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)

A 12 year-old girl developed a late relapse of acute lymphoblastic leukaemia (ALL) 10 years from first presentation. Initial chemotherapy included vincristine, methotrexate, prednisolone, and L-asparaginase with cranial radiotherapy (18 Gy) for central nervous system prophylaxis. Documented growth failure led to recombinant human growth hormone (rhGH) replacement therapy being instituted in May 1989, 6 years from end of therapy and 2 years prior to relapse. Three independent experiments demonstrated no increased cell proliferation in vitro when the patient's thawed cryopreserved fresh leukemic cells were incubated with rhGH. However, a pre-T ALL cell line (PER-255) consistently demonstrated enhanced proliferation when incubated with rhGH (132.1 +/- 13.4%, P < 0.01). Growth hormone has been associated with an increased incidence of leukemia and may be implicated in the late relapse of this child. The use of growth hormone in children with a past history of ALL needs to be examined critically in the light of the potential risk of inducing leukemic relapse.
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PMID:Late leukemic relapse 10 years from diagnosis in a child on recombinant human growth hormone. 844 49

Growth hormone releasing hormone is one of the hormones secreted by the hypothalamus. Because of its potential applications in agriculture and medicine, its short half-life and its expensive chemical synthesis, an analog with high GHRH activity and prolonged half-life has been looked for. The fusion partner gene with 127 amino acid residues of the C-terminus from L-asparaginase was recombined respectively with asp-pro-pro-hGHRH(1-44), asp-pro-hGHRH(1-44) or asp-1pro-GHRH(2-44) genes synthesized by PCR method to form three kinds of fusion proteins with unique acid labile linker Asp-Pro. The Pro-Pro-hGHRH(1-44), Pro-hGHRH(1-44), and 1Pro-GHRH(2-44) peptides were purified to homogeneity by means of cell disruption, washing of inclusion body, ethanol fraction precipitation, acid hydrolysis, SP-Sephadex C-25 and Sephadex G-10 column chromatography. The peptide molecular mass of 5235, 5139 or 4975 Da was determined by ESI mass spectroscopy and purity was determined by SDS-PAGE. In the study of in vitro activity, the antiserum kit against human GH and peptide doses of 0.1, 1.0 and 10 microg/ml were used. These peptides obviously increased GH releases both from human pituitary and from rat pituitary. The activity comparisons showed that there was significant difference between Pro-Pro-hGHRH(1-44)-Gly-Gly-Cys and Pro-Pro-hGHRH(1-44) at 1.0 microg/ml, or between 1Pro-hGHRH(2-44) and Pro-Pro-hGHRH(1-44) or Pro-hGHRH(1-44) at 10 microg/ml. The structure-activity relationships showed that at the original C-terminus, for rat pituitary the activity of the GHRH analog with 1Tyr-->Pro was more than that of Pro-Pro-hGHRH(1-44) or Pro-hGHRH(1-44). The results showed that the analogs had good GH-releasing activity and species specificity.
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PMID:Study on the constructions and activities of three novel hGHRH analogs with N-terminal prolyl modulation+. 1626 50

Growth hormone releasing hormone is one of the hormones secreted from the hypothalamus. Because of its potential applications in agriculture and medicine, its short half-life and its expensive chemical synthesis, an analog with high GHRH activity and prolonged half-life was sought after. The fusion partner gene with 127 amino acid residues of the C-terminus from L-asparaginase was recombined with asp-pro-hGHRH(1-44) gene synthesized by PCR method to form one kind of fusion protein with unique acid labile linker Asp-Pro. The Pro-hGHRH(1-44) peptide was purified to homogeneity by means of cell disruption, washing, ethanol precipitation, acid hydrolysis, SP-Sephadex C-25, and Sephadex G-10 column chromatography. The peptide's molecular weight of 5,139 Da as measured by EIS-MS was coincident with the actual values. In the study of the activity, the doses of peptide were 0.1, 1.0, and 10 microg/ml for rat pituitary and 5 microg/ml for human pituitary. The peptide increased GH releases from rat pituitary in a concentration-dependent manner (P<0.05; P<0.01). At 1.0 microg/ml, there was a significant difference between Pro-Pro-hGHRH(1-44)-Gly-Gly-Cys and Pro-hGHRH(1-44) or Pro-Pro-hGHRH(1-44) (P<0.05), whereas the standard hGHRH(1-40) showed no measured rGH release. For human fetal pituitary, the Pro-hGHRH(1-44) peptides showed good GH-releasing activity, but there were no significant differences between them. The structure-activity relationship showed that for both rat and human fetal pituitary, the net GH-releasing activity of the Pro-hGHRH(1-44) analog was more than that of Pro-Pro-hGHRH(1-44). The results of the other hormones from human pituitary showed that the analog had good function-selectivity and species specificity.
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PMID:A novel hGHRH analog and its comparative activity. 1653 53