[Psoriasis: physiopathology and immunogenetics]. / Le psoriasis: physiopathologie et immunogénétique.

Psoriasis is a multifactorial disease that involves genetic, immunological and environmental factors. During the last decade, several studies by genome scan on families or cases/controls helped to highlight more than ten loci "PSORS" located on different chromosomes and containing several candidate genes. Psoriasis appears as a genetic disease that follows the mixed model with the involvement of a major gene (PSORS1) and a set of minor genes with a variable penetrance depending on the locus. Genetic data have focused on the involvement of the immune system in the pathogenesis of psoriasis. It is now accepted that psoriasis is an immunological disease involving the response profiles TH1 and TH17. Much remains to be done to better elucidate the mechanisms involved in the genesis of psoriatic lesions to find new therapeutic targets.

Increased rate of spontaneous bacterial peritonitis among cirrhotic patients receiving pharmacologic acid suppression.

BACKGROUND & AIMS: Patients with cirrhosis frequently receive proton pump inhibitor (PPI) or H2-receptor antagonist therapies. We investigated whether acid-suppressive therapy is associated with spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites. METHODS: We compared data from 65 hospitalized cirrhotic patients with paracentesis-proven SBP, collected from 2006 to 2009, with those of 65 contemporaneous, hospitalized cirrhotic patients without SBP (controls). We evaluated PPI use and analyzed the effects of covariates. RESULTS: Patients with SBP had a significantly higher incidence of recent (past 7 days) PPI use (71%) than controls (42%). Of patients with SBP, 68% had no documented indication for PPI therapy. Based on multivariable logistic regression analysis, subjects who had not taken PPIs in the past 90 days were almost 70% less likely to develop SBP than those who had taken PPIs in the previous 7 days. Subjects who took PPIs within 8 to 90 days before hospitalization were 79% less likely to develop SBP than those who took PPIs within 7 days before hospitalization. There was no significant difference between patients who received no PPI therapy in the previous 90 days versus those who had taken PPIs in the previous 8 to 90 days (P = .58). Hyponatremia was associated significantly with SBP. There were no significant differences in length of hospital stay or 30-day survival for the SBP and control groups. CONCLUSIONS: Pharmacologic acid suppression is associated with SBP in patients with advanced cirrhosis. Prospective studies are needed to determine the mechanism of this association and to determine whether reduced use of PPIs and H2-receptor antagonists reduce the incidence of SBP.

Molecular pathways underlying IBD-associated colorectal neoplasia: therapeutic implications.

Chronic inflammatory diseases, depending upon the duration and severity, are frequently associated with an increased risk of developing cancer. A classic paradigm is the enhanced risk of colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD). Carcinogenesis is a multifactorial process that involves accumulation of genetic defects, protein modification, and cell-matrix interaction. In this review, we discuss aspects of chronic inflammation in IBD that influence the development of CRC and highlight the key molecular mediators involved in this process. Also, we identify potential targets that could facilitate earlier detection of dysplasia. The targeted manipulation of specific molecules or pathways could provide opportunities for the development of therapeutic and chemopreventive interventions, which may prove effective in arresting the progression of colitis-associated cancer (CAC), with clinical implications.

The influence of the reflective environment on the absorption of a human male exposed to representative base station antennas from 300 MHz to 5 GHz.

The environment is an important parameter when evaluating the exposure to radio-frequency electromagnetic fields. This study investigates numerically the variation on the whole-body and peak spatially averaged-specific absorption rate (SAR) in the heterogeneous virtual family male placed in front of a base station antenna in a reflective environment. The SAR values in a reflective environment are also compared to the values obtained when no environment is present (free space). The virtual family male has been placed at four distances (30 cm, 1 m, 3 m and 10 m) in front of six base station antennas (operating at 300 MHz, 450 MHz, 900 MHz, 2.1 GHz, 3.5 GHz and 5.0 GHz, respectively) and in three reflective environments (a perfectly conducting wall, a perfectly conducting ground and a perfectly conducting ground + wall). A total of 72 configurations are examined. The absorption in the heterogeneous body model is determined using the 3D electromagnetic (EM) finite-difference time-domain (FDTD) solver Semcad-X. For the larger simulations, requirements in terms of computer resources are reduced by using a generalized Huygens' box approach. It has been observed that the ratio of the SAR in the virtual family male in a reflective environment and the SAR in the virtual family male in the free-space environment ranged from -8.7 dB up to 8.0 dB. A worst-case reflective environment could not be determined. ICNIRP reference levels not always showed to be compliant with the basic restrictions.

