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  • 1995-1999  (4,333)
  • Life and Medical Sciences  (4,332)
  • Nuclear reactions
  • 101
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 575-584 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The role of hsp27 as an inhibitor of actin polymerization was considered in the context of the actin cytoskeleton and its relationship with focal adhesion formation. The aim of this study was to evaluate the potential effects of hsp27 on focal adhesion formation as a relevant biological consequence of actin stress fiber formation. When hsp27 was overexpressed in stably transfected cells, cell attachment was delayed and recovery of disrupted stress fibers and focal adhesions was limited. In ROS 17/2.8 cells, heat shock caused the reversible disruption of stress fibers and focal adhesions. The loss of stress fibers and focal adhesions was associated with reduced phosphotyrosine on the focal adhesion kinase (FAK). Microinjection of recombinant 6-His hsp27 and phosphorylated 6-His hsp27 was used to demonstrate that nonphosphorylated hsp27 prevented the recovery of stress fibers and focal adhesions. These results provide in vivo evidence that hsp27 acts as an inhibitor of actin polymerization that can alter cellular interactions with extracellular environments by perturbation of stress fibers, and subsequently focal adhesions. J Cell Physiol 177:575-584, 1998. © 1998 Wiley-Liss, Inc.
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  • 102
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Hepatocytes entrapped in collagen gel and cultured in serum-free conditions survived longer than cells cultured on plastic (5 days vs. 3 weeks), showed fewer signs of early cell senescence (no increase in c-fos oncoprotein expression), and maintained the expression of differentiated hepatic metabolic functions over a longer period of time. Cells cultured in collagen gels retained their ability to respond to hormones. The insulin-stimulated glycogen synthesis rate remained fairly constant during 18 days in culture (between 5.4 ± 0.37 and 9 ± 2.7 nmol glucose/h/μg DNA). Collagen-cultured hepatocytes recovered glycogen stores to levels similar to those found in liver, or in hepatocytes isolated from fed rats. Urea synthesis from ammonia remained stable for more than 2 weeks (average value, 23 ± 4 nmol urea/h/μg DNA). The rate of albumin synthesis in collagen-entrapped cells was maintained above the day-1 level during 18 days in culture. Cells showed high levels of glutathione (GSH) (1,278 ± 152 pmol/μg DNA). Biotransformation activities CYP4501A1, CYP4502A2, CYP4502B1, and CYP4503A1 remained fairly stable in collagen-cultured hepatocytes. CYP4502E1 and CYP4502C11 decreased but were still measurable after 18 days. After 4 days in culture, GST activity returned to levels observed in isolated hepatocytes. In contrast with plastic cultures, cells responded to CYP450 inducers (methylcholanthrene for CYP4501A1, CYP4501A2, and gluthatione-transferase, and ethanol for CYP4502E1) for more than 2 weeks. CYP4501A1, CYP4501A2, and glutathione-transferase A2 (GST A2) induction was preceded by an increase in specific mRNA, while the effects on CYP4502E1 seemed to be at a posttranslational level. Analysis of the expression of relevant hepatic genes by reverse Northern and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that culturing hepatocytes in collagen gels results in a sustained higher expression of key liver transcription factor genes DBP, C/EBP-α and -β, and HNF-1 and -4, as well as specific liver enzyme genes (phosphoenol pyryvate carboxykinase, and carbamoylphosphate-synthetase I). J Cell Physiol 177:553-562, 1998. © 1998 Wiley-Liss, Inc.
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  • 103
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 535-552 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The viral Crk oncogene (v-Crk) is known to induce sarcomas in chicken and its cellular homologs c-Crk I, c-Crk II, and Crk-like (CRKL) have been implicated in many signal transduction events. These include cell differentiation, cell migration, and the induced nonresponsiveness of T-cells to stimulation of the T-cell receptor (TCR), a state known as anergy. CRKL is also the most prominent substrate of the Bcr-Abl oncoprotein which causes human chronic myelogenous leukemias (CML). The modular composition of the Crk family adapters which largely consist of Src homology (SH2 and SH3) domains has prompted an intensive search for physiological and pathological upstream and downstream signalling partners which selectively bind to these adapters. Upstream proteins include various receptors and large multisite docking proteins, while several protein kinases and guanine nucleotide release proteins (GNRPs) have been suggested to function downstream of c-Crk and CRKL. Most Crk/CRKL SH2- and SH3-binding proteins contain several docking sites with considerable sequence similarity. Thus the binding requirements of Crk/CRKL SH2 and SH3 domains are now well defined, providing a basis for the design of small inhibitory molecules to block the function of these adapter proteins. The enzymatic cascades activated through Crk family adapters are only partially known, but stress kinases (SAPKs/JNKs) and the GTPase Rap1, as well as the B-Raf isoform of the Raf protein kinases, are affected in some systems. Several yet unidentified, highly selective Crk interacting proteins detectable in specific cell types remain to be studied. More detailed analyses of the enzymatic activities triggered through Crk-type adapters will also be crucial to fully define the signalling pathways controlled by this protein family. J Cell Physiol 177:535-552, 1998. © 1998 Wiley-Liss, Inc.
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  • 104
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We have previously described a specific, saturable receptor for rat collagenase-3 in the rat osteosarcoma cell line, UMR 106-01. Binding of rat collagenase-3 to this receptor is coupled to the internalization and eventual degradation of the enzyme and correlates with observed extracellular levels of the enzyme. In this study we have shown that decreased binding, internalization, and degradation of 125I-rat collagenase-3 were observed in cells after 24 h of parathyroid hormone treatment; these activities returned to control values after 48 h and were increased substantially (twice control levels) after 96 h of treatment with the hormone. Subcellular fractionation studies to identify the route of uptake and degradation of collagenase-3 localized intracellular accumulation of 125I-rat collagenase-3 initially in Golgi-associated lysosomes and later in secondary lysosomes. Maximal lysosomal accumulation of the radiolabel and stimulation of general lysosomal activity occurred after 72 h of parathyroid hormone treatment. Preventing fusion of endosomes with lysosomes (by temperature shift, colchicine, or monensin) resulted in no internalized 125I-collagenase-3 in either lysosomal fraction. Treatment of UMR cells with the above agents or ammonium chloride decreased excretion of 125I-labeled degradation products of collagenase-3. These experiments demonstrated that degradation of collagenase-3 required receptor-mediated endocytosis and sequential processing by endosomes and lysosomes. Thus, parathyroid hormone regulates the expression and synthesis of collagenase-3 as well as the abundance and functioning of the collagenase-3 receptor and the intracellular degradation of its ligand. The coordinate changes in the secretion of collagenase-3 and expression of the receptor determine the net abundance of the enzyme in the extracellular space. J Cell Physiol 177:563-574, 1998. © 1998 Wiley-Liss, Inc.
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  • 105
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 585-592 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The effect of metabolic inhibitors on nontransferrin bound iron transport by K562 cells was investigated. Incubation with 1 μM rotenone, 10 μM antimycin, or 0.5 mM 2,4-dinitrophenol effectively reduced ATP levels by ∼50%. Both the rate and extent of Fe+3 uptake were impaired in ATP-depleted cells, which display a reduced Vmax for uptake. K562 cell ferrireductase activity was also lowered by metabolic inhibitors, suggesting that the apparent energy requirements for transport reside in the reduction of Fe+3 to Fe+2. However, ATP depletion was found to inhibit the rate and extent of Fe+2 uptake as well. Thus, the transbilayer passage of Fe+2 and/or Fe+3 appears to be an energy-requiring process. These features possibly reflect properties of the transport mechanism associated with a recently identified K562 cell transport protein, called SFT for “Stimulator of Fe Transport,” since exogenous expression of its activity is also affected by ATP depletion. J Cell Physiol 177:585-592, 1998. © 1998 Wiley-Liss, Inc.
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  • 106
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 593-605 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Clusterin (ApoJ) is an extracellular glycoprotein expressed during processes of tissue differentiation and regression that involve programmed cell death (apoptosis). Increased clusterin expression has also been found in tumors, however, the mechanism underlying this induction is not known. Apoptotic processes in tumors could be responsible for clusterin gene activation. Alternatively, oncogenic mutations could modulate signal transduction, thereby inducing the gene. We examined the response of the rat clusterin gene to two oncogenes, Ha-ras and c-myc, in transfected Rat1 fibroblasts. While c-myc overexpression did not modify clusterin gene activity, the Ha-ras oncogene produced a seven to tenfold repression of clusterin mRNA; this down-regulation was also observed in the presence of c-myc. Since no induction of the clusterin gene was observed by the two oncogenes, we tested the alternative mechanism involving apoptosis. Growth factor withdrawal induced apoptosis, as shown by DNA degradation and micronuclei formation in the floating cells. Concomittantly we observed a three to tenfold increase in the amount of clusterin mRNA in the adhering cells of Rat1 and the c-myc transformed cell lines, and a weaker induction in the Ha-ras transformed cell line. On the basis of our results, we suggest that clusterin gene induction in the vital cells is produced by signaling molecules that are generated by the apoptotic cells. We conclude that apoptotic processes, not oncogenic mutations, are responsible for increased clusterin expression in tumors. J Cell Physiol 177:593-605, 1998. © 1998 Wiley-Liss, Inc.
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  • 107
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 618-627 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: We previously reported that the enterocytic differentiation of human colonic Caco-2 cells correlated with down-regulation of fibronectin (FN) and laminin (LN), two extracellular matrix components interacting with cell surface integrin receptors. We now investigated whether Caco-2 cell differentiation was associated with alterations in integrin signaling with special interest in the expression and activity of focal adhesion kinase (FAK) and mitogen-activated protein (MAP) kinase. The differentiation of Caco-2 cells was associated with: (1) down-regulation of β1 integrin expression at the mRNA and protein levels; (2) increased FAK expression together with decreased FAK autophosphorylation; (3) decreased FAK's ability to associate with PI3-kinase and pp60c-src; and (4) increased MAP kinase expression along with decreased MAP activity. In addition, we show that FAK and MAP kinase belong to distinct integrin signaling pathways and that both pathways remain functional during Caco-2 cell differentiation since the coating of differentiating cells on FN and LN but not on polylysine increased the tyrosine phosphorylation of FAK and of its endogenous substrate paxillin, and stimulated MAP kinase activity. In conclusion, our results provide evidence that FAK and MAP kinase, two signaling molecules activated independently by β1 integrins in Caco-2 cells, undergo alterations of both expression and activity during the enterocytic differentiation of this cell line. J Cell Physiol 177:618-627, 1998. © 1998 Wiley-Liss, Inc.
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  • 108
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Salivary glands contain two major epithelial cell types: acinar cells which produce the primary salivary secretion, including amylase, and ductal cells which reabsorb electrolytes but also secrete kallikrein. Here we investigated salivary acinar cell differentiation in vitro using the activity of the salivary amylase and tissue kallikrein promoters as markers of acinar cell and ductal cell differentiation, respectively. Each of the promoter sequences was cloned into a replication-deficient adenoviral vector containing the luciferase reporter gene. Previous studies showed that a human submandibular gland cell line (HSG) differentiated into acinar cells when cultured on a reconstituted basement membrane matrix (Matrigel). The luciferase activity of the amylase promoter vector (AdAMY-luc) was low in HSG cells cultured on plastic, where they grow as an epithelial monolayer. The promoter activity increased approximately tenfold when HSG cells were cultured on Matrigel and developed an acinar phenotype. Under the same conditions, the luciferase activity of the kallikrein promoter (AdKALL-luc) was not induced. Because HSG cells demonstrate acinar cell morphology, but not amylase gene expression, when cultured on laminin-1, certain soluble components of Matrigel were tested for their ability to induce the amylase promoter during in vitro differentiation of acinar cells. We find that epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α), which are present in the basement membrane, and hepatocyte growth factor (HGF) increase activity of the amylase promoter. Other basement membrane-derived growth factors such as TGF-β, basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PGDF), as well as tumor necrosis factor (TNF-α), keratinocyte growth factor (KGH), nerve growth factor (NGF) and interferon gamma (IFN-γ) were inactive. This system will be further exploited to study the mechanisms by which extracellular matrix molecules and growth factors regulate salivary acinar cell differentiation. J Cell Physiol 177:628-635, 1998. Published 1998 Wiley-Liss, Inc.
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  • 109
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The role of HSP27 in cell growth and resistance to stress was investigated using murine fibrosarcoma L929 cells (normally devoid of constitutively expressed small HSPs) and human osteoblast-like SaOS-2 cells stably transfected with a human hsp27 expression vector. Our data showed that our L929 cells were more resistant to oxidative stress than generally observed for this line. Production of HSP27 in these cells led to a marked decrease in growth rate associated with a series of phenotypical changes, including cell spreading, cellular and nuclear hypertrophy, development of an irregular outline, and a tremendous accumulation of actin stress fibers. By contrast, none of these changes was observable in SaOS-2/hsp27 transfectants overexpressing the protein product. Together, these observations are consistent with a cause-to-effect cascade relationship between increased (or induced) HSP27 expression, changes in cytoskeletal organization, and decreased growth. On the other hand, whereas the transfection of the hsp27 gene increased the cell resistance to heat in both cell lines, only in SaOS-2 cells was this associated with protection to the cytotoxic action of tumor necrosis factor-alpha (TNF-α) and etoposide. Unexpectedly, L929/hsp27 transfectants exhibited an increased sensitivity to both agents and also to H2O2. These data thus imply that different mechanisms are involved in the cell resistance to heat shock and to the cytotoxic action of TNF-α, etoposide, and H2O2. They also plead against the simple view that overexpression of a phosphorylatable HSP27 would necessarily be beneficial in terms of increased cell resistance to any type of stress. Our data further indicate that the role of HSP27 in cellular resistance to stress and in cell proliferation involves different targets and that the ultimate result of its interference with these processes depends on the intracellular context in which the protein is expressed. J Cell Physiol 177:606-617, 1998. © 1998 Wiley-Liss, Inc.
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  • 110
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Using an expression cloning approach, we identified and cloned a novel intracellular protein produced by osteoclasts that indirectly induces osteoclast formation and bone resorption, termed OSF. Conditioned media from 293 cells transiently transfected with the 0.9 kb OSF cDNA clone stimulated osteoclast-like cell formation in both human and murine marrow cultures in the presence or absence 10-9 M 1,25-dihydroxyvitamin D3. In addition, conditioned media from 293 cells transfected with the OSF cDNA clone enhanced the stimulatory effects of 1,25-(OH)2D3 on bone resorption in the fetal rat long bone assay. In situ hybridization studies using antisense oligomers showed expression of OSF mRNA in highly purified osteoclast-like cells from human giant cell tumors of the bone. Northern blot analysis demonstrated ubiquitous expression of a 1.3 kb mRNA that encodes OSF in multiple human tissues. Sequence analysis showed the OSF cDNA encoded a 28 kD peptide that contains a c-Src homology 3 domain (SH3) and ankyrin repeats, suggesting that it was not a secreted protein, but that it was potentially involved in cell signaling. Consistent with these data, immunoblot analysis using rabbit antisera against recombinant OSF demonstrated OSF expression in cell lysates but not in the culture media. Furthermore, recombinant OSF had a high affinity for c-Src, an important regulator of osteoclast activity. Taken together, these data suggest that OSF is a novel intracellular protein that indirectly enhances osteoclast formation and osteoclastic bone resorption through the cellular signal transduction cascade, possibly through its interactions with c-Src or other Src-related proteins. J Cell Physiol 177:636-645, 1998. © 1998 Wiley-Liss, Inc.
