Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.6 (chymopapain)
407 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cysteine proteinase inhibitor cystatin, from chicken egg white, bound with equimolar stoichiometry to the cysteine proteinases actinidin, chymopapain A, and ficin. The changes of near-ultraviolet absorption and fluorescence induced by the binding differed appreciably for the three enzymes, indicating that these spectral changes arise predominantly from aromatic residues in the proteinases. In contrast, the near-ultraviolet circular dichroism changes were similar for all three enzymes, supporting previous evidence that these changes originate mainly from the single tryptophan residue in cystatin, Trp-104. The pseudo-first-order rate constant for the binding increased linearly with the inhibitor concentration up to as high concentrations as could be measured for the three proteinases. This behavior is consistent with the complexes being formed by simple, bimolecular reactions, as was concluded previously for the reaction of cystatin with active and inactivated forms of papain. The second-order association rate constant varied only about 4-fold, from 2.2 X 10(6) to 9.6 X 10(6) M-1.s-1, for the three enzymes, the higher of these values being similar to that measured previously for the reaction with papain. These observations are consistent with the association rate being governed mainly by the frequency of collision between the binding areas of enzyme and inhibitor. All three cystatin-proteinase complexes dissociated to intact inhibitor, demonstrating reversibility. The dissociation rate constants varied about 20000-fold, from 4.6 X 10(-7) s-1 for ficin to 1.1 X 10(-2) s-1 for actinidin, reflecting substantial differences between the enzymes in the nature of the interactions with the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction between chicken cystatin and the cysteine proteinases actinidin, chymopapain A, and ficin. 233 64

This study was undertaken to clarify the effects of topically injected chymopapain on the spinal cord and peripheral nerves in rabbits, and also the effect of ganglioside on sciatic nerves which had been damaged by chymopapain. There were no abnormal macroscopic or microscopic findings when chymopapain was injected around the sciatic nerve sheath or around the spinal dura mater, but when it was injected directly into the nerve sheath there was immediate paralysis and severe axonal necrosis; the Schwann sheath remained intact and there was haemorrhage. Injection into the dura resulted in massive haemorrhage, perivascular neutrophil infiltration and necrosis of grey matter. In those treated with ganglioside, regeneration of the damaged sciatic nerve was shorter than in those not so treated.
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PMID:The response of nerve tissue to chymopapain. 234 Dec 19

The authors report their experience with 60 patients treated for lumbar disc herniation by chemonucleolysis with chymopapain and followed-up 1 to 3 years after treatment. Long-term results were as follows: excellent: 50%; good: 40%; fair: 8.2%; poor: 1.8%. The high percentage of positive results is attributed to the rigid criteria for patient selection used, which resulted in treatment by chemonucleolysis in only 18.6% of the surgical cases of lumbar disc pathology observed. 27.2% of the patients treated complained of disorders which resulted in postoperative complications and/or prolonged convalescence: prolonged low back pain and vertebral stiffness in 20%, persistent contralateral sciatic pain in 5.4%; intense but transitory worsening of the sciatica in 1.8%. The most feared complication of chemonucleolysis is paraplegia occurring after the inadverted injection of the enzyme into the spinal fluid. This risk overshadows the positive attributes of the method. The most important advantage of chemonucleolysis, as compared with surgery, is that it avoids epidural scarring and permanent postoperative anatomical changes. Patients may benefit from these advantages, but they must be willing to accept the negative aspects of the method, as well.
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PMID:Chemonucleolysis: advantages and disadvantages. 236 52

Immediate and long-term microvascular effects of chondroitinase ABC, 200 unit/ml, were analyzed in ten hamsters. The immediate effects on the microcirculation were studied by vital microscopy following local injection in the cheek pouch. There were no detectable effects on the microvascular blood flow during the 60 minutes of observation for chondroitinase ABC or the control. A therapeutic concentration (2000 pKat/ml) of chymopapain stopped the microcirculation in the injected area immediately, with numerous microbleedings at the border zone. Long-term effects were studied after subcutaneous injections in the ears of six rabbits. Chondroitinase ABC and the control did not cause any macroscopic or microangiographic effects. However, light microscopy showed a moderate inflammatory reaction in the subcutaneous layer for both chondroitinase ABC and the control. Chymopapain induced severe effects on the cartilage and surrounding tissues. Microangiography revealed a vessel-free zone at the injection site. Since 200 units/ml of chondroitinase ABC is four to eight times higher than the concentration that might be used for chemonucleolysis, i.e., dissolution of intervertebral discs by local enzyme injection, the present investigation suggests a wide margin of safety regarding the potential effects on blood vessels in tissues surrounding the disc.
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PMID:Microvascular effects of chondroitinase ABC and chymopapain. An in vivo experimental study on hamsters and rabbits. 237 64

