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We evaluated the efficacy of treatment using reduced cumulative doses of anthracyclines in children with acute promyelocytic leukaemia (APL) in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-P05 study. All patients received two and three subsequent courses of induction and consolidation chemotherapy respectively, consisting of all-trans retinoic acid (ATRA), cytarabine and anthracyclines, followed by maintenance therapy with ATRA. Notably, a single administration of anthracyclines was introduced in the second induction and all consolidation therapies to minimize total doses of anthracycline. The 3-year event-free (EFS) and overall survival rates for 43 eligible children were 83·6% [95% confidence interval (CI): 68·6-91·8%] and 90·7% (95% CI: 77·1-96·4%), respectively. Although two patients died of intracranial haemorrhage or infection during induction phases, no cardiac adverse events or treatment-related deaths were observed during subsequent phases. Patients not displaying M1 marrow after the first induction therapy, or those under 5 years of age at diagnosis, showed inferior outcomes (3-year EFS rate; 33·3% (95% CI: 19·3-67·6%) and 54·6% (95% CI: 22·9-78·0%), respectively). In conclusion, a single administration of anthracycline during each consolidation phase was sufficient for treating childhood APL. In younger children, however, conventional ATRA and chemotherapy may be insufficient so that alternative therapies should be considered.

Mutations of LMX1B cause nail-patella syndrome, a rare autosomal dominant disorder. Recently, LMX1B R246Q heterozygous mutations were recognised in nephropathy without extrarenal manifestation. The aim of this study was to clarify characteristics of nephropathy caused by R246Q mutation.Whole exome sequencing was performed on a large family with nonsyndromic autosomal dominant nephropathy without extrarenal manifestation. Clinical and histological findings of patients with LMX1B mutation were investigated.LMX1B R246Q heterozygous mutation was identified in five patients over three generations. Proteinuria or haematoproteinuria was recognized by urinary screening from all patients in childhood. Proteinuria gradually increased to nephrotic levels and renal function decreased in adolescence. Two patients progressed to end-stage renal disease in adulthood. Renal histology demonstrated minimal change in childhood and focal segmental glomerulosclerosis in adulthood. Using electron microscopy, focal collagen deposition could be detected in glomeruli even when a "moth-eaten appearance" was not apparent in the glomerular basement membrane. In addition, podocin expression in glomerular podocytes was significantly decreased, even in the early stages of disease progression.Comprehensive genetic analyses and collagen or tannic acid staining may be useful for diagnosis of LMX1B-associated nephropathy. While renal prognosis of R246Q may be worse than that of typical NPS nephropathy, signs of podocytopathy can be detected during the infantile period; thus, childhood urinary screening may facilitate early detection.

On the basis of results of previous Japanese trials for myeloid leukemia in Down syndrome (ML-DS), the efficacy of risk-oriented therapy was evaluated in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-D05 study.All patients received induction chemotherapy that consisted of pirarubicin, intermediate-dose cytarabine, and etoposide. Patients who achieved complete remission (CR) after initial induction therapy were stratified to the standard risk (SR) group and received four courses of reduced-dose intensification therapy. Patients who did not achieve CR were stratified to the high risk (HR) group and received intensified therapy that consisted of continuous or high-dose cytarabine.A total of 72 patients were eligible and evaluated. One patient died of sepsis during initial induction therapy. Sixty-nine patients were stratified to SR and two patients to HR. No therapy-related deaths were observed during intensification therapy. The 3-year event-free and overall survival rates were 83.3% ± 4.4% and 87.5% ± 3.9%, respectively. Age at diagnosis less than 2 years was a significant favorable prognostic factor for risk of relapse (P = 0.009).The attempt of risk-oriented prospective study for ML-DS was unsuccessful, but despite the dose reduction of chemotherapeutic agents, the overall outcome was good, and further dose reduction might be possible for specific subgroups.

