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)

MHC class I molecules are normally expressed at very low levels in the brain and their up-regulation in response to cytokines and viral infections has been associated with a number of neurological disorders. Here we demonstrate that the down-regulation of surface class I molecules in differentiated primary rat oligodendrocytes was accompanied by reduced steady-state levels of class I heavy-chain mRNA. Transient expression assays were performed in oligodendrocytes and fibroblasts, using a mouse H-2Kb class I promoter chloramphenicol acetyltransferase plasmid termed pH2KCAT (which contained 5'-flanking sequences from -2033 to +5 bp of the H-2Kb gene relative to the transcriptional start site at +1 bp). These assays showed that H-2Kb promoter activity was reduced in oligodendrocytes but not in class I-expressing fibroblasts. H-2Kb promoter activity was up-regulated in oligodendrocytes co-transfected with a plasmid expression vector encoding the transcriptional activator tax of human T-cell leukaemia virus type I, showing that down-regulation of promoter activity was reversible. Deletion mutant analysis of the H-2Kb promoter revealed the presence of negative regulatory elements that were functional in oligodendrocytes at -1.61 to -1.07 kb and -242 to -190 bp. Deletion of sequences in pH2KCAT encompassing the downstream element totally abolished promoter activity in both oligodendrocytes and fibroblasts, whereas a deletion within the upstream negative regulatory element increased promoter activity specifically in oligodendrocytes. The upstream negative regulatory element also down-regulated a linked heterologous herpes simplex virus thymidine kinase promoter in oligodendrocytes, but not in fibroblasts. Gel retardation assays using overlapping DNA probes that spanned the entire -1.61 to -1.07 kb region revealed the presence of a number of DNA-binding activities that were present in oligodendrocyte, but not in fibroblast nuclear extracts.
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PMID:Transcriptional regulation of MHC class I gene expression in rat oligodendrocytes. 946 4

The transactivator protein, Tax, from the human T-cell leukemia virus type I (HTLV-I) transactivates both viral and cellular genes. Previously, we had shown that interleukin 8 (IL-8) is constitutively expressed in HTLV-I-infected cells and in cells transiently expressing Tax. We show here that the IL-8 promoter is Tax responsive in Jurkat T cells. Furthermore, using several deletion and mutated plasmids of the 5'-flanking regulatory region of the IL-8 gene linked to the luciferase gene as a reporter and mutant tax gene expression vectors, we have established that both AP-1 at -126 to -120 and nuclear factor (NF)-kappaB-like cis-element at -80 to -71 are essential and sufficient for the induction of the IL-8 gene by HTLV-I Tax. In addition, overexpression of the dominant-negative mutants of NF-kappaB inhibitor molecules, IkappaBalpha and IkappaBbeta, abolished the Tax-induced activation of IL-8 gene. Gel mobility shift assays detected proteins specifically binding to the AP-1 and NF-kappaB-like sites in Tax-expressing T-cell lines infected with HTLV-I. Similarly, the nuclear translocation of proteins specifically bound to these two motifs was shown in JPX-9 cells, a subclone of Jurkat cells, carrying the Tax sequences under the control of an inducible promoter. Taken together, these results suggest that the cooperation of transcription factors NF-kappaB and AP-1 is essential for transactivation of IL-8 gene by HTLV-I Tax.
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PMID:Human T-cell leukemia virus type I Tax transactivates human interleukin 8 gene through acting concurrently on AP-1 and nuclear factor-kappaB-like sites. 973 13

Patients severely neutropenic, when hospitalized, occasionally receive selective digestive decontamination, and the risk of vancomycin-resistant strain selection is a drawback since glycopeptide resistance is often associated with betalactam and aminoglycosid resistance. Bacterial translocation can lead to multiresistant bacterial sepsis. Eighteen Enterococcus faecium strains were collected from patients hospitalized in the leukemia unit of the Universitary Hospital of Lille (CHRU, Pr Bauters) between October 1992 and July 1997 and were studied. Nosocomial acquisition or endogenous origin were investigated to choose well-adapted prevention. All the vancomycin-resistant strains were shown by Polymerase Chain Reaction having the van A gene. The clonality of these strains was investigated by Pulsed-Field-Gel-Electrophoresis after Sma I restriction. Pulsotype analysis showed variable homology (52%-100%). Our results do not show evidence of patient-to-patient E. faecium transmission and suggest vancomycin-resistant strains were independently selected by antibiotic therapy from individual fecal flora. Except when epidemic events or happen, this strain isolation is more related to antibiotic prescription than misuse of isolation techniques.
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PMID:[Determination of the nosocomial origin of vancomycin-resistance strains of Enterococcus isolated from stool of patients in a hematology department]. 1041 13

