The ADA Letter To Dan Burton
Editors Note: This letter was originally sent to Congressman Dan Burton and published on the ADA website, but has since been removed from public viewing by the ADA. We publish the letter here in its entirety under the "fair use" principle of US copyright law.

May 11, 2001

The Honorable Dan Burton
Chairman
Committee on Government Reform
U.S. House of Representatives
Washington, D.C. 20515

RE: Autism - Why the Increased Rates? A One Year Update

Dear Mr. Chairman:

The American Dental Association (ADA) requests that the Committee on
Government Reform accept this letter as a statement for the record for the
committee's hearing on April 25, entitled "Autism -- Why the Increased Rates? A One Year
Update."

During the hearing, Dr. Boyd E. Haley stated in his testimony that
elementary mercury from dental amalgams could work synergistically with other
ethyl-mercury sources and have a cumulative toxic affect on the body. Dr.
Haley postulated that this could be a potential cause of autism and Alzheimer's disease.

There is no scientifically valid evidence linking either autism or
Alzheimer's disease with dental amalgam. And there is no scientifically valid evidence
demonstrating in vivo transformation of inorganic or mercury vapor into
organo mercury species in individuals occupationally exposed to amalgam mercury
vapor. (Chang, S.B. et al., Factors Affecting Blood Mercury Concentrations
in Practicing Dentists; Journal of Dental Research 1992, 71(1) 66-74).

Based on currently available scientific evidence, the ADA believes that
dental amalgam is a safe, affordable and durable material for all but a handful of
individuals who are allergic to one of its components. It contains a mixture
of metals such as silver, copper and tin, in addition to mercury, which
chemically binds these components into a hard, stable and safe substance.
Dental amalgam has been used for more than 150 years and, during that time, has established
an extensively reviewed record of safety and effectiveness.

Issued in late 1997, the FDI World Dental Federation and the World Health
Organization consensus statement on dental amalgam stated, "No controlled
studies have been published demonstrating systemic adverse effects from
amalgam restorations." The document also states that, aside from rare
instances of local side effects of allergic reactions, "the small amount of mercury
released from amalgam restorations, especially during placement and removal, has not
been shown to cause any, adverse health effects."

The ADA's Council on Scientific Affairs' 1998 report on its review of the
recent scientific literature on amalgam states: "The Council concludes that,
based on available scientific information, amalgam continues to be a safe
and effective restorative material." The Council's report also states, "There
currently appears to be no justification for discontinuing the use of dental
amalgam."

In an article published in the February 1999 issue of the Journal of the
American Dental Association, researchers report finding "no significant
association of Alzheimer's disease with the number, surface area or history
of having dental amalgam restorations" and "no statistically significant
differences in brain mercury levels between subjects with Alzheimer's
disease and control subjects."

The U.S. Public Health Service issued a report in 1993 stating there is no
health reason not to use amalgam, except in the extremely rare case of the
patient who is allergic to a component of amalgam. This supports the
findings of the Food and Drug Administration, the National Institutes of Health
Technology Assessment Conference and the National Institute of Dental and
Craniofacial Research, that dental amalgam is a safe and effective restorative
material.

There have been several peer reviewed scientific studies concerning the
safety of dental amalgam. These studies disprove any link between dental amalgam
and various medical conditions. We have listed some of them below:

* Dahl JE, Sundby J, Hensten-Pettersen A, Jacobsen N. " Dental Workplace
exposure and effect on fertility " Scand J Work Environ Health 1999
Jun;25(3):285-90.
The study groups consisted of 558 female dental surgeons (1/3 of whom placed
more than 50 fillings a week) and 450 high school teachers (control) that
had given birth in Norway to at least 1 living child. The study comprised data
from a total of 1408 pregnancies. The effects of practicing dentistry and of
the given workplace exposure on fertility were analyzed with the discrete
proportional hazard regression method. Conclusions: Occupational exposures had no clear adverse effects on
fertility among the female dental surgeons studied.

* Schuurs AH. " Reproductive toxicity of occupational mercury. A review
of the literature" J. Dent 1999;27(4):249-56. This paper provides insight into the potential reproductive effects on
handling dental silver amalgam. Both animals and case reports and
epidemiological studies were reviewed. Conclusions: The studies conclude that negative
reproductive effects from exposure to mercury in the dental office are
unproven. Consequently, given the low amounts of mercury stemming from
dental amalgam fillings, the population at large are at even less risk than dental
staff.

* Saxe SR, Wekstein MW et al. "Alzheimer's disease, dental amalgam and
mercury", JADA 1999 Feb;130(2):191-9
This study consisted of 68 human subjects with diagnosed Alzheimer's disease
and 33 control subjects without Alzheimer's to determine mercury levels in
multiple brain regions at autopsy and to ascertain the subjects' dental
amalgam status and history. Conclusions: Mercury in dental amalgam
restorations does not appear to be a neurotoxic factor in the pathogenesis of this disease.
The authors found that brain mercury levels are not associated with dental
amalgam, either from existing amalgam restorations or according to subjects'
dental amalgam restoration history. Furthermore, dental amalgam restorations,
regardless of number, occlusal surface area or time, do not relate to brain
mercury level.

* Ahlqwist M, Bengtsson C et al, "Serum mercury concentration in
relation to survival, symptoms, and diseases: results from the prospective
population study of women in Gotherburg, Sweden. Acta Odontol Scand 1999 June;
57(3):168-74
This prospective population study of women in Gothenburg, Sweden was started
in 1968-69 and comprised of 1462 women aged 38-60 years at baseline.
Follow-up studies were conducted in 1974-75, 1980-81 and 1992-93. Conclusions: No
statistically significant correlation was observed between dental amalgam
and the incidence of diabetes, myocardial infarction, stroke, or cancer. No
association was established between disease and mercury on a population
basis in middle-aged and older women.

The National Institute of Dental and Craniofacial Research is currently
supporting two very large clinical trials on the health effects of dental
amalgam. Studies underway for several years each in Portugal and the
Northeastern United States involve not only direct neurophysiological
measures but also behavioral and cognitive functional assessments. In addition, the
trials are monitoring the impact of amalgam on immune function, antibiotic
resistance and renal function. Preliminary findings from these studies are
consistent with any number of small and large epidemiological studies
published over the years concerning the health effects of dental amalgam.

The ADA supports ongoing research in the development of new materials that
it hopes will someday prove to be as safe and effective as dental amalgam.
However, the ADA continues to believe that amalgam is a valuable, viable and
safe choice for dental patients and concurs with the findings of the U.S.
Public Health Service that amalgam has "continuing value in maintaining oral
health."

Sincerely,

Signed

Robert M. Anderton, D.D.S., J.D., LL.M.
President

RMA:MT:chf

Document Posted: May 11, 2001
Page Updated: May 11, 2001




Dr. Boyd Haley Rebuts the American Dental Association
Position on Mercury-Amalgam Safety

  23 May 2001

The Honorable Dan Burton
Chairman
Committee on Government Reform
U.S. House of Representatives
Washington, D.C.

RE: May 11th letter by Robert M. Anderton, D.D.S., J.D., LL.M. and President of the ADA, challenging my statement to the Committee on Government Reform looking at the topic, Autism-Why the Increased Rates? A One Year Update.

Dear Mr. Chairman:

At the April 25th meeting of your committee I gave testimony that the President of the American Dental Association (ADA) takes exception to in a letter sent to you dated 11 May 2001. Quoting from that letter the testimony the ADA dislikes is "that elementary mercury from dental amalgam could work synergistically with other ethyl-mercury sources and have a cumulative toxic effect on the body. Dr. Haley postulated that this could be a potential cause of autism and Alzheimer's disease." I stand by my statement as a sensible concern based on published scientific research regarding synergist toxicities caused by two very toxic agents, mercury and the organic mercury compound thimerosal. This concern is elevated since mercury exposure from amalgams to a pregnant mother concentrates in the fetus and a single vaccine given to a six-pound newborn is the equivalent of giving a 180-pound adult 30 vaccinations on the same day. Include in this the toxic effects of high levels of aluminum and formaldehyde contained in some vaccines, and the synergist toxicity could be increased to unknown levels. Further, it is very well known that infants do not produce significant levels of bile or have adult renal capacity for several months after birth. Bilary transport is the major biochemical route by which mercury is removed from the body, and infants cannot do this very well. They also do not possess the renal (kidney) capacity to remove aluminum. Additionally, mercury is a well-known inhibitor of kidney function. Common sense indicates that the concern I expressed should be taken seriously since we do not know how combined toxicities effect humans, especially in utero. Consider the current epidemic death on birth of over 500 foals from apparently healthy mares around Lexington, KY. These deaths were identified as being due to a low level toxicity delivered by caterpillars eating poison plants and later, on migration, depositing their waste products on grass being eaten by the mares. The point being it is the infant in utero that suffered most on exposure to low level, toxins, not the mother. Combined mercury toxicities can be devastating as I reference below and in the many references available on the www.altcorp.com website. What is needed is research by non-biased scientists to clarify this, something our FDA and NIDCR have refused to do. As the American public find out what has happened regarding this issue, they will be quite angry. This is a biomedical science issue that should have been resolved a long time ago by the responsible federal agencies.

Below I present detailed and referenced information supporting my case and respond to various statements made by the ADA President that I believe to be misleading and sometimes flagrantly wrong. The ADA seems to think it has the right to select which research it believes and to trash that research that says it is wrong, even though the latter represents the bulk of published research. To address the issues raised by the ADA President in his letter I will go in sequential order of the comments made in the letter placing the ADA comments in italics and providing scientific references for my conclusions.

