Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intralobar instillation of cadmium chloride (CdCl2) into the left lungs of rats initiated a sequence of events that culminated in massive unilateral intraluminal fibrosis. Early events (days 1 and 2) after CdCl2 administration included infiltration of the treated lung with polymorphonuclear leukocytes, an increase in the number of alveolar macrophages, activation of the macrophages as assessed by the induction of cathepsin L mRNA, and the induction in liver of mRNA for the acute-phase response protein, alpha 1-acid glycoprotein. By days 5 to 7 in the treated lungs, mRNA for procollagen alpha 1(I) increased 20- to 60-fold, and mRNA for procollagen alpha 1(III) increased 4- to 14-fold. These increases were correlated with the almost complete filling of the alveolar spaces with fibroblasts and collagen. The contralateral lung exhibited no significant change in histology but showed a similar induction of collagen gene expression. These increases were tissue-specific, as the livers of these animals showed no change from the control levels of collagen gene expression. Procollagen messages in the treated and contralateral lungs were equally competent for translation into pro-alpha 1(I) and pro-alpha 2(I) polypeptides. Both the treated and contralateral lungs increased hydroxyproline content about 1.5- to 2-fold over 14 days. The contralateral lung, but not the treated lung, showed a 2-fold increase in lung volume. As a result, the collagen density (mg collagen/ml lung volume) doubled in the treated lung but remained constant in the contralateral lung. These data indicate that CdCl2 caused a rapid induction of pulmonary fibrosis in the treated lungs of rats and stimulated histologically normal growth of the contralateral lung.
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PMID:Induction of unilateral pulmonary fibrosis in the rat by cadmium chloride. 191 Aug 23

Analysis of polymorphic systems, demonstrating differences among ethnic groups, provides a valuable tool for biology and medicine. Blast-1 is a member of the immunoglobulin superfamily and an activation-associated glycoprotein expressed on the surface of mononuclear cells. Blast-1 demonstrates DNA polymorphism in healthy controls and patients with rheumatoid arthritis (RA). The sizes of polymorphic restriction endonuclease fragments of genomic DNA encoding Blast-1 were 2.4 and 1.9 kb. In normal controls, the frequency of the homozygote for the 2.4 kb fragment (L-L) was 0.69 and 0.47, and that for the 1.9 kb fragment (S-S) was 0.04 and 0.11 in Caucasians and Japanese, respectively. The frequency of the heterozygote for both fragments (L-S) was 0.27 and 0.42 in Caucasians and Japanese, respectively. The frequencies of the L and S alleles were 0.83 and 0.17 for Caucasians, respectively, and were 0.68 and 0.32 for Japanese, respectively. The difference in the allele frequency between Caucasians and Japanese was significant. In Japanese patients with RA, the frequency of L-L, L-S and S-S types was 0.45, 0.45 and 0.10, respectively. Lung fibrosis in Japanese RA patients was associated with an increase in the L-S and S-S types and a decrease in the L-L type. The present study indicates that the investigation for gene polymorphisms of Blast-1 among distinct ethnic groups is important because Blast-1 appears to be a genetic marker for the manifestation associated with RA.
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PMID:Restriction fragment length polymorphism of a lymphocyte surface antigen, Blast-1, in Japanese and Caucasians, and in patients with rheumatoid arthritis. 197 77

Alpha 1-antitrypsin is a glycoprotein that functions as the major protease inhibitor in human serum. Many genetic variants of alpha 1-antitrypsin can be detected by electrophoretic techniques. We used isoelectric focusing on ultrathin gels to determine the common M subtypes as well as other variants of alpha 1-antitrypsin in 62 white patients with rheumatoid arthritis (RA) and 51 white patients with systemic sclerosis (SSc). We found no increased prevalence of variant phenotypes in either disease group as a whole. In RA, however, the association between pulmonary interstitial fibrosis and alpha 1-antitrypsin variants was striking. Interstitial fibrosis was seen on chest roentgenogram in only 1 of 30 subjects apparently homozygous for M1 (the "wild type" or "normal" phenotype), compared with 13 of 32 patients with variant phenotypes. Seven of 15 patients with M1M2 (the most common variant phenotype) had pulmonary fibrosis. In contrast, there was no apparent association of variant phenotypes with pulmonary involvement in SSc. Our findings suggest a possible role of alpha 1-antitrypsin in the pathogenesis of interstitial fibrosis in patients with RA. The absence of such an association in SSc suggests that pulmonary involvement in these 2 rheumatic diseases may have different pathogeneses.
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PMID:Alpha 1-antitrypsin phenotypes, including M subtypes, in pulmonary disease associated with rheumatoid arthritis and systemic sclerosis. 348 21

