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Photosystem II (PSII) functions mainly as a dimer to catalyze the light energy conversion and water oxidation reactions. However, monomeric PSII also exists and functions in vivo in some cases. The crystal structure of monomeric PSII has been solved at 3.6 Å resolution, but it is still not clear which factors contribute to the formation of the dimer. Here, we solved the structure of PSII monomer at a resolution of 2.78 Å using cryo-electron microscopy (cryo-EM). From our cryo-EM density map, we observed apparent differences in pigments and lipids in the monomer-monomer interface between the PSII monomer and dimer. One β-carotene and two sulfoquinovosyl diacylglycerol (SQDG) molecules are found in the monomer-monomer interface of the dimer structure but not in the present monomer structure, although some SQDG and other lipid molecules are found in the analogous region of the low-resolution crystal structure of the monomer, or cryo-EM structure of an apo-PSII monomer lacking the extrinsic proteins from Synechocystis sp. PCC 6803. In the current monomer structure, a large part of the PsbO subunit was also found to be disordered. These results indicate the importance of the β-carotene, SQDG and PsbO in formation of the PSII dimer. • We solved the structure of PSII monomer at a resolution of 2.78 Å using cryo-electron microscopy. • A β -carotene and one or two SQDGs located in the monomer-monomer interface contribute to the formation of PSII dimer. • PsbO may also be important for the formation of the dimer. • Some additional differences existed between the present monomer structure and the previous dimer structure. [ABSTRACT FROM AUTHOR]

Abstract: In the present study we evaluated the feasibility of unrelated cord blood transplantation (UCBT) in patients with severe aplastic anemia (SAA). The outcome of 31 SAA patients (median age 28; range: 0.9-72.3 years old) who received UCBT was analyzed. The cumulative incidences of the neutrophil and platelet recovery after UCBT were 54.8 and 72.2%, respectively (95% confidence interval [CI] = 36.0%-70.3% and 51.3%-85.3%, respectively). The cumulative incidences of grade ≥II acute and chronic graft-versus-host disease (aGVHD, cGVHD) were 17.1% (95% CI = 6.2%-32.8%) and 19.7% (95% CI = 6.2%-38.8%), respectively. Currently, 13 patients are alive, having survived for 33.7 months (median; range: 6-77 months) after UCBT. The probability of overall survival (OS) at 2 years was 41.1% (95% CI = 23.8%-57.7%). A conditioning regimen that included low-dose total body irradiation (TBI) (2-5 Gy), fludarabine, and cyclophosphamide resulted in a favorable OS (80%; 95% CI = 20.4%-96.9%). This result suggests that UCBT using the optimal conditioning regimen can be a salvage treatment for patients without a suitable bone marrow donor and warrants evaluation in further prospective studies. [Copyright &y& Elsevier]

Abstract: Amorphous carbon nitride (a–CN x ) coatings were deposited on Si3N4 disks by an ion beam assisted deposition system. The composition, structure and hardness of the a–CNx coatings were characterized by Auger electronic spectroscopy, Raman spectroscopy and nano-indentation tester, respectively. The influences of normal load and sliding speed on the friction coefficients and the specific wear rates for the a–CNx/Si3N4 tribo-pairs were investigated and analyzed synthetically by ball-on-disk tribometer. The worn surfaces were observed by optical microscope. The results showed that the a–CN x coatings contained 12 at.% nitrogen, and their structure was a mixture of sp2and sp3 bonds. The a–CN x coatings’ nanohardness was 29 GPa. The influence of sliding speed on the friction coefficients and the specific wear rate of the CN x coatings was more obvious than that of normal load. The friction coefficients and the specific wear rate of the CN x coatings decreased as the sliding speed increased. At a sliding speed higher than 0.1 m/s, the friction coefficients were less than 0.04. The specific wear rates of the a–CN x coatings were higher than those of Si3N4 balls at a sliding speed below 0.1 m/s, while the specific wear rates of the a–CN x coatings and the Si3N4 balls all fluctuated around a lower level of 10−8 mm3/Nm as the sliding speed increased beyond 0.2 m/s. To describe the wear behavior of a–CN x coatings sliding against Si3N4 balls in water with normal loads of 3–15 N and sliding speeds of 0.05–0.5 m/s, the wear-mechanism map for the a–CN x /Si3N4 tribo-pairs in water was developed. [Copyright &y& Elsevier]

To characterize childhood acute megakaryoblastic leukaemia (AMKL), we reviewed 45 children with AMKL diagnosed between 1986 and 2005 at Nagoya University Hospital and Japanese Red Cross Nagoya First Hospital. Twenty-four patients (53%) had AMKL associated with Down syndrome (DS-AMKL) and 21 (47%) had non-DS-AMKL. The median age of the DS-AMKL patients was 21 months (range, 8–38 months) and that of non-DS-AMKL patients was 15 months (range, 2–185 months). The morphology of blast cells was categorized into three groups according to the stage of megakaryocyte maturation. The blast cells were more immature in DS-AMKL than in non-DS-AMKL in terms of morphology and immunophenotyping. Cytogenetic abnormalities of leukaemic cells were classified into seven categories: normal karyotype including constitutional trisomy 21 in DS-AMKL; numerical abnormalities only; t(1;22)(p13;q13); 3q21q26 abnormalities; t(16;21)(p11;q22); −5/del(5q) and/or −7/del(7q); and other structural changes. The outcome of children with either DS-AMKL or non-DS-AMKL is excellent. The 10-year overall survival estimate was 79% [95% confidence interval (CI): 54–90] for DS-AMKL and 76% (95% CI: 58–91) for non-DS-AMKL ( P = 0·81) with a median follow-up of 78 months (range, 20–243 months). Our study shows the diverse heterogeneity of childhood AMKL and the need for subclassification according to cytogenetic and morphological features. [ABSTRACT FROM AUTHOR]

