Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fumonisin is a recently identified mycotoxin that has been shown to be the cause of pulmonary edema disease in swine and leukoencephalomalacia in horses. Mystery Swine Disease (MSD), is an economically devastating disease complex of unknown etiology that has been reported to have occurred in several swine producing states since 1988. To determine the relationship between MSD and fumonisin, a case-control study was carried out in Illinois in mid-1990. Feed samples collected from 12 case and 9 control farms were analyzed for fumonisin. Sera from swine on all farms was screened for titers against encephalomyocarditis (EMC) virus and concentrations of alpha-1 acid glycoprotein (an acute phase reactive protein). Fumonisin concentrations greater than or equal to 20 ppm were found on 1 control farm (1/9) and 8 case farms (8/12). Titers against EMC virus (greater than or equal to 1:16) were found on 5 control farms (5/9) and on 6 case farms (6/12). Farms with greater than or equal to 20 ppm fumonisin in the feed were at significantly increased risk (OR = 11.2, Fisher's exact test p = 0.037) for MSD. Furthermore, the pi2 test for trend was (p = 0.017), meaning that as the level of fumonisin in the feed increased, the risk of MSD also increased. The presence of EMC virus titers in the sow herd was not a significant risk for MSD (OR = 1.25, Fisher's exact test p = 0.75). Alpha-1 acid glycoprotein concentrations obtained from a 2-week old nursing pigs differed significantly (p = 0.0005) between MSD case and control herds.
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PMID:Relationship between fumonisin contamination of feed and mystery swine disease. A case-control study. 132 37

Interleukin-2 is a glycoprotein physiologically produced by human lymphocytes which is capable of mediating some still unknown immunologic reactions. In vitro, interleukin-2 was seen to induce a lytic reaction against tumor cells through the activation of a cytolytic system of natural killer cells. If administered to man in heavy doses, it causes a clinical response in the treatment of metastases from melanoma and renal cell carcinoma in 20-40% of cases. However, the clinical use of the drug, in therapeutic doses, is prevented by the occurrence of several side-effects, the major one being increased permeability of alveolar vessels with capillary leak and interstitial pulmonary edema (Vascular Leak Syndrome in the English literature). Thus, this work was aimed at evaluating chest radiographs during interleukin-2 treatment to detect, in the pulmonary district, the early stages of the vascular leak syndrome--i.e., pulmonary edema, pleural and pericardial effusions. Forty-three patients had been treated for metastases from renal cell carcinoma and melanoma November 1989 through September 1991: standard chest radiographs demonstrated 26 cases (60%) of pulmonary edema, 14 cases (32%) of bilateral pleural effusions and 12 cases (27%) of pericardial effusions. Daily chest films of the patients undergoing interleukin-2 therapy allowed the early stage of the vascular leak syndrome to be depicted, thus enabling the physician to use the highest tolerated doses and eventually to stop infusion before marked respiratory distress develops.
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PMID:[Radiologic characteristics of the thorax during therapy with interleukin-2]. 145 17

We studied the effects of pretreatment of rabbits with a monoclonal antibody (MoAb) IB4 directed against an epitope on the common beta-chain of leukocyte adhesion glycoprotein CD18 on the development of pulmonary edema following pulmonary artery occlusion and reperfusion. A balloon catheter occluded the right pulmonary artery in rabbits for 24 h, and the balloon was then deflated to allow reperfusion for 2 h. The lungs were removed, attached to a weighing balance, and perfused with Ringer-albumin solution (0.5 g/100 ml). IB4 (0.5 mg/kg) was infused 45 min before the start of reperfusion. In another experiment, we infused OKM-1 (0.5 mg/kg), a control MoAb directed against an irrelevant epitope on the alpha-chain of CD11b/CD18. IB4 prevented rabbit neutrophil adherence to pulmonary artery endothelial cells in vitro in response to a variety of stimuli, whereas OKM-1 was ineffective. Pulmonary artery occlusion and reperfusion increased the lung myeloperoxidase (MPO) content, whereas IB4 prevented the increase in MPO content. The increase in lung weight in the IB4-treated group (400 +/- 40 mg from baseline) was less (P less than 0.001) than in the untreated control group (1,400 +/- 90 mg) and the OKM-1-treated control group (1,320 +/- 125 mg). IB4 pretreatment also prevented the increase in pulmonary capillary filtration coefficient (a measure of capillary permeability to water) occurring in control and OKM-1-treated groups. The results indicate that neutrophil sequestration in the pulmonary microcirculation mediated by CD18 glycoprotein is a major determinant of reperfusion-induced lung vascular injury.
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PMID:Antibody against leukocyte integrin (CD18) prevents reperfusion-induced lung vascular injury. 197 23

