Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncornavirus-like particles of the "A" (both intracisternal and intracytoplasmic) and "B" or "C" (extracellular) types are produced by murine MOPC-460 myeloma cells. This communication describes a comparative study on tracisternal A and extracellular particles. Both types of particles contain an RNA-dependent DNA polymerase activity, traces of 35S and 70 S RNA in addition to larger amounts of degraded RNA, and proteins of approximately 76,000 and 45, 000 daltons. The 76,000-dalton proteins from intracisternal A and extracellular particles have the same cyanogen bromide peptides. Hybridization kinetic analysis indicates that the RNAs in the two particles are identical or very closely related and share partial homology with Moloney leukemia virus RNA. In contrast, the particles appear to have little or no relationship to murine mammary tumor virus as judged by several different criteria. Electron microscope studies indicate that the extracellular particles arise from the budding of core components through the plasma membrane. These results suggest that the intracisternal A and extracellular oncornavirus-like particles produced by MOPC-460 cells are closely related.
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PMID:Relationships between intracisternal type A and extracellular oncornavirus-like particles produced in murine MOPC-460 myeloma cells. 5 64

Ethidium bromide (2,3-diamino-5-ethyl-6-phenylphenanthridinium bromide) significantly inhibited the RNA-dependent DNA polymerase of types A and C particles isolated from transplanted adenovirus 12-induced tumors of CBA mice. It was also cytotoxic for an established in vitro line of adenovirus 12-induced tumor cells of CBA mice and caused cell death, inhibition of [3H]thymidine uptake, and a significant reduction of cells in metaphase. Ethidium bromide significantly inhibited the in vivo growth of transplanted adenovirus 12-induced tumor cells of CBA mice, simian virus 40-induced tumor cells of hamsters, and murine leukemia virus-induced lymphoma cells of BALB/c mice. The compound may have exerted the antitumor activity by selectively affecting oncornavirus in the tumor cells.
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PMID:Effect of ethidium bromide on transplanted virus-induced tumor cells. 6 62

Suramin--a well-known antitrypanosomal agent--was found to exert a strong inhibitory effect on the RNA-directed DNA polymerase (reverse transcriptase) activity of several oncornaviruses such as Moloney murine leukemia virus, murine Rauscher leukemia viruses, Moloney murine sarcoma virus and avian myeloblastosis virus. Inhibition of enzyme activity was obtained with both endogenous viral RNA and (A)n . oligo(dT) as the template-primer. Suramin effected a 50% inhibition of the reverse transcriptase activity of oncornaviruses at a concentration range of 0.1--1 microgram/ml. In this aspect it compared favorably to ethidium bromide, another trypanocide drug which is considered as one of the most powerful inhibitors of oncornaviral DNA polymerases. The inhibition of reverse transcriptase activity by suramin was competitive with the template-primer, (A)n . oligo(dT), suggesting that the drug may interact with the template-primer binding site of the enzyme.
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PMID:Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor viruses. 9 62

In view of the marked antitumor activity of 3-deazauridine, the synthesis of 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene (1,3-dideazauridine) and its dibenzyl derivative was carried out. 4-Bromo-1,3-dihydroxybenzene was converted to its dibenzyl derivative, which, upon reaction with n-butyllithium followed by treatment with anhydrous cadmium chloride, gave bis(1,3-dibenzyloxyphenyl-4)cadmium. Condensation of this intermediate with 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride in refluxing toluene, and subsequent removal of the protecting benzoyl groups, afforded 4-(beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene which, upon catalytic hydrogenation over Pd/C, furnished the desired 4-(beta-D-ribofuranosyl)-1,3-dihydroxybenzene. The beta configuration at the anomeric center was established by NMR and hydrogen bonding studies. 4-(Beta-D-ribofuranosyl)-1,3-dibenzyloxybenzene inhibited the growth of leukemia L1210 cells by 50% at 7 x 10(-6) M, and that of mammary carcinoma TA3 cells at 5 x 10(-5) M. Dideazauridine itself was less active, inhibiting the leukemia L1210 but not the TA3 cells at 1 x 10(-4) M, but the compound was significantly active against herpes simplex (type I) virus in vitro.
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PMID:Synthesis and biological activity of 4-beta-Iribofuranosyl-1,3-dihydroxybenzene ("1,3-dideazauridine"). 16 82

