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Normal and malignant lymphocytes can migrate from the bloodstream into lymph nodes and Peyer's patches. This process helps distribute normal lymphocytes throughout the lymphoid system and may provide a portal of entry for circulating malignant cells. An adhesive interaction between lymphocytes and the endothelium of postcapillary venules is the first step in the migratory process. We have recently shown that the simple sugars L-fucose and D-mannose, and an L-fucose-rich polysaccharide (fucoidin), can inhibit this adhesive interaction in vitro. We now report that mannose-6-phosphate, the structurally related sugar fructose-1-phosphate, and a phosphomannan, core polysaccharide from the yeast Hansenula holstii (PPME) are also potent inhibitors. Inhibitory activity was assessed by incubating freshly prepared suspensions of lymphocytes, containing the various additives, over air-dried, frozen sections of syngeneic lymph nodes at 7-10 degrees C. Sections were then evaluated in the light microscope for the binding of lymphocytes to postcapillary venules. Mannose-6-phosphate and fructose-1-phosphate were potent inhibitors of lymphocyte attachment (one-half maximal inhibition at 2-3 mM). Mannose-1-phosphate and fructose-6-phosphate had slight inhibitory activity, while glucose-1-phosphate, glucose-6-phosphate, galactose-1-phosphate, and galactose-6-phosphate had no significant activity (at 10 mM). In addition, the phosphomannan core polysaccharide was a potent inhibitor (one-half maximal inhibition at 10-20 micrograms/ml); dephosphorylation with alkaline phosphatase resulted in loss of its inhibitory activity. Preincubation of the lymphocytes, but not the lymph node frozen sections, with PPME resulted in persistent inhibition of binding. Neither the monosaccharides nor the polysaccharide suppressed protein synthesis nor decreased the viability of the lymphocytes. Furthermore, inhibitory activity did not correlate with an increase in negative charge on the lymphocyte surface (as measured by cellular electrophoresis). These data suggest that a carbohydrate-binding molecule on the lymphocyte surface, with specificity for mannose-phosphates and structurally related carbohydrates, may be involved in the adhesive interaction mediating lymphocyte recirculation.

Availability, reliability, and technical improvements have led to continued expansion of computed tomography (CT) imaging. During a CT scan, there is substantially more exposure to ionizing radiation than with conventional radiography. This has led to questions and critical conclusions about whether the continuous growth of CT scans should be subjected to review and potentially restraints or, at a minimum, closer investigation. This is particularly pertinent to populations in emergency departments, such as children and patients who receive repeated CT scans for benign diagnoses. During the last several decades, among national medical specialty organizations, the American College of Emergency Physicians and the American College of Radiology have each formed membership working groups to consider value, access, and expedience and to promote broad acceptance of CT protocols and procedures within their disciplines. Those efforts have had positive effects on the use criteria for CT by other physician groups, health insurance carriers, regulators, and legislators., (Copyright © 2014 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

This paper addresses the increasing use of CT in medical radiologic imaging, with a focus on applications in emergency medicine. The rapidly increasing use of CT in medical imaging over the past 3 decades has been a major subject in many recent publications, including a discussion of concerns about patient radiation doses, unnecessary CT examinations, and the costs of CT examinations. One area of these concerns has been the use of CT examinations for triage, selection of treatment options, and release of patients from emergency medical settings. On September 23 and 24, 2009, the National Council on Radiation Protection and Measurements held a workshop on appropriate uses of CT imaging with emergency patients. The workshop was cosponsored by 8 private and government organizations: the American Association of Physicists in Medicine, the American College of Emergency Physicians, the ACR, the American Society of Emergency Radiology, the Centers for Disease Control and Prevention, Landauer, Inc, the Society for Academic Emergency Medicine, and the US Environmental Protection Agency. This paper presents a summary of discussions at the workshop and recommendations for important areas of consideration in a subsequent consensus paper to be prepared on clinical guidance for applications of CT in emergency medicine procedures., (Copyright © 2011 American College of Radiology. All rights reserved.)

This paper summarizes the perspectives of three U.S. federal agencies on the potential long-term influence of new findings on the biological and potential health effects of low dose and low dose-rate radiation on regulatory controls placed on exposures in occupational, medical, and public settings.