Extracellular superoxide dismutase (EC-SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) is a secreted Cu- and Zn-containing tetrameric glycoprotein, the bulk of which is bound to heparan sulfate proteoglycans in the interstitium of tissues. To test the function of EC-SOD in vivo, mice carrying a targeted disruption of the EC-SOD gene were generated. The EC-SOD null mutant mice develop normally and remain healthy until at least 14 months of age. No compensatory induction of other SOD isoenzymes or other antioxidant enzymes was observed. When stressed by exposure to > 99% oxygen, the EC-SOD null mutant mice display a considerable reduction in survival time compared to wild-type mice and an earlier onset of severe lung edema. These findings suggest that while under normal physiological conditions other antioxidant systems may substitute for the loss of EC-SOD; when the animal is stressed these systems are unable to provide adequate protection.
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PMID:Mice lacking extracellular superoxide dismutase are more sensitive to hyperoxia. 760 81

The immunoconjugate XMMCO-791/RTA consists of ricin A chain bound to a murine monoclonal antibody MoAb 791T. This monoclonal antibody (MoAb) binds to a glycoprotein of 72 kD, which is expressed on human colorectal carcinoma, ovarian carcinoma, and osteogenic sarcoma. XMMCO-791/RTA was tested in a Phase I trial with proposed dose escalation steps of 0.02, 0.04, 0.15, and 0.2 mg/kg per day. Twelve patients with metastatic colorectal carcinoma were treated at 0.02, 0.03, and 0.04 mg/kg per day dose levels administered over 1 hour on days 1-5. Study-related toxicities were hypotension (6 patients); greater than 10% weight gain (6 patients); peripheral edema (9 patients); fever (4 patients); confusion (3 patients); diarrhea (3 patients); proteinuria, as identified by dipstick (3 patients), greater than 0.6 mg/dl decrease in serum albumin (11 patients); greater than 25% decrease in oncotic pressure (10 patients), and a decrease in ionized calcium (8 patients). Six patients received a second course of treatment. HAMA levels developed in 9 patients and titers increased with number of courses administered. Decreased overall toxicity, in comparison to the first course, was noted, but one patient had an allergic-type response (hypotension, crushing chest pain, diaphoresis) after the test dose of the second course (HAMA level > 10,000 IgG). Life-threatening toxicity in the form of fluid shift, resulting in noncardiac pulmonary edema and third-spacing occurred after course 1 in 1 of 3 patients at the 0.04 mg/kg per day level. No further dose escalation was attempted and no antitumor activity was seen.
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PMID:Phase I study of monoclonal antibody-ricin A chain immunoconjugate Xomazyme-791 in patients with metastatic colon cancer. 762 72

