81 research outputs found
Development of CMC for nuclear fuel components
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Triple-negative pleomorphic lobular carcinoma and expression of androgen receptor: Personal case series and review of the literature
Pleomorphic lobular carcinoma (PLC) is a histological variant of invasive lobular carcinoma (ILC) and is associated with worse prognosis than classical ILC. It exhibits a greater degree of cellular atypia and pleomorphism and is occasionally accompanied with apocrine morphology. We investigated the immunohistochemical characteristics of samples from 31 Japanese patients with PLC to elucidate the clinicopathological characteristics of PLC including androgen receptor (AR) immunoreactivity. The surrogate molecular subtypes were luminal A-like, luminal B-like, luminal B-like/HER2, HER2-type, and triple-negative in 5, 4, 3, 5, and 14 cases, respectively. AR was positive in 92.8% (13/14) of the triple-negative PLC cases and 100% (10/10) of the non-triple-negative PLC cases. Disease-specific survival was worse in patients with histological grade 3 PLCs than in those with histological grade 2 PLCs (p = 0.007). However, there was no significant difference in the progression-free survival between the two groups (p = 0.152). No other clinicopathological characteristics were associated with prognosis. These results reveal that PLC exhibits various surrogate molecular subtypes and that the triple-negative subtype frequently expresses AR. The observed molecular apocrine differentiation implicates that triple-negative PLC can be categorized into the luminal AR subtype. Furthermore, AR-targeted therapy might be useful for patients with triple-negative PLC
Classifying breast masses in volumetric whole breast ultrasound data: a 2.5-dimensional approach
The aim of this paper is to investigate a 2.5-dimensional approach in
classifying masses as benign or malignant in volumetric anisotropic voxel
whole breast ultrasound data. In this paper, the term 2.5-dimensional refers to
the use of a series of 2-dimensional images. While mammography is very
effective in breast cancer screening in general, it is less sensitive in detecting
breast cancer in younger women or women with dense breasts. Breast
ultrasonography does not have the same limitation and is a valuable adjunct in
breast cancer detection. The current study focuses on a new 2.5-dimensional approach in analyzing the
volumetric whole breast ultrasound data for mass classification
Nagasaki Schizophrenia Study : Outcome of a 15-year Follow-up of an Incident Cohort
The Nagasaki World Health Organization (WHO) Collaborating Center for Research and Training in Mental Health conducted the WHO Coordinated Multi-Center Study of the Long-term Course and Outcome of Schizophrenia as a part of the International Study on Schizophrenia (ISoS). The study used 107 patients who were initially diagnosed as having ICD-9 schizophrenia for the WHO Collaborative Study on the Determinants of Outcome of Severe Mental Disorders (DOSMeD). Subjects were first collected in 1979-1980 for an incidence study of schizophrenia in Nagasaki. In this 15-yearfollow- up study, 7 subjects died, 43 subjects were lost to follow-up and 57 were successfully traced. Among the 7 death cases, 4 suicides were confirmed and 1 was suspected. During the 15-year period, 25 (44%) of the 57 living subjects displayed continuous psychotic course type schizophrenia. During the last 2 years, 14 (25%) were not psychotic ; 31 (54%) were continuously psychotic. Global Assessment of Functioning Scale for Symptomatology (GAF-S) indicated symptomatological outcomes : 16 (28%) had severe symptoms (GAF-S70). Social outcome was evaluated using the Global Assessment of Functioning Scale for Disability (GAF-D): 28 (49%) showed poor adjustment (GAF-D70). The overall time trend was almost evenly divided in thirds : 20 (35%) were getting better, 18 (32%) were the same and 19 (33%) were worse. The present study showed that the outcome of schizophrenia is not always poor, although some patients display a continuous course and poor outcome
Protein kinase A enhances lipopolysaccharide-induced IL-6, IL-8, and PGE2 production by human gingival fibroblasts
<p>Abstract</p> <p>Objective</p> <p>Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss in severe clinical cases. Interleukin (IL)-6, IL-8, and the chemical mediator prostaglandin E<sub>2 </sub>(PGE<sub>2</sub>) are known to play important roles in inflammatory responses and tissue degradation.</p> <p>Recently, we reported that the protein kinase A (PKA) inhibitor H-89 suppresses lipopolysaccharide (LPS)-induced IL-8 production by human gingival fibroblasts (HGFs). In the present study, the relevance of the PKA activity and two PKA-activating drugs, aminophylline and adrenaline, to LPS-induced inflammatory cytokines (IL-6 and IL-8) and PGE<sub>2 </sub>by HGFs were examined.</p> <p>Methods</p> <p>HGFs were treated with LPS from <it>Porphyromonas gingivalis </it>and H-89, the cAMP analog dibutyryl cyclic AMP (dbcAMP), aminophylline, or adrenaline. After 24 h, IL-6, IL-8, and PGE<sub>2 </sub>levels were evaluated by ELISA.</p> <p>Results</p> <p>H-89 did not affect LPS-induced IL-6 production, but suppressed IL-8 and PGE<sub>2 </sub>production. In contrast, dbcAMP significantly increased LPS-induced IL-6, IL-8, and PGE<sub>2 </sub>production. Up to 10 μg/ml of aminophylline did not affect LPS-induced IL-6, IL-8, or PGE<sub>2 </sub>production, but they were significantly increased at 100 μg/ml. Similarly, 0.01 μg/ml of adrenaline did not affect LPS-induced IL-6, IL-8, or PGE<sub>2 </sub>production, but they were significantly increased at concentrations of 0.1 and 1 μg/ml. In the absence of LPS, H-89, dbcAMP, aminophylline, and adrenaline had no relevance to IL-6, IL-8, or PGE<sub>2 </sub>production.</p> <p>Conclusion</p> <p>These results suggest that the PKA pathway, and also PKA-activating drugs, enhance LPS-induced IL-6, IL-8, and PGE<sub>2 </sub>production by HGFs. However, aminophylline may not have an effect on the production of these molecules at concentrations used in clinical settings (8 to 20 μg/ml in serum). These results suggest that aminophylline does not affect inflammatory responses in periodontal disease.</p
Cardiac Conduction Disorders as Markers of Cardiac Events in Myotonic Dystrophy Type 1.
