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Kirill Petrov
Kirill Petrov

Hematología Clínica: una obra de referencia de Shirlyn B. McKenzie

This study is registered in (NCT04260861). Clinical trial registration number is registered. URL: Registration date: 03/20/2020, registration time: 02:35:37 EDT, status: Recruiting Participants

mckenzie hematologia clinica pdf 27

Any other: Clinical trial registration number is registered. URL:, Registration date: 03/20/2020, registration time: 02:35:37 EDT, status: Recruiting Participants

Other: Clinical trial registration number is registered. URL:, Registration date: 03/20/2020, registration time: 02:35:37 EDT, status: Recruiting Participants

A 2.2 kb BAC clone from human genomic library was used to screen a collection of mouse chromosomes by standard techniques. Southern blot analysis and genetic linkage mapping were used to identify the gene. Western blotting analysis of PML proteins indicated the presence of three protein isoforms. A cDNA encoding the longest of these isoforms was isolated by Northern analysis. A novel exon was identified that was not detected in the genomic sequence. The cDNA was used to isolate the human counterpart of the mouse gene from human genomic libraries. The translated amino acid sequence was identical to the mouse orthologue, except for the absence of the predicted internal Zn-binding domain. The mouse genomic sequence was found to contain exons and introns similar to the human sequence. The intron 1 and 2 of the mouse gene were known to be variable. The mouse genomic sequence containing the variable intron 1 was also cloned. Human-mouse homologues of two other genes closely related to PML, Mme, and profilin were also isolated. The mouse and human sequences showed a greater degree of similarity than any other sequence known to be orthologous. A comparison of the different PML isoforms revealed two alternatively spliced types, PML and D2, which differed only by a splice-acceptor site. In this study, a comparison of the related Mme and profilin homologues showed that both genes contained variable intron 2s. This domain seemed to have evolved more rapidly than the rest of the molecule. Together, our data showed that the mouse and human PML, Mme, and profilin genes, despite their distinct evolutionary fates, were all derived from a single ancestral gene. Various tissues of adult mice contained 50-100 molecules of the three proteins, but brain contained about 800 molecules of PML, a higher level than any other tissue. Southern and Northern blot analyses showed that, in contrast to the mouse, human PML contained a minor mRNA species, which corresponds to a different human cDNA and to the longest isoform of mouse PML. Nuclear bodies containing PML and Mme were identified in BHK-21 cells. They formed during interphase and were much less numerous during mitosis. The size and composition of the nuclear body containing Mme varied with the level of expression of the protein. The results suggest that human PML is not exclusively a component of the promyelocytic nuclear body but that it is also present in other nuclear structures. An unexpected feature was the presence of two proteins which are thought to be ubiquitinated. These ubiquitinated proteins might be involved in a rapid turnover of PML in the nucleus, in its cytoplasmic redistribution, or both. The three PML isoforms (with and without the internal Zn-binding domain), as well as the ubiquitinated proteins, had different cellular distributions. While the cytoplasmic distribution of the Zn-binding domain could be influenced by the strength of its interaction with Zn(II), the ubiquitinated proteins were present in the cytoplasm only and not in the nucleus of cells. In the nucleus, all of the three PML isoforms were present in subnuclear bodies. The Zn-binding domain was localized to these structures, whereas the ubiquitinated proteins were found mostly near the periphery of the subnuclear body. Finally, the differences in subcellular distribution of the three isoforms and the ubiquitinated proteins could explain the differences in the spectra of clinical diseases caused by mutations of the PML gene.


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