Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Investigation of the composition and significance of individual components of the surfactant indicated that besides phospholipids an important role is played also by surfactant proteins. They aid not only the reduction of the surface tension of the lungs (SP-B, SP-C), but serve also in regulation of surfactant secretion (SP-A) and in local defense and immune responses in the lungs (SP-A and SP-D). Impairments of surfactant were discovered not only in RDS, but also in cases of meconium aspiration, congenital diaphragmatic hernia, pneumonia, pulmonary edema, idiopathic fibrosis of the lungs, alveolar proteinosis, pneumothorax, and bronchial asthma. Therapy by means of exogenous surfactant was proved effective in therapy of RDS. Occasional cases of exogenous surfactant therapy in other pulmonary diseases are auspicious, it is necessary, though, to develop and produce a sufficient amount of exogenous surfactant of high quality and at an acceptable price and to find an optimal manner of surfactant administration into the lungs. A significant perspective is anticipated to utilization of intrapulmonary administration of the exogenous surfactant as a carrier of further active substances for local administration into the lungs. (Ref. 36.)
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PMID:[The pulmonary surfactant factor. Current knowledge, research trends and use in clinical practice]. 788 59

Bronchoalveolar lavage fluids (BALF) were analyzed for surfactant abnormalities in 153 patients with acute respiratory failure necessitating mechanical ventilation. Diagnoses were acute respiratory distress syndrome (ARDS) in the absence of lung infection (n = 16), severe pneumonia (PNEU; n = 88), ARDS and PNEU (n = 36), and cardiogenic lung edema (CLE; n = 13). The PNEU group was subdivided into groups with alveolar PNEU (n = 35), bronchial PNEU (n = 16), interstitial PNEU (n = 18) and nonclassified PNEU (n = 19). Comparison with healthy controls (n = 20) was undertaken. Total phospholipids (PL), proteins, PL classes (HPTLC) and surfactant apoproteins SP-A and SP-B (ELISA) were quantified in the original BALF. The 48,000 x g pellet from centrifugation of the BAL was used to assess the percentage of large surfactant aggregates (LSA) and the biophysical properties of the surfactant (pulsating bubble surfactometer). All groups with inflammatory lung injury (PNEU and/or ARDS) showed some decrease in the lavageable PL pool, a reduced LSA content in BALF, and a manifold increase in alveolar protein load. Marked changes in the PL profile were noted throughout the groups (a decrease in phosphatidylcholine (PC) and phosphatidylglycerol (PG) and an increase in phosphatidylinositol [PI] and sphingomyelin [SPH]). Concentrations of SP-A but not of SP-B in BALF were reduced. Minimum surface-tension values approached 0 mN/m in controls, and ranged from 10 to 25 mN/m in the absence of supernatant protein and from 20 to 35 mN/m in recombination with leaked protein in the groups with ARDS and/or PNEU. Abnormalities in alveolar PNEU surpassed those in bronchial PNEU, and interstitial PNEU presented a distinct pattern with extensive metabolic changes. All surfactant changes were absent in CLE except for a slight inhibition of surface activity by proteins. We conclude that pronounced surfactant abnormalities, comparable to those in ARDS in the absence of lung infection, occur in different entities of severe PNEU, but not in CLE.
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PMID:Surfactant alterations in severe pneumonia, acute respiratory distress syndrome, and cardiogenic lung edema. 854 13

Respiratory failure secondary to acute lung inflammation is associated with quantitative and qualitative abnormalities of pulmonary surfactant. The surfactant-associated proteins (SP)-A, -B, and -C are critical for normal surfactant function, synthesis, and metabolism. Tumor necrosis factor-alpha (TNF-alpha), a primary mediator of acute lung inflammation, decreased SP gene expression in vitro (32, 34). In the present in vivo study, transient T cell activation and TNF-alpha release were initiated by intraperitoneal administration of anti-CD3 antibody 145-2C11. Serum TNF-alpha was elevated 2 h after injection of the antibody. SP-B and -C mRNA were decreased 12 and 24 h after antibody treatment. Intratracheal murine TNF-alpha also resulted in decreased SP-B and SP-C mRNA levels in the bronchiolar and alveolar epithelium of adult FVB/N mice, as demonstrated by S1 nuclease protection and in situ hybridization assays, despite minimal histological inflammation. SP-A mRNA was not significantly altered after anti-CD3 antibody and was only mildly decreased after TNF-alpha. As previously reported, intercellular adhesion molecule-1 mRNA was elevated after intratracheal TNF-alpha. SP insufficiency contributes to the pathogenesis of pulmonary diseases associated with increased TNF-alpha, such as adult respiratory distress syndrome and pneumonia (8). TNF-alpha-mediated decrease in SP gene expression may contribute to the surfactant dysfunction and atelectasis observed in inflammatory lung diseases.
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PMID:Tumor necrosis factor-alpha decreases surfactant protein B mRNA in murine lung. 896 4