Blood flow in an applied magnetic field gives rise to induced voltages in the aorta and other major arteries of the central circulatory system that can be observed as superimposed electrical signals in the electrocardiogram (ECG). The largest magnetically induced voltage occurs during pulsatile blood flow into the aorta, and results in an increased signal at the location of the T-wave in the ECG. Studies involving the measurement of blood pressure, blood flow rate, heart sounds, and cardiac valve displacements have been conducted with monkeys and dogs exposed to static fields up to 1.5 tesla (T) under conditions producing maximum induced voltages in the aorta. Results of these studies gave no indication of alterations in cardiac functions or hemodynamic parameters. Cardiac activity monitored by ECG biotelemetry during continuous exposure of rats to a 1.5-T field for 10 days gave no evidence for any significant changes relative to the 10 days prior to and following exposure. Theoretical modeling of magnetic field interactions with blood flow has included a complete solution of the equation describing the flow of an electrically conductive fluid in the presence of a magnetic field (the Navier-Stokes equation) using the finite element technique. Magnetically induced voltages and current densities as a function of the applied magnetic field strength have been calculated for the aorta and surrounding tissues structures, including the sinoatrial node. Induced current densities in the region of the sinoatrial node are predicted to be >100 mA/m2 at field levels >5 T in an adult human under conditions of maximum electrodynamic coupling with aortic blood flow. Magnetohydrodynamic interactions are predicted to reduce the volume flow rate of blood in the human aorta by a maximum of 1.3%, 4.9%, and 10.4% at field levels of 5, 10, and 15 T, respectively.

The predecessor organizations of the National Council on Radiation Protection and Measurements (NCRP) were established in 1929 (the U.S. Advisory Committee on X-Ray and Radium Protection) and in 1946 (the National Committee on Radiation Protection and Measurements). In 1964, the NCRP was formally chartered by the U.S. Congress as a national resource for scientific guidance on issues related to radiation measurements and health protection. In this paper the history and scientific contributions of NCRP are reviewed, followed by a discussion of its evolving mission and future scientific goals.

A major limitation on the supply of the short-lived medical isotope 90Y (t1/2 = 64 h) is the available quantity of highly purified 90Sr generator material. A radiochemical production campaign was therefore undertaken to purify 1,500 Ci of 90Sr that had been isolated from fission waste materials. A series of alkaline precipitation steps removed all detectable traces of 137Cs, alpha emitters, and uranium and transuranic elements. Technical obstacles such as the buildup of gas pressure generated upon mixing large quantities of acid with solid 90Sr carbonate were overcome through safety features incorporated into the custom-built equipment used for 90Sr purification. Methods are described for analyzing the chemical and radiochemical purity of the final product and for accurately determining by gravimetry the quantities of 90Sr immobilized on stainless steel filters for future use.

The flow of blood in the presence of a magnetic field gives rise to induced voltages in the major arteries of the central circulatory system. Under certain simplifying conditions, such as the assumption that the length of major arteries (e.g., the aorta) is infinite and that the vessel walls are not electrically conductive, the distribution of induced voltages and currents within these blood vessels can be calculated with reasonable precision. However, the propagation of magnetically induced voltages and currents from the aorta into neighboring tissue structures such as the sinuatrial node of the heart has not been previously determined by any experimental or theoretical technique. In the analysis presented in this paper, a solution of the complete Navier-Stokes equation was obtained by the finite element technique for blood flow through the ascending and descending aortic vessels in the presence of a uniform static magnetic field. Spatial distributions of the magnetically induced voltage and current were obtained for the aortic vessel and surrounding tissues under the assumption that the wall of the aorta is electrically conductive. Results are presented for the calculated values of magnetically induced voltages and current densities in the aorta and surrounding tissue structures, including the sinuatrial node, and for their field-strength dependence. In addition, an analysis is presented of magnetohydrodynamic interactions that lead to a small reduction of blood volume flow at high field levels above approximately 10 tesla (T). Quantitative results are presented on the offsetting effects of oppositely directed blood flows in the ascending and descending aortic segments, and a quantitative estimate is made of the effects of assuming an infinite vs. a finite length of the aortic vessel in calculating the magnetically induced voltage and current density distribution in tissue.

