Prevalence of t(11;19)(q21;p13) Translocation in Mucoepidermoid Carcinoma of the Conjunctiva

Purpose: The genetics events occurring in the development of mucoepidermoid carcinoma of the conjunctiva have not been extensively investigated. A t(11;19)(q21;p13) translocation has been reported in more than 50% of mucoepidermoid carcinoma of the salivary glands. This translocation induces a chimeric MECT1-MAML2 protein that act as a transcription activation factor in CREB and Notch pathways. Sustained expression of MECT1-MALM2 in RKE3 cells was tumorigenic in a mouse model. The presence of this translocation has been correlated with a better prognosis in mucoepidermoid carcinoma of the salivary glands. The purpose of this study was to identify the presence or absence of this translocation in mucoepidermoid carcinoma of the conjunctiva.Methods: We retrospectively reviewed all conjunctival mucoepidermoid carcinoma cases from the pathological files of Jules Gonin Eye Hospital from 1960-2010. The relevant clinico-pathological data was obtained. The presence of the t(11;19)(q21;p13) translocation was investigated by FISH using a dual color break apart probe. 100 nuclei were evaluated in each case. Normal conjunctiva was included as a control.Results: Material for FISH analysis was available in 9 patients (11 tumors). There were 2 females and 7 males. The mean age was years 71, 4 years old. Tumors were involving the bulbar conjunctiva in 6 cases and the tarsal conjunctiva in 5 cases. In a young patient of 30 years old, mucoepidermoid carcinoma was developed in the context of Xeroderma Pigmentosum. Hybridization could successfully be performed in 8 patients (9 tumors). No disruption of the dual color fusion signal was observed in all the cases, suggesting an absence of t(11;19)(q21;p13) translocation in mucoepidermoid carcinoma of the conjunctiva.Conclusions: Although our study encompasses only a limited number of cases due to the rarity of mucoepidermoid carcinoma of the conjunctiva, it demonstrates that a translocation commonly found in this tumor at other locations is not identified in the conjunctiva, suggesting that different mechanisms occur in the development of these tumors.

Clinical review--breast adenoid cystic carcinoma.

OBJECTIVES: To review the published literature on the diagnosis and management of adenoid cystic carcinoma (ACC) of the breast.¦MATERIALS AND METHODS: Papers were identified by searching PubMed using the terms « adenoid cystic carcinoma » and « breast ». Additional papers were identified by reviewing references of relevant articles.¦RESULTS: ACC of the breast is a rare tumour comprising less than 0.1% of breast malignancies. Its cellular origin in the breast remains unclear. The histological characteristics of ACC in the breast are similar to those of ACC of the salivary glands. However the prognosis of ACC of the breast is better than that of other localizations with prolonged survival. Breast-conserving treatment including postoperative radiotherapy seems to be equivalent to mastectomy alone with respect to survival. The value of adjuvant systemic therapies is not established. Late relapses can occur, so long-term follow-up is mandatory for these patients.¦CONCLUSIONS: ACC of the breast has a favourable prognosis. An accurate diagnosis and appropriate treatment are therefore important.

Impact of a smoking ban in hospitality venues on second hand smoke exposure: a comparison of exposure assessment methods

BACKGROUND: In May 2010, Switzerland introduced a heterogeneous smoking ban in the hospitality sector. While the law leaves room for exceptions in some cantons, it is comprehensive in others. This longitudinal study uses different measurement methods to examine airborne nicotine levels in hospitality venues and the level of personal exposure of non-smoking hospitality workers before and after implementation of the law. METHODS: Personal exposure to second hand smoke (SHS) was measured by three different methods. We compared a passive sampler called MoNIC (Monitor of NICotine) badge, to salivary cotinine and nicotine concentration as well as questionnaire data. Badges allowed the number of passively smoked cigarettes to be estimated. They were placed at the venues as well as distributed to the participants for personal measurements. To assess personal exposure at work, a time-weighted average of the workplace badge measurements was calculated. RESULTS: Prior to the ban, smoke-exposed hospitality venues yielded a mean badge value of 4.48 (95%-CI: 3.7 to 5.25; n = 214) cigarette equivalents/day. At follow-up, measurements in venues that had implemented a smoking ban significantly declined to an average of 0.31 (0.17 to 0.45; n = 37) (p = 0.001). Personal badge measurements also significantly decreased from an average of 2.18 (1.31-3.05 n = 53) to 0.25 (0.13-0.36; n = 41) (p = 0.001). Spearman rank correlations between badge exposure measures and salivary measures were small to moderate (0.3 at maximum). CONCLUSIONS: Nicotine levels significantly decreased in all types of hospitality venues after implementation of the smoking ban. In-depth analyses demonstrated that a time-weighted average of the workplace badge measurements represented typical personal SHS exposure at work more reliably than personal exposure measures such as salivary cotinine and nicotine.

