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Objective To review laparoscopy in patients with disorders of sex development (DSD) in order to clarify its usefulness in diagnosis, devising subsequent therapeutic strategies and managing patients with various conditions. Patients and methods Between April 1992 and December 2012, 29 laparoscopic surgeries were performed in 25 DSD patients. Among them, ten were diagnostic laparoscopy including gonadal biopsy, and 19 were therapeutic laparoscopy. Surgical procedures and complications were evaluated. Results For diagnostic laparoscopy, laparoscopic gonadal biopsy was performed in three patients. Inspection, with or without open gonadal biopsy, was performed on four out of seven patients with 46XY DSD or mixed gonadal dysgenesis (MGD). Additional surgery was planned and performed based on diagnostic laparoscopic findings in six out of seven patients. In the three patients with ovotesticular DSD, the gonadal pathology was diagnosed as: testis/ovary in one, testis/ovotestis in one and ovary/ovotestis in one – this was from the laparoscopic inspection and/or gonadal biopsy. However, the final diagnoses were bilateral ovotestis in two patients and ovary/ovotestis in one patient. For therapeutic laparoscopy, surgical procedures were: gonadectomy in 17 patients (bilateral in 13, unilateral in three, partial in two); hysterectomy in two patients; orchiopexy in one; and sigmoid vaginoplasty in one patient (included multiple procedures). There were no severe perioperative complications. In the four patients with a history of diagnostic laparoscopy, no severe intra-abdominal adhesions that would disturb therapeutic laparoscopic surgery were observed. Conclusion While diagnostic laparoscopy was helpful in devising a therapeutic surgical strategy in most of the patients with DSD who were suspected as having complex gonadal status or Mullerian duct derivatives, attention must be paid to precisely diagnosing the gonadal status in ovotesticular DSD. On the other hand, therapeutic laparoscopic surgeries were valuable procedures in treating DSD patients, even with a history of previous diagnostic laparoscopy.

Background Protein phosphatase 2A (PP2A) represents a family of potent tumor suppressors that are often suppressed in human cancers by upregulation of proteins that inhibit subunit assembly into active enzyme complexes. Thus, restoration of PP2A has assumed increasing importance for cancer treatment. In earlier work, we found that perphenazine (PPZ) kills leukemic T cells by activating PP2A (Gutierrez et al. 2014. J Clin Invest.). PPZ also acts to inhibit dopamine D2 receptor (DRD2) in the basal ganglia, which causes movement disorders at dosages less than those needed to kill T-ALL cells, effectively precluding "repurposing" of PPZ for the therapy of T-ALL. Hypothesis We sought to identify PPZ analogues that activate PP2A and induce apoptosis in T-ALL cells but lack the ability to bind and inhibit DRD2. Such analogues would not induce the movement disorders that have limited the usefulness of PPZ as an anti-leukemic drug. Methods PP2A is a heterotrimeric phosphatase that is assembled from three classes of subunits, encoded by two possible "A" genes, 15 "B" genes and 2 "C" genes, providing 60 distinct PP2A holoenzymes that can potentially form in the cell. To identify the key subunits of PP2A required for the antitumor activity of PPZ in T-ALL cells, we knocked out each subunit in human T-ALL cell lines and treated these cells with PPZ. Biochemical reporter assays were established to identify a phenothiazine derivative, iHAP1, that efficiently reactivates PP2A but does not inhibit dopamine signaling. iHAP1 preclinical studies included in vivo efficacy and toxicity in T-ALL xenograft models and in vitro efficacy in 248 cancer cell lines from 35 distinct tumor types. Results Using this approach, we found that knockout of each of three specific subunit genes of PP2A - PPP2R1A, PPP2CA and PPP2R5E - uniquely conferred resistance to PPZ treatment in T-ALL cell lines,. An independent Immunoprecipitation followed by western blotting indicated that all three subunits form a functional PP2A heterotrimeric holoenzyme complex in response to PPZ treatment. Narla and coworkers have published extensively about a series of compounds called "small molecule PP2 activators" or SMAPs (Sangodkar et al. 2017 J Clin Invest.). Intriguingly, we showed that activities of SMAP compounds depend on a different "B subunit" - PPP2R2A - and target different signal transduction pathways. Based on this finding, we sought to identify analogues of PPZ that more potently activate PP2A through this mechanism and kill T-ALL cells but lack inhibitory activity against DRD2. Testing more than 80 analogues of PPZ revealed a highly potent PP2A activator, iHAP1 (improvedHeterocyclic Activators of PP2A 1). iHAP1 is ten times more potent than PPZ in its ability to activate PP2A and kill tumor cells, but does not measurably inhibit dopamine signalling. iHAP1 is highly active as an antitumor drug human T-ALL xenograft models, without causing untoward movement disorders or other toxicity in vivo. Phosphoproteomics analysis followed by detailed biochemical assays revealed that the potent antitumor activity of PPZ and iHAP1 is mediated by dephosphorylation of MYBL2, a transcription factor that is essential for expression of genes whose products mediate prometaphase, and thus for cancer cell growth and survival. SMAP compounds do not dephosphorylate the same transcription factor and rather target other phosphoproteins. Thus, the potent PP2A activator iHAP1 drives three specific PP2A subunits into an active trimeric phosphatase and this drug is highly active against T-ALL and other hematologic malignancies. iHAP1 did not exhibit measurable toxicity up to 80 mg/kg/day PO or IM for 30 days in preclinical studies of human leukemia xenografts growing in immunosuppressed mice, providing a therapeutic index for this lead compound in preclinical studies. Conclusions Our findings show that small molecules promote the assembly of unique PP2A complexes with different regulatory subunits and substrates, allowing detailed structure and function studies of PP2A family members. A goal is to identify small molecules that assemble PP2A enzymes containing each of the remaining 13 regulatory PP2A subunits, thereby targeting a diverse array of substrates crucial to the pathogenesis of cancer and other diseases. Disclosures Gray: Gatekeeper: Equity Ownership; Syros: Equity Ownership; Petra: Equity Ownership; C4: Equity Ownership; B2S: Equity Ownership; Soltego: Equity Ownership; Novartis: Research Funding; Takeda: Research Funding; Astellas: Research Funding; Taiho: Research Funding; Janssen: Research Funding; Kinogen: Research Funding; Voronoi: Research Funding; Her2llc: Research Funding; Deerfield: Research Funding; Sanofi: Research Funding. Fischer:C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Research Funding; Deerfield: Consultancy, Research Funding; Astellas: Research Funding.