Various different effects of ELF magnetic fields have been reported to occur at the cellular, tissue, and animal levels. Certain effects, such as the induction of magnetophosphenes in the visual system, have been established through replication in several laboratories. Many other effects, however, have not been independently verified or, in some cases, replication efforts have led to conflicting results. A substantial amount of experimental evidence indicates that the effects of ELF magnetic fields on cellular biochemistry, structure, and function can be related to the induced current density, with a majority of the reported effects occurring at current density levels in excess of 10 mA/m2. These effects, therefore, occur at induced current-density levels that exceed the endogenous currents normally present in living tissues. From this perspective, it is extremely difficult to interpret the results of recent epidemiological studies that have reported a correlation between cancer incidence and exposure to 50-Hz or 60-Hz magnetic fields with very low flux densities. The levels of current density induced in tissue by occupational or residential exposure to these fields are, in nearly all circumstances, significantly lower than the levels found in laboratory studies to produce measurable perturbations in biological functions. There is a clear need for additional epidemiological research to clarify whether exposure to ELF magnetic fields is, in fact, causally linked to cancer risk. Laboratory animal studies conducted under controlled conditions are also needed to determine whether ELF magnetic fields can initiate or promote tumors. In addition, more studies of both a theoretical and experimental nature are needed to elucidate the molecular and cellular mechanisms through which low-intensity magnetic fields can influence living systems. A growing body of evidence indicates that cell membranes play a key role in the transduction and amplification of ELF field signals. Elucidation of the physical and biochemical pathways that mediate these transmembrane signaling events will represent a major advance in our understanding of the molecular basis of magnetic field effects of biological systems.

Measurements were made of clonogenic cell survival in rat rhabdomyosarcoma tumors as a function of time following in situ irradiation with single or fractionated doses of 225-kVp X rays or with 557-MeV/u neon ions in the distal position of a 4-cm extended-peak ionization region. Single doses of 20 Gy of X rays or 7 Gy of peak neon ions reduced the initial surviving fraction to approximately 0.025 for each modality. Daily fractionated doses (four fractions in 3 days) of either peak neon ions (1.75 Gy per fraction) or X rays (6 Gy per fraction) achieved a cell survival of approximately 0.02-0.03 after the fourth dose of radiation. In the single-dose experiments, significant 5- and 10-fold decreases in the fraction of clonogenic cells were observed between the third and fourth days after irradiation with peak neon ions and X rays, respectively. After the sixth day postirradiation, the residual clonogenic cells exhibited a rapid burst of proliferation leading to doubling times for the surviving cell fractions of approximately 1.5 days. Radiation-induced growth delay was consistent with the cellular repopulation dynamics. In the fractionated-dose experiments with both radiation modalities, a large delayed decrease in cell survival was observed at 1-3 days after completion of the fractionated-dose schedule. Cellular repopulation was consistent with postirradiation tumor volume regression and regrowth for both radiation modalities. The extent of decrease in survival following the four-fraction radiation schedule was approximately two times greater in X-irradiated than in neon-ion-irradiated tumors that produced the same survival level immediately after the fourth dose. Mechanisms underlying the marked reduction in cell survival 3-4 days postirradiation are discussed, including the possible role of a toxic host cell response against the irradiated tumor cells.

The paired survival curve technique was used to characterize the rate at which the fraction of hypoxic cells in rat rhabdomyosarcoma R-1 tumors returns to the preirradiation value of 37% following a single dose of 225-kVp X rays. Tumors were administered a conditioning x-ray dose of 15-Gy, followed at 0, 3, 6, 12, 24, or 48 hr by a 5-Gy, 10-Gy, or 15-Gy dose of X rays under air-breathing conditions or under hypoxic conditions produced by nitrogen-gas asphyxiation 5 min prior to irradiation. Cellular surviving fractions were determined by the tumor excision assay following in vivo irradiation. From the ratio of the survival fractions measured for tumor cells from air-breathing and hypoxic animals, the fraction of hypoxic cells was determined as a function of time postirradiation. These results indicated that immediately following a 15-Gy dose of X rays, essentially 100% of the viable cells remaining were hypoxic. The tumors reoxygenated rapidly, returning to the preirradiation level of 37% during the first 6 hr postirradiation.

