The use of neutral and non-neutral SSRs to analyse the genetic structure of a Tunisian collection of Medicago truncatula lines and to reveal associations with eco-environmental variables.

In this study, we investigated the genetic diversity of a collection of 136 Medicago truncatula lines from 10 Tunisian natural populations collected in well-defined locations and in various ecological conditions of soil, salinity and water availability. The genetic diversity was evaluated using a set of 18 microsatellites (SSRs), representing the 8 chromosomes of M. truncatula. A neutrality test showed that 7 SSRs were non-neutral with evidence of balancing selection. The 11 neutral SSRs revealed a geographical pooling with the Tunisian Dorsale axis restricting migration of alleles. The 7 non-neutral alleles demonstrate a correlation with rainfall, altitude and salinity environmental variables suggesting that these SSRs are linked to genes involved in water use efficiency, resistance to salinity or adaptation to altitude, and that there is local adaptation of M. truncatula to these variables. This demonstrates that the choice of so-called neutral markers should be carefully evaluated in population genetic studies. This study illustrates the genetic diversity occurring in natural Tunisian populations of M. truncatula and describes the first collection of this species dedicated to natural variation involved in adaptation to the environment.

Properties of the six isoforms of p63: p53-like regulation in response to genotoxic stress and cross talk with DeltaNp73.

TP63, a member of the TP53 gene family, encodes two groups of three isoforms (alpha, beta and gamma). The TAp63 isoforms act as transcription factors. The DeltaNp63 isoforms lack the main transcription activation domain and act as dominant-negative inhibitors of transactivation (TA) isoforms. To clarify the role of these isoforms and to better understand their functional overlap with p53, we ectopically expressed each p63 isoform in the p53-null hepatocellular carcinoma cell line Hep3B. All TA isoforms, as well as DeltaNp63alpha, had a half-life of <1 h when transiently expressed and were degraded by the proteasome pathway. The most stable form was DeltaNp63gamma, with a half-life of >8 h. As expected, TA isoforms differed in their transcriptional activities toward genes regulated by p53, TAp63gamma being the most active form. In contrast, DeltaNp63 isoforms were transcriptionally inactive on genes studied and inhibited TA isoforms in a dose-dependent manner. When stably expressed in polyclonal cell populations, TAp63beta and gamma isoforms were undetectable. However, when treated with doxorubicin (DOX), p63 proteins rapidly accumulated in the cells. This stabilization was associated with an increase in phosphorylation. Strikingly, in DOX-treated polyclonal populations, increase in TAp63 levels was accompanied by overexpression of DeltaNp73. This observation suggests complex regulatory cross talks between the different isoforms of the p53 family. In conclusion, p63 exhibits several transcriptional and stress-response properties similar to those of p53, suggesting that p63 activities should be taken into consideration in approaches to improve cancer therapies based on genotoxic agents.

Neuroendocrine effects of a 20-mg citalopram infusion in healthy males. A placebo-controlled evaluation of citalopram as 5-HT function probe.

Pharmacokinetic measurements, neuroendocrine responses, and side effects profiles of intravenous infusions of 20 mg citalopram over 30 minutes during the early afternoon have been studied. Eight healthy male volunteers were enrolled in a placebo- (saline) controlled, single-blind, cross-over protocol. Plasma concentrations of the parent compound showed a double exponential decay. Demethyl and didemethyl metabolites were not detectable, but low concentrations of the propionic acid derivative of citalopram were found. Determination of the citalopram enantiomers yielded a balanced S(+)/R(-) ratio of 0.9 to 1.2. The endocrine response to the drug was characterized by significant increases in plasma prolactin and cortisol. Except for one subject, who developed pronounced side effects, human growth hormone showed a surge following saline that was inhibited following citalopram. Rectal temperature and heart rate were not affected and tolerability was favorable. Because of citalopram's extremely high selectivity for the presynaptic 5-hydroxytryptamine nerve terminals, the present data suggest that it might be a promising tool for the investigation of serotonergic function in the human brain in vivo.

Parallel nocturnal secretion of melatonin and testosterone in the plasma of normal men.

