Dynamic viscoelasticity measurement under alternative torque using electromagnetically spinning method with quadruple electromagnets.

In this study, we developed a novel type of rheological measurement system. Here, a spherical probe is driven to rotate periodically by applying torques using quadruple electromagnets in a noncontact manner. Moreover, this system is an enhancement of our electromagnetically spinning (EMS) viscometer, which is widely used for measuring rheological flow curves in various industrial fields. The quadruple EMS method provides the frequency spectrum of viscoelasticity, in addition to shear viscosity, in a steady flow by switching the operation modes of the driving torque. We show the results obtained for Newtonian fluids and viscoelastic materials and demonstrate the validity of the system.

Non-essential and branched-chain amino acids differentially regulate insulin-like growth factor binding protein-1 production and phosphorylation in HepG2 cells.

Deprivation of branched-chain amino acids (BCAAs) induces insulin-like growth factor binding protein-1 (IGFBP-1) production in HepG2 cells, while the role of non-essential amino acids (NEAAs) remains unknown. We investigated changes in IGFBP-1 production and phosphorylation induced by NEAAs and also examined its significance on IGF-I activity in HepG2 cells. We demonstrated that decreased BCAAs and increased NEAAs stimulated phosphorylated IGFBP-1 secretion. We also revealed that decreased BCAA-to-NEAA ratios enhanced phosphorylated IGFBP-1 secretion, while changes in the total amount of amino acids (AAs) had no effect. Phosphorylation of IGF-I receptor ß-subunits mediated by exogenous IGF-I in HepG2 cells was inhibited by decreased BCAAs, increased NEAAs, and decreased BCAA-to-NEAA ratios, while the total amount of AAs had no effect. In addition to BCAAs, NEAAs are also responsible for the regulation of IGFBP-1 secretion and phosphorylation in HepG2 cells. Moreover, the balance of BCAAs and NEAAs regulated IGFBP-1 secretion and phosphorylation.

Ramelteon, a selective MT1/MT2 receptor agonist, suppresses the proliferation and invasiveness of endometrial cancer cells.

The incidence of endometrial cancer is increasing, making it the fifth most common cancer worldwide. To date, however, there is no standard therapy for patients with recurrent endometrial cancer. Melatonin, a hormone secreted by the pineal gland, has been shown to have anti-tumor effects in various tumor types. Although melatonin is available as a supplement, it has not been approved for cancer treatment. Ramelteon, a selective melatonin receptor type 1 and 2 (MT1/MT2) receptor agonist, has been approved to treat sleep disorders, suggesting that ramelteon may be effective in the treatment of endometrial cancer. To determine whether this agent may be effective in the treatment of endometrial cancer, this study investigated the ability of ramelteon to suppress the proliferation and invasiveness of HHUA cells, an estrogen receptor-positive endometrial cancer cell line. Ramelteon at 10-8 M maximally suppressed the proliferation of HHUA cells, reducing the percentage of Ki-67 positive proliferating cells. This effect was completely blocked by luzindole, a MT1/MT2 receptor antagonist. Furthermore, ramelteon inhibited HHUA cell invasion and reduced the expression of the MMP-2 and MMP-9 genes. These results suggested that ramelteon may be a candidate for the treatment of recurrent endometrial cancer, with activity similar to that of melatonin.

Increased Blood Viscosity in Ischemic Stroke Patients with Small Artery Occlusion Measured by an Electromagnetic Spinning Sphere Viscometer.

