Electromagnetic Radiation and Human Health

EMF Protection

This ebook is the complete guide to learning about electrical sensitivity and how to prevent getting it in your life. You will learn what electrical sensitivity is, and what causes it. Once you have started learning about it you will learn how to get rid of it and protect yourself from the dangers of electrical sensitivity. You will also learn how to heal yourself. This book is the product of careful research by the scientific and medical communities into the dangers and preventative measures of electrical sensitivity. ES is one of the most under-diagnosed conditions in the world right now, and this ebook is designed to education people as to how it works and how to prevent it. Do not let it take hold of your family; take control and prevent it now! Do not let yourself get any more hurt; learn about this condition and fight it! Read more here...

How To Beat Electrical Sensitivity Overview

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Electromagnetic Fields

A very careful study done by National Cancer Institute investigators and their collaborators directly measured magnetic fields in cases' and controls' bedrooms, three or four other rooms, and the front doors of their houses.167 In addition, they measured magnetic fields in homes where case subjects' and controls' families lived during their mothers' pregnancies. The results of this study showed that the risk of acute lymphoblastic leukemia (the most common malignancy of childhood) was not increased among children who lived in homes with the highest exposure to magnetic fields, and there was also no significant associated risk with magnetic-field levels of the homes where the mothers resided when pregnant.

Radiation Exposure

ALLs occur less frequently following radiation exposure than do acute myeloid leukemias (AML), chronic myeloid leukemia (CML), or myelodysplastic syndromes. The incidence of ALL is modestly increased in populations exposed to ionizing radiation from an atomic bomb,26 39 and cases are most prevalent among younger survivors.40 As a general rule, most other forms of radiation may produce an excess of leukemia, again mostly of myeloid origin rather than lymphoid. No study has documented an increase in ALL associated with radiation from diagnostic radiographic pro-cedures.26

Ionizing Radiation

The history of radiation carcinogenesis goes back a long way (reviewed in Reference 107). The harmful effects of X-rays were observed soon after their discovery in 1895 by W. K. Rontgen. The first observed effects were acute, such as reddening and blistering of the skin within hours or days after exposure. By 1902, it became apparent that cancer was one of the possible delayed effects of X-ray exposure. These cancers, which included leukemia, skin cancers, lymphomas, and brain tumors, were usually seen in radiologists only after long-term exposure before adequate safety measures were adopted, thus it was thought that there was a safe threshold for radiation exposure. The hypothesis that small doses of radiation might also April 26, 1986. A steam explosion blew the lid off the reactor. The graphite core caught fire and over 1019 becquerels (Bqs) of radioisotopes were released, producing a fallout that covered much of Belarus, Northern Ukraine, and part of the Russian Federation....

Clinical Features Of Chronic Myeloid Leukemia

CML has an annual incidence of approximately 1.5 105, accounting for some 5000 new patients per year in the United States. Males are slightly more frequently affected than females (ratio 1.7 1), but there is no significant ethnic or geographical predisposition (1). The disease can occur at every age but the incidence greatly increases in the older population. Exposure to ionizing radiation is the only established risk factor, as demonstrated by the increased incidence in the survivors of the atomic bombs in Japan (2). Symptoms include weight loss, fever, and abdominal fullness but at least in the developed countries many patients are asymptomatic at diagnosis, when an abnormal routine blood count leads to a diagnostic work up.

Dna Damage And Repair

The sources of DNA damage are protean. Environmental agents may act as mutagens, thus increasing the likelihood of the occurrence of mutations. Known agents in this category include ultraviolet (UV) light (the major source being exposure to sunlight), ionizing radiation, cigarette smoke, and various carcinogens such as asbestos and possible dietary factors. Whereas exposure to environmental factors frequently can be reduced or minimized by behavioral modification, other sources of DNA alteration are unavoidable errors during DNA replication (which occur with each cell division), damage from by-products of normal cellular metabolism (including reactive oxygen species superoxide anions, hydroxyol radicals, and hydrogen peroxide derived from oxidative respiration), and products of lipid peroxidation. Other weak mutagens, such as thermally promoted hydrolysis of nucleotide residues by water, may occur under physiological conditions. Deamination results in base substitutions, such as the...

Molecular Structure of Biological Systems

During the first step in considering molecular mechanisms of biological systems, a further aspect is taken into consideration. Unfortunately, biologists often ignore the fact that a qualitative jump has to be made in the transition from the visible macrophysical structures, to the microphysical systems such as atoms or molecules. This includes not only the above-mentioned transition from the deterministic behavior of macroscopic systems to the stochastic behavior of single molecules, but many more aspects as well. The biologists, for example, must acknowledge that the term structure receives a new meaning. The visible biological structure, as known in the fields of anatomy, morphology and histology, now appears as concentration profiles or as systems of electric charges or electromagnetic fields. Instead of visible and measurable lengths, diameters or distances, as common in the visible world, in the microphysical world so called effective parameters are used. These sorts of...

Double Strand Breaks

Double-strand breaks (DSBs) result from exposure to ionizing radiation, x-rays, from enzymatic cleavage, or during replication of a single-strand break. DSBs are especially problematic because of the absence of a normal strand to serve as a template. Arrest of the cell cycle to facilitate repair of the DSB is mediated by p53. DNA damage-response proteins, including ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia related (ATR), are recruited. There are two logically alternate pathways for double-strand break repair, homologous recombination or nonhomologous end joining, which are reviewed elsewhere (16,17).

Hypoxia Activated Prodrugs Bioreductives

The imperfect neovascularization that develops in growing solid tumors results in limited and inefficient blood vessel networks and restricted and often chaotic blood flow (340).This generates chronic or diffusion hypoxia, where cells sufficiently distant from the nearest blood capillary are hypoxic for long periods, caused by the steep diffusion gradient of oxygen in tissue. The high and variable interstitial pressures caused by the growing tumor (341) can also result in transient or perfusion hypoxia, resulting from the temporary shut down of blood vessels placing sections of tissue under hypoxia for shorter periods (342). Because severe hypoxia is a common and unique property of cells in solid tumors, it is thus an important potential mechanism for the tumor-specific activation of prodrugs. This concept grew initially out of the development of radiosensitizers, drugs designed to take the place of oxygen in hypoxic tissue by oxidatively fixing the initial DNA radicals...

Image Analysis Inc Columbia

Detector Dxa

Radiation exposure is extremely low for all types of DXA scans. Expressed as skin dose, radiation exposure during a PA lumbar spine or proximal femur study is only 2 to 5 mrem.11 The biologically important effective dose or whole-body equivalent dose is only 0.1 mrem (65). Most devices report both SOS and BUA. However, one manufacturer has mathematically combined SOS and BUA into a proprietary index called the Stiffness Index. Another manufacturer reports a proprietary index called the Quantitative Ultrasound Index (QUI) and an estimated BMD that is derived from the measurements of SOS and BUA. QUS devices are considered peripheral devices and are generally quite portable. They employ no ionizing radiation, unlike their SXA or DXA peripheral counterparts. The calcaneus is the most common skeletal site assessed with QUS, but devices exist that can be applied to the radius, finger, and tibia. In heel QUS measurements, heel width apparently has little if any effect on BUA but may have a...

Mechanisms of Photon Induced Molecular Excitation

The wavelength of visible light lies between 400 and 800 nm. This corresponds to quantum energies between 3.1 eV and 1.6 eV respectively, (cf. Sect. 4.4, Fig. 4.13). The quantum energy of the photons of visible light, therefore, is much lower than the ionization energy of water (12.56 eV), a value which is arrived only in short-wave ultraviolet light (UVC). The energy of thermic noise (kT), which we will consider in detail in Section 2.3.4, in relation to this, is much smaller. At temperatures of biological importance it amounts only to about 0.025 eV. For photosynthesis the organism uses exactly this gap between the quantum energy of thermic noise on the one hand, and the quantum energies causing ionization of water and organic molecules on the other hand, using the energy of visible light. The photons of light are strong enough to be used for an effective process of energy conversion, but they do not endanger the stability of biomolecules. How narrow this biologically usable part of...

Control of DNA Breakdown

Bacq and Alexander proposed that a signif-ficant contribution to the radiobiological effects of ionizing radiation is attributed to cell membrane damage (15). The effect of X-rays n the permeability of Ehrlich ascites tumor membranes has since been studied by measuring loss of potassium from the cells 1309). The radiosensitizing effects of Synkavit and excess oxygen were demonstrated by a marked loss of potassium from the irradiated cells, whereas the protective effects of MEA have been found to protect cells from the damaging effects of ionizing radiation. Interleukin 1 and tumor necrosis factor alpha (TNF-a) protect mice from lethal doses of radiation, given before irradiation. At lower doses of radiation, hemopoietic growth factors, interleukins 1, -4, and -6, TNF-a, interferon, and leukemia inhibitory factor promote recovery when administered after radiation, possibly by initiating autocrine paracrine recovery and repair pathways (312).

