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Introduction: Cervical spine surgery reduces falls and subsequent femoral fractures. Nonetheless, current evidence on the prevalence of cervical cord compression (CCC) and increased signal intensity (ISI) in patients with femoral fractures is limited. We aimed to determine the prevalence of CCC and ISI and characterize the physical status and imaging findings using cervical spine magnetic resonance imaging (MRI) and brain computed tomography (CT) in patients with femoral fractures., Methods: This study included 173 patients (140 women, 33 men) with femoral fractures caused by falling, who underwent both cervical spine MRI and brain CT. CCC cases classified as grade 2 (compression of less than one-third of the spinal cord) or higher were investigated. The ISI of the severely affected intervertebral disc level was evaluated using T2-weighted MRI. Hand grip strength and myelopathic signs were also evaluated. Data analysis was performed using the χ 2 test, Fisher's exact test, and Student's t -test., Results: Among the 173 patients, 83 (48.0%) had CCC, 29 (16.8%) had ISI, and 68 (39.3%) had abnormal brain CT findings. There was no ISI in patients in the non-CCC group. The patients' average age in the CCC group was significantly higher than that in the non-CCC group. There was no significant difference in the proportion of myelopathic sign and abnormal brain CT findings between the CCC and non-CCC groups or between the ISI and non-ISI groups. Bilateral hand grip strength was significantly negatively correlated with the stenosis rate (right, p=0.047; left, p=0.0018)., Conclusions: In conclusion, our study showed that patients with femoral fractures had a high frequency of cervical canal stenosis and intracranial lesions using cervical spine MRI and brain CT., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2022 The Japanese Society for Spine Surgery and Related Research.)

Although minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is the most common procedure in minimally invasive spine stabilization (MISt), details of the technique remain unclear. This technical report shows the mid-long-term clinical outcomes in patients who underwent posterior oblique square decompression (POSDe) with the three-step wanding technique of tubular MIS-TLIF for degenerative lumbar disease. Tubular MIS-TLIF (POSDe) was performed on 50 patients (males, 19; age, 69.2 ± 9.6 years), and traditional open surgery was performed (OS) on 27 (males, 4; age, 67.9 ± 6.6 years). We evaluated the clinical outcomes using the Visual Analog Scale for back pain, Japanese Orthopedic Association (JOA) scores, and JOA Back Pain Evaluation Questionnaire. We also assessed the fusion rate using the Bridwell grading system with computed tomography or plain radiography for at least 2 years postoperatively. Although there was no significant difference in the improvement rate of JOA scores between the two groups, the mean operation time and blood loss were significantly lower with MIS-TLIF than with OS. In the tubular MIS-TLIF group, there were no cases of deep wound infection; four cases had a pseudarthrosis, two had dural injury, and three had cage retropulsion. We revealed good clinical outcomes in patients who underwent POSDe.

Background: It is unknown whether locking or nonlocking superior plate fixation is better for managing displaced midshaft clavicle fractures. Therefore, we aimed to compare the clinical and radiographic outcomes of locking and nonlocking superior plate fixation of displaced midshaft clavicle fractures., Methods: A total of 102 consecutive patients with displaced midshaft clavicle fractures (2B1 and 2B2 in Robinson classification) participated in this randomized controlled trial; 12 patients were excluded. Surgeries were performed using a 3.5-mm Locking Compression Plate (LCP) between 2007 and 2015. Patients were treated either with a locking plate (group L, n = 45) or a nonlocking plate (group N, n = 45). In both groups, the plates were fixed to the proximal and distal clavicle with two and/or three screws, respectively. The main outcome measures were complication rates, time to bone union, and Constant score., Results: Forty-two patients in group L (mean age, 45.9 years) and 41 in group N (mean age, 43.6 years) were followed. The overall complication rates in groups L and N were 7.2% (three peri-implant fractures) and 7.3% (non-union, deformed plate, and peri-implant fracture), respectively (p = .98). The average time to union significantly differed between groups (L vs. N: 13.0 ± 4.1 vs. 17.5 ± 6.3 weeks; p < .01). However, the Constant score at the final follow-up was not significantly different between groups (L vs. N: 87.0 ± 12.3 vs. 89.8 ± 9.1)., Conclusions: Similar complication rates and clinical results were found for locking and nonlocking superior plate fixation for displaced midshaft clavicle fractures. However, the time to bone union was shorter with the locking plate. This study suggests that both plating systems are effective for treating displaced midshaft clavicle fractures., Level of Evidence: Therapeutic, level I., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Precise spectroscopy of the hyperfine level system of 167 Er-doped Y 2 SiO 5 was achieved in the frequency domain. By using an optical frequency comb to stabilize the light source frequency to an accuracy on the order of hertz on a long-term scale, Allan deviation < 10 Hz was achieved for an integration time of 180 s. As a result, spectral hole-burning experiments yielded a more accurate hole spectrum with a narrow homogeneous linewidth. The method opens the way to the straightforward exploration of relaxation mechanisms in the frequency domain by simple steady-state measurements.

We have epitaxially grown high-quality single-crystal rare-earth oxide thin films, including Gd 2 O 3 and erbium-incorporated (ErGd) 2 O 3 , on silicon-on-insulator substrate, and investigated their optical properties when embedded in horizontal slot waveguides. (ErGd) 2 O 3 with an erbium concentration in the mid-10 21 cm -3 range shows well-resolved Stark-split photoluminescence emission peaks in the telecommunications band and a photoluminescence lifetime-concentration product as large as 2.67×10 18 s·cm -3 at room-temperature. Using these materials, horizontal slot waveguides with strong optical confinement in low-refractive-index rare-earth oxide layers, have been fabricated for silicon-based integrated active photonic devices. Thanks to the strong light-matter interaction, a large waveguide modal absorption of 88 dB/cm related to erbium ions is achieved, leading to a large potential optical gain. Intense emissions from the waveguides are also observed, with a radiation efficiency on the order of 10 -4 . These results indicate that a combination of epitaxial rare-earth oxide thin films and horizontal slot waveguides provides a promising platform for light amplification and generation on silicon.

A highly sensitive method for detecting transient reflection in the extreme ultraviolet (XUV) region was developed on the basis of high-order harmonics for tracking carrier and coherent phonon dynamics. The use of lock-in detection and boxcar integration enables us to observe optical modulation (ΔR/R) as high as 1 × 10 -4 , and the data acquisition takes only four minutes. XUV transient reflections of bismuth exhibited exponential decay originating from excited carriers and periodic oscillation originating from A 1g optical phonons. The linear power dependence of the electronic and phonon amplitudes indicated that one-photon excitation occurred under the experimental conditions. The cosine of the initial phase of the phonon oscillation revealed that a displacive excitation mechanism contributed to phonon generation. The phonon parameters obtained by the XUV and NIR probes were consistent even though their penetration depths were different. The result indicated that the XUV and NIR pulses probe the same excited region, which should be near the surface due to the short penetration depth of the NIR pump pulses. The present highly sensitive means of detecting XUV transient reflections in solid-state materials could be utilized for detecting attosecond dynamics in the future.

