Harnessing malE for the study of antigen/antibody recognitions

The construction of hybrids between the variable fragment (Fv) of antibodies and protein MalE of Escherichia coli at the genetic level makes possible their preparation in a functional state, independently of any interaction with the antigen. We used such hybrids and a mutagenesis approach to study the recognition between antibody D1.3 and its antigen lysozyme, and its maturation. We subsequently transformed D1.3 into a reagentless fluorescent biosensor by knowledge-based design.     

Enhancement of Sm-p80 (large subunit of calpain) induced protective immunity against Schistosoma mansoni through co-delivery of interleukin-2 and interleukin-12 in a DNA vaccine formulation

Schistosomiasis afflicts an estimated 200 million people in 76 countries and an additional 600 million people are at risk of acquiring this infection. Even though effective anthelmintic treatment and snail eradication control programs exist, the discovery of an effective vaccine still remains the most potentially powerful means of control for this disease. We have concentrated on a vaccine candidate (large subunit of calpain or Sm-p80) because of its potential in conferring protection against challenge infection and its pivotal role in surface membrane biogenesis of schistosomes. Since surface membrane renewal is a major phenomenon employed by hemohelminths to evade host immune system; an immune response directed against Sm-p80 should make the parasite prone to immune clearance from the host by both providing a well-targeted attack and by potentially inhibiting the surface membrane biogenesis process. In the present study, we have utilized DNA immunization protocols using Sm-p80 with plasmids encoding interleukin-2 (IL-2) and interleukin-12 (IL-12). Sm-p80 by itself provided a 39% protection (P相似文献   

Standards, Options and Recommendations 2002 for the management of adult patients with intracranial gliomas (summary report)

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVE: To define clinical practice guidelines for the management of adult patients with intracranial glioma in collaboration with the Association of French-speaking Neuro-oncologists (Anocef) and the French society of neurosurgeons (SNCLF). These recommendations cover diagnosis, classification, treatment and follow-up of patients with these tumors. METHOD: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: This article is a summary version of the full document presenting the clinical practice guidelines with algorithms. The main recommendations concern the place of the surgery, radiotherapy, chemiotherapy, imagery and concomitant medical treatments in the specific treatment strategy of grade III and IV glioma, grade II glioma, gliomatosis cerebri, pilocytic astrocytoma, subependymoma, xanthoastrocytoma, intracranial ependymoma and brain stem glioma.     

Cell Handling,Membrane-Binding Properties and Membrane-Penetration Modeling Approaches of Pivampicillin and Phthalimidomethylampicillin,Two Basic Esters of Ampicillin,in Comparison with Chloroquine and Azithromycin

Purpose. The purpose of this work was to examine and understand the cellular pharmacokinetics of two basic esters of ampicillin, pivaloyloxymethyl (PIVA) and phthalimidomethyl (PIMA), in comparison with lysosomotropic drugs (chloroquine, azithromycin). Methods. Cell culture studies (J774 macrophages) were undertaken to study uptake and release kinetics and to assess the influence of concentration, pH, proton ionophore (monensin), and MRP and P-gp inhibitors (probenecid, gemfibrozil, cyclosporin A, GF 120918). Equilibrium dialysis with liposomes were performed to directly asses the extent of drug binding to bilayers. Conformational analysis modeling of the drug penetration in bilayers was conducted to rationalize the experimental observations. Results. PIVA and PIMA showed properties in almost complete contrast with those of chloroquine and azithromycin, i.e., fast apparent accumulation and fast release at 4°C as well as at 37°C, saturation of uptake (apparent K _d 40 M), no influence of monensin, MRP, or P-gp inhibitors; tight binding to liposomes (K _d approx. 40 M); and sharp increase in calculated free energy when forced in the hydrophobic domain. Conclusions. Although they are weak organic bases, PIVA and PIMA show none of the properties of lysosomotropic agents. We hypothesize that they remain locked onto the pericellular membrane and may never penetrate cells as such in significant amounts.     

MT1 melatonin receptor mRNA expressing cells in the pars tuberalis of the European hamster: effect of photoperiod

Melatonin, secreted only during the night by the pineal gland, transduces the photoperiodic message to the organism. One important target for the hormone is the pars tuberalis (PT) of the adenohypophysis which displays a very high number of melatonin binding sites in mammals and is implicated in the seasonal regulation of prolactin secretion. To gain insight into the mechanism by which the melatonin signal is decoded in the PT, we studied the effect of photoperiod on the PT cells expressing the MT1 melatonin receptor in a highly photoperiodic species, the European hamster. Recently, we showed that, in the rat, the MT1 receptor mRNA is expressed in PT-specific cells characterized by their expression of beta-thyroid stimulating hormone (beta-TSH) along with the alpha-glycoprotein subunit (alpha-GSU). As the cellular composition of the PT shows variability among species, we first identified the cell type expressing the MT1 receptor in the European hamster by combining immunocytochemistry and nonradioactive in situ hybridization for the MT1 receptor mRNA. Our results show that, in the European hamster, as in the rat, the MT1 receptor is only expressed by the PT-specific-cells, beta-TSH and alpha-GSU positive. In a second step, we analysed the effects of photoperiod on the MT1 mRNA, and on beta-TSH and alpha-GSU both at the mRNA and protein levels. Our data show that, compared to long photoperiod, short photoperiod induces a dramatic decrease of MT1, beta-TSH and alpha-GSU expression. Protein levels of beta-TSH and alpha-GSU were also dramatically reduced in short photoperiod. Together, our data suggest that melatonin exerts its seasonal effects in the PT by signalling to PT specific-cells through the MT1 receptor subtype.     

Continuous growth of mean tumor diameter in a subset of grade II gliomas

Serial magnetic resonance images of 27 patients with untreated World Health Organization grade II oligodendrogliomas or mixed gliomas were reviewed retrospectively to study the kinetics of tumor growth before anaplastic transformation. Analysis of the mean tumor diameters over time showed constant growth. Linear regression, using a mixed model, found an average slope of 4.1mm per year (95% confidence interval, 3.8-4.4mm/year). Untreated low-grade oligodendrogliomas or mixed gliomas grow continuously during their premalignant phase, and their pattern of growth can be predicted within a relatively narrow range. These findings could be of interest to optimize patients management and follow-up.     

Is thyrotropin-releasing hormone receptor involved in thyrotrope adaptation to starvation?

The aim of the present study was to delineate the involvement of TRH receptors in the thyrotrope adaptation to starvation (i.e. plasma TSH and thyroid hormone decrease, increased sensitivity to T3) by measuring [3H]TRH binding in euthyroid, hypothyroid and T3-substituted rats (175 ng/100 g body weight). Our results show that in euthyroid rats, starvation does not significantly modify either the affinity or the number of pituitary binding sites. In hypothyroid and T3-substituted rats, starvation does not alter the negative control exerted by T3 on the number of TRH binding sites. Our data indicate that the adaptation of thyrotrope to starvation does not primarily result from alterations of TRH binding sites.