Juhlin C.C.,Karolinska University Hospital |
Haglund F.,Karolinska University Hospital |
Obara T.,Tokyo Womens Medical College |
Arnold A.,University of Connecticut |
And 2 more authors.
Virchows Archiv | Year: 2011
Hyperparathyroidism 2 (HRPT2) gene mutations underlie hereditary and sporadic forms of primary hyperparathyroidism (PHPT), and the encoded product parafibromin has been established as a marker for facilitating parathyroid tumour classification. HRPT2 mutations and reduced nuclear expression of parafibromin are readily observed in parathyroid carcinomas but rarely in benign tumours, thereby aiding the identification of malignant PHPT. Recently, parafibromin has been shown to localize to the nucleolar compartment, and nucleolar parafibromin exhibits tumour-suppressive properties in vitro. In this study, nucleolar parafibromin immunoreactivity was assessed by high-power magnification microscopy in 82 parathyroid tumours previously analysed for nuclear parafibromin, including 23 carcinomas, 16 atypical adenomas, and 43 adenomas. Absent nucleolar expression was evident in three carcinomas and in one atypical adenoma, which also showed expression of nuclear parafibromin in all or subsets of the tumour cells. All three carcinomas carried HRPT2-inactivating mutations predicted to abolish the three nucleolar localization signals of parafibromin. The demonstrated absence of nucleolar parafibromin in three carcinomas with HRPT2 mutations suggests that parafibromin exhibits nucleolar tumour suppressor properties also in vivo, and disruption of nucleolar localization might propel parathyroid tumorigenesis independent of nuclear parafibromin expression. The loss of nucleolar staining in the presence of nuclear parafibromin suggests that parafibromin immunoreactivity should also be assessed in the nucleoli, as the sensitivity for the detection of malignant and atypical PHPT is increased compared to scoring of nuclear parafibromin alone. © 2011 Springer-Verlag.
PubMed | Red Cross, Juntendo University, National Hospital Organization, Kansai Medical University and 16 more.
Type: Comparative Study | Journal: Clinical colorectal cancer | Year: 2015
The usefulness of adjuvant chemotherapy for stage II colon cancer has not been established. Meanwhile, the presence of stage II colon cancer with high-risk factors for recurrence has been reported. To our knowledge, no prospective study of adjuvant chemotherapy for stage II colon cancer with high-risk factors has been implemented to date.This study is a prospective nonrandomized controlled study based on patients selection of treatment option, including randomized therapeutic decision-making, to evaluate the usefulness of adjuvant chemotherapy with tegafur-uracil (UFT) with leucovorin (LV) for stage II colon cancer with high-risk factors for recurrence, compared with surgery alone. Five courses of UFT/LV therapy will be given as follows: UFT (300 mg/m(2)/d) with LV (75 mg/d) will be orally administered in 3 doses per day. Treatment will be received daily for 28 days, followed by a 7-day rest or will be received daily for 5 days, followed by a 2-day rest. For both regimens, 1 course will last 5 weeks, and 5 courses will be given. The primary end point is disease-free survival. A propensity score matching will be conducted based on 7 variables that represent risk factors to minimize selection bias in a comparison between the nonrandomized arms. For this nonrandomized comparison, a target sample size is set at 1200 (400 and 800 patients for the surgery alone and UFT/LV groups, respectively) and 1720 patients will be enrolled. In this study we aim to evaluate the therapeutic usefulness of adjuvant chemotherapy with UFT/LV for stage II colorectal cancer with risk factors for recurrence.
Nakai K.,Iwate Medical University |
Takahashi S.,Iwate Medical University |
Suzuki A.,Tokyo Womens Medical College |
Hagiwara N.,Tokyo Womens Medical College |
And 7 more authors.
