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)

The equilibrium unfolding transitions for the human M form of alpha 1-antitrypsin have been determined using a number of techniques reflecting changes in tryptophan fluorescence lifetime and quenching, exposure of tryptophan to solvent, secondary structure and the Stokes' radius of the protein. The denaturation curves are more complex than is usual for globular proteins and indicate the presence of multiple equilibrium intermediates in the presence of denaturant. This is in marked contrast to the more co-operative transition of the cleaved inhibitor. In addition, a recombinant non-glycosylated alpha 1-antitrypsin has been shown to have a closely similar conformation to the human M protein and to exhibit very similar reversible unfolding transitions, and hence similar stability and co-operativity. Differences in tryptophan environment are reflected in the dequenching of tryptophan fluorescence and reduced asymmetry in the near ultraviolet circular dichroism of the non-glycosylated protein, suggesting direct interaction of glycosyl residues with a tryptophan. Both the M type and the recombinant protein exhibit similar patterns of folding, with rapid collapse to a compact intermediate reminiscent of the widely observed molten globule state that folds more slowly to the native protein. The papain-cleaved M form also folds through a similar compact state in the absence of the C-terminal peptide that results from cleavage. It is concluded that part of the C-terminal 36 residue peptide interacts strongly with the main body of the protein in the folded inhibitor. This interaction will also be important during early stages of folding of the intact protein to direct the folding pathway. The lack of glycosylation leads to an increase in aggregation of the recombinant protein upon refolding, especially after extended denaturation times. The more rapid turnover of the recombinant protein in vivo is shown not to be due to a lower thermodynamic stability, but may be associated with a lower kinetic stability arising from the increased tendency to aggregation.
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PMID:Effects of glycosylation on the folding and stability of human, recombinant and cleaved alpha 1-antitrypsin. 154 2

1. Values of the kinetic specificity constant, kcat./Km, for the hydrolysis of N-acetyl-L-phenylalanylglycine 4-nitroanilide (I) and of its D-enantiomer (II) catalysed by ficin (EC 3.4.22.3) and by actinidin (EC 3.4.22.14) at pH 6.0, I 0.1 mol/l, 8.3% (v/v) NN-dimethylformamide and 25 degrees C were determined by using initial-rate data with [S] much less than Km and weighted nonlinear regression analysis as: for ficin, (kcat./Km)L = 271 +/- 6 M-1.s-1, (kcat./Km)D = 2.9 +/- 0.1 M-1.s-1, and for actinidin (kcat./Km)L = 13.3 +/- 0.7 M-1.s-1, (kcat/Km)D = 0.34 +/- 0.01 M-1.s-1.2. These data and analogous values for the corresponding reactions catalysed by papain (EC 3.4.22.2), (kcat./Km)L = 2064 +/- 31 M-1.s-1, (kcat./Km)D = 5.5 +/- 0.1 M-1.s-1, demonstrate marked variation in stereochemical selectivity for substrates (I) and (II) among the three cysteine proteinases with the following values for the index of stereochemical selectivity Iss = (kcat./Km)L/(kcat./Km)D: for papain, 375; for ficin 93; for actinidin 39. 3. Model building suggests ways in which, for the papain-catalysed reactions, binding interactions involving the extended acyl groups of the substrates may need to change as the reaction proceeds from adsorptive complex (ES) to tetrahedral intermediate (THI) before its rate-determining, general acid-catalysed collapse to acylenzyme intermediate. In particular, satisfactory alignment in the catalytic site at the THI stage of the acylation process appears to demand rotation of the substrate moiety about its long axis. 4. The different consequences of this rotation for the L- and D-enantiomers suggest that for closely related systems the greater the extent of this rotational adjustment the greater would be the value of Iss.5. For the actinidin-substrate combinations, model building suggests that even at the ES complex stage of catalysis it is not possible to approach optimized P2-S2 contacts and the three hydrogen-bonding interactions deduced for papain-ligand complexes in the absence of significant movement of protein conformation. Possible binding modes in which some of the interactions deduced for papain are relaxed are discussed. Consideration of postulated binding modes in the various transition states is shown to account for the order of reactivity reflected in values kcat./Km for the four reactions involving papain (Pap) and actinidin (Act) with the L- and D-enantiomeric substrates: Pap-L much greater than Act-L greater than Pap-D much greater than Act-D.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Variation in the P2-S2 stereochemical selectivity towards the enantiomeric N-acetylphenylalanylglycine 4-nitroanilides among the cysteine proteinases papain, ficin and actinidin. 173 3

