A Therapeutic Her2/neu Vaccine Targeting Dendritic Cells Preferentially Inhibits the Growth of Low Her2/neu-Expressing Tumor in HLA-A2 Transgenic Mice.

Purpose: E75, a peptide derived from the Her2/neu protein, is the most clinically advanced vaccine approach against breast cancer. In this study, we aimed to optimize the E75 vaccine using a delivery vector targeting dendritic cells, the B-subunit of Shiga toxin (STxB), and to assess the role of various parameters (Her2/neu expression, combination with trastuzumab) in the efficacy of this cancer vaccine in a relevant preclinical model.

Experimental Design: We compared the differential ability of the free E75 peptide or the STxB-E75 vaccine to elicit CD8(+) T cells, and the impact of the vaccine on murine HLA-A2 tumors expressing low or high levels of Her2/neu.

Characterization of effector components from the humoral and cellular immune response stimulated by melanoma cells exhibiting modified IGF-1 expression.

Modified melanoma B16 cells inhibited in their IGF-1 expression (B16MOD), on the contrary to the IGF-1 fully expressed parental wild-type (B16WT) counterpart, were shown to stimulate humoral as well as cellular immune responses. Among humoral components, the neutralizing and complement-fixing antibodies of IgM and essentially IgG2 (a+b) isotypes exhibited in vitro and in vivo effects upon tumour growth, while the IgG1 antibody isotype promoted enhanced tumour proliferation. As for the cellular immunity, it was found that the T CD8(+) lymphocyte subpopulation remained the main potent and long lasting immune active effector regulating tumour growth.

Quinone-based polymers for label-free and reagentless electrochemical immunosensors: application to proteins, antibodies and pesticides detection.

Polyquinone derivatives are widely recognized in the literature for their remarkable properties, their biocompatibility, simple synthesis, and easy bio-functionalization. We have shown that polyquinones present very stable electroactivity in neutral aqueous medium within the cathodic potential domain avoiding side oxidation of interfering species. Besides, they can act as immobilized redox transducers for probing biomolecular interactions in sensors.

Complex interplays in immune T-cell differentiation and developmental fate determination.

Aspects relevant to immune T-cell differentiation and fate determination have been examined and discussed in the context of transcription factors, initiating cytokines in association with cognate antigen activation. It appears that the differentiation optional program, in light of recent results related to genetic as well as epigenetic mechanisms, is not predetermined and irreversibly fixed; rather, there is some degree of flexibility allowing the manipulation of remodeling the already differentiated effector cell subsets/lineages. From the progress obtained it will be possible, in the near future, to tailor and obtain various well-defined and efficient immune effector cell subsets/cell lineages for translational applications in autoimmunity, infectious diseases, graft rejection as well as cancer in safe conditions.

[Intrahepatic biliary cystic lesions].

Intrahepatic biliary cysts encompass a large lesional spectrum including hereditary diseases as polycystic liver disease or Caroli's syndrome, malformative lesions as non hereditary Caroli's disease or simple biliary cyst and true neoplastic lesions as cystadenoma or cystadenocarcinoma. The diagnostic approach of these lesions relies firstly on imaging. Nevertheless, the pathologist not exceptionally receives surgical specimens from cystic fenestration or liver specimen resection with one or several cystic lesions.

[Therapeutic potential of circulating endothelial cells].

The discovery of circulating endothelial progenitors (EPCs) in human blood has completely modified the concept of post natal angiogenesis. Many studies have further confirmed the existence of EPCs, their medullar origin and capacity to be integrated in vascular structures at the sites of neoangiogenesis. They suggest that EPCs could be naturally involved in the prevention of ischemia by participating directly to the formation of collateral vessels.

[Therapeutic use of stem cells. II. Adult stem cells].

Many degenerative diseases are not curable by means of classical medicine. The long term objective of cell therapy is to treat the patients with their own stem cells that could be either purified from the diseased organ or from "reservoirs" of stem cells such as that constituted by the bone marrow. The existence of stem cells in the organs or reservoirs is now established in vitro and in some cases, in animal models.

[Therapeutic use of stem cells].

Stem cells display important capacities of self renewing, proliferation and differentiation. Because those present in the embryo have the more remarkable properties, their potential use in the therapy of until now incurable degenerative diseases have been envisioned. Embryonic stem (ES) cells are located in the inner mass of the balstocyst at early stages of the development.

[Anxiety disorders and somatic diseases].

Anxious disorders and general medical conditions are often associated both in general population and in primary care. Several etiopathological mechanisms may explain this association. Anxious disorders in medical patients are not enough recognized and treated.

Chemokines and CD40 expression in human fibroblasts.

