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)

We describe the clinical spectrum of the L-tryptophan-associated eosinophilia-myalgia syndrome in 20 patients. In all but one case, patients met the Centers for Disease Control (CDC) case definition for the syndrome: peripheral blood eosinophilia (eosinophil count greater than 1.0 x 10(9)/L) and generalized, disabling myalgias without other recognized causes. Three patients with eosinophilia and myalgia developed eosinophilic fasciitis, and 4 other patients developed, respectively, pneumonitis and myocarditis, neuropathy culminating in respiratory failure, encephalopathy, and fibrosis about the common bile duct. No relation was apparent between dose or duration of L-tryptophan exposure and the eosinophilia-myalgia syndrome. No organic contaminants were identified in L-tryptophan preparations taken by patients or asymptomatic users when these preparations were examined by chromatography or mass spectroscopy. Biopsy specimens in 12 patients showed a mononuclear exudate with a variable admixture of eosinophils in affected tissues, including skin, fascia, muscle, and some viscera. Eosinophil toxic granule proteins, major basic protein, and eosinophil-derived neurotoxin were elevated in the serum and urine of patients compared with normal control subjects (P less than 0.01 and P less than 0.02, respectively). Immunofluorescence showed major basic protein deposited outside of eosinophils in affected tissues, indicating that toxic granule proteins are released in diseased organs. Treatment included withdrawal of L-tryptophan in all cases. Corticosteroids were prescribed for 16 patients and diuretics alone for 1 patient; no drugs were prescribed for 3 patients. Four patients have recovered fully, others are stable or slowly recovering, and 1 is gravely ill despite prolonged treatment.
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PMID:The clinical spectrum of the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Clinical features in 20 patients and aspects of pathophysiology. 222 57

Eosinophils remain among the most enigmatic of cells, as our appreciation of their detrimental activities--e.g., asthma and allergic disease--far outweighs our understanding of their beneficial effects. Among the major secretory effector proteins of eosinophils are the ribonucleases eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in primates and their orthologs, the eosinophil-associated ribonucleases (EARs) in rodents. The rapid diversification observed among these ribonucleases suggested that the ultimate target(s) might be similarly efficient at generating sequence diversity while maintaining an unalterable susceptibility to ribonucleolytic cleavage. This has prompted us to consider a role for these proteins and by extension, for eosinophils, in host defense against single-stranded RNA virus pathogens. We detail our studies of the antiviral activity of eosinophils and eosinophil ribonucleases against respiratory syncytial virus (RSV) in vitro and the related, natural rodent pathogen, pneumonia virus of mice (PVM), in vivo, and consider the possibility that antiviral host defense and the dysregulated responses leading to asthma represent opposing sides of an eosinophil-mediated double-edged sword.
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PMID:Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens. 1169 87

The mouse eosinophil-associated ribonucleases (mEars) are species specific, divergent orthologs of the human antiviral RNase A ribonucleases, eosinophil-derived neurotoxin (RNase 2) and eosinophil cationic protein (RNase 3). We show here that mEar 2 is also an antiviral ribonuclease, as micromolar concentrations promote a approximately sixfold reduction in the infectivity of pneumonia virus of mice (PVM) for target respiratory epithelial cells in vitro. Although initially identified as a component of eosinophilic leukocytes, mEar 2 mRNA and protein were also detected in lung tissue accompanied by enzymatically active mEar 2 in bronchoalveolar lavage fluid (BALF). At t=3 days post-inoculation with PVM (strain J3666), we observed the characteristic inflammatory response accompanied by diminished expression of total mEar mRNA and protein in lung tissue and a corresponding fivefold drop in ribonuclease activity in BALF. No change in mEar expression was observed in response to infection with PVM strain 15, a replication-competent strain of PVM that does not elicit a cellular inflammatory response. However, mEar expression is not directly dependent on inflammation per se, as diminished expression of mEar mRNA and BAL ribonuclease activity were also observed in PVM-infected, inflammation-deficient, MIP-1alpha -/- mice. We propose that this mechanism may represent a novel virus-mediated evasion strategy, with a mechanism that is linked in some fashion to virus-specific pathogenicity.
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PMID:Diminished expression of an antiviral ribonuclease in response to pneumovirus infection in vivo. 1292 8

Although eosinophils produce cysteinyl leukotrienes (CysLTs) in large quantities, information on the relationship between CysLTs and eosinophilic pneumonia (EP) is lacking. Inflammatory mediator concentrations in urine were quantified to clarify the relationship between CysLT concentrations and EP severity. Leukotriene (LT)E(4), eosinophil-derived neurotoxin (EDN), 9alpha,11beta-prostaglandin F2 and LTB(4) glucuronide concentrations were quantified in the urine of: EP patients during acute exacerbation and clinical remission; asthmatic patients during acute exacerbation and under stable conditions; and healthy control subjects. The urinary LTE(4) and EDN concentrations of EP patients during acute exacerbation were significantly higher than those of asthmatic patients and healthy subjects, and decreased immediately during clinical remission. The urinary LTE(4) concentration was associated with the urinary EDN concentration of EP patients during acute exacerbation. The urinary LTE(4) concentration significantly correlated with the diffusing capacity of the lung for carbon monoxide in EP patients during acute exacerbation. The increased urinary concentrations of leukotriene and eosinophil-derived neurotoxin were associated with acute exacerbation in eosinophilic pneumonia patients. The increased leukotriene concentration significantly correlated with diffusing capacity of the lung for carbon monoxide, suggesting that the monitoring of leukotriene concentration may aid in the management of eosinophilic pneumonia patients.
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PMID:Increased urinary leukotriene E4 concentration in patients with eosinophilic pneumonia. 1841 15