Postirradiation tumor volume response, cellular repopulation dynamics, cell-cycle perturbations, and phase-specific cell survival were characterized in rat rhabdomyosarcoma R-1 tumors (the R2C5 subline) following an in situ 10-Gy dose of 225-kVp X rays. This X-ray dose produced a 7.5-day delay in tumor growth to twice the volume measured at the time of irradiation, and reduced the initial surviving fraction of R2C5 cells to 0.17 as measured by the excision assay procedure. The surviving fraction of R2C5 cells returned to unity by the 16th day after tumor irradiation. On the basis of flow cytometry measurements of DNA content in tumor cells stained with a noncytotoxic concentration of Hoechst 33342 (5 microM, 2 h, 37 degrees C), a transient G2 block was observed 1 day after irradiation. Flow cytometry measurements also demonstrated that the tetraploid R2C5 cells constituted only 30% of the total tumor cell population, with the remainder being diploid host cells comprised of macrophages, monocytes, lymphocytes, and granulocytes. Large numbers of host cells infiltrated the irradiated tumors, leading to an increase in the percentage of diploid cells by Day 2 and reaching a level of more than 80% of the total tumor cell population by 4 to 8 days after irradiation. The influx of host cells into irradiated tumors was correlated temporally with a significant 12-fold decrease in the surviving fraction of R2C5 cells that occurred between Days 2 and 4 postirradiation. When the diploid host cell population was removed by cell sorting procedures, the surviving fraction of R2C5 cells at Day 4 was substantially greater than that in the presence of the host cells. Experiments involving the mixing of 4/1 and 12/1 ratios of diploid host cells and tetraploid tumor cells isolated from irradiated and unirradiated tumors demonstrated that the cytotoxic effect of the host cells was specific for the irradiated tumor cells. The significant toxic effect of host cells on irradiated tumor cells was observed only at 2 to 4 days after irradiation, and not at earlier or later times. The data obtained in these experiments indicate that the immunogenicity of R2C5 cells is increased significantly by irradiation, and a resultant cell-mediated host immune response produced a delayed decrease in tumor cell survival that is most pronounced 4 days after irradiation. The cell survival characteristics of R2C5 cells in different cell-cycle phases were found to be similar through the 16-day postirradiation interval that was studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Simultaneous measurements were made of the electrocardiogram (ECG) and the intraarterial blood pressure of adult male Macaca monkeys during acute exposures to homogeneous stationary magnetic fields ranging in strength up to 1.5 tesla. An instantaneous, field strength-dependent increase in the ECG signal amplitude at the locus of the T wave was observed in fields greater than 0.1 tesla. The temporal sequence of this signal in the ECG record and its reversibility following termination of the magnetic field exposure are consistent with an earlier suggestion that it arises from a magnetically induced aortic blood flow potential superimposed on the native T-wave signal. No measurable alterations in blood pressure resulted from exposure to fields up to 1.5 tesla. This experimental finding is in agreement with theoretical calculations of the magnetohydrodynamic effect on blood flow in the major arteries of the cardiovascular system.

The receptivity of human erythrocytes to invasion by Plasmodium falciparum merozoites can be decreased by neuraminidase or trypsin treatment, an observation that supports a role for the erythrocyte sialoglycoproteins (glycophorins) in invasion. We have found that alpha 1-acid glycoprotein (AGP), added to in vitro cultures, can restore invasion of enzyme-treated human erythrocytes. AGP is structurally different from the glycophorins although it does carry 12% sialic acid. Its ability to restore receptivity to desialylated cells is dependent on its sialic acid complement, its concentration, and its binding to the erythrocyte surface. We present evidence that AGP forms a bridge between the merozoite and the enzyme-treated erythrocyte that allows the stronger and more complex interactions of invasion to proceed. We suggest that the glycophorins play the same role on the surface of the intact erythrocyte.

