusions: Although females with MYBPC3 mutations showed later onset of the disease, female patients were more symptomatic at diagnosis and had more frequent heart failure events once they had developed hypertrophy., (Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
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- 2015
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20. Airway stent insertion simulated with a three-dimensional printed airway model.
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Miyazaki T, Yamasaki N, Tsuchiya T, Matsumoto K, Takagi K, and Nagayasu T
- Subjects
- Adult, Constriction, Pathologic surgery, Humans, Male, Prosthesis Implantation methods, Bronchi pathology, Lung Transplantation, Models, Anatomic, Postoperative Complications surgery, Printing, Three-Dimensional, Stents
- Abstract
A 30-year-old man underwent right single-lung transplantation for chronic obstructive pulmonary disease. The bronchial anastomosis developed ischemic change, resulting in stenosis of the intermediate bronchus. A modified Y-shaped airway stent with the fabricated orifice of the upper lobe was inserted by rigid bronchoscopy. Before the operation, a three-dimensional printed bronchial model of this patient was made for surgical simulation. This model enabled us to perform the operation easily, quickly, and successfully. The patient's condition improved after airway stent insertion. The three-dimensional printed airway model provided sufficient preoperative understanding of the patient's anatomy for planning the surgical procedure., (Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
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- 2015
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21. Recruitment of Young Medical Apprentices (RYOMA) project: a comprehensive surgical education program at a local academic institute in Japan.
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Nanashima A, Hidaka S, Nonaka T, Yamasaki N, Tsuchiya T, Matsumoto K, Miyazaki T, Hatachi G, Sumida Y, Sawai T, Yasutake T, and Nagayasu T
- Subjects
- Career Choice, Computer Simulation, Humans, Japan, Personnel Selection, Students, Medical, Surgical Procedures, Operative education, User-Computer Interface, Workforce, General Surgery education, Surgeons supply & distribution
- Abstract
Objectives: The number of young surgeons in Japan has significantly decreased in recent years, which may lead to future problems in the medical field. Therefore, comprehensive training programs for young surgeons are needed., Design: Retrospective study, Setting: We developed a specific education program called the "Recruitment of Young Medical Apprentices" (RYOMA) project., Participants: We performed this project between January 2008 and August 2013 on fourth- to sixth-year medical students and internship doctors. The RYOMA project included step-by-step surgical education programs on open and scopic procedures as dry, wet, and animal laboratory training. Our goal was to increase the number of young and specialist surgeons., Results: Based on an interview questionnaire answered by 90 medical students, most young students were interested in surgical training and several chose to become surgeons in the future. The most positive opinions regarding the field of surgery were the impressive results achieved with surgery, whereas negative opinions included the difficulty of the surgical skill, physical concerns related to difficult work environments, and the severity of surgical procedures. The present program has begun to resolve negative opinions through adequate training or simulations. Of the 19 medical students and internship doctors who attended the RYOMA project in 2008, 17 trainees (90%) were satisfied with this special surgical program and 16 (88%) showed interest in becoming surgeons. The number of participants considering the field of surgery increased between 2008 and 2013. Of 23 participants, 19 (83%) had a positive opinion of the program after the training., Conclusions: Gaining experience in surgical training from an early stage in medical school and step-by-step authorized education by teaching staff are important for recruiting students and increasing the number of young surgeons., (Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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22. High expression of dihydropyrimidine dehydrogenase in lung adenocarcinoma is associated with mutations in epidermal growth factor receptor: implications for the treatment of non--small-cell lung cancer using 5-fluorouracil.
- Author
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Mochinaga K, Tsuchiya T, Nagasaki T, Arai J, Tominaga T, Yamasaki N, Matsumoto K, Miyazaki T, Nanashima A, Hayashi T, Tsukamoto K, and Nagayasu T
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma genetics, Adenocarcinoma metabolism, Adenocarcinoma pathology, Aged, Antimetabolites, Antineoplastic therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell metabolism, Carcinoma, Squamous Cell pathology, Dihydrouracil Dehydrogenase (NADP) metabolism, ErbB Receptors metabolism, Female, Follow-Up Studies, Humans, Immunoenzyme Techniques, Lung Neoplasms drug therapy, Lung Neoplasms metabolism, Lung Neoplasms pathology, Male, Neoplasm Staging, Polymerase Chain Reaction, Prognosis, Thymidylate Synthase genetics, Thymidylate Synthase metabolism, Carcinoma, Non-Small-Cell Lung genetics, Dihydrouracil Dehydrogenase (NADP) genetics, ErbB Receptors genetics, Fluorouracil therapeutic use, Lung Neoplasms genetics, Mutation genetics
- Abstract
Background: It has been shown that 5-fluorouracil (5-FU) sensitivity in patients with non-small-cell lung cancer (NSCLC) is associated with epidermal growth factor receptor (EGFR) mutation status. However, the relationship between dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, and EGFR mutation status is unknown. Here, we focus on clinicopathologic factors and in vitro correlations between DPD expression and EGFR mutation status., Patients and Methods: EGFR mutations and messenger RNA (mRNA) levels of DPD and thymidylate synthase (TS) were analyzed in 47 resected NSCLC tumors by laser-capture microdissection. In addition, relationships between EGFR mutation status and the immunohistochemical expression of DPD and TS in 49 patients with primary NSCLC who were treated with a 5-FU derivative of S-1 postoperatively were examined. Correlations among clinicopathologic factors were evaluated. The effect of epidermal growth factor on DPD expression was also investigated in vitro in various cell lines., Results: Adenocarcinoma in situ showed significantly higher DPD mRNA levels and more EGFR mutation frequency than other histological types (P < .05). DPD immunopositive cases were more frequently observed in adenocarcinoma, in females, and in nonsmokers. DPD immunopositive cases were correlated with EGFR mutation status (P < .003). The prognoses of wild-type EGFR and mutated EGFR populations were similarly favorable with postoperative S-1 treatment, which overcomes the problem of 5-FU degradation in mutated EGFR. In vitro, EGFR-mutated cell lines showed high DPD mRNA and protein expression., Conclusion: High DPD expression was shown to be correlated with EGFR mutation in adenocarcinoma cells and tissues. Clinicians should take this finding into consideration when using 5-FU to treat patients with NSCLC., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
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23. Pulmonary artery pseudoaneurysm caused by Streptococcus constellatus.
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Morinaga Y, Yanagihara K, Gyotoku H, Oshima K, Izumikawa K, Yamasaki N, Kakeya H, Hayashi T, Fukuoka J, Nagayasu T, and Kohno S
- Subjects
- Aneurysm, False diagnosis, Aneurysm, False surgery, Humans, Lung pathology, Lung Abscess complications, Lung Abscess diagnosis, Lung Abscess microbiology, Lung Abscess therapy, Male, Middle Aged, Streptococcal Infections diagnosis, Streptococcal Infections therapy, Tomography, X-Ray Computed, Treatment Outcome, Aneurysm, False etiology, Pulmonary Artery microbiology, Pulmonary Artery pathology, Streptococcal Infections complications, Streptococcus constellatus
- Abstract
We report a rare case of mycotic pulmonary artery pseudoaneurysm (PAP) secondary to a lung abscess due to Streptococcus constellatus. PAP was confirmed by the pathological findings of the pseudoaneurysm, the presence of bacteria, and the microbiological analysis. PAP is uncommon, but it is important to recognize this condition because PAP can lead to fatal hemoptysis., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2013
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24. Does the placement of a cystic duct tube after a hepatic resection help reduce the incidence of post-operative bile leak?
