| 1. |
- Capala, J, et al.
(författare)
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Boron neutron capture therapy for glioblastoma multiforme : Clinical studies in Sweden
- 2003
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Ingår i: Journal of Neuro-Oncology. - 1573-7373. ; 62:1, s. 135-144
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Tidskriftsartikel (refereegranskat)abstract
- A boron neutron capture therapy (BNCT) facility has been constructed at Studsvik, Sweden. It includes two filter/moderator configurations. One of the resulting neutron beams has been optimized for clinical irradiations with a filter/moderator system that allows easy variation of the neutron spectrum from the thermal to the epithermal energy range. The other beam has been designed to produce a large uniform field of thermal neutrons for radio-biological research. Scientific operations of the Studsvik BNCT project are overseen by the Scientific Advisory Board comprised of representatives of major universities in Sweden. Furthermore, special task groups for clinical and preclinical studies have been formed to facilitate collaboration with academia. The clinical Phase II trials for glioblastoma are sponsored by the Swedish National Neuro-Oncology Group and, presently, involve a protocol for BNCT treatment of glioblastoma patients who have not received any therapy other than surgery. In this protocol, p-boronophenylalanine (BPA), administered as a 6-h intravenous infusion, is used as the boron delivery agent. As of January 2002, 17 patients were treated. The 6-h infusion of 900 mg BPA/kg body weight was shown to be safe and resulted in the average blood-boron concentration of 24 μg/g (range: 15-32 μg/g) at the time of irradiation (approximately 2-3 h post-infusion). Peak and average weighted radiation doses to the brain were in the ranges of 8.0-15.5 Gy(W) and 3.3-6.1 Gy(W), respectively. So far, no severe BNCT-related acute toxicities have been observed. Due to the short follow-up time, it is too early to evaluate the efficacy of these studies.
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| 2. |
- Persson, Bertil R.R., et al.
(författare)
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Effects of microwaves from GSM mobile phones on the blood-brain barrier and neurons in rat brain
- 2005
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Ingår i: PIERS 2005 - Progress in Electromagnetics Research Symposium, Proceedings. - 1933077077 - 9781933077079 ; , s. 638-641
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Konferensbidrag (refereegranskat)abstract
- Our group has since 1988 studied the effects of different intensities and modulations of 915MHz RF in a rat model where the exposure takes place in a TEM-cell during various time periods and post exposure recovery times. The power fed into TEM-cells was 0.125, 1.25, 12.5 or 125mW corresponding to whole body SAR (determined experimentally): 0.2, 2, 20 or 200mW/kg. The rats were awake and not restrained during exposure and after the recovery period the animals were anaesthetized and sacrificed by perfusion-fixation with 4% formaldehyde. Paraffin embedded 5 μm. thick brain slices were stained for albumin by applying albumin antibodies (Dakopatts), by which albumin is revealed as brownish discolorations. Dark neurons were revealed by staining for RNA/DNA with cresyl violet. In series of more than 1800 Fisher rats, we have proven that sub thermal power levels from both pulse-modulated and continuous RF fields - including those from real GSM mobile phones - have the potency to significantly open the BBB for the animals' own albumin (but not fibrinogen) to pass out into the brain and to accumulate in the neurons and glial cells surrounding the capillaries. Albumin extravasations are most prominent at the lower SAR values. This dose-response behaviour suggests some kind of energy or electromagnetic field strength windowing effect. A linear dose-response relationship for dark neurons was found at 50 days after exposure, with most prominent occurrence at SAR 200mW/kg.
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| 3. |
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| 4. |
- Belyaev, Igor Y, et al.
(författare)
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Microwaves From UMTS/GSM Mobile Phones Induce Long-Lasting Inhibition of 53BP1/gamma-H2AX DNA Repair Foci in Human Lymphocytes
- 2009
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Ingår i: Bioelectromagnetics. - : Wiley. - 0197-8462 .- 1521-186X. ; 30:2, s. 129-141
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Tidskriftsartikel (refereegranskat)abstract
- We have recently described frequency-dependent effects of mobile phone microwaves (MWs) of global system for mobile communication (GSM) on human lymphocytes from persons reporting hypersensitivity to electromagnetic fields and healthy persons. Contrary to GSM, universal global telecommunications system (UMTS) mobile phones emit wide-band MW signals. Hypothetically, UMTS MWs may result in higher biological effects compared to GSM signal because of eventual "effective" frequencies within the wideband. Here, we report for the first time that UMTS MWs affect chromatin and inhibit formation of DNA double-strand breaks co-localizing 53BP1/gamma-H2AX DNA repair foci in human lymphocytes from hypersensitive and healthy persons and confirm that effects of GSM MWs depend oil carrier frequency. Remarkably, the effects of MWs on 53BP1/gamma-H2AX foci persisted up to 72 h following exposure of cells, even longer than the stress response following heat shock. The data are in line with the hypothesis that the type of signal, UMTS MWs, may have higher biological efficiency and possibly larger health risk effects compared to GSM radiation emissions. No significant differences in effects between groups of healthy and hypersensitive subjects were observed, except for the effects of UNITS MWs and GSM-915 MHz MWs on the formation of the DNA repair foci, which were different for hypersensitive (P < 0.02[53BP1)//0.01[gamma-H2AX]) but not for control subjects (P > 0.05). The non-parametric statistics used here did not indicate specificity of the differences revealed between the effects of GSM and UMTS MWs oil cells from hypersensitive subjects and more data are needed to study the nature of these differences, Bioelectromagnetics 30: 129-141, 2009. (C) 2008 Wiley-Liss, Inc.