Bone marrow necrosis (BMN) is a rare phenomenon in children with malignancies, occurring most commonly in patients with acute lymphoblastic leukemia (ALL). The pathophysiology of this phenomenon has not been identified. We analyzed seven BMN cases with ALL in order to elucidate the underlying mechanism. Serum high-mobility group box 1 (HMGB1), cytochrome C, cytokines, and chemokines were measured, and real-time quantitative reverse transcription-polymerase chain reaction (RQ-RT-PCR) and immunochemistry of death-related molecules were analyzed using bone marrow samples. The serum levels of 17 of 27 cytokines and chemokines were found to be significantly elevated in patients with BMN in comparison to those in healthy volunteers; however, IFN-γ and IL-10 were not elevated. The cytokine pattern was different to that reported in hemophagocytic lymphohistiocytosis. The HMGB1 and cytochrome C levels in patients with BMN were not elevated. RQ-RT-PCR revealed significant overexpression of Fas-ligand, perforin, and granzyme B in the bone marrow of patients with ALL complicated with BMN compared with that in healthy volunteers and in patients with ALL without BMN. On immunohistochemistry, we identified leukemic cell-eliciting Fas-ligand and macrophage-eliciting TNF-α. Thus, no close relationship with massive necrosis or the intrinsic pathway of apoptosis was identified in the occurrence of BMN. These results suggest that the massive cell death phenomenon called BMN is partially induced by the extrinsic pathway of apoptosis.

Germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene (SDHB) cause susceptibility to paragangliomas and pheochromocytomas; however, it is exceedingly rare in childhood and especially in sporadic cases. We report the first Japanese pediatric case of paraganglioma with a de novo mutation in the SDHB gene. A 6-year-old girl with convulsions and hypertension was found to have a paravertebral abdominal tumor. Urinary and blood examinations revealed markedly elevated levels of norepinephrine. Following treatment for hypertension, the tumor was removed completely and histological findings were consistent with paraganglioma. Immunohistochemistry studies demonstrated the absence of SDHB protein expression, indicating an underlying SDH mutation with high probability. Germline mutation analysis of the SDHB gene revealed a heterozygous splice site mutation in intron 4 (C.423 + 1G A). Subsequently, a second somatic genetic change was confirmed by multiplex ligation-dependent probe amplification (MLPA) analysis, showing that deletion of the wild-type allele resulted in loss of function of SDHB. No germline mutations in SDHB were detected in her parents.Genetic testing should be considered for pediatric patients with paragangliomas, even in the absence of familial history, as closer lifelong screening to detect the development of malignancy will be required for patients with SDHB mutations.Most sporadic cases of paraganglioma with SDHB mutations occur between adolescence and adulthood. Screening methods for carriers of SDHB mutations assessing recurrence and detecting developing metastases are yet to be standardized.The current case of an extra-adrenal paraganglioma with a de novo SDHB mutation had an onset at 6 years. We suggest much closer periodical observation for these high-risk children.

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In the present study, we established a lung metastasis animal model of CCS and investigated the therapeutic effect of boron neutron capture therapy (BNCT) using p-borono-L-phenylalanine (L-BPA). Biodistribution data revealed tumor-selective accumulation of (10)B. Unlike conventional gamma-ray irradiation, BNCT significantly suppressed tumor growth without damaging normal tissues, suggesting that it may be a potential new therapeutic option to treat CCS lung metastases.

Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT.

The influence of spontaneous polarization on the active driving of V-shaped switching ferroelectric liquid crystals is discussed. Two ferroelectric liquid crystals with a high spontaneous polarization (200 nC/cm2) and a low spontaneous polarization (7 nC/cm2) are used in this study. The field-effect transistor used as an active switch and a storage capacitor is set parallel to a liquid crystal cell. In a high-spontaneous-polarization material, cell voltage increases, while the transistor is in the on-state. After the application of external driving voltage, cell voltage decreases owing to the discharging of the storage capacitor due to the changes induced by spontaneous polarization. On the other hand, in a low-spontaneous-polarization material, the decrease in cell voltage after the application of external driving voltage is very small. The low-spontaneous-polarization material, compared with the high-spontaneous-polarization material, is advantageous for controlling light intensity by active driving.

