235 research outputs found

    Co-culturing of follicles with interstitial cells in collagen gel reproduce follicular development accompanied with theca cell layer formation

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    <p>Abstract</p> <p>Background</p> <p>The mechanism of theca cell layer formation in mammalian ovaries has not been elucidated; one reason is that there is no follicle culture system that can reproduce theca cell layer formation in vitro. Therefore, a three-dimensional follicle culture system that can reproduce theca cell layer formation is required.</p> <p>Methods</p> <p>A collagen gel was used in the follicle culture system. To determine the optimum conditions for follicle culture that can reproduce theca cell layer formation, the effects of hormonal treatment and cell types co-cultured with follicles were examined. In addition, immunohistochemistry was used to examine the properties of the cell layers formed in the outermost part of follicles.</p> <p>Results</p> <p>Follicles maintained a three-dimensional shape and grew in collagen gel. By adding follicle-stimulating hormone (FSH) and co-culturing with interstitial cells, the follicles grew well, and cell layers were formed in the outermost part of follicles. Immunohistochemistry confirmed that the cells forming the outermost layers of the follicles were theca cells.</p> <p>Conclusion</p> <p>In this study, follicle culture system that can reproduce theca cell layer formation <it>in vitro </it>was established. In our opinion, this system is suitable for the analysis of theca cell layer formation and contributes to our understanding of the mechanisms of folliculogenesis.</p

    Methylation Analysis in Treatment-Resistant Schizophrenia

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    Schizophrenia is a mental illness that involves both genetic and environmental factors. Clozapine, an atypical antipsychotic, is a well-established therapy for treatment-resistant schizophrenia. In this study, we focused on a set of monozygotic twins with treatment-resistant schizophrenia in which one twin effectively responded to clozapine treatment and the other did not. Our previous study generated neurons from induced pluripotent stem (iPS) cells derived from these patients and compared the transcriptome profiles between mock- and clozapine-treated neurons. In this study, we performed genome-wide DNA methylation profiling to investigate the mechanisms underlying gene expression changes. First, we extracted the differentially methylated sites from each twin based on statistical analysis. Then, we combined the DNA methylation profiling with transcriptome profiling from our previous RNA-seq data. Among the genes with altered methylation and expression, we found the different proportions of the genes related to neuronal and synaptic functions between the clozapine responder and non-responder (35.7 and 6.7%, respectively). This trend was observed even when the basal differences between the responder and non-responder was excluded. These results suggest that effective clozapine action may correct the abnormalities of neuronal and synapse functions in schizophrenia via changes in methylation

    RacGAP α2-Chimaerin Function in Development Adjusts Cognitive Ability in Adulthood

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    SummaryA major concern in neuroscience is how cognitive ability in adulthood is affected and regulated by developmental mechanisms. The molecular bases of cognitive development are not well understood. We provide evidence for the involvement of the α2 isoform of Rac-specific guanosine triphosphatase (GTPase)-activating protein (RacGAP) α-chimaerin (chimerin) in this process. We generated and analyzed mice with global and conditional knockouts of α-chimaerin and its isoforms (α1-chimaerin and α2-chimaerin) and found that α-chimaerin plays a wide variety of roles in brain function and that the roles of α1-chimaerin and α2-chimaerin are distinct. Deletion of α2-chimaerin, but not α1-chimaerin, beginning during early development results in an increase in contextual fear learning in adult mice, whereas learning is not altered when α2-chimaerin is deleted only in adulthood. Our findings suggest that α2-chimaerin acts during development to establish normal cognitive ability in adulthood

    An Autopsy Case of Ruptured Hepatic Angiosarcoma Treated by Transcatheter Arterial Embolization

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    An 80-year-old Japanese man presented to our hospital with intra-abdominal hemorrhage due to a ruptured liver tumor. Transcatheter arterial embolization (TAE) temporarily achieved hemostasis, but he died following re-rupture 4 days later. Based on autopsy findings, the liver tumor was diagnosed as hepatic angiosarcoma. Embolic agents used during embolization were identified within the hepatic small interlobular arteries. However, there were no findings of tumor cell necrosis or ischemic change in the angiosarcoma. In the present case, TAE alone did not induce ischemia-induced tumor necrosis, suggesting that TAE might be unsuitable to treat hepatic angiosarcoma. Treatment optimization for ruptured hepatic angiosarcoma is desired

    Plasma levels of matrix metalloproteinase‐9 (MMP‐9) are associated with cognitive performance in patients with schizophrenia

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    Aim: Matrix metalloproteinase‐9 (MMP‐9) has been shown to modulate synaptic plasticity and may contribute to the pathophysiology of schizophrenia. This study investigated the peripheral levels of MMP‐9 and its association with cognitive functions in patients with schizophrenia to see the possible involvement of MMP‐9 in pathophysiology of schizophrenia, especially in cognitive decline. Methods: We measured the plasma levels of MMP‐9 in 257 healthy controls and 249 patients with schizophrenia, including antipsychotic drug–free patients. We also explored the possible association between plasma MMP‐9 levels and cognitive performance in healthy controls and patients with schizophrenia using the Wechsler Adult Intelligence Scale, Third Edition (WAIS‐ III), the Wechsler Memory Scale‐Revised (WMS‐R), and the Rey Auditory Verbal Learning Test (AVLT). Results: We found that the plasma levels of MMP‐9 were significantly higher in patients with schizophrenia, including antipsychotic drug–free patients, than in healthy controls. We found a significant negative association between plasma MMP‐9 levels and cognitive performance in controls and patients with schizophrenia. Conclusion: Together, these convergent data suggest a possible biological mechanism for schizophrenia, whereby increased MMP‐9 levels are associated with cognitive impairment