An allele association study of 19 polymorphisms in surfactant proteins SP-A1, SP-A2, SP-B, and SP-D genes in acute respiratory distress syndrome (ARDS) was carried out. Trend-test analysis revealed differences (p < 0.05) in the frequency of alleles for some of the microsatellite markers flanking SP-B, and for one polymorphism (C/T) at nucleotide 1580 [C/T (1580)], within codon 131 (Thr131Ile) of the SP-B gene. The latter determines the presence or absence of a potential N-linked glycosylation site. Multivariate analysis revealed significant differences only for the C/T (1580) polymorphism. When the ARDS population was divided into subgroups, idiopathic (i.e., pneumonia, etc.) or exogenic (i.e., trauma, etc.), significant differences were observed for the C/T (1580), for the idiopathic ARDS group, and the frequency of the C/C genotype was increased in this group. Based on the odds ratio, the C allele may be viewed as a susceptibility factor for ARDS. Although the expression of both C and T alleles occurs in heterozygous individuals, it is currently not known whether these alleles correspond to similar levels of SP-B protein. These data suggest that SP-B or a linked gene contributes to susceptibility to ARDS.
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PMID:Polymorphisms of human SP-A, SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS. 1107 40

Surfactant proteins SP-A and SP-D, members of the collectin family, have been shown to play a significant role in lung host defense. Both proteins selectively bind Pneumocystis carinii (PC) organisms and modulate the interaction of this pathogen with alveolar macrophages. We hypothesized that the expression and distribution of lung collectins SP-A and SP-D is altered by PC lung infection. PC organisms (2 x 10(5)) were inoculated intratracheally into C.B-17 scid/scid mice that do not require steroids for immunosuppression. Four weeks after inoculation, bronchoalveolar lavage (BAL) fluid was fractionated into three fractions-cell pellet, large aggregate (LA), and small aggregate (SA) surfactant-and each fraction was analyzed for the expression of surfactant components. In uninfected mice, the majority of SP-A (62% +/- 10%) was found in association with lipids in the LA fraction, while 55% +/- 14% of SP-D was distributed in the SA fraction. In contrast, both hydrophobic proteins SP-B and SP-C were associated exclusively with LA. PC infection resulted in major changes in the expression of all surfactant components. Total protein content of LA was unchanged by PC infection (115% +/- 18% of control), whereas SA protein content markedly increased (240% +/- 18% of control level, P <.001). In contrast, the phospholipid content of LA was significantly decreased (53% +/- 5% of control level, P <.001), whereas the SA phospholipid content of infected mice was increased (172% +/- 16% of control level, P <.001). By Western blotting, PC pneumonia (PCP) induced a 3-fold increase in the total alveolar SP-D protein that was reflected mainly in increases in SA SP-D (454% +/- 135% of control, P <.05). The total alveolar SP-A protein content was also increased in PCP because of a large increase in SP-A in SA (720% +/- 115% of control, P <.05); SP-A levels in LA were unchanged. The increases in lung collectin expression were selective, because PCP resulted in the down-regulation of both SP-B and SP-C in LA (5% +/- 2% and 13% +/- 2% of control, respectively, P <.001). We conclude that PCP induces marked elevations in alveolar collectin levels because of increased expression and accumulation of SP-A and SP-D protein in SA surfactant.
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PMID:Pneumocystis carinii pneumonia alters expression and distribution of lung collectins SP-A and SP-D. 1138 64