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| 5. |
- Glahder, J, et al.
(författare)
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Transfection of HeLa-cells with pEGFP plasmid power-assisted by impedance electroporation
- 2005
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Ingår i: Biotechnology and Bioengineering. - : Wiley. - 1097-0290 .- 0006-3592. ; 92:3, s. 267-276
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Tidskriftsartikel (refereegranskat)abstract
- Bioimpedance spectrometry was applied to study cell viability and pEGFP plasmid-transfection efficiency in electroporation (EP) of 20,000 HeLa cells with 0.3 mu g DNA in 90 mu l low conductivity 0.32 M sucrose medium of pH 7.5. Monopolar rectangular pulses, of field strength 75 V/mm, and pulse length 0.1 ms were applied in 1-16 repetitions with a 10-sec pause interval between pulses. Surviving cells were stained by crystal violet and counted using a confocal microscope. Transfected cells were fixed with 10% formaldehyde and counted as green spots in a fluorescence microscope. In the present investigation we used the method of bioimpedance spectrometry to analyze the effect of EP on survival and transfection ratio of cells in suspension. DC and low-frequency AC currents preferably pass through the medium due to the high impedance of the cell membrane. At frequencies above 10 kHz the impedance of the cell membrane starts to decrease and the impedance value of the cell suspension approach a lower limit value R-infinity at infinite frequency. Recording of electrical impedance spectra of cells in culture was performed over a frequency range of 10 Hz to 125 kHz, allowing separation of the contribution from extracellular space and that of the cell membranes. A parallel resistance capacitance model of the cell suspension was used to evaluate the response of applying EP pulses. The values of the collective membrane resistance R-M decay exponentially (r(2) = 0.995) with the number of applied pulses. The ratio of the extrapolated value of the intact membrane resistance before pulsing, R-M,(O), and the value R-M,R-N after each pulse makes an index of the effect of electroporation on the cells. The ratio R-M,R-N/R-M,(O) as well as the relative change of the dissipation factor, tan delta, on the "Loss Change Index" (LCI) fits well a dose-response model (r(2) = 0.98) with the number of applied pulses. The changes in the model parameters membrane resistance Delta R-M = [1- R-M,(N)/R-M,o] and loss factor [1- tan delta(O)/tan Omega(N)] correlate well with the transfection ratio and fraction of dead cells. Those parameters were used for power-assisted electroporation in monitoring, controlling, and optimizing the EP procedure.
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| 6. |
- Nittby, Henrietta, et al.
(författare)
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Exposure to radiation from global system for mobile communications at 1,800 MHz significantly changes gene expression in rat hippocampus and cortex
- 2008
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Ingår i: The Environmentalist. - : Springer Science and Business Media LLC. - 0251-1088 .- 1573-2991. ; 28:4, s. 458-465
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Tidskriftsartikel (refereegranskat)abstract
- We have earlier shown that radio frequency electromagnetic fields can cause significant leakage of albumin through the blood-brain barrier of exposed rats as compared to non-exposed rats, and also significant neuronal damage in rat brains several weeks after a 2 h exposure to a mobile phone, at 915 MHz with a global system for mobile communications (GSM) frequency modulation, at whole-body specific absorption rate values (SAR) of 200, 20, 2, and 0.2 mW/kg. We have now studied whether 6 h of exposure to the radiation from a GSM mobile test phone at 1,800 MHz (at a whole-body SAR-value of 13 mW/kg, corresponding to a brain SAR-value of 30 mW/kg) has an effect upon the gene expression pattern in rat brain cortex and hippocampus-areas where we have observed albumin leakage from capillaries into neurons and neuronal damage. Microarray analysis of 31,099 rat genes, including splicing variants, was performed in cortex and hippocampus of 8 Fischer 344 rats, 4 animals exposed to global system for mobile communications electromagnetic fields for 6 h in an anechoic chamber, one rat at a time, and 4 controls kept as long in the same anechoic chamber without exposure, also in this case one rat at a time. Gene ontology analysis (using the gene ontology categories biological processes, molecular functions, and cell components) of the differentially expressed genes of the exposed animals versus the control group revealed the following highly significant altered gene categories in both cortex and hippocampus: extracellular region, signal transducer activity, intrinsic to membrane, and integral to membrane. The fact that most of these categories are connected with membrane functions may have a relation to our earlier observation of albumin transport through brain capillaries.