The pathogenesis of pulmonary oxygen toxicity is postulated to be related in part to neutrophil-mediated injury. This study examined the effect of a monoclonal antibody directed against the CD11a,b,c/CD18 glycoprotein complex (beta 2 leukocyte integrins) on oxygen-induced lung injury. M8, a monoclonal antibody that binds to the beta chain of the guinea pig leukocyte integrins that facilitate neutrophil adherence to vascular endothelium, was injected into adult guinea pigs prior to and during exposure to > 98% oxygen. Control oxygen-exposed animals were injected with a noninhibitory antibody to the CD18 complex or with saline. Survival in oxygen was similar for animals treated with M8 when compared with those treated with saline (102 versus 105 h, respectively, NS). Pulmonary edema as assessed by protein in the supernatant of bronchoalveolar lavage fluid (BALF) was higher in the three groups of oxygen-exposed animals than in the air-exposed groups (p < 0.01), but it did not differ between the M8 antibody treatment group and the other oxygen-exposed groups. M8 antibody treatment did not decrease hyperoxia-induced neutrophil accumulation into the lung as assessed by myeloperoxidase activity (MPO) in lung homogenates or by neutrophil counts in histologic specimens. M8 antibody also did not decrease neutrophil counts or MPO in alveolar lavage fluid, both of which were significantly elevated in all oxygen-exposed groups. These results suggest that hyperoxia-induced neutrophil migration into the lung and acute lung injury occurs by CD18-independent processes in the guinea pig model of pulmonary oxygen toxicity.
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PMID:Oxygen-induced lung injury in the guinea pig proceeds through CD18-independent mechanisms. 790 67

A potential pathogenetic cofactor for the development of acute mountain sickness and high-altitude pulmonary edema is an increase in capillary permeability, which could occur as a result of an inflammatory reaction and/or free radical-mediated injury to the lung. We measured the systemic albumin escape by intravenously injecting 5 muCi of 125I-labeled albumin and the plasma concentrations of cytokines, F2-isoprostanes (products of lipid peroxidation), and acute-phase proteins in 24 subjects exposed to 4,559 m. Ten subjects developed acute mountain sickness, and four subjects developed high-altitude pulmonary edema. The transcapillary escape rate of albumin was 6.9 +/- 2.0%/h (SD) at low (550 m) and 6.3 +/- 1.9%/h at high (4,559 m) altitude (P = 0.23; n = 24). The subjects with high-altitude pulmonary edema had a modest but insignificant increase in the transcapillary escape rate of albumin (4.6 +/- 1.9%/h at low vs. 5.7 +/- 1.9%/h at high altitude; P = 0.42; n = 4). Plasma concentrations of fibrinogen, alpha 1-acid glycoprotein, C-reactive protein, and interleukin-6 were unchanged in the early phases and significantly increased by the end of the observation period in the subjects with high-altitude pulmonary edema, whereas tumor necrosis factor-alpha and F2-isoprostanes did not change at all. This suggests that the inflammatory reaction was rather a consequence than a causative factor of high-altitude pulmonary edema. In summary, these data argue against a dominant role for increased systemic capillary permeability in the development of acute mountain sickness and high-altitude pulmonary edema.
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PMID:Evidence against an increase in capillary permeability in subjects exposed to high altitude. 894 10

Clusterin (CLU) is a multifunctional 75- to 80-kDa glycoprotein that is upregulated during cellular stress and might represent a defense mechanism during local cellular damage. Mechanisms discussed are antiapoptotic, antioxidative, and anticomplement properties as well as chaperone-like features protecting stressed proteins. The aim of this study was to investigate potential protective effects of CLU on pulmonary vasculature after in situ PMN activation in isolated rabbit lungs. The experiments were performed on 24 isolated and ventilated rabbit lungs that were perfused with 200 mL of Krebs-Henseleit-10% blood buffer with a constant flow of 150 mL/min in a recirculating system. It was tested whether pretreatment with CLU (2.5 microg/ml; n = 8) or catalase (CAT, 5000 U/ml; n = 8) before N-formyl-Met-Leu-Phe (fMLP; 10(-8) M) injection influenced pulmonary artery pressure (PAP) peak airway pressures (PAW) and edema formation as compared with controls (n = 8). Baseline values of PAP were 9-11 mmHg and PAW 11-13 cm H2O. Application of fMLP resulted in an acute significant (P < 0.01) increase of PAP (48 +/- 29 mmHg) within 2 min in the control group and PAW increased to 35 +/- 7 cm H2O within 30 min. Pretreatment with CLU completely suppressed the PAP and PAW response as a result of the fMLP challenge (P < 0.001), whereas a transient PAW increase up to 27 +/- 15 mmHg was observed after CAT. Complement factor C3a release was suppressed by CAT, whereas CLU blocked the complement cascade at the level of C5b-9 formation. Moreover, generation of thromboxane A(2) was reduced after CLU and CAT. Lung edema occurred in the fMLP group but was absent (P < 0.001) after CLU and CAT treatment. Both CLU and CAT prevented fMLP-induced lung injury. Stabilizing effects of CLU, point towards complement regulating features at the level of the terminal complement sequence. Elevated levels of CLU during inflammation could reflect a compensatory organ protective mechanism. Further studies are required to elucidate the clinical impact of the observed organ-protective properties of CLU.
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PMID:Clusterin protects the lung from leukocyte-induced injury. 1286 62

