Abstract:
:The mucopolysaccharidoses (MPS) are inherited metabolic disorders resulting from the defective catabolism of glycosaminoglycans. In this report, we find that the stimulation of MPS connective tissue cells by the inflammatory cytokines causes enhanced secretion of several matrix-degrading metalloproteinases (MMPs). In addition, expression of tissue inhibitor of metalloproteinase-1 was elevated, consistent with the enhanced MMP activity. These findings were not restricted to one particular MPS disorder or species, and are consistent with previous observations in animal models with chemically induced arthritis. Bromodeoxyuridine incorporation studies also revealed that MPS chondrocytes proliferated up to 5-fold faster than normal chondrocytes, and released elevated levels of transforming growth factor-beta, presumably to counteract the marked chondrocyte apoptosis and matrix degradation associated with MMP expression. Despite this compensatory mechanism, studies of endochondral ossification revealed a reduction in chondro-differentiation in the growth plates. Thus, although MPS chondrocytes grew faster, most of the newly formed cells were immature and could not mineralize into bone. Our studies suggest that altered MMP expression, most likely stimulated by inflammatory cytokines and nitric oxide, is an important feature of the MPS disorders. These data also identify several proinflammatory cytokines, nitric oxide, and MMPs as novel therapeutic targets and/or biomarkers of MPS joint and bone disease. This information should aid in the evaluation of existing therapies for these disorders, such as enzyme replacement therapy and bone marrow transplantation, and may lead to the development of new therapeutic approaches.
journal_name
Pediatr Resjournal_title
Pediatric researchauthors
Simonaro CM,D'Angelo M,Haskins ME,Schuchman EHdoi
10.1203/01.PDR.0000156510.96253.5Asubject
Has Abstractpub_date
2005-05-01 00:00:00pages
701-7issue
5 Pt 1eissn
0031-3998issn
1530-0447pii
01.PDR.0000156510.96253.5Ajournal_volume
57pub_type
杂志文章abstract::Necrotizing enterocolitis (NEC) remains among the most common and devastating diseases in neonates. Despite advances in neonatal clinical care, specific treatment strategies and diagnostic modalities remain lacking. As a result, morbidity and mortality remain high. Improved understanding of the pathogenesis of NEC has...
journal_title:Pediatric research
pub_type: 杂志文章,评审
doi:10.1038/s41390-020-1077-1
更新日期:2020-08-01 00:00:00
abstract::Thoracoabdominal asynchrony (TAA) and chest wall distortion (CWD) are commonly seen in preterm infants secondary to a highly compliant rib cage and poor compensation of distorting forces by inspiratory rib cage muscles. Continuous positive airway pressure (CPAP) reduces TAA and CWD by stenting the chest wall. We hypot...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-200102000-00008
更新日期:2001-02-01 00:00:00
abstract::Chenodeoxycholic acid labeled with 2H in the 11 and positions was prepared by catalytic reduction of delta 11-12 unsaturated derivatives of cholic acid. To validate the use of this stable isotope for the determination of bile acid kinetics by isotope dilution, it was administered to seven normal male volunteers simult...
journal_title:Pediatric research
pub_type: 杂志文章
doi:
更新日期:1975-10-01 00:00:00
abstract::Respiratory distress syndrome (RDS) due to surfactant deficiency is the most common cause of respiratory failure in preterm infants. Tremendous progress has been made since the original description that surfactant deficiency is the major cause of RDS. Surfactant therapy has been extensively studied in preterm infants ...
