Abstract:
BACKGROUND:Mevalonate kinase deficiency (MKD) is a rare genetic autoinflammatory disease caused by blocking of the enzyme mevalonate kinase in the pathway of cholesterol and isoprenoids. The pathogenic mechanism originating an immune response in MKD patients has not been clearly understood. METHODS:We investigated the dysregulation of expression of selected cytokines and chemokines in the serum of MKD patients. The results have been compared with those observed in an MKD mouse model obtained by treating the mice with aminobisphosphonate, a molecule that is able to inhibit the cholesterol pathway, mimicking the genetic block characteristic of the disease. RESULTS:Interleukin (IL)-1β, IL-5, IL-6, IL-9, IL-17, granulocyte colony-stimulating factor, monocyte chemotactic protein-1, tumor necrosis factor-α, and IL-4 expression were dysregulated in sera from MKD patients and mice. Moreover, geraniol, an exogenous isoprenoid, when administered to MKD mice, restored cytokines and chemokines levels with values similar to those of untreated mice. CONCLUSION:Our findings, which were obtained in patients and a mouse model mimicking the human disease, suggest that these cytokines and chemokines could be MKD specific and that isoprenoids could be considered as potential therapeutic molecules. The mouse model, even if with some limitations, was robust and suitable for routine testing of potential MKD drugs.
journal_name
Pediatr Resjournal_title
Pediatric researchauthors
Marcuzzi A,Zanin V,Kleiner G,Monasta L,Crovella Sdoi
10.1038/pr.2013.96subject
Has Abstractpub_date
2013-09-01 00:00:00pages
266-71issue
3eissn
0031-3998issn
1530-0447pii
pr201396journal_volume
74pub_type
杂志文章abstract::The pathophysiology of kwashiorkor, a severe edematous manifestation of malnutrition, is still poorly understood. The syndrome is, however, known to be associated with alterations in redox metabolism. To further elucidate the role of oxidative stress in kwashiorkor, we carried out a longitudinal study on the major blo...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-200102000-00018
更新日期:2001-02-01 00:00:00
abstract::To determine whether epidermal growth factor (EGF) or EGF-like transforming growth factors (TGFs) are present in ovine fetal tissues, we have tested acid-ethanol extracts of ovine fetal kidney for the ability to induce anchorage-independent growth of normal rat kidney fibroblasts in soft agar and to compete with 125I-...
journal_title:Pediatric research
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doi:10.1203/00006450-198711000-00026
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abstract::We banded the trachea of 4-wk-old male rats and studied lung growth, lung morphometry, and static pulmonary mechanics 4 wk later. We compared the experimental animals to sham-operated male littermates of the same age, 8-wk-old normal male littermates, and weight-matched rats of a younger age. Tracheal banded animals w...
journal_title:Pediatric research
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doi:10.1203/00006450-198103000-00014
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journal_title:Pediatric research
pub_type: 杂志文章,meta分析
doi:10.1038/s41390-019-0409-5
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abstract::DGCR6 is the most centromeric gene in the human DiGeorge critical region and is the only gene in the region with a second functional copy on a repeat localized more distally on chromosome 22. We isolated the chicken ortholog of DGCR6 and showed an embryonic expression pattern that is initially broad but becomes gradua...
journal_title:Pediatric research
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更新日期:2004-09-01 00:00:00
abstract::A patient is reported who presented in the newborn period with an unusual combination of congenital lactic acidosis and bilateral calcifications in the adrenal medulla, visible on standard abdominal x-ray and ultrasound examination. At birth, the proband was hypotonic and dystrophic. She developed respiratory insuffic...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e3181b40a80
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abstract::Immunologic consequences of exposure to HIV-1 in utero are still poorly understood. This study investigates relationships between type-1 [interferon-gamma (IFN-gamma)] and type-2 (IL-10) cytokine production and maternal-infant HIV-1 transmission. Cord blood leukocytes from deliveries of 71 HIV-1-infected and 11 uninfe...
