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The impact of oral administration of mechanically fibrillated cellulose nanofibers (fib-CNF), a commonly used nanofiber, on toxicity and health remains unclear, despite reports of the safety and beneficial effects of chitin-based nanofibers. Thus, evaluating the oral toxicity of fib-CNF in accordance with OECD Test Guideline 407 (TG407) is essential. This study aimed to assess the safety of orally administered fib-CNF through an acute toxicity study in rats, following the OECD TG407 guidelines for 4 weeks. CNF "BiNFi-s" FMa-10005, derived from mechanically fibrillated pulp cellulose, was administered via gavage to male and female Crl:CD(SD) rats at doses of 50, 150, 500, and 1000 mg/kg/day for 28 days, with a control group receiving water for injection. The study evaluated the toxic effects of repeated administration, and the rats were monitored for an additional 14 days post-administration to assess recovery from any toxic effects. The results showed no mortality in either sex during the administration period, and no toxicological effects related to the test substance were observed in various assessments, including general condition and behavioral function observations, urinalysis, hematological examination, blood biochemical examination, necropsy findings, organ weights, and histopathological examination. Notably, only female rats treated with 1000 mg/kg/day of CNF exhibited a consistent reduction in body weight during the 14-day recovery period after the end of treatment. They also showed a slight decrease in pituitary and liver weights. However, hematological and blood biochemical tests did not reveal significant differences, suggesting a potential weight-suppressive effect of CNF ingestion. [ABSTRACT FROM AUTHOR]

Strain energy density functions are used in CAE analysis of hyperelastic materials such as rubber and elastomers. This function can originally be obtained only by experiments using biaxial deformation, but the difficulty of such experiments has made it almost impossible to put the function to practical use. Furthermore, it has been unclear how to introduce the strain energy density function necessary for CAE analysis from the results of biaxial deformation experiments on rubber. In this study, parameters of the Ogden and Mooney–Rivlin approximations of the strain energy density function were derived from the results of biaxial deformation experiments on silicone rubber, and their validity was verified. These results showed that it is best to determine the coefficients of the approximate equations for the strain energy density function after 10 cycles of repeated elongation of rubber in an equal biaxial deformation state, followed by equal biaxial elongation, uniaxial constrained biaxial elongation, and uniaxial elongation to obtain these three stress–strain curves. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we describe the implementation and evaluation of a noncontact type of propagation system, which is an essential element of the communication function of people and robots, which is indispensable for the reality of our proposed community‐centric systems. We implemented this algorithm on JavaVM, which is the most portable, realized real‐time performance and got the possibility of deploying the algorithm on robot system. In addition, in preparation for future expansion, we got the guideline of the improvement to the communication UI by bottleneck analysis. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 1 (DM1) is an RNA gain-of-function disorder in which abnormally expanded CTG repeats of DMPK sequestrate a splicing trans-factor MBNL1 and upregulate another splicing trans-factor CUGBP1. To identify a diverse array of aberrantly spliced genes, we performed the exon array analysis of DM1 muscles. We analyzed 72 exons by RT-PCR and found that 27 were aberrantly spliced, whereas 45 were not. Among these, 25 were novel and especially splicing aberrations of LDB3 exon 4 and TTN exon 45 were unique to DM1. Retrospective analysis revealed that four parameters efficiently detect aberrantly spliced exons: (i) the signal intensity is high; (ii) the ratio of probe sets with reliable signal intensities (that is, detection above background P-value=0.000) is high within a gene; (iii) the splice index (SI) is high; and (iv) SI is deviated from SIs of the other exons that can be estimated by calculating the deviation value (DV). Application of the four parameters gave rise to a sensitivity of 77.8% and a specificity of 95.6% in our data set. We propose that calculation of DV, which is unique to our analysis, is of particular importance in analyzing the exon array data. [ABSTRACT FROM AUTHOR]

Summary: To elucidate the clinical significance of imaging modalities for detection of stitch abscess after surgery in patients with oral squamous cell carcinoma (SCC). In 137 patients with oral SCC suspected of having lymph node metastases, local recurrence of tumor, or stitch abscess after surgery, the characteristic imaging findings related to lymph node metastases, local recurrence of tumor, and stitch abscess on ultrasonography (US), computed tomography (CT), magnetic resonance (MR), and 18fluorodeoxyglucose (18FDG)–positron emission tomography (PET) images were identified and analyzed. In all six patients with stitch abscess, characteristic findings were demonstrated on US, different from those of metastatic lymph nodes and local recurrence on CT, MRI, and 18FDG–PET images. Our results suggest that ultrasonography may be a very useful tool for diagnosis of postoperative stitch abscess and may help improve the quality of life of oral SCC patients. [ABSTRACT FROM AUTHOR]

Biphenotypic acute leukemia (BAL) is a relatively rare subtype of acute leukemia characterized by the presence of both myeloid and lymphoid cell surface antigens. We have now screened for transforming genes in BAL blasts with the use of the focus formation assay with a retroviral cDNA expression library constructed from malignant blasts isolated from a BAL patient. Some of the retroviral inserts recovered from transformed foci were found to encode wild-type purinergic receptor P2Y, G protein coupled, 8 (P2RY8). The oncogenic potential of P2RY8 was confirmed with the in vitro focus formation assay as well as with an in vivo tumorigenicity assay in nude mice. A variety of luciferase-based reporter assays revealed that P2RY8 increased both the trans-activation activities of CREB and Elk-1 as well as the transcriptional activities of the serum response element and enhancer-promoter fragments of the c-Fos and c-Myc genes. Quantitation of P2RY8 mRNA in CD34+ cells of bone marrow showed that P2RY8 expression is frequently increased in leukemia patients, especially in those with refractory disease. Our data thus reveal an abundant expression of P2RY8 in leukemic cells and its unexpected role in the pathogenesis of acute leukemia. [ABSTRACT FROM AUTHOR]

Abstract: Pancreatic ductal carcinoma (PDC) remains one of the most intractable human malignancies. To obtain insight into the molecular pathogenesis of PDC, we constructed a retroviral cDNA expression library with total RNA isolated from the PDC cell line MiaPaCa-2. Screening of this library with the use of a focus formation assay with NIH 3T3 mouse fibroblasts resulted in the identification of 13 independent genes with transforming activity. One of the cDNAs thus identified encodes an NH2-terminally truncated form of the lymphotoxin-β receptor (LTBR). The transforming activity of this short-type LTBR in 3T3 cells was confirmed by both an in vitro assay of cell growth in soft agar and an in vivo assay of tumorigenicity in nude mice. The full-length (wild-type) LTBR protein was also found to manifest similar transforming activity. These observations suggest that LTBR, which belongs to the tumor necrosis factor receptor superfamily of proteins, may contribute to human carcinogenesis. [Copyright &y& Elsevier]