To investigate the effects of airway cartilage softening on tracheal mechanics, pressure-volume (PV) curves of excised tracheas were studied in 12 rabbits treated with 100 mg/kg iv papain, whereas 14 control animals received no pretreatment. The animals were killed 24 h after the injection and the excised specimens studied 24 h later. Treated tracheas exhibited decreased ability to withstand negative transmural pressures, reflected in increased collapse compliance: 6.2 +/- 2.1 vs. 2.0 +/- 0.5% peak volume (Vmax)/cmH2O means +/- SD, P less than 0.001, (Vmax = extrapolated maximal tracheal volume), increased kc (exponential constant that reflects the shape of collapse limb of the PV curve): 0.244 +/- 0.077 vs. 0.065 +/- 0.015 (P less than 0.001). The distension limb of the PV curve greater than 2.5 cmH2O transmural pressure (Ptm) was no different. Compliance between 0 and 2.5 cmH2O Ptm was increased in papain-treated rabbits: 4.97 +/- 1.73 vs. 2.30 +/- 0.31% Vmax/cmH2O (P less than 0.001). Tracheal volume, and therefore mean diameter, was decreased at 0 Ptm: 2.7 +/- 0.26 vs. 3.2 +/- 0.27 mm (P less than 0.001). We conclude that airway cartilage softening increases the compliance of the trachea at pressures less than 2.5 cmH2O Ptm.
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PMID:Effect of intravenous papain on tracheal pressure-volume curves in rabbits. 394 34

Crude papain was administered intravenously to young rabbits and the cartilage of the collapsed ear was examined electron-microscopically. Degeneration and recovery of chondrocytes, and decrease in and recovery of the electron-density of elastic fibers, were observed during the collapse and restoration of the ear. Some samples were stained with ruthenium red. In the collapsed ear, with a marked decrease of proteoglycan in the cartilage, loss of ruthenium red-positive granules was observed in the extracellular matrix. Collagen fibrils in the cartilage appeared to be somewhat increased in number, some of their diameters became slightly greater, and a part were assembled into bundles, occasionally accompanied by periodic cross-striation. Decrease of proteoglycan in the cartilage matrix probably brought about the unmasking and the assembly of collagen fibrils. In one of the experimental animals, collagen fibrous segments of an atypical fibrous long spacing (FLS-)type with symmetrical cross-striation were found around the chondrocytes in the ear cartilage, during the period of recovery. Some kind of the endogenous sulfated carbohydrate may have acted to affect the arrangement of type II collagen or procollagen molecules newly produced by the recovering chondrocytes.
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PMID:An ultrastructural study on the ear cartilage of rabbits after the administration of papain. Appearance of cross-striated collagen segments of an atypical FLS-type. 722 66

Lung volume reduction surgery (LVRS), the removal of damaged, hyperexpanded lung, has been shown to improve respiratory function in many patients with end-stage emphysema. We report the results of an animal study using a new transbronchoscopic alternative to LVRS in which a washout solution and fibrin-based glue are used to collapse, seal, and scar target regions of abnormal lung. Twelve sheep had static and dynamic lung functions measured at baseline. Emphysema was produced by inhaled papain (7,000 U/wk x 4 wk), resulting in a significant increase of lung volumes, compliance, and airway resistance. The animals were then divided into three treatment groups of four animals, and underwent surgical volume reduction (SVR), bronchoscopic volume reduction (BVR), or bronchoscopy alone (Sham-BVR). Response to each intervention was assessed 8 to 12 wk after treatment by measuring lung function and examining lung tissue. BVR and SVR groups responded with significant and similar decreases in TLC and residual volume (RV). Tissue examination demonstrated that BVR caused collapse of the lung with focal scarring in 11 of 20 target territories (55% success rate). Three of the 11 target zones developed sterile abscesses. Postprocedure complications were less frequent with BVR than with SVR. This pilot study suggests that lung volume reduction can be achieved in animals without surgery using a bronchoscopic approach and a novel fibrin-based glue system. BVR has the potential for simplifying volume reduction, extending indications, and reducing morbidity, mortality, and costs in humans.
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PMID:Bronchoscopic volume reduction: a safe and effective alternative to surgical therapy for emphysema. 1146 4

