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)

The RNA binding protein of 56 residues encoded by the extreme 3' region of the gag gene of Rauscher murine leukemia virus (MuLV) has been chemically synthesized by a solid-phase synthesis approach. Since the peptide contains a Cys26-X2-Cys29-X4-His34-X2-Cys39 sequence that is shared by all retroviral gag polyproteins which has been proposed to be a metal binding region, it was of considerable interest to examine the metal binding properties of the complete p10 protein. As postulated, p10 binds the metal ions Cd(II), Co(II), and Zn(II). The Co(II) protein shows a set of d-d absorption bands typical of a tetrahedral Co(II) complex at 695 (epsilon = 565 M-1 cm-1), 642 (epsilon = 655 M-1 cm-1), and 615 nm (epsilon = 510 M-1 cm-1) and two intense bands at 349 (epsilon = 2460 M-1 cm-1) and 314 nm (epsilon = 4240 M-1 cm-1) typical of Co(II)----(-)S- charge transfer. The ultraviolet absorption spectrum also indicates Cd(II) binding by the appearance of a Cd(II)----(-)S- charge-transfer band at 255 nm. The 113Cd NMR spectrum of 113Cd(II)-p10 reveals one signal at delta = 648 ppm. This chemical shift correlates well with that predicted for ligation of 113Cd(II) to three -S- from the three Cys residues of p10. The chemical shift of 113Cd(II)-p10 changes by only 4 ppm upon binding of d(pA)6, indicating that the chelate complex is little changed by oligonucleotide binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:p10 single-stranded nucleic acid binding protein from murine leukemia virus binds metal ions via the peptide sequence Cys26-X2-Cys29-X4-His34-X4-Cys39. 269 61

The relation between the lifetimes of the triplet states of various porphyrins and their photosensitizing effects on the photodynamic therapy (PDT) of tumor has been examined. Diethylene-triamine pentaacetic acid ester of 4-[1-(2-hydroxy-ethyloxy)ethyl]-2-vinyl deuteroporphyrin-IX gallium (III) complex (Ga-DP), zinc (II) complex (Zn-DP), and manganese (III) complex (Mn-DP) and Photofrin II (PII) are used as the photosensitizer. The triplet lifetimes have been measured for the samples adsorbed on filter paper (FP) and found to be 57 ms (Ga-DP), 26 ms (Zn-DP), less than or equal to 10 microseconds (Mn-DP) and 9 ms (PII). The phosphorescence of Ga-DP in tumor-bearing golden hamsters are measured both in tumor tissue and in liver. They show bi-exponential decay with the lifetimes of about 5 and 20 ms. From the values, the generation rate, kct[3O2], of singlet molecular oxygen in living animal tissue may be estimated to be an order of 10(2) s-1. The PDT effects have been quantitatively investigated for in vitro experiments; upon irradiation the growth inhibitions of mouse p388 leukemia cells are obtained as a function of concentration of Ga-DP, Zn-DP, Mn-DP and PII. The experimental results indicate that the PDT effects depend essentially on the triplet lifetimes of the photosensitizers.
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PMID:Critical importance of the triplet lifetime of photosensitizer in photodynamic therapy of tumor. 278 Aug 23

Retroviral gag gene-encoded core nucleic acid binding proteins contain either one or two sequences of the form Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys. Previously, one of us has proposed that these sequences form metal-binding domains in analogy with the "zinc finger" domains first observed in transcription factor IIIA. We report that an 18-amino acid peptide derived from the core nucleic acid binding protein from Rauscher murine leukemia virus binds metal ions such as Co2+ and Zn2+. The absorption spectrum of the peptide-Co2+ complex is highly suggestive of tetrahedral coordination involving three cysteinates and one histidine. Titration experiments indicate that the dissociation constant for the peptide-Co2+ complex is 1.0 microM and that Zn2+ binds more tightly than Co2+. A detailed three-dimensional structure for this domain based on conserved substructures in other crystallographically characterized metalloproteins and on a detailed analysis of the Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys sequences from retroviruses and other related sources is proposed.
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PMID:A retroviral Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys peptide binds metal ions: spectroscopic studies and a proposed three-dimensional structure. 278 6

