Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ELF”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources

Chemotherapy in gastric cancer: an economic evaluation of the FAM (5-fluorouracil, adriamycin, mitomycin C) versus ELF (etoposide, leucovorin, 5-fluorouracil) regimens.

The prognosis in gastric cancer has been almost unchanged for the last 20 years. At the time of diagnosis the majority of patients have disseminated disease. The 5-year survival is only about 15%. Several efforts with numerous antineoplastic regimens have been studied. The most widely used regimen has been the FAM (5-fluorouracil, adriamycin, mitomycin C) regimen. Because of the cardiotoxicity and dose intensity of the FAM regimen, a low toxicity regimen, the ELF (etoposide, leucovorin, 5-fluorouracil) regimen, has been introduced. We present the data from the treatment of 26 patients (17 FAM, 9 ELF) with advanced gastric cancer at the University Hospital of Tromsø. The monthly costs of FAM and ELF treatment were calculated to a price of 553 pounds and 2976 pounds (British pounds). The median survival of 5 months (FAM) and 6 months (ELF) is in accordance with other studies. Assuming that the median survival in our study is correct, the cost of one year saved was 123,834 pounds, while the cost of one QALY (quality adjusted life year) employing the ELF compared to the FAM regimen was 104,334 pounds. We conclude that the standard ELF regimen too expensive in the treatment of gastric cancer.

Adult↗

MEF, a novel transcription factor with an Elf-1 like DNA binding domain but distinct transcriptional activating properties.

To isolate novel ETS genes expressed in hematopoietic cells we used a nested, degenerate oligonucleotide PCR based technique to obtain a cDNA fragment that encodes an ETS domain from a human megakaryocytic cell line. This fragment was used to isolate a full length, 4.2 kb cDNA that encodes a 663 amino acid protein which we call MEF (myeloid elf-1-like factor). MEF contains a central ETS domain and is expressed in a variety of myeloid leukemia cell lines and in normal adult hematopoietic tissue such as spleen, thymus and peripheral blood, as well as non-hematopoietic tissue such as ovary, placenta and colon. Using an oligonucleotide binding selection assay, and bacterially expressed MEF, we demonstrated that MEF recognizes a consensus DNA binding sequence nearly identical to elf-1 (..WGGA..) and then showed that MEF specifically bound to known elf-1 binding sites in the human GM-CSF and IL-3 promoters. To characterize the functional effect of MEF on transcription, we performed co-transfection experiments in myeloid cells, and T cells, and demonstrated transactivation of both promoters by MEF, but not by elf-1. MEF is a new member of the elf-1/E74 family of ETS proteins, that has DNA binding properties similar to elf-1 but distinct transcriptional activating effects in several hematopoietic cell lineages.

Adult↗

Bioeffects induced by exposure to microwaves are mitigated by superposition of ELF noise.

We have previously demonstrated that microwave fields, amplitude modulated (AM) by an extremely low-frequency (ELF) sine wave, can induce a nearly twofold enhancement in the activity of ornithine decarboxylase (ODC) in L929 cells at SAR levels of the order of 2.5 W/kg. Similar, although less pronounced, effects were also observed from exposure to a typical digital cellular phone test signal of the same power level, burst modulated at 50 Hz. We have also shown that ODC enhancement in L929 cells produced by exposure to ELF fields can be inhibited by superposition of ELF noise. In the present study, we explore the possibility that similar inhibition techniques can be used to suppress the microwave response. We concurrently exposed L929 cells to 60 Hz AM microwave fields or a 50 Hz burst-modulated DAMPS (Digital Advanced Mobile Phone System) digital cellular phone field at levels known to produce ODC enhancement, together with band-limited 30-100 Hz ELF noise with root mean square amplitude of up to 10 microT. All exposures were carried out for 8 h, which was previously found to yield the peak microwave response. In both cases, the ODC enhancement was found to decrease exponentially as a function of the noise root mean square amplitude. With 60 Hz AM microwaves, complete inhibition was obtained with noise levels at or above 2 microT. With the DAMPS digital cellular phone signal, complete inhibition occurred with noise levels at or above 5 microT. These results suggest a possible practical means to inhibit biological effects from exposure to both ELF and microwave fields.

Animals↗

Resting EEG is affected by exposure to a pulsed ELF magnetic field.