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Nanashima A, Abo T, Shibuya A, Tominaga T, Matsumoto A, Tou K, Kunizaki M, Takeshita H, Hidaka S, Tsuchiya T, Yamasaki N, and Nagayasu T
- Subjects
- Abdominal Abscess epidemiology, Adolescent, Adult, Aged, Aged, 80 and over, Anastomotic Leak epidemiology, Biliary Tract Diseases epidemiology, Chi-Square Distribution, Drainage adverse effects, Female, Humans, Incidence, Japan epidemiology, Length of Stay, Logistic Models, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Proportional Hazards Models, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, Young Adult, Anastomotic Leak prevention & control, Biliary Tract Diseases prevention & control, Cystic Duct surgery, Drainage instrumentation, Hepatectomy adverse effects
- Abstract
Background: In this retrospective study, the effects of cystic duct (C) tube use on the incidence of post-hepatectomy bile leak were assessed., Methods: The subjects were 550 patients who underwent a hepatectomy during 1990-2011, with (n = 83) and without (n = 467) C tube drainage. The use of a C tube was based on the surgeon's choice., Results: Bile leakage was observed in 44 (8%) patients, and its incidence post-operatively correlated with intrahepatic cholangiocarcinoma, parenchymal transection with forceps fracture and tie, a major hepatectomy, prolonged surgery and excessive blood loss (P < 0.050) but not with the use of a C tube. The incidence of an intra-abdominal infection was higher and the hospital stay was longer in the leak (49 days) than non-leak group (21 days, P < 0.001). ISGLS grade B and C bile leak post-hemi-hepatectomy and extended-hepatectomy were more frequent in the non-C than C tube group (P = 0.016). The duration of hospitalization was not different between the two groups; however, 7 patients in the non-C tube group had prolonged hospitalization (> 60 days) compared with none in the C tube group (P = 0.454)., Conclusion: The usefulness of the C tube in preventing post-hepatectomy bile leak could not be confirmed; however, both bile leak requiring clinical management and long hospitalization after a major hepatectomy could be reduced with C tube use., (© 2012 International Hepato-Pancreato-Biliary Association.)
- Published
- 2013
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25. A multicenter phase II study of adjuvant chemotherapy with oral fluoropyrimidine S-1 for non-small-cell lung cancer: high completion and survival rates.
- Author
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Tsuchiya T, Nagayasu T, Yamasaki N, Matsumoto K, Miyazaki T, Tagawa T, Nakamura A, Minami H, Taniguchi H, Akamine S, Hisano H, and Taniguchi Y
- Subjects
- Administration, Oral, Aged, Ambulatory Care methods, Antimetabolites, Antineoplastic administration & dosage, Antimetabolites, Antineoplastic adverse effects, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung surgery, Chemotherapy, Adjuvant methods, Combined Modality Therapy, Dose-Response Relationship, Drug, Drug Combinations, Feasibility Studies, Female, Follow-Up Studies, Humans, Incidence, Lung Neoplasms pathology, Lung Neoplasms surgery, Male, Middle Aged, Neoplasm Recurrence, Local, Oxonic Acid administration & dosage, Oxonic Acid adverse effects, Tegafur administration & dosage, Tegafur adverse effects, Treatment Outcome, Antimetabolites, Antineoplastic therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Oxonic Acid therapeutic use, Tegafur therapeutic use
- Abstract
Background: Oral adjuvant chemotherapy without hospitalization might reduce the physiological and psychological burden on patients if effectiveness could be guaranteed. We conducted a multicenter feasibility study using S-1, an oral derivative of 5-fluorouracil, as postoperative adjuvant chemotherapy in patients with curatively resected pathologically stage IB-IIIA non-small-cell lung cancer., Patients and Methods: Adjuvant chemotherapy comprised 8 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg per day. Fifty-one patients from 7 institutions were enrolled in this pilot study, from June 2005 to March 2007. The primary end point was the completion rate of scheduled adjuvant chemotherapy. Secondary end points were the incidence and grade of adverse reactions., Results: Fifty patients were eligible. The completion rate for the planned 8 courses of S-1 administration was 72.0% (36 patients). Total percentage administration amount was 71.1%. Grade 3 adverse reactions such as neutropenia (4.0%), anorexia (4.0%), thrombopenia (2.0%), anemia (2.0%), elevated total bilirubin (2.0%), hypokalemia (2.0%), nausea (2.0%), and diarrhea (2.0%) were observed, but no grade 4 adverse effects were encountered. Overall and relapse-free survival rates at 3 years were 87.7% and 69.4%, respectively., Conclusions: Postoperative 1-year administration of S-1 seems feasible as oral adjuvant chemotherapy for lung cancer. The oral formulation and low incidence of adverse reactions permit treatment on an outpatient basis. The present study would be reasonable to follow up with a properly powered phase III trial., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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26. Three-dimensional computed tomography for a mediastinal basal pulmonary artery.
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Matsumoto K, Yamasaki N, Tsuchiya T, Miyazaki T, Tomoshige K, Hayashi H, Ashizawa K, and Nagayasu T
- Subjects
- Aged, Humans, Male, Mediastinum, Imaging, Three-Dimensional, Pulmonary Artery abnormalities, Pulmonary Artery diagnostic imaging, Tomography, X-Ray Computed
- Abstract
Anatomic variations of the pulmonary artery increase the risks for vessel injury and critical mistakes during pulmonary artery resection. A patient who underwent left lower lobectomy for lung cancer with a mediastinal lingular and basal pulmonary artery that had been detected preoperatively by three-dimensional computed tomography is presented. During thoracoscopic surgery, the mediastinal basal pulmonary arteries were found with careful dissection. The pulmonary arteries were divided, and left lower lobectomy was performed safely. This rare variation of the left pulmonary artery is important to detect before lobectomy to ensure safe surgery. In such cases, three-dimensional computed tomography is necessary., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
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27. α-Synuclein BAC transgenic mice as a model for Parkinson's disease manifested decreased anxiety-like behavior and hyperlocomotion.
- Author
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Yamakado H, Moriwaki Y, Yamasaki N, Miyakawa T, Kurisu J, Uemura K, Inoue H, Takahashi M, and Takahashi R
- Subjects
- Animals, Anxiety prevention & control, Anxiety psychology, Chromosomes, Artificial, Bacterial metabolism, Humans, Mice, Mice, Transgenic, Motor Activity genetics, Parkinson Disease metabolism, Parkinson Disease psychology, Psychomotor Agitation metabolism, Psychomotor Agitation psychology, alpha-Synuclein biosynthesis, Anxiety genetics, Chromosomes, Artificial, Bacterial genetics, Disease Models, Animal, Parkinson Disease genetics, Psychomotor Agitation genetics, alpha-Synuclein genetics
- Abstract
α-Synuclein (α-syn), the main component of Lewy bodies, was identified as a genetic risk factor for idiopathic Parkinson's disease (PD). As a model for PD, we generated human α-syn bacterial artificial chromosome transgenic mice (BAC tg mice) harboring the entire human α-syn gene and its gene expression regulatory regions. The α-syn BAC tg mice manifested decreased anxiety-like behaviors which may reflect non-motor symptoms of early PD, and they exhibited increased SERT expression that may be responsible for decreased anxiety-like behaviors. Our α-syn BAC tg mice could be a valuable tool to evaluate α-syn gene dosage effects in vivo., (Copyright © 2012 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)
- Published
- 2012
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28. Serum tenascin-C levels as a prognostic biomarker of heart failure events in patients with hypertrophic cardiomyopathy.