The p10 murine leukemia virus (MuLV) protein is a basic single-stranded nucleic acid binding protein encoded by the extreme 3' region of the gag gene of MuLV type C. It contains the Cys-X2-Cys-X4-His-X4-Cys sequence shared by all retroviral gag polyproteins. A similar sequence is found in the gene 32 single-stranded DNA binding protein of bacteriophage T4 and is believed to be the zinc binding region of the protein. Solid phase synthesis of p10 was carried out based on the known primary structure of the native protein, with the exception that the acetamidomethyl (Acm) derivative of cysteine was incorporated at all three cysteine positions. The structure of the synthetic p10 was confirmed by direct amino-acid sequencing, as well as by amino acid analysis and FAB mass spectrometry of endoproteinase Lys-C peptides derived from p10. A Chou and Fasman analysis of the primary sequence predicts that p10 contains 9% beta strand and/or sheet and 36% alpha helix. Circular dichroism experiments carried out on the Acm derivatized peptide gave somewhat different results, in that they suggest that p10 contains approximately 70% random coil, less than 30% beta strand and/or sheet and less than 10% alpha helix. With a Ka of greater than 10(8) M-1 for single-stranded RNA, the synthetic peptide binds as tightly as the p10 protein does when isolated directly from infected HTG-2 cells. The Acm groups can be removed from the synthetic p10 peptide by the use of mercuric acetate, followed by treatment with dithiothreitol to sequester the mercuric ion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Synthesis of the p10 single-stranded nucleic acid binding protein from murine leukemia virus. 285 55

The 1916 painters and the 1948 electricians who resided in the Canton of Geneva at the time of the 1970 census were identified and followed up to 1984. During the study period 121 disability pensions were awarded to painters and 59 to electricians. Age standardised incidence of disability per 1000 man-years at risk was higher among painters than among electricians for all neuropsychiatric causes (1.23/1000 and 0.68/1000, respectively) and for all other causes (5.50/1000 and 3.41/1000, respectively). No case of presenile dementia was diagnosed among painters. There was inadequate evidence to indicate that the higher risk of neuropsychiatric disability for painters might have been due to their occupational exposure to organic solvents. A possible toxic effect of these substances on the central nervous system was confounded with alcoholism which was associated with disability from neuropsychiatric disease in 12 of 20 painters and in only one of 10 electricians. Mortality and incidence of cancer were assessed among both cohorts and compared with the expected figures calculated from Geneva rates. Among painters there was a significant increase in overall mortality (O = 254, E = 218.5), in mortality from all cancers (O = 96, E = 75.4), and in incidence from all cancers (O = 159, E = 132.0). For the specific cancer sites, there was a significant excess risk for lung cancer (mortality: O = 40, E = 23.0), which was possibly related to occupational exposure to asbestos and to zinc chromate, although cigarette smoking was not controlled. The significant excesses of biliary tract cancer and of bladder cancer were in accordance with previous observations among painters from other countries. There was also a significant increase in incidence from testicular cancer (O=5, E=1.6), which has not been reported before. For causes of death other than cancer the excesses for alcoholism (O=5, E=0.8). for liver cirrhosis (O=14, E=8.8), for motor vehicle accidents (O=12, E=5.9), and for cerebrovascular disease when allowing for ten years of latency (O=8, E=4.0), were consistent with a probable increased risk of alcohol abuse. Among electricians overall mortality was similar to that expected (O=137, E=139.0). No significant excess risk was found for all cancers or for any specific cancer site. Because of the small number of expected deaths the statistical power was low for the assessment of a possible risk for leukaemia or for brain tumour.
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PMID:Disability, mortality, and incidence of cancer among Geneva painters and electricians: a historical prospective study. 292 Jan 39

Several derivatives and analogs of the recently reported antiproliferative and antitumor agent trans-bis(salicylaldoximato)copper(II) (CuSAO2) have been prepared and tested for antiproliferative activity against L1210 leukemia cells in vitro. The salicylaldimine analog of CuSAO2 had a very strong antiproliferative activity, the 2-day IC50 value being lower than 3 micrograms/ml. The 2,3-dihydroxybenzaldoxime analog was equally active with CuSAO2, while the corresponding 2,5-dihydroxy derivative had a slightly lower activity. The 2,3,4-trihydroxybenzaldoxime derivative had a much lower activity than had the dihydroxybenzaldoxime derivatives. The zinc(II) analog of CuSAO2 had only a low antiproliferative activity. The ligand of CuSAO2, salicylaldoxime, resembles pyridoxal oxime, a vitamin B6 antagonist and a powerful inhibitor of pyridoxal kinase. An attempt to reduce the toxicity of CuSAO2 in vivo with pyridoxal hydrochloride led to increased toxicity.
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PMID:Antiproliferative activity of derivatives of trans-bis(salicylaldoximato)copper(II) in vitro. Some in vivo properties of the parent compound. 294 33