A nematic liquid crystal director orientation in a vicinity of a glass/liquid-crystal interface is investigated in relation to an acoustic phase change of a shear horizontal (SH) wave propagating in a cell structure. The relationships between phase change and electric field applied to the liquid crystal layer are given for various layer thicknesses. The numerical analysis of wave penetration in the liquid crystal cell is performed by considering distribution profiles of liquid crystal direction in relation to shear stress at the glass/liquid-crystal interface. The experimental acoustic phase changes are well consistent with the calculated shear stresses as flow resistance. The acoustic phase is strongly dependent on viscosity distribution and particle velocity in the liquid crystal layer.

OBJECTIVES Viral infections may complicate the diagnosis of juvenile myelomonocytic leukemia (JMML) in a substantial proportion of patients, but this possibility has not been tested in a prospective study. The authors therefore measured the cellular expression of the MxA protein, a reliable marker of viral infection, at diagnosis in children with JMML to estimate the prevalence of such infections. METHODS Eighteen children, aged 1 to 69 months, who met the diagnostic criteria of the International JMML Working Group were prospectively studied. MxA expression was assessed by flow cytometric analysis of peripheral blood mononuclear cells stained with an antihuman MxA antibody. All data were obtained through the MDS Committee of the Japanese Society of Pediatric Hematology. RESULTS Twelve patients (67%) had elevated levels of the MxA protein, with rotavirus, RS virus, or CMV infection documented in three of these patients. Although none of the patients had primary Epstein-Barr virus (EBV) infection, reactivation of the virus was strongly suspected in four children, including two with monosomy 7, each having increased levels of MxA. Southern blot analysis revealed monoclonal integration of the EBV genome into bone marrow mononuclear cells from one of these patients. There was no discernible correlation between increases in the marker protein and the presenting features or course of the disease. CONCLUSIONS Viral infection may be present in two thirds of children with newly diagnosed JMML, but it does not constitute a basis for revising clinical management. The possibility that EBV or other viruses contribute to JMML pathogenesis by stimulating pre-exiting malignant clones warrants further investigation.

BACKGROUND: Epidemiologic studies of electromagnetic fields and childhood cancers have focused on home exposure. The authors investigated whether residence in districts near high-voltage power lines is associated with childhood hematological malignancies, using small area analysis. METHODS: Among 50,000 children in a city in Japan, 14 cases aged younger than 15 years were diagnosed with these malignancies in the period from 1992 through 2001. A total of 294 districts constituting this city were classified according to their proximity to high-voltage power lines (either 66 kV or 220 kV). Mantel-Haenszel rate ratio is used to calculate incidence rate ratio and its 95% confidence interval (CI). RESULTS: Compared to districts of which no area fell within 300 m of high-voltage power lines, districts in which at least 50% of the area fell within 300 m of high-voltage power lines demonstrated an increased risk (incidence rate ratio: 2.2; 95% CI: 0.5-9.0). The association was strengthened for homes in which patients had resided for the longest interval of their lives (incidence rate ratio: 3.4; 95% CI: 0.9-13.2). Point-in-time measurements showed no increase in magnetic field levels for patient homes in districts near the lines. CONCLUSION: An increased, albeit nonsignificant, risk of childhood hematological malignancies associated with residential proximity to high-voltage power lines warrants further investigations.

In support of the application of liquid crystals to adaptive devices such as variable delay lines in the microwave and millimeter band, the complex permittivities and response times of five different nematic liquid crystals after voltage application were measured. We measured both the real part of the relative permittivity, when the long axis of the liquid crystal molecule is parallel to the high-frequency electric field, and the relative permittivity when it is perpendicular to the high-frequency electric field. The values and were measured. In the range from 10 kHz to 13 MHz, the capacitance and conductance of a liquid crystal cell sandwiched between ITO glass plates processed by rubbing were directly measured. For 100 MHz to 40 GHz, we propose the new cutback method, in which two coaxial tubes with different lengths are filled with the liquid crystal and the dielectric properties are measured on the basis of their respective group delay and transmission loss. Dielectric relaxation is verified in the low frequency range. In particular, in the range from 3 to 40 GHz, dielectric properties are shown for a continuous change of frequency. It is found that and are kept almost constant regardless of the frequency, taking values of approximately 3 and 2.5, respectively. , which is the difference between the permittivities in two orientations, exhibits a large variation, from 0.4 to 0.8, depending on the material, which provides crucial data for selecting the optimal material. The response time was measured by placing the liquid crystal cell between two polarizers with the polarizing directions set parallel. The light from a He-Ne laser (632.8 nm) is directed onto the liquid crystal cell, and the transmitted light is detected by a photodiode. Assuming that the liquid crystal is used in an adaptive device, the speed of operation is investigated. Based on the measurement results for two different nematic liquid crystals, the design of a variable delay line for 20, 30, and 40 GHz is considered, and a principle of liquid crystal material selection is presented. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(8): 49–60, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10130

