Members of the hSWI/SNF chromatin remodeling complex associate with and are phosphorylated by protein kinase B/Akt.

In an adenosine triphosphate (ATP)-dependent process, the hSWI/SNF chromatin remodeling complex functions to alter chromatin structure, thereby regulating transcription factor access to DNA. In addition to interactions with transcription factors and recognition of acetylated histone residues, the chromatin remodeling activity of hSWI/SNF has also been shown to respond to a variety of cell signaling pathways. Our results demonstrate a novel interaction between the serine/threonine kinase Akt and members of the hSWI/SNF chromatin remodeling complex. Activation of Akt in HeLa cells resulted in its association with hSWI/SNF subunits: INI1, BAF155 and BAF170, as well as actin. BAF155 became preferentially recognized by an antibody that detects phosphorylated Akt substrates upon activation of Akt, suggesting that BAF155 may be an in vivo target for phosphorylation by Akt. Glutathione-S-transferase (GST) pulldown experiments demonstrated that INI1 and BAF155 were both capable of directly interacting with Akt. Finally, in vitro kinase assays provided additional evidence that BAF155 and potentially INI1 are substrates for Akt phosphorylation. These data provide the first evidence that Akt signaling may modulate function of the hSWI/SNF complex.

Impedance-gradient electrode reduces skin irritation induced by transthoracic defibrillation.

A new type of disposable external defibrillation electrode has been developed to reduce the skin irritation commonly associated with defibrillation and synchronised cardioversion. This design employs an impedance gradient to reduce the proportion of current delivered to the electrode periphery. The temperature distribution under the new electrode was compared with that of four other types of commercially available electrodes after repeated high-energy biphasic defibrillation discharges to domestic swine. Skin temperature distributions were acquired using non-invasive thermography. Measurements of the maximum temperature rise at each electrode site, taken 3.6s after the fifth defibrillation discharge, demonstrated that the new impedance-gradient electrode produced 50-60% less skin heating than two of the three uniform-impedance electrode designs. Histological examination of erythematous sites excised 24 h after defibrillation quantified the associated skin damage using a scoring protocol developed for this study. In contrast to previous studies, histological examinations demonstrated second-degree skin burns following defibrillation. The new electrode design, however, induced 44-46% less skin damage than two of the traditional uniform-impedance electrodes.

An adaptive noise reduction stethoscope for auscultation in high noise environments.

Auscultation of lung sounds in patient transport vehicles such as an ambulance or aircraft is unachievable because of high ambient noise levels. Aircraft noise levels of 90-100 dB SPL are common, while lung sounds have been measured in the 22-30 dB SPL range in free space and 65-70 dB SPL within a stethoscope coupler. Also, the bandwidth of lung sounds and vehicle noise typically has significant overlap, limiting the utility of traditional band-pass filtering. In this study, a passively shielded stethoscope coupler that contains one microphone to measure the (noise-corrupted) lung sound and another to measure the ambient noise was constructed. Lung sound measurements were made on a healthy subject in a simulated USAF C-130 aircraft environment within an acoustic chamber at noise levels ranging from 80 to 100 dB SPL. Adaptive filtering schemes using a least-mean-squares (LMS) and a normalized least-mean-squares (NLMS) approach were employed to extract the lung sounds from the noise-corrupted signal. Approximately 15 dB of noise reduction over the 100-600 Hz frequency range was achieved with the LMS algorithm, with the more complex NLMS algorithm providing faster convergence and up to 5 dB of additional noise reduction. These findings indicate that a combination of active and passive noise reduction can be used to measure lung sounds in high noise environments.

Skin-temperature distribution under a new type of defibrillating electrode.

The temperature rises under a new type of x-ray-transparent, improved current-density-distribution defibrillation electrode applied to pig skin were measured at four sites with fiberoptic thermal probes. Three anesthetized pigs, ranging in weight from 79 to 92 lb, were used. Temperature-time curves were obtained and the maximum temperature was identified. For 17 measurements at each site, the maximum temperature rise for a 360-joule shock was 317.3 +/- 53.0 millidegrees Celsius.

The effect of elevated intracranial pressure on the vibrational response of the ovine head.

