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Free radical bulk and solution polymerizationsof a divinyl monomer,ethylene glycol dimethacrylate (EGDMA), in the presence of methyl2-(bromomethyl)acrylate as an addition–fragmentation chaintransfer agent were investigated to synthesize thermally curable hyperbranchedpolymers by a one-step reaction. Soluble polymers were obtained upto high conversion of EGDMA, and the molecular weight and molecularweight distribution of the polymers increased with increasing EGDMAconversion. 1H NMR and MALDI-MS analyses revealed thatthe soluble polymers were obtained after the consumption of a considerableamount of the pendant methacryloyl groups, and one polymer chain containeda number of end groups indicating the formation of hyperbranched polymers.The isolated hyperbranched polymers underwent thermal curing above110 °C without curing agents, and the polymers having a largenumber of pendant methacryloyl groups resulted in a significant increasein glass transition temperature, i.e., from around room temperatureto above 210 °C. [ABSTRACT FROM AUTHOR]

Abstract: The polymerization of ω-haloalkyl propiolates initiated by [Rh(norbornadiene)Cl]2 in methanol has been investigated in detail together with the geometrical forms of the resulting polymers. The polymer yield and molecular weight of poly(2-haloethyl propiolate)s (P(2XEPA)s) were markedly reduced in the order of X=Cl, Br, and I. 1H NMR, electron spin resonance, and diffuse reflective UV–vis spectroscopic studies of P(2XEPA)s revealed that the content of cis form regarding the Ckedly decreased from 60% for P(2ClEPA) to 15% for P(2IEPA). The decrease in the cis content also resulted in notable reduction of the crystallinity of the polymer from 30% for P(2ClEPA) to less than 10% for P(2IEPA). Compression of P(2XEPA)s at room temperature induced the so-called cis-to-trans isomerization accompanied with decomposition of the polymers. [Copyright &y& Elsevier]

We investigated the pharmacokinetics and pharmacodynamics of paclitaxel with carboplatin or gemcitabine in patients with urogenital cancer to clarify the significance of monitoring of the serum concentration of paclitaxel. Paclitaxel was administered at 175 mg/m2 or 150 mg/m2 to patients with hormone-refractory prostate cancer ( n = 10) or advanced transitional cell carcinoma ( n = 6) along with carboplatin or gemcitabine, respectively. The relationships between pharmacokinetic parameters and hematological adverse effects, as well as pharmacological effects, were examined. The effects of patient characteristics, including single-nucleotide polymorphisms of MDR1(ABCB1), CYP2C8, CYP3A4, and CYP3A5, on the total body clearance of paclitaxel were evaluated. Total body clearance and volume of distribution at a steady-state after the intravenous infusion of paclitaxel were not significantly different between patients with carboplatin or gemcitabine. The percent decreases in neutrophils and platelets for the regimen with gemcitabine were significantly greater than those with carboplatin, and showed a significant positive relationship with the observed concentration at the end of infusion or time above 0.1-µM concentration of paclitaxel. Post-therapy decreases in prostate-specific antigen were not positively correlated with the extent of paclitaxel exposure in the prostate cancer patients. Neither the polymorphisms at exon 26 (C3435T) and at exon 21 (G2677A/T) in MDR1 nor the CYP3A5*1 allele significantly affected the total body clearance of paclitaxel. The hematological side effects of paclitaxel were intensified by gemcitabine, and were correlated with paclitaxel pharmacokinetics. Monitoring of the serum concentration of paclitaxel will facilitate the therapy, with less myelosuppression and without any loss of therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Background: The medial collateral ligament (MCL) is one of the most common knee injuries in competitive and recreational football. It can occur by itself or in combination with other ligaments. Mechanism of injury may be due to extrinsic forces to the knee, combined extrinsic forces and external rotation of the knee or through a non-contact fall with the foot firmly fixed. In general, it is said that majority of the MCL injury are due to these extrinsic mechanisms. Objective: The objective of this study is to investigate whether extrinsic factors lead to more knee MCL injuries in football players compared with intrinsic factors. Design: We performed a retrospective study by reviewing our electronic medical record from March 2010 to March 2018. Patients injured while playing football with a final diagnosis of MCL injury or MCL tear were included. Contact with other players and strong forces applied from the ball or ground during a kick were defined as extrinsic factors. Change of body direction, twisting of the leg, or simple landing from a jump without contact were defined as intrinsic factors. The number of patients injured from extrinsic and intrinsic factors were calculated. Results: Of the thirty seven (37) patients included in the study, 25 cases (67.5%) were due to extrinsic factors, 9 cases (24.3%) were due to intrinsic factors, and in 3 cases (8.1%) the injury mechanism was unclear. Conclusion: The majority of the knee MCL injuries in football players were due to extrinsic factors. Injuries caused by these extrinsic factors may be preventable. [ABSTRACT FROM AUTHOR]