Radiosensitization by Alteration of Energy Absorption

The probability of ionization is essentially proportional to the number of electrons in the target molecule, regardless of chemical composition for the types of ionizing radiation that are normally used in radiation therapy (high energy photons or electrons). However, preferential energy absorption by particular elements can occur with certain energies or types of radiation. Two such cases are boron neutron capture and k-edge absorption of photons by atoms of high atomic weight. The tumoricidal mechanism of PDT has two components direct tumor cell killing and damage to the vasculature leading to tumor necrosis. The number of tumor cells from excised murine tumors that produce colonies in vitro decreases markedly with time between treatment and excision (379,380), in support of the importance of damage to the vasculature. In contrast, tumor cell killing by ionizing radiation is evident when tumors are excised immediately after irradiation and plated for clonogenic assay (381). Hypoxia...

Radiosensitization by Reaction with DNA Radicals

The principal mechanism of cell killing by ionizing radiation is the formation of clustered DNA lesions (386,392,393) by a combination of direct ionizations in the DNA molecule (the direct effect) and reaction of DNA with free radicals produced in the vicinity of DNA (the indirect effect). The reactions that produce the DNA radicals that are the precursors cf these clustered lesions are complete within nanoseconds (387). However, the chemical reactions of these free radicals that result in damage fixation are not complete until 10 ms after irradiation (394), and there is an opportunity to alter the outcome of these reactions (Fig. 4.2). Damage fixation is a process that renders the damage nonrestorable by chemical protectors.

Radiosensitization by inhibition of DNA Repair

The sensitivity of mammalian cells to ionizing radiation is very dependent on DNA doublestrand break repair capacity (553), particularly at the radiation doses that are used in cancer therapy. Cell lines that are deficient in DNA double-strand break repair are radiosensitive (554,555). Inhibition of DNA repair has great potential for tumor radiosensitization (556,557), but strategies for selective sensitization of tumors remain elusive (558). tration about 50 times lower than 3AB, and sensitizes both exponentially growing and stationary phase mammalian cells to ionizing radiation (564). It has long been recognized that thiol oxi-dants or thiol-binding reagents sensitize cells to ionizing radiation (577-580). Part of this effect is attributed to depletion of endogenous radioprotectors. However, this does not explain radiosensitization that is observed when thiol reagents are added after irradiation because endogenous chemical radioprotectors will have acted within 10 ms of irradiation...

Covalent Bonds Molecular Orbitals

The calculation of molecular orbitals provides the basis for the theoretical interpretation of atomic interactions. A mutual approach of atoms is accompanied by an overlapping of their electromagnetic fields and, consequently, by a change in the wave function of their electrons. The energy levels of the wave functions, modified in such a way, can sink lower than the sum of the levels of energy of the undisturbed atoms. In this case the connection of the two atoms becomes a stable chemical bond.

Perturbation of Energy Metabolism

Ionizing radiation induces cell-cycle arrest at both the Gx and the G2 M checkpoints (596).The purpose of cell-cycle arrest is presumed to be to allow time for DNA repair before progressing through the cell cycle (597), although the precise mechanism of repair involved is not clear. In the case of a GL arrest, abrogation of the arrest, for example, by transfection of a mutated form of thep53 gene, does not result in increased cell killing (598), but has been associated with increased mutagenicity and carcinogenicity (599). Abrogation of the G2 M arrest, on the other hand, can enhance radiation cell killing. The classic example of a radio-sensitizer that acts by this mechanism is caffeine (92) (600-602).

Summary And Prospects For Future Development Of Clinical Radiation Modifiers

A variety of approaches have been developed for diminishing the effects of radiation on normal tissues or enhancing tumor cell killing by ionizing radiation. Nevertheless, it is not yet clear that these strategies will provide a therapeutic gain in radiation therapy. Results obtained with model systems do not always apply to more complicated biological systems. Many of these compounds have multiple pharmacological actions, which are sometimes antagonistic. Most often, agents have been tested clinically at suboptimal doses because of limiting toxicities, and the results have been inconclusive. The possibility that radioprotec-tors could protect the tumor makes it difficult to test radioprotectors in the clinic. Unless the rationale for selective radioprotection of normal tissues or radiosensitization of the tumor is foolproof, there is a risk in clinical testing because the clinical impact is often not known for several years. Nevertheless, several clinical trials are in progress,...

Oxygen Free Radicals Aging And Cancer

8-hydroxyadenine, and formamido derivatives of altered purines.119 Some of these products appear in the urine and may be an index of oxidative damage. They are also produced by exposure of DNA to ionizing radiation and oxygen-radical generators. 8-Hydroxyguanine appears to be the most frequently altered base to result from oxi-dative damage to DNA, and if this base is left unrepaired in DNA it produces G T trans-

Cell Cycle Responses to DNA Damage

Early studies with mammalian cells uncovered a delay in G2 that occurred within 2 h of exposure to ionizing radiation (reviewed in 53). This delay was found to be transient, with cells entering mitosis after a time that depends on the dose of ionizing radiation. A division delay in response to DNA damage was observed in diverse cell types, including amoeba, yeast, sea urchin eggs, and mammalian cervical cancer cells (53). Part of the basis for the division delay is that cells are blocked in G2 in response to DNA damage. The early method of determining the G2 delay was to count mitotic cells shortly after irradiation or adding DNA-damaging chemicals. G2 delay is characterized by a rapid reduction in the number of mitotic cells. Mitosis must be analyzed quickly to eliminate possible contributions of alternate points of arrest in the cell cycle. For example, if the reduction in mitotic cells occurs after 8 or 10 h (significantly longer than the G2 M period of approx 4-5 h) the blockage...

Ku At The Mammalian Telomere

In contrast to the action of yeast Ku in response to DNA-damaging agents (73), human Ku does not dissociate from the telomere upon exposure to ionizing radiation and the radiomimetic drug phleomycin (60). Since Ku is distributed throughout the mammalian nucleus, apparently its recruitment from the telomere to sites of DNA repair is not necessary (73).

Logistical Requirements

Of active-fixation leads, lead removal procedures, and the identification of problems such as fractures of a conductor or J retention wire. Digital acquisition and storage capabilities have proven to be advantageous. Such technology can be used to road-map or superimpose real-time fluoroscopy on a stored image. Thus, we can bring up a stored image of the subclavian venogram (obtained by injecting contrast into an ipsilateral upper extremity vein) to document the vein patency and to serve as a target for an exploring needle being advanced under fluoroscopic monitoring (Fig. 5.1). The use of pulsed digital fluoroscopy can reduce radiation exposure to patient and operator. Newer imaging systems may also increase patient safety by providing on-line measurements that more accurately reflect radiation exposure than does the traditional total fluoroscopy time.

Contribution of p53 to G2 Arrest

The first clue that p53 was important for DNA-damage responses was that the levels of p53 protein were elevated when cells were exposed to ultraviolet radiation (126). Proof for this idea was provided by the observation that p53 was required for the Gl arrest that occurred in response to ionizing radiation (127). Human cells lacking p53 bypass the Gl checkpoint, progress through S phase, and accumulate in G2, showing that G2 arrest still occurs in cells lacking p53 (127). However, we found that when p53 is overexpressed in the absence of any other stress, this could also arrest cells in G2 (128). These and other studies showed that p53-independent pathways are sufficient to induce G2 arrest, and that p53 is also involved, probably to ensure the long-term sta

Directions For Future Studies

To conclude, primary brain tumors probably stem from multiple exogenous and endogenous events. To date, the few proven causes (i.e., inherited genetic syndromes, therapeutic ionizing radiation giving rise to brain lymphomas) account for only a small proportion of cases. Brain malignancies are devastating diseases, but there is hope that a continuing explication of their cause and biologic course and new concepts about neuro-oncogenesis might emerge to advance the study of brain tumor epidemiology and the possibilities for prevention and cure.

Other Imaging Modalities

To better understand IVUS, it is important to compare it to other cardiovascular imaging. X-ray angiography remains the gold standard for coronary arteries. Its main advantages are high spatial resolution (0.15 mm) and relatively low cost compared to other modalities (23). The main drawbacks are the radiation exposure for the patient during an intervention as multiple injections of radioactive contrast agent are delivered. Also, angiography is a minimally invasive procedure using a catheter to deliver the radioactive contrast agent. Furthermore, planar X-ray imaging captures a projection of the vasculature and can often misdiagnose asymmetric lesions (23).

Bionanotechnology a Gold Nanoparticles AuNP

SPR is excited at a metal or dielectric interface by a monochromatic light source. SPR is observed as a deep minimum in the p-polarized reflected light as the angle of incidence is increased. The plasmon, a ray of light bound onto a surface, propagates among the surface and presents itself as an electromagnetic field 17 .

