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)

To evaluate the adjunctive effect of interferon-gamma (IFN-gamma) in treatment of Pseudomonas aeruginosa pneumonia, neutropenic and non-neutropenic mice received LD(100) of the organism intratracheally, followed by subcutaneous administration of IFN-gamma, ceftazidime (TAZ) or a combination of both agents 2 h post-inoculation. Treatment with IFN-gamma alone showed no significant increase in survival when compared with control. Addition of IFN-gamma to TAZ resulted in no significant change in survival compared with TAZ alone. Survival in TAZ and TAZ + IFN-gamma groups, was significantly higher than in control and IFN-gamma groups. This suggests that adjunctive treatment with IFN-gamma in combination with ceftazidime may not be more beneficial than the antibiotic alone when managing acute P. aeruginosa pneumonia in both immunocompromised and immunocompetent hosts.
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PMID:Effect of adjunctive treatment with gamma interferon against Pseudomonas aeruginosa pneumonia in neutropenic and non-neutropenic hosts. 1532 24

Human metapneumovirus (hMPV), a recently identified virus, causes upper and lower respiratory tract diseases. In this study, we show that BALB/c mice inoculated with hMPV exhibited significant morbidity on 1--2 days post-infection, when airway obstruction was found. Increased airway hyper-responsiveness to metacholine was found on day 4 concurrent with lung viral replication. Both IgG1 and IgG2a hMPV-specific antibodies were found in sera, while interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were found in bronchoalveolar lavage. Lung histology showed parenchymal pneumonia and increased lymphocytic infiltration. We present here an animal model that may be helpful in studying hMPV pathogenesis and evaluating the effects of vaccines.
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PMID:Immune response and alteration of pulmonary function after primary human metapneumovirus (hMPV) infection of BALB/c mice. 1592 22

Circulating endothelial cells (CECs) are increased in sickle cell disease, myocardial infarction, and acute lung injury. The purpose of this study was to determine whether CECs are a prognosticating marker for the development of pneumonia in burn patients with/without inhalation injury in addition to their relationship to proinflammatory cytokines. There were 24 patients: 6 with inhalation injury, 5 with burn only,and 13 with burn plus inhalation injury. CECs were measured by anchored cytometry (Clarient ChromaVision, San Juan Capistrano, CA). In addition, plasma levels of tumor necrosis factor-alpha, interferon-gamma, and interleukins (IL)-10, IL-6, IL-4, and IL-2 were compared with CEC levels. Patients with inhalation injury had a significant (P < .001) paucity of CECs compared with the thermally injured with inhalation. There was a statistically significant increase in inteferon-gamma, tumor necrosis factor-alpha, and IL-6, IL-4, and IL-2 compared with control patients (P < .01), with a concomitant increase in the number of CECs. The numbers of CEC levels did not prognosticate which patients would develop pneumonia. Burn patients with/without inhalation injury had concurrent increase in CECs and proinflammatory cytokines during the acute phase of injury.
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PMID:Circulating endothelial cell levels correlate with proinflammatory cytokine increase in the acute phase of thermal injury. 1615 Dec 88

Adenovirus pneumonia is uncommon but its severe infection has a mortality as high as 10%, and survivors may have residual airway damages, manifested by bronchiectasis, bronchiolitis obliterans, or pulmonary fibrosis. We report a case of adenovirus pneumonia demonstrating fatal respiratory distress. Adenovirus was isolated from pharyngeal specimens using cell culture and typed as serotype 3 by a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis. The patient characteristically showed hypercytokinemia, characterized by increased levels of lactate dehydrogenase, ferritin, and several cytokines including interferon-gamma and interleukin-6. We treated the patient with pulse methylprednisolne therapy (25 mg/kg/day, for 3 days), resulting in the rapid amelioration of respiratory distress. This is the first report describing the treatment of pulse methylprednisolone therapy in fatal adenovirus pneumonia. During the clinical course, serum Krebs von den Lungen-6 (KL-6), which is a marker for the activity of diffuse interstitial lung disease, was elevated, suggesting that serum KL-6 could be available as a marker of pulmonary prognosis in viral pneumonia.
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PMID:Pulse methylprednisolone therapy in type 3 adenovirus pneumonia with hypercytokinemia. 1663 25

