Prognostic significance of adjuvant chemotherapy in stage I-II endometrial carcinoma patients who underwent lymphadenectomy.

BACKGROUND: Endometrial carcinoma, the most common gynecologic carcinoma, has an excellent prognosis post-surgery when diagnosed early. The role of postoperative adjuvant chemotherapy in stages I-II endometrial carcinoma remains controversial. This study assesses the efficacy of adjuvant chemotherapy in improving prognosis for these patients. METHODS: A retrospective analysis was conducted on 1223 stage I-II endometrial carcinoma patients who underwent surgical treatment including total hysterectomy, bilateral salpingo-oophorectomy, and lymph-node biopsy or dissection across four Jikei University School of Medicine-affiliated facilities between 2001 and 2018. Patients were divided into low intermediate risk (LIR) and high intermediate risk (HIR) groups based on recurrence risk. Propensity score matching adjusted for various covariates was used to compare progression-free survival (PFS) and overall survival (OS) between patients who received adjuvant chemotherapy and those who did not. RESULTS: The study included 443 eligible patients, with 288 in the LIR group and 155 in the HIR group. Post propensity score matching, no significant difference in PFS or OS was observed between the observation and adjuvant chemotherapy groups within both risk categories. Notably, the 5-year OS for LIR was 97.6% in the observation group and 96.7% in the chemotherapy group; for HIR, the 5-year OS was similarly high with no significant difference. CONCLUSIONS: The findings suggest that postoperative adjuvant chemotherapy does not significantly contribute to the improvement of recurrence or prognosis in patients with stage I-II endometrial carcinoma who are categorized outside the low-risk group and have no lymph-node metastasis.

Delivery-Dependent Shift in Oxytocin-Responsive Cell Population in the Central Amygdala of the Female Rat.

INTRODUCTION: Despite its recent reputation as prosocial neurohormone, the most important physiological role of oxytocin (OT) is stimulating uterine contractions. Though it is well known that plasma OT concentrations change drastically during delivery, it remains unexplored whether and how OT receptors in the maternal brain are activated. We examined whether the responses of cells in the central amygdala (CeA), an OT receptor-rich limbic site involved in pain and fear memory regulation, to exogenously applied OT analogue, Thr-Gly-OT (TGOT), vary depending on delivery. METHODS: Intracellular Ca2+ dynamics of the CeA cells were visualized in brain slices from female rats at virgin (VG), during pregnancy term (PT) days 16-21, within 24 h after delivery (G0), and within 1-3 days after delivery (G3). The Ca2+ responses to 1 µM TGOT, 20 mM KCl (high K), and 300 µM ADP were compared. RESULTS: We found that fraction of cells responding to TGOT, high K, and ADP differed significantly between the four delivery-associated terms. In particular, the fraction of cells responding to TGOT (TGOT responders) significantly increased from VG and PT at G0 and G3. Furthermore, the significant positive correlation between TGOT and high K response in TGOT and high K responders was reduced at G0, while that between TGOT and ADP responses in TGOT and ADP responders was increased at G0. CONCLUSION: These results indicate that the responses of CeA cells to an OT receptor agonist markedly change around delivery, which might play a role in controlling the labor-related pain and post-delivery emotional complications.

Phase II study of gemcitabine, cisplatin, and bevacizumab for first recurrent and refractory ovarian clear cell carcinoma Kansai Clinical Oncology Group-G1601.

