Neonatal lesions of the ventral hippocampus in rats lead to prefrontal cognitive deficits at two maturational stages

This experiment assessed the effect of neonatal ventral hippocampus lesions in rats, a heuristic approach to model schizophrenia, on continuous delayed alternation and conditional discrimination learning performance before and after complete cerebral maturation. Delays (0, 5, 15, and 30 s) were introduced in the tasks to help dissociate between a hippocampal and a prefrontal cortex dysfunction. At postnatal day (PND) 6 or 7, rats received bilateral microinjections of ibotenic acid or phosphate-buffered saline in the ventral hippocampus. From PND 26 to PND 35, rats were tested on the alternation task in a T-maze; from PND 47 to PND 85, the same rats were tested in the discrimination task where a stimulus and a response location had to be paired. Deficits in ventral hippocampus-lesioned rats were observed in both tasks whether a delay was introduced before a response or not. Impaired performance regardless of delay length, combined with high rates of perseverative errors, suggested a post-lesional prefrontal cortex dysfunction which persisted from the juvenile stage into adulthood. Premature cognitive impairments could not be predicted on the basis of the neurodevelopmental animal model of schizophrenia. Nevertheless, they appear consistent with accounts of premorbidly compromised memory, both immediate and delayed, in subgroups of schizophrenia patients.     

Antimicrobial susceptibility of Proteus mirabilis urinary tract isolates from 1999 to 2005 at Nîmes University Hospital

Aim of the studyTo analyse antimicrobial resistance trends of Proteus mirabilis urinary tract isolates from 1999 to 2005 at the Nîmes University hospital.Materials and methodsWe retrospectively collected non-duplicate urinary tract infections and colonization isolates from inpatients between 1 January 1999 and 31 December 2005.ResultsOne thousand and eight non-duplicate urinary tract isolates were studied, 63.1% were from females and the mean age was 76 years. The mean resistance rate was 59.0% for amoxicillin (AMX), 48.0% for piperacillin (PIP), 3.9% for cefotaxim, 33.9% for amoxicillin plus clavulanic acid (AMC) and 2.8% for piperacillin plus tazobactam (TZP). A significant increase in resistance was observed for AMC and TZP. The mean resistance rate was 35.0% for norfloxacin, 34.8% for ofloxacin and 23.5% for ciprofloxacin. No significant increase in resistance to fluoroquinolones was seen except for ciprofloxacin whereas a significant increase was observed for aminoglycosides. The mean rate resistance for cotrimoxazole was 33.2% with a significant decrease in the resistance during the study period.ConclusionP. mirabilis stilled sensitive to cefotaxim or ceftazidim and to TZP. The significant increase in the rate resistance to AMC and TZP could be explained by production of β-lactamases and in particular extended-spectrum β-lactamases. The increase in resistance observed for fluoroquinolones become a major concern. Amikacine was the most active aminoglycosides. These data suggested for the re-enforcement of the antimicrobial susceptibility surveillance in order to optimise the rational use of antibiotics.     

Hydrophobic cluster analysis and modeling of the human Rh protein three-dimensional structures.

Rh (Rhesus) is a major blood group system in man, which is clinically significant in transfusion medicine. Rh antigens are carried by an oligomer of two major erythroid specific polypeptides, the Rh (D and CcEe) proteins and the RhAG glycoprotein, that shared a common predicted structure with 12 transmembrane a-helices (M0 to M11). Non erythroid homologues of these proteins have been identified (RhBG and RhCG), notably in diverse organs specialized in ammonia production and excretion, such as kidney, liver and intestine. Phylogenetic studies and experimental evidence have shown that these proteins belong to the Amt/Mep/Rh protein superfamily of ammonium/methylammonium permease, but another view suggests that Rh proteins might function as CO2 gas channels. Until recently no information on the structure of these proteins were available. However, in the last two years, new insight has been gained into the structural features of Rh proteins (through the determination of the crystal structures of bacterial AmtB and archeaebacterial Amt-1. Here, models of the subunit and oligomeric architecture of human Rh proteins are proposed, based on a refined alignment with and crystal structure of the bacterial ammonia transporter AmtB, a member of the Amt/Mep/Rh superfamily. This alignment was performed considering invariant structural features, which were revealed through Hydrophobic Cluster Analysis, and led to propose alternative predictions for the less conserved regions, particularly in the N-terminal sequences. The Rh models, on which an additional Rh-specific, N-terminal helix M0 was tentatively positioned, were further assessed through the consideration of biochemical and immunochemical data, as well as of stereochemical and topological constraints. These models highlighted some Rh specific features that have not yet been reported. Among these, are the prediction of some critical residues, which may play a role in the channel function, but also in the stability of the subunit structure and oligomeric assembly. These results provide a basis to further understand the structure/function relationships of Rh proteins, and the alterations occurring in variant phenotypes.     

