Martin L Pall

Martin L Pall
Washington State University | WSU · Molecular Biosciences

36.2
 · 
B.A., Ph.D.

About

113
Publications
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Introduction
Since 1998, I have focused on the mechanisms of chronic inflammatory diseases and how various stressors initiate cases of such diseases. The local mechanism involved in such many such diseases, called the NO/ONOO- cycle, has been recently been confirmed in a recent 57 page paper on heart failure, and to a lesser extent in a recent paper in pulmonary hypertension. I have focused in recent years on how stressors cause human disease, with special emphasis on electromagnetic fields (EMFs) and also chemicals. Non-ionizing, low-intensity EMFs act primarily via activation of voltage-gate calcium channels (VGCCs) and to a lesser extent activation of other voltage-gated ion channels via forces on their voltage sensor. VGCCs act via calcium signaling and the peroxynitrite pathway.

Publications

Publications (113)
Article
Full-text available
Repeated Wi-Fi studies show that Wi-Fi causes oxidative stress, sperm/testicular damage, neuropsychiatric effects including EEG changes, apoptosis, cellular DNA damage, endocrine changes, and calcium overload. Each of these effects are also caused by exposures to other microwave frequency EMFs, with each such effect being documented in from 10 to 1...
Article
Full-text available
It has been shown that low intensity microwave/lower frequency electromagnetic fields (EMFs) act in animals via activation of voltage-gated calcium channels (VGCCs) in the plasma membrane, producing excessive intracellular calcium [Ca²⁺]i, with excessive [Ca²⁺]i leading to both pathophysiological and also in some cases therapeutic effects. The path...
Article
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Dozens of reviews and thousands of primary literature studies have shown the existence of many different non-thermal health effects of microwave and lower frequency electromagnetic fields (EMFs); however current safety guidelines and standards only recognize thermal effects. This leaves both individuals and companies unprotected, particularly with...
Article
Full-text available
Non-thermal microwave/lower frequency electromagnetic fields (EMFs) act via voltage-gated calcium channel (VGCC) activation. Calcium channel blockers block EMF effects and several types of additional evidence confirm this mechanism. Low intensity microwave EMFs have been proposed to produce neuropsychiatric effects, sometimes called microwave syndr...
Article
Full-text available
This review considers a paradigm shift on microwave electromagnetic field (EMF) action from only thermal effects to action via voltage-gated calcium channel (VGCC) activation. Microwave/lower frequency EMFs were shown in two dozen studies to act via VGCC activation because all effects studied were blocked by calcium channel blockers. This mode of a...
Article
Full-text available
The transcription factor Nrf2, nuclear factor erythroid-2-related factor 2, activates the transcription of over 500 genes in the human genome, most of which have cytoprotective functions. Nrf2 produces cytoprotection by detoxification mechanisms leading to increased detoxification and excretion of both organic xenobiotics and toxic metals; its acti...
Article
Full-text available
The NO/ONOO-cycle is a primarily local, biochemical vicious cycle mechanism, centered on elevated peroxynitrite and oxidative stress, but also involving 10 additional elements: NF-κB, inflammatory cytokines, iNOS, nitric oxide (NO), superoxide, mitochondrial dysfunction (lowered energy charge, ATP), NMDA activity, intracellular Ca2+, TRP receptors...
Article
Full-text available
A series of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients have been studied to test two previous predictions: 1. Sauna therapy acts, at least in part, by raising the availability of tetrahydrobiopterin (BH4) and 2. ME/CFS is caused by a biochemical vicious cycle mechanism known as the NO/ONOO- cycle. Sauna therapy is shown he...
Article
Full-text available
The direct targets of extremely low and microwave frequency range electromagnetic fields (EMFs) in producing non-thermal effects have not been clearly established. However, studies in the literature, reviewed here, provide substantial support for such direct targets. Twenty-three studies have shown that voltage-gated calcium channels (VGCCs) produc...