Heart and Vessels | Year: 2011
The noninvasive evaluation of ventricular T-wave alternans (TWA) in patients with lethal ventricular arrhythmias is an important issue. In this study, we propose a novel algorithm to identify T-wave current density alternans (TWCA) using synthesized 187-channel vector-projected body surface mapping (187-ch SAVP-ECG). We recorded 10 min of 187-ch SAVP-ECG using a Mason-Likar lead system in the supine position. A recovery time (RT) dispersion map was obtained by averaging the 187-ch SAVP-ECG. The TWCA value was determined from the relative changes in the averaged current density in the T-wave zone (Tpeak ± 50 ms) for two T-wave types. We registered 20 ECG recordings from normal controls and 11 ECG recordings from nine subjects with long QT syndrome (LQT). We divided LQT syndrome subjects into two groups: group 1 provided 9 ECG recordings without visually apparent TWAs, and group 2 provided 2 ECG recordings with visually apparent TWAs. The QTc interval values in the LQT groups were higher than those in the control (515 ± 60 ms in LQT G-1, 600 ± 27 ms in LQT G-2 vs. 415 ± 19 ms in control, P < 0.001). The RTendc dispersion values among the LQT subjects were higher than those of the control subjects (48 ± 19 ms in LQT G-1, 65 ± 30 ms in LQT G-2 vs. 24 ± 10 ms in control, P < 0.01). The mean TWCA value was significantly higher in the LQT G-2 group with visually apparent TWCAs (0.5 ± 0.2% in control, 2.1 ± 1.2% in LQT G-1, and 32.3 ± 6.9% in LQT G-2). Interestingly, the two-dimensional distribution of TWCA in LQT was inhomogeneous and correlated with the distribution of increased RT dispersion. We conclude that a novel algorithm using 187-ch SAVP-ECG might provide new insights into body surface TWCA. © 2010 Springer.
Miyatake S.-I.,Osaka Medical College |
Furuse M.,Osaka Medical College |
Kawabata S.,Osaka Medical College |
Maruyama T.,Tokyo Womens Medical College |
And 3 more authors.
Neuro-Oncology | Year: 2013
BackgroundBevacizumab, an anti-vascular endothelial growth factor antibody, has been used for the treatment of radiation necrosis. Thus far, however, there has been no definitive report on its use for the treatment of symptomatic pseudoprogression. Here we report 2 cases of successful treatment with bevacizumab for symptomatic pseudoprogression after boron neutron capture therapy (BNCT) was applied for recurrent malignant gliomas.MethodsTwo recurrent malignant gliomas received BNCT. Both cases were treated with intravenous administration of bevacizumab at the deterioration that seemed to be symptomatic pseudoprogression.ResultsThe first case was recurrent glioblastoma multiforme and the second was recurrent anaplastic oligoastrocytoma. Both cases recurred after standard chemoradiotherapy and were referred to our institute for BNCT, which is tumor-selective particle radiation. Just prior to neutron irradiation, PET with an amino acid tracer was applied in each case to confirm tumor recurrence. Both cases showed deterioration in symptoms, as well as on MRI, at intervals of 4 months and 2 months, respectively, after BNCT. For the first case, a second PET was applied in order to confirm no increase in tracer uptake. We diagnosed both cases as symptomatic pseudoprogression and started the intravenous administration of 5 mg/kg bevacizumab biweekly with 6 cycles. Both cases responded well to this, showing rapid and dramatic improvement in neuroimaging and clinical symptoms. No tumor progression was observed 8 months after BNCT.ConclusionsBevacizumab showed marked effects on symptomatic pseudoprogression after BNCT. BNCT combined with bevacizumab may prolong the survival of patients with recurrent malignant gliomas. © 2013 The Author(s).
Motoyama O.,Toho University |
Hasegawa A.,Toho University |
Aikawa A.,Toho University |
Shishido S.,Tokyo Metropolitan Kiyose Childrens Hospital |
And 9 more authors.