Patients with advanced ovarian clear cell carcinoma (CCC) have a poor prognosis in the absence of an effective standard treatment. Combination therapy with gemcitabine, cisplatin, and bevacizumab (GPBev) is promising for ovarian CCC. Thus, we conducted a multi-institutional, phase II trial in Japan to examine the efficacy and safety of GPBev for CCC. This is the first study on the use of GPBev for CCC. Eighteen patients (median age, 56.5 years) with pathologically confirmed first recurrent or refractory CCC and having evaluable regions, as assessed using RECIST, were recruited between January 2017 and May 2019. Gemcitabine (1000 mg/m 2 ), cisplatin (40 mg/m 2 ), and bevacizumab (10 mg/kg) were administered intravenously on days 1 and 15, every 28 days, for 6-10 cycles, until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR). The secondary endpoints included disease control rate (DCR) and adverse events (AEs). Fifteen patients (83.3%) completed 6-10 cycles of treatment; three patients (two with AEs and one with progressive disease) did not. The ORR was 61.1% [complete response (CR) 3 and partial response (PR) 8] and DCR was 88.9% (CR 3, PR 8, and stable disease 5). Grade 3 and 4 hematological AEs were observed in 16.7 and 5.6% of the patients, respectively. Nonhematological AEs of grades 3 and 4 were observed in 27.8 and 5.6% of the patients, respectively. GPBev is a promising therapy for CCC owing to the high ORR and acceptable toxicity for the first recurrence and refractory CCC.

Re-thinking the prognostic significance of positive peritoneal cytology in endometrial cancer.

BACKGROUND: Whether abnormal peritoneal cytology (PC) is an independent prognostic factor in endometrial cancer (EC) remains controversial. This study aimed to re-think the prognostic significance of PC in not only all EC patients but also in various subgroups with similar clinicopathological and biological characteristics. METHODS: EC patients who underwent primary surgery of at least a hysterectomy and were pathologically diagnosed with EC in four hospitals affiliated with the Jikei University School of Medicine were retrospectively reviewed. The prognostic significance of PC was evaluated with univariate and multivariate analyses in the entire cohort and subgroups stratified by surgical stages (early/advanced stages), tumor types (types 1/2), and risk classifications (low/intermediate/high). RESULTS: Of 1963 EC cases, 1616 met the inclusion criteria. Positive PC was identified as an adverse prognostic factor in analyses of all EC cases and in all subgroup analyses stratified by surgical stages and tumor types. In survival curve comparisons, the progression-free survival (PFS) and disease-specific survival in early-stage patients with positive PC were clearly located between those of stage II patients with negative PC and stage III patients. In the subgroup analyses stratified by risk classification in early-stage EC, positive PC was related to poorer PFS in the intermediate- and high-risk groups but not in the low-risk group. CONCLUSION: PC status was an independent prognostic factor of EC in all stages and tumor types. Early PC-positive cases, except for the low-risk group, may be recommended for upstaging and should be carefully managed compared with PC-negative cases.

[Elucidation of Influential Factors on Nausea Associated with Olaparib Administration].

Olaparib, an anticancer drug, requires daily administration, frequently causing nausea. Elucidation of the influential factors for nausea is important for continuing treatment. We retrospectively examined 23 patients who received olaparib treatment and were divided into nausea and no-nausea groups, according to antiemetic prescriptions during treatment. We compared the patients' background and laboratory values between the 2 groups. Nine patients developed nausea and 14 did not, with mean body weights at treatment initiation of 49.9±9.8 kg and 60.0±13.9 kg, respectively. Body weights were significantly lower in the nausea than in the no-nausea group. Four weeks after olaparib administration, the logarithmic difference in the fluctuation of the neutrophil count was -0.145±0.154 and 0.095±0.242, while the fluctuation of the lymphocyte count was -0.169±0.053 and -0.060±0.110 in the nausea and no-nausea groups, respectively, with the former significantly lower than the latter. The treatment period for the nausea group was significantly longer than that for the no-nausea group. Since olaparib is administrated as a flat dose, the dose per body weight increased in underweight patients. Thus, being underweight might have impacted the efficacy of olaparib, including the development of side effects such as nausea and hematotoxicity.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Dimensions of catenated ring polymers in dilute solution studied by Monte-Carlo simulation.