journal_title:Pediatric research
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doi:10.1203/00006450-200109000-00018
更新日期:2001-09-01 00:00:00
abstract::All-trans retinoic acid (ATRA) stimulates platelet-derived growth factor (PDGF)-A expression and enhances alveolarization in rat lungs. On d 16 of gestation, pregnant Sprague-Dawley rats were randomly assigned to either a retinoic acid group (intragastric ATRA at 10 mg/kg body weight) or a vehicle group. We punctured ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e31815685b9
更新日期:2007-11-01 00:00:00
abstract::Cancer stem cells (CSC) are recently proposed to be the cancer initiating cells responsible for tumorigenesis and contribute to cancer resistance. Advances have been made in identifying and enriching CSC in leukemia and several solid tumors, including breast, brain and lung cancers. These studies suggest that, like no...
journal_title:Pediatric research
pub_type: 杂志文章,评审
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更新日期:2006-04-01 00:00:00
abstract::A substantial proportion of the "apparently normal" preterm infants exhibit minor and moderate dysfunctions in neuromotor outcome as they grow older. Birth characteristics, minor abnormalities on the neonatal ultrasound scan of the brain, and motor milestones have only limited value in the early detection of these chi...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.PDR.0000170898.60160.09
更新日期:2005-08-01 00:00:00
abstract::Argininosuccinate synthetase and argininosuccinate lyase catalyze the conversion of citrulline to arginine in kidney. Immunohistochemical staining of mouse kidney sections with antibodies to these two enzymes, compared with the staining patterns of known markers for proximal tubules, demonstrated that these enzymes ar...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199102000-00010
更新日期:1991-02-01 00:00:00
abstract::The effects of passive respiratory syncytial virus (RSV) immune serum given as preinoculation prophylaxis, postinoculation prophylaxis, and as therapy on d 5 after inoculation were evaluated in an illness model of RSV infection in BALB/c mice. Pre- and postinoculation prophylaxis reduced RSV replication in lung after ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199308000-00013
更新日期:1993-08-01 00:00:00
abstract::Studies in adult animal and human subjects have suggested that the methylxanthine drugs can delay the onset or attenuate the severity of diaphragmatic fatigue. We have investigated the effect of aminophylline and caffeine on the pressure-generating capacity of the fatigued diaphragm in 1-mo-old piglets. Measurements o...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199211000-00019
更新日期:1992-11-01 00:00:00
abstract::Magnesium-deficient fetuses exhibited malformations (44%), anemia, and edema. Maternal plasma magnesium levels at day 21 of pregnancy reflected the level of dietary magnesium (2.43 +/- 0.09 mg Mg/100 ml, control; 0.74 +/- 0.02 mg Mg/100 ml, deficient). Plasma magnesium levels of deficient fetuses showed similar decrea...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-197706000-00013
更新日期:1977-06-01 00:00:00
abstract:BACKGROUND:To understand the increased susceptibility of preterm neonates to infection. METHODS:A murine listeriosis model using immunohistochemistry, microarray technology, and real-time polymerase chain reaction (PCR). RESULTS:We report that recombinant serum amyloid A (SAA) administered prophylactically 18 h befor...
journal_title:Pediatric research
pub_type: 杂志文章
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更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:The pathogenesis of BPD includes inflammation and oxidative stress in the immature lung. Corticosteroids improve respiratory status and outcome, but the optimal treatment regimen for benefit with low systemic effects is uncertain. METHODS:In a pilot dose escalation trial, we administered ≤5 daily doses of b...