Circadian and wake-dependent effects on the pupil light reflex in response to narrow-bandwidth light pulses.

PURPOSE: Nonvisual light-dependent functions in humans are conveyed mainly by intrinsically photosensitive retinal ganglion cells, which express melanopsin as photopigment. We aimed to identify the effects of circadian phase and sleepiness across 24 hours on various aspects of the pupil response to light stimulation. METHODS: We tested 10 healthy adults hourly in two 12-hour sessions covering a 24-hour period. Pupil responses to narrow bandwidth red (635 ± 18 nm) and blue (463 ± 24 nm) light (duration of 1 and 30 seconds) at equal photon fluxes were recorded, and correlated with salivary melatonin concentrations at the same circadian phases and to subjective sleepiness ratings. The magnitude of pupil constriction was determined from minimal pupil size. The post-stimulus pupil response was assessed from the pupil size at 6 seconds following light offset, the area within the redilation curve, and the exponential rate of redilation. RESULTS: Among the measured parameters, the pupil size 6 seconds after light offset correlated with melatonin concentrations (P < 0.05) and showed a significant modulation over 24 hours with maximal values after the nocturnal peak of melatonin secretion. In contrast, the post-stimulus pupil response following red light stimulation correlated with subjective sleepiness (P < 0.05) without significant changes over 24 hours. CONCLUSIONS: The post-stimulus pupil response to blue light as a marker of intrinsic melanopsin activity demonstrated a circadian modulation. In contrast, the effect of sleepiness was more apparent in the cone contribution to the pupil response. Thus, pupillary responsiveness to light is under influence of the endogenous circadian clock and subjective sleepiness.

Second hand tobacco smoke exposure in Switzerland

A passive sampling device called Monitor of NICotine or "MoNIC", was constructed and evaluated by IST laboratory for determining nicotine in Second Hand Tobacco Smoke (SHTS) or Environmental Tobacco Smoke (ETS). Vapour nicotine was passively collected on a potassium bisulfate treated glass fibre filter as collection medium. Analysis of collected nicotine on the treated filter by gas chromatography equipped with Thermoionic-Specific Detector (GC-TSD) after liquid-liquid extraction of 1mL of 5N NaOH : 1 mL of n-heptane saturated with NH3 using quinoline as internal standard. Based on nicotine amount of 0.2 mg/cigarette as the reference, the inhaled Cigarette Equivalents (CE) by non-smokers can be calculated. Using the detected CE on the badge for non-smokers, and comparing with amount of nicotine and cotinine level in saliva of both smokers and exposed non-smokers, we can confirm the use of the CE concept for estimating exposure to ETS. The regional CIPRET (Center of information and prevention of the addiction to smoking) of different cantons (Valais (VS), Vaud (VD), Neuchâtel (NE) and Fribourg (FR)) are going to organize a big campaign on the subject of the passive addiction to smoking. This campaign took place in 2007-2008 and has for objective to inform clearly the Swiss population of the dangerousness of the passive smoke. More than 3'900 MoNIC badges were gracefully distributed to Swiss population to perform a self-monitoring of population exposure level to ETS, expressed in term of CE. Non-stimulated saliva was also collected to determine ETS biomarkers nicotine/cotinine levels of participating volunteers. Results of different levels of CE in occupational and non-occupational situations in relation with ETS were presented in this study. This study, unique in Switzerland, has established a base map on the population's exposure to SHTS. It underscored the fact that all the Swiss people involved in this campaign (N=1241) is exposed to passive smoke, from <0.2 cig/d (10.8%), 1-2 to more than 10 cig/d (89.2%). In the area of high exposure (15-38 cig/d), are the most workers in public restaurant, cafe, bar, disco. By monitoring ETS tracer nicotine and its biomarkers, salivary nicotine and cotinine, it is demonstrated that the MoNIC badge can serve as indicator of CE passive smoking. The MoNIC badge, accompanied with content of salivary nicotine/cotinine can serve as a tool of evaluation of the ETS passive smoking and contributes to supply useful data for future epidemiological studies. It is also demonstrated that the salivary nicotine (without stimulation) is a better biomarker of ETS exposure than cotinine.

Alimentation et hypertension artérielle: au-delà du sel de table [Nutrition and hypertension: more than table salt].

