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Expression of CD56 has recently been introduced as one of the adverse prognostic factors in acute promyelocytic leukemia ( APL). However, the clinical significance of CD56 antigen in APL has not been well elucidated. We assessed the clinical significance of CD56 antigen in 239 APL patients prospectively treated with all- trans retinoic acid and chemotherapy according to the Japan Adult Leukemia Study Group APL97 protocol. All patients were prospectively treated by the Japan Adult Leukemia Study Group APL97 protocol. The median follow-up period was 8.5 years. Positive CD56 expression was found in 23 APL patients (9.6%). Expression of CD56 was significantly associated with lower platelet count ( P = 0.04), severe disseminated intravascular coagulation ( P = 0.04), and coexpression of CD2 ( P = 0.03), CD7 ( P = 0.04), CD34 ( P < 0.01) and/or human leukocyte antigen- DR ( P < 0.01). Complete remission rate and overall survival were not different between the two groups. However, cumulative incidence of relapse and event-free survival ( EFS) showed an inferior trend in CD56+ APL ( P = 0.08 and P = 0.08, respectively). Among patients with initial white blood cell counts of 3.0 × 109/L or more, EFS and cumulative incidence of relapse in CD56+ APL were significantly worse (30.8% vs 63.6%, P = 0.008, and 53.8% vs 28.9%, P = 0.03, respectively), and in multivariate analysis, CD56 expression was an unfavorable prognostic factor for EFS ( P = 0.04). In conclusion, for APL with higher initial white blood cell counts, CD56 expression should be regarded as an unfavorable prognostic factor. [ABSTRACT FROM AUTHOR]

For patients with relapsed acute promyelocytic leukemia ( APL), all -trans retinoic acid-based salvage regimens can achieve second complete remission ( CR2), but the optimal post-remission strategy for APL patients after CR2 remains unclear. Hematopoietic stem cell transplantation ( HSCT) during CR2 might be effective, but data on the role of HSCT for APL patients after CR2 are limited in Japan. We retrospectively analyzed outcomes for 57 relapsed APL patients who achieved CR2 in the JALSG APL97 study. Of those, six received autologous (auto)- HSCT, 21 received allogeneic (allo)- HSCT, and 30 received various regimens other than HSCT. The 5-year event-free survival ( EFS) rate, overall survival (OS) rate and cumulative incidence of relapse ( CIR) were 50.7%, 77.4% and 51.0% in the non- HSCT group, 41.7%, 83.3% and 58.3% in the auto- HSCT group and 71.1%, 76.2% and 9.8% in the allo- HSCT group, respectively. Both the EFS rate and CIR were significantly better in the allo- HSCT group than in other groups. Allo- HSCT appears effective in APL patients in CR2, with a low relapse rate beyond a relatively early transplantation-related mortality (19%). Among older patients (age ≥40 years), the 5-year OS was significantly better in the non- HSCT group than in the HSCT group (78.0% vs 40.5%; P = 0.04). Further prospective studies with larger patient numbers are required to confirm the impact of HSCT alone and in combination with arsenic trioxide on outcomes for patients with APL in CR2. [ABSTRACT FROM AUTHOR]

Summary: Intermittent fasting is one of the most effective dietary restriction regimens that extend life span in C. elegans and mammals. Fasting-stimulus responses are key to the longevity response; however, the mechanisms that sense and transduce the fasting stimulus remain largely unknown. Through a comprehensive transcriptome analysis in C. elegans, we find that along with the FOXO transcription factor DAF-16, AP-1 (JUN-1/FOS-1) plays a central role in fasting-induced transcriptional changes. KGB-1, one of the C. elegans JNKs, acts as an activator of AP-1 and is activated in response to fasting. KGB-1 and AP-1 are involved in intermittent fasting-induced longevity. Fasting-induced upregulation of the components of the SCF E3 ubiquitin ligase complex via AP-1 and DAF-16 enhances protein ubiquitination and reduces protein carbonylation. Our results thus identify a fasting-responsive KGB-1/AP-1 signaling pathway, which, together with DAF-16, causes transcriptional changes that mediate longevity, partly through regulating proteostasis. [Copyright &y& Elsevier]