Bone morphogenetic protein (BMP) is known to induce mesenchymal cell production of cartilage. During the regeneration process after chemonucleolysis, fibroblastic cells are supposed to migrate into the disc space. These migrated cells could contain BMP-responding cells. The present study was undertaken to investigate anterior spinal fusion of rabbits produced by intradisc injection of BMP after chemonucleolysis with chymopapain. After intradisc injection of BMP, roentgenographs revealed calcification of disc space. Calcification was more obvious in discs pretreated with chymopapain than in non-pretreated discs. Histology showed this calcification to be ossification of the nucleus pulposus and the anterior longitudinal ligament. Ossification was more obvious along the anterior longitudinal ligament than in the nucleus pulposus. In some cases, ossification led to the formation of bony bridges along the anterior longitudinal ligament. These results indicate that anterior spinal fusion can be produced by intradisc injection of chemicals.
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PMID:[Experimental study of chemical spinal fusion in the rabbit by means of bone morphogenetic protein]. 238 May 96

Percutaneous lumbar discectomy has gained growing interest during recent years as an alternative to open surgery for protrusions and non-sequestrated subligamentous intervertebral disc herniations. As a less invasive method it competes with chemonucleolysis. At least two modifications are known to date: automated percutaneous lumbar discectomy (APLD) with a 2-mm suction probe and non-automated, discoscopy-monitored percutaneous lumbar discectomy with a suction rongeur and a motor-driven shaver (NAPLD). In this study these two methods are compared for the amount of material extracted, dependence upon the degree of degeneration of the disc and intrinsic technical problems, using 20 human cadaver lumbar specimens for experimental testing. Total nucleotomy was not possible with either method. APLD yielded significantly less material and proved to be less effective in severely degenerated intervertebral discs than the NAPLD procedure, as preexisting gaps within the degenerated nucleus pulposus allowed the tissue to shift away from the tip of the 2-mm probe and facilitated displacement of the probe within the anulus fibrosus. By contrast, the rongeur, which first cuts the material to be removed and then carries it away by suction, was much more effective. Further data to support the advantages of non-automated percutaneous nucleotomy are discussed. Pretreatment of the disc with chymopapain did not result in a higher yield of nucleus material when combined with APLD.
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PMID:Automated percutaneous lumbar discectomy with and without chymopapain pretreatment versus non-automated discoscopy-monitored percutaneous lumbar discectomy. An experimental study in human cadaver spines. 238 50

The specificity of papaya proteinase IV (PPIV) has been examined with small substrates and a protein. With both classes of substrate, the enzyme shows a marked selectivity for cleaving glycyl bonds. Boc-Ala-Ala-Gly-NHPhNO2 is a convenient substrate for routine assays that discriminate well against chymopapain, the most common contaminant of PPIV. Sixteen cleavage points in beta-trypsin were identified, of which 13 are glycyl bonds. Tentative suggestions are made as to the reasons for lack of cleavage of some other glycyl bonds. The structure of PPIV has been modelled on that of papain, and we suggest that the replacement of the highly conserved residues Gly-65 and Gly-23 by arginine and glutamic acid, respectively, can account for the specificity of PPIV.
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PMID:Selective cleavage of glycyl bonds by papaya proteinase IV. 240 97