AML1 plays a critical role during hematopoiesis and chromosomal translocations involving AML1 are commonly associated with different forms of leukemia, including pre-B acute lymphoblastic leukemia. To understand the function of AML1 during B cell differentiation, we analyzed regulatory regions of B cell-specific genes for potential AML1-binding sites and have identified a putative AML1-binding site in the promoter of the B cell-specific tyrosine kinase gene, blk. Gel mobility shift assays and transient transfection assays demonstrate that AML1 binds specifically to this site in the blk promoter and this binding site is important for blk promoter activity. Furthermore, in vitro binding analysis revealed that the AML1 runt DNA-binding domain physically interacts with the paired DNA-binding domain of BSAP, a B cell-specific transcription factor. BSAP has been shown previously to be important for B cell-specific regulation of the blk gene. Physical interaction of AML1 with BSAP correlates with functional cooperativity in transfection studies where AML1 and BSAP synergistically activate blk promoter transcription by more than 50-fold. These results demonstrate physical and functional interactions between AML1 and BSAP and suggest that AML1 is an important factor for regulating a critical B cell-specific gene, blk.
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PMID:AML1 (CBFalpha2) cooperates with B cell-specific activating protein (BSAP/PAX5) in activation of the B cell-specific BLK gene promoter. 1045 34

F 11782 is a newly identified catalytic inhibitor of topoisomerases I and II, without any detectable interaction with DNA. This study aimed to establish whether its catalytic inhibition of topoisomerase II was mediated by mechanisms similar to those identified for the bisdioxopiperazines. In vitro combinations of F 11782 with etoposide resulted in greater than additive cytotoxicity in L1210 cells, contrasting with marked antagonism for combinations of etoposide with either ICRF-187 or ICRF-193. All three compounds caused a G2/M blockade of P388 cells after an 18-h incubation, but by 40 h polyploidization was evident only with the bisdioxopiperazines. Gel retardation data revealed that only F 11782, and not the bisdioxopiperazines, was capable of completely inhibiting the DNA-binding activity of topoisomerase II, confirming its novel mechanism of action. Furthermore, unlike ICRF-187 and ICRF-193, the cytotoxicity of F 11782 appeared mediated, at least partially, by DNA damage induction in cultured GCT27 human teratoma cells, as judged by a fluorescence-enhancement assay and monitoring p53 activation. Finally, the major in vivo antitumor activity of F 11782 against the murine P388 leukemia (i.v. implanted) and the B16 melanoma (s.c. grafted) contrasted with the bisdioxopiperazines' general lack of activity. Overall, F 11782 and the bisdioxopiperazines appear to function as quite distinctive catalytic topoisomerase II inhibitors.
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PMID:Characterization of the biological and biochemical activities of F 11782 and the bisdioxopiperazines, ICRF-187 and ICRF-193, two types of topoisomerase II catalytic inhibitors with distinctive mechanisms of action. 1114 91

Here we show that in human T-cell leukemia cells Vav1 and protein kinase C theta (PKCtheta) synergize for the activation of c-Jun N-terminal kinase (JNK) but not p38 MAP kinase. Vav1 and PKCtheta also cooperated to induce transcription of reporter genes controlled either by AP-1 binding sites or the CD28RE/AP composite element contained in the IL-2 promoter by stimulating the binding of transcription factors to these two elements. Dominant negative versions of Vav1 and PKCtheta inhibited CD3/CD28-induced activation of JNK, revealing their relative importance for this activation pathway. Gel filtration experiments revealed the existence of constitutively associated Vav1/PKCtheta heterodimers in extracts from unstimulated T-cells, whereas T-cell costimulation induced the recruitment of Vav1 into high molecular weight complexes. Several experimental approaches showed that Vav1 is located upstream from PKCtheta in the control of the pathway leading to synergistic JNK activation. Vav1-derived signals lead to the activation of JNK by at least two different pathways. The major contribution of Vav1 for the activation of JNK relies on the PKCtheta-mediated Ca(2+)-independent synergistic activation pathway, whereas JNK is also activated by a separate Ca(2+)-dependent signaling route.
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PMID:Protein kinase C theta cooperates with Vav1 to induce JNK activity in T-cells. 1127 47

A novel ribosome-inactivating protein with a molecular weight of 20 kDa was isolated from fruiting bodies of the mushroom Hypsizigus marmoreus. The isolation procedure entailed ion exchange chromatography on CM-cellulose, affinity chromatography on Affi-gel Blue Gel and ion exchange chromatography on Mono Q. The protein designated hypsin demonstrated an inhibitory action against mycelial growth in various fungal species including Mycosphaerella arachidicola, Physalospora piricola, Fusarium oxysporum, and Botrytis cinerea with an IC50 of 2.7, 2.5, 14.2, and 0.06 microM, respectively. Translation in the rabbit reticulocyte lysate system was inhibited with an IC50 of 7 nM and HIV-1 reverse transcriptase activity was inhibited with an IC50 of 8 microM. Antiproliferative activity against mouse leukemia cells and human leukemia and hepatoma cells was observed. About 60% of the translation-inhibitory activity was retained after heating at 100 degrees C for 10 min. No loss of translation-inhibitory activity occurred after brief treatment with trypsin.
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PMID:Hypsin, a novel thermostable ribosome-inactivating protein with antifungal and antiproliferative activities from fruiting bodies of the edible mushroom Hypsizigus marmoreus. 1146 62