Spatial and temporal diffusive spin dynamics in the transient regime for 10-nm-wide InGaAs/InAlAs quantum wells were investigated using time-resolved optical Kerr rotation (TRKR) microscopy. The transient regime of diffusive spin dynamics is a specific regime which appears after local excitation but before the formation of a spin mode. In this regime, the spin precession frequency induced by the spin–orbit (SO) magnetic field decreases with time since the diffusive velocity decreases as the distribution of spins expands. In this study, by decreasing the spot size of the excitation pulse, we examined the spin dynamics in the transient regime. We carefully analyzed the TRKR signals using time-dependent frequency equations established by Kohda et al. [Appl. Phys. Lett. 107, 172402 (2015)]. All the TRKR signals could be well reproduced by the time-dependent frequency equations. Our analysis reveals that the spin precession frequencies arising from the SO interaction gradually decrease with time, and they allowed the extraction of the Rashba and Dresselhaus SO parameters. We revealed that SO parameters can be extracted accurately via scanning measurements in the diffusive motion of local spin excitation even in the time periods before the appearance of the spin mode.

We measured the two-color laser oscillation from a GaAs/AlGaAs-coupled multilayer cavity at 18–42 °C using current injection. We confirmed simultaneous lasing by detecting the sum frequency generation signal generated by the two-color laser light, and performed time-resolved measurement using a streak camera with a spectrometer. From the observed time transient of the spectra at various temperatures, it it is clarified that the temperature change of the device, induced by current injection, modulates the effective cavity length. Therefore, the temperature control of the device is a key factor in stable two-color lasing and THz wave generation.

Temperature and laser energy dependencies of electron g-factors are investigated for the conduction band of In0.53Ga0.47As/In0.52Al0.48As quantum wells using the time-resolved Faraday rotation (TRFR) technique. We found that in- and out-plane g-factors are ∼−3.20 and ∼−3.50 at a temperature of 5 K for the 12-nm wide quantum wells in a tilted sample configuration of the TRFR measurement. A comparison between the experiment and the eight-band Kane model calculation shows that the thermal distribution and dilatational change of the energy gap play an important role in explaining the temperature dependence of optically measured g-factors. We also found that the measured g-factor is influenced by the laser wavelength, which clearly shows that detection energy is the one of the significant factors for determining the optically measured g-factor.

Two-color lasing in a GaAs/AlAs coupled multilayer cavity has been studied for a novel type of terahertz emitting devices. In the structure, two cavity layers based on GaAs were connected by the intermediate GaAs/AlAs distributed Bragg reflector multilayer and three layers of self-assembled InAs quantum dots (QDs) were inserted only in the top-side cavity layer as optical gain materials. The broadened QD emissions around 1.25 µm are very useful to realize the optical gain because they could cover the wide range of the mode frequency difference. Two mode emissions with an optical frequency difference of 3.2 THz were successfully demonstrated under room temperature cw operation by optical pumping. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Time-resolved transmission change of Er-doped InAs quantum dots (QDs) embedded in strain-relaxed In0.45Ga0.55As barriers has been studied using different excitation wavelengths (1.4–1.55μm) to understand the QD-size dependence of the photocarrier relaxation. Each measured temporal profile was well reproduced by a sum of three exponential decays. Ultrafast (∼1.6ps) and fast (∼6–9ps) components are dominant in the initial stage of decay, and then the slow (∼70–130ps) component due to the radiative recombination in the QDs appears to be seen. The first two components come from photocarrier relaxation into the nonradiative centers related to Er dopants or the lattice relaxation. The difference is considered to result from whether the nonradiative centers are positioned inside or outside the QDs. The decay time for the outside case becomes shorter as the excitation wavelength is shortened, which might be due to the weaker confinement of photocarriers in the smaller-size QDs. Suppression of the QDs contributing to the radiative recombination is also more significant for the smaller-size QD excitation.

Electro-magnetic Induced Transparency (EIT) has been studied as a mechanism of lasers without population inversion. Little attention has been given to EIT on phonon systems, while it has a potential of application to EIT and thus THz laser and modulator. Quantum interference of multiple longitudinal optical (LO) phonon modes and the continuum of inter-valence band transition is studied in this report. p-type Ga 0.5 In 0.5 P alloy system is studied by Raman spectroscopy. The detailed analysis by spectrum fitting reveals the superposition of characteristic asymmetric profile and the contribution of a trigonal phonon mode due to ordering effect of Ga 0.5 In 0.5 P. These results indicate that Ga 0.5 In 0.5 P is a possible material of EIT on phonon systems. It is expected that the change of the degree of ordering leads to the control of quantum interference for application of EIT.

Cytomegalovirus (CMV) infection is the most common infectious complication following solid organ transplantation. Ganciclovir (GCV)-resistant CMV infection may be fatal, and is difficult to treat while avoiding allograft rejection. A 31-year-old woman received a second ABO-incompatible kidney transplant, from her father. Induction therapy consisted of basiliximab and rituximab followed by maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and methylprednisolone. Her CMV serostatus was D(+) /R(-) at second transplant and she received prophylactic low-dose valganciclovir (VGCV). BK polyoma virus nephropathy (BKVN) developed 7 months after transplant concurrent with CMV hepatitis and retinitis. VGCV was increased to a therapeutic dose combined with reduced immunosuppression with minimal methylprednisolone (2 mg/day) and everolimus (0.5 mg/day). However, pp65 antigenaemia continued to increase for 6 weeks. Her CMV was defined as ganciclovir (GCV)-resistant. Foscarnet was therefore administered and her CMV disease resolved within 2 weeks. Kidney allograft dysfunction developed 9 months after transplant, and graft biopsy showed tubulointerstitial injury with crystal deposition suggesting foscarnet nephrotoxicity, with no findings of BKVN or rejection. Kidney function recovered after cessation of foscarnet and the patient had good graft function 18 months after transplant. This case demonstrates the successful use of foscarnet to treat GCV-resistant CMV infection after ABO-incompatible kidney transplant complicated with BKVN, without acute allograft rejection. This case further highlights the need to establish appropriate management for CMV D(+) /R(-) patients to avoid the acquisition of GCV-resistant gene mutations.

