Dominant-negative Fas mutation is reversed by down-expression of c-FLIP.

Fas triggering by agonistic antibodies or by its cognate ligand, FasL, induces apoptotic cell death, whereas mutation in the Fas death domain is associated with lymphoma progression. On prolonged culture in the presence of an agonistic anti-Fas antibody, we raised a Jurkat cell line resistant to agonistic antibodies but still sensitive to soluble FasL, which carried at the heterozygous state, a point mutation into the Fas death domain. Down-modulation of c-FLIP expression reversed the blockade of the Fas pathway.

Effects of combinations of Fusarium mycotoxins on the inhibition of macromolecular synthesis, malondialdehyde levels, DNA methylation and fragmentation, and viability in Caco-2 cells.

We studied the interactive effects of either binary or tertiary mixtures of Fusarium mycotoxins, deoxynivalenol (DON), zearalenone (ZEA), and fumonisin B1 (FB1) on the human intestinal cell line, Caco-2, using the endpoints including malonedialdehyde (MDA) production, inhibition of protein and DNA syntheses, DNA methylation, DNA fragmentation, and cell viability as measured by the neutral red (NR) test. The mixtures of mycotoxins reduce cellular viability in increasing order: [FB1+ZEA]<[FB1+DON]<[ZEA+DON]<[FB1+DON+ZEA] in NR test. Because FB1 antagonizes the effects of estrogenic Zearalenone, FB1 was assayed against estradiol.

Sex differences in sleep: the response to sleep deprivation and restraint stress in mice.

Study Objectives: Numerous clinical studies and sleep surveys have shown pronounced sex differences in the occurrence of insomnia and other sleep pathologies. It has been suggested that sex differences in sleep, while subtle under baseline conditions, may increase in magnitude under biological or environmental challenges. However, controlled and experimental studies on sleep under challenged conditions rarely include female subjects.

Splitting bone marrow trephines into frozen and fixed fragments allows parallel histological and molecular detection of B cell malignant infiltrates.

Clonality analysis of the immunoglobulin heavy chain (IgH) gene is helpful in identifying malignant B cell infiltrates in the bone marrow and is usually carried out on separate aspirates or on the same formalin-fixed decalcified bone marrow specimen. To determine whether the removal of the decalcification step would improve the molecular analysis, we first studied 12 bone marrow specimens with lymphoma infiltration split into a fixed and a small frozen fragment. Both the detection rate of IgH gene monoclonality and DNA quality were found to be superior in the frozen part than in the fixed part.

Galanin receptor 1 is expressed in a subpopulation of glutamatergic interneurons in the dorsal horn of the rat spinal cord.

The 29/30 amino acid neuropeptide galanin has been implicated in pain processing at the spinal level and local dorsal horn neurons expressing the Gal(1) receptor may play a critical role. In order to determine the transmitter identity of these neurons, we used immunohistochemistry and antibodies against the Gal(1) receptor and the three vesicular glutamate transporters (VGLUTs), as well as in situ hybridization, to explore a possible glutamatergic phenotype. Gal(1) protein, which could not be demonstrated in Gal(1) knockout mice, colocalized with VGLUT2 protein, but not with glutamate decarboxylase, in many nerve endings in lamina II.

Co-occurrence of aflatoxin B1, fumonisin B1, ochratoxin A and zearalenone in cereals and peanuts from Côte d'Ivoire.

This survey examined 30 samples of rice (n = 10), maize (n = 10) and peanuts (n = 10) from Côte d'Ivoire for aflatoxin B1, fumonisin B1 and zearalenone using immunoassays, and ochratoxin A using a validated HPLC method with fluorescence detection. In Côte d'Ivoire, as in other countries, several mycotoxins are present in the same commodities. These mycotoxins are from different structural families: aflatoxin B1, fumonisin B1, zearalenone and ochratoxin A, normally produced by fungal species from Aspergillus, Penicillium and Fusarium genera.

Preferences for routines in older people: associations with cognitive and psychological vulnerability.

Objectives: Although routine activities are important to normal functioning across all phases of life, their expression in older people may be associated with cognitive and psychological vulnerability.

Methods: The relationship between these variables was explored in 235 elderly French participants from the PAQUID cohort study.

Results: Cross-sectional positive associations were found between preferences for routines, anxiety and depression levels, and cognitive complaints.

Blood velocity assessment using 3D bright-blood time-resolved magnetic resonance angiography.

Blood velocity is a functional parameter that is not easily assessed noninvasively, especially in small animals. A new noninvasive method that uses magnetic resonance angiography (MRA) to measure blood flows is proposed. This method is based on the time-of-flight (TOF) phenomenon.

Cytokine, sickness behavior, and depression.