The water-soluble carbodiimide salt 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide. HCl (EDCI-HCl) has been shown to increase the complement-dependent lysis of cultured mouse neuroblastoma C1300 cells by two types of antibody: (1) natural antibodies in the sera of normal (nonimmunized) rabbits, and (b) serum antibodies from snygeneic tumor-bearing A/HeJ mice. In the latter case, both the level of serum antibodies and the extent of carbodiimide enhancement of immune lysis were demonstrated in vitro to be substantially greater with sera from mice bearing 21-day-old tumors relative to 4-day-old tumors. The carbodiimide EDCI-HCl has also been found to increase the complement-dependent lysis of cultured TA3 carcinoma cells by serum antibodies from isogeneic LAF1/J mice bearing ascites tumors in advanced stages of growth. Finally, it has been shown that EDCI-HCl exerts an antitumor activity in vivo that is significantly greater against 21-day-old than against 4-day-old neuroblastoma c1300 tumors. The increase in EDCI-HCl activity with tumor age is contrary to the response that would be expected if this drug were serving as an antimetabolite. This is evidenced by data showing that the antimetabolite 6-thioguanine is most effective against young rapidly growing neuroblastoma C1300 tumors. The correlation between carbodiimide antitumor activity and host production of cytotoxic antibodies suggests that EDCI-HCl may operate in vivo by an immunological mechanism comparalbe to that demonstrated in vitro.

Results are reported of studies to measure the extent of recovery of potentially lethal damage (PLD) in rat rhabdomyosarcoma tumor cells after irradiation both in vivo and in vitro with either high-LET or low-LET radiation. Stationary-phase cultures were found to exhibit repair of PLD following irradiation in vitro either with low-LET X rays or with high-LET neon ions in the extended-peak ionization region. Following a 9-Gy dose of 225-kVp X rays or a 3.5-Gy dose of peak neon ions, both of which reduced the initial cell survival to 6-8%, the maximum PLD recovery factors were 3.4 and 1.6, respectively. In contrast, the standard tumor excision assay procedure failed to reveal any recovery from PLD in tumors irradiated in situ with either X rays or peak neon ions. PLD repair by the in vivo tumor cells could be observed, however, when the excision assay procedure was altered by the addition of a known PLD repair inhibitor beta-arabinofuranosyladenine (beta-ara-A). When a noncytotoxic 50 microM concentration of beta-ara-A was added to the excised tumor cells immediately following a 14.5-Gy in situ dose of X rays, cell survival in the inhibitor-treated cells was lower than in the untreated cells (0.018 compared to 0.056), resulting in a PLD repair inhibition factor of 3.1. Delaying the addition of beta-ara-A for 1, 2, or 3 h following tumor excision reduced the PLD repair inhibition factor to 1.6, 1.5, and 0.9, respectively. Following tumor irradiation in situ with neon ions in the extended-peak ionization region (median LET = 145 keV/micron), less PLD repair was observed than after X irradiation. For 5.8 Gy of peak neon ions, the PLD repair inhibition factors were 2.1, 1.5, 1.3, and 1.1 at 0, 1, 2, and 3 h, respectively. We interpret the absence of measurable PLD repair using the standard tumor excision assay procedure as resulting from undetectable repair occurring during the long interval (about 2 h) required for the cell dissociation and plating procedures. We conclude that at least for our tumor system, PLD repair does occur after irradiation of tumors in situ, even though it is not detectable using the standard tumor excision assay procedure. Thus a failure to measure such repair by this assay in a given tumor system does not necessarily mean the cells are incapable of PLD repair.

A growth inhibitory effect on adenocarcinoma TA3 ascites tumors in LAF1/J mice resulted from the repeated IP administration of subtoxic doses of 3 rifamycin derivatives: rifampicin (Rif)1, dimethylbenzyldesmethylrifampicin (DMB), and rifazone-82 (R-82). A high-viscosity methylcellulose vehicle was found to be essential for obtaining a uniform drug suspension and a significant antitumor effect by the least water soluble derivatives, DMB and R-82. The more hydrophilic derivative, Rif, was found to have a comparable growth inhibitory effect on TA3 cells when prepared in 0.9% NaCl solution with or without added methylcellulose. Oral or SC drug injections did not have an antitumor effect. The results of this study point to the importance of vehicle and route of administration in chemotherapy trials with these compounds.