Abstract: A method is proposed for controlling the grain boundary character distribution of high-temperature B2 phase in Ti–Ni–Fe alloys. The method utilizes the lattice correspondence between the deformation twins in B19′ martensite and the residual planar defects in the B2 parent phase. The optimal conditions for recrystallization and additional annealing of the tensile-deformed specimen with residual strain of about 20% were determined to be 873 K for 0.9 ks and 773 K for 3.6 ks, respectively. In the specimen annealed under these optimal conditions, over 90% of grain boundaries were coincidence boundaries with Σ ≤ 27. In particular, 33% of the grain boundaries were low-angle boundaries, that is, Σ1 boundaries. The atomic structures of the Σ9 coincidence grain boundaries and the Σ1 low-angle boundaries were observed by high-angle annular dark field scanning transmission electron microscopy. The atomic structure of these boundaries was explained well by theoretical predictions. [Copyright &y& Elsevier]

Studies focused on elderly acute promyelocytic leukemia ( APL) are relatively limited. To evaluate prognostic impact in elderly APL, we compared the long-term outcome of elderly APL patients (60-70 years) with younger patients (15-59 years) treated with all-trans retinoic acid combined with anthracycline and cytarabine in the Japan Adult Leukemia Study Group ( JALSG) APL97 study. Of 283 evaluable patients, 46 (16.3%) were elderly who had more frequent lower platelet ( P = 0.04), lower albumin ( P = 0.006) and performance status 3 ( P = 0.02), higher induction death rate due to differentiation syndrome ( P = 0.03), and non-relapse mortality ( NRM) during consolidation therapy ( P = 0.001). Overall survival was significantly inferior in elderly patients ( P = 0.005), but disease-free survival and cumulative incidence of relapse were not. Better therapeutic approaches should be considered to reduce NRM during induction and consolidation therapy in elderly APL. This study was registered at http://www.umin.ac.jp/ctrj/ under C000000206. [ABSTRACT FROM AUTHOR]

Deformation-induced martensite in type 304 stainless steel during micro-tension testing was characterized. The stress-strain behavior of uncharged and hydrogen-charged specimens revealed that hydrogen hastened the onset of hardening but decreased the strain-hardening rate, leading to premature plastic instability. In both specimens, a set of twin-related α′-martensite variants with Kurdjumov-Sachs relationships was prevalent. The Nishiyama-Wasserman relationship variant was also formed, but it was suppressed by hydrogen. This may be attributed to differences in the underlying deformation microstructure. [ABSTRACT FROM AUTHOR]

Microstructural evolution during tensile deformation in ternary Zr-Co-Ni alloys were investigated using transmission electron microscopy to clarify the mechanism of the enhancement of ductility observed in these alloys. In ZrCoNi alloy deformed at room temperature, lenticular martensite is observed in the B2 parent phase immediately after yielding, in addition to dislocations with the <100>-type Burgers vector. The orientation relationship between the B2 parent phase and B33 martensite is determined to be [001]//[100], (010)//(021), and (110)//(010). A midrib-like contrast is observed at the center of the lenticular martensite variant, and it is found to be a (021) twin. A trace analysis indicates that this contrast is nearly parallel to the {100}, which may correspond to the habit plane of the martensite. The martensite variants grow into the B2 parent phase along the {100} with increasing tensile loading, and then grid-shaped martensite variants are formed at the failure of the specimen. The martensite would be dominantly formed and grow in the regions where the stress concentration occurs during tensile deformation. It is likely that the plastic deformation mainly proceeds in the untransformed B2 parent phase because this martensite is harder than the B2 parent phase. Consequently, the authors conclude that the remarkable enhancement of ductility can be attributed to a transformation-induced plasticity associated with deformation-induced martensite. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to autosomal recessive congenital ichthyosis due to pathogenicity of transglutaminase 1 gene (TGM1) missense mutations. Topics discussed include similar levels of proteins found by immunofluorescence in mutant TGM1 and wild-type proteins, difference in enzymatic activity of proteins in cytoplasmic and membrane fractions, and as per immunoblotting protein levels stability was not affected by missense mutations.

