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Biomedical subjects

W R Adey

Publications and source records attributed to W R Adey.

At least 55 records · Page 3Linked to original sources

Alterations in protein kinase activity following exposure of cultured human lymphocytes to modulated microwave fields.

Cultures of human tonsil lymphocytes were exposed in a Crawford cell to a 450-MHz field (peak envelope intensity 1.0 mW/cm2), sinusoidally amplitude modulated (depth 80%) at frequencies between 3 and 100 Hz for periods up to 60 min. The Crawford cell was housed in a temperature-controlled chamber (35 degrees C) and control cultures were placed in the same chamber. Activity of cAMP-dependent protein kinase relative to controls remained unaltered by fields modulated at 16 or 60 Hz with exposures of 15, 30, and 60 min. By contrast, total non-cAMP-dependent kinase activity fell to less than 50% of unexposed control levels after 15 and 30 min exposures, but, despite continuing field exposure, returned to control or preexposure levels by 45 and 60 min. A smaller reduction (20-25%) also occurred with 60-Hz modulation and was also restricted to exposure durations of 15 and 30 min. CW 450-MHz fields were without effect. Reduced enzyme activity occurred with 16-, 40-, and 60-Hz modulation frequencies, but not with 3-, 6-, 80-, or 100-Hz modulation. The specific identity of this kinase is unknown. This rapid but transient reduction in lymphocyte protein kinase activity restricted to modulation frequencies between 16 and 60 Hz and to less than 30 min exposure is consistent with "windowing" with respect to modulation frequency and exposure duration.

Cells, Cultured↗

Migration of cell surface concanavalin A receptors in pulsed electric fields.

Concanavalin A (con A) receptors on the surface of cultured Xenopus myoblasts redistributed in response to monopolar, pulsed electric fields. The prefield uniform distribution of the receptors became asymmetrical, and was polarized toward the cathodal pole, in the same way as in DC fields. The extent of asymmetry depended on the duration of field exposure, pulse width (or alternatively, interpulse interval), frequency, and intensity. This relationship was most conveniently expressed by using duty cycle, a quantity determined by both pulse width and frequency. Pulses of average intensity 1.5 V/cm induced detectable asymmetry within 5 min. At the lowest average field intensity used, 0.8 V/cm, significant asymmetry was detected at 150 min. For pulses of high duty cycle (greater than 25%), steady state was reached after 30 min exposure and the steady state asymmetry was dependent on average field intensity. For low duty cycle fields, the time required to reach steady state was prolonged (greater than 50 min). Before reaching a steady state, effectiveness of the pulses, as compared with DC fields of equivalent intensity, was a function of duty cycle. A low duty cycle field (fixed number of pulses at low frequency or long interpulse interval) was less effective than high duty cycle fields or DC.

Animals↗

Suppression of T-lymphocyte cytotoxicity following exposure to sinusoidally amplitude-modulated fields.

Significant inhibition of allogeneic cytotoxicity of the target cell MPC-11 by the murine cytotoxic T-lymphocyte line CTLL-1 was observed when the 4-h cytotoxicity assay was conducted in the presence of a 450-MHz field sinusoidally amplitude-modulated at 60 Hz. Exposure of the effector cells to the field prior to adding them to the target cells in the cytolytic assay resulted in a similar inhibition, suggesting a direct interaction of the field with the cytolytic T lymphocyte. The inhibition was preferentially expressed during the early allogeneic recognition phase. Field-exposed cytolytic cells recovered their full cytolytic capacity in 12.5 h. A differential susceptibility was observed with modulation frequencies from 0 to 100 Hz. Peak suppression occurred at 60 Hz modulation, with progressively smaller effects at 40, 16, and 3 Hz. The unmodulated carrier wave did not affect the cytotoxicity. Effects with 80- and 100-Hz modulation were smaller than at 60 Hz. These results demonstrate an inhibitory but recoverable effect by certain amplitude modulations of weak nonionizing radiation upon the cell-mediated cytolytic immune response.

Animals↗

Effects of weak amplitude-modulated microwave fields on calcium efflux from awake cat cerebral cortex.

