Dysglycaemia in small-for-gestational-age neonates: a matched case-control study in monochorionic twins.

Objective: Small-for-gestational-age (SGA) neonates (birth weight <10th centile) are at higher risk of altered glucose homeostasis compared to appropriate for gestational age (AGA) neonates. The aim of this matched case-control study was to estimate the incidence of hypoglycaemia and/or hyperglycaemia in monochorionic (MC) twins with selective intrauterine growth restriction (sIUGR).

Methods: We included all MC twins with sIUGR (2002-2013).

Neonatal outcome in alloimmune thrombocytopenia after maternal treatment with intravenous immunoglobulin.

Background: Weekly maternal intravenous immunoglobulin (IVIG) is the cornerstone of antenatal treatment of foetal and neonatal alloimmune thrombocytopenia (FNAIT). The aim of this study was to describe the neonatal outcome and management in neonates with FNAIT treated antenatally with IVIG.

Materials And Methods: All neonates treated antenatally and delivered at our centre between 2006 and 2012 were included in the study.

Outcome and management in neonatal thrombocytopenia due to maternal idiopathic thrombocytopenic purpura.

Background And Objectives: Pregnant women with Idiopathic thrombocytopenic purpura (ITP) can deliver neonates with severe thrombocytopenia. Clear evidence declaring the pathophysiological cause of this neonatal thrombocytopenia is lacking, as antiplatelet antibodies are not always detectable in maternal serum. Severe neonatal thrombocytopenia below 50 × 10(9) /l is reported in 8-13% of the neonates from mothers with ITP and intracranial haemorrhage (ICH) in 0-2·9%.

Repeated courses of ibuprofen are effective in closure of a patent ductus arteriosus.

Patent ductus arteriosus (PDA) is a frequent complication in preterm infants. Ibuprofen and indomethacin (both COX inhibitors) are used for pharmacological closure of PDA. In most centers, a failed second course of COX inhibitors is followed by surgical closure.

Use of rifampin in persistent coagulase negative staphylococcal bacteremia in neonates.

Background: Coagulase negative staphylococci (CoNS) are the most common cause of neonatal sepsis in the Neonatal Intensive Care Unit (NICU). A minority of neonates does not respond to vancomycin therapy and develops persistent bacteremia, which may be treated with rifampin. We evaluated the use of rifampin in persistent CoNS bacteremia.

Short and long term outcome of neonatal hyperglycemia in very preterm infants: a retrospective follow-up study.

Background: Hyperglycemia in premature infants is associated with increased morbidity and mortality, but data on long-term outcome are limited. We investigated the effects of neonatal hyperglycemia (blood glucose > or = 10 mmol/l, treated with insulin for > or = 12 hours) on growth and neurobehavioral outcome at 2 years of age.

Methods: Retrospective follow-up study at 2 years of age among 859 infants < or =32 weeks of gestation admitted to a tertiary neonatal center between January 2002 and December 2006.

Mice doubly deficient for the Polycomb Group genes Mel18 and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expression.

Polycomb group genes were identified as a conserved group of genes whose products are required in multimeric complexes to maintain spatially restricted expression of Hox cluster genes. Unlike in Drosophila, in mammals Polycomb group (PcG) genes are represented as highly related gene pairs, indicative of duplication during metazoan evolution. Mel18 and Bmi1 are mammalian homologs of Drosophila Posterior sex combs.

Mammalian Trithorax and polycomb-group homologues are antagonistic regulators of homeotic development.

Control of cell identity during development is specified in large part by the unique expression patterns of multiple homeobox-containing (Hox) genes in specific segments of an embryo. Trithorax and Polycomb-group (Trx-G and Pc-G) proteins in Drosophila maintain Hox expression or repression, respectively. Mixed lineage leukemia (MLL) is frequently involved in chromosomal translocations associated with acute leukemia and is the one established mammalian homologue of Trx.

Genetic interactions and dosage effects of Polycomb group genes in mice.

In Drosophila and mouse, Polycomb group genes are involved in the maintenance of homeotic gene expression patterns throughout development. Here we report the skeletal phenotypes of compound mutants for two Polycomb group genes bmi1 and M33. We show that mice deficient for both bmi1 and M33 present stronger homeotic transformations of the axial skeleton as compared to each single Polycomb group mutant, indicating strong dosage interactions between those two genes.

The Polycomb-group homolog Bmi-1 is a regulator of murine Hox gene expression.

Drosophila homeotic genes and vertebrate Hox genes are involved in the anteroposterior organization of the developing embryo. In Drosophila, the Polycomb- and trithorax-group genes are required to maintain the homeotic genes throughout development in the repressed or activated state, respectively. The murine Bmi-1 proto-oncogene was shown to exhibit homology to the Polycomb-group gene Posteior sex combs.

Directed expression of the growth-associated protein B-50/GAP-43 to olfactory neurons in transgenic mice results in changes in axon morphology and extraglomerular fiber growth.

B-50/GAP-43, a neural growth-associated phosphoprotein, is thought to play a role in neuronal plasticity and nerve fiber formation since it is expressed at high levels in developing and regenerating neurons and in growth cones. Using a construct containing the coding sequence of B-50/GAP-43 under the control of regulatory elements of the olfactory marker protein (OMP) gene, transgenic mice were generated to study the effect of directed expression of B-50/GAP-43 in a class of neurons that does not normally express B-50/GAP-43, namely, mature OMP-positive olfactory neurons. Olfactory neurons have a limited lifespan and are replaced throughout adulthood by new neurons that migrate into the upper compartment of the epithelium following their formation from stem cells in the basal portion of this neuroepithelium.

