Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity.
Wu Z,Rosen E D,Brun R,Hauser S,Adelmant G,Troy A E,McKeon C,Darlington G J,Spiegelman B M
Mice deficient in C/EBP alpha have defective development of adipose tissue, but the precise role of C/EBP alpha has not been defined. Fibroblasts from C/EBP alpha(-/-) mice undergo adipose differentiation through expression and activation of PPAR gamma, though several clear defects are apparent. C/EBP alpha-deficient adipocytes accumulates less lipid, and they do not induce endogenous PPAR gamma, indicating that cross-regulation between C/EBP alpha and PPAR gamma is important in maintaining the differentiated state. The cells also show a complete absence of insulin-stimulated glucose transport, secondary to reduced gene expression and tyrosine phosphorylation for the insulin receptor and IRS-1. These results define multiple roles for C/EBP alpha in adipogenesis and show that cross-regulation between PPAR gamma and C/EBP alpha is a key component of the transcriptional control of this cell lineage.
Fanconi anemia in twins with neutropenia: A case report.
Deng Wenjun,Zhao Mingyi,Liu Yingting,Cao Lizhi,Yang Minghua
Fanconi anemia (FA) is a rare inherited disease caused by mutations in genes that are primarily involved in DNA damage response or repair. The disease is often characterized by congenital malformations, progressive bone marrow failure, abnormal skin pigmentation patterns and susceptibility to cancer. The present study describes a pair of 4-year-old male twins, both of whom had been suffering from upper respiratory tract infections for >2 years. There was no indication of discomfort including fever, coughing, bleeding or fatigue from either child when the upper respiratory tract infection disappeared. Physical examination of the twins did not reveal anything significant, and no external anomalies were observed. In order to obtain additional diagnostic evidence, next-generation gene sequencing, chromosome breakage analysis and comet assays were performed. The results revealed double heterozygous mutations in the Fanconi Anemia Complementation Group D2 gene of the twins, therefore providing a conclusive diagnosis of FA. The case highlights how difficulties in clinical diagnosis may be overcome by including genetic screening tests into the range of diagnostic tests, which may also reveal unexpected results.
[X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia: report of a family and literature review].
He T Y,Xia Y,Li C G,Li C R,Qi Z X,Yang J
Zhonghua er ke za zhi = Chinese journal of pediatrics
To investigate the clinical features and genetic characteristics of cases with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN). Characteristics of clinical material, immunological data and gene mutation of two cases with XMEN in the same family in China were retrospectively analyzed. The related reports literature were searched by using search terms'MAGT1 gene'or'XMEN'. The proband, a 2-year-eight-month old boy, was admitted due to 'Urine with deepened color for two days and yellow stained skin for one day'. He had suffered from recurrent upper respiratory tract infection and sinusitis previously. Hemoglobin level was 38 g/L. The absolute count of reticulocytes was 223.2×10(9)/L. Urobilinogen level was 38 μmol/L (3-16 μmol/L). Coomb's test was positive. Both total (77.2 μmol/L) and indirect bilirubin (66 μmol/L) levels were elevated. There was an inverted CD4(+)/CD8(+)T cell ratio (0.89). The gene sequencing results showed MAGT1 gene c.472delG, p.D158Mfs*6 mutation. His 1-year-6-month old brother, was also identified to have MAGT1 gene c.472delG, p.D158Mfs*6 mutation.The younger brother mainly suffered from recurrent upper respiratory tract infection, accompanied by an inverted CD4(+)/CD8(+)T cell ratio (0.45), an elevated ratio and number of total B cells (45.7%). A total of 7 reports were retrieved including 11 male cases caused by MAGT1 gene mutation. These 11 cases were characterized by EBV viremia (11 cases), recurrent upper respiratory tract infection, otitis media or sinusitis (10 cases), secondary neoplasia diseases (8 cases), reduction of CD4(+)/CD8(+) T cell ratio (7 cases),and autoimmune thrombocytopenia or hemolytic anemia (2 cases). XMEN often manifests as male onset, recurrent upper respiratory tract infection, otitis media or sinusitis, EBV viremia, lymphoproliferative disease or lymphoma, autoimmune diseases and reduction of CD4(+)/CD8 (+)T cell ratio. NKG2D expression in NK cells is significantly reduced, and gene sequencing analysis shows a pathogenic mutation in MAGT1 gene.