Abstract:
:We recently reported that PAF acetylhydrolase (PAF-Ah) mRNA level and PAF-Ah activity in lamb lungs are up-regulated in the immediate newborn period, thereby facilitating the fall in postnatal PAF levels as well as a fall in pulmonary vascular resistance (B. O. Ibe, F. C. Sardar, and J. U. Raj, Mol Genet Metab 69:46-55, 2000). We have studied hypoxia effects on PAF synthesis and PAF-Ah activity in fetal lamb pulmonary arterial smooth muscle cells (FPASMC) and endothelial cells (FPAEC). We also studied PAF synthesis by platelets, and PAF-Ah activity in plasma of perinatal lambs at different ages. PAF synthesis (means +/- SEM, pmol/10(6) cells) by SMC in baseline was 168 +/- 27 and increased 3-fold on stimulation with A23187. Hypoxia augmented A23187-stimulated PAF synthesis by 30%. In FPAEC, baseline synthesis was 0.54 +/- 0.062 and increased 3-fold to 1.72 +/-.34. Hypoxia had no effect on PAF synthesis by EC. FPASMC produced over 300-fold more PAF than FPAEC. PAF synthesis by platelets was 47.02 +/- 7.1, 63.4 +/- 6.6, 71.5 +/- 9.9, and 62.2 +/- 5.2 for fetal, and newborn lambs <2 h, <1 day, and 6-12 days, old, respectively. PAF synthesis by platelets of <1 day-old lambs was different from that of fetal lambs. PAF-Ah activity (nmol lyso-PAF/min/mg protein) by FPASMC in normoxia was 3.41 +/- 0.38 which was 50% higher than the rate in hypoxia. Activity in FPAEC was 1.75 +/- 0.37 which was not different from hypoxia. PAF-Ah activity in fetal lamb plasma was 47.83 +/- 6.87 which was different from 155.32 +/- 12.10, the activity in plasma of newborn <1 day old. Activity in the other perinatal lambs did not differ from fetal or newborn <1 d. Our data suggest that lower pulmonary vascular PAF synthesis in normoxia together with higher PAF-Ah activity during immediate postnatal period is necessary to ensure rapid catabolism of PAF in vivo so as to facilitate postnatal adaptation of the pulmonary and systemic circulations.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Ibe BO,Pham HH,Kääpä P,Raj JUdoi
10.1006/mgme.2001.3253subject
Has Abstractpub_date
2001-11-01 00:00:00pages
385-95issue
3eissn
1096-7192issn
1096-7206pii
S1096-7192(01)93253-6journal_volume
74pub_type
杂志文章abstract:BACKGROUND:Sapropterin dihydrochloride (BH4, tetrahydrobiopterin) can lower plasma phenylalanine (Phe) concentrations for a subset of patients with phenylketonuria (PKU), an inborn error of metabolism. Studies suggest that monoamine neurotransmitter concentrations are low in PKU patients. Sapropterin functions as a cof...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2013.04.017
更新日期:2013-07-01 00:00:00
abstract::Pyruvate dehydrogenase complex (PDC) deficiency is one of the major recognized causes of congenital lactic acidosis. The most common form is due to PDHA 1 gene (Xp22.12) defects. Here, we report the case of a Polynesian girl presenting with delayed neurological development, cortical atrophy, and posterior corpus callo...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2005.08.009
更新日期:2005-12-01 00:00:00
abstract::Canine junctin is a 26-kDa transmembrane protein found in the sarcoplasmic reticulum (SR) membrane in cardiac and skeletal muscle. Junctin has recently been shown to bind directly to calsequestrin, the ryanodine receptor, and triadin. Junctin is thought to play a role in facilitating (and perhaps regulating) Ca(2+) re...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.2000.2966
更新日期:2000-03-01 00:00:00
abstract::Most newborn screening (NBS) laboratories use second-tier molecular tests for cystic fibrosis (CF) using dried blood spots (DBS). The Centers for Disease Control and Prevention's NBS Quality Assurance Program offers proficiency testing (PT) in DBS for CF transmembrane conductance regulator (CFTR) gene mutation detecti...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2011.10.013
更新日期:2012-02-01 00:00:00
abstract::The association of fetal hydrops with Congenital Disorders of Glycosylation (CDG) has been reported previously. Pericardial fluid accumulation and ascites were also observed in a few young patients with CDG type Ia. Here we describe the clinical and biochemical features in three children developing life-threatening ex...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2008.05.005
更新日期:2008-08-01 00:00:00
abstract::Screening for Smith-Lemli-Opitz Syndrome (SLOS) using elevated 7-dehydrocholesterol (7DHC) as a marker is sensitive, but not always specific. Elevations of 7DHC can be seen in patients who do not have a defect in 7-dehydrocholesterol reductase. These results have often been attributed to medication artifacts, but spec...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2013.04.004
更新日期:2013-09-01 00:00:00
abstract::2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency, also known as beta-ketothiolase deficiency, is an inborn error of ketone body utilization and isoleucine catabolism. It is caused by mutations in the ACAT1 gene and may present with metabolic ketoacidosis. In order to obtain a more comprehensive view on this di...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2017.06.012
更新日期:2017-09-01 00:00:00
abstract::Abetalipoproteinemia (ABL) is a rare autosomal recessive metabolic disorder, characterized by the absence of plasma apolipoprotein B-containing lipoproteins and very low levels of plasma triglycerides and cholesterol. ABL is caused by mutations of the MTP gene. We investigated the genetic basis for ABL in a cohort of ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2006.12.010
更新日期:2007-04-01 00:00:00
abstract::Gaucher disease is caused by the defective catabolism of the simple glycosphingolipid, glucosylceramide (GlcCer), due to mutations in the GBA1 gene which encodes for acid β-glucosidase (GCase), the lysosomal enzyme that degrades GlcCer. Today, Gaucher disease patients are routinely treated with recombinant GCase, in a...