An increasing number of reports have demonstrated a significant effect of extremely low frequency magnetic fields (ELF MFs) on aspects of animal and human behavior. Recent studies suggest that exposure to ELF MFs affects human brain electrical activity as measured by electroencephalography (EEG), specifically within the alpha frequency (8-13 Hz). Here we report that exposure to a pulsed ELF MF with most power at frequencies between 0 and 500 Hz, known to affect aspects of analgesia and standing balance, also affects the human EEG. Twenty subjects (10 males; 10 females) received both a magnetic field (MF) and a sham session in a counterbalanced design for 15 min. Analysis of variance (ANOVA) revealed that alpha activity was significantly higher over the occipital electrodes (O1, Oz, O2) [F(1,16) = 6.858; P =.019, eta2 = 0.30] and marginally higher over the parietal electrodes (P3, Pz, P4) [F(1,16) = 4.251; P =.056, eta2 = 0.21] post MF exposure. This enhancement of alpha activity was transient, as it marginally decreased over occipital [F(1,16) = 4.417; P =.052; eta2 = 0.216] and parietal electrodes [F(1,16) = 4.244; P =.056; eta2 = 0.21] approximately 7 min after MF exposure compared to the sham exposure. Significantly higher occipital alpha activity is consistent with other experiments examining EEG responses to ELF MFs and ELF modulated radiofrequency fields associated with mobile phones. Hence, we suggest that this result may be a nonspecific physiological response to the pulsed MFs.

Adult↗

Non-linearity in combined effects of ELF magnetic field and amphetamine on motor activity in rats.

The effects of short-term (15 min) pre-exposure of rats to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 6 mT) on their motor (locomotor and stereotypic) activity induced by d-amphetamine sulphate (AMPH) at different doses (0.5, 1.5 and 4.5mg/kg, i.p.) were studied in the open field test. In saline-treated rats both parameters of motor activity were unaffected by ELF-MF irradiation. The rats pre-exposed to ELF-MF and injected with the lowest dose of AMPH showed the same locomotor activity as control animals, while their stereotypic behaviour was significantly elevated. ELF-MF in combination with AMPH at higher doses significantly enhanced motor activity when compared with values obtained in both control and combined experiments with the lowest dose of the drug. However, only combined locomotor effect at the middle dose of AMPH was significantly greater than those observed in corresponding experiments with AMPH alone. These results demonstrate that acute short-term exposure to ELF-MF is able to modify a motor activity in dependence on the extent of AMPH-induced neurotransmitter imbalance.

Amphetamine↗

Topographically specific effects of ELF-1 on retinal axon guidance in vitro and retinal axon mapping in vivo.

Topographic maps, which maintain the spatial order of neurons in the order of their axonal connections, are found throughout the nervous system. In the visual retinotectal projection, ELF-1, a ligand in the tectum, and its receptors in the retina show complementary gradients in expression and binding, indicating they may be positional labels for map development. Here we show that ELF-1 acts as a repellent axon guidance factor in vitro. In vivo, when the tectal ELF-1 pattern is modified by retroviral overexpression, retinal axons avoid ectopic ELF-1 patches and map to abnormally anterior positions. All these effects were seen on axons from temporal but not nasal retina, indicating that ELF-1 could determine nasal versus temporal retinotectal specificity, and providing a direct demonstration of a cell recognition molecule with topographically specific effects on neural map development.

Animals↗

Comparison of extremely low frequency (ELF) magnetic field personal exposure monitors.

The MultiWave System III (MW III), a recently developed personal monitor for extremely low frequency (ELF) magnetic fields, was compared with the standard EMDEX Lite (Electric and Magnetic Field Digital Exposure System), the type of monitor widely used in epidemiology and other exposure assessments. The MW III captures three-axis magnetic field waveforms for the calculation of many exposure metrics, while the EMDEX monitors measure only the root-mean-squared (RMS) vector magnitude (or resultant). Thirty-eight partial period personal samples were monitored in six different job classifications. The sampling time for each personal sample ranged from 90 to 133 min, with a mean sample time of 110 min. The EMDEX Lite and MW III were evaluated by comparing the maximum and partial period time-weighted average (TWA) of the ELF magnitude. TWA exposures measured for the 38 partial period samples by the EMDEX Lite ranged from 1.2 to 65.3 mG, with a mean of 18.1 mG, while corresponding values for the MW III ranged from 1.1 to 65.8 mG, with a mean of 17.7 mG. The maximum magnetic field exposures measured for the 38 partial period personal samples by the EMDEX Lite ranged from 27.0 to 420.2 mG, with a mean of 216.3 mG, while corresponding values for the MW III ranged from 40.2 to 1311.8 mG, with a mean of 368.4 mG. The maximum and TWA ELF magnetic field exposures measured by the EMDEX Lite and MW III were compared using a two-tailed, paired t-test. Analyses indicate that there was no significant difference in the TWA magnetic field magnitude measured by the EMDEX Lite and MW III. On the other hand, the EMDEX Lite reported significantly lower (P=0.002) maximum magnetic field measurements compared to the MW III. From a detailed analysis of the time traces, the EMDEX Lite appears to measure the ELF magnitude inaccurately when the field changes rapidly over a 4-s sampling interval. The results of this comparison suggest that the standard EMDEX Lite and MW III provide similar measure of the TWA magnetic field in a variety of occupational settings and ELF magnetic field magnitudes. However, the EMDEX Lite underestimates maximum exposures when compared to the MW III.

