Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of macrophages of phagocytize particulate matter is largely dependent on fibronectin, a nonspecific opsonin found in plasma. Fibronectin depletion, resulting in reticuloendothelial system (RES) depression, occurs following a variety of physical insults. RES depression may contribute to postinjury sequelae such as respiratory distress syndrome and septicemia. Fibronectin concentration was measured in the plasma of sheep with chronic lung lymph fistulas subjected to controlled thermal injury. Fibronectin levels were significantly (p < 0.05) decreased at 4, 24, 48, and 72 hours following burning. Fibronectin concentration decreased in parallel with serum albumin concentration; serum globulin concentrations did not decrease. Fibronectin concentration had an inverse relationship to lung lymph flow, a reflection of pulmonary transvascular fluid filtration rate. The role of fibronectin in the pathogenesis of postinjury respiratory distress syndrome deserves further exploration.
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PMID:Response of plasma fibronectin to major body burn. 743 53

Quantitative changes in plasma wound healing factors in cirrhotic patients after esophageal transection were evaluated and compared with those of non-cirrhotic esophageal cancer patients (controls) after esophageal resection. Serum total protein, albumin and fibronectin were maintained at the same levels as those in controls when multiple units of fresh frozen plasma and albumin products were employed. Nevertheless, the principle protease inhibitors including alpha-1-antitrypsin and alpha-1-acid-glycoprotein showed little increase by the 3rd postoperative day, while those of controls increased as much as twofold at this time. Levels of complements C3 and C4 showed consistent depression, with little change during the study period. We conclude that the levels of some of the plasma proteins essential in wound healing are depressed in cirrhotic patients during the critical period after surgery.
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PMID:Changes in wound healing factors in liver cirrhosis after esophageal transection for esophageal varices. 778 33

Burn wound sepsis is the most common and severe complication in the patients with severe burn. To know the systemic and local defect in immunity of burned patients, we measured the luminol-enhanced chemiluminescence (CL) response of normal polymorphonuclear leukocytes (PMNs) upon exposure to zymosan particles, bacteria or Candida albicans that were opsonized with any of patient's serum, blister fluid of burn wound or pooled normal serum (blood type AB). Sera from patients exhibited lower opsonic activities than those of pooled normal serum in the early postburn days. The levels of serum immunoglobulins, complement components and plasma fibronectin were found to correlate well with opsonin-index (OI), which was determined based on the CL response data obtained during the course of infusion therapy with fresh frozen plasma. Furthermore, patient's blister fluid showed much lower opsonic activity against bacteria such as Pseudomonas aeruginosa than patient's own serum. These results indicate that blister fluid is also not effective to opsonize bacteria because of the marked depression of the levels of immunoglobulins and complement components. Destruction of the skin barrier by thermal injury and impairment of systemic or local humoral immunity may predispose these patients to burn wound sepsis.
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PMID:Opsonic activity of sera and blister fluid from severely burned patients evaluated by a chemiluminescence method. 793 62

A shock model was experimentally produced by intravenous injection of a lethal dose (3 mg/kg) of endotoxin under general anesthesia induced by pentobarbital sodium using 7 beagles. The effect of this endotoxic shock on the reticuloendothelial function was investigated. The blood endotoxin concentration peaked immediately after administration and decreased subsequently. However, the value still remained on an increased level (1,051 pg/ml) even at 360 min after endotoxin treatment. The lipid emulsion test as an index of reticuloendothelial phagocytotic activity and the arterial ketone body ratio as an index of the energy charge in the liver decreased after endotoxin treatment and failed to recover during the experiment. Fibronectin, one of opsonic proteins, tended to decrease after injection of the endotoxin and was significantly (p < 0.01) low at 180 and 360 min compared with the value before injection of the endotoxin. These results suggested the depression of the reticuloendothelial function during endotoxin-induced shock.
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PMID:Changes in reticuloendothelial function in dogs with endotoxin-induced shock. 839 41

