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The existing evidence suggesting a link between exposure to Extremely Low Frequency (ELF) magnetic fields and an increased incidence of cancer is reviewed and evaluated.
The effects of a ELF magnetic field (50 Hz) of low intensity (5 x 10(-4) T) were studied on the growth of 3 cell cultures: fibroblasts L 929, keratinocytes and HeLa. After a 24 to 72 hours exposure to the field no modification of growth rate and viability of the cells was observed in comparison to controls. This conclusion can be expressed for the conditions adopted in our experiments.
Two new cases of leprechaunism are reported, one of which from consanguinous parents. Both cases show the clinical picture characteristic of this syndrome: severe pre- and postnatal growth failure, psychic backwardness, lack of adipose tissue, cutis laxa; elf-like face, large ears, globular eyes, hypertelorism, micrognathia and various degrees of external genitalia hypertrophy. Endocrinologically, one of the patients shows the syndrome of low T3. The role of the endocrine alterations in the etiology of the syndrome is discussed.
Video display terminals (VDTs) are in widespread use and can be found in practically every modern office. Assessment of possible health effects of electromagnetic emissions from these devices is necessary. The intensity of the magnetic field and the frequency spectrum of the emissions at extremely low frequencies (ELF) (5-500 Hz) were measured for a few VDTs and compared with the background field intensities and emissions from other devices. The emissions in the frequency range investigated are of such low intensities that they are very unlikely to have any biological effects, let alone represent a health hazard.
A ribosome dissociation factor(s) has been partially purified from extracts of wheat germ. This factor can be detected by its ability to prevent the reassociation of ribosomal subunits when the magnesium concentration is raised from 1 mM to 5 mN. The majority of the dissociation factor activity is found in the postribosomal supernatant of the cell and can be precipitated between 0 and 40% ammonium sulfate. Chromatography of this material on DEAE-cellulose yields a fraction which contains both the dissociation factor activity and initiation factor eLF-3. However, the majority of the dissociation factor activity can be readily separated from eIF-3 by chromatography on phosphocellulose. The dissociation factor appears to be distinct from any of the othe known wheat germ initiation factors.
It was observed that "medical diagnosis utilizing Magnetic Resonance (MR) scanners may be one of the first modalities in which there is more risk for the operator of the equipment than for the patient" (Young, 1984). Despite this statement, only a few studies have been devoted to the assessment of occupational hazard in MR imaging personnel. The principal features associated with MR systems are: static magnetic fields, time-varying magnetic fields, and radiofrequency irradiation. Potential medical effects related to these hazards are reviewed. Static magnetic fields are known to induce in vitro changes in enzyme kinetics, orientation changes of macromolecules and subcellular components, distortion of ion currents and magnetohydrodynamic effects. Possible mechanisms for static magnetic field bioeffects include the exertion of magnetic forces, the induction of voltages, and other mechanisms (proton tunneling, ion cyclotron resonance) that are yet scarcely known. Human epidemiological studies on static magnetic fields are mainly based on subjective observations, and lack adequate control for confounding factors. Time-varying magnetic fields in the extremely-low frequency range have been associated with both occupational and non-occupational adverse health effects. Exposure to electromagnetic fields in office workers has been related to an increased rate of abortion; the vast majority of studies in this field, however, did not reach any significant result. Many literature reports support the evidence of an elevation of cancer risk in subjects exposed to residential and occupational ELF fields. Although such observations are not yet proved, the alleged occupational risk in magnetic fields exposure should induce to optimize exposure in MR imaging workers.
Meta-analysis provides a powerful statistical tool for epidemiological study. The basic principle of meta-analysis is introduced in this paper, and some problems about its application in epidemiology are discussed. This method was used by the authors to study the relationship between exposure to extreme low frequency electromagnetic fields (ELF) and childhood leukemia, and the result showed that there is a significant association between them.
Promoter elements accounting for HER2 (c-erbB-2/neu) overexpression were searched for in several human breast cancer cell lines (MDA-453, BT-474, ZR-75-1, MCF-7) known to express constitutively a 30-fold range in HER2 transcripts per gene copy. HER2 overexpressing cells showed a single prominent DNase I hypersensitive site near a conserved and hitherto unrecognized ets response element (GAGGAA), located 38 bases down-stream from the CAAT box and directly 5' of the TATA box in the human HER2 promoter. Transient transfection of HER2 promoter constructs (0.125, 0.5, and 2.0 kilobase pairs (kb)) demonstrated that the most proximal promoter region (0.125 kb) was capable of conferring up to 30-fold enhanced activity in HER2-overexpressing cell lines relative to low HER2-expressing control lines. Site-directed mutagenesis of the ets response element (GAGGAA-->GAGAGA) caused a > or = 60% reduction in promoter activity affecting at least 0.5 kb of upstream HER2 regulatory sequence. Gel-shift assays with nuclear extracts and oligonucleotide sequences spanning the 0.125-kb promoter region detected an ETS-immunoreactive complex, present most abundantly in cells overexpressing HER2, whose high-affinity binding depended on the GAGGAA response element. Methylation interference confirmed the ETS-specific pattern of protein binding by this complex to guanine bases in the ets response element. UV cross-linking and immunoprecipitation implicate a approximately 60-kDa ETS protein, and candidate ETS genes expressed in these breast cancer cells include GABP alpha, elk-1, elf-1, and PEA3.
