Interleukin-10 Produced by Myeloid-Derived Suppressor Cells Provides Protection to Carbapenem-Resistant Sequence Type 258 by Enhancing Its Clearance in the Airways.

Carbapenem-resistant sequence type 258 (CRKP-ST258) can cause chronic infections in lungs and airways, with repeated episodes of bacteremia. In this report we addressed whether the recruitment of myeloid cells producing the anti-inflammatory cytokine interleukin-10 (IL-10) modulates the clearance of CKRP-ST258 in the lungs and establishes bacterial persistence. Our data demonstrate that during pneumonia caused by a clinical isolate of CRKP-ST258 (KP35) there is an early recruitment of monocyte-myeloid-derived suppressor cells (M-MDSCs) and neutrophils that actively produce IL-10.

Dramatic Reduction in 30-Day Readmissions Through High-Risk Screening and Two-Phase Interdisciplinary Care.

Objectives: Thirty-day readmissions are common, serious, and costly. Most important, often they are preventable. The purpose of this quality improvement study was to evaluate an interdisciplinary, two-phase intervention to reduce 30-day readmissions among high-risk medical patients.

Advancing Clinicopathologic Diagnosis of High-risk Neuroblastoma Using Computerized Image Analysis and Proteomic Profiling.

A subset of patients with neuroblastoma are at extremely high risk for treatment failure, though they are not identifiable at diagnosis and therefore have the highest mortality with conventional treatment approaches. Despite tremendous understanding of clinical and biological features that correlate with prognosis, neuroblastoma at ultra-high risk for treatment failure remains a diagnostic challenge. As a first step towards improving prognostic risk stratification within the high-risk group of patients, we determined the feasibility of using computerized image analysis and proteomic profiling on single slides from diagnostic tissue specimens.

Variant discovery and breakpoint region prediction for studying the human 22q11.2 deletion using BAC clone and whole genome sequencing analysis.

Velo-cardio-facial syndrome/DiGeorge syndrome/22q11.2 deletion syndrome (22q11.2DS) is caused by meiotic non-allelic homologous recombination events between flanking low copy repeats termed LCR22A and LCR22D, resulting in a 3 million base pair (Mb) deletion.

Gestational Hypothyroidism Improves the Ability of the Female Offspring to Clear Streptococcus pneumoniae Infection and to Recover From Pneumococcal Pneumonia.

Maternal thyroid hormones are essential for proper fetal development. A deficit of these hormones during gestation has enduring consequences in the central nervous system of the offspring, including detrimental learning and impaired memory. Few studies have shown that thyroid hormone deficiency has a transient effect in the number of T and B cells in the offspring gestated under hypothyroidism; however, there are no studies showing whether maternal hypothyroidism during gestation impacts the response of the offspring to infections.

Mammalian TBX1 preferentially binds and regulates downstream targets via a tandem T-site repeat.

Haploinsufficiency or mutation of TBX1 is largely responsible for the etiology of physical malformations in individuals with velo-cardio-facial/DiGeorge syndrome (VCFS/DGS/22q11.2 deletion syndrome). TBX1 encodes a transcription factor protein that contains an evolutionarily conserved DNA binding domain termed the T-box that is shared with other family members.

GJB2 mutation spectrum in 209 hearing impaired individuals of predominantly Caribbean Hispanic and African descent.

Objective: The purpose of the study is to determine whether Caribbean Hispanic and African admixture populations have a paucity of mutations in GJB2, encoding connexin 26.

Methods: We reported the paucity of mutations in GJB2 and deletions in GJB6 in Caribbean Hispanic and African admixture populations in the Bronx, NY, in 2007 [1]. We have now collected 102 additional probands with non-syndromic sensorineural hearing impairment (NSHI), for a total of 209.

Mitochondrial dysfunction in SOD1G93A-bearing astrocytes promotes motor neuron degeneration: prevention by mitochondrial-targeted antioxidants.

Mitochondrial dysfunction and oxidative stress contribute to motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Recent reports indicate that astrocytes expressing the mutations of superoxide dismutase-1 (SOD1) may contribute to motor neuron injury in ALS. Here, we provide evidence that mitochondrial dysfunction in SOD1(G93A) rat astrocytes causes astrocytes to induce apoptosis of motor neurons.

Nogo receptor antagonizes p75NTR-dependent motor neuron death.

The Nogo-66 receptor (NgR) plays a critical role in restricting axon regeneration in the central nervous system. This inhibitory action is in part mediated by a neuronal receptor complex containing p75NTR, a multifunctional receptor also well known to trigger cell death upon binding to neurotrophins such as NGF. In the present study, we show that Pep4 and NEP1-40, which are two peptides derived from the Nogo-66 sequence that modulate NgR-mediated neurite outgrowth inhibition, prevent NGF-stimulated p75NTR-dependent death of cultured embryonic motor neurons.

Astrocyte activation by fibroblast growth factor-1 and motor neuron apoptosis: implications for amyotrophic lateral sclerosis.

Fibroblast growth factor-1 (FGF1 or acidic FGF) is highly expressed in motor neurons. FGF-1 is released from cells by oxidative stress, which might occur from SOD-1 aberrant function in amyotrophic lateral sclerosis (ALS). Although FGF-1 is known to be neuroprotective after spinal cord injury or axotomy, we found that FGF-1 could activate spinal cord astrocytes in a manner that decreased motor neuron survival in co-cultures.

Astrocytic production of nerve growth factor in motor neuron apoptosis: implications for amyotrophic lateral sclerosis.

Reactive astrocytes frequently surround degenerating motor neurons in patients and transgenic animal models of amyotrophic lateral sclerosis (ALS). We report here that reactive astrocytes in the ventral spinal cord of transgenic ALS-mutant G93A superoxide dismutase (SOD) mice expressed nerve growth factor (NGF) in regions where degenerating motor neurons expressed p75 neurotrophin receptor (p75(NTR)) and were immunoreactive for nitrotyrosine. Cultured spinal cord astrocytes incubated with lipopolysaccharide (LPS) or peroxynitrite became reactive and accumulated NGF in the culture medium.

Involvement of nitric oxide on kainate-induced toxicity in oligodendrocyte precursors.

The vulnerability of oligodendrocytes to excitatory amino acids may account for the pathology of white matter occurring following hypoxia/ischemia or autoimmune attack. Here, we examined the vulnerability of immature oligodendrocytes (positively labeled by galactocerobroside-C and not expressing myelin basic protein) from neonatal rat spinal cord to kainate, an agonist of excitatory amino acid receptors that induces long-lasting inward currents in immature oligodendrocytes. In particular, we studied whether kainate toxicity was linked to the endogenous production of nitric oxide.