Surfactant has led to a significant reduction in neonatal mortality for premature infants with lung immaturity and respiratory distress. However, surfactant therapy has been shown to be effective in the treatment of a number of other neonatal respiratory disorders and the evidence for surfactant use in such circumstances is presented. Meconium aspiration is characterised by severe atelectasis, the influx of neutrophils, edema, and hyaline membranes, with decreased levels of SP-A and SP-B and the large aggregate fraction of lung surfactant, and altered surfactant surface morphology. Meconium contains cholesterol, free fatty acids and bilirubin all of which can interfere with surfactant function in a dose-dependent fashion. Providing larger amounts of surfactant can overcome some of this inhibition. Animal models of meconium aspiration treated with surfactant have improved histology, lung mechanics and gas exchange. Studies in human infants with meconium aspiration have found elevated concentrations of total protein, albumin, and membrane-derived phospholipid in lung lavage fluid, and haemorrhagic pulmonary edema. Clinical studies in such neonates have reported improved gas exchange and clinical outcomes following surfactant treatment. More recently surfactant lavage has been shown to be a potentially efficacious therapy for such infants. The inflammatory exudate containing plasma proteins and cytokines which accompanies neonatal pneumonia may inactivate surfactant. Surfactant treatment given to animals following the tracheal instillation of group B Streptococcal resulted in significantly less bacterial growth and improved lung function. Small clinical experiences have demonstrated the benefit of surfactant to infants with pneumonia/sepsis. Pulmonary haemorrhage, which some consider a complication of surfactant therapy, has also been effectively managed using surfactant instillation. The hemoglobin and red blood cell lipids may act to inhibit natural surfactant and treatment with surfactant has been shown to improve outcome for infants with pulmonary haemorrhage. Animal models of congenital diaphragmatic hernia (CDH) have hypoplastic lungs with evidence of decreased lamellar bodies in their type II pneumocytes and resultant surfactant deficiency, and respond to surfactant replacement with improved gas exchange and lung mechanics. The lungs of human infants with CDH contain less phospholipids and phosphatidylcholine per milligram of DNA than control infants. Case reports have reported a benefit of surfactant for infants with CDH. In the near-term infants with severe respiratory distress, surfactant is one of the therapies along with inhaled nitric oxide and high frequency ventilations, that have resulted in improved outcomes. Surfactant treatment may be of significant benefit in newborn infants with respiratory compromise secondary to a number of insults, and further prospective evidence of its efficacy in such disorders is needed.
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PMID:Surfactant use for neonatal lung injury: beyond respiratory distress syndrome. 1498 Feb 86

Thyroid transcription factor-1 (TTF-1) deficiency syndrome is characterized by neurologic, thyroidal, and pulmonary dysfunction. Children usually have mild-to-severe respiratory symptoms and occasionally die of respiratory failure. Herein, we describe an infant with a constitutional 14q12-21.3 haploid deletion encompassing the TTF-1 gene locus who had cerebral dysgenesis, thyroidal dysfunction, and respiratory insufficiency. The clinical course was notable for mild hyaline membrane disease, continuous ventilatory support, and symmetrically distributed pulmonary cysts by imaging. He developed pneumonia and respiratory failure and died at 8 months. Pathologically, the lungs had grossly visible emphysematous changes with "cysts" up to 2 mm in diameter. The airway generations and radial alveolar count were diminished. In addition to acute bacterial pneumonia, there was focally alveolar septal fibrosis, pneumocyte hypertrophy, and clusters of airspace macrophages. Ultrastructurally, type II pneumocytes had numerous lamellar bodies, and alveolar spaces contained fragments of type II pneumocytes and extruded lamellar bodies. Although immunoreactivity for surfactant protein SP-A and ABCA3 was diminished, that for SP-B and proSP-C was robust, although irregularly distributed, corresponding to the distribution of type II pneumocytes. Immunoreactivity for TTF-1 protein was readily detected. In summation, we document abnormal airway and alveolar morphogenesis and altered expression of surfactant-associated proteins, which may explain the respiratory difficulties encountered in TTF-1 haploinsufficiency. These findings are consistent with experimental evidence documenting the important role of TTF-1 in pulmonary morphogenesis and surfactant metabolism.
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PMID:Pulmonary pathology in thyroid transcription factor-1 deficiency syndrome. 2020 40