- Author
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Kitaoka H, Kubo T, Baba Y, Yamasaki N, Matsumura Y, Furuno T, and Doi YL
- Subjects
- Echocardiography, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Biomarkers blood, Cardiomyopathy, Hypertrophic complications, Heart Failure diagnosis, Tenascin blood
- Abstract
Background and Purpose: Although serum tenascin-C (TN-C) levels are related to left ventricular (LV) remodeling in patients with myocardial infarction and are useful as a prognostic biomarker of heart failure in patients with dilated cardiomyopathy, the clinical significance of TN-C levels has not yet been studied in patients with hypertrophic cardiomyopathy (HCM). Therefore, the purpose of this study is to elucidate whether serum TN-C levels are a prognostic biomarker for heart failure in patients with HCM., Methods: The relationship between serum TN-C levels and heart failure events was studied in 36 patients with HCM during follow-up., Results: Levels of serum TN-C were 28±13 ng/ml (range 11-80 ng/ml). Although patients with LV systolic impairment showed higher TN-C levels than those with preserved LV systolic function (33±11 ng/ml vs. 27±14 ng/ml; p=0.16), TN-C levels were not related to any echocardiographic parameters. During the follow-up period of 4.8±1.4 years, heart failure events were observed in six patients and TN-C levels in patients with events were higher than those in patients without events. Kaplan-Meier analysis showed that the prognosis was worse in patients with high TN-C levels (≥39.2 ng/ml) than in those with low TN-C levels., Conclusions: Heart failure events were more frequently observed in patients with high serum TN-C levels than in those with low TN-C levels. Serum TN-C levels may be a new prognostic biomarker for heart failure in patients with HCM., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2012
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29. Plasma metalloproteinase levels and left ventricular remodeling in hypertrophic cardiomyopathy in patients with an identical mutation.
- Author
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Kitaoka H, Kubo T, Okawa M, Takenaka N, Baba Y, Yamasaki N, Matsumura Y, Furuno T, and Doi YL
- Subjects
- Adult, Biomarkers blood, Cardiomyopathy, Hypertrophic pathology, Cardiomyopathy, Hypertrophic physiopathology, Echocardiography, Female, Follow-Up Studies, Heart Ventricles pathology, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Stroke Volume, Systole, Ventricular Function, Left, Cardiomyopathy, Hypertrophic diagnosis, Cardiomyopathy, Hypertrophic genetics, Carrier Proteins genetics, Frameshift Mutation, Matrix Metalloproteinase 2 blood, Matrix Metalloproteinase 9 blood, Ventricular Remodeling
- Abstract
Background and Purpose: Although it has been reported that matrix metalloproteinases (MMPs) are associated with left ventricular (LV) remodeling in patients with hypertrophic cardiomyopathy (HCM), the impact of plasma MMP levels in patients with HCM is somewhat vague., Methods and Subjects: Plasma levels of MMP-2, MMP-9, and clinical/echocardiographic findings were evaluated in 16 HCM patients with preserved LV ejection fraction (defined as LV ejection fraction more than 50%) caused by an identical frameshift mutation (S593fs: a one-base deletion of a thymidine at nucleotide 11,645) in the cardiac myosin-binding protein C gene., Results: MMP-2 levels were inversely related to LV ejection fraction (r(2)=-37, p=0.01). MMP-9 levels were inversely related to LV end-diastolic dimension (r(2)=-0.24, p=0.06) and positively related to the maximum LV wall thickness (r(2)=0.25, p=0.04). During follow-up period of 4.1 ± 1.2 years, LV ejection fraction decreased from 68.5 ± 7.4% to 64.9 ± 9% (p=0.03). Among clinical, echocardiographic findings at baseline and levels of biomarkers, high MMP-9 levels were only related to the decrease of LV ejection fraction from baseline to follow-up (r(2)=0.39, p=0.009)., Conclusions: MMP-2 levels are related to reduced LV systolic function in HCM patients with preserved LV ejection fraction caused by an identical cardiac myosin-binding protein C gene abnormality. On the other hand, MMP-9 levels are associated with small LV size and the degree of LV hypertrophy and related to the deterioration in LV systolic function during follow-up. These results suggest that MMPs are important in the process of LV remodeling in HCM., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2011
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30. Analysis of 5-fluorouracil-related enzymes in pulmonary neuroendocrine carcinoma: differences in biological properties compared to epithelial carcinoma.
- Author
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Nagasaki T, Tsuchiya T, Tagawa T, Honda S, Yamasaki N, Miyazaki T, Hidaka S, Hayashi T, and Nagayasu T
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma enzymology, Aged, Antimetabolites, Antineoplastic pharmacology, Carcinoma, Large Cell drug therapy, Carcinoma, Large Cell enzymology, Carcinoma, Neuroendocrine drug therapy, Carcinoma, Neuroendocrine enzymology, Carcinoma, Small Cell drug therapy, Carcinoma, Small Cell enzymology, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell enzymology, Drug Resistance, Neoplasm, Female, Fluorouracil pharmacology, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms drug therapy, Male, RNA, Messenger metabolism, Retrospective Studies, Dihydrouracil Dehydrogenase (NADP) genetics, Lung Neoplasms enzymology, Orotate Phosphoribosyltransferase genetics, Thymidylate Synthase genetics
- Abstract
Background: Dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT), and thymidylate synthase (TS) levels correlate with sensitivity and resistance to 5-fluorouracil (5-FU). Few data are available on these enzymes in pulmonary neuroendocrine carcinoma, because 5-FU appears to have minimal effect on such carcinomas., Patients and Methods: This study investigated 5-FU-related enzymes in large-cell neuroendocrine carcinoma (LCNEC; n = 31) and small-cell lung carcinoma (SCLC; n = 15), comparing expression levels with epithelial carcinomas including adenocarcinoma (ADC; n = 34) and squamous cell carcinoma (SCC; n = 13) obtained from 93 patients with primary lung tumors. Levels of 5-FU-related enzyme mRNA were analyzed by laser capture microdissection, compared with immunohistochemical findings and correlated with clinicopathologic factors., Results: LCNEC and SCLC showed significantly higher TS and OPRT mRNA levels than ADC. SCLC exhibited significantly higher TS mRNA levels than LCNEC (P = .002). LCNEC displayed significantly lower DPD mRNA levels than ADC (P < .001), with a similar tendency in SCLC. SCC showed significantly lower DPD (P < .01) and higher OPRT (P < .001) mRNA levels than ADC. When we divide the data by pathology into epithelial carcinoma and neuroendocrine carcinoma, malignant potentials and prognoses correlated with mRNA levels in epithelial carcinoma, but not in neuroendocrine carcinoma. Immunohistochemically, neuroendocrine carcinomas were immunonegative for DPD. A significant correlation was found between enzymatic mRNA and protein expression for DPD (R = .500) and a weak correlation was observed for TS (R = .294)., Conclusion: Neuroendocrine carcinomas show characteristic patterns of expression for 5-FU-related enzymes, including low DPD mRNA and protein level and high TS mRNA level compared with adenocarcinomas. These results partially explain why 5-FU-based chemotherapy shows minimal efficacy against SCLC. Conversely, clinicopathological data and survival analysis indicates that 5-FU-related enzymes themselves might not affect the malignant potential of neuroendocrine carcinoma. Expressional differences in 5-FU-related enzymes among pathologies may provide valuable information for tailor-made chemotherapy.
- Published
- 2010
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31. Gender-specific differences in the clinical features of hypertrophic cardiomyopathy in a community-based Japanese population: results from Kochi RYOMA study.
