Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476273 (respiratory distress)
 19,632 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe deficiencies of protein C, a pivotal coagulation-regulatory protein, have been reported in neonates as an apparently transient condition. In this prospective study, cord blood was collected at 193 deliveries and assays of protein C were correlated with clinical status, other coagulation results, and outcome. Protein C levels of less than 0.1 unit/ml were found most frequently in preterm infants with respiratory distress, infants of diabetic mothers, and infants of twin gestations. Levels of protein C correlated with levels of factor VIII activity but did not correlate with markers of consumptive coagulopathy. A protein C level less than 0.1 unit/ml was significantly correlated with the subsequent onset of thrombosis, even when the effects of gestational age and birth weight were excluded. Low cord blood levels of protein C may reflect delayed maturation or increased turnover in certain infants and appear to convey an independent risk of thrombosis, but the critical concentration of protein C necessary to maintain neonatal hemostasis is not known.
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PMID:Severe neonatal protein C deficiency: prevalence and thrombotic risk. 183 22

Pulmonary surfactant is produced in late gestation by developing type II epithelial cells lining the alveolar epithelium of the lung. Lack of surfactant at birth is associated with respiratory distress syndrome in premature infants. Surfactant protein C (SP-C) is a highly hydrophobic peptide isolated from pulmonary tissue that enhances the biophysical activity of surfactant phospholipids. Like surfactant phospholipid, SP-C is produced by epithelial cells in the distal respiratory epithelium, and its expression increases during the latter part of gestation. A chimeric gene containing 3.6 kilobases of the promoter and 5'-flanking sequences of the human SP-C gene was used to express diphtheria toxin A. The SP-C-diphtheria toxin A fusion gene was injected into fertilized mouse eggs to produce transgenic mice. Affected mice developed respiratory failure in the immediate postnatal period. Morphologic analysis of lungs from affected pups showed variable but severe cellular injury confined to pulmonary tissues. Ultrastructural changes consistent with cell death and injury were prominent in the distal respiratory epithelium. Proximal components of the tracheobronchial tree were not severely affected. Transgenic animals were of normal size at birth, and structural abnormalities were not detected in nonpulmonary tissues. Lung-specific diphtheria toxin A expression controlled by the human SP-C gene injured type II epithelial cells and caused extensive necrosis of the distal respiratory epithelium. The absence of type I epithelial cells in the most severely affected transgenic animals supports the concept that developing type II cells serve as precursors to type I epithelial cells.
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PMID:Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice. 238 87

Neonatal mink kits infected with Aleutian mink disease parvovirus (ADV) develop an acute interstitial pneumonia with clinical symptoms and pathological lesions that resemble those seen in preterm human infants with respiratory distress syndrome and in human adults with adult respiratory distress syndrome. We have previously suggested that ADV replicates in the alveolar type II epithelial cells of the lung. By using double in situ hybridization, with the simultaneous use of a probe to detect ADV replication and a probe to demonstrate alveolar type II cells, we now confirm this hypothesis. Furthermore, Northern (RNA) blot hybridization showed that the infection caused a significant decrease of surfactant-associated protein C mRNA produced by the alveolar type II cells. We therefore suggest that the severe clinical symptoms and pathological changes characterized by hyaline membrane formation observed in ADV-infected mink kits are caused by a dysfunction of alveolar surfactant similar to that observed in respiratory distress syndrome in preterm infants. However, in the infected mink kits the dysfunction is due to the replication of ADV in the lungs, whereas the dysfunction of surfactant in preterm infants is due to lung immaturity.
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PMID:Role of alveolar type II cells and of surfactant-associated protein C mRNA levels in the pathogenesis of respiratory distress in mink kits infected with Aleutian mink disease parvovirus. 813 47