BACKGROUND AND PURPOSE: High blood viscosity causes blood stagnation and subsequent pathological thrombotic events, resulting in the development of ischemic stroke. We hypothesize that the contribution of blood viscosity may differ among ischemic stroke subtypes based on specific pathological conditions. We tried to verify this hypothesis by measuring blood viscosity in acute ischemic stroke patients using a newly developed electromagnetic spinning sphere (EMS) viscometer. METHODS: Measurements in acute ischemic stroke patients were performed 4 times during admission and data were compared with those obtained from 100 healthy outpatient volunteers. RESULTS: We enrolled 92 patients (cardioembolism: 25, large artery atherosclerosis: 42, and small artery occlusion [SAO]: 25) in this study. Comparisons of blood viscosity between the ischemic stroke subgroups and control group revealed that blood viscosity at the date of admission was significantly higher in the SAO group (5.37 ± 1.11 mPa⋅s) than in the control group (4.66 ± .72 mPa⋅s) (P < .01). Among all subtype groups showing a reduction in blood viscosity after 2 weeks, the SAO group showed the highest and most significant reduction, indicating that SAO patients had the most concentrated blood at the onset. CONCLUSIONS: Blood viscosity was significantly increased in the SAO group at the date of admission, which indicated the contribution of dehydration to the onset of ischemic stroke. The importance of dehydration needs to be emphasized more in the pathogenesis of SAO. The clinical application of the EMS viscometer is promising for understanding and differentiating the pathogenesis of ischemic stroke.

Measurement of human blood viscosity by an electromagnetic spinning sphere viscometer.

We herein applied an electromagnetic spinning sphere (EMS) viscometer to the measurement of human blood viscosity for the first time. We collected blood samples from 100 healthy outpatient volunteers in order to analyse viscosity dependence on blood cell parameters and on the shear rate with a simple approximation formula [ηi (γ)\, = Ai γ(- pi) + η0]. Viscosity dependence on blood cell parameters was relatively high at a high shear rate, but became lower as the shear rate decreased. The approximation formula with appropriate parameters of Ai and pi nearly faithfully reproduced actual blood rheological behaviour with a standard deviation of 1.5%. The distributions of Ai and pi values were broad, suggesting that the pattern of viscosity dependence on the shear rate varied with individual differences. The results obtained using the EMS viscometer suggest that blood viscosity values are individual-specific and actual individual measurements are important for understanding rheological conditions.

Branched-chain amino acids regulate insulin-like growth factor-binding protein 1 (IGFBP1) production by decidua and influence trophoblast migration through IGFBP1.

STUDY QUESTION: Do branched-chain amino acids (BCAAs) influence the migration of human extravillous trophoblast (EVT) cells through changes in insulin-like growth factor-binding protein 1 (IGFBP1) production in decidual cells? STUDY FINDING: Decidua-derived IGFBP1 had a stimulating effect on migration of EVT. WHAT IS KNOWN ALREADY: IGFBP1 is abundantly secreted from human decidual cells and influences trophoblast migration in human placenta of early pregnancy. In hepatic cells, the expression of IGFBP1 is influenced by nutritional status and BCAAs regulate IGFBP1 production. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: This is a laboratory-based study using human decidual cells and trophoblast cells isolated from placental tissue of early pregnancy (n = 50) and grown as primary cultures. Production of IGFBP1 from decidual cells was examined by enzyme-linked immunosorbent assay and immunoblotting after incubation with or without BCAAs. EVT migration was evaluated using the media conditioned by decidual cells. The effect of conditioned media on phosphorylation of focal adhesion kinase (FAK) in EVT was also analyzed by immunoblotting. The same experiments were repeated in the presence of RGD peptide, which inhibits IGFBP1 binding to α5ß1 integrin. An EVT migration assay and the immunoblotting of phosphorylated FAK were also conducted with exogenous IGFBP1. The effect of the conditioned media on cytotrophoblast cell number was also assessed using WST-1 in a cell proliferation assay. MAIN RESULTS AND THE ROLE OF CHANCE: Deprivation of BCAAs on decidual cells significantly suppressed IGFBP1 secretion (P < 0.05, versus BCAA+). Exogenous IGFBP1-stimulated EVT migration (P < 0.05) and phosphorylation of FAK (P < 0.05), and the RGD peptide inhibited these effects. EVT migration and phosphorylation of FAK were stimulated by the conditioned media, presumably by IGFBP1 in the media. RGD treatment abrogated the stimulating effects of conditioned media. The conditioned media deprived of BCAAs had suppressive effects on EVT migration (P < 0.05, versus BCAA+) and phosphorylation of FAK (P < 0.05, versus BCAA+). The conditioned media did not affect number of cytotrophoblast cells. LIMITATIONS, REASONS FOR CAUTION: The conclusions are based on in vitro experiments with human decidual cells and trophoblast cells isolated from placental tissue of early pregnancy, and we were unable to ascertain whether these mechanisms actually operate in vivo. We investigated the effect of decidua-derived IGFBP1 on EVT migration, however, we cannot completely rule out the possibility that endogenous IGF could also influence cell migration. WIDER IMPLICATIONS OF FINDINGS: Interruption of the BCAA supply to uterine decidual cells in early pregnancy may suppress EVT migration through reduced IGFBP1 secretion, which may be one of the pathophysiological conditions responsible for pre-eclampsia. LARGE SCALE DATA: None. STUDY FUNDING/ AND COMPETING INTERESTS: All funds were obtained through Kyorin University School of Medicine. The authors have no conflict of interest to declare.

