Effect of a 2.45-GHz radiofrequency electromagnetic field on neutrophil chemotaxis and phagocytosis in differentiated human HL-60 cells

The potential public health risks of radiofrequency (RF) fields have been discussed at length, especially with the use of mobile phones spreading extensively throughout the world. In order to investigate the properties of RF fields, we examined the effect of 2.45-GHz RF fields at the specific absorption rate (SAR) of 2 and 10 W/kg for 4 and 24 h on neutrophil chemotaxis and phagocytosis in differentiated human HL-60 cells. Neutrophil chemotaxis was not affected by RF-field exposure, and subsequent phagocytosis was not affected either compared with that under sham exposure conditions. These studies demonstrated an initial immune response in the human body exposed to 2.45-GHz RF fields at the SAR of 2 W/kg, which is the maximum value recommended by the International Commission for Non-Ionizing Radiation Protection (ICNIRP) guidelines. The results of our experiments for RF-field exposure at an SAR under 10 W/kg showed very little or no effects on either chemotaxis or phagocytosis in neutrophil-like human HL-60 cells

NMR Spectroscopy of Membrane Proteins in Phospholipid Bilayers

Solid-state nuclear magnetic resonance (NMR) spectroscopy is a powerful method for the study of membrane proteins under native environments. G protein-coupled receptors (GPCRs) are highly challenging integral membrane proteins that are often hard to study using the available biophysical techniques. Limited information about their structures and dynamics has been elucidated with x-ray crystallography as well as various biochemical techniques, such as Föster resonance energy transfer (FRET), and mutation studies. Obtaining site resolved NMR spectra for GPCRs can help to better understand their structures and behaviors. Here CXC-chemokine receptor 2 (CXCR2) is studied with various NMR tools, and the functional relevance of the obtained protein is verified with ligand binding assays as well as NMR. A comparison of CXCR2 interaction with two of its ligands: interleukin 8 and CXCL5 is also presented. At the same time, methods such as protein perdeuteration, and 1H detection were developed for the study of complex membrane proteins using the oriented-sample solid-state NMR technique. NMR developments are also made on the MerFTC chimeric protein, to help experiments for the more complex CXCR2. Combining various NMR techniques, optimized NMR spectra are presented, providing insights into the structure and function of the CXCR2 protein

Directed cell migration in multi-cue environments

Cell migration plays a critical role in development, angiogenesis, immune response, wound healing and cancer metastasis. During these processes, cells are often directed to migrate towards targets by sensing aligned fibers or gradients in concentration, mechanical properties or electric field. Often times, cells must integrate migrational information from several of these different cues. While the cell migration behavior, signal transduction and cytoskeleton dynamics elicited by individual directional cues has been largely determined, responses to multiple directional cues are much less understood. However, initial work has pointed to several interesting behaviors in multi-cue environments, including competition and cooperation between cues to determine the migrational responses of cells. Much of the work on multi-cue sensing has been driven by the recent development of approaches to systematically and simultaneously control directional cues in vitro coupled with analysis and modeling that quantitatively describe those responses. In this review we present an overview of multi-cue directed migration with an emphasis on how cues compete or cooperate. We outline how multi-cue responses such as cue dominance might change depending on other environmental inputs. Finally, the challenges associated with the design of the environments to control multiple cues and the analysis and modeling of cell migration in multi-cue environments as well as some interesting biological questions associated with migration in complex environments are discussed. Understanding multi-cue migrational responses is critical to the mechanistic description of physiology and pathology, but also to the design of engineered tissues, where cell migration must be orchestrated to form specific tissue structures