Legionella pneumophila causes community-acquired pneumonia with high mortality, but little is known about its interaction with the alveolar epithelium. The aim of this study was to investigate whether L. pneumophila infection of lung epithelial cells (A549) resulted in pro-inflammatory activation. L. pneumophila infection induced liberation of interleukin (IL)-2, -4, -6, -8 and -17, monocyte chemoattractant protein-1, tumour necrosis factor-alpha, IL-1beta, interferon-gamma and granulocyte colony-stimulating factor, but not of IL-5, -7, -10, -12 (p70) or -13 or granulocyte-macrophage colony-stimulating factor. The present study focused on IL-8 and found induction by L. pneumophila strains 130b, Philadelphia 1, Corby and, to a lesser extent, JR32. Knockout of dotA, a central gene involved in type IVB secretion, did not alter IL-8 induction, whereas lack of flagellin significantly reduced IL-8 release by Legionella. Moreover, p38 mitogen-activated protein kinase (MAPK) was activated and kinase inhibition reduced secretion of induced cytokines, with the exception of IL-2 and granulocyte colony-stimulating factor. In contrast, inhibition of the MAPK kinase 1/extracellular signal-regulated kinase pathway only reduced the expression of a few cytokines. L. pneumophila also induced binding of nuclear factor-kappaB subunit RelA/p65 and RNA polymerase II to the il8 promoter, and a specific inhibitor of the inhibitor of nuclear factor-kappaB complex dose-dependently lowered IL-8 expression. Taken together, Legionella pneumophila activated p38 mitogen-activated protein kinase- and nuclear factor-kappaB/RelA pathway-dependent expression of a complex pattern of cytokines by human alveolar epithelial cells, presumably contributing to the immune response in legionellosis.
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PMID:Legionella pneumophila-induced NF-kappaB- and MAPK-dependent cytokine release by lung epithelial cells. 1697 6

Protective mechanisms underlying the responses to mucosal vaccination are not yet clearly defined. Using the natural mouse pneumovirus pathogen, pneumonia virus of mice (PVM), we explore responses of wild type and interferon-gamma (IFNgamma) receptor gene-deleted mice to virulent challenge after mucosal vaccination with an attenuated virus strain. Serum neutralizing antibodies develop after intranasal inoculation with 30 pfu of attenuated, replication-competent PVM strain 15, which correlate with diminished gross and microscopic pulmonary pathology and protection from weight loss in response to subsequent challenge with the virulent parent PVM strain J3666. Virus replication in response to challenge was blunted in PVM strain 15 vaccinated mice, as was local production of secretory mediators IFNgamma, TNF-alpha, MIP-1 alpha, and MIP-2. Interestingly, responses of vaccinated IFNgamma receptor gene-deleted mice were indistinguishable from those of the wild type, suggesting that IFNgamma signaling may not be crucial for the generation of adaptive responses to pneumovirus infection in vivo.
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PMID:Mucosal inoculation with an attenuated mouse pneumovirus strain protects against virulent challenge in wild type and interferon-gamma receptor deficient mice. 1705 20

Chlamydia trachomatis is a kind of obligate intracellular bacterial pathogen that causes ocular and sexually transmitted diseases. In this study, we analyzed the codon usage patterns of the C. trachomatis mouse pneumonitis biovar (MoPn) and Homo sapiens. We found large differences between MoPn and human codon usages. To enhance the expression of Chlamydia protein in mammalian cells, the DNA sequence encoding the major outer-membrane protein (MOMP) of MoPn was modified to substitute the human-preferred codons for rarely used codons. The huma-optimized MOMP gene was synthesized and cloned into the pcDNA3 vector, as was the wild-type MOMP gene. The protein expression levels of the human-optimized MOMP and wild-type MOMP genes were compared. The experiments showed that the human-optimized MOMP gene produced significantly higher levels of MOMP protein than the wild-type MOMP, both in vitro and in vivo, but no obvious difference was observed in the levels of modified and native MOMP mRNA expression. The immunogenicity of the 2 constructs was examined using BALB/c mice following intramuscular immunization. The results showed that the mice immunized with the human-optimized MOMP produced higher levels of antigen-specific IgG antibody and showed stronger delayed-type hypersensitivity reactions and proliferative T cell responses than those immunized with the wild-type MOMP. Antigen-specific stimulation of spleen cells obtained from human MOMP DNA immunized mice produced higher levels of interferon-gamma than those obtained from wild-type MOMP DNA immunized mice. Taken together, the data show that human-optimized codon optimization can significantly enhance the gene expression and immunogenicity of the C. trachomatis MOMP DNA vaccine.
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PMID:Codon usage bias in Chlamydia trachomatis and the effect of codon modification in the MOMP gene on immune responses to vaccination. 1753 3