journal_title:Molecular genetics and metabolism
pub_type: 传,历史文章,杂志文章,评审
doi:10.1016/j.ymgme.2016.11.390
更新日期:2017-01-01 00:00:00
abstract::Medicine is rapidly applying exome and genome sequencing to the diagnosis and management of human disease. Somatic mosaicism, however, is not readily detectable by these means, and yet it accounts for a significant portion of undiagnosed disease. We present a rapid and sensitive method, the Continuous Distribution Fun...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2011.12.015
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND:The etiology of liver disease remains elusive in some adults presenting with severe hepatic dysfunction. METHODS AND RESULTS:Here we describe a woman of Pakistani descent who had elevated aminotransferases at age 23. She developed muscle weakness in her mid-20s, and was diagnosed with hepatocellular carcino...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2015.10.009
更新日期:2015-12-01 00:00:00
abstract::The aim of this study was to evaluate the activity of daily living (ADL) and surgical interventions in patients with mucopolysaccharidosis IVA (MPS IVA). The factor(s) that affect ADL are age, clinical phenotypes, surgical interventions, therapeutic effect, and body mass index. The ADL questionnaire comprises three do...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2016.04.005
更新日期:2016-06-01 00:00:00
abstract::We report 10 children (7 male, 3 female), 3 homozygous for c.319C>T mutation and 7 heterozygous for c.319C>T on one allele and c.625G>A variant on the other in the short-chain acyl-CoA dehydrogenase (SCAD) gene (ACADS). All were of Ashkenazi Jewish origin in which group we found a c.319C>T heterozygote frequency of 1:...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2007.09.021
更新日期:2008-02-01 00:00:00
abstract::Cerebral folate deficiency is characterized by low cerebrospinal fluid (CSF) concentrations of 5-methyltetrahydrofolate and a broad spectrum of clinical signs and symptoms. A patient with progressive spasticity, gait disturbance, speech difficulties, initially diagnosed as a recessive spastic paraplegia recovered on f...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2004.12.001
更新日期:2005-04-01 00:00:00
abstract::The only known Japanese child with biotinidase deficiency was identified by newborn screening in Japan. He has 10.8% of mean normal serum biotinyl-hydrolase activity and trace biotinyl-transferase activity. The mutation results in 16% of normal cross-reacting material in serum with antibody to purified normal biotinid...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.1998.2706
更新日期:1998-06-01 00:00:00
abstract::Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism with copper accumulation in the liver as well as in the central nervous system. Treatment of WD includes oral chelating agents and diet and it is effective. However, once irreversible damage has occurred, the effect of treatment is diminishe...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/s1096-7192(02)00026-4
更新日期:2002-06-01 00:00:00
abstract:OBJECTIVE:To evaluate glycerol phenylbutyrate (GPB) in the treatment of pediatric patients with urea cycle disorders (UCDs). STUDY DESIGN:UCD patients (n=26) ages 2months through 17years were treated with GPB and sodium phenylbutyrate (NaPBA) in two short-term, open-label crossover studies, which compared 24-hour ammo...