DNA microarray analysis has been applied to identify molecular markers of human hematological malignancies. However, the relatively low correlation between the abundance of a given mRNA and that of the encoded protein makes it important to characterize the protein profile directly, or 'proteome,' of malignant cells in addition to the 'transcriptome.' To identify proteins specifically expressed in leukemias, here we isolated AC133+ hematopoietic stem cell-like fractions from the bone marrow of 13 individuals with various leukemic disorders, and compared their protein profiles by two-dimensional electrophoresis. A total of 11 differentially expressed protein spots corresponding to 10 independent proteins were detected, and peptide fingerprinting combined with mass spectrometry of these proteins revealed them to include NuMA (nuclear protein that associates with the mitotic apparatus), heat shock proteins, and redox regulators. The abundance of NuMA in the leukemic blasts was significantly related to the presence of complex karyotype anomalies. Conditional expression of NuMA in a mouse myeloid cell line resulted in the induction of aneuploidy, cell cycle arrest in G2-M?phases, and apoptosis. These results demonstrate the potential of proteome analysis with background-matched cell fractions obtained from fresh clinical specimens to provide insight into the mechanism of human leukemogenesis.Oncogene (2003) 22, 5720-5728. doi:10.1038/sj.onc.1206855 [ABSTRACT FROM AUTHOR]

Although large exons cannot be readily recognized by the spliceosome, many are evolutionarily conserved and constitutively spliced for inclusion in the processed transcript. Furthermore, whether large exons may be enriched in a certain subset of proteins, or mediate specific functions, has remained unclear. Here, we identify a set of nearly 3,000 SRSF3‐dependent large constitutive exons (S3‐LCEs) in human and mouse cells. These exons are enriched for cytidine‐rich sequence motifs, which bind and recruit the splicing factors hnRNP K and SRSF3. We find that hnRNP K suppresses S3‐LCE splicing, an effect that is mitigated by SRSF3 to thus achieve constitutive splicing of S3‐LCEs. S3‐LCEs are enriched in genes for components of transcription machineries, including mediator and BAF complexes, and frequently contain intrinsically disordered regions (IDRs). In a subset of analyzed S3‐LCE‐containing transcription factors, SRSF3 depletion leads to deletion of the IDRs due to S3‐LCE exon skipping, thereby disrupting phase‐separated assemblies of these factors. Cytidine enrichment in large exons introduces proline/serine codon bias in intrinsically disordered regions and appears to have been evolutionarily acquired in vertebrates. We propose that layered splicing regulation by hnRNP K and SRSF3 ensures proper phase‐separation of these S3‐LCE‐containing transcription factors in vertebrates. Synopsis: Although their recognition poses a challenge to spliceosomes, large exons are often conserved and spliced. Here, this is linked to their nucleotide composition, which drives splicing factor recruitment and endows encoded proteins with specific properties. Analysis of ˜ 3,000 SRSF3‐dependent large exons reveals enrichment for cytidine nucleotidesCytidine enrichment favors recruitment of splicing factors SRSF3 and hnRNP KInclusion of cytidine‐rich large exons encoding serine/proline‐rich intrinsically disordered regions (IDRs) is found in vertebrate transcription factorsLoss of IDR inclusion upon SRSF3 depletion‐induced exon‐skipping disrupts transcription factor phase separation. [ABSTRACT FROM AUTHOR]

Background: High-Mobility Group Box 1 (HMGB1) and HMGB2 are chromatin-associated proteins that belong to the HMG protein family, and are involved in the regulation of DNA transcription during cell differentiation, proliferation and regeneration in various tissues. However, the role of HMGB2 in ovarian folliculogenesis is largely unknown. Methods: We investigated the functional role of HMGB1 and HMGB2 in ovarian folliculogenesis and fertilization using C57BL/6 wild type (WT) and HMGB2-knockout (KO) mice. Ovarian tissues were obtained from WT and HMGB2-KO mice at postnatal days 0, 3, 7, and 2, 6 months of age, then performed immunohistochemistry, qPCR and Western blotting analyses. Oocyte fertilization capability was examined by natural breeding and in vitro fertilization experiments. Results: In HMGB2-KO mice, ovary weight was decreased due to reduced numbers of oocytes and follicles. Natural breeding and in vitro fertilization results indicated that HMGB2-KO mice are subfertile, but not sterile. Immunohistochemistry showed that oocytes expressed HMGB2, but not HMGB1, in neonatal and adult WT ovaries. Interestingly, in HMGB2-KO ovaries, a compensatory increase in HMGB1 was found in oocyte nuclei of neonatal and 2-month-old mice; however, this was lost at 6 months of age. Conclusions: The depletion of HMGB2 led to alterations in ovarian morphology and function, suggesting that HMGB2 plays an essential role in ovarian development, folliculogenesis and fertilization. [ABSTRACT FROM AUTHOR]

We succeeded in hydrogen evolution using InGaN photocatalysts grown on conductive Ga2O3 substrates. These photocatalysts exhibited a conversion efficiency of 0.8% from incident light energy to stored H2 chemical energy. Their quantum efficiency was determined to be more than 1% at 404 nm by incident photon-to-current conversion efficiency (IPCE) measurement. We found that the wavelength response of the InGaN structure can be extended to the visible region. These results indicate that the conductive Ga2O3 substrates are suitable for the photocatalysts. [ABSTRACT FROM AUTHOR]

Abstract: We developed an analysis program for predicting the movement of magnetic particles in flow and magnetic fields. This magnetic particle movement simulation was applied to a capturing process in a flow cell and a magnetic separation process in a small vessel of an in-vitro diagnostic system. The distributions of captured magnetic particles on a wall were calculated and compared with experimentally obtained distributions. The calculations involved evaluating not only the drag, pressure gradient, gravity, and magnetic force in a flow field but also the friction force between the particle and the wall, and the calculated particle distributions were in good agreement with the experimental distributions. Friction force was simply modeled as static and kinetic friction forces. The coefficients of friction were determined by comparing the calculated and measured results. This simulation method for solving multiphysics problems is very effective at predicting the movements of magnetic particles and is an excellent tool for studying the design and application of devices. [Copyright &y& Elsevier]