We describe a 5-year-old female with acute lymphoblastic leukemia (ALL) who suffered from cytomegalovirus (CMV) retinitis during maintenance therapy consisting of 6-mercaptopurine (6-MP) and methotrexate (MTX) with pulses of vincristine (VCR) and dexamethasone (DEX). Administration of anticytomegaloviral drugs led to a complete regression of active retinitis. Her low CD4 positive T cells and serum immunoglobulin G (IgG) recovered when maintenance therapy was resumed without VCR and DEX. The patient has been in complete remission (CR) for more than 5 months after completion of maintenance therapy without recurrence of CMV retinitis.

The nematic liquid-crystal director-orientation in the vicinity of the interface between a liquid-crystal layer and a glass substrate is evaluated in various orientations under an applied electric field, using shear horizontal (SH) wave propagation. The measured acoustic phase delay is related to numerical analysis of the propagation characteristics of the SH wave in a trilayer structure containing a nematic liquid-crystal layer (4-cyano-4′-pentylbiphenyl: 5CB) between two glass plates. This technique using SH wave propagation in a liquid-crystal cell is promising for evaluating the nematic liquid-crystal director angle in the vicinity of the interface.

Mechanical vibration characteristics of a freely suspended film of ferroelectric liquid crystal are investigated via measurements of the transmitted and reflected lights. The frequency spectrum of the mechanical vibration induced by applying electric field has several peaks corresponding to a resonance phenomenon. The mechanical vibration induced by irradiating an ultrasound in air has harmonic components in addition to the fundamental component of the carrier wave frequency of the ultrasound. The mechanical vibration is also observed under irradiation of ultrasound in the form of pulsed RF or amplitude-modulation (AM). The frequency components correspond to the eigenmodes of the resonance vibration. An AM ultrasound is demodulated by using the freely suspended film.

A 3-year-old male presented with a large retroperitoneal mass and multiple metastases. Biopsy results suggested alveolar rhabdomyosarcoma bearing a methylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. Serum microRNA-206 levels were elevated and remained high after three cycles of vincristine, dactinomycin, and cyclophosphamide (VAC). Replacement of vincristine, irinotecan, and temozolomide (VIT) for VAC induced a marked tumor reduction and normalization of the miR-206 levels. The patient completed 14 cycles of VIT with local radiotherapy and has been in remission for 31 months. Temozolomide could be effective for tumors with a methylated MGMT gene promoter. Individualized therapy is warranted for such patients.

We report the spectral broadening of selective reflection (SR) with higher response speed in cholesteric liquid crystals (ChLCs). A planarly aligned ChLC was applied with an in-plane electric field with an inhomogeneous intensity in the cell-depth direction by using common interdigitated electrodes and selecting the cell gap and the interval between electrodes. The electric field normal to the helix increased the helical pitch of the ChLC, while the inhomogeneous field intensity caused the spatial distribution of the helical pitch in the cell-depth direction, increasing the SR band width from 100 to 300 nm with the response time of 3 ms.