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  • 111
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The addition of dexamethasone (dex) to human fibroblast cultures has been found to elicit enhanced proliferation. This enhancement is manifested by an increase in the initial growth rate, saturation density, and proliferative life span of WI-38 fibroblast cultures grown in the presence of dex. We examined the acute effects of dex on a number of growth-related genes in WI-38 cells. Our results show a decrease in the level of the cyclin-dependent kinase inhibitor p21Waf1/Cip1/Sdi1 in response to dex. In addition, the level of the insulin-like growth factor type 1 receptor (IGF-1R) is increased in dex-treated cells. These changes are correlated with changes in the activity of the p21Waf1/Cip1/Sdi1 and IGF-1R promoters. The results presented in this report suggest that dex may delay growth arrest in response to contact inhibition, as well as during cellular senescence. Thus, dex may act at multiple levels to enhance cellular proliferation in WI-38 cells: first, to decrease the level of an inhibitor of cell-cycle progression, and second, to increase the sensitivity of WI-38 cells to the proliferative effects of IGF-1. These acute effects may cooperate with other, as yet uncharacterized effects, to result in the enhanced proliferation seen in the presence of dex. J. Cell. Physiol. 177:396-401, 1998. © 1998 Wiley-Liss, Inc.
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  • 112
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 402-410 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Potassium (K+) conductances are known to be involved in cell proliferation of a number of nonexcitable cell types. The nature of the mechanism by which K+ channel inhibition reduces cell proliferation has remained elusive despite intensive search. We investigated whether such a phenomenon could be demonstrated in excitable cells, using the GH3 pituitary cell line as a cell model. Our aims were: (1) to study the effect of K+ channel inhibition on the proliferation of GH3 cells; and (2) to investigate the putative intracellular signals involved in this inhibition. Tetraethylammonium chloride (TEA), a blocker of the calcium (Ca2+)-dependent K+ conductances of GH3, was found to reversibly inhibit cell proliferation, as measured by 3H-thymidine incorporation. Cell cycle block specifically occurred at the G1/S phase of the cell cycle. This inhibition of proliferation was observed for 1-4 mM TEA, which suppressed most of the Ca2+-activated K+ current and part of the inward rectifying K+ current, as shown by electrophysiological experiments. Increasing extracellular K+ concentrations with KCl also inhibited cell proliferation in a dose-dependent manner. Both TEA and KCl depolarized the cells and increased intracellular Ca2+ levels ([Ca2+]i), showing that, in this type of excitable cell, inhibition of cell proliferation can be associated with elevated Ca2+ levels. Ca2+ and membrane resting potential (MRP) were considered as possible messengers of this inhibition. Our results suggest that cell cycle arrest of GH3 cells by K+ channel block probably involves an additional pathway, distinct from those of Ca2+ and MRP. J. Cell. Physiol. 177:402-410, 1998. © 1998 Wiley-Liss, Inc.
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  • 113
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 177 (1998), S. 387-395 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Previously, we reported that unaggressive, growth factor-dependent FET human colon carcinoma cells downregulated their transforming growth factor alpha (TGFα) expression in a quiescent state (G0/G1) induced by growth factor and nutrient deprivation (Mulder, 1991, Cancer Res., 51:2256-2262). In contrast, highly aggressive, growth factor-independent HCT116 human colon carcinoma cells aberrantly upregulated this autocrine activity in the quiescent state (Mulder, 1991, Cancer Res., 51:2256-2262; Howell et al., 1998, Mol. Cell. Biol., 18:303-313). In this report, the role of autocrine TGFα and the mechanism of its regulation of expression during reentry into the cell cycle from a noncycling growth state were determined in FET cells. Optimal induction of DNA synthesis from a quiescent state in FET cells is dependent upon autocrine TGFα as well as exogenous transferrin and insulin. Reentry into the cell cycle resulting from treatment with exogenous transferrin and insulin resulted in ∼3-fold induction of TGFα expression within 1 hr. TGFα induction was controlled at the transcription level, and the cis-controlling element was localized to the region between bp -370--201 relative to the translation start codon within the TGFα promoter. Thus neutralization of autocrine TGFα protein revealed that the induced TGFα autocrine activity was necessary for DNA synthesis and acted only in the early G1 phase of the cell cycle. Blockade of autocrine TGFα expression early in the cell cycle resulted in the reduction of DNA synthesis, whereas treatment with neutralization antibody at later times had no effect. This suggested that autocrine TGFα functions to initiate cell growth from noncycling states. This was further confirmed by the dependence of FET cells upon autocrine TGFα for colony formation in experiments where the plating density was sufficiently low to generate a lag phase in tissue culture. In contrast, TGFα autocrine activity was not required for exponential phase cells, as evidenced by the failure of TGFα neutralizing antibody to inhibit proliferation in this growth state. Taken together, these results suggest that autocrine TGFα acts primarily in the process of growth initiation by moving cells from a noncycling state back into the cell cycle, rather than supporting cell growth already initiated. J. Cell. Physiol. 177:387-395, 1998. © 1998 Wiley-Liss, Inc.
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  • 114
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Basic fibroblast growth factor (bFGF, FGF-2) is progressively lost from mammary epithelial cells as they become malignant. To investigate the effects of restoring the expression of bFGF in breast cancer cells, we constructed MCF-7 cells that permanently overexpress 18-kD cytoplasm-localizing bFGF (MCF-7/ΔAFGF(18) cells) and cells that express both the 18-kD along with the 22- and 24-kD nucleus-localizing bFGF peptides (MCF-7/NCFFGF(18,22,24) cells), using retroviral transduction. These stable cell constructs grew more slowly and had a larger fraction of their populations in the G0/G1 phase of the cell cycle than control cells. All forms of bFGF were eluted from MCF-7/NCFFGF(18,22,24) cell monolayers with 2 M NaCl, in contrast to fibroblasts that were demonstrated to secrete only the 18-kD bFGF isoform. High-affinity binding of 18-kD 125I-bFGF to these cells was significantly decreased, probably because of competitive binding by the autocrine-secreted bFGF. Recombinant 18-kD bFGF that was previously demonstrated in our laboratory to inhibit proliferation, activate MAP kinase, and induce the cyclin-dependent kinase inhibitor p21WAF1/CIP1 in MCF-7 cells, further inhibited MCF-7/ΔAFGF(18) cells but had no effect on MCF-7/NCFFGF(18,22,24) cells. The total cellular content of the high-affinity FGF receptors 1-3 was unchanged, but FGF receptor 4 was decreased in MCF-7/NCFFGF(18,22,24) cells. Both cell types overexpressing bFGF isoforms had elevated levels of the cyclin-dependent kinase inhibitor p27Kip1 but not that of p21WAF1/CIP1. In MCF-7/ΔAFGF(18) cells, FGFR1 and MAP kinase were constitutively phosphorylated. Exogenous recombinant 18-kD bFGF did not accentuate these effects but did induce an increase in the levels of p21WAF1/CIP1 corresponding to the further inhibition induced by exogenous bFGF in these cells. In MCF-7/NCFFGF(18,22,24) cells, FGFR1 and MAP kinase were not phosphorylated at baseline nor upon stimulation with recombinant bFGF, and exogenous bFGF only had a minimal effect on low steady-state p21WAF1/CIP1 levels. However, stimulation of these cells with phorbol ester or insulin did result in MAP kinase phosphorylation. While growth-inhibited in the G1 phase of the cell cycle, MCF-7/NCFFGF(18,22,24) cells retained active isoforms of cdk2 and the hyperphosphorylated form of Rb. These data suggest that high molecular weight forms of bFGF overexpressed in MCF-7 cells do not activate the receptor-mediated MAP kinase pathway, and do not induce p21WAF1/CIP1 in an autocrine manner, but inhibit proliferation through other, possibly direct nuclear signalling mechanisms. J. Cell. Physiol. 177:411-425, 1998. © 1998 Wiley-Liss, Inc.
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  • 115
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Bone marrow stromal cells (BMSCs) are a heterogeneous population of cells derived from colony-forming units-fibroblastic (CFU-Fs). These cells reside in the bone marrow cavity and are capable of differentiating into several cell phenotypes including osteoblasts, chondroblasts, hematopoiesis-supporting stromal cells, and adipocytes. However, the factors that regulate the proliferation and differentiation of the BMSC population are for the most part unknown. Since many members of the receptor tyrosine kinase (RTK) family have been shown to participate in growth control of various mesenchymal cell populations, in this study we examined the expression and function of RTKs in the BMSC population. Degenerate oligonucleotides corresponding to two conserved catalytic domains of the RTK family and RT-PCR were used initially to determine which RTKs are expressed in the human BMSC (hBMSC) system. After subcloning the amplification product generated from mRNA of a multicolony-derived hBMSC strain, PDGF receptor (β), EGF receptor, FGF receptor 1, and Axl were identified by DNA sequencing of 26 bacterial colonies. Furthermore, PDGF and EGF were found to enhance BMSC growth in a dose-dependent manner and to induce tyrosine phosphorylation of intracellular molecules, including the PDGF and EGF receptors themselves, demonstrating the functionality of these receptors. On the other hand, bFGF was found to have little effect on proliferation or tyrosine phosphorylation. Since single colony-derived hBMSC strains are known to vary from one colony to another in colony habit (growth rate and colony structure) and the ability to form bone in vivo, the expression levels of these RTKs were determined in 18 hBMSC clonal strains by semiquantitative RT-PCR and were found to vary from one clonal strain to another. While not absolutely predictive of the osteogenic capacity of individual clonal strains, on average, relatively high levels of PDGF-receptor were found in bone-forming strains, while on average, nonbone-forming strains had relatively high levels of EGF-receptor. Taken together, these results indicate that RTKs play a role in the control of hBMSC proliferation, and that the differential pattern of RTK expression may be useful in correlating the biochemical properties of individual clonal strains with their ability to produce bone in vivo. J. Cell. Physiol. 177:426-438, 1998. © 1998 Wiley-Liss, Inc.
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  • 116
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Vascular endothelial growth factor-C (VEGF-C) is a recently characterized member of the VEGF family of angiogenic polypeptides. We demonstrate here that VEGF-C is angiogenic in vitro when added to bovine aortic or lymphatic endothelial (BAE and BLE) cells but has little or no effect on bovine microvascular endothelial (BME) cells. As reported previously for VEGF, VEGF-C and basic fibroblast growth factor (bFGF) induced a synergistic in vitro angiogenic response in all three cells lines. Unexpectedly, VEGF and VEGF-C also synergized in the in vitro angiogenic response when assessed on BAE cells. Characterization of VEGF receptor (VEGFR) expression revealed that BME, BAE, and BLE cell lines express VEGFR-1 and -2, whereas of the three cell lines assessed, only BAE cells express VEGFR-3. We also demonstrate that VEGF-C increases plasminogen activator (PA) activity in the three bovine endothelial cell lines and that this is accompanied by a concomitant increase in PA inhibitor-1. Addition of α2-antiplasmin to BME cells co-treated with bFGF and VEGF-C partially inhibited collagen gel invasion. These results demonstrate, first, that by acting in concert with bFGF or VEGF, VEGF-C has a potent synergistic effect on the induction of angiogenesis in vitro and, second, that like VEGF and bFGF, VEGF-C is capable of altering endothelial cell extracellular proteolytic activity. These observations also highlight the notion of context, i.e., that the activity of an angiogenesis-regulating cytokine depends on the presence and concentration of other cytokines in the pericellular environment of the responding endothelial cell. J. Cell. Physiol. 177:439-452, 1998. © 1998 Wiley-Liss, Inc.
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  • 117
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Cell cycle control of histone H4 gene transcription is mediated by the multipartite promoter domain H4-Site II, which supports transcriptional activation at the G1/S phase transition and modulates basal H4 gene transcription. Proliferation-specific transcription is determined by the integrated activities of three distinct promoter factors interacting with H4-Site II: the interferon regulatory factor IRF-2 (synonymous with HiNF-M), HiNF-D (a complex between the homeodomain protein CDP-cut and the cell cycle mediators CDC2, cyclin A and pRB), as well as HiNF-P/H4TF-2. However, the contribution of HiNF-D to the enhancement and/or suppression of H4 gene transcription at specific cell cycle stages remains to be established. We used a panel of synchronized HeLa S3 cell lines containing stably integrated H4 promoter/CAT reporter gene constructs with mutations in H4-Site II. The temporal regulation of CAT mRNA accumulation under the control of the H4 promoter was analyzed by RNase protection analysis. Our main finding is that mutation of the HiNF-D/CDP-cut binding site alters the timing of histone gene activation during the cell cycle. Furthermore, our data indicate that HiNF-P/H4TF-2 may functionally compensate for HiNF-M/IRF-2 at Site II to regulate histone H4 gene transcription in HeLa S3 cervical carcinoma cells during early S phase. We postulate that HiNF-D (CDP-cut/cyclin A/CDC2/pRB containing complex) promotes HiNF-M/IRF-2 (and/or HiNF-P/H4TF-2) dependent histone H4 gene activation at the G1/S phase transition and attenuates H4 gene transcription at later cell cycle stages. The mechanistic division in the gene regulatory functions of the three H4-Site II binding proteins may ensure that histone H4 gene expression is stringently coupled with the onset of S phase in response to growth factor/cytokine-induced cell cycle progression. J. Cell. Physiol. 177:453-464, 1998. © 1998 Wiley-Liss, Inc.
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  • 118
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    Journal of Cellular Physiology 177 (1998), S. 465-473 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Human dermal fibroblasts suspended in a collagen matrix exhibit a 4-day delay in cell division, while the same cells in monolayer divided by day 1. The initial rates of 3H-thymidine incorporation by cells in monolayer or suspended in collagen were not significantly different. When suspended in collagen, there was a threefold increase in the proportion of cells in a tetraploidal (4N) DNA state compared to the same cells in monolayer. Flow cytometry analysis and 3H-thymidine incorporation studies identified the delay of cell division as a consequence of a block in the G2/M of the cell cycle and not an inhibition of DNA synthesis. The inclusion of 150 μ/ml of hyaluronic acid (HA) in the manufacture of fibroblast populated collagen lattices (FPCL) caused a stimulation of cell division, as determined by cell counting; increased the expression of tubulin, as determined by Western blot analysis; and reduced the proportion of cells in a 4N state, as determined by flow cytometry. HA added to the same cells growing in monolayer produced a minimal increase in the rate of cell division or DNA synthesis. HA supplementation of FPCLs stimulated cell division as well as tubulin concentrations, but it did not enhance lattice contraction. The introduction of tubulin isolated from pig brain or purchased tubulin into fibroblasts by electroporation prior to their transfer into collagen lattices promoted cell division in the first 24 hours and enhanced FPCL contraction. It is proposed that tubulin protein, the building blocks of microtubules, is limited in human fibroblasts residing within a collagen matrix. When human fibroblasts are suspended in collagen, one effect of added HA may be to stimulate the synthesis of tubulin which assists cells through the cell cycle. J. Cell. Physiol. 177:465-473, 1998. © 1998 Wiley-Liss, Inc.
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  • 119
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    Journal of Cellular Physiology 177 (1998), S. 474-482 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: In this study we examined the regulation of cdk1 expression in normal human epidermal keratinocytes (HEKs) and neoplastic keratinocytes. Keratinocytes were growth-arrested by allowing the cells to grow to confluence or by treating them with interferon-gamma (IFNγ) or 12-O-tetradecanoyl phorbol-13-acetate (TPA). RT-PCR and Western blot analysis demonstrated that cdk1 was profoundly reduced in growth-arrested HEKs when compared with dividing HEKs. In contrast, a squamous carcinoma cell line, SCC25, did not growth-arrest in response to growth inhibitors and did not downregulate cdk1 expression. Transfection of HEKs with a reporter gene driven off a 2.5-kb fragment of the human cdk1 promoter indicated that the downregulation of cdk1 upon growth arrest was transcriptional. Deletion mapping of the cdk1 promoter indicated that a repressor region was located between -949--722 bp. This repressor region was not operative in the SCC25 cells. Examination of DNA:protein binding complexes by gel-shift analysis indicated that nuclear factors from both proliferative and growth-arrested cells bound to the DNA fragment spanning -949--722 bp. Further analysis revealed that this binding could be resolved into a constitutive and growth arrest-specific complex that bound in a similar fashion to regions spanning -892--831 bp and -831--774 bp, respectively. The putative growth arrest-specific complex was not found in contact-inhibited fibroblasts and was found at very low levels in SCC25 cells, indicating that the putative repressor binding was growth arrest-specific and possibly keratinocyte-specific. The binding complexes bound to these two fragments were localized, by competition analysis, to regions -874--853 bp and -830--800 bp. This is the first report of a transcriptional repressor being operative during keratinocyte growth arrest. J. Cell. Physiol. 177:474-482, 1998. © 1998 Wiley-Liss, Inc.
