Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary surfactant consists of phospholipids and proteins that form a stable monolayer at the surface of the alveoli to prevent lung collapse. Surfactant protein C (SP-C) is a hydrophobic 4-kDa palmitoylated protein derived from a 21-kDa precursor. We determined the membrane insertion, proteolytic processing, and subcellular location of 21-kDa proSP-C. In vitro, proSP-C associated with canine microsomes, and the NH2-terminal of proSP-C was protected from digestion with proteinase K, suggesting that proSP-C was inserted in a type III transmembrane configuration. Treatment of freshly isolated rat type II cells with cerulenin blocked acylation of the 21-kDa precursor. Pulse-chase labeling of type II cells demonstrated proSP-C processing intermediates of 19, 16, and 13 kDa that contained the NH2-terminal of proSP-C. Proteolytic processing of proSP-C was inhibited by incubation at 20 degrees C, suggesting that processing of proSP-C begins in a late Golgi or post-Golgi compartment. Immunogold labeling of rat lung with an antiserum to the NH2-terminal of proSP-C identified proSP-C in the trans-Golgi and multivesicular bodies but not in lamellar bodies. These findings suggest that proSP-C processing takes place in the trans-Golgi and multivesicular bodies before SP-C is incorporated into lamellar bodies.
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PMID:Posttranslational processing of surfactant protein C in rat type II cells. 857 34

Spread phospholipid monolayers are particularly useful as model membranes in that changes in surface pressure (Deltapi) can be monitored in response to protein adsorption to the monolayer, thus providing a unique manner of assessing protein-membrane contact. In the present study, spread monolayers below their collapse pressures have been utilized to evaluate Ca2+-specific adsorption of several vitamin K-dependent coagulation proteins to monolayers that contain negatively charged phospholipid. From combined measurements of Deltapi and Gamma (the surface excess protein concentration), values of dGamma/dpi have been evaluated for different proteins with varying lipid composition of the monolayers. Using mixed, liquid-expanded monolayers at equivalent initial surface pressures (pii) and which contain different amounts of phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine, the dGamma/dpi of bovine prothrombin was shown to decrease monotonically with increasing protein affinity for the monolayer. For example, KD values of 7, 20, and 60 nM produced dGamma/dpi values of 14, 17, and 21 nmol m-1 mN-1, respectively. However, the trend in dGamma/dpi appears to originate from characteristics of the monolayer and not from those of the protein, since a much different adsorbate (i.e., a positively charged pyrene derivative) exhibited a similar trend in dGamma/dpi with monolayer composition. On the other hand, dGamma/dpi values of bovine prothrombin, human factor IX, human protein S, bovine protein C, and human protein C, determined using liquid-expanded phosphatidylserine monolayers, were essentially equivalent. Therefore, the five vitamin K-dependent proteins that were examined were equivalent in terms of the manner in which the gamma-carboxyglutamic acid (Gla) domain of each protein perturbed the surface pressure. This study shows that Ca2+-specific membrane contact sites in the Gla domain of the five proteins tested are similar despite the naturally occurring differences in the normal Gla domain sequence of these proteins.
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PMID:Adsorption of vitamin K-dependent blood coagulation proteins to spread phospholipid monolayers as determined from combined measurements of the surface pressure and surface protein concentration. 960 92

This work is to establish theoretical and experimental relationships for the scale-up of Immobilized Metal Affinity Chromatography (IMAC) and Immuno Affinity Chromatography for the low cost production of large quantities of Protein C. The external customer requirements for this project have been established for Protein C deficient people with the goal of providing prophylactic patient treatment. Deep vein thrombosis is the major symptom for protein C deficiency creating the potential problem of embolism transport to important organs, such as, lung and brain. Gel matrices for protein C separation are being analyzed to determine the relationship between the material properties of the gel and the column collapse characteristics. The fluid flow rate and pressure drop is being examined to see how they influence column stability. Gel packing analysis includes two considerations; one is bulk compression due to flow rate, and the second is gel particle deformation due to fluid flow and pressure drop. Based on the assumption of creeping flow, Darcy's law is being applied to characterize the flow through the gel particles. Biot's mathematical description of three-dimensional consolidation in porous media is being used to develop a set of system equations. Finite difference methods are being utilized to obtain the equation solutions. In addition, special programs such as finite element approaches, ABAQUS, will be studied to determine their application to this particular problem. Experimental studies are being performed to determine flow rate and pressure drop correlation for the chromatographic columns with appropriate gels. Void fraction is being measured using pulse testing to allow Reynolds number calculations. Experimental yield stress is being measured to compare with the theoretical calculations. Total Quality Management (TQM) tools have been utilized to optimize this work. For instance, the "Scatter Diagram" has been used to evaluate and select the appropriate gels and operating conditions via Taguchi techniques. Targeting customer requirements under the structure of TQM represents a novel approach to graduate student research in an academic institution which is designed to simulate an industrial environment.
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PMID:Gel compression considerations for chromatography scale-up for protein C purification. 988 51