Interaction between two simple ring chains catenated in a molecule was estimated by a Metropolis Monte Carlo simulation, and the result was compared with a model. We employed catenated ring chains in this study; they were composed of two simple ring chains, and the topology was kept as 2 1 2 . The temperature dependence of the distance between two ring chains in a molecule was discussed using Flory's scaling exponent, ν, in R g ∝ N ν , where R g is the radius of gyration of a simple ring chain catenated in a molecule. In the simulation, the topology of the component rings and their links were kept because chain crossing was prohibited. The excluded volume of chains was screened by the attractive force between polymer segments, and the strength of the attractive force depends on temperature, T. At the θ temperature for trivial ring polymers, where the condition ν = 1/2 holds, their trajectories can be described statistically as a closed-random walk, i.e., a closed-phantom chain model. The temperature at which interaction between trivial ring polymers, i.e., inter-molecular interaction, is repulsive; trivial ring polymer molecules show the excluded volume generated with keeping their own topology, 01. A catenated molecule is composed of two simple rings, and so forth a component ring can be affected by the existence of the counterpart rings. Under that temperature, the mean-square distance between two rings in a catenated molecule, ⟨L 2⟩, was obtained and compared with that of the simple model composed of two circles in three-dimensions, where interaction between circles is set as zero. It has been found that the simulated ⟨L 2⟩ values were constantly larger than those of the model owing to the excluded volume of rings in a molecule.

Adjuvant therapy after radical surgery for stage IB-IIB cervical adenocarcinoma with risk factors.

OBJECTIVE: Patients with adeno/adenosquamous carcinoma may have a poorer prognosis than patients with squamous cell carcinoma. Radiotherapy and concurrent chemoradiotherapy are used as adjuvant therapies for cervical cancer, regardless of the histological subtype. The aim of this study was to investigate the prognostic outcome of adjuvant therapy for patients with adeno/adenosquamous carcinoma with pathological risk factors. METHODS: The medical records of 135 patients with stage IB-IIB cervical cancer with squamous cell carcinoma or adeno/adenosquamous carcinoma who underwent primary surgery followed by adjuvant therapy were retrospectively reviewed. Patients with a pathologically confirmed bulky tumor (≥4 cm), nodal metastasis and/or parametrium invasion were included in the study. RESULTS: The median follow-up period was 48 (1-132) months. Of the 135 patients, 90 with squamous cell carcinoma and 23 with adeno/adenosquamous carcinoma were treated with adjuvant radiotherapy and concurrent chemoradiotherapy (SCC-RT/CCRT and AC-RT/CCRT groups), and 22 with adeno/adenosquamous carcinoma were treated with adjuvant systemic chemotherapy (AC-CT group). There were no significant differences in clinicopathological factors between the SCC-RT/CCRT and AC-RT/CCRT groups and between the AC-RT/CCRT and AC-CT groups. Progression-free survival was significantly shorter in the AC-RT/CCRT group compared to the SCC-RT/CCRT group (P = 0.002). Adeno/adenosquamous carcinoma histology and multiple lymph node metastasis were independent prognostic factors for shorter progression-free survival in patients treated with adjuvant radiotherapy and concurrent chemoradiotherapy. Progression-free survival was also significantly shorter in the AC-RT/CCRT group compared to the AC-CT group (P = 0.026). CONCLUSIONS: Adjuvant radiotherapy and concurrent chemoradiotherapy may be less effective for patients with adeno/adenosquamous carcinoma than for those with squamous cell carcinoma. Adjuvant systemic chemotherapy may be beneficial for adeno/adenosquamous carcinoma and further studies are warranted.

Morphology of symmetric ABCD tetrablock quaterpolymers studied by Monte Carlo simulation.

Morphology of symmetric ABCD tetrablock quaterpolymers in melt was studied by the Monte Carlo (MC) simulation, where the volume fractions of the block chains, f, kept the relationships of fA=fD and fB=fC, and the volume fraction of the two mid-blocks φ was defined as φ=fB+fC. Previous self-consistent field theory for ABCD reported morphological change including several structures; however, the scope was limited within a two-dimensional system. To the contrary, in this paper, MC simulations were carried out in three dimensions with changing the φ value finely, which resulted in finding a tetracontinuous structure in the range of 0.625≤φ≤0.75. Moreover the tetracontinuous structure has been found to be the gyroid structure, and the mean curvature of the B/C interface is nearly zero. We concluded that the B/C interface must be the Schoen gyroid surface, one of three-dimensional periodic minimal surfaces. The geometrical nature of the A/B interface should be equivalent to that of the C/D interface, and they stand as level surfaces to the Schoen gyroid surface.

