The differentiation of normal and transformed human fibroblasts in vitro is influenced by electromagnetic fields.

We studied the effect of symmetric, biphasic sinusoidal electromagnetic fields (EMF) (20 Hz, 6 mT) on the differentiation of normal human skin fibroblasts (HH-8), normal human lung fibroblasts (WI38), and SV40-transformed human lung fibroblasts (WI38SV40) in in vitro cultures. Cells were exposed up to 21 days for 2 x 6 h per day to EMF. Normal mitotic human skin and lung fibroblasts could be induced to differentiate into postmitotic cells upon exposure to EMF. Concomitantly, the synthesis of total collagen as well as total cellular protein increased significantly by a factor of 5-13 in EMF-induced postmitotic cells. As analyzed by two-dimensional gel electrophoresis of [35S]methionine-labeled polypeptides, EMF-induced postmitotic cells express the same differentiation-dependent and cell type-specific marker proteins as their spontaneously arising counterparts. In SV40-transformed human lung fibroblasts (cell line WI38SV40) the exposure to EMF induced the differentiation of mitotic WI38SV40 cells into postmitotic and degenerating cells in subpopulations of WI38SV40 cell cultures. Other subpopulations of WI38SV40 cells did not show any effect of EMF on cell proliferation and differentiation. These results indicate that long-term EMF exposure of fibroblasts in vitro induces the differentiation of mitotic to postmitotic cells that are characterized by differentiation-specific proteins and differentiation-dependent enhanced metabolic activities.

Loosely coupled coaxial TEM applicators for deep-heating.

The development of a coaxial TEM (transverse electromagnetic) deep-heating, non-contacting applicator employing two axially spaced concentric sleeves is described which has electrostatic characteristics and has been named the ESA. Thermal data obtained with the FDA/CDRH elliptic-shaped human torso phantom (with fat overlay) showed nearly uniform heating (+/- 10%) throughout the inner cross-section. Saline tank measurements on a torso cross-section confirmed similar SAR uniformity. Animal experiments with a pig, both with and without blood flow, verified deep-heating and suggested that some preferential central heating occurred. The absence of excessive surface heating indicated that the major portion of the E-field excitation is axially aligned. The non-contacting applicator does not require a water bolus, and experiments showed that moderate patient movement had minor effect on performance.

Continual monitoring of reaching in rat using magnetic induction law.

A method enabling the continual monitoring of movement has been developed based on the law of magnetic induction. The method was concretely applied in the handedness model of the rat. A sensing loop was implanted under the forearm skin of a rat. Electric voltage was induced by the movement of the sensing loop in a DC magnetic field. This voltage is proportional to the movement velocity and its polarity to the direction. The continuous character of the movement record allows convenient analysis and a more exact correlation with the bioelectric concomitants of the movement.

Addition of magnetic field capability to existing extremely-low-frequency electric field exposure systems.

Magnetic field systems were added to existing electric field exposure apparatuses for exposing cell suspensions in vitro and small animals in vivo. Two horizontally oriented, rectangular coils, stacked one directly above the other, have opposite electric currents. This configuration minimizes leakage fields and allows sham- and field-exposure systems to be placed in the same room or incubator. For the in vitro system, copper plates formed the loop-pair, with up to 900 A supplied by a 180:1 transformer. Electric fields were supplied via electrodes at the ends of cell-culture tubes, eight of which can be accommodated by each exposure system. Two complete systems are situated in an incubator to allow simultaneous sham and field exposure up to 1 mT. For the in vivo system, four pairs of 0.8 x 2.7-m coils made of copper bus bar are employed. This arrangement is energized from the power grid via a 30:1 transformer; horizontal magnetic flux densities up to 1 mT can be generated. Pairs of electrode plates spaced 30.5 cm apart provide electric field exposure of up to 130 kV/m. Four systems with a capacity of 48 rats each are located in one room. For both the in vitro and in vivo systems, magnetic exposure fields are uniform to within +/- 2.5%, and sham levels are at least 2,500-fold lower than exposure levels. Potential confounding factors, such as heating and vibration, were examined and found to be minimal.

Analysis of head movement and position using hall effect devices.

We describe a system for the analysis of head displacement and angle. This system utilizes an inexpensive array of Hall effect transducers and associated electronics. Computer analysis of the output of the system permits real time display of head angle, position and associated velocity measures.

Biological effects of magnetic fields: chronic exposure of the nematode Panagrellus redivivus.