Rectal temperatures were recorded in mice and rats during exposure to a stationary 7.55 Tesla (1 T = 10(4) Gauss) homogeneous magnetic field, and to magnetic field gradients ranging from 58.1 - 58.6 T/m. Contrary to observations reported recently by other investigators, no evidence was found for a change in the body temperature of rodents exposed to strong homogeneous or gradient magnetic fields.

Radiation-induced growth delay was measured in rat rhabdomyosarcoma tumors exposed to split doses of high-LET (linear energy transfer) neon ions in the extended-peak ionization region and low-LET X rays. Top-off doses of 7.5, 15, and 25 Gy of 225-kVp X rays were administered to the tumors at 0.5, 4.0, and 24.0 hr following priming doses of either peak neon ions or X rays. The priming doses used were 7 Gy of peak neon ions and 20 Gy of X rays, both of which produced a 10 day delay in tumor regrowth to a volume twice that measured on the day of irradiation. The tumor response to split doses of X rays indicated rapid repair of sublethal damage, with significant recovery occurring at 0.5 hr and complete recovery by 4 hr after the initial 20-Gy X ray dose. The top-off doses of X rays required to produce an additional 10 or 20 days of tumor growth delay were 18 and 7% larger, respectively, when the priming dose was 20 Gy of X rays as compared to 7 Gy of peak neon ions. This result indicates that relatively little interaction of the neon-ion and X ray radiations occurred, even when the time interval between split-dose irradiations was as short as 0.5 hr. Our data indicate that the interaction of high- and low-LET radiation modalities is small, and approaches a simple additivity of effects when the tumors repair a major portion of the sublethal radiation injury imparted by a priming dose before the second dose is administered.

The response of a rat rhabdomyosarcoma tumour was assessed by measurements of radiation-induced growth delay resulting from administration of the hypoxic cell sensitizer misonidazole in combination with single and fractionated doses of X-rays and charged-particle radiation. Enhancement ratios of 1.8--2.1 were obtained following single doses of misonidazole (500 mg/kg i.p.) and 225 kV X-rays. Single doses of misonidazole with either carbon-ion or neon-ion radiation in the 4 cm extended-peak ionization region led to enhancement ratios of 1.2--1.3. When combined misonidazole (300 mg/kg i.p.) and X-ray treatments were given in four daily fractions, the enhancement ratios decreased to 1.2--1.5. However, a four-fraction schedule using either carbon-ion or neon-ion radiation in combination with misonidazole gave enhancement ratios of 1.1--1.3, which are similar to the values obtained for single-dose schedules with the sensitizer and charged-particle radiation.

Comparative measurements have been made of the transplantation and electrical surface charge properties of the near-diploid TA3-Ha ascites tumor and a new hypotetraploid ascites subline designated TA3-L. The negative surface charge density and the density of electrophoretically detectable sialic acid residues were determined to be twice as great for TA3-L as TA3-Ha cells. The two TA3 sublines were found to have identical growth properties in isogeneic mice and to exhibit progressive growth in three allogeneic strains of mice. The lethal tumor cell inoculum in allogeneic mice was lower in all cases for the TA3-L cells. From a comparison of several TA3 ascites tumor sublines, it can be concluded that their transplantability into allogeneic strains of mice is correlated with the density of negative surface charge but is independent of the degree of tumor aneuploidy.

Liposome vesicles maintained in a uniform static magnetic field release a chemotherapeutic drug (ARA-C, MW = 243) at temperatures approaching the phase-transition region where these liposomes are not normally leaky. Drug release is rapid, and a maximum difference between treated and unexposed liposomes of 30% of the total maximal release of ARA-C was observed within 1 min in a magnetic field. Dose-effect studies conducted between 0.01 and 7.5 T (1 T = 10(4) G) reveal that this permeability effect has a sigmoidal dependence on magnetic flux density. The ED50 is 15 mT, with a 95% confidence interval of 6.50-34.9 mT. Magnetic field exposures were conducted using a superconducting magnet with the liposomes maintained at +/- 0.08 degrees C. For comparison, samarium-cobalt permanent magnets induced a comparable drug release at 0.4 T. These results indicate that a static magnetic field of 10 mT or greater can increase passive transport in phospholipid membrane bilayers maintained at or near their membrane phase-transition temperature. Lipid clustering which occurs at prephase-transition temperatures may predispose phospholipid domains to diamagnetic orientation in a magnetic field and thereby facilitate drug release.