Proteoglycans were extracted from nuclease-digested sonicates of 10(9) rat basophilic leukemia (RBL-1) cells by the addition of 0.1% Zwittergent 3-12 and 4 M guanidine hydrochloride and were purified by sequential CsCl density gradient ultracentrifugation, DE52 ion exchange chromatography, and Sepharose CL-6B gel filtration chromatography under dissociative conditions. Between 0.3 and 0.8 mg of purified proteoglycan was obtained from approximately 1 g initial dry weight of cells with a purification of 200-800-fold. The purified proteoglycans had a hydrodynamic size range of Mr 100,000-150,000 and were resistant to degradation by a molar excess of trypsin, alpha-chymotrypsin, Pronase, papain, chymopapain, collagenase, and elastase. Amino acid analysis of the peptide core revealed a preponderance of Gly (35.4%), Ser (22.5%), and Ala (9.5%). Approximately 70% of the glycosaminoglycan side chains of RBL-1 proteoglycans were digested by chondroitinase ABC and 27% were hydrolyzed by treatment with nitrous acid. Sephadex G-200 chromatography of glycosaminoglycans liberated from the intact molecule by beta-elimination demonstrated that both the nitrous acid-resistant (chondroitin sulfate) and the chondroitinase ABC-resistant (heparin/heparan sulfate) glycosaminoglycans were of approximately Mr 12,000. Analysis of the chondroitin sulfate disaccharides in different preparations by amino-cyano high performance liquid chromatography revealed that 9-29% were the unusual disulfated disaccharide chondroitin sulfate di-B (IdUA-2-SO4----GalNAc-4-SO4); the remainder were the monosulfated disaccharide GlcUA----GalNAc-4-SO4. Subpopulations of proteoglycans in one preparation were separated by anion exchange high performance liquid chromatography and were found to contain chondroitin sulfate glycosaminoglycans whose disulfated disaccharides ranged from 9-49%. However, no segregation of subpopulations without both chondroitin sulfate di-B and heparin/heparan sulfate glycosaminoglycans was achieved, suggesting that RBL-1 proteoglycans might be hybrids containing both classes of glycosaminoglycans. Sepharose CL-6B chromatography of RBL-1 proteoglycans digested with chondroitinase ABC revealed that less than 7% of the molecules in the digest chromatographed with the hydrodynamic size of undigested proteoglycans, suggesting that at most 7% of the proteoglycans lack chondroitin sulfate glycosaminoglycans.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Purification and characterization of protease-resistant secretory granule proteoglycans containing chondroitin sulfate di-B and heparin-like glycosaminoglycans from rat basophilic leukemia cells. 241 30

Chemonucleolysis is widely used in the treatment of disease of the lumbar intervertebral disk. From a series of 34 patients the authors report their experience using this technique at the cervical level using aprotinin instead of chymopapain in cervical soft disk protrusion. They underline the technique, mechanism of aprotinin and indications.
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PMID:[Treatment of soft cervical hernia by percutaneous intradiscal injection of aprotinin]. 242 1

The effect of in vivo protease treatment on glomerular immune complex deposits was investigated in passive serum sickness in mice and rats. BALB/c mice were injected intravenously with soluble immune complexes (IC) of cationic bovine gamma-globulin (BGG) antigen and rabbit anti-BGG antibody, or IC of native BGG and rabbit antibody. One hour after receiving IC, the time of maximal deposition, the mice were treated with chymopapain and subtilisin via five intraperitoneal doses at 10-minute intervals, and they were sacrificed 20 minutes after the last treatment. Only 2 of 15 treated mice given cationic IC had capillary wall deposits of antibody versus 13 of 16 control mice (p less than 0.001); only 1 of 16 treated mice given the more neutral IC had mesangial antibody deposits versus 11 of 16 control mice (p less than 0.001). Differences in BGG antigen were not apparent. In parallel studies, soluble IC containing rabbit antibody and cationic BGG antigen were administered intravenously to rats. After 1 hour, the rats received a single intravenous dose of chymopapain and subtilisin. Ninety minutes later the rats were sacrificed. As determined by immunofluorescence microscopy only 1 of 13 enzyme-treated rats had bright capillary wall deposits of BGG antigen versus 10 of 11 control rats (p less than 0.001); only 6 of 13 treated rats had deposits of rabbit antibody versus 10 of 11 control rats (p less than 0.05). Glomeruli isolated from enzyme-treated rats that had been injected with radioactive IC contained 44% less radioactivity (p less than 0.005). These observations indicate that treatment with proteases can promote the removal of glomerular IC deposits in vivo.
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PMID:Removal of glomerular immune complexes in passive serum sickness nephritis by treatment in vivo with proteolytic enzymes. 243 Jan 39


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