The role of dietary sodium intake in the development, and its impact on the treatment, of hypertension are well recognized. However, many other nutritional compounds have been shown, or are believed, to influence blood pressure. Some compounds, such as caffeine and fructose, may raise arterial blood pressure, whereas others might lower arterial blood pressure, for example garlic, dark chocolate, fibers and potassium. In this article, we review several alimentary compounds and their (hypothesized) mechanisms of action, as well as the available evidence supporting a role of these compounds in the "non pharmacological" treatment and prevention of hypertension.

Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates.

Drugs of abuse, such as psychostimulants and opiates, are generally considered as exerting their locomotor and rewarding effects through an increased dopaminergic transmission in the nucleus accumbens. Noradrenergic transmission may also be implicated because most psychostimulants increase norepinephrine (NE) release, and numerous studies have indicated interactions between noradrenergic and dopaminergic neurons through alpha1-adrenergic receptors. However, analysis of the effects of psychostimulants after either destruction of noradrenergic neurons or pharmacological blockade of alpha1-adrenergic receptors led to conflicting results. Here we show that the locomotor hyperactivities induced by d-amphetamine (1-3 mg/kg), cocaine (5-20 mg/kg), or morphine (5-10 mg/kg) in mice lacking the alpha1b subtype of adrenergic receptors were dramatically decreased when compared with wild-type littermates. Moreover, behavioral sensitizations induced by d-amphetamine (1-2 mg/kg), cocaine (5-15 mg/kg), or morphine (7.5 mg/kg) were also decreased in knock-out mice when compared with wild-type. Ruling out a neurological deficit in knock-out mice, both strains reacted similarly to novelty, to intraperitoneal saline, or to the administration of scopolamine (1 mg/kg), an anti-muscarinic agent. Finally, rewarding properties could not be observed in knock-out mice in an oral preference test (cocaine and morphine) and conditioned place preference (morphine) paradigm. Because catecholamine tissue levels, autoradiography of D1 and D2 dopaminergic receptors, and of dopamine reuptake sites and locomotor response to a D1 agonist showed that basal dopaminergic transmission was similar in knock-out and wild-type mice, our data indicate a critical role of alpha1b-adrenergic receptors and noradrenergic transmission in the vulnerability to addiction.

Frequency, characterisation and therapies of fatigue after stroke.

Post-stroke objective or subjective fatigue occurs in around 50% of patients and is frequent (30%) even after minor strokes. It can last more than one year after the event, and is characterised by a different quality from usual fatigue and good response to rest. Associated risk factors include age, single patients, female, disability, depression, attentional impairment and sometimes posterior strokes, but also inactivity, overweight, alcohol and sleep apnoea syndrome. There are few therapy studies, but treatment may include low-intensity training, cognitive therapy, treatment of associated depression, wakefulness-promoting agents like modafinil, correction of risk factors and adaptation of activities.

Molecular genetics and treatment of narcolepsy.

Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy. The hypocretin/orexin deficiency is likely to be the key to its pathophysiology in most of cases although the cause of human narcolepsy remains elusive. Acting on a specific genetic background, an autoimmune process targeting hypocretin neurons in response to yet unknown environmental factors is the most probable hypothesis in most cases of human narcolepsy with cataplexy. Although narcolepsy presents one of the tightest associations with a specific human leukocyte antigen (HLA) (DQB1*0602), there is strong evidence that non-HLA genes also confer susceptibility. In addition to a point mutation in the prepro-hypocretin gene discovered in an atypical case, a few polymorphisms in monoaminergic and immune-related genes have been reported associated with narcolepsy. The treatment of narcolepsy has evolved significantly over the last few years. Available treatments include stimulants for hypersomnia with the quite recent widespread use of modafinil, antidepressants for cataplexy, and gamma-hydroxybutyrate for both symptoms. Recent pilot open trials with intravenous immunoglobulins appear an effective treatment of cataplexy if applied at early stages of narcolepsy. Finally, the discovery of hypocretin deficiency might open up new treatment perspectives.

Nouveaux modes de consommation du tabac et de la nicotine [New modes of tobacco and nicotine use]

New ways of consuming tobacco or nicotine have recently been developed attracting smokers not only because of their novelty but also because they hope that it will decrease their health risks or will help them in smoking banned places. The objective of this paper is to review the current state of knowledge concerning the waterpipe, oral tobacco, nasal snuff, the electronic cigarette and tobacco heating devices. Although some products seem less harmful than cigarettes, we cannot encourage people to use them because we still do not have sufficient scientific data regarding their safety. Moreover, most of these products are addictive and we still do not know if they will play a role in harm reduction.

Association of T-zone reticular networks and conduits with ectopic lymphoid tissues in mice and humans.

