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)

The current mainstay of treatment for pulmonary alveolar proteinosis (PAP) is whole-lung lavage. Therapy with granulocyte-macrophage colony-stimulating factor is a possibility, although its long-term safety has not been determined. An alternative procedure is selected lobar lavage by fiberoptic bronchoscopy (FOB). We report here our experiences with lobar lavage by FOB in treating three patients with PAP. PAP was diagnosed in three patients (two men, one woman) who had dyspnea and hypoxemia after undergoing open-lung biopsy. The patients underwent lobar lavage by FOB under local anesthesia. The bronchoscope was wedged into a lobar bronchus. Approximately 2,000 mL warm normal saline solution was instilled via syringe in 50-mL aliquots through a fiberoptic bronchoscope. After undergoing multiple lobar lavages, two patients showed clinical, physiologic, and radiologic improvement. The third patient, who had more advanced disease, showed improvement only in oxygenation. The major complications were severe cough and hypoxemia during lavage. Our experience suggests that bronchoscopic lobar lavage is simple and safe, and may find application in patients in whom a whole-lung lavage with generalized anesthesia may be hazardous, and in patients with less advanced disease whose proteinaceous substances can be removed with a small volume of lavage fluid.
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PMID:Pulmonary alveolar proteinosis: treatment by bronchofiberscopic lobar lavage. 1237 31

A 79-year-old woman was admitted to hospital due to a four-month history of a cough and dyspnea on exertion. Chest CT scans revealed ground glass opacity with thickened interlobular septa in both lungs. Bronchoalveolar lavage fluid (BALF) had milky appearance and revealed large acellular eosinophilic amorphous bodies positively stained with periodic acid-Schiff (PAS). Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) were present in sera and BALF from the patient. Ambroxol was started in a daily dose of 45 mg orally. Her oxygen saturation improved and abnormal shadows in CT scan disappeared 6 months after beginning the therapy.
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PMID:Pulmonary alveolar proteinosis successfully treated with ambroxol. 1252 Nov 91

A 47-year-old man, who had been diagnosed as myelodysplastic syndrome (MDS), complained of a severe cough and a high-grade fever. Chest CT disclosed scattered small nodules and ground-glass opacities with interlobular septal thickening in both lung fields and a mass lesion in the right lower lobe. Pathological findings of the ground-glass opacities and the mass lesion obtained by video-assisted thoracoscopic surgery revealed the accumulation of eosinophilic amorphous material in the alveoli and confirmed the diagnosis of pulmonary alveolar proteinosis (PAP). Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in sera were below sensitivity, while the GM-CSF level was elevated in bronchoalveolar lavage fluid. He was diagnosed as secondary PAP associated with MDS.
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PMID:Secondary pulmonary alveolar proteinosis associated with myelodysplastic syndrome. 1263 40

Schisandra fructus has been used for treatment of cough and thirst in Korea. However, its therapeutic mechanisms remain largely unclear. To investigate the biological effect of Schisandra fructus water extract (SFWE), we examined the effect of SFWE on the phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187-induced pro-inflammatory cytokine secretion in the human mast cell line HMC-1. HMC-1 cells were stimulated with PMA plus A23187 in the presence or absence of SFWE. Tumor necrosis factor (TNF)-alpha, interleukin 6 (IL-6), and granulocyte-macrophage colony-stimulating factor (GM-CSF) productions were measured by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction. Inhibitory IkappaB/nuclear factor-kappaB (NF-kappaB) expression was assessed by western blot. SFWE suppressed PMA plus A23187-induced TNF-alpha, IL-6, and GM-CSF production in dose-dependent manners. Furthermore, SFWE inhibited IkappaB degradation and NF-kappaB nuclear translocation. These results suggest that SFWE inhibits the secretion of pro-inflammatory cytokines in HMC-1 cells through blockade of IkappaB degradation and NF-kappaB activation. Taken together, these findings may help elucidate the mechanism of action of this medicine in the modulation of mast cell activation in inflammatory conditions.
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PMID:Effects of the Schisandra fructus water extract on cytokine release from a human mast cell line. 1720 33