Short-chain fatty acids play a critical role in colonic homeostasis because they stimulate pathways of growth arrest, differentiation, and apoptosis. These effects have been well characterized in colonic cell lines in vitro. We investigated the role of beta-catenin-Tcf signaling in these responses to butyrate and other well-characterized inducers of apoptosis of colonic epithelial cells. Unlike wild-type APC, which down-regulates Tcf activity, butyrate, as well as sulindac and trichostatin A, all inducers of G0-G1 cell cycle arrest and apoptosis in the SW620 colonic carcinoma cell line, up-regulate Tcf activity. In contrast, structural analogues of butyrate that do not induce cell cycle arrest or apoptosis and curcumin, which stimulates G2-M arrest without inducing apoptosis, do not alter Tcf activity. Similar to the cell cycle arrest and apoptotic cascade induced by butyrate, the up-regulation of Tcf activity is dependent upon the presence of a mitochondrial membrane potential, unlike the APC-induced down-regulation, which is insensitive to collapse of the mitochondrial membrane potential. Moreover, the butyrate-induced increase in Tcf activity, which is reflected in an increase in beta-catenin-Tcf complex formation, is independent of the down-regulation caused by expression of wild-type APC. Thus, butyrate and wild-type APC have different and independent effects on beta-catenin-Tcf signaling. These data are consistent with other reports that suggest that the absence of wild-type APC, associated with the up-regulation of this signaling pathway, is linked to the probability of a colonic epithelial cell entering an apoptotic cascade.
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PMID:Butyrate-induced apoptotic cascade in colonic carcinoma cells: modulation of the beta-catenin-Tcf pathway and concordance with effects of sulindac and trichostatin A but not curcumin. 1054 75

The pulmonary surfactant prevents alveolar collapse and is required for normal pulmonary function. One of the important components of the surfactant besides phospholipids is surfactant-associated protein C (SP-C). SP-C shows complex oligomerization behavior and a transition to beta-amyloid-like fibril structures, which are not yet fully understood. Besides this nonspecific oligomerization, MS and chemical cross-linking data combined with CD spectra provide evidence of a specific, mainly alpha-helical, dimer at low to neutral pH. Furthermore, resistance to CNBr cleavage and dual NMR resonances of porcine and human recombinant SP-C with Met32 replaced by isoleucine point to a dimerization site located at the C-terminus of the hydrophobic alpha-helix of SP-C, where a strictly conserved heptapeptide sequence is found. Computational docking of two SP-C helices, described here, reveals a dimer with a helix-helix interface that strikingly resembles that of glycophorin A and is mediated by an AxxxG motif similar to the experimentally determined GxxxG pattern of glycophorin A. It is highly likely that mature SP-C adopts such a dimeric structure in the lamellar bilayer systems found in the surfactant. Dimerization has been shown in previous studies to have a role in sorting and trafficking of SP-C and may also be important to the surfactant function of this protein.
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PMID:Structural model for an AxxxG-mediated dimer of surfactant-associated protein C. 1515 98

The thrombin mutant W215A/E217A features a drastically impaired catalytic activity toward chromogenic and natural substrates but efficiently activates the anticoagulant protein C in the presence of thrombomodulin. As the remarkable anticoagulant properties of this mutant continue to be unraveled in preclinical studies, we solved the x-ray crystal structures of its free form and its complex with the active site inhibitor H-d-Phe-Pro-Arg-CH(2)Cl (PPACK). The PPACK-bound structure of W215A/E217A is identical to the structure of the PPACK-bound slow form of thrombin. On the other hand, the structure of the free form reveals a collapse of the 215-217 strand that crushes the primary specificity pocket. The collapse results from abrogation of the stacking interaction between Phe-227 and Trp-215 and the polar interactions of Glu-217 with Thr-172 and Lys-224. Other notable changes are a rotation of the carboxylate group of Asp-189, breakage of the H-bond between the catalytic residues Ser-195 and His-57, breakage of the ion pair between Asp-222 and Arg-187, and significant disorder in the 186- and 220-loops that define the Na(+) site. These findings explain the impaired catalytic activity of W215A/E217A and demonstrate that the analysis of the molecular basis of substrate recognition by thrombin and other proteases requires crystallization of both the free and bound forms of the enzyme.
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PMID:The anticoagulant thrombin mutant W215A/E217A has a collapsed primary specificity pocket. 1525 33