We demonstrate optical coherent transients in a Λ-like hyperfine energy-level system of Er167 3+ in yttrium orthosilicate (Y 2 SiO 5 ) with telecom-band photons at a zero magnetic field. Spectral hole burning was used to study the temperature dependence of the induced spectral antihole. We find that temperatures below 3.0 K suppress population dissipation induced by electron-phonon interactions sufficiently to enable population initialization in the Λ-like system. Further, the pulse area dependence of photoluminescence (PL) from the Λ-like system was measured at 2.2 K. An optical pump power dependence of PL intensity shows Rabi oscillations that contain two full Rabi cycles at the frequency of 2π×810  kHz. A two-pulse photon echo measurement reveals an optical coherence time of 12 μs. To date, this measured optical coherence time is the longest observed for Er 3+ in solids at zero magnetic field. These findings will facilitate optical coherent manipulation of Λ-like Er167 3+ electronic states as a quantum memories operating at telecom-band wavelengths.

Introduction: Fluoroscopy-guided selective nerve root block (SNRB) is useful for the diagnosis and treatment of nerve root pain. However, the procedure exposes the surgeon's hands to radiation. Therefore, the purpose of this randomized prospective study was to assess the radiation exposure per unit time of the surgeon's fingers during performance of a lumbosacral SNRB and to calculate the annual exposure time limits for four hand-protection methods., Methods: We prospectively recruited patients scheduled for an SNRB and measured the radiation exposure using a ring-type passive radiation dosimetry device attached to the distal phalanx of the index finger of the hand performing the needle placement. Patients were randomly divided into the following four groups: a) the direct exposure group, b) the 0.03-mmPb glove group, c) the 0.25-mmPb glove group, and d) the forceps group (in which the needle was held using forceps such that the fingers did not enter the irradiation field)., Results: We recruited 40 consecutive patients (16 men and 24 women), with a mean age of 69 years. In all cases, SNRB was successfully performed without complications. The average exposure per hour for each of the four groups was as follows: 0.67 ± 0.56 mSv/s in the direct exposure group, 0.12 ± 0.07 mSv/s in the 0.03-mmPb glove group, 0.019 ± 0.02 mSv/s in the 0.25-mmPb glove group, and 0.001 ± 0.004 mSv/s in the forceps group (p < 0.01). The average annual exposure time limit was 12.4 min in the direct exposure group, 67.9 min in the 0.03-mmPb glove group, 7.5 h in the 0.25-mmPb glove group, and 5.0 days in the forceps group., Conclusions: Using a radiation reduction glove or forceps greatly decreased the radiation exposure and increased the annual exposure time limit for SNRB., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest.

In Japan, bevacizumab has not been proven either effective or safe for the treatment of recurrent cervical cancer. The present study reported two cases in which bevacizumab combination chemotherapy was safely administered for recurrent cervical cancer following pelvic radiotherapy. Case 1 was a 62-year-old woman with stage IIIB squamous cell carcinoma of the cervix who had received whole pelvic external beam radiotherapy (WPEBRT) at a dose of 50.4 Gy and high dose rate intra-cavitary brachytherapy at a dose of 24 Gy to the pelvis one year earlier. For recurrent cervical cancer, chemotherapy with paclitaxel, carboplatin and bevacizumab was administered for six cycles. Case 2 was a 52-year-old woman with stage IIB squamous cell carcinoma of the cervix who had received WPEBRT at a dose of 50.4 Gy to the pelvis 11 years earlier. For lymph node and liver metastases, chemotherapy with paclitaxel, cisplatin, and bevacizumab was administered for six cycles. Although grade 2 proteinuria was observed in one of these patients, there were no intestinal perforation, fistula, hypertension, proteinuria or thrombosis events, which are the characteristic adverse reactions associated with bevacizumab. Hematotoxicity was also manageable. Regarding the antitumor effect, case 1 demonstrated a complete response, whereas case 2 resulted in stable disease.

The purpose of this phase II trial was to assess the efficacy and toxicity of paclitaxel and nedaplatin (TN) as the initial postoperative adjuvant chemotherapy for uterine cervical cancer with lymph node metastases (LNM). Patients with FIGO stage IB1-IIA2 squamous cell carcinoma of the uterine cervix were enrolled. Histological confirmation of LNM was mandatory. Intravenous paclitaxel at 175 mg/m 2 and nedaplatin at 80 mg/m 2 were administered every 28-day cycle, of which there were 5 cycles after radical hysterectomy. Sixty-two patients were enrolled in the study from November 2011 to July 2015. Their median age was 48.5 years (range 28-64). The median tumor diameter was 37 mm (5-64). Overall, 30 patients (48.4%) had 1 metastatic lymph node, 11 (17.7%) had 2, 3 (4.8%) had 3, 5 (8.1%) had 4, and 13 (21.0%) had 5 or more. With a median follow-up of 45.7 months (range 23.4-69.5), the 2-year relapse-free survival and 2-year overall survival rates were 79.0% (90% CI, 69.0%-86.2%) and 93.5% (95% CI, 83.7%-97.5%), respectively. Almost all adverse events were relatively mild. Grade 3-4 adverse events (NCI-CTC ver. 4.0) that occurred in 5% or more of patients were neutropenia (60.7%) and infection (6.6%). The proportion of patients who completed 5 cycles of treatment was 90.3%. Postoperative adjuvant chemotherapy with TN for cervical cancer with LNM was demonstrated to be an effective and feasible treatment. A phase III trial is warranted to compare this with concurrent chemoradiotherapy., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Aim: We compared the nutritional and dietary intakes of users of mobile vendor vehicles and users of stores to clarify the problems in the nutritional intake of users of mobile vendor vehicles., Methods: We conducted a questionnaire about the food accessibility among 257 elderly women (age: ≥65 years) who used mobile vendor vehicles and/or stores to shop. The nutritional intake was assessed using the 24-hour recall method. We used an analysis of covariance (ANCOVA) to calculate the age-adjusted mean values for the total nutritional intake., Results: The nutritional intake among users of mobile vendor vehicles included significantly lower intakes of energy (168 kcal), green vegetables, other vegetables, and meats. Furthermore, those who only shopped at mobile vendor vehicles consumed less energy and fewer nutrients than those who shopped at places other than mobile vendor vehicles. The comparison of the shopping frequency and nutritional intake of the subjects who used mobile vendor vehicles alone revealed that the energy and protein intakes of those who shopped once per week was significantly lower in comparison to those who shopped twice per week., Conclusions: Users of mobile vendor vehicles had lower intakes of macronutrients and various minerals and vitamins. Among the food groups, intakes of vegetables, meat, and dairy products were low. These findings suggest that the lack of means of shopping other than mobile vendor vehicles and shopping once per week may be associated with an inadequate dietary intake among users of mobile vendor vehicles. It would be desirable to develop the shopping environment is desirable.

Purpose: Arthroscopic treatment of shoulder instability has some advantages (including short surgical time, less morbidity, less postoperative pain, reduced hospitalization time, and decreased risk of complications) compared with open procedures. We performed a prospective study comparing open repair with arthroscopic repair for recurrent anterior shoulder instability. The aim was to clarify the relative effectiveness of open Bankart repair plus inferior capsular shift (OBRICS) and arthroscopic Bankart (AB) repair without augmentations with approximately 5 years of follow-up., Methods: We investigated 32 shoulders of 30 patients (24 men and 6 women) undergoing OBRICS (15 shoulders of 17 patients; two patients were bilateral) and AB (15 shoulders of 15 patients). The average follow-up was 5 years and 2.5 months (range: 60-66 months). The clinical evaluation included recurrent instability rate, range of motion, and postoperative rehabilitation. All patients were assessed using the scoring systems of Rowe and the University of California at Los Angeles (UCLA) preoperatively and during the final evaluation., Results: Recurrent instability rates were significantly different between the OBRICS (0%) and AB (26.6%) groups ( p = 0.022). There were fewer limitations of external rotation (ER), ER at 90° abduction, and horizontal extension for AB than for OBRICS postoperatively ( p < 0.05). The mean Rowe and UCLA scores for both methods were not significantly different at final follow-up., Conclusion: Our data suggest that OBRICS leads to a lower rate of recurrent instability. However, those with AB had fewer ER and horizontal extension limitations.

