Clinical progression of transplanted large granular lymphocytic leukemia in Fischer 344 rats exposed to 60 Hz magnetic fields

The purpose of this study was to determine if 60 Hz magnetic fields can alter the clinical progression of leukemia in an animal model. Large granular lymphocytic (LGL) leukemia cells from spleens of leukemic rats were transplanted into young male Fischer 344 rats, producing signs of leukemia in approximately 2–3 months. The animals were randomly assigned to 4 treatment groups (108/group) as follows: 1) 10 G (1.0 mT) linearly polarized 60 Hz magnetic fields, 2) sham exposed [null energized unit with residual 20 mG (2 μT) fields], 3) ambient controls [<1 mG (0.1 μT)], and 4) positive controls (a single 5 Gy whole body exposure to ⁶⁰Co 4 days prior to initiation of exposure). All rats were injected intraperitoneally (ip) with 2.2 × 10⁷ LGL leukemic cells at the initiation of exposure or sham exposure. The magnetic fields were activated for 20 h/day, 7 days/week, allowing time for animal care. The experimental fields were in addition to natural ambient magnetic fields. Eighteen rats from each treatment group were bled, killed, and evaluated at 5, 6, 7, 8, 9, and 11 weeks of exposure. Peripheral blood hematological endpoints, changes in spleen growth, and LGL cell infiltration into the spleen and liver were measured to evaluate the leukemia progression. No significant or consistent differences were detected between the magnetic field exposed groups and the ambient control group, although the clinical progress of leukemia was enhanced in the positive control animals. These data indicate that exposure to sinusoidal, linearly polarized 60 Hz, 10 G magnetic fields did not significantly alter the clinical progression of LGL leukemia. Furthermore, the data are in general agreement with previous results of a companion repeated‐bleeding study in which animals were exposed for 18 weeks. Bioelectromagnetics 20:48–56, 1999. © 1999 Wiley‐Liss, Inc.     

A distinct DNA methylation signature defines pediatric pre-B cell acute lymphoblastic leukemia

Pre-B cell acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy and remains one of the highest causes of childhood mortality. Despite this, the mechanisms leading to disease remain poorly understood. We asked if recurrent aberrant DNA methylation plays a role in childhood ALL and have defined a genome-scale DNA methylation profile associated with the ETV6-RUNX1 subtype of pediatric ALL. Archival bone marrow smears from 19 children collected at diagnosis and remission were used to derive a disease specific DNA methylation profile. The gene signature was confirmed in an independent cohort of 86 patients. A further 163 patients were analyzed for DNA methylation of a three gene signature. We found that the DNA methylation signature at diagnosis was unique from remission. Fifteen loci were sufficient to discriminate leukemia from disease-free samples and purified CD34+ cells. DNA methylation of these loci was recurrent irrespective of cytogenetic subtype of pre-B cell ALL. We show that recurrent aberrant genomic methylation is a common feature of pre-B ALL, suggesting a shared pathway for disease development. By revealing new DNA methylation markers associated with disease, this study has identified putative targets for development of novel epigenetic-based therapies.     

The impact of extremely low frequency electromagnetic fields on stream periphyton: an eleven-year study

Potential effects of extremely low frequency (ELF) electromagnetic fields on periphyton were studied from 1983 to 1993 using a Before, After, Control and Impact design. The study was conducted at two sites on the Ford River, a fourth-order brown water trout stream in Dickinson County, Michigan. The Reference site received 4.9–6.5 times less exposure to ground electric fields and from 300 to 334 times less exposure to magnetic flux from 1989 to 1993 when the antenna was operational at 76 Hz than did the Antenna site. The objective of the study was to determine if ELF electromagnetic fields had caused changes in structure and/or function of algal communities in the Ford River. Significant differences in chlorophyll a standing crop and daily accumulation rate (a surrogate for primary productivity), and organic matter standing crop and daily accumulation rate were observed between the Reference and Antenna site after the antenna became operational. These four related community function variables all increased at the Antenna site with largest and most consistent increases occurring for chlorophyll measures. Compared to pre-operational data, the increase in chlorophyll at the Antenna site also occurred during a period of low amperage testing in 1986–1988, and did not increase further when the antenna became fully operational in 1989, indicating a low threshold for response. There was no significant differences between the Antenna and Reference sites in community structure variables such as diversity, evenness and the relative abundance of dominant diatoms. Thus, 76 Hz ELF electromagnetic radiation apparently did not change the basic makeup of the diatom community but did increase accumulation rates and standing crops of chlorophyll a and organic matter.     

