Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice

Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.     

Sources of cortical rhythms change as a function of cognitive impairment in pathological aging: a multicenter study.

OBJECTIVE: The present study tested the hypothesis that cortical electroencephalographic (EEG) rhythms. change across normal elderly (Nold), mild cognitive impairment (MCI), and Alzheimer's disease (AD) subjects as a function of the global cognitive level. METHODS: Resting eyes-closed EEG data were recorded in 155 MCI, 193 mild AD, and 126 age-matched Nold subjects. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). EEG cortical sources were estimated by LORETA. RESULTS: Occipital delta and alpha 1 sources in parietal, occipital, temporal, and 'limbic' areas had an intermediate magnitude in MCI subjects compared to mild AD and Nold subjects. These five EEG sources presented both linear and nonlinear (linear, exponential, logarithmic, and power) correlations with the global cognitive level (as revealed by mini mental state examination score) across all subjects. CONCLUSIONS: Cortical EEG rhythms change in pathological aging as a function of the global cognitive level. SIGNIFICANCE: The present functional data on large populations support the 'transitional hypothesis' of a shadow zone across normality, pre-clinical stage of dementia (MCI), and AD.     

The role of donor and recipient factors in initial renal graft non-function

ATN is a deleterious problem in the outcome of kidney transplantation. This complication is usually related to multiple factors including donor parameters, surgical technique, ischemic time, and recipient variables. In order to develop prophylactic measures, out of 430 kidney transplants performed in our Department, a series of 90 consecutive cadaveric renal allografts has been considered in this study. The overall incidence of IGNF was 23/90 (25.5%). Kidneys from MOD revealed a lower rate of IGNF (7/35 = 20%) when compared with organs from SOD (16/55 = 29%, P = NS). No difference was noted when kidneys were removed together with heart and/or liver and/or pancreas. Out of the donor factors, only CID was significant (17 +/- 9 hours in IGNF v 11 +/- 10 hours in patients with IGF, P = less than .05). Analysis of data concerning the fate of paired kidneys revealed two cases of IGNF in both kidneys from the same donor v 14 cases of IGNF in only one of the two paired grafts (P = NS). We conclude that: 1. Donor factors are clearly associated with a minority of IGNF. 2. The introduction of multiorgan procurement programs does not complicate early function. 3. Recipient factors (immunological events and intraoperative fluid management) provides important additive effects on initial graft nonfunction.     

Gamma interferon modifies CD4+ subset expression in murine candidiasis.

A single injection of monoclonal antibody to gamma interferon administered in conjunction with a live Candida albicans yeast cell vaccine resulted in the detection of nonprotective Th2 rather than protective Th1 responses and altered the early expression of interleukin 4 and gamma interferon mRNA in CD4+ cells.     

Dystonia gravidarum: a new case with a long follow-up.

We report a case of cervical dystonia occurring in a 33-year-old without personal history of movement disorder but with family history of essential tremor, primigravid, primiparous woman at 1 weeks' amenorrhea, resolved completely after delivery in the course of 3 months. Dystonia never recurred in the following 5 years. Several neurological disorders are known to occur or worsen during pregnancy. As far as we know, this is the second reported case of dystonia occurring during pregnancy, thus confirming that dystonia gravidarum represents a new entity and should be considered in women of reproductive age affected by dystonia, especially when presenting with rapid-onset cervical dystonia.     

An antigen-independent contact mechanism as an early step in T cell- proliferative responses to dendritic cells

Dendritic cells bearing antigen efficiently aggregate and stimulate antigen-specific T cells. We describe an experimental model in which an initial, apparently antigen-independent binding step is followed by ligation of the TCR. The model is the polyclonal response to mAb to the CD3 portion of the TCR complex. Epidermal and thymic dendritic cells utilize low levels of Fc receptors to present the anti-CD3 mAb and induce mitogenesis. Within 3 h of coculture, most of the dendritic cells have formed clusters with the resting T lymphocytes, and these clusters are the site for subsequent DNA synthesis and cell growth. However, the binding of dendritic cells to T cells proceeds as efficiently in the absence of anti-CD3 as in its presence, and anti-FcR mAb does not block. CD3 and Fc receptors are essential for the subsequent mitogenesis response in dendritic-T cell clusters. Because an exogenous ligand for the TCR does not seem to be required for the extensive polyclonal clustering of resting lymphocytes to dendritic cells, we suggest that an antigen-independent mechanism mediates the initial interaction. This clustering seems essential for T cell growth since we do not detect, in two-chamber experiments, soluble lymphocyte-activating factors that originate from dendritic-T cell aggregates and that activate anti-CD3-coated T cells.     

Eye movement quantitative evaluation before and after high-dose 6-methylprednisolone in multiple sclerosis

We studied saccadic and smooth pursuit eye movements in 24 patients suffering from multiple sclerosis during disease worsening, before and after high-dose 6-methylprednisolone infusions. Quantitative evaluation of saccades was based on amplitude/duration and amplitude/peak velocity relationships, precision (i.e. the ratio of actual to desired saccade amplitude) and the latency, whereas smooth pursuit eye movements were studied using target velocity/performance index relationship. At basal recordings, 22/24 (91.7%) of the patients showed at lest one abnormality. Eleven of the 24 patients (45.8%) showed modification of one or several parameters: improvement in 6 patients, worsening in 2, coexistence of both trends in 3. Latency improvement was the only significant modification when patients were considered as a group. Neurophysiological modifications did not correspond to clinical changes.