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1.
Leukemia ; 28(8): 1676-86, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24504023

ABSTRACT

In addition to their cytoprotective role in stressful conditions, heat shock proteins (HSPs) are involved in specific differentiation pathways, for example, we have identified a role for HSP90 in macrophage differentiation of human peripheral blood monocytes that are exposed to macrophage colony-stimulating factor (M-CSF). Here, we show that deletion of the main transcription factor involved in heat shock gene regulation, heat shock factor 1 (HSF1), affects M-CSF-driven differentiation of mouse bone marrow cells. HSF1 transiently accumulates in the nucleus of human monocytes undergoing macrophage differentiation, including M-CSF-treated peripheral blood monocytes and phorbol ester-treated THP1 cells. We demonstrate that HSF1 has a dual effect on SPI1/PU.1, a transcription factor essential for macrophage differentiation and whose deregulation can lead to the development of leukemias and lymphomas. Firstly, HSF1 regulates SPI1/PU.1 gene expression through its binding to a heat shock element within the intron 2 of this gene. Furthermore, downregulation or inhibition of HSF1 impaired both SPI1/PU.1-targeted gene transcription and macrophage differentiation. Secondly, HSF1 induces the expression of HSP70 that interacts with SPI1/PU.1 to protect the transcription factor from proteasomal degradation. Taken together, HSF1 appears as a fine-tuning regulator of SPI1/PU.1 expression at the transcriptional and post-translational levels during macrophage differentiation of monocytes.


Subject(s)
Cell Differentiation , DNA-Binding Proteins/physiology , Macrophages/cytology , Monocytes/cytology , Proto-Oncogene Proteins/genetics , Trans-Activators/genetics , Transcription Factors/physiology , Animals , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Cells, Cultured , Gene Expression Regulation , Heat Shock Transcription Factors , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Proteasome Endopeptidase Complex/metabolism , Receptors, Cell Surface/analysis
3.
Nucleic Acids Res ; 25(12): 2448-54, 1997 Jun 15.
Article in English | MEDLINE | ID: mdl-9171098

ABSTRACT

Ciliated protozoa undergo thousands of site-specific DNA deletion events during the programmed development of micronuclear genomes to macronuclear genomes. Two deletion elements, W1 and W2, were identified in the Paramecium primaurelia wild-type 156 strain. Here, we report the characterization of both elements in wild-type strain 168 and show that they display variant deletion patterns when compared with those of strain 156. The W1 ( 168 ) element is defective for deletion. The W2 ( 168 ) element is excised utilizing two alternative boundaries on one side, both are different from the boundary utilized to excise the W2156 element. By crossing the 156 and 168 strains, we demonstrate that the definition of all deletion endpoints are each controlled by cis -acting determinant(s) rather than by strain-specific trans-acting factor(s). Sequence comparison of all deleted DNA segments indicates that the 5'-TA-3'terminal sequence is strictly required at their ends. Furthermore the identity of the first eight base pairs of these ends to a previously established consensus sequence correlates with the frequency of the corresponding deletion events. Our data implies the existence of an adaptive convergent evolution of these Paramecium deleted DNA segment end sequences.


Subject(s)
DNA, Protozoan/genetics , Paramecium/genetics , Sequence Deletion , Alleles , Animals , Base Sequence , Cloning, Molecular , DNA Primers , Genes, Protozoan , Molecular Sequence Data , Polymerase Chain Reaction , Restriction Mapping , Sequence Alignment , Sequence Homology, Nucleic Acid , Species Specificity
6.
Dev Genet ; 13(4): 306-17, 1992.
Article in English | MEDLINE | ID: mdl-1339337

ABSTRACT

The Paramecium primaurelia cell surface is covered with a high molecular weight protein called the surface antigen. Several genes encode alternative surface antigens, but only one is expressed at a time. In addition, each of these genes shows a high degree of allelic polymorphism. Paramecium primaurelia strains 156 and 168 have different alleles of the G antigen gene whose respective antigens can be distinguished in vivo using specific antibodies. An interallelic exclusion phenomenon has been previously described: 94% of the 156/168 heterozygotes express only the 156 allele of the G gene; 6% express both the 156 and the 168 alleles. The phenotype of the heterozygotes is determined at the time of macronuclear differentiation. We have investigated the molecular basis for the different heterozygous phenotypes. Both mRNAs are always produced, and the 156 mRNA is always more abundant than the 168 mRNA. The relative amounts of these messages, however, vary greatly between different heterozygotes and parallel their phenotype. Pushing the analysis further, we show that the copy number of each allele in the macronucleus correlates with the relative amounts of the mRNAs. However, allelic dosage alone is not sufficient to explain the variations of the mRNA ratio. The G antigen gene is located near a telomere in the macronucleus. We show that the distance between the 156G gene and the telomere is different in homozygotes and heterozygotes. It also varies among heterozygotes and is correlated with the mRNA ratio. Thus, we have identified two different parameters, both linked to the genome rearrangements occurring during macronuclear differentiation, that correlate with the relative expression of the two alleles. Two hypotheses concerning the influence of the telomere position on the expression of the gene are discussed.


Subject(s)
Antigens, Protozoan/analysis , Antigens, Surface/analysis , Gene Rearrangement/genetics , Paramecium/chemistry , RNA, Messenger/analysis , Alleles , Animals , Antigens, Protozoan/genetics , Antigens, Surface/genetics , Base Sequence , Cell Line , Cell Nucleus/chemistry , DNA, Protozoan/chemistry , Gene Expression/physiology , Molecular Sequence Data , Paramecium/genetics , Phenotype , Restriction Mapping
10.
Eur J Radiol ; 1(3): 245-9, 1981 Aug.
Article in English | MEDLINE | ID: mdl-7341263

ABSTRACT

Traumatic lesions involving the parenchyma of liver and spleen give heterogeneous echo patterns on sonograms. Associated haematomas appear as sonolucent or sonotransparent areas. Subcapsular haematomas appear as peripheral sonolucent or sonotransparent areas. High resolution sectorial real-time ultrasound demonstrates such abnormalities. When examining for splenic or hepatic lesions, associated lesions such as renal contusion, juxta-renal or retroperitoneal haematoma and haemoperitoneum are sought. Haemoperitoneum may be shown in Morrison's pouch, in the vicinity of the spleen (moon-crescent sign) and also in the sac of Douglas. None of the abnormalities is entirely specific for trauma. However, the sensitivity of ultrasound in the evaluation of trauma is sufficient to render other diagnostic procedures such as C.T. and angiography only rarely necessary.


Subject(s)
Liver/injuries , Spleen/injuries , Ultrasonography , Wounds, Nonpenetrating/diagnosis , Humans
11.
J Radiol ; 61(4): 251-6, 1980 Apr.
Article in French | MEDLINE | ID: mdl-7392002

ABSTRACT

Morrison's pouch, and, accessorily, the spleno-peritoneal recess, constitute specific indicators of the presence of intraperitoneal fluid. Intraperitoneal fluid gives rise to sonolucent atraip between the reflectivity of mean intensity of the liver and spleen, and the intense reflectivity of the perirenal fat. That image, which the authors term the "moon crescent sign", is displayed even when the fluid volume is as small as 30 to 40 ml. It is encountered in presence of ascites, but also in presence of fluid of inflammatory origin, of fluid due to pancreatic autolysis, or of blood. Hence the display of a moon crescent sign is of particular interest in the radiologic evaluation of an acute abdomen.


Subject(s)
Abdomen, Acute/diagnosis , Ascitic Fluid , Ultrasonography , Ascites/diagnosis , Ascites/etiology , Diagnosis, Differential , Humans
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