Distribution of Langerhans cells and mast cells within the human oral mucosa: new application sites of allergens in sublingual immunotherapy?

Background:  Sublingual immunotherapy (SLIT) represents an alternative to subcutaneous immunotherapy. While antigen-presenting cells such as Langerhans cells (LCs) are thought to contribute to the effectiveness of SLIT, mast cells (MCs) most likely account for adverse reactions such as sublingual edema. As little is known about LCs and MCs within the oral cavity, we investigated their distribution in search for mucosal sites with highest LCs and lowest MCs density.
Methods:  Biopsies were taken simultaneously from human vestibulum, bucca, palatum, lingua, sublingua, gingiva, and skin. Immunohistochemistry and flow cytometry were used to detect MCs, LCs and high affinity receptor for IgE (FcεRI) expression of LCs. Mixed lymphocyte reactions were performed to assess their stimulatory capacity.
Results:  Highest density of MCs was detected within the gingiva, while the lowest density of MCs was found within the palatum and lingua. However, sublingual MCs were located within glands, which might explain swelling of sublingual caruncle in some SLIT patients. Highest density of LCs was detected within the vestibular region with lowest density in sublingual region. Highest expression of FcεRI was detected on LCs within the vestibulum. Furthermore LCs from different regions displayed similar stimulatory capacity towards allogeneic T cells.
Conclusions:  In view of our data, different mucosal regions such as the vestibulum might represent alternative SLIT application sites with potent allergen uptake. Our data might serve as a basis for new application strategies for SLIT to enhance efficiency and reduce local adverse reactions.     

Identification of tumor necrosis factor signaling-related proteins during Epstein-Barr virus-induced B cell transformation

Epstein-Barr virus (EBV) infection in vitro transforms primary B cells into continuously proliferating lymphoblastoid cell lines (LCLs) that have been widely used as a genomic resource for variety of immunological and genetic studies. However, the biochemical and biological characteristics that distinguish LCLs from the B cells have not been thoroughly investigated. Our proteomic approach showed that EBV infection induced changes in the profiles of tumor necrosis factor (TNF) signaling-related proteins in LCLs including heat shock protein family members TNF receptor-associated protein 1 (TRAP-1), heat shock 70-kDa protein 9 (HSPA9)) and superoxide dismutase 2 (SOD2). In addition, our literature co-occurrence study placed TNF at the center of a gene cluster network of differentially expressed proteins in LCLs. This study suggested that deregulation of TNF signaling pathway could contribute to the cellular transformation and immortalization of the EBV-infected B cells.     

