Quantitative RT-PCR reveals a ubiquitous but preferentially neural expression of the KIS gene in rat and human

KIS is the only known protein kinase that possesses an RNA recognition motif. This original structure indicates a role for KIS in the maturation of RNAs possibly by phosphorylating and regulating the activities of RNA associated factors. Another function of KIS has recently been unravelled--it negatively regulates the cdk inhibitor p27Kip1 and thus promotes cell cycle progression through G1. In order to explore the functional expression of this kinase, we quantified its mRNA in a wide range of rat and human tissues, during development and in tumors. In both species, the highest level of KIS gene expression was in adult neural tissues. Interestingly, within the adult rat brain, KIS mRNA is enriched in several areas including the substantia nigra compacta and nuclei of the brain stem. Furthermore, KIS gene expression increases dramatically during brain development. Altogether our results point to a ubiquitous function for KIS together with a particular implication during neural differentiation or in the function of mature neural cells. No dysregulation of KIS gene expression was detected in human tumors from breast, bladder, prostate, liver and kidney origins. On the other hand, the KIS gene was overexpressed in NF1-associated plexiform neurofibromas and malignant peripheral nerve sheath tumors (MPNSTs) as compared to dermal neurofibroma which suggests a possible implication of KIS in the genesis of NF1-associated tumors.     

Neurochemical development of the brainstem catecholaminergic cell groups in rat

The postnatal development of tyrosine hydroxylase activity has been studied in the brainstem catecholaminergic cell groups (A1C1, A2C2, A5, A6, A7), involved in cardiorespiratory control. In rat, at birth and at postnatal days P3, P7, P14, P21 ant P68, we used a microdissection technique followed by in vivo measurement of the tyrosine hydroxylase (TH) activity, the rate-limiting enzyme in catecholamine synthesis. There is two successive marked increases in TH activity: at P3 in every catecholaminergic cell groups (A1C1, +225%; A2C2, +300%; A5, +190%; A6, +205% compared to birth) and during the third postnatal week with a peak of TH activity at P14 (A6, +90% above the P7 level) or at P21 (A1C1, +715%; caudal A2C2, +585%; rostral A2C2, +15%; A5, +445%; A7, +180% compared to P7). The data suggest the existence of two temporal windows during the neurochemical development of the catecholaminergic cell groups, which correspond to two metabolic transitions. The first one could be related to the intra-, extrauterine transition and the second one, to a deep energetic phase of maturation in the rat brain, closely related to the maturation of cardiorespiratory processes.     

Association between TAFI antigen and Ala147Thr polymorphism of the TAFI gene and the angina pectoris incidence. The PRIME Study (Prospective Epidemiological Study of MI)

Thrombin activatable fibrinolysis inhibitor (TAFI), a recently described inhibitor of fibrinolysis, has been hypothesized as playing a role in atherothrombosis. However, the evidence from retrospective studies, which have evaluated the role of TAFI in vascular risk, is conflicting. In a prospective cohort (the PRIME Study) of nearly 10 000 apparently healthy men recruited in France (Lille, Strasbourg, Toulouse) and Northern Ireland (Belfast), we measured baseline plasma concentration of TAFI antigen among 143 participants (81 from France and 62 from Ireland) who subsequently developed angina pectoris and among 286 age-matched participants who remained free of disease during the 5 years of follow-up. Genotyping of the Ala147Thr polymorphism located in the TAFI gene was performed using an allele specific PCR. In France, mean levels of TAFI were significantly higher at baseline among men who subsequently developed angina pectoris compared with their control subjects (119 versus 107 %; p = 0.02). The risk of future angina pectoris increased with increasing tertiles of TAFI (p = 0.02), such that men in the highest tertile at study entry had a 5-fold higher relative risk than those in the lowest tertile (95% confidence interval, 1.38 to 18.58) after controlling for the conventional cardiovascular risk factors. No such difference was observed in Northern Ireland. In France, Thr/Thr carriers of the Ala147Thr polymorphism were significantly more frequent in cases than in controls (p = 0.01) leading to a relative risk of angina pectoris of 2.7 (95%CI 1.2-5.8). Increase in plasma TAFI antigen levels is a risk factor for angina pectoris in France. Genotyping for the Ala147Thr polymorphism seems to be a reliable tool to assess the risk mediated by TAFI.     