A field strength dependent increase in the amplitude of the T-wave signal in the rat electrocardiogram (ECG) was observed during exposure to homogeneous, stationary magnetic fields. For 24 adult Sprague-Dawley and Buffalo rats of both sexes, the T-wave amplitude was found to increase by an average of 408% in a 2.0 Tesla (1 Tesla - 10(4) Gauss) field. No significant magnetically induced changes were observed in other components of the ECG record, including the P wave and the QRS complex. The minimum field level at which augmentation of the T wave could be detected was 0.3 Tesla. The magnetically induced increase in T-wave amplitude occurred instantaneously, and was immediately reversible after exposure to fields as high as 2.0 Tesla. No abnormalities in any component of the ECG record, including the T wave, were noted during a period of 3 weeks following cessation of a continuous 5-h exposure of rats to a 1.5-Tesla field. The heart rate and breathing rate of adult rats were not altered during, or subsequent to, application of fields up to 2.0 Tesla. The effect of animal orientation within the field was tested using juvenile rats 3-14 days old. The maximum increase in T-wave amplitude was observed when subjects were placed with the long axis of the body perpendicular to the lines of magnetic induction. These experimental observations, as well as theoretical considerations, suggest that augmentation of the signal amplitude in the T-wave segment of the ECG may result from a superimposed electrical potential generated by aortic blood flow in the presence of a stationary magnetic field.

The analysis of growth delay data of a rat rhabdomyosarcoma tumor system with and without misonidazole and irradiated with spread-peak heavy-ion radiation yields two conclusions that bear on the relative efficacy of the two modes of treatment and imply a complementary role of the two modes which enhances the effects of either given separately. 1. For both carbon and neon ion peak radiation given in four fractions, RBE values for tumor growth delay are significantly greater than the enhancement ratio for an X ray plus misonidazole fractionation scheme [2.0-2.3 (carbon) and 2.6-2.8 (neon) vs. 1.2-1.5 (X rays plus misonidazole)]. This implies that high LET killing is considerably more effective in this tumor system (hypoxic fraction of about 35%) than the hypoxic cell sensitization caused by misonidazole. 2. When misonidazole is given in conjunction with the heavy ion beam irradiations, an increased growth delay is seen, greater than when either heavy ions or misonidazole plus X rays are given separately. The product of the sensitizer enhancement ratio for heavy ions and the RBE for no sensitizer yields a measure of the overall enhancement of effect relative to an X ray treatment. The values of this product for the carbon beam (2.4-2.5) and neon beam (3.4) show high effectiveness for either beam plus misonidazole. The interpretation is that heavy ion beams reach and kill hypoxic cells not penetrated by the misonidazole, and some hypoxic cells not killed by the high LET component receive low LET damage which is made lethal by the drug. Thus, the net hypoxic cell killing is enhanced by the high LET beams and in a complementary way by the combination of the drug and the low LET portion of the radiation.

Humoral and cell-mediated immune responses were assayed following a 6-day exposure of LAF1/J mice to a 1.50 Tesla (1 T = 10(4) Gauss) stationary magnetic field. In tests of the immune response to sheep erythrocytes, the number of Jerne plaques formed by spleen lymphocytes and the level of serum IgM were not significantly different for the exposed mice in comparison with control animals. Tests for mitogen-induced lymphocyte proliferation also demonstrated no significant differences in the response of spleen lymphocytes from exposed and control groups of mice.

