Long-term outcome in relationship to neonatal transfusion volume in extremely premature infants: a comparative cohort study

<p>Abstract</p> <p>Background</p> <p>In premature born infants red blood cell (RBC) transfusions have been associated with both beneficial and detrimental sequels. Upon RBC transfusion, improvement in cerebral blood flow and oxygenation have been observed, while a more liberal transfusion policy may be associated with a better developmental outcome. The effect of the transfusion volume on long-term outcome is not known.</p> <p>Methods</p> <p>Observational follow-up study of a cohort of extremely premature born infants, treated in 2 neonatal intensive care units using a different transfusion volume (15 ml/kg in Unit A and 20 ml/kg in Unit B). The primary outcome was a composite of post discharge mortality, neuromotor developmental delay, blindness or deafness, evaluated at a mean corrected age (CA) of 24 months related to the transfusion volume/kg bodyweight administered during the postnatal hospital stay.</p> <p>Results</p> <p>Despite the difference in transfusion volume in clinically comparable groups of infants, they received a similar number of transfusions (5.5 ± 3.2 versus 5.5 ± 2.3 respectively in Unit A and B). The total transfused volume in unit A was 79 ± 47 ml/kg and 108 ± 47 ml/kg in unit B (p = 0.02). Total transfused RBC volume per kg bodyweight was not an independent predictor of the composite outcome (p = 0.96, OR 1.0 (CI 0.9-1.1).</p> <p>Conclusion</p> <p>There was no relationship between the composite outcome at 24 months CA and transfusion volume received during the post natal hospital stay. As there was no clinical advantage of the higher transfusion volume, a more restrictive volume will reduce total transfusion volume and donor exposure. Future research on the optimal transfusion volume per event to extreme preterm infants should include larger, prospective studies with a longer follow-up period through to childhood or even adolescence.</p

TSPY potentiates cell proliferation and tumorigenesis by promoting cell cycle progression in HeLa and NIH3T3 cells

BACKGROUND: TSPY is a repeated gene mapped to the critical region harboring the gonadoblastoma locus on the Y chromosome (GBY), the only oncogenic locus on this male-specific chromosome. Elevated levels of TSPY have been observed in gonadoblastoma specimens and a variety of other tumor tissues, including testicular germ cell tumors, prostate cancer, melanoma, and liver cancer. TSPY contains a SET/NAP domain that is present in a family of cyclin B and/or histone binding proteins represented by the oncoprotein SET and the nucleosome assembly protein 1 (NAP1), involved in cell cycle regulation and replication. METHODS: To determine a possible cellular function for TSPY, we manipulated the TSPY expression in HeLa and NIH3T3 cells using the Tet-off system. Cell proliferation, colony formation assays and tumor growth in nude mice were utilized to determine the TSPY effects on cell growth and tumorigenesis. Cell cycle analysis and cell synchronization techniques were used to determine cell cycle profiles. Microarray and RT-PCR were used to investigate gene expression in TSPY expressing cells. RESULTS: Our findings suggest that TSPY expression increases cell proliferation in vitro and tumorigenesis in vivo. Ectopic expression of TSPY results in a smaller population of the host cells in the G(2)/M phase of the cell cycle. Using cell synchronization techniques, we show that TSPY is capable of mediating a rapid transition of the cells through the G(2)/M phase. Microarray analysis demonstrates that numerous genes involved in the cell cycle and apoptosis are affected by TSPY expression in the HeLa cells. CONCLUSION: These data, taken together, have provided important insights on the probable functions of TSPY in cell cycle progression, cell proliferation, and tumorigenesis

Inactivation of a Single Copy of Crebbp Selectively Alters Pre-mRNA Processing in Mouse Hematopoietic Stem Cells

Global expression analysis of fetal liver hematopoietic stem cells (FL HSCs) revealed the presence of unspliced pre-mRNA for a number of genes in normal FL HSCs. In a subset of these genes, Crebbp+/− FL HSCs had less unprocessed pre-mRNA without a corresponding reduction in total mRNA levels. Among the genes thus identified were the key regulators of HSC function Itga4, Msi2 and Tcf4. A similar but much weaker effect was apparent in Ep300+/− FL HSCs, indicating that, in this context as in others, the two paralogs are not interchangeable. As a group, the down-regulated intronic probe sets could discriminate adult HSCs from more mature cell types, suggesting that the underlying mechanism is regulated with differentiation stage and is active in both fetal and adult hematopoiesis. Consistent with increased myelopoiesis in Crebbp hemizygous mice, targeted reduction of CREBBP abundance by shRNA in the multipotent EML cell line triggered spontaneous myeloid differentiation in the absence of the normally required inductive signals. In addition, differences in protein levels between phenotypically distinct EML subpopulations were better predicted by taking into account not only the total mRNA signal but also the amount of unspliced message present. CREBBP thus appears to selectively influence the timing and degree of pre-mRNA processing of genes essential for HSC regulation and thereby has the potential to alter subsequent cell fate decisions in HSCs