A substance has been demonstrated in solutions of crude papain, which, when injected intravenously into 1 kilo rabbits, in amounts less than 5 mg., results in complete collapse of both ears. The phenomenon becomes visible 4 hours after injection, and is complete within 24 hours. 3 or 4 days after papain, the ears gradually reassume their normal form. Ear collapse is associated with depletion of the ear cartilage matrix, and the disappearance of basophilia from the matrix. Similar changes occur in all other cartilage tissues, including bones, joints, larynx, trachea, and bronchi. At the time when the ears are restored to normal shape, the basophilic matrix reappears in cartilage. Repeated injections of papain, over a period of 2 or 3 weeks, bring about immunity to the phenomenon of ear collapse. When the arterial circulation to one ear is occluded for 15 minutes at the time of injection of papain, this ear is protected against collapse. The effect of crude papain could not be reproduced by crystalline papain protease or crystalline papain lysozyme, which together comprise a considerable portion of the dry weight of papain. The nature of the responsible factor has not been determined, and the possibility that chymopapain may be implicated is currently under study. Cortisone prevents the return of papain-collapsed ears to their normal shape and rigidity. Possibly this reflects a capacity of cortisone to impede the synthesis or deposition of sulfated mucopolysaccharides in tissues.
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PMID:Reversible collapse of rabbit ears after intravenous papain, and prevention of recovery by cortisone. 1334 69

The intravenous injection of crystalline papain into young rabbits results in depletion of cartilage matrix throughout the body, with loss of rigidity and collapse of the ears, provided the enzyme is inactivated by oxidation or sulfhydryl blocking agents prior to administration. Cysteine-activated crystalline papain, when injected intravenously, produces little or no change in cartilage. The changes which occur in cartilage following an injection of inactivated crystalline papain are indistinguishable from those produced by crude papain. Activation of crude papain by cysteine prior to injection results in loss of its capacity to produce in vivo changes in cartilage. The progressive changes which take place in cartilage in vivo also occur in vitro in isolated rabbit ears removed shortly after an injection of crude papain or inactivated crystalline papain. In vitro ear collapse occurs rapidly at 37 degrees C. and does not occur at 4 degrees C. Collapse is enhanced by exposing the cartilage to cysteine and prevented by exposure to iodoacetamide or p-chloromercuribenzoate. The direct action of crystalline papain on plates of normal cartilage, in vitro, results in the same gross and histological changes which were observed in vivo. The direct action is accelerated by cysteine and inhibited by iodoacetamide or p-chloromercuribenzoate. The intravenous injection of iodoacetamide-treated bromelin produces the same in vivo changes in cartilage as papain. Untreated bromelin has no demonstrable effect on cartilage. It is suggested that the reason for the failure of activated papain to enter cartilage, after being injected intravenously, is that it probably reacts with a substrate or substrates in the blood. Oxidized or otherwise inactivated papain, in contrast, is readily taken up by cartilage and there converted to its active form.
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PMID:The removal of cartilage matrix, in vivo, by papain; identification of crystalline papain protease as the cause of the phenomenon. 1357 73

