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.     

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.     

Short-term brain ‘plasticity’ in humans: transient finger representation changes in sensory cortex somatotopy following ischemic anesthesia

Transient rearrangements of finger representation in primary somatosensory cortex induced by an anesthetic block of the sensory information from adjacent fingers have been shown invasively in animals. Such a phenomenon has been now replicated in seven healthy human volunteers. Somatosensory Evoked Fields (SEFs) have been recorded during separate electrical stimulation of the 1st, 3rd, or 5th finger. Recordings were obtained in control conditions (stage A), following complete ischemic anesthesia of the 4 non-stimulated fingers (stage B), and after regaining sensation (stage C). SEFs were recorded using a 28-channel DC-SQUID magnetometer; a single position of the sensor was enough to identify the source of N20m, P30m and following components using the Equivalent Current Dipole (ECD) model. The amount of afferent input during stages A through C was monitored with surface electrodes placed on the nerve at wrist and elbow. No variation of the nerve compound potential was observed during stages A through C. In stage A, the localizing algorithm was able to discriminate the individual finger representation in accordance with the somatotopic organisation of the sensory homunculus. It was observed that the ECDs responsible for the cortical responses from the unanesthetized finger were significantly changing following a relatively brief period of sensory deprivation from the adjacent fingers. Such changes of the ECDs with respect to the control conditions were characterized by an increase in strength and deepening for the middle finger, and by a shift on the coronal plane for the thumb and the little finger (medial for the former, lateral for the latter). Such changes became progressively evident in stage B, but were persisting in stage C.     

Antigen-specific cytolysis of infected cells in murine candidiasis

Immune L3T4+ and Lyt-2+ lymphocytes play an important role in the acquired resistance of mice to challenge with virulent Candida albicans, and release macrophage-activating cytokines in response to yeast cells in vitro. To determine whether antigen (Ag)-specific cytotoxic T lymphocytes are generated during fungal infection, purified L3T4+ and Lyt-2+ lymphocytes from immunized mice were cultured in the presence of syngeneic accessory cells, Candida Ag, and IL-2. Yeast-infected bone marrow macrophages and peritoneal exudate neutrophils were used as target cells in a standard ⁵¹Cr release assay. Ag-specific, MHC-unrestricted lysis of infected macrophages was evident with immune Lyt-2+ cells after 5–10 days in culture. Under the same experimental conditions, the cytotoxic activity of L3T4+ cells was negligible, but its expression could be induced by the addition of anti-CD3 antibody.Culturing immune Lyt-2+ cells for shorter periods of time (1–2 days) resulted in preferential lysis of infected neutrophils. In addition, at limiting effector cell numbers, Ag-specific MHC-restricted lymphocytes with cytotoxic activity to infected macrophages could be identified. We suggest that C. albicans infection stimulates multiple cytotoxic T-cell precursors with varying recognition stringency, wich may have an important role in antifungal resistance in vivo.     

Short latency somatosensory evoked responses to median nerve stimulation in healthy humans: electric and magnetic recordings

Somatosensory Evoked Potentials (SEPs) and Somatosensory Evoked magnetic Fields (SEFs) to median nerve stimulation at wrist were recorded in 5 healthy subjects and the components between 15 and 30 ms after the stimulus were evaluated on the hemiscalp contralateral to the stimulated wrist. SEPs were measured by means of a 32-channel recorder and compared with SEFs obtained via multiple measurements with a 4-channel sensor. Equivalent dipole localization was carried out for the magnetic components peaking at about 15, 20 and 24 ms. The scalp distribution of SEPs, illustrated by bit mapped color images, were qualitatively explained by three separate sources. The first is described as a tangentially oriented dipole placed behind the Central Sulcus and responsible for the parietal N20-"late P25" waves and for the frontal P20-N30 ones. The second is represented by a radieal dipole placed just in front of the Central Sulcus and pointing towards the motor strip, responsible for the rolandic P22 component. The third is just behind the Central Sulcus and is radieally oriented towards the surface of the postcentral sensory area for the "early P25" parietal wave. The SEFs distributions, illustrated by color isofield contour maps, were quantitatively explained by a unique tangential dipole localized, with good resolution, well behind the Sulcus for the 15 ms waves and slightly frontal to this site for the waves peaking at around 20 and 24 ms. The equivalent dipole has been localized at a depth of about 5 cm (15 ms component), 2 cm (20 ms components) and 4 cm (24 ms component), across the studied subjects. It is stressed that the dipole responsible for the magnetic pattern is likely to be the same tangential dipole responsible for a part of the electric pattern. Due to their radieal orientation, the other two dipoles, proposed for the SEPs maps, would be mostly undetectable by a magnetic investigation.     

Determination of rate-constants as a method to describe passive expiration

To describe the relaxed expiration by a two-compartment model, we introduced a gas/energy transfer between the lung compartment (V₁) and a second one (V₂). If V₂ were a real volume, the rate-constants (i.e. the flow/volume ratios) of the compartments would describe a real gas-exchange. Alternatively, if a viscoelastic behaviour of the lung or an energy-exchange between compartments was simulated, V₂ would become a "pseudo-volume". We studied nine mechanically ventilated subjects. Changes in volume were transduced by respiratory inductive plethysmography. The rate-constants were assumed (together with the initial volumes of the compartments) as parameters to fit the total volume [V₁(t)+V₂(t)]. Once the best fitting was performed using these "physiological" parameters, the system was directly identified and the compartments were independently analysed. The time profile of the second compartment showed a maximum that depended on the value of the rate-constants. Appropriate tests confirmed the reliability of our procedure. In conclusion, our analysis demonstrated that the energy/volume of the second compartment may increase at the beginning of expiration and then decrease, showing a maximum, even though the total curve can only be a decreasing one. In other words, the slowing down of the curve representing expiratory volume is due not only to the longer emptying of the second compartment, but also to the interaction between the two compartments. As presently proposed, this interaction can be represented by either a gas exchange between two actual volumes, or a mechanical energy transfer between the lung and the tissue compartment.     

Protection of killer antiidiotypic antibodies against early invasive aspergillosis in a murine model of allogeneic T-cell-depleted bone marrow transplantation

Antiidiotypic monoclonal antibodies (MAbs) representing the internal image of a yeast killer toxin (KT) have therapeutic potential against several fungal infections. The efficacy of KT MAbs against Aspergillus fumigatus was investigated in a mouse model of T-cell-depleted allogeneic bone marrow transplantation (BMT) with invasive pulmonary aspergillosis. Mice were highly susceptible to infection at 3 days post-BMT, when profound neutropenia was observed both in the periphery and in the lungs. Treatment with KT MAbs protected the mice from infection, as judged by the long-term survival and decreased pathology associated with inhibition of fungal growth and hyphal development in the lungs. In vitro, similar to polymorphonuclear neutrophils, KT MAbs significantly inhibited the hyphal development and metabolic activity of germinated Aspergillus conidia. These results indicate that mimicking the action of neutrophils could be a strategy through which KT MAbs exert therapeutic efficacy in A. fumigatus infections.