Physical features do not reliably distinguish premature infants with bacterial infections from those with noninfectious conditions. We evaluated the association of depressed plasma fibronectin with sepsis among hospitalized very low birth weight infants (< 1500 gm). Reference values were determined by sequential plasma sampling from 60 healthy very low birth weight infants. Among 17 very low birth weight infants with proved late-onset sepsis (mean age, 20 days; range, 10 to 42 days), 9 had plasma fibronectin levels more than 1 SD below the age- and birth weight-associated mean. Overall, the sensitivity and specificity of the finding of depressed fibronectin levels were 53% and 94%, respectively. These data suggest that depression of plasma fibronectin occurs commonly in association with late-onset sepsis among hospitalized premature infants.
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PMID:Fibronectin levels in premature infants with late-onset sepsis. 844 54

In this study, cultured glomerular epithelial cells (GEC) were exposed to a diabetic milieu containing glycated proteins to determine whether such proteins cause metabolic alterations that may lead to defects seen in the extracellular matrix in diabetic nephropathy. Cultured glomerular epithelial cells were cloned and maintained in RPMI media containing 10% fetal bovine serum (FBS). The medium was changed to RPMI-1% glycated FBS (experimental) or RPMI-1% control FBS, and cells were incubated for 1 or 4 d. Mitogenicity was tested by 3H-thymidine uptake. The media were collected and analyzed for collagenase activity by a quantitative fluorescence assay and by zymography. The cell layers were processed for matrix antigen (collagen I, glomerular basement membrane antigens, laminin, and fibronectin) and for the proteins of the tight junction (cadherin, desmosomal protein) by quantitative immunoperoxidase and immunofluorescence. Cell lysates were tested for cadherin and desmosomal protein by immunoblotting. Cells were also grown on 0.2-microM filter membranes to test for permeability to 3H-inulin and 125I-albumin. Glycated FBS resulted in a 1.8-fold increase in 3H-thymidine uptake in subconfluent layers accompanied by an increase in cell number. The treatment caused accumulation of laminin (18% above control, P < 0.05) and basement membrane antigens (33% above control, P < 0.05). Collagen I and fibronectin were unchanged. Exposing cells to glycated FBS changed the distribution of cadherin from a linear to a diffuse pattern associated with a decrease in cadherin observed on immunoblots. The media of glycated FBS-treated cells contained 45% lower collagenase activity (72-, 92-, and 150-kD species). Permeability to inulin increased by 550% and to albumin by 320% in glycated FBS-treated monolayers compared with controls. It is concluded that glycated proteins increased the accumulation of matrix proteins in the GEC, associated with a concomitant depression in collagenase activity. There were qualitative and quantitative changes in the tight junction protein cadherin. These matrix changes resulted in a functional defect in the permselective properties of the GEC tight junctions and manifested as increased leakage of inulin and albumin. Thus, the GEC are metabolically sensitive to the presence of glycated proteins, and this could play a role in the pathogenesis of diabetic nephropathy.
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PMID:Effect of glycated proteins on the matrix of glomerular epithelial cells. 959 77