Differential effects of oral and transdermal postmenopausal estrogen replacement therapies on C-reactive protein

C-reactive protein (CRP) is one of the main independent predictors of cardiovascular events. Oral post-menopausal estrogen replacement therapy (ERT) increases CRP levels, but the effect of transdermal ERT is not well documented. CRP, interleukine-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels were evaluated in a randomised study of 196 healthy postmenopausal women, who were allocated to receive continuous oral estradiol-1beta, (n=63) or transdermal estradiol-1beta, (n=68) both combined with micronised progesterone, or place-bo (n=65). Oral estrogen increased CRP levels compared with both placebo (p=0.010) and transdermal estrogen (p=0.004) at 6 months. There was no significant effect of transdermal estrogen on CRP levels compared with placebo (p=0.997). No significant difference was found in the median changes for IL-6 and TNF-alpha between the three treatment groups. In conclusion, transdermal estrogen has no significant effect on CRP levels at 6 months, but CRP concentrations increased significantly with oral estrogen although no changes in cytokine levels were detected. The clinical relevance of these effects remains to be determined.     

Slowing of electroencephalogram in rapid eye movement sleep behavior disorder

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by a loss of atonia and an increase in phasic muscle activity during REM sleep, leading to complex nocturnal motor behaviors. Brainstem structures responsible for the pathogenesis of RBD are also implicated in cortical activation. To verify the hypothesis that electroencephalogram (EEG) activation will be impaired in RBD, we performed quantitative analyses of waking and REM sleep EEG in 15 idiopathic RBD patients and 15 age- and gender-matched healthy subjects. During wakefulness, RBD patients showed a considerably higher theta power in frontal, temporal, and occipital regions with a lower beta power in the occipital region. The dominant occipital frequency was significantly lower in RBD. During REM sleep, beta power in the occipital region was lower in RBD. This study shows for the first time an impaired cortical activation during both wakefulness and REM sleep in idiopathic RBD, despite an absence of changes on sleep architecture compared with controls. EEG slowing in these patients may represent an early sign of central nervous system dysfunction, perhaps paralleled by subclinical cognitive deficits. The topographical distribution of EEG slowing and possible pathophysiological mechanisms are discussed in light of the known association between RBD and neurodegenerative disorders.     

Reappraisal of the human vestibular cortex by cortical electrical stimulation study

The cortical areas with vestibular input in humans were assessed by electrical stimulation in 260 patients with partial epilepsy who had undergone stereotactic intracerebral electroencephalogram recordings before surgery. Vestibular symptoms were electrically induced on 44 anatomical sites in 28 patients. The patients experienced illusions of rotation (yaw plane: 18, pitch plane: 6, roll plane: 6), translations (n = 6), or indefinable feelings of body motion (n = 8). Almost all vestibular sites were located in the cortex (41/44): in the temporal (n = 19), parietal (n = 14), frontal (n = 5), occipital (n = 2), and insular (n = 1) lobes. Among these sites, we identified a lateral cortical temporoparietal area we called the temporo-peri-Sylvian vestibular cortex (TPSVC), from which vestibular symptoms, and above all rotatory sensations, were particularly easily elicited (24/41 cortical sites, 58.5%). This area extended above and below the Sylvian fissure, mainly inside Brodmann areas 40, 21, and 22. It included the parietal operculum (9/24 TPSVC sites) which was particularly sensitive for eliciting pitch plane illusions, and the mid and posterior part of the first and second temporal gyri (15/24 TPSVC sites) which preferentially caused yaw plane illusions. We suggest that the TPSVC could be homologous with the monkey's parietoinsular vestibular cortex.     

Brain processing of visual sexual stimuli in healthy men: a functional magnetic resonance imaging study

The brain plays a central role in sexual motivation. To identify cerebral areas whose activation was correlated with sexual desire, eight healthy male volunteers were studied with functional magnetic resonance imaging (fMRI). Visual stimuli were sexually stimulating photographs (S condition) and emotionally neutral photographs (N condition). Subjective responses pertaining to sexual desire were recorded after each condition. To image the entire brain, separate runs focused on the upper and the lower parts of the brain. Statistical Parametric Mapping was used for data analysis. Subjective ratings confirmed that sexual pictures effectively induced sexual arousal. In the S condition compared to the N condition, a group analysis conducted on the upper part of the brain demonstrated an increased signal in the parietal lobes (superior parietal lobules, left intraparietal sulcus, left inferior parietal lobule, and right postcentral gyrus), the right parietooccipital sulcus, the left superior occipital gyrus, and the precentral gyri. In addition, a decreased signal was recorded in the right posterior cingulate gyrus and the left precuneus. In individual analyses conducted on the lower part of the brain, an increased signal was found in the right and/or left middle occipital gyrus in seven subjects, and in the right and/or left fusiform gyrus in six subjects. In conclusion, fMRI allows to identify brain responses to visual sexual stimuli. Among activated regions in the S condition, parietal areas are known to be involved in attentional processes directed toward motivationally relevant stimuli, while frontal premotor areas have been implicated in motor preparation and motor imagery. Further work is needed to identify those specific features of the neural responses that distinguish sexual desire from other emotional and motivational states.