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An isothermal method was applied to measure the thermal decomposition of reactive solids in a sensitive heat flux reaction calorimeter, C80. This technique experimentally clarified the decomposition mechanisms of unstable substances based on the shapes of the heat flow curves, from which autocatalysis, first-order reaction or pseudo-autocatalytic reaction could be recognized. Kinetic parameters were derived from the measured data. [ABSTRACT FROM AUTHOR]

Summary By targeted disruption of the MIF gene, we have established a mouse strain deficient in macrophage (Mφ) migration inhibitory factor (MIF). Despite previous reports indicating an essential role of MIF in endotoxaemia, an injection of lipopolysaccharide (LPS) into the MIF‐deficient mice (maintained under specific pathogen‐free conditions) caused shock. No significant difference was detected between the MIF‐deficient mutant and normal mice in susceptibility to LPS for endotoxaemia or tumour necrosis factor‐α (TNF‐α) formation upon LPS injection. Peritoneal Mφ from the two strains produced TNF‐α in response to LPS with similar dose responses. Dexamethasone suppressed the LPS‐induced TNF‐α response of Mφ, but no difference was detected between the Mφ from the two strains. These results suggest that endogenous MIF has no significant effect on the LPS‐induced TNF‐α production and no effect on suppression of the response by glucocorticoids. Thus, MIF is not crucial for LPS‐induced immune responses leading to shock. [ABSTRACT FROM AUTHOR]

An automatic pressure tracking adiabatic calorimeter (APTAC) has been developed to obtain the thermokinetic and vapor pressure data during runaway reactions. The heat onset temperature is important data for estimating the thermal hazardous materials. DTBP(di- tert-butyl peroxide)/toluene was chosen for evaluating the measurement values and the thermokinetic parameters. The relationships between the sample mass and the heat onset temperature in the addition to the maximum temperature were investigated to explain the heat of reaction measured by the APTAC. The apparatus properties and the reliability of the data obtained by the APTAC were examined on the basis of the experimental data. [ABSTRACT FROM AUTHOR]

The IGF2/ H19-imprinting control region ( ICR1) functions as an insulator to methylation-sensitive binding of CTCF protein, and regulates imprinted expression of IGF2 and H19 in a parental origin-specific manner. ICR1 methylation defects cause abnormal expression of imprinted genes, leading to Beckwith-Wiedemann syndrome ( BWS) or Silver-Russell syndrome ( SRS). Not only ICR1 microdeletions involving the CTCF-binding site, but also point mutations and a small deletion of the OCT-binding site have been shown to trigger methylation defects in BWS. Here, mutational analysis of ICR1 in 11 BWS and 12 SRS patients with ICR1 methylation defects revealed a novel de novo point mutation of the OCT-binding site on the maternal allele in one BWS patient. In BWS, all reported mutations and the small deletion of the OCT-binding site, including our case, have occurred within repeat A2. These findings indicate that the OCT-binding site is important for maintaining an unmethylated status of maternal ICR1 in early embryogenesis. [ABSTRACT FROM AUTHOR]

SF3B1 is a core component of the mRNA splicing machinery and frequently mutated in myeloid neoplasms with myelodysplasia, particularly in those characterized by the presence of increased ring sideroblasts. Deregulated RNA splicing is implicated in the pathogenesis of SF3B1-mutated neoplasms, but the exact mechanism by which the SF3B1 mutation is associated with myelodysplasia and the increased ring sideroblasts formation is still unknown. We investigated the functional role of SF3B1 in normal hematopoiesis utilizing Sf3b1 heterozygous-deficient mice. Sf3b1+/− mice had a significantly reduced number of hematopoietic stem cells (CD34−cKit+ScaI+Lin− cells or CD34−KSL cells) compared with Sf3b1+/+ mice, but hematopoiesis was grossly normal in Sf3b1+/− mice. When transplanted competitively with Sf3b1+/+ bone marrow cells, Sf3b1+/− stem cells showed compromised reconstitution capacity in lethally irradiated mice. There was no increase in the number of ring sideroblasts or evidence of myeloid dysplasia in Sf3b1+/− mice. These data suggest that SF3B1 plays an important role in the regulation of hematopoietic stem cells, whereas SF3B1 haploinsufficiency itself is not associated with the myelodysplastic syndrome phenotype with ring sideroblasts. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to evaluate the effects of long-term cryopreservation on the isolated human periodontal ligament cells (PDL) and pulp tissues. In the first part of study, 10 freshly extracted teeth were selected and divided into two groups. In the cryopreserved group, the teeth were frozen for 5years using a programmed freezer combined with a magnetic field, known as Cells Alive System “CAS”. As for the control group, freshly extracted teeth were used. In each group, extracted PDL tissues were cultured and gene expression and protein concentration of collagen type I, alkaline-phosphatase (ALP) and vascular endothelial growth factor (VEGF) was compared between the two groups. In the second part, pulp tissues were obtained from 10 mature and immature third molars which were freshly extracted or cryopreserved for three months. Expression of VEGF and nerve growth factor (NGF) mRNAs and the protein concentration in the supernatant were investigated. Results indicated that long-term cryopreservation with the use of CAS freezer cannot affect the growth rate and characteristics of PDL cells. There was no significant difference in VEGF expression and VEGF and NGF protein concentration of pulp cells derived from cryopreserved teeth with immature apex and control group with mature root formation. Finally, proper PDL regeneration and appropriate apexogenesis after transplanting magnetically cryopreserved immature tooth was clinically confirmed. These findings demonstrate that teeth banking with the use of magnetic field programmed freezer can be available for future autotransplantation as a treatment modality for replacing missing teeth. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to establish a long-term tooth cryopreservation method that can be used for tooth autotransplantation. Human periodontal ligament (PDL) cells were frozen in 10% dimethyl sulfoxide (Me2SO) using a programmed freezer with a magnetic field. Cells were cryopreserved for 7days at −150°C. Immediately after thawing, the number of surviving cells was counted and the cells were cultured; cultured cells were examined after 48h. Results indicated that a 0.01mT of a magnetic field, a 15-min hold-time, and a plunging temperature of −30°C led to the greatest survival rate of PDL cells. Based on these findings, whole teeth were cryopreserved under the same conditions for 1year. The organ culture revealed that the PDL cells of cryopreserved tooth with a magnetic field could proliferate as much as a fresh tooth, although the cells did not appear in the cryopreserved tooth without a magnetic field. Histological examination and the transmission electron microscopic image of cryopreserved tooth with a magnetic field did not show any destruction of cryopreserved cells. In contrast, severe cell damage was seen in cells frozen without a magnetic field. These results indicated that a magnetic field programmed freezer is available for tooth cryopreservation. [ABSTRACT FROM AUTHOR]

