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Search Results: 1 - 10 of 1997 matches for " Hamilton Vernon "
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Interferon-α Regulates Glutaminase 1 Promoter through STAT1 Phosphorylation: Relevance to HIV-1 Associated Neurocognitive Disorders
Lixia Zhao, Yunlong Huang, Changhai Tian, Lynn Taylor, Norman Curthoys, Yi Wang, Hamilton Vernon, Jialin Zheng
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032995
Abstract: HIV-1 associated neurocognitive disorders (HAND) develop during progressive HIV-1 infection and affect up to 50% of infected individuals. Activated microglia and macrophages are critical cell populations that are involved in the pathogenesis of HAND, which is specifically related to the production and release of various soluble neurotoxic factors including glutamate. In the central nervous system (CNS), glutamate is typically derived from glutamine by mitochondrial enzyme glutaminase. Our previous study has shown that glutaminase is upregulated in HIV-1 infected monocyte-derived-macrophages (MDM) and microglia. However, how HIV-1 leads to glutaminase upregulation, or how glutaminase expression is regulated in general, remains unclear. In this study, using a dual-luciferase reporter assay system, we demonstrated that interferon (IFN) α specifically activated the glutaminase 1 (GLS1) promoter. Furthermore, IFN-α treatment increased signal transducer and activator of transcription 1 (STAT1) phosphorylation and glutaminase mRNA and protein levels. IFN-α stimulation of GLS1 promoter activity correlated to STAT1 phosphorylation and was reduced by fludarabine, a chemical that inhibits STAT1 phosphorylation. Interestingly, STAT1 was found to directly bind to the GLS1 promoter in MDM, an effect that was dependent on STAT1 phosphorylation and significantly enhanced by IFN-α treatment. More importantly, HIV-1 infection increased STAT1 phosphorylation and STAT1 binding to the GLS1 promoter, which was associated with increased glutamate levels. The clinical relevance of these findings was further corroborated with investigation of post-mortem brain tissues. The glutaminase C (GAC, one isoform of GLS1) mRNA levels in HIV associated-dementia (HAD) individuals correlate with STAT1 (p<0.01), IFN-α (p<0.05) and IFN-β (p<0.01). Together, these data indicate that both HIV-1 infection and IFN-α treatment increase glutaminase expression through STAT1 phosphorylation and by binding to the GLS1 promoter. Since glutaminase is a potential component of elevated glutamate production during the pathogenesis of HAND, our data will help to identify additional therapeutic targets for the treatment of HAND.
A Brief Overview of How Male Medicine Co-Opted the Midwife’s Role in the Birth Process  [PDF]
Leonard F. Vernon
Open Journal of Nursing (OJN) , 2015, DOI: 10.4236/ojn.2015.59079
Abstract: The term medicalization has been defined as the process by which non-medical issues come to be defined and treated as medical problems. There are no better examples of this than pregnancy and childbirth. Prior to the intervention of physicians and hospitals, most females delivered unassisted or assisted by a relative or a midwife who usually had no formal education. As long as this remained the practice, pregnancy could not become a medical procedure. Through systematic changes, discussed in detail herein, this primarily female-oriented event involving family and amateur aids would come to be dominated by males who were the sole legally authorized providers of obstetrical care [1]. The increasing cultural authority of medicine facilitated the transfer of home delivery to hospital delivery and changed normal birth into a surgical procedure. This paper will examine the history of obstetrics and how a profession comes to redefine a normal life event as a disease state.