The article presents a study that investigates synonymous mutation in Netherton syndrome (NS) in a Japanese male infant. Topics discussed include NS disorder observed to be caused by mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, two mutations detected from study of genomic DNA and examination of RNA obtained from the patient skin by Reverse transcriptase polymerase chain reaction (RT-PCR) from exon 4-9 region and study showing severe mutation in SPINK5.

Abstract: The crystallization behaviors and microstructure changes by heat treatments in the rapidly solidified Nb20Ti40Ni40 hydrogen permeation alloy have been investigated. There are two exothermic peaks at 872 and 914K in DSC heating curve. The first and second peaks correspond to the crystallization of B2-TiNi and bcc-Nb phases, respectively. The orientation relationship of these two phases is cube-on-cube relation. The specimens annealed from 773 to 923K are quite brittle, although those microstructures consist of fine equiaxed grains less than 50nm. With prolonged annealing above 948K the grain size is increased to about 150nm or more and the hardness is decreased around 250Hv, thus the ductility is recovered. These results suggest that the high temperature annealing is required for the application of the melt-spun ribbon to the hydrogen permeation membrane. [Copyright &y& Elsevier]

We performed a randomized, controlled study comparing the prophylactic effects of capsule forms of fluconazole (n = 110) and itraconazole (n = 108) in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) during and after chemotherapy. There were 4 cases with possible systemic fungal infection in the itraconazole group, and there were 8 possible and 3 probable cases in the fluconazole group. Adverse events did not significantly differ in the 2 groups. In patients with MDS or in the remission-induction phase of chemotherapy, the numbers of cases with probable or possible infections were lower in the itraconazole group than in the fluconazole group, whereas no difference was seen in patients with AML or in the consolidation phase of therapy. In patients with neutrophil counts of >0.1 x 10(9)/L lasting for more than 4 weeks, the frequency of infection in the fluconazole group (5 of 9 patients) was significantly higher than in the itraconazole group (0 of 7 patients; P = .03). Our results suggest that both drugs were well tolerated in patients with AML or MDS who received chemotherapy and that the efficacy of itraconazole for prophylaxis against systemic fungal disease is not inferior to that of fluconazole. [ABSTRACT FROM AUTHOR]

Microinflammation is a common major mechanism in the pathogenesis of diabetic vascular complications, including diabetic nephropathy. Macrophage scavenger receptor-A (SR-A) is a multifunctional receptor expressed on macrophages. This study aimed to determine the role of SR-A in diabetic nephropathy using SR-A-deficient (SR-A-/-) mice. Diabetes was induced in SR-A-/- and wild-type (SR-A+/+) mice by streptozotocin injection. Diabetic SR-A+/+ mice presented characteristic features of diabetic nephropathy: albuminuria, glomerular hypertrophy, mesangial matrix expansion, and overexpression of transforming growth factor-β at 6 months after induction of diabetes. These changes were markedly diminished in diabetic SR-A-/- mice, without differences in blood glucose and blood pressure levels. Interestingly, macrophage infiltration in the kidneys was dramatically decreased in diabetic SR-A-/- mice compared with diabetic SR-A+/+ mice. DNA micro-array revealed that proinflammatory genes were overexpressed in renal cortex of diabetic SR-A+/+ mice and suppressed in diabetic SR-A-/- mice. Moreover, anti-SR-A antibody blocked the attachment of monocytes to type IV collagen substratum but not to endothelial cells. Our results suggest that SR-A promotes macrophage migration into diabetic kidneys by accelerating the attachment to renal extracellular matrices. SR-A may be a key molecule for the inflammatory process in pathogenesis of diabetic nephropathy and a novel therapeutic target for diabetic vascular complications. Diabetes 56:363-372, 2007 [ABSTRACT FROM AUTHOR]

