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Type 1 neurofibromatosis (NF1) gene encodes for a member of the GTPase activating protein family and is considered to be a tumor suppressor gene. Its very high rate of de novo mutation in humans led us to study a specific feature of this gene: the presence of numerous NF1-related sequences. According to our results, the human genome contains at least 11 NF1-related sequences, nine of which are scattered near centromeric sequences of seven different chromosomes. These NF1-related sequences, whose extent is quite varied according to loci, are unprocessed copies of the NF1 gene, and bear numerous mutations. A phylogenetic analysis of the six largest sequences indicates that they are all derived from a common ancestor, which would have appeared 22-33 million years ago, and was subsequently duplicated several times during hominoid evolution. The most recent duplication and interchromosomal transposition occurred in the last million years suggesting that the process could still be ongoing. Intriguing similarities between the evolution of alpha- satellite DNA and NF1-related sequences suggest the involvement of a common genetic mechanism for the generation and pericentric spreading of these NF1 partial copies.   相似文献   
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Dlx4 is a member of a family of homeobox genes with homology to Drosophila distal‐less (dll) gene. We show that Dlx4 expression pattern partially overlaps with its cis‐linked gene Dlx3 during mouse development as well as in neonatal and adult skin. In mice, Dlx4 is expressed in the branchial arches, embryonic limbs, digits, nose, hair follicle and in the basal and suprabasal layers of mouse interfollicular epidermis. We show that inactivation of Dlx4 in mice did not result in any overtly gross pathology. Skin development, homeostasis and response to TPA treatment were similar in mice with loss of Dlx4 compared to wild‐type counterparts.  相似文献   
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Objectives

From manic-depressive psychosis to bipolar spectrum, today's psychiatry allows us to observe a widening of bipolar criteria. This article aims at studying this evolution, its consequences with a critical look and the psychopathology of mood changes and morbid euphoria.

Methods

All of our considerations refer to current data on bipolar disorders (review with Medline and Science Direct) compared with studies from classical psychiatrists (Kraepelin, Ey) and various authors inspired by psychoanalysis (Freud, Racamier) and phenomenology (Binswanger, Tellenbach, Tatossian).

Results

Many contemporary authors encourage clinicians to detect bipolar disorders from symptoms, early signs and attenuated or atypical expressions. The concept of a widened spectrum is supposed to be closer to clinical reality and it would be an opportunity to diagnose this disease and its deleterious consequences better and thus to set up an appropriate therapy at an early stage. Other authors, on the other hand, deplore a dilution of bipolar disorders together with harmful diagnostic inflation around a concept that has become too heterogeneous to be effective, that subjugates or interferes with other pathologic entities in an excessive manner and abandoning a psychopathological approach. In this view, we shall analyze the nosographic shifts of bipolar disorders throughout the history of psychiatry, from manic-depressive psychosis to bipolar disorder and spectrum. We shall then scrutinize the autonomy and limitations related to bipolar disorders as opposed to normality, confusing clinical presentations and other major mental diseases: Psychosis, depression, pathological personality, anxiety, impulse-control, attention deficit-hyperactivity, addiction and psycho-organic disorders. This work shall first introduce a discussion on the concept of bipolar disorders for children, and then through the case of some historical figures. Then we will deal with the contemporary social factors that are currently furthering the extension of this diagnosis. Last, this article sheds a light on psychopathological specificities of mania – the cornerstone in bipolar disorders – mood changes and morbid euphoria.

Conclusion

We think that classic psychiatry, phenomenology and psychoanalysis would act as a guiding light through this debate and could help the clinician in this daily practice. Mood variations require a careful clinical observation and a rigorous set of interpretation, before being specified too excessively or hastily as a symptom of a real bipolarity.  相似文献   
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Postmenopausal osteoporotic (PMOP) women treated with ibandronate had higher bone mineral density, lower bone turnover, and decreased incidence of new vertebral fractures. The aim of this study was to investigate the effect of daily or intermittent oral ibandronate on the degree of mineralization (DMB) of bone and microhardness (Hv) at the bone tissue and bone structural unit (BSU) levels. A total of 110 iliac biopsies were taken from patients treated for 22 or 34 months with an oral placebo (n = 36), 2.5 mg daily oral ibandronate (n = 40), or 20 mg intermittent oral ibandronate (n = 34). These regimens provide annual cumulative exposures (ACEs) that are about half of the therapeutic doses currently licensed for PMOP women. DMB and Hv were measured at the global level (i.e., cortical or cancellous) and the focal level (i.e., BSU). At the global level, DMB and its distribution were not significantly different from placebo after 22 and 34 months of treatment. Hv was significantly higher in the cortical, cancellous, and total bone after 22 and 34 months of ibandronate versus placebo for both regimens. At the focal level, DMB and Hv, measured simultaneously in 3,760 BSUs, were significantly and positively correlated in all groups (r = 0.59–0.65, p < 0.0001). However, analysis of covariance highlighted the differences in the y intercepts of the linear regressions of the placebo- and ibandronate-treated groups. We infer that a low ACE of oral ibandronate altered the bone micromechanical properties irrespective of changes in secondary mineralization.  相似文献   
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