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)

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

Sequence analysis of the mutant Dbm13, Dbm14, and Dbm24 genes indicate that they differ from the parental Db gene by 4, 1, and 8 nucleotides, respectively. The mutant sequences substituted into Dbm13 and Dbm24 are identical to those found in the Kb gene, at the homologous positions. Thus, similar to the Kb gene, the Db gene is able to undergo micro-recombination (gene conversion) events with other class I genes. Such data suggest that micro-recombination events could be an important mechanism for the diversification of all H-2 genes. The Db mutant products share a common theme: the alterations in all occur at amino acid residues whose side chains in the homologous class I HLA-A2 molecule project into the postulated peptide antigen-binding cleft, and hence, would be expected to alter the binding of foreign or self peptides. Due to such changes, the bm14 mouse has become a nonresponder in the CTL response to Moloney murine leukemia virus (M-MuLV), as the alteration of one amino acid residue at position 70 (a Gln to His) is sufficient to entirely abrogate the cell-mediated response to the virus. On the other hand, the bm13 mouse has shifted the major part of its M-MuLV restriction to Kb, a profound alteration in CTL responsiveness due to the alteration of three amino acids (Leu to Gln at 114, Phe to Tyr at 116, and Glu to Asp at 119) in a peptide stretch of beta-pleated sheet structure lining the bottom of the antigen-binding cleft. Thus, study of these mutants reveals that, in one step, micro-recombination at the genetic level has resulted at the protein level in profound changes in the immune response to viral infection. Such a mechanism operating at the population level can be a driving force during evolution for modulating the character of CTL immunity.
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PMID:Three spontaneous H-2Db mutants are generated by genetic micro-recombination (gene conversion) events. Impact on the H-2-restricted immune responsiveness. 319 70

A 30-yr-old man with chronic granulocytic leukaemia received a bone marrow transplant from his histocompatible sister in December 1982. His post-transplant course was complicated by Grade III graft-versus-host disease and multiple infectious episodes until his death from pneumonia on d + 190. He was later found to be seropositive for anti-HIV at the time of his death. Retrospective analysis of stored sera showed a transient period of seropositivity from d + 11 to d + 20 thought to reflect passive transfer of antibody from a blood product transfused prior to d + 11 when he was also exposed to infectious virus. He remained seronegative until d + 78 when anti-HIV was again found. Seropositivity persisted until his death and was attributed to endogenous antibody response. Although it is unclear whether his clinical course was due to AIDS, exposure of an immunosuppressed patient to HIV may be associated with more rapid development of clinical disease.
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PMID:HIV infection due to a platelet transfusion after allogeneic bone marrow transplantation. 331 96

L-Histidinol, an analogue of the amino acid L-histidine, has been reported to be able to increase the specificity of 5-fluorouracil (FUra), through both protection of normal tissues at risk and potentiation of leukemic cell killing. It is postulated that this occurs through prevention of the entry of normal cells into the cell cycle through protein deficiency, while allowing malignant cells, permissive for protein starvation, to continue to cycle, thus maintaining sensitivity for cycle specific anticancer agents. Reported in this paper is the confirmation of these L-histidinol-FUra effects. However, a modification was made by which more L-histidinol could be given and more consistent protection of whole animals demonstrated. Further, an optimal schedule of L-histidinol was defined in which FUra preceded L-histidinol infusion. Finally, the specificity and proliferation dependence of this schedule was evaluated on colony forming units-spleen in resting and proliferating state, colony forming units-granulocyte-macrophage, and L1210 leukemia. This demonstrates that the FUra/L-histidinol combination indeed protects only normal cells but that the postulated proliferation dependence is absent, indicating an alternate biological mechanism.
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PMID:Specificity, schedule, and proliferation dependence of infused L-histidinol after 5-fluorouracil in mice. 334 20

When rat basophilic leukemia (2H3) cells were stimulated by higher oligomer, the chemically cross-linked oligomers of IgE, in the presence of calcium the activity of histidine decarboxylase (HDC, L-histidine carboxylase, E.C.4.1.1.22), a histamine-forming enzyme, was increased by 1 hr, reaching maximum activity by 2 hr, and returning to the original level by 8 hr. A similar increase in enzyme activity was observed in cells treated with phorbol myristate acetate (PMA) or oleoyl-acetylglycerol (OAG), which are known activators of protein kinase C. Removal of calcium from medium abolished the increase in HDC activity in response to higher oligomer but not that induced by PMA or OAG, suggesting that the increase in HDC activity may be mediated by protein kinase C. The increase in the HDC activity probably required induction of enzyme synthesis, because it was prevented by cycloheximide.
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PMID:Induction of histidine decarboxylase of rat basophilic leukemia (2H3) cells stimulated by higher oligomeric IgE or phorbol myristate acetate. 335 61

