A Field-Compatible Method for Interpolating Biopotentials

Mapping of bioelectric potentials over a given surface (e.g., the torso surface, the scalp) often requires interpolation of potentials into regions of missing data. Existing interpolation methods introduce significant errors when interpolating into large regions of high potential gradients, due mostly to their incompatibility with the properties of the three-dimensional (3D) potential field. In this paper, an interpolation method, inverse-forward (IF) interpolation, was developed to be consistent with Laplace's equation that governs the 3D field in the volume conductor bounded by the mapped surface. This method is evaluated in an experimental heart–torso preparation in the context of electrocardiographic body surface potential mapping. Results demonstrate that IF interpolation is able to recreate major potential features such as a potential minimum and high potential gradients within a large region of missing data. Other commonly used interpolation methods failed to reconstruct major potential features or preserve high potential gradients. An example of IF interpolation with patient data is provided to illustrate its applicability in the actual clinical setting. Application of IF interpolation in the context of noninvasive reconstruction of epicardial potentials (the inverse problem) is also examined. © 1998 Biomedical Engineering Society. PAC98: 8710+e, 0260Ed     

Contribution of redox-active iron and copper to oxidative damage in Alzheimer disease

Metal-catalyzed hydroxyl radicals are potent mediators of cellular injury, affecting every category of macromolecule, and are central to the oxidative injury hypothesis of Alzheimer disease (AD) pathogenesis. Studies on redox-competent copper and iron indicate that redox activity in AD resides exclusively within the neuronal cytosol and that chelation with deferoxamine, DTPA, or, more recently, iodochlorhydroxyquin, removes this activity. We have also found that while proteins that accumulate in AD possess metal-binding sites, metal-associated cellular redox activity is primarily dependent on metals associated with nucleic acid, specifically cytoplasmic RNA. These findings indicate aberrations in iron homeostasis that, we suspect, arise primarily from heme, since heme oxygenase-1, an enzyme that catalyzes the conversion of heme to iron and biliverdin, is increased in AD, and mitochondria, since mitochondria turnover, mitochondrial DNA, and cytochrome C oxidative activity are all increased in AD. These findings, as well as studies demonstrating a reduction in microtubule density in AD neurons, suggest that mitochondrial dysfunction, acting in concert with cytoskeletal pathology, serves to increase redox-active heavy metals and initiates a cascade of abnormal events culminating in AD pathology.     

Ontogenesis of learning. II. Variation in the rat's reflexive and learned responses to acoustic stimulation

The onotogenesis of the rat's reflexive and simple learned reactions to acoustic stimulation was investigated in five experiments. The pattern of restults suggests that (a)reflexive reactions to tonal stimulation emerge earleir in ontogenesis that the capacity to learn about thses stimuli, and (b)the age at which simple Pavlovian conditioning is first obsrved depedens on the nature of the acoustic conditioned stimulus (CS). Specifically, these data suggest that pups are not capable of simple Pavlovian conditioning to a 2000hyphen;Hz tone (CS) paired with an oral infusion of sucrose (US) until they are 14–15 days old. The same acoustic stimulus will, however, evoke reflexive reactions (startle inspiration) in pups as young as 10–12 days old. Additionally when a different auditory stimulus (an intermittent trains of clicks) serves as the CS, there is evidence of conditioning in pups only 12–13 days old. It is suggested that these age-related dissociations in the emergence of reflexive and simple learned responses to sound reflect a caudal-to-rostral maturational sequence of the components of the ascending auditory system.     

Moderation of physiological stress responses by personality traits and daily hassles: less flexibility of immune system responses

Previously we demonstrated that stressors varying on the dimension of mental effort and controllability have distinctive effects on cardiovascular, endocrine and immune system responses. The purpose of the present study was to relate individual differences in physiological stress responsivity to task appraisal and stress-induced mood changes (issue 1), trait characteristics (issue 2) and daily hassles (issue 3). Appraisal and mood changes did not mediate the differential effects of the stressors. The trait characteristics, aggression and external locus of control and daily hassles moderated the effect of the stressor on physiological parameters, especially immune parameters. Moreover, the moderation effect was different in the high versus the low effort stress task. High aggression, high external locus of control and more daily hassles were associated with increased reactivity in the low effort condition and decreased reactivity in the high effort condition, which is suggested to reflect less differentiated responding to changing task demands and hence, less flexibility in the immune system.     

Destruction of the sodium conductance inactivation by a specific protease in perfused nerve fibres from Loligo.