Article
Imbalancen im Stickoxid(NO)-Metabolismus können zu einem Teufelskreis aus oxidativem/nitrosativem Stress und Inflammation und somit zu Gesundheitsstörungen führen. Dr. Hans-Peter Friedrichsen sprach auf der Medizinischen Woche 2012 in Baden-Baden mit Martin L. Pall, Professor em. für Biochemie an der Washington State Universität, über Ursachen und...
Article
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The NO/ONOO− cycle is a primarily local biochemical/physiological vicious cycle that appears to cause a series of chronic inflammatory diseases. This paper focuses on whether the cycle causes pulmonary arterial hypertension (PAH) when located in the pulmonary arteries. The cycle involves 12 elements, including superoxide, peroxynitrite (ONOO−), nit...
Article
ABSTRACT Cobalamin (vitamin B12) in the form of hydroxocobalamin or cyanocobalamin injections has been widely used to treat chronic fatigue syndrome (CFS). Hydroxocobalamin is a nitric oxide scavenger and is proposed here to act as such a scavenger in CFS treatment. Its possible efficacy in CFS treatment, if further substantiated, may provide confi...
Article
ABSTRACT In an earlier paper, I proposed that chronic fatigue syndrome (CFS) is caused by a response to infection, involving the induction of inflammatory cytokines which induce, in turn, the inducible nitric oxide synthase, producing elevated nitric oxide. Nitric oxide reacts with superoxide to form the potent oxidant, peroxynitrite. Six positive...
Article
Full-text available
The label 'chronic fatigue syndrome' (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term 'myal...
Article
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Chronic NF-κB activation has been supposed as a key event in chronic fatigue syndrome (CFS) and many other better-defined pro-inflammatory diseases. Knowledge about the impact of deficiency vitamin D on chronic NF-κB activation could open a new disease approach. Whereas NF-κB activation leads at first to a pro-inflammatory immune response, later on...
Article
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Pauling suggested that responses to high-dose vitamin therapy were due primarily to small increases in response due to lack of complete saturation of enzyme targets. He also suggested that they may be due, in part to "local vitamin deficiencies" although the origin of such deficiencies were unclear. Ames suggested that such therapy might be explain...
Chapter
Cases of multiple chemical sensitivity (MCS) are reported to be initiated by seven classes of chemicals. Each of the seven acts along a specific pathway, indirectly producing increases in NMDA activity in the mammalian body. Members of each of these seven classes have their toxicant responses lowered by NMDA antagonists, showing that the NMDA respo...
Article
Sauna therapy has been used to treat a number of different diseases known or thought to have a tetrahydrobiopterin (BH4) deficiency. It has been interpreted to act in multiple chemical sensitivity by increasing chemical detoxification and excretion but there is no evidence that this is its main mode of action. Sauna therapy may act to increase BH4...
Article
Full-text available
Cases of chronic fatigue syndrome/mylagic encephalomyelitis (CFS) are reported to be initiated by nine different short-term stressors, each of which increase levels of nitric oxide in the body. Elevated nitric oxide, acting through its oxidant product, peroxynitrite, initiates a local biochemical vicious cycle, the NO/ONOO-cycle, which is proposed...
Article
Post-radiation syndrome is proposed to be chronic fatigue syndrome (CFS) or a chronic fatigue syndrome-like illness, initiated by exposure to ionizing radiation. This view is supported by the nitric oxide/peroxynitrite (NO/ONOO-) cycle mechanism, the putative etiologic mechanism for CFS and related illnesses. Ionizing radiation may initiate illness...
Article
Peripheral tinnitus is a good candidate for inclusion under the NO/ONOO cycle etiological mechanism, fitting each of the five principles of this mechanism. Cases of tinnitus are initiated by at least 11 short-term stressors increasing nitric oxide or other cycle mechanisms. Such cycle elements as N-methyl-D-aspartate activity; oxidative stress; nit...