We report fast electro-optic response independent of cell thickness in cholesteric liquid crystals (ChLCs). Usually, an electric field normal to the helix axis of ChLCs induces two fast and one slow response components: helical elongation (slow one), helical deformation (fast one), and flexoelectric effect (fast one). In this study, we found that a planarly aligned ChLC applied with an in-plane electric field exhibited only fast response components because the glass substrates suppressed the motion of the helical elongation. Furthermore, we demonstrated complete separation of the remaining fast components by using dielectric measurement system. Consequently, we were able to analyze dynamics of the helical deformation in detail, in which response times exhibited quadratic dependence on the helical pitch and no dependence on the cell thickness.

Predicting the response to immunosuppressive therapy could provide useful information to help the clinician define treatment strategies for patients with aplastic anemia. In our current study, we evaluated the relationship between telomere length of lymphocytes at diagnosis and the response to immunosuppressive therapy in 64 children with aplastic anemia, using flow fluorescence in situ hybridization. Median age of patients was ten years (range 1.5-16.2 years). Severity of the disease was classified as very severe in 23, severe in 21, and moderate in 20 patients. All patients were enrolled in multicenter studies using antithymocyte globulin and cyclosporine. The response rate to immunosuppressive therapy at six months was 52% (33 of 64). The probability of 5-year failure-free survival and overall survival were 56% (95% confidence interval (CI): 41-69%) and 97% (95%CI: 87-99%), respectively. Median telomere length in responders was -0.4 standard deviation (SD) (-2.7 to +3.0 SD) and -1.5 SD (-4.0 to +1.6 (SD)) in non-responders (P

We describe a 6-month-old infant with classic medulloblastoma. Gross total resection of the left cerebellar tumor was performed; however, relapse occurred during the administration of intrathecal and intravenous methotrexate-based chemotherapy. After undergoing resection, high-dose chemotherapy was administered consisting of topotecan, melphalan, and cyclophosphamide with autologous peripheral stem cell rescue followed by local irradiation and intrathecal topotecan, which resulted in a complete response for more than two years. The administration of high-dose chemotherapy followed by intrathecal topotecan as maintenance therapy is an effective strategy, without losses in the cognitive function, for avoiding the use of whole-brain irradiation for infantile classic medulloblastoma.

An electrorheology (ER) effect of a ferroelectric liquid crystal (FLC) is described on the basis in numerical analysis and experiment. Propagation characteristics of a shear-horizontal (SH) wave in a liquid crystal layer between a piezoelectric ceramic thin plate and a glass thin plate is numerically analyzed. The phase velocity of the SH wave depends predominantly on the viscosity of the FLC. The ER effect is measured using a SH wave device under the construction of delay line oscillator. The observed DC electric field dependence of oscillation frequency under the use of a helical structure of FLC is related to the observed microscopic result. This method has the advantage of simplicity and a small amount of liquid sample for evaluating the ER effect of the FLC.

The light diffraction properties of a shorter periodical domain, which is caused by an elastic wave propagating along one of two glass plates composing a liquid crystal cell, are described. The shorter periodical domain is controllable for the application of an electric field to the liquid crystal cell. The response time of the disappearance of the shorter periodical domain decreases with increasing the applied voltage. On the other hand, the response time of the domain formation is independent of the applied voltage. These response times agree quantitatively with those of the birefringence electrooptic effect. The domain disappearance by applying the voltage to the liquid crystal indicates the Freedericksz transition.

An interaction between an elastic wave and a liquid crystal is investigated from the view point of evaluation of the elastic properties of the liquid crystal. A periodical stripe domain pattern is induced by an interaction between the elastic wave and the nematic liquid crystal, the pattern is observed by a polarizing microscope. In the numerical analysis of elastic wave propagation in a nematic liquid crystal cell, the 0th mode depends on the liquid crystal properties, on the other hand the 1st mode is influenced predominantly by the properties of two sheets of glasses composing the cell. The 0th and 1st mode phase velocities are estimated from the periodic length of the stripe domain pattern. The 0th mode phase velocity in the nematic liquid crystal cell strongly depends on the cell layer thickness. The phase velocity obtained from the observed result is in good agreement with the numerical analysis result.

