Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sarcoidosis affecting the lungs may cause obstructive and/or restrictive lung function impairment. The bronchial reactivity is related to the release of histamine from the mast cells. Upon activation mast cells also release tryptase. This enzyme may activate latent collagenase and thus possibly contribute to the fibrosis formation observed in sarcoidosis. We analyzed the bronchoalveolar lavage fluid (BALF) from 13 nonsmoking and untreated patients with sarcoidosis and from 30 healthy volunteers (18 smokers) with regard to the number of mast cells and the tryptase concentration. Concomitantly albumin, fibronectin and hyaluronan were measured as markers of the inflammatory reaction in the alveoli and interstitium. The number of mast cells was higher (p < 0.001) in patients with sarcoidosis than in controls. Also, the concentration of tryptase was significantly higher in patients (225.3 +/- 83.9 [SEM] mU/L) compared to nonsmoking and smoking controls (34.7 +/- 7.8 and 44.7 +/- 13.0 mU/L, respectively; p < 0.01 for both). In addition, the concentrations of albumin, fibronectin and hyaluronan were higher in patients with sarcoidosis compared to the nonsmoking controls (p < 0.001 for all). However, there was no relationship between either the mast cell number or the tryptase concentration and the lung function parameters (VC, TLC, FEV1, FEV%, DLCO). As our patients did not show any functional signs of bronchial obstruction (FEV1 91.7% +/- 13.3 [SD] and FEV% 99.5% +/- 6.4 of predicted) the lack of correlation is not surprising. The high concentrations observed in the BALF of the noncellular components may just reflect an ongoing inflammatory process that may resolve or, if exaggerated, lead to fibrosis.
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PMID:Elevated levels of tryptase in bronchoalveolar lavage fluid from patients with sarcoidosis. 813 9

IH764-3, a potent component isolated from Salviae miltiorrhizae (a component of TML) was used to study the effect on proliferation and functions of cultured fibroblasts. The fibroblast growth curve demonstrated a dose-dependent relationship between growth and IH764-3 concentration. The incorporation of 3H-TdR and 3H-proline into fibroblasts was significantly inhibited by IH764-3. Calmodulin level, fibronectin and thrombospondin contents in the test group were obviously lower than those in the control group. Flow-cytometry showed that in the IH764-3 treated group, the percentage of cells in G0 + G1 phase was higher than that in the control. Electron microscopic observation (TEM and SEM) showed that in the treated group, the secretory function of collagen had decreased. All the results indicated that IH764-3 exerts a direct inhibitory effect on fibroblast proliferation and affects their ability to synthesize and secrete collagenous substances.
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PMID:[The effect of IH764-3 on proliferation and function of fibroblasts]. 822 6

Cryptogenic organizing pneumonia (COP) is a fibrotic process that primarily involves the alveolar spaces, alveolar ducts, and small conducting airways. The pathogenesis is not understood. Recent histopathologic studies have shown that during the cellular phase of COP, fibronectin deposits are present in the lung. Moreover, a neutrophil alveolitis is frequently seen in COP. Little is known about the involvement of alveolar macrophages in the pathogenesis of COP. However, alveolar macrophages are the principal resident cells in the airways, and they are thought to play a central role in the fibrotic process by virtue of their ability to express and release cytokines such as interleukin-8 (IL-8; a neutrophil chemotactic factor) and fibronectin (FN; a fibrogenic matrix-associated protein). We have quantified the spontaneous gene expression of IL-8 and FN by alveolar macrophages from five nonsmoking individuals with COP and compared them with 10 normal, healthy volunteers (five smokers, five nonsmokers). Expression of IL-8 and FN was measured by a quantitative assay employing reverse transcription of mRNA and the polymerase chain reaction. beta-actin mRNA expression was quantified as an internal standard, and the expression of FN and IL-8 transcripts was calculated as a ratio with beta-actin. The mean +/- SEM of the IL-8/beta-actin ratio in alveolar macrophages from patients with COP was 0.45 +/- 0.07, which was significantly higher than the level from either normal smokers (0.19 +/- 0.02, P = 0.008) or normal nonsmokers (0.16 +/- 0.01, P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cryptogenic organizing pneumonia: increased expression of interleukin-8 and fibronectin genes by alveolar macrophages. 829 74