Pediatric Transplantation | Year: 2012
A prospective trial of corticosteroid (steroid) withdrawal after pediatric renal transplantation was started in 1990. Fifty-eight recipients with functioning grafts reached their final height. They were transplanted at a mean age of 10.7 yr. Immunosuppressive therapy with CyA, MP, and MZ was started after transplantation. MP was reduced to an alternate-day dose in 49 patients and was withdrawn in 23. Their mean height SDS was -2.4 at the time of transplantation and -2.1 at their final height. Mean final height was 157.9 cm in men and 147.6 cm in women. In 18 patients who had been withdrawn from MP for more than two yr before reaching final height, mean age at transplantation was 8.9 yr. Their mean height SDS of -2.2 at the time of transplantation increased to -1.6 at their final height (p = 0.02), and mean final height was 163.8 cm in men and 147.8 cm in women. The height SDS in all 58 patients was maintained during the immunosuppressive therapy with steroid minimization, and final height SDS increased in recipients older than five yr at transplantation with steroid withdrawal. © 2011 John Wiley & Sons A/S.
Yamaya M.,Tohoku University |
Azuma A.,Nippon Medical School |
Takizawa H.,Kyorin University |
Kadota J.-I.,Oita University |
And 2 more authors.
European Respiratory Journal | Year: 2012
The number of senile patients with chronic obstructive pulmonary disease (COPD) has recently increased due to an increase in life expectancy, the habit of smoking and the inhalation of toxic particles. COPD exacerbations are caused by airway bacterial and viral infections, as well as the inhalation of oxidative substrates. COPD exacerbations are associated with the worsening of symptoms and quality of life, as well as an increased mortality rate. Several drugs, including long-acting anti-cholinergic agents, long-acting β2-agonists and inhaled corticosteroids, have been developed to improve symptoms in COPD patients and to prevent COPD exacerbations. Treatment with macrolide antibiotics has been reported to prevent COPD exacerbations and improve patient quality of life and symptoms, especially in those patients who have frequent exacerbations. In addition to their antimicrobial effects, macrolides have a variety of physiological functions, such as anti-inflammatory and anti-viral effects, reduced sputum production, the inhibition of biofilm formation and the inhibition of bacterial virulence factor production. These unique activities may relate to the prevention of exacerbations in COPD patients who receive macrolides. Herein, we review the inhibitory effects that macrolides have on COPD exacerbations and explore the possible mechanisms of these effects. Copyright©ERS 2012.
Isojima T.,University of Tokyo |
Harita Y.,University of Tokyo |
Furuyama M.,Tokyo Womens Medical College |
Sugawara N.,Tokyo Womens Medical College |
And 7 more authors.
Nephrology Dialysis Transplantation | Year: 2014
BackgroundNail-patella syndrome (NPS) is a rare autosomal-dominant disorder caused by LMX1B mutation. In patients with the renal lesions typical of NPS without skeletal or nail findings, it is described as nail-patella-like renal disease (NPLRD). However, the pathogenesis of NPLRD is largely unknown.MethodsA 6-year-old girl with microscopic haematuria and mild proteinuria was diagnosed with NPLRD because of an aberrantly thickened glomerular basement membrane (GBM) and deposition of Type III collagen in the GBM observed by electron microscopy. Immunohistological analyses of podocyte protein expression were performed on biopsy tissues. Sequence analysis of LMX1B was performed, and the functional consequences of the detected mutation were analysed by luciferase reporter assay.ResultsWhen analysing molecules that are important for podocyte development, maintenance and maturation, CD2AP expression was found to be altered in the podocytes. A novel LMX1B missense mutation (R246Q) was identified. Functional analyses revealed partial but significant impairment of R246Q transcriptional activity. However, no dominant-negative effect of R246Q was detected, which suggests that NPLRD is caused by LMX1B haploinsufficiency. ConclusionsThis is the first report on LMX1B mutation identified in a patient with NPLRD. Residual transcriptional activity would account for normality of the nails and patella in this case. Genetic and pathological analyses of additional cases would clarify the role of LMX1B in glomerulopathy without systemic symptoms, which, together with nephropathy in NPS, can be designated as 'LMX1B nephropathy'. © 2013 The Author.