Electromagnetic Fields↗

ELF-1 interacts with and transactivates the IgH enhancer pi site.

We previously identified a B-cell-specific regulatory element in the immunoglobulin heavy chain (IgH) enhancer, pi, with striking similarity to binding sites for ets-related transcription factors. Whereas the ability of ets-related factors to bind to and transactivate the pi site has been substantiated, the identification of the particular member of the ets family responsible for B-cell-specific regulation of the pi site has remained controversial. We have used antibodies specific for individual members of the ets family to evaluate which ets-related factor in B-cell nuclear extracts interacts with the IgH pi site. We present strong evidence that ELF-1 is highly expressed in B-cells and is one of two major factors specifically interacting with the murine IgH enhancer pi site in B-cell nuclear extracts. Binding of ELF-1 correlates with activity of the pi site, since mutations abolishing function of pi also inhibit binding of ELF-1. Furthermore, we demonstrate that ELF-1 can transactivate the IgH enhancer in HeLa cells, suggesting a role for ELF-1 in B-cell-specific IgH gene expression.

Animals↗

Developmental function of Elf-1: an essential transcription factor during embryogenesis in Drosophila.

The Drosophila transcription factor Elf-1 binds to a cis-acting element that is essential for neuronal expression of the Dopa decarboxylase gene (Ddc). Elf-1 also stimulates transcription from the Ddc and Ultrabithorax promoters in vitro. To investigate the function of this factor in vivo we have screened for mutations and identified the Elf-1 gene as grainyhead (grh), a previously known embryonic lethal locus. Elf-1/grh mutations cause late embryonic lethality accompanied by multiple defects in the cuticle and head skeleton. Using Ddc-lacZ gene fusions, we show that these mutations affect Ddc expression in the embryo. Surprisingly, however, epidermal expression is disrupted, whereas neuronal expression remains unaffected. Analysis of the mutant phenotype indicates that Elf-1 coordinately regulates multiple genes involved in the differentiation of epidermal structures. The results highlight the importance of genetic analysis in the study of proteins required for developmental regulation of gene expression.

Animals↗

Disruption of transforming growth factor-beta signaling in ELF beta-spectrin-deficient mice.

Disruption of the adaptor protein ELF, a beta-spectrin, leads to disruption of transforming growth factor-beta (TGF-beta) signaling by Smad proteins in mice. Elf-/- mice exhibit a phenotype similar to smad2+/-/smad3+/- mutant mice of midgestational death due to gastrointestinal, liver, neural, and heart defects. We show that TGF-beta triggers phosphorylation and association of ELF with Smad3 and Smad4, followed by nuclear translocation. ELF deficiency results in mislocalization of Smad3 and Smad4 and loss of the TGF-beta-dependent transcriptional response, which could be rescued by overexpression of the COOH-terminal region of ELF. This study reveals an unexpected molecular link between a major dynamic scaffolding protein and a key signaling pathway.

Abnormalities, Multiple↗

Regulation of cell-type-specific interleukin-2 receptor alpha-chain gene expression: potential role of physical interactions between Elf-1, HMG-I(Y), and NF-kappa B family proteins.

The interleukin 2 receptor alpha-chain (IL-2R alpha) gene is rapidly and potently induced in T cells in response to mitogenic stimuli. Previously, an inducible enhancer between nucleotides -299 and -228 that contains NF-kappa B and CArG motifs was identified. We now report the characterization of a second essential positive regulatory element located between nucleotides -137 and -64 that binds Elf-1 and HMG-I(Y). This element had maximal activity in lymphoid cells, paralleling the cell type specificity of Elf-1 expression. Transcription from the IL-2R alpha promoter was inhibited when either the Elf-1 or the HMG-I(Y) binding site was mutated. Coexpression of both proteins activated transcription of the -137 to -64 element in COS-7 cells. Elf-1 physically associated with HMG-I and with NF-kappa B p50 and c-Rel in vitro, suggesting that protein-protein interactions might functionally coordinate the actions of the upstream and downstream positive regulatory elements. This is the first report of a physical interaction between an Ets family member and NF-kappa B family proteins. These findings provide significant new insights into the protein-protein and protein-DNA interactions that regulate cell-type-specific and inducible IL-2R alpha gene expression and also have implications for other genes regulated by Elf-1 and NF-kappa B family proteins.