Sufficient evidence is now available to accept the concept that the brain recognizes cytokines as molecular signals of sickness. Clarifying the way the brain processes information generated by the innate immune system is accompanied by a progressive elucidation of the cellular and molecular components of the intricate system that mediates cytokine-induced sickness behavior. We are still far, however, from understanding the whole.

How much should we involve genetic and environmental factors in the risk assessment of mycotoxins in humans?

Despite consented efforts in prevention, mycotoxins remain a problem of human health concern in several parts of the world including developed countries. Within the same range of toxins concentrations in the blood some people develop a disease while others do not. Could this inequality in front of mycotoxins effects be explained by environment factors and/or genetic predisposition? Among recent advances in environmental health research Correlation between chronic diseases and mycotoxins in humans deserves attention through several questions: Are genetic factors involved in disease causation of mycotoxins? How much are these factors currently taken into account for mycotoxins risk assessment and how much should we involve them? Answers are still to come.

Preliminary survey of ochratoxin A in millet, maize, rice and peanuts in Côte d'Ivoire from 1998 to 2002.

In a preliminary study, samples of millet (n =33) maize (n=41), rice (n=10) and peanuts (n=10) from Côte d'Ivoire were analysed for ochratoxin A (OTA) by HPLC with fluorimetric detection, followed by confirmation by cleavage of the OTA molecule using carboxypeptidase with HPLC separation and fluorimetric quantification of the released ochratoxin alpha (OTh). With the exception of four samples of peanuts, all samples showed OTA contamination, ranging from 3 to 1738 microg/kg. All cereals were contaminated and the OTA concentrations were in the range of 17-204 microg/kg for millet, 3-1738 microg/kg for maize, 9-92 microg/kg for rice and 0.

Ochratoxin A in human blood in Abidjan, Côte d'Ivoire.

Ochratoxin A (OTA) produced by Aspergillus and Penicillium genera contaminates a diversity of foods including cereals; cereals-derived foods; dry fruits; beans; cocoa; coffee; beer; wine; and foodstuffs of animal origin mainly poultry, eggs, pork and milk, including human breast milk. OTA is nephrotoxic to all animal species studied so far and most likely to humans, who show the longest half-life for elimination of this toxin among all species examined. Among other toxic effects, OTA is teratogenic, immunotoxic, genotoxic, mutagenic and carcinogenic, all of which lead to life-threatening pathologies through several molecular pathways.

Blastoid and common variants of mantle cell lymphoma exhibit distinct immunophenotypic and interphase FISH features.

Aims: The recognition of blastoid variant (BV) of mantle cell lymphoma (MCL) is based on morphological criteria. Our aim was to analyse 18 MCL cases including four BV-MCL for their clinicopathological features, proliferation index, cyclin D1 and CDK4 expression and interphase fluorescence in-situ hybridization (FISH) pattern.

Methods And Results: BV-MCL versus common MCL was characterized by a shorter overall duration of response after first-line therapy (11 months versus 28 months) and shorter overall survival (20 months versus 42 months).

A clinical-scale expansion of mobilized CD 34+ hematopoietic stem and progenitor cells by use of a new serum-free medium.

Background: The autologous transplantation of CD 34+ cells expanded ex vivo in serum-free conditions dramatically reduces post-myeloablative neutropenia in myeloma patients. In our cell therapy unit, cells for this clinical assay have been expanded under GMP with serum-free Irvine Scientific (IS) medium with stem cell factor (SCF), granulocyte-colony-stimulating factor (G-CSF), and megakaryocyte growth and development factor (MGDF; 100 ng/mL, respectively). Because this clinical-grade IS medium is no longer available, a new serum-free medium, Maco Biotech HP 01 (Macopharma), was evaluated.

Resistance to diet-induced obesity in mu-opioid receptor-deficient mice: evidence for a "thrifty gene".

Using pharmacological tools, a role for opioid receptors in the regulation of food intake has been documented. However, the involvement of specific receptor subtypes remains questionable, and little information is available regarding a role for opioid receptors in energy metabolism. Using adult male mice lacking the mu-opioid receptor (MOR) gene (MOR-/-), we show that the MOR is not essential for the maintenance of normal levels of ad libitum food intake but does modulate the efficiency of energy storage during high-fat diets through the regulation of energy partitioning.

[Magnetic resonance imaging (MRI)-directed focussed ultrasound. Methods and applications in oncological treatment].

Focussed ultrasound is the only known technology that allows non-invasive local hyperthermia. Since MRI may be employed to obtain real-time temperature maps non-invasively, the combination of these two technologies offers great advantages, specifically aimed towards oncological studies. Real-time identification of the target region and accurate control of the temperature evolution during the treatment are now possible.

Disability-free life expectancy of older French people: gender and education differentials from the PAQUID cohort.