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| 7. |
- Persson, Bertil R.R., et al.
(författare)
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A Model for Evaluating Therapeutic Response of Combined Cancer Treatment Modalities : Applied to Treatment of Subcutaneously Implanted Brain Tumors (N32 and N29) in Fischer Rats with Pulsed Electric Fields (PEF) and 60Co-gamma Radiation (RT)
- 2003
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Ingår i: Technology in Cancer Research and Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 2:5, s. 459-470
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study is to develop a mathematical model for evaluating therapeutic response of combined treatment modalities. The study was performed in rats of the Fischer-344 strain with rat glioma N32 or N29 tumors implanted subcutaneously on the thigh of the hind leg. Pulsed electric fields, PEF, with 16 exponentially decaying pulses with a maximum electric field strength of 140 V/mm and t1/e = 1 ms were first applied to the tumors. Then within 5 min radiation therapy with 60Co-gamma radiation, RT, was given in daily fractions of 5 Gy. The animals were arranged into one group of controls and 3 groups of different kind of treatments: PEF only, RT only or combination of PEF + RT. At about 4 weeks after inoculation, the tumors were given the treatment sessions during one week. In 2 experimental series with totally 52 rats with N32 tumors, of which 16 were controls, were given 4 sessions of PEF treatments and RT (totally 20 Gy). In a special experimental series with totally 56 rats with N32 tumors, of which 10 were controls, the different groups were given 1, 2, 3 or 4 treatment sessions respectively, Another strain of glioma tumor, N29 with 62 tumors of which 14 were controls was studied in 2 series given 4PEF + 4RT and 2PEF + 4RT respectively. Fitting the data obtained from consecutive measurements of tumor volume (TV) of each individual tumor to an exponential model TV = TV 0 · exp[TGR · t] estimated the tumor growth rate (TGR % per day) after the first day of treatment (t = 0). The TGR of N32 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.0001), compared to RT alone (p < 0.0001) and compared to PEF alone (p < 0.001). The combined treatment of N32 gives significant effect on the tumor growth rate after 2, 3 and 4 treatment session while RT alone seems to be most efficient after one treatment of 5 Gy and PEF alone is most efficient after 2 treatments at 2 consecutive days. The TGR of N29 tumors treated with the combination of 4PEF + 4RT are significantly decreased compared to the controls (p < 0.05) but the combination of 2PEF + 4RT was more effective (p < 0.005). The specific therapeutic effect STE is defined as the difference between the average tumor growth rates of controls and exposed tumors divided by the average tumor growth rate of the controls. With 4PEF treatments alone the average STE value was 0.32 for N32 tumors and 0 for N29; for 4RT alone the STE values were 0.29 and 0.42 respectively, and for combined treatments 4PEF + 4RT 0.67 and 0.17 respectively. For the N29 tumors treated with 2PEF + 4RT the STE value was 0.53. The therapeutic enhancement ratio, TER, value increase with the number of treatment sessions and the TER of the combined treatments is above 1 in two of the N32 series, which indicates a synergistic effect of 4PEF + 4RT. This work demonstrate the use of our model for analyzing the combination PEF + RT, but it can also be used for evaluation the therapeutic effects of combining RT with chemotherapy or immunogene-therapy.
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| 8. |
- Salford, Leif G., et al.