- Author
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Kubo T, Kitaoka H, Okawa M, Hirota T, Hayato K, Yamasaki N, Matsumura Y, Yabe T, and Doi YL
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Asian People, Atrial Fibrillation, Cardiomyopathy, Hypertrophic diagnostic imaging, Child, Echocardiography, Electrocardiography, Female, Humans, Japan epidemiology, Male, Middle Aged, Prevalence, Residence Characteristics, Sex Factors, Young Adult, Cardiomyopathy, Hypertrophic epidemiology, Cardiomyopathy, Hypertrophic physiopathology, Registries
- Abstract
Objectives: Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with a broad spectrum of clinical features. Although gender may be one of the important modifying factors in HCM, there has been little information on gender differences., Methods: We investigated gender-specific differences in the clinical features of HCM in a community-based Japanese population. We established cardiomyopathy registration in Kochi Prefecture named Kochi RYOMA study consisting of 9 hospitals as an unselected regional Japanese population., Results: 261 patients with diagnosis of HCM were registered. At registration, 88 patients (34%) were women. Female patients were more frequently diagnosed as having HCM at ≥65 years (41% versus 27%) and had a higher ratio of familial HCM (35% versus 19%). More female patients had diagnosis of HCM due to cardiac symptoms (64% versus 40%) and were symptomatic both at diagnosis and at registration. Although the prevalence of atrial fibrillation was not different between males and females, embolic events occurred less frequently in female patients at registration than in male patients (2% versus 10%). In female patients, there were more obstructive HCM patients and fewer patients with apical HCM. Left ventricular and left atrial diameters were smaller and fractional shortening was higher in females than in males., Conclusions: The manifestations of HCM in unselected Japanese patients differed in men and women, which suggest that hormonal, social, and genetic factors may influence the clinical presentation of HCM., (Copyright © 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
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- 2010
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32. A 5' untranslated region containing the IRES element in the Runx1 gene is required for angiogenesis, hematopoiesis and leukemogenesis in a knock-in mouse model.
- Author
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Nagamachi A, Htun PW, Ma F, Miyazaki K, Yamasaki N, Kanno M, Inaba T, Honda Z, Okuda T, Oda H, Tsuji K, and Honda H
- Subjects
- Animals, Cell Differentiation, Gene Expression Regulation, Leukemic, Gene Knock-In Techniques, Heterozygote, Liver pathology, Mice, Models, Animal, Ribosomes metabolism, 5' Untranslated Regions, Core Binding Factor Alpha 2 Subunit genetics, Hematopoiesis genetics, Leukemia genetics, Neovascularization, Physiologic genetics
- Abstract
Although internal ribosome entry site (IRES)-mediated translation is considered important for proper cellular function, its precise biological role is not fully understood. Runx1 gene, which encodes a transcription factor implicated in hematopoiesis, angiogenesis, and leukemogenesis, contains IRES sequences in the 5' untranslated region. To clarify the roles of the IRES element in Runx1 function, we generated knock-in mice for either wild-type Runx1 or Runx1/Evi1, a Runx1 fusion protein identified in human leukemia. In both cases, native promoter-dependent transcription was retained, whereas IRES-mediated translation was eliminated. Interestingly, homozygotes expressing wild-type Runx1 deleted for the IRES element (Runx1(Delta IRES/Delta IRES)) died in utero with prominent dilatation of peripheral blood vessels due to impaired pericyte development. In addition, hematopoietic cells in the Runx1(Delta IRES/Delta IRES) fetal liver were significantly decreased, and exhibited an altered differentiation pattern, a reduced proliferative activity, and an impaired reconstitution ability. On the other hand, heterozygotes expressing Runx1/Evi1 deleted for the IRES element (Runx1(+/RE Delta IRES)) were born normally and did not show any hematological abnormalities, in contrast that conventional Runx1/Evi1 heterozygotes die in utero with central nervous system hemorrhage and Runx1/Evi1 chimeric mice develop acute leukemia. The findings reported here demonstrate the essential roles of the IRES element in Runx1 function under physiological and pathological conditions., ((c) 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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33. A novel cardiac myosin-binding protein C S297X mutation in hypertrophic cardiomyopathy.
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Hirota T, Kubo T, Kitaoka H, Hamada T, Baba Y, Hayato K, Okawa M, Yamasaki N, Matsumura Y, Yabe T, and Doi YL
- Subjects
- Adult, Aged, Aged, 80 and over, Atrial Fibrillation etiology, Cardiomyopathy, Hypertrophic physiopathology, Child, Echocardiography, Female, Heart Failure etiology, Humans, Hypertrophy, Left Ventricular genetics, Male, Middle Aged, Phenotype, Cardiomyopathy, Hypertrophic genetics, Carrier Proteins genetics, Codon, Nonsense
- Abstract
Background: Mutations in the cardiac myosin-binding protein C gene (MYBPC3) have been reported to be associated with delayed expression of hypertrophic cardiomyopathy (HCM) and a relatively good prognosis., Purpose: The aim of this study was to evaluate clinical manifestations in patients with familial HCM caused by a novel nonsense mutation, S297X, in MYBPC3., Methods: We analyzed the sarcomere protein genes in 93 probands with HCM., Results: The nonsense mutation S297X in MYBPC3 was present in nine subjects from two unrelated families. Eight of those nine subjects with this mutation were found to be phenotype-positive and the remaining individual was not affected phenotypically. The age range at diagnosis was 9-75 years. There was no family history of sudden death in either family. At presentation, there were various left ventricular hypertrophy (LVH) patterns, including Maron type III hypertrophy from the LV base to apex, hypertrophy confined to the anterolateral wall at the basal LV wall. Two patients showed a significant LV outflow tract gradient and one patient showed intra-right-ventricular obstruction. During follow-up, one patient was repeatedly hospitalized for the treatment of heart failure after development of paroxysmal atrial fibrillation at the age of 86 years and the remaining eight subjects were in relatively stable condition and did not require hospitalization for the treatment of HCM-related events., Conclusion: The novel mutation S297X in MYBPC3 causes HCM in a broad range of ages and heterogeneous clinical manifestations, though the clinical course in patients with this mutation seems to be benign., (Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2010
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34. Hemolytic anemia in a patient with hypertrophic obstructive cardiomyopathy.
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Kubo T, Kitaoka H, Terauchi Y, Tamura S, Okawa M, Yamasaki N, Yabe T, and Doi YL
- Subjects
- Aged, Anti-Arrhythmia Agents therapeutic use, Atenolol therapeutic use, Cardiomyopathy, Hypertrophic diagnosis, Echocardiography, Female, Humans, Imidazoles therapeutic use, Mitral Valve Insufficiency etiology, Ventricular Outflow Obstruction etiology, Anemia, Hemolytic etiology, Cardiomyopathy, Hypertrophic complications
- Abstract
A 66-year-old woman was referred for further evaluation and treatment of normocytic and normochromic anemia with hemoglobin level of 8.6 g/dL. A peripheral blood smear showed fragmented erythrocytes. The patient was then referred to the department of cardiology because of systolic murmur, ECG abnormality, and red cell fragmentation. Transthoracic echocardiography revealed hypertrophic cardiomyopathy with particularly increased interventricular septal thickness of 24 mm and a hyperkinetic wall motion, resulting in marked obstruction to left ventricular outflow tract (pressure gradient of 200 mmHg). Mitral regurgitation due to systolic anterior motion of the mitral valve leaflets was also seen. The cause of anemia was thought to be mechanical intravascular hemolysis due to left ventricular outflow tract obstruction and mitral regurgitation. She was treated with atenolol and the class Ia antiarrhythmic drug cibenzoline to relieve the outflow tract obstruction, and the pressure gradient was reduced to 70 mmHg. After 3 months of treatment, her hemoglobin level had increased to 11.4 g/dL without additional treatment for anemia., (2009 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2010
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35. Utility of tissue Doppler imaging to predict exercise capacity in hypertrophic cardiomyopathy: comparison with B-type natriuretic peptide.