Article
Short-term stressors, capable of increasing nitric oxide levels, act to initiate cases of illnesses including chronic fatigue syndrome, multiple chemical sensitivity, fibromyalgia and posttraumatic stress disorder. These stressors, acting primarily through the nitric oxide product, peroxynitrite, are thought to initiate a complex vicious cycle mech...
Article
Full-text available
Cases of fibromyalgia (FM) are initiated by any of four short-term stressors known to increase levels of nitric oxide. Related illnesses including chronic fatigue syndrome and multiple chemical sensitivity have similar patterns of case initiation. The chronic phase of illness is thought to be caused by a biochemical vicious cycle mechanism called t...
Article
The vanilloid receptor (TRPV1 or VR1), widely distributed in the central and peripheral nervous system, is activated by a broad range of chemicals similar to those implicated in Multiple Chemical Sensitivity (MCS) Syndrome. The vanilloid receptor is reportedly hyperresponsive in MCS and can increase nitric oxide levels and stimulate N-methyl-D-aspa...
Article
Full-text available
The elevated nitric oxide/peroxynitrite and the neural sensitization theories of multiple chemical sensitivity (MCS) are extended here to propose a central mechanism for the exquisite sensitivity to organic solvents apparently induced by previous chemical exposure in MCS. This mechanism is centered on the activation of N-methyl-D-aspartate (NMDA) r...
Article
Protein carbonyl levels, a measure of protein oxidation, were found to be significantly elevated (p < 0.0005) in the sera of chronic fatigue syndrome (CFS) patients vs. controls. In contrast, the total protein levels in sera CFS patients were unchanged from those of controls. The elevated protein carbonyl levels confirm earlier reports suggesting t...
Article
Full-text available
Multiple chemical sensitivity (MCS) is a condition where previous exposure to hydrophobic organic solvents or pesticides appears to render people hypersensitive to a wide range of chemicals, including organic solvents. The hypersensitivity is often exquisite, with MCS individuals showing sensitivity that appears to be at least two orders of magnitu...
Article
Serum levels of citrulline, a product of nitric oxide synthase activity, were measured in 36 CFS patients and 16 controls to determine whether synthase activity may be elevated in CFS patients. Serum citrulline levels were found to be significantly elevated in CFS patients and, in addition, there was a trend towards higher levels in CFS patients wi...
Article
Three types of overlap occur among the disease states chronic fatigue syndrome (CFS), fibromyalgia (FM), multiple chemical sensitivity (MCS) and posttraumatic stress disorder (PTSD). They share common symptoms. Many patients meet the criteria for diagnosis for two or more of these disorders and each disorder appears to be often induced by a relativ...
Article
Various types of evidence implicate nitric oxide and an oxidant, possibly peroxynitrite, in MCS and chemical intolerance (CI). The positive feedback loops proposed earlier for CFS may explain the chronic nature of MCS (CI) as well as several of its other reported properties. These observations raise the possibility that this proposed elevated nitri...
Article
T HE peer-reviewed scientific literature is central to the deliberative structure of science. It has been described as ''the major factor in keeping the scientific enterprise relatively honest''(Abelson 1980). A real understanding of the scientific literature is essential to grasping how science works and how it differs from other human endeavors....
Article
The etiology of chronic fatigue syndrome (CFS) has been both obscure and highly contentious, leading to substantial barriers to both clear diagnosis and effective treatment. I propose here a novel hypothesis of CFS in which either viral or bacterial infection induces one or more cytokines, IL-1beta IL-6, TNF-alpha and IFN-gamma. These induce nitric...
Article
In an earlier paper, I proposed that chronic fatigue syndrome (CFS) is caused by a response to infection, involving the induction of inflammatory cytokines which induce, in turn, the inducible nitric oxide synthase, producing elevated nitric oxide. Nitric oxide reacts with superoxide to form the potent oxidant, peroxynitrite. Six positive feedback...
Article
We have previously constructed lambda/plasmid hybrid vectors designed for both fungal cDNA and genomic library construction (Brunelli and Pall, 1994 Fungal Genet. Newslet. 41:63-65). The genomic library inserts, however, were limited to about 11 kb in size due to the size limitations of lambda packaging. We have constructed a similar vector that ha...