Proviral tagging in E mu-myc transgenic mice lacking the Pim-1 proto-oncogene leads to compensatory activation of Pim-2.

The Pim-1 proto-oncogene is one of the most potent collaborators of the myc proto-oncogenes in inducing lymphomagenesis in mice. Contrary to the profound effects when overexpressed in vivo, Pim-1-deficient mice showed only subtle phenotypic alterations, which could indicate the presence of redundantly acting genes. In line with this, a PCR-based screen has led to the identification of a closely homologous gene, Pim-2.

Transformation of axial skeleton due to overexpression of bmi-1 in transgenic mice.

The oncogene bmi-1, which was originally found to be involved in B- and T-cell lymphoma formation encodes a protein with a domain of homology to the Drosophila protein Posterior sex combs (Psc) and its relative Suppressor 2 of Zeste (Su(z)2) (refs 4 and 5). Psc is a member of the Polycomb-group gene family, which is required to maintain the repression of homeotic genes that regulate the identities of Drosophila segments. The possibility that bmi-1 may play a similar role in vertebrates was suggested by our previous finding that mice lacking the bmi-1 gene show posterior transformations of the axial skeleton.

Developmental rescue of an embryonic-lethal mutation in the retinoblastoma gene in chimeric mice.

The requirement for a functional retinoblastoma gene, Rb-1, in murine development around days 12-15 of gestation precludes monitoring the effect of loss of Rb-1 function on later stages of development and on tumorigenesis in adult mice. Here we describe the developmental rescue of embryonic stem cells carrying two inactive Rb-1 alleles in chimeric mice. Rb-1- cells contributed substantially to most tissues in adult chimeras, including blood, liver and central nervous system, which were severely affected in pure Rb-1- embryos.

Thymic lymphomas in interleukin 9 transgenic mice.

Transgenic mice overexpressing the interleukin 9 gene were generated to study the biological activity of this cytokine in vivo. Although no major histological or morphological modifications of the lymphoid system were observed in most animals, approximately 7% of transgenic mice developed thymic lymphomas at the age of 3-9 months. The tumor cells, which were clonal, with unique T cell rearrangements, were double positive for the expression of CD4 and CD8.

Posterior transformation, neurological abnormalities, and severe hematopoietic defects in mice with a targeted deletion of the bmi-1 proto-oncogene.

The bmi-1 proto-oncogene has been implicated in B-cell lymphomagenesis in E mu-myc transgenic mice. Distinct domains of the Bmi-1 protein are highly conserved within the Drosophila protein Posterior Sex Combs, a member of the Polycomb group involved in maintaining stable repression of homeotic genes during development. We have inactivated the bmi-1 gene in the germ line of mice by homologous recombination in ES cells.

Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease.

Two types of P-glycoprotein have been found in mammals: the drug-transporting P-glycoproteins and a second type, unable to transport hydrophobic anticancer drugs. The latter is encoded by the human MDR3 (also called MDR2) and the mouse mdr2 genes, and its tissue distribution (bile canalicular membrane of hepatocytes, B cells, heart, and muscle) suggests a specialized metabolic function. We have generated mice homozygous for a disruption of the mdr2 gene.

Pim-1 levels determine the size of early B lymphoid compartments in bone marrow.

The mouse proto-oncogene Pim-1, which encodes two cytoplasmic serine-threonine-specific protein kinases, is frequently activated by proviral insertion in murine leukemia virus-induced hematopoietic tumors. Transgenic mice overexpressing Pim-1 show a low incidence of spontaneous T cell lymphomas, whereas null mutant mice lack an obvious phenotype. We have analyzed the early B lymphoid compartment from both null mutant and E mu-Pim-1 transgenic mice.

In vivo analysis of Pim-1 deficiency.

The Pim-1 proto-oncogene encodes a highly conserved serine/threonine phosphokinase which is predominantly expressed in hematopoietic organs and gonads in mammals. Overexpression of Pim-1 predisposes to lymphomagenesis in mice. To develop a further understanding of Pim-1 in molecular terms, as well as in terms of its potential role in hematopoietic development, we have generated mice deficient in Pim-1 function.

Impaired interleukin-3 response in Pim-1-deficient bone marrow-derived mast cells.

The mouse Pim-1 gene encodes two cytoplasmic serine-threonine-specific protein kinases. The gene has been found to be activated (overexpressed) by retroviral insertion in hematopoietic tumors in mice. Transgenic mice that overexpress Pim-1 (E mu-Pim-1) have a low incidence of spontaneous T-cell lymphomas and an increased susceptibility to Moloney murine leukemia virus and N-ethyl-N-nitrosourea-induced lymphomas.

Analysis of Pim-1 function in mutant mice.

The Pim-1 gene has frequently been found activated by proviral insertion in haematopoietic tumors in mice. The fact that overexpression of Pim-1 can contribute to lymphomagenesis was formally proven by overexpressing a Pim-1 transgene in lymphoid cells. The transgene induces a low incidence of T cell lymphomas and an increased susceptibility to chemically (ENU) and virally (MoMuLV) induced lymphomas.

Requirement for a functional Rb-1 gene in murine development.

Human retinoblastomas can occur both as hereditary and as sporadic cases. Knudson's proposal that they result from two mutational events, of which one is present in the germ line in hereditary cases, has been confirmed by more recent molecular analysis, which has shown both events to involve loss or mutational inactivation of the same gene, RB-1 (ref. 2).