Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032290 (aspiration pneumonia)
 2,291 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipose tissue is the major site of estrogen formation in postmenopausal women. We have previously reported (Simpson, E.R., Ackerman, G.E., Smith, M.E. and Mendelson, C.R. (1981) Proc. Natl. Acad. Sci. (U.S.A.) 78, 5690-5694; Mendelson, C.R., Cleland, W.H., Smith, M.E. and Simpson, E.R. (1982) Endocrinology 111, 1077-1085) that aromatase activity of human adipose stromal cells in culture is stimulated by glucocorticoids and by dibutyryl cyclic AMP (Bt2-cAMP). In order to establish which physiological factors might stimulate aromatase activity of these cells by activation of adenylate cyclase, we have investigated the roles of adrenocorticotropin (ACTH) and isoproterenol to increase cyclic AMP levels and stimulate the aromatization of androstenedione. In the presence of methylisobutylxanthine (MIX), ACTH stimulated cyclic AMP formation and aromatase activity in a time- and concentration-dependent manner. The concentration of ACTH required for half-maximal stimulation was approximately 10(-8) M. Isoproterenol, in the presence of MIX, stimulated cyclic AMP formation in a time- and concentration-dependent fashion, and also stimulated aromatase activity. These effects of isoproterenol appeared to be mediated by binding of the agonist to a population of beta-adrenergic receptors. On the basis of these and our previous studies, we suggest that ACTH may play an important role in stimulating estrogen formation by human adipose tissue, both directly, and by stimulating the adrenal cortex to produce both substrate, androstenedione, and inducing agent, namely cortisol.
Mol Cell Endocrinol 1984 Aug
PMID:Regulation of aromatase activity of cultured adipose stromal cells by catecholamines and adrenocorticotropin. 620 18

Hydrodynamic calculations lead to the conclusion that chymotryptic (or ethylenediaminetetraacetic acid) myosin S1 in solution (hydrated), at 1-5 degrees C, can be modeled as a prolate ellipsoid, with an axial ratio lying between p = 1.0 and 2.5 (major axis between 100.5 A, for p = 1.0, and 162.5 A, for p = 2.5). The degree of hydration is considerable (1.24 g/g for p = 2.5 and 2.02 g/g for p = 1.0). The dehydrated myosin head is pear-shaped under the electron microscope, and its narrowest part is located near the junction with the tail [Elliott, A., & Offer, G. (1978) J. Mol. Biol. 123, 505-519]. Mendelson & Kretzschmar [Mendelson, R. A., & Kretzschmar, K.M. (1980) Biochemistry 19, 4103-4108] have shown that the pear-shaped molecule does not predict the experimental X-ray scattering curve. Nor is this model able to predict the hydrodynamic values. The three-dimensional model for S1 used by Mendelson and Kretzschmar gives a rather good fit to the experimental X-ray scattering curve, but it does not predict the hydrodynamic values. In order to try to reconcile the three models and to fit the X-ray scattering curve and the hydrodynamic data, we suggest that, in solution, the S1 monomer has the shape of a prolate ellipsoid and that an inclusion of bound water exists at one extremity of the protein. The rest of bound water surrounds the protein. As first approximation, the dry protein and the hole are assumed to have the same shape as the hydrated molecule (prolate ellipsoid; p).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reinvestigation of the shape and state of hydration of the skeletal myosin subfragment 1 monomer in solution. 663 38

To evaluate the physiological role of G-CSF following surgery, we measured the serum levels of immunoreactive IL-6 and G-CSF sequentially in nine patients after major elective thoracoabdominal surgery for esophageal carcinoma. Both G-CSF and IL-6 levels reached their maxima at the first postoperative day and decreased thereafter. There was a significant correlation between serum G-CSF (y) and IL-6 (x) levels (y = 3.273x + 3.991; r = 0.787, n = 78, p < 0.001). In the case that developed aspiration pneumonia and ARDS at the second postoperative day, the measured G-CSF level was less than half the predicted value. The relationship between serum G-CSF and IL-6 levels supports the central role of G-CSF as the host defense response modifier and, thus, low G-CSF levels in the circulation is one reason for the immunodeficient state after major surgery.
Res Commun Mol Pathol Pharmacol 1995 Mar
PMID:Changes in serum granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6) after surgical intervention. 754 36