Angiogenesis is essential for development, growth and advancement of solid tumors. Cyclooxygenase (COX)-2 is recognized as an angiogenic factor in various tumors. This prompted us to study the clinical implications of COX-2 expression related to angiogenesis in uterine cervical cancers. There was a significant correlation between microvessel counts and COX-2 levels in uterine cervical cancers. COX-2 localized in the cancer cells, but not in the stromal cells of uterine cervical cancer tissues. COX-2 levels increased with advancement, and the prognosis of the 30 patients with high COX-2 expression in uterine cervical cancers was poor (60%), while the 24-month survival rate of the other 30 patients with low COX-2 expression was 90%. Furthermore, COX-2 levels significantly correlated with VEGF levels in uterine cervical cancers. VEGF associated with COX-2 might work on angiogenesis in advancement. Therefore, long-term administration of COX-2 inhibitors might be effective on the suppression of regrowth or recurrence after intensive treatment for advanced uterine cervical cancers. [ABSTRACT FROM AUTHOR]

Angiogenesis is essential for the development, growth and advancement of solid tumors. Angiogenesis is induced by hypoxia with angiogenic transcription factor hypoxia inducible factors (HIF). This prompted us to study the clinical implications of HIF relative to angiogenesis in uterine cervical cancers. Although there was no significant difference in HIF-1α histoscores and mRNA levels according to histopathological type or lymph node metastasis, HIF-1α histoscores and mRNA levels increased significantly with advancing cancer stages. The prognosis of 30 patients with high HIF-1α in uterine cervical cancers was poor (73% survival), whereas the 24-month survival rate of the other 30 patients with low HIF-1α was 93%. HIF-1α histoscores and mRNA levels were correlated with the levels of the angiogenic factors thymidine phosphorylase and interleukin-8, and HIF-1α might be linked with these factors in cervical cancer tissue. HIF-1α is a candidate for prognostic indicator as an angiogenic mediator in uterine cervical cancer. ( Cancer Sci 2006; 97: 861–867) [ABSTRACT FROM AUTHOR]

Highly stereospecific polymerization of a novel sulfur containing aromatic acetylenes, i.e., (p-n-alkylsulfidephenyl)acetylene (pRSPA), (p-n-alkylsulfoxidephenyl) acetylene (pRSOPA), and (p-n-alkylsulfonephenyl) acetylene (pRSO2PA) was successfully performed using the Rh complex, [Rh (norbornadiene) Cl]2-TEA catalyst in the presence of various solvents under mild conditions. The resulting polymers were characterized in detail by H NMR, ESR, laser Raman, diffuse reflective UV-vis (DRUV-vis), and wide angle X-ray diffraction methods. The data showed that the resulting polymers bear cis-transoid form which can induce the cis-to-trans isomerization when the cis polymers were pressured at room temperature under vacuum. The cis C = C bonds in the main-chain are broken rotationally, giving two kinds of π-radicals called the cis radical and trans radical. Further, the resulting cis polymers were found to have a helical main-chain which is packed in pseudohexagonal crystal, called a π-conjugated columnar or nano π-conjugated columnar, as a novel color-controllable material. [ABSTRACT FROM AUTHOR]

