[Ovarian hyperstimulation syndrome].
Explore the source record for details and available documents.
Chorionic Gonadotropin↗
Biomedical subjects
Yasushi Shimizu
Publications and source records attributed to Yasushi Shimizu.
E1AF/PEA3 activates the Rho/Rho-associated kinase pathway to increase the malignancy potential of non-small-cell lung cancer cells.
E1AF/PEA3, an Ets family transcription factor, is frequently overexpressed in non-small-cell lung cancers (NSCLCs). Overexpression of E1AF increases motility and invasion of VMRC-LCD and NCI-H226 NSCLC cells, which lack endogenous E1AF expression, and the effect is synergistically increased by hepatocyte growth factor (HGF). The small GTPase Rho/Rho-associated kinase (ROCK) pathway is also involved in motility and invasion. To determine the role of the Rho/ROCK pathway in malignant phenotypes induced by E1AF, we analyzed VMRC-LCD cells transfected with an E1AF expression vector (LCD-E1AF cells) or with empty vector (LCD-vector cells). LCD-E1AF cells had more GTP-bound (active) Rho than LCD-vector cells and Rho activation was synergistically increased by HGF. The Rho activation by E1AF and HGF was also shown in NCI-H226 cells. Phosphorylation of myosin light chain (MLC), a downstream effector of ROCK signaling, was higher in LCD-E1AF cells than in LCD-vector cells, especially under HGF treatment. A specific ROCK inhibitor, Y27632, strongly suppressed MLC phosphorylation, cell motility, and invasion. In nude mice implanted s.c. and intrapulmonarily, LCD-E1AF cells made more local tumors than LCD-vector cells (six of six versus one of seven mice and four of seven versus one of seven mice, respectively). Three of the four mice with lung tumors from LCD-E1AF cells had lymph node metastases whereas the mouse with LCD-vector tumors did not. LCD-E1AF tumors showed higher MLC phosphorylation than LCD-vector tumors. These results suggest that E1AF activates the Rho/ROCK pathway in an HGF-enhanced manner and its activation is important in E1AF-induced motility and invasion as well as tumorigenesis and metastasis in NSCLC cells.
Adenovirus E1A Proteins↗
Survivin contributes to the anti-apoptotic activities of transforming growth factor alpha in mouse blastocysts through phosphatidylinositol 3'-kinase pathway.
Transforming growth factor alpha (TGFA) is produced by epithelial cells in the oviducts and uteri and has the potential to act as an anti-apoptotic factor on preimplantation embryos expressing its receptor. Previously, we demonstrated that survivin (also known as BIRC5), an anti-apoptotic gene expressed in mouse preimplantation embryos, protects embryos from apoptosis. In this study, we investigated the role of survivin on TGFA-mediated inhibition of apoptosis in mouse blastocysts. Under the suboptimal conditions produced by single embryo culture, blastocysts showed an increase of apoptosis that correlated with a decrease of survivin expression. TGFA treatment significantly decreased apoptosis and increased the levels of survivin mRNA in a dose-dependent manner in blastocyst, and conversely, these activities were neutralized by an anti-TGFA antibody. Antibody treatment alone exerted little effect on either the occurrence of apoptosis or the levels of survivin mRNA. Upregulation of survivin expression by TGFA treatment was insignificant before the blastocyst stage. Using an antisense approach, we examined whether upregulation of survivin is responsible for the anti-apoptotic effect of TGFA in blastocysts. Apoptosis was inhibited by TGFA treatment in blastocysts, but the effect was abrogated by cotreatment with antisense oligonucleotides directed against survivin. These data suggest that survivin contributes to the anti-apoptotic activities of TGFA in blastocysts. We also found that the upregulation of survivin expression was mediated by activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Thus, TGFA inhibits apoptosis in mouse blastocysts through upregulation of survivin expression via the PI3K pathway.
Animals↗
Gonadotropin-releasing hormone I analog acts as an antiapoptotic factor in mouse blastocysts.