High-mobility group box 2 (HMGB2) is a chromatin-associated protein that is an important regulator of gene transcription, recombination, and repair processes. The functional importance of HMGB2 has been reported in various organs, including the testis, heart, and cartilage. However, its role in the ovary is largely unknown. In this study, ovary tissues from wild-type (WT) and HMGB2-knock-out (KO) mice were examined by histopathological staining and immunohistochemistry. The ovary size and weight were significantly lower in HMGB2-KO mice than in age-matched WT littermates. Histopathological analysis revealed ovarian atrophy and progressive fibrosis in 10-month-old HMGB2-KO mouse ovaries. Compared to age-matched WT mice, the numbers of oocytes and developing follicles were significantly decreased at 2 months of age and were completely depleted at 10 months of age in HMGB2-KO mice. Immunohistochemistry revealed the expression of HMGB2 in the granulosa cells of developing follicles, oocytes, some corpora lutea, and stromal cells. Importantly, HMGB2-positive cells were co-localized with estrogen receptor beta (ERβ), but not ERα. Estrogen response element-binding activity was demonstrated by southwestern histochemistry, and it was decreased in HMGB2-KO mouse ovaries. Cell proliferation activity was also decreased in HMGB2-KO mouse ovaries in parallel with the decreased folliculogenesis. These results indicated that the depletion of HMGB2 induced ovarian atrophy that was characterized by a decreased ovarian size and weight, progressive fibrosis, as well as decreased oocytes and folliculogenesis. In conclusion, we demonstrated the crucial role of HMGB2 in mouse ovarian folliculogenesis through ERβ expression. [ABSTRACT FROM AUTHOR]

Background: Using in vivo mouse models, the mechanisms of CD4+ T cell help have been intensively investigated. However, a mechanistic analysis of human CD4+ T cell help is largely lacking. Our goal was to elucidate the mechanisms of human CD4+ T cell help of CD8+ T cell proliferation using a novel in vitro model . Methods/Principal Findings: We developed a genetically engineered novel human cell-based artificial APC, aAPC/mOKT3, which expresses a membranous form of the anti-CD3 monoclonal antibody OKT3 as well as other immune accessory molecules. Without requiring the addition of allogeneic feeder cells, aAPC/mOKT3 enabled the expansion of both peripheral and tumor-infiltrating T cells, regardless of HLA-restriction. Stimulation with aAPC/mOKT3 did not expand Foxp3+ regulatory T cells, and expanded tumor infiltrating lymphocytes predominantly secreted Th1-type cytokines, interferon-γ and IL-2. In this aAPC-based system, the presence of autologous CD4+ T cells was associated with significantly improved CD8+ T cell expansion in vitro. The CD4+ T cell derived cytokines IL-2 and IL-21 were necessary but not sufficient for this effect. However, CD4+ T cell help of CD8+ T cell proliferation was partially recapitulated by both adding IL-2/IL-21 and by upregulation of IL- 21 receptor on CD8+ T cells. Conclusions: We have developed an in vitro model that advances our understanding of the immunobiology of human CD4+ T cell help of CD8+ T cells. Our data suggests that human CD4+ T cell help can be leveraged to expand CD8+ T cells in vitro. [ABSTRACT FROM AUTHOR]

The EML4 (echinoderm microtubule-associated protein-like 4)–ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non–small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. Here, we report the discovery of two secondary mutations within the kinase domain of EML4-ALK in tumor cells isolated from a patient during the relapse phase of treatment with an ALK inhibitor. Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors. (Funded by the Ministry of Health, Labor, and Welfare of Japan, and others.) [ABSTRACT FROM AUTHOR]

Epigenetic alterations are implicated in the development of cardiac hypertrophy and heart failure, but little is known of which epigenetic changes in which regions of the genome play such a role. We now show that trimethylation of histone H3 on lysine-4 (K4TM) or lysine-9 (K9TM) is markedly affected in cardiomyocytes in association with the development of heart failure in a rat disease model. High-throughput pyrosequencing performed with ChIP products for K4TM or K9TM prepared from human left ventricular tissue with retained or damaged function also revealed that protein-coding genes located in the vicinity of K4TM marks differ between functional and disabled myocytes, yet both sets of genes encode proteins that function in the same signal transduction pathways for cardiac function, indicative of differential K4TM marking during the development of heart failure. However, K9TM mark-profile was less dependent on the disease status compared to that of K4TM. Our data collectively reveal global epigenetic changes in cardiac myocytes associated with heart failure. [ABSTRACT FROM AUTHOR]

Although acetylation-deacetylation of histones contributes to regulation of gene expression, few methods have been available to determine the whole-genome histone acetylation profile in specific cells or tissues. We have now developed a genome-wide screening method, differential chromatin scanning (DCS), to isolate genome fragments embedded in histones subject to differential acetylation. This DCS screening was applied to a human gastric cancer cell line incubated with or without an inhibitor of histone deacetylase (HDAC) activity, resulting in the rapid identification of more than 250 genome fragments. Interestingly, a number of cancer-related genes were revealed to be the targets of HDAC in the cancer cells, including those for tumour protein 73 and cell division cycle 34. Such differential acetylation of histone was also shown to be linked to the regulation of transcriptional activity of the corresponding genes. Among the isolated genome fragments, 94% (32/34) of them were confirmed to be bound to differentially acetylated histones, and the genes corresponding to 78% (7/9) of them exhibited differential transcriptional activity consistent with the level of histone acetylation. With its high fidelity, the DCS method should open a possibility to rapidly compare the genome-wide histone acetylation profiles and to provide novel insights into molecular carcinogenesis. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is a clonal disorder of haematopoietic stem cells. Despite the high incidence of MDS in the elderly, effective treatment of individuals in its advanced stages is problematic. DNA microarray analysis is a potentially informative approach to the development of new treatments for MDS. However, a simple comparison of ‘transcriptomes’ of bone marrow mononuclear cells among individuals at distinct stages of MDS would result in the identification of genes whose expression differences only reflect differences in the proportion of MDS blasts within bone marrow. Such a ‘population shift’ effect has now been avoided by purification of haematopoietic stem-like cells that are positive for the cell surface marker AC133 from the bone marrow of healthy volunteers and 30 patients at various stages of MDS. Microarray analysis with the AC133+ cells from these individuals resulted in the identification of sets of genes with expression that was specific to either indolent or advanced stages of MDS. The former group of genes included that for PIASy, which catalyses protein modification with the ubiquitin-like molecule SUMO. Induction of PIASy expression in a mouse myeloid cell line induced apoptosis. A loss of PIASy expression may therefore contribute directly to the growth of MDS blasts and stage progression. [ABSTRACT FROM AUTHOR]