All-trans-retinoic acid (RA) is a potent inhibitor of leukemia cell proliferation and induces differentiation of acute promyelocytic leukemia cells in vitro and in vivo. For RA to induce its biological effects in target cells, binding to specific retinoic acid nuclear receptors is required. The resulting complexes bind to RA-responsive elements (RAREs) in the promoters of RA-inducible genes to initiate gene transcription and to generate protein products that mediate the biological effects of RA. In this report, we provide evidence that a member of the protein kinase C (PKC) family of proteins, PKC delta, is activated during RA treatment of the NB-4 and HL-60 acute myeloid leukemia cell lines as well as the MCF-7 breast cancer cell line. Such RA-dependent phosphorylation was also observed in primary acute promyelocytic leukemia cells and resulted in activation of the kinase domain of PKC delta. In studies aimed at understanding the functional relevance of PKC delta in the induction of RA responses, we found that pharmacological inhibition of PKC delta (but not of other PKC isoforms) diminished RA-dependent gene transcription via RAREs. On the other hand, overexpression of a constitutively active form of the kinase strongly enhanced RA-dependent gene transcription via RAREs. Gel shift assays and chromatin immunoprecipitation studies demonstrated that PKC delta associated with retinoic acid receptor-alpha and was present in an RA-inducible protein complex that bound to RAREs. Pharmacological inhibition of PKC delta activity abrogated the induction of cell differentiation and growth inhibition of NB-4 blast cells, demonstrating that its function is required for such effects. Altogether, our data provide strong evidence that PKC delta is activated in an RA-dependent manner and plays a critical role in the generation of the biological effects of RA in malignant cells.
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PMID:Activation of protein kinase C delta by all-trans-retinoic acid. 1280 78

Cellular homeoproteins have been shown to regulate the transcription of several viruses, including herpes simplex viruses, human papillomaviruses, and mouse mammary tumor viruses. Previous studies investigating the anti-viral mechanisms of several cyclin-dependent kinase inhibitors showed that the homeoproteins, pre B-cell leukemia transcription factor 1 (PBX1) and PBX-regulating protein-1 (PREP1), function as transcriptional activators of Moloney murine leukemia virus. Here, we examined the involvement of cellular homeoproteins in regulating the activity of the human cytomegalovirus immediate early (CMV IE) promoter. We identified a 45-bp element located at position -593 to -549 upstream of the transcription start site of the CMV IE gene, which contains multiple putative homeoprotein binding motifs. Gel shift assays demonstrated the physical association between a homeodomain protein, pancreatic-duodenal homeobox factor-1 (PDX1) and the 45-bp cytomegalovirus (CMV) region. We further determined that PDX1 represses the CMV IE promoter activity in 293 cells. Overexpression of PDX1 resulted in a decrease in transcription of the CMV IE gene. Conversely, blocking PDX1 protein synthesis and mutating the PDX1 binding sites enhanced CMV IE-dependent transcription. Collectively, our results represent the first work demonstrating that a cellular homeoprotein, PDX1, may be a repressor involved in regulation of human CMV gene expression.
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PMID:PDX1, a cellular homeoprotein, binds to and regulates the activity of human cytomegalovirus immediate early promoter. 1476 5

The review describes the history of creation and development of the microchip technology and its role in the human genome project in Russia. The emphasis is placed on the three-dimensional gel-based microchips developed at the Center of Biological Microchips headed by A.D. Mirzabekov since 1988. The gel-based chips of the last generation, IMAGE chips (Immobilized Micro Array of Gel Elements), have a number of advantages over the previous versions. The microchips are manufactured by photo-initiated copolymerization of gel components and immobilized molecules (DNA, proteins, and ligands). This ensures an even distribution of the immobilized probe throughout the microchip gel element with a high yield (about 50% for oligonucleotides). The use of methacrylamide as a main component of the polymerization mixture resulted in a substantial increase of gel porosity without affecting its mechanical strength and stability, which allowed one to work with the DNA fragments of up to 500 nt in length, as well as with rather large protein molecules. At present, the gel-based microchips are widely applied to address different problems. The generic microchips containing a complete set of possible hexanucleotides are used to reveal the DNA motifs binding with different proteins and to study the DNA-protein interactions. The oligonucleotide microchips are a cheap and reliable tool of diagnostics designed for mass application. Biochips have been developed for identification of the tuberculosis pathogen and its antibiotic-resistant forms; for diagnostics of orthopoxviruses, including the smallpox virus; for diagnostics of the anthrax pathogen; and for identification of chromosomal rearrangements in leukemia patients. The protein microchips can be adapted for further use in proteomics. Bacterial and yeast cells were also immobilized in the gel, maintaining their viability, which open a wide potential for creation biosensors on the basis of microchips.
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PMID:[Microchips based on three dimensional gel cells: history and perspective]. 1504 31


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