Paraquat, a widely used herbicide, can cause severe and often fatal pulmonary fibrosis in humans and in laboratory animals. Although paraquat is known to be directly cytotoxic to lung parenchymal cells, the mechanism by which this leads to pulmonary fibrosis is not completely understood. In a model of paraquat-induced pulmonary fibrosis using the cynomolgus monkey, the administration of paraquat (10 mg/kg/wk subcutaneously for 2 consecutive wk) was followed by an alveolitis comprised of neutrophils and macrophages in the exposed animals as evaluated by lung morphologic examination and bronchoalveolar lavage. The lungs of the exposed animals showed typical interstitial fibrosis within 4 to 8 wk. At 1 to 2 wk after paraquat exposure, bronchoalveolar lavage cells harvested from the paraquat-exposed animals were spontaneously releasing a chemotactic factor for neutrophils, thus providing a possible mechanism for the recruitment of neutrophils to the alveolar structures. Lavage fluid from paraquat-exposed animals contained increased amounts of the fibroblast chemoattractant fibronectin (paraquat, 3.1 +/- 0.3 ng/micrograms albumin; control, 1.6 +/- 0.7 ng/micrograms albumin; p less than 0.05), and alveolar macrophages from these animals showed increased fibronectin production suggesting that local production accounted for part of the increased amounts of this glycoprotein (paraquat, 6.1 +/- 2.5 ng/10(6) cell/h; control, 1.4 +/- 0.5 ng/10(6) cell/h; p less than 0.05). In addition, alveolar macrophages from the exposed animals were spontaneously releasing a growth factor for fibroblasts, and normal alveolar macrophages exposed to paraquat in vitro were induced to release this growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Paraquat-induced pulmonary fibrosis. Role of the alveolitis in modulating the development of fibrosis. 670 75

Paraffin sections were obtained of human fetal, adult, and pathological lung (pulmonary fibrosis after radiotherapy or chemotherapy). The localization of epithelial adhesion molecules E-cadherin and Ep-CAM (former epithelial surface 40 kDa glycoprotein) was investigated by immunoperoxidase and/or immunofluorescence techniques with monoclonal antibodies. During development, the epithelia of the primary pulmonary primordium, the secondary bronchi and the adult bronchial epithelium retained immunoreactivity for E-cadherin and Ep-CAM with lateral immunostaining of cell membranes. In normal adult lungs, Ep-CAM was detected in type I and II alveolar epithelial cells, whereas E-cadherin was confined to the basolateral domain of type II cells. In pulmonary fibrosis, Ep-CAM could be further detected on the cell surface of epithelial remnants. In contrast, E-cadherin expression was characterized by a change of the membrane localization to a spotty, cytoplasmic pattern in the alveolar epithelium, possibly indicating functional inactivation of the protein during fibrogenesis.
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PMID:Distribution of E-cadherin and Ep-CAM in the human lung during development and after injury. 764 3

Vitronectin is a multifunctional glycoprotein which is involved in several of the processes of inflammation and repair. In previous studies we demonstrated that increased concentrations of vitronectin can be detected in bronchoalveolar lavage fluids (BAL) of patients with interstitial lung disease (e.g. sarcoidosis). The outcome of sarcoidosis is generally favorable, however, some patients progress to pulmonary fibrosis. There is a need for markers indicating early fibrotic changes in the lung in patients with sarcoidosis. The present study was designed to evaluate the potential of BAL-vitronectin measurements for the assessment of disease activity in subjects with sarcoidosis. BAL-vitronectin concentrations were determined in 19 patients with biopsy proven sarcoidosis and sequential analysis of BAL-vitronectin levels were performed in 11 patients before and after therapy. Patients with active sarcoidosis had higher BAL-vitronectin concentrations (1.56 +/- 0.89 microgram/ml) than patients with inactive disease (0.68 +/- 0.33 microgram/ml; p < 0.01). Patients with active sarcoidosis received high-dose glucocorticoid treatment for four weeks followed by low-dose glucocorticoid therapy for eleven months. After high-dose medication BAL-vitronectin concentrations fell significantly (1.08 +/- 0.9 microgram/ml; p < 0.01). A further decrease in vitronectin levels resulted when therapy was continued for a year (0.75 +/- 0.48 micrograms/ml). Clinical deterioration correlated with an increase in BAL-vitronectin concentrations. Thus, measurement of BAL-vitronectin levels might be a useful marker for assessing disease activity and response to therapy in patients with sarcoidosis, but does not provide prognostic information.
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PMID:[Vitronectin in bronchoalveolar lavage--a parameter of disease activity in sarcoidosis]. 769 Jan 72