Both GnRH-I and its receptor (GnRHR)-I have been shown to be expressed in the mammalian preimplantation embryo. In this study, we investigated the molecular mechanisms of GnRH-I in the regulation of early embryonic development in mouse. We found that GnRH-I and GnRHR-I mRNAs were detectable throughout early embryonic stages and that expression levels of both increased significantly after the early blastocyst stage. In blastocysts, GnRH-I and GnRHR-I expression was detected in both inner cell mass and trophectoderm cells. The pregnant uterus also expressed both genes, suggesting that preimplantation embryos could be affected by GnRH through both paracrine and autocrine signaling. Treatment with GnRH-I agonist, buserelin, promoted development of two-cell-stage embryos to the expanded and hatched blastocyst stages and inhibited apoptosis in a dose-dependent manner. In contrast, treatment with GnRH-I antagonist, ganirelix acetate, inhibited development of preimplantation embryos beyond the expanded blastocyst stage and induced apoptosis; both effects could be reversed by cotreatment with GnRH-I agonist. GnRH-I antagonist-induced cell death was mediated by disruption of mitochondrial function, release of cytochrome c, and activation of caspase-3. Furthermore, treatment with GnRH-I antagonist decreased expression of two antiapoptotic growth factors, epidermal growth factor and IGF-II, in blastocysts. These results indicate that GnRH-I, acting as an antiapoptotic factor, is an important growth factor in development of mouse blastocysts.
Animals↗
Expression of Smac/DIABLO in mouse preimplantation embryos and its correlation to apoptosis and fragmentation.
Regulation of early embryonal development during fertilization and implantation is crucial for mammalian reproduction. Several studies have described cell death during preimplantation embryogenesis in a range of mammalian species, both in vivo and in vitro. Therefore, apoptosis may be involved in early embryonic arrest and the characteristic cytoplasmic fragments are the equivalents of apoptotic bodies, the end-product of apoptosis. Although apoptosis is expected to associate with fragmentation in early preimplantation embryos, the mechanism through which this fragmentation occurs has not been elucidated. Recently, second mitochondria-derived activator of caspase/Direct IAP Binding Protein with Low pI (Smac/DIABLO) was identified as a mitochondrial protein that is released into the cytosol during apoptosis. Once released, the Smac/DIABLO blocks the anti-apoptotic activity of inhibitor of apoptosis proteins (IAPs). We hypothesized that the Smac/DIABLO may be involved in the fragmentation of mouse preimplantation embryos. Therefore, we investigated the expression of Smac/DIABLO mRNA and protein and its localization in mouse oocytes and preimplantation embryos. Smac/DIABLO mRNA was detected by RT-PCR in the oocytes and the preimplantation embryos. Immunohistochemistry studies showed that the Smac/DIABLO protein localized in mitochondria and was released into the cytosol in both fragmented embryos and embryos in which apoptosis was induced by staurosporine. These observations indicate that the Smac/DIABLO is involved in the fragmentation and apoptosis of preimplantation embryos.
Animals↗
HCG up-regulates survivin mRNA in human granulosa cells.
The apoptosis of granulosa cells is involved in follicular atresia and degeneration of the corpus luteum. The mechanisms that regulate follicular atresia and luteal degeneration remain obscure. Survivin is a member of the family of inhibitors of apoptosis protein that is expressed during fetal development and in cancer tissues. The present study investigates the expression of survivin, as well as its regulation and function in granulosa cells. We identified survivin at the protein level in granulosa cells and detected not only survivin but also splice-variant transcripts in human and mouse granulosa-luteal cells. One-step real-time PCR analysis revealed that HCG increases the amount of survivin mRNA expressed in cultured human granulosa cells. These results suggest that survivin is involved in supporting luteal function, and that HCG contributes to this role.
Alternative Splicing↗
Statistical-acoustics models of energy decay in systems of coupled rooms and their relation to geometrical acoustics.
An improved statistical-acoustics model of high-frequency sound fields in coupled rooms is developed by incorporating into prior models geometrical-acoustics corrections for both energy decay within subrooms and energy transfer between subrooms. The conditions under which statistical-acoustics models of coupled rooms are valid approximations to geometrical acoustics are examined by comparison of computational geometrical-acoustics predictions of decay curves in two- and three-room systems with those of both improved and prior statistical-acoustics models. The accuracy of the decay model used within subrooms is found to have a primary influence on the accuracy of predictions in coupled systems. Likewise, nondiffuse transfer of energy is shown to significantly affect decay of energy in systems of coupled rooms. The decrease in energy density of the reverberant field with distance from the source, which is predicted by geometrical acoustics, is found to result in spatial dependence of decay-curve shape for certain coupling geometries. Geometrical effects are shown to contribute to the failure of statistical-acoustics models in the case of strong coupling between subrooms; thus, previously proposed statistical-acoustics criteria cannot predict the point at which the models break down with consistent accuracy.