In this report, the authors present a detailed immunological and virological assessment of an immunocompetent 17-year-old Caucasian male with a fatal Epstein-Barr virus (EBV) infectious mononucleosis presenting with meningoencephalitis and hemophagocytic syndrome. The patient with serologically confirmed EBV infectious mononucleosis was admitted to the hospital because of 3 weeks' fever. Fine-needle aspiration of lymph nodes showed reactive hyperplasia with prominent hemophagocytosis. Percentages of intracellular interferon-gamma (IFN-gamma) in CD4(+) and CD8(+) T cells in the peripheral blood progressively increased during the course of disease (10.2% and 8.5% on day 35; 30.1% and 53.2% on day 44; 42.2% and 75.2% on day 50; 36.1% and 50.6% on day 59, respectively). On day 50, the patient developed meningoencephalitis. Brain computed tomography (CT) was normal. Brain magnetic resonance imaging (MRI) showed multifocal inflammatory lesions in frontal and temporal cortex of the right hemisphere as well as severe perivascular inflammatory reaction. The patient was treated with steroids, cyclosporin A, and methotrexate intratecally. Following treatment, EBV viremia in the blood and cerebrospinal fluid (CSF) decreased from pretreatment values (54,490 copies of EBV DNA/ml and 39,500 copies/ml, respectively) to 8715 copies/ml in the blood and 14,690 in the CSF. Despite treatment, the patient remained unconscious and died of sepsis and pneumonia 3 months after initial symptoms. Immunohistochemical staining showed the presence of EBV in both perivascular infiltrates and grey matter. Enhanced Th1 response as shown by high levels of IFN-gamma in peripheral blood lymphocytes may be a predictor of severe complications during acute EBV infection. Early implementation of immunosuppressive therapy in these patients should be considered.
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PMID:Virological and immunological characteristics of fatal Epstein-Barr virus mononucleosis in a 17-year-old Caucasian male presenting with meningoencephalitis and hemophagocytic syndrome. 1784 23

In the early stage of Mycobacterium tuberculosis infection, macrophages, in cooperation with interferon-gamma, a Th1 effector, are the first line of defense. Interleukin (IL)-4, a Th2 effector, is known to downregulate interferon-gamma. It is believed that the expression levels of IL-4 and its splicing variant-IL-4delta2 might be associated with Mycobacterium tuberculosis infection and chest radiographic patterns. The IL-4 and IL-4delta2 expressions in stimulated peripheral blood mononuclear cells of 76 tuberculosis patients, 48 pneumonic patients. and 36 healthy control subjects were evaluated by nested reverse transcriptase-polymerase chain reaction, and the expression of glyceraldehydes-3-phosphate dehydrogenase was used as an internal reference. The results showed that IL-4 mRNA expression was significantly decreased in patients with tuberculosis and nontubercular pneumonia compared with that in controls. The IL-4delta2 mRNA expression was positively correlated with IL-4 mRNA expression in all cases. The ratio of IL-4delta2 to IL-4 mRNA expression in tubercular patients with a cavity on chest radiography was significantly lower than that in patients without a chest cavity. In conclusion, the ratio of IL-4delta2 to IL-4 mRNA expression may play a key role in disease severity for patients with pulmonary tuberculosis. From our observations, the IL-4 mRNA expression efficiency was attenuated in patients with pulmonary infection, either tuberculosis or pneumonia.
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PMID:Efficiency of interleukin-4 expression in patients with tuberculosis and nontubercular pneumonia. 1796 71

A boy who had been diagnosed with chronic granulomatous disease (CGD) at the age of 6.5 years had a medical history of multiple bacterial infections, including pneumonia, staphylococcal liver abscesses and septicemia, from birth. At the age of 10 years and 4 months he developed an infection that was accompanied by high fever and pulmonary, mediastinal and paravertebral infiltrations. Aspergillus niger was cultured on bronchial secretions obtained by bronchoscopy. Shortly thereafter, proteinuria manifested and progressed to the nephrotic level. A skin biopsy indicated a diagnosis of amyloidosis. An anti-fungal treatment with amphotericin B and other agents, along with surgical pus drainage, intravenous leukocyte mass, interferon-gamma and immunoglobulin infusions, was ineffective, and the patient eventually died from multi-organ failure. The postmortem examination revealed the presence of disseminated aspergillosis and systemic amyloidosis. Although no direct evidence is available that would confirm the causative role of aspergillosis in the development of systemic amyloidosis, to the best of our knowledge this is the first report of a CGD case with complications of both invasive aspergillosis and systemic amyloidosis.
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PMID:Renal amyloidosis in a child with chronic granulomatous disease and invasive aspergillosis. 1818 9


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