The aim of this study was to assess paclitaxel resistant-epithelial ovarian carcinoma (EOC) cells for cellular morphology, motility, and molecular changes consistent with epithelial-mesenchymal transition (EMT). The human EOC cell lines NOS-2, TAOV and SKOV-3 were continuously exposed to increasing doses of paclitaxel to establish three stable cell lines resistant to paclitaxel (NOS-PR, TAOV-PR, and SKOV-PR cells, respectively). Using these cell lines, cellular functions such as motility, invasive ability, and proliferative potential were assessed. Several molecules involved in EMT or cell invasiveness were assessed using Western blot analysis. In a peritoneal metastasis model using mice inoculated with NOS-2 or NOS-PR cells, we investigated the differences of peritoneal dissemination and survival time. NOS2-PR cells showed phenotypic changes consistent with EMT; with spindle-shaped morphology and enhanced pseudopodia formation. Western blot analysis revealed decreased expression of the epithelial adhesion molecule, E-cadherin and an increase in mesenchymal markers such as vimentin, fibronectin and smooth-muscle actin in NOS-PR cells compared to NOS-2 cells. The NOS2-PR cells displayed increased expression of Snail and Twist, EMT-regulatory transcription factors. Migratory potential in a wound assay and metastatic potential to the peritoneum of mice were markedly enhanced in NOS2-PR cells compared to NOS-2 cells. These data suggest that there is a possible link between chronic paclitaxelresistance and induction of the EMT in EOC cells. It is possible that therapeutic benefits such as the restoration of chemosensitivity or suppression of metastasis will be enabled by gaining further insight into the mechanisms underlying chemoresistance and EMT.

We have studied the frustration between ferro- and antiferro-electricity in chiral smectic C like liquid crystalline phases, which is not only fundamentally interesting but also very attractive from an application point of view. It causes temperature induced successive phase transitions as characterized by a devil's staircase and the thresholdless, hysteresis-free, V-shaped switching induced by an applied electric field. The devil's staircase indicates some type of interlayer ordering, while the V-shaped switching suggests considerably diminished tilting correlation. These two are apparently contradictory to each other, but result from the same cause, i.e. the frustration. We have first summarized experimental facts regarding subphases and successive phase transitions observed in many compounds and mixtures, which we believe are related to one another and result from the frustration. We have introduced several different theoretical explanations for these observed facts, and shown that only the axial next nearest neighbor Ising (ANNNI) model can explain almost all of the facts, provided that it is unified with the XY model appropriately. The unified model can make a comprehensive explanation in the most natural way based on the most probable molecular interactions. We have then emphasised that there are several modes regarding the V-shaped switching, because the system becomes so soft with respect to the tilting direction and sense that any additional external or internal force modifies the in-plane local director alignments. For the practically usable ones, we have emphasised the need for some type of randomization in the molecular alignment at the tip of the V and/or the switching process. In particular, the two dimensional (ideally, cylindrically symmetric) azimuthal angle distribution of local in-plane directors around the smectic layer normal is most attractive. Such a randomized state at the tip of the V is thermodynamically unique under a given condition imposed by interfaces. It stays stable even when the smectic layer structure, such as a chevron, changes with temperature. Finally, we have summarized the so-far reported compounds and mixtures for the V-shaped switching and introduced some prototypes of LCDs using them.

Loss of E-cadherin triggers peritoneal dissemination, leading to an adverse prognosis for most patients with epithelial ovarian carcinoma (EOC). Because TWIST mainly regulates the epithelial-to-mesenchymal transition and is one of the E-cadherin repressors, we investigated the possibility that TWIST expression affects peritoneal metastasis of EOC using siRNA technique. In the present study, we showed a correlation between TWIST expression and EOC cellular morphology. Furthermore, we demonstrated that the suppression of TWIST expression in EOC cells (HEY) alters the cellular morphology from a fibroblastic and motile phenotype to an epithelial phenotype, and inhibits the adhesion of these cells to mesothelial monolayers. To investigate the mechanism by which down-regulation of TWIST leads to inhibition of adhesion to mesothelial cells (MCs), expression of adhesion molecules (CD29, CD44 and CD54) were observed. Moreover, matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase, important markers associated with invasive and metastatic potential, were remarkably reduced. This findings suggests that reduced expression of TWIST suppresses the multistep process of peritoneal dissemination (detachment from the primary lesion, adhesion to MCs and invasion of MCs) and may be a potential therapeutic target for the treatment of this carcinoma.