Beta-adrenergic agonists (beta-AA) enhance protein accretion in skeletal muscles. This stimulation is characterized by increased protein synthesis, increased expression of myofibrillar protein genes and a depression in protein degradation in animals, and increased proliferation and DNA synthesis in muscle cells in vitro. The mechanism or signal path in muscle whereby beta-AA would elicit these physiological effects upon binding to the G protein-coupled beta-adrenergic receptor (beta-AR) is unclear. C2C12 myoblasts were used to determine beta-AR ligand binding characteristics, cyclic AMP synthesis in response to isoproterenol (ISO) stimulation, and effects of ISO on DNA synthesis, mitogen activated protein kinase (MAPK), and fibronectin (FN) gene expression. Results showed that C2C12 cells possess beta-AR which are specific, saturable, and of high affinity (Kd = 0.2 nM). Forskolin and ISO stimulated cAMP production by = 20-fold (P<0.001) and 17-fold (P<0.001), respectively. ISO and the cAMP analog, 8-bromo-cAMP (8-BC) stimulated DNA synthesis in proliferating cells by 150% (P<0.05) and 200% (P<0.01), respectively, without modulating MAPK activity, whereas addition of fetal bovine serum to culture resulted in a 500% increase (P<0.01) in DNA synthesis and MAPK activation. DNA synthesis in C2C12 cells treated with ISO, 8-BC, or FBS was abolished in the presence of 25 microM PD098059, an MAPK-kinase inhibitor, suggesting that an MAPK-dependent pathway is likely involved in C2C12 proliferation. During cAMP elevating agent stimulation, basal MAPK activity may be sufficient, in the presence of other putative signaling molecules, to support proliferation in these cells. ISO or 8-BC treatment increased FN mRNA by three- and seven-fold, respectively, in growing C2C12 cells implying a connection between increased DNA synthesis and FN gene expression.
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PMID:Beta-adrenergic agonist hyperplastic effect is associated with increased fibronectin gene expression and not mitogen-activated protein kinase modulation in C2C12 cells. 1071 44

Cardiovascular disease is considered a probable risk factor of particulate matter (PM)-related mortality and morbidity. It was hypothesized that rats with hereditary systemic hypertension and underlying cardiac disease would be more susceptible than healthy normotensive rats to pulmonary injury from inhaled residual oil fly ash (ROFA) PM. Eight spontaneously hypertensive (SH) and eight normotensive Wistar-Kyoto (WKY) rats (12-13 weeks old) were implanted with radiotelemetry transmitters on Day -10 for measurement of electrocardiographic (ECG) waveforms. These and other nonimplanted rats were exposed to filtered air or ROFA (containing leachable toxic levels of metals) on Day 0 by nose-only inhalation (ROFA, 15 mg/m(3) x 6 h/day x 3 days). ECGs were monitored during both exposure and nonexposure periods. At 0 or 18 h post-ROFA exposure, rats were assessed for airway hyperreactivity, pulmonary and cardiac histological lesions, bronchoalveolar lavage fluid (BALF) markers of lung injury, oxidative stress, and cytokine gene expression. Comparisons were made in two areas: (1) underlying cardiopulmonary complications of control SH rats in comparison to control WKY rats; and (2) ROFA-induced cardiopulmonary injury/inflammation and oxidative burden. With respect to the first area, control air-exposed SH rats had higher lung and left ventricular weights when compared to age-matched WKY rats. SH rats had hyporeactive airways to acetylcholine challenge. Lung histology revealed the presence of activated macrophages, neutrophils, and hemorrhage in control SHrats. Consistently, levels of BALF protein, macrophages, neutrophils, and red blood cells were also higher in SH rats. Thiobarbituric acid-reactive material in the BALF of air-exposed SH rats was significantly higher than that of WKY rats. Lung inflammation and lesions were mirrored in the higher basal levels of pulmonary cytokine mRNA expression. Cardiomyopathy and monocytic cell infiltration were apparent in the left ventricle of SH rats, along with increased cytokine expression. ECG demonstrated a depressed ST segment area in SH rats. With regard to the second area of comparison (ROFA-exposed rats), pulmonary histology indicated a slightly exacerbated pulmonary lesions including inflammatory response to ROFA in SH rats compared to WKY rats and ROFA-induced increases in BALF protein and albumin were significantly higher in SH rats than in WKY rats. In addition, ROFA caused an increase in BALF red blood cells in SH rats, indicating increased hemorrhage in the alveolar parenchyma. The number of alveolar macrophages increased more dramatically in SH rats following ROFA exposure, whereas neutrophils increased similarly in both strains. Despite greater pulmonary injury in SH rats, ROFA-induced increases in BALF GSH, ascorbate, and uric acid were attenuated when compared to WKY rats. ROFA inhalation exposure was associated with similar increases in pulmonary mRNA expression of IL-6, cellular fibronectin, and glucose-6-phosphate dehydrogenase (relative to that of beta-actin) in both rat strains. The expression of MIP-2 was increased in WKY but attenuated in SH rats. Thus, SH rats have underlying cardiac and pulmonary complications. When exposed to ROFA, SH rats exhibited exacerbated pulmonary injury, an attenuated antioxidant response, and acute depression in ST segment area of ECG, which is consistent with a greater susceptibility to adverse health effects of fugitive combustion PM. This study shows that the SH rat is a potentially useful model of genetically determined susceptibility with pulmonary and cardiovascular complications.
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PMID:The spontaneously hypertensive rat as a model of human cardiovascular disease: evidence of exacerbated cardiopulmonary injury and oxidative stress from inhaled emission particulate matter. 1079 35

