Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages

Alternatively activated macrophages (aaMphi) display molecular and biological characteristics that differ from those of classically activated macrophages (caMphi). Recently, we described an experimental model of murine trypanosomosis in which the early stage of infection of mice with a Trypanosoma brucei brucei variant is characterized by the development of caMphi, whereas in the late and chronic stages of infection, aaMphi develop. In the present study, we used suppression subtractive hybridization (SSH) to identify genes that are expressed differentially in aaMphi versus caMphi elicited during infection with this T. b. brucei variant. We show that FIZZ1 and Ym1 are induced strongly in in vivo- and in vitro-elicited aaMphi as compared with caMphi. Furthermore, we demonstrate that the in vivo induction of FIZZ1 and Ym1 in macrophages depends on IL-4 and that in vitro, IFN-gamma antagonizes the effect of IL-4 on the expression of FIZZ1 and Ym1. Collectively, these results open perspectives for new insights into the functional properties of aaMphi and establish FIZZ1 and Ym1 as markers for aaMphi.     

Behavioral and neurochemical effects induced by subchronic combined exposure to toluene at 40 ppm and noise at 80 dB-A in rats

We investigated whether exposure to noise, in addition to its well-known potentiating effect on toluene-induced ototoxicity, may also exacerbate behavioral disturbances and brain neurochemical alterations produced by subchronic exposure to low toluene concentration. To test this hypothesis, we evaluated whether subchronic combined exposure (16 weeks, 104 h per week) to noise at 80 dB-A and toluene at 40 ppm potentiates the recently reported neurotoxic effects of subchronic exposure to 40 ppm toluene. Locomotor and rearing activities, sensitization to narcosis induced by acute toluene at high concentration, and tyrosine and tryptophan hydroxylase activities in the caudate-putamen and hippocampus were investigated in both male and female rats. Our results confirm that subchronic exposure to 40 ppm toluene significantly decreases rearing activity and leads to a sensitization to toluene-induced narcosis, as evaluated by loss of righting reflex, but fails to demonstrate any adverse effect of noise, alone or in combination with toluene. Given that toluene has addictive properties, the lack of potentiating behavioral and neurochemical effect of noise is discussed with regards to a recent study that has shown that methamphetamine neurotoxicity is potentiated by exposure to loud noise.     

Prognostic values of galectin-3 and the macrophage migration inhibitory factor (MIF) in human colorectal cancers.

This study aims to investigate whether the immunohistochemical levels of expression of galectin-3 and the macrophage migration inhibitory factor (MIF) are associated with prognostic values in human colorectal tumors. This was performed on 99 specimens including 69 colorectal tumors (17 Dukes A, 19 Dukes B, 15 Dukes C and 18 metastatic tumors that we labeled as D), 10 hepatic metastases from colorectal cancers and 20 normal specimens (biopsies). The immunohistochemical levels of expression of MIF and galectin-3 were quantified on routine histological slides by means of computer-assisted microscopy. Separate analyses were performed on epithelial and connective tissue. The levels of expression of both MIF and galectin-3 were very significantly higher in epithelial tumor tissue when compared with normal epithelial specimens. A positive and significant correlation between MIF and galectin-3 expression was evidenced in connective tumor tissue, and in particular in the cases associated with short survival periods (less than 5 years). In the case of the Dukes A or B tumors, we established two new prognostic groups (labeled I and II) on the basis of the levels of galectin-3 expression measured in the tumor epithelium. In the case of the Dukes C or D tumors, we established two other prognostic groups (labeled III and IV) on the basis of the levels of MIF expression measured in the connective tissue. Kaplan-Meyer analyses confirmed the additional prognostic values (as compared with conventional clinical staging) given by this new classification (groups I to IV). They show that the Dukes A or B tumors characterized by low levels of galectin-3 expression in the tumor epithelium are associated with significantly better prognoses than those characterized by high levels. In addition, the Dukes C or D tumors characterized by high levels of MIF expression in the connective tumor tissue are associated with significantly better prognoses than those characterized by low levels. In conclusions, MIF and galectin-3 expression levels in colorectal tumors are related to their levels of biological aggressiveness. These markers could be used to identify patients at risk, for whom more aggressive adjuvant therapy seems to be indicated.     