Purpose: We report a phase II clinical study of the combination of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in platinum- and taxane-resistant recurrent ovarian cancer, based on the recommended doses determined in a phase I trial., Methods: PLD was administered intravenously at a dose of 30 mg/m 2 on day 3. CPT-11 was administered intravenously at a dose of 80 mg/m 2 on days 1 and 15, according to the recommendations of the phase I study. A single course of chemotherapy lasted 28 days, and patients underwent at least 2 courses until disease progression. The primary endpoint was antitumor efficacy, and the secondary endpoints were adverse events, progression-free survival (PFS), and overall survival (OS)., Results: The response rate was 32.3% and the disease control rate was 64.5%. Grade 3 and 4 neutropenia, anemia, and a decrease in platelet count were observed in 17 (54.9%), 3 (9.7%), and 1 patient (3.2%), respectively. In terms of grade 3 or higher non-hematologic toxicities, grade 3 nausea occurred in 1 patient (3.2%), vomiting in 3 patients (9.7%), and grade 3 diarrhea and fatigue in 1 patient (3.2%). The median PFS and OS rates were 2 months and not reached, respectively. Of the 11 patients with a treatment-free interval (TFI) of ≥3 months, the response rate was 63.3%, and the median PFS was 7 months., Conclusions: The treatment outcomes for the 31 patients enrolled in this study were unsatisfactory. However, sub-analysis suggested that patients with a TFI of ≥3 months had a good response rate and PFS. This suggests that CPT-11/PLD combination therapy may be a chemotherapy option for platinum-resistant recurrent ovarian cancer.

Background: We examined the efficacy and safety of neoadjuvant chemotherapy (NAC) with the CPT-11 + CDDP regimen in combination with radical hysterectomy., Subjects and Methods: The subjects were 42 patients with stages IB2 to IIIB squamous cell carcinoma of the uterine cervix with a bulky mass. CDDP at 70 mg/m 2 was intravenously administered on day 1 and CPT-11 at 70 mg/m 2 was intravenously administered on days 1 and 8 of a 21-day cycle. In principle, two cycles were administered followed by radical hysterectomy. We examined antitumor efficacy, adverse events, completion rate of radical hysterectomy, operative time, surgical blood loss, progression-free survival (PFS), and overall survival (OS)., Results: The antitumor effect was complete response in 7 patients, partial response in 28, stable disease in 6, and progressive disease in 1; the response rate was 83.3 % (95 % confidence interval, 68.6-93.0). Grade 3 or more severe neutropenia, anemia, and platelet count decreases were noted in 23 (54.8 %), 4 (9.5 %), and 1 (2.4 %) patient, respectively. Grade 3 nausea occurred in 3 patients (7.1 %), vomiting in 1 (2.4 %), and grade 3 febrile neutropenia in 2 (7.1 %). The completion rate of radical hysterectomy was 88.1 %. The median operative time and surgical blood loss were 260 min (range, 210-334) and 500 ml (range, 393-898), respectively. The 5-year PFS rate was 67.2 %, and the 5-year OS rate was 68.0 %. In multivariate analysis, lymph node metastasis before NAC [hazard ratio (HR), 34.88] and non-response to NAC (HR 30.58) were significant prognostic factors., Conclusion: NAC with the CDDP/CPT-11 regimen achieves a high antitumor efficacy with moderate adverse reactions, allowing safe radical hysterectomy, and is thus considered to be a useful therapeutic method that can improve prognosis., Competing Interests: None of the authors of this manuscript has any conflicts of interest to declare.

Objective: In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC) for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group) with patients who underwent RH without NAC (Ope group)., Patients and Methods: The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan-Meier method was performed to compare disease-free survival (DFS) and overall survival (OS) between the groups., Results: There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14-25 days) in the NAC group and 25 days (21-34 days) in the Ope group; the patients in the NAC group were discharged earlier ( P =0.032). The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08-0.91), and the 3-year DFS rates were 81.2% and 41.0%, respectively ( P =0.028). Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11-1.24), and the 3-year OS rates were 82.3% and 66.4%, respectively ( P =0.101)., Conclusion: NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous cell carcinoma presenting as a bulky mass.

Objective: The aim of this study was to compare the efficacy of nedaplatin-based concurrent chemoradiotherapy (CCRT) with that of cisplatin-based CCRT in patients with cervical cancer., Methods: The medical records of patients with cervical cancer who had undergone CCRT between 2003 and 2007 were retrospectively reviewed. Of these, 129 patients were treated postoperatively with CCRT (n = 52) or primary CCRT (n = 77). A total of 29 patients were treated with nedaplatin-based postoperative CCRT and 23 patients were treated with cisplatin-based postoperative CCRT. A total of 28 patients were treated with nedaplatin-based postoperative CCRT, and 49 patients were treated with cisplatin-based postoperative CCRT. Progression-free survival (PFS) and overall survival (OS) were compared between the treatment groups., Results: With postoperative CCRT, there were no significant differences in recurrence rate (P = 1.0000), PFS (log-rank: P = 0.8503), and OS (log-rank: P = 0.8926) between the two treatment groups. With primary CCRT, there were no significant differences in PFS (log-rank: P = 0.7845) and OS (log-rank: P = 0.3659). The frequency of acute toxicity was not significantly different between the cisplatin-based postoperative CCRT group and the nedaplatin-based postoperative CCRT group., Conclusions: Nedaplatin-based postoperative CCRT is an effective and well-tolerated regimen for both early-stage and advanced-stage cervical cancer patients.

Background: Neoadjuvant chemotherapy (NAC) is not yet widely recommended for the treatment of stage I/II cervical cancer. However, it may be possible to achieve a favorable outcome by selecting appropriate patients. In the present study, prognostic factors were retrospectively investigated to obtain data for devising individualized NAC., Patients and Methods: The subjects were 33 patients with bulky stage Ib2-IIb squamous cell carcinoma (SCC) of the uterine cervix who gave consent and were scheduled to undergo radical hysterectomy. The patients intravenously received irinotecan 70 mg/m(2) on days 1 and 8 and cisplatin 70 mg/m(2) on day 1 of a 21-day course, and two courses were performed in principle. The potential prognostic factors investigated were age, performance status (PS), clinical stage, lymph node metastasis and tumor size before NAC, SCC antigen value, anti-tumor response, histological effect of NAC, lymph node metastasis in resected specimens, and postoperative adjuvant therapy after NAC. The impacts of these factors on overall survival (OS) were calculated with the Cox regression model., Results: According to the univariate analysis, lymph node metastasis before NAC, SCC antigen value after NAC, anti-tumor response, and histological effect of NAC significantly influenced OS. These factors were tested in a multivariate model, and significant prognostic factors were lymph node metastasis before NAC (hazard ratio 0.116, P = 0.027) and anti-tumor response (hazard ratio 0.025, P = 0.003)., Conclusion: The presence or absence of lymph node metastasis by computed tomography imaging was the only significant prognostic factor identified during the pre-NAC period.