C-type lectin receptors (CLRs), pattern recognition receptors (PRRs) with a characteristic carbohydrate recognition domain (CRD) in the extracellular portion, mediate crucial cellular functions upon recognition of glycosylated pathogens and self-glycoproteins. CLEC4A is the only classical CLR that possesses an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM), which possibly transduces negative signals. However, how CLEC4A exerts cellular inhibition remains unclear. Here, we report that the self-interaction of CLEC4A through the CRD is required for the ITIM-mediated suppressive function in conventional dendritic cells (cDCs). Human type 2 cDCs (cDC2) and monocytes display a higher expression of CLEC4A than cDC1 and plasmacytoid DCs (pDCs) as well as B cells. The extracellular portion of CLEC4A specifically binds to a murine cDC cell line expressing CLEC4A, while its extracellular portion lacking the N -glycosylation site or the EPS motif within the CRD reduces their association. Furthermore, the deletion of the EPS motif within the CRD or ITIM in CLEC4A almost completely impairs its suppressive effect on the activation of the murine cDC cell line, whereas the absence of the N -glycosylation site within the CRD exhibits partial inhibition on their activation. On the other hand, antagonistic monoclonal antibody (mAb) to CLEC4A, which inhibits the self-interaction of CLEC4A and its downstream signaling in murine transfectants, enhances the activation of monocytes and monocyte-derived immature DCs upon stimulation with a Toll-like receptor (TLR) ligand. Thus, our findings suggest a pivotal role of the CRD in self-interaction of CLEC4A to elicit the ITIM-mediated inhibitory signal for the control of the function of cDCs. [ABSTRACT FROM AUTHOR]

The integrin αE known as CD103 binds integrin β7 to form the complete heterodimeric integrin molecule αEβ7. CD103 is mainly expressed by lymphocytes within epithelial tissues of intestine, lung, and skin as well as subsets of mucosal and dermal conventional dendritic cells (cDCs). CD103 has been originally implicated in the attachment of lymphocytes to epithelium in the gut and skin through the interaction with E-cadherin expressed on intestinal epithelial cells, keratinocytes, and Langerhans cells (LCs). However, an impact of CD103 on the cutaneous immune responses and the development of inflammatory skin diseases remains elusive. Here, we report that CD103 regulates the development of psoriasiform dermatitis through the control of the function of cDCs. Deficiency in CD103 exacerbates psoriasiform dermatitis, accompanied by excessive epidermal hyperplasia and infiltration of inflammatory leukocytes. Furthermore, deficiency in CD103 not only accelerates the production of proinflammatory cytokines in psoriatic lesions but also promotes the generation of lymphocytes producing interleukin (IL)-17 in the skin-draining peripheral lymph nodes (PLNs). Under the deficiency in CD103, cDCs localized in PLNs enhance cytokine production following activation. Thus, our findings reveal a pivotal role for CD103 in the control of the function of cDCs to regulate cutaneous inflammation in psoriasiform dermatitis. [ABSTRACT FROM AUTHOR]

In multinodular lesions or tumors with mixed benign and malignant components, malignant elements may be undetectable using fine‐needle aspiration biopsy/cytology in preoperative pathological diagnosis of some cases, because of sampling error. [ABSTRACT FROM AUTHOR]

Abstract We had previously reported that in addition to p53 inactivation, overexpression of the DNA sensor protein—absent in melanoma 2 (AIM2)—contributes to tumorigenesis of oral squamous cell carcinoma (OSCC). Given that AIM2 is highly expressed in the OSCC tumors from patients with metastasis, we investigated whether AIM2 expression contributes to the progression of OSCC metastasis. In in vitro assays using OSCC cell lines, the high migration and invasion capacity of OSCC cells were dependent on the increased expression of AIM2, resulting in enhanced epithelial-mesenchymal transition (EMT), with EMT-related gene expression. Moreover, the in vivo short-term metastasis assay using orthotopic implantation into immunodeficient mice demonstrated that OSCC cells with high levels of AIM2 expression exhibited enhanced tumor growth in the tongue, resulting in decreased survival of the mice. Further, the cells overexpressing AIM2 dominantly invaded into the tumor lymphatic vessels, unlike OSCC cells with low AIM2 expression. Thus, the high expression of AIM2 in OSCC enhances progression of tumor growth. Highlights • AIM2 is highly expressed in primary tumors from OSCC patients with metastasis. • High expression of AIM2 enhances the invasion and migration ability of OSCC. • High expression of AIM2 induces EMT in OSCC. • High expression of AIM2 enhances lymphatic invasion in mouse tongue tumors. [ABSTRACT FROM AUTHOR]

Objective A new mammalian tachykinin peptide encoded in a TAC4 gene was identified and designated as hemokinin-1 (HK-1). A representative of the tachykinin peptide family is substance P (SP), and the function of SP has been well characterized as a pain transmitter or modulator, while it is possible that HK-1 is involved in pruriceptive processing, but, as yet, the distribution of HK-1 peptide in the trigeminal sensory system is still unknown. Thus, the aim of the present study was to elucidate the distribution of HK-1, while comparing the expression of SP, in the trigeminal ganglion and trigeminal sensory nuclear complex. Design The trigeminal ganglion and the brain stem of male SD rats were used in the immunohistochemical study. Since the amino acid sequence in the carboxyl-terminal regions of HK-1 and SP is common, polyclonal antibodies of HK-1 and SP derived from 6 amino acids consisting of amino-terminal regions of these peptides were produced in guinea pig and rabbit, respectively. The immunohistochemical staining of HK-1 and SP was conducted using frozen sections of the trigeminal ganglion and brain stem in rats. Results Immunohistochemical studies revealed the expression of HK-1 in small- and medium-sized trigeminal ganglion neurons, in the paratrigeminal nucleus, and in lamina I of the trigeminal nucleus caudalis, while there was no immunoreactivity of HK-1 in the trigeminal nucleus principalis, trigeminal nucleus oralis, and trigeminal nucleus interpolaris. Conclusion These findings indicate that HK-1 is a target molecule for treatment of itch in the orofaicial regions. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Although Mohs paste can control bleeding, exudates, and odors from tumors, there have been no reports of the combination of Mohs paste with other treatments, such as chemotherapy, in oral cancer. Here, we report the combination of Mohs paste and chemotherapy for a case of metastatic oral cancer to the precordium skin and bilateral axillary lymph nodes. The tumors almost completely disappeared after the treatment. Combination therapy of Mohs paste and chemotherapy appears to have a better antitumor effect than Mohs paste alone. [ABSTRACT FROM AUTHOR]