In Arabidopsis thaliana, a number of clock-associated protein factors have been identified. Among them, TOC1 (TIMING OF CAB EXPRESSION 1) is believed to be a component of the central oscillator. TOC1 is a member of a small family of proteins, designated as ARABIDOPSIS PSEUDO-RESPONSE REGULATOR, including PRR1/TOC1, PRR3, PRR5, PRR7 and PRR9. It has not been certain whether or not other PRR family members are also implicated in clock function per se. To clarify this problem, here we constructed a double mutant line, which is assumed to have severe lesions in both the PRR5 and PRR7 genes. Resulting homozygous prr5-11 prr7-11 young seedlings showed a marked phenotype of hyposensitivity to red light during de-etiolation. In addition, they displayed a phenotype of extremely late flowering under long-day photoperiod conditions, but not short-day conditions. The rhythms at the level of transcription of certain clock-controlled genes were severely perturbed in the double mutant plants when they were released into continuous light (LL) and darkness (DD). The observed phenotype was best interpreted as ‘arrhythmic in both LL and DD’ and/or ‘very short period with markedly reduced amplitude’. Even under the light entrainment (LD) conditions, the mutant plants showed anomalous diurnal oscillation profiles with altered amplitude and/or phase with regard to certain clock-controlled genes, including the clock component CCA1 (CIRCADIAN CLOCK-ASSOCIATED 1) gene. Such events were observed even under temperature entrainment conditions, suggesting that the prr5-11 prr7-11 lesions cannot simply be attributed to a defect in the light signal input pathway. These pleiotropic circadian-associated phenotypes of the double mutant were very remarkable, as compared with those observed previously for each single mutant. Taking these results together, we propose for the first time that PRR5 and PRR7 coordinately (or synergistically) play essential clock-associated roles close to the central oscillator. [ABSTRACT FROM AUTHOR]

Reactions of the adduct radical obtained by addition of the initiator-derived 2-carbomethoxy-2-propyl radical to methyl α-[(2-methyl-2-carbomethoxy)propyl]acrylate (the unsaturated dimer of methyl methacrylate (MMAD)) have been monitored by electron paramagnetic resonance spectroscopy. Rate constants for addition of the 2-carbomethoxy-2-propyl radical to MMAD, mutual reactions between the adduct radicals, and reactions of the adduct radical and the 2-carbomethoxy-2-propyl radical, and β-fragmentation of the adduct radical were evaluated by steady-state and non-steady-state kinetic analysis in tandem with computer modeling and simulations involving parameter optimization procedures. The resulting rate constants showed that addition and radical–radical reactions between low molecular weight radicals are suppressed due to the marked steric congestion of the carbon-carbon double bond and radical center, respectively, and that β-fragmentation can compete with radical–radical reactions of the adduct radicals depending on the radical concentration. [Copyright &y& Elsevier]

ETS-1 has been identified as a transcription factor for angiogenesis, which is essential for the development and growth of the uterine endometrium. This characteristic prompted us to study whether ETS-1 functions as an angiogenic mediator in uterine endometrium. Immuno-histochemical staining revealed that the localization of ETS-1 was similar to that of vascular endothelial cells. There was a significant correlation between microvessel counts and both ETS-1 histoscores and ets-1 mRNA levels in uterine endometrium. The ETS-1 histoscores and ets-1 mRNA levels increased in the proliferative phase, reached a peak during peri-ovulation and decreased in the secretory phase. Furthermore, the ETS-1 histoscores and ets-1 mRNA levels correlated with vascular endothelial growth factor (VEGF) levels in the proliferative phase. This indicates that ETS-1 might be an angiogenic mediator in uterine endometrium linked to VEGF in the proliferative phase. [ABSTRACT FROM AUTHOR]