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Kitaoka H, Kubo T, Okawa M, Hirota T, Hayato K, Yamasaki N, Matsumura Y, and Doi YL
- Subjects
- Adult, Aged, Biomarkers blood, Female, Humans, Male, Middle Aged, Natriuretic Peptide, Brain blood, Predictive Value of Tests, Cardiomyopathy, Hypertrophic diagnostic imaging, Cardiomyopathy, Hypertrophic physiopathology, Echocardiography, Doppler, Exercise Tolerance
- Abstract
Background: Recent reports suggest that left ventricular diastolic function assessed by tissue Doppler imaging (TDI) and plasma B-type natriuretic peptide (BNP) levels can relate to functional status in patients with hypertrophic cardiomyopathy (HCM). However, it is unclear which is more useful to predict the exercise capacity in HCM patients without systolic impairment and/or atrial fibrillation, TDI or BNP levels., Purpose: The present study directly compared the clinical relevance of assessing diastolic function using TDI and measuring the plasma BNP level in patients with HCM., Methods and Subjects: We evaluated diastolic function using TDI as well as plasma BNP levels in 31 patients (52.2+/-16.9 years of age; 20 males) with HCM and examined the relationship of these values to exercise capacity (peak O(2) consumption (VO(2))) measured by cardiopulmonary exercise tests., Results: Average peak VO(2) was 18.5+/-4.7 ml/(kg min). Although the E/A ratio by transmitral flow was not correlated with peak VO(2), the lateral E/E(a) ratio assessed by TDI was significantly correlated with peak VO(2) (r=-0.52, p=0.003). On the other hand, plasma BNP level was not significantly related to peak VO(2) but NYHA class., Conclusions: Assessment of diastolic function using TDI, not plasma BNP levels, is more useful for predicting objective exercise capacity in HCM patients without systolic impairment and/or atrial fibrillation.
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- 2009
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36. Enhanced expression of p210BCR/ABL and aberrant expression of Zfp423/ZNF423 induce blast crisis of chronic myelogenous leukemia.
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Miyazaki K, Yamasaki N, Oda H, Kuwata T, Kanno Y, Miyazaki M, Komeno Y, Kitaura J, Honda Z, Warming S, Jenkins NA, Copeland NG, Kitamura T, Nakamura T, and Honda H
- Subjects
- Animals, Blotting, Northern, Blotting, Southern, Blotting, Western, Bone Marrow Transplantation, Cell Proliferation, Colony-Forming Units Assay, DNA-Binding Proteins antagonists & inhibitors, Female, Flow Cytometry, Gene Rearrangement, Humans, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Male, Mice, Mice, Knockout, Phenotype, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Small Interfering pharmacology, Retroviridae, Reverse Transcriptase Polymerase Chain Reaction, Survival Rate, Transcription Factors antagonists & inhibitors, Zinc Fingers, B-Lymphocytes pathology, Blast Crisis genetics, DNA-Binding Proteins physiology, Fusion Proteins, bcr-abl physiology, Gene Expression Regulation, Leukemic, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Transcription Factors physiology
- Abstract
Chronic myelogenous leukemia (CML) is a hematopoietic disorder originating from p210BCR/ABL-transformed stem cells, which begins as indolent chronic phase (CP) but progresses into fatal blast crisis (BC). To investigate molecular mechanism(s) underlying disease evolution, CML-exhibiting p210BCR/ABL transgenic mice were crossed with BXH2 mice that transmit a replication-competent retrovirus. Whereas nontransgenic mice in the BXH2 background exclusively developed acute myeloid leukemia, p210BCR/ABL transgenic littermates developed nonmyeloid leukemias, in which inverse polymerase chain reaction detected 2 common viral integration sites (CISs). Interestingly, one CIS was transgene's own promoter, which up-regulated p210BCR/ABL expression. The other was the 5' noncoding region of a transcription factor, Zfp423, which induced aberrant Zfp423 expression. The cooperative activities of Zfp423 and p210BCR/ABL were demonstrated as follows: (1) introduction of Zfp423 in p210BCR/ABL transgenic bone marrow (BM) cells increased colony-forming ability, (2) suppression of ZNF423 (human homologue of Zfp423) in ZNF423-expressing, p210BCR/ABL-positive hematopoietic cells retarded cell growth, (3) mice that received a transplant of BM cells transduced with Zfp423 and p210BCR/ABL developed acute leukemia, and (4) expression of ZNF423 was found in human BCR/ABL-positive cell lines and CML BC samples. These results demonstrate that enhanced expression of p210BCR/ABL and deregulated expression of Zfp423/ZNF423 contribute to CML BC.
- Published
- 2009
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37. Improvement in prognosis of dilated cardiomyopathy in the elderly over the past 20 years.
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Kubo T, Matsumura Y, Kitaoka H, Okawa M, Hirota T, Hamada T, Hitomi N, Hoshikawa E, Hayato K, Shimizu Y, Yamasaki N, Yabe T, Nishinaga M, Takata J, and Doi Y
- Subjects
- Aged, Aged, 80 and over, Atrial Fibrillation epidemiology, Cardiomyopathy, Dilated drug therapy, Electrocardiography, Female, Follow-Up Studies, Humans, Japan epidemiology, Male, Prognosis, Ventricular Fibrillation epidemiology, Cardiomyopathy, Dilated mortality
- Abstract
Background and Purpose: Although dilated cardiomyopathy (DCM) had a poor prognosis in the past, recent studies have shown better survival. However, little is known about the improvement of prognosis in the elderly. This study sought to clarify the changes in prognosis in elderly patients with DCM over the past 20 years., Methods and Subjects: We studied 54 consecutive patients with DCM (38 men and 16 women, aged 65-83 years) who were diagnosed at over 65 years of age. The patients were divided into two groups (group A: 12 patients diagnosed before 1990; group B: 42 patients diagnosed after 1990) because after 1990, based on growing evidence from large-scale, randomized clinical studies, we intentionally increased the use of angiotensin-converting enzyme inhibitors (ACEI) and then beta-blockers at our hospital., Results: There were no significant differences in age, gender, NYHA functional class, and the prevalence of atrial fibrillation and ventricular tachycardia between the two groups. Left ventricular (LV) size assessed by echocardiography was larger (LV end-diastolic diameter, 67+/-5.9 versus 62+/-6.6 mm; p=0.039) and LV ejection fraction measured by left ventriculography was lower (ejection fraction, 24+/-9 versus 35+/-10%; p=0.004) in group A. ACEI/angiotensin II type 1 receptor blockers (ARB) (0% versus 88%) or beta-blockers (0% versus 52%) were more frequently used in group B. Antiarrhythmics (class Ia or Ib) (75% versus 14%) were less often used in group B. The 5- and 10-year event-free survival rates for cardiac death were 75.4% and 22.0% in group A versus 81.2% and 71.3% in group B (log-rank test, p=0.014)., Conclusions: The prognosis of DCM patients in the elderly has significantly improved over the past 20 years. The advances in the pharmacologic treatment and earlier diagnosis may have contributed to the better survival.
- Published
- 2008
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38. Hypertrophic cardiomyopathy with mild left ventricular remodeling: echocardiographic assessment using left ventricular wall motion score.