Polycrystalline Er-Sc silicates (Er(x)Sc(2-x)SiO₅ and Er(x)Sc(2-x)Si₂O₇) were fabricated using multilayer nanostructured films of Er₂O₃/SiO₂/Sc₂O₃ deposited on SiO₂/Si substrates by RF- sputtering and thermal annealing at high temperature. RBS, TEM, GIXD, and PL results show the presence of Er(x)Sc(2-x)SiO₅ with an emission peak at 1528 nm for annealing from 900 to 1100 °C, and Er(x)Sc(2-x)Si₂O₇ with an emission peak at 1537 nm for higher annealing temperature. The PL intensity of the Er(x)Sc(2-x)Si₂O₇ phase is five times stronger than that of the Er(x)Sc(2-x)SiO₅ phase at 1250 °C. From PLE and PL spectra of Er(x)Sc(2-x)Si₂O₇ thin film, we schematically illustrate the Er³⁺ Stark energy levels of ⁴I(13/2) to ⁴I(15/2) manifolds due to the crystal field strength effect of Sc³⁺. Temperature-dependent PL of the Er(x)Sc(2-x)Si₂O₇ phase exhibits a variation of the full-width at half-maximum (FWHM) from 1.1 to 2.3 nm. The narrow FWHM is due to the small ionic radii of Sc³⁺, which enhance the crystal field strength affecting the optical properties of Er³⁺ ions located at the well-defined lattice sites of Sc silicate. A large excitation cross-section (σ(ex)) is equal to 3.0x10⁻²⁰ cm² at λ(ex) = 1527.6 nm.

There are currently no studies demonstrating the effects of palonosetron on delayed chemotherapy-induced nausea and vomiting (CINV) in gynecological cancer patients receiving chemotherapy with moderately emetogenic chemotherapeutic agents. We conducted a phase II clinical trial to assess the efficacy and safety of palonosetron in patients receiving paclitaxel/carboplatin (TC) therapy. The study population consisted of 42 patients who had been diagnosed with gynecological malignancies and treated with TC. On day 1, 0.75 mg/body palonosetron and 19.8 mg/body dexamethasone were administered intravenously immediately prior to TC therapy. Dexamethasone in daily doses of 6.6 mg/body was also administered intravenously on days 2 and 3. The efficacy and safety of palonosetron + dexamethasone were evaluated by the self-completion method using the Multinational Association of Supportive Care in Cancer Antiemesis Tool during an observation period lasting from day 1 through day 8 of the initial cycle of TC therapy. The severity of the nausea was assessed using a visual analog scale. During the acute (0-24 h), delayed (24-96 h) and overall (0-96 h) periods, the complete response rates were 95.2, 90.5 and 85.7%, respectively, whereas the complete control rates were 90.5, 85.7 and 78.6%, respectively. Grade ≥ 2 constipation and diarrhea developed in 1 patient (2.4%) each. The palonosetron + dexamethasone regimen proved to be effective for delayed CINV in gynecological cancer patients receiving TC therapy. This combined antiemetic regimen was associated with only mild adverse reactions and may serve as supportive therapy, allowing cancer chemotherapy to be continued while maintaining an adequate quality of life.

Purpose: The purpose of this study was to assess the ability of short inversion time inversion-recovery (STIR) in magnetic resonance imaging for predicting the prognosis of osteoporotic vertebral fractures., Methods: We analyzed 63 vertebrae of 56 patients who had osteoporotic vertebral fracture (Th10-L2) prospectively. Image finding of a homogeneous high signal change on a fractured vertebra was evaluated and all vertebrae were divided into "homogenous high signal change group" or "non-homogenous high signal change group". On the other hand, image finding of linear black signal area was evaluated and all vertebrae were divided into "linear black signal area group" or "non-linear black signal area group"., Results: Sixteen and 24 vertebrae were included in the homogenous high signal change group or the linear black signal area group, respectively. The 16 homogenous high signal change cases did not result in non-union, and 47 non-homogenous high signal change cases resulted in 14 non-unions, a significant difference. Twenty-four linear black signal area and 39 non-linear black signal area cases resulted in 10, and 4 non-unions, respectively, also a significant difference. The kyphosis progression rate of the linear black signal area group (mean 35%) was significantly higher than that of non-linear black signal area group (mean 23%). The visual analog scale of back pain of the linear black signal area group (mean 35 mm) was significantly higher than that of the non-linear black signal area group (mean 23 mm)., Conclusions: STIR was useful for predicting bone union, kyphosis, and back pain in patients with osteoporotic vertebral fracture.

Polycrystalline Er-Sc silicates (Er x Sc2-x Si2O7 and Er x Sc2-x SiO5) were fabricated using multilayer nanostructured films of Er2O3/SiO2/Sc2O3 deposited on SiO2/Si substrates by RF sputtering and thermal annealing at high temperature. The films were characterized by synchrotron radiation grazing incidence X-ray diffraction, cross-sectional transmission electron microscopy, energy-dispersive X-ray spectroscopy, and micro-photoluminescence measurements. The Er-Sc silicate phase Er x Sc2-x Si2O7 is the dominant film, and Er and Sc are homogeneously distributed after thermal treatment because of the excess of oxygen from SiO2 interlayers. The Er concentration of 6.7 × 10(21) atoms/cm(3) was achieved due to the presence of Sc that dilutes the Er concentration and generates concentration quenching. During silicate formation, the erbium diffusion coefficient in the silicate phase is estimated to be 1 × 10(-15) cm(2)/s at 1,250°C. The dominant Er x Sc2 - x Si2O7 layer shows a room-temperature photoluminescence peak at 1,537 nm with the full width at half maximum (FWHM) of 1.6 nm. The peak emission shift compared to that of the Y-Er silicate (where Y and Er have almost the same ionic radii) and the narrow FWHM are due to the small ionic radii of Sc(3+) which enhance the crystal field strength affecting the optical properties of Er(3+) ions located at the well-defined lattice sites of the Sc silicate. The Er-Sc silicate with narrow FWHM opens a promising way to prepare photonic crystal light-emitting devices.

Objective: Patients with end-stage cancer have poorly controlled ascites retention resulting due to cancerous peritonitis. We intraperitoneally administered triamcinolone acetonide (TA) to patients with end-stage gynecological cancer as a pilot study, and our treatment results are reported herein., Patients and Methods: We enrolled 26 patients with end-stage gynecological cancer requiring frequent abdominal paracentesis for ascites drainage between April 2010 and September 2012. The volume of ascites drainage was 2000 to 3000 mL per drainage session, and TA at 10 mg/kg was intraperitoneally administered after drainage. We compared abdominal paracentesis intervals, performance status (PS), total protein level, albumin level, white blood cell count, changes in C-reactive protein (CRP) level, and adverse events before and after TA use., Results: Triamcinolone acetonide was administered to 26 patients for a total of 59 times. The abdominal paracentesis intervals, PS, and mean (SD) of C-reactive protein before and after TA use were 13.2 (12.6) days and 21.9 (23.6) days (P = 0.0117), 2.4 (0.7) and 1.6 (1.1) (P < 0.0001), and 7.5 (5.2) mg/dL and 5.5 (5.0) mg/dL (P = 0.007), respectively. With regard to adverse events, abdominal pain of grade 2 was observed once (1.7%), but there were no other acute adverse events. Four subjects (15.4%) had intestinal perforation., Conclusions: Intraperitoneal administration of TA after drainage was considered to be a useful treatment, as it seems to extend paracentesis intervals and improve PS while maintaining quality of life for end-stage gynecological cancer patients with massive ascites.