Abstract: Umbilical cord blood (UCB) transplantation is limited by the low number of hematopoietic stem cells in UCB units, which results in a low engraftment rate in transplant recipients. Here, we measured the total nucleated cell count and CD34+, CD3+, CD4+, CD8+, CD14+, and CD16+/56+ cell doses in each UCB unit and evaluated their influence on engraftment and other outcomes in 146 recipients. Multivariate analysis showed a significant association between a higher incidence of successful engraftment and a dose of CD34+ and CD8+ cells above the median (1.4 × 105 and 15.7 × 105 cells/kg, respectively). Engraftment occurred 4 days earlier in patients who received UCB with more than the median dose of CD34+ cells than those receiving UCB at or below the median. Stratification of the group according to CD34+ cell dose revealed a significant influence of the CD8+ cell dose on the time to achieve neutrophil engraftment in patients receiving a lower CD34+ cell dose, whereas there was no significant influence in the patients receiving a higher CD34+ cell dose. These results suggest that consideration of CD34+ and CD8+ cell doses in UCB units may improve the engraftment in recipients of UCB transplantation. [Copyright &y& Elsevier]

Abstract: Dry sliding of two bodies in contact generates a wide range of effects like friction, wear, heat and sound among others. The main interest of this study is in the frequency characteristics of the generated sound. In the past, frequency spectrum and sound pressure level with relation to surface topography (surface roughness in particular), have been studied mainly for concentrated contacts like stylus or hemispherical tip pin on a rough surface. Studies on flat–flat contacts were mainly focused on the topography of contacting surfaces and its relation to occurrence or non-occurrence of squeal (high pitch, high sound pressure level sound) in brake systems. The present study aims to clarify the effect of surface roughness on the frequency of non-squealing frictional sound generated in dry flat–flat sliding contact. Sound was generated by the dry contact in rubbing by hand of two rectangular cross-section stainless-steel plates having similar surface roughness. The roughness of the contacting surfaces varied in the range –12.4μm. The sound spectra had 5 peaks (P1, P2, P3, P4 and P5) in order of increasing frequency and it was found that the peak frequency was shifted when the roughness of the rubbed surfaces changed. The first peak P1 was most sensitive to change of surface roughness and it shifted from 3.0 to 4.5kHz when the maximum surface roughness changed from to . When the surface was relatively rough, this peak was close to the first bending natural frequency of the plate at 2.377kHz. [Copyright &y& Elsevier]

Abstract: The formation of an oil bridge between adhesive seeds was observed microscopically. The geometry of the oil bridge was affected by the shape of the adhesive seeds. The capillary force of the oil bridge was estimated from the image captured by the microscope. The average capillary force was 127μN, which was five times higher than the average gravity of the seeds. It was observed that several oil bridges formed between two seeds. These results indicated an adequate ability of the seeds to adhere. The capillary force of the oil bridge increased with surface oil content. The probability of formation of an oil bridge increased with surface oil content when the surface oil content was above 0.63%. The probability of formation of an oil bridge markedly increased when sucrose was added to the seeds. [Copyright &y& Elsevier]

Abstract: An iron oxide layer (mixture of Fe3O4 and FeO) was formed by water-vapor treatment on tool steel plates. Bearing steel cylinders were slid against the plates in PAO with and without 1% zinc dialkyldithiophosphate (ZDDP) at 80°C. The friction coefficient was below 0.06–0.08 with ZDDP, which is more than 20% lower than that without ZDDP and about a half of a steel/steel contact under the same condition. The formation of multi-layered tribofilm of 30–130nm on the iron oxide was identified by TEM. The bottom part of the tribofilm is a layer of 10–30nm that contains Zn, Fe, S, P, and O with a gradient composition, where distribution peaks of Zn and S were found by EDX. [Copyright &y& Elsevier]

The incidence of graft rejection was determined in 66 children with acquired aplastic anaemia (AA) following bone marrow transplantation (BMT) from a related donor. Eleven of 65 evaluable patients experienced either early or late rejection. Multivariate analysis identified previous immunosuppressive therapy with antithymocyte-globulin (ATG) and ciclosporin (CsA) as a risk factor for graft rejection (relative risk: 16·6, P = 0·001). Patients who received ATG and CsA had a significantly lower probability of failure-free survival than those who did not (69·7 ± 6·2% vs. 87·9 ± 8·0%, P = 0·044). These results suggest that BMT should be instituted immediately in children with severe AA who have human leucocyte antigen-identical siblings. [ABSTRACT FROM AUTHOR]

