80 research outputs found
Inflammation Triggers Emergency Granulopoiesis through a Density-Dependent Feedback Mechanism
Normally, neutrophil pools are maintained by homeostatic mechanisms that require
the transcription factor C/EBPα. Inflammation, however, induces neutrophilia
through a distinct pathway of “emergency” granulopoiesis that is
dependent on C/EBPβ. Here, we show in mice that alum triggers emergency
granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R
neutralization impairs proliferative responses of hematopoietic stem and
progenitor cells (HSPC) to alum, but also abrogates the acute mobilization of BM
neutrophils, raising the possibility that HSPC responses to inflammation are an
indirect result of the exhaustion of BM neutrophil stores. The induction of
neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1,
elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic
responses indistinguishable from those induced by adjuvant. Notably, C/EBPβ,
thought to be necessary for enhanced generative capacity of BM, is dispensable
for increased proliferation of HSPC to alum or neutropenia, but plays a role in
terminal neutrophil differentiation during granulopoietic recovery. We conclude
that alum elicits a transient increase in G-CSF production via IL-1RI for the
mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF
for accelerated granulopoiesis
Prenatal exposure to cigarette smoke or alcohol and cerebellum volume in attention-deficit/hyperactivity disorder and typical development
Prenatal exposure to teratogenic substances, such as nicotine or alcohol, increases the risk of developing attention-deficit/hyperactivity disorder (ADHD). To date, studies examining this relationship have used symptom scales as outcome measures to assess the effect of prenatal exposure, and have not investigated the neurobiological pathways involved. This study explores the effect of prenatal exposure to cigarettes or alcohol on brain volume in children with ADHD and typically developing controls. Children with ADHD who had been exposed prenatally to either substance were individually matched to children with and without ADHD who had not been. Controls who had been exposed prenatally were also individually matched to controls who had not been. For prenatal exposure to both smoking and alcohol, we found a pattern where subjects with ADHD who had been exposed had the smallest brain volumes and unexposed controls had the largest, with intermediate volumes for unexposed subjects with ADHD. This effect was most pronounced for cerebellum. A similar reduction fell short of significance for controls who had been exposed to cigarettes, but not alcohol. Our results are consistent with an additive effect of prenatal exposure and ADHD on brain volume, with the effects most pronounced for cerebellum
An Integrative multi-lineage model of variation in leukopoiesis and acute myelogenous leukemia
Current understanding of hypospadias: relevance of animal models
Hypospadias is a congenital abnormality of the penile urethra with an incidence of approximately 1:200-1:300 male births, which has doubled over the past three decades. The aetiology of the overwhelming majority of hypospadias remains unknown but appears to be a combination of genetic susceptibility and prenatal exposure to endocrine disruptors. Reliable animal models of hypospadias are required for better understanding of the mechanisms of normal penile urethral formation and hence hypospadias. Mice and/or rats are generally used for experimental modelling of hypospadias, however these do not fully reflect the human condition. To use these models successfully, researchers must understand the similarities and differences between mouse, rat and human penile anatomy as well as the normal morphogenetic mechanisms of penile development in these species. Despite some important differences, numerous features of animal and human hypospadias are shared: the prevalence of distal penile malformations; disruption of the urethral meatus; disruption of urethra-associated erectile bodies; and a common mechanism of impaired epithelial fusion events. Rat and mouse models of hypospadias are crucial to our understanding of hypospadias to ultimately reduce its incidence through better preventive strategies
Experiments with a mechanical skin scuffing device
SIGLEAvailable from British Library Document Supply Centre- DSC:3554.5012(SCAE-DN--30) / BLDSC - British Library Document Supply CentreGBUnited Kingdo
Access to interproximal tooth surfaces by different bristle designs and stiffnesses of toothbrushes
Evaluation of the effect of EDTA, EDTAC and citric acid on the microhardness of root dentine
- …