Improvement of bone properties in children with osteogenesis imperfecta after pamidronate: a bone biopsy study.

OI, or bone brittle disease, is characterized by increased mineralization of bone matrix independently of clinical severity. So, a beneficial effect of antiresorptive treatments such as bisphosphonates (BP) is questionable. We aim to compare the bone matrix characteristics before and after BP pamidronate (PAM).

[Urinary incontinence in children].

URINARY INCONTINENCE IN CHILDREN. Urinary incontinence in children and adolescents is most often of functional origin. Questioning and clinical examination with a bladder diary should look for underlying urological or neurological causes.

Acute axonal neuropathy subtype of Guillain Barré syndrome in a French pediatric series: Adequate follow-up may require repetitive electrophysiological studies.

Different subtypes of Guillain Barré Syndromes (GBSs) are defined by their electrophysiological characteristics, acute inflammatory demyelinating neuropathy (AIDP), and acute motor/motor-sensory axonal forms (AMAN/AMSAN) with either reversible nerve conduction failure (RCF) or axonal degeneration. Our aim was to describe initial clinical and electrophysiological characteristics of axonal forms of GBS in a pediatric population and their short- and long-term evolution. Electroneuromyogram (ENMG) results were collected at diagnosis and at two months of evolution and interpreted using the recently proposed pattern of RCF vs axonal degeneration.

Unilateral predominance of abnormal movements: A characteristic feature of the pediatric anti-NMDA receptor encephalitis?

Anti-NMDA receptor encephalitis is a treatable autoimmune disease characterized by cognitive, motor and psychiatric features that primarily affects young adults and children. We present a case of a 7-year-old boy with asymmetrical (mainly right hemibody) and abnormal polymorphic movements without concomitant scalpictal EEG changes but had background slowing predominating over the left hemisphere. This report illustrates previous descriptions of asymmetric presentation of abnormal movements in pediatric anti-NMDA receptor encephalitis and emphasizes the importance of video-EEG interpreted within the overall clinical context, to differentiate epileptic from non-epileptic abnormal movements in patients with autoimmune encephalitis.

Exploring the Early Organization and Maturation of Linguistic Pathways in the Human Infant Brain.

Linguistic processing is based on a close collaboration between temporal and frontal regions connected by two pathways: the "dorsal" and "ventral pathways" (assumed to support phonological and semantic processing, respectively, in adults). We investigated here the development of these pathways at the onset of language acquisition, during the first post-natal weeks, using cross-sectional diffusion imaging in 21 healthy infants (6-22 weeks of age) and 17 young adults. We compared the bundle organization and microstructure at these two ages using tractography and original clustering analyses of diffusion tensor imaging parameters.

Extracranial vertebral artery dissection in children: natural history and management.

Introduction: The objective of this study is to describe clinical and imaging presentation and outcome in extracranial vertebral artery dissection.

Methods: Single-centre retrospective study over a 14-year period included 20 consecutive patients under the age of 16 years with extracranial vertebral artery dissection. The diagnosis was based on vascular imaging performed at the acute phase and clinical symptoms.

Low glucose microenvironment of normal kidney cells stabilizes a subset of messengers involved in angiogenesis.

As glucose is a mandatory nutrient for cell proliferation and renewal, it is suspected that glucose microenvironment is sensed by all cell types to regulate angiogenesis. Several glucose-sensing components have been partially described to respond to high glucose levels. However, little is known about the response to low glucose.

TRIM8 anti-proliferative action against chemo-resistant renal cell carcinoma.

In some tumours, despite a wild-type p53 gene, the p53 pathway is inactivated by alterations in its regulators or by unknown mechanisms, leading to resistance to cytotoxic therapies. Understanding the mechanisms of functional inactivation of wild-type p53 in these tumours may help to define prospective targets for treating cancer by restoring p53 activity. Recently, we identified TRIM8 as a new p53 modulator, which stabilizes p53 impairing its association with MDM2 and inducing the reduction of cell proliferation.