"There is no scientifically valid evidence linking either autism or Alzheimer's disease with dental amalgam". First, mercury is a well-known, potent neurotoxicant, and common sense would lead to the conclusion that severe neurotoxins would exacerbate all neurological disorders, including Parkinson's, ALS, MS, autism and AD. Several research papers in refereed, high quality journals and scientific publications have shown that mercury inhibits the same enzymes in normal brain tissues as are inhibited in AD brain samples (1a-c, 2, 3). AD is pathologically confirmed post-mortem by the appearance of neuro-fibillary tangles (NFTs) and amyloid plaques in brain tissue. Published research, within the past year, has shown that exposure of neurons in culture to sub-lethal doses of mercury (much less than is observed in human brain tissue) causes the formation of NFTs (4), the increased secretion of amyloid protein and the hyper-phosphorylation of a protein called Tau (5). All three of these mercury-induced aberrances are regularly identified as the major diagnostic markers for AD. In the manuscript published in the J. of Neurochemistry (5) the authors state "These results indicate that mercury may play a role in the patho-physiological mechanisms of AD." In most of these experiments, mercury and only mercury among the several toxic heavy metals tested, caused the AD related responses reported. Many medically trained individuals would agree that if something causes the appearance of the pathological hallmarks confirming the disease then it likely causes the disease. I at least have limited my claims to exacerbation of these diseases to err on the side of caution.

Further, consider this about AD. A study of 500 sets of identical twins from World War II era lead to the conclusion that sporadic AD which represents 90% of the cases was not a directly inherited disease. In many cases one twin would get AD and the other would not. Genetic susceptibility is involved, but a toxic exposure is required (e.g., if you are genetically susceptible to being an alcoholic you still need to be exposed to alcohol to become one). The work by Rose's group at Johns Hopkins University implicates APO-E genotype as a "risk" factor with APO-E2 being protective and APO-E4 being a major risk factor. APO-E2 has the ability to protect the brain from mercury by having two additional thiol-groups to bind mercury appearing in the cerebrospinal fluid whereas APO-E4 does not have this additional capability (1). This may explain the proven genetic susceptibility to AD of the APO-E4 carriers.

NIH has spent hundreds of millions of dollars to find a causal factor for AD. Yet, no virus, yeast or bacteria has been identified so the cause remains unknown to general science. The rate of AD per 1,000 population is nearly the same in California, Michigan, Maine, North Carolina, Florida, Texas, etc. It is not significantly different for rural versus urban individuals, or factory workers versus those with outside jobs. So the primary toxicant that may be involved is most likely not environmental. Therefore, it must be a very personal toxicant, like what you put in your mouth. Since we place grams of a neurotoxic metal, mercury, in our mouths in the form of dental amalgam this makes it a good suspect for the exacerbation of AD---not that all would be affected, just those that are genetically susceptible, or those who become ill enough to fall prey to the toxicity, or those that are also exposed to another synergistic toxin (see below).

The one fact that ties mercury into a major suspect for AD is the fact that most of the proteins/enzymes that are inhibited in AD brain are thiol-sensitive enzymes. Mercury is one of the most potent chemical inhibitors of thiol-sensitive enzymes and mercury vapor easily penetrates into the central nervous system (2). Mercury is not the only toxicant to inhibit thiol-sensitive enzymes. Thimerosal and lead will do this also as well as reactive oxygen compounds created in oxidative stress and many other industrial compounds. However, mercury has been reported to be significantly elevated in AD brain (14a,b, 15). Mercury is in many mouths being emitted from dental amalgam and absolutely would exacerbate the clinical condition identified as AD. Therefore, mercury should be considered as a causal contributor since mercury can produce the two pathological hallmarks of the disease and inhibits the same thiol-sensitive enzymes that are dramatically inhibited in AD brain.

It is documented by a 1991 World Health Organization report that dental amalgams constitute the major human exposure to mercury. Grams of mercury are in the mouths of individuals with several amalgam fillings. Further, the level of blood and urine mercury positively correlates with the number of amalgam fillings. This was confirmed by a recently published NIH funded study (6). Therefore, I fail to see the ADA's viewpoint that there is no scientifically valid evidence linking mercury from amalgams to exacerbating AD, especially since mercury produces the diagnostic hallmarks of AD (4,5). The ADA hides behind the fact that there has not been an epidemiological study to attempt to correlate mercury exposure and AD. However, absence of proof is not proof of absence. This also begs the question why the ADA, the FDA and the National Institutes of Dental Craniofacial Research (NIDCR) have not pushed for such a study? These agencies know this would be immensely expensive and only the U.S. government could afford to support any reliable long-term study. Yet, these same responsible agencies have failed to confirm as safe the placing into the mouth of Americans grams of the most toxic heavy metal Americans are exposed to. The dental branch of the FDA has steadfastly refused to investigate the toxic potential of dental amalgam.

Look at the references in the ADA letter! Even they must quote Scandinavian literature to support their contentions of safety, and even then they have to reference papers on fertility instead of neurotoxicity! Where is the ADA, FDA and NIDCR supported U.S. research in this area? Go to the NIH web-sites and look for research on the safety of mercury from amalgams, or try to find an NIH study concerning possible mercury involvement in any common neurological diseases. NIH does support research on methyl-mercury, as we seem to like beating up on the fishing industry whilst leaving the dental industry alone. However, according to the NIH study about 90% of the mercury in our bodies is elemental mercury, not methyl-mercury, showing the exposure is more likely from dental amalgams rather than fish (6). Support at NIH has been very sparse for investigating the relationship of elemental mercury exposure to neurological diseases.

"And there is no scientifically valid evidence demonstrating in vivo transformation of inorganic mercury into organo mercury species in individuals occupationally exposed to amalgam mercury vapor". There was a paper published entitled "Methylation of Mercury from Dental Amalgam and Mercuric Chloride by Oral Streptococci in vitro" (19). This strongly indicates that "organo mercury species" are indeed capable of being made in the human body and may explain the appearance of methyl-mercury in the blood and urine of individuals who don't eat seafood.

Further, periodontal disease is considered one of the major risk factors for stroke, heart and cardiovascular disease and late onset, insulin independent diabetes. Many studies of the toxicants produced in periodontal disease have identified hydrogen sulfide (H2S) and methane-thiol (CH3SH) as major toxic products of infective anerobic bacteria in the mouth metabolizing the amino acids cysteine and methionine, respectively. These volatile thiol-compounds are what cause bad-breath! Methane-thiol (CH3SH) would react immediately and spontaneously in the mouth with amalgam generated mercury cation to produce the following two compounds, CH3S-HgCl and CH3S-Hg-SCH3, which are organo-mercurial compounds (check this out with any competent chemist). They are also very similar in structure to methyl-mercury (CH3-HgCl) and dimethyl-mercury (CH3-Hg-CH3), the latter which caused the highly publicized death of a University of Dartmouth chemistry professor 10 months after she spilled two drops on her gloved hand. We have synthesized CH3S-HgCl and CH3-Hg-CH3 in my laboratory and tested their toxicity in comparison to Hg2+. As expected, they were both more toxic than Hg2+ and this data is available on the www.altcorp.com web-site. Therefore, the ADA President is badly misinformed on this issue. Additionally, I am amazed that the researchers at the ADA and NIDCR did not previously report on this obvious chemistry as I would imagine this is the kind of topic they should be addressing.

"Based on currently available scientific evidence, the ADA believes that dental amalgam is a safe, affordable and durable material for all but a handful of individuals who are allergic to one of its components. It contains a mixture of metals such as silver, copper and tin, in addition to mercury, which chemically binds these components into a hard, stable and safe substance." This is a totally wrong statement unless you underline the "ADA believes" and define how big is a "handful of individuals". Sensible people want "believes" replaced with "knows" and a "handful" replaced with a "hard number". Amalgams emit dangerous levels of mercury and the ADA absolutely refuses to accept this fact or even to study the possibility. Otherwise, the ADA administrators seem to be unable to separate fact from fiction. Consider, if they wanted to destroy my argument on amalgam toxicity they would reference several solid, refereed publication showing that mercury is not emitted from dental amalgams---but they cannot do this with even one article. They always state the "estimate" is that a very, very, very small amount. Competent, well-informed researchers don't use the evasive language used in the ADA President's letter. They would state the amount is so many micrograms mercury released per centimeter squared amalgam surface area and a "handful of individuals" would be a percentage of our population! Lets look at the published literature.

First, careful evaluation of the amount of mercury emitted from a commonly used dental amalgam in a test tube with 10 ml of water was presented in an article entitled "Long-term Dissolution of Mercury from a Non-Mercury-Releasing Amalgam". This study showed that "the over-all mean release of mercury was 43.5 ± 3.2 micrograms per cm2/day, and the amount remained fairly constant during the duration of the experiments (2 years)" (7). This was without pressure, heat or galvanism as would have occurred if the amalgams were in a human mouth. Further, research where amalgams containing radioactive mercury were placed in sheep and monkeys, showed the radioactivity collecting in all body tissues and especially high in the jaw and facial bones. (8,9). Another publication, from a major U.S. School of Dentistry, stated that solutions in which amalgams had been soaked were "severely cytotoxic initially when Zn release was highest" (13). Zn is a needed element for body health and is found in very low percentages in dental amalgams when compared to mercury and why mercury was not mentioned in the abstract of this publication baffles me. Why would the statement be true? Because Zn2+ is a synergist that enhances mercury toxicity! However, does this sound like amalgams are a safe, stable material? We have repeated similar amalgam soaking experiments in my laboratory and the results can be seen at www.altcorp.com. Cadmium (from smoking), lead, zinc and other heavy metals enhanced mercury toxicity as expected (this research is currently being prepared for publication).

The ADA claim that a zinc oxide layer is formed on the amalgams that decreases mercury release is true, if you don't use the teeth. The zinc oxide layer would be easily removed by slight abrasion such as chewing food or brushing the teeth. Further, my laboratory has confirmed that solutions in which amalgams have been soaked can cause the inhibition of brain proteins that are inhibited by adding mercury chloride, and these are the same enzymes inhibited in AD brain samples.