Cancer chemotherapy plays a central role in the treatment of recurrent or unresectable scirrhous gastric cancers classified mainly as Borrmann type 4. Though we have no specifically effective drugs for scirrhous gastric cancer, 5-FU and its derivative, MMC, anthracyclines, CDDP, CQ and ACNU are known to be relatively effective single agents against this tumor. In an attempt to enhance the effect of single agents, several combined chemotherapy regimens have been devised and tested. These regimens included 5-FU + MMC, UFT + MMC, UFT + CDDP, MTX.5-FU, FAM, FAP, EAP and ELF regimen. At present, combined therapies using 5-FU and MTX or CDDP may be the most attractive of these combined regimens.
Industrial use of induction heaters generating electromagnetic energy of frequencies below 9 kHz makes an exposure of their operators to magnetic field H of high intensity and to electric field E of relatively low intensity. The operators of such heaters have suffered repeatedly from infections in the upper respiratory tract and in the skin of the forearm. The experimental exposure of rats to E or H fields of frequencies of 10 Hz, 50 Hz or 1-45 kHz induced changes in growth rate of exposed animals and weight changes in the pituitary-adrenal glands. These results support the suggestion about the involvement of the endocrine system in the biological reaction to incident electromagnetic fields of VLF and ELF.
561 chemotherapy-cycles administered to 191 patients during the period 1990-92 at the University Hospital, Tromsø, were retrospectively analysed for combination with ondansetron. 65% of the cycles were combined with ondansetron. The frequency increased from 1991 (50%) to 1992 (69%). Among moderate emetogenic regimens (MIME, MMM, High-dose MTX, EBVP, ELF) the frequency had changed from 44% to 91%. The increased ondansetron-treatment in moderate emetogenic regimens raised the total cost of treatment. Better cost-effectiveness can possibly be achieved by "low dose-ondansetron" (4 mg x 2) and more frequent supplementary use of diazepam, corticosteroids or haloperidol. Use of ondansetron regimens extending beyond 24 hours is not cost-effective. Peroral treatment is less expensive and usually adequate to control acute emesis.
Although bronchoalveolar lavage (BAL) is useful in studying a variety of lung diseases, it results in substantial dilution of cells and soluble proteins recovered from the lower respiratory tract. Surprisingly little is known about regional differences in BAL recovery in normals and patients with lung disorders. In order to assess regional differences in BAL in normals, we performed a prospective study of BAL in twenty non-smoking volunteers. With the subjects supine, BAL was performed in the right middle lobe (RML), right lower lobe (RLL) and Lingula (LING). The volumes recovered, cell numbers, and angiotensin converting enzyme (ACE) activities were determined separately for each BAL site. ACE was chosen as a representative soluble protein found in the lower respiratory tract which was easily measured in the BAL of normals. BAL volumes recovered from the RLL were significantly smaller than from the RML or LING, perhaps related to the dependent location of the RLL (P = 0.0002). The concentration of ACE and cells recovered per ml of BAL were significantly greater in the RLL than either the RML or LING (P = 0.05). In contrast, the total numbers of cells and total ACE recovered were similar from all sites sampled. This suggests that the differences in measured concentrations were due to different fluid recovery from these sites, resulting in variable dilution of proteins and cells. Urea measurement has been proposed as a means to quantify the epithelial lining fluid (ELF) volume sampled by BAL and estimate the actual concentrations of proteins present in the lower respiratory tract (J Appl Physiol 1986; 60:532-538).(ABSTRACT TRUNCATED AT 250 WORDS)
Both copies of a repeated sequence CATT(A/T), located between bp -53 and -39 in the upstream region of the human GM-CSF gene, are required for mitogen-inducible promoter activity in T lymphocytes. However, the proteins that recognize this region of the granulocyte-macrophage colony-stimulating factor (GM-CSF) promoter, and are responsible for its transcriptional regulatory activity, have not been clearly identified. Using transient transfection assays, we demonstrate that a 19-bp oligonucleotide containing the CATT(A/T) repeats has strong constitutive enhancer activity in both T cell and non-T-cell lines, even though GM-CSF is not normally constitutively expressed by these cells. A 12-bp oligonucleotide, containing only the sequence CATTAATCATTT, lacks enhancer activity indicating that the nucleotides surrounding these sequences are critical for this enhancer activity. The sequence TTTCCT, which can bind members of the ets family of transcription factors, is located just 3' of these CATT(A/T) repeats, and mutagenesis of the CCT sequence abolishes (1) the constitutive (and mitogen inducible) enhancer activity of the 19-bp GM-CSF sequences, (2) the responsiveness to transactivation by ets-1, and (3) the ability to specifically bind ets-1 and elf-1 in electrophoretic mobility shift assays (EMSA). We demonstrate that although T cells contain nuclear proteins capable of independently recognizing the ets binding site and the CATT(A/T) repeats in EMSAs, both of these regulatory elements are required for enhancer function. The strong constitutive activity of this 19-bp region suggests that negative regulation of the GM-CSF promoter is critical for the restricted expression pattern of GM-CSF mRNA.