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  • 120
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    Journal of Cellular Physiology 177 (1998), S. 483-492 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Treatment with the sulfhydryl oxidant diamide denatures and aggregates cellular proteins, which prior studies have implicated as an oxidative damage that activates the heat shock transcription factor and induces thermotolerance. This study was initiated to further characterize cellular response to diamide-denatured proteins, including their involvement in diamide cytotoxicity. Cytotoxic diamide exposures at 37.0°C denatured and aggregated cellular proteins in a manner that was proportional to cell killing, but this correlation was different than that established for heated cells. Diamide exposures at 24.0°C were orders of magnitude less cytotoxic, with little additional killing occurring after diamide was removed and cells were returned to 37.0°C. Thus, protein denaturation that occurred at 37.0°C, after proteins were chemically destabilized by diamide at 24.0°C [Freeman et al., J. Cell. Physiol., 164:356-366 (1995) Senisterra et al., Biochemistry 36: 11002-11011 (1997)], had little effect on cell killing. Thermotolerance protected cells against diamide cytotoxicity but did not reduce the amount of denatured and aggregated protein observed immediately following diamide exposure. However, denatured/aggregated proteins in thermotolerant cells were disaggregated within 17 h following diamide exposure, while no disaggregation was observed in nontolerant cells. This more rapid disaggregation of proteins may be one mechanism by which thermotolerance protects cells against diamide toxicity, as it has been postulated to do against heat killing. As with heat shock, nontoxic diamide exposures induced maximal tolerance against heat killing; however, there was no detectable, increased synthesis of heat shock proteins. Thus, diamide treatment proved to be a reproducible procedure for inducing a phase of thermotolerance that does not require new heat shock protein (HSP) synthesis, without having to use transcription or translation inhibitors to suppress HSP gene expression.These results complement those from studies with other stresses to establish the importance of protein denaturation/aggregation as a cytotoxic consequence of stress and a trigger for thermotolerance induction. The data also illustrate that differences in how proteins are denatured and aggregated can affect their cytotoxicity and the manner in which thermotolerance is expressed. J. Cell. Physiol. 177:483-492, 1998. © 1998 Wiley-Liss, Inc.
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  • 121
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    Journal of Cellular Physiology 177 (1998), S. 499-499 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: No abstract.
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  • 122
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    Journal of Cellular Physiology 177 (1998), S. 501-506 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: CDK9 is a cdc2-related kinase protein. Previously named PITALRE, this protein is a serine-threonine kinase involved in many physiological processes. Unlike most of the cdc2-like kinases, its activity is not cell cycle-regulated. CDK9 acts preferentially in processes different from cell-cycle regulation, such as differentiation. Its cyclin partners, cyclins of T family, recently have been isolated. CDK9 immunoprecipitates with several unidentified polypeptides that may regulate its kinase activity. CDK9 has been shown to associate with the HIV-Tat protein, suggesting a possible involvement in AIDS. CDK9 recently was shown to be responsible for the kinase activity associated with the TAK complex and with the P-TEFb complex, suggesting activity also in the transcription process. J Cell Physiol 177:501-506, 1998. © 1998 Wiley-Liss, Inc.
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  • 123
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    Journal of Cellular Physiology 177 (1998), S. 493-498 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Ultraviolet light A (UVA) is shown to play an augmentative or synergistic role with UVB in pathophysiological conditions induced by solar radiation. Thus, UVA would contribute significantly to the development of skin malignancies. It remains unclear, however, how UVA contributes to solar radiation-induced immune suppression. Keratinocytes (KC) produce cytokines which are a significant mediator of inflammatory and immunologic reactions in skin exposed to solar radiation and are a potent mediator in the induction of immune suppression. To examine if UVA alters the expression and production of cytokines from KC, normal human keratinocytes (HuSK) were cultured and exposed to UVA at doses ranging between 2.5 and 20 kJ/m2. Constitutive expression of the p35 subunit of interleukin (IL)-12 was detected by reverse transcription-polymerase chain reaction (RT-PCR) and the p40 subunit was induced by UVA irradiation dose dependently. IL-12 protein was also detected in the supernatants from UVA-irradiated HuSK by enzyme-linked imuunosorbent assay (ELISA) and confirmed by a bioassay. On the other hand, the same doses of UVA did not induce IL-10 mRNA or IL-10 protein which has been shown to be one of the cytokines responsible for the induction of UVB-induced immunosuppression. Considering that IL-12 promotes activation of Th1 cells and prevents the activation of Th2 cells and that administration of IL-12 has been shown to block the induction of immune suppression in UV-irradiated animals, our results suggest that UVA modulates skin immune function distinctively from UVB by affecting the balance between IL-10 and IL-12 produced from KC. J. Cell. Physiol. 177:493-498, 1998. © 1998 Wiley-Liss, Inc.
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  • 124
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    Journal of Cellular Physiology 177 (1998), S. 507-517 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Neuropeptides, including mammalian bombesin-like peptides, act as potent cellular growth factors and have been implicated in a variety of normal and abnormal processes, including development, inflammation, and malignant transformation. These signaling peptides exert their characteristic effects on cellular processes by binding to specific G protein-coupled receptors (GPCR) on the surface of their target cells. Typically, the binding of a neuropeptide to its cognate GPCR triggers the activation of multiple signal transduction pathways that act in a synergistic and combinatorial fashion to relay the mitogenic signal to the nucleus and promote cell proliferation. A rapid increase in the synthesis of lipid-derived second messengers with subsequent activation of protein phosphorylation cascades is an important early response to neuropeptides. An emerging theme in signal transduction is that these agonists also induce rapid and coordinate tyrosine phosphorylation of cellular proteins including the nonreceptor tyrosine kinase p125fak and the adaptor proteins p130cas and paxillin. This tyrosine phosphorylation pathway depends on the integrity of the actin cytoskeleton and requires functional Rho. The purpose of this article is to review recent advances in unraveling the pathways that play a role in transducing mitogenic and migratory responses induced by G protein-coupled neuropeptide receptor agonists. J Cell Physiol 177:507-517, 1998. © 1998 Wiley-Liss, Inc.
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  • 125
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The pentameric B subunit of verotoxin (VT) mediates the attachment to cell surface globotriaosyl ceramide (Gb3) to facilitate receptor-mediated endocytosis of the toxin. In highly toxin-sensitive tumor cells, the holotoxin and VT1 B subunit is targeted intracellularly to elements of the endoplasmic reticulum (ER)/nuclear membrane. In less sensitive cells, the toxin is targeted to components of the Golgi apparatus. We have studied two cell systems: the induced VT hypersensitivity of human astrocytoma cell lines cultured in the presence of sodium butyrate (compared to sodium propionate and capronate) and the increased VT sensitivity of multiple drug-resistant mutants as compared to parental human ovarian carcinoma cells. In both cases, a difference in the intracellular retrograde transport of the receptor-bound internalized toxin to the ER/nuclear envelope, as opposed to the Golgi, correlated with a 〉1,000-fold increase in cell sensitivity to VT. This change in intracellular routing may be due to sorting of Gb3 fatty acid isoforms, since nuclear targeting was found in turn to correlate with the preferential synthesis of Gb3 containing shorter chain (primarily C16) fatty acid species. We propose that the isoform-dependent traffic of Gb3 from the cell surface to the ER/nuclear membrane provides a new signal transduction pathway for Gb3 binding proteins. J Cell Physiol 177:646-660, 1998. © 1998 Wiley-Liss, Inc.
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  • 126
    ISSN: 0197-8462
    Keywords: ELF ; ODC ; EMF ; Noise ; embryonic development ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Previously, we have shown that the application of a weak (4 μT) 60 Hz magnetic field (MF) can alter the magnitudes of the ornithine decarboxylase (ODC) activity peaks which occur during gastrulation and neurulation of chick embryos. We report here the ODC activity of chick embryos which were exposed to the superposition of a weak noise MF over a 60 Hz MF of equal (rms strength). In contrast to the results we obtain with a 60 Hz field alone, the activity of ODC in embryos exposed to the superposition of the incoherent and 60 Hz fields was indistinguishable from the control activity during both gastrulation and neurulation. This result adds to the body of experimental evidence which demonstrates that the superposition of an incoherent field inhibits the response of biological systems to a coherent MF. The observation that a noise field inhibits ODC activity changes is consistent with our speculation that MF-induced ODC activity changes during early development may be related to MF-induced neural tube defects at slightly later stages (which are also inhibited by the superposition of a noise field). Bioelectromagnetics 19:53-56, 1998. © 1998 Wiley-Liss, Inc.
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  • 127
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    Bioelectromagnetics 19 (1998), S. 75-78 
    ISSN: 0197-8462
    Keywords: electromagnetic fields ; pulsed magnetic fields (PEMFs) ; osteoporosis ; bone density ; microgravity ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: A 1984 study determined the effect of a 72 Hz pulsating electromagnetic field (PEMF) on bone density of the radii of post-menopausal (osteoporosis-prone) women, during and after treatment of 10 h daily for 12 weeks. Bone mineral densities of the treated radii increased significantly in the immediate area of the field during the exposure period and decreased during the following 36 weeks. Bone density determination of the radii of these women, remeasured after eight years, suggests no long-term changes. The bone density-enhancing effect of PEMFs should be further studied, alone and in combination with exercise and pharmacologic agents such as the bisphosphonates and hormones, as prophylaxis in the osteoporosis-prone postmenopausal woman and as a possible block to the demineralization effect of microgravity. Bioelectromagnetics 19:75-78, 1998. © 1998 Wiley-Liss, Inc.
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  • 128
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    Bioelectromagnetics 19 (1998), S. 79-84 
    ISSN: 0197-8462
    Keywords: memory ; radial arm maze ; rodents ; ELF ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: A series of four experiments was performed to determine the effect of exposure to a 50 Hz magnetic field on memory-related behaviour of adult, male C57BL/6J mice. Experimental subjects were exposed to a vertical, sinusoidal magnetic field at 0.75 mT (rms), for 45 min immediately before daily testing sessions on a spatial learning task in an eight-arm radial maze. Control subjects were only exposed to a background time-varying field of less than 50 nT and the ambient static field of about 40 μT. In each experiment, exposure significantly reduced the rate of acquisition of the task but did not affect overall accuracy. This finding is consistent with the results of another study that found that prior exposure to 60 Hz magnetic fields affected spatial learning in rats. Bioelectromagnetics 19:79-84, 1998. © 1998 Wiley-Liss, Inc.
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  • 129
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    Bioelectromagnetics 19 (1998), S. 107-111 
    ISSN: 0197-8462
    Keywords: culture growth cycle ; in vitro cell differentiation ; short- and long-term exposure ; adaptation ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The generalized polarization function of the fluorescent probe 2-dimethylamino-6-lauroylnaphthalene has been used to evaluate the lipid dynamics in Friend erythroleukemia cell membrane. The values of this function varied during the culture growth cycle, showing decreased lipid dynamics 24-48 h from the cell seeding. When the cycle occurred in a solenoid producing a magnetic field of 70 μT at 50 Hz in addition to the 45 μT DC of the earth (short-term 4-day exposure), the membrane lipid dynamics during this same time-period decreased by about 10% (P 〈 .04). After long-term (184 days) or extremely long-term (395 days) exposure of the cells to the magnetic field, little additional variation in the membrane lipid dynamics was observed, suggesting an adaptation phenomenon. A variation of membrane lipid dynamics was also observed due to in vitro cell differentiation (P 〈 .02). Nevertheless, the exposure of both undifferentiating and differentiating cells to a highly attenuated magnetic field in a magnetically shielded room (20 nT DC plus 2.5 pT AC) did not induce any modification of membrane lipid dynamics. Bioelectromagnetics 19:107-111, 1998. © 1998 Wiley-Liss, Inc.
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  • 130
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    Bioelectromagnetics 19 (1998), S. 279-292 
    ISSN: 0197-8462
    Keywords: magnetic field ; resonance theory ; thermal noise ; cyclotron frequency ; macromolecule ; ion motion ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: This is an attempt to solve the energetic problem of the primary detection of weak parallel static (DC) and alternating (AC) extremely low frequency (ELF) magnetic fields. We studied the equations of motion for an ion situated inside a macromolecule under the influence of these fields. The main concern is with the magnetic field influence on thermal motion of the ion in the macromolecule. The resonance effects are revealed at discrete frequencies of the ion thermal oscillations determined by the DC field magnitude and the AC field frequency. These phenomena result from the Larmor precession of the ion thermal motion. When the DC field or, to a greater extent, the combined DC and AC fields with the specific frequencies are turned on or cut off, changes occur in the energy of the ion thermal motion. If, inside the macromolecule, the ion is sufficiently protected against immediate impacts of particles of the medium surrounding the macromolecule, these changes may be enough to trigger alteration in the quantum state of the macromolecule. Bioelectromagnetics 19:279-292, 1998. © 1998 Wiley-Liss, Inc.
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  • 131
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    Bioelectromagnetics 19 (1998), S. 310-317 
    ISSN: 0197-8462
    Keywords: extremely low frequency ; statistical power ; human performance ; visual discrimination ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: A two-alternative, forced-choice visual duration discrimination task was used to examine the effect of an intermittent, 50 Hz, 100 μT magnetic field on accuracy at two different times of the day. A total of 59 female and 40 male subjects with an age range of 18 to 46 years were studied under both field-exposed and sham-exposed conditions. The subject's task was to decide which of two sequentially presented light flashes had the longer duration, percentage correct being the measure of performance. The data were gathered under double-blind conditions with sham and real exposure counterbalanced. Exposure to the magnetic field produced a small improvement in accuracy but only at the most difficult level of the task, with female subjects showing a larger improvement than males. The time of day at which the study was run had no effect on performance. Despite the relatively large number of subjects used and a relaxed alpha level (P = .3), the statistical power of the test to detect the observed effect was still only 0.71. Bioelectromagnetics 19:310-317, 1998. © 1998 Wiley-Liss, Inc.
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  • 132
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    Bioelectromagnetics 19 (1998), S. 335-340 
    ISSN: 0197-8462
    Keywords: Curly/Plum accumulation method ; non-lethal mutation ; recessive lethal mutation ; second chromosome ; viability ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Mutations, other than dominant lethals, were accumulated on wild type second chromosomes (+) of Drosophila melanogaster during exposure to 50 Hz sinusoidal alternating magnetic fields of 0.5 or 5 mT (rms) for 40 generations by the Curly/Plum(Cy/Pm) accumulation method. We maintained, for 40 generations under continuous exposure, each (+) chromosome as a heterozygote with (Cy) chromosome. Viability of the (+) chromosome was tested by sib-mating of (Cy/+) male and (Cy/+) female in a culture every 10th generation to obtain the homozygote. Viability indices, defined as twice the ratio of number of (+/+) flies to that of (Cy/+) flies plus 1 in the progeny of the test mating, also were calculated, which equaled 1.00 at the starting point. For the control and 0.5 and 5 mT exposed groups, percent frequencies of recessive lethal lines, defined as a line with (+/+) flies less than 0.3% in the test mating, were, respectively, 1.9, 0.9, and 2.9% (10th), 9.0, 4.9, and 9.5% (20th), 30.3, 22.9, and 30.4% (30th), and 39.9, 32.4, and 43.3% (40th generation). For the control and 0.5 and 5 mT groups, average viability indices, excluding lethals and markedly deleterious, were, respectively, 0.778, 0.796, and 0.752 (20th), 0.704, 0.698, and 0.694 (30th), and 0.669, 0.678, and 0.595 (40th generation). Their decreasing rates were 0.0054, 0.0059, and 0.0078 per generation. No significant difference was detected among the exposure levels in either the recessive lethal mutation frequency or the viability index. Bioelectromagnetics 19:335-340, 1998. © 1998 Wiley-Liss, Inc.