Cellular immunosuppression in children with acute lymphoblastic leukemia: Effect of consolidation chemotherapy

Summary The present study was designed to evaluate the chemotherapy-induced cellular immunosuppression in 20 children with acute lymphoblastic leukemia (ALL) in remission and receiving maintenance chemotherapy. Peripheral blood was serially obtained from leukemic children during vincristine/cyclophosphamide/6-mercaptopurine/prednisone combined consolidation chemotherapy. The mean absolute number of peripheral blood lymphocytes as well as the mean absolute numbers of lymphocyte subsets (T cells, T cell subsets, B cells, and natural killer cells) from leukemic children before consolidation chemotherapy were all significantly lower than in control subjects; however, the percentages of lymphocyte subsets were similar in both groups. After consolidation chemotherapy, the percentages of CD4⁺ T lymphocytes and natural killer (NK) cells were significantly decreased and the percentages of monocytes and CD8⁺ T lymphocytes were significantly increased. Phytohemagglutinin- and 12-O-tetradecanoylphorbol-13-acetate-induced production of interleukin-2 (IL-2) and NK-cell-mediated cytotoxic activity by peripheral blood mononuclear cells (PBMC) were also substantially decreased in the post-therapy groups. NK activity correlated with the percentage of NK cells in PBMC. In contrast, OK432-induced production of tumor necrosis factor (TNF) and killer activity against NK-resistant target cells were significantly increased after therapy as compared with the pre-therapy and control groups. TNF production correlated with the percentage of monocytes in PBMC. These results demonstrate that substantial quantitative and qualitative chemotherapy-induced abnormalities of the cellular immune system are present in the majority of patients treated with ALL. It is also suggested that the increased TNF production by monocytes and the appearance of potent killing activity against NK-resistant targets might compensate for the defects of IL-2 production and NK activity during intensive consolidation chemotherapy.This work was supported by a grant-in-aid for cancer research from the Ministry of Health and Welfare, Japan, and a grant-in-aid from the Association for the Support of Children with Cancer     

Protein kinase C activity is altered in HL60 cells exposed to 60 Hz AC electric fields

We examined the effects of electric fields (EFs) on the activity and subcellular distribution of protein kinase C (PKC) of living HL60 cells. Sixty Hertz AC sinusoidal EFs (1.5–1.000 mV/cm p-p) were applied for 1 h to cells (10⁷/ml) in Teflon chambers at 37 °C in the presence or absence of 2 μM phorbol 12-myristate 13-acetate (PMA). PMA stimulation alone evoked intracellular translocation of PKC from the cytosolic to particulate fractions. In cells that were exposed to EFs (100–1,000 mV/cm) without PMA, a loss of PKC activity from the cytosol, but no concomitant rise in particulate PKC activity, was observed. In the presence of PMA. EFs (33–330 mV/cm) also accentuated the expected loss of PKC activity from the cytosol and augmented the rise in PKC activity in the particulate fraction. These data show that EFs alone or combined with PMA promote down-regulation of cytosolic PKC activity similar to that evoked by mitogens and tumor promoters but that it does not elicit the concomitant rise in particulate activity seen with those agents. © 1996 Wiley-Liss, Inc.     

儿童急性淋巴细胞白血病血清乳酸脱氢酶的临床研究

目的:探讨儿童急性淋巴细胞白血病(ALL)患者不同时期血清LDH水平的变化及其临床意义。方法:回顾性分析我院2010年1月-2014年12月收治的90例儿童ALL患者,并抽选同期52例健康儿童作为对照组,采用酶法检测ALL患者初诊前、d19诱导缓解化疗后、ALL复发时及正常对照组的LDH值,分析LDH与ALL疾病进程的关系。结果:90例ALL患者初诊组血清LDH水平为684.70±906.57 U/L,89例d19化疗后组为233.83±39.53 U/L,其中13例ALL复发前经诱导缓解治疗d19的LDH水平为196.30±54.48 U/L,13例复发组为877.61±1230.69 U/L,52例对照组为202.59±54.09 U/L,初发ALL患者血LDH水平明显高于d19化疗后组和对照组,差异有统计学意义(P0.01),13例ALL复发前d19诱导缓解后与复发时血清LDH水平相比,差异有统计学意义(P0.01)。d19诱导缓解化疗后组患儿骨髓白血病细胞数百分比与ALL初诊组相比显著降低,差异有统计学意义(P0.01)。骨髓白血病细胞百分比与血清LDH水平对于评估儿童ALL预后的影响是一致的,但二者不具有直线相关关系(P0.05)。结论:血清LDH水平可有助于儿童ALL的诊断、疾病进展及预后评估。     

Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia

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A comprehensive overview on utilizing electromagnetic fields in bone regenerative medicine

Stem cells are one of the most important sources to develope a new strategy for repairing bone lesions through tissue engineering. Osteogenic differentiation of stem cells can be affected by various factors such as biological, chemical, physiological, and physical ones. The application of ELF-EMFs has been the subject of many research in bone tissue engineering and evidence suggests that this exogenous physical stimulus can promote osteogenic differentiation in several types of cells. The purpose of this paper is to review the current knowledge on the effects of EMFs on stem cells in bone tissue engineering studies. We recapitulated and analyzed 39 articles that were focused on the application of EMFs for bone tissue engineering purposes. We tabulated scattered information from these articles for easy use and tried to provide an overview of conducted research and identify the knowledge gaps in the field.     

Childhood cancer in relation to indicators of magnetic fields from ground current sources

This study examines childhood cancer risk in relation to certain factors likely to indicate magnetic field exposure from ground currents in the home. Substantial ground currents are most often found in homes having conductive plumbing, in which an uninterrupted metallic path in the water pipes and water main connects the grounding systems of neighboring houses. Information on plumbing conductivity was obtained from water suppliers for the homes of 347 cases and 277 controls identified in an earlier study of magnetic field exposure and childhood cancer in the Denver area. An increased cancer risk was observed for children in homes with conductive plumbing: The matched odds ratio was 1.72 (1.03–2.88) and increased to 3.00 (1.33–6.76) when analysis was limited to cases and controls who were residentially stable from the reference date to the study date. A measurement metric likely to indicate active ground currents (measurements having above-median intensity and a nonvertical orientation of <55° from the horizontal) was identified. In contrast to measured field intensity alone, for which only modest associations with cancer have been reported, this metric shows a high and significant cancer risk [matched O.R. = 4.0 (1.6–10.0)] consistent over a range of intensity and angle cutpoints. Such elevated nonvertical fields were also associated with cancer in an independent data set, which was gathered to study adult nonlymphocytic leukemia in the Seattle area. The associations of cancer with conductive plumbing and with this exposure metric both suggest that cancer risk is increased among persons with elevated magnetic field exposure from residential ground currents. © 1995 Wiley-Liss, Inc.     

聚乙二醇修饰重组人天冬酰胺酶的研究

天冬酰胺酶对治疗急性淋巴细胞白血病和某些肿瘤疾病有很好的疗效,但由于其在人体内所产生的副作用———过敏反应限制了它的应用。目的:运用化学修饰剂聚乙二醇对天冬酰胺酶进行化学修饰,以降低其免疫原性,提高其在体内的半衰期;并使修饰后的天冬酰胺酶的活性保持较高的水平。结果:修饰后的天冬酰胺酶的免疫原性降低为原来的20-30%;用胰酶水解24h没有变化;而其比活力为未修饰酶的23%。该结果已经具备了很大的临床应用价值。     

Magnesium and iron contents of leukemic lymphocytes in acute leukemias and hemolytic anemia

In this study, magnesium and iron concentrations were measured in lymphocytes from patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and hemolytic anemia (HA) before and after chemotherapy treatment. The results were compared with those of control subjects. Magnesium concentrations were significantly lower in the patient groups, compared with control values. However, no significant differences, except in the HA group, were found among magnesium concentrations of the patient groups them-selves. Iron level values were at physiological range in all groups. Similarly, no statistically significant differences were found between lymphocyte magnesium concentrations before and after chemotherapy treatment in the patient groups. Fe⁺³ values were higher in the ALL and HA groups with respect to the group before chemotherapy.     

Myelogenous leukemia and electric blanket use

In a case-control study of adult acute and chronic myelogenous leukemia in Los Angeles County, we tested the hypothesis that excess exposure to electromagnetic fields from electric blankets was associated with risk of leukemia. We did this by studying 116 cases of acute myelogenous leukemia (AML) and 108 cases of chronic myelogenous leukemia (CML) along with matched neighborhood controls. The cases and controls were queried as to electric blanket use and the risks computed. For AML the risk was 0.9 (95% CI 0.5-1.6) and for CML the risk was 0.8 (95% CI 0.4-1.6). Cases did not differ from controls by duration of use, year of first regular use, year since last use, or socioeconomic status. Our best estimates of exposure indicate that electric blanket use increases overall exposure to electric fields by less than 50% and magnetic fields by less than 100%. We conclude that there is no major leukemogenic risk associated with electric blanket use in Los Angeles County.