Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have reviewed the neurological complications not directly attributable to leukaemic infiltration in a group of 438 children with leukaemia or lymphoma. 61 children had one or more complications due chiefly to bleeding, infection, or drug toxicity. Early death from intracranial haemorrhage occurred in 1% of children with lymphoblastic leukaemia and 7% of children with myeloblastic leukaemia. Measles and chicken pox were the most serious infective complications; one child remains severely retarded after presumed measles encephalitis, one child with chicken pox died, and a second remains disabled. 2 additional cases of measles encephalitis and one of progressive multifocal leucoencephalopathy are described. Drugs which caused neurotoxicity included vincristine, cytosine arabinoside, L-asparaginase, and phenothiazines, but most problems were caused by methotrexate. Methotrexate toxicity was more prevalent and more serious in children who had had previous central nervous system leukaemia. We conclude that viral infections and methotrexate pose the greatest neurological hazards to children with leukaemia.
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PMID:Neurological complications of childhood leukaemia. 59 22

We reported the treatment outcome of Protocol 8704T, which included repeated L-asparaginase, for childhood T cell malignancies. Fifteen cases of acute lymphoblastic leukemia (T-ALL) and 11 cases of non-Hodgkin's lymphoma (T-NHL), aged 3 to 14 yrs (median 6 yrs), were enrolled. Twelve T-ALL had mediastinal mass. Murphy's stages of T-NHL were 6 with III and 5 with IV. Types of histology consisted of 8 lymphoblastic and 3 large cell. Treatment was performed for 2 years. Observation periods were from 14 months to 78 months (median 42 months). Twenty-three achieved remission and 6 of them were transplanted with bone marrow or peripheral stem cells in the first remission. The protocol was continued in 17 cases. Fourteen of them remain in first remission, but one died of measles and 2 died of relapse. The 5-year event-free survival was 76.1% for ALL and 65.5% for NHL. In terms of histology, it was 87.5% for lymphoblastic NHL and 33.3% for large cell NHL (p = 0.19). In terms of phenotypes in ALL, it was 88.7% for ALL positive to CD2, 5 and 7, while 2 ALL positive to CD7 alone both failed. Therefore, it was shown that this treatment protocol is very effective for T-lymphoblastic leukemia and lymphoma.
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PMID:[Outcome of treatment protocol 8704T for childhood T cell leukemia and lymphoma]. 806 18

In this study, we designed two linear peptides, GnRH-hinge-MVP, which consists of human gonadotrophin-releasing hormone (GnRH), hinge fragment 225-232/225'-232' of human IgG1 and a T helper peptide from measles virus protein (MVP), and GnRH3-hinge-MVP, which contains three copies of GnRH (so termed GnRH3). The DNA constructs encoding for the two peptides were fused to the C-terminal encoding sequence of asparaginase, encompassing residues 199-326, through an acid-labile aspartyl-prolyl linker. The chimeric genes were expressed at high levels in Escherichia coli. The fusion proteins were purified to approximate homogeneity by means of washing the inclusion bodies and by ethanol precipitation. The GnRH-hinge-MVP or the GnRH3-hinge-MVP was released from the fusion proteins by cleavage with hydrochloric acid and further oxidized into double-chain miniproteins after purification. Both dimeric constructs proved to be efficient immunogens. It was shown that rats immunized with the immunogens generated antibodies specific for GnRH. The dimeric GnRH3-hinge-MVP containing three copies of GnRH in each chain induced a higher titre of anti-GnRH antibodies than the GnRH-hinge-MVP, containing a single copy of GnRH in each chain. These results demonstrate that combining multicopies or single copies of peptide with hinge fragment of human IgG and T helper peptide from measles virus protein can induce anti-peptide immune responses. Our data also suggest that these methods of preparation and dimerization of the recombinant polypeptides may provide a useful strategy for other polypeptide vaccine developments.
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PMID:The immunogenicity of recombinant and dimeric gonadotrophin-releasing hormone vaccines incorporating a T-helper epitope and GnRH or repeated GnRH units. 1525 17