Further, mercury emitting from a dental amalgam can be easily detected using the same mercury vapor analysis instrument used by OSHA and the EPA to monitor mercury levels. Anyone who does not believe mercury is emitted from amalgams should consider doing the following. Have your local dentist make 10 amalgams using the same material he/she places in your mouth. Take these 10 amalgams to your nearest research university's department of chemistry or toxicology department and have them determine how much mercury is being emitted. For example, have them calculate how long it would take a single spill of hardened amalgam to make a gallon of water too toxic to pass EPA standards as drinking water. You will then have an answer from an unbiased, solid group of scientists who are trained to do such determinations. Also, remember the level of mercury they measure would not include the increase that would occur with amalgams in the mouth where chewing, grinding your teeth, drinking hot liquids and galvanism greatly increase the release of mercury. Since this approach can be easily done by anyone don't you think the ADA, FDA and other amalgam supporters would have this published by now if the level of mercury released was below the danger level?

Here is their attempt. According to an ADA spokesman he has "estimated" that only 0.08 micrograms of mercury per amalgam per day is taken into the human body. Applying simple math to this "estimate" of 0.08 micrograms/ day one would divide this amount by 8,640 (24 hours/day X 60 minutes/hour X 6 ten second intervals/minute) to determine the amount of mercury in micrograms available for a ten second mercury vapor analysis. Consider that somewhere between one-half to five-sixths of the mercury released would be into the tooth (that area of the amalgam that exists below the visibly exposed amalgam surface) and not into the oral air. In addition, some mercury in the oral air would be rapidly absorbed into the saliva and oral mucosa (mercury loves hydrophobic cell membranes) and also not be measured by the mercury analyzer. Further, as the mercury analyzer pulls mercury containing oral air into the analysis chamber, mercury free ambient air rushes into the oral cavity decreasing the mercury concentration. Taking all of this into account you can calculate that most mercury analyzers could not detect this "estimated" 0.08 micrograms/day level of mercury even if you had several amalgams. However, the fact is that it is quite easy to detect mercury emitting from one amalgam using these analyzers. Therefore, the "estimate" by this ADA spokesman is way to low. Also, if you gently rub the amalgam with a tooth-brush the amount of mercury emitted goes up dramatically. This is a test anyone can do and demonstrate to any group. The ADA spokesmen state that the mercury vapor analyzer is not accurate at determining oral mercury levels and they are quite correct. However, using this instrument would greatly underestimate the amount of mercury exiting the amalgam. The very fact that the mercury analyzer detects high levels of oral mercury strongly indicates the emitted amount of mercury is too high to be acceptable.

Mercury release from dental amalgams is also the reason OSHA has used this analyzer to make the dentists place unused amalgam in a sealed container under liquid glycerin. This is done so that the mercury vapors from the amalgams will not contaminate the dental office making it an unsafe place to work. This is also the reason the EPA insists that removed amalgam filling and extracted teeth containing amalgam material be picked up and disposed of as toxic waste. Apparently, the only safe place for amalgams is in the human mouth if you believe what the ADA believes.

"Amalgams have been used for 150 years and, during that time, has established an extensively reviewed record of safety and effectiveness." First, what other aspect of industry or medicine is still using the same basic manufactured material that they used 150 years ago? One has to ask the question as to what has hindered the progress of development of better and safer dental materials? Also, consider that in the early 1900s the average life expectancy of most Americans was about 50 years of age and most of them could not afford dental fillings. Fifty to sixty years is much less than the average age of onset of AD. Further, amalgams became more available to most working class Americans after World War II, or in the early 1950s. The greatest increase in the use of amalgam occurred at about this time and these 'baby boomers are the great ongoing amalgam experiment'. They are now reaching the age where AD appears and have lived most of their lives carrying amalgam fillings. They also wonder what is causing their chronic fatigue as the physicians can find nothing systemically wrong with them. I would encourage all concerned to contact the health experts on the rate of increase of AD in the U.S.A. at this time. Consider the cost it will place on the taxpayer and how much we would save if we could even remove the exacerbation factors that might speed up the onset of AD. I must point out that the "extensively reviewed record of safety" mentioned in the ADA letter was mostly done by dentists and committees dominated by ADA dentists. Also, much of the "safety opinion" was developed long before words like Alzheimer's disease and chronic fatigue were commonplace. Further, these were "reviews" and not carefully documented studies based on scientific experimentation and done by unqualified dentists, not medical scientists. Dentists are not trained to do basic research, nor are they trained in toxicology. Furthermore, the ADA does have a vested interest in keeping amalgam use legitimate. The ADA was founded on using amalgam technology and participated in patenting and licensing amalgam technology. One has to question why there has not been a general outcry by the bulk of well-meaning dentists and their patients and this question should be addressed. The International Association of Oral Medicine and Toxicology, started by American & Canadian dentists, does adamantly disagree with the ADA on the issue of safety of dental amalgams and this organization has the mantra of "Show me your science" with regards to all dental issues.

The ADA, through state dental boards stacked with ADA members, has instigated a "gag order" preventing dentists from even mentioning to their patients that amalgams are 50% mercury. Dentists cannot state that mercury is neurotoxic and emits from amalgams and that the dental patient should consider this as they select the tooth filling material they want used. If a dentist informs a patient of these very truthful facts he will be consider not to be practicing good dentistry and his license will be in jeopardy. Attacking a person's freedom of speech because he is telling the truth and causing serious questions to be asked about the protocols pushed by a bureaucracy (the ADA) makes me seriously question the commitment the ADA has for the health of the American people. The negative stand taken by many state dental boards against even informing the patients about the mercury content of amalgams and the other filling choices they have does not speak well for the organized dental profession. What medical group would give a treatment to a patient without telling them of the risks involved?

"Issued late in 1997, the FDI World Dental Federation and the World Health Organization consensus statement on dental amalgam stated "No controlled studies have been published demonstrating systemic adverse effects from amalgam restorations."" My first comment would be to question "who staffed these committees and what percentage were connected to the ADA though the NIDCR or the FDA dental materials branch or other relationships?" We appear to have the foxes guarding the henhouse! Then I would again point out that "absence of proof is not proof of absence". I would then ask 'have any controlled studies been done and if not, why not?' If the ADA dentists insist on placing amalgams in the mouth, are they not required to show it is safe, not the other way around? Should not the ADA and others concerned push to require the FDA to prove amalgams are safe instead of totally ducking this issue. Go to the FDA dental materials web-site and try to find any evaluation of amalgam safety---you will not succeed. The dental branch of the FDA refuses to do a safety study on amalgams and this is shame on our government.

"the small amount of mercury released from amalgam restorations, especially during placement and removal, has not been shown to cause anyadverse effects." This increase in mercury exposure has also not been shown to be safe by proving it does not cause any adverse effects! Are we to believe this elevated exposure to a toxic metal is good for us? If one were in a building that caused the rise in blood/urine mercury that appears after dental amalgam removal, then OSHA would shut the building down. In fact, no study by the ADA or NIDCR has been completed that specifically and accurately addresses this issue. Yet, the ADA leads us to believe that additional exposure to toxic mercury from these procedures is not dangerous to our health. Mercury toxicity is a retention toxicity that builds up during years of exposure. The toxicity of a singular level of mercury is greatly increased by current or subsequent, low exposures to lead or other toxic heavy metals (12). Therefore, the damage caused by amalgams could occur years after initial placement and at mercury levels now deemed safe by the ADA.

Our ability to protect ourselves from the toxic damage caused by exposure to mercury depends on the level of protective natural biochemical compounds (e.g. glutathione, metallothionine) in our cells and the levels of these protecting agents is dependent upon our health and age. If we become ill, or as we age, the cellular levels of glutathione drop and our protection against the toxic effects of mercury decreases and damage will be done. This is strongly supported by numerous studies where rodents have been chemically treated to decrease their cellular levels of protective glutathione and then treated with mercury, always with dramatic injurious effects when compared to controls. Therefore, published science indicates that mercury toxicity is much more pronounced in infants, the very old and the very ill.

A recent NIH study on 1127 military men showed the major contributor to human mercury body burden was dental amalgams. The amount of mercury in the urine increased about 4.5 fold in soldiers with the average number of amalgams versus the controls with no amalgams. In extreme cases it was over 8 fold higher. Since the total mercury included that from diet and industrial pollution are we to expect that this 4.5 to 8 fold average increase in mercury is not detrimental to our health? Does this indicate that amalgams are a "safe and effective restorative material"? Is the public and Congress expected to be so naïve as to believe that increased exposure above environmental exposure levels is not damaging? Then why are pregnant mothers told to limit seafood intake when mercury exposure from amalgams is much greater? Then why is the EPA pushing regulations to force the chloro-alkali plants and fossil fuel plants to clean up their mercury contributions to our environment? Obviously, from this study most of the human exposure to mercury is from dental amalgams, not fossil fuel plants. Yet, the FDA lets the dental profession continue to expose American citizens to even greater amounts of mercury. They do this by refusing to test amalgam fillings as a source of mercury exposure. Also, remember that the amalgam using ADA dentists are a major contributor to mercury in our water and air through mercury leaving the dental offices, and even when we are cremated.

"The ADA's Council on Scientific Affairs 1998 report on its review of the recent scientific literature on amalgam states: "The Council concludes that, based on available scientific information, amalgam continues to be a safe and effective restorative material." and "There currently appears to be no justification for discontinuing the use of dental amalgam." What would you expect an ADA Council to say? The ADA, as evidenced in the current letter by the President of the ADA, only quotes and considers valid the published research that supports their desire to continue placing mercury containing amalgam fillings in American citizens. When were dentists trained to evaluate neurological and toxicological data and manuscripts? What is needed is an international conference where both the pro- and anti-amalgam researchers show up and present their data in front of a world-class scientific committee. I would challenge the ADA to line up their scientists and supporters to participate in such a conference. This could be held in Washington, D.C. so the FDA officials could easily attend. Perhaps we could persuade the FDA to sponsor such a conference. However, this is unlikely since a recent written request to have a conference to evaluate the safety of amalgams was rejected in a letter from the FDA and signed by three FDA/ADA dentists who presented the ADA line on this issue. Doesn't it seem a bit fraudulent to have FDA/ADA dentists deciding on whether or not a safety study should be done on mercury emitting amalgams being placed in human mouths with the blessing of the ADA? This does seem like a conflict in interest that Congress should address.