The gene order of the ml Moloney sarcoma virus (mlMSV) specific pP60gag (P60) was determined by direct chemical analysis of the polyprotein. P60 was cleaved with cyanogen bromide (CNBr) into eight partial and complete fragments ranging in mass from 10,000 daltons to 58,000 daltons. Peptide maps of these fragments were compared to maps of p15, p12, and three CNBr fragments of p30. The polarity of p15 and p12 in a CNBr fragment of P60 was determined by carboxypeptidase A digestion; likewise the CNBr fragments of p30 were ordered by aminopeptidase digestion. The linear arrangement of P60 CNBr fragments gave the gene order of NH2-p15-p12-p30-COOH. The m3 isolate of MSV expresses a P70 gag polyprotein. Peptide maps of 48,000-dalton CNBr fragments of m3 P70 and ml P60 were similar and suggested that both polyproteins were similar through the NH2-terminal two-thirds of p30. However, the presence of peptides unique to the 10,500-dalton COOH-terminal fragment of m1MSV p30 and not present in the p30 of either m3MSV or Moloney leukemia virus suggested that the gag gene deletion in the m1 isolate begins in the p30 reading frame.
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PMID:Chemical determination of the m1 Moloney sarcoma virus pP60gag gene order: evidence for unique peptides in the carboxy terminus of the polyprotein. 21 95

Mouse germ line DNA was isolated from sperm by a physicochemical procedure that preferentially destroys contaminating somatic cell DNA. The use of reducing conditions and chelating agents in combination with phenol permitted extraction of molecular weight DNA from mature sperm nuclei with approximately 80% efficiency. Less than 0.1% somatic cell DNA contamination remained in sperm DNA prepared by this method. Germ line DNA was characterized by determination of its ultraviolet absorbance spectrum, buoyant density in cesium chloride, and melting profile on a hydroxyapatite column. Contamination by mitochondrial DNA was assessed by cesium chloride/ethidium bromide gradient centrifugation. The significance of the mouse germ line DNA isolation procedure is discussed with respect to the possible genetic transmission of mammary tumor virus and leukemia virus, the origin of antibody diversity, and the origin of testicular teratomas.
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PMID:Isolation and characterization of germ line DNA from mouse sperm. 29 Oct 53

The rosette-forming capacity of bovine peripheral blood lymphocytes (PBL) was determined with dextran and 2-aminoethylisothiouronium bromide (AET)-treated sheep erythrocytes (SRBC). Both dextran and AET-enhanced rosette formation; however, AET-treated SRBC detected a larger percentage of rosette-forming cells and thus was used in this study. The specificity of rosette formation by bovine thymus-derived (T) lymphocytes was shown by (1) demonstration of rosettes and surface-membrane immunoglobulins sIg) on different cells in PBL and nylon-wool fractionated lymphocyte populations and (2) rosette formation by a large percentage (83--90%) of thymocytes from three bovine foetuses and two 14-month-old heifers. A procedure was also developed to identify bovine monocytes by latex phagocytosis and 10--30% latex-ingesting cells were detected in PBL preparations isolated by Ficoll-Hypaque flotation. The frequency of sIg-bearing latex-ingesting, and sIg-bearing latex non-ingesting cells in bovine peripheral blood was also determined. These procedures were utilized to determine the distribution of T and bone-marrow derived (B) lymphocytes in peripheral blood of normal and lymphocytotic cattle. PBL from twenty normal cattle contained approximately 63% T and 11% B (sIg+ latex non-ingesting) lymphocytes. In peripheral blood of three cattle with persistent lymphocytosis, a prodromal stage of bovine leukaemia, the percentage of B cells was elevated approximately to 59% whereas T lymphocytes decreased to 35%, thus providing additional evidence that persistent lymphocytosis is a B-cell disease.
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PMID:Enumeration of T cells, B cells and monocytes in the peripheral blood of normal and lymphocytotic cattle. 31 76