Interactions between ring polymers in dilute solution studied by Monte Carlo simulation.

The second virial coefficient, A2, for trivial-ring polymers in dilute condition was estimated from a Metropolis Monte Carlo (MC) simulation, and the temperature dependence of A2 has been discussed with their Flory's scaling exponent, ν, in Rg ∝ N(ν), where Rg is radius of gyration of a polymer molecule. A limited but not too small number of polymer molecules were employed in the simulation, and the A2 values at various temperatures were calculated from the molecular density fluctuation in the solution. In the simulation, the topology of ring polymers was kept, since chain crossing was prohibited. The excluded volume effects can be screened by the attractive force between segments, which depends on the temperature, Tα, defined in the Metropolis MC method. Linear and trivial-ring polymers have the ν value of 1/2 at Tα = 10.605 and 10.504. At Tα = 10.504, the excluded volume effects are screened by the attractive force generated between segments in a ring polymer, but the A2 value for ring polymers is positive. Thus, the temperature at A2 = 0 for a ring polymer is lower than that at ν = 1/2, and this fact can be explained with the following two reasons. (a) Rg value for a ring polymer is much smaller than that for a linear polymer at the same temperature and molecular weight, where interpenetration of a ring polymer chain into neighboring chains is apparently less than a linear chain. (b) The conformation of trivial rings can be statistically described as a closed random walk at ν = 1/2, but their topologies are kept, being produced topological constraints, which strongly relate not only to the long-distance interaction between segments in a molecule but also the inter-molecular interaction.

Impact of surgical staging in stage I clear cell adenocarcinoma of the ovary.

AIM: The aim of this study was to evaluate the impact of surgical staging in stage I clear cell adenocarcinoma of the ovary (CCC). METHODS: We performed a retrospective review of 165 patients with stage I CCC treated with optimal or nonoptimal staging surgery. RESULTS: The median follow-up period in this study was 67 months. No significant difference was detected in recurrence-free survival (RFS) or overall survival (OS) between patients optimally and nonoptimally staged (RFS: P = 0.434; OS: P = 0.759). The estimated 5-year RFS and OS rates were 92.1% and 95.3% in patients with stages IA/IC1 and 81.0% and 83.7% in stages IC2/IC3, respectively. The multivariate analysis indicated that stages IC2/IC3 predicted worse RFS and OS than stages IA/IC1 in stage I CCC patients (RFS: P = 0.011; OS: P = 0.011). Subsequently, we investigated the impact of surgical staging, respectively, in stages IA/IC1 and stages IC2/IC3. Significant differences were observed in PFS and OS between patients optimally and nonoptimally staged with stages IA/IC1 (RFS: P = 0.021; OS: P = 0.024), but no significant difference was found in those with stages IC2/IC3. The multivariate analysis indicated that nonoptimal staging surgery predicted worse RFS than the optimal staging surgery in stages IA/IC1 CCC patients (P = 0.033). In addition, we investigated the impact of surgical staging for stages IA/IC1 in the adjuvant chemotherapy group. The 5-year RFS and OS rates in patients optimally and nonoptimally staged with stages IA/IC1 in the adjuvant chemotherapy group were 97.8% and 100%, and 85.2% and 89.4%, respectively. The multivariate analysis indicated that nonoptimal staging surgery predicted worse RFS than the optimal staging surgery for stages IA/IC1 patients in the adjuvant chemotherapy group (P = 0.019). CONCLUSIONS: The prognosis for women with stage 1A/IC1 is very good. Surgical staging category was the only independent prognostic factor for RFS in stages IA/IC1 CCC.

Validate robot-assisted total laparoscopic hysterectomy with four equally-spaced ports without an assistant port.