Intrapartum group B Streptococcus screening using real-time polymerase chain reaction in Japanese population.

OBJECTIVE: The objective of this study was to analyze the diagnostic accuracy of a commercial real-time polymerase chain reaction (PCR) assay for group B streptococcus (GBS) colonization status and to compare results of the intrapartum PCR with the antepartum conventional GBS culture in Japanese pregnant women. METHODS: This prospective observational study enrolled Japanese pregnant women at 35-37 weeks' gestation. Paired recto-vaginal swabs were obtained for PCR and conventional culture, both at 35-37 weeks' gestation and at admission for delivery. Performance of PCR was analyzed by comparing with the culture results. Furthermore, using the intrapartum culture results as the gold standard, the test of both the antepartum culture and the intrapartum PCR were characterized. RESULTS: We prospectively enrolled 79 pregnant women at 35-37 weeks' gestation, and the intrapartum results were obtained from 73 of those women. The sensitivity of PCR was 86.2%, and concordance rate with the conventional culture was 96.7% overall. Compared with the intrapartum culture, the sensitivity and the specificity of the intrapartum PCR were 83.3% and 98.4%, respectively, while the sensitivity and the specificity of the antepartum culture were 100.0% and 95.1%. CONCLUSIONS: The intrapartum real-time PCR assay for GBS screening has the accuracy similar to the antepartum conventional culture method.

Prenatal diagnosis of Klippel-Trenaunay-Weber syndrome with Kasabach-Merritt syndrome in utero.

Klippel-Trenaunay-Weber syndrome (KTWS), a congenital disease characterized by cutaneous hemangiomas, soft tissue and bone hypertrophy, and occasionally arteriovenous malformations, is extremely rare and its natural history in utero is unknown. We present a prenatally diagnosed case of KTWS complicated with Kasabach-Merritt syndrome in utero and fetal hydrops from acute anemia. The fetus was diagnosed with KTWS at 24 weeks of gestation based on the ultrasound findings of hemangiomas and unilateral hypertrophy of the lower extremity. Acute enlargement of the hemangiomas and the appearance of new retroperitoneal hemangiomas were detected at 27 weeks, along with skin edema and cardiomegaly. Doppler examination showed elevated peak systolic velocity in the middle cerebral artery, indicating acute fetal anemia. We believe the fetus's condition was complicated with Kasabach-Merritt syndrome in utero, which caused acute hemolytic anemia leading to high-output cardiac failure and fetal hydrops.

Antepartum reversible cerebral vasoconstriction syndrome with pre-eclampsia and reversible posterior leukoencephalopathy.