Purpose: A phase I clinical study was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan hydrochloride (CPT-11) in CPT-11/pegylated liposomal doxorubicin (PLD) combination therapy, a novel treatment regimen for platinum- and taxane-resistant recurrent ovarian cancer., Methods: Pegylated liposomal doxorubicin was administered intravenously on day 3 at a fixed dose of 30 mg/m(2). CPT-11 was administered intravenously on days 1 and 15, at a dose of 50 mg/m(2) on both days. One course of chemotherapy was 28 days, and patients were given a maximum of six courses, with the CPT-11 dose being increased in increments of 10 mg/m(2) (level 1, 50 mg/m(2); level 2, 60 mg/m(2); level 3, 70 mg/m(2); level 4, 80 mg/m(2)) to determine MTD and RD., Results: During the period from April 2010 to March 2013, three patients were enrolled for each level. In the first course, no dose-limiting toxicity occurred in any of the patients. Grade 4 neutropenia was observed in two of three patients at level 4. At level 4, the antitumor effect was a partial response (PR) in two of the three patients and stable disease (SD) in one. At level 3, one of the three patients showed PR and two had SD. At level 4, the start of the next course was postponed in two of three patients. In addition, one patient at level 4 experienced hemotoxicity that met the criteria for dose reduction in the next course. The above results suggested that administration of CPT-11 at dose level 5 (90 mg/m(2)) would result in more patients with severe neutropenia and in more patients requiring postponement of the next course or a dose reduction. Based on the above, the RD of CPT-11 was determined to be 80 mg/m(2)., Conclusions: The results suggest that CPT-11/PLD combination therapy for recurrent ovarian cancer is a useful treatment method with a high response rate and manageable adverse reactions. In the future phase II study, the safety and efficacy of this therapy will be assessed at 80 mg/m(2) of CPT-11 and 30 mg/m(2) of PLD.

We previously reported the generation of lipopolysaccharide (LPS)-binding peptides by phage display and chemical modification. Among them, a dodecapeptide designated Li5-025 (K'YSSSISSIRAC'; K' and C' denote d-lysine and d-cysteine, respectively) showed a high binding affinity for LPS and was resistant to protease digestion (Suzuki et al., 2010). In the current study, Li5-025-bound silica beads, hereafter referred to as P-beads, were generated and found to be devoid of LPS-neutralizing activity. Thus, LPS bound to the P-beads could be directly used in the Limulus amebocyte lysate (LAL) assay. P-beads bound LPS dissolved in solutions of ethanol, pH4, pH10, and 0.5M NaCl and LPS bound to the P-beads was quantitatively assayed. The sensitivity of this assay was observed to be approximately 0.1pg/mL LPS. P-beads bound LPS dissolved in antithrombin III (AT III) solution which is a strong inhibitor of activated factors C and B as well as the clotting enzyme in the LAL assay; the inhibitory effect of AT III was completely reversed upon washing the P-beads with 25% acetonitrile. This was employed as the first step for the detection of free LPS in plasma using the LAL assay. LPS added to human plasma at 0°C followed by application to the P-beads and subsequent washing with 25% acetonitrile resulted in low LPS activity as detected by the LAL assay. However, further washing of the P-beads with 0.1% Triton X100 in 25% acetonitrile resulted in high LPS activity. This is the first instance of quantitative detection of free LPS in plasma using the LAL assay, and the sensitivity of this method was observed to be 1pg/mL of LPS. The proteins eluted in the 0.1% Triton X-100 wash were analyzed using sodium dodecyl sulfate polyacrylamide gel electrophoresis. Two protein bands of 28kDa and 18kDa were predominantly observed. Mass spectrometry analysis revealed that the 28kDa and 18kDa bands corresponded to apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II), respectively. ApoA-I and apoA-II are components of high density lipoprotein (HDL). Thus, it is likely that the P-beads-bound LPS was sequestered by HDL, resulting in neutralization of its toxicity. This study showed that by using P-beads, free LPS in plasma can be quantitatively measured by the LAL assay at a concentration of 1pg/mL., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: There are no reports on the use of neoadjuvant chemotherapy (NAC) in non-squamous cell cervical carcinoma. We examined the effectiveness and safety of paclitaxel/carboplatin (TC) and docetaxel/carboplatin (DC)., Methods: Stage Ib2 to IIb disease was present in 23 patients scheduled for radical hysterectomy. We administered 1-3 courses of either the TC or the DC regimen. Anti-tumor effects were found superior by Response Evaluation Criteria in Solid Tumors. Safety was assessed with National Cancer Institute Common Terminology Criteria for Adverse Events., Results: Median age was 50 years (range 32-63 years), with stage Ib2 in 6 cases (26.1%) and IIb in 17 cases (73.9%). Complete response was achieved in 5 cases (21.7%), partial response in 13 (56.5%), stable disease in 5 (21.7%); the response rate was 78.3%, and surgery completion rate was 78.3%. Leukopenia or neutropenia ≥grade 3 was seen in 12 (52.2%) and 21 (91.3%) cases, respectively, with grade 3 febrile neutropenia in 2 cases (8.7%) and no anemia or thrombocytopenia ≥grade 3. Median progression-free survival was 26 months (95% Cl, 13.5-38.5 months); median overall survival was 35 months (95% Cl, 20.9-49.1 months)., Conclusion: NAC for non-squamous cell cervical carcinoma showed potent anti-tumor effects and manageable adverse events.

The pentaspan membrane glycoprotein CD133 (also known as prominin-1) has been widely used as a marker for both cancer and normal stem cells. However, the function of CD133 has not been elucidated. Here we describe a cancer stem cell line established from clear cell carcinoma of the ovary (CCC) and show that CD133 interacts with plakoglobin (also known as γ-catenin), a desmosomal linker protein. We further demonstrate that knockdown of CD133 by RNA interference (RNAi) results in the downregulation of desmoglein-2, a desmosomal cadherin, and abrogates cell-cell adhesion and tumorigenicity of CCC stem cells. We speculate that CD133 may be a promising target for cancer chemotherapy.

Mucocele of the appendix (MA) is an uncommon disease. Preoperative differential diagnosis of MA and a peritoneal inclusion cyst (PIC) from gynecologic diseases is still a challenge. We herein report a very rare case with MA and PIC. As far as we know, this is the first report of a case having MA and PIC found simultaneously at surgery. A 31-year-old woman complained of lower abdominal pain and high fever. Based on her symptoms and laboratory tests, pelvic inflammatory disease (PID) was considered to be the most probable diagnosis. She underwent antibiotics therapy and her conditions subsided. However, ascites reappeared in a month, and ultrasound and MRI demonstrated a right ovarian cyst and a suspected right hydrosalpinx. Laparotomy revealed large PIC and MA with normal bilateral adnexa. Patients with an adnexal mass or symptoms suggesting PID should be examined carefully considering such conditions in a daily gynecologic practice.

Background: We herein describe a surgical technique for the repair of complete tear of the pectoralis major (PM) tendon using endobuttons to strengthen initial fixation., Methods: Five male patients (3 judo players, 1 martial arts player, and 1 body builder) were treated within 2 weeks of sustaining complete tear of the PM tendon. Average age at surgery and follow-up period were 28.4 years (range, 23-33) and 28.8 months (range, 24-36). A rectangular bone trough (about 1 × 4 cm) was created on the humerus at the insertion of the distal PM tendon. The tendon stump was introduced into this trough, and fixed to the reverse side of the humeral cortex using endobuttons and non-absorbable suture. Clinical assessment of re-tear was examined by MRI. Shoulder range of motion (ROM), outcome of treatment, and isometric power were measured at final follow-up., Results: There were no clinical re-tears, and MRI findings also showed continuity of the PM tendon in all cases at final follow-up. Average ROM did not differ significantly between the affected and unaffected shoulders. The clinical outcomes at final follow-up were excellent (4/5 cases) or good (1/5). In addition, postoperative isometric power in horizontal flexion of the affected shoulder showed complete recovery when compared with the unaffected side., Conclusions: Satisfactory outcomes could be obtained when surgery using the endobutton technique was performed within 2 weeks after complete tear of the PM tendon. Therefore, our new technique appears promising as a useful method to treat complete tear of the PM tendon.