Ataxiatelangiectasia

The first clue that defects in the ATM gene disrupt normal cellular responses to DNA damage were provided by case reports of AT patients who died from severe reactions to radiation therapy directed at their lymphoid tumors (33-37). Although not unusually susceptible to the induction of DNA breaks by ionizing radiation (38,39), cultured cells from AT patients are typically three to five times more sensitive than control cells to the cytotoxic effects of ionizing radiation as well as other agents that induce DSBs (40-44). AT radiosensitivity is also manifest by an increase in number of chromosomal aberrations induced by ionizing radiation or radiomimetic agents (reviewed in Ref. 23). Cells from AT homozygotes can be exquisitely sensitive to the cytotoxic effects of ionizing radiation, but they differ from most other radiosensitive mammalian cells in that their ability to repair DNA damage appears to be largely intact. Base excision repair is apparently normal (45), and multiple...

Frequent Inactivation Of Atm In Sporadic Leukemias

The latter possibility is supported by multiple studies that have found that cells from some, but not all, heterozygote members of AT families respond abnormally to DNA damage. These abnormalities are mild compared to those seen in AT patients, but include increased sensitivity to the cytotoxic and clastogenic effects of ionizing radiation and radiomimetic drugs, persistence of radiation-induced chromosome breaks, postirradiation DNA synthesis abnormalities, and prolonged G2 arrest (reviewed in Ref. 3). ATM heterozygotes also are more likely than normal individuals to suffer from late in vivo side effects of radiation therapy (267,268). Data from Atm+' mice support the conclusion that individuals with one functional ATM allele have impaired responses to DSBs. Fibroblasts and lymphocytes from Atm+' mice have cell cycle checkpoint abnormalities and are sensitive to the killing effects of ionizing radiation (100,269), Atm+' mouse embryonic fibroblasts (MEFs) are more readily transformed...

Lessons For Cancer Screening

ATM heterozygotes would appear to be a high-risk group that could benefit from mammographic screening. However, it has been suggested that physicians consider alternatives to mammography in ATM heterozygotes (214,279). This issue has provoked much discussion, both pro and con (e.g., see Refs. 280-284). Typical radiation exposures to the breasts from mammography average 2-3 mGy AT patients respond poorly to treatment regimens that include ionizing radiation, radiomimetic drugs, and topoisomerase inhibitors. Care must be taken to modify standard protocols so as to minimize iatrogenic damage, but reduced therapeutic regimens can be tolerated for these individuals (e.g., see Refs. 15, 36, and 290). ATM heterozygotes could, in theory, represent a significant fraction of cancer patients who have adverse responses to radiation and chemotherapy. Experimental evidence for this possibility is mixed (reviewed in Ref. 3). Many studies have demonstrated a group correlation between in vitro...

The Great Cancer Myths

While there is a tendency to blame environmental causes for cancer in children, this probably plays a small role. Hereditary gene mutations probably play a larger role. Most experts agree that a mother's smoking during pregnancy, electromagnetic fields from power lines, or other environmental toxicants play little role.152

Biochemical Spectroscopy Overview

Spectroscopic methods are used in the structural characterization of biomolecules (Bell, 1981 Campbell and Dwek, 1984 Greve et al., 1999 Hammes, 2005). These methods are usually rapid and noninvasive, require small amount of samples, and can be adapted for analytical purposes. Spectroscopy is defined as the study of the interaction of electromagnetic radiation with matter, excluding chemical effects (photochemistry refers to the interaction with chemical effects). The electromagnetic spectrum covers a wide range of wavelengths (Figure 7.1). The interaction of electromagnetic radiation with matter gives rise to scattering, absorption or emission of the radiation. Scattering is usually detected by measuring the intensity of radiation at some angle 0 to the incident wave (turbidity refers to measuring the reduced transmitted light at 0 0). Electrons are the usual scatterers in molecules, while nuclei scatter neutrons. If the scattered radiation has the same frequency as the incident...

B NBS Cellular Phenotypes

The documented clinical radiosensitivity of patients with NBS is reflected by at least a two-fold increase in cellular hypersensitivity to ionizing radiation (IR) of primary and immortalized NBS cells (2,10). This hypersensitivity is also evident following exposure of NBS cells to bleomycin, streptonigrin, etoposide, camp-tothecin, and the cross-linking agent mitomycin C, but not to ultraviolet wavelength C (UV-C) (32-34), indicating that DNA double-strand breaks (DSBs), produced through different mechanisms by these agents, are the crucial molecular lesions for cell killing in NBS. However, the mechanism leading to NBS cell death following induction of DSBs has not been determined (e.g., no evidence for increased apoptosis has been described). Indeed, one report even showed diminished IR-induced apoptosis in leukocytes from a patient with NBS (35).

Infrared Spectroscopy

The energy of most molecular vibrations corresponds to that of the IR region of the electromagnetic spectrum. Molecular vibrations may be detected and measured either in an IR spectrum or indirectly in a Raman spectrum. The common region of the IR spectrum is 2.5-16 i (4000-625 cm-1), which most IR spectrometers cover. Infrared light is absorbed when the oscillating dipole moment (due to a molecular vibration) interacts with the oscillating electric vector of the infrared beam. A simple rule for deciding if this interaction (and hence absorption of light) occurs is that the dipole moment at one extreme of a vibration must be different from the dipole moment at the other extreme of the vibration. Thus the selection rule for a vibration to be IR active is that the vibration must result in a change in the dipole moment. The important consequence of this selection rule is that in a molecule with a center of symmetry, those vibrations symmetrical about the center of symmetry are inactive...

Radiolabeled Monoclonal Antibodies

Lym-1 has been conjugated to 131I in order to effect targeted delivery of this radioactive isotope to tumor cells of B-cell origin. Although 131I-Lym-1 has been tested primarily in patients with advanced NHL, the antibody has been given to several patients with B-CLL. Twenty-five patients with previously treated, advanced B-NHL and five patients with relapsed B-CLL were treated with fractionated, low-dose 131I-Lym-1, with a goal of 300 mCi per patient (122). Thirty percent of patients developed HAMAs, but only three patients had therapy interrupted as a result. Four of the five CLL patients responded (80 ). The same group also reported that patients who responded to 131I-Lym-1 therapy enjoyed improved survival (84 vs 22 wk) (123). Radiation dosimetry studies revealed a lower tumor radiation dose and a higher liver radiation exposure in CLL patients, compared with NHL patients, resulting in a lower therapeutic index for patients with CLL (124). Toxicity was acceptable, and the...

Genetic Instability And Dna Repair

An issue that has been hotly debated in the literature is whether FA cells are sensitive toward ionizing radiation (reviewed recently in Ref. 75). Within the context of the conditioning regimen for bone marrow transplantation, there has been a longstanding clinical impression of increased radiosensitivity of patients with FA who also seem to tolerate cyclophosphamide less well than patients who do not have FA. However, in vitro studies with FA cells have yielded conflicting results. An unpublished study from our laboratory shows that FA fibroblasts of all known complementation groups respond to increasing x-ray doses in the same way as control cells (Fig. 2). Moreover, when fibroblasts from patients with ataxia-telangiectasia (which are known to be highly radiosensitive) are taken as positive controls, studies from our laboratory provide no evidence for increased radiosensitivity of FA fibroblasts under in vitro conditions. A surprising result has been obtained when primary...

Occupational exposure

The effects of low-grade protracted exposure to radiation in older age as seen in nuclear workers and individuals living in high-risk areas are at least intriguing. Several case-controlled studies reported an increased risk of MM among nuclear workers exposed to external penetrating ionizing radiation. In the international combined analyses of mortality data on 95,673 workers, more than 85.4 men, employed for at least 6 months in the nuclear industry in the United States, United Kingdom, and Canada, were monitored for external exposure to ionizing radiation. The analyses covered a total of 2,124,526 person-years at risk and 15,825 deaths, 3976 of which were due to cancer. Among the 31 specific types of cancers studied, a significant association was observed only for MM (P 0.037 44 deaths).76 In the Sellafield British nuclear plant the cancer mortality and incidence among 14,282 workers employed between 1947 and 1975 were studied up to 1988. Overall cancer mortality and incidence were...

Potential Biomedical Applications Of Polymer Nanostructures

Femtosecond 100

For smaller feature sizes (down to one micron or less), photolithographic methods, e-beam lithography, or scanning probe lithography (e.g. AFM dip pen lithography 44 ) are often employed (i.e. surface machining). Here, a liquid photoresist is spin-coated or a self-assembly monolayer (SAM) is deposited on a galvanic starting layer. The mi-cro nanofeatures are formed after radiation exposure through a photomask and development or direct e-beam or scanning probe writing. Figure 3.3 shows a schematic of these surface machining methods. For prototyping, this photoresist structure can serve as a device itself or be used as a mold (called photoresist mold) in low temperature and low pressure molding processes. More generally, this structure is either used directly for electroplating or for wet dry etching of silicon (which subsequently is electroplated) 17 . Both technologies yield a metal tool, usually nickel or nickel-cobalt. For features with a low aspect ratio (defined as the ratio of...