PubMed | Tokyo Womens Medical College and Tokyo Medical and Dental University
Type: Journal Article | Journal: Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology | Year: 2015
Many factors, including superoxides, contribute to tissue damage in acute myocardial infarction (AMI). Excess nitric oxide (NO) produced by inducible NO synthase (iNOS) has also been reported to participate in myocardial injury associated with AMI, but its exact role remains unclear. To elucidate the role of NO and peroxynitrite in the pathogenesis of myocardial injury associated with AMI, we examined the expression of iNOS in the autopsied specimens of the left ventricle obtained from 15 patients with AMI and five with old MI by immunohistochemistry using an anti-iNOS polyclonal antibody. The distribution of nitrotyrosine was also examined immunohistochemically. In patients who died from 12 hours to 3 weeks after the infarction, positive immunoreactivity for iNOS was observed in residual myocytes, macrophages, and vascular endothelial cells in the peri-infarcted area. Degenerating myocytes in that area in all of that group showing positive staining for iNOS were also stained positive for anti-nitrotyrosine antibody selfsame. These findings were not observed in the myocardial specimens obtained from patients who died within 12 hours after the onset of AMI, showing a minimal number of inflammatory cells, or in the specimens from patients with an old myocardial infarction, which showed scar tissue and no cellular infiltration. Inducible NOS and nitrotyrosine were expressed in damaged myocardium from patients with AMI, suggesting that the NO radical and peroxynitrite are involved in the pathogenesis of myocardial damage.
Hasegawa T.,Health Science University |
Fujikawa M.,Tokyo Womens Medical College
International Medical Journal | Year: 2015
Objective: We studied the municipal spatial patterns of cerebrovascular disease-related mortality in men and women aged 65 to 69 years, and 85 to 89 years in Japan. Further, to determine regional variations in health, we examined comprehensively the association between the cause-specific death rate and lifestyles, socioeconomic and environmental factors. Methods: Vital statistics for 2010 in Japan were employed. Multiple regression analyses were conducted to clarify these associations. Dependent valuables were death rate of cerebrovascular disease (CVD), and independent variables were as follows: salt intake, body mass index (BMI), pedometer, mean ambient temperature, altitude, medical cost, annual income, GiNi coefficient, and the number of nursing homes. Results: Within the 65-69 year age group, the CVD mortality rate was significantly associated with ambient temperature in men (β =-0.478, p < 0.001) and medical expenditures in women (β =-0.379, p = 0.009). Within the older group (85-89 years), the CVD mortality rate was significantly associated with salt intake in men (β = 0.637, p = 0.001) and salt intake (β = 0.512, p = 0.001), the number of nursing homes (β = 0.286, p = 0.012), and altitude (β = 0.310, p = 0.013) in women. Conclusion: A prefecture-based study of cause-specific death rates revealed that risk factors for CVD mortality may differ by age and gender groups. © 2015 Japan Health Sciences University.
Serizawa H.,Kitasato University |
Iwasaki N.,Tokyo Womens Medical College |
Morinaga S.,Kitasato University |
Tsunematsu S.,Kitasato University
Journal of Japanese Society of Gastroenterology | Year: 2015
A 19-year-old Japanese woman had been diagnosed with diabetes at the age of 9 years. She had a strong family history of diabetes, and genetic screening showed she had maturity-onset diabetes of the young type 3 (MODY3). Ultrasonography of the liver and magnetic resonance imaging showed multiple nodules consistent with hepatocellular adenoma (HA). Biopsy of the liver tumors revealed hepatocyte nuclear factor (HNF) 1α-inactivated HA. HA is known as a MODY3-related disease due to mutations in HNF1α. We present the first report of HA associated with MODY3 in Japan.