In Arabidopsis thaliana, the transcripts of the APRR1/TOC1 family genes each start accumulating after dawn rhythmically and one after another at intervals in the order of APRR9→APRR7→APRR5→APRR3→APRR1/TOC1 under continuous light. Except for the well-characterized APRR1/TOC1, however, no evidence has been provided that other APRR1/TOC1 family genes are indeed implicated in the mechanisms underlying circadian rhythms. We here attempted to provide such evidence by characterizing transgenic plants that constitutively express the APRR5 gene. The resulting APRR5-overexpressing (APRR5-ox) plants showed intriguing properties with regard to not only circadian rhythms, but also control of flowering time and light response. First, the aberrant expression of APRR5 in such transgenic plants resulted in a characteristic phenotype with regard to transcriptional events, in which free-running rhythms were considerably altered for certain circadian-regulated genes, including CCA1, LHY, APRR1/TOC1, other APRR1/TOC1 members, GI and CAB2, although each rhythm was clearly sustained even after plants were transferred to continuous light. With regard to biological events, APRR5-ox plants flowered much earlier than wild-type plants, more or less, in a manner independent of photoperiodicity (or under short-day conditions). Furthermore, APRR5-ox plants showed an SRL (short-hypocotyls under red light) phenotype that is indicative of hypersensitiveness to red light in early photomorphogenesis. Both APRR1-ox and APRR9-ox plants also showed the same phenotype. Therefore, APRR5 (together with APRR1/TOC1 and APRR9) must be taken into consideration for a better understanding of the molecular links between circadian rhythms, control of flowering time through the photoperiodic long-day pathway, and also light signaling-controlled plant development. [ABSTRACT FROM PUBLISHER]

Synthesis of the A/D/E-ring core compounds of maoecrystal V was achieved. The key Diels-Alder reactions between tricyclic α-methylene lactones and Kitahara-Danishefsky dienes afforded the spirocyclic core compounds in a regioselective and stereoselective manner. [ABSTRACT FROM AUTHOR]

T(3;14)(q27;q32) is frequently detected in B-cell non-Hodgkin's lymphomas, especially the diffuse large cell type and the follicular type. The BCL6 gene encoding a putative transcriptional factor which resides on 3q27 rearranges to the immunoglobulin heavy chain (IgH) gene on 14q32 in this chromosomal translocation. The upstream regulatory region of the BCL6 gene is replaced by the IgH gene. Deregulation of the BCL6 gene may contribute to tumourigenesis of these diseases. The rearrangement between the IgH and BCL6 genes generates chimaeric transcripts in which the joining (J) region of the IgH gene fuses to exon 3 of the BCL6 gene. We established a method to detect these chimaeric transcripts by reverse transcriptase polymerase chain reaction (RT-PCR) using the consensus sequence of the J region and the sequence of exon 3 of the BCL6 gene as primers. Using the semi-nested RT-PCR method and a cell line carrying t(3;14)(q27;q32), we detected one lymphoma cell among 10 000 background cells. We detected these chimaeric transcripts in two out of 13 clinical samples by this method. This method can detect t(3;14)(q27;q32) easily, whereas this alteration is frequently overlooked by routine karyotype analysis. Since this technique is sensitive enough to detect a small number of lymphoma cells with this genetic abnormality, it could be employed to detect contaminating lymphoma cells in bone marrow and peripheral blood and minimal residual diseases. [ABSTRACT FROM AUTHOR]