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe headache and diffuse segmental constriction of the cerebral arteries that resolves spontaneously within a few months. Pregnancy is one of the precipitating factors of RCVS and most of the reported cases occurred in the post-partum period. We report a case of RCVS that occurred in a pregnant women with pre-eclampsia during her antepartum period. A 34-year-old woman in full-term pregnancy presented with a severe and acute headache. Magnetic resonance angiography (MRA) showed multiple segmental constrictions of the cerebral arteries. Magnetic resonance imaging revealed a high-intensity lesion in the left occipital lobe, consistent with reversible posterior leukoencephalopathy syndrome, on fluid attenuated inversion recovery sequences. The case was also complicated by severe pre-eclampsia and the patient underwent emergency cesarean section. Although her symptoms resolved rapidly, MRA revealed new lesions of arterial constriction 4 days after onset. The vasoconstriction completely resolved on MRA after 10 days and the patient was discharged without neurological sequelae.

Paracellular route is the major urate transport pathway across the blood-placental barrier.

Urate, the final oxidation product of purine metabolism, is excreted into urine in humans. Clinically, increased serum urate levels are indicative of pregnancy-induced hypertension (PIH). However, how urate is handled in the placenta is still largely unknown. In this study, we compared maternal serum urate levels with those of umbilical cord blood and investigated urate transport mechanisms in BeWo cells, a trophoblast-derived cell line. The maternal and umbilical cord blood samples and placentas were collected from patients undergoing cesarean section at Kyorin University Hospital after obtaining informed consents. There were no significant differences in serum urate levels between maternal blood and umbilical cord blood, and between umbilical cord vein and arterial blood, suggesting that urate is freely movable at the placenta and that fetus is not a major source of urate production. RT-PCR and immunohistochemistry showed that urate transporters including OAT4, OAT10, GLUT9/URATv1 and ABCG2 were expressed in the syncytiotrophoblast cells in the placenta as well as BeWo cells. Despite expressing aforementioned urate transporters BeWo cells did not take up urate. After confirming the formation of tight junctions of these cells cultured on the transwell, urate transport between upper and lower chambers was measured. Urate moved through BeWo cell monolayers with nonsaturation kinetics and this movement was observed even when the cells were incubated at 4°C, suggesting that urate moves through the paracellular route by simple diffusion.

Prenatal diagnosis of umbilical artery thrombosis.

Umbilical artery thrombosis (UAT) is rare and few prenatally diagnosed cases have been reported. We describe 2 cases of fetal growth restriction prenatally diagnosed as UAT by ultrasound examination. In each case the cross section of the umbilical cord showed one normal artery and a small echogenic area which was suspected as an occluded thrombotic artery and they were surrounded by a highly curving 'C-shaped' vein. UAT was confirmed by histological examinations after deliveries in both cases. The characteristic ultrasound finding of the umbilical vessel, which is the so-called 'orange grabbed sign', enables the prenatal diagnosis of UAT and it is valuable with respect to perinatal fetal management because UAT is associated with increased perinatal morbidity and mortality.

Hypoxia alters phosphorylation status of insulin-like growth factor (IGF)-binding protein-1 and attenuates biological activities of IGF-I in HepG2 cell cultures.