Background Myotonic dystrophy type 1 involves cardiac conduction disorders. Cardiac conduction disease can cause fatal arrhythmias or sudden death in patients with myotonic dystrophy type 1. Methods and Results This study enrolled 506 patients with myotonic dystrophy type 1 (aged ≥15 years; >50 cytosine-thymine-guanine repeats) and was treated in 9 Japanese hospitals for neuromuscular diseases from January 2006 to August 2016. We investigated genetic and clinical backgrounds including health care, activities of daily living, dietary intake, cardiac involvement, and respiratory involvement during follow-up. The cause of death or the occurrence of composite cardiac events (ie, ventricular arrhythmias, advanced atrioventricular blocks, and device implantations) were evaluated as significant outcomes. During a median follow-up period of 87 months (Q1-Q3, 37-138 months), 71 patients expired. In the univariate analysis, pacemaker implantations (hazard ratio [HR], 4.35; 95% CI, 1.22-15.50) were associated with sudden death. In contrast, PQ interval ≥240 ms, QRS duration ≥120 ms, nutrition, or respiratory failure were not associated with the incidence of sudden death. The multivariable analysis revealed that a PQ interval ≥240 ms (HR, 2.79; 95% CI, 1.9-7.19, P<0.05) or QRS duration ≥120 ms (HR, 9.41; 95% CI, 2.62-33.77, P < 0.01) were independent factors associated with a higher occurrence of cardiac events than those observed with a PQ interval <240 ms or QRS duration <120 ms; these cardiac conduction parameters were not related to sudden death. Conclusions Cardiac conduction disorders are independent markers associated with cardiac events. Further investigation on the prediction of occurrence of sudden death is warranted
Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group
The superiority of the pediatric protocol for adolescents with acute lymphoblastic leukemia (ALL) has already been demonstrated, however, its efficacy in young adults remains unclear. The ALL202-U protocol was conducted to examine the efficacy and feasibility of a pediatric protocol in adolescents and young adults (AYAs) with BCR\u27ABL-negative ALL. Patients aged 15\u2724 years (n = 139) were treated with the same protocol used for pediatric B-ALL. The primary objective of this study was to assess the disease-free survival (DFS) rate and its secondary aims were to assess toxicity, the complete remission (CR) rate and the overall survival (OS) rate. The CR rate was 94%. The 5-year DFS and OS rates were 67% (95% confidence interval (CI) 58\u2775%) and 73% (95% CI 64\u2780%), respectively. Severe adverse events were observed at a frequency that was similar to or lower than that in children treated with the same protocol. Only insufficient maintenance therapy significantly worsened the DFS (hazard ratio 5.60, Po0.001).These results indicate that this protocol may be a feasible and highly effective treatment for AYA with BCR\u27ABL-negative ALL
Heme oxygenase-1 contributes to pathology associated with thrombin-induced striatal and cortical injury in organotypic slice culture
The blood coagulation factor thrombin that leaks from ruptured vessels initiates brain tissue damage after intracerebral hemorrhage. We have recently shown that mitogen-activated protein kinases (MAPKs) activated by thrombin exacerbate hemorrhagic brain injury via supporting survival of neuropathic microglia. Here, we investigated whether induction of heme oxygenase (HO)-1 is involved in these events. Zinc protoporphyrin IX (ZnPP IX), a HO-1 inhibitor, attenuated thrombin-induced injury of cortical cells in a concentration-dependent manner (0.3-3 microM) and tended to inhibit shrinkage of the striatal tissue at 0.3 microM. HO-1 expression was induced by thrombin in microglia and astrocytes in both the cortex and the striatum. The increase of HO-1 protein was suppressed by a p38 MAPK inhibitor SB203580, and early activation of p38 MAPK after thrombin treatment was observed in neurons and microglia in the striatum. Notably, concomitant application of a low concentration (0.3 microM) of ZnPP IX with thrombin induced apoptotic cell death in striatal microglia and significantly decreased the number of activated microglia in the striatal region. On the other hand, a carbon monoxide releaser reversed the protective effect of ZnPP IX on thrombin-induced injury of cortical cells. Overall, these results suggest that p38 MAPK-dependent induction of HO-1 supports survival of striatal microglia during thrombin insults. Thrombin-induced cortical injury may be also regulated by the expression of HO-1 and the resultant production of heme degradation products such as carbon monoxide
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