Abstract: Surface texturing has been recognized as an effective means to improve the tribological performances of sliding surfaces. Usually, generation additional hydrodynamic pressure to increase the load carrying capacity is regarded as the most significant effect of surface texture. In the case of silicon carbide sliding against identical material in water, the experimental results indicate that surface texture is also helpful to improve the running-in progress to smooth the contact surfaces, showing another reason to result in low friction. Based on the consideration of enhancing the generation of hydrodynamic pressure and improving running-in progress, a surface texture pattern, which was combined with large (circle, 350μm in diameter) and small (rectangular, 40μm in length) dimples, was designed to maximize the texture effect on the load carrying capacity of SiC surfaces sliding in water. The friction coefficient of such textured surface was evaluated and compared with that of untextured and those only with large or small dimples only. The friction reduction mechanisms of the patterns with different dimples in size are discussed. [Copyright &y& Elsevier]

The article presents a study which examined the effect of oil and sugar contents of seed on the surface of dehulled-roasted sesame seeds on adhesion of the seeds. The researchers compared the adhesive and nonadhesive dehulled-roasted sesame seeds. The results suggested that surface mono- and oligosaccharides were an important factor in adhesion of dehulled-roasted seeds, and high surface oil content of the seeds causes the formation of an oil bridge between seeds.

Posterior reversible encephalopathy has been reported in patients who receive immunosuppressants. Compared with radiologic studies, electroencephalographic (EEG) findings are not well described. We performed EEG serially in three children who suffered from posterior reversible encephalopathy associated with tacrolimus or cyclosporine. EEG showed continuous focal rhythmic activities in the acute period. EEG findings normalized after the clinical manifestations had disappeared. We conclude that EEG is useful for the diagnosis and follow-up of posterior reversible encephalopathy. [ABSTRACT FROM AUTHOR]

Abstract: Cytomegalovirus (CMV) loop-mediated isothermal amplification (LAMP) was performed on DNA extracted from CMV (AD-169)-, herpes simplex virus (HSV) 1 (KOS)-, HSV-2 (186)-, varicella-zoster virus (Oka-vaccine)-, human herpesvirus (HHV)-6 A (U1102)-, HHV-6 B (Z29)-, and HHV-7 (RK)-infected cells. Although amplified CMV demonstrated typical ladder patterns, no LAMP product was detected in reactions performed with other viral DNAs. The sensitivity of the CMV LAMP was 500 copies/tube, as determined by either agarose gel electrophoresis or turbidity assay. To determine whether CMV LAMP could be used for quantitative analysis of viral DNA, threshold times, defined as the time (in seconds) to reach the threshold level (0.1), were measured by amplification of serial dilutions of the plasmid DNA. The standard curve exhibited a correlation coefficient of 0.944, a slope of −208.1, and a y-intercept of 3261.4. Following these initial validation experiments, we analyzed 180 samples collected serially from 20 pediatric hematopoietic stem cell transplant recipients. Detection of CMV DNA in whole blood (WB) was tested by CMV LAMP and real-time polymerase chain reaction (PCR). When >500 copies/tube (>5000 copies/200μl of WB) was defined as positive for CMV infection, the sensitivity, specificity, positive predictive value, and negative predictive values of the CMV LAMP were 80.0, 98.9, 66.7, and 99.4%, respectively. [Copyright &y& Elsevier]

Abstract: Tomato fruit paste prepared by hot-or cold-break processing was extracted with water to obtain a water-soluble pectin (HP or CP) and a water-insoluble matter (HR or CR). HP yield was approximately twice that of CP, while those of the water-insoluble matters were similar. Comparing sugar compositions, HP (GalA-rich) was remarkably different from CP (neutral sugars-rich), although their water-insoluble matters were similar. This result indicates that the solubilizations of cell-wall-associated pectins in HB and CB were similar, but the release of GalA by endogenous pectin-degrading enzymes in CB was remarkable. Fractions separated by a DEAE–cellulose column from HP (HP3, HP4, HP5) were also rich in GalA, while those from CP (CP2, CP3, CP4) were all rich in neutral sugar. However, the ratios of individual sugars of CP fractions were very different. Unlike the neutral sugar-rich fractions, the GalA-rich ones treated with polygalacturonase were mostly degraded. In addition, the chemical structure of HP5 (homogalacturonan) and CP4 (rhamnogalacturonan) were compared after mild acid hydrolysis. [Copyright &y& Elsevier]

Abstract: Physical properties of water-soluble pectins (HP and CP) obtained from hot- and cold-break tomato pastes, respectively, and purified by anion-exchange chromatography were compared on the basis of their viscosities. The differences in viscosities between HP and CP solutions depended, not only on the average molecular mass, but also on the chemical structure. Neutral sugar-rich pectin, CP, was more flexible than galacturonic acid-rich pectin, HP. The three-dimensional structure of homogalacturonan was a hollow helix with ionic strength lower than 5 mM NaCl, which was built through hydrogen bonds between intramolecular free carboxyl groups. Such conformation was destroyed by ionic force (>5 mM NaCl). The effects of kinking structures on the physical properties of the rhamnogalacturonan were remarkable, as a consequence of (1→2) linkages of the rhamnosyl residues in the pectic backbone, and induced the molecular conformation of the pectin to sphere-like shape, which was unfavourable for Ca2+-gelling. [Copyright &y& Elsevier]