Some biochemical aspects of the collapse of the rabbit ears produced by the intravenous injection of papain have been studied. A marked depletion of chondromucoprotein (M.C.S.) and a reduction of the S(35) content of cartilage matrix were found to coincide with the gross and histologic changes in the cartilage. At the same time there was a marked increase in the amount of S(35) in the serum and an increase of S(35) and glucuronic acid excreted in the urine. Alteration in the composition of the M.C.S. remaining in the cartilage of the papain-injected animals was detected. The findings indicate that the collapse of the rabbit ears is due to loss of chondromucoprotein from cartilage and reduction of chondroitin sulfate in the chondromucoprotein that remains. All these changes were reversed in recovery.
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PMID:Papain-induced changes in rabbit cartilage; alterations in the chemical structure of the cartilage matrix. 1357 81

EXPERIMENTS DESIGNED TO CHARACTERIZE AN UNIDENTIFIED TRANSMISSIBLE AGENT BROUGHT FORTH THE FOLLOWING FINDINGS: The cytopathology consisted of the formation of intranuclear globules, collapse of the involved nuclei, and the extrusion of nuclear materials. The relatively dormant primary human amnion cells were less susceptible than the rapidly growing cell lines. Similarly, the slowly multiplying ribose variants were less susceptible than their corresponding parent cell lines. Interferon-like activity was released from infected cells. Infectivity was readily demonstrated following storage at 0-4 degrees C for at least 8 months or at 37 degrees C for at least 2 weeks. Freeze-thawing, however, markedly reduced or completely destroyed its infectivity. Infectivity was destroyed completely by ether and chloroform; partially by desoxycholate, and not affected by trypsin, papain, RNAse, DNAse, hyaluronidase, lysozyme, lecithinase, or pancreatic lipase. The rate of inactivation by 0.025 per cent formalin was much slower than that of vaccinia and herpes viruses. Its synthesis was suppressed by 5-fluorodeoxyuridine. This suppression was not reversed by thymidine and/or uracil. Heat-stable neutralizing antibody could not be demonstrated in 379 human and animal serums, in human gamma globulins, or in serums from animals "immunized" with this agent. Heat-labile inhibitors (lipoprotein-like) capable of inhibiting the infectivity of this agent were demonstrated in 154 of the 157 serums tested. Experimental evidence indicated the non-identity of this ubiquitous inhibitor and the properdin system. The non-infectious complex between this agent and the ubiquitous serum inhibitor may be dissociated (hence, become infectious) by simple dilution. Repeated attempts to reisolate a similar agent have not been successful. We have hypothesized that this agent is a virus consisting of DNA wrapped in a surface coat rich in lipid, and suggest that this virus be referred to tentatively as a lipovirus.
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PMID:The biological, immunological, and physicochemical characterization of a transmissible agent capable of inducing DNA and thymine degradation in cultured human cells. 1387 2

The ricinosome (precursor protease vesicle) is an organelle found exclusively in plant cells. Ricinosomes contain a 45-kDa pro-cysteine endopeptidase (CysEP) with a C-terminal KDEL endoplasmic reticulum retention signal. CysEP is a member of a unique group of papain-type cysteine peptidases found specifically in senescing and ricinosome-containing tissues. During seed development in the castor oil plant (Ricinus communis L.), the cells of the nucellus are killed as the major seed storage organ, the cellular endosperm, expands and begins to accumulate reserves. The destruction of the maternal seed tissues is a developmentally programmed cell death. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling revealed that nuclear DNA fragmentation occurs in the nucellar cells adjacent to the expanding endosperm. These cells exhibit ultrastructural features consistent with programmed cell death, including vesiculation of the cytosol, development of irregularly shaped nuclei, vacuolar collapse, and shrinkage of the cytoplasm. Ricinosomes containing the CysEP were identified in the nucellar cells by light and electron microscopy and immunocytochemistry. Both proCysEP and mature CysEP are present in protein extracts of the nucellar tissues during seed development. Upon collapse of the nucellar cells, the content of the ricinosomes is released into the cytoplasm, where the activated CysEP digests the remaining proteinaceous cellular debris. Digestion products of the nucellar cells are presumed taken up by the outermost cells of the endosperm, which have labyrinthine ingrowths of the outer walls typical of transfer cells.
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PMID:Ricinosomes and endosperm transfer cell structure in programmed cell death of the nucellus during Ricinus seed development. 1568 56


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