Ectopic or tertiary lymphoid tissues (TLTs) are often induced at sites of chronic inflammation. They typically contain various hematopoietic cell types, high endothelial venules, and follicular dendritic cells; and are organized in lymph node-like structures. Although fibroblastic stromal cells may play a role in TLT induction and persistence, they have remained poorly defined. Herein, we report that TLTs arising during inflammation in mice and humans in a variety of tissues (eg, pancreas, kidney, liver, and salivary gland) contain stromal cell networks consisting of podoplanin(+) T-zone fibroblastic reticular cells (TRCs), distinct from follicular dendritic cells. Similar to lymph nodes, TRCs were present throughout T-cell-rich areas and had dendritic cells associated with them. They expressed lymphotoxin (LT) β receptor (LTβR), produced CCL21, and formed a functional conduit system. In rat insulin promoter-CXCL13-transgenic pancreas, the maintenance of TRC networks and conduits was partially dependent on LTβR and on lymphoid tissue inducer cells expressing LTβR ligands. In conclusion, TRCs and conduits are hallmarks of secondary lymphoid organs and of well-developed TLTs, in both mice and humans, and are likely to act as important scaffold and organizer cells of the T-cell-rich zone.

Analytical progresses of the International Olympic Committee and World Anti-Doping Agency Olympic laboratories.

The Summer Olympic Games constitute the biggest concentration of human sports and activities in a particular place and time since 776 BCE, when the written history of the Olympic Games in Olympia began. Summer and Winter Olympic anti-doping laboratories, accredited by the International Olympic Committee in the past and the World Anti-Doping Agency in the present times, acquire worldwide interest to apply all new analytical advancements in the fight against doping in sports, hoping that this major human event will not become dirty by association with this negative phenomenon. This article summarizes the new analytical progresses, technologies and knowledge used by the Olympic laboratories, which for the vast majority of them are, eventually, incorporated into routine anti-doping analysis.

A conserved transcript pattern in response to a specialist and a generalist herbivore.

Transcript patterns elicited in response to attack reveal, at the molecular level, how plants respond to aggressors. These patterns are fashioned both by inflicted physical damage as well as by biological components displayed or released by the attacker. Different types of attacking organisms might therefore be expected to elicit different transcription programs in the host. Using a large-scale DNA microarray, we characterized gene expression in damaged as well as in distal Arabidopsis thaliana leaves in response to the specialist insect, Pieris rapae. More than 100 insect-responsive genes potentially involved in defense were identified, including genes involved in pathogenesis, indole glucosinolate metabolism, detoxification and cell survival, and signal transduction. Of these 114 genes, 111 were induced in Pieris feeding, and only three were repressed. Expression patterns in distal leaves were markedly similar to those of local leaves. Analysis of wild-type and jasmonate mutant plants, coupled with jasmonate treatment, showed that between 67 and 84% of Pieris-regulated gene expression was controlled, totally or in part, by the jasmonate pathway. This was correlated with increased larval performance on the coronatine insensitive1 glabrous1 (coi1-1 gl1) mutant. Independent mutations in COI1 and GL1 led to a faster larval weight gain, but the gl1 mutation had relatively little effect on the expression of the insect-responsive genes examined. Finally, we compared transcript patterns in Arabidopis in response to larvae of the specialist P. rapae and to a generalist insect, Spodoptera littoralis. Surprisingly, given the complex nature of insect salivary components and reported differences between species, almost identical transcript profiles were observed. This study also provides a robustly characterized gene set for the further investigation of plant-insect interaction.

Effect of modafinil on subjective fatigue in multiple sclerosis and stroke patients.

BACKGROUND: Modafinil has anecdotal response to neurological fatigue, but such an effect may depend on the type and location of cerebral impairment. OBJECTIVES: It was the aim of this study to compare fatigue observed in different neurological pathologies, to evaluate the tolerability to modafinil, and to describe changes in subjective fatigue. METHODS: We enrolled 14 brainstem or diencephalic stroke (BDS) patients, 9 cortical stroke (CS) patients and 17 multiple sclerosis (MS) patients. The Fatigue Assessment Instrument severity scale was performed at baseline, after 3 months of modafinil and after 1 month of washout. Cognition, mood and somnolence were assessed. A subgroup of 14 patients underwent activity measures before and during treatment. RESULTS: Thirty-one patients completed the study (10 BDS, 9 CS, 12 MS). The responder profile is more frequent in MS than in CS (p = 0.04), and in BDS than in CS patients (p = 0.04). Actiwatch measures showed no changes in activity during, before and after therapy. CONCLUSION: Modafinil was tolerated in 75% of patients at small doses and seemed to improve the severity of fatigue in the MS and BDS groups but not in the CS group. There was no modification in measured physical activity.