Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.2.1.7 (BAL)
1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocyte-macrophage colony-stimulating factor (GM-CSF), in addition to being a haematopoietic growth factor, has been shown to stimulate in vitro the production of interleukins 1, 6 and 8 (IL-1, IL-6 and IL-8), tumour necrosis factor-alpha (TNF-alpha) and GM-CSF by polymorphonuclear cells (PMNs), alveolar macrophages (AMs), fibroblasts and endothelial cells of the lung, and the growth and differentiation of resident alveolar macrophages. The aim of this study was to establish whether recombinant GM-CSF (rhGM-CSF), administered subcutaneously at a dose of 5 micrograms.kg-1 for 3 days in five patients with unresectable non-small cell lung cancer before starting chemotherapy, induces an increase in the alveolar cell count, and whether these cellular lung variations may be related to increases in the above-mentioned cytokines. In the bronchoalveolar lavage fluid (BALF) total cell count, polymorphonuclear cells, neutrophils, and alveolar macrophages increased significantly in comparison with the baseline, and the extent of variation of the BAL cell count was considerably greater than that of the circulating leucocytes. The mean levels of all the cytokines increased, but a significant difference with respect to the basal condition was observed only for IL-6 and IL-8. After rhGM-CSF treatment, significant correlations were found between neutrophil counts and the levels of IL-6 and IL-8. In conclusion, rhGM-CSF administration induces a cellular expansion in the lung, and the neutrophil increase appears to be related to increased levels of IL-8.
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PMID:Blood cell redistribution in the lung after administration of recombinant human granulocyte-macrophage colony-stimulating factor. 857 86

Granulocyte-macrophage colony stimulating factor (GM-CSF) is an important hematopoietic growth factor which has been shown to induce proliferation and activation of inflammatory cells and may play a role in allergic diseases. An activity of GM-CSF was determined in serum and BAL-fluid of 12 asthma patients with bronchial hyperreactivity to histamine before and 24 hours after challenge test. It was found statistically significant increase (p < 0.05) of GM-CSF activity in patients with bronchial hyperreactivity to histamine.
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PMID:[Granulocyte-macrophage colony stimulating factor (GM-CSF) in material from broncho-alveolar lavage and serum of patients with bronchial asthma]. 875 60

A recently developed sandwich ELISA, which detects Aspergillus galactomannan, was tested retrospectively in serial serum samples from an allogeneic bone marrow transplant recipient with proven invasive aspergillosis (patient 1) and another with suspected disease (patient 2). Galactomannan was detected in the serum 4 and 28 days, respectively, before pulmonary infiltrates suggestive of fungal infection first became apparent on the chest X-ray. Aspergillus was detected by ELISA and PCR in BAL fluid samples from both patients, and in CSF from patient 1. The diagnosis was confirmed at autopsy for patient 1 by histopathology and the recovery of Aspergillus fumigatus from the lung and brain. Furthermore, in both patients the course of the antigen titer in the serum during antifungal treatment corresponded with the clinical outcome. These results confirm that the sandwich ELISA appears to be useful for the early diagnosis of invasive aspergillosis. The value of the test for monitoring the response to antifungal treatment remains to be established in prospective trials.
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PMID:Serial monitoring of Aspergillus antigen in the early diagnosis of invasive aspergillosis. Preliminary investigations with two examples. 910 82

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by an excessive accumulation of surfactant lipids and proteins in the alveolar space. In mice with a homozygous deletion of granulocyte macrophage-colony stimulating factor (GM-CSF), their phenotype mimics PAP. To evaluate whether the knockout mouse model mimics human disease, we evaluated GM-CSF expression in alveolar macrophages from a patient with PAP. We performed multiple whole lung lavages on a patient with PAP, and cultured BAL cells in the presence or absence of LPS. In contrast to the GM-CSF knockout mouse, human BAL cells from a patient with PAP expressed mRNA for GM-CSF following LPS stimulation. However, similar to the knockout mouse, GM-CSF protein release from BAL cells was undetectable with or without LPS. BAL cells from normal human controls released GM-CSF in abundance after LPS stimulation. In BAL cells from the patient with PAP, neutralization of interleukin-10 (IL-10) by anti-IL-10 antibody, resulted in enhanced GM-CSF production. Thus, alveolar macrophages from a PAP lung have deficient GM-CSF production analogous to the GM-CSF knockout mice; in contrast, human cells from a PAP lung have an intact GM-CSF gene. This case report illustrates an important difference between the knockout mouse model of PAP and the human disease.
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PMID:GM-CSF gene expression is normal but protein release is absent in a patient with pulmonary alveolar proteinosis. 941 86

