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Yasunori Fujimoto

Publications and source records attributed to Yasunori Fujimoto.

13 recordsLinked to original sources

Real-time monitoring of cAMP response element binding protein signaling in porcine granulosa cells modulated by ovarian factors.

The present study was performed to establish a real-time monitoring of the cAMP response element binding protein (CREB) signalling using granulosa cells, and to assess the modulation of CREB activity by potential ovarian autocrine/paracrine and oocyte-derived factors. Granulosa cells were isolated from porcine follicles and cultured for 2 days, and then transfected with CRE-containing pGL3. The cells were directly stimulated or cultured with FSH, LH, forskolin, or a permeable cAMP analog, and/or IGF-I, EGF, bFGF, TGF-beta2 or TNF-alpha, or cumulus-oocyte complex (COCs) for the real-time monitoring of CREB signaling. The activation pattern of CREB signaling consisted of three distinct phases, i.e., burst, attenuation and refractory. In contrast to FSH, LH, and forskolin, a cAMP analog induced the prolonged activation, although three distinct phases were observed at its high concentration. Of all the autocrine/paracrine factors, only IGF-I slightly induced CREB activity. On the other hand, TGF-beta2 and TNF-alpha significantly repressed FSH-stimulated transcriptional activation of CREB by 30% (P < 0.05) and 45% (P < 0.05), respectively. Additionally, coculture with COCs caused a significant suppression of transcriptional activation of CREB signaling stimulated by FSH. These results indicate that ovarian autocrine/paracrine factors such as IGF-I, TGF-beta2, TNF-alpha and oocyte-derived factors modulate the CREB signaling. The present study provides a new approach for direct signaling study on transcription factors under the influences of potential factors.

Animals↗

Synergetic effects of pressure and chemical denaturant on protein unfolding: stability of a serine-type carboxyl protease, kumamolisin.

Kumamolisin, a serine carboxyl proteinase, is very stable and hardly denatured by single perturbation of a chemical denaturant (urea), pressure (<500 MPa) or temperature (<65 degrees C). In order to investigate the cooperative effects of these three denaturing agents, DSC, CD, intrinsic fluorescence, and fourth derivative UV absorbance were measured under various conditions. By application of pressure to kumamolisin in 8 M urea solution, substantial red-shift in the center of fluorescence emission spectral mass was observed, and the corresponding blue-shift was observed for two major peaks in fourth derivative UV absorbance, under the similar urea-containing conditions. The denaturation curves were analyzed on the basis of a simple two-state model in order to obtain thermodynamic parameters (DeltaV, DeltaG, and m values), and the combined effects of denaturing agents are discussed, with the special interest in the large cavity and neighboring Trp residue in kumamolisin.

Aspartic Acid Endopeptidases↗

Inhibition of glioma cell proliferation by neural stem cell factor.

Neural stem cells (NSC) have unique differentiation-, proliferation-, and motility properties. To investigate whether they secrete factors that interfere with the proliferation of glioma cells, we grew glioma cells in conditioned medium (CM) obtained from cultures of neurospheres including neural stem / progenitor cells (NSPC) isolated from embryonic (E14)- or adult mouse brain or fetal human brain. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and BrdU-labeling assays showed that CM from NSPC (NSPC/CM) contained factor(s) that inhibited the proliferation of glioma cells by 28-87%. Filter-fractionation of NSPC/CM revealed that the 50,000-100,000 nominal molecular weight limit (NMWL) fraction contained the inhibitory activity. On the basis of these observations we transplanted 203G glioma cells and/or NSPC into the intrathecal space of the cisterna magna of mice to investigate whether NSPC interfere with the proliferation of glioma cells in vivo. Mice transplanted with both 203G and NSPC survived significantly longer than did mice transplanted only with 203G. We concluded that NSPC secrete factor(s) that may control glioma cell proliferation.

Animals↗

Ganglioside GM3 inhibits proliferation and invasion of glioma.

GM3, the simplest ganglioside, modulates cell adhesion, proliferation and differentiation in the central nervous system and exogenously added GM3 regulates cell-cell and cell-extracellular matrix adhesion and induces apoptosis. To assess the anti-tumor action of exogenous GM3, we examined its effect on the proliferation and invasion of glioma cells. Its inhibitory effect on cell proliferation was demonstrated in vitro by 3-(4,5-dimethyl-2-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay and in vitro in rats with meningeal gliomatosis whose survival was significantly prolonged by the intrathecal injection of GM3. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay revealed that GM3 induced glioma cell apoptosis in vitro and in vitro. In rat brain slice cultures, GM3 suppressed the invasion of glioma cells; this effect manifested earlier than the inhibition of cell proliferation and before apoptosis induction. Our results suggest exogenous GM3 as a potential therapeutic agent in patients with glioma requiring adjuvant therapy.