How Silencing of Dissent in Science Impacts Woman. The Gardasil® Story  [PDF]
Leonard F. Vernon
Advances in Sexual Medicine (ASM) , 2017, DOI: 10.4236/asm.2017.74015
Abstract:

The issues of safety and efficacy of certain vaccines remains extremely contentious. The venues for this debate have included periodicals, documentary films, and an ever-increasing number of on-line sites. While debate in science is not only a common occurrence but a fundamental tenet of the scientific community, it only works when divergent opinions can be heard. When those who hold an opposing opinion are denigrated and/or marginalized by those holding the majority opinion such as in the issue of vaccination, where cultural authority for the issue is owned by the profession of medicine, both science and the public lose. What is often forgotten are the benefits derived from the questioning of drug safety that not only extends to the public but to physicians who rely on the truthfulness and accuracy of the information that is being supplied to them by manufactures and government agencies. While most physicians believe they are functioning in their patient’s best interest when making vaccine recommendations, these recommendations by in large have become a matter of rote and are made because most physicians have bought into the “vaccines are safe” mantra. What most physicians don’t realize is they have unknowingly been recruited by big pharma to assist in shutting down the vaccination debate. This suppression of vaccine opposition even among academics, is becoming more commonplace and will lead down a slippery slope that will silence opposition science, and the dangers that come with this. Those who question vaccine safety have been ostracized, misquoted and even made to appear mentally ill by those who hold the majority opinion on the issue. Physicians who question vaccine safety have had their licenses threatened or have been fired from positions. Tactics such as name calling and the use of terms such as pseudo-science, (even when the evidence being presented is from widely accepted peer-reviewed journals) or “conspiracy theorists” which has the effect of placing those holding the minority opinion in the category of such groups as 9/11 truthers, are not uncommon. Other methods of curtailing the presentation of opposing vaccine views have included pressuring venues not to allow anti-vaccination proponents to appear, or using the media to “expose” anti-vaccination groups as “crack-pots” while simultaneously presenting the majority opinion and the presenters as the sole arbiters on the issue. The more extreme elements of the pro-vaccine group will even make the statement that the issue is settled and there is no need for discussion.

A Universal Condition Satisfied by the Action of Electromagnetic Radiation Fields  [PDF]
Vernon Cooray, Gerald Cooray
Journal of Electromagnetic Analysis and Applications (JEMAA) , 2017, DOI: 10.4236/jemaa.2017.911015
Abstract: The action (the product of radiated energy and the time of emission) of the radiation fields generated by four types of radiators, namely, short electric dipole, small magnetic dipole, travelling wave antenna and bi-conical antenna is investigated with special reference to the charge associated with the current waveform which is responsible for the radiation. The results obtained can be summarized by the order of magnitude inequality \"\"where A is the action (product of the radiated energy and the time of emission), h is the Planck constant, q is the charge associated with the current that gave rise to the radiation and e is the electronic charge. The condition\"\" is obtained when the length of the antenna and its radius are pushed to its extreme natural limits. Based on the results obtained here and elsewhere, it is suggested that this inequality is valid in general for electromagnetic radiation fields as predicted by classical electrodynamics.
Classical Electromagnetic Fields of Moving Charges as a Vehicle to Probe the Connection between the Elementary Charge and Heisenberg’s Uncertainty Principle  [PDF]
Vernon Cooray, Gerald Cooray
Natural Science (NS) , 2017, DOI: 10.4236/ns.2017.97022
Abstract: The radiation fields generated when a charged particle is incident on or moving away from a perfectly conducting plane are obtained. These fields are known in the literature as transition radiation. The field equations derived thus are used to evaluate the energy, momentum and the action associated with the radiation. The results show that for a charged particle moving with speed ν, the longitudinal momentum associated with the transition radiation is approximately equal to ΔU/c for values of ?1- ν/c smaller than about 10-3 where ΔU is the total radiated energy dissipated during the interaction and cis the speed of light in free space. The action of the radiation, defined as the product of the total energy dissipated and the duration of the emission, increases as 1- ν/c decreases and, for an
Remarkable Predictions of Classical Electrodynamics on Elementary Charge and the Energy Density of Vacuum  [PDF]
Vernon Cooray, Gerald Cooray
Journal of Electromagnetic Analysis and Applications (JEMAA) , 2018, DOI: 10.4236/jemaa.2018.105006
Abstract: In a recent paper, we have studied the nature of the electromagnetic energy radiated over a single period of oscillation by an antenna working in frequency domain under ideal conditions and without losses when the oscillating charge in the antenna is reduced to the elementary charge. Here we extend and expand that study. The energy radiated by an oscillating current in an antenna occurs in bursts of duration T/2, where T is the period of oscillation. The results obtained here, based purely on classical electrodynamics, can be summarized by the inequality U ≥hvq0e where U is the energy radiated in a single burst of duration T/2, h is the Planck constant, ν is the frequency of oscillation and q0 is the magnitude of the oscillating charge associated with the current. The condition U=hvq0=e is obtained when the length of the antenna is equal to the ultimate Hubble radius of the universe (i.e. the maximum value of the antenna length allowed by nature) and the wavelength is equal to the Bohr radius (resulting from the smallest possible radius of the conductor allowed by nature). The ultimate Hubble radius is directly related to the vacuum energy density. The inequality obtained here is in general agreement with the one obtained in the previous study. One novel feature of this extended analysis is the discovery of an expression, in terms of the elementary charge and other atomic constants, for the vacuum energy density of the universe. This expression predicts the vacuum energy density to be about 4×10-10?J/m3 which is in reasonable agreement with the measured value of 6×10-10 J/m3.