In the present study, we have characterized the mRNA transcripts and intron-exon organization of the human surfactant protein (SP)A1 and SP-A2 genes. By primer extension analysis of mRNA isolated from human fetal lung explants using an oligonucleotide primer to exon II (as delineated in the SP-A1 gene), a minimum of nine primer extended transcripts was observed. Rapid amplification of cDNA ends was used to amplify the primer extended transcripts for sequence analysis. Sequence analysis of 47 full-length primer extended cDNAs and comparison with the sequences of the genes encoding SP-A1 and SP-A2 revealed four different classes of transcripts of the SP-A2 gene and five different classes of transcripts of the gene encoding SP-A1. A major difference between SP-A2 and SP-A1 mRNA transcripts is that SP-A2 transcripts are always comprised of sequences contained within six exons; the extra exon in SP-A2 (exon II of VI) encodes additional 5'-untranslated sequence and is located between exons I and II of SP-A1. By contrast, the majority of transcripts of the SP-A1 gene are comprised of sequences contained within five exons. In the cases of both SP-A1 and SP-A2 genes, a small proportion of the mRNA transcripts contain sequences present in alternate exons. In addition, the majority of the SP-A1 mRNA transcripts are initiated 5 bp downstream of the transcription initiation site of SP-A2. In our companion paper [McCormick and Mendelson. Am. J. Physiol. 266 (Lung Cell. Mol. Physiol. 10): L367-L374, 1994], we report that the SP-A1 and SP-A2 genes are differentially regulated during development and by adenosine 3',5'-cyclic monophosphate and glucocorticoids in human fetal lung in culture.
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PMID:Characterization of mRNA transcripts and organization of human SP-A1 and SP-A2 genes. 817 12

Expression of the surfactant protein A (SP-A) gene is lung specific, developmentally induced, and regulated by adenosine 3',5'-cyclic monophosphate (cAMP) and glucocorticoids. Humans have two highly similar genes encoding SP-A (SP-A1 and SP-A2). In the companion paper [S.M. McCormick, V. Boggaram, and C.R. Mendelson Am. J. Physiol. 266 (Lung Cell. Mol. Physiol. 10): L354-L366, 1994] we report that SP-A1 and SP-A2 RNA transcripts are alternatively spliced at their 5' ends, resulting in nine different primer-extended transcripts. In the present study, primer extension was used to assess the relative levels of expression of the SP-A1 and SP-A2 genes in human adult lung tissue and in fetal lung tissues maintained in organ culture in the absence or presence of dibutyryl (DB)cAMP (1 mM) and dexamethasone (Dex, 10(-4) M). Primer extension and Northern analysis were used to assess the effects of these agents on the levels of expression of these genes. In human adult lung tissue, 65% of the SP-A mRNA transcripts were derived from the SP-A2 gene, whereas only 35% were from SP-A1. On the other hand, in lung tissue from a 28-wk gestation neonate, only SP-A1 mRNA transcripts were detected, and, in midgestation fetal lung cultured in control medium, 65% of the SP-A mRNA was found to be SP-A1 and 35% was SP-A2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human SP-A1 and SP-A2 genes are differentially regulated during development and by cAMP and glucocorticoids. 817 13

Symptomless dysphagia and swallowing disorders play a very important role in the pathogenesis of aspiration pneumonia. A videofluoroscopic examination and a simple two-step swallowing provocation test (STS-SPT) could be useful for detection of swallowing disorders in elderly patients with stroke, however, there is no report on such a test for detection of symptomless dysphagia. We administered 1 ml Technetium Tin Colloid (99mTC) to the patient during sleep via a nasal catheter placed in the mouth. At 09:00 h the next day, symptomless dysphagia was checked for by imaging. Improvement of the symptomless dysphagia was observed, and thus we could prevent the occurrence of aspiration pneumonia. The 99mTC test was particularly useful in detecting symptomless dysphagia in elderly patients with stroke.
Int J Mol Med 2000 Jun
PMID:Technetium tin colloid test detecting symptomless dysphagia and ACE inhibitor prevented occurrence of aspiration pneumonia. 1081 9

Previously we have demonstrated that prolonged exposure to 100% ambient oxygen leads to a marked loss in functional lung volume and lung compliance, hypoxemia, and surfactant system abnormalities similar to acute respiratory distress syndrome (ARDS). However, 50% oxygen administration is believed to be safe in most clinical settings. In the present study, we have evaluated the effects of a 24-h exposure to 50% oxygen in rabbits immediately following experimental gastric acid aspiration. Mild hypoxemia, but no changes in mortality, lung volume, lung compliance, surfactant metabolism, or edema formation occurred after 24 h of normoxia postacid aspiration. Conversely, a relatively short (24-h) exposure to 50% oxygen after acid aspiration results in increased pulmonary edema, physical signs of respiratory distress, and mortality, as well as decreased arterial oxygenation, lung volume, lung compliance, and type II alveolar cell surfactant synthesis. These results suggest that acid aspiration alters the "set point" for oxygen toxicity, possibly by "priming" cells through activation of inflammatory pathways. This pathogenic mechanism may contribute to the progression of aspiration pneumonia to ARDS.
Am J Physiol Lung Cell Mol Physiol 2000 Jun
PMID:Acid aspiration increases sensitivity to increased ambient oxygen concentrations. 1083 30