Article
Lambda/plasmid hybrid vectors have been previously constructed in which the plasmid sequences are separated from flanking lambda arms by lox sites. The lox sequence is the substrate of Cre-mediated site-specific recombination, allowing easy excision of plasmid sequences (automatic subcloning). We have developed a simple procedure to construct other...
Article
In the previous Fungal Genetics Newsletter, we described a series of plasmid vectors constructed carrying the bar gene as a selectable marker for use in filamentous fungi (Pall and Brunelli 1993 Fungal Genetics Newsl. 40:59-63; Pall 1993 Fungal Genetics Newsl. 40:58). In this note, we describe an additional plasmid expression vector carrying this s...
Article
Expression/shuttle vectors for the yeast Saccharomyces cerevisiae have usually been large plasmids with only one or a small number of sites that are suitable for cloning and expression. We report here the construction and properties of a series of 12 expression vectors with multiple (four to eight) unique sites in their polylinkers which allow dire...
Article
A series of Saccharomyces cerevisiae/Escherichia coli lambda/plasmid expression vectors have been constructed which allow easy excision of the plasmid sequences from lambda. Features of six are described, and two designated lambda PG15 and lambda AD5, are characterized in detail. Transcription of cloned sequences is controlled by the alternative pr...
Article
The natural death (nd) mutant of the fungus Neurospora crassa, unlike the wild-type, undergoes an aging process, which leads to the cessation of growth. It is shown here that the ATP/ADP ratio of the mutant declines with age to about 3:1 whereas other strains of Neurospora in the same growth medium maintain ratios of about 8 to 9:1. The decline in...
Article
Purine nucleotide pools in the fungus Neurospora crassa decline in response to carbon, nitrogen, or sulfur deprivation. There is, in addition, a decline in GTP/ATP ratios on nitrogen or sulfur deprivation in wild type. The GTP/ATP decline is missing on nitrogen deprivation of the nitrogen control mutant, nit-2, and on sulfur deprivation of the sulf...
Article
An effective HPLC method for detecting deoxyribonucleoside triphosphates in hyphae from the fungus Neurospora crass has been developed. In rapidly growing cells the nucleotide levels vary from 11.8 pmoles/μg DNA for dGTP to 24.2 pmoles/μg DNA for dTTP. These levels fall by approximately one half in stationary-phase cultures but the ration of each p...
Article
Previous studies have shown that GTP and cyclic AMP have similar effects on the regulation of sporulation in the yeast Saccharomyces cerevisiae. Declines in either nucleotide can trigger sporulation. These results raise the question whether either nucleotide influences the pool of the other. The current study shows that a cyclic AMP deficiency prod...
Article
Cyclic AMP is thought to have a general role in stimulating the breakdown of carbohydrate reserves and subsequent glycolytic activity. This would be expected to increase the availability of reducing equivalents in the form of cytoplasmic NADH. The current study examines another potential reaction controlling cytoplasmic NADH in the fungus Neurospor...
Article
Previous studies have shown that GTP and cyclic AMP have similar effects on the regulation of sporulation in the yeast . Declines in either nucleotide can trigger sporulation. These results raise the question whether either nucleotide influences the pool of the other. The current study shows that a cyclic AMP deficiency produces a decline in GTP po...
Article
Cyclic AMP is thought to have a general role in stimulating the breakdown of carbohydrate reserves and subsequent glycolytic activity. This would be expected to increase the availability of reducing equivalents in the form of cytoplasmic NADH. The current study examines another potential reaction controlling cytoplasmic NADH in the fungus , that of...
Article
UDPglucuronic acid and erythroascorbic acid were identified in extracts of the fungus Neurospora crassa. The concentrations of these two compounds are estimated, in growing wild type N. crassa, to be about 0.10 and 0.28 mumol/ml of cell water, respectively. The pools of these two compounds are regulated by cyclic AMP in Neurospora, both being eleva...