Members of the RAS superfamily of small guanosine triphosphatases (GTPases) transition between GDP-bound, inactive and GTP-bound, active states and thereby function as binary switches in the regulation of various cellular activities. Whereas HRAS, NRAS, and KRAS frequently acquire transforming missense mutations in human cancer, little is known of the oncogenic roles of other small GTPases, including Ras-related C3 botulinum toxin substrate (RAC) proteins. We show that the human sarcoma cell line HT1080 harbors both NRAS(Q61K) and RAC1(N92I) mutant proteins. Whereas both of these mutants were able to transform fibroblasts, knockdown experiments indicated that RAC1(N92I) may be the essential growth driver for this cell line. Screening for RAC1, RAC2, or RAC3 mutations in cell lines and public databases identified several missense mutations for RAC1 and RAC2, with some of the mutant proteins, including RAC1(P29S), RAC1(C157Y), RAC2(P29L), and RAC2(P29Q), being found to be activated and transforming. P29S, N92I, and C157Y mutants of RAC1 were shown to exist preferentially in the GTP-bound state as a result of a rapid transition from the GDP-bound state, rather than as a result of a reduced intrinsic GTPase activity. Activating mutations of RAC GTPases were thus found in a wide variety of human cancers at a low frequency; however, given their marked transforming ability, the mutant proteins are potential targets for the development of new therapeutic agents. [ABSTRACT FROM AUTHOR]

The scirrhous subtype of gastric cancer is a highly infiltrative tumor with a poor outcome. To identify a transforming gene in this intractable disorder, we constructed a retroviral complementary DNA (cDNA) expression library from a cell line (OCUM-1) of scirrhous gastric cancer. A focus formation assay with the library and mouse 3T3 fibroblasts led to the discovery of a transforming cDNA, encoding for MAP2K1 with a glutamine-to-proline substitution at amino acid position 56. Interestingly, treatment with a MAP2K1-specific inhibitor clearly induced cell death of OCUM-1 but not of other two cells lines of scirrhous gastric cancer that do not carry MAP2K1 mutations, revealing the essential role of MAP2K1(Q56P) in the transformation mechanism of OCUM-1 cells. By using a next-generation sequencer, we further conducted deep sequencing of the MAP2K1 cDNA among 171 human cancer specimens or cell lines, resulting in the identification of one known (D67N) and four novel (R47Q, R49L, I204T and P306H) mutations within MAP2K1. The latter four changes were further shown to confer transforming potential to MAP2K1. In our experiments, a total of six (3.5%) activating mutations in MAP2K1 were thus identified among 172 of specimens or cell lines for human epithelial tumors. Given the addiction of cancer cells to the elevated MAP2K1 activity for proliferation, human cancers with such MAP2K1 mutations are suitable targets for the treatment with MAP2K1 inhibitors. [ABSTRACT FROM PUBLISHER]

In the present case of a 9-year-old girl with prominent swelling in the mental and facial regions after trauma, repeated magnetic resonance (MR) examinations were performed to evaluate areas of incision, because the swelling became worse and more prominent despite intravenous antibiotic treatment. However, there was no evidence of respiratory tract impingement or deformation, including obliteration, on MR imaging. Therefore, surgical treatment involving an incision because of facial region swelling was cancelled, and the intravenous antibiotic therapy was continued. To prevent misdiagnosis and over-treatment of young children with inflammation of the oral and maxillofacial regions, dentists, including pediatric dentists, should be aware of the clinical usefulness of MR examinations. In particular, MR examinations are non-invasive for young children, because there is no X-ray exposure, and they can be used repetitively. At the same time, the present case demonstrated that it is very difficult to understand and predict changes in the inflammation process associated with children's facial trauma. [ABSTRACT FROM AUTHOR]

Abstract: REV3 is the catalytic subunit of DNA polymerase ζ (pol ζ), which is responsible for the damage-induced mutagenesis that arises during error-prone translesion synthesis in eukaryotes. The related REV3L genes in human and mouse encode proteins of approximately 350kDa, twice as large as yeast REV3, but full-length REV3L has not been identified in any vertebrate cell. We report that Xenopus laevis REV3L encodes a 352-kDa protein that has high overall amino acid sequence similarity to its mammalian counterparts, and, for the first time in a vertebrate species, we have detected putative REV3L polypeptides of 300 and 340kDa in X. laevis oocytes. Only the 300-kDa form is stored in eggs, where its concentration of about 65pM is much lower than those of other replication and repair proteins including the accessory pol ζ subunit REV7. In fertilized eggs, the levels of this polypeptide did not change until neurula; the larger 340-kDa form first appeared at stages after gastrula, suggesting a pattern of regulation during development. These observations indicate the existence of REV3L as a scarce protein, of approximately the full predicted size, whose level may impose severe constraints on the assembly of pol ζ in X. laevis. [Copyright &y& Elsevier]

MEL1 (MDS1/EVI1-like gene 1/PRDM16), a zinc finger protein, is located near the chromosomal breakpoint at 1p36 in human acute myeloid leukemia (AML) cells with the t (1; 3) (p36; q21) translocation. Mel1/Prdm16 is not only a causative gene of leukemia, but also has multiple regulatory functions, such as the regulation of fat metabolism. To investigate the function of Mel1/Prdm16 , we generated Mel1/Prdm16 -deficient mice, but homozygous deficiency (Mel1/Prdm16 −/− ) was embryonic lethal at E 11.5. Heterozygous mice showed abnormal cartilage and bone formation in the postnatal skull and long bones, suggesting that Mel1/Prdm16 expression plays an important role in bone development. In osteoblast and chondrocyte cell lines, Mel1/Prdm16 promotes the differentiation of chondrocytes and regulates the differentiation of osteoblasts. Transient repression of the master regulator Runx2 is required for chondrocyte differentiation at an early stage of differentiation. However, in Mel1/Prdm16 -suppressed ATDC5 cells, the initial suppression of Runx2 was lacking and its expression was upregulated at the beginning of differentiation, suggesting that chondrogenic differentiation is suppressed in Mel1/Prdm16 +/− mesenchymal progenitor cells because Runx2 expression is upregulated during the early stage of differentiation. Thus, the Mel1/Prdm16 gene may be involved in the early repression of Runx2 expression during osteochondral differentiation and promote chondrogenic differentiation. • Expression of Prdm16/Mel1 during fetal life promotes cartilage differentiation. • Loss of fetal Prdm16/Mel1 expression promotes bone differentiation. • Prdm16/Mel1 represses transcription of Runx2 via Nkx3.2. • Prdm16/Mel1 is located on human chromosome 1p36. • The phenotype of Prdm16/Mel1 KO mice is similar to that of 1p36 deletion syndrome. [ABSTRACT FROM AUTHOR]