Radiation Therapy and Centrosome Anomalies in Pancreatic Cancer

Radiation therapy has been widely used as a major treatment option for patients with malignant tumors, including pancreatic adenocarcinoma. Nevertheless, the precise mechanism by which radiation-induced cellular damage leads to cell death or growth arrest is not yet fully understood. Ionizing radiation has been shown to induce extensive induction of aberrations in centrosome number in various solid tumor cell lines. Importantly, such supernumerary centrosomes have been associated with the formation of multipolar spindles and chromosome mis-segregation. Possible mechanisms leading to abnormal centrosome numbers in response to radiation include dissociation between centrosome duplication and DNA replication cycles coupled with loss of a centrosome-intrinsic mechanism to block reduplication, failure of cell division (cytokinesis) associated with polyploidization, and centrosome fragmentation. Integrity of DNA damage checkpoint pathways as well as tumor microenvironment (extracellular...

Modernity and symptoms

This increase in health stories in the media has a number of effects. One important outcome is that people see themselves as vulnerable from many features of modern life. Current diets are seen as having too many additives or genetically modified substances. The air and water we drink is seen as containing pollutants that may cause illness. Threats are also perceived in new features of modern life such as electromagnetic emissions from mobile phones, power lines, computers, microwaves and radio towers.

The Relationship Between Sun Exposure and Other Diseases

There is in Australia unanimous agreement by the ACOD, OA, ANZBMS, and CCA that there is high-level evidence for the harmful effects of sun exposure in terms of skin cancer and for the beneficial effects of sun exposure in maintaining adequate vitamin D levels to protect against bone fracture (Trivedi et al. 2003). However, all parties agree that substantially more evidence is required before conclusions can be drawn between sun exposure and a possible beneficial effect with other cancers such as breast, prostate, bowel, or non-Hodgkin lymphoma and autoimmune diseases such as multiple sclerosis. The biological pathways underlying these empirically observed observations are still not clear and in some instances the epidemiological evidence is equivocal. It was agreed by all parties that it is not appropriate to make statements about a protective effect of UV radiation exposure for these diseases because substantially more studies with good individual exposure measures by season is...

Radiationinduced Cell Death Apoptosis or Mitotic Cell Death

Radiation therapy, either alone or in combination with surgery and chemotherapy, has long been used in the management of a majority of patients with different types of solid tumors. It has been generally accepted that ionizing radiation induces two types of cell death that are routinely referred to as apoptosis and mitotic cell death 28, 29 . Apoptosis (or programmed cell death) is an active form of cell death which appears to occur preferentially in lymphoma and leukemia cells after irradiation 30, 31 . In most solid tumor cell types, however, cell death after radiation occurs predominantly as a result of aberrant mitotic events, namely, mitotic cell death or mitotic catastrophe 28, 32-34 . This form of cell death has been defined as loss of reproductive integrity after inappropriate entry into mitosis, and is characterized by the emergence of large nonviable cells containing multiple nuclear fragments or micronuclei 28, 32, 35 . In our study, a panel of 10 solid tumor cell lines...

Accelerated Stem Cell Aging After Significant DNA Damage

Mice and humans show evidence of premature aging and loss of stem cells after radiation and chemotherapy exposure. For instance, after chemotherapy or radiation exposure, patients may show evidence of chronic pancytopenia, a conversion to myeloplastic syndrome, and acute leukemia and have delayed onset of secondary lymphoid malignancies as well. Each of these disorders suggests an abnormality of stem cell maintenance, perhaps due to the chronic effects of the mutation caused by radiation and chemotherapy or due to other more subtle changes within the stem cell population. We have observed that C57BL 6J mice 6 months after chemotherapy or radiation exposure develop evidence of premature aging with a vertebral hump and premature graying hair they also have a shorter life span of approximately 16-18 months compared to the normal life span of over 26 months (Fig. 1). In our studies, mice occasionally develop late evidence of stem cell failure after chemotherapy or radiation exposure, with...

Imaging for Early Detection of Atherosclerotic Disease

Rotating mechanical CTs are used (MSCT with 16 or more slices simultaneously acquiring the data), while in the US, electron beam CT (EBCT, no mechanically moving parts) is the prevailing technology. Besides the considerably lower costs of MSCT, the spatial resolution of MSCT is superior to EBCT with the temporal resolution still a matter of debate using the sector technology for MSCT. In contrast to cardio-MR, cardio-CT easily depicts the presence of calcified plaques of more than 1 mg. In general, there is clinically good agreement between the calcium scores measured by EBCT and MSCT.28-30 As regards radiation exposure, the effective dose for calcium scoring is 0.7 mSv for EBCT and 1.0 mSv for (prospectively triggered) MSCT.31 For a practical comparison, the German government allows a radiation dose of 1.0 mSv during pregnancy for an unborn child.

Metaphase Micronuclei Multinucleation

These authors have also shown that calmodulin-dependent protein kinase II (CaMKII), which is known to be associated with centrosomes 76, 77 , is involved in apoptosis induced by ionizing radiation. We have observed that a subset of irradiated cells with multiple centrosomes appear to undergo apoptosis as determined by TUNEL staining 27 . Bunz and coworkers also noted apoptotic cell death after y-radiation in a subset of p53 or p21 cells containing multiple centrosomes 41 . These studies, however, did not establish causality between centro-some defects and apoptosis. It is also possible that nuclear fragmentation associated with centrosome anomalies could trigger apoptosis. Merritt and colleagues described a p53-independent delayed apoptosis in small intestinal epithelia after irradiation, which was associated with the appearance of giant cells with fragments of condensed chromatin in their nucleus 78 . In addition, several investigators have shown that p53 protein is...

Factors Affecting Centrosome Anomalies after Irradiation

DNA damage after exposure to ionizing radiation activates checkpoint pathways that inhibit progression of cells through the G1 and G2 phases 81 . In many cancer cells, these checkpoint pathways are inactivated by different mechanisms. Importantly, the integrity of the DNA damage checkpoint pathways could affect centrosome anomalies after irradiation for the following reasons. First, in the presence of intact checkpoint pathways cells with heavily damaged DNA are likely to be arrested and eliminated by apoptosis before acquisition of abnormal centrosome phenotypes. Second, considering the time required for centrosome duplication, the extent of abnormal centrosome duplication may be dependent on the duration of G2 arrest, which in turn is determined by checkpoint mechanisms. Among the genes involved in DNA checkpoint pathways, the p53 tumor suppressor is frequently mutated in human cancers 82 . In addition to its established role in the G1 checkpoint and apoptosis, p53 also blocks entry...

Conclusions and Future Directions

In conclusion, exposure of human solid tumor cells to ionizing radiation induces numerical aberrations of the centrosomes, multipolar spindle formation, and micro- or multinucleated phenotypes characteristic of mitotic cell death. The origin of supernumerary centrosomes in response to radiation is unknown, but possible mechanisms include dissociation between centrosome duplication and DNA replication cycles coupled with the loss of a centrosome-intrinsic mechanism to block reduplication, failure of cytokinesis associated with polyploidization, and centro-some fragmentation. Although there is no direct evidence to indicate that centro-some anomalies contribute to the killing of tumor cells after irradiation, supernumerary centrosomes or centrosome-like structures that retain microtubule-nucleat-ing activity provide an attractive model for radiation-induced nuclear fragmentation and subsequent cell death. A better understanding of the origins and consequences of centrosome anomalies in...

Computing The Uncomputable

We can now propose an answer to the question of why and how mathematics works. It works because the iterative processes of the world correspond to the iterative processes of mathematics. Sometimes these iterations are explicit, as in the case of counting, multiplying, or forecasting the orbits of variables in phase space. Sometimes they are implicit, as when we use differential operators to model the gradient of an electromagnetic field. In the first type of case the correspondence is obvious in the second we have to make a roundabout approach by summing tiny slices of space time infinitesimals. However, in both cases the iterative process is still there.

Emergence And Evolution

The interpretation I have suggested implies that the only properties that can emerge are those that can be produced by a given sequence. This may help to explain why more and more properties appear as the universe evolves. At first, when there were only short sequences possible, only a limited set of properties could appear. As the universe grows, more and more properties can emerge, because sequence lengths can grow also. For example, small particles were the first to appear, the free movement of electromagnetic radiation came later, condensed matter formed later still, and so on, culminating in the long molecules basic to life, in which sequence is all-important.