Novel Features of Classical Electrodynamics and Their Connection to the Elementary Charge, Energy Density of Vacuum and Heisenberg’s Uncertainty Principle—Review and Consolidation  [PDF]
Vernon Cooray, Gerald Cooray
Journal of Modern Physics (JMP) , 2019, DOI: 10.4236/jmp.2019.101007
Abstract: The paper provides a review and conciliation of the results pertinent to the energy and action associated with electromagnetic radiation obtained using classical electrodynamics and published in several journal papers. The results presented in those papers are based on three systems that generate electromagnetic radiation, namely, frequency domain antennas, time domain antennas and decelerating (or accelerating) charged elementary particles. In the case of radiation generated by a frequency domain antenna, the energy dissipated as radiation within half a period, U, satisfies the order of magnitude inequality U hvq e where q is the magnitude of the oscillating charge in the antenna, e is the elementary charge, v is the frequency and h is the Planck constant. In the case of transient radiation fields generated by time domain antennas or the radiation emitted by decelerating (or accelerating) charged elementary particles, the energy dissipated by the system as radiation satisfies the order of magnitude inequality Uτr h/4πq e where U is the energy dissipated as radiation by the system τr, is the duration of the energy emission and q is either the charge in the current pulse in the case of the time domain antenna or the charge of the elementary particle giving rise to the radiation. These results are derived while adhering strictly to the principles of classical electrodynamics alone. These results were interpreted in different papers in different ways using different assumptions. In this paper, we provide a unified interpretation of the results, and combining these results with two simple quantum mechanical concepts, expression for the elementary charge as a function of other natural constants and the energy density of vacuum is derived. The expressions predict the elementary charge to an accuracy higher than about 1%.
What is different about spinal pain?