Animals↗

ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somites.

The Eph receptors are the largest known family of receptor tyrosine kinases and are notable for distinctive expression patterns in the nervous system and in early vertebrate development. However, all were identified as orphan receptors, and only recently have there been descriptions of a corresponding family of ligands. We describe here a new member of the Eph ligand family, designated ELF-2 (Eph ligand family 2). The cDNA sequence for mouse ELF-2 indicates that it is a transmembrane ligand. It shows closest homology to the other known transmembrane ligand in the family, ELK-L/LERK-2/Cek5-L, with 57% identity in the extracellular domain. There is also striking homology in the cytoplasmic domain, including complete identity of the last 33 amino acids, suggesting intracellular interactions. On cell surfaces, and in a cell-free system, ELF-2 binds to three closely related Eph family receptors, Elk, Cek10 (apparent ortholog of Sek-4 and HEK2), and Cek5 (apparent ortholog of Nuk/Sek-3), all with dissociation constants of approximately 1 nM. In situ hybridization of mouse embryos shows ELF-2 RNA expression in a segmental pattern in the hindbrain region and the segmenting mesoderm. Comparable patterns have been described for Eph family receptors, including Sek-4 and Nuk/Sek-3, suggesting roles for ELF-2 in patterning these regions of the embryo.

Amino Acid Sequence↗

A potential role for Elf-1 in terminal transferase gene regulation.

The terminal deoxynucleotidyltransferase (TdT) gene represents an attractive model for the analysis of gene regulation during an early phase of lymphocyte development. In previous studies, we identified a DNA element, termed D', which is essential for TdT promoter activity in immature lymphocytes, and two classes of D'-binding factors, Ikaros proteins and Ets proteins. Here, we report a detailed mutant analysis of the D' element which suggests that an Ets protein, rather than an Ikaros protein, activates TdT transcription. Since multiple Ets proteins are expressed in developing lymphocytes and are capable of binding to the D' element, DNA affinity chromatography was used to determine if one of the Ets proteins might bind to the D' element with a uniquely high affinity, thereby implicating that protein as a potential TdT activator. Indeed, one binding activity was greatly enriched in the high-salt eluates from a D' affinity column. Peptide microsequencing revealed that the enriched protein was Elf-1. Immunoblot analyses confirmed that in nuclear extracts, Elf-1 has a significantly higher affinity for the D' sequence than does another Ets protein, Ets-1. Transactivation and expression studies support the hypothesis that Elf-1 activates TdT transcription in immature T and B cells. Finally, a D' mutation which selectively reduces Elf-1 binding, but not the binding of other Ets proteins, was found to greatly reduce TdT promoter activity. Although Elf-1 previously had been implicated in the inducible activation of genes in mature T and B cells, our results suggest that it also plays an important role in regulating genes during an early phase of lymphocyte development.

Amino Acid Sequence↗

Phosphorylation and O-linked glycosylation of Elf-1 leads to its translocation to the nucleus and binding to the promoter of the TCR zeta-chain.

Elf-1, a member of the E 26-specific transcription factor family with a predicted molecular mass of 68 kDa, is involved in the transcriptional regulation of several hematopoietic cell genes. We demonstrate that Elf-1 exists primarily as a 98-kDa form in the nucleus and as an 80-kDa form in the cytoplasm. Phosphorylation and O-linked glycosylation contribute to the increased posttranslational molecular mass of Elf-1. The 98-kDa Elf-1 is released from the cytoplasm tethering retinoblastoma protein and moves to the nucleus, where it binds to the promoter of the TCR zeta-chain gene. Finally, the cytoplasmic 98-kDa form enters the proteasome pathway and undergoes degradation. In conclusion, different forms of Elf-1 are the products of posttranslational modifications that determine its subcellular localization, activity, and metabolic degradation.

Acetylglucosamine↗

Recent studies in the behavioral toxicology of ELF electric and magnetic fields.

