Introduction of a cis-acting mutation in the capsid-coding gene of moloney murine leukemia virus extends its leukemogenic properties.

Inoculation of newborn mice with the retrovirus Moloney murine leukemia virus (MuLV) results in the exclusive development of T lymphomas with gross thymic enlargement. The T-cell leukemogenic property of Moloney MuLV has been mapped to the U3 enhancer region of the viral promoter. However, we now describe a mutant Moloney MuLV which can induce the rapid development of a uniquely broad panel of leukemic cell types. This mutant Moloney MuLV with synonymous differences (MSD1) was obtained by introduction of nucleotide substitutions at positions 1598, 1599, and 1601 in the capsid gene which maintained the wild-type (WT) coding potential. Leukemias were observed in all MSD1-inoculated animals after a latency period that was shorter than or similar to that of WT Moloney MuLV. Importantly, though, only 56% of MSD1-induced leukemias demonstrated the characteristic thymoma phenotype observed in all WT Moloney MuLV leukemias. The remainder of MSD1-inoculated animals presented either with bona fide clonal erythroid or myelomonocytic leukemias or, alternatively, with other severe erythroid and unidentified disorders. Amplification and sequencing of U3 and capsid-coding regions showed that the inoculated parental MSD1 sequences were conserved in the leukemic spleens. This is the first report of a replication-competent MuLV lacking oncogenes which can rapidly lead to the development of such a broad range of leukemic cell types. Moreover, the ability of MSD1 to transform erythroid and myelomonocytic lineages is not due to changes in the U3 viral enhancer region but rather is the result of a cis-acting effect of the capsid-coding gag sequence.

Stimulated thyrotropin and prolactin secretion in lactating and non-lactating women.

During the postpartum period, lactation is initiated by a massive release of prolactin which, in turn, reflects reduced dopaminergic inhibition of the pituitary lactotrophs. This postpartum prolactin rise can be prevented by administration of dopamine agonists. The release of thyrotropin (TSH) is also controlled by dopaminergic inputs and, therefore, TSH secretion may also be affected by postpartum alterations in dopaminergic activity. To gain further insight into the regulation of TSH and prolactin secretion during the postpartum period, we compared the basal and stimulated TSH and prolactin levels of postpartum lactating (n = 10) and non-lactating women (treated with 5 mg bromocriptine daily, n = 9) with those of normal cycling women (n = 9). Frequent blood samples were obtained on postpartum day 5 or in the early follicular phase before and after administration of thyrotropin-releasing hormone (TRH) for serial determination of TSH and prolactin by immunoradiometric assay (IRMA). Based serum prolactin levels were high (p < 0.001) in lactating women and low in both non-lactating and normal cycling women. When these differences in the basal prolactin concentrations were taken into account, the stimulated prolactin release (relative prolactin increase and area under the prolactin curve) was found to be highest (p < 0.05) in non-lactating women and lowest in lactating women. Basal TSH secretion was not significantly different between the groups of women (p > 0.2). Yet, both the relative TSH increases and the response curves following TRH stimulations were high (p < 0.05) in normal cycling women and low in both lactating and non-lactating postpartum women. These observations confirm a difference in the basal and stimulated prolactin release between lactating and non-lactating women. They also indicate that the TRH-stimulated TSH release is greatly affected by the postpartum state, irrespective of lactation or therapeutic weaning. The observation of a decreased sensitivity of pituitary thyrotrophs in concert with unchanged basal TSH secretion is suggestive of changes in hypothalamic TRH secretion and/or in the TSH metabolic half-life during the postpartum period.

[Laryngeal masks in emergency medicine]. / Le masque laryngé en médecine d'urgence.

Airway control and maintenance of effective assisted ventilation are an absolute priority in emergency medicine. Developed by Brain in 1988, the laryngeal mask offers a new means of ventilation management and is a reliable compromise between the face mask and endotracheal tubing. The laryngeal mask ensures no protection against gastric contents inhalation and its use is limited in patients with decreased thoracopulmonary compliance. However, compared to the face mask, the laryngeal mask offers several benefits in the management of cardiorespiratory arrests by paramedical staff and rescue teams: the procedure is easy to learn, the device improves airway patency, leaves the operator's hands free, allows endotracheal aspiration to be performed and reduces the risk of hyperinsufflation. These advantages make the use of the laryngeal mask a technique which should be taught to any staff liable to face and manage cases of cardiorespiratory arrest. The laryngeal mask cannot and does not replace endotracheal tubing which remains the only technique that guarantees upper airway patency and protection as well as efficient ventilation control. However, in some situations tubing may prove difficult and even, at times, impossible to perform. This is when the laryngeal mask will come in handy, either as a temporary solution or as an alternative to difficult or impossible tubing techniques.