Abstract: The natural history of X-linked adrenoleukodystrophy (ALD) was investigated, using a nation-wide retrospective study based on a questionnaire survey. The data on 145 patients, including 46 patients with the childhood cerebral form, 39 with adrenomyeloneuropathy (AMN), 33 with the adult cerebral form, 14 with the adolescent form and 13 with the olivo-ponto-cerebellar (OPC) form, were analyzed. Initial symptoms of the childhood cerebral form were intellectual (n=16) and visual (n=11) disturbances, whereas those of AMN were gait (n=37) and sensory (n=3) disturbances; the adult cerebral form, psychic (n=19) and gait (n=11) disturbances; the adolescent form, visual n=5) and gait (n=4) disturbances; and the OPC form, gait (n=9) disturbance. Patients with onset under the age of 8 years progressed more rapidly than those over 8 years old. Visual, hearing, gait and swallowing disturbances progressed more slowly in the older group. About half of AMN patients showed cerebral involvement about 10 years after onset. Patients with the OPC form also showed a similar progression. A Kaplan–Meier plot clarified the characteristic pattern of progression of neurological symptoms in each phenotype. These finding will improve the understanding of the natural history of X-linked ALD and will provide a basis for the evaluation of specific treatment for X-linked ALD. [Copyright &y& Elsevier]

A 38-year-old woman was admitted with superior mesenteric vein (SMV) thrombosis, which was refractory to anticoagulation therapy. The plasma antithrombin activity was decreased and hardly compensated by concentrated antithrombin preparation due to high consumption rate. However, successful anticoagulation was achieved by administration of direct thrombin inhibitor, argatroban. Family studies of antithrombin activity revealed that she had type 1 congenital antithrombin deficiency. A novel heterozygous mutation in the gene for antithrombin (single nucleotide T insertion at 7916 and 7917, Glu 272 to stop in exon 4) was identified. Argatroban administration would be effective in the treatment of congenital antithrombin deficiency with SMV thrombosis. [ABSTRACT FROM AUTHOR]

Abstract: Active-head sliders with a unimorph piezoelectric actuator for flying height control were experimentally evaluated. It was found that the stroke of the actuator is 1.3 to 1.5nm/V without flying over the disk. The adjustment amount of flying height is about 1.4nm/V when the active-head slider is flying over the disk. It was found that flying height could be reduced and decrease from 24 to 10nm by applying 10V to the actuator under flying condition. Both the air pressure generated at the active-pad and the impact pressure due to the head/disk contact must be taken into account for precise control of flying height. [Copyright &y& Elsevier]

Abstract: A new experimental apparatus which can evaluate particle erosion at high temperature is proposed. This apparatus has the following characteristics:[•] Particles are accelerated by centrifugal force of a rotating nozzle. So, particle impingement velocity is easily adjusted by rotating speed of the nozzle. [•] Nine test pieces can be supplied for one test, and temperature of the test pieces is controlled independently. So, erosion data under various temperature conditions can be obtained in only one test. [•] A test piece is heated by a cartridge heater directly. So temperature of test pieces rise in short duration, and electric power required for erosion tests is lower than blast type high temperature erosion apparatuses. To confirm that the new apparatus can obtain similar erosion data to the data obtained by conventional apparatuses, some preliminary experiments have been performed. As a result, it was confirmed that the new centrifugal erosion apparatus can obtain similar erosion rates and velocity exponents to the data obtained by conventional erosion apparatuses. The erosion rates of steels containing various amount of Cr obtained by the new centrifugal erosion apparatus showed similar tendency to the data obtained by Levy and Man [A.V. Levy, Y.-F. Man, Erosion–corrosion mechanisms and rates in Fe–Cr steels, Wear 131 (1989) 51] using a blast type erosion apparatus. [Copyright &y& Elsevier]

We established a real-time PCR method that can simultaneously detect 10 different fusion transcripts (major, minor and micro BCR/ABL, AML1/MTG8, PML/RARα, CBFβ/MYH11, TEL/AMLI, E2A/PBX1, MLL/AF4, and MLUAF9) together with Wilms' tumor gene (WT1) transcripts. This screening method allowed the processing of six specimens concomitantly and required only one working day from RNA extraction to final results. Fifty-seven bone marrow (BM) samples from patients with acute leukemia were retrospectively screened for the presence of fusion and WT1 transcripts without knowledge of the cytogenetic data, and the fusion transcripts were detected in 20 of 57 samples (35.1%). The concordance between the present method and cytogenetic analysis was examined in 38 samples in which the cytogenetic data were available. In 12 of 38 samples, the PCR results agreed with the cytogenetic data, whereas in 4 of the remaining 26 samples, the translocations were detected by real-time PCR alone because of the insufficient number of metaphases obtained and presumably the submicroscopic or masked translocations. The WT1 levels ranged from 400 to 690,000 copies/µg RNA in BM from leukemia patients, whereas 0-470 copies/µg RNA were found in BM cells from BMT donors. This real-time PCR method enables rapid and efficient characterization of acute leukemia in addition to subsequent evaluation of minimal residual diseases. [ABSTRACT FROM AUTHOR]