Crosssectional Studies Of Quantitative Mr Techniques In People With The Clinical Diagnosis Of Ad

Cerebral blood volume MR measurements using contrast agents indicate a reduction in temporoparietal blood volume in patients with AD (38-40). Another technique sensitive to cerebral blood flow but does not require injection of contrast agents is arterial spin labeling (ASL). Significant blood flow reductions were identified in the temporal, parietal, frontal, and posterior cingulate cortices of patients with AD relative to controls (41). ASL is an appealing technique for blood flow measurements because it does not require contrast injection or ionizing radiation. Studies comparing the accuracy of ASL to nuclear medicine imaging modalities as surrogate markers for blood flow changes in AD are needed.

Patients With Implantable Cardioverterdefibrillators Undergoing Procedures

All sources of electromagnetic interference (EMI) including electrocautery, transcutaneous electrical neurologic stimulation units, radiofrequency ablation, lithotripsy, magnetic resonance imaging, radiation therapy have the potential to trigger or inhibit ICD therapy or damage the ICD.

Tumors of the Meninges

Meningiomas in children are rare, constituting only 3 of pediatric brain tumors no female predominance is noted. They are more common during the second decade of life but may occur at any age, including in fetuses and infants. In a significant number of children, meningiomas are associated with neurofibromatosis type 2 (NF2), often in the absence of a family history. Ionizing radiation is a potential risk for the development of a menin-

Isolated Implantable Cardioverter Defibrillator Discharge

Flow diagram for evaluating ICD shocks. ATP antitachycardia pacing EGM electrocardiograms EMI electromagnetic interference SVT supraventricular tachycardia. *See Box 10.1 **class III drugs include sotalol and dofetilide not programmable in all devices. Figure 10.8. Flow diagram for evaluating ICD shocks. ATP antitachycardia pacing EGM electrocardiograms EMI electromagnetic interference SVT supraventricular tachycardia. *See Box 10.1 **class III drugs include sotalol and dofetilide not programmable in all devices.

Effect of Bcrabl on DNA Repair and Genomic Stability

In the first study investigating such a relationship, Deutsch et al. (66) looked at the effects of BCR-ABL on the catalytic subunit, DNA-PKCS, of the DNA-PK complex formed with the heterodimeric Ku protein. Repair of DSBs by the DNA-PK-dependent pathway nonhomologous end-joining (NHEJ) recombination is the preferred pathway utilized by human cells (67), and in mice, NHEJ deficiency accelerates lymphoma formation and promotes the development of soft tissue sarcomas that possess clonal amplifications, deletions, and translocations (68,69). In BCR-ABL-expressing cells (including primary CML cells), levels of DNA-PKCS were markedly downregulated (66) and were reversed by proteasome inhibitors, suggesting the activation of a BCR-ABL-dependent pathway leading to enhanced proteasome-dependent protein degradation (66). Downregulation of DNA-PKCS levels was associated with a higher frequency of chromosomal abnormalities after exposure of BCR-ABL-expressing cells to ionizing radiation (IR) and...

Maintenance Of The Germ Line

Related research indicates that ionizing radiation transiently blocks Ocell proliferation and induces programmed cell death (i.e., apoptosis) in the germ line (46). In some organisms, apoptosis serves to eliminate cells that have been extensively damaged. The genetic control of apoptosis in the somatic cells of C. elegans has been extensively studied (47,48) and is meditated by the same core apoptotic machinery (e.g., ced-9, ced-4, ced-3) as employed in the germ line. The dual responses of cell cycle arrest and apoptosis upon irradiation suggest that an active checkpoint is operative in the C. elegans germ line. Indeed, these phenotypes are reversed by mutations in three genes, mrt-2, rad-5, and him-7 that is, irradiation of these mutants does not inhibit germ line proliferation and induces apoptosis as it does in wild type. Interestingly, these mutants were isolated using three different types of mutant hunts namely, for a mortal germ line (mrt-2 42 ), for somatic cell radiation...

The Molecular Basis of G2 Arrest

A number of other Rad mutants that fail to arrest in the cell cycle in response to ionizing radiation have been uncovered, and orthologs in various organisms including mammals have been identified (reviewed in 5961). Studies on the components of the DNA-damage response have uncovered three main groups of proteins involved in initiating G2 arrest. The sensors recognize damaged DNA, and the transducers transmit the signal downstream to the effectors, whose activity is modulated to bring about arrest (61,62). Although these groups of proteins are sufficient to induce the arrest, in time, many checkpoints become spontaneously inactivated, and additional mechanisms are used to maintain the arrest. Studies with mammalian cells in tissue culture showed that Cdc2 is an important effector for the G2 checkpoint. Ionizing radiation and other forms of DNA damage blocked the dephosphorylation of Cdc2 at tyrosine 15 and threonine 14, causing it to remain inactive (63,64). Inhibition of...

Special Situations Encountered By The Pacemaker Patient

The pacer physician is often asked to evaluate a pacemaker patient before surgery. In addition to obtaining details from the history and physical examination outlined previously, it is most essential to establish the degree of pacer dependence and, via telemetry, the current programmed settings. Operating room personnel including the surgeon, nursing staff, and anesthesiologists all need to be aware of the presence of the device, the potential EMI encountered in the operating room, and corrective techniques. An external defibrillator with transcutaneous pacing capabilities should be easily accessible. Electrocautery, often required intraoperatively, may result in a variety of pacemaker phenomena. Electrocautery may cause transient inhibition of pacer output because of oversensing of electromagnetic interference. If pacer dependence has been demonstrated preoperatively, the device may be programmed to either an asynchronous mode or a triggered mode to preempt undue inhibition of pacer...

Dna Repair And Telomeric Function

Telomerase-Deficient Mice with Short Telomeres Are Hypersensitive to Ionizing Radiation Double-strand breaks (DSBs) are generated by reactive by-products of oxygen metabolism, by exposure to ionizing radiation, and in V(D)J recombination in lymphocytes. Efficient DSB DNA repair machinery eliminates these breaks, which might otherwise cause increased death or tumorigenesis. There is increasing evidence that short telomeres result in increased organismal sensitivity to ionizing radiation. Short telomeres render yeast and Caenorhabditis elegans more radiosensitive. Based on work in yeast, it has been proposed that short telomeres may directly impair the efficiency of DSBs generated by ionizing radiation, since they may be the storage sites for DNA-repair proteins (90,91), although this has not been formally addressed to date. Terc ' mice with progressively shorter telomeres provide a unique system with which to address whether there is a causal relationship between short telomeres and...

See also Reactive Oxygen Oxygen Metabolism and Human Disease Superoxide Dismutase Catalase Glutathione Peroxidase

Hydroxyl Radical - Hydroxyl radical damages proteins, nucleic acids, and the fatty acids in membrane lipids (lipid peroxidation). Lipid peroxidation occurs as a chain reaction. Hydroxyl radical is produced as a result of ionizing radiation and represents the most active mutagen derived from ionizing radiation. It is also produced from H2O2 in the Fenton reaction

Electric Fields in Cells and Organism 351

In the following text we enter a further region in the hierarchic structure. We will consider electric fields in the extracellular space, in tissues and organs. This is the region of classical electrodynamics. In this case the Maxwell equations allow us to calculate electric fields in inhomogeneous dielectrics. The question arises how does the field spread inside the body, which consists of organs with different conductivities, like bones, soft tissue, air filled cavities etc We will come back to this question again in Section 4.4., where we will discuss the influence of electromagnetic fields on biological systems.

Alphaglucosidase inhibitor blocks hydrolysis of an

Blood causing metabolic acidosis laser - light amplification by stimulated emission of radiation device using a high-energy beam of electromagnetic radiation law of mass action - the rate of any given chemical reaction is proportional to the product of the activities (or concentrations) of the reactants lecithin cholesterol acyltransferase - an enzyme that

Using MR Technology What Are We Learning

All of us who were the first subjects for MR studies of course wondered if something in our bodies might dislike having our hydrogen protons subjected to such military discipline, but by now millions and millions of people have been scanned, and no adverse effects have been found. Unlike all other imaging procedures, this one requires no exposure to ionizing radiation and can therefore be used safely in large samples of healthy people. The simple description of how MR works in the paragraph above does not do justice to all the ways that collecting MR signals can be tweaked to produce information. The use of MR to obtain measurements of function is described in more detail in the next section. However, the application of MR to study brain structure is a fascinating and steadily developing discipline in and of itself. fMR has many advantages over PET. While maintaining a PET center is expensive, and few medical centers have one, every medical center has an...

Other Applications For Fluosol

Fluosol was also studied as an adjunct to cancer therapy. Solid tumors contain hypoxic cells, and this can impair the efficiency of many anticancer agents, including ionizing radiation and chemotherapeutic drugs, which depend on oxygen to be effective. Extensive preclinical studies evaluated the effectiveness of Fluosol with oxygen or carbogen (95 oxygen, 5 carbon dioxide) breathing in conjunction with ionizing radiation as an anti-cancer therapy, with generally positive outcomes (Teicher, 1992, 1995 Rockwell, 1994). Additional beneficial effects of this treatment regimen with radiosensitizing drugs, including nicotinamide, which improves microregional blood flow (Horsman, 1995), were similarly effective (Teicher, 1995). Related pre-clinical investigations reported increased tumor cell killing by chemotherapeutic drugs, including cyclophosphamide, when used in conjunction with Fluosol and carbogen (Teicher, 1994). escalating dose regimen with a maximum of 56 ml kg in eight...

