The retrospectroscope: electrocorticography

Recording the electrical activity of the exposed brain, known as an electrocorticogram (ECoG), has had a long history. Multichannel recordings from the exposed brain cortex of conscious human patients as a diagnostic procedure to localize epileptic foci began in the early 1940s. Two centers, one at McGill University and the other at Harvard University launched this new field. Relatively unrecognized at that time were the severe requirements for recording microvolt signals in the electrically hostile environment of the operating room. Not only did the electrodes have to be electrically stable initially, but they had to be stable and noise-free after steam sterilization. In 1945, one of the authors (LAG) joined the staff of the Montreal Neurological institute and the Department of Electrical Engineering, both of McGill University, and became deeply involved with the development of ECoG equipment for permanent installation in Wilder Penfield's operating room. The design goal was that the ECoG and electrodes would function on command. Because it required less than one half hour to steam sterilize the electrodes, a surgical procedure could be scheduled at any time, providing the ECoG and electrodes would perform on command     

A common factor regulates both Th1- and Th2-specific cytokine gene expression

Murine T helper cell clones are classified into two distinct subsets, T helper 1 (Th1) and T helper 2 (Th2), on the basis of cytokine secretion patterns. Th1 clones produce interleukin-2 (IL-2), tumor necrosis factor-beta (TNF-beta) and interferon-gamma (IFN-gamma), while Th2 clones produce IL-4, IL-5, IL-6 and IL-10. These subsets differentially promote delayed-type hypersensitivity or antibody responses, respectively. The nuclear factor NF-AT is induced in Th1 clones stimulated through the T cell receptor-CD3 complex, and is required for IL-2 gene induction. The NF-AT complex consists of two components: NF-ATp, which pre-exists in the cytosol and whose appearance in the nucleus is induced by an increase of intracellular calcium, and a nuclear AP-1 component whose induction is dependent upon activation of protein kinase C (PKC). Here we report that the induction of the Th2-specific IL-4 gene in an activated Th2 clone involves an NF-AT complex that consists only of NF-ATp, and not the AP-1 component. On the basis of binding experiments we show that this 'AP-1-less' NF-AT complex is specific for the IL-4 promoter and does not reflect the inability of activated Th2 cells to induce the AP-1 component. We propose that NF-ATp is a common regulatory factor for both Th1 and Th2 cytokine genes, and that the involvement of PKC-dependent factors, such as AP-1, may help determine Th1-/Th2-specific patterns of gene expression.     

In vitro isolation and identification of human immunodeficiency virus (HIV) variants with reduced sensitivity to C-2 symmetrical inhibitors of HIV type 1 protease

Protease inhibitors are another class of compounds for treatment of human immunodeficiency virus (HIV)-caused disease. The emergence of resistance to the current anti-HIV drugs makes the determination of potential resistance to protease inhibitors imperative. Here we describe the isolation of an HIV type 1 (HIV-1) resistant to an HIV-protease inhibitor. Serial passage of HIV-1 (strain RF) in the presence of the inhibitor, [2-pyridylacetylisoleucylphenylalanyl-psi (CHOH)]2 (P9941), failed to yield a stock of virus with a resistance phenotype. However, variants of the virus with 6- to 8-fold reduced sensitivity to P9941 were selected by using a combination of plaque assay and endpoint titration. Genetic analysis and computer modeling of the variant proteases revealed a single change in the codon for amino acid 82 (Val-->Ala), which resulted in a protease with lower affinity and reduced sensitivity to this inhibitor and certain, but not all, related inhibitors.     

Adam-Gibbs Formulation of Enthalpy Relaxation Near the Glass Transition

The entropically based nonlinear Adam-Gibbs equation is discussed in the context of phenomenologies for nonlinear enthalpy relaxation within the glass transition temperature range. In many materials for which adequate data are available, the nonlinear Adam-Gibbs parameters are physically reasonable and agree with those obtained from linear relaxation data and thermodynamic extrapolations. Observed correlations between the traditional Tool-Narayanaswamy-Moynihan parameters are rationalized in terms of the Adam-Gibbs primary activation energy (Δμ) determining how close the kinetic glass transition temperature can get to the thermodynamic Kauzmann temperature. It is shown that increased nonlinearity in the glass transition temperature range is associated with greater fragility in the liquid/rubber state above T_g.     

Dispersed phase destabilization in table spreads

Commercially available butter, regular-fat margarine, and a fat-reduced margarine (38% fat w/w) were stored between 10 and 35°C for up to 4 d to elaborate on the relationship between droplet size and solid fat content (SFC) that exists in these spreads. At 10°C, the mean volume-weighted droplet size for butter was 4.22±0.40 μm followed by margarine (6.22±0.10 μm) and fat-reduced margarine (12.62±0.28 μm). At higher temperatures, as a result of decreasing SFC, the mean droplet size increased as did the droplet size distribution, leading to eventual coalescence and destabilization in all spreads. In butter, the critical SFC was ∼9%, whereas in margarine notable coalescence occurred at ∼5% SFC. The fat-reduced margarine destabilized at lower temperatures than the other spreads (∼20°C vs. ∼30°C), at an SFC of ∼6.5%. In these spreads, two different mechanisms influenced dispersed phase stability: (i) steric stabilization against coalescence via fat crystals located at the droplet interface, known as Pickering stabilization, and (ii) stabilization against droplet sedimentation (and droplet encounters) due to the presence of the fat crystal network.     

Amino-hexose-reductones as antioxidants. I. Vegetable oils

Summary Amino-hexose-reductones were evaluated as antioxidants in soybean, cottonseed, and corn oils and were shown to be highly effective by all oxidative and chemical tests. The activity of the eight different reductones was approximately the same in any one substrate. Slightly higher activities were given by reductones of lower molecular weight. Activity was demonstrated at concentrations as low as 0.001% and was shown to be a linear function of the concentration up to 0.02%, the approximate limit of solubility. Out-standing features of the reductone-treated oils were long induction periods, slow absorption of oxygen, and low rates of peroxide development. Reductones are believed not to react directly with peroxides but to prevent peroxide formation by reacting with some precursor. The combination of reductones with other antioxidants showed synergistic effects in only one sample of corn oil. The activity of combinations in soybean and cottonseed oils was for the most part strictly additive. In soybean oil, citric acid-reductone combinations with each at the 0.01% level gave a slight improvement over the expected activity. Oils stabilized with multiple-component, antioxidant mixtures in which an amino reductone replaced propyl gallate showed less peroxide development and were equally acceptable according to organoleptic scores. Aged oils did not show the organoleptic improvement that would be expected from the marked improvement observed in the oxidative stability. Significant improvements in flavor stability could be observed with reductones only when they were used in combination with an-other antioxidant. Reductone-treated soybean and cottonseed oils did not show an appreciable improvement in flavor stability. Only the di-n-butylamino-and diallylamino-reductones contributed foreign flavors to the oil. Atypical flavors are believed associated with the amine moiety of the reductone. At high temperatures and at higher concentrations of reductones a brown melanoid color develops in the oil. The anhydro derivatives developed more color than the normal reductone. The reductones do not withstand oil deodorization conditions. Presented at the meeting of the American Oil Chemists' Society, Chicago, Ill. September 23–26, 1956.