To evaluate the usefulness of robot-assisted total laparoscopic hysterectomy with four equally-spaced ports (RA-TLH/4e) without an assistant port. In RA-TLH/4e, four da Vinci ports were placed horizontally at a height of 4 cm above the umbilicus with 8 cm equal spacing. Poor development of the surgical field or difficult forceps manipulations were handled with the endoscope and forceps movement (port-hopping). Patient background, surgical outcomes, complications, port-hopping frequency were compared in three groups: RA-TLH/4e, RA-TLH with four unequally-spaced ports (RA-TLH/4u), and conventional RA-TLH with five ports (RA-TLH/5). There were no significant differences in patient background or surgical outcomes among the three groups except for age, preparation time, and hospital stay, and no cases of laparotomy conversion or serious complications. RA-TLH/4e had fewer port-hoppings than RA-TLH/4u. The minimum abdominal width showed a weak negative correlation with port-hopping frequency in RA-TLH/4u, but not in RA-TLH/4e. RA-TLH/4e allowed for a reduction in personnel and costs compared to RA-TLH/5. The equal placement of four ports allowed sufficient port spacing even for patients with narrow abdominal widths. In addition, the port-hopping technique was able to fully compensate for the lack of an assistant port. RA-TLH/4e is a highly useful technique that not only excels in safety but also reduces costs.

Prognostic impact of the number of resected pelvic nodes in endometrial cancer: Japanese Gynecologic Oncology Group Study JGOG2043 post hoc analysis.

OBJECTIVE: This study aimed to determine whether the number of resected pelvic lymph nodes (PLNs) affects the prognosis of endometrial cancer (EC) patients at post-operative risk of recurrence. METHODS: JGOG2043 was a randomized controlled trial to assess the efficacy of three chemotherapeutic regimens as adjuvant therapy in EC patients with post-operative recurrent risk. A retrospective analysis was conducted on 250 patients who underwent pelvic lymphadenectomy alone in JGOG2043. The number of resected and positive nodes and other clinicopathologic risk factors for survival were retrieved. RESULTS: There were 83 patients in the group with less than 20 PLNs removed (group A), while 167 patients had 20 or more PLNs removed (group B). There was no significant difference in patients' backgrounds between the two groups, and the rate of lymph node metastasis was not significantly different. There was a trend toward fewer pelvic recurrences in group B compared with group A (3.5% vs. 9.6%; p=0.050). Although Kaplan-Meier analysis showed no statistically significant difference in survival rates between the two groups (5-year overall survival [OS]=90.3% vs. 84.3%; p=0.199), multivariate analysis revealed that resection of 20 or more nodes is one of the independent prognostic factors (hazard ratio=0.49; 95% confidence interval=0.24-0.99; p=0.048), as well as surgical stage, high-risk histology, and advanced age for OS. CONCLUSION: Resection of 20 or more PLNs was associated with improved pelvic control and better survival outcomes in EC patients at risk of recurrence who underwent pelvic lymphadenectomy alone and were treated with adjuvant chemotherapy.

A survey of carboplatin desensitization therapy in Japan: A multicenter retrospective study.

INTRODUCTION: Hypersensitivity reactions (HSRs) to chemotherapy are serious adverse events associated with cancer drug therapy and can occur with any antitumor drug. This study investigated the safety and efficacy of carboplatin desensitization therapy in Japan and established a method for treating carboplatin HSRs. METHODS: Patients diagnosed with gynecological (ovarian, endometrial, or cervical) cancers who underwent carboplatin desensitization therapy between 2016 and 2020 at the Gynecologic Cancer Study Group of Japan Clinical Oncology Group were included. The carboplatin desensitization therapy at each institution and the implementation cases were registered in an online case report form. RESULTS: This retrospective study enrolled 136 patients (ovarian, 108; endometrial, 17; and cervical cancer, 11). Pre-existing allergies were present in 37 (27.2%) patients, and 32 (23.5%) patients exhibited prodromal symptoms during treatment before HSR onset. Erythema was the most common symptom at HSR onset, affecting 93 (68.4%) patients, followed by itching in 72 (52.9%) patients and decreased oxygen saturation in 43 (31.6%) patients. Loss of consciousness occurred in three (2.2%) patients. The most common timing of HSR onset was during the first recurrence treatment (47%). The mean total carboplatin dose until HSR onset was 7331 (2620-18,282) mg, and the mean number of doses was 14 (4-63). Desensitization treatment was completed in 75% of cases, and breakthrough HSRs occurred in 25% (34/136). No deaths occurred in the study cohort. The risk factors for HSRs were not identified. CONCLUSION: Although carboplatin desensitization therapy has high success rates in Japan, erythema and pruritus are important HSRs to consider.

