Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.5.1.1 (asparaginase)
2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The following in vitro methods are predominantly discussed: Specific IgE determination (RAST). The test can be used to detect allergies of the immediate type such as anaphylactic shock and urticaria. Antibodies can be detected to a limited number of drugs such as penicillin, ACTH, TSH, insulin, asparaginase and proteins of animal sources. Degranulation of basophil leucocytes and histaminliberation have been used for many years. The practical value of the test has been limited but improved methods for analysis have given the tests hopes for a come-back. Cellular tests like lymphocyteproliferation and macrophage inhibition test (MIF) do not yet give such information which make them helpful as practical tests to detect drug allergy.
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PMID:[Methods for the detection of drug allergies]. 7 90

One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than in children (16%, 17%, and 25% respectively). There was a clear association between these three parameters. Thus hypersensitive reactions generally developed at the time of or after the decrease in plasma Asnase activity. Antibodies were detected only where Asnase activity had disappeared from the plasma. This time sequence, and in vitro experiments, suggest the formation of antigen-antibody complexes which might be responsible for inactivation of Asnase and for the development of hypersensitive reactions. However in many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies to Asnase of IgE type (reagins) were found in only 10 children and 6 adults. There was no correlation between hypersensitive reactions, decrease in Asnase activity, and IgE antibodies. The frequency of remission among patients developing bivalent antibodies to Asnase was 68% (13/19) in contrast to 27% (3/11) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.
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PMID:Hypersensitive reactions and antibody formation during L-asparaginase treatment of children and adults with acute leukemia. 106 36

All cancer chemotherapeutic agents, except altretamine, the nitrosoureas, and dactinomycin, have produced at least an isolated instance of a HSR. Certain drugs, such as L-asparaginase and mitomycin (administered intravesically), cause HSRs of significant degree in approximately 10% of patients. All four types of HSRs are represented in the reactions produced by antitumor drugs, although Type I is the most common. Some of the Type I reactions are IgE-mediated, and others are probably mediated by nonspecific release of vasoactive substances from targets such as mast cells. It is possible to continue therapy with some drugs, despite a prior HSR, if the prophylactic measures outlined in Table 2 are taken. An example of this is provided by taxol in which the lengthening of the infusion time and the administration of preventive medication allowed some patients to continue taxol therapy. The mechanisms of the HSRs have been carefully assessed in only a minority of patients who sustained such toxicity. Such evaluation would increase our understanding of this form of drug toxicity and perhaps lead to means of effectively reducing the risk and severity.
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PMID:Hypersensitivity reactions. 138 49

By using a modification of the microtiter solid-phase radioimmunoassay, we have measured Escherichia coli L-asparaginase (L-ASP) specific IgG, IgG4, and IgE antibodies in children who received L-ASP as part of their chemotherapy for leukemia and lymphoma. In 13 children with acute lymphoblastic leukemia induced with vincristine, prednisone, and L-ASP (10,000 IU/M2 i.v. each week for 3 weeks), seven developed high titer specific IgG antibodies. Four of the seven relapsed at the time of their peaking IgG response (6-10 months). None of the six with low or absent L-ASP antibody response have relapsed (followed for 20-35 months). In six children with allergic reactions to L-ASP reinduction, all had high titers of L-ASP specific IgG4 (greater than or equal to 20 U/ml) at the time of their reaction. In 16 other children with low L-ASP IgG4 (less than 13 U/ml), none demonstrated allergic reactions to rechallenge. Specific IgE was not consistently detectable in either group. In 21 patients with leukemia or lymphoma on L-ASP with cyclophosphamide-containing regimens, none developed significant IgG antibody response, compared with seven of 13 not receiving cyclophosphamide (p less than 0.001). We conclude: (a) development of L-ASP antibodies may have prognostic significance; (b) the detection of specific IgG4 can predict L-ASP allergy; and (c) cyclophosphamide-containing regimens reduce antibody formation to L-ASP and may allow repetitive (without anaphylaxis) and more effective (avoiding neutralizing antibodies) use of L-ASP.
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PMID:Antibody response to Escherichia coli L-asparaginase. Prognostic significance and clinical utility of antibody measurement. 352 39

Suppression of anti-L-asparaginase (anti-A-ase) IgG and IgE antibody responses was achieved in Balb/c mice with polyethylene glycol (PEG, MW, 5,000) conjugated Escherichia coli A-ase. Following the administration of the mixture of A-ase and PEG-A-ase, antibody production to A-ase was reduced. PEG-A-ase administration prior to A-ase suppressed the primary and secondary responses to A-ase antibody. The suppression could be transferred to normal mice with spleen cells from A-ase tolerant mice. The cell transfer experiment showed that the suppression was caused by suppressor T cells. Since PEG-A-ase administration failed to suppress antibody response to ovalbumin, the suppression seemed to be A-ase specific. PEG-A-ase administration also suppressed the delayed type hypersensitivity reaction. IgG and IgE antibodies to PEG or PEG-A-ase were not detected in mice immunized with PEG or PEG-A-ase in the presence of Freund's complete adjuvant or A1(OH)3, respectively.
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PMID:Immune responses to polyethylene glycol modified L-asparaginase in mice. 398 Jan 11