Under normal conditions activated protein C is a natural anticoagulant that cleaves 2 activated coagulation factors, factor Va and factor VIIIa, thereby inhibiting the conversion of factor X to factor Xa and of prothrombin to thrombin. Additionally, activated protein C enhances tissue-plasminogen activator-mediated fibrinolysis by inhibition of plasminogen activator inhibitor-1. This results in an increase in circulatory plasminogen activator levels. Protein C deficiency, a genetic or acquired thrombophilic abnormality, has been demonstrated to predispose to episodes of potentially blinding and lethal thromboembolic events. Heterozygous-deficient subjects usually remain asymptomatic until adolescence or adulthood. In homozygous-deficient patients, protein C activity is usually less than 1% (reference range, 70%-140%), resulting in thromboembolism as early as in the neonatal period. The major clinical symptoms in affected newborn infants have been purpura fulminans, vitreous hemorrhage, and central nervous system thrombosis. The age of onset of the first symptoms has ranged from a few hours to 2 weeks after birth, usually after an uncomplicated full-term pregnancy and delivery. In contrast to the genetic form, acquired neonatal protein C deficiency occurs particularly in ill preterm babies. Typical complications of prematurity such as respiratory distress syndrome, necrotizing enterocolitis, and neonatal sepsis may also be present. In the medical literature, there are only a few reports of homozygous protein C deficiency in neonates. We present 2 cases of homozygous protein C deficiency with ocular and extraocular manifestation.
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PMID:Ophthalmic manifestation of congenital protein C deficiency. 1042 94

Previous studies suggest that there is a systemic activation of clotting and fibrinolysis in preterm infants with advanced respiratory distress syndrome (RDS). However, there are no data on the hemostatic status in the early stages of the disease; therefore, we studied some of the hemostatic parameters in these patients and made several studies at different times in preterm infants who did or did not develop RDS, using similar protocols. We found normal plasma fibrinogen, protein C, protein S, C4b-binding protein, thrombomodulin, antithrombin III, thrombin-antithrombin III complex, prothrombin fragment 1.2, plasminogen, tissue plasminogen activator, alpha-1 antitrypsin, alpha-2-macroglobulin and protein Z. However, lower D-dimer and higher plasminogen activator inhibitor and von Willebrand factor antigen levels were found within six hours of life in infants who later developed RDS compared to the control group. These findings suggest that disseminated intravascular coagulation is not prominent in the early stages of RDS. Moreover, reduced D-dimer and increased plasminogen activator inhibitor and von Willebrand factor antigen levels are probably related to the abnormalities in the fibrinolytic mechanism due to lung damage in RDS, but further studies are needed to show their pathogenic significance in RDS.
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PMID:Hemostatic system in early respiratory distress syndrome: reduced fibrinolytic state? 1077 Jan 17

Intrauterine growth retardation and neonatal transient mucocutaneous lesions ("transient Behcet syndrome") have been reported in pregnancies complicated by Behcets disease (BD). Neonatal neurological manifestations have not been reported in such pregnancies. Vascular and neurological involvement is known to worsen the prognosis in adults with BD. The clinical course and outcome of a 34-weeks' gestation neonate born to a mother with BD is reported. Progressive recovery from minimal respiratory distress syndrome was followed by catastrophic presentation on 6th day of life with generalized seizures. Cranial ultrasound revealed multiple hyperechoic lesions in the frontal, parietal, and periventricular regions with a few surrounded by a ring of reduced echogenicity suggesting haemorrhage into ischemic areas. Death occurred after withdrawal of life support on Day 9, after extensive discussions with parents in view of the progressive deterioration in the neonates' general condition and the cranial ultrasound findings. Strong family history of BD, clinical course, and laboratory results (no evidence of disseminated intravascular coagulation, normal levels of protein C and S, absence of factor V Leiden and anticardiolipin antibodies) suggested neurological manifestations of BD as the most probable diagnosis.
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PMID:Unusual presentation of neonatal Behcets disease. 1155 81

In neonates and infants numerous clinical and environmental conditions such as the use of central lines, cardiac diseases and polycythemia, renal diseases such as congenital nephrotic syndrome and neonatal hemolytic uremic syndrome, peripartal asphyxia, infants of diabetic mothers, dehydration, septicemia, necrotizing enterocolitis, acute respiratory distress syndrome, and extracorporeal membrane oxygenation lead to elevated thrombin generation and subsequent thrombus formation. Genetic prothrombotic defects [protein C, protein S and antithrombin deficiency, mutations of coagulation factor V and factor II, elevated lipoprotein (a)] have been established as risk factors for thromboembolic events. The interpretation of laboratory results relies on age-dependent normal reference values. Because appropriate clinical trials are missing in these age groups, treatment recommendations are adapted from small-scale studies in neonates and infants and from guidelines relating to adult patient protocols. Secondary long-term anticoagulation should be administered on an individual basis.
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PMID:Neonatal thromboembolism. 1270 27

