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)

RNA synthesis in mouse leukemia L5178Y cells was inhibited depending upon the time of treatment by blasticidin S or by ricin, which inhibits specifically protein synthesis. When blasticidin S or ricin blocked protein synthesis by more than 90% of the control, marked accumulation of monosome was accompanied by the decrease of pulse-labeled RNA (20% of that in the control) in the polysomes and monosome fraction. The size distribution of pulse-labeled RNA among polysomal fractions including monosome obtained from the cells treated with either blasticidin S, ricin of L-asparaginase showed that the size of presumptive mRNA was shifted from 18 S to 9--10 S. TReatment of a blasticidin S-resistant (Bla-R) subline derived from L5178Y cells (Kuwano, M., Matsui, K., Takenaka, K., Akiyama, S. and Endo, H. (1977) Int. J. Cancer 20, 296--302) with L-asparaginase or ricin induced smaller size (9--10 S) RNA, but treatment of Bla-R cells with blasticidin S did not. Such shorter RNA fragments could not be observed even when cellular protein synthesis was inhibited by treatment for short time with blasticidin S (40--80% of the control activity). Smaller RNA fragments accumulated after drastic inhibition of protein synthesis were composed of 74% of polyadenylate sequence lacking poly(A)(-)RNA with peak of approx. 10 S and 26% of polyadenylate sequence containing poly(A)(+)RNA with a peak of 18 S, whereas cytoplasmic polysomal RNA of the control contained 46% poly(A)(+) with a peak of 18 S and 54% poly(A)(-)RNA with a 10--18 S peak. Cytoplasmic poly(A)(+)RNA degraded biphasically with half-lives of approx. 2 h and 8--10 h in exponentially growing mouse cells. However, in degradation of poly(A)(+)RNA molecules being formed in the cells pretreated with blasticidin S for 3 h, the rapid phase of decay with a half-life of approx. 2 h was interrupted by successively appearing poly(A)(+)RNA with a longer half-life of 8--10 h in cytoplasm. However, when the cells were pretreated with blasticidin S for 6 h, there appeared no poly(A)(+)RNA population with the rapid-decay in cytoplasm.
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PMID:The synthesis and degradation of presumptive messenger RNA in cultured mouse leukemia cells during the inhibition of protein synthesis. 71 32

Cell extracts of Bacillus polymyxa var. Ross.--producer of the polypeptide antibiotic polymyxin M. showed activity of L-asparaginase-2 (L-asparagine aminohydrolase EC 3.5.1.1). The enzyme activity in the growing culture increased with the biomass. The highest specific activity was detected in the cells at the onset of the stationary stage. The synthesis of L-asparaginase-2 was subjected to glucose catabolite repression in response to its addition to the culture at the logarithmic stage. After purification L-asparaginase-2 was obtained that was 350 times more active than the initial preparation. The enzyme properties were examined.
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PMID:[Biosynthesis of L-asparaginase-2 by cultures of Bacillus polymyxa var. Ross]. 72 59

Combination chemotherapy with cytosine arabinoside, cyclophosphamide and L-asparaginase (Asnase) was given to 22 children with acute lymphocytic leukaemia (ALL) with a white-cell count greater than 30 X 10(9)/1, and other features suggestive of poor prognosis. Complete remission was induced in all patients--in 19 after 2 courses of chemotherapy and in the remainder after a third course. During induction, neutropenia occurred in 18 and severe infection in 3. Anaphylaxis to Asnase occurred in 8 patients after the second course and one other had transient Asnase-induced diabetes. All patients received central-nervous-system prophylaxis after achieving remission, during which they were also treated with weekly vincristine and a 2-week course of prednisolone. Continuation therapy consisted of short cycles of intermittent chemotherapy and BCG inoculation or long cycles of intermittent chemotherapy +/- BCG. Life-table analysis shows 46% complete remission rate at 28 months, with 6 patients all in complete remission followed up between 28 and 41 months. There were minimal complications of continuation therapy, and BCG inoculation was well tolerated.
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PMID:Treatment of childhood lymphocytic leukaemia with high white-cell counts. 72 50

L-asparaginase content was studied in 67 different microorganisms, bacterial strains of E. coli, Pseudomonas, Erwinia, Proteus, Alcaligenes, Bacillus, Bacteria. Xanthomonas, and yeasts and fungi-Saccharomyces, Candida, Aspergillus, Epidermophyton, Trichophyton. All the bacterial strains studied possessed L-asparaginase activity, which varied greatly depending on the representative (10-1200 IU/g dry weight of cells). Yeasts and fungi displayed low L-asparaginase activity.
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PMID:[L-asparaginase activity of microorganisms]. 74 12

L-asparaginase pretreatment prior to sublethal whole body irradiation resulted in decrease of endogenous spleen colonies. This effect was abolished by the simultaneous addition of L-asparagine. L-asparaginase administered after sublethal irradiation did not reduce the number of spleen colonies. This result agrees with the suggestion that L-asparaginase inhibits the proliferation of undifferentiated but not of differentiated cells.
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PMID:Influence of L-asparaginase on spleen colony formation in mice. 74 22