To investigate changes in renal function after retroperitoneal laparoscopic partial nephrectomy (LPN) with renal hypothermia induced by ice-slush cooling.Seventy-one patients undergoing retroperitoneal LPN with renal hypothermia were included. Perioperative outcomes were reviewed retrospectively. The total renal function was evaluated by an estimated glomerular filtration rate (eGFR) preoperatively and 6 months postoperatively in 69 patients. Split renal function (SRF) was also evaluated by 99mTc-mercaptoacetyltriglycine scintigraphy preoperatively and 6 months postoperatively in 61 patients.The median operative time was 246 minutes (range, 155-424). The median cold ischemic time, including the initial 15 minutes of hypothermia, was 57 minutes (range, 34-112). In the 21 patients whose renal temperature was monitored, median lowest renal temperature was 20.7°C (range, 12.1-27.6). The median baseline eGFR and 6-month postoperative eGFR were 77.2 mL/min/1.73 m(2) (range, 36.1-121.3) and 68.3 mL/min/1.73 m(2) (range, 33.2-103.4), and the median baseline SRF and 6-month postoperative SRF of the affected kidney were 49.3% (range, 40.3-57.6) and 40.7% (range, 13.8-54.5). Using multivariate analysis, the baseline eGFR (p0.0001) and the ischemic time (p=0.0073) were associated with the 6-month postoperative eGFR, and the 6-month postoperative SRF was only associated with a baseline SRF (p=0.0185).Ice-slush cooling could provide renal hypothermia also under LPN. The decrease in renal function was small, whereas our ischemic time was longer than experts' warm ischemic series. These observations suggested the protective effect of our cooling methods against ischemic injury.

Lymphoma occurring in the pituitary gland is an exceedingly infrequent event. Here, we describe a case of pituitary lymphoma complicating recurrent pituitary adenoma. A 56-year-old male with a history of pituitary adenoma was diagnosed with diffuse large B-cell lymphoma (DLBCL) of the left ocular adnexa, which was successfully treated by standard chemotherapy and local radiotherapy. Eight months later, he complained of diplopia and bitemporal hemianopia. Brain magnetic resonance imaging detected a suprasellar tumor. Transsphenoidal biopsy of the mass was performed, and histopathological examination revealed DLBCL admixed with pituitary adenoma. On a review of the literature, we found that pituitary lymphoma developing within adenoma is a recurrent phenomenon. The composite tumor is likely to be characterized by suprasellar involvement and presentation of visual disturbances. Moreover, in the present case, the suprasellar tumor remained visible after autologous peripheral stem cell transplant, likely due to the residual pituitary adenoma. We therefore recommend that refractory pituitary lymphoma should be vigorously biopsied in search of possibly underlying adenoma.

Continuous fermentation by retaining cells with a membrane-integrated fermentation reactor (MFR) system was found to reduce the amount of supplied sub-raw material. If the amount of sub-raw material can be reduced, continuous fermentation with the MFR system should become a more attractive process for industrialization, due to decreased material costs and loads during the refinement process. Our findings indicate that the production rate decreased when the amount of the sub-raw material was reduced in batch fermentation, but did not decrease during continuous fermentation with Sporolactobacillus laevolacticus. Moreover, continuous fermentation with a reduced amount of sub-raw material resulted in a productivity of 11.2 g/L/h over 800 h. In addition, the index of industrial process applicability used in the MFR system increased by 6.3-fold as compared with the conventional membrane-based fermentation reactor previously reported, suggesting a potential for the industrialization of this D-lactic acid continuous fermentation process.

Purpose: To evaluate the speed and precision of split renal volume (SRV) measurement (SRV), which is the ratio of unilateral renal volume to bilateral renal volume, using a newly developed software for computed tomographic (CT) volumetry and to investigate the usefulness of SRV for the estimation of split renal function (SRF) in kidney donors. Method: Both dynamic CT and renal scintigraphy in 28 adult potential living renal donors were the subjects of this study. We calculated SRV using the newly developed volumetric software built into a PACS viewer (n-SRV), and compared it with SRV calculated using a conventional workstation, ZIOSOFT (z-SRV). The correlation with split renal function (SRF) using 99mTc-DMSA scintigraphy was also investigated. Results: The time required for volumetry of bilateral kidneys with the newly developed software (16.7 ± 3.9 sec) was significantly shorter than that of the workstation (102.6 ± 38.9 sec, p < 0.0001). The results of n-SRV (49.7 ± 4.0%) were highly consistent with those of z-SRV (49.9 ± 3.6%), with a mean discrepancy of 0.12 ± 0.84%. The SRF also agreed well with the n-SRV, with a mean discrepancy of 0.25 ± 1.65%. The dominant side determined by SRF and n-SRV showed agreement in 26 of 28 cases (92.9%). Conclusion: The newly developed software for CT volumetry was more rapid than the conventional workstation volumetry and just as accurate, and was suggested to be useful for the estimation of SRF and thus the dominant side in kidney donors.

Spontaneous nanostructure formations on roughened and smooth silicon surface by the femtosecond laser irradiation with the repetition rate of 100 kHz were systematically studied. In addition to the widely accepted so-called coarse ripple, which has the period analogous to the wavelength of the laser beam and aligns perpendicularly to the electric field of the incident laser beam, the ripple which has the period similar to the wavelength of the incident laser beam but aligns parallel to the electric field of the laser beam was observed on the roughened surface for the lower fluence and the higher number of pulse irradiation. Furthermore, the ensemble of dots formed by the enhancement of the local electric field was found on the roughened surface. This structure is preferentially formed around the scratches aligned perpendicularly to the electric field of the laser beam. These novel nanostructures are considered to be peculiar to the femtosecond laser irradiation and open the possibilities for precise control of the spontaneous nanostructure formation by femtosecond laser irradiation.