Calcium (45Ca2+) efflux was studied from preloaded cortex in cats immobilized under local anesthesia, and exposed to a 3.0-mW/cm2 450-MHz field, sinusoidally amplitude modulated at 16 Hz modulation depth 85%). Tissue dosimetry showed a field of 33 V/m in the interhemispheric fissure (rate of energy deposition 0.29 W/kg). Field exposure lasted 60 min. By comparison with controls, efflux curves from field exposed brains were disrupted by waves of increased 45Ca2+ efflux. These waves were irregular in amplitude and duration, but many exhibited periods of 20-30 min. They continued into the postexposure period. Binomial probability analysis indicates that the field-exposed efflux curves constitute a different population from controls at a confidence level of 0.96. In about 70% of cases, initiation of field exposure was followed by increased end-tidal CO2 excretion for about 5 min. However, hypercapnea induced by hypoventilation did not elicit increased 45Ca2+ efflux. Thus this increase with exposure does not appear to arise as a secondary effect of raised cerebral CO2 levels. Radioactivity measurements in cortical samples after superfusion showed 45Ca2+ penetration at about 1.7 mm/hr, consistent with diffusion of the ion in free solution.

Animals↗

Low frequency amplitude modulated microwave fields change calcium efflux rates from synaptosomes.

Calcium (45Ca2+) efflux from preloaded synaptosomes was studied with a continuous perfusion technique and the rate constants of a two-phase efflux process calculated. When 16-Hz sinusoidally amplitude modulated 450-MHz microwave field (maximal incident intensity 0.5 mW/cm2, modulation depth 75%) was applied during the second phase, the rate constant increased by 38%. Unmodulated or 60-Hz modulated signals were not effective. This microwave field-induced change can be distinguished from CaCl2-stimulated 45Ca2+ efflux which is most probably derived intracellularly. These data suggest that the microwave-field induced change in calcium efflux probably did not involve intracellular calcium. Also, this change in the dynamic property of synaptosomes did not require gross anatomically intact tissue as a substrate for field-tissue interaction.

Animals↗

Effects of electromagnetic stimuli on bone and bone cells in vitro: inhibition of responses to parathyroid hormone by low-energy low-frequency fields.

Low-energy electromagnetic fields pulsed at frequencies of 10-90 Hz significantly increase healing of chronic fracture nonunions in man. These fields are effective at tissue current levels several orders of magnitude lower than those required for transmembrane depolarization of normal cells. We have examined the effects of two clinically used pulsed electromagnetic fields on cultures of the osteoblast-like mouse bone cell line MMB-1. Both fields significantly reduced cellular production of cAMP in response to parathyroid hormone and osteoclast activating factor. Neither basal nor fluoride-activated levels of adenylate cyclase were altered in membranes from cells cultured in the fields; however, the same membrane preparations exhibited markedly inhibited responses to parathyroid hormone. The fields blocked the inhibitory effects of the hormone on collagen synthesis by MMB-1 cells. However, there was no effect on the inhibition of collagen synthesis by 1,25-dihydroxyvitamin D(3), which is believed to act primarily by a nuclear, rather than by a membrane-dependent, mechanism. No significant differences were noted between effects of the two fields, one generating continuous pulse trains (72 Hz) and the other generating recurrent bursts (15 Hz) of shorter pulses. We hypothesize that these field effects are mediated primarily at the plasma membrane of osteoblasts, either by interference with hormone-receptor interactions or by blocking of receptor-cyclase coupling in the membrane. These responses occurred with induced extracellular fields of 1 mV/cm or less, even though transmembrane potential gradients are typically 10(5) V/cm.

Animals↗

Nonlinear wave mechanisms in interactions between excitable tissue and electromagnetic fields.

It is now well established that intrinsic electromagnetic fields play a key role in a broad range of tissue functions, including embryonic morphogenesis, wound healing, and information transmission in the nervous system. These same processes may be profoundly influenced by eletromagnetic fields induced by an external force. Tissue exposure to extremely low frequency (ELF) and ELF-modulated microwave fields at levels below those inducing significant thermal effects has revealed highly nonlinear mechanisms as a basis for observed effects. Interactions of phonons and excitons along linear molecules may produce nonlinear molecular vibrations in the form of soliton waves. Solitons exist in a minimal energy state and are extremely long-lived in comparison to linear oscillations. Solitons may convey energy released by chemical reactions from one site to another in enzymes of other long-chain proteins. These nonlinear waves may also couple reaction-diffusion processes in the intracellular and extracellular domains. A model is proposed for interaction between excitable tissue and electromagnetic fields, based on nonlinear waves in the cell membrane, with ionic interactions as an essential step. Calcium fluxes in the extracellular space of the central system are modeled by a nonlinear reaction-diffusion system. Membrane molecular solitons may exist in long-chain molecules (Davydov type) and play a significant role in charge transfer; or they may exist as nonlinear waves conveying energy along gel-lipid domains from one protein site to another (Sine-Gordon soliton). Soliton movements occur at subsonic velocities.