Summary. Human leucocyte antigen (HLA)-Cw-reactive cytotoxic T lymphocytes (CTL) were generated from cord blood (CB) lymphocytes of two cases used for cord blood stem cell transplantation (CBSCT). In both cases, the CTL were cytotoxic against the patient's leukaemic cells, as well as the patient's Epstein–Barr virus (EBV)-lymphoblastoid cell line (EBV-LCL) and phytohaemagglutinin blasts, and the cytotoxicity was blocked by anti-HLA-class I monoclonal antibodies. In the first case, the CTL recognized Cw 3 (Cw 9 and Cw 10)-positive EBV-LCL, while in the second case, the CTL recognized Cw1 and/or Cw7. These cases suggest that CB T cells may be competent enough for generating CTL to induce a graft-versus-leukaemia effect and/or graft-versus-host disease in patients with CBSCT and that the mismatching of Cw antigens between patient and CB may be related to the outcome of CBSCT. [ABSTRACT FROM AUTHOR]

Human herpesvirus 6 (HHV-6) infection was studied in 82 bone marrow transplant (BMT) re-cipients (72 allogeneic, 10 autologous). All recipients and 30 donors were seropositive for HHV-6 antibody at the time of bone marrow transplantation. Thirty-one recipients (37.8%) had HHV-6 viremia 2--4 weeks after transplantation. The incidence of HHV-6 viremia was significantly high-er among allogeneic BMT recipients than in autologous BMT recipients (P .011). Therefore, the following analyses of allogeneic BMT recipients were carried out (n 72). Geometric mean antibody titers (log10) were significantly higher in recipients without viremia than in those with viremia (1.84 ^ 0.39 vs. 1.61 ^ 0.42; P .022). Logistic regression analysis demonstrated that leukemia or lymphoma is an independent risk factor (P .031) for HHV-6 viremia. Rash occur-ring within 1 month after transplantation was observed in 17 (54.8%) of 31 recipients with HHV-6 viremia but in only 8 (19.5%) of 41 recipients without HHV-6 viremia (P .001). [ABSTRACT FROM AUTHOR]

α-Tocopherol was reacted with 1-palmitoyl-2-[(9Z,11E)-(S)-13-hydroperoxy-9,11-octadecadienoyl]-3-sn-phosphatidylcholine (13-PLPC-OOH) in the presence of a lipid-soluble iron chelate, Fe(III) acetylacetonate, in methanol at 37 °C. The reaction product was isolated and identified as a mixture of 1-palmitoyl-2-[(10E)-(12S,13S)-9-(8a-dioxy-α-tocopherone)-12,13-epoxy-10-octadecenoyl]-3-sn-phosphatidylcholine and 1-palmitoyl-2-[(9Z)-(12S,13S)-11-(8a-dioxy-α-tocopherone)-12,13-epoxy-9-octadecenoyl]-3-sn-phosphatidylcholine (TOO-epoxyPLPC), in which the 12,13-epoxyperoxyl radicals derived from 13-PLPC-OOH attacked the 8a-position of the α-tocopheroxyl radical. The iron and ascorbate-catalyzed reaction of 13-PLPC-OOH with α-tocopherol in phosphatidylcholine (PC) liposomes was assessed by measuring the reaction products of α-tocopherol. When 13-PLPC-OOH and α-tocopherol were added in saturated dimyristoyl-PC liposomes, the products were TOO-epoxyPLPC, α-tocopherylquinone, and epoxy-α-tocopherylquinones. In 1-palmitoyl-2-linoleoyl-PC (PLPC) liposomes, α-tocopherol could react with both the 13-PLPC-OOH derived 12,13-epoxyperoxyl radicals and the PLPC-derived peroxyl radicals and formed the addition products together with α-tocopherylquinone and epoxy-α-tocopherylquinones. Therefore, the iron-catalyzed decomposition of phospholipid hydroperoxides primarily produces epoxyperoxyl radicals, which react with the 8a-carbon centered radical of α-tocopherol in liposomal systems. [Copyright &y& Elsevier]