(författare)
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Non-thermal effects of EMF upon the mammalian brain : The Lund experience
- 2007
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Ingår i: The Environmentalist. - : Springer Science and Business Media LLC. - 0251-1088 .- 1573-2991. ; 27:4, s. 493-500
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Tidskriftsartikel (refereegranskat)abstract
- The environment in which biology exists has dramatically changed during the last decades. Life was formed during billions of years, exposed to, and shaped by the original physical forces such as gravitation, cosmic irradiation and the terrestrial magnetism. The existing organisms are created to function in harmony with these forces. However, in the late 19th century mankind introduced the use of electricity and during the very last decades, microwaves of the modern communication society spread around the world. Today one third of the world's population is owner of the microwave-producing mobile phones. The question is: to what extent are living organisms affected by these ubiquitous radio frequency fields? Since 1988 our group has studied the effects upon the mammalian blood-brain barrier (BBB) by non-thermal radio frequency electromagnetic fields (RF-EMF). These have been revealed to cause significantly increased leakage of albumin through the BBB of exposed rats as compared to non-exposed animals-in a total series of about two thousand animals. One remarkable observation is the fact that the lowest energy levels give rise to the most pronounced albumin leakage. If mobile communication, even at extremely low energy levels, causes the users' own albumin to leak out through the BBB, also other unwanted and toxic molecules in the blood, may leak into the brain tissue and concentrate in and damage the neurons and glial cells of the brain. In later studies we have shown that a 2-h exposure to GSM 915 MHz at non-thermal levels, gives rise to significant neuronal damage, seen 28 and 50 days after the exposure. In our continued research, the non-thermal effects (histology, memory functions) of long-term exposure for 13 months are studied as well as the effects of short term GSM 1,800 MHz upon gene expression. Most of our findings support that living organisms are affected by the non-thermal radio frequency fields. Studies from other laboratories in some cases find effects, while in other cases effects are not seen. Our conclusion is that all researchers involved in this field have the obligation to intensify this research in order to reduce, or avoid, the possible negative effects of the man made microwaves!
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| 9. |
- Sarimov, R, et al.
(författare)
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Nonthermal GSM microwaves affect chromatin conformation in human lymphocytes similar to heat shock
- 2004
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Ingår i: IEEE Transactions on Plasma Science. - 0093-3813. ; 32:4, s. 1600-1608
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Tidskriftsartikel (refereegranskat)abstract
- Here we investigated whether microwaves (MWs) of Global System for Mobile Communication (GSM) induce changes in chromatin conformation in human lymphocytes. Effects of MWs were studied at different frequencies in the range of 895-915 MHz in experiments with lymphocytes from seven healthy persons. Exposure was performed in transverse electromagnetic transmission line cell (TEM-cell) using a GSM test-mobile phone. All standard modulations included 2 W output power in the pulses, specific absorbed rate (SAR) being 5.4 mW/kg. Changes in chromatin conformation, which are indicative of stress response and genotoxic effects, were measured by the method of anomalous viscosity time dependencies (AVTD). Heat shock and treatment with the genotoxic agent camptothecin, were used as positive controls. 30-min exposure to MWs at 900 and 905 MHz resulted in statistically significant condensation of chromatin in lymphocytes from 1 of 3 tested donors. This condensation was similar to effects. of heat shock within the temperature window of 40degreesC-44degreesC. Analysis of pooled data from all donors showed statistically significant effect of 30-min exposure to MWs. Stronger effects of MWs was found following I-h exposure. In replicated experiments, cells from four out of five donors responded to 905 MHz. Responses to 915 MHz were observed in cells from I out of 5 donors, p < 0.002. Dependent on donor, condensation, 3 donors, or decondensation, 1 donor, of chromatin was found in response to I-h exposure. Analysis of pooled data from all donors showed statistically significant effect of 1-h exposure to MWs. In cells from one donor, this effect was frequency-dependent (p < 0.01). Effects of MWs correlated statistically significantly with effects of heat shock and initial state of chromatin before exposure. MWs at 895 and 915 MHz affected chromatin conformation in transformed lymphocytes. The conclusion-GSM microwaves under specific conditions of exposure affected human lymphocytes similar to stress response. The data suggested that the MW effects differ at various GSM frequencies and vary between donors.
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| 10. |
- Baureus Koch, Catrin, et al.
(författare)
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Interaction between weak low frequency magnetic fields and cell membranes.
- 2003
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Ingår i: Bioelectromagnetics. - : Wiley. - 0197-8462. ; 24:6, s. 395-402
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Tidskriftsartikel (refereegranskat)abstract
- The question of whether very weak low frequency magnetic fields can affect biological systems, has attracted attention by many research groups for quite some time. Still, today, the theoretical possibility of such an interaction is often questioned and the site of interaction in the cell is unknown. In the present study, the influence of extremely low frequency (ELF) magnetic fields on the transport of Ca2+ was studied in a biological system consisting of highly purified plasma membrane vesicles. We tested two quantum mechanical theoretical models that assume that biologically active ions can be bound to a channel protein and influence the opening state of the channel. Vesicles were exposed for 30 min at 32 °C and the calcium efflux was studied using radioactive 45Ca as a tracer. Static magnetic fields ranging from 27 to 37 T and time varying magnetic fields with frequencies between 7 and 72 Hz and amplitudes between 13 and 114 T (peak) were used. We show that suitable combinations of static and time varying magnetic fields directly interact with the Ca2+ channel protein in the cell membrane, and we could quantitatively confirm the model proposed by Blanchard. Bioelectromagnetics 24:395-402, 2003. © 2003 Wiley-Liss, Inc.
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