Introduction: Shock index (SI), calculated by dividing heart rate by systolic blood pressure, is used to detect hemodynamic instability and hypovolemia. In obstetric practice, limited evidence is available regarding its usefulness in detecting postpartum hemorrhage (PPH). We aimed to evaluate the usefulness of SI in detecting PPH in vaginal deliveries using clinical data from 12 primary maternity care units in Japan. Material and methods: In this multicenter retrospective study, a total of 30,820 women who delivered vaginally at term at 12 primary maternity care units from January 2012 to December 2018 were included. Systolic and diastolic blood pressures and heart rate were measured at five different time points from admission to postpartum 2 h, and postpartum blood loss was measured. We evaluated the trend of average SI and the performance of each vital sign for detection of PPH. Results: The trend of average SI during labor and the immediate postpartum period was approximately 0.7 in women with blood loss of <500 mL. SI from the time of delivery of the placenta increased with an increase in blood loss. SI had the highest area under the receiver operating characteristic curve of 0.699 [95% confidence interval (CI), 0.682-0.716] and 0.758 (95% CI, 0.729-0.788) for PPH of !1,000 and !1,500 mL, respectively. However, both sensitivity of SI (1.0) for PPH (!1,000 mL; 29.9%, and !1,500 mL; 40.5%, respectively) and correlation between maximum SI and blood loss (coefficient of correlation, 0.263) were low. Conclusions: SI is a better parameter for PPH detection in vaginal deliveries than other vital signs. However, clinical judgment must incorporate other vital signs and symptoms associated with hypovolemic shock due to the low sensitivity of SI.

BackgroundLow back pain (LBP) during pregnancy might be strongly related to posture and movements of the body, and its management is a clinically important issue. The purpose of this study was to investigate the activities related to LBP during pregnancy.MethodsParticipants included 275 women before 12 weeks of pregnancy. The women were evaluated at 12, 24, 30, and 36 weeks of pregnancy. The intensity of LBP was assessed using the Numerical Rating Scale (NRS). Movements related to LBP were investigated by free descriptive answers. Descriptive statistics were used to compile the movements that pregnant women thought induced LBP at each evaluation. Subsequently, a linear regression analysis was performed to evaluate the degree of association of certain movements with LBP using the data of participants who had LBP. The intensity of LBP (NRS score) was specified as the dependent variable, the movements that were related to pain were specified as the independent variables at the analysis. A significance threshold was set at 0.05.ResultsThe final sample used in the analyses was 254, 249, 258, and 245 women at 12, 24, 30, and 36 weeks of pregnancy, respectively. There were 16 kinds of movements that induced LBP and all of them were daily activities rather than special movements that require extra task or effort. As pregnancy progressed, less number of participants attributed pain to a specific movement. At all evaluations, movements, especially sitting up, standing up from a chair, and tossing and turning were thought to be related to LBP. Furthermore, standing up from a chair and tossing and turning were significantly related to LBP throughout the pregnancy. In contrast, lying down and sitting up were significantly related to LBP but the relationship did not continue till late pregnancy.ConclusionsDaily routine activity is related to LBP during pregnancy. These results suggest that recommendations for pregnant women about basic physical movements, such as ways of standing up that reduce the load on the body might be useful in the management of LBP.

From a heat capacity measurement in high magnetic fields and at low temperatures, we have obtained evidence for a magnetic ordering in the S = 1 quasi-one dimensional Heisenberg antiferromagnet . The transition temperature is at 12 T parallel to the chain axis.

Waterproofing agents consist of mixtures of solvents, repellents and propellants. Because of a fatality and a number of acute respiratory illnesses in humans following the exposure to a waterproofing agent, the aerosol mixtures were tested in mice. Inhalation of the waterproofing agent resulted in pulmonary collapse and pneumonia in mice. By testing fractions of the waterproofing agent it was determined that the fluororesin repellents in the waterproofing agent were responsible for the acute respiratory illness. The water-repelling agent, such as fluororesin, may counteract the surfactant in the alveoli of the lung and cause diffuse pulmonary collapse followed by acute respiratory distress. The recent substitution of less toxic and environmentally more friendly solvents in waterproofing agents may facilitate fluororesin inhalation by increasing the amount of airborne aerosol and changing the diameter of the aerosol particles. This would explain the apparent recent increase of respiratory symptoms following the use of these agents. In this experiment the mice were exposed intermittently to overcome the CNS effects of the solvents.

We investigated the effect of hyperbaric oxygen treatment (HBO) on cytokine induction after hemorrhage, because hypoxia induces cytokines in vitro. Chronically cannulated conscious rats were subjected to 40 ml/kg of hemorrhage and resuscitated with the shed blood and twice the volume of saline either under room air (room air group) or under 100% oxygen at 3 atmospheres absolute (hyperbaric group). Rats exposed to HBO with no hemorrhage served as controls. Time course changes in plasma endotoxin level, arterial ketone body ratio (AKBR), serum tumor necrosis factor (TNF), interleukin-6 (IL-6), and their hepatic mRNA were detected in the three groups. Plasma endotoxin levels increased significantly after hemorrhage, and there were no significant differences between the room air group and the hyperbaric group. In the room air group, AKBR dropped rapidly after hemorrhage and became minimal at hour 1, which was associated with significant increases in TNF-alpha and IL-6 at both mRNA and circulating levels. HBO significantly attenuated decreases in AKBR after hemorrhage with a significant reduction of mortality and cytokine induction. These results indicate that HBO attenuated the cytokine induction after hemorrhage by improving liver ischemia, and they suggest that tissue hypoxia may be responsible, at least in part, for cytokine induction after massive hemorrhage.