National Institute of Neuroscience, NationalCenter of Neurology and Psychiatry, 4-1-1 Ogawakawahigashi-cho, Kodaira, Tokyo 187-8502Little is known about the signal transduction pathways of TRK family receptors in neuroblastoma(NB) cells. In this study, an NB cell line, designated MP-N-TS, was established from an adrenaltumor taken from a 2-year-old boy. This cell line expressed both TRK-A and TRK-B receptors,which is rare in a single NB cell line. Therefore, the MP-N-TS cell line was used to determinewhether the signal transduction through these constitutive receptors is functional. Three neurotro-phins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), induced tyrosine phosphorylation of panTRK, and BDNF and NT-4/5 induced tyrosinephosphorylation of TRK-B. Tyrosine phosphorylation of panTRK and/or TRK-B by the neurotro-phins was inhibited in the presence of a tyrosine kinase inhibitor K252a. Tyrosine phosphorylationof Src homologous and collagen (Shc), extracellular signal-regulated kinase (ERK)-1 and ERK-2,and phospholipase C-γ1 (PLC-γ1) was increased by the three neurotrophins and the increase wasinhibited in the presence of K252a. Activation of Ras, detected as the GTP-bound form of Ras, wasinduced by the three neurotrophins. The neurotrophins did not modulate the expressions of TRK-A or TRK-B mRNA, but they did induce the expression of c-fos mRNA. Exogenous NGF inducedweak neurite outgrowth, whereas exogenous BDNF and NT-4/5 induced distinct neurite out-growth. Exogenous BDNF and NT-4/5 increased the number of viable cells, while NGF did not.Our results demonstrate that the signal transduction pathways through TRK-A and TRK-B inMP-N-TS cells are functional and similar, and the main downstream signaling pathways from thethree neurotrophins are mitogen-activated protein kinase (MAPK) cascades through Shc, activatedRas, ERK-1 and ERK-2, and the transduction pathway through PLC-γ1. Further, BDNF and NT-4/5 increased cell viability. The MP-N-TS cell line should be useful for clarifying the TRK-A andTRK-B signaling pathways responsible for the different prognoses in patients with NB.Key words: Signal transduction — Neuroblastoma — TRK-A — TRK-B — Neurotrophins

We describe an infant with cytomegalovirus (CMV) infection presenting as transient myeloproliferation resembling juvenile myelomonocytic leukemia (JMML). The patient fulfilled the international diagnostic criteria of JMML, including hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF). Viral studies using serologic assays and polymerase chain reaction (PCR) were positive for CMV. Clinical symptoms disappeared and laboratory values returned to normal without specific treatment within 1 year. Follow-up showing a decrease in viral titers suggested CMV infection as an etiologic factor for the development of myeloproliferative features. We conclude that the CMV infection transiently induced abnormal myelopoiesis in this infant.

Switching mechanism of thick cell of ferroelectric liquid crystals has been studied by means of light scattering measurement and polarizing microscope observation adopting stroboscopic technique. The transmitted light through the cell at the instant of polarity reversal of applied voltage has been diffracted by the formation of periodical stripe texture. This transient stripe texture has a tilt from the smectic layer. The period of the transient stripe texture is independent of temperature and depends on applied voltage. The oblique angle from smectic layer depends on applied voltage.

The microwave variable phase shifter of a coplanar waveguide using ferroelectric liquid crystal with float electrodes, which are used for applying a dc voltage to a liquid crystal layer, is discussed. We confirmed the performance of the phase shifter in the frequency range from 10 to 30 GHz and found that phase shift is proportional to the frequency of the microwave according to the theory. The measured phase shift increases with an increase in applied voltage. The response time of this phase shifter was less than 1 ms above 120 V and a very high speed variable phase shifter was achieved.

We have demonstrated the reorientation of cholesteric liquid crystal (CLC) molecules in a thick cell by acoustic streaming. In the thick cell, the initial CLC does not have a planar alignment but a focal conic state in spite of the surface being coated with a planar polyimide and rubbed unidirectionally. The acoustic streaming effect changes the CLC alignment from a focal conic state to a planar alignment. The alignment of the treated cell including its defects is improved by storing the cell at room temperature for several days. Although the focal conic cell shows a low transmittance and a broad stop band due to light scattering, the treated cell reduces scattering and has the sharp band edges in the stop band.