Expression of the pulmonary surfactant protein A (SP-A) gene is lung specific, developmentally regulated, and enhanced by hormones and factors that increase cAMP. We previously identified two E-box-like enhancers termed distal binding element (DBE) and proximal binding element (PBE) in the 5'-flanking region of the rabbit (r) SP-A gene that are essential for cAMP induction of rSP-A promoter activity (Gao E, Alcorn JL, and Mendelson CR. J Biol Chem 268: 19697-19709, 1993). We also found that DBE and PBE serve as binding sites for the basic helix-loop-helix-leucine zipper transcription factor, upstream stimulatory factor-1 (USF1) (Gao E, Wang Y, Alcorn JL, and Mendelson CR. J Biol Chem 272: 23398-23406, 1997). In the present study, PBE was used to screen a rabbit fetal lung cDNA expression library; a cDNA insert encoding the structurally related rabbit upstream stimulatory factor-2 (rUSF2) was isolated. The levels of rUSF2 mRNA reach peak levels in fetal rabbit lung at 28 days of gestation, in concert with the time of maximal induction of SP-A gene transcription. In yeast two-hybrid analysis, rUSF2 was found to preferentially form heterodimers, compared with homodimers, with rUSF1. Binding complexes of nuclear proteins isolated from fetal rabbit lung type II cells with the DBE and PBE were supershifted by anti-rUSF2 antibodies. Binding activity was enriched in nuclear proteins from type II cells compared with fibroblasts. Overexpression of rUSF2 in transfected lung A549 cells increased rSP-A promoter activity and acted synergistically with rUSF1. We suggest that heterodimers of USF2 and USF1 bound to two E-box elements in the SP-A gene 5'-flanking region serve a key role in developmental and hormonal regulation of SP-A gene expression in pulmonary type II cells.
Am J Physiol Lung Cell Mol Physiol 2003 Jun
PMID:Transcription factor USF2 is developmentally regulated in fetal lung and acts together with USF1 to induce SP-A gene expression. 1257 97

Aspiration pneumonia is a common cause of death in older people, and the pathophysiology is a chronic respiratory failure with a mild airway inflammation. In this study, we established a mild inflammatory pneumonia model using Porphyromonas gingivalis (Pg) pathogen-infected mice. It elucidated the effects of Pg-infected pneumonia on proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6), and IL-1beta production in both lung tissue and serum. We also elucidated production of soluble (s) TNF receptor (R) s, because TNF-alpha is considered to be a dominant inflammatory mediator. Lung TNF-alpha levels significantly increased at 2 h after infection, and rapidly returned to basal level at 24 h. Consistent with increase of TNF-alpha, remarkable increase of sTNFR2 but not sTNFR1 was detected in lung tissue from 2 to 72 h. Interestingly, sTNFR2/sTNFR1 ratio was significantly enhanced at 2 h in serum. In addition, lung IL-1beta and IL-6 levels also significantly increased from 2 to 24 h. Importantly, we found that IL-6 levels in serum reflected its local level. These results may suggest that systemically produced sTNFR2 and IL-6 could be a key role to modulate proinflammatory activities of TNF-alpha in Pg-induced lung inflammation simulated aspiration pneumonia.
Exp Mol Pathol 2004 Feb
PMID:Systemic up-regulation of sTNFR2 and IL-6 in Porphyromonas gingivalis pneumonia in mice. 1473 72

Elderly individuals display increased susceptibility to chronic inflammatory diseases and microbial infections, such as periodontitis and oral aspiration pneumonia. The resurgent interest in innate immunity in the 2000s has been accompanied by parallel studies to understand the impact of aging on the function of the innate immune system, which not only provides first-line defense but is essential for the development of adaptive immunity. This review summarizes and discusses our current understanding of age-associated molecular alterations in neutrophils and macrophages, key inflammatory phagocytes implicated in both protective and destructive host responses. The analysis of recent literature suggests that, in advanced age, phagocytes undergo significant changes in signal transduction pathways that may affect their ability to perform antimicrobial functions or regulate the inflammatory response. These abnormalities are expected to contribute to the pathology of oral infection-driven inflammatory diseases in the elderly. Moreover, the elucidation of age-associated defects in the innate immune system will facilitate the development of intervention therapeutic strategies to promote or restore innate immune function and improve the quality of health in old age.
Mol Oral Microbiol 2010 Feb
PMID:Too old to fight? Aging and its toll on innate immunity. 2030 5


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