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  • 133
    ISSN: 0197-8462
    Keywords: 60 Hz electric field ; receptor-operated ion channels ; intracellular free calcium concentration ; purinergic receptor ; histamine receptor ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The mechanism of biological effects of extremely-low-frequency electric and magnetic fields may involve induced changes of Ca2+ transport through plasma membrane ion channels. In this study we investigated the effects of externally applied, low-intensity 60 Hz electric (E) fields (0.5 V/m, current density 0.8 A/m2+) on the agonist-induced Ca2+ fluxes of HL-60 leukemia cells. The suspensions of HL-60 cells received E-field or sham exposure for 60 min and were simultaneously stimulated either by 1 μM ATP or by 100 μM histamine or were not stimulated at all. After E-field or sham exposure, the responses of the intracellular calcium levels of the cells to different concentrations of ATP (0.2-100 μM) were assessed. Compared with control cells, exposure of ATP-activated cells to an E-field resulted in a 20-30% decrease in the magnitude of [Ca2+]i elevation induced by a low concentration of ATP (〈1 μM). In contrast, exposure of histamine-activated HL-60 cells resulted in a 20-40% increase of ATP-induced elevation of [Ca2+]i. E-field exposure had no effect on non-activated cells. Kinetic analysis of concentration-response plots also showed that compared with control cells, exposure to the E-field resulted in increases of the Michaelis constant, Km, value in ATP-treated cells and of the maximal [Ca2+]i peak rise in histamine-treated HL-60 cells. The observed effects were reversible, indicating the absence of permanent structural damages induced by acute 60 min exposure to electric fields. These results demonstrate that low-intensity electric fields can alter calcium distribution in cells, most probably due to the effect on receptor-operated Ca2+ and/or ion channels. Bioelectromagnetics 19:366-376, 1998. © 1998 Wiley-Liss, Inc.
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    Bioelectromagnetics 19 (1998), S. 192-198 
    ISSN: 0197-8462
    Keywords: magnetic fields ; mast cells in vitro ; histamine release ; compound 48/80 ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Reports have indicated effects of electromagnetic fields on inflammatory processes in vivo. To begin a systematic approach toward separating and examining the many components of such responses, we created and tested a temperature-controlled device to develop 5 mT 60 Hz magnetic fields for studies of the effects of fields on mast cells, a key component in acute inflammatory responses. Such fields have been reported to modulate cell activity, including changes in membrane function, in various systems. The magnetic field was generated using a solenoid and calibrated with an induction probe. Tests of mast cell function were determined by histamine release response to stimulation by compound 48/80, using both an “expose then test” and a “test during exposure” protocol. Aliquots not treated with 48/80 were used to evaluate field treatment effects on spontaneous histamine release. Freshly harvested rat peritoneal mast cells were exposed to the magnetic field for periods of 30 min to 2 h at 37 °C. They showed no significant degranulation during treatment, nor did they show reduced sensitivity to the degranulating agent 48/80. These observations are consistent with a model in which such processes are exclusively reflexive by the cells using field-independent membrane systems. This observation is very useful and was needed before examining longer term exposures in which gene expression in the cells might be influenced; this is the first such report of in vitro exposure of purified mast cells under these conditions and will further the study of the effects of electromagnetic fields on cell types active in acute inflammation. Bioelectromagnetics 19:192-198, 1998. © 1998 Wiley-Liss, Inc.
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  • 135
    ISSN: 0197-8462
    Keywords: cellular phone ; sleep EEG ; REM sleep ; spectral power density ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: To investigate the influence of radiofrequency electromagnetic fields (EMFs) of cellular phone GSM signals on human sleep electroencephalographic (EEG) pattern, all-night polysomnographies of 24 healthy male subjects were recorded, both with and without exposure to a circular polarized EMF (900 MHz, pulsed with a frequency of 217 Hz, pulse width 577 μs, power flux density 0.2 W/m2. Suppression of rapid eye movement (REM) sleep as well as a sleep-inducing effect under field exposure did not reach statistical significance, so that previous results indicating alterations of these sleep parameters could not be replicated. Spectral power analysis also did not reveal any alterations of the EEG rhythms during EMF exposure. The failure to confirm our previous results might be due to dose-dependent effects of the EMF on the human sleep profile. Bioelectromagnetics 19:199-202, 1998. © 1998 Wiley-Liss, Inc.
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  • 136
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    Bioelectromagnetics 19 (1998), S. 246-258 
    ISSN: 0197-8462
    Keywords: combined model ; facial shape ; aerosol size ; air currents ; VDU ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: This study investigates electrostatic fields surrounding the human head and particle deposition onto facial skin and eyes caused by the combined effect of electrostatic and wind fields. The electrostatic fields are calculated by a three-dimensional numerical model calculating the field strength between a field source and a human head. The deposition velocity can be viewed as determined by the sum of two contributions: that of an electrostatic field and that of a wind field. Deposition velocities are calculated by a semiempirical particle deposition model that considers particle transport from the free stream to the human face. The particle deposition model uses the electrostatic field model results as input parameters and is applied to the forehead and eyes of two facial shapes for two different turbulence conditions and aerosol charge distributions. The results of different practical working conditions, under which the potential difference between head (person) and source ranges from 5.6 to 15.0 kV, indicates that the presence of electrostatic fields always increases particle deposition for industrial aerosols. For aged aerosols an effect is only present for submicron particles. Bioelectromagnetics 19:246-258, 1998. © 1998 Wiley-Liss, Inc.
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  • 137
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    Bioelectromagnetics 19 (1998), S. 293-299 
    ISSN: 0197-8462
    Keywords: numerical simulation ; dosimetry ; power lines ; safety guidelines ; electric field ; induced currents ; FDTD method ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The finite-difference time-domain (FDTD) method has previously been used to calculate induced currents in anatomically based models of the human body at frequencies ranging from 20 to 915 MHz and resolutions down to about 1.25 cm. Calculations at lower frequencies and higher resolutions have been precluded by the huge number of time steps that would be needed in these simulations. This paper describes a method used to overcome this problem and efficiently calculate induced currents in an MRI-based, 6-mm-resolution model of the human under a high-voltage transmission line. This model is significantly higher resolution than the 1.31-cm-resolution model previously used; therefore, it can be used to pinpoint locations of peak current densities in the body. Proposed safety guidelines would allow external electric fields of 10 kV/m and 25 kV/m for exposure to 60 Hz fields of the general public and workers, respectively. For this external electric field exposure of 10 kV/m, local induced current densities as high as 20 mA/m2 are found in the head and trunk with even higher values (above 150 mA/m2) in the legs. These currents are considerably higher than the 4 or even 10 mA/m2 that have been suggested in the various safety guidelines, thus indicating an inconsistency in the proposed guidelines. In addition, several ratios of E/H typical of power line exposures were examined, and it was found that the vertical electric field couples strongly to the body, whereas the horizontal magnetic field does not. Bioelectromagnetics 19:293-299, 1998. © 1998 Wiley-Liss, Inc.
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  • 138
    ISSN: 0197-8462
    Keywords: radiofrequency radiation ; heart rate ; blood pressure ; cardiovascular system ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Exposure to fast-rise-time ultra-wideband (UWB) electromagnetic pulses has been postulated to result in effects on biological tissue (including the cardiovascular system). In the current study, 10 anesthetized Sprague-Dawley rats were exposed to pulses produced by a Sandia UWB pulse generator (average values of exposures over three different pulse repetition rates: rise time, 174-218 ps; peak E field, 87-104 kV/m; pulse duration, 0.97-0.99 ns). Exposures to 50, 500 and 1000 pulses/s resulted in no significant changes in heart rate or mean arterial blood pressure measured every 30 s during 2 min of exposure and for 2 min after the exposure. The results suggest that acute UWB whole-body exposure under these conditions does not have an immediate detrimental effect on these cardiovascular system variables in anesthetized rats. Bioelectromagnetics 19:330-333, 1998. Published 1998 Wiley-Liss, Inc.
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  • 139
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    Bioelectromagnetics 19 (1998), S. 354-365 
    ISSN: 0197-8462
    Keywords: childhood leukemia ; Swedish study ; magnetic fields ; exposure assessment ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: A recent study conducted in Sweden reported that 1) leukemia risk in children who lived near 220 or 400 kV electric-power transmission lines was associated with calculated historical magnetic field levels; 2) children living within a distance of 50 m of transmission lines had an elevated risk of leukemia; and 3) there was no association between leukemia and residential magnetic fields measured many years after diagnosis. Subsequently, these investigators found through logistic regression analysis that disease was more strongly associated with calculated historical fields than with distance. Since the calculated historical fields in that study depended predominantly on distance and transmission-line load current, the logistic regression results suggest that historical load current plays an important role in the epidemiological results. Thus, we studied hourly 1974 load-current data for six transmission lines, and we examined 1958-1985 annual load-current data for 112 transmission lines. Most lines exhibited marked diurnal load-current rhythms during 1974, and all six showed systematic weekday weekend differences. During 1958-1985, average loadings of Swedish 220 and 400 kV lines increased by about 1.3% year. Predictive-value and kappa-statistic analyses indicated that Swedish transmission-line load currents were not stable over long periods, so that contemporaneous load current (or a contemporary magnetic field measurement) was not a good surrogate for historical load current (or historical magnetic fields). The results provide a potential explanation of the failure of the Swedish Study to find an association between leukemia and contemporaneous magnetic field levels measured many years after the etiologic period, and suggest that the inclusion of load-current data could significantly improve the quality of historical field calculations. Bioelectromagnetics 19:354-365, 1998. © 1998 Wiley-Liss, Inc.
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  • 140
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    Bioelectromagnetics 19 (1998), S. 388-391 
    ISSN: 0197-8462
    Keywords: extremely low frequency ; electromagnetic field ; skin ; ODC ; putrescine ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: We studied the influence of magnetic fields (MFs) and simulated solar radiation (SSR) on ornithine decarboxylase (ODC) and polyamines in mouse epidermis. Chronic exposure to combined MF and SSR did not cause persistent effects on ODC activity or polyamines compared to the animals exposed only to UV, although the same MF treatment was previously found to accelerate skin tumor development. In an acute 24-h experiment, an elevation of putrescine and down-regulation of ODC activity was observed in the animals exposed to a 100-μT MF. No effect was seen 24 h after a single 2-MED (minimal erythemal dose) exposure to SSR. The results indicate that acute exposure to 50 Hz MF does exert distinctive biological effects on epidermal polyamine synthesis. Bioelectromagnetics 19:388-391, 1998. © 1998 Wiley-Liss, Inc.
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  • 141
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    Bioelectromagnetics 19 (1998), S. 414-419 
    ISSN: 0197-8462
    Keywords: RF electromagnetic fields ; buccal epithelium ; inerphase nucleus ; bioelectric properties ; heterochromatin ; electrokinetics ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Changes of electrokinetic properties of cell nuclei and the quantity of granules of heterochromatin located near the nuclear envelope in nuclei of human buccal epithelium cells were studied under the influence of electromagnetic fields in vitro. Irradiation of cells was realized by means of a semiconductor generator of millimeter radiation (wavelength 7.1 mm, frequency 42.2 GHz), the Yav-1 apparatus for extremely high frequency therapy. It was shown that irradiation of cells induced a decrease in electric charge of native human buccal epithelium cell nuclei and an increase in chromatin condensation in nuclei. The observed effects depend on irradiation dose and individual peculiarities of donors. Bioelectromagnetics 19:414-419, 1998. © 1998 Wiley-Liss, Inc.
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  • 142
    ISSN: 0197-8462
    Keywords: 60 Hz magnetic field ; cholinergic activity ; frontal cortex ; hippocampus ; opiate receptor subtypes ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: In previous research, we have found that acute exposure to a 60 Hz magnetic field decreased cholinergic activity in the frontal cortex and hippocampus of the rat as measured by sodium-dependent high-affinity choline uptake activity. We concluded that the effect was mediated by endogenous opioids inside the brain because it could be blocked by pretreatment of rats before magnetic field exposure with the opiate antagonist naltrexone, but not by the peripheral antagonist naloxone methiodide. In the present study, the involvement of opiate receptor subtypes was investigated. Rats were pretreated by intracerebroventricular injection of the mu-opiate receptor antagonist, β-funaltrexamine, or the delta-opiate receptor antagonist, naltrindole, before exposure to a 60 Hz magnetic field (2 mT, 1 hour). It was found that the effects of magnetic field on high-affinity choline uptake in the frontal cortex and hippocampus were blocked by the drug treatments. These data indicate that both mu- and delta-opiate receptors in the brain are involved in the magnetic field-induced decreases in cholinergic activity in the frontal cortex and hippocampus of the rat. Bioelectromagnetics 19:432-437, 1998. © 1998 Wiley-Liss, Inc.
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  • 143
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    Bioelectromagnetics 19 (1998), S. 117-122 
    ISSN: 0197-8462
    Keywords: 60 Hz ; magnetic field ; water-maze ; spatial learning ; memory ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Rats were trained in six sessions to locate a submerged platform in a circular water-maze. They were exposed to a 1 mT, 60 Hz magnetic field for one hour in a Helmholtz coil system immediately before each training session. In addition, one hour after the last training session, they were tested in a probe trial during which the platform was removed and the time spent in the quadrant of the maze in which the platform was located during the training sessions was scored. Control animals were sham-exposed using the exposure system operating with the coils activated in an anti-parallel direction to cancel the fields. A group of “non-exposed” control animals was also included in the study. There was no significant difference between the magnetic field-exposed and control animals in learning to locate the platform. However, swim speed of the magnetic field-exposed rats was significantly slower than that of the controls. During the probe trial, magnetic field-exposed animals spent significantly less time in the quadrant that contained the platform, and their swim patterns were different from those of the controls. These results indicate that magnetic field exposure causes a deficit in spatial “reference” memory in the rat. Rats subjected to magnetic field exposure probably used a different behavioral strategy in learning the maze. Bioelectromagnetics 19: 117-122, 1998. © 1998 Wiley-Liss, Inc.
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  • 144
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    Bioelectromagnetics 19 (1998), S. 136-137 
    ISSN: 0197-8462
    Keywords: mechanisms ; theoretical models ; transcription ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Blank and Goodman [(1997): Bioelectromagnetics 18:111-115] suggest that weak extremely low frequency (ELF) electric and magnetic fields affect intracellular DNA directly. We show that such a conclusion is not in accord with physical principles. Bioelectromagnetics 19: 136-137, 1998. © 1998 Wiley-Liss, Inc.
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  • 145
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    Bioelectromagnetics 19 (1998), S. 140-151 
    ISSN: 0197-8462
    Keywords: PCA ; principal component analysis ; effects function ; exposure metrics ; exposure indices ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Epidemiologic studies examining the risk of cancer among occupational groups exposed to electric fields (EF) and or magnetic fields (MF) have relied on traditional summaries of exposure such as the time weighted arithmetic or geometric mean exposure. Findings from animal and cellular studies support the consideration of alternative measures of exposure capable of capturing threshold and intermittent measures of field strength. The main objective of this study was to identify a series of suitable exposure metrics for an ongoing cancer incidence study in a cohort of Ontario electric utility workers. Principal components analysis (PCA) and correlational analysis were used to explore the relationships within and between series of EF and MF exposure indices. Exposure data were collected using personal monitors worn by a sample of 820 workers which yielded 4247 worker days of measurement data. For both EF and MF, the first axis of the PCA identified a series of intercorrelated indices that included the geometric mean, median and arithmetic mean. A considerable portion of the variability in EF and MF exposures were accounted for by two other principal component axes. The second axes for EF and MF exposures were representative of the standard deviation (standard deviation) and thresholds of field measures. To a lesser extent, the variability in the exposure variable was explained by time dependent indices which consisted of autocorrelations at 5 min lags and average transitions in field strength. Our results suggest that the variability in exposure data can only be accounted for by using several exposure indices, and consequently, a series of metrics should be used when exploring the risk of cancer owing to MF and EF exposure in this cohort. Furthermore, the poor correlations observed between indices of MF and EF reinforce the need to be take both fields into account when assessing the risk of cancer in this occupational group. Bioelectromagnetics 19:140-151, 1998. © 1998 Wiley-Liss, Inc.
