Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.25 (chymopapain)
 430 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complete yet nontoxic removal of tumor cells from autologous marrow grafts has proved difficult. New methods for separating normal stem cells from tumor cells are needed. The CD34+ cells in bone marrow, 1-2% of the low-density leukocytes, include precursors of all lymphohematopoietic lineages and probably also the primitive cells responsible for engraftment. A nontoxic, inexpensive, reproducible, and clinically applicable method for positive selection of CD34+ cells was developed. Paramagnetic microspheres coated with goat anti-mouse IgG1 are used to partition the cells; brief incubation with chymopapain is used to release them from the beads. Chymopapain exposure does not injury colony-forming cells or delay engraftment in rodents. Clinical volumes of bone marrow can be processed rapidly. In pilot experiments, the resulting grafts have a purity of 85-99% CD34+ cells and 40% median recovery of the assayable colony-forming cells. These studies form the background for a Phase I trial of autologous BMT using CD34+ stem cells.
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PMID:Selection of normal human hematopoietic stem cells for bone marrow transplantation using immunomagnetic microspheres and CD34 antibody. 171 50

To help clarify the comparative effects of chemonucleolysis and discectomy, the author studied 178 consecutive patients with sciatica who did not respond to conservative treatment. None had previously undergone laminectomy or chemonucleolysis or had spinal stenosis. All received postmyelography computerized tomography (CT) and, if the radiological interpretation was that of an extruded migrated disc, a laminectomy was performed; otherwise, the patient was given a choice of the two procedures. Of the 178 patients, 106 underwent chemonucleolysis and 72 laminectomy. Workers' compensation was being paid to 21.6% of the chemonucleolysis patients and 20.8% of the laminectomy patients. Postoperatively, substantial improvement was noted in 82.7% of the chemonucleolysis patients and 92.5% of the laminectomy patients at 6 weeks and in 92.8% of the chemonucleolysis patients and 89.7% of the laminectomy patients at 6 months. The majority of patients in both groups had improved neurological signs. Follow-up questionnaires at 1 to 4 years postoperatively revealed an overall success rate of 86.5% for chemonucleolysis patients and 83.8% for laminectomy patients. In patients not receiving workers' compensation, 90.1% of the chemonucleolysis patients and 88.6% of the laminectomy patients had a successful outcome; in those receiving workers' compensation, 69.6% of the chemonucleolysis patients and 60.0% of the laminectomy patients had a successful outcome. No statistically significant differences in improvement rate in neurological symptoms or signs were identified between the two procedures. Overall, 85.1% of the chemonucleolysis patients and 78.5% of the laminectomy patients were employed at follow-up review. To achieve optimum results and eliminate noncandidates for chemonucleolysis, routine use of postmyelography CT is recommended. When properly used, chymopapain chemonucleolysis is an acceptable alternative to surgical discectomy.
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PMID:A 1- to 4-year follow-up review of treatment of sciatica using chemonucleolysis or laminectomy. 173 Sep 46

Two forms of proteinase omega were isolated from a commercial preparation of chymopapain (EC 3.4.22.6) by means of cation-exchange liquid chromatography. Their circular dichroism (CD) spectra in the 182-320 nm region indicated that the two forms possess closely related structures. For comparison, we also recorded the CD spectra of chromatographically purified samples of papain (EC 3.422.2) and the most abundant form of chymopapain. According to the qualitative criteria proposed by Manavalan and Johnson (1983) Nature 305, 831-832), the spectral characteristics of papain correctly indicate that this protein belongs to the alpha + beta class. Proteinase omega is also placed in the alpha + beta category, while chymopapain seems to be an alpha/beta protein. Quantitative estimation of secondary structures yielded contents of helices and parallel beta-sheet that were higher in the case of chymopapain. Thus, the results of this work suggest that there are some differences in the folding pattern of chymopapain with respect to the other two proteinases. This proposal seems unexpected when the high amino acid sequence identity among these enzymes is considered.
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PMID:Circular dichroism of cysteine proteinases from papaya latex. Evidence of differences in the folding of their polypeptide chains. 173 51

A group of 100 patients submitted to microsurgical treatment for herniated lumbar disc following unsuccessful chemonucleolysis with chymopapain were retrospectively compared to a statistically comparable group of patients primarily submitted to microsurgery. This comparison demonstrated that previous unsuccessful chemonucleolysis has no influence on either the short-term or the long-term results of subsequent microsurgery.
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PMID:The results of "lumbar disc surgery" following unsuccessful chemonucleolysis. 176 86

Because pruritus, erythema and tachycardia are observed in some patients during chemonucleolysis, a prospective study was designed to investigate the plasma levels of histamine and catecholamines occurring after an injection of chymopapain. Thirteen patients (11 men and 2 women), mean age 38 +/- 11 years, were studied. They all had negative prick skin tests, human basophil degranulation tests (HBDT) and radio-absorbent tests (RAST) to chymopapain. The patients were premedicated with 100 mg hydroxyzine and 3 g tranexamic acid. Sedation was carried out using 0.1 mg.kg-1 droperidol and 0.02 mg.kg-1 phenoperidine. The nucleosus pulposus was visualized with 3 ml of contrast medium (lopamiron 300); 2 ml of chymopapain were then injected. Blood samples were obtained at T1 (after the contrast medium, but before the chymopapain), and then 5, 10, 15, 20 and 30 minutes after the chymopapain. The usual haemodynamic parameters were recorded at the same times. Four patients had clinical signs (group I), whereas the other nine (group II) did not. There was an increase in histamine levels in three patients from group 1, as well as in two in group II (up to 33 nmol.l-1). However, mean histamine and catecholamines levels were comparable in both groups at all times, and between times, of sampling. There therefore was no relationship between clinical signs and the release of histamine or catecholamines. The premedication with an antihistamine may have protected the patients, but the signs reported by four patients may also be due to the chymopapain itself.
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PMID:[Changes in plasma histamine and catecholamines levels after injection of chymopapain in chemonucleolysis]. 178