AIM: Insulin-like growth factor (IGF)-I is known to stimulate fetal growth. One of the IGF-binding proteins, IGFBP-1, suppresses IGF-I activity, and thereby inhibits fetal growth. Because hypoxic stress in the uterus is known to cause fetal growth restriction, we examined the effects of hypoxia on IGFBP-1 production and phosphorylation status. METHODS: Because liver is a main IGFBP-1 production site in the fetus, we used a hepatoma cell line, HepG2 cells, that secrete a large amount of IGFBP-1, express IGF-I receptors and model fetal liver metabolism in vitro. IGFBP-1 was analyzed by sodium dodecylsulfate polyacrylamide gel electrophoresis (PAGE) following immunoblotting, and IGFBP-1 phosphorylation status was analyzed by native PAGE following immunoblotting. RESULTS: Total concentrations of IGFBP-1 in media were higher and the highly phosphorylated isoforms were dominant in low oxygen conditions. Phosphorylation of IGF-I receptor by IGF-I was attenuated in low oxygen conditions. IGF-I-induced phosphorylation of insulin receptor substrate-1 (IRS-1) was attenuated in low oxygen conditions as well. However, attenuated phosphorylation of IGF-I receptor and IRS-1 were not observed in low oxygen conditions if the cells were stimulated with LR³IGF-I that has a similar binding affinity to IGF-I receptor but much less binding affinity to IGFBP-1 compared to those of native IGF-I. While IGF-I-induced cell proliferation was also inhibited in low oxygen conditions, LR³IGF-I-stimulated cell proliferation was not inhibited. These findings indicate that low oxygen conditions inhibit IGF-I action by increasing IGFBP-1, especially phosphorylated IGFBP-1, which inhibits IGF-I action. CONCLUSION: This study has indicated that hypoxia-induced IGFBP-1 production in the fetus may be a conserved physiological mechanism for restricting IGF-I-stimulated fetal growth.

Noncontact measurement of liquid-surface properties with knife-edge electric field tweezers technique.

We have developed a technique for the simultaneous measurement of the surface tension and the viscosity of a liquid in a noncontact manner. In this method, a small linear deformation of the liquid surface is induced by a local dielectric force that is brought about by a knife-edge electrode. The surface tension and the viscosity are obtained from the shape of the induced meniscus and from the dynamic response of the surface, respectively. The surface tension obtained was examined in comparison with the values measured by the Wilhelmy plate method. We also measured time constants of the surface deformation for a variety of standard viscosity samples and obtained the relation between the time constant and the viscosity. The demonstrated advantage of the system is the ability to uniquely determine the surface tension and the viscosity.

Blood viscometer applying electromagnetically spinning method.

Viscosity is an important parameter which affects hemodynamics during extracorporeal circulation and long-term cardiac support. In this study, we have aimed to develop a novel viscometer with which we can easily measure blood viscosity by applying the electromagnetically spinning (EMS) method. In the EMS method, we can rotate an aluminum ball 2 mm in diameter indirectly in a test tube with 0.3 ml sample of a liquid by utilizing the moment caused by the Lorentz force as well as separate the test tube from the viscometer body. First, we calibrated the EMS viscometer by means of liquid samples with known viscosities and computational fluid dynamics. Then, when we measured the viscosity of 9.4 mPa s silicone oil in order to evaluate the performance of the EMS viscometer, the mean viscosity was found to be 9.55 ± 0.10 mPa s at available shear rates from 10 to 240 s(-1). Finally, we measured the viscosity of bovine blood. We prepared four blood samples whose hematocrit levels were adjusted to 23, 45, 50, and 70% and a plasma sample without hemocyte components. As a result, the measurements of blood viscosities showed obedience to Casson's equation. We found that the viscosity was approximately constant in Newtonian silicone oil, whereas the viscosity decreased with increasing shear rate in non-Newtonian bovine blood. These results suggest that the EMS viscometer will be useful to measure blood viscosity at the clinical site.

Improvement of insulin sensitivity promotes extravillous trophoblast cell migration stimulated by insulin-like growth factor-I.