"In an article published in the February 1999 issue of the Journal of the American Dental Association, researchers report finding "no significant association of Alzheimer's disease with the number, surface area or history of having dental amalgam restorations." This research was lead by a dentist, Dr. Sax. It was submitted to the J. of the American Medical Association and rejected. It was then submitted to the New England Journal of Medicine and rejected. It was then published in the ADA trade journal, JADA, that is not a refereed, scientific journal. JADA is loaded with commercial advertisements for dental products. They even called a "press conference" announcing the release of this article! Calling a press conference for a twice-rejected publication that is to appear in a trade journal is playing politics with science at its worst! At this press conference two of the authors made unbelievable statements that were not supported by any of the data in the article and conflicted with numerous major scientific reports, including the 1998 NIH study (6). Some of these were high-lighted in the side-bars of the ADA publication. I would suggest that those concerned with this article visit Medline and look at the publication records of the two individuals who made these statements. Also, look at the three earlier excellent publications in refereed journals by some of the other authors showing significant mercury levels in the brains of AD subjects compared to controls (14a,b, 15). However, put a dentist in charge of the project and the data gets reversed!

Apply some common sense. The ancillary comments by some of the authors and the results of the JADA publication are in total disagreement with the vast majority of research published that looks at elevated mercury levels in subjects with amalgam fillings. For example, the NIH study on military men discussed above showed a very significant elevation of mercury in the blood that correlated with number of dental amalgams (6). Another recent publication demonstrated elevated mercury in the blood of living AD patients in comparison to age-matched controls (10). These studies clearly show that there should be increased mercury in your blood if you have amalgams and especially if you have AD and amalgams (6,10). Does not the brain have blood in it? This makes it a total mystery as to how could the authors of the JADA article not find elevated brain mercury levels in patient with existing amalgams and/or AD. Even cadavers have brain mercury levels that correlate with the number of amalgam fillings they had on death.

Further, if you are addressing the contribution of amalgams to brain mercury and AD wouldn't it be important to divide the AD and control subjects into those with and without existing amalgams on death? In the JADA article this was not done and represents a major research flaw! That this was not done also arouses suspicion. I participated in submitting a letter pointing out this flaw to editors of JADA but they refused to acknowledge the letter and did not publish our comments. It is my opinion that the entire situation around this singular supportive publication of the ADA position on amalgams, brain mercury levels and AD represents a weak attempt at controlling the mind-set of well-meaning dentists, scientists, physicians and medical research administrators. It definitely impedes honest scientific debate. It also explains the cavalier attitude of the ADA and NIDCR about elemental mercury exposure and toxicity when compared to the more serious approaches taken by the EPA and OSHA.

With regards to the JADA article summary that "no statistically significant differences in brain mercury levels between subjects with Alzheimer's disease and control subjects." Here I must quote Mark Twain on honesty, "There are liars, damned liars and statisticians." Comparing the level of mercury in the AD versus control alone using straight-forward statistics previously showed a significant difference on mercury levels in AD versus control subjects (14a,b, 15). However, there are anomalies, confounders and other factors that can be considered in this situation, especially if you don't like the initial results. This allows one to invoke a Bon-Feroni statistical manipulation. With Bon-Feroni you include the comparison of one pair of data (that may be statistically significantly different taken alone, e.g. mercury levels in the brains of AD versus control subjects) with several other pairs of data rendering the difference statistically insignificant. One known weakness of the Bon-Feroni treatment of several coupled pairs of comparisons is that one very likely will miss a single comparison that is significantly different, and clever people know this. It is my opinion that application of the Bon-Feroni manipulation is what happened in this JADA study that reversed the previous significance of the mercury levels in AD versus control brain previously reported. Research previously reported by some of the very same researchers involved in the JADA study consistently indicated that mercury levels were higher in AD versus age-matched control brains (14a,b, 15). Only when an ADA dentist became involved did the results change to being insignificant. I think the data used in this JADA article and funded by NIH needs to be re-evaluated by a different statistician if we are to ever really know if the mercury levels in the AD brains differed significantly from controls.

The letter from the ADA President then lists four publications as proof of amalgams having no statistically significant negative effects. Two of these were published in Scandinavian Journals, another was a review of the literature in a Dental Journal, and one was the JADA article mentioned above. Sweden is well known to have lead the world in the restriction and replacement of dental amalgams with non-mercury containing materials. Forces are pushing hard to get the use of amalgams accepted again in Sweden to eliminate this embarrassment to our ADA. The current situation in Sweden and some other European countries, Canada and Japan seriously questions the ADA contention of amalgam safety. What if people in Sweden become healthier without amalgams?

Additionally, the studies quoted by the ADA President were epidemiological studies. These are very complex as many confounders are included which make finding a statistically significant difference very difficult. So the results are negative, nothing found, and not surprising. However, they are in disagreement with numerous other similar reports and appear to be hand-selected to support the ADA position. One has to wonder, since the ADA President seemed to visit Swedish journals to support the ADA position, how he missed the research of the Nylander group in Sweden that showed increased mercury content in brains and kidneys of humans in relationship to exposure to dental amalgams (17,18). Also, the referenced studies in the ADA letter did not involve neurotoxicity, autism or neurological disease---which is the question at hand. Rather, they addressed fertility, reproduction and other systemic illnesses. Could not the ADA find references to focus on neurotoxiological studies? What about the 1989 study that showed elevated levels of mercury in 54 individuals with Parkinson's disease when compared to 95 matched controls (16)? Further, one ought to consider who was doing these touted ADA studies and any vested interest they may have in the outcome. I am also aware of studies done in the U.S.A. by major research universities that would disagree with the conclusions drawn by the ADA on this subject yet these articles are not considered in the ADA letter.

At the end of the last publication the quote "Conclusions: No statistically significant correlation was observed between dental amalgam and the incidence of diabetes, myocardial infarction, stroke, or cancer." How does this relate to an article published in the J. of the American College of Cardiology where the mercury levels in the heart tissue of individuals who died from Idiopathic Dilated Cardiomyopathy (IDCM) contained mercury levels 22,000 times that of individuals who died of other forms of heart disease? Where did this tremendous amount of mercury come from? Even a Bon-Feroni manipulation could not make this difference insignificant! Many who die of IDCM are well-conditioned, young athletes who drop dead during sporting events---and they live in locations and in economic environments where sea-food is not a dietary mainstay. Perhaps the victims of IDCM are within the ADA Presidents "handful of individuals who are allergic to one of its components."

"The National Institute of Dental and Craniofacial Research is currently supporting two very large clinical trials on the health effects of dental amalgam. Studies underway for several years each in Portugal and the Northeastern United States involve not only direct neurophysiological measures but also cognitive and functional assessments." Do we really think that the NIDCR and associated ADA personnel are going to deliver up a conclusion to American parents saying "we put a mercury containing toxic material in your child's mouth that lowered his/her I.Q. and made him more susceptible to neurological problems in comparison to the children whom we selected to not get exposed to this toxic material"? It is my opinion that most bureaucracies don't have a brain or a heart, but they do have a very strong survival instinct. Therefore, the results presented from this study will likely follow previously ADA supported research, i.e. no significant results.

Since the NIDCR started this project only 4 years ago one has to ask why it took so long for them to get involved since the "amalgam wars" have been going on for scores of years? Was it the overwhelming amount of modern science showing mercury from amalgams being a major part of the daily exposure that forced their hand and they had to develop a defense? Would I trust the conclusions of this study without knowing who put it together and who did the statistics? Not any more than I trust the conclusions of the JADA article mentioned in the ADA letter that stupendously concludes that mercury from dental amalgams does not get into the brain.

As was proven by the tobacco situation, trying to find any significant negative effect of one product (amalgams) related to any disease through epidemiological studies is very difficult and complex. To do this with mercury would be difficult because of the synergistic effect two or more toxic metals or compounds (e.g. cadmium from smoking) may have on the toxicity of the mercury emitted from amalgams. For example, one publication showed that combining mercury and lead both at LD1 levels caused the killing rate to go to 100% or to an LD100 level (12). An LD1 level is where, due to the low concentrations, the mercury or the lead alone was not very toxic alone (i.e., killed less than 1% of rats exposed when metal were used alone). The 100% killing, when addition of 1% plus 1% we would expect 2%, represents synergistic toxicity. Therefore, mixing to non-lethal levels of mercury plus lead gave an extremely toxic mixture! What this proves is that one cannot define a "safe level of mercury" unless you absolutely know what others toxicants the individual is being exposed to. The combined toxicity of various materials, such as mercury, thimerosal, lead, aluminum, formaldehyde, etc., is unknown. The effects various combinations of these toxicants would have is also not defined except that we know they would be much worse than any one of the toxicants alone. So how could the ADA take any exception, based on intellectual considerations, to my contention that combinations of thimerosal and mercury could exacerbate the neurological conditions identified with autism and AD? Autism and AD have clinical and biological markers that correspond to those observed in patients with toxic mercury exposure. Why would the ADA take this position? I personally feel like I have been in a ten year argument with the town drunk on this issue. Facts don't count and data is only valid if it meets the pro-amalgam agenda.

The ADA was founded on the basis that mercury-containing amalgams are safe and useful for dental fillings. This may have been an acceptable position in 1850. However, modern science has proven that amalgams constantly emit unacceptable levels of mercury. Especially as the average life span has increased from 50 to 75-78 years of age where AD and Parkinson's become prevalent diseases. The ADA can try to verify its position using selected epidemiological studies. But the bottom line is that amalgams emit significant levels of neurotoxic mercury that are injurious to human health and would exacerbate the medical condition of those individuals with neurological diseases such as ALS, MS, Parkinson's, autism and AD.