journal_title:Pediatric research
pub_type: 历史文章,杂志文章,评审
doi:10.1038/pr.2016.203
更新日期:2017-01-01 00:00:00
abstract::Changes in high-density lipoprotein (HDL) subclass distribution were evaluated in a group of premature infants during the early postnatal period to ascertain whether enteral feeding brought about a rapid shift from neonatal to adult-like distributions. All infants were fed a combination of breast milk and formula. Cor...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198806000-00001
更新日期:1988-06-01 00:00:00
abstract::The short-term (0-48 h) effects of maternal betamethasone administration on computerized fetal heart rate (FHR) parameters were studied in 36 pregnancies at increased risk for preterm delivery. FHR was recorded for 90 min immediately before the start of betamethasone treatment and again at 6-h intervals during the nex...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.PDR.0000155948.83570.EB
更新日期:2005-04-01 00:00:00
abstract::The relationship between cerebral blood flow (CBF) and the evolution of brain edema was investigated in an experimental model of perinatal hypoxic-ischemic brain damage. Seven-d postnatal rats were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen at 37 degrees C. This in...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199005000-00007
更新日期:1990-05-01 00:00:00
abstract::Experiments were done to investigate the effects of increased inspired oxygen on the arousal response from sleep to upper airway obstruction in 10 newborn lambs. Each lamb was anesthetized and instrumented for recordings of electrocorticograms, electrooculogram, nuchal and diaphragm electromyograms, and measurements o...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198702000-00002
更新日期:1987-02-01 00:00:00
abstract::The presence of high concentrations of sodium in the sweat of patients with cystic fibrosis is widely accepted by all investigators as one of the most important manifestations of the genetic defect. However, the simple means of sweat collection utilized for diagnostic purposes has been extended to the biochemical and ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198508000-00020
更新日期:1985-08-01 00:00:00
abstract::Respiratory parameters of skeletal muscle were determined in permeabilized muscle fibers by adapting a technique described by Veksler et al. for cardiac fibers (Biochim Biophys Acta, 892:191-196, 1987). This method consists of the permeabilization of muscle fibers by saponin by allowing respiratory substrates and inhi...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199207000-00004
更新日期:1992-07-01 00:00:00
abstract::We have shown that cerebellar injury in the premature infant is followed by significant growth impairment of the contralateral cerebral hemisphere evident as early as term adjusted age. In this study, we hypothesize that this remote growth restriction is region specific in the cerebrum. In a prospectively enrolled coh...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e3181e1d032
更新日期:2010-08-01 00:00:00
abstract::Although obstructive nephropathy is a frequent cause of renal insufficiency in infancy, factors influencing adaptation to chronic partial ureteral obstruction (CPUO) are poorly understood. Guinea pigs were subjected to unilateral CPUO within the first 2 days of life (Group I) and microsphere studies were performed at ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198412000-00008
更新日期:1984-12-01 00:00:00
abstract::Neutrophils (PMN) from newborn calves generate significantly less superoxide anion (O2-) than do their adult counterparts after stimulation with direct protein kinase C agonists. To better understand this observation, we compared the activity and kinetics of NADPH oxidase in membrane fractions from phorbol 12-myristat...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199010000-00005
更新日期:1990-10-01 00:00:00
abstract::The zeta subunit of the CD3 T-cell receptor complex and the major histocompatibility complex class 1 (MHC-I) are important not only for the immune response to antigens, they also function as signal molecules in the brain, where they play a role in the postnatal maturation process. The expression of these molecules can...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.pdr.0000238246.74817.a0
更新日期:2006-10-01 00:00:00
abstract::The objective of this study was to determine the plasma leptin concentrations in twin pregnancies in relation to chorionicity and discordant fetal growth. We studied 53 twin pregnancies of which 26 had growth discordance of > or =20% and 27 were concordant for growth (discordance of < or =10%). Paired maternal and fet...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-200105000-00010
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND:Early recognition of patients at risk for sepsis is paramount to improve clinical outcomes. We hypothesized that subtle signatures of illness are present in physiological and biochemical time series of pediatric-intensive care unit (PICU) patients in the early stages of sepsis. METHODS:We developed multivar...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/s41390-019-0518-1
更新日期:2019-11-01 00:00:00
abstract::Young adult macrosomic offspring of streptozotocin-induced mildly hyperglycemic rats exhibit accelerated growth through the first 10 wk of age. At 10 wk, oral glucose loading resulted in elevated plasma insulin and glucose concentrations compared to controls. To assess the mechanism of the abnormal glucose tolerance i...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199107000-00008
更新日期:1991-07-01 00:00:00