- Author
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Hayato K, Okawa M, Matsumura Y, Kitaoka H, Kubo T, Hitomi N, Yamasaki N, Yabe T, Furuno T, Takata J, Nishinaga M, and Doi YL
- Subjects
- Adult, Aged, Child, Female, Heart Ventricles diagnostic imaging, Humans, Male, Middle Aged, Myocardial Contraction, Ventricular Function, Cardiomyopathy, Hypertrophic diagnostic imaging, Cardiomyopathy, Hypertrophic physiopathology, Echocardiography methods, Ventricular Remodeling
- Abstract
Objectives: The present study sought to investigate the echocardiographic features of hypertrophic cardiomyopathy (HCM) with mild left ventricular (LV) remodeling, particularly in relation to wall motion abnormalities., Methods: Among the 137 consecutive patients with HCM, 13 patients (mean age 52 +/- 13 years) who progressed to mild LV systolic dysfunction (LV ejection fraction (LVEF) of 35-50%) were studied. By reviewing the echocardiograms of these patients, wall motion score index (WMSI) was scored using 16 segments model., Results: HCM patients with mild LV systolic dysfunction exhibited mild LV dilatation, mild left atrial dilatation, septal hypertrophy, and LV wall motion impairment localized in the septal and apical regions (septal WMSI 1.94 +/- 0.33 vs. total WMSI 1.51 +/- 0.25 and posterior WMSI 1.02 +/- 0.07; p < 0.001). During follow-up, further deterioration of LV systolic function (LVEF< 35%) was noted in five patients, who had less severe hypertrophy at the initial echocardiograms. These patients developed progressive LV cavity enlargement and more severe and extensive wall motion abnormalities, accompanied by septal akinesis and wall thinning, although posterolateral wall motion impairment was relatively mild (posterior WMSI 1.80 +/- 0.27 vs. septal WMSI 2.95 +/- 0.11; p < 0.001)., Conclusions: Septal and apical wall motions are reduced in HCM with mild LV remodeling. As LV dysfunction progresses, septal akinesis and wall thinning develop and LV cavity enlargement becomes more prominent, though posterolateral wall motion impairment is relatively mild.
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- 2008
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39. Upstaging by vessel invasion improves the pathology staging system of non-small cell lung cancer.
- Author
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Tsuchiya T, Hashizume S, Akamine S, Muraoka M, Honda S, Tsuji K, Urabe S, Hayashi T, Yamasaki N, and Nagayasu T
- Subjects
- Adult, Aged, Aged, 80 and over, Blood Vessels pathology, Female, Humans, Male, Middle Aged, Neovascularization, Pathologic pathology, Predictive Value of Tests, Prognosis, Regression Analysis, Retrospective Studies, Survival Rate, Carcinoma, Non-Small-Cell Lung blood supply, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms blood supply, Lung Neoplasms pathology, Neoplasm Invasiveness, Neoplasm Staging methods
- Abstract
Background: There is a need for a more complete classification system of lung cancer. To address this issue, we assessed whether the new staging could differentiate patients with early-stage cancers who have poorer prognosis and improve the unbalanced patient numbers with overlapping prognoses arising from the current TNM staging system., Methods: The study included 995 patients with pathology stages I and II non-small cell lung cancer (NSCLC) who underwent surgical resection at two institutions. We subclassified patients with stage IA and IB NSCLC based on the presence of vessel invasion (Vi). Stage IA Vi and stage IB non-Vi were combined into new stage IB, as were stages IB Vi and IIA into new stage IIA., Results: The numbers of patients of stages IA, IB, IIA, and IIB were 477, 314, 55, and 149, and their 5-year survival rates were 86.0%, 66.2%, 60.7%, and 50.4%, respectively. Vi groups showed significantly poorer prognosis than non-Vi groups at stage IA (p = 0.011) and at stage IB (p = 0.036). The numbers of patients of new stages IA, IB, and IIA were 333, 260, and 253, and their 5-year survival rates were 88.7%, 76.4%, and 61.2%, respectively. Regression analysis indicated that the new staging improved predictability of overall survival according to disease stage, and Akaike information criterion (3023.7) was significantly lower than that for current staging system (3032.5)., Conclusion: Upstaging of Vi groups allows differentiation of patients with early-stage cancers with poor prognosis and improves the unbalanced numbers of patients and prediction of prognosis in cases of lung cancer.
- Published
- 2007
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40. Impact of brain-behavior phenotypying of genetically-engineered mice on research of neuropsychiatric disorders.
- Author
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Takao K, Yamasaki N, and Miyakawa T
- Subjects
- Animals, Disease Models, Animal, Humans, Mice, Phenotype, Behavior, Animal physiology, Brain physiology, Mental Disorders genetics, Mental Disorders pathology, Mental Disorders physiopathology, Mice, Transgenic anatomy & histology, Mice, Transgenic genetics, Mice, Transgenic physiology
- Abstract
Despite massive research efforts, the exact pathogenesis and pathophysiology of psychiatric disorders, such as schizophrenia and bipolar disorder, remain largely unknown. Animal models can serve as essential tools for investigating the etiology and treatment of such disorders. Since the introduction of gene targeting techniques, the functions of more than 10% of all known mouse genes have been investigated by creating mutant mice. Some of these mutant mouse strains were found to exhibit behavioral abnormalities reminiscent of human psychiatric disorders. In this review, we discuss the general requirements for animal models of human psychiatric disorders. We also outline our unique approach of extrapolating findings in mice to humans, and present studies on forebrain-specific calcineurin knockout mice as an example. We also discuss the impact of a large-scale mouse phenotyping on studies of psychiatric disorders and the potential utility of an "animal-model-array" of psychiatric disorders for the development of suitable therapeutic agents.
- Published
- 2007
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41. Severe tricuspid regurgitation in the aged: atrial remodeling associated with long-standing atrial fibrillation.
- Author
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Yamasaki N, Kondo F, Kubo T, Okawa M, Matsumura Y, Kitaoka H, Yabe T, Furuno T, and Doi Y
- Subjects
- Aged, Aged, 80 and over, Atrial Natriuretic Factor metabolism, Female, Follow-Up Studies, Heart Failure etiology, Humans, Male, Retrospective Studies, Severity of Illness Index, Syndrome, Atrial Fibrillation complications, Heart Atria pathology, Tricuspid Valve Insufficiency etiology, Tricuspid Valve Insufficiency physiopathology
- Abstract
Objectives: Severe idiopathic tricuspid regurgitation (TR) occurs in the aged, but the mechanism of TR is unclear and there is little information on atrial abnormalities associated with this condition. This study retrospectively analyzed patients with severe functional TR presenting with common clinical features suggesting a distinct syndrome., Methods: Eleven patients with severe functional TR were identified by reviewing the records of 16,235 consecutive patients. All patients had undergone clinical evaluation including echocardiography, electrocardiography and laboratory data., Results: The median age of patients with severe functional TR was 78 years. All had a long-standing history of atrial fibrillation (median duration, 23 years). Clinical features are characterized by severe functional TR due to annular dilation, markedly dilated right atrium, episodes of right-sided heart failure, absent or diminished fibrillation waves on electrocardiogram, bradycardia probably due to partial atrial standstill, and decreased atrial natriuretic peptide secretion. During long-term follow up, right atrial size progressively increased in association with worsening TR., Conclusions: Severe functional TR occurs with long-standing atrial fibrillation and causes right-sided heart failure. The TR is caused by tricuspid valve systolic coaptation loss due to tricuspid annular dilation associated with atrial dilation. This condition is associated with atrial abnormalities, such as atrial standstill and impaired atrial natriuretic peptide secretion. We propose that atrial remodeling associated with atrial fibrillation is central to the occurrence of the syndrome.
- Published
- 2006
42. [Discrete subaortic stenosis with pressure recovery: a case report].
- Author
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Hoshikawa E, Matsumura Y, Okawa M, Hitomi N, Yamasaki N, Kitaoka H, Furuno T, Takata J, and Doi Y
- Subjects
- Blood Pressure, Discrete Subaortic Stenosis physiopathology, Electrocardiography, Female, Humans, Middle Aged, Cardiac Catheterization, Discrete Subaortic Stenosis diagnosis, Echocardiography, Doppler
- Abstract
A 54-year-old woman with subvalvular aortic stenosis was admitted to our hospital. The pressure gradient across the left ventricular outflow tract was estimated as 88 mmHg (peak) and 45 mmHg (mean) by Doppler echocardiography, but only 14 mmHg (peak to peak) and 31 mmHg (mean) by cardiac catheterization. We considered this discrepancy attributable to the presence of moderate aortic regurgitation and the pressure recovery phenomenon. Pressure recovery has clinical relevance particularly in a patient with tunnel-like stenosis, with gradual lumen re-expansion beyond the limiting orifice. Therefore, if Doppler echocardiography shows significant left ventricular outflow tract gradient, precise evaluation of the stenosis geometry is required to investigate the effect of pressure recovery.