Nonlinear optical phenomena such as second harmonic generation (SHG) have been studied in various ferroelectric liquid crystals. SHG efficiency depends on the molecular structure of ferroelectric liquid crystal and can be controlled by applied voltage. Phase matching of SHG has been well realized in these ferroelectric liquid crystals. SHG in polymeric ferroelectric liquid crystals, ferroelectric liquid crystal-conducting polymer composites, thin ferroelectric liquid crystal films and liquid crystals which exhibit flexoelectric effect have also been discussed.

Aggregation states and transient light scattering in the chiral smectic C phase of a ferroelectric liquid crystalline polymer (FLCP) were studied. The smectic phase shows an interlayer spacing of 38-39.5 A, which is about 1.41 times the length of the side chain mesogenic group. The transient scattering mode was obtained by repeated voltage polarity reversal. A reversible transparent-opaque (light scattering) change was observed in the chiral smectic C state upon application of electric fields with low and high frequencies, respectiely. Both transparent and opaque states were maintained stably even when the electric field was turned off (bistable light swiching). A novel type of electro-optical effect based on light scattering was obtained for the FLCP in the chiral smectic C state.

Thin films prepared by mixing ferroelectric liquid crystal with conducting polymer whose main chains are composed of highly extended conjugated electron system exhibit novel ferroelectric and optical properties, which are strongly dependent on the combination of ferroelectric liquid crystal and conducting polymer and their concentration. Ferroelectric behavior appears in the system with low conducting polymer ratio. Dependence of dielectric constant and spontaneous polarization on the composite ratio has been explained by taking the microstructure of the composite films into consideration. Various electrooptical effects in these systems have also been found, which depends on the molecular structure of both ferroelectric liquid crystal and conducting polymer.

With a large number of children surviving cancer worldwide, numerous investigations have assessed psychological and social adjustment among childhood cancer survivors. According to these studies, it is unclear whether childhood cancer survivors successfully adjust to daily life after being discharged from hospital, especially for adolescent and young adult survivors who have unique needs and concerns. The primary aim of this study was to identify the factors underlying psychosocial difficulties faced by adolescent and young adult survivors in their day-to-day lives after being discharged from hospital.Semi-structured interviews were conducted. Twenty-five childhood cancer survivors were recruited from two regional cancer institutions in Japan. Content analysis was applied to the responses.Nineteen attributes were extracted and classified into four categories as follows: physical difficulties, interpersonal difficulties, behavioral difficulties, and uncertainty about the future. The attributes indicated by50% of the participants were "I am worried about not feeling well," "I have difficulty continuing treatment in daily life," "I have difficulty moving my body," "I have to be absent from school or work because of illness," and "I am left behind academically."This study identified important factors of psychosocial day-to-day difficulties. Clinically, these results suggest that it is important to watch for these signs and to provide early support to survivors so that their daily life and development are not hindered by the treatment and its side-effects, and to offer long-term support focusing on individual patient characteristics such as sex, age, and cancer history.

Excess treatment reduction including anthracyclines results in higher incidence of relapse in core binding factor acute myeloid leukemia in children

We here report a 2-year-old female with relapsed acute myeloid leukemia (AML) with MLL gene rearrangement in the bone marrow and central nervous system. The 3'-RACE (Rapid Amplification of cDNA Ends) method identified the MLLT10 gene as a fusion partner of the MLL gene. The patient was complicated with hemophagocytic lymphohistiocytosis (HLH) and invasive aspergillosis (IPA) after re-induction treatment with FLAG-IDA following etoposide, cytarabine, and mitoxantrone. Although treatment with systemic anti-fungal drugs was effective for IPA, HLH did not improve. We considered tumor-associated HLH to be initiated from leukemic stem cells (LSCs) in the bone marrow niche because reverse transcription-polymerase chain reaction (RT-PCR) analysis of a bone marrow biopsy sample was positive for MLL-MLLT10. Gemtuzumab ozogamicin and sorafenib had no major effect on acquiring complete remission, and the patient died of progressive AML with an exacerbation of HLH and aspergillosis. LSCs are known to be resistant to conventional chemotherapy due to their quiescence in the cell cycle. Novel therapeutic concepts are important to eradicate LSCs in order to cure AML patients.