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  • 146
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    Bioelectromagnetics 19 (1998), S. 210-221 
    ISSN: 0197-8462
    Keywords: aversive stimuli ; incandescent light ; electric fields ; reinforcement schedules ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Several reports have shown that animals will sometimes engage in behaviors that reduce their exposure to a 60 Hz electric field (E-field). The field, therefore, can function as an aversive stimulus. In other studies, the E-field at equivalent strengths failed to function as an aversive stimulus. The present experiment, using rats, demonstrates how factors other than field strength can influence whether a subject engages in behavior that reduces field exposure. The general design consisted of giving the rat a choice between two alternatives, one of which sometimes included an added stimulus. Each subject was trained to press each of two levers to obtain food. Pressing one lever was reinforced intermittently under a variable interval 2 min schedule (VI 2); pressing the other lever was reinforced by a second VI 2 schedule operating independently of the first. Under this concurrent schedule the rat spent 50% of the daily 50 min session responding to each of the levers, indicating that they were equally “valued.” Next, while the schedules remained in effect, the first response to one of the levers turned on a 100 kV/m E-field which remained on until the rat pressed the other lever. The time spent responding under the schedule associated with the field was reduced by about 5-10%. When the procedure was changed so that no lever presses produced food, i.e., extinction, but the added stimulus contingency remained, the rats spent even less time in the presence of the field. Similar outcomes were observed during both the concurrent food or extinction schedules when incandescent light was used. Thus, both an E-field and incandescent light functioned as aversive stimuli, but the magnitude of the aversiveness was small. Aversiveness depended not only on stimulus intensity, but also on behavioral factors. Bioelectromagnetics 19:210-221, 1998. © 1998 Wiley-Liss, Inc.
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  • 147
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    Keywords: thermoregulation ; sweating ; metabolic rate ; body temperature ; thermal sensation ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Thermoregulatory responses of heat production and heat loss were measured in seven adult volunteers (four women and three men, aged 21-57 yr) during 45-min dorsal exposures of the whole body to 450 MHz continuous wave radio frequency (RF) fields. Two power densities (PD) (local peak PD = 18 and 24 mW/cm2; local peak specific absorption rate = 0.320 [W/kg]/[mW/cm2]) were tested in each of three ambient temperatures (Ta = 24, 28, and 31 °C) plus Ta controls (no RF). No changes in metabolic heat production occurred under any exposure conditions. Vigorous increases in sweating rate on back and chest, directly related to both Ta and PD, cooled the skin and ensured efficient regulation of the deep body (esophageal) temperature to within 0.1 °C of the normal level. Category judgments of thermal sensation, comfort, sweating, and thermal preference usually matched the measured changes in physiological responses. Some subtle effects related to gender were noted that confirm classic physiological data. Our results indicate that dorsal exposures of humans to a supra-resonant frequency of 450 MHz at local peak specific absorption rates up to 7.68 W/kg are mildly thermogenic and are counteracted efficiently by normal thermophysiologic heat loss mechanisms, principally sweating. Bioelectromagnetics 19:232-245, 1998. Published 1998 Wiley-Liss, Inc.
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  • 148
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    Bioelectromagnetics 19 (1998), S. 271-278 
    ISSN: 0197-8462
    Keywords: human study ; radiation ; non ionising ; pituitary hormone secretion ; mobile telephone ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: It is known that the endocrine system of experimental animals is susceptible to perturbation by radiofrequency (RF) radiation. Because of the recent interest in health and safety issues of cellular telephones, an experiment was designed to evaluate the effect of a 900 MHz RF radiation emitted by a Global System for Mobile radiotelephone (217 Hz impulses, one-eighth duty cycle, 2 W peak power) on human endocrine functions. Twenty healthy male volunteers aged from 19 to 40 were inducted in the present experiment. Each subject was exposed to RF radiation through the use of a cellular phone 2 h/day, 5 days/wk, for 1 month. Subjects were their own control. End points were serum adrenocorticotropin, thyrotropin, growth hormone, prolactin, luteinizing hormone, and follicle stimulating hormone concentrations. These end points were determined in nine weekly blood samples obtained starting 3 weeks before the commencement of the exposure and ending 2 weeks after exposures. All but one blood sample was drawn 48 h after each weekly session. The seventh drawing was performed the morning after the last weekly exposure. Within each individual, the preexposure hormone concentration was used as a control. Results indicated that all hormone concentrations remained within normal physiologic ranges. A difference was not noted among the nine weekly samples in five of six hormones studied. There was a significant change only in thyrotropin concentration, showing a 21% decrease on the seventh sampling. Because this change recovered fully during the postexposure period, it is concluded that 1 month of intermittent exposures to RF radiation from a cellular telephone does not induce a long-lasting or cumulative effect on the hormone secretion rate of the anterior pituitary gland in humans. Bioelectromagnetics 19:271-278, 1998. © 1998 Wiley-Liss, Inc.
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  • 149
    ISSN: 0197-8462
    Keywords: cortex ; electromagnetic fields ; heat stress ; hypothalamus ; thermoregulation ; nonuniform heating ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Nonuniform heating may result from microwave (MW) irradiation of tissues and is therefore important to investigate in terms of health and safety issues. Hypothalamic (Thyp), cortical (Tctx), tympanic (Tty), and rectal (Tre) temperatures were measured in rats exposed in the far field, k-polarization (i.e., head pointed toward the transmitter horn and E-field in vertical direction) to two power densities of 2.06 GHz irradiation. The high-power density (HPM) was 1700 mW/cm2 [specific absorption rate (SAR): hypothalamus 1224 W/kg; cortex 493 W/kg]; the low-power density (LPM) was 170 mW/cm2 (SAR: hypothalamus 122.4 W/kg; cortex 49.3 W/kg). The increase (rate-of-rise, in °C/s) in Thyp was significantly greater than those in Tctx or Tre when rats were exposed to HPM. LPM produced more homogeneous heating. Quantitatively similar results were observed whether rats were implanted with probes in two brain sites or a single probe in one or the other of the two sites. The qualitative difference between regional brain heating was maintained during unrestrained exposure to HPM in the h-polarization (i.e., body parallel to magnetic field). To compare the temperature changes during MW irradiation with those produced by other modalities of heating, rats were immersed in warm water (44 °C, WWI); exposed to a warm ambient environment (50 °C, WSED); or exercised on a treadmill (17 m/min 8% grade) in a warm ambient environment (35 °C, WEX). WWI produced uniform heating in the regions measured. Similar rates-of-rise occurred among regions following WSED or WEX, thus maintaining the pre-existing gradient between Thyp and Tctx. These data indicate that HPM produced a 2-2.5-fold difference in the rate-of-heating within brain regions that were separated by only a few millimeters. In contrast, more homogeneous heating was recorded during LPM or nonmicrowave modalities of heating. Bioelectromagnetics 19:341-353, 1998. © 1998 Wiley-Liss, Inc.
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  • 150
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    Bioelectromagnetics 19 (1998), S. 420-428 
    ISSN: 0197-8462
    Keywords: microwaves ; thermal response of tissue ; bioheat equation ; thermal averaging time ; history of averaging times ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: We consider the thermal response times for heating of tissue subject to nonionizing (microwave or infrared) radiation. The analysis is based on a dimensionless form of the bioheat equation. The thermal response is governed by two time constants: one(τ1) pertains to heat convection by blood flow, and is of the order of 20-30 min for physiologically normal perfusion rates; the second (τ2) characterizes heat conduction and varies as the square of a distance that characterizes the spatial extent of the heating. Two idealized cases are examined. The first is a tissue block with an insulated surface, subject to irradiation with an exponentially decreasing specific absorption rate, which models a large surface area of tissue exposed to microwaves. The second is a hemispherical region of tissue exposed at a spatially uniform specific absorption rate, which models localized exposure. In both cases, the steady-state temperature increase can be written as the product of the incident power density and an effective time constant τeff, which is defined for each geometry as an appropriate function of τ1 and τ2. In appropriate limits of the ratio of these time constants, the local temperature rise is dominated by conductive or convective heat transport. Predictions of the block model agree well with recent data for the thresholds for perception of warmth or pain from exposure to microwave energy. Using these concepts, we developed a thermal averaging time that might be used in standards for human exposure to microwave radiation, to limit the temperature rise in tissue from radiation by pulsed sources. We compare the ANSI exposure standards for microwaves and infrared laser radiation with respect to the maximal increase in tissue temperature that would be allowed at the maximal permissible exposures. A historical appendix presents the origin of the 6-min averaging time used in the microwave standard. Bioelectromagnetics 19:420-428, 1998. © 1998 Wiley-Liss, Inc.
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  • 151
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    Bioelectromagnetics 19 (1998), S. 477-485 
    ISSN: 0197-8462
    Keywords: electromagnetic fields ; embryogenesis ; teratology ; low frequency magnetic fields ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Effects of alternating magnetic fields (MFs) on the embryonic and fetal development in CBA/Ca mice were studied. Mated females were exposed continuously to a sinusoidal 50 Hz (13 μT or 0.13 mT root mean square) or a sawtooth 20 kHz (15 μT peak-to-peak) MF from day 0 to day 18 of pregnancy for 24 h/day until necropsied on day 18. Control animals were kept under the same conditions without the MF. MFs did not cause maternal toxicity. No adverse effects were seen in maternal hematology and the frequency of micronuclei in maternal bone marrow erythrocytes did not change. The MFs did not increase the number of resorptions or fetuses with major or minor malformations in any exposure group. The mean number of implantations and living fetuses per litter were similar in all groups. The corrected weight gain (weight gain without uterine content) of dams, pregnancy rates, incidences of resorptions and late fetal deaths, and fetal body weights were similar in all groups. There was, however, a statistically significant increase in the incidence of fetuses with at least three skeletal variations in all groups exposed to MFs. In conclusion, the 50 Hz or 20 kHz MFs did not increase incidences of malformations or resorptions in CBA/Ca mice, but increased skeletal variations consistently in all exposure groups. Bioelectromagnetics 19:477-485, 1998. © 1998 Wiley-Liss, Inc.
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  • 152
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    Keywords: chick embryos ; anoxia ; stress proteins ; protective effect ; magnetic field ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Stress proteins are important in protection during cardiac ischemia/reperfusion (cessation and return of blood flow) and are reportedly induced by electromagnetic (EM) fields. This suggests a possible ischemia protection role for EM exposures. To test this, chick embryos (96 h) were exposed to 60 Hz magnetic fields prior to being placed into anoxia. Survival was 39.6% (control), and 68.7% (field-exposed). As a positive control, embryos were heated prior to anoxia (57.6% survival). We conclude that: 1) 60 Hz magnetic field exposures reduce anoxia-induced mortality in chick embryos, comparable to reductions observed following heat stress, and 2) this is a simple and rapid experiment to demonstrate the existence of weak EM field effects. Bioelectromagnetics 19:498-500, 1998. © 1998 Wiley-Liss, Inc.
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  • 153
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    Bioelectromagnetics 19 (1998), S. 98-106 
    ISSN: 0197-8462
    Keywords: power-frequency ; heart rate variability ; EKG ; HRV ; EMF ; Fourier transform ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Heart rate variability (HRV) results from the action of neuronal and cardiovascular reflexes, including those involved in the control of temperature, blood pressure and respiration. Quantitative spectral analyses of alterations in HRV using the digital Fourier transform technique provide useful in vivo indicators of beat-to-beat variations in sympathetic and parasympathetic nerve activity. Recently, decreases in HRV have been shown to have clinical value in the prediction of cardiovascular morbidity and mortality. While previous studies have shown that exposure to power-frequency electric and magnetic fields alters mean heart rate, the studies reported here are the first to examine effects of exposure on HRV. This report describes three double-blind studies involving a total of 77 human volunteers. In the first two studies, nocturnal exposure to an intermittent, circularly polarized magnetic field at 200 mG significantly reduced HRV in the spectral band associated with temperature and blood pressure control mechanisms (P = 0.035 and P = 0.02), and increased variability in the spectral band associated with respiration (P = 0.06 and P = 0.008). In the third study the field was presented continuously rather than intermittently, and no significant effects on HRV were found. The changes seen as a function of intermittent magnetic field exposure are similar, but not identical, to those reported as predictive of cardiovascular morbidity and mortality. Furthermore, the changes resemble those reported during stage II sleep. Further research will be required to determine whether exposure to magnetic fields alters stage II sleep and to define further the anatomical structures where field-related interactions between magnetic fields and human physiology should be sought. Bioelectromagnetics 19: 98-106, 1998. © 1998 Wiley-Liss, Inc.
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  • 154
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    Bioelectromagnetics 19 (1998), S. 469-476 
    ISSN: 0197-8462
    Keywords: HL60 cells ; 60 Hz magnetic fields ; transduction mechanism(s) ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: We examined the separate and combined effects of 60 Hz sinusoidal magnetic fields (MFs) and a phorbol ester on protein kinase C (PKC) activity in HL60 cells. No enhancement in PKC activity was observed when a cell culture was exposed to a 1.1 mT (rms) MF alone or to a combination of MF and 2 μM phorbol 12-myristate 13-acetate (PMA) for 1 h. In a second set of experiments, cells were preexposed to a less than optimal concentration of PMA (50 nM) for 45 min, followed by a 15 min exposure to both PMA and MF. The data showed a greater decrease in cytosolic PKC activity and a larger increase in membrane activity than was induced by either 1 h PMA treatment alone or PMA and sham MF exposure. One logical conclusion from these data is that MFs may be acting in a synergistic manner on a pathway that has already been activated. Therefore, we suggest that MFs, rather than producing biological effects by a new pathway or mechanism of interaction, exert their effect(s) by interacting with already functioning reactions or pathways. If correct, the question of an MF's mechanism of interaction refocuses on how weak fields might enhance or depress a molecular reaction in progress, rather than on finding a new transduction pathway. Bioelectromagnetics 19:469-476, 1998. © 1998 Wiley-Liss, Inc.
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  • 155
    ISSN: 0197-8462
    Keywords: pineal gland ; melatonin ; DC magnetic field exposure ; rat ; pulsed magnetic fields ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The purpose of these experiments was to determine whether the exposure of rats at night to pulsed DC magnetic fields (MF) would influence the nocturnal production and secretion of melatonin, as indicated by pineal N-acetyltransferase (NAT) activity (the rate limiting enzyme in melatonin production) and pineal and serum melatonin levels. By using a computer-driven exposure system, 15 experiments were conducted. MF exposure onset was always during the night, with the duration of exposure varying from 15 to 120 min. A variety of field strengths, ranging from 50 to 500 μT (0.5 to 5.0 G) were used with the bulk of the studies being conducted using a 100 μT (1.0 G) field. During the interval of DC MF exposure, the field was turned on and off at 1-s intervals with a rise/fall time constant of 5 ms. Because the studies were performed during the night, all procedures were carried out under weak red light (intensity of 〈5 μW/cm2). At the conclusion of each study, a blood sample and the pineal gland were collected for analysis of serum melatonin titers and pineal NAT and melatonin levels. The outcome of individual studies varied. Of the 23 cases in which pineal NAT activity, pineal melatonin, and serum melatonin levels were measured, the following results were obtained; in 5 cases (21.7%) pineal NAT activity was depressed, in 2 cases (8.7%) studies pineal melatonin levels were lowered, and in 10 cases (43.5%) serum melatonin concentrations were reduced. Never was there a measured rise in any of the end points that were considered in this study. The magnitudes of the reductions were not correlated with field strength (i.e., no dose-response relationships were apparent), and likewise the reductions could not be correlated with the season of the year (experiments conducted at 12-month intervals under identical exposure conditions yielded different results). Duration of exposure also seemed not to be a factor in the degree of melatonin suppression. The inconsistency of the results does not permit the conclusion that pineal melatonin production or release are routinely influenced by pulsed DC MF exposure. In the current series of studies, a suppression of serum melatonin sometimes occurred in the absence of any apparent change in the synthesis of this indoleamine within the pineal gland (no alteration in either pineal NAT activity or pineal melatonin levels). Because melatonin is a direct free radical scavenger, the drop in serum melatonin could theoretically be explained by an increased uptake of melatonin by tissues that were experiencing augmented levels of free radicals as a consequence of MF exposure. This hypothetical possibly requires additional experimental documentation. Bioelectromagnetics 19:318-329, 1998. © 1998 Wiley-Liss, Inc.
