ABSTRACT
A cyclic tetrapeptide FR235222, a novel immunosuppressant, has been isolated from the fermentation broth of a fungus, Acremonium sp. No. 27082. FR235222 showed potent and selective inhibitory effects on both T cell proliferation and lymphokine production. Further study has revealed this compound exhibits potent inhibitory effects on the activity of mammalian histone deacetylases (HDACs).
Subject(s)
Acremonium/metabolism , Enzyme Inhibitors/isolation & purification , Histone Deacetylase Inhibitors , Immunosuppressive Agents/isolation & purification , Peptides, Cyclic/isolation & purification , Acremonium/chemistry , Acremonium/classification , Acremonium/immunology , Animals , Enzyme Inhibitors/immunology , Enzyme Inhibitors/pharmacology , Female , Fermentation , Hepatocytes/drug effects , Hepatocytes/immunology , Immunosuppressive Agents/immunology , Immunosuppressive Agents/pharmacology , Interleukin-2/immunology , Interleukin-2/metabolism , Interleukin-4/immunology , Interleukin-4/metabolism , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Lymphocyte Culture Test, Mixed , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Nude , Peptides, Cyclic/immunology , Peptides, Cyclic/pharmacology , Rats , Soil Microbiology , T-Lymphocytes/cytology , T-Lymphocytes/drug effects , T-Lymphocytes/immunologyABSTRACT
A 64-year-old man was hospitalized for productive cough and dyspnea. Both chest radiographs and CT scans showed areas of ground-glass opacity in the middle and lower lung fields on both sides. The BAL and TBLB findings were compatible with hypersensitivity pneumonitis. The serum was negative for antibodies against Trichosporon species, and the result of a lymphocyte stimulating test for administered drugs including a Chinese medicine was also negative. A humidifier was suspected as the cause because it had been used for more than 10 years in the factory where the patient had been working. An inhalation test using the humidifier fluid successfully provoked dyspnea, fever and fine crackle, and laboratory tests demonstrated hypoxemia, reduction in vital capacity and the elevation of CRP. Agar gel diffusion using the patient's serum showed a precipitating line against Cephalosporium acremonium, but this line did not fuse with any precipitating line formed between the humidifier fluid and the serum, indicating that no Cephalosporium was Present in the humidifier fluid. Since a high level of beta-D glucan was detected in the humidifier fluid, an unidentified fungus was suspected to be the antigen.
Subject(s)
Alveolitis, Extrinsic Allergic/etiology , Humidity/adverse effects , Occupational Diseases/etiology , Acremonium/immunology , Alveolitis, Extrinsic Allergic/microbiology , Antibodies, Fungal/analysis , Humans , Male , Middle Aged , Occupational Diseases/microbiologyABSTRACT
Twenty-five horses with chronic pulmonary disease were skin tested with allergenic extracts of 24 molds, 4 thermophilic actinomyces, barn dust, hay dust, soya-bean mill dust, and grain mill dust. The results were compared with those obtained on 25 normal horses. Between the 2 groups of horses, there was a highly significant difference in positive skin test results at 30 minutes and 4 hours.
Subject(s)
Horse Diseases/immunology , Lung Diseases, Obstructive/veterinary , Respiratory Hypersensitivity/veterinary , Acremonium/immunology , Animals , Antigens, Bacterial , Antigens, Fungal , Dust , Edible Grain , Horse Diseases/etiology , Horses , Lung Diseases, Obstructive/etiology , Lung Diseases, Obstructive/immunology , Micromonosporaceae/immunology , Respiratory Hypersensitivity/immunology , Rhizopus/immunology , Skin Tests , Glycine maxABSTRACT
In 5 patients with respiratory symptoms consistent with humidifier or air conditioner disease, a hypersensitivity pneumonitis, no identifiable organism was cultured from the humidifier water (HW). The water source to the humidifier or air conditioner was investigated for possible antigens which might explain the occurrence of the disease. Three subjects who lived in the same city supplied by Lake Michigan had increased IgG antibody activity against the city water supply when compared with another patient from a different city and a control subject. Both of the latter lived in cities with water supplied from Lake Michigan. Two of the 5 patients showed definite inhibition by concentrated tap water (TW) of IgG antibody against HW. The source of antigens in water was not determined but must be considered in cases of this type of hypersensitivity pneumonitis. A sixth case consistent with humidifier disease had Cephalosporium cultured from her HW. On gel diffusion there was a band of identity with her serum against Cephalosporium extract and her own HW, and by radioimmunoassay (RIA) there was over 50% inhibition of her IgG antibody activity against HW by Cephalosporium. No antibody against her city TW was demonstrated.