国内小児腎移植におけるミコフェノール酸モフェチル (MMF) の有効性・安全性，薬物動態を評価するために，多施設共同オープンラベル臨床試験を行った。 小児腎移植患者25例に，多剤免疫抑制薬併用下にMMF (600∼1,200mg/m2/日 分2経口投与) を1年間投与し，経過観察した。評価項目は，腎移植後6か月の拒絶反応発現割合，腎移植後1年の生着割合および生存割合，有害事象発現頻度とした。AUC0-12，Cmax，Tmaxなどの薬物動態態パラメータを算出した。 腎移植後6か月の拒絶反応発現割合は24%，腎移植後1年の生着割合は100%であった。有害事象発現頻度は68%であった。MMF投与後3か月時平均AUC0-12は，48.7±27.6μg hr/mLであった。推定AUC0-12の経時的推移は，米国小児腎移植患者と同様であった。 本試験には試験デザインと登録症例数が少ないという制限があるものの，国内小児腎移植患者における，MMFの拒絶反応抑制効果と安全性が示唆された。また国内小児腎移植患者は，国内成人患者，米国小児患者と同様の薬物動態を示すことが認められた。

症例は35歳，男性．1998年にGoodpasture症候群にて血液透析を導入されたが，ブラッドアクセストラブルのため2000年より腹膜透析に変更された．2003年12月より高P血症が原因でCa・P積が90(mg/dL)2を超え，右肩に手拳大，左臀部に小児頭大の異所性石灰化を認めるようになった．2004年10月より血液透析へ移行されたが異所性石灰化は改善しなかった．2005年2月24日に母をドナーとした生体腎移植を希望し，当院を初診．石灰化部はGaシンチで集積を認め，排膿よりメチシリン耐性黄色ブドウ球菌が検出されたことから感染を伴う石灰化と診断され，腎移植は見送られた．以後血液透析の継続，抗生剤治療を行ったが，異所性石灰化は増悪し続けたため，週22時間の長時間透析が施行された．長時間透析開始後，Ca・P積は是正され，異所性石灰化は改善し，2009年1月14日に腎移植が施行された．高度に進展した異所性石灰化は治療困難であるが，その治療として長時間透析は有用であることが示唆された．巨大な異所性石灰化が長時間透析により改善し腎移植を施行できた報告はこれまでになく，貴重な1例を経験したので，文献的考察を加えて報告する．

Selective thermal emission at approximately 284 cm−1 with a line width of 13 cm–1 at 628 K is obtained by heating the Au-GaAs mesa-type line and space structures. This emission demonstrates a characteristic polar radiation distribution of electric dipoles and a wavelength independent of the structure size or the direction of emission; thus, it is ascribed to thermally generated electric dipoles resonating with the longitudinal optical phonon energy. This dipole is formed by the interface polarization charges of metal-GaAs-metal stripes. These distinct features are different from the radiation properties of interface phonon polaritons or electronic systems such as intersubband transitions of quantum wells. It is estimated that the mesa height and GaAs space width ranging from hundreds of nanometers to several micrometers provide high generation efficiency of electric dipoles and resultant radiation at high temperatures.

A strong and ultrafast optical Kerr signal at ∼ 1.5 μ m has been demonstrated in a GaAs/AlAs multilayer cavity containing self-assembled InAs quantum dots (QDs) embedded in strain-relaxed In 0.35 Ga 0.65 As barriers. Time-resolved optical measurements using 100 fs pulses with 100 kHz repetition rate were carried out in the various excitation powers at room temperature. Although only 2 layers of the InAs QDs were inserted in the half-wavelength ( λ / 2 ) cavity layer, the strongly enhanced optical Kerr signal was observed compared to that of a GaAs λ / 2 cavity which had no QDs, in the whole range of excitation power (1–10 mW). The signal enhancement becomes more significant with decreasing excitation power because two-photon absorption is suppressed in the λ / 2 cavity consisting of the 2 QD layers and strain-relaxed In 0.35 Ga 0.65 As barrier. In the low-excitation power regime of 1–2 mW, the optical Kerr signal was about 2 orders of magnitude larger than that of the GaAs λ / 2 cavity due to the large nonlinearity of the resonant InAs QDs.

We have studied effects of Si and Be δ -doping on photocarrier lifetime in self-assembled InAs quantum dots (QDs) with strain-relaxed In 0.35 Ga 0.65 As barriers grown on (1 0 0) GaAs substrates by molecular beam epitaxy. Relaxation of photocarriers generated in the QDs was characterized by time-resolved transmission change measurements at room temperature. Fast and slow decay components were observed in the temporal profile of each QD sample at an excitation wavelength of 1.5 μ m . A slow decay component attributed to the radiative recombination process in the QDs was rather suppressed by Be δ -doping after the QD formation. On the other hand, Si δ -doping resulted in shortening of the decay time of the fast component due to the nonradiative process arising from the crystal defects related to the lattice-mismatch. The decay time observed in the Si δ -doped QD sample was 9 ps, which was the half of those (18 ps) observed in the undoped and Be δ -doped QD samples.

Optical Kerr signals from GaAs/AlAs multilayer micro-cavities with GaAs/AlGaAs multi-quantum wells (MQW) in the half-wavelength cavity layer were investigated. The cavity-mode-wavelengths were set at the resonance region of two-photon absorption of the MQWs in the 1.5-μm band. The measured intensities of the signals depended strongly on the cavity-mode wavelength, although the cavity layers including the MQW and multilayers maintained approximately the same structure. The nonlinearity of the MQW is considered to vary considerably at the resonant wavelength of the two-photon absorption. The results indicate that the optical Kerr signal of the multilayer micro-cavity is dominated by the nonlinearity of the cavity layer, although the cavity layer is only a small part of the total cavity thickness. This experimentally confirms the results of a previous simulation study on the multilayer cavities. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Photoluminescence (PL) as a consequence of a two-photon absorption excitation was measured in a GaAs/AlGaAs (001) multiple quantum well (MQW) at room temperature and an optical anisotropy of the two-photon absorption was investigated by PL intensity depending on the polarization direction of the normal-incidence excitation light. The anisotropic behavior with a four-fold rotation symmetry was observed in the polarization dependence. Strength of the two-photon absorption reaches its maximum when the excitation light is polarized to the [110] and [10] directions. It was found that the anisotropic behavior becomes more significant as the excitation energy approaches near the two-photon absorption edge. The anisotropy parameter |σ| determined by the theoretical fitting curve reaches ∼ 2 at the two-photon absorption edge, which was about 4 times larger than that of the bulk GaAs (|σ| ∼ 0.5). (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

To achieve the phase matching condition in terahertz (THz) pulse generation by the tilted pulse front technique, it is necessary to rebuild the entire optical setup if the optical conditions, such as excitation wavelength, temperature of nonlinear crystal, and output THz frequency, are changed. We propose THz pulse generation by the tilted pulse front technique using an M-shaped configuration. This system allows us to change the optical conditions only by tuning a few optics and without rebuilding the entire setup. We change the excitation wavelength at a fixed radiation frequency and assess the performance of the proposed system.