Behavioral responses to ELF electric and magnetic fields are reviewed starting with the simple sensory awareness or detection by an animal and moving on through more-complicated behavioral responses such as behavior that averts exposure. The literature selected in this review is taken primarily from the area of behavioral toxicology. As such, it does not review work on specialized response systems to ELF fields. The most notable of these omitted specialized response systems are electroreception, (see Kalmijn, this volume), which occurs in a number of fish species, and homing/navigation and communication of the location of food that occurs in several species of birds and in honeybees, respectively. The toxicologic orientation of most researches that evaluate the effects of exposure to ELF electric and magnetic fields has been influenced primarily by the "missions" of DOE and the power industry programs to determine the health effects of power frequency (50- and 60-Hz) electric and magnetic fields. Because of these large programmatic efforts, most of the recent research has in fact been done at 50 or 60 Hz. In the context of the above limitations, remarkably few robust behavioral effects have been reported. Those that have been reported probably relate to an animal's perception of the electric field, although there are some exceptions to this generalization. The apparent lack of deleterious effects in animals is consistent with recent studies on humans that have been conducted in the UK. With this in mind, it is tempting to conclude that exposure to an ELF field is a rather innocuous event and, other than possible mini-shocks, is without hazard. However, if this is the case, then what sense are we to make of reports of altered neural function (other than behavior) that result from exposure to ELF fields (e.g., suppressed melatonin and SNAT activity in the rat pineal; efflux of calcium ions from brain cortices; histological change in the cerebellum and hippocampus following perinatal exposure, etc.)? Are these neural effects no more than "noise" to the behaving organism? Possible reasons form the disparity between cell biology, neurochemistry, and behavior have been presented in this chapter, and based on the hypothesized reasons for the existing disparity, a number of experiments were suggested.

Animals↗

General properties of the interaction between animals and ELF electric fields.

An analysis is given of the interaction between extremely low-frequency (ELF) electric fields and animals of arbitrary body shape. This analysis is based on three approximations which are valid in the ELF range: In living tissues, capacitive (displacement) currents are negligible compared to conduction currents; effects resulting from the finite velocity of propagation of electromagnetic fields are negligible; skin effect in living tissues is negligible. Major conclusions of the analysis are: (a) The electric field outside the body, the induced charge on the surface of the body, and the total current crossing any section through the body (eg, through the neck or limbs) are completely determined by the characteristics of the applied ELF electric field, the shape of the body, its location relative to ground and other conductors, and any conduction currents from the body to ground or other conductors. (b) All of the quantities in (a) can be measured using conducting animal models. (c) The magnitudes of the electric field outside the body and the induced charge density on the surface of the body are independent of frequency, in the ELF range, when the body is either insulated from or shorted to ground (and any other conductors in the system). (d) The only quantities affected by the electrical properties of the tissues comprising the body are the current density and electric field inside the body. (e) The electric field outside and inside a body will be unchanged by a scaled change in its size.

Air↗

Chronic exposure to ELF fields may induce depression.

Exposure to extremely-low-frequency (ELF) electric or magnetic fields has been postulated as a potentially contributing factor in depression. Epidemiologic studies have yielded positive correlations between magnetic- and/or electric-field strengths in local environments and the incidence of depression-related suicide. Chronic exposure to ELF electric or magnetic fields can disrupt normal circadian rhythms in rat pineal serotonin-N-acetyltransferase activity as well as in serotonin and melatonin concentrations. Such disruptions in the circadian rhythmicity of pineal melatonin secretion have been associated with certain depressive disorders in human beings. In the rat, ELF fields may interfere with tonic aspects of neuronal input to the pineal gland, giving rise to what may be termed "functional pinealectomy." If long-term exposure to ELF fields causes pineal dysfunction in human beings as it does in the rat, such dysfunction may contribute to the onset of depression or may exacerbate existing depressive disorders.

Animals↗

Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map.

Topographic maps with a defined spatial ordering of neuronal connections are a key feature of brain organization. Such maps are believed to develop in response to complementary position-specific labels in presynaptic and postsynaptic fields. However, the complementary labeling molecules are not known. In the well-studied visual map of retinal axons projecting to the tectum, the labels are hypothesized to be in gradients, without needing large numbers of cell-specific molecules. We recently cloned ELF-1 as a ligand for Eph family receptors. Here, RNA hybridization shows matching expression gradients for ELF-1 in the tectum and its receptor Mek4 in the retina. Binding activity detected with alkaline phosphatase fusions of ELF-1 and Mek4 also reveals gradients and provides direct evidence for molecular complementarity of gradients in reciprocal fields. ELF-1 and Mek4 may therefore play roles in retinotectal development and have properties predicted of topographic mapping labels.

Amino Acid Sequence↗