Acoustics↗
Survivin acts as an antiapoptotic factor during the development of mouse preimplantation embryos.
Apoptosis is an essential physiologic process used in almost all tissues to remove damaged or superfluous cells. However, the early embryos are unique because no cell death is found up to the blastocyst stage during normal development. Survivin, a member of the IAP family, is capable of binding to caspases to modulate their functions. Here, we investigated the expression of survivin, and its role in preventing apoptosis in mouse preimplantation embryos. Transcripts for survivin and a splice variant lacking exon 2 were detected from unfertilized oocytes up to hatched blastocyst stage. At the protein level, survivin was also detected at all stages of early embryos. The antisense approach was used to demonstrate the role of survivin on embryo development. Development of early embryos treated with antisense survivin oligonucleotides was arrested at the morula or early blastocyst stage with disruption of tubulin formation and abnormal nuclei, associated with apoptosis. The effect of the antisense was enhanced by cotreatment with an apoptosis-inducing reagent, staurosporine. In contrast, apoptosis induced by the antisense treatment was inhibited by caspase-3 and -9 inhibitors. These results indicate that survivin is an essential antiapoptotic gene expressed in preimplantation embryos and could protect the embryos from apoptosis by inhibiting an apoptotic pathway involving caspases.
Alternative Splicing↗
Efficacy of direct injection of calcitriol into the parathyroid glands in uraemic patients with moderate to severe secondary hyperparathyroidism.
INTRODUCTION: Secondary hyperparathyroidism (2HPT) is a common complication in uraemic patients. When medical therapy, including high doses of intravenous calcitriol, fails to suppress the pathological secretion of parathyroid hormone (PTH), one of the newly developed interventional techniques, such as percutaneous ethanol injection therapy (PEIT), is an option before taking the surgical solution. A protocol for direct calcitriol injection therapy and a discussion of its effectiveness and limitations for an enlarged parathyroid gland(s) are presented. METHODS: Nine patients were selected according to the Japanese Guideline for Selective PEIT. Using the same technique as PEIT, a dose of calcitriol that was approximately 200-300% of the calculated volume of the selected parathyroid gland was injected directly into the gland under ultrasonographic guidance. RESULTS: In six cases, the intact PTH concentration decreased to <360 pg/ml. The total volume of the enlarged parathyroid gland(s) also decreased to 54.7% of the initial volume. The blood supply to the treated glands, as evaluated by colour Doppler imaging, appeared to diminish transiently after injection, probably from the volume effect of this procedure. The number of enlarged parathyroid glands was not a limiting factor for this therapy; however, a grossly enlarged parathyroid gland (>2000 mm(3)) appeared to be resistant to this intervention and an intrathoracic parathyroid gland was found in a non-responsive case. None of the patients had any severe complications, such as nerve palsy or massive haemorrhage. CONCLUSION: This new approach to the control of 2HPT is recommended as an alternative pharmacological parathyroidectomy to surgical therapy.
Calcitriol↗
[A case of Mycobacterium avium pulmonary disease detected as multiple small nodular shadows and diagnosed by CT guided transbronchial biopsy with ultrathin bronchoscopy].
A 65-year-old man was admitted to our hospital because multiple small nodular shadows measuring five to 12 mm in diameter in both lung fields were noticed on chest radiographs and CT scans during a regular checkup for pulmonary emphysema. The levels of ESR and CRP were within normal limits, but those of CEA and CYFRA were slightly elevated. Mycobacterium avium (M. avium) was detected in sputum cultures and in a sputum examination using PCR. Non-necrotizing granulomas were detected in the specimens obtained from a lesion of the right S6b by CT-guided transbronchial biopsy using an ultrathin bronchoscope after navigation with virtual bronchoscopy. On the basis of these findings, M. avium pulmonary disease was diagnosed. The patient is being followed up, but because he has no symptoms, without medication. To our knowledge, there have been no previous reports of M. avium-intracellulare complex pulmonary disease, which is characterized by multiple small nodular shadows. It is speculated that multiple centrilobular lesions developed simultaneously without extension to the bronchial walls, leading in this case to multiple small nodules in both lung fields.
Aged↗