abstract::The aim of this study was to produce a neonatal piglet model which, avoiding vessel ligation, exposed the whole animal to hypoxia and produced dose-dependent clinical encephalopathy and neuropathologic damage similar to that seen after birth asphyxia. Twenty-three piglets were halothane-anesthetized. Hypoxia was induc...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199611000-00014
更新日期:1996-11-01 00:00:00
abstract::To study the normal development of blood coagulation factor activities in a growing fetus while avoiding the effects of labor and delivery, a chronic fetal lamb model was developed in which serial blood samples from 10 fetuses were studied during the third trimester of pregnancy and 24 hr after birth. Under operating ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198107000-00014
更新日期:1981-07-01 00:00:00
abstract::We have shown previously that polynucleotides enhance in vitro antibody and Ig production in response to T-dependent antigens in mice and augment Ig production by adult human peripheral blood mononuclear cells. Herein, we report their effects on umbilical cord blood mononuclear cells (CBMNC) obtained from full-term ba...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199311000-00003
更新日期:1993-11-01 00:00:00
abstract::Bone disease is an important complication among very low birth weight (VLBW, <1500 g) infants. In adults, osteoporosis is associated with polymorphisms of vitamin D receptor (VDR), estrogen receptor (ER), and collagen Ialpha1 (COLIA1) genes. However, limited information is available regarding the role of these polymor...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.pdr.0000242340.45676.5d
更新日期:2006-11-01 00:00:00
abstract::The mechanisms of how glutamine benefits critically ill patients have not been established. The purpose of this study was to determine the effects of dietary and endogenously produced glutamine on small intestinal morphology using light and transmission electron microscopy in artificially reared rat pups. It was hypot...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-200209000-00021
更新日期:2002-09-01 00:00:00
abstract::We analyzed by means of immunoblot technique the patterns of antibodies binding to polypeptides of Borrelia burgdorferi B31 in the sera of 21 children with different stages of Lyme disease. All sera but one recognized the flagellar protein 41 kD and all but two the 83-kD protein. The number of proteins recognized rose...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-198910000-00019
更新日期:1989-10-01 00:00:00
abstract::This study reports the Hb, erythropoietin (Epo), and reticulocyte course at different postnatal ages (range, 8-83 d) of 56 blood samples from 30 newborns (range, one or two blood samples from each newborn) with erythroblastosis fetalis (18 intrauterine transfused (IUTd) and 12 non-IUTd). Hb, Epo, and reticulocyte valu...
journal_title:Pediatric research
pub_type: 临床试验,杂志文章
doi:10.1203/00006450-199608000-00027
更新日期:1996-08-01 00:00:00
abstract:INTRODUCTION:To examine the immune-modulatory effects of probiotics during early infancy, Bifidobacterium breve M-16V (B. breve) was administered to rat pups during the newborn or weaning period, and the expression of inflammatory genes was investigated using a cDNA microarray and real-time PCR. RESULTS:After B. breve...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/pr.2011.11
更新日期:2012-01-01 00:00:00
abstract::Bronchopulmonary dysplasia (BPD) is a common pulmonary complication in preterm infants that leads to fibrosis of the bronchoalveolar walls and often to severe clinical consequences. Type III collagen is deposited early in progressive fibrosis. Because the N-terminal propeptide of type III collagen (PIIINP), a by-produ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/00006450-199204000-00007
更新日期:1992-04-01 00:00:00
abstract::Injuries continue to be the leading cause of morbidity and mortality for children, adolescents, and young adults aged 1-24 years in industrialized countries in the twenty-first century. In this age group, injuries cause more fatalities than all other causes combined in the United States (U.S.). Importantly, many of th...
journal_title:Pediatric research
pub_type: 杂志文章,评审
doi:10.1038/s41390-019-0549-7
更新日期:2020-01-01 00:00:00
abstract::Up to 20% of pregnant women smoke and there is indirect evidence that certain tobacco-specific metabolites can cross the placental barrier and are genotoxic to the fetus. The presence of micronuclei results from chromosome damage and reflects the degree of underlying genetic instability. Fetal blood was obtained from ...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/01.pdr.0000228327.63820.41
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND:Oral propranolol, a nonselective β-blocker, is able to reduce the progression of retinopathy of prematurity in newborns, but it appeared unsafe. This study aimed to find, in rabbits, a propranolol eye drop concentration able to induce lower plasma but higher retinal concentrations than those obtained after o...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1038/pr.2014.108
更新日期:2014-10-01 00:00:00
abstract::Music is widely used to enhance well-being. We wished to assess music's effect on pediatric oncology outpatients. Patients who had leukemia and were in maintenance or consolidation outpatient treatment served as their own control at two visits. At visit 1, children rested for 20 min; at visit 2, for 20 min they listen...
journal_title:Pediatric research
pub_type: 杂志文章
doi:10.1203/PDR.0b013e318174e6fb
更新日期:2008-07-01 00:00:00