It has been reported that L-histidinol, a structural analogue of the essential amino acid L-histidine, can transiently inhibit proliferative cycling in cells with normal phenotype while allowing continued cell cycle transit in tumor cells. Thus, in the presence of L-histidinol, the toxicity of a proliferation-dependent drug such as 5-fluorouracil (FUra) was found to be reduced in normal tissue cells of the DBA/2J mouse, but not in L1210 leukemia cells in the same mouse. Because of the potential clinical significance of this approach to reduce chemotherapy-associated host toxicity, we evaluated the L-histidinol-FUra combination in a nonleukemic, solid murine tumor model, the BALB/c X DBA/8 F1 (hereafter called CD8F1) breast tumor. The results of these studies indicate that the administration of L-histidinol can protect the CD8F1 mouse from FUra-associated leukopenia, body weight loss, and ultimately, from mortality. However, in contrast to results reported in the L1210 leukemic system, L-histidinol also reduced the cytotoxic activity of FUra against CD8F1 breast tumors. Therefore, although the dose of FUra that could be administered with safety was higher in mice receiving L-histidinol, the therapeutic results of the combination of FUra and L-histidinol were not superior to those obtained with FUra alone at a lower dose.
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PMID:Failure of L-histidinol to improve the therapeutic efficiency of 5-fluorouracil against murine breast tumors. 379 Dec 3

The possibility was investigated that L-histidinol-anticancer drug combinations may provide increased tumor cell eradication and eliminate in vivo bone marrow toxicity of proliferation-dependent anticancer agents in animals bearing an established, intrafemoral bone marrow disease. It was previously demonstrated that L-histidinol, a structural analogue of the essential amino acid L-histidine, improves the specificity of cytarabine (ara-C) and 5-fluorouracil (FUra) in DBA/2J mice bearing intraperitoneal L 1210 leukemia. Accordingly, DBA/2J mice were given iv injections of 1 X 10(6) L1210 leukemia cells 3 days before histidinol-anticancer drug treatments. During the postinjection, pretreatment interval, injected tumor cells populated the femoral marrows, shown by clonogenic assays and flow cytometric analyses. Following various drug treatments, quantitative and selective survival assays were performed of normal femoral cells and of clonogenic L1210 leukemia cells isolated from the femurs of treated mice. These experiments demonstrated that L-histidinol not only protected the marrow cell population from both ara-C and FUra, but also increased significantly the toxicities of these agents for the intrafemoral tumor cells. Thus L-histidinol mediates a substantial increase in the specificities of ara-C and FUra in mice bearing an established bone marrow leukemic condition.
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PMID:Histidinol-mediated enhancement of the specificity of two anticancer drugs in mice bearing leukemic bone marrow disease. 385 76

Rat basophil leukemia (2H3) cells, like normal rat peritoneal mast cells, were shown to take up and decarboxylate histidine. Uptake was mediated by a temperature-dependent system with high affinity (apparent Km 24 +/- 4 microM) for histidine. Newly formed histamine was incorporated into the intracellular pool of histamine. In confluent cultures, substantial amounts of histamine were lost to the medium while intracellular histamine levels remained constant. As calculated from the rate of appearance of histamine in the medium, the maximum turnover time for the intracellular histamine pool (2-7 nmol/10(6) cells) was about 12 hr. Variation in histamine content, histidine uptake and histidine decarboxylation was noted with different passages of 2H3 cells, but with all passages there were characteristic changes in these parameters during growth and division of the cells. Separation of cells into fractions of different size by elutriation indicated low rates of histidine uptake and decarboxylation in the smallest 2H3 cells, a progressive increase in ability to take up and decarboxylate histidine as the cells approached the S phase of growth and marked decline in this ability in fractions containing the larger cells. The changes in kinetic constants suggested that fluctuation in histidine uptake during the life cycle of the 2H3 cell was due to changes in the number of active carriers or sites of histidine transport and that during cell division all components associated with histamine synthesis (i.e., histidine uptake and decarboxylation) were diminished.
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PMID:Changes in histidine uptake and histamine synthesis during the growth cycle of rat basophilic leukemia (2H3) cells. 396 91

1. (14)C-L-histidine was given i.v. to one normal subject and two patients with chronic myelocytic leukaemia. Urinary excretion of histamine and two of its metabolites methylhistamine and methylimidazoleacetic acid, total as well as (14)C-labelled, was measured, as well as blood (14)C-histamine. In addition the total urinary and pulmonary elimination of (14)C was followed.2. Total (14)C elimination was high during the first days, then declined slowly except for a plateau at the 10th-14th day in the two patients. There was a measurable elimination even after some months.3. (14)C-histamine appeared in the blood of the leukaemic patient, whereas in the normal subjects the values were hardly measurable.4. The leukaemic patients excreted much more of the two (14)C-labelled histamine metabolites than the normal subject. The difference in excretion of the (14)C-labelled metabolites was largest around the 12th day after the infusion of (14)C-L-histidine.5. The results indicate that the leukaemic patients formed at least 20 times more histamine daily than the normal subject.
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PMID:Histamine formation from 14 C-L-histidine in man. 451 Feb 13

Urinary amino acid chromatograms were studied from 33 patients with various types of leukaemia and 71 control subjects. Marked variations were found in the excretion of methionine, threonine, valine, leucine, tyrosine, histidine, and aspartic acid.
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PMID:Urinary amino acid excretion in subjects with leukaemia. 522 27


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