Assessing the potential leukemogenic effects of 50 Hz magnetic fields and their harmonics using an animal leukemia model.

To answer the still unresolved question of the possible leukemogenic effects of extremely low frequency magnetic fields (ELF-MFs) and of their harmonics on the incidence of B acute lymphoblastic leukemia in children, we used an animal model to explore the possible co-initiating or co-promoting effects of ELF-MFs on the development of leukemia. We used a rat model in which B acute lymphoblastic leukemia is chemically induced by a nitrosurea derivative. From the onset of the chemical treatment, the animals were also exposed to ELF-MFs (100 microT, sinusoidal 50 Hz MFs), with or without harmonics.

A new model of pre-B acute lymphoblastic leukemia chemically induced in rats.

Objective: Although B acute lymphoblastic leukemia (B-ALL) is the most common leukemia among children, no chemically inducible model of this leukemia has yet been described in vivo.

Methods: Leukemia was chemically induced in male WKAH/Hkm rats by a nitrosourea derivative, N-butylnitrosourea (BNU), an alkylating agent, administered orally 5 days a week for 24 weeks. Development of leukemia was monitored by clinical observation, follow-up of blood parameters, and appearance of blast cells in peripheral blood samples.

Mast cells as a source and target for nitric oxide.

Mast cells (MC), which are tissue-resident cells found widely distributed in the body, are derived from primitive hematopoietic cells. MC produce a variety of biologically active substances such as histamine, proteases, lipid derivatives and numerous cytokines and chemokines in response to immunologic or non-immunologic stimuli. Of interest, it has been reported that rodent MC can also be a source of nitric oxide (NO) derivatives, that they synthesize spontaneously, or only after activation, depending on their subtype.

Autocrine regulation of cord blood-derived human mast cell activation by IL-10.

Background: Ligation of the high-affinity receptor for IgE on human mast cells (MCs) induces the release of proinflammatory mediators, including vasoactive amines and cytokines (TNF-alpha, IL-5, and IL-8). Moreover, we have recently shown that IL-10 inhibits the release of proinflammatory mediators by activated MCs.

Objective: We investigated whether human cord blood-derived MCs (CBMCs) could produce IL-10 and whether this production could inhibit their activation in an autocrine fashion.

Role of iron in tumor cell protection from the pro-apoptotic effect of nitric oxide.

F2The host defense against tumor cells is in part based upon the production of nitric oxide (NO) by activated macrophages. However, carcinogenesis may involve mechanisms that protect tumor cells from NO-mediated apoptosis. In the present study, we have assessed the effects of exogenous NO on the proliferation and survival of human liver (AKN-1), lung (A549), skin (HaCat), and pancreatic (Capan-2) tumor cell lines, compared with normal skin-derived epithelial cell cultures.

Inhibition of IgE-induced activation of human mast cells by IL-10.

Background: IL-10 exhibits anti-inflammatory effects on activated rodent mast cells (MC) in vitro and inhibits allergen-induced airway inflammation in vivo in murine models. The effects of IL-10 on the allergic activation of human MC are presently unknown.

Objective: In light of the well-known heterogeneity of mast cell reactivity between animal species, one cannot readily predict the response of human MC to IL-10.

Perioperative activation of hemostasis in vascular surgery patients.

Background: Perioperative activation of hemostasis could play an important role in the occurrence of postoperative cardiac events. The authors conducted a prospective study to assess platelet function, coagulation, and fibrinolysis status during and after infrarenal aortic surgery.

Methods: Seventeen patients were studied.

Can 50 Hz magnetic fields alter iron metabolism and induce anaemia?

Unlabelled: PURPOSE. Some changes in tissue iron concentration have been reported in animals exposed to electromagnetic fields. In other studies, variations in the haemoglobin level were occasionally observed.

Absence of the effects of 50 Hz magnetic fields on the progression of acute myeloid leukaemia in rats.