Hyaluronic acid (HA), type III procollagen, fibronectin, and fibroblast growth factors (FGF) were measured in 43 bronchoalveolar lavage fluid (BALF) specimens obtained from 38 patients with farmer's lung (FL) and in BALF of 9 nonexposed normal control subjects. Bronchoalveolar lavage was done in 21 farmers with acute FL (acute) and in 22 with a history of previous FL (Ex) who were still in daily contact with dairy barns. All farmers from the acute and Ex groups had a lymphocytic alveolitis, respectively, 62.7 (3.5) percent (mean [SEM]) and 48.1 (4.3) percent. Hyaluronic acid, type III procollagen, fibronectin, and FGF were all highly increased in acute disease. These substances were also increased in the BALF of subjects of the Ex group who had no clinical symptoms or signs of acute disease at the time of lavage, but were actively farming. The increase in type III procollagen, however, was less in this group than in the subjects with acute disease. These observations suggest that the fibrosing activities and potentialities of the allergic alveolitis of FL are fully expressed at the time of clinical presentation and also in the subclinical phase of the disease in susceptible farmers who remain exposed after an initial acute phase of the disease.
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PMID:Fibrogenic activities in bronchoalveolar lavage fluid of farmer's lung. 840 62

In vitro effects of human recombinant IL-6 (1-1000 U/ml) on highly enriched human NK CD3-CD56+ cells (94% +/- 2; mean +/- SEM; n = 8), obtained from PBL were studied. IL-6 induced low levels of NK cell proliferation (7- to 30-fold during 6-day incubation), which was IL-2-independent, because IL-6 did not induce detectable IL-2 production by NK cells. Two-color flow cytometry analysis demonstrated that incubation of NK cells with IL-6 at the optimal concentration of 250 U/ml for 6 days significantly increased the proportion of NK cells expressing the following activation Ag: CD25 (26% +/- 17, mean +/- SEM vs 4% +/- 1 in control, n = 5), CD54 (44% +/- 17 vs 9% +/- 3), HLA-DR (29% +/- 13 vs 12% +/- 4), CD69 (45% +/- 7 vs 12% +/- 3), and CD71 (34% +/- 17 vs 6% +/- 2). The mean fluorescence intensity of these activation Ag was increased as well. IL-6 induced expression of CD49b (alpha-chain of VLA-2, 20% +/- 11 vs 2% +/- 1) and CD49c (alpha-chain of VLA-3, 43% +/- 17 vs 5% +/- 3), which are not expressed on resting NK cells. IL-6 also enhanced the fluorescence intensity of beta 1 integrins, CD49d, CD49e, and CD49f, expressed on NK cells. IL-6-stimulated NK cells showed significantly increased integrin-mediated adhesion to fibronectin- or laminin-coated plates (26 +/- 3 mean % cells adhering +/- SEM vs 15 +/- 4 in control for FN and 19 +/- 1 vs 11 +/- 1 for LM, p < 0.05 for both) as determined in a 3 h binding assay. As assessed by inhibition of adhesion using mAb to the VLA-2, -3, -4, -5, and -6, NK cell adhesion to fibronectin was mediated by VLA-4 and 5, and their adhesion to laminin by VLA-3 and -6. NK cells incubated in the presence of IL-6 were found to produce a factor cytostatic to WEHI-164 clone 13 target cells. This effect was partly, although significantly, blocked by neutralizing antibodies to TNF-alpha or TNF-beta. Our data demonstrate that IL-6 can directly activate human NK cells, but is a less potent NK cell activator, for all activation and functional parameters studied, than IL-2.
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PMID:Response of human NK cells to IL-6 alterations of the cell surface phenotype, adhesion to fibronectin and laminin, and tumor necrosis factor-alpha/beta secretion. 849 90