Article
Both wild type and cr-1 mutant (adenylate cyclase and cyclic AMP-deficient) strains of Neurospora crassa contain fructose 2,6-bisphosphate at levels of 27 nmol/g dry tissue weight. This level decreases by about 50% in both strains upon depriving the cells of carbon or nitrogen sources for 3 h. An increase in cyclic AMP levels produced by addition o...
Article
6 polycyclic aromatic hydrocarbon or similar amine carcinogens were tested as inducers of genetic tandem duplications in a rough strain of Salmonella typhimurium. When metabolically activated by rat-liver microsomes, all 6 were active in inducing genetic tandem duplications, yielding from over 3 times to almost 14 times as many tandem duplicants pe...
Article
Several saturated, monosaturated, and polyunsaturated fatty acids produce rapid increases in cyclic AMP levels in the fungusNeurospora crassa when added to the growth medium at 10–50 µM. The time courses of cyclic AMP increase resembled those previously shown to be induced by other agents, reaching peak cyclic AMP levels at about 2 min after fatty...
Article
Selection for 3-amino-1,2,4-triazole (AT) resistance in certain strains of Salmonella typhimurium has been previously shown to select for genetic tandem duplications of the histidine operon. We show here that agents which induce tandem duplications are less effective in such induction in the presence of the pKM101 plasmid. The presence of the plasm...
Article
Wild-typeNeurospora crassa shows a clear hyphal dominance growth pattern with a hierarchy of hyphal diameters containing wide main hyphae, narrow primary branch hyphae, and still narrower secondary branches. Mutants (cr-1), lacking cyclic AMP, lack this size hierarchy when grown in medium without cyclic AMP. When grown in media containing sufficien...
Article
Extensive studies have shown that chemical carcinogenesis involves an initiation-promotion pattern. A gene amplification model of carcinogenesis predicts that initiation involves induction of a genetic tandem duplication. We use a system developed by Anderson and Roth to select for tandem duplication of the histidine operon of Salmonella typhimuriu...
Article
Unequal crossing-over is involved in genetic duplication and deletion in such diverse genetic systems as Drosophila, bacteria, and animal viruses. It is proposed to be involved in the form of unequal sister chromatid exchange in gene amplification in cultured animal cells and during carcinogenesis. Studies of the process of unequal crossing-over ha...
Article
This chapter explores the hypothesis that GTP, possibly acting through high guanine nucleotide energy charge, acts to stimulate a wide variety of anabolic processes involved in growth and cell proliferation. It is, according to this view, a mediator of the pleiotropic response. There are five main types of evidence that support the proposed hypothe...
Article
The cyclic AMP control system in eukaryotes has been highly conserved evolutionarily in four of its central properties. Such conservation suggests conservation of the regulatory function of cyclic AMP. Conservation is seen in the properties of adenylate cyclase, cyclic AMP-dependent protein kinase and, among diverse lower eukaryotes, the control of...
Article
Coupling of ions to the uptake of neutral and basic amino acids via a general amino acid transport system (System II), was studied in a mutant of Neurospora crassa (bat mtr) which lacks other transport systems for these solutes. All amino acids tested--including ones bearing no net charge--elicited rapid membrane depolarization, as expected for ion...
Article
A filtration technique is described to purify Escherichia coli chi 1488 minicells much more rapidly than the usual method involving sucrose gradient centrifugation, and to produce minicells that have not been subjected to osmotic stress. The minicells so prepared are metabolically active as indicated by the in vivo incorporation of [35S]methionine...
Article
The ATP-Mg2+-dependent, guanine nucleotide-stimulated adenylate cyclase of Neurospora crassa was shown to be composed of distinct components which, when mixed, can reconstitute a holoenzyme. After brief heat treatment, the adenylate cyclase activity in crude homogenates of Neurospora was found to have reduced activity and greatly reduced sensitivit...