The Largest Unethical Medical Experiment in Human History

This monograph describes the largest unethical medical experiment in human history: the implementation and operation of non-ionizing non-visible EMF radiation (hereafter called wireless radiation) infrastructure for communications, surveillance, weaponry, and other applications. It is unethical because it violates the key ethical medical experiment requirement for “informed consent” by the overwhelming majority of the participants. The monograph provides background on unethical medical research/experimentation, and frames the implementation of wireless radiation within that context. The monograph then identifies a wide spectrum of adverse effects of wireless radiation as reported in the premier biomedical literature for over seven decades. Even though many of these reported adverse effects are extremely severe, the true extent of their severity has been grossly underestimated. Most of the reported laboratory experiments that produced these effects are not reflective of the real-life environment in which wireless radiation operates. Many experiments do not include pulsing and modulation of the carrier signal, and most do not account for synergistic effects of other toxic stimuli acting in concert with the wireless radiation. These two additions greatly exacerbate the severity of the adverse effects from wireless radiation, and their neglect in current (and past) experimentation results in substantial under-estimation of the breadth and severity of adverse effects to be expected in a real-life situation. This lack of credible safety testing, combined with depriving the public of the opportunity to provide informed consent, contextualizes the wireless radiation infrastructure operation as an unethical medical experiment

Protein Structure

Since the dawn of recorded history, and probably even before, men and women have been grasping at the mechanisms by which they themselves exist. Only relatively recently, did this grasp yield anything of substance, and only within the last several decades did the proteins play a pivotal role in this existence. In this expose on the topic of protein structure some of the current issues in this scientific field are discussed. The aim is that a non-expert can gain some appreciation for the intricacies involved, and in the current state of affairs. The expert meanwhile, we hope, can gain a deeper understanding of the topic

Long-Term Health Impacts of Cell Phone-Driven Radiofrequency Radiation Exposure in Humans

Uncertainties still exist about the safety of cell phone use and the level of cell phone-driven radiation. The purpose of the current inquiry was to determine the long-term health impacts of cell phone-driven radiation via the use of cell phones. In this cross-sectional study, which was based on socio-ecological theory, secondary data from the 2012 National Health Interview Survey were analyzed to assess the difference in the prevalence of thyroid cancer, mouth/tongue/lip cancer, and heart disease between exposed and non-exposed/less exposed cell phone-driven radiation groups in the United States. Logistic regression was used to address three research questions. Findings initially showed that cell phone use was associated with cancer outcome. However, there was no statistically significant relationship between individuals who were heavy users or sometimes users of cell phones and thyroid or mouth/tongue/lip cancer when compared to individuals who rarely or do not use cell phones. There was a relationship between heavy/sometimes users and heart disease when compared to individuals who rarely/do not use cell phones. Yet, when all the confounders/covariates were included in the model, there was no statistically significant difference between the groups compared. For assessment of thyroid cancer cases among individuals who received \u27all/almost all calls\u27 via the cell phones and those who received calls \u27sometimes\u27 on cell phones, age and sex were added in the model. Based on the study findings, policy-makers could further explore the implementation of comprehensive regulatory measures to address cell phone safety

Development of probes for molecular imaging : evaluation in models of inflammation and atherosclerosis