journal_title:Molecular genetics and metabolism
pub_type: 临床试验,杂志文章
doi:10.1016/j.ymgme.2014.02.007
更新日期:2014-05-01 00:00:00
abstract::In mammals the initiation of testis determination usually depends on the Y-chromosomal gene SRY. A few species, however, escape from this rule with a testis determination that is independent of SRY. The mole vole Ellobius lutescens is one of these species. It is not known how testis determination is initiated in this ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.2000.3105
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Treatment of Fabry disease (FD) with recombinant alpha-galactosidase A (r-αGAL A) is complicated by the formation of anti-drug antibodies in the majority of male patients with the classical disease phenotype. Detailed information regarding antibody subtypes, onset and persistence of antibody development and ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2018.11.008
更新日期:2019-02-01 00:00:00
abstract::Patients with neonatal urea cycle defects (UCDs) typically have high mortality and poor neurological outcome unless they receive liver transplantation. Neurologic outcome may be better with liver transplantation before age one year. We report on a follow up on an initial prospective study performed to assess developme...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.02.012
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:The feasibility of carotid artery intima-media thickness (C-IMT), an established cardiovascular disease marker, as a cardiac risk marker in mucopolysaccharidosis (MPS) patients was explored. OBJECTIVES:To determine if C-IMT is abnormal in MPS versus unaffected controls, and if C-IMT correlates with coronary...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2011.09.004
更新日期:2011-12-01 00:00:00
abstract::This 24-week, Phase I/II, double-blind, randomized, placebo-controlled study investigated the safety and efficacy of extended-release albuterol in late-onset Pompe disease stably treated with enzyme replacement therapy at the standard dose for 4.9 (1.0-9.4) years and with no contraindications to intake of albuterol. T...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ymgme.2019.12.008
更新日期:2020-02-01 00:00:00
abstract::Propionyl-CoA carboxylase (PCC) is the enzyme which catalyzes the carboxylation of propionyl-CoA to methylmalonyl-CoA and is encoded by the genes PCCA and PCCB to form a hetero-dodecamer. Dysfunction of PCC leads to the inherited metabolic disorder propionic acidemia, which can result in an affected individual present...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2017.10.002
更新日期:2017-12-01 00:00:00
abstract::We describe three novel deletions in the human AGT gene in three patients with primary hyperoxaluria type 1, an autosomal recessive disease resulting from a deficiency of the liver peroxisomal enzyme, alanine glyoxylate aminotransferase (AGT; EC 2.6.1.44). A deletion of 4 nucleotides in the exon 6/intron 6 splice junc...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.2001.3222
更新日期:2001-11-01 00:00:00
abstract::Mevalonate kinase deficiency is a rare autosomal recessively inherited organic aciduria with a complex multi-systemic phenotype. We describe two deceased patients with clinically severe mevalonate kinase (MK) deficiency confirmed by MK mutation analysis. The phenotype in our patients ranged from neonatal hydrops in th...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.10.019
更新日期:2012-12-01 00:00:00
abstract:BACKGROUND:Phenylketonuria (PKU) is an autosomal recessive disorder caused by deficiency of hepatic phenylalanine hydroxylase (PAH) leading to increased levels of phenylalanine in the plasma. Phenylalanine levels and phenylalanine hydroxylase (PAH) activity monitoring are currently limited to conventional blood dot tes...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2015.04.005
更新日期:2015-06-01 00:00:00
abstract::Pompe Disease (PD) is a lysosomal storage disease caused by acid α-glucosidase deficiency. The infantile form typically results in death in the first year of life. Patient survival has improved with enzyme replacement therapy (ERT), but new complications are being recognized. We report three cases of infantile onset P...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.11.013
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND:Gaucher Disease type 1 (GD1) often manifests in childhood. Early treatment with enzyme replacement therapy (ERT) may prevent disease complications. We report the assessment of velaglucerase alfa ERT in pediatric GD1 patients who participated in a long-term extension study (HGT-GCB-044, ClinicalTrials.gov Ide...
journal_title:Molecular genetics and metabolism
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.ymgme.2015.05.012
更新日期:2016-02-01 00:00:00
abstract::To elucidate the basis of mucopolysaccharidosis type VI (MPS VI) from the point of view of enzyme structure, we built structural models of mutant N-acetylgalactosamine-4-sulfatase (4S) resulting from 34 missense mutations (17 severe and 17 attenuated), and analyzed the influence of each amino acid replacement on the s...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2007.11.017
更新日期:2008-04-01 00:00:00
abstract::Maple syrup urine disease (MSUD) is a rare, autosomal-recessive disorder of branched-chain amino-acid metabolism. In the Philippines, many MSUD cases have been diagnosed clinically. Here, molecular analysis of the dihydrolipoyl transacylase (E2) gene was done in 13 unrelated families from the Philippines. A novel dele...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2003.10.006
更新日期:2004-02-01 00:00:00