Coumarin-containing vinyl homopolymers, such as poly(7-methacryloyloxycoumarin) (P1a) and poly(7-(2′-methacryloyloxyethoxy)coumarin) (P1b), show a lower critical solution temperature (LCST) in chloroform, which can be controlled by the [2 + 2] photochemical cycloaddition of the coumarin moiety, and they are recognized as monofunctional dual-stimuli-responsive polymers. A single functional group of monofunctional dual-stimuli-responsive polymers responds to dual stimuli and can be introduced more uniformly and densely than those of dual-functional dual-stimuli-responsive polymers. In this study, considering a wide range of applications, organogels consisting of P1a and P1b, i.e., P1a-gel and P1b-gel, respectively, were synthesized, and their thermo- and photoresponsive behaviors in chloroform were investigated in detail. P1a-gel and P1b-gel in a swollen state (transparent) exhibited phase separation (turbid) through a temperature jump and reached a shrunken state (transparent), i.e., an equilibrium state, over time. Moreover, the equilibrium degree of swelling decreased non-linearly with increasing temperature. Furthermore, different thermoresponsive sites were photopatterned on the organogel through the photodimerization of the coumarin unit. The organogels consisting of homopolymers of coumarin-containing methacrylate exhibited unique thermo- and photoresponsivities and behaved as monofunctional dual-stimuli-responsive organogels. [ABSTRACT FROM AUTHOR]

In this study, we consider the control of a liquid droplet movement rolling down on an inclined plate with gravitational force using a micro-wrinkle on a wall. The micro-wrinkle was manufactured by the buckling of a thin polymer film (poly(N-vinylcarbazole), PVK) on a base polymer (poly(vinyl chloride), PVC). The PVC was stretched once and then PVK (~ 100-nm thickness) was spin-coated on the surface of the base polymer at ambient temperature. When the strain was released in a thermostatic chamber heated above the glass transition temperature of PVC, a two-dimensional micro-wrinkle having a wavelength of several micrometers was formed on the surface. The advancing and receding contact angles were measured in directions parallel and perpendicular to the wrinkle. It was observed that there were several degrees of contact angle anisotropy. When the droplet was set on the wrinkle surface inclined at 45° to the gravitational force, the direction of droplet movement could be changed by ~ 20° from the gravitational direction. The deflection angle was estimated from a theoretical model with the principle of minimum work of the contact line. The micro-wrinkle was manufactured by the buckling of a thin polymer film (poly(N-vinylcarbazole), PVK) on a base polymer (poly(vinyl chloride), PVC). It was observed that there were several degrees of contact angle anisotropy dependent on the direction in normal and parallel to the wrinkle. When the droplet was set on the oblique wrinkle, the direction of droplet sliding movement could be changed by ~20° from the gravitational direction in the plane as shown in the figure below. The deflection angle β can be roughly estimated from a theoretical model with the principle of minimum work of the droplet. [ABSTRACT FROM AUTHOR]

Treatment with a tyrosine kinase inhibitor (TKI) is the standard of care for patients with chronic myeloid leukemia (CML). The new-generation TKIs, nilotinib and dasatinib, are found to have deeper and faster treatment response rates compared to imatinib in the first-line setting. However, a direct comparison between nilotinib and dasatinib has never been reported previously. Our study aims to compare the outcomes and molecular responses achieved following the first-line use of these two agents in patients with CML-CP. The database of the CML Cooperative Study Group was reviewed and patients with CML in the chronic phase (CP) who were given nilotinib or dasatinib as first-line therapy were identified. Out of 361 patients with CML-CP enrolled in our database, 58 and 63 had been treated with conventional doses of nilotinib (300 mg twice daily) and dasatinib (100 mg once daily), respectively, as first-line therapy. The patient demographics did not show significant differences between the groups. The event-free survival rates did not differ between these two groups. The major molecular response (MMR) and the deep molecular response (DMR) rates by 6, 12, 18, and 24 months did not differ between groups. Among the three scoring systems, only the Hasford score could predict the achievement of DMR, and all of them failed to predict the achievement of MMR in the entire cohort. Our data suggest that both nilotinib and dasatinib have comparable efficacies and promising outcomes. [ABSTRACT FROM AUTHOR]