The imaging field is rapidly evolving and in the last two decades there have been tremendous developments in the field of multimodal imaging. Multimodal molecular imaging approaches that utilize ultrasound/magnetic resonance imaging (US/MRI), single-photon emission computed tomography/computed tomography (SPECT/CT), or positron emission tomography/MRI (PET/MRI) may provide additional detailed information at the cellular and molecular level to help identify patients with vulnerable plaques that are at risk of rupture. The search for specific biomarkers in combination with specific and optimized molecular probes may help to prevent adverse events such as myocardial infarctions or strokes. Current clinical contrast agents do not provide information on the inflammatory components of atherosclerotic plaques; thus, more specific molecular probes are needed. This thesis focuses on probe development for different molecular imaging techniques using multimodal and targeting approaches. Several types of molecular probe were evaluated: bimodal and multimodal microbubbles, as well as chemically modified human serum albumin (HSA)-based probes (aconitylated (Aco) and maleylated (Mal)) for targeting markers of inflammation; adhesion molecules on endothelial cells or macrophages, and scavenger receptor A1 (SR-A1) on macrophages. Evaluation of these molecular probes was facilitated by their physical properties enabling assessment with fluorescence microscopy, flow cytometry, and nuclear imaging properties for in vivo molecular imaging with SPECT/CT and PET/MRI. We found that functionalizing molecular probes with targeting moieties greatly improved the targeting specificity and avidity to the target compared to non-targeted molecular probes. Furthermore, these molecular probes were successfully radiolabeled with a detectable in vivo signal by 99mTc-anti-ICAM-1- MBs imaging of inflammation with SPETC/CT, and atherosclerosis by 89Zr-Mal-HSA with PET/MRI. Ex vivo evaluation of HSA-based probes showed significant accumulation in atherosclerotic lesions of Apoe-/- mice, as quantified by gamma counter and phosphor imaging autoradiography, compared to wild type (WT) mice. In conclusion, adhesion molecule targeting and scavenger receptor targeting with functionally modified probes in this thesis showed potential for the imaging of inflammation and atherosclerosis. Of the evaluated probes, modified HSA-based probes seem to have the greatest potential for clinical application in molecular imaging of atherosclerosis

A Gal-MS Device to Evaluate Cell Migratory Response to Combined Galvano-Chemotactic Fields

Electric fields have been studied extensively in biomedical engineering (BME) for numerous regenerative therapies. Recent studies have begun to examine the biological effects of electric fields in combination with other environmental cues, such as tissue-engineered extracellular matrices (ECM), chemical gradient profiles, and time-dependent temperature gradients. In the nervous system, cell migration driven by electrical fields, or galvanotaxis, has been most recently studied in transcranial direct stimulation (TCDS), spinal cord repair and tumor treating fields (TTF). The cell migratory response to galvano-combinatory fields, such as magnetic fields, chemical gradients, or heat shock, has only recently been explored. In the visual system, restoration of vision via cellular replacement therapies has been limited by low numbers of motile cells post-transplantation. Here, the combinatory application of electrical fields with other stimuli to direct cells within transplantable biomaterials and/or host tissues has been understudied. In this work, we developed the Gal-MS device, a novel microfluidics device capable of examining cell migratory behavior in response to single and combinatory stimuli of electrical and chemical fields. The formation of steady-state, chemical concentration gradients and electrical fields within the Gal-MS were modeled computationally and verified experimentally within devices fabricated via soft lithography. Further, we utilized real-time imaging within the device to capture cell trajectories in response to electric fields and chemical gradients, individually, as well as in combinatory fields of both. Our data demonstrated that neural cells migrated longer distances and with higher velocities in response to combined galvanic and chemical stimuli than to either field individually, implicating cooperative behavior. These results reveal a biological response to galvano-chemotactic fields that is only partially understood, as well as point towards novel migration-targeted treatments to improve cell-based regenerative therapies

Evaluation of Effect of Pulsed electromagnetic field therapy in chronic non healing Diabetic foot ulcers

Among the various chronic serious complications of Diabetes mellitus foot related complications top the list. The life time risk of developing foot ulcer is 25 % and the annual incidence is 2-3% and leads to devastating consequence limb amputation. Diabetic foot ulcers fail to heal and become chronic due to repetitive trauma, infection and ischemia that are characterized by inappropriate inflammation, disproportionate collagen synthesis, degradation and deficient growth factors such as VEGF. Conventional treatments fail to treat underlying pathogenesis. Pulsed Electromagnetic Field therapy is a new modality which is found to interact at various steps in wound healing and up-regulates growth factors such as VEGF Decreased wound dimensions, formation of healthy granulation tissue, reduction in exudate and elevated serum VEGF levels indicate that PEMF enhance wound healing. No side effects were reported .Thus PEMF can be an effective and safe adjunct therapy for treating chronic non healing diabetic foot ulcers