In a series of 40 patients treated with L-asparaginase for various neoplastic diseases, 6 patients had generalized anaphylactic reactions to L-asparaginase. Each of these reactors had antibodies detectable by passive hemagglutination, but precipitins were detectable in only one of this group of six patients. That patient had received two courses of the enzyme. 1 wk after the anaphylactic reaction, complement-fixing antibodies were present in all the patients that were studied. Specific reagin antibodies (IgE) were demonstrated in one patient by the release of histamine from his leukocytes after incubation in vitro with L-asparaginase. Binding of L-asparaginase to serum antibodies after incubation in vitro was detected by selective precipitation of the complexes with 30% ammonium sulfate or by ultracentrifugation. Total inactivation of the enzyme did not occur even at optimal proportions or at antibody excess. Passive hemagglutinating antibodies to L-asparaginase were present in all patients who had an allergic reaction at least 1 day before the reaction occurred, when that sample was available, and were absent in all patients who did not manifest clinical allergy. Titration of antibodies by passive hemagglutination may thus provide a means of predicting impending anaphylaxis in this system, particularly when coupled with a sudden decrease in circulating levels of L-asparaginase activity.
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PMID:Immunological responses to L-asparaginase. 410 90

X-linked hyper-immunoglobulin M (IgM) syndrome (XHIGM) is a rare genetic primary immunodeficiency disease caused by mutations of the CD40 ligand (CD40L) gene with normal or elevated levels of IgM and markedly decreased serum IgG, IgA, and IgE. Liver disease may occur as a clinical manifestation in XHIGM. This complication appears to increase with age. We report an 18-year-old male patient who had recurrent episodes of acalculous cholecystitis (AC) and sclerosing cholangitis (SC). The diagnosis of XHIGM was confirmed by the finding of CD40L expression < 1% of normal and a tyrosine 169 asparaginase (t526a) mutation in exon 5 (the tumor necrosis factor domain) of the CD40L gene. The patient had direct hyperbilirubinemia (direct bilirubin 5.5 mg/dL, total bilirubin 8.7 mg/dL), cholestasis (alkaline phosphatase 1133 U/L, gamma-glutamyl transferase 1019 U/L) and elevated transaminases (aspartate aminotransferase 70 U/L, alanine aminotransferase 101 U/L). Findings on abdominal ultrasound and abdominal computed tomography were compatible with AC. After the fourth episode of cholecystitis, cholecystectomy and liver biopsy were performed. Operative cholangiography revealed poor opacification of the hepatic duct and proximal common bile duct; the upstream intrahepatic bile ducts were not visualized. The biopsy specimen showed marked fibrosis of the portal areas. Enterococcus species was cultured from the bile. Children or adolescents with recurrent AC and SC should be evaluated for an underlying immunodeficiency syndrome such as XHIGM.
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PMID:Recurrent acalculous cholecystitis and sclerosing cholangitis in a patient with X-linked hyper-immunoglobulin M syndrome. 1603 32

The number of drugs used for the treatment of different types of cancers is constantly increasing and actually exceeds 100 distinct chemical formulations. The use of most cytotoxic agents is associated with potential hypersensitivity reactions, and the constant increase of their administration has caused an increase in incidence of these adverse effects, thus becoming a relevant problem for clinicians. Hypersensitivity reactions are common with platinum compounds, L-asparaginase, taxanes, procarbazine, and epipodophyllotoxins, whereas they are unusual, but always possible, with the other chemotherapeutic drugs. Reactions associated with individual drugs are discussed in detail. The mechanism underlying these hypersensitivity reactions involves IgE-mediated hypersensitivity reactions, nonallergic hypersensitivity reactions, and a few pathogenetically unclear reactions. More studies are needed to better understand, diagnose, treat, and prevent these reactions. To achieve this goal, a multidisciplinary approach to treat patients with cancer who have potential allergies is needed.
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PMID:The complex clinical picture of presumably allergic side effects to cytostatic drugs: symptoms, pathomechanism, reexposure, and desensitization. 2060 66

Immediate allergy to l-asparaginase (ASP) is a major obstacle in treating lymphoid malignancies. ASP-specific immunoglobulin G (ASP-IgG) has been used as a surrogate marker. Recently, the CD203c-basophil activation test (BAT) was found to be useful in diagnosing IgE-mediated allergies. We compared the diagnostic utility of the CD203c-BAT to that of ASP-IgG levels in determining ASP allergies in children. Eight ASP allergic reactions occurred over 75 ASP treatment courses. The sensitivity, specificity and area under the receiver operating characteristic curve of CD203c-BAT were similar to the ASP-IgG levels (0.75 vs. 0.85, 0.82 vs. 0.78 and 0.81 vs. 0.85, respectively). Positive skin prick test results in patients with ASP allergy suggested that ASP-IgE was one of the key players in ASP allergy. A combination of the BAT with the ASP-IgG level had the highest specificity (0.95) and positive predictive value (0.62), which permitted us to identify ASP allergy more effectively.
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PMID:Expression of CD203c on basophils as a marker of immunoglobulin E-mediated (L)-asparaginase allergy. 2358 40

Use of cytotoxic agents is associated with potential hypersensitivity reactions which are common with platinum compounds, L-asparaginase, taxanes, procarbazine and epipodophyllotoxins. Mechanisms underlying the reactions may involve IgE, non-allergic or a number of pathogenetically unclear events. Targeted therapies produce less collateral damage but demonstrate their own unique reactions. Cytopenias occur less often and mucocutaneous reactions to EGFR inhibitors, including papulopustular rash, are common. Fifteen currently approved mAbs provoke all four types of hypersensitivities including immune cytopenias, vasculitis, serum sickness and pulmonary events. Some successful desensitization protocols have been developed. Prevention of hypersensitivity reactions is based on skin testing, premedication and/or desensitization.
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PMID:Adverse events to nontargeted and targeted chemotherapeutic agents: emphasis on hypersensitivity responses. 2501 78


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