Granulocyte-macrophage colony stimulating factor (GM-CSF) deficient mice develop a pulmonary alveolar proteinosis (PAP) syndrome which is corrected by the administration/expression of GM-CSF. These observations implicate GM-CSF in the pathogenesis of human PAP. We hypothesized that human PAP may involve an intrinsic cellular defect in monocytes/macrophages with an inability to produce GM-CSF and/or respond to GM-CSF. Thus, we investigated the cytokine responses to GM-CSF and LPS from peripheral blood monocytes and alveolar macrophages from patients with idiopathic PAP and healthy controls. Macrophage inflammatory protein-1-alpha (MIP) was measured from GM-CSF-stimulated cells and GM-CSF was measured from LPS-stimulated cells by ELISA. The MIP and GM-CSF production by monocytes and alveolar macrophages did not differ between PAP patients and healthy controls. Growth of the GM-CSF-dependent human myeloid cell line TF-1 was inhibited by serum from all patients studied (n = 10) and all patients had anti-GM-CSF antibody in their serum. The BAL from PAP patients had less detectable GM-CSF by ELISA than healthy controls (P = 0.05); in contrast, the inhibitory cytokine, interleukin-10 (IL-10), was increased in PAP compared to controls (P = 0.04). IL-10 is a potent inhibitor of LPS-stimulated GM-CSF production from healthy control alveolar macrophages. These studies are the first to demonstrate that circulating monocytes and alveolar macrophages from PAP patients are able to synthesize GM-CSF and respond to GM-CSF, suggesting no intrinsic abnormalities in GM-CSF signaling. In addition, these observations suggest that PAP in a subset of patients is the result of decreased availability of GM-CSF due to GM-CSF blocking activity and reduced GM-CSF production by IL-10.
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PMID:Pulmonary alveolar proteinosis is a disease of decreased availability of GM-CSF rather than an intrinsic cellular defect. 1077 1

The impact of cigarette smoke on allergic asthma remains controversial both clinically and experimentally. The objective of this study was to investigate, in a murine model, how cigarette smoke affects immune inflammatory processes elicited by a surrogate allergen. In our experimental design, mice were concurrently exposed to cigarette smoke and ovalbumin (OVA), an innocuous antigen that, unless introduced in the context of an adjuvant, induces inhalation tolerance. We show that cigarette smoke exposure has adjuvant properties, allowing for allergic mucosal sensitization to OVA. Specifically, concurrent exposure to cigarette smoke and OVA for 2 weeks led to airway eosinophilia and goblet cell hyperplasia. In vivo OVA recall challenge 1 month after the last smoke exposure showed that concurrent exposure to OVA and cigarette smoke induced antigen-specific memory. Robust eosinophilia and OVA-specific IgG1 and IgE characterized the ensuing inflammatory response. Mechanistically, allergic sensitization was, in part, granulocyte macrophage colony-stimulating factor (GM-CSF) dependent, as a significant reduction in BAL eosinophilia was observed in mice treated with an anti-GM-CSF antibody. Of note, continuous smoke exposure attenuated the OVA recall response; decreased airway eosinophilia was observed in mice continuously exposed to cigarette smoke compared with mice that ceased the smoke exposure protocol. In conclusion, we demonstrate experimentally that while cigarette smoke acts as an adjuvant allowing for allergic sensitization, it also attenuates the ensuing eosinophilic inflammatory response.
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PMID:Adjuvant and anti-inflammatory properties of cigarette smoke in murine allergic airway inflammation. 1863 15

In 1997, while still working at NeXstar Pharmaceuticals, several of us made a proteomic bet. We thought then, and continue to think, that proteomics offers a chance to identify disease-specific biomarkers and improve healthcare. However, interrogating proteins turned out to be a much harder problem than interrogating nucleic acids. Consequently, the 'omics' revolution has been fueled largely by genomics. High-scale proteomics promises to transform medicine with personalized diagnostics, prevention, and treatment. We have now reached into the human proteome to quantify more than 1000 proteins in any human matrix - serum, plasma, CSF, BAL, and also tissue extracts - with our new SOMAmer-based proteomics platform. The surprising and pleasant news is that we have made unbiased protein biomarker discovery a routine and fast exercise. The downstream implications of the platform are substantial.
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PMID:Advances in human proteomics at high scale with the SOMAscan proteomics platform. 2215 39

Dysphagia is a rare manifestation of sarcoidosis. It is more commonly the result of esophageal compression by enlarged mediastinal lymph nodes rather than direct esophageal involvement and rarely secondary to neurosarcoidosis and oropharyngeal dysphagia. We report a 54 year old female presenting with a six month history of worsening dysphagia. She denied respiratory symptoms. Physical exam was normal. ESR was 61 mm/hr. Serum ACE level was 65 mcg/L. Chest X-ray was normal. Esophagram revealed a large amount of contrast pooling in pharyngeal recesses with intermittent laryngeal aspiration. Swallow videofluorography showed a decreased retraction of the base of the tongue, limited laryngeal elevation, and a large amount of contrast pooling in pharyngeal recesses with intermittent laryngeal aspiration. EGD showed a normal opening of the upper esophageal sphincter and the cricopharyngeus appeared normal. Proximal esophageal biopsies were normal. Brain MRI with gadolinium was normal. Lumbar puncture was performed. CSF showed a moderate pleocytosis, a WBC count of 19 with 97% lymphocytes, an elevated total protein level of 85 mg/dl (15-60). Neck CT scan showed no oropharyngeal tissue thickening or infiltration, no masses or enlarged lymph nodes. Chest CT scan showed enlarged intrathoracic lymph nodes and no esophageal compression. Bronchoscopy showed the vocal cords to be intact, and the CD4/CD8 ratio in BAL was 5.3. Subcarinal lymph node EBUS biopsy revealed non caseating granulomas. The patient was started on IV methylprednisolone. Three days later, the swallow videofluorography showed a near complete response to steroids. The patient tolerated regular consistency diet with thin liquids, and she was discharged on a slow taper of prednisone over a period of three months. A unique case of isolated dysphagia unmasking bulbar neurosarcoidosis and pulmonary sarcoidosis is herein reported.
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PMID:Isolated dysphagia unmasking bulbar neurosarcoidosis and pulmonary sarcoidosis. 2509 53