The Panagrellus redivivus bioassay, an established monitor of adverse toxic effects of different environments, has been used to study the biological effects of exposure to static and time-varying uniform and gradient magnetic fields, and to time-varying magnetic field gradients superimposed on a static uniform magnetic field of 2.35 Tesla. Temporally stationary magnetic fields have no effect on the fitness of the test animals. Time-varying magnetic fields cause some inhibition of growth and maturation in the test populations. The combination of pulsed magnetic field gradients in a static uniform magnetic field also has a small detrimental effect on the fitness of the test animals.

Total-body electrical conductivity method for estimating body composition: validation by direct carcass analysis of pigs.

Determination of body composition by measuring total-body electrical conductivity (TOBEC) is based on the principle that body fat and fat-free mass (FFM) differ in electrical properties. In humans, we are able to estimate body composition only by indirect methods, which have been used to validate the TOBEC instrument. Relationships between TOBEC and body composition were examined using direct carcass analysis of 24 pigs differing widely in body weight and composition (48-137 kg and 14-45% fat, respectively). Highly significant correlations (p less than 0.0001) were found between body conductivity and empty-body water (H2O) (r = 0.979), empty-body FFM (r = 0.980), empty-body crude protein (r = 0.962), and empty-body potassium (r = 0.949). Prediction of empty-body H2O or FFM from TOBEC had a SEE of 2.1 or 2.8 kg, respectively. Thus, the TOBEC method can predict body H2O and FFM over a wide range of body weight and fatness.

Biomagnetic measurements using squids.

Systematic studies of the magnetoencephalogram (MEG) in normal and pathological subjects (mainly with focal epilepsies) showed that the MEG may evidence significant brain activities even if they are not present in the electroencephalogram (EEG). They also showed that the MEG has a considerably higher spatial resolution than the EEG. A novel mapping technique was introduced to get such a representation of the data that would enable the investigator to draw his conclusions mainly from inspecting the plots. This technique is characterized by an isospectral amplitude (iso-SA) mapping of the scalp distribution of specified spectral components or frequency bands of the MEG power spectrum. With the above method we were able to localize an epileptiform focus using a noninvasive technique without applying an eliciting stimulus. Furthermore using SQUID measurements we were able to describe the behavior of the MEG when the brains of different subjects were subjected to low frequency sinusoidal binaural stimuli. Under these conditions it has been shown that the MEG tends to organize around discrete frequencies that depend on the interference pattern (beat) between the two inputs.

Effect of pulsed electromagnetic fields on orthodontic tooth movement.

The purpose of this study was to determine whether the application of a simple surgically noninvasive, pulsed electromagnetic field could increase both the rate and amount of orthodontic tooth movement observed in guinea pigs. In addition, the objective was to evaluate the electromagnetic field's effects on bony physiology and metabolism and to search for possible systemic side effects. Laterally directed orthodontic force was applied to the maxillary central incisors of a sample of 40 young male, Hartley guinea pigs (20 experimental, 20 control) by means of a standardized intraoral coil spring inserted under constricting pressure into holes drilled in the guinea pigs' two maxillary central incisors. During the experimental period, the guinea pigs were placed in specially constructed, plastic animal holders with their heads positioned in an area of uniform electromagnetic field. Control animals were placed in similar plastic holders that did not carry the electrical apparatus. The application of a pulsed electromagnetic field to the experimental animals significantly increased both the rate and final amount of orthodontic tooth movement observed over the 10-day experimental period. The experimental animals also demonstrated histologic evidence of significantly greater amounts of bone and matrix deposited in the area of tension between the orthodontically moved maxillary incisors. This increase in cellular activity was also reflected by the presence of significantly greater numbers of osteoclasts in the alveolar bone surrounding the maxillary incisors of the experimental animals. After a 10-day exposure to pulsed electromagnetic field, minor changes in serologic parameters relating to protein metabolism and muscle activity were noted. The results of this study suggest that it is possible to increase the rate of orthodontic tooth movement and bone deposition through the application of a noninvasive, pulsed electromagnetic field.

Magnetic stimulation of human peripheral nerve and brain: response enhancement by combined magnetoelectrical technique.

The authors describe the technique of magnetic stimulation from a pulsed induction coil (4.0 T) and the enhanced (5-fold) electromyogram response from hyperthenar muscles obtained when electric and magnetic stimuli are applied simultaneously. The enhancement results have been confirmed for central brain vertex stimulation using the Sheffield magnet. Results obtained with slow (1 to 6 seconds) depth electrode stimulation and recording in humans are compared and are used to predict probable developments in the magnetic field. Because magnetic and magnetoelectrical techniques are painless, noninvasive, and noninjurious, it is believed that they are an important advance in both research and clinical applications of instrumental modification of brain circuits and behavior. There are many diagnostic and therapeutic uses at peripheral and central levels, and some ethical problems need consideration.