The authors previously reported the mRNA expression of Glutathione S-transferases theta (GSTT)-1, wild type (623 bp) and mutant (500 bp) in MDS patients. The deletion of 123 bp creates a sequence that is homologues to mammalian target of repamycin (mTOR). To analyse the function of mutant GSTT-1 gene, stable transformants for the mutant and wild-type GSTT-1 gene, respectively, were established. In this study, the expression of wild and mutant type GSTT-1 gene of those stable tramsformants and bone marrow cells from MDS patients by RT-PCR was observed in the presence or absence of rapamycin. In result, exposure of rapamycin led to the disappearance of just the mutant gene band. This phenomenon possibly indicates that rapamycin only attacked the mutant GSTT-1 expressing clone. [ABSTRACT FROM AUTHOR]

Background. 5-Fluorouracil remains a key drug in the treatment of colorectal cancer, and the development of a simple and effective test for selecting patients likely to benefit from postoperative adjuvant chemotherapy is an important objective. Aim of the Study. This study aimed to clarify the feasibility of measuring apoptotic cell rate (AI%) in tumor after short-term oral 5-fluorouracil administration prior to surgery with the objective of establishing a simpler method to test for sensitivity. Methods. Forty-five colorectal cancer patients were allocated to two groups, and 21 patients were given oral 5-FU for 3 d prior to surgery. The AI% in surgical specimen, detected by TUNEL staining, was compared in the 5-FU-loaded and control groups. The correlation of AI% with 5-FU metabolic enzyme mRNA levels in tumor was also evaluated. Results. The AI% was significantly higher in the tumor tissue of patients receiving 5-FU than in the control group ( p<0.0005). Although insignificant, thymidylate synthase mRNA level and orotate phosphoribosyl transferase mRNA demonstrated a weak positive correlation with AI%. Conclusions. The AI% measurement in tumor tissue following a 5-FU oral load for 3 d prior to surgery was feasible. It remains to be elucidated if this measurement as a new 5-FU sensitivity test reflects the prognosis with 5-FU-based postoperative adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Fractalkine (CX3CL1) and its receptor CX3CR1 play an important role in natural killer (NK) cell- and cytotoxic T cell-mediated endothelium damage. Here we describe the cytotoxicity of myelodysplastic syndrome (MDS)-derived T cell line, K2-MDS, through the fractalkine–CX3CR1 system. K2-MDS cells induced apoptosis against CD34+ cells from normal bone marrow (BM) in a direct cell contact manner. K2-MDS cells expressed perforin and granzyme B, but they lacked Fas ligand expression. A specific inhibitor for perforin, concanamycin A, blocked K2-MDS-dependent cytotoxicity. Furthermore, a CX3C-chemokine, fractalkine, was expressed in CD34+ cells, and its receptor, CX3CR1, was expressed on K2-MDS cells. The neutralizing monoclonal antibody (MoAb) for fractalkine and soluble fractalkine significantly inhibited K2-MDS-dependent cytotoxicity. K2-MDS cells also induced the cytotoxicity against human umbilical cord endothelial cells (HUVECs) expressing fractalkine. These data indicate that K2-MDS may be a perforin–granzyme-positive T cell line that exerts a cytotoxic effect on CD34+ cells mediated through the fractalkine–CX3CR1 system. [Copyright &y& Elsevier]

In our previous studies, sintered and heat-treated alloy steels (Fe−6Ni−0.5Mo−0.4C (mass%)) produced by a MIM process showed excellent mechanical properties of 2000 MPa tensile strength and 5% elongation. This was attributed to the solid solution strengthening and the mezzo-heterogenous microstruture, which consisted of martensite or retained austenite (Ni and Mo rich phases) surrounded by a network of tempered martensite. This study has been performed to clarify the effect of Mo on the mezzo-heterogeneous microstructure and the mechanical properties of MIM processed and sintered alloy steels (Fe−6Ni−0.4C) with varying Mo content (0.5–2 mass%). The tensile properties of the heat-treated steels with added 2 mass% Mo were lower than those of the steels with added 0.5 mass% Mo. The reduction in the tensile properties, particularly the appearance of large pores formed at the original location of Mo power through the transient liquid phase formation and the low hardness of the matrix, was due to the low sintered density. By using mechanically milled fine Ni and Mo powders, the heat-treated steel (Fe−6Ni−2Mo−0.4C) showed excellent properties, including tensile strength of 1800 MPa and ductility of 2.2% elongation. [ABSTRACT FROM AUTHOR]