Insulin-like growth factor-I (IGF-I) has been shown to stimulate extravillous trophoblast (EVT) cell migration and invasion, and to play a crucial role in placental function, thereby, influencing placental development and fetal growth. Insufficient invasion of EVT cells into the uterine endometrium leads to pregnancy-related complications, including spontaneous abortion, fetal growth restriction (FGR), and pregnancy-induced hypertension (PIH). Insulin-resistant conditions such as polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) have also been associated with abortion and PIH. However, the effects of IGF-I on EVT cells under insulin-resistant conditions have not been elucidated yet. The current study was undertaken to analyze the effects of IGF-I under insulin-resistant conditions and to determine whether improvement in insulin sensitivity alters IGF signaling and cell migration in the EVT. Incubation with pioglitazone, an insulin sensitizer, increased peroxisome proliferator-activated receptor-γ (PPARγ) expression after 48 h. A 48-h pre-incubation with insulin reduced the phosphorylation and concentration of the insulin receptors, which were increased by insulin treatment. Long-term exposure to insulin reduced phosphorylation of the IGF-I receptor, insulin receptor substrate-1 (IRS-1), and Akt, and also reduced EVT cell migration. However, when the cells were incubated with pioglitazone in addition to insulin for 48 h, the phosphorylation of these proteins was restored. This combination partially reversed the inhibitory effect of insulin on EVT cell migration. These results suggest that abnormalities in pregnancy that are induced by loss of insulin sensitivity can be treated by improving insulin sensitivity.

Measurement of the skin layer in the drying process of a polymer solution.

When a polymer solution is dried in air, a polymer-concentrated region, called a "skin" layer, often appears near the surface. In this paper, an experimental method is proposed for detecting the initial process of the formation of the skin layer. An electric field is applied on the surface of polymer solutions by a wedge-type "electric field tweezers," and the dynamic response of the surface profile is measured by an optical lever technique. Our experiments and theory indicate that when a skin layer is formed, (i) the slow relaxation process appears in the time domain and (ii) the long-persisting dip region appears in the surface profile. A parameter to quantify the difference of the surface response is proposed in this paper.

Polymerization of insulin-like growth factor-binding protein-1 (IGFBP-1) potentiates IGF-I actions in placenta.

Insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1), the main secretory protein of decidua that binds to IGFs and has been shown to inhibit or stimulate IGFs' bioactivities. Polymerization, one of the posttranslational modifications of IGFBP-1, has been shown to lead to loss of inhibiting effect of IGFBP-1 on IGF-I actions. The current studies were undertaken to elucidate the effects of steroid hormones on IGFBP-1 polymerization in trophoblast cell cultures. Placental tissues were obtained during legal, elective procedures of termination of pregnancy performed between 7 and 10 weeks of gestation, and primary trophoblast cells were separated. IGFBP-1 polymerization was analyzed by SDS-PAGE and immunoblotting. IGFBP-1 was polymerized when IGFBP-1 was added to trophoblast cell cultures. Polymerization of IGFBP-1 was inhibited by the addition of anti-tissue transglutaminase antibody into the culture media. There was an increase in the intensity of polymerized IGFBP-1 bands with the addition of medroxyprogesterone acetate (MPA), while no such difference was observed upon treatment with estradiol. MPA also increased the expression of tissue transglutaminase on trophoblast cell membranes. IGF-I stimulated trophoblast cell migration, while IGFBP-1 inhibited this IGF-I-induced trophoblast response. Addition of MPA attenuated the inhibitory effects of IGFBP-1 on IGF-I-induced trophoblast cell migration. IGFBP-1 was polymerized by tissue transglutaminase on the cell surface of trophoblasts, and MPA increased tissue transglutaminase expression on the cell surface and facilitated IGFBP-1 polymerization. These results suggest that progesterone might facilitate polymerization of decidua-secreted IGFBP-1 and increase IGF-I actions at feto-maternal interface, thereby stimulating trophoblast invasion of maternal uterus.

Tumor necrosis factor-alpha (TNF-alpha) inhibits insulin-like growth factor-I (IGF-I) activities in human trophoblast cell cultures through IGF-I/insulin hybrid receptors.