2-Deaminoactinomycin D has been synthesized and characterized. It binds to DNA by intercalation according to NMR, CD, thermal denaturation, and unwinding studies on the drug-DNA complex. Loss of the 2-amino group does not seriously affect binding parameters relative to actinomycin D; affinity for calf thymus DNA may even be increased, according to deltaTm measurements. The unwinding of circular DNA caused by this compound is at least as large as that effected by actinomycin D and ethidium bromide. Nevertheless, 2-deaminoactinomycin D is less effective than actinomycin D in inhibiting nucleic acid syntheses in L1210 cell culture and in in vivo antitumor activity against P388 leukemia.
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PMID:2-Deaminoactinomycin D, synthesis and interaction with deoxyribonucleic acid. 33 Aug 57

Three versions of the E-rosette test, one using untreated sheep erythrocytes at 37 degrees C, another using such cells at 4 degrees C, and a third using sheep erythrocytes treated with S-(2-aminoethyl)isothiouronium bromide hydrobromide (AET), were applied to each of 72 bone marrow specimens from as many unselected patients with untreated acute lymphocytic leukemia (ALL). The same specimens were also examined for T-cell antigens, based on reactivity with an antithymocyte serum. Lymphoblasts in eight ALL specimens formed E rosettes at 37 degrees C; no other E-positive specimens were identified when the assay was done at 4 degrees C. With AET-treated erythrocytes, lymphoblasts from these eight specimens and six additional specimens readily formed rosettes. T-cell antigens were detectable in all specimens positive for rosette formation withe untreated erythrocytes, in four of the six specimens positive for rosette formation with AET-treated erythrocytes, and in four specimens that showed no rosette formation under any of the experimental conditions used. Altogether, 18 specimens contained lymphoblasts with one or more surface markers characteristic of T-cell leukemia. These findings indicate that more specimens are likely to be identified at T-cell luekemias when E-rosette tests of increasing sensitivity and assayss for T-cell antigens are used. Some leukemic blasts do not possess the full array of membrane receptors and antigens usually associated with T cells. A combination of E-rosette tests and serologic tests is necessary to determine reliably the relationship of the test specimen to either T-cell ALL or common ALL and to establish the clinical significance of blasts that express membrane properties intermediate between those of T-cell ALL and common ALL.
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PMID:Comparison of techniques for detecting T-cell acute lymphocytic leukemia. 37 2

Synthetic approaches to anthracyclines bearing novel 9-acyl substituents were investigated. Reaction of the lithium enolate of N-(trifluoroacetyl)daunorubicin (9) with methyl iodide in tetrahydrofuran afforded only the 9-propionyl derivative 10 in high yield. Reaction of 10 under identical conditions cleanly afforded the 9-isobutyryl derivative 11. Extension of this procedure to other alkylating agents (ethyl iodide, benzyl bromide, and heptyl iodide) required hexamethylphosphoramide as cosolvent and afforded mixtures of mono- and dialkylated products as well as recovered 9. The amino group was deblocked with NaOH in aqueous tetrahydrofuran, except in the case of the dibenzyl derivative 13 which was inert under these conditions. The 9-formyl analogue 23 was prepared via NaIO4 cleavage of 13-dihydroadriamycin (21). Antitumor evaluation against P388 leukemia in mice showed 23 to have activity comparable to the parent compounds, while the C-alkylated analogues were less active.
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PMID:Synthesis of daunorubicin analogues with novel 9-acyl substituents. 42 82


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