Room-temperature two-color lasing was demonstrated by current injection into a GaAs/AlGaAs coupled multilayer cavity for terahertz emitting devices utilizing its difference-frequency generation (DFG) inside the structure. We prepared two epitaxial wafers with (001) and (113)B orientations and they were directly bonded to form the coupled multilayer cavity. The (001) side cavity contains two types of InGaAs multiple quantum wells to realize optical gain for two-color lasing while a single GaAs layer of the (113)B side cavity is a nonlinear medium for efficient DFG. Lasing behavior was clearly observed for two modes under pulsed current conditions at room temperature. We found that intensity relation between two-color lasing was dependent on the pulse duration due to the different temporal profiles of emission intensity. Simultaneous two-color lasing in the device was also confirmed by measuring the sum-frequency generation signal using a beta barium borate crystal.

Interface phonon polaritons (IPhPs) in nano-structures excluding metal components are thoroughly investigated because they have lower loss in optical emission or absorption and higher quality factors than surface plasmon polaritons. In previous reports, it is found that strong infrared (IR) absorption is based on the interaction of p-polarized light and materials, and the resonance photon energy highly depends on the structure size and angle of incidence. We report the optical absorption by metal/semiconductor (bulk-GaAs and thin film-AlN)-stripe structures in THz to mid-IR region for the electric field of light perpendicular to the stripes, where both of s- and p-polarized light are absorbed. The absorption resonates with longitudinal optical (LO) phonon or LO phonon-plasmon coupling (LOPC) modes, and thus is independent of the angle of incidence or structure size. This absorption is attributed to the electric dipoles by the optically induced polarization charges at the metal/semiconductor, heterointerfaces, or interfaces of high electron density layers and depression ones. The electric permittivity is modified by the formation of these dipoles. It is found to be indispensable to utilize our form of altered permittivity to explain the experimental dispersion relations of metal/semiconductor-IPhP and SPhP in these samples. This analysis reveals that the IPhPs in the stripe structures of metal/AlN-film on a SiC substrate are highly confined in the AlN film, while the permittivity of the structures of metal/bulk-GaAs is partially affected by the electric-dipoles. The quality factors of the electric-dipole absorption are found to be 42–54 for undoped samples, and the value of 62 is obtained for Al/AlN-IPhP. It is thought that metal-contained structures are not obstacles to mode energy selectivity in phonon energy region of semiconductors.

Optical Kerr signals of GaAs/AlAs multilayer cavities with various quality factor (Q) were measured by an optical pump and probe technique with ultrashort pulses. Although the light intensity is enhanced in the cavities by Q, light power is restricted by the narrower spectrum of the cavity mode than that of the input ultrashort pulse. The measured Kerr signals showed larger dependence on the quality factor than that expected by simple consideration for the field enhancement effect by cavities. It seems that the nonlinear phase shift in the cavity is enhanced by the photon life time in addition to the field enhancement. This indicates that multilayer cavities are useful for enhancement of the optical Kerr signals. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The aim of the current study was to evaluate long-term outcomes of pediatric live kidney transplantation in patients with genitourinary anomalies relative to those with primary kidney diseases. The study included 35 pediatric patients who received a live kidney transplantation during the last 25 yr (28 males, six females). Median age at the time of transplantation was nine yr (range 1–15 yr), and the median follow-up period was 151 months (range 6–239 month). The patients were divided into two groups. The urological group (n = 14) included patients with primary obstructive/reflux nephropathy. The renal group (n = 20) included patients with primary renal disorders. Differences between groups in graft survival, clinical course, and final graft function were evaluated. Original diseases represented in the urological group included five cases with primary VUR and eight cases with secondary VUR. Diseases in the renal group included eight cases with bilateral hypo-dysplastic kidney, three cases with focal/segmental glomerular sclerosis, two cases with membranous proliferative glomerulonephritis, two cases with congenital nephrotic syndrome and five cases with other forms of chronic nephritis. Ten of 14 cases in the urological group, relative to six of 20 in the renal group, were preemptive. Median age at transplantation was 7.5 or 10 yr old, respectively, in the urological or renal group. Twelve kidney recipients in the urological group had also undergone other urinary surgeries, including upper urinary tract drainage, ureteroneocystostomy, augmentation cystoplasty, endoscopic incision of posterior-urethral valve, urethroplasty, etc. Cumulative post-operative complications occurred in nine or 16, respectively, in the urological or renal group. The acute rejection free and overall graft survival were similar in both groups. One patient in the urological group lost his graft while six patients in the renal group lost their grafts. Thus, the post-transplant clinical outcome of pediatric transplantation in patients with urological anomalies is comparable to that of recipients with primary renal disease. Appropriate urinary tract reconstruction and management is essential to reduce the risk of graft dysfunction because of urinary problems.