In countries with low mortality rates, the quality of the years of life is more important to consider than total life expectancy (TLE). Disability-free life expectancy (DFLE) is one of the most relevant indicators of health and the quality of life. This paper aims to estimate TLE and DFLE with four levels of severity of disability and to explore gender and educational differences in older French people.

Local delivery of magnetic resonance (MR) contrast agent in kidney using thermosensitive liposomes and MR imaging-guided local hyperthermia: a feasibility study in vivo.

Purpose: To investigate the feasibility of local delivery of a magnetic resonance (MR) contrast agent in vivo using paramagnetic thermosensitive liposomes and infrared (IR) laser-induced local hyperthermia under real-time MR thermometry on rabbit kidney.

Materials And Methods: Respiratory gated, radio frequency (RF)-spoiled gradient-echo sequences were used for precise MR temperature mapping (SD = 1 degrees C). In vivo heating experiments confirmed local release of MR contrast agent from liposomes.

Shaping ability of two rotary instruments in simulated canals: stainless steel ENDOflash and nickel-titanium HERO Shaper.

Aim: To compare the shaping ability of two rotary instruments in simulated curved canals: stainless steel ENDOflash Files (KaVo, Biberach, Germany) and the recently introduced nickel-titanium HERO Shaper instruments (Micro-Mega, Besançon, France).

Methodology: Simulated root canals with 35 degree curves in resin blocks were prepared to size 30, .04 taper (HERO Shaper) using a crowndown technique or size 30, .

Mood alterations during interferon-alfa therapy in patients with chronic hepatitis C: evidence for an overlap between manic/hypomanic and depressive symptoms.

Background: Psychiatric side effects are common during interferon-alfa (IFN-alfa) therapy and often responsible for early treatment discontinuation, thus limiting its therapeutic potential. Depression is considered the hallmark of these side effects. However, irritability, anger/hostility, and manic/hypomanic episodes have also been reported, suggesting that these symptoms are important features of IFN-alfa-induced neuropsychiatric side effects.

Comparative study of cytotoxicity and oxidative stress induced by deoxynivalenol, zearalenone or fumonisin B1 in human intestinal cell line Caco-2.

Fusarium species infestations of cereals crops occur worldwide. Fusarium toxins such as, deoxynivalenol (DON), zearalenone (ZEN) and fumonisin B1 (FB1) have been shown to cause diverse toxic effects in animals and also suspected of disease causation in humans. From the literature and mechanistic point of view, DON binds to the ribosomal peptidyl-transferase and inhibits protein synthesis specifically and DNA synthesis consequently.

Overnight urinary cortisol and cortisone add new insights into adaptation to training.

Purpose: To examine the effects of training on the HPA axis using two new noninvasive tools: salivary cortisol response to awakening and overnight urinary cortisol and cortisone excretion, and on the sympathoadrenal system using overnight catecholamines excretion. To dissociate the effects of training to those of seasonal hormonal variations, endurance-trained men were compared with sedentary men.

Methods: Nine untrained (UT) men and 10 triathletes were followed during a 10-month season.

Synergistic effects of fumonisin B1 and ochratoxin A: are in vitro cytotoxicity data predictive of in vivo acute toxicity?

Contamination of food and feeds by mycotoxins is a major problem of human and animals health concern which is also extremely detrimental to economy. Mycotoxins producing moulds may produce a diversity of toxins such as aflatoxins, ochratoxins, trichothecenes, zearalenone, fumonisins, tremorgenic toxins and ergot alkaloids. Although toxicological, environmental and epidemiological studies have addressed the problem of these toxins one by one, more than one mycotoxin are found usually in the same contaminated commodities.

Prostanoids and their receptors that modulate dendritic cell-mediated immunity.

Dendritic cells (DC) are essential for the initiation of immune responses by capturing, processing and presenting antigens to T cells. In addition to their important role as professional APC, they are able to produce immunosuppressive and pro-inflammatory prostanoids from arachidonic acid (AA) by the action of cyclooxygenase (COX) enzymes. In an autocrine and paracrine fashion, the secreted lipid mediators subsequently modulate the maturation, cytokine production, Th-cell polarizing ability, chemokine receptor expression, migration, and apoptosis of these extremely versatile APC.

Value of interphase FISH for the diagnosis of t(11:14)(q13;q32) on skin lesions of mantle cell lymphoma.

The diagnosis of skin lesions of mantle cell lymphoma (MCL) may be difficult at the onset of the disease. We observed 2 patients with papules of the trunk and 1 with diffuse infiltration of the trunk and the face and 2 subcutaneous nodules. Skin samples showed diffuse infiltration of the dermis (n = 1) or perivascular infiltration (n = 2).