Objective: To evaluate the efficacy and safety of the combination chemotherapy regimen of irinotecan plus oral etoposide for the treatment of patients with recurrent ovarian cancer after previous treatment with platinum and taxane agents., Patients and Methods: A total of 42 patients with recurrent ovarian cancer who had an evaluable lesion and provided informed consent for participation in the present study were analyzed. Irinotecan was administered intravenously at a dose of 60 mg/m on days 1 and 15. Etoposide was administered orally at a daily dose of 50 mg/body weight from days 1 to 21. A 28-day period comprised one cycle. The tumor response, adverse events, progression-free survival, and overall survival were examined. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors and the serum CA125 levels (Gynecologic Cancer Intergroup criteria). Adverse events were assessed according to the NCI-CTCAE (version 3.0)., Results: Partial response was observed in 21 patients, stable disease in 14 patients, and progressive disease in 7 patients. The response rate was 50.0%, and the clinical benefit (partial response + stable disease) rate was 83.3%. Hematological toxicities of at least grade 3 severity included leukopenia in 21 patients (50.0%), neutropenia in 22 patients (52.4%), thrombocytopenia in 1 patient (2.4%), anemia in 9 patients (21.4%), and febrile neutropenia in 3 patients (7.1%). Nonhematological toxicities of at least grade 3 severity included queasy feeling in 5 patients (11.9%), vomiting in 3 patients (7.1%), and diarrhea in 2 patients (4.8%). Acute myeloid leukemia occurred in one patient (2.4%)., Conclusions: It is suggested that combination chemotherapy with irinotecan plus oral etoposide offers significant clinical benefit to patients with recurrent ovarian cancer previously treated with platinum and taxane agents.

Total-external-reflection (TER) x-ray diffraction is the depth-sensitive technique for evaluating layered structures, including epitaxial heterostructures, ion-doped bulk crystals and several quantum-well structures. This technique can control the depth of observation by changing both incident and exit angles of x-rays from the surface. In this review, the principle of the TER technique and measurement apparatus are briefly described, and applications of layered-semiconductor samples evaluated using the TER technique are introduced.

Mechanisms of cAMP/PKA-induced meiotic arrest in oocytes are not completely identified. In cultured, G2/M-arrested PDE3A(-/-) murine oocytes, elevated PKA activity was associated with inactivation of Cdc2 and Plk1, and inhibition of phosphorylation of histone H3 (S10) and of dephosphorylation of Cdc25B (S323) and Cdc2 (Thr14/Tyr15). In cultured WT oocytes, PKA activity was transiently reduced and then increased to that observed in PDE3A(-/-) oocytes; Cdc2 and Plk1 were activated, phosphorylation of histone H3 (S10) and dephosphorylation of Cdc25B (S323) and Cdc2 (Thr14/Tyr15) were observed. In WT oocytes, PKAc were rapidly translocated into nucleus, and then to the spindle apparatus, but in PDE3A(-/-) oocytes, PKAc remained in the cytosol. Plk1 was reactivated by incubation of PDE3A(-/-) oocytes with PKA inhibitor, Rp-cAMPS. PDE3A was co-localized with Plk1 in WT oocytes, and co-immunoprecipitated with Plk1 in WT ovary and Hela cells. PKAc phosphorylated rPlk1 and Hela cell Plk1 and inhibited Plk1 activity in vitro. Our results suggest that PKA-induced inhibition of Plk1 may be critical in oocyte meiotic arrest and female infertility in PDE3A(-/-) mice.

Lipopolysaccharide (LPS), a major constituent of the outer membrane of Gram-negative bacteria, is highly toxic and can cause sepsis or septic shock. Therefore, detection of LPS and the ability to neutralize its toxicity is important. We previously obtained a strong LPS-binding peptide, Li5-001, using the phage display method (Matsumoto et al., 2010. J. Microbiol. Methods. 82, 54-58). We modified the sequence the amino acid sequence of this peptide (KNYSSSISSIHAC), by replacing and deleting amino acids to obtain higher LPS-binding affinity and greater resistance to protease digestion. Consequently we obtained a dodecapeptide, Li5-025 (K'YSSSISSIRAC', K' and C' are D-forms of K and C, respectively) which showed a high affinity for LPS, approximately 1000 folds higher affinity than Li5-001 and Kd value of 0.01 nM. By replacing both N- and C-terminal amino acids from L-type to D-type, the peptide was rendered resistant to protease digestion without altering its overall binding capacity., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria. It has strong toxicity and might cause sepsis or septic shock. Thus early detection of LPS and neutralization of LPS toxicity are required. We obtained several new LPS-binding peptides using a phage display method. We synthesized 3 of these peptides and analyzed their binding affinity and capacity to LPS. One of these peptides, named Li5-001, showed high binding affinity to LPS and lipid A; the K(d) values were 10 and 1 nM, respectively. Li5-001 showed a high binding capacity to LPS, and was estimated to bind 130 ng LPS/mg, which is higher than that of polymyxin B (80 ng LPS/mg); however, its LPS-neutralizing activity was low. Li5-001 coupled with beads will be useful for eliminating endotoxin contamination from pharmaceuticals. Its low LPS-neutralizing activity allows to be used in the Limulus amebocyte lysate test without eluting LPS from the Li5-001 coupled beads., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Purpose: To investigate the ability of three-dimensional (3D) ultrasonography and anti-Mϋllerian hormone (AMH) to predict successful embryo development in patients undergoing in vitro fertilization (IVF) treatment., Methods: We prospectively studied 28 patients undergoing IVF treatment, using 3D ultrasound Sono automatic volume calculation (AVC) and a 3D-power Doppler volume histogram. Sono AVC was used to automatically measure the number and volume of follicles. The volume histogram was used to measure the vascularization index (VI), flow index, and vascularization flow index in the ovaries. Serum AMH (S-AMH) was determined by enzyme immunoassay (ng/ml)., Results: The number of embryos isolated was 3.3 ± 2.8. The S-AMH of the patients who were under 35 years of age (0.570 ± 0.216 ng/ml) was higher than that in the patients over 40 years of age (0.377 ± 0.071 ng/ml; p = 0.0003). Principal component analyses determined that the quality of the embryo depended on the patients's age, S-AMH, and VI of the ovary. The receiver operating characteristic (ROC) curve showed that the cutoff for the S-AMH was 0.2855 ng/ml, and the optimal age of the patient was 32.5 years, when implanted with an embryo on day 16., Conclusions: We demonstrated that investigating the relationships between the number of the embryo and ovarian function, using a combination of AMH with a volume histogram, might be useful to predict the response to IVF treatment.