Abstract: This study deals with the control of the movement of liquid droplets rolling down an inclined plate based on the differences in the wettability of the plate. We used a photoreactive polymer poly(7-methacryloyloxy coumarin) (PMC) whose molecular structure can be changed reversibly to realize different wettabilities by ultraviolet irradiation. We proposed employing sawtooth patterns at boundaries between areas with different contact angles to control the droplet trajectory. Furthermore, we experimentally observed that the droplet moves along a line inclined to the direction of gravity. The droplet behavior can be analyzed using a theoretical model based on the droplet dynamics wherein the surface tension acting on the contact line and the gravitational force are considered. The theoretical results suggest that inclination from the gravitational direction can be increased if the advancing contact angle is reduced. In the experiments conducted herein, ultrasonic vibration was applied to the inclined plate to reduce the contact angle hysteresis. The results showed that the advancing contact angle actually decreased and that the droplet trajectory was controlled to realize motion along a line with inclination angle almost twice of that realized without vibration.Graphical abstract: A saw-tooth pattern of boundary between the areas with different contact angles was proposed to control the trajectory of a droplet rolling down on an inclined plate. As shown in the right figure, the droplet immediately diverges from the direction of gravity and moves in accordance with the target lines. [ABSTRACT FROM AUTHOR]

We performed a retrospective study to evaluate the incidence of second malignancies (SMs) in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). We analyzed data from 339 patients with CML who were extracted from the CML Cooperative Study Group database. The standardized incidence ratio (SIR) was calculated to assess the risk of SMs using data from the Cancer Registries in Japan. The median follow-up was 65 months. SMs developed in 14 patients (4.1%, 10 men, 4 women) after the start of TKIs. The median age was 69 years at the time of the CML diagnosis and 72.5 years at the time of the SM diagnosis. Ten patients were treated with imatinib, three with dasatinib, and one with nilotinib as the initial treatment. The SIR for all malignancies was 1.05 (95% CI 0.50-1.93) for men and 1.08 (95% CI 0.29-2.76) for women. The difference in the overall survival (OS) of patients with or without SMs was not statistically significant (5-year OS: 82.5% vs. 92.9%; p = 0.343). A subgroup analysis of 166 patients treated with second-generation TKIs (92 dasatinib, 74 nilotinib) showed that the SIRs for all malignancies were 1.33 (95% CI 0.36-3.41) for men and 0 for women. In conclusion, the incidence of SMs in CML patients during TKI treatment was the same as that in the general Japanese population. There was no evidence of an increase in the incidence of SMs during second-generation TKI treatment. Furthermore, the occurrence of SMs during TKI treatment did not affect the survival or mortality in our cohort. [ABSTRACT FROM AUTHOR]

ABL1-tyrosine kinase inhibitors (TKIs) have led to dramatic changes in treatment strategies for chronic myeloid leukemia in the chronic phase (CML-CP). However, clinical studies have highlighted increasing numbers of adverse events (AE) with TKIs. Although TKI modification plays a key role in AE management, this process is poorly understood, particularly in terms of the TKI nilotinib. In the present study, we retrospectively analyzed the records of 70 patients with newly diagnosed (ND)-CML-CP who were treated with nilotinib to investigate the drug potency of nilotinib and treatment management. During a median observation period of 3.4 years, 76% of patients continued nilotinib as a first-line treatment. The 1-year and overall major molecular response (MMR) rates and the overall molecular response (MR) 4.5 rate for all patients receiving first-line nilotinib therapy were 70, 84.2, and 50%, respectively. No case progressed to the accelerated or blast phase during the study. To avoid AEs during the early phase, nilotinib doses were reduced to < 600 mg/day in a third of patients (Reduced group); these patients experienced better therapeutic efficacy and a lower rate of AEs relative to those in Standard group (300 mg twice daily). Ten patients who received < 600 mg/day of nilotinib throughout the study had a 1-year MMR rate and overall MR4.5 rate of 90 and 60%, respectively. In summary, our findings indicate that careful management, including dose reduction, can yield better outcomes in patients with ND-CML-CP. [ABSTRACT FROM AUTHOR]