The acquired form of pulmonary alveolar proteinosis was determined in 3 patients, a woman of 31 and 2 men of48 and 38 years, respectively. Their symptoms consisted of progressive dyspnoea, with or without coughing and a tight feeling in the chest. Bronchoscopy with bronchoalveolar lavage yielded milky white, frothy material, and high resolution CT revealed parenchymal densification. All 3 patients were successfully treated with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim); in addition, the first and last patient underwent total pulmonary lavage. During the pregnancy of the woman, the GM-CSF treatment was suspended; this was resumed after parturition, which took place via caesarean section. Pulmonary alveolar proteinosis is a rare disease characterised by accumulation of surfactant in the alveoli. Until recently, the treatment consisted only of total lung lavage under general anaesthesia. It has recently been discovered that IgG autoantibodies play an important role in the development ofthe disease, namely in the accumulation of surfactant in the alveoli. IgG autoantibodies appear to neutralise the biological activity of natural GM-CSF, which leads to accumulation of used surfactant in the alveoli and a decrease of the pulmonary diffusion capacity. These cases and other publications from the past few years underline the important role of GM-CSF, in addition to a total lung lavage, in the treatment of pulmonary alveolar proteinosis.
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PMID:[Pulmonary alveolar proteinosis: a disease caused by surfactant accumulation, and new treatment with sargramostim]. 1866 60

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

A 63-year-old man visited our department due to dry cough in September 2005. Chest radiography showed an infiltrative shadow extending from the bilateral hila to the peripheral areas. Chest CT scanning revealed a crazy-paving appearance. Bronchoalveolar lavage and transbronchial lung biopsy confirmed alveolar proteinosis. In addition, based on the absence of an underlying disease and a high titer of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody, a diagnosis of autoimmune alveolar proteinosis was made. His course was observed on an outpatient basis because of mild symptoms, but dyspnea on exertion gradually increased. In July 2007, GM-CSF inhalation therapy was initiated in another hospital, but no improvement was observed. In November of the same year, he underwent whole-lung lavage for one lung followed by that for the other at our department. The symptoms rapidly improved after the lavage but were aggravated again after 6 months. In May 2008, whole-lung lavage was performed again. There have been no reports of adults with autoimmune alveolar proteinosis who did not respond to GM-CSF inhalation therapy and who underwent whole-lung lavage twice. GM-CSF inhalation therapy for autoimmune alveolar proteinosis is a pathogenesis-based epoch-making therapy, but the response rate is about 60%. In patients with treatment-resistant autoimmune alveolar proteinosis showing repeated aggravation of symptoms, whole-lung lavage under general anesthesia is a reliable therapeutic method.
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PMID:[Patient with autoimmune alveolar proteinosis who did not respond to GM-CSF inhalation therapy and underwent repeated whole-lung lavage]. 1982 90

Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease characterized by abnormal accumulation of surfactant-associated phospholipoproteinaceous material in the pulmonary alveoli. The clinical findings of slow-onset dyspnea or dyspnea on exertion and persistent dry cough are nonspecific; radiographic findings of "bat-wing configuration" and "crazy paving" appearance in high-resolution computed tomography are suggestive, but not diagnostic of PAP. The current gold standard of PAP diagnosis involves histopathological examination of alveolar specimens obtained from bronchoalveolar lavage and transbronchial lung biopsy. The characteristic histopathological features are intraalveolar periodic acid Schiff (PAS)-positive eosinophilic homogeneous material with well-preserved architecture ofalveolar septa. The current standard medical treatment of PAP involves the physical removal of the surfactant-associated phospholipoproteinaceous alveolar deposit by whole lung lavage, which causes clinical and radiological improvement in a majority of patients. Some patients have been successfully treated with recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF).
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PMID:Pulmonary alveolar proteinosis: an overview for internists and hospital physicians. 2046 23

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) - an unusual diffuse lung disease characterized by alveolar accumulation of phospholipoprotein material, with a peak incidence in third to fourth decade and male predominance is also described in children. Recorded prevalence is 0.1/100,000 individuals. Major clinicopathogenetic subtypes include autoimmune (idiopathic) associated with granulocyte-macrophage colony-stimulating factor autoantibodies, secondary form, and the congenital form (associated with surfactant gene mutations). Common presenting features include dyspnea, cough, low-grade fever, inspiratory crackles, and digital clubbing. Pulmonary function shows a restrictive ventilatory defect. X-rays show bilateral patchy to extensive consolidations, and bronchial lavage yields a milky fluid. Characteristic microscopic findings on lung biopsy include filling of terminal bronchioles and alveolar spaces by deep pink granular PAS-positive material. Whole lung lavage is the safest and most effective form of treatment. We present brief profiles of two young children identified as having PAP, along with follow-up data on one of them.
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PMID:Pulmonary alveolar proteinosis in children: An unusual presentation with significant clinical impact. 3000 70


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