"Second generation" combination chemotherapy regimens were developed in the 1980s with high activity in locally advanced and metastatic disease. Among them were etoposide plus doxorubicin plus cisplatin (EAP), etoposide plus 5-fluorouracil plus leucovorin (ELF), continuous infusion of 5-fluorouracil plus cisplatin (FP) and high-dose methotrexate plus S-fluorouracil plus doxorubicin (FAMTX). In locally advanced disease a resectability rate of +/- 50% was reported with these protocols. FAMTX was felt to be superior to 5-fluorouracil, doxorubicin and mitomycin (FAM), which regimen had been considered "standard" treatment for many years. Randomized studies, however, did not reveal significant differences among various second generation regimens. Future studies should focus on innovative protocols in advanced disease, the role of neoadjuvant chemotherapy in clinically staged locally advanced disease, the role of local "consolidation treatment," ie, radiotherapy or intraperitoneal chemotherapy after primary chemotherapy plus resection, and preoperative and postoperative chemotherapy in operable disease.
Interleukin-3 (IL-3) is a potent stimulator of megakaryocyte proliferation, and autocrine production of IL-3 by megakaryocytic leukemia cell lines and bone marrow-derived megakaryocytes has recently been demonstrated. To characterize the transcriptional regulation of IL-3 in megakaryocytes, we transiently transfected IL-3 promoter CAT constructs that contain variable amounts of 5' flanking sequences into the human CMK and CMK-6 megakaryocytic cell lines and identified two positive acting transcriptional regulatory regions, one located between bp -315 and -284, which contains consensus AP-1 and ets binding sites, and a second located between bp -173 and -61. DNase I footprinting assays using CMK or CMK-6 nuclear extracts demonstrate DNA-protein interactions in the identical region protected by T cell or natural killer cell nuclear extracts (between bp -165 to -128), and electrophoretic mobility shift assays demonstrate the binding of proteins to three distinct portions of this region. To characterize the transcription factors in megakaryocytic cells that could bind to these two regulatory regions, we performed Northern blot analyses, which showed the presence of ets-1, elf-1 (which is thought to be restricted to T cells), NF-IL3A and AML1 mRNAs, as well as c-fos, jun B, and jun D, but not c-jun mRNA. These studies show that the transcriptional regulation of IL-3 expression in megakaryocytic leukemia cell lines is similar, but not identical to normal human T cells.
Relating the concentrations of active antimicrobial at the potential site of infection to MIC, may give some indication of clinical efficacy. Where relatively insusceptible pathogens are involved, site concentrations are likely to be important predictors of efficacy. Unfortunately, there are sources of errors in measurement which make the values obtained imprecise. Despite this, broad trends are beginning to emerge, especially with bronchial biopsy concentrations. In bronchial biopsies, cephalosporins reach approximately 35 to 55% of simultaneous serum concentrations, in whole lung tissue 15 to 50% and in ELF 15 to 35%. The observed site to serum ratios are consistent with the permeability characteristics of cephalosporins and the barriers to movement of drugs into sites of infection. There is evidence that inflammation may alter the barriers to infection and for the cephalosporins site penetration may be higher. Further work is necessary to establish a clear relationship between site concentrations in the lung and clinical efficacy.
The present research is based on the premise that magnetic fields stimulate biological tissues, as many international works assert. They believe in the real aid of this therapeutical treatment in orthopedy and traumatology. The authors work in Rehabilitation Department of a traumatological hospital, so they have studied therapeutical results in ELF magnetotherapy on their patients for as long as six months.
Lentiviruses characteristically form latent integrated proviruses whose transcription can be induced by cell regulatory signals. The HIV-1 LTR responds to multiple signals, including the Ras pathway. We report here that Ras-responsive HIV-1 transcription requires two previously undescribed factors, RBF-1 and RBF-2 in Jurkat T cells. RBF-1 binds to Ets-like motifs located between nucleotides -151 and -142, and within the NF-kappaB binding sites, but is distinct from Ets-1 or Elf-1. RBF-2 binds the HIV-1 LTR at nucleotides -131 and -121 and immediately 3' of the TATA box. Both RBF-1 and RBF-2 contain DNA binding subunits of relative molecular weight 100 kilodaltons. Mutation of the RBF-1 and RBF-2 binding elements (RBEs) prevents Ras stimulation of HIV-1 LTR-directed transcription. These data define a mechanism for Ras responsiveness of HIV-1 transcription that involves the previously uncharacterized factors RBF-1 and RBF-2.