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.

[Adolescents and suicide. Some comments on the role of the pediatrician in researching the motivations for suicidal behaviors]. / Adolescenti e suicidio. Alcune considerazioni sul ruolo del pediatra nella ricerca delle motivazioni delle condotte suicidarie.

The modern pediatric is interested also in the adolescent. Sometimes disorders of the behaviour lived of a teenager in a family on risk can lead to attempts of suicide. The authors will analyze at the basis of their experience like pediatrics this problematic.

[The abuse of anabolic substances by an adolescent going in for sports]. / L'abuso di sostanze anabolizzanti nell'adolescente che fa sport.

The authors describe the case of an elder adolescent who showed an imposing symptomatology due to the abuse of anabolic drugs. They urge the pediatricians to warn their patients about the use of such drugs.

[The risk of infection after a tick bite in an endemic area. The experience of the use of an effective protocol on a cohort of Tuscan children]. / Rischio di infezione dopo puntura di zecca in una zona endemica. Esperienza sull'applicazione di un protocollo operativo su una coorte di bambini toscani.

The authors suggest an executive protocol for the infections due to the sting of a tick in a child. They report the experience they had observing 92 children in the period between spring and autumn in the year 1996.

[Adolescent emergencies: the need for active prevention to the spread of STDs (sexually transmitted diseases)]. / Emergenza adolescenti: la necessità di fare una prevenzione attiva alla diffusione delle M.S.T. (malattie sessualmente trasmesse).

The authors suggest a program of diffusion of posters which invite young adolescents to pay attention to the symptoms of the S.T.D. They suggest also to found a telephone line where the adolescent can call for any problem or question.

[Subdural effusion during bacterial meningitis]. / Versamento sottodurale in corso di meningite batterica.

Twelve children of age ranged from 4 to 34 months with Haemophilus influenzae type b meningitis treated at Meyer Hospital of Florence, were retrospectively reviewed. Eight patients had subdural effusion demonstrated with TC, RM and transfontanellar ultrasonography. All patients are cured without sequelae.

[Adolescents and the conflict between generations. The role of the pediatrician]. / Gli adolescenti e il conflitto generazionale. Il ruolo del Pediatra.

In the period of adolescence the problems due to diseases go down and those due to the personality of young boys and girls increase. While the former can be cured by drugs, the latter need much reflection and help from Pediatricians.

[Evaluation of pediatric patients hospitalized for acute diarrhea from 1990 to 1996]. / Valutazioni su pazienti pediatrici ricoverati per diarrea acuta dal 1990 al 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.

[Emergency laboratory in the pediatric module]. / Il Laboratorio di Urgenza nel modulo pediatrico.

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.

[Urine analysis in a pediatric laboratory using reagent strips read visually (visual dip sticks)]. / L'esame delle urine in un laboratorio pediatrico effettuato mediante strisce reattive ad osservazione diretta (dip sticks visual).

The Authors studied the possibility of using some dip sticks visual for urinalysis. One hundred of urine samples have been analyzed at the beginning with the instrumental laboratory analytical system and then with the dip sticks visual; the results put in evidence that there is a real discrepancy as far as glucose is concerned. Glucose is overestimated in dip sticks visual method. Bilirubin, blood and proteins are in a decreasing order the most different items. Concerning to pH the results have been comparable. Specific weight cannot be compared to the laboratory method, on the other hand it can be used for screening. On the whole the Authors are quite satisfied about dip sticks visual method; it can be used in order to accelerate diagnosis and avoid pre-analytical mistakes.

[Visceral leishmaniasis in children in the province of Florence]. / La leishmaniosi viscerale in età pediatrica in provincia di Firenze.

Three cases of visceral leishmaniasis are presented: two children who got the disease in Florence and the imported case of a girl coming from Albania with her disease in act. The diagnosis was made showing Leishmania in bone marrow specimen. Therapy with melglumine antimonate was effective and well borne, leading the three children to a complete healing. In the province of Florence visceral leishmaniasis is very rare, but such protozoa and the sand flies are present as shown by the high number of dog with leishmaniasis.

[Adolescent sexual behavior and sexually transmitted diseases (STD). A preliminary study]. / II comportamento sessuale dell'adolescente e le malattie sessualmente trasmesse (MST). Indagine preliminare.

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.

[Hematuria due to an unusual cause in an adolescent]. / Ematuria da causa insolita in un adolescente.

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.

[Animal bites in children]. / I morsi da animale nel bambino.

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.

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.

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).

[Middle lobe syndrome in children. Critical review]. / La sindrome del lobo medio nel bambino. Rivisitazione critica.

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.