Purpose: As the most recent epidemiological studies provide no definite conclusions about the effects of 50/60 Hz magnetic fields (MFs) on the incidence of leukaemia in humans, animal models in a well-controlled environment are useful for evaluating the possibility of an association between MFs and leukaemia. The present study was designed to determine whether 50 Hz magnetic fields can alter the progression of leukaemia.

Materials And Methods: A well-characterized model of transplantable acute myeloid leukaemia in rats was used for the first time.

c-Kit and c-kit mutations in mastocytosis and other hematological diseases.

Mast cells (MC) are tissue elements derived from hematopoietic stem cells. Their differentiation and proliferation processes are under the influence of cytokines, including one of utmost importance known as stem cell factor (SCF). SCF receptor is encoded by the protooncogene c-kit, belongs to the type III receptor tyrosine kinase subfamily, and is also expressed on other hematopoietic or non-hematopoietic cells.

Early steps of replication of moloney murine leukemia virus in resting lymphocytes.

We explored the role of cell type in the early steps of replication of Moloney murine leukemia virus (Mo-MLV) by comparing viral entry and reverse transcription in physiologically quiescent peripheral blood B and T lymphocytes. Virus entry was identical in both cell types. In contrast to previous results, full-length viral DNA was synthesized in resting B lymphocytes, but in agreement with earlier reports, reverse transcription was abortive in resting T lymphocytes.

Inhibition of mouse mast cell proliferation and proinflammatory mediator release by benzodiazepines.

Mast cell (MC) activation may occur in vitro and in vivo following stimulation with various immunologic or nonimmunologic agents. Such activation leads to the release of several biological mediators, including vasoactive amines, nitric oxide and cytokines, which account for the adverse effects observed during allergic reactions. While high affinity binding sites for benzodiazepines (BZDs) have been reported on MC, the effects of the ligation of these receptors on the proliferation of, and the mediator release from, these cells are poorly documented.

Cardiac troponin I cutoff values to predict postoperative cardiac complications after circulatory arrest and profound hypothermia.

Objective: Cardiac failure and myocardial infarction are complications of thoracic aorta, thoracoabdominal aorta, or aortic arch surgery, especially when surgery is performed using profound hypothermia and circulatory arrest (PHCA). Moreover, the diagnosis of non-Q-wave postoperative myocardial infarction (PMI) is challenging because there is no gold standard. The aims of this study were to determine values for cardiac troponin I (cTnl) in patients undergoing aortic arch or thoracoabdominal aortic surgery with PHCA who were free of cardiac complications in the postoperative period, and to test the validity of cutoff values of cTnl to predict postoperative cardiac complications in such patients.

Role of the hematocrit in a rabbit model of arterial thrombosis and bleeding.

Background: A decrease in hematocrit lengthens bleeding time. The authors studied the role of hematocrit variations in an experimental model of arterial thrombosis and bleeding.

Methods: The Folts model was used in 24 rabbits.

A new anthracycline with potent anti-leukemic activity overcomes P-glycoprotein multidrug resistance.

In this study, we assessed the ability of a new anthracycline, moflomycin, to circumvent multidrug resistance. Moflomycin showed superior anti-proliferative activity compared to daunorubicin and doxorubicin on two resistant cell lines: leukemic HL-60 cell line resistant to daunorubicin (HL-60/DR) and breast cancerous cell line resistant to doxorubicin (MCF-7/AR). The effect of moflomycin on cell proliferation was correlated with an increased uptake and a decreased cellular efflux.

Ketorolac and enoxaparin affect arterial thrombosis and bleeding in the rabbit.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with hemostasis during the perioperative period, and the combination of NSAID and enoxaparin could increase this effect. The aim of this prospective, blinded experimental study was to assess these effects using a model of arterial thrombosis and bleeding in the rabbit.

Methods: After anesthesia was induced and monitors placed, the common carotid arteries were exposed, and 60% stenosis of the right common carotid artery was produced.

Induction of IL-10 synthesis by human keratinocytes through CD23 ligation: a cyclic adenosine 3',5'-monophosphate-dependent mechanism.