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  • 156
    ISSN: 0197-8462
    Keywords: sperm size and shape ; image analysis ; magnetism ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Morphologic and morphometric sperm characteristics of mouse epididymal extracts from animals exposed to static magnetic fields were evaluated. For this purpose, animals were exposed for 35 days to a field of 0.7 T generated by a commercial permanent magnet for either 1 or 24 h per day. The values of morphometric parameters were obtained using the morphometric module of the Sperm Class Analyzer® computerized image analysis system, and percentages of abnormalities were calculated. The size of sperm heads was unaffected by exposure to static magnetic fields. Lack of hook was a sperm head abnormality found significantly more frequently in animals exposed continually than in nonexposed animals, showing a possible alteration to the spermatogenic process after exposure to static magnetic fields. The percentage of sperm with coiled tails or of sperm with abnormal midpiece or tail was not altered by exposure. Bioelectromagnetics 19:377-383, 1998. © 1998 Wiley-Liss, Inc.
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  • 157
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    Bioelectromagnetics 19 (1998), S. 429-431 
    ISSN: 0197-8462
    Keywords: ELF ; magnetic fields ; testosterone ; Leydig cell ; in vitro ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: This study evaluated the effect of sinusoidal 50 Hz magnetic field on the basal and human chorionic gonadotropin (hCG)-stimulated testosterone (T) production of 48-h mouse Leydig cell culture. The luteinizing hormone (LH) analog hCG was used to check the T response of the controls and to evaluate the possible effect of the applied magnetic field on the steroidogenic capacity of the exposed cells. Leydig cells were obtained from the testes of 35- to 45-g CFLP mice and isolated by mechanical dissociation without enzyme treatment. The cell cultures were exposed to sinusoidal 50 Hz 100 μT (root mean square) AC magnetic field during the entire time of a 48-h incubation. Testosterone content of the culture media was measured by radioimmunoassay. In cultures exposed to the magnetic field, a marked increase of basal T production was found (P 〈 .05), compared with the unexposed controls, whereas no significant difference was seen between the exposed or unexposed cultures in the presence of maximally stimulating concentration of hCG. These findings demonstrate that sinusoidal 50 Hz 100 μT magnetic fields are able to stimulate the basal T production of primary mouse Leydig cell culture, leaving the steroidogenic responsiveness to hCG unaltered. Bioelectromagnetics 19:429-431, 1998. © 1998 Wiley-Liss, Inc.
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  • 158
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    Bioelectromagnetics 19 (1998), S. 452-458 
    ISSN: 0197-8462
    Keywords: low frequency electric fields and currents ; amplitude modulation ; HL-60 cells ; cytosolic free calcium ; cyclic AMP ; cyclic GMP ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The action of interferential current (IFC), an amplitude-modulated 4000 kHz current used in therapeutic applications, upon intracellular calcium, adenosine 3′:5′-cyclic monophosphate (cAMP), and guanosine 3′:5′-cyclic monophosphate (cGMP) was investigated. Human promyelocytes (HL-60) were differentiated to granulocytes by dimethylsulfoxide (DMSO) treatment and exposed for 5 min at 25, 250, and 2500 μA/cm2 current density. No significant changes in cytosolic free calcium were detected as a function of modulation frequency of the IFC. However, intracellular cAMP reacted in a complex way to modulation frequency, resulting in stimulations and depressions within the range of frequencies studied (0-125 Hz). The “windows” of modulation frequency, where statistically significant increases or decreases in cAMP were noted, coincided with those published earlier for mouse fibroblasts. Cellular cGMP content was always lowered by IFC treatment. Furthermore, no significant influence of IFC current density upon the three second messengers was noted. These results, which also include data relating to treatment with sinusoidal 50 Hz current, contribute to a more detailed understanding of the primary biophysical mechanisms of signal transduction by time-varying electric fields. Bioelectromagnetics 19:452-458, 1998. © 1998 Wiley-Liss, Inc.
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  • 159
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    Bioelectromagnetics 19 (1998), S. 32-40 
    ISSN: 0197-8462
    Keywords: ELF ; electric fields ; calcium ; cytosolic free calcium ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The effect of sinusoidal electric fields on the cytosolic free [Ca2+]i concentration in differentiated HL-60 cells was measured. The calcium concentration was measured in a fluorescence spectrometer using the fluorescence sample fluo-3. In the fluorescence spectrometer two samples can be measured simultaneously, one as the sham-exposed control and the other as the field-exposed sample. The effects of an external field, applied using two capacitor plates outside the cuvettes, and a field applied directly to the medium, using two platinum electrodes inside the cuvettes, were measured at selected frequencies between 0 and 100 Hz and field strengths from 1 to 2000 Vpp/m (external field) and from 0.1 to 1000 Vpp/m (in medium). No significant effects of the fields on the cytosolic free [Ca2+]i concentration in HL-60 cells have been observed at the measured frequencies and field strengths. Bioelectromagnetics 19:32-40, 1998. © 1998 Wiley-Liss, Inc.
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  • 160
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    Bioelectromagnetics 19 (1998), S. 67-67 
    ISSN: 0197-8462
    Keywords: Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: No abstract.
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  • 161
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    Bioelectromagnetics 19 (1998), S. 68-74 
    ISSN: 0197-8462
    Keywords: dermal wound model ; human skin fibroblasts in collagen matrices ; electrical stimulation ; [3H]thymidine assay ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: In a dermal wound model, consisting of human skin fibroblasts in collagen matrix, continuous sinusoidal electrical current stimulation elicited a maximum increase of [3H]thymidine relative to control at 41 mV/m amplitude, 10 Hz. In this paper we elaborate cell cycle kinetics, using the same parameters. Labeling occurred over 4-h intervals beginning at 12 to 20 h after onset of electric exposure. The results suggest a significant increase in [3H]thymidine incorporation over an 8-h period extending from 16-24 hours after stimulus initiation. Bioelectromagnetics 19:68-74, 1998. © 1998 Wiley-Liss, Inc.
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  • 162
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    Bioelectromagnetics 19 (1998), S. 92-97 
    ISSN: 0197-8462
    Keywords: action potentials ; excitable membrane ; postsynaptic potentials ; electronic circuit ; stimulation ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Entrainment of output action potentials from repetitively firing pacemaker cells, brought about by regularly spaced excitatory or inhibitory postsynaptic inputs, is a well-known phenomenon. Synchronization of neural firing patterns by extremely low frequency (ELF) external electric fields has also been observed. Whereas current densities of ≈10 A-m-2 are required for direct excitation of otherwise quiescent neural tissue, much lower peak current densities (≈10-2 A-m2) have been reported to entrain spontaneously firing molluscan pacemaker cells. We have developed a neural spike generator circuit model that simulates repetitive spike generation by a space clamped patch (area ≈ 10-7 m2) of excitable membrane subjected to depolarizing current. Picoampere (pA) range variation of DC depolarizing current causes a corresponding smooth variation of neural spike frequency, producing a physiologically realistic stimulus-response (S-R) characteristic. When lower pA range 60 Hz AC current is superposed upon the DC depolarizing current, smooth variation of the S-R characteristic is distorted by subharmonic locking of the spike generator at 30, 20, 15, 12, 10 Hz, and higher order subharmonic frequencies. Although the additional superposition of a physiologically realistic level of “white” current noise, covering the bandwidth 4-200 Hz, suffices to obscure higher order subharmonic locking, locking at 30, 20, and 15 Hz is still clearly evident in the presence of noise. Subharmonic locking is observed at a root mean square AC simulated tissue current density of ≈10-5 A-m-2. Bioelectromagnetics 19:92-97, 1998. © 1998 Wiley-Liss, Inc.
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  • 163
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    Bioelectromagnetics 19 (1998), S. 203-203 
    ISSN: 0197-8462
    Keywords: Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: No abstract.
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  • 164
    ISSN: 0197-8462
    Keywords: electromagnetic field ; myositis ossificans ; osteoblastic cells ; in vitro ; 3-D cell culture ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Human osteoblastic cells were grown in a three-dimensional (3-D) cell culture model and used to test the effects of a 20 Hz sinusoidal electromagnetic field (EMF; 6 mT and 113 mV/cm max) on collagen type I mRNA expression and extracellular matrix formation in comparison with the effects of growth factors. The cells were isolated from trabecular bone of a healthy individual (HO-197) and from a patient presenting with myositis ossificans (MO-192) and grown in a collagenous sponge-like substrate. Maximal enhancement of collagen type I expression after EMF treatment was 3.7-fold in HO-197 cells and 5.4-fold in MO-192 cells. Similar enhancement was found after transforming growth factor-β (TGF-β) and insulin-like growth factor-I (IGF-I) treatment. Combined treatment of the cells with EMF and the two growth factors TGF-β and IGF-I did not act synergistically. MO-192 cells produced an osteoblast-characteristic extracellular matrix containing collagen type I, alkaline phosphatase, and osteocalcin, together with collagen type III, TP-1, and TP-3, two epitopes of an osteoblastic differentiation marker. The data suggest that the effects of EMFs on osteoblastic differentiation are comparable to those of TGF-β and IGF-I. We conclude that EMF effects in the treatment of skeletal disorders and in orthopedic adjuvant therapy are mediated via enhancement of collagen type I mRNA expression, which may lead to extensive extracellular matrix synthesis. Bioelectromagnetics 19:222-231, 1998. © 1998 Wiley-Liss, Inc.
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  • 165
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    Bioelectromagnetics 19 (1998), S. 300-309 
    ISSN: 0197-8462
    Keywords: electromagnetic field ; genome ; viscosity ; intercellular communication ; extremely low frequency (ELF) ; anomalous viscosity time dependence (AVTD) ; genome conformational state (GCS) ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The effects of weak magnetic fields of extremely low frequency (ELF) on E. coli K12 AB1157 cells were studied by the method of anomalous viscosity time dependencies (AVTD). E. coli cells at different densities within a range of 5 × 105-109 cell/ml were exposed to ELF (sinusoidal, 30 μT peak, 15 min) at a frequency of 9 Hz. A transient effect with maximum 40-120 min after exposure was observed. Kinetics of the per-cell-normalised ELF effects fitted well to a Gaussian distribution for all densities during exposure. A maximum value of these kinetics and a time for this maximum were strongly dependent on the cell density during exposure. These data suggest a cell-to-cell interaction during response to ELF. Both dependencies had three regions close to a plateau within the ranges of 3 × 105 - 2 × 107 cell/ml, 4 × 107 - 2 × 108 cell/ml and 4 × 108-109 cell/ml and two rather sharp transitions between these plateaus. The effect reached a maximum value at a density of 4 × 108 cell/ml. Practically no effect was observed at the lowest density of 3 × 105 cell/ml. The data suggested that the ELF effect was mainly caused by a secondary rather than a primary reaction. The filtrates from exposed cells neither induced significant AVTD changes in unexposed cells nor increased the ELF effect when were added to cells before exposure. The data did not provide evidence for significant contribution of stable chemical messengers, but some unstable compounds such as radicals could be involved in the mechanism of cell-to-cell interaction during response to ELF. The results obtained were also in accordance with a model based on an re-emission of secondary photons during resonance fluorescence. Bioelectromagnetics 19:300-309, 1998. © 1998 Wiley-Liss, Inc.
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  • 166
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    Bioelectromagnetics 19 (1998), S. 384-387 
    ISSN: 0197-8462
    Keywords: Bereitschaftspotential ; preparation ; visual monitoring task ; GSM system ; human performance ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The influence of electromagnetic fields (EMF) emitted by cellular phones on preparatory slow brain potentials (SP) was studied in two different experimental tasks: In the first, healthy male human subjects had to perform simple self-paced finger movements to elicit a Bereitschaftspotential; in the second, they performed a complex and cognitive demanding visual monitoring task (VMT). Both tasks were performed with and without EMF exposure in counterbalanced order. Whereas subjects' performance did not differ between the EMF exposure conditions, SP parameters were influenced by EMF in the VMT: EMF exposure effected a significant decrease of SPs at central and temporo-parieto-occipital brain regions, but not at the frontal one. In the simple finger movement task, EMF did not affect the Bereitschaftspotential. Bioelectromagnetics 19:384-387, 1998. © 1998 Wiley-Liss, Inc.
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  • 167
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    Bioelectromagnetics 19 (1998), S. 445-451 
    ISSN: 0197-8462
    Keywords: electromagnetic fields ; interleukin-1 ; interleukin-2 ; tumor necrosis factor α ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: We evaluated the effects of a 50-Hz pulsed electromagnetic field on the production of cytokines by both resting and mitogen-treated peripheral blood mononuclear cells. Our results demonstrate that after exposure of normal cells to EMFs for 12 h, the levels of neither interleukin-1β, nor interleukin-2 were increased. Indeed, the concentration of tumor necrosis factor α decreased significantly immediately after the exposure period. The results were, however, markedly different when cells were stimulated with phytohemagglutinin immediately before the exposure to EMFs. In this case the levels of cytokines, measured 24 and 48 h after the treatment, were 630 ± 440 pg/ml and 910 ± 530 pg/ml for interleukin-1β, 530 ± 330 pg/ml, and 860 ± 560 pg/ml for tumor necrosis factor α, respectively. These values were significantly higher (P 〈 0.05) when compared with the controls. Interleukin-2 levels were significantly higher at the end of the EMF exposure only in supernatants of phytohemagglutinin-stimulated cells and, as a consequence of this increase, the proliferation indexes also were significantly increased 48 h after the EMFs' treatment. The comparison between biological activity and the cytokine antigen present in our samples indicated that the amount of antigen was paralleled by an equal recovery of biological activity. This suggests either the absence of qualitative differences in these proteins or the impairment of both the transcriptional and translational processes. Bioelectromagnetics 19:445-451, 1998. © 1998 Wiley-Liss, Inc.
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  • 168
    ISSN: 0197-8462
    Keywords: magnetic fields ; ionic current ; neurotransmitter ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Combined parallel static and alternating magnetic fields cause a rapid change in the ionic current flowing through an aqueous glutamic acid solution when the alternating field frequency is equal to the cyclotron frequency. The current peak is 20-30% of the background direct current. The peak is observed with slow sweep in the alternating magnetic field frequency from 1 Hz-10 Hz. Only one resonance peak in the current is observed in this frequency range. The frequency corresponding to the peak is directly proportional to the static magnetic field. The above effect only arises at very small alternating field amplitude in the range from 0.02 μT-0.08 μT. Bioelectromagnetics 19:41-45, 1998. © 1998 Wiley-Liss, Inc.
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  • 169
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    Bioelectromagnetics 19 (1998), S. 46-52 
    ISSN: 0197-8462
    Keywords: EMF ; MTT ; malignancy marker ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The effect of sinusoidally varying magnetic fields (SVMF) on chick embryo fibroblasts (CEF) was examined by two independent methods: 1) measurement of cell proliferation at 0.06-0.7 mT (100, 60 and 50 Hz) using a colorimetric assay (MTT); 2) monitoring of specific activity of adenosine deaminase (ADA) at 0.3 and 0.7 mT, 60 Hz. Both increased cell proliferation and reduced ADA specific activity are associated with cell transformation. The MTT test showed an increase in cell proliferation of up to 64% after a 24 h exposure to SVMF at 100 Hz, 0.7 mT. Cell proliferation at constant frequency (100 Hz) depended on SVMF intensity. Cell proliferation at constant intensity (0.7 mT) increased with increasing field frequency. At 0.7 mT, 60 Hz cell proliferation increased by 31%, 28%, and 26% when measured by hemocytometry, 3H-thymidine incorporation, and the MTT assay, respectively. ADA specific activity in CEF decreased by circa 48% on exposure to SVMF at 60 Hz, 0.3 mT for 24 h; only a statistically insignificant trend was seen at 0.7 mT, 60 Hz. Our findings showed that CEF cell proliferation and ADA specific activity were modified by SVMF. Both methods, independently, qualitatively detect a magnetic field effect. Bioelectromagnetics 19:46-52, 1998. © 1998 Wiley-Liss, Inc.