Parents' behavior in response to infant crying: abusive head trauma education.

Abusive head trauma (AHT) is still too common, and probably underestimated. It is the leading cause of death from child abuse. Crying is thought to contribute to the act of shaking.

Conventional techniques to monitor mitochondrial oxygen consumption.

Following several key discoveries on hypoxia-inducible factors, we have observed an explosion of studies investigating how the hypoxic microenvironment provokes bioenergetic alterations. This is particularly relevant for cancer cells, as they are often exposed to hypoxic conditions in the course of tumor progression. Thus, interest in the measurement of oxygen consumption at the tissue, cell, or mitochondrion level has been revived.

Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence.

Senescence is involved in various pathophysiological conditions. Besides loss of retinoblastoma and p53 pathways, little is known about other pathways involved in senescence. Here we identify two calcium channels; inositol 1,4,5-trisphosphate receptor, type 2 (ITPR2) (also known as inositol 1,4,5-triphosphate receptor 2 (IP3R2)) and mitochondrial calcium uniporter (MCU) as new senescence regulators in a loss-of-function genetic screen.

Repression of PLA2R1 by c-MYC and HIF-2alpha promotes cancer growth.

Loss of secreted phospholipase A2 receptor (PLA2R1) has recently been found to render human primary cells more resistant to senescence whereas increased PLA2R1 expression is able to induce cell cycle arrest, cancer cell death or blockage of cancer cell transformation in vitro, suggesting that PLA2R1 displays tumor suppressive activities. Here we report that PLA2R1 expression strongly decreases in samples of human renal cell carcinoma (RCC). Knockdown of PLA2R1 increases renal cancer cell tumorigenicity supporting a role of PLA2R1 loss to promote in vivo RCC growth.

Glucose metabolism and hexosamine pathway regulate oncogene-induced senescence.

Oncogenic stress-induced senescence (OIS) prevents the ability of oncogenic signals to induce tumorigenesis. It is now largely admitted that the mitogenic effect of oncogenes requires metabolic adaptations to respond to new energetic and bio constituent needs. Yet, whether glucose metabolism affects OIS response is largely unknown.

The CXCL7/CXCR1/2 axis is a key driver in the growth of clear cell renal cell carcinoma.

Mutations in the von Hippel-Lindau gene upregulate expression of the central angiogenic factor VEGF, which drives abnormal angiogenesis in clear cell renal cell carcinomas (ccRCC). However, the overexpression of VEGF in these tumors was not found to correlate with overall survival. Here, we show that the proangiogenic, proinflammatory cytokine CXCL7 is an independent prognostic factor for overall survival in this setting.

PLA2R1 mediates tumor suppression by activating JAK2.

Little is known about the physiological role of the phospholipase A2 receptor (PLA2R1). PLA2R1 has been described as regulating the replicative senescence, a telomerase-dependent proliferation arrest. The downstream PLA2R1 signaling and its role in cancer are currently unknown.

PLA2R1 kills cancer cells by inducing mitochondrial stress.

Little is known about the biological functions of the phospholipase A2 receptor (PLA2R1) except that it has the ability to bind a few secreted phospholipases A2 (sPLA2's). We have previously shown that PLA2R1 regulates senescence in normal human cells. In this study, we investigated the ability of PLA2R1 to control cancer cell growth.

Early electro-clinical features may contribute to diagnosis of the anti-NMDA receptor encephalitis in children.

Objective: To describe initial and follow-up electroencephalographic (EEG) characteristics in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis.

Methods: Consecutive polygraphic video-EEG recordings were analyzed in nine pediatric patients with anti-NMDAR encephalitis at the initial stage of the disease and during the intermediate period until motor recovery. EEG characteristics in waking and sleep stages as well as EEG correlates of abnormal movements are described.

Acceleration of clear cell renal cell carcinoma growth in mice following bevacizumab/Avastin treatment: the role of CXCL cytokines.

