French Institute of Health and Medical Research

About: French Institute of Health and Medical Research is a government organization based out in Paris, France. It is known for research contribution in the topics: Population & Receptor. The organization has 109367 authors who have published 174236 publications receiving 8365503 citations.

Effects of poor and short sleep on glucose metabolism and obesity risk

Abstract: The importance of sleep to hormones and glucose metabolism was first documented more than four decades ago. Since then, sleep curtailment has become an endemic behavior in modern society. In addition, the prevalence of sleep disorders, particularly obstructive sleep apnea (OSA), has increased. OSA is very common in endocrine and metabolic disorders, but often remains undiagnosed. This Review summarizes the laboratory and epidemiologic evidence that suggests how sleep loss, either behavioral or disease-related, and poor quality of sleep might promote the development of obesity and diabetes mellitus, and exacerbate existing endocrine conditions. Treatment of sleep disorders has the potential to improve glucose metabolism and energy balance. Screening for habitual sleep patterns and OSA might be critically important for patients with endocrine and metabolic disorders.

Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion

Abstract: The gene for spinocerebellar ataxia 7 (SCA7) has been mapped to chromosome 3p12-13. By positional cloning, we have identified a new gene of unknown function containing a CAG repeat that is expanded in SCA7 patients. On mutated alleles, CAG repeat size is highly variable, ranging from 38 to 130 repeats, whereas on normal alleles it ranges from 7 to 17 repeats. Gonadal instability in SCA7 is greater than that observed in any of the seven known neuro-degenerative diseases caused by translated CAG repeat expansions, and is markedly associated with paternal transmissions. SCA7 is the first such disorder in which the degenerative process also affects the retina.

Mitochondrial defect in Huntington's disease caudate nucleus

Abstract: Although the Huntington's disease (HD) gene defect has been identified, the structure and function of the abnormal gene product and the pathogenetic mechanisms involved in producing death of selective neuronal populations are not understood. Indirect evidence from several sources indicates that a defect of energy metabolism and consequent excitotoxicity are involved in HD. Toxin models of HD may be induced by 3-nitropropionic acid or malonate, both inhibitors of succinate dehydrogenase, complex II of the mitochondrial respiratory chain. We analyzed mitochondrial respiratory chain function in the caudate nucleus (n = 10) and platelets (n = 11) from patients with HD. In the caudate nucleus, severe defects of complexes II and III (53-59%, p < 0.0005) and a 32-38% (p < 0.01) deficiency of complex IV activity were demonstrated. No deficiencies were found in platelet mitochondrial function. The mitochondrial defect identified in HD caudate parallels that induced by HD neurotoxin models and further supports the role of abnormal energy metabolism in HD. The relationship of the mitochondrial defect to the role of huntingtin is not known.

Diffuse noxious inhibitory controls (DNIC). II. Lack of effect on non-convergent neurones, supraspinal involvement and theoretical implications.

Abstract: (1) Diffuse noxious inhibitory controls (DNIC) were tested for their effect on noxious only, non-noxious and proprioceptive cells in the dorsal horn of the intact anaesthetized rat. Unlike convergent neurones, as described in the previous paper, there was no effect of DNIC on these neurones. It is concluded that convergent neurones are specifically inhibited by DNIC. (2) The effect of DNIC could not be demonstrated for convergent neurones in the spinal animal. Thus the neuronal substrate for DNIC must involve supraspinal structures. (3) Because of the level of firing in convergent neurones induced by hair and touch receptors, presumably constantly and randomly activated in the freely moving animal, a noxious message arriving at higher centres may be partly masked by this background noise. On the basis of the known role of convergent neurones in nociception, we propose the following mechanism which may interpret this paradoxical convergence: two pools of convergent neurones are influenced by a painful peripheral stimulation, one segmental pool being activated whilst the remaining population of cells is inhibited; the "contrast" between the messages from these two pools may well produce a significant pain signalling output from the convergent dorsal horn cells. (4) These results and their theoretical implications are discussed with regard to the concept of the "analgesic system", certain clinical observations and the paradoxical pain relieving effects of counterirritation and some forms of acupuncture.

Cell death modalities: classification and pathophysiological implications

Abstract: Cell death can be classified according to the morphological appearance of the lethal process (that may be apoptotic, necrotic, autophagic or associated with mitosis), enzymological criteria (with and without the involvement of nucleases or distinct classes of proteases, like caspases or cathepsins), functional aspects (programmed or accidental, physiological or pathological) or immunological characteristics (immunogenic or non-immunogenic). Thanks to the advancing comprehension of cellular demise, it has become clear that the textbook equation ‘programmed cell death1⁄4 apoptosis1⁄4 caspase activation1⁄4 non-immunogenic cell death’, although applicable to some instances of cell death, constitutes an incorrect generalization, at several levels. Thus, necrosis can be programmed both in its course and its occurrence. Apoptosis can be lethal without caspase activation, and caspase activation does not necessarily cause cell death. Finally, cell death with an apoptotic appearance can be immunogenic, in which case the immunogenicity is caspasedependent. These examples illustrate the urgent need to strive towards a more detailed comprehension of cell death subroutines, with far-reaching implications for the pharmacological management of pathological cell loss and growth. In conditions of homeostasis, in the adult organism, each event of cell duplication must be compensated by the elimination of another cell. Although in the human body cell deaths occur at the dazzling frequency of several millions per second, the subtle regulation of cell death – coupled to a perfect waste management – allows us to enjoy a peaceful existence for several years, until we are affected by disease. Pathological conditions are often, if not always, tied to deregulated (excessive or deficient) cell death (Figure 1). The loss of post-mitotic cells such as neurons and cardiomyocytes occurs acutely in stroke and infarction or progressively in degenerative diseases. Moreover, AIDS is caused by the loss of proliferating immune cells at a pace that cannot be compensated for by proliferation. Conversely, oncogenesis is characterized by the (at least) partial suppression of cell death programs, which in turn causes chemoand radio-therapy resistance, thus ultimately sealing the patient’s fate. The physiological importance and pathological impact of cell death has spurred great interest, leading to the accumulation of more than 150 000 research papers over the last 20 years. Nonetheless, apparently simple questions on the very definition of cell death (Table 1) and on the classification of cell death modalities in stereotyped patterns have not yet been solved. In this review, we will synthetically and critically enumerate the current classifications of cell death, laying special emphasis on the link between the morphological, biochemical and pathophysiological characteristics of different cell death modalities.