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Biomedical subjects

T Casini

Publications and source records attributed to T Casini.

At least 19 recordsLinked to original sources

A function of p21 during promyelocytic leukemia cell differentiation independent of CDK inhibition and cell cycle arrest.

Retinoic Acid (RA) treatment induces disease remission of Acute Promyelocytic Leukemias (APL) by triggering differentiation of neoplastic cells. Differentiation is mediated by the APL-specific transforming protein PML/RAR alpha and involves its activity as ligand-dependent enhancer factor on RA-target genes. We report here the identification of p21 as a transcriptional target of PML/RAR alpha during RA-induced differentiation of APL cells. We found that RA-treated APL cells undergo two rounds of cell division before entering post mitotic G1, that progression through the G1-S is indispensable for differentiation and coincides with the duration of commitment. RA-treatment induced two peaks of p21 synthesis: early (from the 2nd to the 6th hour), dependent on PML/RAR alpha expression and associated with G1-S transition and high CDK activity; late (from 3rd to the 4th day), independent from PML/RAR alpha and associated with G1 block and low CDK activity. Increased p21 in PML/RAR alpha cells during G1-S had no effect on the cell cycle while an antisense p21 prevented RA-induced differentiation without altering G1-S transition and the late G1 block. These results demonstrate that p21 is an effector of the activity of PML/RAR alpha on differentiation and suggest that p21 exerts a function in G1-S connected to differentiation-commitment and uncoupled from cell cycle and CDK inhibition.

CDC2-CDC28 Kinases↗

Bicistronic retroviral vector reveals capacity of v-erbA to induce erythroleukemia and to co-operate with v-myb.

Previous studies have shown that v-erbA and v-myb can induce the proliferation of avian erythroid cells in culture. To study the combined effects of v-erbA and v-myb, the two oncogenes were engineered into a retrovirus bicistronic vector with an internal ribosomal entry site (IRES) or into a vector with a splice acceptor (SPL). This allowed coexpression of the two proteins and a comparison with the same vector containing either v-erbA or v-myb only. Both the erbA IRES and the erbA/myb IRES virus constructs transformed erythroid cells after infection of bone marrow or blastoderm cultures. The erbA/myb IRES virus exhibited a 5-10-fold higher transformed colony forming efficiency than the erbA IRES virus in the blastoderm assay. Surprisingly, when injected into chicken embryos in the presence of helper virus, both viruses induced an erythroleukemia in about half of the animals. In contrast, no leukemia was observed with a myb IRES virus, with spliced vectors containing v-erbA alone or v-erbA in combination with v-myb, nor with erbA IRES and erbA/myb IRES viruses produced in the absence of helper virus. The average latency of leukemia induction was shorter for the erbA/myb IRES virus (3.5 weeks) than for the erbA IRES virus (5 weeks). Nevertheless, for both viruses the leukemic blasts retained full factor dependence for growth. These results show that v-erbA is capable of inducing an erythroleukemia when expressed by a high titer bicistronic retrovirus under conditions of virus spreading and that its in vitro and in vivo transforming potential can be enhanced by v-myb.

Animals↗

Characterization of a new monoclonal antibody (PG-M3) directed against the aminoterminal portion of the PML gene product: immunocytochemical evidence for high expression of PML proteins on activated macrophages, endothelial cells, and epithelia.

PG-M3 is a new monoclonal antibody (MoAb) specifically directed against a peptide sequence located in the aminoterminal region of the human PML protein. PML gene fuses with the retinoic acid receptor alpha (RAR alpha) gene during the t(15; 17) chromosomal translocation of acute promyelocytic leukemia (APL). The epitope recognized by PG-M3 is species-specific and fixative-resistant and is shared by most PML isoforms and PML/RAR alpha fusion proteins. PML is consistently located within the nucleus, although a minority of cells (about 20%), both in vitro and in vivo, show positivity for PML also in the cytoplasm. The nuclear staining pattern of PG-M3 varies from speckled (cells other than APL) to micropunctate (APL cells). Although two physiologically expressed PML isoforms are detectable by immunocytochemistry only or predominantly in the cytoplasm of transfected cells, the cytoplasmic localization of PML is a property also shared by the PML isoforms that predominantly localize to the nuclei. Immunohistologic analysis of normal human tissues with the PG-M3 MoAb showed variable PML expression, with the highest levels of the protein in postmitotic, differentiated cell types, such as endothelial cells, epithelia, and tissue macrophages, especially activated ones. In keeping with this in vivo finding, PML appears strongly upregulated in the U937 promonocyte cell line after exposure to agents that induce monocyte/macrophage activation (interferon gamma) or maturation (vitamin D3 and transforming growth factor beta 1).

3T3 Cells↗

Myb and NF-M: combinatorial activators of myeloid genes in heterologous cell types.