The bioelectric properties of frog sciatic nerves have been measured during exposure to homogeneous, stationary magnetic fields. The action potential amplitude, conduction velocity, absolute refractory period and relative refractory period were found to be unaffected by a continuous 4-h exposure to perpendicular or parallel 2.0 T (1 T equal 10(4) G) magnetic fields. These parameters also remained unchanged during a 1-h post-exposure period. The conduction velocity was similarly found to be unchanged when the field was applied continuously for 17 h. Exposure of sciatic nerves to a 1.0-T field led to no alteration in the threshold for neural excitation. The absence of magnetic field effects on nerve electrical activity observed in the present experiments contrasts with the positive findings reported previously by other investigators. These discrepancies may be attributable to an inadequate control of ambient temperature in the earlier studies.

Behavioral measures were evaluated in adult CD-1 and LAF-1 mice continuously exposed for 72 h to a 1.5-Tesla (1 T = 10(4) Gauss) homogeneous DC magnetic field, and in LAF-1 mice continuously exposed for 72 h to a sinusoidal 60-Hz, 1.65-mT (rms) homogeneous AC field. Three types of behavioral tests were employed: (1) Memory of an electroshock-motivated passive avoidance task was assessed in animals that had been trained immediately prior to the field exposure. The strength of memory was varied either by altering the strength of the electric footshock during training, or by administering a cerebral protein synthesis inhibitor, anisomycin, at the time of training. (2) General locomotor activity was measured using a quadrant-crossing test immediately after termination of the magnetic field exposure. (3) Sensitivity of the experimental subjects to the seizure-inducing neuropharmacological agent, pentylenetrazole , was assessed immediately after the field exposure on the basis of three criteria: (a) the percentage of subjects exhibiting a generalized seizure, (b) the mean time to seizure, and (c) the mean seizure level. The results of these studies revealed no behavioral alterations in exposed mice relative to controls in any of the experimental tests with the 1.5-T DC field or the 60-Hz, 1.65-mT (rms) AC field.

Regression of TA3 ascites carcinoma tumors occurred following i.p. injection of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide-HC1. An immunological mechanism of drug action was indicated by the fact that no significant antitumor activity was demonstrable in mice that had previously received an immunosuppressive 700 rad dose of 60Co radiation.

The dosimetry and physical interaction mechanisms of electromagnetic fields with frequencies in the extremely low frequency (ELF) range (below 300 Hz) are described. The mechanisms through which ELF electric and magnetic fields induce electric currents in living organisms are summarized, with particular emphasis on humans. Topics that are discussed include: (1) sources and measurements of ELF electric and magnetic fields; (2) direct and indirect coupling of these fields to humans; (3) transient discharges and contact currents, and the thresholds for human response to these phenomena; (4) protective measures for the mitigation of potential ELF field effects on humans; and (5) mechanisms of interaction of ELF fields with cellular and tissue systems, with emphasis on field transduction mechanisms involving the cell membrane.

A rhabdomyosarcoma in a WAG/Rij rat with capacity for colony growth after tumour excision and enzymatic dissociation has been used to study response to high and low LET radiation. End points are tumor volume response, TCD50/180, clonogenic capability after tumour irradiation in situ, and in vitro cell survival after irradiation in both the well-oxygenated and the hypoxic conditions. Experience has shown that sublines with different growth rates, radiosensitivity and plating efficiency can arise from the same frozen stock. The conclusions that can be drawn from an analysis of the data obtained to date are as follows: 1. There is no correlation between the doubling times of our two cell lines growing in culture and in the animal. 2. RBE values obtained from growth delay and from TCD50 end points are in fair agreement. 3. Cell survival curves obtained after in situ irradiation show the cells to be more radioresistant than cells irradiated in suspension in vitro. 4. RBE values for cell survival after in situ irradiation compare favourably with those obtained both for tumour growth delay and in vitro cell survival. 5. Not enough is known at present about radiation-altered cell kinetics to develop a self-consistent model of tumour response after irradiation.

A considerable body of evidence now indicates that electromagnetic and geomagnetic detection systems exist in both simple, unicellular organisms and in more complex species such as avians, bees, and marine animals. A major challenge that faces researchers in this field is the identification of physiological mechanisms through which the detection of weak fields provides significant somatosensory cues for direction finding, foraging, and predation. Many of the anatomical, physiological, and biophysical approaches that are being taken in studies of this nature are described in the series of review articles that appear in this issue of Bioelectromagnetics.