Interaction of the sensor with its environment

Noncontacting sensors produce only a minimal perturbation of the sample to be monitored. In general, such measurements are limited to the use of electromagnetic radiation such as light, or sampling the gas or liquid phase near a sample. It may be even necessary to add a probe molecule to the sample to make the determination. Two examples are monitoring the temperature of a sample by its infrared emission intensity, and spectroscopic monitoring of pH dependence of the optical absorption of a pH-sensitive dye. No damage is done to the sample, but limited types of information are available, and chemical selectivity is difficult to achieve in vivo.

Physical Factors of the Environment

- Very small amounts of energy, occasionally being absorbed at particular targets, can significantly disturb biological mechanisms of control. The place of interaction in this case is not a specific receptor, but rather a crucial point in the network of reactions. An example of this is the induction of mutations by ionizing radiation. In this context it should be pointed out that the organism has and is adapting through evolution to all physical parameters of its environment. So, for example, the double strand of the DNA is an adaptation to overcome single strand breaks by ionizing radiation. Additionally, a large number of mechanisms have been developed to repair these kinds of damage. On the other hand, during evolution an astonishing number of mechanisms have been developed to sense minimal amounts of energy, in the form of receptors for vibration, for temperature, for light and for other kinds of radiation.

Artery Calcifications

Cardiac CT is extremely sensitive in the detection and quite accurate in the quantification of coronary artery calcifications 9 . In addition, cardiac CT is a noninvasive and quick method that is easy to perform. Thus, cardiac CT is currently regarded as the standard-of-care for the detection and quantification of coronary artery calcifications although the radiation exposure of this technique must be taken into account. However, there was recently a controversial debate about the most suitable cardiac CT imaging technique for coronary artery calcium scoring. The arguments advanced in discussing the pros and cons of the potential techniques pertain to temporal resolution, spatial resolution, image noise, radiation exposure, availability and reference values (see below) 10 .

Scientific Foundations

Electricity and magnetism are like two different aspects of the phenomenon called electromagnetism, one of the fundamental forces of the universe. Every electrical charge causes an invisible electric field to exist around itself. An electric field pushes or pulls against other charges. Like charges repel each other opposite charges attract. Electrical charges that are moving, or electric fields that change over time, also create (induce) magnetic fields. In turn, magnetic fields that change over time make electric fields. A ray of visible light or a radio wave (both electromagnetic waves) is really a pair of ever-changing electric and magnetic fields that bring each other into being as they move together through space. This self-creation and propulsion system is why light can travel across the vacuum of space and does not need a medium like a wave in ocean water.

Snp Detection Electronic Detection

Although robotic spotted arrayers are becoming increasingly popular and much more cost-effective, some companies have taken advantage of the fact that DNA behaves in a predictable manner in an electrical field in the presence of certain chemicals or metals. Electronic biomolecular detection relies on the ability to produce an electromagnetic field that provides a method for discriminating biomolecules in an extremely heterogeneous mixture of biological detritus.

Anticarcinogenic Effects

An alcoholic extract from the leaves of O.sanctum at doses of 400 and 800 mg kg (p.o.) for 15 days significantly elevated the activity of cytochrome P-450, cytochrome b , aryl hydrocarbon hydroxylase and glutathione S-transferase in mice. The effect was dose-responsive. The above mentioned enzymes are important in the detoxification of carcinogens and mutagens. Glutathione S-transferase represents an important defense mechanism in protecting cells against oxygen-derived free radicals and also from cellular lethality after exposure to anticancer drugs or ionizing radiation. These findings suggest that Ocimum leaf extract has the potential to block or suppress the events associated with chemical carcinogenesis (Banerjee et al., 1996).

Studies of DNA Damage by Polarographic Techniques

The seminal electrochemical studies of DNA were connected with the dropping mercury electrode (DME) and polarographic methods (see Sections 5.1 and 5.2). Oscillographic polarography at controlled a.c. and later DPP revealed striking differences between native (ds) and denatured (ss) DNA at the DME 7-10, 37, 294, 337, 338 (Figure 5.1 see Section 5.2.2.1). Importantly, intensity of the dsDNA-specific peak II responded sensitively to subtle dsDNA structural transitions, including premelting changes of the DNA double helix 9 and perturbations related to DNA damage. Height of the DPP peak II increased with the number of ssb and or dsb resulting from DNA treatment with ultrasound, DNase I or ionizing radiation 294, 295 . Covalently closed circular DNAs (possessing no strand ends) did not yield any peak II under the same conditions 291, 339 . Formation of DNA lesions involving conformational distortions of the DNA double helix such as pyrimidine dimers in UV-irradiated DNA 296 or DNA adduct...

Alternative Methods for Applying Strain

Magnets are used to provide a high degree of control in devices capable of stretching a substrate, and such magnetostrictive actuators have been used in order to generate up to 22,000 e on particular substrates. The electromagnetic elements placed at either end of the substrate are attached to clamps mounted on a guide plate that ensures unidirectional travel. It is an aspect of these devices that they generate powerful electromagnetic fields that may directly affect cell behavior, and shielding from these fields should always be used.

Detection of DNA Strand Breaks with Mercury and Amalgam Electrodes

In addition to the effects of transient DNA double helix opening around the ssb, detectable polarographically (see Section 5.4.2.1), ccc (lacking free chain ends) and open circular (oc, containing one or more ssb per molecule) or linear (lin) DNA molecules remarkably differ also in their susceptibilities to irreversible denaturation. A procedure involving differential thermal DNA denaturation in solution followed by AdTS voltammetric microanalysis at HMDE was proposed 276 . The technique was utilized for determination of ocDNA in samples of cccDNA (such as plasmid scDNA) and for quantification of ssb induced by ionizing radiation. Nicked or linear DNAs, but not the scDNA, were irreversibly denatured at 85 C. Only the former DNAs (i.e., the products of DNA damage) contributed to the observed changes in the intensity of CV 276 or a.c. voltammetric 26 DNA signals.

Application Of Mri To Study Metabolic Disorders

MRI is based on the principles of nuclear magnetic resonance, a spectroscopic technique used by scientists to obtain microscopic chemical and physical information about molecules (1). MRI became widely available in the mid 1980s and has become the preferred imaging modality for clinical and research anatomical imaging (2). Unlike computed tomography (CT) scanning, MRI can be obtained in multiple planes and can produce highly resolute images. By using different pulse sequences for image acquisition, tissue contrast can be manipulated to yield images that are suited for specific purposes. The lack of ionizing radiation makes it safe for repeated scanning of an individual and particularly for the scanning of infants and young children.

Vertebral Morphometry and Fractures

Grading Vertebral Fractures

Fan-array DXA spine imaging is one of the newer applications for DXA. The spine can be imaged from T4 to L5 in the lateral or PA projection. DXA spine imaging can be performed in seconds to minutes, depending on the scan mode, but always at a fraction of the radiation exposure of conventional spine radiographs.

Magnetic Resonance Imaging

MRI is based on the spontaneous alignment of magnetic moments of the nuclei contained in tissues when an external electromagnetic field is applied. Because H+ is abundant in the human body and has a high gyromagnetic ratio, MRI is almost exclusively carried out with protons. Images are produced by applying multiple radiofrequency signals (256 -512 pulses) over several minutes. Fat satura-

Nuclear Magnetic Resonance Spectroscopy

Nuclei with a net magnetic dipole such as 1H and 13C will orient the dipole axis in an external magnetic field in certain quantized orientations. The number of possible orientations is given by 2I + 1. If a nucleus with I 1 2 is placed in a uniform magnetic field, it may take up one of two orientations with respect to the field (the external magnetic field H defines the z-axis). Those may be considered as a low-energy orientation in which the nuclear magnet is aligned with the field (having quantum numbers ms +1 2), and those referred to as a high-energy orientation in which the magnet is aligned against the field (having quantum numbers ms -1 2). The transition between these two energy states can be brought about by the absorption of suitable electromagnetic radiation of energy.

Research On The Environment

Illumination is provided by light, which is a form of electromagnetic radiation. Three concepts are particularly important in the measurement of illumination intensity radiant flux, radiance, and irradiance193-195 (Figure 2.44). Radiant flux refers to the power of the emitted light source (radiant power) and, accordingly, is expressed in watts (W). When you buy a light bulb for your house, the bulb is rated according to its consumption of energy, not by the emitted light. Typically, radiant power is about one-quarter of the consumed power, so that a 100 W bulb puts out only 25 W (the rest is lost as heat). Radiance, which is more commonly used by vision researchers, measures the fraction of radiant power that can reach you. It indicates the radiant power per unit area per unit solid angle (see Figure 2.44) and, therefore, is expressed in watts per A problem related to light measurement is that human vision is extremely limited. What humans call light is a very narrow range of...

