73 research outputs found

    Antisense retinoic acid receptor γ-1 oligonucleotide enhances chondrogenesis of mouse limb mesenchymal cells in vitro

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    AbstractRetinoic acid receptor (RAR) γ gene is expressed in the precartilaginous cells during chondrogenesis in mouse embryos, but the role of the gene products is still unclear. To examine the role during chondrogenesis, we isolated mesenchymal cells from the limb bud of mouse embryos and exposed them to antisense RAR γ-1 oligodeoxynucleotide in micromass culture. The antisense oligodeoxynucleotide inhibited RAR γ-1 protein expression and enhanced chondrogenesis in the exposed cells. These results suggest that the complex of RAR γ-1 protein and its ligand RA acts as a suppressor of the chondrogenesis in the limb development

    Lrp4 Modulates Extracellular Integration of Cell Signaling Pathways in Development

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    The extent to which cell signaling is integrated outside the cell is not currently appreciated. We show that a member of the low-density receptor-related protein family, Lrp4 modulates and integrates Bmp and canonical Wnt signalling during tooth morphogenesis by binding the secreted Bmp antagonist protein Wise. Mouse mutants of Lrp4 and Wise exhibit identical tooth phenotypes that include supernumerary incisors and molars, and fused molars. We propose that the Lrp4/Wise interaction acts as an extracellular integrator of epithelial-mesenchymal cell signaling. Wise, secreted from mesenchyme cells binds to BMP's and also to Lrp4 that is expressed on epithelial cells. This binding then results in the modulation of Wnt activity in the epithelial cells. Thus in this context Wise acts as an extracellular signaling molecule linking two signaling pathways. We further show that a downstream mediator of this integration is the Shh signaling pathway

    Resection of Hepatic Metastasis from Colorectal Cancer : Survival, Factors Influencing Prognosis, and Follow-up

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    The purpose of this retrospective study was to analyze the surgical results of hepatic resection in our patients with colorectal hepatic metastasis. During a 26-year period, 223 patients among 1,484 patients with colorectal cancer suffered liver metastasis. In 44 curatively resected patients, the one-, three- and five-year cumulative survival rates were 85.9%, 44.9% and 23.0%, respectively. The prognostic importance of seven factors was evaluated. Synchronous or metachronous resection, the type of liver resection, and histologic differentiation did not influence the prognosis, whereas the number and size of metastases, and lymph node involvement did significantly affect prognosis as single factors. The mean diameter of metastatic lesions in the liver was 2.5 cm in the synchronous group and 4.5 cm in the metachronous group, the difference being significant (p = 0.0005). The presence of tumors with large diameters in the metachronous group might mean our failure of early detection of the recurrence of hepatic metastases. It is necessary to make steady efforts such as introducing regular follow-up imaging of colorectal cancer. The median interval between the primary operation and liver metastasis resection was 15.7 months in the lymph node involvement group and 37.7 months in the no lymph node involvement group. In 19 patients among 21 metachronously resected patients, the hepatic resection was done within three years. In conclusion, it was considered that hepatectomy could be done safely, that detection of an earlier lesion could improve the surgical results, and that follow-up for liver metastasis should be done intensively between 12 and 36 months after colorectal cancer surgery

    Personalized prediction of overall survival in patients with AML in non‐complete remission undergoing allo‐HCT

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    Allogenic hematopoietic stem cell transplantation (allo-HCT) is the standard treatment for acute myeloid leukemia (AML) in non-complete remission (non-CR); however, the prognosis is inconsistent. This study aimed to develop and validate nomograms and a web application to predict the overall survival (OS) of patients with non-CR AML undergoing allo-HCT (cord blood transplantation [CBT], bone marrow transplantation [BMT], and peripheral blood stem cell transplantation [PBSCT]). Data from 3052 patients were analyzed to construct and validate the prognostic models. The common significant prognostic factors among patients undergoing allo-HCT were age, performance status, percentage of peripheral blasts, cytogenetic risk, chemotherapy response, and number of transplantations. The conditioning regimen was a significant prognostic factor only in patients undergoing CBT. Compared with cyclophosphamide/total body irradiation, a conditioning regimen of ≥3 drugs, including fludarabine, with CBT exhibited the lowest hazard ratio for mortality (0.384; 95% CI, 0.266-0.554; p < 0.0001). A conditioning regimen of ≥3 drugs with CBT also showed the best leukemia-free survival among all conditioning regimens. Based on the results of the multivariable analysis, we developed prognostic models showing adequate calibration and discrimination (the c-indices for CBT, BMT, and PBSCT were 0.648, 0.600, and 0.658, respectively). Our prognostic models can help in assessing individual risks and designing future clinical studies. Furthermore, our study indicates the effectiveness of multi-drug conditioning regimens in patients undergoing CBT

    Combined In Silico and In Vivo Analyses Reveal Role of Hes1 in Taste Cell Differentiation

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    The sense of taste is of critical importance to animal survival. Although studies of taste signal transduction mechanisms have provided detailed information regarding taste receptor calcium signaling molecules (TRCSMs, required for sweet/bitter/umami taste signal transduction), the ontogeny of taste cells is still largely unknown. We used a novel approach to investigate the molecular regulation of taste system development in mice by combining in silico and in vivo analyses. After discovering that TRCSMs colocalized within developing circumvallate papillae (CVP), we used computational analysis of the upstream regulatory regions of TRCSMs to investigate the possibility of a common regulatory network for TRCSM transcription. Based on this analysis, we identified Hes1 as a likely common regulatory factor, and examined its function in vivo. Expression profile analyses revealed that decreased expression of nuclear HES1 correlated with expression of type II taste cell markers. After stage E18, the CVP of Hes1−/− mutants displayed over 5-fold more TRCSM-immunoreactive cells than did the CVP of their wild-type littermates. Thus, according to our composite analyses, Hes1 is likely to play a role in orchestrating taste cell differentiation in developing taste buds

    Peptide foldamers composed of six-membered ring α,α-disubstituted α-amino acids with two changeable chiral acetal moieties

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    Chiral cyclic α,α-disubstituted α-amino acids with four chiral centers at their acetal moieties were synthesized. An X-ray crystallographic analysis of homo-chiral tripeptide with (2R,3R)-butane-2,3-diol acetal moieties revealed that the tripeptide formed both (P) and (M) helical structures, and all peptide main-chain N(i)-H were intramolecularly hydrogen-bonded with the side-chain acetal -O- of the same amino acid residues (i). The effect of the four chiral centers in the amino acid residue on the peptide backbone helical-screw control was very weak

    CAUSAL FACTORS FOR INTERDENTAL SPACES IN THE CANINE REGIONS OF INFANTILE TWINS

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    Examinations on causal factors for interdental spaces in the deciduous canine regions were made mainly by the twin method. Observations on the interdental space and dental arch at the age of 4 years: It was found that (1) the source for variation in the size of precanine space was due to the tooth size and dental arch size, and that of postcanine space was due to the tooth size, and that (2) genetic factors were small for variation in interdental space, though genetic factors were large for variations in tooth size and dental arch size. These results possibly suggest that genetic factors for variation in tooth size and dental arch size are independent and would be regarded as being a part of environmental factors for variation in interdental space
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