Howard Vernon
Chiropractic & Manual Therapies , 2012, DOI: 10.1186/2045-709x-20-22
Abstract: Targeted searches of the literature were conducted and the relevant materials reviewed for applicability to the thesis that deep spinal pain is distinctive from deep pain in the peripheral limb structures. Topics related to the neuroanatomy and neurophysiology of deep spinal pain were organized in a hierarchical format for content review.Since the 1980’s the innervation characteristics of the spinal joints and deep muscles have been elucidated. Afferent connections subserving pain have been identified in a distinctive somatotopic organization within the spinal cord whereby afferents from deep spinal tissues terminate primarily in the lateral dorsal horn while those from deep peripheral tissues terminate primarily in the medial dorsal horn. Mechanisms underlying the clinical phenomena of referred pain from the spine, poor localization of spinal pain and chronicity of spine pain have emerged from the literature and are reviewed here, especially emphasizing the somatotopic organization and hyperconvergence of dorsal horn “low back (spinal) neurons”. Taken together, these findings provide preliminary support for the hypothesis that deep spine pain is different from deep pain arising from peripheral limb structures.This thesis addressed the question “what is different about spine pain?” Neuroanatomic and neurophysiologic findings from studies in the last twenty years provide preliminary support for the thesis that deep spine pain is different from deep pain arising from peripheral limb structures.A 45-year old male presents with chronic lumbosacral pain and some pain in the posterior thigh. Examination rules out any overt disc herniation with radiculopathy. X-rays show no spinal pathology.Basic differential diagnosis options:1. Back pain with referred leg pain (one problem with two clinical manifestations: one primary, the other secondary)2. Back pain and an associated, but not causally connected problem in the posterior thigh (two separate problems)Both of these options
Update on the treatment of phenylketonuria: long-term safety and efficacy of sapropterin dihydrochloride
Vernon H
Research and Reports in Endocrine Disorders , 2012, DOI: http://dx.doi.org/10.2147/RRED.S24770
Abstract: ate on the treatment of phenylketonuria: long-term safety and efficacy of sapropterin dihydrochloride Review (1390) Total Article Views Authors: Vernon H Published Date June 2012 Volume 2012:2 Pages 11 - 17 DOI: http://dx.doi.org/10.2147/RRED.S24770 Received: 16 March 2012 Accepted: 16 April 2012 Published: 06 June 2012 Hilary Vernon1,2 1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, 2Kennedy Krieger Institute, Baltimore, MD, USA Abstract: Phenylketonuria (PKU) is an inborn error of metabolism caused by a defect in the enzyme phenylalanine hydroxylase, which is responsible for converting phenylalanine to tyrosine. Untreated, this disorder will result in severe intellectual disability. However, with proper management, outcome is excellent. For many years, this disorder was managed exclusively with dietary measures which consisted of a phenylalanine-restricted diet. However, with the recent introduction of a stable, orally bioavailable form of tetrahydrobiopterin (BH4), the cofactor for phenylalanine hydroxylase, treatment in this disorder has been drastically altered. This stable form of BH4, sapropterin dihydrochloride, has a very good safety profile and is very effective in many patients with PKU in lowering plasma phenylalanine levels and allowing for liberalization of the phenylalanine-restricted diet. The introduction of BH4 has posed many new challenges in the treatment of PKU, including developing the best protocol to determine whether or not a patient will respond to BH4, and how to treat atypical populations including young children, fully affected, untreated adults, and pregnant patients. In this review, we will examine the history of treatment in PKU, the history of treatment with BH4, protocol options for determining if a patient is a drug responder, and considerations for treatment in special populations.
Update on the treatment of phenylketonuria: long-term safety and efficacy of sapropterin dihydrochloride
Vernon H
Research and Reports in Endocrine Disorders , 2012,
Abstract: Hilary Vernon1,21McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, 2Kennedy Krieger Institute, Baltimore, MD, USAAbstract: Phenylketonuria (PKU) is an inborn error of metabolism caused by a defect in the enzyme phenylalanine hydroxylase, which is responsible for converting phenylalanine to tyrosine. Untreated, this disorder will result in severe intellectual disability. However, with proper management, outcome is excellent. For many years, this disorder was managed exclusively with dietary measures which consisted of a phenylalanine-restricted diet. However, with the recent introduction of a stable, orally bioavailable form of tetrahydrobiopterin (BH4), the cofactor for phenylalanine hydroxylase, treatment in this disorder has been drastically altered. This stable form of BH4, sapropterin dihydrochloride, has a very good safety profile and is very effective in many patients with PKU in lowering plasma phenylalanine levels and allowing for liberalization of the phenylalanine-restricted diet. The introduction of BH4 has posed many new challenges in the treatment of PKU, including developing the best protocol to determine whether or not a patient will respond to BH4, and how to treat atypical populations including young children, fully affected, untreated adults, and pregnant patients. In this review, we will examine the history of treatment in PKU, the history of treatment with BH4, protocol options for determining if a patient is a drug responder, and considerations for treatment in special populations.Keywords: sapropterin dihydrochloride, phenylketonuria, phenylalanine
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