Topological constraint in ring polymers under theta conditions studied by Monte Carlo simulation.

We studied equilibrium conformations of trivial-, 3(1)-, and 5(1)-knotted ring polymers together with a linear counterpart over the wide range of segment numbers, N, from 32 up through 2048 using a Monte Carlo simulation to obtain the dependence of the radius of gyration of these simulated polymer chains, R(g), on the number of segments, N. The polymer chains treated in this study are composed of beads and bonds placed on a face-centered-cubic lattice respecting the excluded volume. The Flory's critical exponent, ν, for a linear polymer is 1/2 at the θ-temperature, where the excluded volume is screened by the attractive force generated among polymer segments. The trajectories of linear polymers at the θ-condition were confirmed to be described by the Gaussian chain, while the ν values for trivial-, 3(1)-, and 5(1)-knots at the θ-temperature of a linear polymer are larger than that for a linear chain. This ν value increase is due to the constraint of preserving ring topology because the polymer chains dealt with in this study cannot cross themselves even though they are at the θ-condition. The expansion parameter, ß, where N-dependence vanishes by the definition, for trivial-, 3(1)-, and 5(1)-knotted ring polymers is obtained at the condition of ν = 1/2. It has been found that ß decreases with increasing the degree of the topological constraint in the order of trivial (0.526), 3(1) (0.422), and 5(1) knot (0.354). Since the reference ß value for a random knot is 0.5, the trivial ring polymer is swollen at ν = 1/2 and the other knotted ring polymers are squeezed.

Chain conformations of ring polymers under theta conditions studied by Monte Carlo simulation.

We studied equilibrium conformations of trivial-, 31-knot, and 51-knot ring polymers with finite chain length at their θ-conditions using a Monte Carlo simulation. The polymer chains treated in this study were composed of beads and bonds on a face-centered-cubic lattice respecting the excluded volume. The Flory's critical exponent ν in Rg ~ N(ν) relationship was obtained from the dependence of the radius of gyration, Rg, on the segment number of polymers, N. In this study, the temperatures at which ν equal 1∕2 are defined as θ-temperatures of several ring molecules. The θ-temperatures for trivial-, 31-knot, and 51-knot ring polymers are lower than that for a linear polymer in N ≤ 4096, where their topologies are fixed by their excluded volumes. The radial distribution functions of the segments in each molecule are obtained at their θ-temperatures. The functions of linear- and trivial-ring polymers have been found to be expressed by those of Gaussian and closed-Gaussian chains, respectively. At the θ-conditions, the excluded volumes of chains and the topological-constraints of trivial-ring polymers can be apparently screened by the attractive force between segments, and the values for trivial ring polymers are larger than the half of those for linear polymers. In the finite N region the topological-constraints of 31- and 51-knot rings are stronger than that of trivial-ring, and trajectories of the knotted ring polymers cannot be described as a closed Gaussian even though they are under θ-conditions.

Neuronal mechanism of epileptogenesis in EL mouse.

The convulsions of the EL mouse (EL) were described by Imaizumi et al. in 1954 and were established as epilepsy by Suzuki in 1976. The EL mouse has been kept as an inbred strain and is considered one of the best animal models originated in Japan. The mode of inheritance is autosomal dominant, and environmental risk factors for seizure occurrence are hypothesised to contribute to the polygenic background. Paroxysmal activities in the EL brain arise from the parietal cortex (PCX) and are augmented in the hippocampus, demonstrated by electrophysiology and autoradiography using 2-deoxy glucose when clinical symptoms of seizures appeared. The neurons in the EL PCX, where GABA activity is lower than that of DDY PCX demonstrate increased excitability to proprioceptive sensory input. After repetitive seizure-provoking stimuli, seizures are more easily induced, eventually occurring spontaneously. This phenomenon of "abnormal plasticity" is also observed in the EEG, decreasing GABA activity, expression of the immediately early gene, and various biochemical and molecular processes. This phenomenon is similar to the learning or progressive process of certain neurological diseases.