DNA Damage Checkpoint Genes

DNA damage and replication checkpoint response pathways in eukaryotes. (A) Components of a checkpoint signaling pathway arising from the replication block or DNA damage (DSB SSB) are shown. Rad17-Rad9-Hus1-Rad1 and MRE11-Rad53-Nbs1-ATM complexes can act as sensors after double-strand breaks. Similarly, Rad17-Rad9-Hus1-Rad1 and ATR-ATRIP complexes act after replication or other types of DNA damage. BRCA1 claspin can act as adaptors in the DNA damage response. Chk1 Chk2 act as effector kinases. (B) ATR-Chk1 or ATR-Chk2 can be activated after replication stress or UV damage and cause phosphorylation of Cdc25 or p53 for checkpoint responses. However, after ionizing radiation, ATM can activate Chk1 Chk2, which phosphorylate Mus81, p53, or Brca1 to perform checkpoint and repair responses. Fig. 7. DNA damage and replication checkpoint response pathways in eukaryotes. (A) Components of a checkpoint signaling pathway arising from the replication block or DNA damage (DSB SSB) are shown....

Structural Chromosomal Aberrations

Chromosomal translocations are structural aberrations characterized by relocations of chromosomal segments within one or among different chromosomes. As chromosomal translocations are relatively stable structural changes (76-78), they would be expected to accumulate with age. Several investigators have found that the increase in translocation frequencies in a nonsmoking normal population follows a curvilinear relationship with age (79,80). Although ionizing radiation is known to induce chromosomal translocations, it cannot alone account for the strong age-related increase of chromosomal translocations (80). It has been argued that age may play a role in an individual's response to radiation exposure, as the capacity of DNA repair mechanisms may decline with age (81,82). However, it has been demonstrated that the susceptibility to translocation formation induced by acute (83) and chronic (80) ionizing radiation does not change with age. Apparently, other factors are involved in this...

Classification Of Aa Based On Etiology And Pathophysiologic Mechanisms

Bone marrow aplasia is a well-known toxicity of ionizing radiation. Myeloablation using 7-radiation is used therapeutically as a conditioning regimen for stem cell transplantation. The bone marrow is affected directly by 7-rays, and secondarily by a- and p-particles. Certain cell types, such as lymphocytes, are very sensitive and are killed directly, while hematopoietic progenitors require cell division for severe damage thus, mitotically active cells are most sensitive. The onset and severity of pancytopenia is dose dependent. However, the regeneration capacity of the irradiated marrow is remarkable, likely due to the presence of quiescent, more resistant stem cells. While the exact LD50 dose is not precisely known in humans, 1.5-2 Gy of whole body radiation can induce marrow aplasia. The dose of 4.5 Gy (Shields-Warren number) has been estimated to constitute the LD50.1147 The estimation of marrow toxicity is hampered by the toxicity to other organ systems that may limit survival. At...

Imaging Modalities

Propagated new imaging modalities, such as fluorescence tomography, spectrally resolved whole-body imaging and intravital multiphoton imaging. However, high autofluorescence in the blue-green optical window, photo-bleaching, and limited quantification of photon output are major pitfalls for fluorescence imaging. In contrast to bioluminescence imaging, the lack of a requirement for an injectable substrate is highly advantageous. Nuclear imaging (SPECT and PET) is highly sensitive, quantitative, and tomo-graphic. However, it demands sophisticated instrumentation and readily available in-house production of radiopharmaceuticals. MRI does not involve ionizing radiation, generates high spatial resolution and combined physiologic-anatomic information can be obtained simultaneously. However, the low sensitivity of MRI requires high concentration of contrast material or signal amplification to monitor molecular events in vivo. While targeted bubbles in principle may be used in molecular...

Targets

One example of a biochemical target produced by carcinogens is reactive oxygen species (ROS). Ionizing radiation is a complete carcinogen and produces much of its DNA damage through ROS (102). Several strategies for preventing ROS-in-duced cell damage have been developed. The aminothiol, amifostine, inhibits radiation-induced DNA damage to a large degree by scavenging free radicals produced by ionizing radiation. Amifostine and its derivatives suppress ionizing radiation-induced transformation and carcinogenesis. Antioxidants, including protein and non-protein sulfhydrals and certain vitamins, are effective modulators of ROS produced by physical and chemical carcinogens (103). Antioxidants are effective in inhibiting carcinogenesis in some experimental models, but their roles in human cancer prevention remains unclear. At least some agents with antioxidant activity may increase carcinogenesis in some tissues. Heavy smokers receiving combinations of...

Patients

During my career as a cancer scientist, I have frequently received calls from individuals who recently heard a physician tell them the ominous words ''You have cancer,'' or from people who have heard that statement about a family member or close friend. The first question usually is ''What can you tell me about this kind of cancer '' They may have already visited several Internet sites and have some information, not always accurate or scientifically based. If the patient is a child and the inquiry comes from parents, they frequently have a great feeling of guilt and want to know what they did wrong, or they may lash out at some perceived environmental agent that they think is the cause, such as water pollutants or electromagnetic fields from high-power lines in their neighborhood. Individuals or their family members then want to know what caused the cancer, what the meaning of the test results is, what the treatment options are, and, if the tumor has spread, if there are any...

Radionuclide Imaging

The limitations of radionuclide testing are the need for intravenous injection, high cost (approximately 2,000 in most laboratories), radiation exposure, as well as a slow imaging protocol. The images take up to 4 hours to obtain, requiring the patient remain immobile. Furthermore, often the rest and stress imaging cannot be done on the same day so the patient must spend two days in testing.

Epidemiology

The specific cause of ALL is unknown in most patients, and specific epidemiologic associations can be identified in no more than 10 of childhood ALL and in a much lower proportion of adults.26 27 An extensive review of ALL in children by Buffler et al. details potential occupational exposures in parents of patients, and exposures to aromatic hydrocarbons and household chemicals and pesticides, ionizing radiation, low-frequency magnetic fields, diet, infections, and genetic polymorphisms.26 Numerous potential predisposing features studied or established include positive associations with the specific genetic syndromes noted below, high birth weight,28 ethnicity,29 and a paradoxically negative relation with maternal smoking.30 While extensively investigated, none of these factors offer potent predictive value for improved diagnosis and increased survival other than the increased risk of leukemia in some hereditary and genetic syndromes (see below). In adults, even fewer associations are...

Analysis

Women who intend to become pregnant should be advised to avoid, whenever possible, potentially harmful agents such as radiation, drugs, alcohol, over-the-counter (OTC) medications, herbs, and other environmental agents. Radiation exposure greater than 5 rads is associated with fetal harm. Most commonly performed x-ray procedures, including dental, chest, and extremity x-rays, expose a fetus to only very small fractions of this amount of radiation. Whenever possible, the abdomen and pelvis should be shielded and x-rays performed only when the benefit outweighs the potential risk. Magnetic resonance imaging studies have not been proven to cause harm, but are not recommended in pregnancy, if avoidable. Ultrasound has not been shown to be harmful.

Risk Factors

Almost all cases of CML have no identifiable predisposing factors, and even when there might be a plausible causal link, it is extremely difficult to incriminate any factor in individual patients. Exposure to ionizing radiation is the only known etiological factor the incidence of CML was increased to a minor but significant degree in patients treated with radiation therapy for ankylosing spondylitis or metropathia hemorrhag-ica.1011 The most compelling link between radiation exposure and CML comes from a Life Span study of survivors of the atomic bomb explosions in Hiroshima and Nagasaki (Japan) in 1945.12 13 There was an increased risk of CML among the survivors. An increased risk of leukemia, but not of CML, has also been reported in an area immediately surrounding the British nuclear fuel facility at Calder Hall in Cumbria, U.K. (although a government commission of enquiry was unable to confirm this).

Radiation therapy

Compared to children, adolescents and young adults are less vulnerable to the adverse effects of ionizing radiation. This is particularly true for the central nervous system, the cardiovascular system, connective tissue, and the musculoskeletal system, each of which may be irradiated to higher doses and or larger volumes with less long-term morbidity than in younger patients. By analogy, older adolescents who are still maturing may be more vulnerable to radiation toxici-ties than older persons at those sites and tissues that are still undergoing development such as the breast and gonads. Breast cancer, for example is more likely in women who received radiation for Hodgkin lymphoma if the radiation was administered between the onset of puberty and the age of 30 years 43 . Remarkably little is actually known about the differential normal-tissue effects of radiotherapy in patients between 15 and 30 years of age.