Ligation of the low affinity receptor for IgE, CD23/Fc epsilonRII, in human keratinocytes (HK) and monocytes induces the synthesis of proinflammatory cytokines (IL-6 and TNF-alpha), partly under the dependence of cAMP and nitric oxide pathways. Moreover, CD23 ligation induces IL-10 production in human monocytes. Since synthesis of IL-10 by HK is still a matter of debate, we investigate whether keratinocytes could produce IL-10 upon CD23 stimulation.

Evidence for direct interaction between mast cells and Leishmania parasites.

When stimulated through IgE-(or IgG-) immune complexes with parasite antigens, mast cells can release several cytokines, including IL-4, IL-6, IL-10, IL-12, Interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) that may influence the host response to Leishmania major in modulating lesion size and persistence during experimental infection in the mouse. Moreover, recent data demonstrated that mast cells are able to be antibody-independently activated by direct contact with bacteria, making them important elements in innate immunity. Given these data, we asked whether cell-parasite contact could directly induce mast cell mediator release and whether mast cells could be infected by L.

Nitric oxide pathway is induced by Fc epsilon RI and up-regulated by stem cell factor in mouse mast cells.

Murine stem cell factor (SCF) induces the differentiation of mucosal mast cells (MMC) into connective tissue mast cells (CTMC) and potentiates mediator release induced by aggregation of high-affinity IgE receptors (Fc epsilon RI). In the present work, we investigated the effect of Fc epsilon RI aggregation on nitric oxide (NO) pathway induction in the different subsets of mast cells, as well as the contribution of SCF in this induction. Inducible NO synthase (iNOs) expression was not evidenced in non-stimulated MMC obtained by culture of hematopoietic progenitors in the presence of interleukin-3, whereas IgE-antigen-stimulated MMC expressed iNOs mRNA and protein and synthesized nitrites.

Investigation of the effects of 50 Hz magnetic fields on purified human hematopoietic progenitors.

Epidemiological reports suggest a possible association between exposure to extremely low frequency electromagnetic fields (ELF-EMFs) and the frequency of leukemia in men working in the field of electricity or in children living near power lines. At present, there is no experimental evidence for such an association. In this study we investigated the effects of 50 Hz EMFs (sinusoidal EMF of 10 microT or 1 mT) on human purified hematopoietic progenitor cells which are the first targets of a leukemogenic process.

Enhanced topoisomerase II-induced DNA breaks and free radical production by a new anthracycline with potent antileukemic activity.

In a previous study we reported that a new anthracycline derivative (moflomycin) exhibited a higher antileukemic activity compared to other anthracyclines, such as daunorubicin and doxorubicin. To explain the superior antileukemic effect of moflomycin and to disclose a possible structure-activity relationship, we investigated the three main mechanisms by which anthracyclines are though to exert their antitumor effect: DNA binding, free radical production and topoisomerase II inhibition. The DNA interaction was assessed both by DNA binding and DNA unwinding assays, free radical generation was studied by electron spin resonance, and topoisomerase II interaction by analysis of the stimulation of enzyme-induced DNA breaks.

[Hematopoietic growth factors: general presentation].

Modern molecular haematology is characterized by the great strides made in the use of cytokines, especially haematopoïetic growth factors (HGFs). These factors constitute a heterogeneous group of molecules that ensure the survival, proliferation and differentiation of the haematopoïetic cells. Present detailed knowledge of the structure of the chief HGFs and their receptors, and of the cloning and sequencing of their genes, permits the use of genetic engineering to produce recombinant human growth factors whose therapeutic applications have raised very great hopes for clinical haematology.

A new anthracycline with potent antileukemic activity exhibits reduced mutagenicity.

The mutagenicity of a new anthracycline (moflomycin) with potent antileukemic activity was studied by the Ames test in four strains of Salmonella typhimurium (TA97a, TA98, TA100 and TA102), and compared to the mutagenicity of doxorubicin, widely used as antineoplastic agent. Unlike doxorubicin, moflomycin displayed no mutagenic activity in strains TA98 and TA100. Low mutagenicity was only observed in TA102 strain and was not enhanced after metabolic activation.