- Published
- 2005
43. [Aortic stenosis and mitral regurgitation complicated by hemolytic anemia and positive Direct Coombs test: a case report].
- Author
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Tamura S, Kitaoka H, Yamasaki N, Okawa M, Kubo T, Matsumura Y, Furuno T, Takata J, Nishinaga M, Sasaguri S, and Doi Y
- Subjects
- Aged, Aged, 80 and over, Anemia, Hemolytic, Autoimmune diagnosis, Heart Valve Prosthesis Implantation, Humans, Male, Mitral Valve surgery, Mitral Valve Insufficiency surgery, Anemia, Hemolytic, Autoimmune etiology, Aortic Valve Stenosis complications, Coombs Test methods, Mitral Valve Insufficiency complications
- Abstract
A 83-year-old man was admitted because of heart failure due to severe aortic stenosis and mitral regurgitation secondary to chordal rupture of the anterior leaflet. Mild anemia and elevated serum lactate dehydrogenase were present with reticulocytosis and haptoglobinemia. Direct Coombs test was positive. Coexistence of autoimmune hemolytic anemia was identified, but the main cause of his hemolysis was thought to be mechanical hemolysis due to stenotic valve and/or ruptured chordae because of the presence of red cell fragmentation. The patient successfully underwent double valve replacement. Improvement of anemia was coupled with reduction of the serum lactate dehydrogenase level. Valvular shear stress on the red cells and reduction of red cell deformability secondary to autoimmune hemolytic anemia were thought to be responsible for his hemolysis.
- Published
- 2005
44. Thallium scintigraphy for the prognosis of idiopathic dilated cardiomyopathy.
- Author
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Yabe T, Furuno T, Kitaoka H, Matsumura Y, Yamasaki N, and Doi Y
- Subjects
- Cardiomyopathy, Dilated mortality, Female, Humans, Male, Middle Aged, Prognosis, Radionuclide Imaging, Survival Rate, Thallium Radioisotopes, Cardiomyopathy, Dilated diagnostic imaging
- Abstract
Objectives: This study evaluated the significance of perfusion defects demonstrated by thallium-201 and age in the prognosis of patients with idiopathic dilated cardiomyopathy., Methods: Seventy-four dilated cardiomyopathy patients underwent thallium scintigraphy as well as clinical and hemodynamic examination., Results: Abnormal perfusion defects were present in 23 of 38 patients aged < 60 years (61%) and in 26 of 36 elderly patients aged > or = 60 years (72%; NS). Univariate analysis showed that such perfusion defects were a significant predictor of cardiac death only in patients aged < 60 years (p = 0.015). Stepwise discriminant analysis also revealed that perfusion defects were a significant predictor in patients aged < 60 years (Wilks' lambda 0.499, chi-square test 20.2, p = 0.003). Perfusion defects were not more important than the history of syncope or stroke in elderly dilated cardiomyopathy patients. Twenty-one patients died of disease-related causes during 58 +/- 43 months. The five-year survival rate was better in patients aged < 60 years without than in those with perfusion defects (100% vs 58.4%, respectively), but not affected in patients aged > or = 60 years (66.7% vs 62.2%)., Conclusions: Thallium scintigraphy is valuable for the prognosis of patients with dilated cardiomyopathy aged < 60 years who are usually candidates for heart transplantation. Absence of thallium perfusion defects may indicate good long-term prognosis.
- Published
- 2002
45. Myocardial enhancement on magnetic resonance imaging with gadolinium-diethylenetriamine pentaacetic acid and improvement of left ventricular function in patients with dilated cardiomyopathy.
- Author
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Akisawa M, Matsumura Y, Kitaoka H, Yamasaki N, Takata J, and Doi Y
- Subjects
- Adult, Aged, Cardiac Catheterization, Cardiomyopathy, Dilated diagnosis, Echocardiography, Doppler, Color, Echocardiography, Doppler, Pulsed, Electrocardiography, Ambulatory, Female, Follow-Up Studies, Humans, Male, Middle Aged, Prognosis, Cardiomyopathy, Dilated physiopathology, Contrast Media, Gadolinium DTPA, Magnetic Resonance Imaging, Ventricular Function, Left physiology
- Abstract
Objectives: This study evaluated the significance of myocardial gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement on magnetic resonance imaging for the improvement of left ventricular function in patients with dilated cardiomyopathy., Methods: Twenty-seven patients with dilated cardiomyopathy (mean age 59 +/- 11 years) were studied. The magnitude of myocardial Gd-DTPA enhancement was quantitatively assessed using signal intensity ratio and compared to changes in left ventricular function and adverse cardiac events during a relatively long follow-up period., Results: Regional high signal intensity ratio, defined as > or = mean + 2SD in seven normal subjects, was found in 14 patients: in three or more regions out of five myocardial regions analyzed in six patients (extensive enhancement) and in only one or two regions in eight patients (limited enhancement). The remaining 13 patients had no high signal ratio in any of the five regions analyzed (no enhancement). During the follow-up period of 3.9 +/- 1.9 years, four patients died of cardiac causes. The incidence of cardiac death was 33.3% in patients with extensive enhancement, 12.5% in those with limited enhancement and 7.7% in those without enhancement, but there was no statistical difference. Mild improvement in fractional shortening was observed in patients without enhancement during the follow-up (19 +/- 4%-->27 +/- 10%, p = 0.03)., Conclusions: Evaluation of myocardial Gd-DTPA enhancement on magnetic resonance imaging may provide useful prognostic information for patients with dilated cardiomyopathy.
- Published
- 2002
46. Crystal structures of the ribonuclease MC1 from bitter gourd seeds, complexed with 2'-UMP or 3'-UMP, reveal structural basis for uridine specificity.
- Author
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Suzuki A, Yao M, Tanaka I, Numata T, Kikukawa S, Yamasaki N, and Kimura M
- Subjects
- Amino Acid Sequence, Crystallography, X-Ray, Molecular Sequence Data, Mutagenesis, Site-Directed, Ribonucleases chemistry, Ribonucleases genetics, Sequence Homology, Amino Acid, Substrate Specificity, Uridine Monophosphate chemistry, Ribonucleases metabolism, Uridine metabolism, Uridine Monophosphate metabolism
- Abstract
Ribonuclease MC1 (RNase MC1) isolated from seeds of bitter gourd (Momordica charantia) consists of 190 amino acids and is characterized by a preferential cleavage at the 5'-side of uridine. This uridine specificity distinguishes RNase MC1 from other enzymes belonging to the RNase T2 family. The three-dimensional structures of RNase MC1, in a complex with either 2'-UMP or 3'-UMP, were determined at 1.48 and 1.77 A resolutions, respectively. The side chains of Gln9 and Asn71 interact with O4 and N3, respectively, of the uracil base by hydrogen bondings. In addition, the uracil base is sandwiched by the hydrophobic side chains of Leu73 and Phe80. Compared with these amino acid residues and corresponding residues in RNases in the RNase T2 family, Gln9 and Phe80 are highly conserved in the RNases in T2 family, while Asn71 and Leu73 in RNase MC1 are variant in sequences. It is thus likely that interactions of the side chains of Asn71 and Leu73 with the uracil base are responsible for the absolute uridine specificity of RNase MC1. Site-directed mutagenesis experiments showed that replacement of Asn by Thr decreased both the catalytic efficiency and the binding affinity by 2.3- and 7.0-fold, respectively, and substitution of Leu73 for Ala predominantly decreased the binding affinity by 14. 5-fold, compared with findings in case of wild-type RNase MC1. It is thus demonstrated that Asn71 and Leu73 play an essential role in uridine preference for RNase MC1., (Copyright 2000 Academic Press.)