Summary Umbilical cord blood (CB) has been widely used instead of bone marrow (BM) and peripheral blood (PB) for stem cell transplantation (SCT). However, problems of sustained immunodeficiency after CB transplantation remain to be resolved. To elucidate the mechanism of immunodeficiency, we compared the characteristics of B cells differentiated in vitro from CD34+ cells of CB with those of PB. Purified CD34+ cells from CB and PB were cultured on murine stroma cell-line MS-5 with stem cell factor and granulocyte colony-stimulating factor for 6 weeks. The B-cell precursors (pre-B cells) that differentiated in this culture system, were analysed as to their immunoglobulin heavy chain (IgH) variable region gene repertoire and the expression of B-cell differentiation-related genes. CD10+ CD19+ pre-B cells were differentiated from both PB and CB. Although the usages of IgH gene segments in pre-B cells differentiated from CB and PB were similar, the N region was significantly shorter in CB-derived than PB-derived cells. Productive rearrangements were significantly fewer in cells of CB than PB in the third week. Among a number of B-cell differentiation-related genes, the terminal deoxynucleotidyl transferase (TdT) gene was not expressed in CB-derived cells during the culture. These results indicated that immature features of pre-B cells from CB, such as lack of TdT expression, and a short N region and few productive rearrangements in the IgH gene, might cause the delay in mature B-cell production. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV)-related lymphoproliferative disorder (LPD) is a serious complication of haematopoietic stem cell transplantation (HSCT). To clarify the frequency, natural course and risk factors for LPD, we prospectively monitored 38 allogeneic (allo)-HSCT patients, focusing on the use of anti-thymocyte globulin (ATG). We used a recently developed real-time polymerase chain reaction assay to monitor EBV genome load. The subjects consisted of 19 patients given ATG for conditioning and 19 patients not given ATG. Of the 19 patients given ATG, 47·4% (nine patients) had a significant increase in EBV genome load (102·5 copies/µg DNA). Of these nine patients, two developed LPD. Therefore, 10·5% of the patients receiving allo-HSCT with ATG developed LPD. In contrast, none of the 19 patients without ATG had a significantly increased EBV load. The increases in viral load were observed in the second or third month after HSCT. We found that the peak viral loads of LPD patients were > 104·0 copies/µg DNA. On the other hand, the viral loads of most patients with no symptoms were < 102·5 copies/µg DNA. In conclusion, routine monitoring of EBV load during the second and third months after transplantation may benefit patients undergoing HSCT with ATG. We propose that an EBV load > 102·5 copies/µg DNA is the reactivation of EBV, and that an EBV load > 104·0 copies/µg DNA is indicative of developing LPD. [ABSTRACT FROM AUTHOR]

We report a favourable outcome in 15 patients with severe aplastic anaemia (SAA) who were < 20 years of age and who underwent bone marrow transplantation (BMT) from a human leucocyte antigen (HLA)-matched unrelated donor. All patients were non-responders to intensive immunosuppressive therapy (IST) and were multiply transfused. The conditioning regimen consisted of cyclophosphamide (60 mg/kg/d, on d -4 and -3), anti-thymocyte globulin (2·5 mg/kg/d, on d -5 to -2) and total body irradiation (2·5 Gy × 2/d, on d -2 and -1). Patients received cyclosporine and methotrexate for prophylaxis of graft-versus-host disease (GVHD), except for the last four who received tacrolimus instead of cyclosporine. Donor/recipient pairs were identical for HLA class I and II antigens by serological typing, but four pairs were found to have a mismatch at the HLA-A, -B or -DRB1 locus by high-resolution typing. All patients achieved rapid engraftment and are alive at 2–86 months after transplantation (median follow-up, 51 months). Moderate to severe acute GVHD occurred in 5 out of 15 patients (33%); only one patient developed extensive chronic GVHD. Considering our encouraging results, unrelated donor transplantation for SAA is recommended as a salvage therapy in non-responders to IST. [ABSTRACT FROM AUTHOR]

A total of 100 children under the age of 17 years with acquired aplastic anaemia (AA) were initially treated with immunosuppressive therapy (IST) (n = 63) or bone marrow transplantation (BMT) (n = 37) from an HLA-matched family donor. The projected 10-year survival rates were 55 ± 8% and 97 ± 3% respectively (P = 0·004). Because the IST group included 11 non-responders who were salvaged by BMT from an HLA-matched unrelated donor, we compared failure-free survival (FFS) between the groups. The probability of FFS at 10 years was 97 ± 3% for the BMT group, compared with 40 ± 8% for the IST group (P = 0·0001). Seven patients evolved to myelodysplastic syndrome (MDS) with monosomy 7 and the estimated cumulative incidence of MDS 10 years after diagnosis was 20 ± 7% in the IST group. We compared the outcome of children treated with IST during the two consecutive periods of 1983–91 (group A, n = 40) and 1991–8 (group B, n = 23) to assess the impact of combined therapy with anti-thymocyte globulin and cyclosporin. The probability of FFS at 7 years follow-up was the same in the two groups (50 ± 8% vs. 40 ± 15%, P = 0·40). We recommend BMT as first-line therapy in paediatric severe AA patients with an HLA-matched family donor. Alternative donor BMT is recommended as salvage therapy in patients who relapse or do not respond to initial IST. [ABSTRACT FROM AUTHOR]

We report a method of femtosecond crystallography for solving radiation damage-free crystal structures of large proteins at sub-angstrom spatial resolution, using a large single crystal and the femtosecond pulses of an X-ray free-electron laser (XFEL). We demonstrated the performance of the method by determining a 1.9-Å radiation damage-free structure of bovine cytochrome c oxidase, a large (420-kDa), highly radiation-sensitive membrane protein. [ABSTRACT FROM AUTHOR]