Role of embolization in the management of uterine fibroids

Uterine artery embolization using non spherical PVA particles or calibrated trisacryl microspheres above 500 μm is effective to treat menorrhagia, bulk-related symptoms and pelvic pain in more than 90% of cases in the short-term. In the long-term, embolization is effective in 75% of cases at 5-7 years. At 6 months, uterine volume reduction and dominant fibroid volume reduction varies between 30-60% and 50-80% respectively. During hospital stay, the complication rate is 3%. Secondary hysterectomy for complication is less than 2% at 3 months. Definitive amenorrhea is reported in less than 5% of cases in women of less than 45 years of age. No significant impact of embolization on hormonal function has been reported in women less than 45 years with normal baseline function. Secondary hysterectomy for clinical failure or recurrence is reported in 14-28% of cases at 5 years. Non-spherical PVA particles are associated with more microcatheter occlusion than trisacryl microspheres. No difference between PVA particles and trisacryl microspheres was found in terms of post-embolization pain or analgesic doses. PVA microspheres (Contour SE et Bead Block) are associated with lower clinical success and lower fibroid devascularization using MRI than trisacryl microspheres. No difference between PVA particles and trisacryl microspheres was found in terms of clinical efficacy, uterine volume reduction and complication rate. Randomized studies comparing embolization to hysterectomy demonstrate that reinterventions are more frequently performed after embolization. Secondary hysterectomy is performed in 13 to 24% of cases at 2 years and in up to 28% of cases at 5 years. Hospital stay, duration of recovery and time off work are shorter after embolization compared to hysterectomy. Embolization is cheaper than hysterectomy at 12 and 24 months even taking into consideration the additional costs of imaging and reinterventions. Randomized studies comparing embolization to myomectomy demonstrate that in the short- and mid-term there is no difference in terms of control of menorrhagia and bulk-related symptoms. Uterine volume reduction and quality of life were not different at 6 months. Periprocedural and 30-day complication rates are not different. At 6 months, the rate of complications is higher after myomectomy. Reinterventions are more frequent after embolization compared to myomectomy. Hospital stay, duration of recovery and time off work are shorter after embolization compared to myomectomy. Embolization should be considered with caution in pregnancy-seeking women since there is still a lack of good quality data available in the specific group of patients. FSH level is more frequently elevated after embolization compared to myomectomy. Pregnancy rate and term pregnancy rate are higher after myomectomy compared to embolization. Spontaneous abortion is more frequent after embolization than after myomectomy. There is no difference between embolization and myomectomy for the rates of pre-term delivery, cesarean section, post-partum hemorrhage, pre-eclampsia or intra-uterine growth retardation. Embolization performed before myomectomy (preoperative or combined procedures) can be discussed for an individual patient but there is not enough data to support its routine use.     

Increased Production of Interferon‐γ by Leishmania Homologue of the Mammalian Receptor for Activated C Kinase‐Reactive CD4+ T cells among Human Blood Mononuclear Cells: An Early Marker of Exposure to Leishmania?

A prospective study was undertaken to define early predictive immunological marker(s) of exposure to Leishmania in naïve subjects who have never been exposed to any Leishmania and who were also free of any cutaneous leishmaniasis lesions. These naïve subjects could have been exposed to Leishmania in a rain forest where Leishmania guyanensis and their natural vectors and mammalian host are cocirculating. The production of interferon (IFN)‐γ in response to the Leishmania homologue of the mammalian receptor for activated c kinase (LACK), a candidate for vaccine against leishmaniasis was analysed. At the end of their stay in the rain forest, LACK‐specific CD8⁺ T cells were detected in subjects whose peripheral blood mononuclear cell (PBMC) produced IFN‐γ in response to soluble Leishmania antigens (SLA) and in those whose PBMC remained unresponsive to SLA. However, LACK‐specific CD4⁺ T cells were detected only in PBMCs from individuals who became IFN‐γ responders to SLA. In subjects whose PBMC became positive to SLA, LACK‐reactive CD4⁺ T cells producing high level of IFN‐γ were detectable before the SLA‐reactive IFN‐γ producing CD4⁺ T cells, suggesting that the former readout assay could be used as an early predictive immunological marker of exposure to Leishmania in subjects who remained disease free.     

Association between polymorphisms in the human chemokine receptor genes CCR2 and CX3CR1 and rheumatoid arthritis

Cell trafficking into the rheumatoid synovium is thought to play an important role in the inflammation seen in rheumatoid arthritis. Chemokine receptors play a central role in this process, and several common variants are known, including the CCR2 variant, CCR2-64I, and two variants of the CX3CR1 gene, V249I and T280M. All three variants result in functional amino acid substitutions. We studied the association of these chemokine receptor variants with susceptibility to and severity of rheumatoid arthritis in two Dutch patient populations; 282 consecutive rheumatoid arthritis patients from a rheumatology outpatient clinic, and a cohort of 101 female rheumatoid arthritis patients, followed closely for a 12-year period, from whom hand and feet X-rays taken at three year intervals were scored and analyzed in this study. Although there was a trend towards increased severity of disease in patients carrying CX3CR1 variants, this was not independent of known risk factors. We found no evidence for a significant independent role for the CCR2 and CX3CR1 variants in the susceptibility to or severity of rheumatoid arthritis.     

Diffusion-weighted magnetic resonance imaging of the temporal bone

This paper summarizes the value of diffusion-weighted magnetic resonance imaging in the evaluation of temporal bone pathology. It highlights the use of different types of diffusion-weighted magnetic resonance imaging in the different types of cholesteatoma, prior to first stage surgery and prior to second look surgery. The value of diffusion-weighted magnetic resonance imaging in the evaluation of pathology of the apex of the petrous bone and the cerebellopontine angle is also discussed.