Although potentially fatal increases in intracranial pressure (ICP) can occur in a number of pathological conditions, there is no reliable and noninvasive procedure to detect ICP elevation and quantitatively monitor changes over time. In this experimental study, the relationships between ICP elevation and the vibrational response of the head were determined. An ovine animal model was employed in which incremental increases in ICP were elicited and directly measured through intraventricular cannulae. At each ICP increment, a vibration source elicited a flexural response of the animal's head that was measured at four locations on the skull using accelerometers. Spectral analysis of the responses showed changes in proportion to ICP change up to roughly 20 cm H2O (15 mm Hg) above normal; a clinically significant range. Both magnitude and phase changes at frequencies between 4 and 7 kHz correlated well (gamma > 0.92) with ICP across the study group. These findings suggest that the vibrational response of the head can be used to monitor changes in ICP noninvasively.

Detection of pulse and respiratory signals from the wrist using dry electrodes.

A dry, tetrapolar electrode array was used to detect the differential impedance signal at the wrists of 11 adult human subjects. Experiments were conducted to determine the importance of potential-sensing electrode spacing to detect each wearer's pulse rate and respiratory rate. The current-injecting electrodes were at the sides of the wrist; the potential-sensing electrodes were on the volar wrist surface. The bandwidth-filtered root-mean-square amplitudes of the pulse and respiratory components were computed and found to increase with increasing electrode spacing. Optimum spacings were slightly different for the pulse and respiration and were slightly different in the male and female subjects. A spacing for the potential electrodes of about 60% of the wrist hemicircumference is a good compromise for detecting respiration and pulse.

Closed-chest cardiac stimulation with a pulsed magnetic field.

Magnetic stimulators, used medically, generate intense rapidly changing magnetic fields, capable of stimulating nerves. Advanced magnetic resonance imaging systems employ stronger and more rapidly changing gradient fields than those used previously. The risk of provoking cardiac arrhythmias by these new devices is of concern. In the paper, the threshold for cardiac stimulation by an externally-applied magnetic field is determined for 11 anaesthetised dogs. Two coplanar coils provide the pulsed magnetic field. An average energy of approximately 12 kJ is required to achieve closed-chest magnetically induced ectopic beats in the 17-26 kg dogs. The mean peak induced electric field for threshold stimulation is 213 V m-1 for a 571 microseconds damped sine wave pulse. Accounting for waveform efficacy and extrapolating to long-duration pulses, a threshold induced electric field strength of approximately 30 V m-1 for the rectangular pulse is predicted. It is now possible to establish the margin of safety for devices that use pulsed magnetic fields and to design therapeutic devices employing magnetic fields to stimulate the heart.

Use of an electrocardiograph to record the skin-resistance response with a new type of electrode.

A new method is described for recording the emotion-induced decrease in skin resistance area, which is known as the skin-resistance response (SRR). The method employs a simple current source and a new type of tetrapolar electrode in which the SRR is measured with the non-current-carrying electrodes. The signal produced can be recorded with a standard electrocardiograph. Typical SRRs from two subjects are presented.

Comparison of rectangular and exponential current pulses for evoking sensation.

There exists a paucity of quantitative information comparing the stimulating currents for different waveforms. Thus, the objectives of this study was to compare the threshold peak current (I) for sensation using rectangular and exponential; that is, capacitor-discharge, cathodal pulses of equivalent pulse duration (d). In 10 human subjects, stimuli were applied to the skin of the forearm, and I was determined alternately for each current waveform at each of several pulse durations (d). Strength-duration curves for sensation were obtained using d of 0.01-50 ms. The threshold peak current (Ir) for a rectangular pulse of duration d was compared to the threshold peak current (Icd) for a capacitor-discharge pulse of duration d, where d was the time constant; that is, the time required for the current to decrease to 1/e, or 37% of its peak value. Chronaxie, the pulse duration at which I is twice the infinite-duration current asymptote (i.e., the rheobase), was calculated for each waveform and subject using the Weiss-Lapicque expression for excitability. Icd was found to be always higher than Ir of equivalent duration. Chronaxie for the capacitor-discharge pulse was, on the average, twice that for the rectangular pulse (p less than 0.01). Moreover, the ratio Icd/Ir increased with decreasing d. These results indicate that these two waveforms are not equivalent on the basis of an equal-charge requirement for excitation, particularly at the short pulse durations. Furthermore, they suggest the need of a better expression to describe the excitability characteristics of tissues.

