Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several clinical trials have demonstrated that granulocyte colony-stimulating factor (G-CSF) accelerates the recovery of neutropenia in chemotherapy-induced bone marrow suppression. In this report, we describe a 46-year-old female with glioblastoma multiforme who developed interstitial pneumonia due to administration of G-CSF during the phase of immunochemoradiotherapy-induced neutropenia. Thirty-three days after starting immunochemoradiotherapy (ACNU, VCR, IFN -beta, radiation), she developed neutropenia (1,000/microliters). Administration of G-CSF at doses of 125-250 micrograms/day led to an increase of peripheral neutrophil counts. Eleven days later, the patient developed sudden severe respiratory failure and cyanosis with worsening of lung shadows. Blood gas levels on room air were PaO2 49.3mmHg, PaCO2 28.0mmHg, and pH 7.46. At this time, her neutrophil count had risen to 26,080/microliters. LDH and alpha - HBD had also increased to 1,439 IU/l and 1,117IU/l respectively. Chest radiograph and CT scan demonstrated interstitial pneumonia. After treatment with methyl prednisolone, her respiratory symptoms were gradually resolved. A number of side-effects have been reported with granulocyte-macrophage colony-stimulating factor (GM-CSF). These include fluid retention with pericardial and pleural effusion, fever, bone pain, fatigue, and rash. This report also suggests that G-CSF might be a cause of interstitial pneumonia during the phase of immunochemoradiotherapy-induced neutropenia.
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PMID:[A case report of interstitial pneumonia caused by granulocyte colony-stimulating factor]. 750 62

Deficiency of the granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin-3 (IL-3)/IL-5 receptors common beta chain (betac) is a cause of fatal respiratory failure. betac deficiency manifests as pulmonary alveolar proteinosis (PAP). PAP has heterogenous etiologies that may be genetic or aquired. Some cases of PAP have been reported to be associated with hematologic malignancies such as acute myeloid leukemia (AML). In mice, the PAP phenotype was generated by targeted deletion of the gene for betac and can be treated by transplantation of wild-type bone marrow into betac -/- mice. Thus, our findings in betac -/- mice provide evidence for a causal relationship between the lung disease and the hematopoietic system. We describe here expression defects of betac or betac plus GM-CSF receptor alpha chain (GM-CSFR alpha) in 3 pediatric patients with AML and PAP symptoms. All of the patients' leukemic cells failed to express normal levels of betac. The leukemic cells of patients no. 2 and 3 additionally lacked the expression of GM-CSFR alpha, as shown by flow cytometry. Strikingly reduced or absent function of betac was demonstrated in clonogenic progenitor assays with absent colony-forming unit (CFU) growth after GM-CSF or IL-3 stimulation. The response to growth factors acting via a growth factor receptor distinct from the GM-CSF/IL-3/IL-5 system (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was normal. After antileukemic treatment, the pulmonary symptoms resolved and betac or betac plus GM-CSFR alpha expression was normal. Our findings provide evidence that a defect in the expression of betac or betac plus GM-CSFR alpha on AML blasts can be associated with respiratory failure in patients with AML.
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PMID:Defective expression of granulocyte-macrophage colony-stimulating factor/interleukin-3/interleukin-5 receptor common beta chain in children with acute myeloid leukemia associated with respiratory failure. 969 96

Pulmonary alveolar proteinosis is a rare clinical syndrome that was first described in 1958. Subsequently, over 240 case reports and small series have described at least 410 cases in the literature. Characterized by the alveolar accumulation of surfactant components with minimal interstitial inflammation or fibrosis, pulmonary alveolar proteinosis has a variable clinical course ranging from spontaneous resolution to death with pneumonia or respiratory failure. The most effective proven treatment--whole lung lavage--was described soon after the first recognition of this disease. In the last 8 years, there has been rapid progress toward elucidation of the molecular mechanisms underlying both the congenital and acquired forms of pulmonary alveolar proteinosis, following serendipitous discoveries in gene-targeted mice lacking granulocyte-macrophage colony-stimulating factor (GM-CSF). Impairment of surfactant clearance by alveolar macrophages as a result of inhibition of the action of GM-CSF by blocking autoantibodies may underlie many acquired cases, whereas congenital disease is most commonly attributable to mutations in surfactant protein genes but may also be caused by GM-CSF receptor defects. Therapy with GM-CSF has shown promise in approximately half of those acquired cases treated, but it is unsuccessful in congenital forms of the disease, consistent with the known differences in disease pathogenesis.
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PMID:Pulmonary alveolar proteinosis: progress in the first 44 years. 1266 43