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  • 170
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    Bioelectromagnetics 19 (1998), S. 112-116 
    ISSN: 0197-8462
    Keywords: combined magnetic fields ; gamma rays ; rat tracheal epithelial cells ; AP-1 ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The effect of magnetic fields (50 Hz, 100 μTrms sinusoidal magnetic field combined with a 55 μT geomagnetic-like field) and/or gamma rays of 60 Cobalt on the expression of the c-jun and c-fos proteins was investigated in primary rat tracheal epithelial cells and two related immortalized cell lines. Quite similar patterns and amplitudes of induction of these proteins were evidenced after either ionizing radiation or magnetic field exposure. No synergism after both treatments was observed. These findings suggest that magnetic fields explored in the present study may be considered as an insult at the cellular level. Bioelectromagnetics 19: 112-116, 1998. © 1998 Wiley-Liss, Inc.
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  • 171
    ISSN: 0197-8462
    Keywords: melatonin ; magnetic fields ; rat ; single cells ; gland dissociation ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The objective of this study was to develop a model for testing various hypotheses concerning possible mechanisms whereby electromagnetic fields might induce suppression of nighttime melatonin production in rodents. A published method for digesting freshly obtained pineal glands to the single cell level was modified, yielding better than 95% viability. An in vitro exposure facility developed for the Food and Drug Administration was used for 12-h overnight exposures of primary pinealocyte cultures to 0.05 mT, 60 Hz, vertical AC and 0.06 μT, DC fields. After exposure, cells were separated from the supernatant by centrifugation. Supernatant melatonin was measured by ELISA assays. Data from 10 experiments demonstrated an average 46% reduction in norepinephrine-induced production of melatonin in the pinealocytes. The results support the hypothesis that EM exposure can produce pineal gland melatonin suppression by affecting individual cells. Bioelectromagnetics 19:123-127, 1998. Published 1998 Wiley-Liss, Inc.
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  • 172
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    Bioelectromagnetics 19 (1998), S. 1-19 
    ISSN: 0197-8462
    Keywords: RF fields ; nonthermal ; biological effects ; research agenda ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The World Health Organization (WHO), the International Commission on Non-Ionizing Radiation Protection (ICNIRP), and the German and Austrian Governments jointly sponsored an international seminar in November of 1996 on the biological effects of low-level radiofrequency (RF) electromagnetic fields. For purposes of this seminar, RF fields having frequencies only in the range of about 10 MHz to 300 GHz were considered. This is one of a series of scientific review seminars held under the International Electromagnetic Field (EMF) Project to identify any health hazards from EMF exposure. The scientific literature was reviewed during the seminar and expert working groups formed to provide a status report on possible health effects from exposure to low-level RF fields and identify gaps in knowledge requiring more research to improve health risk assessments.It was concluded that, although hazards from exposure to high-level (thermal) RF fields were established, no known health hazards were associated with exposure to RF sources emitting fields too low to cause a significant temperature rise in tissue. Biological effects from low-level RF exposure were identified needing replication and further study. These included in vitro studies of cell kinetics and proliferation effects, effects on genes, signal transduction effects and alterations in membrane structure and function, and biophysical and biochemical mechanisms for RF field effects. In vivo studies should focus on the potential for cancer promotion, co-promotion and progression, as well as possible synergistic, genotoxic, immunological, and carcinogenic effects associated with chronic low-level RF exposure. Research is needed to determine whether low-level RF exposure causes DNA damage or influences central nervous system function, melatonin synthesis, permeability of the blood brain barrier (BBB), or reaction to neurotropic drugs. Reported RF-induced changes to eye structure and function should also be investigated.Epidemiological studies should investigate: the use of mobile telephones with hand-held antennae and incidence of various cancers; reports of headache, sleep disturbance, and other subjective effects that may arise from proximity to RF emitters, and laboratory studies should be conducted on people reporting these effects; cohorts with high occupational RF exposure for changes in cancer incidence; adverse pregnancy outcomes in various highly RF exposed occupational groups; and ocular pathologies in mobile telephone users and in highly RF exposed occupational groups.Studies of populations with residential exposure from point sources, such as broadcasting transmitters or mobile telephone base stations have caused widespread health concerns among the public, even though RF exposures are very low. Recent studies that may indicate an increased incidence of cancer in exposed populations should be investigated further. Bioelectromagnetics 19:1-19, 1998. © 1998 Wiley-Liss, Inc.
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  • 173
    ISSN: 0197-8462
    Keywords: microwaves ; long-term exposure ; mammary tumors ; tumor incidence ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The purpose of this study was to determine whether chronic, low-level exposure of mammary-tumor-prone mice to 2450 MHz radiofrequency radiation (RFR) promotes an earlier onset (decreased latency), a greater total incidence, or a faster growth rate of mammary tumors. One hundred C3H/HeJ mice were exposed in circularly polarized waveguides (CWG) for 18 months (20 h/day, 7 days/wk) to continuous-wave, 2450 MHz RFR at a whole body average specific absorption rate (SAR) of 0.3 W/kg; 100 mice were sham exposed. Before exposure, SARs were determined calorimetrically; during experimentation, SARs were monitored by differential power measurement. All animals were visually inspected twice daily and were removed from the CWG cages for a weekly inspection, palpation, and weighing. From the time of detection, tumor size was measured weekly. Animals that died spontaneously, became moribund, or were killed after 18 months of exposure were completely necropsied; tissues were fixed and subjected to histopathological evaluations. Results showed no significant difference in weight profiles between sham-irradiated and irradiated mice. Concerning mammary carcinomas, there was no significant difference between groups with respect to palpated tumor incidence (sham = 52%; irradiated = 44%), latency to tumor onset (sham = 62.3 ± 1.2 wk; irradiated = 64.0 ± 1.6 wk), and rate of tumor growth. In general, histopathological examination revealed no significant differences in numbers of malignant, metastatic, or benign neoplasms between the two groups; a significantly greater incidence of alveolar-bronchiolar adenoma in the sham-irradiated mice was the only exception. In addition, survival analysis showed no significant difference in cumulative percent survival between sham and irradiated animals. Thus, results indicate that under the conditions of this study, long-term, low-level exposure of mammary-tumor-prone mice to 2450 MHz RFR did not affect mammary tumor incidence, latency to tumor onset, tumor growth rate, or animal longevity when compared with sham-irradiated controls. Bioelectromagnetics 19:20-31, 1998. © 1998 Wiley-Liss, Inc.
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  • 174
    ISSN: 0197-8462
    Keywords: UWB ; recombination ; mutagenesis ; yeast ; ultraviolet light ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Cell samples of the yeast Saccharomyces cerevisiae were exposed to 100 J/m2 of 254 nm ultraviolet (UV) radiation followed by a 30 min treatment with ultra-wide band (UWB) electromagnetic pulses. The UWB pulses (101-104 kV/m, 1.0 ns width, 165 ps rise time) were applied at the repetition rates of 0 Hz (sham), 16 Hz, or 600 Hz. The effect of exposures was evaluated from the colony-forming ability of the cells on complete and selective media and the number of aberrant colonies. The experiments established no effect of UWB exposure on the UV-induced reciprocal and non-reciprocal recombination, mutagenesis, or cell survival. Bioelectromagnetics 19: 128-130, 1998. © 1998 Wiley-Liss, Inc.
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  • 175
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    Bioelectromagnetics 19 (1998), S. 138-138 
    ISSN: 0197-8462
    Keywords: Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: No abstract.
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  • 176
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    Bioelectromagnetics 19 (1998), S. 172-180 
    ISSN: 0197-8462
    Keywords: melatonin ; electromagnetic field ; pineal gland ; circadian rhythm ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Four separate experiments were carried out to investigate the effect of extremely low frequency magnetic field (MF) exposure (60 Hz, 1 mT rms) on urinary 6-sulphatoxymelatonin (aMT6s) levels in Sprague-Dawley rats. In the first experiment, immature male rats maintained under a regular 12 h daily photoperiod (white fluorescent light) were exposed to a 20 h daily MF exposure for 6 weeks. The second experiment was similar to the first, except that the MF exposure was limited to 10 days. In the third experiment, adult male rats acclimated to a combination of continuous dim red light and regular 12 h daily photoperiod (white fluorescent) were subjected to a single 1 h exposure to intermittent MF (1 min on and 1 min off cycles), 2 h before fluorescent lights went off. The fourth experiment was similar to the third, except that the animals received 2 consecutive days of 20 h daily exposure to intermittent MF, beginning 1 h before the fluorescent lights went off each day. In all four experiments, the circadian profile of urinary aMT6s was examined before, during, and after the MF exposure. No significant effect of 1 mT MF on indoleamine metabolism was observed in any of the above experiments. However, in one of the experiments (no. 4), both the control and the MF groups showed a lower aMT6s level during the exposure days, when compared with that of pre- and post-exposure days, suggesting that the existence of possible effects with lower field strengths at the range of stray field cannot be ruled out. Bioelectromagnetics 19:172-180, 1998. © 1998 Wiley-Liss, Inc.
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  • 177
    ISSN: 0197-8462
    Keywords: electromagnetic fields ; bioeffects ; mm wave band ; millimeter waves, review ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: In recent years, research into biological and medical effects of millimeter waves (MMW) has expanded greatly. This paper analyzes general trends in the area and briefly reviews the most significant publications, proceeding from cell-free systems, dosimetry, and spectroscopy issues through cultured cells and isolated organs to animals and humans. The studies reviewed demonstrate effects of low-intensity MMW (10 mW/cm2 and less) on cell growth and proliferation, activity of enzymes, state of cell genetic apparatus, function of excitable membranes, peripheral receptors, and other biological systems. In animals and humans, local MMW exposure stimulated tissue repair and regeneration, alleviated stress reactions, and facilitated recovery in a wide range of diseases (MMW therapy). Many reported MMW effects could not be readily explained by temperature changes during irradiation. The paper outlines some problems and uncertainties in the MMW research area, identifies tasks for future studies, and discusses possible implications for development of exposure safety criteria and guidelines. Bioelectromagnetics 19:393-413, 1998. © 1998 Wiley-Liss, Inc.
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  • 178
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    Bioelectromagnetics 19 (1998), S. 438-443 
    ISSN: 0197-8462
    Keywords: progesterone ; electric field ; magnetic field ; cows ; extremely low frequency ; alternating current ; estrous cycle ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Sixteen multiparous nonpregnant lactating Holstein cows (each weighing 662 ± 65 kg in 150.4 ±40 day of lactation) were confined to wooden metabolic cages with 12:12 h light:dark cycle during the experiment. The cows were divided into two sequences of eight cows each and exposed to electric and magnetic fields (EMF) in an exposure chamber. This chamber produced a vertical electric field of 10 kV/m and a uniform horizontal magnetic field of 30 μT at 60 Hz. One sequence was exposed for three estrous cycles of 24 to 27 days. During the first estrous cycle, the electric and magnetic fields were off; during the second estrous cycle, they were on; and during the third estrous cycle, they were off. The second sequence was also exposed for three 24 to 26 days estrous cycles, but the exposure to the fields was reversed (first estrous cycle, on; second estrous cycle, off; third estrous cycle, on). The length of each exposure period (21 to 27 days) varied according to the estrous cycle length. No differences were detected in plasma progesterone concentrations and area under the progesterone curve during estrous cycles between EMF nonexposed and exposed periods (2.28 ±0.17 and 2.25 ± 0.17; and 24.5 ± 1.9 vs. 26.4 ± 1.9 ng/ml, respectively). However, estrous cycle length, determined by the presence of a functional corpus luteum detected by concentrations of progesterone equal to or more than 1 ng/ml plasma, was shorter in nonexposed cows than when they were exposed to EMF (22.0 ± 0.9 vs. 25.3 ± 1.4 days). Bioelectromagnetics 19:438-443, 1998. © 1998 Wiley-Liss, Inc.
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  • 179
    ISSN: 0197-8462
    Keywords: electromagnetic shielding ; cellular telephone communications ; experimental logistics ; microwave radiation ; mobile telephones ; exposure systems ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: To carry out in vivo studies of the possible health effects of radiation from cellular telephone handsets, it is necessary to expose large numbers of small mammals at realistic power densities, modulations, and frequencies. Because even microwatt leakage could compromise the local cellular system, extreme care in shielding is required. Experimental logistics dictate, however, that the irradiated animals be easily accessed and that it be possible to irradiate them in small groups, while other groups are being loaded into or unloaded from the irradiators. This problem has been resolved by exposing the animals in aluminum-sheathed rectangular parallelepipeds, lined with microwave absorber and having doors that can be opened readily. Inside each of these microwave anechoic “chamberettes” is a vertical, four-element collinear array of dipole antennas; and around each antenna, 10 animal restrainers can be arranged like spokes on a wheel. The system has worked efficiently in studies of up to 480 rats. There is negligible coupling between antennas, and back reflection at an antenna's feed line is down 7-9 dB. Received CDMA power at the local base station is below the receiver's noise floor. Interior illumination reinforces the rats' diurnal rhythms, and the rats sleep during irradiation. Experimental logistics are excellent. In this paper, the irradiator design is presented. Bioelectromagnetics 19:459-468, 1998. © 1998 Wiley-Liss, Inc.
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  • 180
    ISSN: 0197-8462
    Keywords: magnetic fields ; apoptosis ; dexamethasone-induced apoptosis ; thymocytes ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: To address the effect of extremely low frequency electromagnetic fields on programmed cell death we assessed both the spontaneous and dexamethasone (Dex)-induced apoptosis of thymocytes and spleen cells from mice submitted to a long-term continuous exposure of a 0.4-1.0 μT 60 Hz magnetic field or an 8-20 μT direct current (DC) magnetic field. Dex-induced apoptosis but not spontaneous apoptosis was substantially increased in thymocytes from 0.4 to 1.0 μT 60 Hz field-exposed animals. Spontaneous apoptosis and Dex-induced apoptosis of spleen cells were not affected by the 0.4-1.0 μT 60 Hz field exposure. In addition, spontaneous apoptosis and Dex-induced apoptosis of thymocytes and spleen cells from mice exposed to an 8-20 μT DC field were similar to the controls. These findings represent the first demonstration that thymocytes from mice exposed to a long-term 0.4-1.0 μT 60 Hz field may show abnormal response to Dex apoptotic stimuli. Bioelectromagnetics 19:131-135, 1998. © 1998 Wiley-Liss, Inc.
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  • 181
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    Bioelectromagnetics 19 (1998), S. 139-139 
    ISSN: 0197-8462
    Keywords: Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: No abstract.
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  • 182
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    Bioelectromagnetics 19 (1998), S. 162-171 
    ISSN: 0197-8462
    Keywords: organogenesis ; electromagnetic fields ; rat toxicity ; high-frequency inductive power distribution ; health effects magnetic fields ; 10 kHz ; reproductive study ; rodent ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: New technology involving the use of high-frequency inductive power distribution (HID) has recently been developed for use in materials handling and personnel transfer. Sinusoidal magnetic fields at a frequency of 10 kHz with field intensities of approximately 0.2 mT are generated directly between the current-carrying coils of this equipment. Effects of 10 kHz magnetic fields on cell division, migration, and differentiation have never been previously investigated. To evaluate potential effects on these parameters, a rodent reproductive study was undertaken using Wistar rats. Exposures were at 0.095, 0.24, and 0.95 mT with a background exposure of 5-10 μT. Three sets of parental rats were exposed continuously for 20-23.5 h/day to the fields: maternal rats during gestation, paternal rats for at least 45 days prior to mating and maternal rats 1 month prior to mating. Exposure phases thus covered spermatogenesis, maturation of the ovum and ovulation, fertilization, implantation, embryogenesis, organogenesis, and maturation of the fetus immediately prior to parturition. In all experiments pregnancy outcome was assessed. These studies failed to demonstrate any reproductive toxicity resulting from maternal or fetal exposure during gestation or following paternal or maternal exposure for several weeks prior to mating. No quantitative or qualitative effects on spermatogenesis occurred after exposure, and no effects on the estrous cycle or ovulation could be demonstrably linked to the 10 kHz magnetic field exposure at 0.095, 0.25, or 0.95 mT. Where possible, parental clinical chemistry and hematology were also examined. As in mouse toxicology studies previously reported, minor differences were observed between control and treated groups. These were regarded as statistically, but not biologically, significant and could not categorically be attributed to magnetic field exposure. Bioelectromagnetics 19:162-171, 1998. © 1998 Wiley-Liss, Inc.