Animals↗

Effects of noinionizing radiation on the central nervous system, behavior, and blood: a progress report.

This paper presents a progress report on the U. S. research which has been designated as collaborative research with the Soviet Union to study the biological effects of nonionizing radiation on the central nervous system, behavior, and blood. Results of investigations to study the effects of microwaves on isolated nerves, synaptic function, transmission of neural impulses, electroencephalographic recordings, behavior, and on chemical, cytochemical and immunological properties of the blood are presented. Specifically, the effects of microwave exposure on chick brain and cat spinal cords, on EEG patterns of rats, on behavioral of neonatal rats exposed during development, on behavior of adult rats, on behavior of rhesus monkeys and on the pathology, hematology, and immunology of rabbits will be reported in a summary format. Much of the information is new and has not been published previously.

Action Potentials↗

Ionic factors in release of 45Ca2+ from chicken cerebral tissue by electromagnetic fields.

Electrical stimulation with radiofrequency fields amplitude-modulated at brain wave frequencies increased 45Ca2+ efflux from isolated chicken cerebral tissue. The response was not sensitive to variations of the calcium concentration (0-4.16 mM) in the bathing solution but was enhanced by addition of H+ (0.108 mM HCl) and inhibited in the absence of normal bicarbonate levels (2.4 mM). Addition of lanthanum to the bicarbonate-free solution restored electrical responsiveness, but the stimulus decreased instead of increasing 45Ca2+ efflux. It is suggested that low-frequency, weak, extracellular electric gradients may be transduced in a specific class of extracellular negative binding sites normally occupied by Ca2+ and susceptible to competitive H+ binding.

Animals↗

Models of membranes of cerebral cells as substrates for information storage.

The past decade has seen a growing understanding of functional capacities and structural organization of cell membranes. Studies in immunology, endocrinology and neurobiology have led to some unifying concepts about processes of transduction at the membrane surface, and the coupling of surface events to the interior of the cell. My interest in these problems has been directed in no small measure by interactions with Lars Onsager. His kindly tutelage and rigorous criticism have been a source of endless encouragement to those who sought the full measure of his wisdom in the difficult area of the energetics of membrane excitation. Onsager's unflagging interest in mechanisms of ion transportation led him to earnest consideration of a variety of non-classical models of conduction in proteins, always tempered by his deep insight essential aspects of physical chemistry. My discussions with him at the MIT Neuroscience Research Program were a regular stimulus to the experiments which our groups have undertaken in search of answers to questions raised by the models presented here. Above all, Lars Onsager was a kindly, gentle man. In this personal example, he will be as sadly missed as for his broad and imaginative approach to critical questions in the physical and biological sciences.

Animals↗

Sensitivity of calcium binding in cerebral tissue to weak environmental electric fields oscillating at low frequency.

Weak sinusoidal electric fields modify the calcium efflux from freshly isolated chick and cat cerebral tissues bathed in Ringer's solution, at 36 degrees. Following incubation (30 min) with radioactive calcium (45Ca2+), each sample, immersed in fresh solution, was exposed for 20 min to fields at 1, 6, 16, 32, or 75 Hz, with electric gradients of 5, 10, 56, and 100 V/m in air. 45Ca2+ efflux in the solution was then measured in 0.2 ml aliquots and compared with efflux from unexposed control samples. Field exposures resulted in a general trend toward a reduction in the release of the preincubated 45Ca2+. Both frequency and amplitude sensitivities were observed. Maximum decreases occurred at 6 and 16 Hz (12-15%). Thresholds were around 10 and 56 V/m for chick and cat tissues, respectively. Similar but nonsignificant trends occurred during other field exposures. All results were statistically compared with matched samples of controls. Tissue gradients could not be measured, but estimates were of the order of 0.1 muV/cm. The susceptibility of the electrochemical equilibrium in the neuronal membrane to small extracellular perturbations is discussed and a possible role for weak intrinsic cerebral fields in neuronal excitability is suggested.

Animals↗