Lentiviral PU.1 overexpression restores differentiation in myeloid leukemic blasts.

PU.1, a transcription factor of the ETS family, plays a pivotal role in normal hematopoiesis, and particularly in myeloid differentiation. Altered PU.1 function is possibly implicated in leukemogenesis, as PU.1 gene mutations were identified in some patients with acute myeloid leukemia (AML) and as several oncogenic products (AML1-ETO, promyelocytic leukemia-retinoic acid receptor alpha, FMS-like receptor tyrosine kinase 3 internal tandem duplication) are associated with PU.1 downregulation. To demonstrate directly a role of PU.1 in the blocked differentiation of leukemic blasts, we transduced cells from myeloid cell lines and primary blasts from AML patients with a lentivector encoding PU.1. In NB4 cells we obtained increases in PU.1 mRNA and protein, comparable to increases obtained with all-trans retinoic acid-stimulation. Transduced cells showed increased myelomonocytic surface antigen expression, decreased proliferation rates and increased apoptosis. Similar results were obtained in primary AML blasts from 12 patients. These phenotypic changes are characteristic of restored blast differentiation. PU.1 should therefore constitute an interesting target for therapeutic intervention in AML.

How to assess hemodynamic status in very preterm newborns in the first week of life?

BACKGROUND: Assessing hemodynamic status in preterm newborns is an essential task, as many studies have shown increased morbidity when hemodynamic parameters are abnormal. Although oscillometric monitoring of arterial blood pressure (BP) is widely used due to its simplicity and lack of side effects, these values are not always correlated with microcirculation and oxygen delivery. OBJECTIVES: This review focuses on different tools for the assessment of hemodynamic status in preterm newborns. These include the measurement of clinical (BP, capillary refill time and urinary output (UO)) or biological parameters (lactate analysis), functional echocardiography, and near-infrared spectroscopy (NIRS). We describe the concepts and techniques involved in these tools in detail, and examine the interest and limitations of each type of assessment. CONCLUSIONS: This review highlights the complementarities between the different parameters used to assess hemodynamic status in preterm newborns during the first week of life. The analysis of arterial BP measured by oscillometric monitoring must take into account other clinical data, in particular capillary refill time and UO, and biological data such as lactate levels. Echocardiography improves noninvasive hemodynamic management in newborns but requires specific training. In contrast, NIRS may be useful in monitoring the clinical course of infants at risk of, or presenting with, hypotension. It holds the potential for early and noninvasive identification of silent hypoperfusion in critically ill preterm infants. However, more data are needed to confirm the usefulness of this promising tool in significantly changing the outcome of these infants.

Influence of organized media on the absorption and fluorescence spectra of Auramine-O dye.

The spectral characteristics of the aqueous solutions of Auramine O dye in the presence of organized media have been examined. The absorbance and fluorescence of the dye are significantly enhanced in cyclodextrins and surfactants. The dye forms a predominant 1:1 complex with beta-CD, whereas a 1:2 complex is formed with alpha-CD. The dissociation constants of the complexes have been determined by use of a non-linear regression method. Premicellar solutions of the sodium dodecyl sulphate exert maximum influence on the fluorescence and absorbance spectra of the dye. The microviscosity in cyclodextrins and micelles of SDS and Brij-78 have been estimated from fluorescence measurements.

[Contribution of liver biopsy and serology of hepatitis C virus to the diagnosis of a moderate and prolonged elevation of aminotransferases]. / Apports de la biopsie hépatique et de la sérologie du virus de l'hépatite C au diagnostic d'une augmentation modérée et prolongée des aminotransférases.

The aim of this study was to evaluate the diagnostic usefulness of percutaneous liver biopsy and screening for hepatitis C virus antibodies with 1st and 2nd generation ELISA in asymptomatic blood donors with persistent (> 1 year) and moderate elevation (> 1.5 times the upper limit of normal) of serum alanine aminotransferase. The diagnosis was established from clinical, biological and ultrasound data before biopsies were obtained, then compared to the histological diagnosis. Thirty one of 56 blood donors who satisfied the preceding criteria accepted liver biopsy and were subsequently included in the study. An accurate diagnosis was proposed before biopsy in 20 cases. This was in agreement with the histological results in 19 cases but in 2 of these, unexpected lobular hepatitis was associated with the expected steatosis. Positive hepatitis C virus tests corresponded to chronic hepatitis in all cases (n = 5). No accurate diagnosis could be proposed in the 11 remaining cases owing to the lack of evidence of any etiology (n = 4) or because several potential etiologies were possible for the same subject (n = 7). Histological diagnoses were: isolated steatosis (n = 12), steatosis associated with lobular hepatitis (n = 7) or with chronic persistent hepatitis (n = 1), chronic active (n = 2) or chronic persistent hepatitis (n = 3), alcoholic hepatitis (n = 2), hemochromatosis (n = 1), and normal liver (n = 3). Liver biopsy is essential to the accurate etiological diagnosis of persistent and moderate elevation of aminotransferases despite hepatitis virus C tests which are associated with the correct diagnosis of chronic hepatitis in 16% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Neonatal seizures management]. / Prise en charge des crises du nouveau-né