Recent advances in neuroblastoma (NB) research addressed that epigenetic alterations such as hypermethylation of promoter sequences, with consequent silencing of tumor-suppressor genes, can have significant roles in the tumorigenesis of NB. However, the exact role of epigenetic alterations, except for DNA hypermethylation, remains to be elucidated in NB research. In this paper, we clarified the direct binding of MYCN to Bmi1 promoter and upregulation of Bmi1 transcription by MYCN. Mutation introduction into an MYCN binding site in the Bmi1 promoter suggests that MYCN has more important roles in the transcription of Bmi1 than E2F-related Bmi1 regulation. A correlation between MYCN and polycomb protein Bmi1 expression was observed in primary NB tumors. Expression of Bmi1 resulted in the acceleration of proliferation and colony formation in NB cells. Bmi1-related inhibition of NB cell differentiation was confirmed by neurite extension assay and analysis of differentiation marker molecules. Intriguingly, the above-mentioned Bmi1-related regulation of the NB cell phenotype seems not to be mediated only by p14ARF/p16INK4a in NB cells. Expression profiling analysis using a tumor-specific cDNA microarray addressed the Bmi1-dependent repression of KIF1Bβ and TSLC1, which have important roles in predicting the prognosis of NB. Chromatin immunoprecipitation assay showed that KIF1Bβ and TSLC1 are direct targets of Bmi1 in NB cells. These findings suggest that MYCN induces Bmi1 expression, resulting in the repression of tumor suppressors through Polycomb group gene-mediated epigenetic chromosome modification. NB cell proliferation and differentiation seem to be partially dependent on the MYCN/Bmi1/tumor-suppressor pathways. [ABSTRACT FROM AUTHOR]

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR), which alleviates protein overload in the secretory pathway. Although the UPR is activated under diverse pathological conditions, its physiological role during development and in adulthood has not been fully elucidated. Binding immunoglobulin protein (BiP) is an ER chaperone, which is central to ER function. We produced knock-in mice expressing a mutant BiP lacking the retrieval sequence to cause a defect in ER function without completely eliminating BiP. In embryonic fibroblasts, the UPR compensated for mutation of BiP. However, neonates expressing mutant BiP suffered respiratory failure due to impaired secretion of pulmonary surfactant by alveolar type II epithelial cells. Expression of surfactant protein (SP)-C was reduced and the lamellar body was malformed, indicating that BiP plays a critical role in the biosynthesis of pulmonary surfactant. Because pulmonary surfactant requires extensive post-translational processing in the secretory pathway, these findings suggest that in secretory cells, such as alveolar type II cells, the UPR is essential for managing the normal physiological ER protein overload that occurs during development. Moreover, failure of this adaptive mechanism may increase pulmonary susceptibility to environmental insults, such as hypoxia and ischemia, ultimately leading to neonatal respiratory failure.Cell Death and Differentiation (2007) 14, 1475–1485; doi:10.1038/sj.cdd.4402151; published online 20 April 2007 [ABSTRACT FROM AUTHOR]

Differential screening-selected gene aberrative in neuroblastoma (Dan) protein is produced in small neurons of dorsal root ganglia. Thermal and mechanical allodynia and Fos expression in the spinal dorsal horn evoked by inflammation and neuropathic pain were investigated using Dan-deficient mice. Mice showed pain reactions induced by the introduction of complete Freund''s adjuvant (CFA) into their hind paw (inflammatory pain model) and after sciatic nerve ligation (neuropathic pain model). In the inflammatory pain model, thermal and mechanical pain thresholds in Dan-deficient mice were significantly higher than those of wild-type mice. The number of Fos-immunoreactive cells in the dorsal horn during the inflammatory period was significantly less in Dan-deficient mice. However, in the neuropathic pain model, no differences in thermal hypersensitivity, mechanical allodynia, or the number of Fos-immunoreactive cells in the dorsal horn were observed between the mice. These data suggest that Dan may be a neuromodulator in inflammatory pain. [Copyright &y& Elsevier]

Abstract: Our recent studies showed that a programmed freezer with a magnetic field (CAS freezer) is helpful in the survival of periodontal ligament (PDL) cells after cryopreservation. The theory is that a magnetic field can prevent the cluster from growing by causing it to vibrate. In this letter, we commented in detail on the influence of a magnetic field during cryopreservation. [Copyright &y& Elsevier]