Dolichol-phosphate-mannose-3 (DPM3)/prostin-1 is a novel phospholipase C-gamma regulated gene negatively associated with prostate tumor invasion.

The most ominous development in tumor progression is the transition to an invasive and metastatic phenotype. Little is known, however, about the molecular alterations that cause a tumor to become invasive. In view of this, we have used microarray expression analysis to evaluate the expression profiles of a unique panel of human DU145 prostate cancer sublines that vary in their invasive potential. The three DU145 sublines expressed epidermal growth factor (EGF) receptors that differed in their ability to activate phospholipase C-gamma (PLC gamma). Three-way analyses yielded 11 genes out of 4608 genes screened that associated directly or inversely with invasive potential. The gene whose expression correlated most strongly with lack of invasion was identified as a potential invasion suppressor and called prostin-1. Pharmacological inhibition of PLC gamma (U73122) confirmed that PLC gamma signaling suppressed prostin-1 in that U73122 treatment caused induction of prostin-1 in PLC gamma competent cells. The prostin-1 gene, conserved through phylogeny, is induced by androgen in LNCaP cells and encodes a 92 amino acid protein. The protein shares no extensive homologies with other known genes, yet was recently identified as a small stabilizer subunit of the dolichol-phosphate-mannose (DPM) synthase complex. That DPM3/prostin-1 might suppress tumor progression was supported by the finding that exogenous expression in COS cells leads to apoptosis. These findings support the use of model cell lines to identify putative tumor suppressors and promoters.     

Molecular biomarkers of oxidative stress in aquatic organisms in relation to toxic environmental pollutants

The potential of oxygen free radicals and other reactive oxygen species (ROS) to damage tissues and cellular components, called oxidative stress, in biological systems has become a topic of significant interest for environmental toxicology studies. The balance between prooxidant endogenous and exogenous factors (i.e., environmental pollutants) and antioxidant defenses (enzymatic and nonenzymatic) in biological systems can be used to assess toxic effects under stressful environmental conditions, especially oxidative damage induced by different classes of chemical pollutants. The role of these antioxidant systems and their sensitivity can be of great importance in environmental toxicology studies. In the past decade, numerous studies on the effects of oxidative stress caused by some environmental pollutants in terrestrial and aquatic species were published. Increased numbers of agricultural and industrial chemicals are entering the aquatic environment and being taken up into tissues of aquatic organisms. Transition metals, polycyclic aromatic hydrocarbons, organochlorine and organophosphate pesticides, polychlorinated biphenyls, dioxins, and other xenobiotics play important roles in the mechanistic aspects of oxidative damage. Such a diverse array of pollutants stimulate a variety of toxicity mechanisms, such as oxidative damage to membrane lipids, DNA, and proteins and changes to antioxidant enzymes. Although there are considerable gaps in our knowledge of cellular damage, response mechanisms, repair processes, and disease etiology in biological systems, free radical reactions and the production of toxic ROS are known to be responsible for a variety of oxidative damages leading to adverse health effects and diseases. In the past decade, mammalian species were used as models for the study of molecular biomarkers of oxidative stress caused by environmental pollutants to elucidate the mechanisms underlying cellular oxidative damage and to study the adverse effects of some environmental pollutants with oxidative potential in chronic exposure and/or sublethal concentrations. This review summarizes current knowledge and advances in the understanding of such oxidative processes in biological systems. This knowledge is extended to specific applications in aquatic organisms because of their sensitivity to oxidative pollutants, their filtration capacity, and their potential for environmental toxicology studies.     

Evidence for left ventricular dysfunction in patients with obstructive sleep apnoea syndrome.