Iron-stress-induced-A proteins (IsiAs) are expressed in cyanobacteria under iron-deficient conditions, and surround photosystem I (PSI) trimer with a ring formation. A cyanobacterium Anabaena sp. PCC 7120 has four isiA genes; however, it is unknown how the IsiAs are associated with PSI. Here we report on molecular organizations and function of the IsiAs in this cyanobacterium. A deletion mutant of the isiA1 gene was constructed, and the four types of thylakoids were prepared from the wild-type (WT) and Δ isiA1 cells under iron-replete (+Fe) and iron-deficient (−Fe) conditions. Immunoblotting analysis exhibits a clear expression of the IsiA1 in the WT−Fe. The PSI-IsiA1 supercomplex is found in the WT−Fe, and excitation-energy transfer from IsiA1 to PSI is verified by time-resolved fluorescence analyses. Instead of the IsiA1, both IsiA2 and IsiA3 are bound to PSI monomer in the Δ isiA1 −Fe. These findings provide insights into multiple-expression system of the IsiA family in this cyanobacterium. • We construct a deletion mutant of isiA1 in a cyanobacterium Anabaena sp. PCC 7120. • IsiA1s are associated with PSI in the WT−Fe. • Both IsiA2s and IsiA3s are bound to PSI in the Δ isiA1 −Fe. • Excitation-energy transfer is observed from IsiAs to PSI. • Anabaena has the preferential expression system of IsiA1 > IsiA2 and IsiA3. [ABSTRACT FROM AUTHOR]

• AS2819899 is a newly synthesized PI3Kδ selective inhibitor. • AS2819899 suppressed B cell activation in vitro. • AS2819899 suppressed antibody production in vivo mouse models. • AS2819899 prevented worsening of kidney function in lupus-prone mouse model. • We identified useful pharmacodynamics marker of PI3Kδ inhibitor. Phosphoinositide 3-kinases generate lipid-based second messengers that control an array of intracellular signaling pathways. In particular, phosphoinositide 3-kinases delta (PI3Kδ) is expressed primarily in hematopoietic cells and plays an important role in B-cell development and function. B cells play a critical role in autoimmune diseases by producing autoantibodies. Studies have therefore increasingly focused on PI3Kδ as a therapeutic target for the treatment of inflammatory and autoimmune diseases. One such autoimmune disease is systemic lupus erythematosus (SLE). SLE is a chronic systemic autoimmune disease with repeated recurrence and remission, and autoantibodies play an important role in its pathogenesis. Here, we examined the pharmacological profile of the novel PI3Kδ selective inhibitor AS2819899 and investigated its therapeutic potential against SLE in a NZB/W F1 mouse lupus-like nephritis model, a widely-used SLE mouse model. AS2819899 prevented B and T cell activation in vitro, and inhibited antibody production in a T-cell independent de novo antibody production mouse model. In the spontaneous NZB/W F1 mouse model, AS2819899 treatment significantly reduced anti-dsDNA antibody titers and improved kidney dysfunction. Further, AS2819899 inhibited the memory recall reaction in a T-cell dependent antibody production mouse model, suggesting that AS2819899 can potentially maintain remission of SLE. Moreover, we identified a pharmacodynamics marker for AS2819899 that may be useful in clinical studies. These results indicate that AS2819899 may be an attractive therapeutic candidate for SLE, including the maintenance of remission. [ABSTRACT FROM AUTHOR]

The article focuses on a method developed to treat children with acute myeloid leukemia (AML) which consists of administering low-dose gemtuzumab ozogamicin (GO) in combination chemotherapy followed by stem cell transplantation. It adds that GO, a monoclonal anti-CD33 antibody conjugated with calicheamicin, is a promising agent for patients with AML who are resistant to conventional chemotherapy. It also talks about GO not being recommended as part of combination chemotherapy.

• Three-year OS and DFS rates of KMT2A -rearrageged pediatric AML was 52.1% and 46.7%. • Complete remission at HSCT was the most significant prognostic factor. • Supportive therapy and considering donor source might improve treatment outcomes. Pediatric acute myeloid leukemia (AML) with KMT2A rearrangement is detected in 15–20% of all pediatric AML patients and is associated with adverse outcomes even after allogeneic hematopoietic stem cell transplantation (HSCT). To investigate outcomes and prognostic factors, we investigated 90 pediatric AML patients with KMT2A rearrangement after allogeneic HSCT. We retrospectively analyzed Japanese registration data for patients who had received allogeneic HSCT between 1988 and 2011. Median age was 3 years (range, 0–15 years), and no gender difference was evident. Median observation period was 119 months. The 3-year overall survival (OS) rate of KMT2A -rearranged AML was 52.1% (95% confidence interval (CI), 42.4–64%, n = 90), and the 3-year disease-free survival (DFS) rate was 46.7% (95%CI, 36.8–58.2%). The 3-year DFS of KMT2A -rearranged AML was not significantly poorer than that of other AML (P = 0.09), and no significant difference was also seen in 3-year OS rate (P = 0.21). Multivariate analysis showed disease status (complete remission) at HSCT was associated with better outcomes. A significant difference in treatment-related mortality (TRM) was apparent between HSCT from a HLA full-matched related donor and that from a haploidentical donor (P = 0.001). HSCT is a curative option for pediatric AML with KMT2A rearrangement. Pretransplant status was the most significant prognostic indicator for relapse and survival. Enhancing supportive therapy to reduce TRM will further improve treatment outcomes of KMT2A -rearranged pediatric AML. [ABSTRACT FROM AUTHOR]

Presents a study which developed a magnetic disc active-head slider with a piezoelectric actuator for controlling flying height. Simulation methods and results; Slider design and fabrication; Experimental methods and results.