Laminin is a 900,000-dalton extracellular matrix glycoprotein involved in a variety of functions, including cellular movement, growth, and differentiation. The aim of this work was to investigate the presence and biologic significance of this substance in the bronchoalveolar lavage fluid (BALF) of diffuse interstitial lung diseases (DILD). Levels of laminin fragment P1 (LFP) were measured by radioimmunoassay in BALF and sera from controls (n = 8) and patients with several types of DILD: sarcoidosis (n = 10), neoplastic pulmonary infiltration (n = 8), pulmonary fibrosis (n = 5), and hypersensitivity pneumonitis (n = 5). Furthermore, their relation to signs of alveolitis (cellular profiles and albumin concentration in BALF) and evidence of pulmonary fibroblast activation (BALF aminoterminal propeptide of type III procollagen) was examined. Laminin fragment P1 immunoreactivity was detectable in BALF, even in the control group, but patients with all types of DILD had higher concentrations than the control subjects. The serum levels of LFP were similar in all groups studied. Neutrophil and lymphocyte proportions were significantly higher in all DILD groups than in the control group. A positive correlation was seen between lymphocyte proportion and laminin fragment P1 in BALF. Moreover, in BALF a positive correlation was found between LFP and albumin and between LFP and the aminoterminal propeptide of type III procollagen. The BALF macrophage-associated laminin fragment P1 was significantly higher in the active sarcoidosis subgroup compared with the control group. Thus, laminin is a normal constituent of the epithelial lining fluid. The increase of laminin in BALF of patients with DILD suggests that laminin may contribute to their pathogenesis.
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PMID:Laminin fragment P1 is increased in the lower respiratory tract of patients with diffuse interstitial lung diseases. 840 85

This review summarizes knowledge on various aspects of paracoccidioidomycosis. Mycelial propagules, chlamydospores, and arthroconidia exhibit thermal dimorphism; arthroconidia are infectious in animals and, by electron microscopy, appear well provided for survival. The mycelial-to-yeast-phase transformation requires a strict control of glucan synthesis probably mediated by membrane enzymes. Hormonal influences on the transformation of the fungus (mycelium or conidium to yeast phase) have been demonstrated. Estrogen-binding proteins have been detected in the fungal cytosol, and during the transformation novel proteins are produced as a result of estradiol incorporation. Clinical forms have been better defined on the basis of better experimental models. Emphasis has been placed on the lungs as the portal of entry and on the existence of silent pulmonary infections. A specific Paracoccidioides brasiliensis antigen, the 43-kDa glycoprotein (Gp43), has been identified, characterized, and cloned. This has led to improved reproducibility and specificity of serologic tests. The depression of cell-mediated immune responses has been associated with severe disease in humans and in the experimental host. T-cell subsets in patients' tissues were characterized by means of monoclonal antibodies, and a reduced CD4/CD8 ratio was demonstrated. This has been related to alterations in lymphokine and tumor necrosis factor production, production of antigen-antibody complexes, etc. Amphotericin B has provided effective therapy. Azole derivatives have also improved prognosis and facilitated therapy. Itraconazole is presently the drug of choice, yet incapacitating sequelae (mainly pulmonary fibrosis) still constitute major problems.
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PMID:Paracoccidioidomycosis: an update. 847 49

KL-6 is a high-molecular-weight glycoprotein that is classified in cluster 9 among pulmonary cell antigens. Levels of KL-6 were found to be abnormally high in sera from patients with various types of interstitial pneumonitis such as idiopathic interstitial pneumonia, which can progress to pulmonary fibrosis. Levels of KL-6 in serum can be useful serum markers in the diagnosis of idiopathic interstitial pneumonia, in monitoring in the evaluation of disease activity, as a prognostic factor, and as a predictor of response to therapy.
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PMID:[Clinical usefulness of KL-6 as a serum marker of idiopathic interstitial pneumonia]. 921 13

The present study investigated the glycosylation state of proteins in lung tissue of a cyclophosphamide-induced model of pulmonary fibrosis in rats. In fibrotic lung, the carbohydrate constituents (total hexose, fucose, sialic acid and hexosamine) of salt-soluble, collagenase, elastase and papain digested glycoproteins were significantly higher compared to normal lungs. Interestingly, fibrotic lung tissues had higher activities of mannosyl, glucosyl, galactosyl, sialyl and fucosyl transferases than normal lung tissues. Similarly, mannosyl, glucosyl, galactosyl, sialyl and fucosyl transferases were higher in serum from rats with fibrosis than in that from normals. These data indicate that glycoprotein metabolism is significantly altered from normal in animals with interstitial lung fibrosis.
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PMID:Glycoprotein composition in cyclophosphamide-induced lung fibrosis. 968 8


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