There is limited information on the development of left ventricular (LV) dysfunction in patients with obstructive sleep apnoea (OSA) in the absence of lung and cardiac comorbidity. This study aimed to investigate whether OSA patients without heart morbidity develop LV dysfunction, and to assess the effect of continuous positive airway pressure (CPAP) on LV function. Twenty-nine OSA patients and 12 control subjects were studied using technetium-99m ventriculography to estimate LV ejection fraction (LVEF), LV peak emptying rate (LVPER), time to peak emptying rate (TPER), peak filling rate (LVPFR) and time to peak filling rate (TPFR) before and after 6 months of treatment with CPAP. A significantly lower LVEF was found in OSA patients, compared to control subjects, (53+/-7 versus 61+/-6%) along with a reduced LVPER (2.82+/-0.58 versus 3.82+/-0.77 end-diastolic volumes x s(-1)). Furthermore, OSA patients had significantly lower LVPFR (2.67+/-0.71 versus 3.93+/-0.58 end-diastolic volumes x s(-1)) and delayed TPFR (0.19+/-0.04 versus 0.15+/-0.03 s) in comparison with the control group. Six-months of CPAP treatment was effective in significantly improving LVEF, LVPER, LVPFR and TPFR. In conclusion, obstructive sleep apnoea patients without any cardiovascular disease seem to develop left ventricular systolic and diastolic dysfunction, which may be reversed, either partially or completely, after 6 months of continuous positive airway pressure treatment.     

Identification of gram-negative bacilli using the Autobac IDX

The Autobac IDX is a new system for the rapid identification of clinically significant members of the Enterobacteriaceae and Aeromonas, Acinetobacter, Alcaligenes, Flavobacterium, Moraxella, and Pseudomonas species. The use of 18 differentially inhibitory compounds such as dyes and antibiotics along with a computerized algorithm based on a multivariate analysis provides the basis for the identification of 30 different groups of gram-negative bacilli. Required preliminary tests include observations on the presence or absence of swarming on a sheep blood agar plate and noting the following: growth, lactose fermentation, and bile precipitation from a MacConkey plate. Spot indole and spot oxidase tests must be performed as well. Identification by the Autobac IDX System takes 3-6 hr after completion of the preliminary tests. From a total of 403 isolates tested, the Autobac system agreed with the MicroID AND N/F systems on 382 identifications (94.8%). Four isolates, two Acinetobacter anitratus, one Serratia marcescens and one Moraxella osloensis could not be identified by IDX. Additional testing was required on 35 (8.7%) of the isolates.     

Importance of neoadjuvant chemotherapy in olfactory neuroblastoma treatment: Series report and literature review

Introduction and objectives

Olfactory neuroblastoma (ONB) is a rare entity that constitutes less than 5% of nasosinusal malignancies. Mainstream treatment consists in surgical resection +/? adjuvant radiotherapy. By exposing results observed with apparition of new therapeutic options as neoadjuvant chemotherapy, the objective is to evaluate a series and a review of the current literature.

Looking into myself: Changes in interoceptive sensitivity during mirror self‐observation

Interoceptive sensitivity is an essential component of recent models of “the self.” Increased focus on the self (e.g., self‐observation in a mirror) can enhance aspects of self‐processing. We examined whether self‐observation also enhances interoceptive sensitivity. Participants performed a heartbeat detection task while looking at their own face in a mirror or at a black screen. There was significant improvement in interoceptive sensitivity in the mirror condition for those participants with lower interoceptive sensitivity at baseline. This effect was independent of the order of conditions, gender, age, body mass index, habitual exercise, and changes in heart rate. Our results suggest that self‐observation may represent a viable way of manipulating individuals' interoceptive sensitivity, in order to directly test causal relations between interoceptive sensitivity and exteroceptive self‐processing.     

The impact of experiential avoidance and obsessive beliefs on obsessive-compulsive symptoms in a severe clinical sample

The present study sought to replicate and extend a study by Abramowitz et al. (2009), who examined how well experiential avoidance (EA) and obsessive beliefs predicted obsessive-compulsive (OC) symptoms in a non-clinical sample. The current study utilized a severe, clinical, treatment-seeking sample (N = 108), and examined how well EA and obsessive beliefs predicted changes in OC symptoms from pre- to post-treatment. Findings were generally consistent with Abramowitz et al. EA was generally not related to OC severity and did not add significantly to the prediction of OC symptom domains above and beyond depression or general anxiety, whereas obsessive beliefs did. Pre- to post-treatment change in one type of obsessive belief (perfectionism/certainty), but not change in EA, predicted global change in OC severity. Results suggest that EA as it is measured currently may not play a significant role in OC severity or changes in OC severity across treatment.     