The c-Myb transcription factor regulates the differentiation of immature erythroid, lymphoid, and myeloid cells, although only the latter cells become transformed by the v-myb oncogene. These are also the only cells that express the Myb-regulated gene mim-1, suggesting that Myb requires tissue-specific, cooperating factors to activate such genes. Here, we investigated the tissue-specific regulation of the mim-1 promoter and found that it not only contains binding sites for Myb but also for NF-M, a myeloid-specific transcription factor that probably corresponds to mammalian C/EBP beta. Both types of binding sites were found to be required for full activity of the promoter. Remarkably, ectopic coexpression of Myb and NF-M proteins in erythroid cells or fibroblasts was sufficient to induce endogenous markers of myeloid differentiation, like the mim-1 and lysozyme genes. Our results indicate that c-Myb and NF-M proteins act as a bipartite, combinatorial signal that regulates the expression of myeloid-specific genes, even in heterologous cell types.

Acetyltransferases↗

Effect of ethanol chronic use on hepatotoxicity in rats exposed to tetrachloroethylene.

Tetrachloroethylene, an industrial halogenated solvent, shows several toxic effects. Also at hepatic level this substance can induce a damage but this effect is present only after high exposure, but such high levels have not been found in work environments. Using Wistar rats, we wanted to check whether the chronic administration of ethyl alcohol can modify the action of tetrachloroethylene. Tetrachloroethylene was administered by aerosol and alcohol at the concentration of 15% in drinking water. We observed an increase in plasma triglycerides, and evident histological alteration as a result of steatosis, in rats drinking alcohol as compared to a control group; the administration of tetrachloroethylene to rat drinkers of alcohol did not cause an increase in plasma triglycerides and steatosis as compared to rat drinkers of alcohol, but on the contrary we observed a decrease in alcohol-induced liver damage.

Animals↗

[Middle lobe syndrome in children. Critical review].

The clinical, radiological and anatomo-evolutive pictures of this syndrome are typical. It is suggested that cases are more frequent than is generally thought and that their recognition is delayed on account of the considerable time that often elapses before repeated infection of the respiratory system, particularly the middle lobe, results in the onset of the syndrome.

Adolescent↗

[Leukorrhea in adolescents: an underestimated problem].

It is by now clear that pediatrician's interest about adolescent's matters is very much increasing. The Authors take into consideration vulvovaginitis, a particular matter which is very frequent during this period of life and describe its most important clinical aspects.

Adolescent↗

[Recurrent cystitis in children: do predisposing factors exist for its onset?].

It is known that a great number of subjects, mainly little girls, frequently go to pediatric's observation for recurrent episodes of pollakiuria, dysuria or burning miction. They often complain enuresis, sometimes tenesmus so intense that they arrive at the incontinence (urge incontinence). Many of these cases, quickly defined as cystitis, really revealed that they weren't. Repetitively negative bacteriologic examinations allow us to classify them as "sham syndromes", as Stephens called them. According to what we said above, we wondered whether any recurrent cystitis are not favoured by missed observation of definite rules.

Anti-Bacterial Agents↗

[Animal bites in children].

Our experiences at the "Centro di Profilassi Antirabbica" of the "Dipartimento di Pediatria" suggest to us some thoughts: though the seriousness of the lesions is important also for the patient's aestethics, mostly for girls, the physician must always take into consideration the infectious consequences of the bite itself. Among these bacterial infections mostly frequent enough are those overlapping the deepest wounds as the bites of cates are. Therefore adequate early preventive attendances (within the 24 hours) are necessary. The importance of prevention against rabies, luckily very rare in our country, but to be always afraid of and to be always taken into consideration because of its emotional impact, is to be highlighted.

Age Factors↗

[Adolescent sexual behavior and sexually transmitted diseases (STD). A preliminary study].

Great changes have occurred in the adolescent behaviour in the last twenty years; this has caused a great increase in the number of the transmitted by sexual intercourse diseases. These, along with the adolescent habits changing, have so widely spread among young people, that one third of the recorded case are actually referred to this group of age. So, a matter of great social interest, which would require a common effort by the adolescents' families, the teachers and by the adolescents themselves, to be faced in the most proper way, has arisen. But the greatest commitment is asked for to the specialized in infectious diseases pediatricians, who are called to state the best strategy to efficaciously fight adolescents' STD. Pediatricians' specific competence and experience can build up the major security to face the prevention and diagnostic matters and their therapy as well.

Adolescent↗

[Hematuria due to an unusual cause in an adolescent].

The authors describe a case of haematuria due to the von Willebrand disease. The purpose of this article is to stimulate the performing of coagulation tests in patients with a pre-renal haematuria.

Adolescent↗

[Evaluation of pediatric patients hospitalized for acute diarrhea from 1990 to 1996].

Infectious diarrhea is a common disorder in children in Italy, which may lead to hospitalization especially during infancy. In order to obtain data about epidemiology and clinic pictures of acute diarrhea, the carts of 1295 paediatric outpatients, hospitalized for this pathology in the time between 1990-1996 at the Children's Hospital "Meyer" of Florence, were analyzed. An offending organism could be isolate in 43.3% of patients; Rotaviruses are the leading cause of diarrhea, followed by salmonella spp. Furthermore the role of Campylobacter as common bacterial pathogen worldwide has been clarified.

Acute Disease↗

[Emergency laboratory in the pediatric module].

The emergency in the laboratory is a serious problem. The Authors, starting from management evaluations, try to analyse the problems related to the urgent examinations in the Laboratory of a Pediatric Hospital. They propose executive ways for the best working of the same laboratory.

Age Factors↗