Intracellular perfusion of giant axons from Loligo forbesi with a crude protein extract of Pronase dissolved in a KF solution suppresses the process of fast inactivation of the Na conductance (the h-process in the Hodgkin-Huxley terminology). 2. The results with protease inhibitors indicate that the most substrate specific endopeptidase present in pronase, alkaline proteinase b, destroys the h-process. 3. After destruction of the inactivation the conductance rise upon depolarization followed cube law kinetics. Values of the time constant taum before and after destruction of the h-process were very similar. 4. After destruction of the inactivation process the following properties were tested: cation selectivity, instantaneous conductance and internal receptor sites for tetrodotoxin (TTX) and tetraethylammonium (TEA). No detectable changes in selectivity or instantaneous conductance were observed. No internal receptors for TTX affecting the Na conductance were found but a TEA receptor is exposed by the protein hydrolysis. 5. TEA derivatives (triethylammonium, TEA-, with an aliphatic chain, Cn) induce a partial block of the steady-state sodium current and induce a time-dependent blockage of the conductance. 6. The first effect of TEA-Cn could be described in terms of a unimolecular reaction with the following equilibrium constants: 50, 2-5, 1-0, 0-4 and 0-025 mM for TEA-C2, TEA-C4, TEA-C5, TEA-C7 and TEA-C9 respectively. 7. From the dependence of the equilibrium dissociation constant on the length of the alkyl chain we estimated the free-energy change in 560 cal/mole of CH2. The gain in free energy per CH2 group transferred from aqueous medium to the interior of a non-polar medium is 1000 cal. 8. Although with the data at hand it is impossible to propose the amino-acid sequence of the site cleaved by alkaline proteinase b, we propose that an important functional component is arginine (or lysine).     

Cluster-Randomized Controlled Trial of An Athletic Trainer-Directed Spit (Smokeless) Tobacco Intervention for Collegiate Baseball Athletes: Results After 1 Year

Context: Athletes in the United States are at high risk for using spit (smokeless) tobacco (ST) and incurring its associated adverse health effects.Objective: To examine whether an athletic trainer-directed ST intervention could decrease initiation and promote cessation of ST use among male collegiate baseball athletes.Design: Stratified, cluster-randomized controlled trial.Setting: Fifty-two California colleges.Patients or Other Participant(s): A total of 883 subjects in 27 intervention colleges and 702 subjects in 25 control colleges participated, as did 48 certified athletic trainers.Intervention(s): For college athletic trainers and associated dental professionals, a 3-hour video conference, and for collegiate athletes, an oral cancer screening with feedback and brief counseling during the preseason health screenings, athletic trainer support for cessation, and a peer-led educational baseball team meeting.Main Outcome Measure(s): The subjects' ST use over 1 year was assessed by self-report. At the end of the study, the certified athletic trainers were mailed a survey assessing their tobacco use and perceptions and behavior related to tobacco control in the athletic environment. We used multivariable logistic regression models for clustered responses (generalized estimating equations) to test the difference between groups in ST-use initiation and cessation and to identify significant overall predictors of noninitiation and cessation of ST use.Results: Of the 1585 athletes recruited, 1248 (78.7%) were followed up at 12 months. In addition, 48 of the 52 athletic trainers (92%) responded to the 1-year follow-up survey. The ST-use initiation (incidence) was 5.1% in intervention colleges and 8.4% in control colleges (generalized estimating equation odds ratio = 0.58, 95% confidence interval = 0.35-0.99). Predictors of ST noninitiation were low lifetime tobacco and monthly alcohol use (odds ratio = 1.98, 95% confidence interval = 1.40- 2.82) and athletic trainers' report that the baseball coach supported ST-use prevention activities (odds ratio = 1.43, 95% confidence interval = 1.11-1.83). Although at 1 year, cessation of ST use was relatively high in both groups (36%), we noted no significant difference between the groups (odd ratio = 0.94, 95% confidence interval = 0.70-1.27).Conclusions: The intervention was significantly effective in preventing incident ST use but did not significantly increase cessation beyond that seen in the control group. The latter finding is inconsistent with previous studies and may be explained by spillover of the intervention to control colleges, other anti-tobacco activity in control colleges, and/or the small sample of dependent ST users enrolled in the study.     

Gene transfer of costimulatory molecules into a human colorectal cancer cell line: requirement of CD54, CD80 and class II MHC expression for enhanced immunogenicity.

Colorectal cancer is considered a non-immunogenic malignany. One strategy to augment the immunogenicity of such tumours is represented by the expression of costimulatory molecules by gene transfer. Using transfected variants of the human colorectal cancer cell line SW480 we tested various costimulatory molecules (CD80, CD86, CD54) and a class II major histocompatibility complex (MHC) allele (HLA-DR3) alone or in combination on their ability to support primary T-lymphocyte activation in vitro. Expression of CD80 or CD86 similarly as the combination of both was not sufficient to induce proliferation of human allogeneic T cells. Expression of CD54 together with CD80 strongly augmented the costimulatory function of CD80, as observed in the presence of a CD3 monoclonal antibody (mAb), but did not lead directly to a T-cell response against modified tumour cells. Importantly, SW480 cells coexpressing CD54, CD80 and the HLA-DR3 allele effectively promoted T-lymphocyte proliferation. Moreover, the use of such CD54+/CD80+/HLA-DR3+ SW480 variants for repetitive stimulations resulted in the generation of T-cell lines predominantly composed of CD8+ T cells exhibiting class I MHC restricted cytolytic activity towards untransfected SW480 tumour cells. This demonstrates that the generation of immunogenic tumour cell variants, i.e. for the use as cellular vaccines, requires multiple genetic alterations in the case of non-immunogenic human tumours cells, such as colorectal cancer cells.