Necrotizing fasciitis and purpura fulminans are two destructive infections that involve both skin and soft tissue. Necrotizing fasciitis is characterized by widespread necrosis of subcutaneous tissue and the fascia. Historically, group A beta-hemolytic streptococcus has been identified as a major cause of this infection. However, this monomicrobial infection is usually associated with some underlying cause, such as diabetes mellitus. During the last two decades, scientists have found that the pathogenesis of necrotizing fasciitis is polymicrobial. The diagnosis of necrotizing fasciitis must be made as soon as possible by examining the skin inflammatory changes. Magnetic resonance imaging is strongly recommended to detect the presence of air within the tissues. Percutaneous aspiration of the soft tissue infection followed by prompt Gram staining should be conducted with the "finger-test" and rapid-frozen section biopsy examination. Intravenous antibiotic therapy is one of the cornerstones of managing this life-threatening skin infection. Surgery is the primary treatment for necrotizing fasciitis, with early surgical fasciotomy and debridement. Following debridement, skin coverage by either Integra Dermal Regeneration Template or AlloDerm should be undertaken. Hyperbaric oxygen therapy complemented by intravenous polyspecific immunoglobulin are useful adjunctive therapies. Purpura fulminans is a rare syndrome of intravascular thrombosis and hemorrhagic infarction of the skin; it is rapidly progressive and accompanied by vascular collapse. There are three types of purpura fulminans: neonatal purpura fulminans, idiopathic or chronic purpura fulminans, and acute infectious purpura fulminans. Clinical presentation of purpura fulminans involves a premonitory illness followed by the rapid development of a septic syndrome with fever, shock, and disseminated intravascular coagulation. The diagnosis and treatment of these conditions is best accomplished in a regional burn center in which management of multiple organ failure can be conducted with aggressive debridement and fasciotomy of the necrotic skin. The newest revolutionary advancement in the treatment of neonatal purpura fulminans is the use of activated protein C.
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PMID:Massive soft tissue infections: necrotizing fasciitis and purpura fulminans. 1571 17

This article presents a case study of a 49-year-old male admitted to the Intensive Care Unit (ICU) via Accident and Emergency following a collapse at home with a diagnosis of severe sepsis. The pathophysiology of sepsis is discussed together with a physiological assessment of the patient's cardiovascular, respiratory and renal systems, coagulation and metabolic responses. The discussion focuses on the period from ICU admission to commencement of drotrecogin alpha (activated) treatment (also known as recombinant human activated protein C). The management of sepsis and the treatment the patient received are outlined with particular focus on the strategic and procedural issues of the drug administration. The article concludes by presenting nursing clinical guidelines which will provide helpful guidance for nurses when caring for patients receiving drotrecogin alpha (activated) treatment. This is especially welcome, as drotrecogin alpha (activated) is internationally recommended in the treatment of severe sepsis.
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PMID:Severe sepsis: patient management focusing on administration of drotrecogin alpha (activated) infusion. 1647 Dec 93

Surfactant protein C is part of the surfactant complex lining up the alveoles and thereby inhibiting collapse of the airways. In addition it is involved in innate immune responses. Rare polymorphisms within surfactant protein C have been linked to sporadic paediatric lung diseases, like proteinosis or interstitial lung diseases. One study in the Finnish population described association of common polymorphisms with neonatal respiratory syndrome. Other common lung diseases have not yet been investigated for association with this gene. The aim of this study was to test surfactant protein C for association with bronchial asthma and with severe respiratory syncytial virus associated diseases in infancy. The two common amino acid variants Asn138Thr and Asn186Ser were genotyped on 322 children with asthma, 131 children with severe respiratory syncytial virus associated diseases and 270 controls. Statistical analyses of single polymorphisms made use of the Armitage's trend test; haplotypes were calculated with FAMHAP and FASTEHPLUS. Polymorphisms were in Hardy-Weinberg equilibrium and in tight linkage equilibrium in all populations. Single polymorphisms showed no association with the diseases, however, surfactant protein C haplotypes were associated with severe respiratory syncytial virus associated diseases (p = 0.013). Furthermore, an inverse haplotype distribution was found between children with asthma and respiratory syncytial virus infection (p = 0.00025). The results of our study might suggest opposing roles of surfactant Protein C in the genetic predisposition for respiratory syncytial virus associated diseases vs. asthma. The causal mechanism for this observation has still to be shown.
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PMID:Haplotypes of surfactant protein C are associated with common paediatric lung diseases. 1712 84

Various haemostasis disorders can occur following snakebite. Almost all ophidian species that are responsible for serious, even lethal, human envenomations are concerned. Venoms of these snakes are rich in proteins interfering with haemostasis, including many enzymes. These proteins can be classified in four groups according to their action. The haemorrhagins induce capillary permeability disorders. The proteins disturbing the primary haemostasis can activate as well as inhibit platelets: phospholipases A2, serine proteases and metalloproteinases, L-amino-acido-oxydases, phosphoesterases, disintegrins, C-type lectins, dendropeptin, agregoserpentin, thrombolectin. The proteins interfering with coagulation are separated into procoagulant proteases (prothrombin activator, thrombin-like enzymes, factor X and factor V activators) and anticoagulant proteases (factor IX and X inhibitors, protein C activator, anticoagulant phospholipases A2). The venom components acting on fibrinolysis are the fibrinolytic enzymes and the plasminogene activators. The clinical consequence of these mechanisms is a local as well as diffuse haemorrhagic syndrome. A hypofibrinogenemy, even an afibrinogenemy is frequently noted. Other haemostasis parameters are disturbed: PT collapse, a patient's ACT several times higher than the control and non-systematic thrombopenia. Ophidian venoms take part in many medical, diagnostic or therapeutic, applications in medicine. Currently, the antivenomous immunotherapy is the only efficient treatment in these haemorrhagic disorders.
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PMID:[Haemostasis disorders caused by snake venoms]. 1842 Mar 71


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