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  • 183
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    Bioelectromagnetics 19 (1998), S. 181-191 
    ISSN: 0197-8462
    Keywords: mechanisms ; theoretical models ; ion resonances ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: We show, in elementary terms, using for the most part only elementary mathematics, the physical bases for the ion parametric resonance model so as to clarify the assumptions and consequences of the model. The analysis shows why, contrary to earlier conclusions, no combination of weak DC and AC magnetic fields can modify the transition rate to the ground state of excited ions. Although reinterpretations of the biological consequences of the motion of the excited ions circumvent that particular objection to the model, those changes introduce other difficulties. Also, other objections to the mechanism still stand; hence the model cannot account for any purported biological effects of weak extremely low frequency magnetic fields. Bioelectromagnetics 19:181-191, 1998. © 1998 Wiley-Liss, Inc.
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  • 184
    ISSN: 0197-8462
    Keywords: electric and magnetic fields ; neurotransmitters ; brain receptors ; histology ; hematology ; serum chemistry ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Groups of adult male Sprague Dawley rats (64 rats each) were exposed for 8 months to electromagnetic fields (EMF) of two different field strength combinations: 5μT - 1kV/m and 100μT - 5kV/m. A third group was sham exposed. Field exposure was 8 hrs/day for 5 days/week. Blood samples were collected for hematology determinations before the onset of exposure and at 12 week intervals. At sacrifice, liver, heart, mesenteric lymph nodes, bone marrow, and testes were collected for morphology and histology assessments, while the pineal gland and brain were collected for biochemical determinations. At both field strength combinations, no pathological changes were observed in animal growth rate, in morphology and histology of the collected tissue specimens (liver, heart, mesenteric lymph nodes, testes, bone marrow), and in serum chemistry. An increase in norepinephrine levels occurred in the pineal gland of rats exposed to the higher field strength. The major changes in the brain involved the opioid system in frontal cortex, parietal cortex, and hippocampus. From the present findings it may be hypothesized that EMF may cause alteration of some brain functions. Bioelectromagnetics 19:57-66, 1998. © 1998 Wiley-Liss, Inc.
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  • 185
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    Bioelectromagnetics 19 (1998), S. 85-91 
    ISSN: 0197-8462
    Keywords: extremely low-frequency electromagnetic fields (ELF-EMF) ; micronucleus formation ; apoptosis ; SCL II cells ; amniotic fluid cells (AFC cells) ; cytogenetic effects ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Effects of applying extremely low-frequency electromagnetic fields (ELF-EMF) for different durations (24, 48, and 72 h) and different field intensities (0.1-1.0 mT) on micronucleus (MN) formation and induction of apoptosis were examined in a human squamous cell carcinoma cell line (SCL II) and in a human amniotic fluid cell line (AFC). A statistically significant increase of MN frequency and of induction of apoptosis in SCL II cells after 48-h and 72-h continuous exposure to 50 Hz magnetic field (MF) (0.8 and 1.0 mT) was found. However, exposure of AFC cells to EMF of different intensities and for different exposure times showed no statistically significant differences when compared with controls. These results demonstrate that different human cell types respond differently to EMF. Dose-dependent induction of apoptosis and genotoxic effects, resulting in increased micronucleus formation, could be demonstrated in the transformed cell line, whereas the nontransformed cell line did not show statistically significant effects. These findings suggest that EMF could be a promotor but not an initiator of carcinogenic effects. Bioelectromagnetics 19:85-91, 1998. © 1998 Wiley-Liss, Inc.
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  • 186
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    Bioelectromagnetics 19 (1998), S. 152-161 
    ISSN: 0197-8462
    Keywords: alternating ; cell cycle ; modelling ; breakages ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Vicia faba seedlings were subjected to one of the following magnetic fields continuously for 3 days: 0 Hz (DC) at 5 mT, 50 Hz at 1.5 mT, 60 Hz at 1.5 mT, and 75 Hz at 1.5 mT. The lengths of all the phases of mitosis differed from the controls in all treatments using alternating magnetic fields and for prophase and metaphase in the DC condition. In particular, all treatments increased the length of prophase significantly in meristematic root-tip cells compared with the controls. The implications of these results for chromosome coiling are discussed. The length of prophase, however, did not vary significantly between any of the treatments. Furthermore, none of the exposed seedlings had a greater frequency of chromosome breakages above that of the control plants. Bioelectromagnetics 19:152-161, 1998. © 1998 Wiley-Liss, Inc.
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  • 187
    ISSN: 0197-8462
    Keywords: IPR model ; nerve growth factor ; static magnetic field ; PC-12 cells ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Previous work reported that nerve growth factor-stimulated neurite outgrowth in PC-12 cells could be altered by exposure to parallel alternating current (AC) and direct current (DC) magnetic fields under a variety of exposure conditions, producing results that are consistent with the predictions of the ion parametric resonance (IPR) model. The credibility of these results, considered extraordinary by some scientists, could be strengthened if the cell response were found to persist under alternate assay conditions. We replaced part of our standard assay procedure with a double blind procedure. This new procedure obscured 1) whether a particular set of dishes of cells was exposed or not, and 2) which individual dish was in which exposure system. The goal was to determine whether the previously observed responses of PC-12 cells to magnetic fields would be sufficiently robust to decode the imposed blinding, thereby removing any question of experimenter bias in reported results. We placed three coded dishes of cells in each of two otherwise identical exposure systems, one not energized and one energized to produce exposure conditions predicted to maximally suppress neurite outgrowth (Bdc of 36.6 μT, parallel 45 Hz AC of 23.8 μT rms). Each of the six dishes were recoded before assay to further obscure the exposure identity of any individual dish. The combined results of four distinct runs of these double blind experiments unequivocally demonstrated that 1) there was a clear, distinctive, repeatable consistency with the actual energization of the exposure systems and location of each dish, and with the predictions of the IPR model; 2) only the explicitly stated experimental variables influenced the experiment; and 3) the reported response of the cells was very improbably due to chance (P = .000024). Bioelectromagnetics 19:204-209, 1998. © 1998 Wiley-Liss, Inc. This article was prepared by a group consisting of both United States government employees and non-United States government employees, and as such is subject to 17 U.S.C. Sec. 105.
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  • 188
    ISSN: 0197-8462
    Keywords: immune system ; electromagnetic fields ; T lymphocytes ; cancer ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: In previous studies we have demonstrated that 50 Hz, 100 μT magnetic field (MF) exposure of female Sprague-Dawley rats for 13 weeks significantly enhances the development and growth of mammary tumors in a breast cancer model. The present study was designed to test the hypothesis that, at least in part, the tumor (co)promoting effect of MF exposure is due to MF effects on the immune surveillance system, which is of critical importance in protecting an organism against the development and growth of tumors. For this purpose, female Sprague-Dawley rats of the same age as in the mammary tumor experiments were continuously exposed for different periods (2, 4, 8, and 13 weeks) to a 50 Hz, 100 μT MF. Control groups were sham-exposed simultaneously. Following the different exposure periods, splenic lymphocytes were cultured and the proliferative responses to the T-cell-selective mitogen concanavalin A (Con A) and the B-cell-selective pokeweed mitogen (PWM) were determined. Furthermore, the production of interleukin-1 (IL-1) was determined in the splenocyte cultures. The mitogenic responsiveness of T cells was markedly enhanced after 2 weeks of MF exposure, suggesting a co-mitogenic action of MF. A significant, but less marked increase in T-cell mitogenesis was seen after 4 weeks of MF exposure, whereas no difference from sham controls was determined after 8 weeks, indicating adaptation or tolerance to this effect of MF exposure. Following 13 weeks of MF exposure, a significant decrease in the mitogenic responsiveness of lymphocytes to Con A was obtained. This triphasic alteration in T-cell function (i.e., activation, tolerance, and suppression) during prolonged MF exposure resembles alterations observed during chronic administration of mild stressors, substantiating the hypothesis that cells respond to MF in the same way as they do to other environmental stresses. In contrast to T cells, the mitogenic responsiveness of B cells and IL-1 production of PWM-stimulated cells were not altered during MF exposure. The data demonstrate that MF in vivo exposure of female rats induces complex effects on the mitogenic responsiveness of T cells, which may lead to impaired immune surveillance after long-term exposure. Bioelectromagnetics 19:259-270, 1998. © 1998 Wiley-Liss, Inc.
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  • 189
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    Bioelectromagnetics 19 (1998), S. 486-493 
    ISSN: 0197-8462
    Keywords: ELF ; magnetic fields ; memory ; power frequency ; spatial learning ; radial arm maze ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: Intense magnetic fields have been shown to affect memory-related behaviours of rodents. A series of experiments was performed to investigate further the effects of a 50 Hz magnetic field on the foraging behaviour of adult, male C57BL/6J mice performing a spatial learning task in an eight-arm radial maze. Exposure to vertical, sinusoidal magnetic fields between 7.5 μT and 7.5 mT for 45 min immediately before daily testing sessions caused transient decreases in performance that depended on the applied flux density. Exposure above a threshold of between 7.5 and 75 μT significantly increased the number of errors the animals made and reduced the rate of acquisition of the task without any effect on overall accuracy. However, the imposition of a 45-minute delay between exposure at 0.75 mT and behavioural testing resulted in the elimination of any deficit. Similarly, exposure to fields between 7.5 μT and 0.75 mT for 45 min each day for 4 days after training had no amnesic effects on the retention and subsequent performance of the task. Overall, these results provide additional evidence that 50 Hz magnetic fields may cause subtle changes in the processing of spatial information in mice. Although these effects appear dependent on field strength, even at high flux densities the field-induced deficits tend to be transient and reversible. Bioelectromagnetics 19:486-493, 1998. © 1998 Wiley-Liss, Inc.
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  • 190
    ISSN: 0197-8462
    Keywords: sea urchin egg ; static and sinusoidal magnetic fields ; first division ; effect of temperature ; Life and Medical Sciences ; Occupational Health and Environmental Toxicology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Physics
    Notes: The early divisions of sea urchin eggs was used as a model to study the effects of static and of 60 Hz sinusoidal magnetic fields. Two species were used (Sphaerechinus granularis and Paracentrotus lividus). Eggs were fertilized and exposed in two separate coils to the fields (up to 8 mT). Great care was taken to control the temperature of each sample. No difference was found in the time of the first division that could not be attributed to a temperature difference between samples. Comparison is made with other published data on various species. Bioelectromagnetics 19:494-497, 1998. © 1998 Wiley-Liss, Inc.
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  • 191
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    Biologie in unserer Zeit 28 (1998), S. 47-47 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
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  • 192
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    Biologie in unserer Zeit 28 (1998), S. 41-41 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
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  • 193
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    Biologie in unserer Zeit 28 (1998), S. 118-118 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
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  • 194
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    Biologie in unserer Zeit 28 (1998), S. VI 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 195
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    Biologie in unserer Zeit 28 (1998), S. 223-223 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 196
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    Biologie in unserer Zeit 28 (1998), S. 224-225 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 197
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    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 28 (1998) 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 198
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    Weinheim : Wiley-Blackwell
    Biologie in unserer Zeit 28 (1998), S. 342-347 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Die moderne Bevölkerungswissenschaft ist von der Theorie des demographischen übergangs (auch Transformationstheorie genannt) geprägt. Eigentlich werden hierunter zwei übergänge zusammengefaßlig;t, nämlich, im Verlauf von einigen Generationen, der Wechsel von einem hohen Niveau der Geburten- und Sterberate zu einem jeweils niedrigeren Niveau. Zuerst sinkt die Sterberate, später die Geburtenrate, so daßlig; die mittlere Phase dieses übergangs durch ein ausgeprägtes Bevölkerungswachstum gekennzeichnet ist (Abbildung 1). Es ist derzeit umstritten, in welchem Ausmaßlig; beide übergänge ursächlich zusammenhängen oder ob sie nur zufällig zeitlich aufeinander folgen. Strikte Abhängigkeit würde bedeuten, daßlig;alle Staaten der Erde diese Entwicklung irgendwann einmal durchlaufen und ein zukünftiger Wachstumsstillstand für die Weltbevölkerung bei etwa zwölf Milliarden Menschen angenommen werden kann. Derzeit wächst jedoch der relative Anteil der Weltbevölkerung, der sich nicht theoriekonform verhält. Die Entwicklung von Sterbe- und Geburtenrate kann sich also gegensinnig verhalten, das heißlig;t, auch bei sinkender Sterberate kann die Geburtenrate auf einem hohen Niveau verharren. Dies führt in einigen Staaten zuungebremstem Wachstum, obwohl sich die Lebensbedingungen rapide verschlechtern.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 199
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    Biologie in unserer Zeit 28 (1998), S. 371-380 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Die Entwicklung der heute in der Landwirtschaft und im Gartenbau genutzten Kulturpflanzen ist eine der wichtigsten Leistungen in der Geschichte der Menschheit. Züchterische Maßlig;nahmen des Menschen haben zum Ziel, Pflanzen so zu verändern, daßlig; sie besser an seine Bedürfnisse angepaßlig;t sind. Die Eingriffe durch Züchtung nennt man „gelenkte Evolution“. Ausgehend von wild vorkommenden Arten hat der Mensch Nutzpflanzen geschaffen, die ohne seine Hilfe in der freien Natur auf Dauer nur geringe überlebenschancen hätten. Neben den Nutzpflanzen findet man in der Natur noch viele wilde Arten, die mit den Kulturpflanzen verwandt sind und sich häufig mit ihnen kreuzen lassen. Die wilden Arten verfügen über ein genetisches Potential, auf das in den letzten Jahren immer häufiger zurückgegriffen worden ist, um Zuchtziele des Menschen zu verwirklichen. Vor allem müssen ständig neue Resistenzen gegen Krankheiten und Schädlinge gefunden werden, um dem Infektionsdruck der Krankheitserreger zu widerstehen. Aber auch Gene für Toleranz gegenüber abiotischem Streßlig;, wie Kälte, Dürre, Salz oder Aluminiumtoxizität, sind in den Wildarten vorhanden. Sie können in die Kulturpflanzen eingekreuzt werden, um sie gegen diese Streßlig;faktoren widerstandsfähiger zu machen.Voraussetzung für den Gentransfer von einer Wildart in eine Kulturart ist ihre Kreuzbarkeit. Darüber hinaus mußlig; im Kreuzungsbastard crossing over zwischen homologen Chromosomen gewährleistet sein. Wenn die Chromosomen nicht zu natürlichem crossing over in der Lage sind, können genetische Paarungsmechanismen in der Meiose eingesetzt werden, die zu dem gewünschten Gentransfer führen.Im folgenden soll anhand von drei Beispielen die Bedeutung des genetischen Potentials wilder und verwandter Pflanzenarten für die Verbesserung der Krankheitsresistenz und Inhaltsstoffe sowie Toleranz gegen abiotischen Streßlig; bei Kulturpflanzen demonstriert werden.
    Additional Material: 8 Ill.
    Type of Medium: Electronic Resource
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  • 200
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    Biologie in unserer Zeit 28 (1998), S. 381-383 
    ISSN: 0045-205X
    Keywords: Life and Medical Sciences
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Type of Medium: Electronic Resource
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