Clear cell sarcoma (CCS) is a rare malignant tumor with a poor prognosis. In our previous study, the tumor disappeared under boron neutron capture therapy (BNCT) on subcutaneously-transplanted CCS-bearing animals. In the present study, the tumor disappeared under this therapy on model mice intramuscularly implanted with three different human CCS cells. BNCT led to the suppression of tumor-growth in each of the different model mice, suggesting its potentiality as an alternative to, or integrative option for, the treatment of CCS.

Clear cell sarcoma (CCS) is an aggressive soft tissue malignant tumor characterized by a unique t(12;22) translocation that leads to the expression of a chimeric EWS/ATF1 fusion gene. However, little is known about the mechanisms underlying the involvement of EWS/ATF1 in CCS development. In addition, the cellular origins of CCS have not been determined. Here, we generated EWS/ATF1-inducible mice and examined the effects of EWS/ATF1 expression in adult somatic cells. We found that forced expression of EWS/ATF1 resulted in the development of EWS/ATF1-dependent sarcomas in mice. The histology of EWS/ATF1-induced sarcomas resembled that of CCS, and EWS/ATF1-induced tumor cells expressed CCS markers, including S100, SOX10, and MITF. Lineage-tracing experiments indicated that neural crest-derived cells were subject to EWS/ATF1-driven transformation. EWS/ATF1 directly induced Fos in an ERK-independent manner. Treatment of human and EWS/ATF1-induced CCS tumor cells with FOS-targeted siRNA attenuated proliferation. These findings demonstrated that FOS mediates the growth of EWS/ATF1-associated sarcomas and suggest that FOS is a potential therapeutic target in human CCS.

Well-aligned thin films of polymeric ferroelectric liquid crystal have been prepared by means of a spin-coating method. Several types of electro-optical effects and the optical second-harmonic generation in these films have been measured. The characteristics of spin-coated polymeric ferroelectric liquid crystal film with a free surface have been discussed in comparison with those of conventional sandwich cells. The influences of the glass plates on the PFLC are also discussed.

The transient scattering mode (TSM) at the polarity reversal of applied field and the deformation of helicoidal structure (DHS) effect upon applying a stepwise field in polymeric ferroelectric liquid crystal have been studied. The response time of the TSM decreases with increasing applied field and increases with decreasing temperature. A stripe pattern parallel to the smectic layer has been observed at the instant of polarization reversal. This stripe pattern is similar to that of the helicoidal structure in the absence of field and has been maintained after removal of pulse field. A new type of bistable electrooptic effect has been demonstrated, in which the switching between the transparent state and the opaque state can be realized by application of pulse field.

This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishing. This article appeared in Sadahito Uto, Hiroshi Moritake, Masanori Ozaki, Kent Skarp, and Bertil Helgee, Journal of Applied Physics 79, 4444 (1996) and may be found at https://doi.org/10.1063/1.361754., Thin films of a chiral side‐chain polymer with a ferroelectric phase were deposited on a substrate by spin coating. Electro‐optic switching in the films were observed by applying an external field using in‐plane electrodes. Characteristics of the switching are presented, together with an analysis of the switching dynamics that takes into account the inhomogenous field distribution in the active area.

The electric field-induced second harmonic generation (SHG) in the cholesteric liquid crystal with small dielectric anisotropy has been studied. The SHG intensity is in proportion to the square of ...

The rotation of smectic layer in the antiferroelectric liquid crystals upon application of asymmetric voltage pulses has been observed. The influence of the cell configuration upon this layer rotation has been investigated. This layer rotation is not directly related with the interaction between liquid crystal molecules and the spacer at the liquid crystal-spacer interface. The rotation of smectic layer has been observed not only in a monodomain cell but also in a multidomain cell. This layer rotation has also been observed in ferroelectric liquid crystal as the same manner in antiferroelectric liquid crystals.