    Plasma Levels of Soluble Tumor Necrosis Factor Receptor 2 (sTNFR2) Are Associated with Hippocampal Volume and Cognitive Performance in Patients with Schizophrenia

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    Background: An imbalance in the inflammatory tumor necrosis factor system, including soluble tumor necrosis factor receptor 2 (sTNFR2), may contribute to the pathophysiology of schizophrenia. Methods: We measured the plasma levels of sTNFR2 in 256 healthy controls and 250 patients with schizophrenia including antipsychotic drug-free patients and treatment-resistant patients. We also explored the possible association between plasma sTNFR2 levels and cognitive performance in healthy controls and patients with schizophrenia using the Wechsler Adult Intelligence Scale, Third Edition, the Wechsler Memory Scale-Revised, and the Rey Auditory Verbal Learning Test. An association between plasma sTNFR2 levels and hippocampal volume in controls and patients with schizophrenia was also investigated via MRI. Results: We found that the plasma levels of sTNFR2 were significantly higher in patients with schizophrenia, including both antipsychotic drug-free patients and treatment-resistant patients. We found a significant negative association between plasma sTNFR2 levels and cognitive performance in controls and patients with schizophrenia. Hippocampal volume was also negatively associated with plasma sTNFR2 levels in patients with schizophrenia. Conclusion: Together, these convergent data suggest a possible biological mechanism for schizophrenia, whereby increased sTNFR2 levels are associated with a smaller hippocampal volume and cognitive impairment

    Decreased Wave V Amplitude in Auditory Brainstem Responses of Children with Cerebellar Lesions

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    【Background】 This study aims to elucidate the effect of isolated cerebellar lesions sparing the brainstem on the auditory brainstem responses in children. 【Methods】 We enrolled 10 children (aged 1?16 years) with cerebellar lesions on neuroimaging but lacking clinical brainstem involvement signs and with normal brainstem volumes on magnetic resonance imaging. 【Results】 The interpeak latency of waves I and V was normal in 9 patients and was marginally prolonged in 1 patient. While amplitudes of waves I and III were normal, we noted a decreased amplitude of wave V and/or an increased I/V amplitude ratio in 6 patients; these included 5 of 8 patients with cerebellar hypoplasia/atrophy and 1 patient with acute cerebellar ataxia. 【Conclusion】 Our results support the hypothesis of an inhibitory input from the cerebellar fastigial nucleus on the inferior colliculus, which might be disinhibited because of Purkinje cells dysfunction due to cerebellar cortex lesions, especially within the cerebellar vermis

    Differential gene expression profiles in neurons generated from lymphoblastoid B-cell line-derived iPS cells from monozygotic twin cases with treatment-resistant schizophrenia and discordant responses to clozapine

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    Schizophrenia is a chronic psychiatric disorder with complex genetic and environmental origins. While many antipsychotics have been demonstrated as effective in the treatment of schizophrenia, a substantial number of schizophrenia patients are partially or fully unresponsive to the treatment. Clozapine is the most effective antipsychotic drug for treatment-resistant schizophrenia; however, clozapine has rare but serious side-effects. Furthermore, there is inter-individual variability in the drug response to clozapine treatment. Therefore, the identification of the molecular mechanisms underlying the action of clozapine and drug response predictors is imperative. In the present study, we focused on a pair of monozygotic twin cases with treatment-resistant schizophrenia, in which one twin responded well to clozapine treatment and the other twin did not. Using induced pluripotent stem (iPS) cell-based technology, we generated neurons from iPS cells derived from these patients and subsequently performed RNA-sequencing to compare the transcriptome profiles of the mock or clozapine-treated neurons. Although, these iPS cells similarly differentiated into neurons, several genes encoding homophilic cell adhesion molecules, such as protocadherin genes, showed differential expression patterns between these two patients. These results, which contribute to the current understanding of the molecular mechanisms of clozapine action, establish a new strategy for the use of monozygotic twin studies in schizophrenia research

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    Tokushima Park (originally named Tokushima Central Park) is the Japan’s second western-style park that was opened in 1906. We investigated landscape architecture of Tokushima Park based on a blueprint made in 1905 to understand its purpose and function of the park, and compared with Hibiya Park that is the Japan’s first western-style park. Tokushima Park consisted of five areas. The central area included Mt. Shiroyama (Castle Mountain), and primeval forest was protected without allowing to make a big building within the area. A commercial museum, an athletic field, and a botanical garden and a library were placed in the southern, western and eastern areas respectively, so that each area was designed to exhibit each function. Tokushima Park and Hibiya Park were designed by the same two persons Seiroku Honda and Takanori Hongo. The two parks were equipped with a wide road, an athletic field, a botanical garden and so on, and these facilities were adopted to the park made since them. Because Seiroku Honda adopted three design drawings of German parks from the book GĂ€rtnerisches Planzeichnen into a blueprint of Hibiya Park, we investigated the book to ascertain whether any design drawing was also used in Tokushima Park. We found that Seifersdorf Castle, the castle of count BrĂŒhl that was built at Seifersdorf in Germany in 13th century, is similar to the southern area of Tokushima Park
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