A number of chemotherapeutic agents, including L-asparaginase, actinomycin D, chloroethylcyclohexy-nitrosourea, 5-flourouracil, cyclophosphamide, hydroxyurea, cis-platinum, adriamycin and methotrexate, alone and in combination and at variable dose levels, were applied against the Dunning R3327 rat prostatic adenocarcinoma-subline G. We found a continuing parallel between responses of the human and rat tumors and conclude that the usefulness of this animal model as a screening system for agents against the human tumor is further supported.
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PMID:Further experience with chemotherapy in the Dunning prostatic adenocarcinoma. 75 23

Yeast strains sigma1278b and Harden and Young, which synthesize only an internal constitutive form of L-asparaginase, do not grow on D-asparagine, as a sole source of nitrogen, and whole cell suspensions of these strains do not hydrolyze D-asparagine. Strains X2180-A2 and D273-10B, which possess an externally active form of asparaginase, are able to grow slowly on D-asparagine, and nitrogen-starved suspensions of these strains exhibit high activity toward the D-isomer. Nitrogen starvation of strain X218O-A2 results in coordinate increase of D- and L-asparaginase activity; the specific activity observed for the D-isomer is approximately 20% greater than that observed for the L-isomer. It was observed, in studies with cell extracts, that hydrolysis of D-asparagine occurred only with extracts from nitrogen-starved cells of strains that synthesize the external form of asparaginase. Furthermore, the activity of the extracts toward the D-isomer was always higher than that observed with the L-isomer. A 400-fold purified preparation of external asparaginase from Saccharomyces cerevisiae X218U-A2 hydrolyzed D-asparagine with an apparent Km of 0.23 mM and a Vmax of 38.7 mumol/min per mg of protein. D-Asparagine was a competitive inhibitor of L-asparagine hydrolysis and the Ki determined for this inhibition was approximately equal to its Km. These data suggest that D-asparagine is a good substrate for the external yeast asparaginase but is a poor substrate for the internal enzyme.
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PMID:Utilization of D-asparagine by Saccharomyces cerevisiae. 76 32

22 patients received intravenously infused L-asparaginase (Escherichia coli) on a protocol for 5 weekly doses. 13 patients received 100 U/kg, 1 patient 500 U/kg, and 8 patients 1,500 U/kg. Only 3 of the 9 patients receiving 500 U/kg or more were able to complete the 5-week protocol. 11 of the 13 patients receiving 100 U/kg were able to complete the 5-week protocol. Significant tumor responses were not seen. CNS toxicity and allergic reactions were observed at high- and low-dose levels. There was no difference as to the degree of protein changes, BUN elevation, or liver function abnormalities at the different dose levels.
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PMID:Phase I study of L-asparaginase (NSC 109229). 76 51

The influence of L-asparaginase (Crasnitin) on cellular reactions in the course of immunologically specific and nonspecific processes was studied. The preparation exerted particularly strong inhibitory action on the appearance of hemolysin-producing cells (Jerne's test) and on formation of rosette forms. A somewhat weaker effect on nonspecific inflammatory reactions, by the xylene and granulation tests, was noted. It was concluded that L-asparaginase depresses cellular reactions regardless of their immunologic component, but that immunologic reactions are more sensitive to this drug. It was established that L-asparaginase acts on bursal and thymus-dependent lymphocytes and, moreover, influences the hyperemic and proliferative reactions that accompany immunologically nonspecific processes.
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PMID:Studies on the immunosuppressive and anti-inflammatory action of L-asparaginase. 77 21

Current therapy has resulted in improved prognosis in previously untreated children with acute lymphocytic leukemia less than 16 years of age. The induction phase of chemotherapy should include the use of at least prednisone and vincristine. This combination should result in a hematologic remission in about 90 per cent of the patients. The efficacy of the addition of either L-asparaginase or daunomycin, the consolidation phase or the periodic readministration of induction drugs has not been established. Specific central nervous system treatment, early in the course of therapy, is an integral component of recently reported effective protocols. Several modalities of prophalytic central nervous system therapy have been utilized. These include cranial irradiation plus intrathecal methotrexate, craniospinal irradiation and intrathecal methotrexate alone. An encephalopathy syndrome has been reported as a complication in 10 to 66 per cent of these patients. The most effective form of central nervous system therapy, associated with the least toxicity, has not been established. Maintenance chemotherapy should include a combination of two or more drugs. Complications are numerous, and include hematopoietic depression, immunosuppression, overwhelming infections, and, possibly, the development of secondary primary cancers. In the most successful protocols maintenance chemotherapy has been administered for 3 years. Because of the potential significant toxicity there is a need to define the optimal duration of maintenance therapy. Psychological complications developing in a patient with a disease now considered a potential long term chronic illness, rather than a disease once considered universally fatal, are also discussed. The possibility of an immunologic deficiency allowing for the initial development of acute lymphocytic leukemia and the role of immunotherapy are presented. While the use of intensive combination chemotherapy and specific central nervous system prophylactic therapy have resulted in an improved prognosis in childhood acute lymphocytic leukemia, because of a significant incidence of failures, a standardized single form of therapy has not been established.
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PMID:The definitive treatment of children with acute leukemia. 78 18


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