Bronchiectasis is associated with sputum containing high levels of the proteolytic enzyme elastase, which is thought to be involved in the pathogenesis of the disease. Agents which inhibit neutrophil function and interfere with neutrophil elastase release may have a beneficial effect on the development and progression of such diseases. We have studied the effects of the nonsteroidal anti-inflammatory agent indomethacin on neutrophil function in nine patients with clinically stable bronchiectasis. All patients remained clinically stable during the study. We observed a significant reduction in peripheral neutrophil chemotaxis to 10 nmol.L-1 N-formyl-methionyl-leucyl-phenylalanine (FMLP) from a mean of 19.86 (SEM 1.35) to 8.46 (0.68) cells.field-1 after 4 weeks of therapy. There was also a significant reduction in fibronectin degradation both by resting and FMLP-stimulated neutrophils, from a mean of 1.90 (0.19) micrograms x 3 x 10(5) cells at the start of therapy to 0.87 (0.08) micrograms after 4 weeks, and from 3.17 (0.35) micrograms to 1.48 (0.05) micrograms, respectively. There was no effect on spontaneous or stimulated superoxide anion generation by neutrophils. Despite the marked changes in peripheral neutrophil function, no adverse effect was observed on viable bacterial load in the bronchial secretions. In addition, there was no difference in sputum albumin, elastase or myeloperoxidase levels, and only minor changes in the chemotactic activity of the sputum. These results suggest that nonsteroidal anti-inflammatory agents have a major effect on peripheral neutrophil function but do not appear to have an adverse effect on bacterial colonization of the airways.
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PMID:In vivo study of indomethacin in bronchiectasis: effect on neutrophil function and lung secretion. 857 72

To compare the effect of matrix on glucose-stimulated insulin release, we cultured neonatal (3- to 5-day-old) rat islets of Langerhans, devoid of mesenchymal cell, on fibronectin, Cell-Tak, or endothelial basement membranes, free-floating, or dispersed into single cells. We also examined the rate of DNA synthesis during the culture period. Compared to free-floating islets [0.386 +/- 0.03 (SEM) ng per 24 h/ng total], single-cell cultures had the lowest basal insulin release (0.159 +/- 0.03 ng per 24 h/ng total; p < 0.0001), which was also low in islets attached to endothelial basement membrane (0.294 +/- 0.02 ng per 24 h/ng total; p = 0.01). The spontaneous insulin release (1 h in medium with 2.7 mM glucose) was lowest in islets attached to endothelial basement membrane (0.003 +/- 0.00023 ng per h/ng total; p < 0.0001 vs. free-floating) and highest in single-cell cultures (0.01153 +/- 0.00259 ng per h/ng total; p = 0.039 vs. free-floating). The ability to increase insulin release following a glucose challenge (16.1 mM for 1 h) was highest in islets grown on endothelial basement membranes (16.4-fold) and fibronectin (12.6-fold) compared to free-floating islets (8.7-fold), Cell-Tak (7.9-fold), and single-cell cultures (5.4-fold).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin secretion and DNA synthesis of cultured islets of Langerhans are influenced by the matrix. 857 87

A primary culture system of virgin rat mammary epithelial cells, grown in a serum-free medium, was developed as a means of assaying the efficacy of compounds with known anti-progestational properties. Cells were grown in 24-well plates on hydrated collagen gels and could be cultured for at least seven days. Experiments were routinely stopped three days after overnight attachment of cells using fibronectin (4 micrograms/ml). DNA synthesis, measured by thymidine incorporation, was significantly increased by the addition of ovine prolactin (43 nM; P < 0.01) or progesterone (0.15 microM; P < 0.05) or both (P < 0.01) to the basal medium. When added to medium containing progesterone plus prolactin (complete medium), RU486 (mifepristone) and ZK98734 (lilopristone) significantly depressed DNA synthesis in a dose-dependent manner using doses ranging from 0.015 microM to 15 microM. Maximum inhibition was achieved at 15 microM for both compounds. DNA synthesis was 24.5 +/- 2.6% (mean +/- SEM, n = 4) and 32.0 +/- 2.2% (n = 3) of that in complete medium for RU486 and ZK98734, respectively (both P < 0.001). There was no inhibitory effect of either compound in basal medium or basal medium plus prolactin, indicating the absence of toxicity and that the inhibitory effect is specific for a progesterone-mediated process.
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PMID:Activity of progesterone and anti-progestins in a rat mammary primary cell culture system. 880 93