All retroviruses encode a nucleic acid-binding or nucleocapsid protein that is believed to be associated with RNA in the virion. Further, all retroviral nucleocapsid proteins contain either one or two copies of the sequence Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys. The conservation of this sequence suggested that it is important for virus replication, and its resemblance to the "zinc-finger" sequences found in eukaryotic transcription factors raised the possibility that it recognizes specific sequences in viral RNA during retrovirus assembly. We used oligonucleotide-directed mutagenesis to generate a series of mutations in the nucleocapsid protein-coding region of Moloney murine leukemia virus. These mutations changed single amino acids, including each of the cysteines, to serine. The mutant viral genomes direct the synthesis of virus particles; these particles lack detectable viral RNA but do contain significant levels of cellular RNAs. Thus it appears that the mutations have destroyed the ability of the viral proteins to specifically package viral RNA during virus assembly. We propose that the conserved sequence in retroviral nucleocapsid proteins functions in RNA sequence recognition and suggest that it is evolutionarily related to the zinc fingers that recognize specific sequences in double-stranded DNA.
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PMID:Point mutants of Moloney murine leukemia virus that fail to package viral RNA: evidence for specific RNA recognition by a "zinc finger-like" protein sequence. 314 27

In the mice of high leukemic strain, sick with natural lymphatic leukemia, levels of copper, zinc and cadmium in blood and inner organs were determined by the method of atomic absorption spectrophotometry. Mice were killed on the 0 day (when 10 weeks old) and after 90, 180 and 270 days of observation. In plasma the level of ceruloplasmin (EC1.12.3.1) was determined. It has been proved that in mice with lymphatic leukemia the levels of copper, zinc and cadmium are higher than in control animals. It was also found out that there is some disturbance in the natural antagonism between these metals. The activity of ceruloplasmin in the course of leukemia was determined. We have also tried to interpret the role of heavy metals in leukemogenesis in mice.
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PMID:[Levels of copper and its antagonists in mice with natural lymphocytic leukemia]. 326 10

Synthesis of ferritin, a constitutive protein, is increased by iron. This protein is well recognized as a protein which detoxifies, stores and transports iron. The 24 subunits of ferritin assemble to form a protomer of Mr 480,000. This protein shell can sequester up to 4500 g atoms of iron as ferrichydroxyphosphate. Ferritin in vitro and in vivo binds other metal ions such as Cu, Zn, Cd, Pb, Be and Al. Next to Fe it binds large quantities of Be. Therefore, in vitro ferritin protects against and reverses the inhibition by Be of enzymes susceptible to this metal ion. Also, rats pretreated with Fe survive otherwise toxic levels of either pulmonary or intravenous exposure of Be. Liver ferritin from rats injected with Zn contains some of the injected metal ion. Incubation of such ferritin-zinc complex with zinc-requiring apoenzymes restores their activity. Fe(III) of ferritin is released only after its reduction to Fe(II) by a reductant. Incubation of phosphoglucomutase, a phosphoserine containing enzyme with ferritin and a reductant causes irreversible inactivation of the enzyme and removes 70% of its phosphate. Some other phosphoproteins are similarly inactivated but without the loss of the bound phosphate. Thus, uncontrolled release of iron from ferritin, in the presence of a reductant and oxygen can modify several biomolecules and can affect metabolic processes. A subclass of ferritin, acidic isoferritins, have been implicated in leukemia-associated inhibitory activity and has been suggested to inhibit production of Ia+ macrophage progenitors.
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PMID:Ferritin: an expanded role in metabolic regulation. 327 34

Copper, zinc, and iron were quantitated in the serum and lymphoid cells of the peripheral blood of healthy children and children with acute lymphocytic leukemia. Copper and iron concentrations in serum and cells were significantly higher and zinc concentration in the cells significantly lower in leukemic patients than in healthy donors, whereas the increase of zinc in the serum was not significant. The concentration of all minerals was higher in T-cell enriched preparations. There was a significant correlation between copper and iron and between copper and zinc, but not between iron and zinc in normal and leukemic lymphocytes. No correlation was demonstrated among the three minerals in the serum. There were no significant differences associated with ethnicity, age, sex, type of leukemia, or number of leukemic cells. However, a group of five children with non-B-, non-T-cell acute lymphocytic leukemia, nonreactive skin tests, and low serum immunoglobulins had high concentrations of copper and iron and low concentration of zinc in their leukemic cells. Since copper, zinc, and iron are associated with lymphocyte maturation and regulation of immune function, these new data will provide a tool for the study of the relationship between changes in concentrations of these metals and the modification of the immune response often present in hematologic cancers.
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PMID:Copper, zinc, and iron in normal and leukemic lymphocytes from children. 345 80


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