Statistical analysis of whole-body absorption depending on anatomical human characteristics at a frequency of 2.1 GHz.

In this paper, we propose identification of the morphological factors that may impact the whole-body averaged specific absorption rate (WBSAR). This study is conducted for the case of exposure to a front plane wave at a 2100 MHz frequency carrier. This study is based on the development of different regression models for estimating the WBSAR as a function of morphological factors. For this purpose, a database of 12 anatomical human models (phantoms) has been considered. Also, 18 supplementary phantoms obtained using the morphing technique were generated to build the required relation. This paper presents three models based on external morphological factors such as the body surface area, the body mass index or the body mass. These models show good results in estimating the WBSAR (<10%) for families obtained by the morphing technique, but these are still less accurate (30%) when applied to different original phantoms. This study stresses the importance of the internal morphological factors such as muscle and fat proportions in characterization of the WBSAR. The regression models are then improved using internal morphological factors with an estimation error of approximately 10% on the WBSAR. Finally, this study is suitable for establishing the statistical distribution of the WBSAR for a given population characterized by its morphology.

Urinary steroid measurements in some endocrine and psychiatric diseases.

In 1990, the worldwide accepted Shackleton method, which provides a possibility of determining the steroid metabolites from urine, was adopted in our laboratory. The procedure is very useful in the diagnosis of different endocrine diseases and in the recognition of dysfunction or absence of enzymes with an important role in steroid metabolism, and it gives possibility to control the treatment in patients with these diseases. Besides the proximate clinical application, the method gives a convenient tool to study the steroid background of these disorders, helping us understand the mechanism of their development. In the last few years, we have examined the steroid profile of patients with hair (androgen alopecia /AA/, effluvium /E/), psychiatric problems (major depression /MD/, eating disorders /EDS/, especially anorexia nervosa and bulimia) and osteoporosis (OP). In all of the examined hair loss diseases, the levels of main androgen metabolites were increased, and elevated 5alpha-reductase activity were found. We could observe the alteration of the activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzyme and marked gender differences in the changes of the steroid metabolism in patients with major depression (MD). In women with OP, the significantly decreased level of certain metabolites points to the role of testosterone, androstenedione and DHEA in postmenopausal bone loss in women. Our experiences contribute to the knowledge of the nature and steroid background of some endocrine and psychiatric diseases.

Tumor escape from killing: role of killer inhibitory receptors and acquisition of tumor resistance to cell death.

Immunotherapy of cancer has always been a very attractive fourth-modality therapeutic approach. Over the past few years, advances in the identification of tumor antigens have offered new perspectives and provided new opportunities for more accurate immunotherapy for cancer. However, when applied to patients with established tumors, it rarely leads to an objective response. This is partly due to the fact that tumors evade host immunity at both the induction and effector phases. Thus, understanding tumor escape mechanisms may be the key to successful immunotherapy for cancer. In the present review, we will focus on how the expression of killer Ig receptors (KIR) on tumor infiltrating lymphocytes can compromise their function and how tumors evade apoptotic death - two additional mechanisms of tumor escape.

Tumor cells regulate the lytic activity of tumor-specific cytotoxic t lymphocytes by modulating the inhibitory natural killer receptor function.

Tumor-infiltrating p58+ T cells from a renal tumor were specifically expanded in response to tumor cell stimulation and cloned. These p58+ T cells were found to express a memory phenotype and corresponded to clonal TCRBV3 T-cell expansion. Functionally, p58(+) CTLs displayed a low lytic activity for HLA-A2 tumor and normal cells. However, this lytic activity was significantly increased after blockade of p58 with specific monoclonal antibodies. Interestingly, we demonstrated that stimulation by tumor cells was required to trigger the inhibitory effect of p58 on the lytic activity of antigen-specific CTLs and that stimulation of the inhibitory function of p58 by tumor cells correlated with an inhibition of nuclear factor-kappaB activation in p58+ tumor-specific CTLS.

Risks associated with childbearing in schizophrenia.

The authors report about the catamnestic study of 919 schizophrenic women who gave birth to a child after their first schizophrenic episode, 112 (12.2%) of the patients suffered a new psychotic breakdown in connection with generation process. The overwhelming majority, 109 (11.9%) decompensated during the post partum periode (within 6 months after parturition). In a significantly lesser degree, 3 (0.32%) of the cases, the psychotic episode occurred during pregnancy (in the first trimester). The authors emphasize the importance of careful pharmacological and psychotherapeutical management of pregnant schizophrenic women.