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1.
Genes Dev ; 30(22): 2475-2485, 2016 11 15.
Article in English | MEDLINE | ID: mdl-27913604

ABSTRACT

In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage. We found that these developmentally arrested T-cell precursors gave rise to functional B cells upon transfer to immunodeficient mice. We further demonstrated that the arrest was almost completely canceled by additional deletion of Pax5 These results indicate that the maintenance of T-cell fate critically requires epigenetic suppression of the B-lineage gene program.


Subject(s)
B-Lymphocytes/cytology , Cell Transformation, Neoplastic/genetics , Epigenesis, Genetic/genetics , Gene Silencing , Polycomb-Group Proteins/metabolism , T-Lymphocytes/cytology , Animals , Cell Lineage , Gene Deletion , Gene Expression Regulation, Developmental , Immunoglobulin Heavy Chains/genetics , Mice, Inbred C57BL , PAX5 Transcription Factor/genetics , PAX5 Transcription Factor/metabolism , Polycomb Repressive Complex 1/genetics , Promoter Regions, Genetic/genetics , Ubiquitin-Protein Ligases/genetics
2.
Gan To Kagaku Ryoho ; 35 Suppl 1: 19-21, 2008 Dec.
Article in Japanese | MEDLINE | ID: mdl-20443294

ABSTRACT

Dyspnea is one of the most common problems we encounter in the palliative care setting of patients with life-threatening illness including malignancy. Dyspnea is considered especially a troublesome symptom in the management of in-home hospice care services. We examined effects of anti-cholinergic agents against such symptoms associated with dyspnea in patients with serious illness treated at home. The effectiveness was observed in 51% of patients who were given anti-cholinergic drugs. According to the outcome of this study, anti-cholinergic drugs may be effective for alleviating the suffering of terminally-ill patients due to dyspnea. Further investigation would be expected to clarify the usefulness of anti-cholinergic agents in the field of palliative care.


Subject(s)
Cholinergic Agents/therapeutic use , Dyspnea/drug therapy , Home Care Services , Palliative Care , Aged , Aged, 80 and over , Female , Hospice Care , Humans , Male , Middle Aged
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