AUR memorial Award. Induced alignment of flowing sickle erythrocytes in a magnetic field. A preliminary report.

Deoxygenated sickle erythrocytes in static suspension align perpendicular to a magnetic field. To assess the importance of this observation to MRI of sickle-cell disease, an in vitro flow apparatus was devised and the orientation of sickle erythrocytes flowing through a 0.38 T magnetic field was investigated. We showed a significant perpendicular alignment of fully deoxygenated sickle erythrocytes flowing at 3 to 4 mm/minute (P less than .001). These results suggest that deoxygenated erythrocytes in a sickle-cell patient could orient perpendicular to a magnetic field, and therefore that MRI of such patients could possibly result in worsening of vaso-occlusive complications. Further studies are needed to assess the possible hazards of MRI of sickle-cell disease, especially at high field strengths.

Comments on the use of electromagnetic fields in biological studies.

For biological or cellular experiments using electromagnetic fields it is essential that the parameters defining the field be accurately specified if the results are to be meaningful and are to be compared with the same experiment conducted in a different laboratory. The interaction of living systems with electric and magnetic fields can come only through forces exerted on the charges on the system. If the charges are stationary the only origin of the force is the electric field. The electric field may be established by charge distributions, as in "capacitative plate" experiments, or by time-varying magnetic fields consists of a pair of coaxial coils each of equal radius and separated by a distance about equal to the radius. The electric field induced by a varying current in such a pair of coils varies both in space and in time. The field is always zero on the axis of symmetry, and increases to a maximum near the radius of the coils. The strength is proportional to the time-rat-of-change of the current in the coil, which depends not only on the amplitude and shape of the voltage pulse applied to the coil but also on the resistance and inductance of the coil. The purpose of this note is to describe how the important physical parameters may be determined.

The effect of pulsating electromagnetic fields on condylar growth in guinea pigs.

The purpose of this study was to determine if a simple, noninvasive method could be developed for the application of pulsed electromagnetic fields that would lend itself to future clinical applications. Specifically, the modulation and control of condylar cellular metabolism and the stimulation of cellular proliferation were attempted in order to increase the amount of mandibular condylar growth. A pulsed electromagnetic field with a frequency of 100 hertz was applied for 8 hours per day to the mandibular condylar area of rapidly growing, male, Hartley guinea pigs. Ten guinea pigs were exposed for 10 days and a second group of 10 guinea pigs was exposed for 30 days. In addition, 5 guinea pigs were used as controls for each experimental period. During the experimental period the guinea pigs were placed in specially constructed, plastic animal holders with their heads positioned in an area of uniform magnetic field. After 10 days of pulsed electromagnetic field exposure, there were increases in vascularity, secretion of cartilagenous intercellular matrix, and woven-bone formation in the guinea pig condyle. After 30 days, there were continued but attenuated vascular and calcification responses with an increase noted in marrow hemopoietic elements. An increase in the number of osteoclasts was also noted after 10 days. This effect was transient and was not present at the end of the 30-day experimental period. The application of the pulsed electromagnetic field did not result in a significant increase in the overall anteroposterior or vertical size of the guinea pig mandible compared to controls. The results of this study suggest that it is possible to affect condylar cartilagenous and bony metabolism through the application of a noninvasive, pulsed electromagnetic field.

A comparison of deep regional hyperthermia from an annular array and a concentric coil in the same patients.

Twenty-two patients with advanced pelvic or abdominal malignancy (or both) were treated on successive occasions with hyperthermia produced by an annular array (AA) (60-80 MHz, 500-1800 W forward power) and a concentric coil (CC) (13.56 MHz, 350-1000 W forward power). Both devices were compared with respect to acute toxicity and power limitations. There was no power limiting factor in pelvic heating in 7/14 patients treated with the AA, however 13/14 experienced power limiting sacrococcygeal pain with the CC. The 9 patients who underwent abdominal heating had a variety of power limitations with both devices. Thermal mapping was performed in 23 treatments with the AA and in 19 with the CC. Composite thermal maps of patients with similar thermometry sites show that heating patterns produced by the CC were predictable from theory and static phantom measurements. The AA achieved broader regional heating, particularly at depth, but heating patterns were less predictable. Spatial thermal dose (TD) analysis revealed higher minimum tumor TDs and more favorable mean tumor/normal tissue TD ratios with the AA than with the CC. We conclude that the AA is superior to the CC for pelvic treatment and that both devices have limitations in abdominal treatment.