Animals↗

Immunohistochemical detection of female sex hormone receptors in craniopharyngiomas: correlation with clinical and histologic features.

BACKGROUND: Although craniopharyngiomas have a histologically benign nature, their treatment can be difficult. The correlation among clinical, proliferative, and immunohistologic features of female sex hormone receptors was determined in craniopharyngiomas to analyze whether they influence the growth of the tumor. METHODS: The study subjects were 43 patients with previously untreated craniopharyngioma who underwent surgery at our department over the past 15 years. Serial tissue sections were immunostained with the antibodies against estrogen receptor (ER), progesterone receptor (PR), and Ki-67. RESULTS: The Ki-67 labeling index was significantly higher in patients with regrowth (7.8%) than without regrowth (3.9%). ER and PR were detected in 9 of 30 (30%) craniopharyngiomas, and the incidence of postoperative tumor regrowth was significantly higher in patients negative for ER and PR (29%) than in those positive for both receptors (11%). CONCLUSIONS: A high Ki-67 labeling index suggests a high possibility of tumor regrowth, and the presence of ER and PR is suggestive of a high tissue differentiating potential. ER and PR assay may be useful for determining the indication for additional radiation therapy in craniopharyngioma patients treated by incomplete resection.

Adolescent↗

Chromosomal and genetic abnormalities in benign and malignant meningiomas using DNA microarray.

BACKGROUND: Meningioma is the commonest brain tumor and many genetic abnormalities, such as the loss of chromosome 22q and the mutation of NF2, have been reported. METHODS: These classical abnormalities were detected using Southern blot, PCR, fluorescence in situ hybridization and comparative genomic hybridization, but these methods examine only very limited regions or limited mapping resolution of the tumor genome. In this study, we used DNA microarray assay, which detects numerous genetic abnormalities simultaneously and analyses a global assessment of molecular events in meningioma cells. We studied 31 meningiomas by GenoSensor Array 300 in order to detect the chromosomal aberrations and genetic abnormalities in the whole genome. RESULTS: This study demonstrated not only classical chromosomal aberration, such as loss of chromosome 22q in 19 meningiomas (61.3%), but also new genetic characteristics of meningiomas, such as amplification of MSH2 in 16 meningiomas (51.6%), deletion of GSCL in 13 meningiomas (41.9%) and deletion of HIRA in seven meningiomas (22.6%). CONCLUSIONS: These results suggest that DNA microarray assay is useful in research for the genetic characters of meningiomas and understanding tumorigenesis.

Adolescent↗

Genetic analysis of human glioblastomas using a genomic microarray system.

Genomic microarray systems can simultaneously provide substantial genetic and chromosomal information in a relatively short time. We have analyzed genomic DNA from frozen sections of 30 cases of primary glioblastomas by GenoSensor Array 300 in order to characterize gene amplifications, gene deletions, and chromosomal information in the whole genome. Genes that were frequently amplified included RFC2/CYLN2 (63.3%), EGFR (53.3%), IL6 (53.3%), ABCB1 (MDR1) (36.7%), and PDGFRA (26.7%). Genes that were frequently deleted included (56.7%), FGFR2 (66.7%), MTAP (60.0%), DMBT1 CDKN2A (p16)/MTAP (50.0%), PIK3CA (43.3%), and EGR2 (43.3%), but deletion of RB1 or TP53 was rarely detected. Chromosomal gains were observed frequently for 7q (33.3%), 7p (20.0%), and 17q (13.3%). Loss of the 10q was frequently detected in 13 of 30 cases (46.7%). Loss of the entire chromosome 10 was seen in 9 of 30 cases (30.0%), and was often accompanied by EGFR amplification (7 cases, 77.8%). The GenoSensor Array 300 proved to be useful for identification of genome-wide molecular changes in glioblastomas. The obtained microarray profile can also yield valuable insight into the molecular events underlying carcinogenesis of brain tumors and may provide clues about clinical correlations, including response to treatment.

Adult↗

Chromosomal and genetic aberrations differ with meningioma subtype.

Meningioma is one of the most common brain tumors, and a variety of genetic abnormalities have been detected by the Southern blotting, polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH) methods. However, these methods detect only a very limited portion of the tumor genome or have a limited mapping resolution. In this study, we used DNA microarray assay, which detects numerous genetic abnormalities and analyzes a global assessment of molecular events in tumor cells. We analyzed genomic DNA from 26 patients with benign meningiomas by GenoSensor Array 300 in order to characterize gene amplifications, gene deletions, and chromosomal information in the whole genome. Loss of chromosome 22q was found most frequently. This chromosomal aberration was detected in 14 meningiomas (53.8%), particularly in transitional and fibrous meningiomas. In meningothelial meningiomas, amplification of INS and TCL1A was detected more frequently than in other meningioma subtypes. DNA microarray assay revealed new genetic differences among the meningioma subtypes, thus indicating that this novel technique is useful for understanding tumor genesis and for the diagnosis of meningioma subtype.