Differences and similarities in the temporal organization of hormone secretion in plasma reflect the activity of CNS pacemakers. One aspect of this activity, the temporal synchronization of the secretion of different hormones is still poorly understood. We report the analysis of melatonin and testosterone plasma concentrations during two nights in 6 normal healthy young men. Blood was collected every 20 min between 2040 and 0640. Plasma testosterone concentrations increased by 1.5- to 2-fold during the second part of the night, and melatonin by 2.5- to 4-fold. In each subject, the individual temporal pattern of melatonin was quite stable over the two nights of sampling, while testosterone profiles showed fluctuations. There was a high degree of parallelism in these two hormones nocturnal secretion. These results, together with previous studies, suggest that melatonin might entrain the nocturnal secretion of testosterone.

[Hypercarotenemia, amenorrhea and a vegetarian diet]. / Hypercarotinémie, aménorrhée et régime végétarien.

In order to analyse the role of hypercarotenemia in amenorrhoea, we have studied the ovarian function of 20 patients presenting with hypercarotenemia (serum carotene greater than 5 mumol/l). 12 of these were complaining of secondary amenorrhoea (group I), 7 with a normal weight (group I A) and 5 with a weight below 85% of ideal weight (group I B). Another group of 8 patients had normal menstrual cycles and a body weight within normal limits (group II). Group I presented an ovarian insufficiency of hypothalamic origin with an increase in the FSH/LH ratio. The patients in group I A although of normal weight differed from group II by a history of important weight variations, strenuous sports activity and an essentially vegetarian diet, the most likely reason for their hypercarotenemia. The high carotene levels however do not seem to be directly responsible for the amenorrhoea, in view of the normal menstrual cycles of the patients in group II. Hypercarotenemia can be considered as a biologic marker of weight loss with fat mobilisation and low T3 levels. It can also be due to a vegetarian diet. The latter may be an aetiological factor in anovulation by increasing faecal excretion of oestrogens and thus decreasing blood levels of oestradiol particularly when associated with other compounding factors such as excessive physical activity, loss of weight or affective problems.

[Undesirable psychiatric effects of drugs]. / Les effets indésirables psychiatriques des médicaments.

The aim of this review of the literature is to indicate several characteristics of undesirable drug-induced psychiatric side effects and give a non-exclusive list of the responsible agents. For more detailed information and to facilitate the identification of iatrogenic effects, the clinician can consult available manuals, computerized data banks or specialists from pharmacological control centers.

[Semiology of benign diseases of the breast in mammography (author's transl)]. / La sémiologie mammographique des mastopathies bénignes. Etude expérimentale et clinique. Critique conceptuelle.

Mammography is a basic examination which must never be dissociated from the clinical background. A statistical blind study of 330 cases shows that only well definite syndroms are reliable. The presence of absence of a single sign has no value. Difficulties arise in the diagnosis of suspect nodule in a dense dystrophic breast. Hydratation of the connecting tissue is a fundamental concept for analysis of mammographic pictures. The densities change according to hormonal influence, growth of dystrophy and specific signs of fibrillary or hyalin fibrosis. A histological study of serial cuts of the breast shows that the must reliable signs are found in the center of the nodule ande immediately around it. As in the histological study, serial cuts are indispensable in X-ray examination. Tomography improves the examination of dystrophies.

[Mammotomography, a new technic of breast examination]. / La mammotomographie, nouvelle méthode d'exploration mammaire

The authors present the first results of a new technique of breast examination: tomo-mammography. This new method allows a complete study of the whole gland without any compression and any modification of histological and anatomical structures, and an analysis of the center of breast lesions in which are rassembled the most reliable radiological signs. These first results enable to hope a large increase of possibilities of diagnosis of breast lesions in the most difficult anatomical and clinical cases.

[Anatomical and histological approach to the radioraphic appearance of the breast (author's transl)]. / Approche anatomo-histologique de la radio-anatomie mammaire

The authors present first correlations between histology, anatomy and serial radiography of the breast, in order to establish a new understanding of the mammographic picture, with respect to the tridimensional histological structures. Several essential points are considered: - Mammographic pictures only show fibrous, connecting and fatty tissues. The epithelium of the galactophores is not shown, because of its low radio-opacity. Mammographic densities are due above all to fibrous connecting tissue, which has a high percentage of water. Benign or malignant breast tumors present with a proliferation of epithelium and connecting tissue, but only connecting tissue, more or less hydrated is shown on the mammographic picture. Many mammographic patterns are related to various superimposed fibrous strands, appearing as pseudotumoral opacities. The benign or malignant tumoral opacities are hidden or modified by multiple superimposed adjacent structures. - The mammographic patterns is related to the degree of hydratation and components of the connecting tissue.