Objective: To investigate lower urinary tract symptoms (LUTS) and their impact on quality of life (QOL) in patients having undergone renal transplantation (RTX). Methods: Forty-three patients (25 males and 18 females; age 20–68 years) undergoing RTX at Hokkaido University Hospital were included in this study. Median follow-up after RTX was 41 months (range 6–184). Pre-transplant dialysis had been carried out in 38 patients (median: 4.3 years, range: 1 month–31 years). All patients were assessed by uroflowmetry (UFM), postvoid residual urine volume (PVR), 24 h bladder diary, and International Prostate Symptom Score (IPSS). QOL score and King's Health Questionnaire (KHQ) were used for the assessment of LUTS-related QOL. Results: Mean fluid intake volume and urine output volume for 24 h were 2136 mL (1150–3430 mL) and 2446 mL (1336–4733 mL), respectively. Voiding dysfunction assessed by UFM and PVR was observed in 12 patients (28%) showing higher IPSS. QOL score and overall QOL in KHQ were not different between patients with and without voiding dysfunction. Although 19 (49%) had polyuria, 20 (51%) had nocturnal polyuria, which affected nocturia in IPSS as well as sleep/energy disturbances in KHQ compared with patients without nocturnal polyuria. Conclusions: Patients having RTX frequently present voiding dysfunction and nocturia basically caused by nocturnal polyuria. We should focus on LUTS in these patients to provide an appropriate management.

We investigate anisotropic properties of strained InGaAs quantum wells on the high index (11n)A (n = 3,4,5) GaAs substrates. The polarization dependence of photoluminescence of strained InGaAs quantum wells were measured, and optical anisotropy was observed. We calculated anisotropy of the optical transition matrix elements based on the 4x4 and 6x6 Luttinger model for the quantum wells with uniaxial strain. The calculated anisotropy taking into account of split-off band qualitaively agree with our experiment. This indicates that the band mixing of split-off band into the heavy-hole band largely contributes to the the optical anisotropy in the strained InGaAs quantum wells on the high index substrates. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

本稿は,学校をめぐるステークホルダーの人たちが教師に求める資質能力を明らかにし,それを実現するための教員養成および現職教育のプログラムを開発することを目的とした研究プロジェクトのうち,幼稚園教師に求める資質能力に関する予備調査の分析結果をまとめたものである。予備調査では,幼稚園教師に求める資質能力は,保護者と教師自身で差異が見られ,また小学校教師に求める資質能力とも差異が認められた。, This paper reports the results of preliminary survey about the competence and ability of kindergarten teacher. This survey is the part of the research project that explores the teacher competence and ability. This project attempts to clarify the quality and ability that stakeholders over the schools seek and expect, and to develop a teacher training program and incumbent program to train the qualified teacher. The results of the survey show that the competence and ability of kindergarten teacher that parents expect is different from ones that kindergarten teachers expect, and the competence and ability of kindergarten teacher is different from the ones of elementary school teacher.

The impact of post-transplant donor-specific antibody (DSA) on the development of chronic rejection has been focused recently. The aim of this study was to evaluate the significance of DSA, graft function and pathological factors of chronic rejection. Seventy-three kidney recipients who underwent protocol biopsy were included in the study. The median follow-up period after transplant was 40 months. The presence of anti-HLA antibody (aHLAAb) and DSA was tested using flow beads analysis (FlowPRA®). The patients were divided into a group with DSA, a group with non-donor-specific aHLAAb and a group without aHLAAb. Protocol biopsy specimen were compared for transplant glomerulopathy (cg), vasculopathy (cv), C4d deposition at peritubular capillary (PTC), peritubular capillaritis (ptc score 0-3) and thickening of PTC basement membrane (ptcbm score 0-3) as recently proposed. The presence of DSA was significantly associated with the presence of cg, ptcbm. The group with non-donor-specific aHLAAb had ptcbm but did not have cg. The group without aHLAAb rarely showed ptcbm. The presence of DSA was associated with impaired graft function. C4d was not specific for the patients with DSA. These histopathological markers are useful in the detection of immunological chronic rejection. Early detection by screening tests will be important for treatment before irreversible change occurs.

Background We investigated risk factors for lower urinary tract (LUT) dysfunction and LUT symptoms in patients who successfully underwent renal transplantation (RTX). Material and methods Ninety-five patients (54 males and 41 females) undergoing RTX (median age: 45 years old) at Hokkaido University Hospital were included in this study. Uroflowmetry (UFM), postvoid residual urine volume (PVR), and 24-h bladder diaries were performed. We analyzed risk factors for voiding dysfunction, urinary frequency, polyuria, nocturia, and nocturnal polyuria after RTX using logistic regression analysis. Results End-stage renal disease arose from diabetes mellitus in 18 patients (19%). Pre-transplant dialysis had been carried out in 74 patients. Voiding dysfunction as assessed by UFM and PVR was observed in 24 patients (27%). Based on the 24-h bladder diaries, we identified frequent micturition in 29 patients (35%), polyuria in 44 (54%), nocturia in 30 (37%), and nocturnal polyuria in 46 (56%). A multivariable logistic regression analysis revealed that diabetes mellitus, which may cause autonomic disorders, was a risk factor for voiding dysfunction and nocturnal polyuria. A risk factor for frequent micturition and nocturia was older age at RTX. Being female was a risk factor for polyuria, which suggested that fluid intake in relation to body weight was higher in females. Conclusions LUT dysfunction and LUT symptoms were not uncommon in patients who successfully underwent RTX. LUT dysfunction and LUT symptoms need to be considered in patients with risk factors such as diabetes mellitus, older age at RTX, and being female, even after successful RTX.

Induced pluripotent stem cell (iPSC) technology provides new opportunities in regenerative medicine to generate grafts from donors for transplantation. However, particularly when allogeneic iPSCs are used, immune suppression is required to avoid rejection of iPSC-derived grafts. In this study, we examine a concept that protection of iPSCs-derived allografts can be achieved when transplantation is accompanied with the administration of immunosuppressive cells generated from the same iPSCs resource.Mouse iPSCs were differentiated into immunosuppressive cells by a culture protocol using granulocyte macrophage-colony-stimulating factor, macrophage-colony-stimulating factor, IL-4, and lipopolysaccharide. Adherent clusters were collected and examined for the ability to suppress allogeneic T- and B-cell responses, as well as for the contribution to prolonged allogeneic graft survival in transplantation models.Myeloid cells with immunosuppressive features were successfully induced from iPSCs, and thus referred to as iPSC-derived suppressor cells (iPS-SCs). The iPS-SCs resemble macrophages in terms of cell surface molecules and gene expressions. Furthermore, iPS-SCs efficiently suppressed allogeneic T- and B-cell proliferation in a nitric oxide-dependent manner, and iPS-SCs were found to suppress alloantibody production and prolong substantially the survival of iPSC-derived grafts, such as embryoid bodies and cardiomyocytes, in in vivo allogeneic transplantation models.A certain fraction of macrophage-like cells with immunosuppressive functions can be generated from donor iPSCs, which contribute to the prolonged survival of grafts derived from the same iPSCs in allogeneic recipients. These results suggest a new immunosuppressive strategy of combined donor iPSC-derived graft and immunosuppressive cell transplantation in regenerative medicine using iPSCs.