Platelets are known to contribute to ischemia/reperfusion in several organs, but their role in inflammation and organ injury after hemorrhagic shock (HS) has not been examined. To address this issue, we rendered mice thrombocytopenic (20% of normal platelet count) by treatment with pOp3, a rat monoclonal antibody against platelet glycoprotein Ibalpha, 24 h before subjecting them to either a standard HS or sham protocol. Liver apoptosis increased 3- to 5-fold (P<0.05), and focal liver necrosis increased 11-fold (P<0.01) in placebo-treated shock mice compared with sham; these increased indices of liver injury were completely prevented by pOp3 pretreatment. Neutrophils infiltrating the liver increased nearly 3-fold in placebo-treated shock mice versus sham (P<0.05); this shock-induced increase in neutrophil infiltration was also eliminated by pretreatment with pOp3. Alveolar cross-sectional area, used to histologically assess interstitial lung edema and cellular infiltration, was reduced by 25% in pOp3-treated shock mice versus placebo-treated shock mice (P<0.05). Similar to the results in liver, pOp3 pretreatment decreased neutrophil infiltration in the lung after HS. Thus, platelets contribute to the inflammatory injuries of the liver and lung after HS, in part, perhaps by facilitating neutrophil infiltration into tissues.
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PMID:Essential role for platelets in organ injury and inflammation in resuscitated hemorrhagic shock. 1698 Aug 86

Host-mediated recognition of mannose-rich glycans on the surface of pathogens represents an ancient mechanism of innate immune defence. In this study, we demonstrate that the virus strains that differ in the degree of N-linked glycosylation on the globular head of their hemagglutinin glycoprotein also differed in their (i) sensitivity to neutralization by a mannose-specific lectin in mouse lung fluids and (ii) ability to infect (and, therefore, to be destroyed) by airway macrophages. Virus strain BJx109 (H3N2), but not PR8 (H1N1), was sensitive to neutralization by mouse lung fluids and infected airway macrophages efficiently in vitro and these antiviral activities were blocked by mannan, a complex polymer of mannose residues. Although intranasal (i.n.) infection of mice with PR8 led to severe disease and mortality, mice infected with an equivalent dose of BJx109 displayed no signs of disease. However, i.n. treatment of BJx109-infected mice with mannan led to viral pneumonia, severe disease and death characterized by excessive virus replication, pulmonary inflammation, vascular leak and lung edema. Thus, when mannose-specific innate defences were inhibited in vivo, virus strain BJx109 induced severe viral pneumonia similar to that of PR8. Together, these findings highlight the importance of N-linked glycans as a target for recognition and destruction of influenza viruses by the innate immune system. Moreover, soluble and cell-associated lectins coordinate to modulate disease severity following influenza virus infection of mice.
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PMID:Inhibition of lectin-mediated innate host defences in vivo modulates disease severity during influenza virus infection. 2093 55


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