- Published
- 2000
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47. An assay for lectin activity using microtiter plate with chemically immobilized carbohydrates.
- Author
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Hatakeyama T, Murakami K, Miyamoto Y, and Yamasaki N
- Subjects
- Animals, Body Fluids chemistry, Carbohydrate Metabolism, Carrier Proteins analysis, Carrier Proteins metabolism, Evaluation Studies as Topic, Gold Colloid, Lectins metabolism, Methods, Sea Cucumbers, Carbohydrates, Lectins analysis
- Abstract
A simple microtiter plate assay for lectins or carbohydrate-binding proteins was developed. The method utilizes carbohydrates immobilized in the wells of the microtiter plate containing primary amino groups on their surface. After incubation of the lectins, bound proteins are measured by the protein assay using the colloidal gold solution. When the binding of Ricinus communis agglutinin, concanavalin A, and wheat germ agglutinin was measured using the microtiter plate wells coated with lactose, mannose, or N-acetylglucosamine, binding of the lectins according to their known specificity was observed. Inhibition experiments with various carbohydrates also demonstrated that the specificity of lectins for different carbohydrates could be determined quantitatively. Since there is no need for modification of the lectins, such as biotinylation or conjugation with marker enzymes, the carbohydrate-binding ability of intact proteins can be easily determined by this method. When gel filtration fractions from the extract of the marine invertebrate Cucumaria echinata were subjected to this assay, different carbohydrate-binding activities were observed with different elution profiles, suggesting that this assay could also be widely applicable for the simultaneous detection of lectins from various sources.
- Published
- 1996
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48. Cloning of a cDNA coding for porcine zona pellucida glycoprotein ZP1 and its genomic organization.
- Author
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Taya T, Yamasaki N, Tsubamoto H, Hasegawa A, and Koyama K
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Blotting, Northern, Blotting, Southern, Cloning, Molecular, DNA Primers, DNA, Complementary, Female, Humans, In Situ Hybridization, Mice, Molecular Sequence Data, Organ Specificity, RNA Probes, Restriction Mapping, Sequence Homology, Amino Acid, Transcription, Genetic, Zona Pellucida Glycoproteins, Egg Proteins biosynthesis, Egg Proteins genetics, Membrane Glycoproteins biosynthesis, Membrane Glycoproteins genetics, Ovary metabolism, Receptors, Cell Surface, Swine genetics, Zona Pellucida metabolism
- Abstract
The zona pellucida composed of three or four glycoproteins plays important roles in fertilization. Our previous study showed that porcine ZP1, one of the major glycoproteins of porcine zona pellucida, was divided into two components (porcine ZP4 and ZP2), and suggested it was a homologue of mouse ZP2. In this paper we report the cloning of a cDNA for porcine ZP1 and its genomic organization. The deduced amino acid sequence of porcine ZP1 shared a 54% and 63% identity with those of mouse and human ZP2, respectively. Genomic organization of porcine ZP1 was also similar to that of mouse ZP2. The transcript of porcine ZP1 gene was detected only in growing oocytes.
- Published
- 1995
- Full Text
- View/download PDF
49. Sequence of a rabbit sperm zona pellucida binding protein and localization during the acrosome reaction.
- Author
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Richardson RT, Yamasaki N, and O'Rand MG
- Subjects
- Acrosome chemistry, Amino Acid Sequence, Animals, Antigens, Surface, Autoantigens genetics, Base Sequence, Calmodulin-Binding Proteins, Carrier Proteins metabolism, Cloning, Molecular, DNA Primers chemistry, DNA, Complementary genetics, Dextrans metabolism, Female, Gene Expression, Humans, Lectins metabolism, Male, Membrane Proteins, Mice, Molecular Sequence Data, Protein Kinases chemistry, RNA, Messenger genetics, Rabbits, Sequence Alignment, Sequence Homology, Amino Acid, Sperm-Ovum Interactions, Testis metabolism, Acrosome metabolism, Carrier Proteins genetics, Zona Pellucida metabolism
- Abstract
The interaction of the mammalian spermatozoon with the oocyte's extracellular matrix or zona pellucida is a critical first step leading to successful fertilization. In this cell-extracellular matrix interaction it is the carbohydrate of the zona pellucida which serves as the sperm receptor and the surface of the spermatozoon which provides the lectin-like adhesion molecules. To better understand sperm-zona pellucida binding we have analyzed one specific zona binding protein (ZBP). This study has determined the mRNA sequence encoding a mammalian testis and sperm specific protein of 16,891 Da, which we have designated Sp17. Analysis of Sp17 revealed that the mRNA is present in rabbit, mouse, and human testes but not in any somatic tissue tested. In the rabbit, Sp17 is the 17-kDa member of the rabbit sperm autoantigen family of sperm specific autoantigens and is encoded by two mRNAs of 0.9 and 1.1 kb. Each mRNA has a unique 5' untranslated region but both have identical coding regions. The deduced amino acid sequence of the Sp17 ZBP showed several interesting features, including a similarity to the N-terminal of human testis cAMP-dependent protein kinase. Localization of Sp17 on live spermatozoa using antibodies to recombinant Sp17 or to the Sp17 peptide, G22C, revealed that the peptide backbone of Sp17 is inaccessible until the acrosome reaction begins. However, on paraformaldehyde fixed, acrosome intact spermatozoa, the peptide backbone is accessible to the antibodies which localize Sp17 to the apical surface. In the rabbit as well as other similar species in which the corona radiata (granulosa) cells adhere tightly to the zona pellucida and synthesize zona glycoproteins, the fertilizing spermatozoon may have already begun the acrosome reaction within the cumulus oophorus. Thus, the rabbit sperm surface would be modified to expose the Sp17 polypeptide during the final phase of cumulus passage and consequently Sp17 would be available for initial zona binding. The present study has also demonstrated that recombinant Sp17 can bind zona pellucida, dextran, and dextran sulfate.
- Published
- 1994
- Full Text
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50. Botulinum neurotoxin type G proteolyses the Ala81-Ala82 bond of rat synaptobrevin 2.
- Author
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Yamasaki S, Binz T, Hayashi T, Szabo E, Yamasaki N, Eklund M, Jahn R, and Niemann H
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Binding Sites genetics, Botulinum Toxins chemistry, Botulinum Toxins genetics, DNA Primers genetics, Endopeptidases chemistry, Endopeptidases genetics, Endopeptidases toxicity, In Vitro Techniques, Membrane Proteins genetics, Molecular Sequence Data, Nerve Tissue Proteins genetics, Neurotransmitter Agents metabolism, Protein Conformation, R-SNARE Proteins, Rats, Sequence Deletion, Substrate Specificity, Synaptic Vesicles drug effects, Synaptic Vesicles physiology, Botulinum Toxins toxicity, Membrane Proteins metabolism, Nerve Tissue Proteins metabolism
- Abstract
Tetanus toxin and the botulinum neurotoxins types A to F inhibit neurotransmitter release from presynaptic nerve endings by selectively proteolysing the synaptic proteins synaptobrevin, syntaxin, or SNAP-25. Here, we show that botulinum toxin type G cleaves rat synaptobrevin 2 between Ala81 and Ala82, a peptide bond that differs from those attacked by tetanus toxin and the botulinal toxins types B, D, and F. Synaptobrevin isoforms carrying a Gly in the P1 position are poor substrates. Analyses of N-terminal deletion mutants of rat synaptobrevin 2 showed that a substrate starting at Leu54 is cleaved efficiently, whereas substrates beginning at Leu60 or Phe77 are cleaved partially or not at all, respectively.
- Published
- 1994
- Full Text
- View/download PDF
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