The present study aimed to assess the antitumor response and safety of a tri-weekly neoadjuvant chemotherapy regimen consisting of cisplatin and irinotecan for the treatment of locally advanced cervical cancer with a bulky mass. Between June 2002 and March 2008, 20 patients with locally advanced squamous cell carcinoma of the uterine cervix at clinical stage Ib2-IIIb were studied. Two 21-day cycles consisting of intravenous administration of cisplatin at 70 mg/m(2) (Day 1) and irinotecan at 70 mg/m(2) (Days 1 and 8) were performed. Antitumor responses, adverse events and the surgery completion rate were investigated. The response rate of the 15 stage I-II patients was 86.7%, while that of the 5 stage III patients was 20%. Grade 3 or 4 neutropenia was noted in 12 patients, and 4 patients had grade 3 or 4 anemia. Queasiness and vomiting, as grade 3 or 4 non-hematotoxic events, occurred in 1 patient, but none of the patients had diarrhea. The surgery completion rate was 75%. The present data indicate that the tri-weekly cisplatin and irinotecan combination neoadjuvant chemotherapy involves only controllable toxicity and yields a high response rate, suggesting that this combination is a useful therapy regimen.

Proton diffusion in the room-temperature phase (phase II) of [(NH4)1-xRbx]3H(SO4)2 (0

Objective: We assessed the antitumor response and safety of neoadjuvant chemotherapy (NAC) using cisplatin (CDDP) and irinotecan(CPT-11)given every three weeks for locally advanced cervical cancer with a bulky mass., Subjects and Methods: Nineteen patients with cervical squamous cell cancer in FIGO stage of Ib2 to IIb were enrolled in this study. The FIGO stages were Ib2 in 5 patients, IIa in 2 patients, and IIb in 12 patients. One course of the chemotherapy regimen consisted of intravenous administrations of CDDP at a dose of 70 mg/m 2(day 1)and CPT-11 at 70 mg/m 2 (days 1 and 8) for 21 days, and two courses were administered. This chemotherapy was assessed for antitumor response, adverse events, complete surgical removal rate, progression-free survival time, and overall survival time. RECIST and NCI-CTCAE were used to determine antitumor response and adverse events, respectively., Results: The results of assessment of the antitumor response showed CR in 3 patients(15. 8%), PR in 14(73. 7%), SD in 1 (5. 3%), and PD in 1(5. 3%). Neutropenia of grade 3 or higher occurred in 13 patients(68. 4%). Anemia occurred in 2 patients(10. 5%), and thrombocytopenia in 1 patient(5. 3%). Nausea and vomiting were observed in 2 patients(10. 5%). All patients underwent a chemotherapy regimen consisting of two courses, and the rate of complete surgical removal was 94. 7%. The median observation period was 27 months; the progression-free survival time was 18 months, and survival time was 27 months., Conclusion: Adverse drug reactions to NAC with the CDDP/CPT-11 combination administered every three weeks were controllable. The antitumor response rate for this chemotherapy was high. These assessment results indicate that NAC with a CDDP/CPT-11 combination was useful for local advanced cervical cancer.

A new type of scanning probe microscope, combining features of the scanning tunnelling microscope, the scanning tunnelling luminescence microscope with a transparent probe and the aperture scanning near-field optical microscope, is described. Proof-of-concept experiments were performed under ultrahigh vacuum conditions at varying temperature on GaAs/AlAs heterostructures.

Investigation into the function of human trophoblasts has been largely restricted by a lack of suitable cell models. We aimed to produce normal human trophoblast cell lines with a long lifespan and to provide an ideal in vitro cell model. Primary human trophoblast cells were derived from a placenta that had undergone elective abortion at the 7th week of gestation. The cells were immortalized by infection with retroviral expression vectors containing the type 16 human papillomaviruses E6 and E7 in combination with human telomerase reverse transcriptase (hTERT). Characterization of the cell line was performed by immunocytochemistry using a panel of antibodies, Western blotting, real-time RT-PCR, an invasion assay, gelatin zymography, karyotype analysis and a nude mouse assay. Gene expression profiles under hypoxia (1% O2, 1 h) and subsequent reoxygenation (20% O2, 6 h) were analyzed using cDNA microarray. Immunocytochemistry revealed an extravillous trophoblastic phenotype by positive staining for hCGbeta, cytokeratin 7, HLA-G and CD9. A transwell insert invasion assay showed the invasiveness of this cell line and gelatin zymography detected the secretion of MMP-2 and MMP-9. Karyotype analysis exhibited an almost normal chromosomal number which ranged from 46 to 48 and the cells showed no tumorigenecity in a nude mouse assay. Forty-three genes showing reversible up- or down-regulation during hypoxia were detected using an oligonucleotide array. This newly immortalized cell line, HChEpC1b, is a useful model for the study of extravillous trophoblast function.

An analysis of the emitted light distribution for a single emitter located at the planar interface of two optical media was performed. The interface of a varying refractive index substrate with air was considered, which is a common case in luminescence microscopy (spectroscopy) experiments. A modification of the radiative recombination rate induced by the variation of the substrate together with the emitted radiation spatial redistribution were taken into account. Simulation results show that the collection efficiency of the emitted light can vary several times depending on the substrate choice and the emitter intrinsic quantum efficiency.

We investigated the induction of apoptosis via deamidation of Bcl-xL and translocation of Bax to the mitochondria by treatment with GSH-DXR. GSH-DXR treatment of HepG2 cells, which did not express GST P1-1, exhibited deamidation of Bcl-xL, and the degree of deamidation was related to the activation of caspase-3. Overexpression of GST P1-1 in HepG2 cells decreased both the Bcl-xL deamidation and caspase-3 activation induced by treatment with GSH-DXR. Bcl-xL deamidation and caspase-3 activation were also suppressed by co-treatment with SP600125, a specific inhibitor of JNK activity. Overexpression of wild-type Bcl-xL in HepG2 decreased GSH-DXR-induced apoptosis although deamidation was observed. However, expression of the deamidated mutant of Bcl-xL, in which aspartic acid was substituted for both arginine 52 and 66 (N52,66D-Bcl-xL), exhibited high sensitivity for the induction of apoptosis. Expression of the Bcl-xL mutant, in which alanine was substituted for both arginine 52 and 66 (N52,66A-Bcl-xL), suppressed deamidation and showed resistance to the induction of apoptosis by treatment with GSH-DXR. On the other hand, endogenous Bax and overexpressed Flag-Bax were localized in the cytosolic fraction of HepG2 cells. Treatment of the cells with GSH-DXR caused translocation of Flag-Bax to the mitochondrial fraction following the induction of apoptosis. The induced apoptosis was enhanced by the expression of Flag-Bax. Moreover, Flag-Bax was partly located in the mitochondrial fraction in N52,66D-Bcl-xL-expressed cells without the induction of apoptosis. Therefore, the induction of apoptosis by treatment of HepG2 with GSH-DXR was enhanced, thereby facilitating the release of cytochrome c by both deamidated inactivation of Bcl-xL and functional translocation of Bax to the mitochondria via JNK activation. Deamidation of Bcl-xL might be induced in order to translocate Bax to the mitochondria.

Recent studies have reported that low-intensity pulsed ultrasound (LIPUS) stimulates cell proliferation and proteoglycan production in rabbit intervertebral disc cells, and moreover promotes the secretion of MCP-1 (monocyte chemotaxis protein-1) from macrophages in a disc organ culture model. These findings suggest the possible application of LIPUS for biological repair of disc degeneration and herniation. Although the mechanisms involved are not well understood, several cytokine pathways may play a role. Therefore, in order to evaluate the effect of LIPUS stimulation on cytokine production by nucleus pulposus cells and macrophages, in vitro culture studies were designed. Nucleus pulposus cells and macrophages were collected from Sprague-Dawley rats, cultured separately in a monolayer, and stimulated with LIPUS for 7 days. After culture, the culture medium and the cells were analyzed by cytokine array, RT-PCR, and ELISA. Cytokine array showed that LIPUS stimulation significantly upregulated TIMP-1 (tissue inhibitor of metalloproteinase-1) in the nucleus pulposus and MCP-1 in macrophages in comparison with the control. This was confirmed at the gene level by RT-PCR in nucleus pulposus cells and macrophages after stimulation with LIPUS. Quantitative evaluation of these proteins by ELISA showed higher levels in nucleus pulposus cells and macrophages stimulated by LIPUS than in controls. These results showed that LIPUS stimulation significantly activated TIMP-1 and MCP-1 in nucleus pulposus cells and macrophages at both the protein and gene levels, suggesting that LIPUS may be a promising supplemental treatment for intervertebral disc herniation., ((c) 2008 Orthopaedic Research Society.)