Pulmonary alveolar proteinosis is a rare syndrome characterized by intra-alveolar accumulation of surfactant components and cellular debris, with minimal interstitial inflammation or fibrosis. The condition has a variable clinical course, from spontaneous resolution to respiratory failure and death due to disease progression or superimposed infections. The standard of care for alveolor proteinosis therapy is represented by whole lung lavage. Important discoveries have been made in the last decade with respect to disease pathogenesis and therapy of both congenital and acquired forms of the disease. Granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway has been shown to be involved in the disease pathogenesis of both acquired and congenital disease. Furthermore, anti-GM-CSF blocking autoantibodies have been found in the serum and bronchoalveolar lavage fluid and seem to interfere with the surfactant clearance by alveolar macrophages in many acquired cases. In the congenital form, the most common defects identified to date are several mutations of the genes encoding GM-CSF receptor subunits or surfactant proteins. Using GM-CSF as a therapeutic tool has also been shown to be effective in at least half of the acquired cases treated, while the importance of quantitative determination of anti-GM-CSF antibodies before and during the course of the therapy, as well as the autoantibody titer-GM-CSF dose relationship are to be elucidated. The congenital form of the disease does not respond to therapy with GM-CSF, consistent with the known primary defects and differences in disease pathogenesis.
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PMID:Pulmonary alveolar proteinosis. 1691 9

Systemic and inhalation therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) is usually effective in controlling autoimmune pulmonary alveolar proteinosis (PAP), but some cases are refractory to GM-CSF therapy and subjected to whole lung lavage (WLL). A 9-year-old girl developed severe respiratory failure due to autoimmune PAP was treated with inhalational 250 microg of GM-CSF daily, however, it was ineffective. Unilateral WLL was performed three times and subsequent GM-CSF inhalation therapy yielded marked physiological and radiological improvement and was continued for 1 year.
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PMID:A combination therapy of whole lung lavage and GM-CSF inhalation in pulmonary alveolar proteinosis. 1861 17

To describe the clinical, radiological and pathological characteristics of idiopathic pulmonary alveolar proteinosis (I-PAP) and to evaluate the methods of diagnosis and treatment. Three patients were successfully diagnosed and treated in our hospital and the literature on the subject was reviewed. Three patients, two males and one female (mean age 46 years), were diagnosed averagely in 4 months. Two severe patients presented with progressive dyspnea and type I respiratory failure, and one mild patient only with dry cough and hypoxemia. Chest X-ray radiographs all showed perihilar "butterfly" shadow and chest CT scans showed diffused ground-glass opacities (GGO), typically with "map" changes and "crazy paving" patterns. All the patients underwent bronchoscope, branchoalveolar lavage fluid (BALF) had grossly opaque and/or milky appearance and its sediment was periodic acid-Schiff stain positive. Trans-bronchoscopic lung biopsy (TBLB) specimens were obtained and under light microscopy alveoli and some of the small bronchioles were filled with eosinophilic proteinaceous material with needle-like clefts. By electron microscopy numerous cellular debris and extracellular multilamellated bodies were found. Two severe patients were successfully treated with sequential whole-lung lavage and one required repeated lavages. I-PAP is rare and prone to be misdiagnosed. The radiological features may indicate the diagnosis and examinations of TBLB and BALF can make the accurate diagnosis. Whole-lung lavage is the most effective therapy by now and granulocyte-macrophage colony-stimulating factor (GM-CSF) may be beneficial in some patients.
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PMID:[Idiopathic pulmonary alveolar proteinosis: report of three cases and literature review]. 1893 23