True sciatica, and the back pain associated with it, are symptoms stemming from a common anatomical lumbar distortion--compression of a spinal nerve root. Two therapeutic approaches have evolved: surgical laminectomy and discectomy for relief of compression of a lumbar nerve root; and chemonucleolysis, a tissue modification technique using the intradiscal injection of the proteolytic enzyme chymopapain. Chemonucleolysis has been demonstrated to have a successful outcome at the 75% level in 6 weeks and at the 80% level in 6 months. Lumbar microdiscectomy appears to be 85% effective at 3 months.
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PMID:Sciatica management: chemonucleolysis vs. surgical discectomy. 192 1

The pathophysiologic effects of histamine in anaphylaxis have been shown to be mediated through H1 and H2 receptors, individually and in combination. H1 receptors mediate coronary artery vasoconstriction, wheezing, cutaneous vascular permeability, and possibly an increase in pulse rate. H2 receptors stimulate ventricular and atrial inotropy, arterial chronotropy, coronary vasodilation, and rises in basophil cyclic adenosine 3':5' monophosphate (cyclic AMP). (Neither receptor mediates increases in cyclic AMP in mast cells.) H1 and H2 receptors in combination seem to be most potent in mediating flush, headache, increases in pulse pressure, and decreases in diastolic blood pressure. Clinical trials have been conducted to determine the efficacy of H1 and H2 antagonists in preventing anaphylactic reactions to plasma expanders, anesthesia-inducing agents, morphine, and radiocontrast material. Concurrently, retrospective observations of the prevention of anaphylactic reactions to chymopapain have been recorded. Despite some conflicting and inconclusive data, the sum of these studies indicates that pretreatment with a combination of H1 and H2 antagonists is more effective than H1 antagonists alone in preventing reactions to these agents. These results, when added to the available knowledge of the physiology of histamine release, support the preferential use of H1/H2 antagonist combinations in the prevention and treatment of anaphylaxis and anaphylactoid reactions.
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PMID:The use of antihistamines in the prevention and treatment of anaphylaxis and anaphylactoid reactions. 197 85

This article provides an updated review of chemonucleolysis and percutaneous discectomy. Dr. Herkowitz recommends discontinuing the use of chymopapain. Percutaneous discectomy may play a small role in the invasive management of a lumbar disc herniation.
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PMID:Current status of percutaneous discectomy and chemonucleolysis. 201 21

The present study on chemonucleolysis was conducted to determine the influence of chymopapain dose level and patient age on the degree and mode of the response and regeneration of the intervertebral disc. Chymopapain at various doses was injected into the intervertebral discs of young (8-week-old) and mature (20-week-old) rabbits respectively for a histological study. In rabbits undergoing high dose injection, not only the nucleus pulposus but also the inner layer of the annulus fibrosus was digested. Regeneration hardly occurred, and only a slight amount of scar tissue appeared in many animals. At lower dose, the annulus fibrosus remained intact and the posterior inner layer of the annulus fibrosus mainly proliferated toward the anterior portion of the disc, filled the space of digested nucleus pulposus, and restored disc height. This regeneration process was not thought to be specific to the damages caused by chymopapain but rather a common response of injured intervertebral discs.
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PMID:[Histological study on chemonucleolysis with special reference to the relationship between the dose of chymopapain and disc regeneration]. 205 37

A spinal cord injury model is described using chymopapain as a neurotoxic agent in rats. The trauma was evaluated by neurophysiological and morphological methods. Electrically evoked compound action potentials were used to quantify the neurophysiological effects caused by the injection of chymopapain into the lumbar dural theca in rats. A branch of the sciatic nerve was stimulated with voltage impulses of constant amplitude (40 V) and duration (0.1 ms) at the right external malleolus. The responses were recorded at the dorsal root entry zone L1. We used different doses of the enzyme (1000 i.u./ml; 2500 i.u./ml; 5000 i.u./ml). A total amount of 0.1 ml was injected into the rats' lumbar spinal canal intrathecally (n = 18). The control rate (n = 8) were subjected to exactly the same stimulus and recording procedures but the test solution was a corresponding volume of isotonic saline. Two hours after injection the animals were examined clinically and then sacrificed for histology. The prolongation of the latency of the electrically evoked potentials caused by the enzyme was very clear at the doses of 2500 i.u. and 5000 i.u. being about 10-15% relative to the mean latency before administration of the drug. The histological evaluation showed hemorrhage, vascular damage and indirect signs of myelin edema of the lumbar nerve tissue. Our study indicates that chymopapain injections into the lumbar spinal canal can be used as a reproducible model for spinal cord injury research.
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PMID:Intrathecal injection of a specific enzyme in rats as a model for chemically induced spinal cord injury. 207 8


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