A wide array of PCR tests has been developed to aid the diagnosis of invasive aspergillosis (IA), providing technical diversity but limiting standardisation and acceptance. Methodological recommendations for testing blood samples using PCR exist, based on achieving optimal assay sensitivity to help exclude IA. Conversely, when testing more invasive samples (BAL, biopsy, CSF) emphasis is placed on confirming disease, so analytical specificity is paramount. This multicenter study examined the analytical specificity of PCR methods for detecting IA by blind testing a panel of DNA extracted from a various fungal species to explore the range of Aspergillus species that could be detected, but also potential cross reactivity with other fungal species. Positivity rates were calculated and regression analysis was performed to determine any associations between technical specifications and performance. The accuracy of Aspergillus genus specific assays was 71.8%, significantly greater (P < .0001) than assays specific for individual Aspergillus species (47.2%). For genus specific assays the most often missed species were A. lentulus (25.0%), A. versicolor (24.1%), A. terreus (16.1%), A. flavus (15.2%), A. niger (13.4%), and A. fumigatus (6.2%). There was a significant positive association between accuracy and using an Aspergillus genus PCR assay targeting the rRNA genes (P = .0011). Conversely, there was a significant association between rRNA PCR targets and false positivity (P = .0032). To conclude current Aspergillus PCR assays are better suited for detecting A. fumigatus, with inferior detection of most other Aspergillus species. The use of an Aspergillus genus specific PCR assay targeting the rRNA genes is preferential.
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PMID:Determining the analytical specificity of PCR-based assays for the diagnosis of IA: What is Aspergillus? 2833 44

Cryptococcus-macrophage interaction is crucial in the development of cryptococcocal diseases. C. neoformans and C. gattii are major pathogenic species that occupy different niches and cause different clinical manifestations. However, the differences of macrophage interaction among these species in affecting different disease outcomes and immune responses have not been clearly addressed. Here, we examined the macrophage uptake rates, intracellular loads and intracellular proliferation rates of C. neoformans and C. gattii clinical isolates from Thailand and analyzed the effect of those interactions on fungal burdens and host immune responses. C. neoformans isolates showed a higher phagocytosis rate but lower intracellular proliferation rate than C. gattii. Indeed, the high intracellular proliferation rate of C. gattii isolates did not influence the fungal burdens in lungs and brains of infected mice, whereas infection with high-uptake C. neoformans isolates resulted in significantly higher brain burdens that associated with reduced survival rate. Interestingly, alveolar macrophages of mice infected with high-uptake C. neoformans isolates showed distinct patterns of alternatively activated macrophage (M2) gene expressions with higher Arg1, Fizz1, Il13 and lower Nos2, Ifng, Il6, Tnfa, Mcp1, csf2 and Ip10 transcripts. Corresponding to this finding, infection with high-uptake C. neoformans resulted in enhanced arginase enzyme activity, elevated IL-4 and IL-13 and lowered IL-17 in the bronchoalveolar lavage. Thus, our data suggest that the macrophage interaction with C. neoformans and C. gattii may affect different disease outcomes and the high phagocytosis rates of C. neoformans influence the induction of type-2 immune responses that support fungal dissemination and disease progression. Abbreviation: Arg1: Arginase 1; BAL: Bronchoalveolar lavage; CCL17: Chemokine (C-C motif) ligand 17; CNS: Central nervous system; CSF: Cerebrospinal fluid; Csf2: Colony-stimulating factor 2; Fizz1: Found in inflammatory zone 1; HIV: Human immunodeficiency virus; ICL: Intracellular cryptococcal load; Ifng: Interferon gamma; Ip10: IFN-g-inducible protein 10; IPR: Intracellular proliferation rate; Mcp1: Monocyte chemoattractant protein 1; Nos2: Nitric oxide synthase 2; PBS: Phosphate-Buffered Saline; Th: T helper cell; Tnfa: Tumor necrosis factor alpha.
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PMID:Cryptococcus neoformans and Cryptococcus gattii clinical isolates from Thailand display diverse phenotypic interactions with macrophages. 3052 Jun 85


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