The anti-VEGF targeted antibody bevacizumab (BVZ) has been approved for treating renal cell carcinomas (RCCs). Although BVZ increases the progression-free survival of patients with metastatic RCC, the effect on overall survival is poor. To gain insight into the limited efficacy of BVZ on overall survival, we analyzed patient samples of RCC for angiogenic factors that may participate in escape from anti-VEGF therapy.

HIF and reactive oxygen species regulate oxidative phosphorylation in cancer.

A decrease in oxidative phosphorylation (OXPHOS) is characteristic of many cancer types and, in particular, of clear cell renal carcinoma (CCRC) deficient in von Hippel-Lindau (vhl) gene. In the absence of functional pVHL, hypoxia-inducible factor (HIF) 1-alpha and HIF2-alpha subunits are stabilized, which induces the transcription of many genes including those involved in glycolysis and reactive oxygen species (ROS) metabolism. Transfection of these cells with vhl is known to restore HIF-alpha subunit degradation and to reduce glycolytic genes transcription.

Clonal expansion of mutated mitochondrial DNA is associated with tumor formation and complex I deficiency in the benign renal oncocytoma.

Mutations in mitochondrial DNA (mtDNA) are frequent in cancers but it is not yet clearly established whether they are modifier events involved in cancer progression or whether they are a consequence of tumorigenesis. Here we show a benign tumor type in which mtDNA mutations that lead to complex I (CI) enzyme deficiency are found in all tumors and are the only genetic alteration detected. Actually renal oncocytomas are homogeneous tumors characterized by dense accumulation of mitochondria and we had found that they are deficient in electron transport chain complex I (CI, NADH-ubiquinone oxidoreductase).

Actuality of Warburg's views in our understanding of renal cancer metabolism.

More than 50 years ago, Warburg proposed that the shift in glucose metabolism from oxidative phosphorylation (OXPHOS) to glycolysis occurring in spite of an adequate oxygen supply was at the root of cancer. This hypothesis often disregarded over the following years has recently stirred up much interest due to progress made in cancer genetics and proteomics. Studies related to renal cancers have been particularly informative to understand how abnormal use of glucose and decrease in OXPHOS are linked to cell proliferation in tumors.

Mitochondria and reactive oxygen species in renal cancer.

In most cancer cells, the ATP necessary for survival and proliferation is derived from glycolysis rather than from oxidative phosphorylations (OXPHOS) even when oxygen supply would be adequate to sustain them. This phenomenon, named "aerobic glycolysis" by Warburg many years ago, can now be explained by a mechanism up-regulating the expression of genes involved in glucose transport, glucose metabolism, lactate formation and exit from the cell. In clear cell renal carcinoma, this mechanism is due to the stabilization of the hypoxia-inducible transcription factor HIF occurring when the tumor suppressor gene vhl is invalidated.

Inhibition of cytochrome c oxidase subunit 4 precursor processing by the hypoxia mimic cobalt chloride.

Cobalt is often used as a hypoxia mimic in cell culture, because it stabilizes the alpha subunits of the transcription factor, HIF (hypoxia-inducible factor). We have previously shown that HIF stabilization due to a deficiency of the von Hippel Lindau protein (pVHL) in clear cell renal carcinoma (CRCC) was correlated to a down-regulation of oxidative phosphorylation. To better understand this mechanism, we have used CoCl2 in CRCC expressing stably transfected vhl.

Physiological oxygenation status is required for fully differentiated phenotype in kidney cortex proximal tubules.

Hypoxia has been suspected to trigger transdifferentiation of renal tubular cells into myofibroblasts in an epithelial-to-mesenchymal transition (EMT) process. To determine the functional networks potentially altered by hypoxia, rat renal tubule suspensions were incubated under three conditions of oxygenation ranging from normoxia (lactate uptake) to severe hypoxia (lactate production). Transcriptome changes after 4 h were analyzed on a high scale by restriction fragment differential display.