Quality of Survival

Many adolescent and young adult cancer survivors cite fertility as a primary concern that impacts the quality of their life. Most do not recall an adequate discussion of the risks of infertility or methods to decrease the risks with their physician at the initiation of therapy. The risk of infertility for an individual is difficult to predict. Direct radiation exposure of the gonad had been studied more extensively than other chemotherapy exposures. Permanent ovarian damage occurs between 5 and 20 Gy, with higher doses required in younger females 68 . The male germinal epithelium is much more sensitive to radiation-induced damage, with changes to spermatogonia resulting from as little as 0.2 Gy. Testicular doses of less than 0.2 Gy had no significant effect on follicle-stimulating hormone

Radiation Damage

Biologic effects of radiation have been reviewed in detail by a number of authors, including von Sonntag (7), Pizzarello and Wit-cofski (8), Casarett (9), Okada (10), and Dertinger and Jung (11). Ionizing radiation can have three types of biological effect perturbation of cellular regulation, mutation, or cell death. Most of the research on radiopro-tection has focused on cell death and consequences at the level of tissue injury and death of the organism. In mammals, death can result from damage to the blood-forming organs, gastrointestinal system, or central nervous system, depending on radiation dose. Hematopoietic death from bleeding, infection, or anemia is the endpoint that was used in most of the early studies on radioprotection, and follows 7-30 days after exposure to a potentially lethal single dose ( 400 rads) in mice. These whole-body effects of relatively high doses of ionizing radiation are most easily explained in terms of depletion of stem cells by cell killing that in...

Radionuclide Studies

Vesicoureteral reflux This abnormality may be assessed directly or indirectly. The direct method is identical to a micturating cystogram but has the disadvantage of offering no anatomical detail. On the other hand, it uses less radiation exposure and is more easily quantifiable. The indirect technique employs a standard dynamic 99mTc-DTPA renal scan. Upon completion of the test, the patient drinks until the bladder feels full and there is an urge to void. Baseline renal and bladder counts are taken at this point. The patient then voids while the gamma camera updates data for several minutes after voiding. The presence of reflux into the kidney is detected in the time-activity curves as a peak. Lesser degrees of reflux are more prone to error and not easily identified by this method.

Figure

Into categories based on the degree of certainty of the association, and include demographic, environmental, genetic, and exposure-related factors (Table 6.2). Age, gender, race ethnicity, socioeconomic status, genetic syndromes, and radiation exposure (in utero and or therapeutic) are known risk factors for leukemias in younger age groups 8 .

Etiology

There are only a few proven etiologic factors for childhood AML, for example in utero exposure to alcohol, exposure to benzene, ionizing radiation, or different drugs that may contribute to AML in young children. The risk of AML is increased in children with congenital syndromes such as Fanconi anemia, Shwachman syndrome, and Down syndrome. Somatic mutations of the GATA 1 gene are seen in virtually all cases of AML associated with Down syndrome and may be implicated in

Molecular aspects

Exposure of renal cells to a hostile environment initiates a complex molecular response including the activation of phosphorylation cascades and the expression of many genes. Many of these molecular responses are not confined to areas of regeneration and in fact are localized to nephron segments not undergoing obvious injury or repair. For example, a typical immediate early gene response (IEG), as indicated by c-fos and c-jun activation, occurs most prominently in areas not undergoing an increase in DNA synthesis. Because the sites of increased DNA synthesis are spatially separated from those of IEG expression and many of the responses, including the expression of chemokine genes, resemble the response observed in cells exposed to adverse environmental conditions such as ionizing radiation, oxidants, and hypertonicity, the expression of these genes under these circumstances has been termed the Stress Response. This response is thought to be a major determinant of whether cells survive...

Radiotherapy

The use of ionizing radiation to destroy cancer cells and tumors is known as radiation therapy, X-ray therapy, irradiation, or simply radiotherapy. This therapy relies on high-energy electromagnetic beams or subatomic particles to damage the DNA in cancer cells so that the cell is incapable of dividing and quickly dies. The main goal is to kill the cancer cells while leaving the normal cells intact. This can be achieved in some cases by focusing the beam of radiation on specific parts of the body or, if possible, directly on the cancerous tumor. Thus radiotherapy has the potential for greater precision than chemotherapy and produces fewer side effects.

Ultraviolet

Ionizing Radiation The carcinogenic effects of ionizing radiation were discovered from studies of pioneer radiation workers who were occupationally exposed, individuals who were exposed to diagnostic or therapeutic radiation, and atomic bomb survivors. Malignant epitheliomas of the skin were observed in the earliest experimenters with X-rays and radium within a few years after their discovery in 1895 and 1898, respectively. By 1914, a total of 104 case reports of radiation cancers had been noted and analyzed.108 In 1944, the role of ionizing radiation in the in The types of neoplasms produced in individuals exposed to ionizing radiation depend on a number of factors, including dose of radiation, age at time of exposure, and sex of the individual. Within 25 to 30 years after whole-body or trunk irradiation, there is an increased incidence of leukemia and cancers of the breast, thyroid, lung, stomach, salivary glands, other gastrointestinal organs, and lymphoid tissues. Other malignant...

Safety hazards

35S emits -rays with a maximum energy of 0.167 MeV and a half-life of 87.4 days. A Geiger-Muller counter is suitable for the detection of -emitters. particles can affect superficial layers of tissues and represent an external hazard. They are also potential internal hazards, if radioactivity gets inside the body via inhaled gas particles or via the mouth or via skin cuts. Best protection from the external hazard can be attained by reducing exposure time to radioactive material. This can be achieved by planning and preparing the experiments carefully before starting bench work. Furthermore, intensity of electromagnetic radiation decreases with the square of the increasing distance. The use of shields between the body and the radioactive samples is also highly recommended, as -rays may have a range of up to a few metres in air, while 1 cm of Plexiglas will stop any rays. This will, however, generate Bremsstrahlung, a form of X-rays, which are also potentially harmful. To protect from...

Nbs1 Gene

As nuclear foci, termed IRIF (ionizing radiation-induced foci), formed in response to treatment with DSB-inducing agents (65-67). Nuclear hMre11 hRad50 foci formation was absent in cells from patients with NBS (Fig. 2), strongly supporting a functional role of p95 in the relocalization of hMre11 and hRad50 to the nucleus and formation of the trimeric DSB repair complex, thus demonstrating the equivalence of p95 and nibrin.

Spindle Check Point

Chk2 Chk1 Pathway

As a cellular response to ultraviolet light (UV)-induced DNA damage, Cdc25A is highly degraded by ubiquitin- and proteasome-dependent proteoly-sis (96). The same degradation also occurs after hydroxyurea (HU)-triggered stalling of replication forks (97) as well as during the midblastula transition in Xenopus embryos under physiological conditions (98). Following DNA damage, Cdc25A is phosphorylated by checkpoint kinase 1 (CHK1) or checkpoint kinase 2 (CHK2) (Fig. 2B). This phosphorylation is recognized as a tag by the proteolysis system and Cdc25A is degraded. Thus, CHK1 or CHK2 induces the G1 S phase checkpoint by phosphorylating Cdc25A (see Subheading 4.2.). Supporting this is the finding that the elimination of CHK1 expression through the use of siRNA not only abrogated the S or G2 arrest, it also protected Cdc25A from degradation(88). During the basal turnover in unperturbed S phase, CHK1 phosphorylates serines 75, 123, 178, 278, and 292 of Cdc25A. In contrast, ionizing radiation...

Summary

Troubleshooting Pacemakers

Simplified schematic for pacemaker troubleshooting. EMI electromagnetic interference *greater than 300 ohm change in impedance as measured at the time of malfunction **or programmed to asynchronous mode can have no change in impedance with concomitant insulation failure. Figure 7.31. Simplified schematic for pacemaker troubleshooting. EMI electromagnetic interference *greater than 300 ohm change in impedance as measured at the time of malfunction **or programmed to asynchronous mode can have no change in impedance with concomitant insulation failure.

Gender Effects

The age-adjusted incidence rates for MM are higher in men (in the United States, 8090 cases were diagnosed in men versus 7180 cases in women, in the year 2004). This gender-related difference is noted across all age groups and is maintained worldwide in all reported age-specific incidence rates. This is despite the fact that MM is a disease of the elderly, and that women in general live longer than men. This gender-related difference is not only limited to the incidence of MM. There are indications that women may be more resistant than men to carcinogen exposure from occupation, radiation exposure, or smoking. In some studies, women have a better prognosis after therapy than do men.8-12

Series Introduction

Normal metabolism is dependent on oxygen, a free radical. Through evolution, oxygen was chosen as the terminal electron acceptor for respiration. The two unpaired electrons of oxygen spin in the same direction thus, oxygen is a biradical, but is not a very dangerous free radical. Other oxygen-derived free radical species, such as superoxide or hydroxyl radicals, formed during metabolism or by ionizing radiation are stronger oxidants and are therefore more dangerous.

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