A critical review of assessment strategies to measure the behavioral activation model of depression

Behavioral activation (BA) treatments for depression are based on a model of psychopathology indicating that losses of, reductions in, or chronically low levels of positive reinforcement produce behavioral and emotional changes in depression. The corresponding mechanism theory is that using BA techniques to increase activation will lead to a subsequent increase in positive reinforcement, which will decrease depressive symptoms. We attempt to review BA literature relevant to its psychopathology and mechanism models, paying particular attention to attempts to measure activation as conceptualized within BA treatments and attempts to measure reinforcement. Suggestions on ways in which to improve these measurements in order to better evaluate the psychopathology and mechanism models are provided.     

Sputum carcinoembryonic antigen, neuron-specific enolase and cytokeratin fragment 19 levels in lung cancer diagnosis

OBJECTIVE: The aim of the present study was to examine the impact of sputum carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and cytokeratin fragment 19 (CYFRA 21-1) levels in lung cancer diagnosis and to compare the diagnostic usefulness of sputum assays with that of serum assays. METHODOLOGY: Forty-seven patients with lung cancer and 62 with benign lung disease were studied. Tumour marker levels in sputum (sp.) and serum (ser) were measured by immunoradiometric assays. RESULTS: Sputum and serum tumour marker levels were significantly higher in lung cancer than in benign disease. When the specificity was 95%, the sensitivity was 57%, 43%, 36%, 30%, 28% and 19%, for spCEA, serCYFRA 21-1, spCYFRA 21-1, serCEA, serNSE, and spNSE, respectively. Bayesian analysis showed that the best predictive values correspond to spCEA and serCYFRA 21-1. The maximum overall gain was obtained in pretest probability of 0.35 for both spCEA and serCYFRA 21-1, with predictive values of 84% and 80% for spCEA and serCYFRA 21-1, respectively. CONCLUSION: Sputum tumour marker levels were no more useful than the serum levels in lung cancer diagnosis. SpCEA offered the best predictive values but these were still not sufficiently satisfactory for spCEA to be proposed for routine use.     

Minimal main pancreatic duct dilatation in small branch duct intraductal papillary mucinous neoplasms associated with high-grade dysplasia or invasive carcinoma

BackgroundThe aim of this study was to determine the incidence of high-grade dysplasia (HGD) or invasive carcinoma in patients with small branch duct intraductal papillary mucinous neoplasms (BD-IPMNs).Methods923 patients who underwent surgical resection for an IPMN were identified. Sendai-negative patients were identified as those without history of pancreatitis or jaundice, main pancreatic duct size (MPD) <5 mm, cyst size <3 cm, no mural nodules, negative cyst fluid cytology for adenocarcinoma, or serum carbohydrate antigen 19-9 (CA 19-9) <37 U/L.ResultsBD-IPMN was identified in 388 (46.4%) patients and 89 (22.9%) were categorized as Sendai-negative. Overall, 68 (17.5%) of BD-IPMN had HGD and 62 (16.0%) had an associated invasive-carcinoma. Among the 89 Sendai-negative patients, 12 (13.5%) had IPMNs with HGD and only one patient (1.1%) had invasive-carcinoma. Of note, older age (OR 1.13, 95% CI 1.03–1.23; P = 0.008) and minimal dilation of MPD (OR 11.3, 95% CI 2.40–53.65; P = 0.002) were associated with high-risk disease in Sendai-negative patients after multivariable risk adjustment.ConclusionThe risk of harboring a high-risk disease remains low in small BD-IPMNs. However, Sendai-negative patients who are older than 65 years old and those with minimal dilation of MPD (3–5 mm) are at greater risk of high-risk lesions and should be given consideration to be included as a “worrisome feature” in a future guidelines update.