I am hoping that the ADA sent this letter to your committee and also placed it on the ADA web-site to indicate that they are now willing for a wide-open discussion to take place on the issue of dental amalgams. I, for one, would welcome a major scientific conference on this issue. The ADA should feel free to post my letter in response and address any issue they feel that I am mistaken about. However, in closing I urge your committee to push forward on the study of the potential dangers of mercury in our dentistry and medicines. This includes mercury exposures from amalgams, vaccines and other medicaments containing thimerosal. The synergistic effects of mercury with many of the toxicants commonly found in our environment make the danger unpredictable and possibly quite severe, especially any mixture containing elemental mercury, organic mercury and other heavy metal toxicants such as aluminum.

Sincerely,

 

Boyd E. Haley
Professor and Chair
Department of Chemistry
University of Kentucky

 

REFERENCES:

1. a. Duhr, E.F., Pendergrass, J. C., Slevin, J.T., and Haley, B. HgEDTA Complex Inhibits GTP Interactions With The E-Site of Brain b-Tubulin Toxicology and Applied Pharmacology 122, 273-288 (1993).; b. Pendergrass, J.C. and Haley, B.E. Mercury-EDTA Complex Specifically Blocks Brain b-Tubulin-GTP Interactions: Similarity to Observations in Alzheimer"s Disease. p 98-105 in Status Quo and Perspective of Amalgam and Other Dental Materials (International Symposium Proceedings ed. by L. T. Friberg and G. N. Schrauzer) Georg Thieme Verlag, Stuttgart-New York (1995).; c. Pendergrass, J.C. and Haley, B.E. Inhibition of Brain Tubulin-Guanosine 5'-Triphosphate Interactions by Mercury: Similarity to Observations in Alzheimer's Diseased Brain. In Metal Ions in Biological Systems V34, pp 461-478. Mercury and Its Effects on Environment and Biology, Chapter 16. Edited by H. Sigel and A. Sigel. Marcel Dekker, Inc. 270 Madison Ave., N.Y., N.Y. 10016 (1996).
2. Pendergrass, J. C., Haley, B.E., Vimy, M. J., Winfield, S.A. and Lorscheider, F.L. Mercury Vapor Inhalation Inhibits Binding of GTP to Tubulin in Rat Brain: Similarity to a Molecular Lesion in Alzheimer's Disease Brain. Neurotoxicology 18(2), 315-324 (1997).
3. David, S., Shoemaker, M., and Haley, B. Abnormal Properties of Creatine kinase in Alzheimer's Diseased Brain: Correlation of Reduced Enzyme Activity and Active Site Photolabeling with Aberrant Cytosol-Membrane Partitioning. Molecular Brain Research 54, 276-287 (1998).
4. Leong, CCW, Syed, N.I., and Lorscheider, F.L. Retrograde Degeneration of Neurite Membrane Structural Integrity and Formation of Neurofibillary Tangles at Nerve Growth Cones Following In Vitro Exposure to Mercury. NeuroReports 12 (4): 733-737, 2001.
5. Olivieri, G., Brack, Ch., Muller-Spahn, F., Stahelin, H.B., Herrmann, M., Renard, P; Brockhaus, M. and Hock, C. Mercury Induces Cell Cytotoxicity and Oxidative Stress and Increases b-amyloid Secretion and Tau Phosphorylation in SHSY5Y Neuroblastoma Cells. J. Neurochemistry 74, 231-231, 2000.
6. Kingman, A., Albertini, T. and Brown, L.J. Mercury Concentrations in Urine and Whole-Blood Associated with Amalgam Exposure in a U.S. Military Population. J. Dental Research 77(3) 461-71, 1998.
7. Chew, C. L., Soh, G., Lee, A. S. and Yeoh, T. S. Long-term Dissolution of Mercury from a Non-Mercury-Releasing Amalgam. Clinical Preventive Dentistry 13(3): 5-7, May-June (1991).
8. Hahn, L.J., Kloiber, R., Vimy, M. J., Takahashi, Y. and Lorscheider, F.L. Dental "Silver" Tooth Fillings: A Source of Mercury Exposure Revealed by Whole-Body Image Scan and Tissue Analysis. FASEB J. 3, 2641-2646, 1989.
9. Hahn, L.J., Kloiber, R., Leininger, R.W., Vimy, M. J., and Lorscheider, F.L. Whole-body Imaging of the Distribution of Mercury Released from Dental Filling Into Monkey Tissues. FASEB F. 4, 3256-3260, 1990.
10. Hock, C., Drasch, G., Golombowski, S., Muller-Span, F., Willerhausen-Zonnchen, B., Schwarz, P., Hock, U., Growdon, J.H., and Nitsch, R.M. Increased Blood Mercury Levels in Patients with Alzheimer's Disease. J. of Neural Transmission v105(1) 59-68, 1998.
11. Frustaci, A., Magnavita, N., Chimenti, C., Caldarulo, M., Sabbioni, E., Pietra, R., Cellini. C., Possati, G. F. and Maseri, A. Marked Elevation of Myocardial Trace Elements in Idiopathic Dilated Cardiomyopathy Compared With Secondary Dysfunction. J. of the American College Cardiology v33(6) 1578-1583, 1999,
12. Schubert, J., Riley, E.J., and Tyler, S.A. Combined Effects in Toxicology-A Rapid Systemic Testing Procedure: Cadmium, Mercury and Lead. J. of Toxicology and Environmental Health v4, 763-776,1978.
13. Wataha, J. C., Nakajima, H., Hanks, C. T., and Okabe, T. Correlation of Cytotoxicity with Element Release from Mercury and Gallium-based Dental Alloys in vitro. Dental Materials 10(5) 298-303, Sept. (1994)
14. a. Ehmann, W., Markesbery, W., and Alauddin, T., Hossain, E. and Brubaker, E., Brain Trace Elements in Alzheimer's Disease. Neurotoxicology 7(1) p197-206, 1986. b. Thompson, C. M., Markesbery, W.R., Ehmann, W.D., Mao, Y-X, and Vance, D.E. Regional Brain Trace-Element Studies in Alzheimer's Disease. Neurotoxicology 9, 1-8 (1988).
15. Wenstrup, D., Ehmann, W., and Markesbery, W. Brain Research, 533, 125-131, 1990.
16. Ngim, C.H., Devathasan, G. Epidemiologic Study on the Assocaiation Between Body Burden Mercury Level and Idiopathic Parkinson's Disease. Neuroepidemiology, 8, 128-141, 1989.
17. Nylander, M., Friberg, L. and Lind, B. Mercury Concentrations in the Human Brain and Kidneys in Relation to Exposure from Dental Amalgam Fillings. Swedish Dentistry J. 11:179-187, 1987.
18. Nylander, M., Friberg, L., Eggleston, D., Bjorkman, L. Mercury Accumulation in Tissues from Dental Staff and Controls in Relation to Exposure. Swedish Dental J. 13, 235-243, 1989
19. Heintze, U. Edwardsson, S., Derand, T. and Birkhed, D. Methylation of Mercury from Dental Amalgam and Mercuric Chloride by Oral Streptococci in vitro. Scand. J. Dental Research 91(2) 150-152, 1983.



Dr. Boyd Haley's Curriculum Vitae
  CURRICULUM VITAE

BOYD E. HALEY, Ph.D. Born 22-09-40 Greensburg, Indiana

ADDRESS: Advanced Science Technology Commercialization Center, ASTeCC
Room A057
University of Kentucky
Lexington, KY 40506-0286
Laboratory: Telephone; (606) 257-2300 ext 246 FAX; (606) 257-3040
Chemistry Office: Telephone; (606) 257-7082

EDUCATION:
Institution Year Degree/Area

Franklin College 1963 B.A./Chemistry-Physics
University of Idaho 1967 M.S./Organic Chemistry
Washington State University 1971 Ph.D./Chemistry-Biochemistry
Yale University Medical Center 1971-74 Postdoctoral Fellow

RESEARCH AND PROFESSIONAL EXPERIENCE:

1963-1964 Research Scholar, Food and Drug Administration.
1964-1966 U.S. Army Medic
1966-1967 Graduate Student, University of Idaho
1967-1971 Graduate Student, Washington State University
1971-1974 Postdoctoral Scholar, Yale University
1974-1979 Assistant Professor, Department of Biochemistry, University of Wyoming, Laramie, WY
1979-1981 Associate Professor, Department of Biochemistry, University of Wyoming, Laramie, WY
1981-1985 Professor, Department of Biochemistry, University of Wyoming, Laramie, WY
1985-1997 Professor of Medicinal Chemistry, College of Pharmacy, University of Kentucky, with
joint appointments in Biochemistry & Chemistry
1997-present Chairman & Professor, Department of Chemistry with joint appointment in College of
Pharmacy

PROFESSIONAL ORGANIZATIONS, SOCIETIES, HONORS AND RESPONSIBILITIES

1959 President's Scholarship, Franklin College, Indiana
1962 Chi Beta Phi, Franklin College
1962 James M. Sprague Award - $400 award to outstanding
undergraduate junior majoring in science.
1963 Kennedy Scholar, Food and Drug Administration,
Washington, D.C.
1970 Sigma Xi
1975 Dreyfus Foundation Visiting Researcher, Enzyme Institute University of Wisconsin
1977 American Society of Biological Chemists
1981 Biophysical Society
1981 Served on NIH Physiological Chemistry Study Section
1981 Research was presented as a "highlight" in NIH report on
"Cellular and Molecular Basis of Disease Program"
1984 "TOP" Professor Award, University of Wyoming
1982 Served on NIH Physiological Chemistry Study Section
1983 Served on NIH Physiological Chemistry Study Section
1985 Permanent member NIH Biomedical Sciences, Study Section
1991 Honorary Doctorate in Arts & Sciences, Franklin College
1992 Society for Neuroscience