Fibronectin (FN), expressed primarily by macrophages, endothelial cells, and smooth muscle cells, represents an integral feature of the rejection response in transplant recipients. Here we demonstrate a unique pattern of cellular FN expression in rat recipients of cardiac allografts rendered tolerant in an infectious manner with either nondepleting CD4 mAb or regulatory spleen cells. Unlike in rejecting controls, cellular FN in tolerant hosts was restricted to the graft vessels and no vascular cell adhesion molecule-1 or intercellular adhesion molecule-1 expression could be found, supporting the role of FN in leukocyte sequestration at the graft site. The lack of myocardial FN in tolerant rats, despite dense macrophage infiltration, correlated with profound depression of Th1 (interleukin-2 and interferon-gamma) cytokines. Treatment with CD4-depleting mAb prevented tolerance induction and restored myocardial expression of FN in parallel with marked increase in the expression of interleukin-2 and interferon-gamma mRNA/protein. Furthermore, connective segment-1 peptide-facilitated adjunctive blockade of FN-alpha4beta1 interactions in recipients conditioned with CD4 depleting mAb, significantly depressed intragraft expression of interleukin-2 and interferon-gamma mRNA/protein. Hence, the lack of FN associated with infiltrating leukocytes plays an important role in the maintenance of tolerance in transplant recipients by depressing local expression of Th1 cytokines that otherwise facilitate acute graft rejection.
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PMID:Fibronectin-mononuclear cell interactions regulate type 1 helper T cell cytokine network in tolerant transplant recipients. 1102 25

Activation of alpha-smooth muscle actin-positive myofibroblast cells is a key event in the progression of chronic renal diseases that leads to end-stage renal failure. Although the origin of these myofibroblasts in the kidney remains uncertain, emerging evidence suggests that renal myofibroblasts may derive from tubular epithelial cells by a process of epithelial to mesenchymal transition. It was demonstrated that hepatocyte growth factor (HGF) exhibited a remarkable ability to block this phenotypic transition both in vitro and in vivo. HGF abrogated the alpha-smooth muscle actin expression and E-cadherin depression triggered by transforming growth factor-beta1 in tubular epithelial cells in a dose-dependent manner. HGF also blocked morphologic transformation of tubular epithelial cells and inhibited the expression and extracellular deposition of fibronectin. In a mouse model of renal fibrosis disease induced by unilateral ureteral obstruction, transforming growth factor-beta type I receptor expression was specifically increased in renal tubules, and myofibroblastically phenotypic transition of the tubules was evident in vivo. Remarkably, injections of exogenous HGF blocked myofibroblast activation and drastically prevented renal interstitial fibrosis in the obstructed kidneys. These results suggest that tubular epithelial to myofibroblast conversion may play an important role in the pathogenesis of renal fibrosis and that blocking this phenotypic transition could provide a novel therapeutic strategy for the treatment of fibrotic diseases.
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PMID:Blockage of tubular epithelial to myofibroblast transition by hepatocyte growth factor prevents renal interstitial fibrosis. 1175 26


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