Interaction of a semiconductor surface or interface and p-polarized infrared light has been investigated from the viewpoint of THz application. In this study the electric dipole absorption at the resonant energy to a longitudinal optical phonon is clearly observed also for s-polarization for lateral Ti/GaN/Ti and Ti/GaAs/Ti stripe structures. Modification of permittivity is found by the analysis of Raman and IR spectra.

Quantum interference between two LO phonon modes and valence band states is investigated by Raman spectra of p-type Ga 0.5 In 0.5 P. The spectrum fitting analysis reveals the quantum interference features in asymmetric line shape, broadening, and peak shift. This finding suggests the possibility of the control of the absorption profile in THz frequency region.

To evaluate the safety and effectiveness of transcatheter arterial embolization (TAE) with ethanol in symptomatic patients with enlarged polycystic kidney disease.This prospective study was institutional review board approved and was planned for patients with symptoms related to enlarged polycystic kidney disease, such as a markedly distended abdomen, gastroesophageal reflux, and abdominal pain. At the time of TAE, all patients were undergoing dialysis therapy for chronic renal failure, and their urinary volume had decreased to less than 500 mL per day. Bilateral renal TAE with absolute ethanol was performed, and changes in kidney volume, clinical symptoms, laboratory data, and complications were evaluated after TAE. The differences in patients' kidney volumes, clinical symptoms, abdominal circumference, and dry weights before and after TAE were analyzed with a mixed effect model.Fifteen patients (seven men and eight women; mean age, 57.7 years ± 5.3 [standard deviation]) were treated. Among the 15 patients, the follow-up period was 24 months in 13 patients, 6 months in one patient, and 3 months in one patient. The mean kidney volume was 3380 mL before renal TAE, and at 3, 12, and 24 months after TAE, it significantly decreased to 60.9%, 39.8%, and 32.1% of the pretherapeutic value, respectively (P.001). All patients reported improved clinical symptoms within 3 months after TAE (P.001). Abdominal circumferences were significantly decreased after TAE (P.001). The dry weights also continued to significantly decreased until 6 months after TAE (P.001), at which point they began to slightly increase until 24 months after TAE. Abdominal pain, nausea, and inflammatory response developed in all patients after TAE, but these symptoms improved with conservative treatment. Abscess formation was found in one kidney, and drainage catheter placement was performed. No major complications related to TAE occurred in the remaining patients.Renal contraction therapy by TAE with ethanol injection appears to be a safe and effective treatment in patients with symptomatic enlarged polycystic kidney disease.

A 30-yr-old woman underwent kidney transplantation from a flow cytometric lymphocyte crossmatch-negative donor. Immunosuppression consisted of tacrolimus, mycophenolate mofetil, basiliximab and three days of steroid. On day 5 post-transplant, she developed acute rejection and underwent anti-rejection therapy consisting of steroid pulse and deoxyspurgualin. Retrospective analyses of anti-human leukocyte antigen antibody revealed high flow panel reactive antibody (PRA) in the pre-transplant serum without donor specific antibody (DSA) and positive DSA at the time of rejection. Anti-rejection therapy was successful in treating cellular rejection but her graft function further deteriorated after three months post-transplant and graft biopsy revealed chronic allograft nephropathy with positive staining for C4d in peritubular capillary, suggesting the presence of chronic antibody-mediated rejection. Pre-transplant positive flow PRA without DSA may also be a risk for acute and chronic rejection.

OBJECTIVE To present five cases of renal arteriovenous fistula (RAVF) seen at our institution, with an emphasis on surgical treatment. PATIENTS AND METHODS We assessed five patients with giant high-flow RAVF. The affected kidney was evaluated functionally using 99mTc-diethylenetriamine pentaacetic acid renal scintigraphy. The size, location, involvement of branched arteries, and renal function dictated the choice of operative method. Four patients were treated with in situ ligation of the feeding artery for extrarenal RAVF, and the remaining patient had a nephrectomy of the nonfunctioning kidney. The clinical outcome was analysed by renal function, blood pressure control, radiographic cardiothoracic ratio (CTR), occlusion of RAVF, and renal artery patency. RESULTS Of two patients with hypertension, the blood pressure was normalized in one. The renal function of the affected side was preserved in four patients. CTR was normalized or improved in all four patients with preoperative cardiomegaly. There was no recurrence of RAVF in any of the five patients and there was no major morbidity after surgery. CONCLUSIONS Surgery for giant high-flow RAVF is safe and feasible from the perspective of complications and recurrence, even though transarterial embolization has become the first line of therapy for RAVF.

α-galactosidase Aの酵素補充療法を開始後に腎移植を施行したFabry病の症例報告はこれまでになく, 私たちは貴重な1例を経験したので, 若干の文献的考察を加えて報告する. 症例は32歳男性, 13歳時にFabry病と診断された. 28歳で腎機能障害を指摘され, 32歳ですでに慢性腎不全であった. 2004年7月より慢性腎不全の改善を期待して保険承認された酵素補充療法を開始された. 酵素補充療法により, 四肢末梢の疼痛や血漿および尿中globotriaosylceramide (GL-3) は著明に減少したが, 徐々に腎機能障害は進行した. 2004年10月には血清クレアチニンが21.4mg/dLとなり, 尿毒症症状も出現したため, 血液透析を導入し, その約2週間後に父をドナーとした生体腎移植を施行した. 腎移植後の経過は良好であり, 現在も酵素補充を継続している. 腎移植後の酵素補充療法は移植腎へのGL-3沈着防止のために必要なだけでなく, むしろFabry病の重大な合併症である心血管疾患の予防に大変重要な治療であり, その指標には尿中よりも血漿中のGL-3を用いるべきと考えられた.