The development of myelodysplastic syndrome/acute myeloblastic leukaemia (MDS/AML) has been reported in patients with aplastic anaemia (AA) after administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Similarly, patients with severe congenital neutropenia (SCN) have an increased risk of developing MDS/AML after treatment with rhG-CSF. Point mutations in the G-CSF receptor gene are found in about 20% of SCN patients who are predisposed to MDS/AML. We investigated the occurrence of mutations in the G-CSF receptor in eight patients with AA who developed MDS/AML. No mutations were detected around the cytoplasmic domain of the gene in our patients, indicating that the mechanisms of clonal evolution to MDS/AML in patients with AA might be different from those with SCN. [ABSTRACT FROM AUTHOR]

Adult T‐cell leukemia‐lymphoma (ATL) is a peripheral T‐cell lymphoma caused by human T‐cell lymphotropic virus type I. Previous retrospective studies suggested the presence of graft‐vs‐ATL (GV‐ATL) effects associated with acute graft‐vs‐host disease (GVHD), which suggests that intentional induction of acute GVHD to facilitate the efficacy of GV‐ATL effects might reduce the risk of relapse and contribute to improved survival after allogeneic hematopoietic stem cell transplantation. However, it is impractical to conduct a prospective study to assess the benefit of intentional induction of acute GVHD. In a simulation analysis using a Markov model, we assessed the impact on overall survival (OS) of changing the probability of overall acute GVHD and severe acute GVHD. When the probability of grade III‐IV acute GVHD changed from 0% to 100%, the expected 2‐year OS rate changed from 57.0% to 21.8% (48.2% of baseline at 2 years). When the probability of all grades of acute GVHD changed from 0% to 100%, the expected 2‐year OS rate changed from 48.2% to 49.5%. In conclusion, increasing the probability of overall acute GVHD was beneficial only when the proportion of grade III‐IV acute GVHD was lower than that in the original data. Based on the simulation results, preventive management of grade III‐IV acute GVHD is mandatory to achieve the clinical benefit associated with grade I‐II GVHD. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have provided more options in the treatment of lung cancer. However, ICIs can cause several unfavorable reactions generally referred to as immune-related adverse effects. Case presentation: In this report, we present the case of a 52-year-old woman with successful regression of pleomorphic carcinoma of the lung following nivolumab therapy. She developed purpura fulminans (PF) ultimately resulting in amputation of both lower extremities. Blood tests revealed thrombocytopenia with increased serum soluble IL-2 receptor, ferritin, and triglyceride levels suggesting hemophagocytic lymphohistiocytosis (HLH). In addition, serum A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 activity was decreased, suggesting thrombotic thrombocytopenic purpura (TTP). Further detailed analysis revealed severe hypercytokinemia including increased levels of IL-1β, IL-6, IL-10, TNFα, IFNγ, and G-CSF. Conclusion: The severe systemic inflammatory reaction and impaired peripheral circulation in this patient was attributed to excessive immunological effect induced by nivolumab resulting in cytokine release syndrome (CRS). This is the first report of a patient with multiple pathological conditions including HLH, TTP-like condition, and PF presumably arising from ICI-induced CRS. Further accumulating thoroughly investigated cases would lead to better understanding of the disease and development of reliable cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Unfortunately, in the original publication of this article, the copyright line was incorrectly published in PDF as "© The Author(s) 2017" instead of "©The Author(s) 2017 This article is an open access publication" and also the CC-BY description was not included. The description should be as follows. [ABSTRACT FROM AUTHOR]

The cellular properties of leukemia stem cells (LSCs) are achieved at least through Class I and Class II mutations that generate signals for enhanced proliferation and impaired differentiation, respectively. Here we show that in t(8;21) acute myelogenous leukemia (AML), hematopoietic stem cells (HSCs) transform into LSCs via definitively-ordered acquisition of Class II ( AML1/ETO ) and then Class I ( c-KIT mutant) abnormalities. Six t(8;21) AML patients with c-KIT mutants maintaining > 3 years of complete remission were analyzed. At diagnosis, all single LSCs had both AML1/ETO and c-KIT mutations. However, in remission, 16 out of 1,728 CD34 + CD38 − HSCs and 89 out of 7,187 single HSC-derived myeloerythroid colonies from these patients had AML1/ETO , whose breakpoints were identical to those found in LSCs. These cells had wild-type c-KIT , which expressed AML1/ETO at a low level, and could differentiate into mature blood cells, suggesting that they may be the persistent preleukemic stem cells. Microarray analysis suggested that mutated c-KIT signaling provides LSCs with enhanced survival and proliferation. Thus, in t(8;21) AML, the acquisition of AML1/ETO is not sufficient, and the subsequent upregulation of AML1/ETO and the additional c-KIT mutant signaling are critical steps for transformation into LSCs. [ABSTRACT FROM AUTHOR]