GRANT SUPPORT

1975 - 1978 National Institutes of Health, "Application of Photoaffinity Nucleotide Analogs", $82,000, Prinicipal Investigator

1975 Research Coordination Committee, University of Wyoming $1,800

1978 - 1981 National Institutes of Health, "Application of Photoaffinity Nucleotide Analogs", $183,696, Prinicipal Investigator

1978 - 1981 Eleanor Roosevelt Cancer Institute Grant, $11,400

1979 - 1983 PHS Research Career Development Award, $185,000

1981 - 1986 National Institutes of Health, "Application of Photoaffinity Nucleotide Analogs", $434,000, Prinicipal Investigator

1982 ASBC Travel Award to attend 12th IVB Congress, Perth, Australia

1983 - 1984 National Science Foundation, "Melatonin Photoaffinity Probe", $84,000, Co-Principal Investigator

1983 - 1985 National Institutes of Health, "Epididymal Sperm Nucleotide Binding proteins", $190,000, Co-Principal Investigator

1985 - 1988 U.S. Army Mycotoxin Photoprobes, $390,000, Co-Principal Investigator

1986 - 1989 NIH, "Forskolin Photoaffinity Probes", $170,000, Co-Principal Investigator

1986 - 1991 NIH, "Application of Photoaffinity Nucleotide Analogs" $781,661, Principal Investigator

1989 - 1994 NIH, "Nucleotide-Tubulin Interactions in Alzheimer's Disease", $405,259, Co-Prinicipal Investigator

1990 - 1996 Lexington Clinic Foundation For Medical Education and Research, "Inhibition of Neoplastic Cell Proliferation Through Utilization of Photoactive DNA & RNA Synthesis, $100,000, P.I.

1990 - 1993 Eli Lilly, "Development of a Diagnostic Test for Alzheimer's Disease, $378,000, P.I.

1995 - 1997 Wallace Research Foundation, "Development of Diagnostic Tests Using Nucleotide Photoaffinity Probes". $109,000 for two years.

1997-1998 Wallace Research Foundation, "Development of Diagnostic Tests Using Nucleotide Photoaffinity Probes". $74,344.

1997-2000 NIH, "Application of Photoaffinity Nucleotide Analogs", $378,081, P.I.

1997-1998 Isostent, Inc. "Photoattachment of 32P to angioplastic ballon cathers" $52,000.

Pending NIH, "Identification of CSF proteins Related to ALS"
NIH, "Photomodification of Antibodies for Diagnostic and Therapeutic Applications".

TEACHING EXPERIENCE

Introductory Comparative Biochemistry
General Biochemistry
Problems and Topics in Biochemistry
Mercury Toxicity: Chemistry and Biochemistry Involved
Advanced Problems and Topics in Biochemistry
Nucleic Acids and Protein Biosynthesis
Nucleotides in Regulation of Biological Phenomena
Bioenergetics
Medicinal Chemistry
Natural Products and Bio-organics
Graduate level Biochemistry, Protein Chemistry

INVITED LECTURES:

1975 - Sloan Kettering Memorial Cancer Institute, New York
thru Colorado State University (3)
1979 Albert Einstein University, New York
Hoffman-LaRoche Research Institute, Nutley, New Jersey
University of Colorado Medical School Denver (3)
University of Colorado, Boulder (2)
Yale University Medical School (2)
The Salk Institute, San Diego
University of California, Davis
Stanford University Medical School
University of California, San Diego
University of Washington, Seattle
Washington State University
Kansas State University
1979 Symposium Speaker, ASBC Meeting, Dallas, Texas
1979 Symposium Speaker, New York Academy of Sciences Meeting, New York
Department of Molecular Biology, National Jewish Hospital, Denver
University of California, Riverside
Workshop Speaker, ICN-UCLA Conference on Adenylyl Cyclase
1982 Symposium Speaker, 1982 FASEB Meeting, New Orleans
1982 Guest Lecturer and Scientist, German Cancer Research Center,
Institute of Cell and Tumor Biology, Heidelberg, West Germany,
May
1982 Centre National De La Recherche Scientifique, Laboratoire
D'Enzymologie, Gif Sur Yvette, France, June
1982 Workshop Speaker, ASBC Meeting in New Orleans (Photoprobe
utilization, sponsored by Schwarz-Mann)
1982 Symposium Speaker, Society for the Study of Reproduction, Madison
Wisconsin, August
1982 Department of Biochemistry, University of Wisconsin, November
1982 Department of Chemistry, New Mexico State University, November
1982 Department of Chemistry, University of Colorado, December
1983 Institute of Infectious Diseases, U.S. Army Medical Research
Institute, Ft. Detrick, Michigan, January
1983 Department of Biochemistry and Biophysics, Oregon State University
1983 Department of Biochemistry, Texas Health Science Center, San Antonio, TX
1983 Department of Biochemistry, University of Mississippi Medical Center
1984 Department of Biochemistry, University of Kentucky, Lexington, KY
1985 Department of Physiology and Biophysics, Northwestern University
Medical School, Chicago, Illinois
1985 Department of Chemistry, University of Southern California, Los
Angeles, California
1985 Department of Physiology, University of Illionis at Chicago,
Chicago, Illinois
1985 Department of Biochemistry, Ohio State University, Columbus, Ohio
1985 Department of Physiology, Yale University Medical School, New
Haven, Connecticut
1986 Department of Biochemistry, Case Western University, School of
Medicine, Cleveland, Ohio
1986 Department of Biochemistry, Indiana University, School of Medicine, Indianapolis, Indiana
1986 Department of Biochemistry, Washington University, School of
Medicine, St. Louis, Missouri
1987 Division Fermentation Products Research Division, Eli Lilly
Research Laboratories, Indianapolis, Indiana
1987 Department of Chemistry, University of South Florida, Tampa, Florida
1987 Department of Molecular Biology and Biochemistry, University of
Wyoming, Laramie, Wyoming
1988 Worcester Foundation, Shrewsbury, Massachusetts
1988 Department of Biochemistry, University of Colorado, Denver, Colorado
1988 Department of Biochemistry, University of Delaware, Newark, Delaware
1989 University of California at San Diego
1989 University of California at Los Angeles
1989 Texas College of Osteopathic Medicine, Fort Worth, Texas
1990 Wright State University, Dayton, Ohio
1990 Athena Neurosciences, S. San Francisco, California
1990 Eli Lilly & Co., Indianapolis, Indiana
1990 Connaught Laboratories, Toronto, Canada
1990 University of East Carolina Medical School, Greenville, North Carolina
1990 Hoffman-LaRoche Research Center, Nutley, New Jersey
1991 Eli Lilly & Co., Indianapolis, Indiana
1991 City University of New York, New York, New York
1991 University of Cincinnati, Cincinnati, Ohio
1991 University of Colorado, Boulder, Colorado
1991 University of Missouri at Kansas, Kansas City, Missouri
1992 Williams College at Williamsburg, Massachusetts
1992 Centre College at Danville, Kentucky
1992 University of Colorado, Boulder, Colorado
1992 Eli Lilly & Co., Indianapolis, Indiana
1992 Merck Laboratories, West Point, Pennsylvania
1993 NIH Rocky Mountain Laboratory, Hamilton, MT
1993 Intern. Acad. Oral & Medical Toxicology, Chicago, IL
1993 Univ. Tenn. at Memphis, Memphis, TN
1993 Penn State University, College Station, PN
1993 University California, Riverside, Riverside, CA
1993 Mayo Clinic, Jacksonville, FL
1993 Washington University, St. Louis, MO
1993 University of Arkansas, Little Rock, AR
1994 European Academy of Science, Otzenhausen, Germany
1994 Intern. Acad. Oral & Medical Toxicology, London, England.
1994 Great Lakes College for Advancement of Medicine, Cincinnati, OH
1995 American College for the Advancement of Medicine, Colorado Springs, CO.
1995 Pfizer Pharmaceuticals, Groton, CN
1995 Ohio State University, Dept,. Chemistry, Columbus, OH
1996 Intern. Acad. Oral & Medical Toxicology, Tuscon, AZ
1996 University of Wyoming, Laramie WY
1996 American College for the Advancement of Medicine, Colorado Springs, CO.
1997 American Academy Biological Dentistry, Carmel, CA March 7-9.
1997 International Academy of Oral and Medical Toxicology, Louisville, KY March 14-16
1997 Washington State University, Dept. of Chemistry and Biophysics, Pullman, WA, March 27-30.
1997 American Society of Biochemistry and Molecular Biology, Symposium talk, August 24-28.
1997 Canadian Academy Oral and Medical Toxicology, Toronto, Canada. September 19-21.
1997 Capital University of Integrative Medicine, Washington, DC, October 16-18
1997 American Academy Environmental Medicine, San Diego, CA, October 24-26.
1997 University of Missouri at Kansas City, Dept. Biology & Biophysics, November 20-22.