The transforming growth factor-beta (TGF-beta) and the tumor necrosis factor-alpha (TNF-alpha) families are known to play important roles in intervertebral disc degeneration (IVD). However, molecular interactions between the TGF-beta and TNF-alpha signaling pathways have yet to be elucidated. The purpose of this study was to analyze the expression patterns of Smad transcription factor signaling associated with IVDs with aging and to examine the modulation of Smad signaling by TNF-alpha in IVD cells using SD rats. According to these experimental results, BMP signals in the TGF-beta family were more likely to be a key factor in IVD degeneration by aging, and it was predicted that besides the involvement of catabolic factors like MMPs and ADAMS-TS, there may be a decrease in expression of anabolic factors through cross talk of signaling between TNF-alpha and TGF-beta pathway in pathogenesis of disc degeneration.

Transplantation of mesenchymal stem cells (MSCs) is effective in decelerating disc degeneration in small animals; much remains unknown about this new therapy in larger animals or humans. Fas-ligand (FasL), which is only found in tissues with isolated immune privilege, is expressed in IVDs, particularly in the nucleus pulposus (NP). Maintaining the FasL level is important for IVD function. This study evaluated whether MSC transplantation has an effect on the suppression of disc degeneration and preservation of immune privilege in a canine model of disc degeneration. Mature beagles were separated into a normal control group (NC), a MSC group, and the disc degeneration (nucleotomy-only) group. In the MSC group, 4 weeks after nucleotomy, MSCs were transplanted into the degeneration-induced discs. The animals were followed for 12 weeks after the initial operation. Subsequently, radiological, histological, biochemical, immunohistochemical, and RT-PCR analyses were performed. MSC transplantation effectively led to the regeneration of degenerated discs. FACS and RT-PCR analyses of MSCs before transplantation demonstrated that the MSCs expressed FasL at the genetic level, not at the protein level. GFP-positive MSCs detected in the NP region 8 weeks after transplantation expressed FasL protein. The results of this study suggest that MSC transplantation may contribute to the maintenance of IVD immune privilege by the differentiation of transplanted MSCs into cells expressing FasL., ((c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Low-intensity pulsed ultrasound (LIPUS) has been reported to stimulate the activity of various cells. We have reported that the capacity of human intervertebral nucleus pulposus cell line to synthesize proteoglycan (PG) was increased by exposure to LIPUS, and postulated that one of the mechanisms underlying this response was an increase in expression of the transforming growth factor-beta type I receptor gene (TGFbetaR1). Therefore, the present study was conducted to assess the synergistic effect of LIPUS and TGF-beta on nucleus pulposus cells harvested from canines. The cells were cultured under four different sets of conditions: control group (Group A), LIPUS group (Group B), TGF-beta1 group (Group C), and LIPUS + TGF-beta1 group (Group D). They were evaluated by measuring cell proliferation, PG synthesis, PG content, gene expression of TGFbetaR1, and TGF-beta1 concentration. There were no significant differences in proliferation during culture. However, PG synthesis and endogenous TGF-beta1 production increased and demonstrated a synergistic effect between LIPUS and TGF-beta. Because LIPUS is safe and noninvasive, the results of the present study suggest that it would be a promising new therapy for prevention of intervertebral disc degeneration, which is said to be one of the primary causes of low back pain., (Copyright 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

We investigated the effect of locally administered bisphosphonate on distraction osteogenesis in a rabbit model and evaluated its systemic effect. An osteotomy on the right tibia followed by distraction for four weeks was performed on 47 immature rabbits. They were divided into seven equal groups, with each group receiving a different treatment regime. Saline and three types of dosage of alendronate (low, 0.75 microg/kg; mid, 7.5 microg/kg and high 75 microg/kg) were given by systemic injection in four groups, and saline and two dosages (low and mild) were delivered by local injection to the distraction gap in the remaining three groups. The injections were performed five times weekly during the period of distraction. After nine weeks the animals were killed and image analysis and mechanical testing were performed on the distracted right tibiae and the left tibiae which served as a control group. The local low-dose alendronate group showed a mean increase in bone mineral density of 124.3 mg/cm(3) over the local saline group (analysis of variance, p < 0.05) without any adverse effect on the left control tibiae. The findings indicate that the administration of local low-dose alendronate could be an effective pharmacological means of improving bone formation in distraction osteogenesis.

Neutrophil-endothelial adhesion is a crucial step in vascular inflammation and is recognized as a direct cause of serious atherosclerosis-mediated diseases. We previously demonstrated that high concentrations of glucose increased adhesion in a protein kinase C (PKC)-dependent manner within 48 h of administration by increasing the surface expression of endothelial adhesion molecules. In this study, we focused on the effects of histamine 2 receptor antagonists on endothelial-neutrophil adhesion and on the surface expression of endothelial adhesion molecules mediated by high glucose levels. Histamine 2 receptor antagonists have pleiotropic effects; they not only block the secretion of gastric acid, but also inhibit cell-cell adhesion, resulting in inhibition of metastasis. However, relevant mechanisms of action are not yet fully understood. Of three histamine 2 receptor antagonists (cimetidine, ranitidine, and famotidine), only cimetidine significantly attenuated adhesion mediated by 48-h incubation with 27.8 mM glucose. Cimetidine was found to decrease the surface expression of endothelial adhesion molecules intercellular adhesion molecule-1 and P-selectin, but not E-selectin. To determine the effects of cimetidine on intracellular level, we examined the effects of cimetidine on PKC-induced changes in adhesion, as well as the effects of nitric oxide (NO) synthase inhibitors on cimetidine. We found that NO synthase inhibitors reduced the inhibitory effects of cimetidine, whereas cimetidine did not affect adhesion mediated by a PKC activator. These data suggest that cimetidine acts directly on endothelial cells to inhibit high-glucose-induced expression of adhesion molecules and neutrophil adhesion mediated by increasing endothelial NO production, but not by inhibiting PKC.

Pressure (0-10 MPa) and local density dependence of 129Xe NMR chemical shift of xenon in various microporous materials was investigated using an in situ high-pressure probe. The density dependence of the chemical shift was analyzed using virial expansion of the chemical shift by xenon density. Results indicate that the second virial coefficient depends on the pore size and shape, and that the void space affects xenon-xenon interaction in both microporous and mesoporous materials. Furthermore, to interpret the magnitude of the virial coefficient in terms of the local structure of the adsorbed xenon, we analyzed the local structure of adsorbed xenon in molecular sieve 5A using Xe(n) clusters, thereby allowing description of the density dependence of the chemical shift. We also demonstrated the cluster model's validity by applying it to molecular sieves 13X and ZSM-5. The latter showed that the adsorbed xenon exists as a xenon monomer up to the filling of about 0.6 in micropores. Larger xenon clusters up to n = 4 have been grown with increasing filling of xenon. According to analyses using the Xe(n) cluster model, the second virial coefficient is related closely with the xenon cluster size, which contributes greatly to the chemical shift in the low loading region.