Adolescent↗

Meningioma arising from the trigeminal nerve: a case report and literature review.

We report a 69-year-old woman with a meningioma who presented with a 9-month history of progressive facial numbness in the distribution of the left mandibular nerve and left facial palsy. Magnetic resonance imaging revealed a mass in and around the left Meckel's cave (MC). The tumor was totally resected through a lateral suboccipital and subtemporal combined approach. It appeared to be a schwannoma, because it adhered firmly to the cisternal portion of the trigeminal nerve without dural attachment. Histopathological examination revealed that it was a meningothelial meningioma. We concluded that the tumor originated from the arachnoid cap cells within the trigeminal nerve sheath, not from the dura mater in the MC.

Aged↗

Ruptured aneurysm arising from the proximal end of an azygos anterior cerebral artery--case report.

A 59-year-old woman presented with subarachnoid hemorrhage. Conventional angiography and three-dimensional computed tomography (3-D CT) angiography showed a saccular aneurysm at the junction of the azygos anterior cerebral artery (ACA) and the left A1 segment. This aneurysm was associated with a fenestration of the right hypoplastic A1 segment. The aneurysm neck was completely clipped, preserving the azygos ACA and other perforators. Aneurysm of the azygos ACA is almost always located at the distal bifurcation, and rarely at the proximal end. Proximal azygos ACA aneurysm can mimic anterior communicating artery aneurysm. Therefore, accurate preoperative diagnosis is critical using 3-D CT angiography as well as conventional angiography, and close follow up of patient is necessary to monitor for development of a de novo aneurysm at the distal bifurcation of the azygos ACA.

Aneurysm, Ruptured↗

Volumetric thermal devascularization of large meningiomas.

OBJECT: Controlling hemorrhage is crucial in the safe and efficient removal of large meningiomas. Intravascular embolization is not always a satisfactory means of accomplishing this goal because of the procedure's hemostatic effect and risk of complications. The authors in this study used a volumetric thermal ablation technique incorporating radiofrequency energy, image guidance, and local temperature control to devascularize tumor tissue. METHODS: Five patients with large meningiomas were treated. The target and orientation of the radiofrequency thermal ablation (RFTA) were simulated preoperatively to maximize devascularization of the lesion without thermal injury to adjacent critical structures. Image fusion, three-dimensional reconstruction, and image-guided methods provided for optimized trajectories and targets for insertion of the RFTA needle. During ablation, local temperatures of the tissue being cauterized were monitored continuously to limit the ablated lesion to within the target volume. The effects of devascularization and the softening of the tumor parenchyma facilitated lesion removal. The intracranial ablated meningioma changed into necrotic tissue and shrank within a few months. Histopathological examination of the ablated lesion revealed sharply demarcated coagulation necrosis. CONCLUSIONS: Volumetric thermal devascularization can be applied safely in the treatment of large meningiomas to facilitate surgical manipulation of the lesion as well as to reduce its size palliatively. The procedure's usefulness should be studied further in a larger number of cases with different tumor characteristics.

Adult↗

Craniopharyngioma involving the infrasellar region: a case report and review of the literature.

Craniopharyngiomas are most commonly located in the intradural suprasellar region. However, ectopic craniopharyngiomas can originate in the infrasellar region. The authors present the case of an 8-year-old boy diagnosed with a large cystic craniopharyngioma involving the nasal cavities and maxillary, ethmoid and sphenoid sinuses, in addition to the sella turcica. The primary symptoms of this patient were nasal obstruction, unilateral decreased visual acuity and exophthalmos. He subsequently underwent combined radical resection of the tumor by means of an endonasal transsphenoidal approach followed by radiation therapy. During the surgery, the dura mater of the sellar floor was found to be intact. The neuroradiological and surgical findings suggested that this tumor originated in the extradural infrasellar region and invaded the sella turcica.

Child↗

Hydrocephalus due to diffuse villous hyperplasia of the choroid plexus. Case report and review of the literature.

Diffuse villous hyperplasia of the choroid plexus (DVHCP) that causes hydrocephalus by overproduction of cerebrospinal fluid is a very rare lesion and difficult to diagnose initially. We present a male infant who was diagnosed with communicating hydrocephalus at 16 months of age and treated initially by ventriculoperitoneal shunt. In the postoperative course, he developed massive ascites. Magnetic resonance imaging obtained after the operation revealed DVHCP. Resection of the choroid plexus of the left lateral ventricle was performed, and postoperatively, his ascites was resolved. We review the literature and discuss the diagnosis and treatment of this rare entity.

Brain↗