Tumor necrosis factor-alpha (TNF-alpha) in placenta is believed to be involved in pathogenesis of intrauterine growth restriction. In contrast, insulin-like growth factors (IGFs) are believed to be important for stimulation of fetal and placental growth. IGF-I stimulates metabolic and growth-promoting actions directly through its receptors: IGF-I receptor (IGF-IR), insulin receptor (IR) and IGF-I/insulin hybrid receptor (HR). However, it has not been elucidated which receptor mediates the growth promoting effects in fetal and placental growth. The current studies were undertaken to test whether TNF-alpha affects IGF-I action on placenta using human trophoblast cell cultures, and to test which receptor mediates growth promoting effects of IGF-I in placenta. Primary culture of trophoblast cells, which express IGF-IR, IR, and HR, were exposed to TNF-alpha, and the effects of IGF-I in stimulating trophoblast cell proliferation and migration were determined. Exposure to TNF-alpha attenuated the effects of IGF-I on cell proliferation and migration. To determine which receptors are involved in this inhibitory effect, the ability of IGF-I to stimulate phosphorylation of its receptors was analyzed in the presence of TNF-alpha. TNF-alpha exposure neither attenuated the phosphorylation of IGF-IR homodimer by IGF-I nor changed receptor abundance. In contrast, TNF-alpha reduced the ability of IGF-I to stimulate phosphorylation of HR with reducing amounts of HR. Exposure to TNF-alpha also attenuated phosphorylation of insulin receptor substrate-1 (IRS-1) and the association of IRS-1 with phosphatydilinositol-3 kinase (PI-3 kinase). Taken together, these findings indicate that TNF-alpha induces a loss of sensitivity to stimulation by IGF-I, through reducing amounts of HR and the stimulation of HR tyrosine kinase activity by IGF-I.

Ripplon on high viscosity liquid.

A ripplon is a thermally excited capillary wave propagating on liquid surface. Propagation of the ripplon reflects surface mechanical properties such as surface tension and viscoelasticity of the liquid. An optical beating ripplon spectroscopy technique developed by us was applied mainly to the observation of various surface phenomena on a lowly viscous liquid surface in the frequency range from 1 kHz to several 10 MHz. In this study, we carried out a light scattering observation of the highly damped ripplon on the surface of the viscous liquid. The spectral peak width of the damped ripplon was smaller for the higher viscosity and the optical beating technique could resolve such a structure. A strict description of the dynamic structure factor of the ripplon was employed to fit the experimental power spectrum of overdamped ripplon to viscosity up to 1000 cS.

Insulin-like growth factor binding protein-1 induces decidualization of human endometrial stromal cells via alpha5beta1 integrin.

Progesterone is known to induce decidualization of human endometrial stromal cells in vitro. Decidualized stromal cells produce insulin-like growth factor binding protein-1 (IGFBP-1) as well as prolactin (PRL). In this study, we tested the possibility that IGFBP-1 directly stimulates endometrial stromal cell decidualization. Endometrial stromal cells were obtained from normal menstruating patients with uterine myoma at hysterectomy. Stromal cells were cultured for up to 4 weeks with estradiol (E(2)) and/or medroxy progesterone acetate (MPA) in the presence or the absence of IGFBP-1 and, LR(3)-IGF-I (an IGF-I analogue) that binds to the IGF-I receptor but has reduced affinity for IGFBPs. Decidualization of endometrial stromal cells was evaluated by morphological changes and PRL release into culture media. The binding of IGFBP-1 to endometrial cells was analysed using a biosensor. MPA and E(2) induced decidualization of stromal cells, while LR(3)-IGF-I inhibited decidualization by MPA and E(2) as well as PRL and IGFBP-1 secretion into medium. IGFBP-1 induced decidualization of stromal cells in the absence of MPA and E(2) in the medium. IGFBP-1-induced decidualization was not inhibited by the addition of LR(3)IGF-1 but was inhibited by the addition of an RGD peptide, however, the RGD peptide had no effect on decidualization when added alone. The binding analysis showed that IGFBP-1 bound to the surface of endometrial stromal cells and an anti-alpha5beta1 integrin antibody inhibited its binding. These results suggest that IGFBP-1 produced by endometrium can mediate progesterone-induced decidualization possibly by interacting with alpha5beta1 integrin on the surface of endometrial stromal cells.