Prediction of cerebral vasospasm value of fibrinogen degradation products (FDP) in the cerebro-spinal fluid (CSF) for prediction of vasospasm following subarachnoid haemorrhage due to a ruptured aneurysm

Summary In a new treatment regimen with antifibrinolytic drugs in patients with aneurysmal subarachnoid haemorrhages, we have systematically controlled the level of fibrinogen degradation products (FDP) in the cerebrospinal fluid (CSF). The frequency of severe vasospasm with clinical ischaemia has been compared with the patient's initial level of FDP. Fifty patients have been included in this study. (All in Hunt and Hess's grades I or II on their arrival.) Patients with a secondary deterioration unrelated to vasospasm were excluded. The FDP levels were measured in the first three days following the bleeding and we were informed of them at the end of the study. The diagnosis of severe vasospasm was confirmed by arteriography and computed tomography (CT) and it was named severe when accompanied with signs of clinical ischaemia. Twenty patients developed a severe vasospasm with clinical ischaemia. In these patients, the mean value of the initial FDP level was between 80 and 320 mcg/ml compared with 20 to 80 mcg/ml for those who had not developed clinical ischaemia (p=0.0009). Furthermore, two different groups may be discriminated by their initial FDP level: FDP > 80 mcg/ml; n=23, 65% severe vasospasm; FDP < 80 mcg/ml; n=27, 81% no severe vasospasm (p<0.001). These results do not imply a direct role of FDP in pathophysiological mechanisms of vasospasm, but they suggest a relationship between the clot lysis and the appearance of vasospasm with clinical ischaemia. To our knowledge this is the first time that such a predictive role can be attributed to the initial FDP level in the prognosis of vasospasm.     

Is romantic partner betrayal a form of traumatic experience? A qualitative study

According to a growing body of research, betrayal by a romantic partner is increasingly considered as a form of interpersonal trauma. Between 30% and 60% of betrayed individuals experience symptoms of post-traumatic stress disorder (PTSD), depression and anxiety to clinically meaningful levels. From a clinical perspective, this constellation of symptoms can be conceptualized as a stressor-related adjustment disorder. Yet, no qualitative research has examined the association between romantic betrayal and traumatic stress from the perspective of betrayed individuals. Face-to-face semi-structured interviews were conducted with 13 participants who had completed a clinical trial for a new treatment for adjustment disorder stemming from betrayal. Data were analysed using thematic content analysis. Although betrayal was experienced as a shocking and destabilizing event, and participants used trauma or ‘feeling traumatized’ as a metaphor to describe their experience, few had constructed their reaction as traumatic stress. In fact, participants reported experiencing difficulties understanding the intensity of their experience. However, when exposed to external sources (e.g., books and interviews by psychologists and researchers) that used a trauma and PTSD framework to explain the effects of betrayal, participants reported feeling clarity, validation and relief. Findings are discussed in the light of theoretical and clinical implications.     

Amoeboid Microglial Cells and not Astrocytes Synthesize TNF-alpha in Swiss Mouse Brain Cell Cultures

The role of tumour necrosis factor (TNF-alpha) in brain physiology and pathology has been the focus of several studies. However, the source of this lymphokine in the central nervous system and the regulation of its synthesis is still poorly understood. We have therefore used purified astrocytes and brain macrophages in culture to compare the abilities of these two cell types to synthesize TNF-alpha and its mRNA. We find that, in the Swiss mouse, no significant TNF activity or TNF-alpha mRNA are produced by astrocytes, even following activation with lipopolysaccharides (LPS). On the other hand, purified microglial cells express a cytotoxic activity able to kill TNF-sensitive LM cells. Part of this activity is released into the culture medium and part remains bound to the membrane after mild paraformaldehyde treatment, demonstrating the existence in the culture of the soluble and membrane-bound forms of TNF activity. The fact that amoeboid microglial cells, and not astrocytes, are the actual source of TNF in brain cultures was further demonstrated by Northern blot analysis and in situ hybridization using a TNF-alpha specific oligonucleotide probe. The definition of the cell type which, in the CNS, is responsible for TNF synthesis will allow the regulation of this lymphokine to be analysed and opens the way for a better understanding of the interactions between amoeboid microglial cells and the other cell types which make up the nervous system.