Our objective was to investigate the initial levels of circulating proinflammatory cytokines, such as interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), of certain acute-phase proteins, such as C-reactive protein (CRP), fibrinogen (FBN) and albumin, and of the glycoprotein fibronectin at presentation and their daily variation during the clinical course of community-acquired pneumonia (CAP) in relation to clinical and laboratory indices of infection. Thirty otherwise healthy hospitalized patients aged 48 +/- 3 years (mean +/- SEM) and with bacteriologically confirmed CAP were studied prospectively. IL-1 beta and IL-6 were found to be 15-fold higher on admission (122 +/- 9 pg mL-1 and 60 +/- 4 pg mL-1 respectively), whereas TNF-alpha was three-fold higher (102 +/- 5 pg mL-1) than those of controls, all of them showing a decline towards normal. Initial CRP levels were increased 90-fold (416 +/- 1 mg L-1), whereas fibronectin levels were reduced (242 +/- 9 mg dL-1). The presence of parapneumonic effusion was associated with a higher TNF-alpha serum level (127 +/- 7 vs. 86 +/- 4 pg mL-1, P = 0.0002), a more rapid daily decline in TNF-alpha (-7.2 +/- 0.7 vs. -3.8 +/- 0.5 pg mL-1 day-1, P = 0.0005), a slower rate of decline in CRP (-42.8 +/- 3.0 vs. -54.6 +/- 3.0 mg L-1 day-1, P = 0.02) and a slower rate of increase in FBN (5.9 +/- 1.0 vs. 11.7 +/- 1.0 mg dL-1 day-1), P = 0.001]. Furthermore, daily progression of serum levels of cytokines and acute-phase proteins correlated strongly with pyrexia, erythrocyte sedimentation rate (ESR), neutrophil count, alveolar-arterial oxygen difference and radiographic resolution, clinically manifested by improvement in the patients' condition.
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PMID:Daily variation in circulating cytokines and acute-phase proteins correlates with clinical and laboratory indices in community-acquired pneumonia. 913 79

The interface of implanted True Bone Ceramics (TBC; sintered bovine bone; Koken, Tokyo, Japan) was examined. In the primary experiment, TBC was implanted into the bone marrow of a rabbit's femur. The extracellular matrices (types I, II, and III collagens and fibronectin) of decalcified specimens collected 1-48 weeks postoperatively were immunohistochemically examined. Undecalcified sections collected 6 weeks postoperatively were used for line analyses of calcium and phosphorus, by a scanning electron microscope-electron probe microanalysis (SEM-EPMA) method. In a secondary experiment, TBC was implanted into an osteochondral defect of a femoral condyle, harvested 1-12 weeks postoperatively, and decalcified to examine the extracellular matrices at the interface. In the bone marrow in the early phase, TBC had absorbed quantities of fibronectin. Immature bone (containing both types I and III collagens) in direct apposition to the ceramic surface had matured (containing type I collagen alone) in the TBC pores. SEM-EPMA revealed the continuity of high levels of calcium and phosphorus at the TBC-bone interface. In the secondary experiment, enchondral ossification or fibrous tissue formation was observed near the articular surface. However, in the subchondral layer, direct bone formation was observed in the TBC pores. It was concluded that TBC has excellent bioactivity for inducing maturation of new bone matrix on porous surfaces.
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PMID:Changes in the extracellular matrix on the surface of sintered bovine bone implanted in the femur of a rabbit: an immunohistochemical study. 965 54


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