To reduce skin irritation and allergic symptoms caused by long-term mask use, we produced a mask with a filter effect by laminating nanofibers on habutae silk fabric, a specialty of Japan's Fukui Prefecture, using the electrospinning method. We investigated the filter characteristics of silk fabrics with different weave structures (habutae, flat crepe, and twill). We found that woven fabrics alone could not sufficiently block particles finer than 1 μm, even when the fabric layers were overlapped. Therefore, we had a nanofiber filter layer fabricated on the surface of habutae fabric by the electrospinning method at a weight of 1 g/m2. The nanofibers removed more than 94% of 0.3 μm-particles, which are similar to the size of virus particles. However, the nanofiber layer was so dense that it caused an increase in pressure drop, so we made the nanofiber layer thinner and fabricated the filter on the surface of the habutae fabric at 0.5 g/m2. A three-dimensional mask consisting of two woven fabrics, one with a nanofiber layer on the inside and the other with a normal woven fabric without a nanofiber layer on the outside, was fabricated and tested on 95 subjects. The subjects reported that the nanofiber habutae masks were more comfortable than nonwoven masks. Moreover, the silk woven masks did not cause allergic symptoms such as skin irritation. [ABSTRACT FROM AUTHOR]

Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. Here we show that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells. Mouse 3T3 fibroblasts forced to express this human fusion tyrosine kinase generated transformed foci in culture and subcutaneous tumours in nude mice. The EML4–ALK fusion transcript was detected in 6.7% (5 out of 75) of NSCLC patients examined; these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. Our data demonstrate that a subset of NSCLC patients may express a transforming fusion kinase that is a promising candidate for a therapeutic target as well as for a diagnostic molecular marker in NSCLC. [ABSTRACT FROM AUTHOR]

Abstract: Colorectal cancer (CRC) is one of the leading causes of cancer death in humans. In order to identify novel cancer-promoting genes in CRC, we here constructed a retroviral cDNA expression library from a CRC cell line RKO, and used it for a focus formation assay with mouse 3T3 fibroblasts, leading to the identification of 42 independent cDNAs. One of such cDNAs turned out to encode purinergic receptor P2Y, G-protein coupled, 2 (P2RY2). The oncogenic potential of P2RY2 was confirmed in vitro with the focus formation assay as well as soft agar-growth assay, and also in vivo with a tumorigenicity assay in nude mice. While our P2RY2 cDNA encodes a protein with two amino-acid substitutions compared to the reported one, we have confirmed that the wild-type P2RY2 has a strong transforming potential as well. These results indicate an unexpected role of P2RY2 in the carcinogenesis of human cancers. [Copyright &y& Elsevier]

Abstract: To identify transforming genes in acute myeloid leukemia (AML) we here constructed a retroviral cDNA expression library from an AML patient, and then used this library to infect a mouse cell line 32Dcl3-mCAT. cDNA inserts of the cell clones which proliferated in the presence of granulocyte colony-stimulating factor were derived from JAK3 encoding a JAK3 mutant with a valine-to-alanine substitution at codon 674 and two additional amino acid substitutions. The transforming activity of JAK3(V674A) was confirmed by its introduction into 32Dcl3-mCAT. Sequencing of the original JAK3 cDNA derived from the patient, however, failed to detect the V674A mutation. [Copyright &y& Elsevier]

Abstract: The anti-Müllerian hormone gene (Amh) is responsible for regression in males of the Müllerian ducts. The molecular mechanism of regulation of chicken Amh expression is poorly understood. To investigate the regulation of chicken Amh expression, we have cloned Amh cDNAs from quail and duck as well as the promoter regions of the gene from chicken, quail, and duck. The expression patterns of Amh during embryonic development in these three species were found to be similar, suggesting that the regulatory mechanisms of Amh expression are conserved. The sequence of the proximal promoter of Amh contains a putative binding site for steroidogenic factor 1 (SF1), the protein product of which can up-regulate Amh in mammals. We showed here that SF1 is able to activate the chicken Amh promoter and binds to its putative SF1 binding site. These results suggest that SF1 plays a role in regulation of Amh expression in avian species. [Copyright &y& Elsevier]

Background: Although many histopathological characteristics of oral squamous cell carcinoma (O-SCC) have been identified as prognostic factors, no factor is completely accurate and unequivocal. This study evaluated the association between the loss of syndecan-1 expression and the histological grade of malignancy at the deep invasive front in O-SCC. Methods: The expression of syndecan-1 at the invasive tumor front of O-SCC was examined immunohistochemically using archived tissue from 72 cases. The mean age of the patients was 62.5 years (range: 23–90 years) and the male–female ratio was 1.3:1 (41 men, 31 women). There were 26, 24, 11, and 11 cases classified as stages I–IV respectively. The correlation between the intensity of syndecan-1 immunostaining and the clinicopathological factors, especially the histological grade of malignancy at the deep invasive front (invasive front grade) was analyzed. Results: Of the 72 cases, seven (9.7%), 29 (40.3%), 36 (50.0%) showed strong, intermediate, and weak or negative syndecan-1 staining respectively. There were significant differences between syndecan-1 expression and prognosis, differentiation, and pattern of invasion at the deep invasive front. Moreover, the invasive front grade scores, based on the intensity of syndecan-1 staining, were 5.6 ± 1.0, 8.0 ± 2.1, and 10.2 ± 2.3 points with strong, intermediate, and weak or negative intensity respectively; and the difference was significant ( P < 0.0001). Patients with intermediate or strong intensity for syndecan-1 had significantly better prognoses than did those with negative or weak intensity ( P = 0.0138). Conclusion: This study demonstrated that the reduced expression of syndecan-1 seems to be a useful marker of histological malignancy at the deep tumor invasive front and may be a useful prognostic factor in O-SCC. [ABSTRACT FROM AUTHOR]

Abstract: Sox9 is a member of the Sry-type HMG-box (Sox) gene family. It encodes a transcription factor and is thought to be important for sexual differentiation in chicken. In the present study we have isolated Sox9 cDNAs from quail and duck, and examined the expression patterns of the corresponding genes in early embryonic gonads by whole-mount in situ hybridization. We developed a polymerase chain reaction-based protocol to identify the sex of quail and duck embryos before its morphological manifestation. Sox9 expression was first detected on days 5 and 7 in the gonads of male quail and duck embryos, respectively, and was not apparent in female gonads at these stages. These expression patterns are similar to that of chicken Sox9. Our results thus suggest that the expression of quail and duck Sox9 is associated with testis differentiation. [Copyright &y& Elsevier]