SERVICE TO DEPARTMENT, COLLEGE AND UNIVERSITY:

1975-1979 Faculty Senate
Biological Interdepartmental Seminar Committee
University Grievance Procedure Committee
College of Agriculture Teaching Improvement Committee
College of Agriculture Academic Planning Committee
Faculty Senate Nominating Committee
Division of Biochemistry Undergraduate Teaching Committee
Division of Biochemistry Graduate Program Committee
University Research Coordination Committee
Chairman of the Graduate Committee, Biochemistry Department
1979-1982 College of Agriculture Tenure and Promotion Committee
1979 College of Agriculture Dean Search Committee
1981 Vice-President for Research Search Committee
1981 College of Human Medicine Evaluation Committee
1981-1982 Biomedical Research Funding Committee
1982 Chairman, Department of Zoology and Physiology Review Committee
1986 Research Committee College of Medicine
Ad Hoc Committee to Review Center on Aging
Ad Hoc Medical Center Research Advisory Committee
Working Group for Biotechnology Center
Center for Pharmaceutical Science and Technology Advisory Committee
College of Pharmacy Graduate Program
College of Pharmacy Research and Seminar
1987 Markey Cancer Center Internal Advisory Committee
College of Medicine Research Committee
Tobacco and Health Advisory Committee
1988 College of Pharmacy BRSG Committee, Tenure and Promotion
1989 Chairman, College of Medicine BRSG Committee
Member, Tobacco & Health Advisory Committee
Member, Markey Cancer Center Advisory Committee
1990 Chairman, College of Medicine BRSG Committee
1991-1992 Member, Intellectual Properties Committee
Member, Search Committee Cancer Center Director
Member, Cancer Center Advisory Committee
Member, Search Committee Diagnostic Radiology Chair
Member, Academic Area Committee, Biological Sciences

1993-1995 Chair, Research and Seminar Committee
Member, Appointment, Tenure and Promotion Committee
1996-1997 Chair, Graduate Program task force, College of Pharmacy
Chair, Physical Plant section, College of Pharmacy self-study
University Chemical Safety Committee
College of Medicine Academic Council
College of Pharmacy Tenure and Promotion Committee

PUBLICATIONS (REFEREED JOURNALS)

1. Haley, B. and Yount, R. Gamma-fluoradenosine Triphosphate.Synthesis, Properties and Interaction with Myosin and Heavy Meromyosin. Biochemistry II, 2863-2871 (1972).

2. Haley, B., Yount and Hoffman, J. Selective Inhibition of Divalent Metal Ion Requiring ATPase Activity of Human Red Cell Ghost by an Analog of ATP. The Physiologist 16, 333-334 (1973).

3. Haley, B. and Hoffman, J. Interactions of Photo-Affinity ATP Analog with Cation-Stimulated ATPase Activities of Human Red Cell Ghost. Proc. Natl. Acad. Sci. 71, 3367-3371 (1974).

4. Staros, J.V., Haley, B. and Richards, F.M. Human Erythrocytes and Resealed Ghost: A Comparison of Membrane Topology. J. Biol. Chem. 249, 5004-5007 (1974).

5. Pomerantz, A., Rudolph, S.A., Haley, B. and Greengard, P. Photoaffinity Labeling of a Protein Kinase from Bovine Brain with 8-Azido-adenosine-3', 5'-monophosphate. Biochemistry 14, 3852-3857 (1975).

6. Haley, B. Photoaffinity Labeling of cAMP Binding Sites of Human Red Blood Cell Membranes. Biochemistry 14, 3852-3857 (1975).

7. Staros, J.V., Richards, F.M. and Haley, B. Photochemical Labeling of the Cytoplasmic Surface of the Membranes of Intact Human Erythrocytes. J. Biol. Chem. 250, 8174-8178 (1975).

8. Malkinson, A.M., Krueger, B.V., Rudolph, S.A., Casnelli, J.E., Haley, B. and Greengard, P. Widespread Occurence of a Specific Protein in Vertebrate Tissues and Regulation by cAMP of its Endogenous Phosphorylation and Dephosphorylation. Metabolism 24, 331-341 (1975).

9. Haley, B. Photoaffinity Labeling of Adenosine 3', 5'-Cyclic Monophosphate Binding Sites. Methods in Enzymology, Jacoby and Wilchek, Editors. V 46, pp. 339-346 (1976).

10. Owens, J.R. and Haley, B.E. A Study of Adenosine 3', 5'-Cyclic Monophosphate Binding Sites of Human Erythrocyte Membranes Using 8-Azido-adenosine-3'-5' Cyclic Monophosphate. J. Supra. Mole. Structure 5, 91-102 (1976).

11. Skare, K., Black, J.L., Pancoe, W.L. and Haley, B. Determination of the Cellular Location of Cyclic Nucleotide Binding Sites Using 8-Azido-adenosine-3', 5'-monophosphate, A Photoaffinity Probe. Arch. Biochem. Biophy. 180, 409-415 (1977).

12. Lau, E., Haley, B. and Barden, R. Interactions of a Photoaffinity Analog of CoA with CoA Enzymes. Biochemistry 16, 2581-2585 (1977).

13. Owens, J.R. and Haley, B. A Study of Adenosine 3', 5'-Cyclic Nucleotide Binding Sites of Human Erythrocyte Membranes Using 8-Azido-adenosine 3'-5'-Cyclic Monophosphate. Cell Shape and Surface Architecture: Progress in Clinical and Biological Research 17, 65-76 (1977)

14. Lau, E.P., Haley, B. and Barden, R. The 8-Azidoadenine Analog of S-Benzoyl (3'-dephospho) Coenzyme A-A Photoaffinity Label for Acyl CoA; Glycine N-Acyltransferase. Biochem. Biophys. Res. Commun 76, 843-849 (1977).

15. Geahlen, R.T. and Haley, B. Interactions of a Photoaffinity Analog of GTP with the Proteins of Microtubules. Proc. Natl. Acad. Sci. 74, 4375-4377 (1977).

16. Owens, J.R. and Haley, B. Use of Photoaffinity Nucleotide Analogs to Determine the Mechanism of ATP Regulation of a Membrane Bound, cAMP Activated Protein Kinase. J. Supra. Mole. Structure 9, 57-68 (1978).

17. Czarnecki, J., Geahlen, R.T. and Haley, B. Synthesis and Use of Azido Photoaffinity Analogs of Adenine and Guanine Nucleotides. Methods in Enzymology 56, 642-653 (1979).

18. Marcus, F. and Haley, B. Inhibition of Fructose 1,6-biphosphatase by the Photoreactive AMP Analog, 8-Azido-AMP. J. Biol. Chem. 254, 259-261 (1979).

19. Geahlen, R., Haley, B. and Krebs, E.G. Synthesis and Use of 8-azidoguanosine 3', 5'-cyclic Monophosphate as a Photoaffinity Label for Cyclic GMP-dependent Protein Kinase. Proc. Natl. Acad. Sci. 76, 2213-2217 (1979).

20. Geahlen, R. and Haley, B. Use of GTP Photoaffinity Probe to Resolve Aspects of the Mechanism of Tubulin Polymerization. J. Biol. Chem. 254, 11982-11987 (1979).

21. Haley, B. Application of Photoaffinity Nucleotide Analogs to Biological Membrane Research. Selected Aspects of Cancer-Related Protein, Carbohydrate, Lipid and other Biochemistry, International Cancer Research Data Bank, p. 87 (1979).

22. Owens, J. and Haley, B. Mechanism of MgATP Regulation of Membrane Bound Type I cAMP Activated Protein Kinase. Transmembrane Signaling. Alan R. Liss, Inc. New York, New York, pp. 149-160 (1979).

23. Forrester, I.T., P.K. Schoff, B.E. Haley and R.G. Atherton. Determination of Protein Kinase Activity in Intact Mammalian Sperm. J. of Andrology 1, 70 (1980).

24. Briggs, F. Norman, Al-Jumaily, Walid and Haley, Boyd. Photoaffinity Labeling of the (Ca+Mg) ATPase of Skeletal and Cardiac Sarcoplasmic Reticulum with [32P-]-8-Azido ATP. Cell Calcium 1, 205-215 (1980).

25. Hoyer, P., Owens, J.R. and Haley, B.E. Use of Nucleotide Photoaffinity Probes to Elucidate Molecular Mechanisms of Nucleotide Regulated Phenomena. Annals of New York Academy of Science 346, 280-301 (1980).

26. Takemoto, D.J., B.E. Haley, J. Hanse, P. Pinbett and L.J. Takemoto. GTPase from Rod Outer Segments: Characterization by Photoaffinity Labeling and Tryptic Peptide Mapping. Biochem. Biophys. Res. Commun. 102, 341-347 (1981).

27. Leichtling, B.H., Coffman, D.S., Yaeger, E.S., Rickenberg, H.V., Al-Jumaily, W. and Haley, B.E. Occurrence of the Adenylate Cyclase "G-Protein" in Membranes of Dictyostelium discoidium, Biochem. Biophys. Res. Commun. 102, 1187-1195 (1981).

28. Schoff, P.K., Forester, I.T., Haley, B.E. and Atherton, R. A Study of cAMP Binding Proteins on Intact and Distrupted Sperm Cells Using 8-Azidoadenosine-3', 5'-Cyclic Monophosphate. J. Supra. Molecular Structure 19, 1-15 (1982).

29. King, M.M., Carlson, G. and Haley, B.E. Photoaffinity-Labeling of the Subunit of Phosphorylase Kinase by 8-Azidoadenosine-5'-Triphosphate and its 2', 3' -Dialdehyde Derivative. J. Biol. Chem. 257, 14058-14065 (1982).

30. Potter, R. and Haley, B.E. Photoaffinity Labeling of Nucleotide Binding Sites with 8-Azidopurine Analogs. Meth. Enzymol. 91, 613-633 (1982).

31. Hoyer, P.B. and Haley, B.E. Utilization of Nucleotide Photoaffinity Probes to Study Protein-Nucleotide Interactions in Cell Fractions. J. Cellular Biochemistry, submitted. (1983)

32. Haley, Boyd. Development and Utilization of 8-Azidopurine Nucleotide Photoaffinity Probes. Federation Proceedings 42, 2831-2836 (1983).

33. Khatoon, S., Atherton, R. Al-Jumaily, W. and Haley, B.E. Use of Nucleotide Photoaffinity Probes to Study Hormone Action. Biology of Reproduction 28, 61-73 (1983).

34. Kaiser, I.I., Kladianos, D.M., Van Kirk, E.A., and Haley, B.E. Photoaffinity Labeling of catechol-o-methyltransferase with 8'-Azido-S-adenosylmethionine. J. Biol. Chem. 258, 1747-1751 (1983).