ZSM-5 zeolite membrane, which shows high selectivity toward olefins in the methanol conversion, was developed by controlling the location of the acid sites. First, the ZSM-5 zeolite catalyst membrane without pinholes was successfully prepared by synthesizing a ZSM-5 zeolite layer on an outer surface of a cylindrical alumina ceramic filter. The membrane was used as the catalytic membrane reactor to recover olefins from methanol. Though the olefins were successfully produced from methanol with high selectivity (ca. 80%), production of paraffin and aromatics was observed at the feed side of the zeolite membrane. To prevent the such production, the location of the acid site of the ZSM-5 zeolite membrane was controlled by a new method called the catalytic cracking of silane (CCS) method. Selective deactivation of acid sites at the outer surface of the zeolite membrane (feed side of reactant) by the CCS method allowed us to increase the selectivity of the olefins by 10% as compared to the untreated membrane.

Electron spin dynamics in strained In 0.1 Ga 0.9 As/Al 0.4 Ga 0.6 As quantum wells (QWs) on (1 0 0) and (1 1 0) -oriented substrates are investigated by time-resolved Faraday rotation. We find that the spin relaxation time in (1 1 0) QWs is 6 times longer than that in (1 0 0) QWs at low temperatures, which is strongly reduced by applying magnetic fields. The sign of g -factor is found positive and its magnitude decreases with increasing well width, in the well width range investigated here.

Dear Editor, Little is known about the prognostic factors of posttreatment extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) [1]. To address this issue, we carried out a retrospective cohort study with MALT lymphoma patients treated at our institute. We reviewed the patients with MALT lymphoma treated at The University of Tokyo Hospital between February 1997 and April 2010. Patients who had undergone extensive survey for precise staging at initial presentation and with clinical follow-up data for at least 24 months after initial therapy were included in this study. Impact of clinical variables on survival was assessed using the log-rank test (in univariate analyses), and the factors showing relevant association (P

Although runt-related transcription factor 1 (RUNX1) is well known for its context-dependent oncogenic properties in various malignancies, its role in gastric cancers has been poorly defined. Up-regulation of receptor tyrosine kinase (RTK) ErbB2/HER2 signaling pathway is encountered in the vast majority of gastric cancer cases and contributes to the initiation and maintenance of these cancer cells. This signaling cascade is partly yet arbitrary mediated by son of sevenless gene 1 (SOS1), which functions as an adaptor protein in RTK cascades. Herein we report that RUNX1 regulates ErbB2/HER2 signaling pathway in gastric cancer cells through transcriptionally regulating SOS1 expressions, rendering itself an ideal target in anticancer strategies. Mechanistically, RUNX1 interacts with the consensus RUNX1 binding sequence (5’-TGTGGT-3’) located in the proximal promoter region of SOS1 and positively regulates it. Short hairpin RNA (shRNA)-mediated knockdown of RUNX1 in the gastric cancer cell line MKN45 led to the decreased expression of SOS1 and of phosphorylated form of ErbB2/HER2 as well as the deactivation of its downstream targets such as AKT and ERK. RUNX1 knockdown subsequently induced cell cycle arrest at G0/G1 phase and successive apoptotic cell death in MKN45 cells. Silencing of HER2 or SOS1 in MKN45 cells unalterably suppressed the proliferation of these cancer cells, highlighting the importance of this ErbB2/HER2 signaling cascade in the maintenance of gastric cancer cells. We also found that SOS1 is one of the most consistently up-regulated genes in RUNX1-high expressing primary gastric cancer cells derived from previously reported human clinical samples. These data collectively indicates that inhibition of RUNX1 could be a legitimate therapeutic choice in the management of gastric cancers. Lastly, we examined the efficacy of a novel small molecule specifically binds and inhibits RUNX1 (we named it as CM). Intriguingly, CM was exceptionally effective against MKN45 cells (IC50 value at 403.5 nM). Besides, CM was well-tolerated in mice and fabulously suppressed the growth of xenotransplanted MKN45 cells in immunodeficient mice in vivo. Taken together, our work identified a novel interaction of RUNX1 and ErbB2/HER2 signaling pathway, paving a new way for the management of dismal-prognostic advanced stage HER2-positive gastric cancer patients. Citation Format: Yoshihide Mitsuda, Ken Morita, Shintaro Maeda, Kensho Suzuki, Gengo Kashiwazaki, Junichi Taniguchi, Toshikazu Bando, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo. RUNX1 positively regulates ErbB2/HER2 signaling pathway through modulating the expression of SOS1 in gastric cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1530. doi:10.1158/1538-7445.AM2017-1530

Mast cells develop from hematopoietic progenitors under SCF-dependent activation of KIT encoding a type III receptor tyrosine kinase. In addition, KIT signaling also enhances release of chemical mediators from stimulated mast cells. KIT D816V mutation, a gain-of-function mutation which is often found in mastocytosis, causes SCF-independent activation of KIT, leading to autonomous mast cell survival and proliferation. ChIP-seq analysis of mouse bone marrow-derived mast cells showed that hematopoietic transcription factor RUNX1 bound to several genomic regions between KIT exon 1 and intron 1. We therefore investigated an association between RUNX1 and the transcriptional regulation of KIT in the human mast cell lines. The global gene expression profile revealed that KIT gene expression in the cells was positively linked to RUNX1 gene expression. Using ChIP assay coupled to PCR, we found RUNX1 binding at KIT intron 1 in the cells with KIT D816V mutation. RUNX1 knockdown reduced KIT expression in both cell lines with and without KIT D816V mutation, and led to a significant decrease in cell growth of those with D816V mutation. In the RUNX1-knockdown cells, PI3K-Akt pathway of KIT downstream signaling was suppressed, and G0/G1 cell-cycle arrest occurred, which was followed by apoptosis. The chlorambucil-conjugated compound that we developed to inhibit RUNX1 binding to its DNA targets successfully and effectively decreased the KIT expression of the mast cells with KIT D816V mutation, which resulted in the cell growth suppression. These findings suggested that RUNX1 upregulates KIT expression and may be a potential therapeutic target in mast-cell diseases.