Pulmonary alveolar proteinosis is a rare condition characterized by the accumulation of lipoproteinaceous material within the airspaces, resulting in impaired gas transfer, and clinical manifestations ranging from asymptomatic to severe respiratory failure. To the best of the authors' knowledge, there are only a few conditions whose natural history has been so dramatically changed by the influence of advances in basic science, clinical medicine, and translational research in therapeutic approaches. Whole-lung lavage is the current standard of care and it plays a critical role as a modifier factor of the natural history of proteinosis. That notwithstanding, the identification of autoantibodies neutralizing granulocyte-macrophage colony-stimulating factor in serum and lung of patients affected by the form of proteinosis previously referred to as idiopathic, has opened the way to novel therapeutic options, such as supplementation of exogenous granulocyte-macrophage colony-stimulating factor, or strategies aimed at reducing the levels of the autoantibodies. The aim of this paper is to provide an updated review of the current therapeutic approach to proteinosis.
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PMID:Therapy options in pulmonary alveolar proteinosis. 2064 42

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the accumulation of surfactant lipids and protein in the alveolar spaces, with resultant impairment in gas exchange. The clinical course can be variable, ranging from spontaneous resolution to respiratory failure and death. PAP in all forms is caused by excessive accumulation of surfactant within the alveolar spaces. Autoimmune PAP accounts for the vast majority of cases in humans and is caused by autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF), which results in impaired catabolism and clearance of surfactant lipids and proteins. Inherited or congenital forms of PAP are exceptionally rare and caused by mutations of genes encoding for surfactant proteins. Secondary forms of PAP are associated with diverse clinical disorders and are caused by reduced alveolar macrophage numbers or function with resultant reduced pulmonary clearance of surfactant. PAP is characterized by progressive exertional dyspnea and nonproductive cough with hypoxemia. Bilateral infiltrates are typically present on chest radiograph, and high-resolution computed tomography reveals diffuse ground-glass opacities and airspace consolidation with interlobular septal thickening in a characteristic "crazy paving" pattern. Although surgical lung biopsy will provide a definitive diagnosis, a combination of typical clinical and imaging features with periodic acid-Schiff (PAS)-positive material on bronchoalveolar lavage and transbronchial biopsies is usually sufficient. The standard of care for treatment of PAP remains whole lung lavage, but treatment is not required in all patients. Autoimmune PAP has also been successfully treated with GM-CSF, both inhaled and systemic, but the optimal dose, duration, and route of administration of GM-CSF have not been elucidated.
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PMID:Pulmonary alveolar proteinosis. 2300 4

Pulmonary alveolar proteinosis (PAP) is an orphan disease characterized by the accumulation of excess of surfactant within alveoli and bronchioles. The primary form of PAP (P-PAP; also referred to as idiopathic or autoimmune) is the most common form. It is mediated through a circulating neutralizing antibody against granulocyte-macrophage colony-stimulating factor. Secondary PAP (S-PAP) can be induced by a host of inciting agents and is far more liable to progress to terminal respiratory failure. We describe a rare case of S-PAP occurring in a renal transplant recipient due to mycophenolate and cyclosporine combination-therapy, which resolved spontaneously following withdrawal of these drugs.
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PMID:Pulmonary alveolar proteinosis due to mycophenolate and cyclosporine combination therapy in a renal transplant recipient. 2512 21

A 59-year-old man, ex-smoker, was diagnosed with pulmonary aspergillosis according to chest radiography findings of a fungus ball and Aspergillus fumigatus detection in the bronchial lavage fluid. Two years after anti-fungal therapy, he was diagnosed with autoimmune pulmonary alveolar proteinosis (APAP) according to a crazy paving pattern in computed tomography scans of the chest, milky bronchoalveolar lavage effluent, and positive anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody in the serum. The patient ultimately died of respiratory failure caused by APAP four months after GM-CSF therapy commenced. Aspergillus infection may thus be associated with the onset and progression of APAP and tolerance to GM-CSF therapy.
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PMID:Autoimmune Pulmonary Alveolar Proteinosis Following Pulmonary Aspergillosis. 2666 7


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