The theta-temperature depression caused by topological effect in ring polymers studied by Monte Carlo simulation.

We studied equilibrium conformations of linear and ring polymers in dilute solutions over the wide range of segment number N of up to 2048 with Monte Carlo simulation, and evaluated N dependence of the radii of gyration, R(g), of chains. The polymer molecules treated in this study are assumed to be composed of beads and bonds, and they are put in a three-dimensional face-centered cubic (FCC) lattice. The values of Flory's critical exponent, ν, for linear and ring polymers were estimated from the N dependence of R(g), and the temperatures at which ν reach 1/2 were obtained. Here we define those as Θ-temperatures in this report. The simulation result shows that the Θ-temperature for ring polymers is evidently lower than that of the linear polymers, and the origin of the Θ-temperature depression is discussed. Since R(g) of a ring polymer is smaller than that for a linear polymer at the same N and temperature, the segment density for a ring polymer is increased by the topological effect and the repulsive force between segments of a ring polymer at the Θ-temperature for a linear polymer is stronger. Thus, the origin of the Θ-temperature depression for ring polymers is the repulsive force emphasized by the topological effect of rings.

Hexagonally Packed Cylindrical Structures with Multiple Satellites from Pentablock Quarterpolymers of the AB1CB2D Type and Their Blends with Homopolymers.

Three kinds of hexagonally packed cylindrical (HPC) structures with 10/8 satellites have been found from a neat pentablock quarterpolymer of the AS1IS2P type, composed of poly(4-vinylbenzyldimethylamine) (A), polystyrene (S), polyisoprene (I), and poly(2-vinylpyridine) (P), and block polymer/homopolymer blends. AS1IS2P-2 (M = 276k, ϕA/ϕS1/ϕI/ϕS2/ϕP = 0.08/0.17/0.12/0.33/0.30) shows HPC of P with 10 single-arrayed I satellites and 6 A subsatellites in the S matrix, where the I/P ratio number is 5, while AS1IS2P-2 (M = 325k, ϕA/ϕS1/ϕI/ϕS2/ϕP = 0.07/0.31/0.14/0.18/0.30)/Sh(M;11k) = 90/10 blend reveals another HPC of P with 10 I satellites, giving an I/P ratio of 6, whose array of I is a single/double mixture. Moreover, AS1IS2P-1/Sh/Ah(M;9k) = 90/5/5 blend represents two enantiomeric HPC packings with 8 double-arrayed I satellites having an I/P ratio of 7, which can be considered to be approximants of two enantiomeric 3.3.3.3.6 Archimedean tilings. These structures were conceived to be formed by the enhanced miscibility of tail A-chains with added homopolymers, resulting in an increase of the (A + S)/I interaction leading to the split of I domains.

Triply Helical Giant Domain with Homochirality in a Terpolymer Blend System.

Hexagonally packed coaxial triply helical domains with a mesoscopic length scale in matrices were created from an S1IS2P tetrablock terpolymer/Sh homopolymer blend system, wherein S1, S2, and Sh denote polystyrene, I is polyisoprene, and P represents poly(2-vinylpyridine). Two terpolymers, i.e., S1IS2P-3 (S1/I/S2/P = 0.50/0.17/0.19/0.14, M = 134k) and S1IS2P-4 (S1/I/S2/P = 0.58/0.16/0.10/0.16, M = 173k), were blended with Sh (M = 3k) at various concentrations. In the S1IS2P-3/Sh = 80/20 blend, the helical domain of P (o.d.= 19 nm; h.p. = 34 nm) was displayed by TEM, and the helical I phase (o.d. = 55 nm; i.d. = 29 nm; h.p. = 34 nm) was clearly demonstrated by 3D-TEM tomography. Essentially the same structure was confirmed to be created from the S1IS2P-4/Sh blend. These findings point out that S2 chains fill the gap between the I and P helices, and hence the intermediate S phase also has a helical nature. Moreover, it is worth noting that grains composed of hexagonally packed helices reveal homochirality.