Chemokines are cytokines specialized for recruiting leukocytes in inflammatory responses. Recent data indicate that besides macrophages and leukocytes fibroblasts may also be a source of these important immune molecules. We assayed chemokine expression (mRNA/ protein) in cultured fibroblasts isolated from a variety of human tissues and different pathologic states: normal bone marrow vs.

Agreement between 'time-blind' and 'time-non-blind' assessments of depressive symptomatology.

In a 4-week study, two methods were used simultaneously in the assessment of depressive symptomatology with videotaped structured clinical interviews: a 'time-non-blind' (TNB) method (chronological order, observer aware of the previous duration of drug treatment) and a 'time-blind' (TB) method (no chronological order, rater unaware of the previous duration of treatment). Sixty newly admitted depressed inpatients with Montgomery-Asberg Depression Rating Scale scores higher than 20 were assessed before (D0), after 10 days (D10) and after 28 days (D28) of antidepressant treatment. Agreement between TNB and TB methods on the Montgomery-Asberg Depression Rating Scale, measured by intra-class correlation coefficients, was good at D0 (0.

Rating antidepressant efficacy with naturalistic live versus structured videotaped interviews.

Two different methods were compared in the assessment of depressive symptomatology improvement: live naturalistic (N) performed by the patient's therapist, and from videotape record of structured clinical interview (VSI) assessed by an independent rater out of five psychiatrists. Sixty-one newly admitted depressed inpatients, with a Montgomery and Asberg Depression Rating Scale (MADRS) total score above 20, were assessed before antidepressant treatment (DO), after 10 days (D10) and 4 weeks of treatment (D28). Assessments were based on the MADRS and the Depression Retardation Rating Scale (DRRS) for both N and VSI methods, and on the SCL-90-R for self-rating.

Efficacy of tianeptine in major depressive disorders with or without melancholia.

The efficacy of tianeptine in the treatment of major depressive episodes was assessed in three double-blind placebo-controlled studies. In a first double-blind study comparing tianeptine (37.5 mg/day) with placebo, 126 patients with Major Depression or a Depressed Bipolar Disorder were treated for 42 days; 60% of these patients fulfilled DSM-III-R criteria for melancholia.

Newborn blood used as a source of donor cells in a murine model of transplantation across non-MHC antigens.

Cells derived from human cord blood instead of bone marrow were recently used for transplantation. However, several questions concerning the potential of this source of cells to reconstitute the hematopoietic and immunologic system of the recipient and to induce graft-versus-host disease (GVHD) remain unanswered. We used newborn blood (NBB) cells from B10.

Functional and biochemical properties of a mouse placental immunoregulatory factor.

The authors have a long standing interest in immune regulations which control the absence of rejection of a semi-allogeneic fetus by the mother. A previous work described a soluble 40 kDa factor extracted from mouse placenta and capable of inhibiting secondary immune responses in vitro. The present paper reports the following on its mode of action in vivo: (1) it is active even in a fully allogeneic host; (2) it can be administered i.

Allogenic MHC class II determinant(s) in MRL/Ipr autoimmune disease-prone mice. Unusual expression of an L1 transposable element creates molecular mimicry.

In some aged MRL/Ipr autoimmune disease-prone mice, unexpected reactivity has been observed between lymphoid cells and mAb or polyclonal antibodies directed against the A beta d class II chain of the MHC. However, Southern blot analysis of their genomic DNA, using different class I and class II MHC-specific probes, confirmed their inbred character and their H-2k genotype. In this study, immunoprecipitation experiments with an anti-A beta d mAb indicated that the 45 (and 12)-kD molecule(s) recognized by an anti-A beta d mAb differed from a class II chain.

[Treatment with rilmenidine 1 mg per day: time-lag to maximum response. A multicenter ambulatory study. Le Groupe Français d'étude Multicentrique d'Hyperium].

Forty-four placebo-resistant patients (mean age: 59.2 +/- 2.1 years; mean weight: 70.

Induction and suppression of delayed-type hypersensitivity to non-MHC antigens during lethal graft-versus-host reaction.

A delayed-type hypersensitivity reaction (DTH) to non-MHC Ag was detected during a lethal graft-vs-host reaction (GVH) induced by incompatibility for non-MHC Ag alone. In this model, when appropriate doses of B10.D2 bone marrow and lymphoid cells are grafted to irradiated (DBA/2 x B10.

[Limitations of efficacy of chemotherapies in schizophrenia].

The concept of treatment-resistant schizophrenia cannot be defined as this of resistant depression: schizophrenia is a long-term illness; its evolution is almost always influenced by neuroleptics--but complete recovery is rare. French psychiatry tends to use clinical-empirical criteria, while english speaking studies prefer quantitative criteria, by extended use of clinical and psycho-social scales. The definition of resistant schizophrenia by Kane et al.