Background: Although many histopathologic characteristics of oral squamous cell carcinoma (O-SCC) have been identified as prognostic factors, accurate, and unequivocal factors have not been clearly identified. The purpose of this study was to evaluate a potential association between the histologic grade of malignancy at the deep invasive front and the expression of Ki-67 antigen and p53 protein in O-SCC. Methods: The expression of Ki-67 antigen and p53 at the invasive tumor front area of O-SCC was examined by immunohistochemistry of archived tissue from 62 cases. The mean age of patients was 60.7 years (range: 37–89) and the male–female ratio was 1.6:1 (38 men, 24 women). There were 20, 17, 14, and 11 cases classified as stage I to stage IV, respectively. The correlation between the intensity of immunostaining for Ki-67 antigen and p53 and the histologic grade of malignancy at the deep invasive front (invasive front grade, IFG) was analyzed. The expression of Ki-67 antigen and p53 in normal oral epithelia (10 cases) was also investigated. Results: The mean Ki-67 labeling index (LI) in the O-SCC samples was 32.8 ± 12.0% ( n = 62). The mean total score of IFG (IFG score) was 9.1 ± 2.7 points ( n = 62). There was a significant linear correlation between the IFG score and the Ki-67 antigen ( γ = 0.651, R2 = 0.596, P < 0.0001). Of 50 tumors examined, 27 (54.0%) exhibited p53-positive nuclear immunostaining. The staining patterns for Ki-67 antigen and p53 were similar. Both Ki-67-LI and p53-positive status were significantly correlated with the IFG scores. Conclusion: The findings of this study demonstrate that overexpression of Ki-67 antigen and p53 at the deep tumor invasive front of O-SCC is associated with histologic grade of malignancy. [ABSTRACT FROM AUTHOR]

Abstract: Pancreatic ductal carcinoma (PDC) remains one of the most intractable malignancies in humans. In order to clarify the molecular events underlying the carcinogenesis in PDC, we constructed a retroviral cDNA expression library from a PDC cell line, and used it to screen transforming genes in PDC by a focus formation assay with mouse 3T3 fibroblasts. We could obtain a total of 30 transformed cell foci in the screening, and one of the cDNA inserts harvested from such cell clones turned out to encode a wild-type human ARAF1. Unexpectedly, a long terminal repeat-driven overexpression of ARAF1 mRNA was confirmed to induce transformed foci in fibroblasts. The oncogenic potential of ARAF1 was examined by injecting the transformed fibroblasts into athymic nude mice. Importantly, ARAF1 mRNA was highly expressed in pancreatic ductal cell specimens purified from patients with PDC. These results have unveiled the transforming potential of ARAF1 protein, and also suggest that quantity of intracellular ARAF1 may be important in carcinogenesis of various human cancers. [Copyright &y& Elsevier]

Abstract: Aggressive natural killer cell leukemia (ANKL) is an intractable malignancy that is characterized by the outgrowth of NK cells. To identify transforming genes in ANKL, we constructed a retroviral cDNA expression library from an ANKL cell line KHYG-1. Infection of 3T3 cells with recombinant retroviruses yielded 33 transformed foci. Nucleotide sequencing of the DNA inserts recovered from these foci revealed that 31 of them encoded KRAS2 with a glycine-to-alanine mutation at codon 12. Mutation-specific PCR analysis indicated that the KRAS mutation was present only in KHYG-1 cells, not in another ANKL cell line or in clinical specimens (n =8). [Copyright &y& Elsevier]

The Janus kinase (Jak).Stat pathway plays an essential role in cytokine signaling. Granulocyte colony-stimulating factor (G-CSF) promotes granulopoiesis and granulocytic differentiation, and Stat3 is the principle Stat protein activated by G-CSF. Upon treatment with G-CSF, the interleukin-3-dependent cell line 32D clone 3(32Dc13) differentiates into neutrophils, and 32Dc13 cells expressing dominant-negative Stat3 (32Dc13/DNStat3) proliferate in G-CSF without differentiation. Gene expression profile and quantitative PCR analysis of G-CSF-stimulated cell lines revealed that the expression of C/EBPα was up-regulated by the activation of Stat3. In addition, activated Stat3 bound to CCAAT/enhancer-binding protein (C/EBP)α leading to the enhancement of the transcription activity of C/EBPα. Conditional expression of C/EBPα in 32De13/DNStat3 cells after G-CSF stimulation abolishes the G-CSF-dependent cell proliferation and induces granulocytic differentiation. Although granulocyte-specific genes, such as the G-CSF receptor, lysozyme M, and neutrophil gelatinase-associated lipocalin precursor (NGAL) are regulated by Stat3, only NGAL was induced by the restoration of C/EBPα after stimulation with G-CSF in 32Dc13/DNStat3 cells. These results show that one of the major roles of Stat3 in the G-CSF signaling pathway is to augment the function of C/EBPα, which is essential for myeloid differentiation. Additionally, cooperation of C/EBPα with other Stat3-activated proteins are required for the induction of some G-CSF responsive genes including lysozyme M and the G-CSF receptor. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) develops de novo or secondarily to either myelodysplastic syndrome (MDS) or anticancer treatment (therapy-related leukemia, TRL). Prominent dysplasia of blood cells is apparent in individuals with MDS-related AML as well as in some patients with TRL or even with de novo AML. The clinical entity of AML with multilineage dysplasia (AML-MLD) is likely to be an amalgamation of MDS-related AML and de novo AML-MLD. The aim of this study was to clarify, by the use of high-density oligonucleotide microarrays, whether these subcategories of AML are intrinsically distinct from each other.The AC133+ hematopoietic stem cell–like fractions were purified from the bone marrow of individuals with de novo AML without dysplasia (n=15), AML-MLD (n=11), MDS-related AML (n=11), or TRL (n=2), and were subjected to the synthesis of cRNA which was subsequently hybridized to microarray harboring oligonucleotide corresponding to more than 12,000 probe sets.We could identify many genes whose expression was specific to these various subcategories of AML. Furthermore, with the correspondence analysis/three-dimensional projection strategy, we were able to visualize the independent, yet partially overlapping, nature of current AML subcategories on the basis of their transcriptomes.Our data indicate the possibility of subclassification of AML based on gene expression profiles of leukemic blasts. [Copyright &y& Elsevier]

To obtain insights into the molecular pathogenesis of heart failure in humans, we have analyzed the expression profiles of >12,000 genes in a total of 17 human specimens of right atrial myocytes. From this large data set, we here tried to identify gene clusters, expression level of which is correlated precisely with clinical parameter values of cardiac function. We could reveal that cardiac myocytes with normal sinus rhythm were clearly differentiated, in the point of view of gene expression, from those with atrial fibrillation. Further, an expression profile-based prediction of arrhythmia by a newly developed “weighted-distance method” could efficiently diagnose our samples. We could even construct calculation formulae for the values of left ventricular ejection fraction based on the expression level of selected genes. To our best knowledge, this is the first report to indicate that pumping ability of heart can be predicted by any measures of atrium. [Copyright &y& Elsevier]