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pub_type: 杂志文章
doi:10.1038/s41390-020-01343-z
更新日期:2021-01-19 00:00:00
abstract::Neutrophils contribute to ischemic brain injury in adult animals. The role of neutrophils in perinatal hypoxic-ischemic (HI) brain injury is unknown. Allopurinol reduces neutrophil accumulation after tissue ischemia and is protective against HI brain injury. This study was designed to investigate how neutrophils contr...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199705000-00002
更新日期:1997-05-01 00:00:00
abstract:BACKGROUND:The basal ganglia are vulnerable to injury during cardiac arrest. Movement disorders are a common morbidity in survivors. Yet, neuronal motor network changes post-arrest remain poorly understood. METHODS:We compared function of the motor network in adult rats that, during postnatal week 3, underwent 9.5 min...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/pr.2015.114
更新日期:2015-10-01 00:00:00
abstract::Lipase activities were measured at pH 4 and pH 8 in the placentas of rats made diabetic by streptozotocin treatment and also in the placentas of women classified as having 1) impaired glucose tolerance or type 2 diabetes, 2) type 1 diabetes with no associated vascular complication, and 3) type 1 diabetes with associat...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199112000-00009
更新日期:1991-12-01 00:00:00
abstract:INTRODUCTION:Current advances in neonatology have improved survival among preterm and low-birth-weight infants. However, the risk of neonatal death in preterm infants is much greater than in full-term neonates and is frequently associated with infections. METHODS:Little is known about the immune status of preterm neon...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/pr.2012.6
更新日期:2012-05-01 00:00:00
abstract::Our goal was to determine the relationship between 4 amniotic fluid (AF) proteomic biomarkers (human neutrophil defensins 2 and 1, calgranulins C and A) characteristic of intra-amniotic inflammation, and funisitis and early-onset sepsis in premature neonates. The mass restricted (MR) score was generated from AF obtain...
journal_title:Pediatric research
pub_type: 杂志文章
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journal_title:Pediatric research
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更新日期:2004-08-01 00:00:00
abstract::Labeled choline incorporation into adult rat lung alveolar epithelial cells and adult rat lung fibroblasts in monolayer culture was determined after incubation with insulin (Ins) 10 micrograms/ml, Dexamethasone (Dex) 10(-6)M, or no drug (ND). Incubation periods were 1, 3, 4, and 5 hours. The lecithin (phosphatidyl cho...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198007000-00014
更新日期:1980-07-01 00:00:00
abstract::Mucoid Pseudomonas aeruginosa is an important respiratory pathogen in patients with cystic fibrosis, and once acquired is virtually impossible to eradicate. Although mucoid P. aeruginosa is generally believed to be resistant to phagocytosis, the mechanism is not understood fully. We studied the nonopsonic phagocytosis...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198710000-00013
更新日期:1987-10-01 00:00:00
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journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199606000-00021
更新日期:1996-06-01 00:00:00
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journal_title:Pediatric research
pub_type: 杂志文章,评审
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更新日期:2020-08-01 00:00:00
abstract::Programmed proliferative degeneration of the human fetal ductus arteriosus (DA) preceding definite postnatal closure has a large developmental variability and is controlled by several signaling pathways. Among these vascular endothelial growth factor (VEGF) and its receptors (VEGF-Rs) play an important role. Until now...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e318180a375
更新日期:2008-10-01 00:00:00
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journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e318187dd0e
更新日期:2008-12-01 00:00:00
abstract::Branching morphogenesis, defined as growth and branching of epithelial tubules during embryogenesis, is a fundamental feature of renal, lung, mammary gland, submandibular gland, and pancreatic morphogenesis in mammals. Disruption of branching morphogenesis has been demonstrated to result in maldevelopment of some of t...
journal_title:Pediatric research
pub_type: 杂志文章,评审
doi:10.1203/01.PDR.0000085170.44226.DB
更新日期:2003-10-01 00:00:00
abstract::The purpose of the present study was to determine if autoregulation of cerebral blood flow (CBF) is present in the preterm fetal lamb and, if present, to measure the range of mean arterial blood pressure over which autoregulation exists. Thirty-seven measurements of CBF were made in seven preterm fetal lambs (118-122 ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198502000-00001
更新日期:1985-02-01 00:00:00