Decreased circulating protein C and increased circulating thrombomodulin are markers of the prothrombotic, antifibrinolytic state associated with poor outcomes in sepsis but have not been measured in patients with ALI (acute lung injury)/ARDS (acute respiratory distress syndrome). We measured circulating and intra-alveolar protein C and thrombomodulin in 45 patients with ALI/ARDS from septic and nonseptic causes and correlated the levels with clinical outcomes. Plasma protein C levels were lower in ALI/ARDS compared with normal. Lower levels of protein C were associated with worse clinical outcomes, including death, fewer ventilator-free days, and more nonpulmonary organ failures, even when only patients without sepsis were analyzed. Levels of thrombomodulin in pulmonary edema fluid from ALI/ARDS patients were >10-fold higher than normal plasma and 2-fold higher than ALI/ARDS plasma. Higher edema fluid thrombomodulin levels were associated with worse clinical outcomes. The higher levels in edema fluid compared with plasma suggest local release of soluble thrombomodulin in the lung, possibly from a lung epithelial source. To determine whether lung epithelial cells can release thrombomodulin, A549 cells and primary isolates of human alveolar type II cells were exposed to H2O2 or inflammatory cytokines. Both epithelial cell types released thrombomodulin into the media. In summary, the protein C system is markedly disrupted in patients with ALI/ARDS from both septic and nonseptic causes. The protein C system may be a potential therapeutic target in patients with ALI/ARDS.
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PMID:Protein C and thrombomodulin in human acute lung injury. 1275 94

Surfactant protein C (SP-C) is a small hydrophobic protein component of alveolar surfactant, a lipid-protein complex lining the alveolar surface of the lung. Surfactant deficiency is the main cause of respiratory distress syndrome (RDS) in premature infants. RDS is a major risk factor of a chronic lung disease called bronchopulmonary dysplasia (BPD). The dominant mutations of the SP-C gene have recently been associated with interstitial lung diseases. However, the common genetic variation in the surfactant protein C gene has not been studied in detail. In the present study, the exonic variation of the SP-C gene in the Finnish population (n=472) was defined, and the association of the allelic variants with the susceptibility to RDS and BPD was examined. Conformation-sensitive gel electrophoresis (CSGE) was used to determine the extent of exonic variation in the SP-C gene. Methods of genotyping were generated for three biallelic polymorphisms of the SP-C gene's exons 1, 4 and 5, which encode proSP-C. The frequencies of these polymorphisms were evaluated in a study population consisting of 158 DNA samples from full-term infants. In addition, the linkage disequilibrium between the SP-C alleles was evaluated by haplotype analysis of parent-infant triplets. The role of SP-C gene variation in RDS and in BPD was evaluated in a high-risk population of 245 premature infants. According to the present results, the SP-C polymorphisms were associated with RDS and with very premature birth. The strength of allelic associations differed according to the gender of the premature infants.
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PMID:Surfactant protein C gene variation in the Finnish population - association with perinatal respiratory disease. 1473 58

Decreased circulating protein C is a marker of a prothrombotic state that has been associated with poor clinical outcomes in sepsis. However, protein C has not been measured in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). In this study, we measured circulating and intra-alveolar concentrations of protein C in 45 patients with ALI/ARDS from septic and nonseptic causes. Plasma protein C levels were lower in ALI/ARDS compared with normal controls. Lower levels of plasma protein C were associated with worse clinical outcomes, including death, fewer ventilator-free days, and more nonpulmonary organ failures, even when only patients without sepsis were analyzed. In summary, the protein C system is markedly disrupted in patients with ALI/ARDS from both septic and nonseptic causes. The protein C system may be a therapeutic target in patients with ALI/ARDS.
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PMID:Plasma protein C levels in patients with acute lung injury: prognostic significance. 1511 23


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