Article
A novel adenylate cyclase activity was found in crude homogenates of Neurospora crassa. The adenylate cyclase had substantial activity with ATP-Mg2+ as substrate differing significantly from the strictly ATP-Mn2+-dependent enzyme characterized previously. Additionally, the ATP-Mg2+-dependent activity was stimulated two- to fourfold by GTP or guanyl...
Article
A cyclic AMP-binding protein with a native molecular weight calculated to be 82,000 was purified 2,000-fold from Neurospora crassa. The apparent subunit molecular weight was 47,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting that the native protein exists as a dimer of identically sized subunits. The 8-N3-cyclic [32P]AM...
Article
Full-text available
A two-stage model of carcinogenesis is proposed based on recent evidence for the occurrence of proto-oncogenes in the vertebrate genome, evidence for gene amplification during carcinogenesis, and studies of the action of tumor promoters. The model is baed on the view that an increase in the level of gene product from such proto-oncogenes is suffici...
Article
Full-text available
Strains of Neurospora crassa mutant in either of two genes, Crisp-1 (cr1) and Frost (fr), showed no increase of cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels when subjected to several treatments which produce large increases of cyclic AMP in wild-type Neurospora. Evidently, the previously reported deficiencies of adenylate cyclase in the...
Article
was surveyed for cyclic AMP-dependent protein kinase activity. Two peaks (I and II) of protein kinase activity were demonstrated by DEAE-cellulose chromatography of wild type extracts. Peak I was stimulated by cyclic AMP, eluted below 60 mM NaCl and had high activity using histone H2B as substrate. Peak II eluted at 200–250 mM NaCl; its activity wa...
Article
It has been reported that diverse treatments which depolarize the plasma membrane of Neurospora crassa produce rapid increases in cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels. In the current study, membrane active antibiotics, which are known or putative depolarizing agents, were found to produce similar cyclic AMP increases, not only i...
Article
Studies on the crisp-1 (cr-1), cyclic adenosine 3',5'-monophosphate (cAMP)-deficient mutants of Neurospora crassa were undertaken to characterize the response of these mutants to exogenous cyclic nucleotides and cyclic nucleotide analogs. A growth tube bioassay and a radioimmune assay for cyclic nucleotides yielded the following results. (i) 8-Brom...
Article
A new method for obtaining synchronous germination allowed accurate time-course studies of endogenous levels of cyclic adenosine 3',5'-monophosphate and cyclic guanosine 3',5'-phosphate in germinating conidia of Neurospora crassa. The levels of both cyclic nucleotides remained constant throughout germination, showing that they neither signal nor re...
Article
Diverse treatments, which have been shown by Slayman, C. L. (1977) in Water Relations in Membrane Transport in Plants and Animals (Jungreis, A., Hodges, T. K., Kleinzeller, A., and Schultz, S. G., eds) pp. 69-86, Academic Press, New York, to depolarize the plasma membrane of Neurospora, increase levels of adenosine 3':5'-monophosphate (cyclic AMP)...
Article
DNA replication may produce unoccupied regulatory binding sites on DNA. Such unoccupied sites can disrupt regulatory stability after replication has been completed. A mechanism is proposed which can maximize stability by minimizing production of such unoccupied sites. This mechanism probably acts in stabilizing E. coli lysogenic for λ. The role of...
Article
The inducer of sexuality in binds to the saccharide binding site of concanavalin A. Its activity show heterogeneous and relatively low mobility during electrophoresis on sodium dodecyl sulfate polyacrylamide gels. These and other findings support the view that the inducer of sexuality is a glycoprotein.
Article
A specific amino acid transport system in Neurospora crassa is described with affinity for methionine and several of its analogs. This methionine transport system has a Michaelis constant () for l-methionine of about 23 μM and has lower affinity for , ethionine, and norleucine.The methionine transport system has high activity under conditions of su...
Article
Amino acid transport systems I and III in Neurospora are inhibited by amino acids in the intracellular pool (transinhibition). The transinhibition is system specific. The ability of an amino acid to transinhibit a transport system is highly correlated with its affinity for the system. The significance of the system specificity of transinhibition is...

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