For several decades, experimental studies have sought to explain the biological causes of newborn seizures and to assess the anatomical and functional consequences. Laboratory studies have shown that prolonged or repeated seizures disturb central nervous system development and may predispose to later epilepsy or cognitive deficits. Although these findings have not been clinically demonstrated in humans, several observations suggest that neonatal seizures have a deleterious effect on the immature brain and generate long-term sequelae. No therapeutic trial, however, has directly demonstrated the benefits of treatment, underlining the need for controlled studies that integrate the advances in electroencephalographic monitoring and pharmacology of anticonvulsant drugs.

Regulation of alternative splicing by PTB and associated factors.

PTB (polypyrimidine tract-binding protein) is a repressive regulator of alternative splicing. We have investigated the role of PTB in three model alternative splicing systems. In the alpha-actinin gene, PTB represses the SM (smooth muscle) exon by binding to key sites in the polypyrimidine tract. Repressive binding to these sites is assisted by co-operative binding to additional downstream sites. SM exon splicing can be activated by CELF proteins, which also bind co-operatively to interspersed sites and displace PTB from the pyrimidine tract. Exon 11 of PTB pre-mRNA is repressed by PTB in an autoregulatory feedback loop. Exon 11-skipped RNA gets degraded through nonsense-mediated decay. Less than 1% of steady-state PTB mRNA is represented by this isoform, but inhibition of nonsense-mediated decay by RNA interference against Upf1 shows that at least 20% of PTB RNA is consumed by this pathway. This represents a widespread but under-appreciated role of alternative splicing in the quantitative regulation of gene expression, an important addition to its role as a generator of protein isoform diversity. Repression of alpha-tropomyosin exon 3 is an exceptional example of PTB regulation, because repression only occurs at high levels in SM cells, despite the fact that PTB is widely expressed. In this case, a PTB-interacting cofactor, raver1, appears to play an important role. By the use of 'tethering' assays, we have identified discrete domains within both PTB and raver1 that mediate their repressive activities on this splicing event.

[HBs antigen in the blood donors of Calvados. Epidemiologic study and surveillance of the patients]. / L'antigène HBs chez les donneurs de sang du Calvados. Etude épidémiologique et surveillance des patients.

175 Chronic HBs Ag carriers have been discovered in the blood donors of the Calvados blood transfusion center from 1971 to 1979. 72 of them (41%) gave their consent for a clinical and biological study at the end of 1979, after receiving a convocation letter. This work had two aims: - to study the epidemiological factors in this population. - to evaluate the clinical and biological consequences of persistent antigenemia. 1. Epidemiological Study. Most results agree with the literature (higher prevalence in male, age, stay in endemic countries) but some results disagree for several reasons: our donors are all volunteers, HBs Ag prevalence is low in our region, most of the patients are caucasian and with life conditions and habits which may explain some particularities in contagion. Furthermore, the relative number of blood donors found every year as chronic HBs Ag carriers, does not increase in our country. 2. The Clinical and Biological follow-up of 62 HBs Ag carriers (alcoholics excluded) was carried out for 4,3 years on average. No patients developed clinical and biological features of chronic liver disease. After a mean term follow-up, we conclude that the asymptomatic HBs Ag carriers state seems not to be of bad prognostic. Since long term complications cannot be excluded, the follow-up of these patients must be maintained.

[Differed autotransfusion in orthognathic surgery. Impact on the economics of blood products. Our experience of 40 cases]. / L'autotransfusion différée en chirurgie orthognatique. Incidences sur l'économie de produits sanguins. Notre expérience de 40 cas.

Delayed autotransfusion has been recommended for orthognathic surgery. The authors review and discuss the advantages of this technique. Emphasis is placed on the preventive aspect as it relates to transfusion-associated viral contamination, as well as on the positive implications on health expenditures in the long run. This technique requires excellent intercollaboration on the part of the blood transfusion centers and should definitely be recommended in certain cases of planned surgery. Furthermore, combined with hemodilution methods, it constitutes a very effective means of struggle against edema.