The inductorium: the stimulator associated with discovery.

The inductorium, or induction-coil stimulator, introduced in the late 1830s, provided a means for obtaining repetitive stimuli; thereby allowing the discovery of new properties of excitable tissues. Major physiologic discoveries with the inductorium were tetanic contraction of skeletal muscle, inhibition of the heart, the role of vasomotor nerves, and cortical localization. In the hands of clinicians, it was used to diagnose neuromuscular disease and to produce artificial respiration with body-surface electrodes. Because of the historical importance of this tool, its characteristics are described quantitatively. Although it is no longer used, it has a secure place in the history of biomedical instrumentation.

Electroventilation in the baboon.

The optimum sites for chest-surface electrodes and the relationship between the inspired volume of air and stimulus intensity were determined in six pentobarbital-anesthetized baboons. The optimum stimulation sites were identified using hand-held, trans-chest stimulating electrodes. Thereafter, conducting adhesive electrodes 4 cm in diameter were placed over each of the optimal sites. The relationship between inspired volume and stimulus intensity was determined with the forelimbs restrained and unrestrained using an 800-msec burst of 60/sec stimuli with a pulse duration of 20 microseconds. Two optimum stimulation sites were identified, one in the anterior axillary region, and another just lateral to the xiphoid process. The maximum volume of inspired air was obtained when the stimulating electrodes were placed at the anterior axillary sites. With the forelimbs restrained or unrestrained, an increased stimulus intensity resulted in an inspired volume well in excess of the spontaneous tidal volume of the animal. These studies indicate that, with chest-surface electrodes at the optimal locations, electroventilation can produce inspired volumes greater than spontaneous tidal volume in anesthetized baboons. With electrodes in the xiphoid region a smaller maximum inspired volume was obtained because of the stimulation of expiratory (abdominal) muscles.

Choice of the optimum pulse duration for precordial cardiac pacing: a theoretical study.

In precordial pacing with skin-surface electrodes, the goal is to excite the ventricles with minimal stimulation of overlying tissues. A theoretical analysis is presented to identify the relevant factors; the two most important are electrode location and pulse duration. Using the basic law of stimulation, we developed a model which indicates that the optimum pulse duration for the closed-chest pacing pulse is one that is long with respect to the membrane time constant of cardiac muscle. Current-versus-duration curves are presented for pacing and pain, based on experimentally obtained data. For pacing with minimum pain, the optimum stimulus duration was found to be about 10 ms.

Safety factor for precordial pacing: minimum current thresholds for pacing and for ventricular fibrillation by vulnerable-period stimulation.

Temporary cardiac pacing by means of rapidly applied, precordial electrodes can be of great value in selected patients suffering cardiac arrest or profound bradycardia, post-defibrillation atrioventricular block, or digitalis intoxication. This study provides data pertaining to the safety of precordial pacing measured as the ratio of the minimum current required to induce ventricular fibrillation (VF) to the minimum current required to pace the ventricular myocardium. Single rectangular pulse stimuli having durations of 1-50 ms were evaluated. In 6 anesthetized dogs, a cutaneous electrode was centered over the shaved apex beat area of the left chest and paired with a larger electrode sutured to the right chest wall. Using a specially fabricated, synchronized, high-energy pulse generator, the "most vulnerable" time in the cardiac cycle at which the least current was required to induce VF with a single shock was identified. This current was compared to the much lower current required to pace the heart in the diastolic interval. While the current required to produce either fibrillation or pacing decreased as pulse duration increased, the safety factor (i.e., the ratio of fibrillation current to pacing current) remained nearly constant, averaging 12.6 for all pulse durations examined. That is, on the average, a stimulus of any given duration between 1 and 50 ms required at least 12 times the current required for pacing to produce ventricular fibrillation. We conclude that in normal canine hearts, the risk of inducing VF during precordial pacing is small.