Background: Leukoplakia is an oral pre-cancerous lesion that sometimes develops into squamous cell carcinoma. Therefore, leukoplakia with epithelial dysplasia is useful for studying carcinogenesis at the cellular level. The purpose of this study was to evaluate a potential association between the loss of syndecan-1 expression and the expression of p53 protein and Ki-67 antigen, and to identify reliable markers for predicting malignant changes in oral leukoplakia with epithelial dysplasia.Methods: Changes in the expression of syndecan-1, p53, and Ki-67 were examined immunohistochemically in 43 cases of oral leukoplakia with or without epithelial dysplasia. The subjects were categorized as: none, 13 cases; mild dysplasia, 5 cases; moderate dysplasia, 17 cases; and severe dysplasia, 8 cases. The expression of these molecules in normal oral epithelia (22 cases) was also investigated.Results: Strong syndecan-1 expression was observed on the surface of keratinocytes in normal epithelium. Immunopositivity was lost gradually as the extent of epithelial dysplasia increased. In normal epithelium, p53 and Ki-67 appeared mainly in the basal cell layer, while they were more widely distributed in leukoplakia. Specifically, significant changes were observed in the labeling index of p53 and Ki-67 in leukoplakia as epithelial dysplasia progressed from mild to moderate or severe.Conclusion: Our results reveal that overexpression of p53 protein and Ki-67 antigen, and down-regulation of syndecan-1 expression in the lower part of the epithelium, are associated with dysplastic changes. Therefore, the down-regulation of syndecan-1 expression may be the most important reliable marker for dysplastic changes. [ABSTRACT FROM AUTHOR]

Dahl salt-sensitive rats are genetically hypersensitive to sodium intake. When fed a high sodium diet, they develop systemic hypertension, followed by cardiac hypertrophy and finally heart failure within a few months. Therefore, Dahl rats represent a good model with which to study how heart failure is developed in vivo. By using DNA microarray, we here monitored the transcriptome of >8000 genes in the left ventricular muscles of Dahl rats during the course of cardiovascular damage. Expression of the atrial natriuretic peptide gene was, for instance, induced in myocytes by sodium overload and further enhanced even at the heart failure stage. Interestingly, expression of the gene for the D-binding protein, an apoptotic-related transcriptional factor, became decreased upon the transition to heart failure. To our best knowledge, this is the first report to describe the transcriptome of cardiac myocytes during the disease progression of heart failure. [Copyright &y& Elsevier]

BAZF, a member of Bcl6 gene family, acts as a sequence-specific transcriptional repressor in various cells including NIH3T3 cells. The DNA-binding sequence for BAZF is the same as that for Bcl6 and the repressor activity of BAZF was also inhibited by Tricostatin A, an inhibitor of histone deacetylase, suggesting the functional homology between them. However, BAZF unlike Bcl6 cannot function as a transcriptional repressor in embryonal fibroblasts of Bcl6-deficient mice and in Bcl6-null cell lines such as K562 and WIL2-NS. The BTB/POZ domain and the middle portion of BAZF bound to the BTB/POZ domain and the middle portion of Bcl6, respectively. There is an identical 17 amino acid sequence in their middle portions and the sequence was important for the binding. Since BAZF did not directly bind to mSin3A and histone deacetylase 1 and the repressor activity of BAZF was detected in K562 cells replenished with the BTB/POZ domain or the middle portion of Bcl6, BAZF may display its transrepressor activity by recruiting an mSin3A/histone deacetylase 1 complex through association with Bcl6. [Copyright &y& Elsevier]

Summary. Lymphoproliferative disease of granular lympho- cytes (LDGL) is characterized by the clonal proliferationoflarge granular lymphocytes of either T- or natural killer cell origin. To better understand the nature of T cell-type LDGL, we purified the CD4– CD8+ proliferative fractions from LDGL patients (n =4) and the surface marker-matched T cells isolated from healthy volunteers (n =4), and compared the expression profiles of 3456 genes using DNA microarray. Through this analysis, we identified a total of six genes whose expression was active in the LDGL T cells, but silent in the normal ones. Interestingly, expression of the gene for interleukin (IL) 1β was specific to LDGL T cells, which was further confirmed by the examination of the serum level of IL-1β protein. Given its important role in inflammatory reactions, the disease-specific expression of IL-1β may have a causative relationship with the LDGL- associated rheumatoidarthritis. Spectratyping analysis of the T-cell receptor repertoire also proved the monoclonal or oligoclonal natureof LDGL cells. These data have shown that microarray analysis with a purified T-cell subset is an efficient approach to investigate the pathological condition of Tcell-type LDGL. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) is characterized by the clonal expansion of hematopoietic stem cells (HSCs). Without effective treatment, individuals in the indolent, chronic phase (CP) of CML undergo blast crisis (BC), the prognosis for which is poor. It is therefore important to clarify the mechanism underlying stage progression in CML. DNA microarray is a versatile tool for such a purpose. However, simple comparison of bone marrow mononuclear cells from individuals at different disease stages is likely to result in the identification of pseudo-positive genes whose change in expression only reflects the different proportions of leukemic blasts in bone marrow. We have therefore compared with DNA microarray the expression profiles of 3456 genes in the purified HSC-like fractions that had been isolated from 13 CML patients and healthy volunteers. Interestingly, expression of the gene for PIASy, a potential inhibitor of STAT (signal transducer and activator of transcription) proteins, was down-regulated in association with stage progression in CML. Furthermore, forced expression of PIASy has induced apoptosis in a CML cell line. These data suggest that microarray analysis with background-matched samples is an efficient approach to identify molecular events underlying the stage progression in CML. Oncogene (2001) 20, 8249–8257. [ABSTRACT FROM AUTHOR]

Commingled yarns consisting of thermoplastic nylon fibers and carbon fibers can be used to produce superior carbon fiber reinforced thermoplastics (CFRTP) by applying fiber spreading technology after commingling. In this study, we examined whether spread commingled carbon fiber/nylon fiber yarns could reduce the impregnation distance, as there are few reports on this. From this study, the following are revealed. The impregnation speed of the nylon resin on the carbon fiber was very fast, less than 1 min. As the molding time increased, the tensile strength and tensile fracture strain slightly decreased, and the nylon resin deteriorated. The effects of molding time on flexural strength, flexural modulus, and flexural fracture strain were negligible. From the cross-sectional observation conducted to confirm the impregnation state of the matrix resin, no voids were observed in the molded products, regardless of molding time or molding pressure, indicating that resin impregnation into the carbon fiber bundle of the spread commingled yarn fabric was completed at a molding pressure of 5 MPa and a molding time of 5 min. [ABSTRACT FROM AUTHOR]