35. Abraham, K., Haley, B. and Modak, M. Biochemistry of Terminal Deoxynucleotidyl Transferase: 8-Azido ATP as A Substrate Binding Site-Directed Photoaffinity Labeling Prob. Biochemistry 22, 4197-4203 (1983).

36. Haley, B.E., Ponstingl, H. and Doenges, K.H. Photoaffinity Labeling of Pure Tubulin Using 8-Azidoguanosine triphosphate at the b-Subunit. Hoppe-Seylers J. Physiol. Chem. 364, 1137 (1983).

37. Woody, A.M., Vader, C.R., Woody, R.W. and Haley, B.E. Photoaffinity Labeling of DNA-dependent RNA polymerase from E. coli with 8-azidoadenosine-5'-triphosphate. Biochemistry 23, 2843-2848 (1984).

38. Owens, J.R. and Haley, B.E. Synthesis and Utilization of [5'-32P]-8-Azidoguanosine-3'-phosphate-5'-phosphate: Photoaffinity Studies on Cytosolic Proteins of E. coli. J. Biol. Chem. 259, 14843-14848 (1984).

39. Pfister, K.K. , Haley, B.E. and Witman, G.B. The Photoaffinity Probe 8-azidoadenosine-5'-triphosphate. Selectivity Labels the Heavy Chain of Chlamydomonas 12S Dynein. J. Biol. Chem. 259, 8499-8504 (1984).

40. Atherton, R.W., Khatoon, S., Schoff, P.K. and Haley, B.E. A Study of Rat Epididymal Sperm Adenosine-3', 5'-monophosphate-dependent Protein Kinase: Maturation Differences and Cellular Location. Biol. of Reproduction 32, 155-172 (1985).

41. McMurray, M.M., Hansen, J.S., Haley, B.E., Takemoto, D.J. and Takemoto, L.J. Interspecies Conservation of Retinal Guanosine-5'-triphosphatase: Characterization by Photoaffinity Labeling and Tryptic Peptide Mapping. Biochemical Journal 225, 227-232 (1985).

42. Khatoon, S., Haley, B.E. and Atherton, R.W. A Comparative Analysis of cAMP-dependent Protein Kinase Regulatory Subunits in Sea Urchin and Rat Sperm. J. Andrology 6, 251-260 (1985).

43. DeBortoli, M.E., Issa, H.A., Haley, B.E. and Cho-Chung, Y.S. Elevated Levels of p2l ras Protein in Hormone-Dependent Mammary Carcinomas of Humans and Rodents. Bioch. Biophys. Res. Commun. 127, 699-709 (1985).

44. Evans, R., Haley, B. and Roth, D. Photoaffinity Labeling of a Viral Induced Protein from Tobacco. J. Biol. Chem. 260, 7800-7804 (1985).

45. Nunamaker, R.A., Wilson, W.T. and Haley, B.E. Electrophoretic Detection of Africanized Honey Bees (Apis mellifera scutellata) in Guatemala and Mexico Based on Malate Dehydrogenase Allozyme Patterns. Journal of the Entomological Society 57, 622-631 (1985).

46. Pfister, K.K., Haley, B.E. and Witman, G.B. Labeling of Chlamydomonas 18S Dynein Polypeptides by 8-Azidoadenosine 5'-Triphosphate, a Photoaffinity Analog of ATP. J. Biol. Chem. 260, 12844-12850 (1985).

47. Hoyer, P.B., Fletcher, P. and Haley, B.E. Synthesis of 2', 3'-0-(2,4,6,-trinitrocyclohexadienylidine) guanosine 5'-Triphosphate and study of its Inhibitory Properties with Adenylate Cyclase. Arch. Biochem. Biophys. 245, 368-378 (1986).

48. Evans, R.K., Johnson, J.D. and Haley, B.E. 5'-Azido-2'-deoxyuridine-5'-triphosphate: A Novel Photoaffinity Labeling Reagent and Tool for the Enzymatic Synthesis of Photoactive DNA. Proc. Natl. Acad. Sci. USA. 83, pp. 5382-5386 (1986).

49. Jeganathan, A., Richardson, S.K., Mani, R.S., Haley, B.E. and Watt, D.S. Selective Reactions of Azide-substituted a-Diazoamides with Olefins and Alcohols Using Rhodium (II) Catalysts. J. Org. Chem. 51, 5362-5367 (1986).

50. Malkinson, A.M., Haley, B.E., Macintyre, B.E. and Buthy, M.S. Changes in Pulmonary Adenosine Triphosphate Binding Proteins Detected by Nucleotide Photoaffinity Labeling Following Treatment of Mice with the Tumor-Modulatory Agent Butylated Hydroxytoluene. Cancer Res. 46, 4626-4630 (1986).

51. Evans, R.K. and Haley, B.E. Synthesis and Biological Properties of 5-Azido-2'-deoxyuridine-5'-triphosphate: A Photoactive Nucleotide Suitable for Making Light Sensitive DNA. Biochemistry 26, 269-276 (1987).

52. Richardson, S.K., Jeganathan, A., Mani, R.S., Haley, B.E. and Watt, D.S. Synthesis and Biological Activity of C-4 and C-15 Aryl Azide Derivatives of Anguidine. Tetrahedron Letters 43, 2925 (1987).

53. Droms, K.A., Haley, B.E. and Malkinson, A.M. Decreased Incorporation of the Photoaffinity Probe [g3232P]-8N3 GTP into a 45KD Protein in Lung Tumors. Bioch. Biophys. Res. Commun. 144, 591-597 (1987).

54. Karpel, R.L., Levin, V.Y. and Haley, B.E. Photoaffinity Labeling of T4 Bacteriophage 32Protein. J.Biol.Chem. 262, 9359-66 (1987).

55. Suhadolnik, R.J., Li, Shi Wu, Sobol, Jr. R.W., and Haley, B.E. 2-and 8-Azido Photoaffinity Probes. II. Studies on the Binding Process of 2-5A Synthetase. Biochemistry 27, 8846-8851 (1988).

56. Suhadolnik, R.J., Kariko, K., Sobol, Jr., R.W., Shi Wu, Richenbach, N.L. and Haley, B.E. 2- and 8-Azido Photoaffinity Probes. I. Enzymatic Synthesis, Characterization and Biological Properties of 2- and 8-Azido Photoprobes of 2-5A & Photolabeling of 2-5A Binding Proteins. Biochemistry 27, 8840-8846 (1988).

57. Droms, K.A., Haley, B.E., Smith, G.J. and Malkinson, A.M. Decreased Photolabeling of Gsa With [a-32P]8N3-GTP in Tumorigenic Lung Epithelial Cell Lines: Association with Decreased Hormone Responsiveness and Loss of Contact-Inhibited Growth. Experimental Cell Research 182, 330-339 (1989).

58. Francis, B., Overmeyer, J., John, W., Marshall, E. and Haley, B. Prevalence of Nucleoside Diphosphate Kinase Autophosphorylation in Human Colon Carcinoma versus Normal Colon Homogenates. Molecular Carcinogenesis 2, 168-178 (1989).

59. King, S.M., Haley, B.E. and Witman, G.B. Structure of the a and b Heavy Chains of the Outer Arm Dynein from Chlamydomonas Flagella. J. Biol. Chem. 264, 10210-10218 (1989).

60. Khatoon, S., Campbell, S.R., Haley, B.E. and Slevin, J.T. Aberrant GTP b-Tubulin Interaction in Alzheimer's Disease. Annals of Neurology 26, 210-215 (1989).

61. Lawson, S.G., Mason, T.L., Sabin, R.D., Sloan, M.E., Drake, R.R., Haley, B.E. and Wasserman, B.P. UDP-Glucose: (1,3)-B-Glucan Synthase from Daucas carota L.: Characterization, Photoaffinity Labeling and Solubilization. Journal of Plant Physiology 90, 101-108 (1989).

62. Lewis, C.T., Haley, B.E. and Carlson, G.M. Formation of an Intramolecular Cystine Disulfide During the Reaction of 8-Azido-GTP with Cytosolic Phosphoenolpyruvate Carboxykinase (GTP) Causes Inactivation without Photolabeling. Biochemistry 28, 9248-9255 (1989).

63. Ho, L.T., Nie, Z.M., Mende, T.J., Richardson, S., Chavan, A., Kolaczkowska, E., Watt, D.S., Haley, B.E. and Ho, R.J. Modification of Adenylate Cyclase by Photoaffinity Analogs of Forskolin. J. Second Messengers and Phosphoproteins 12, 209-223 (1989).

64. Wasserman, B.P., Read, S.M., Frost, D.J., Mason, T.L., Drake, R.R. and Haley, B.E. Potential use of Affinity Labels in Subunit Identification Studies of (1,3)-b-Glucan Synthase. J.Applied Polymer Science Symposium (Proceeding of the Tenth Cellulose Conference, Syracuse, NY). C. Schuerch and T. Timell, Eds. 43, 827-837 (1989).

65. Drake, R.R., Evans, R.K., Wolf, M.J. and Haley, B.E. Synthesis and Properties of 5-Azido-UDP-Glucose: Development of Photoaffinity Probes for Nucleotide Diphosphate Sugar Binding Sites. J. Biol. Chem. 264, 11928-11933 (1989).

66. Dholakia, J.N., Francis, B.R., Haley, B.E. and Wahba, A. Photoaffinity Labeling of the Rabbit Reticulocyte Guanine Nucleotide Exchange Factor and Eukaryotic Initiation Factor 2 with 8-Azidopurine Nucleotides. J. Biol. Chem. 264, 20638-20642 (1989).

67. Campbell,S., Kim, H., Doukas, M. and Haley, B. Photoaffinity Labeling of ATP and NAD+ Binding Sites on Recombinant Human Interleukin-2. Proc. Natl. Acad. Sci. 87, 1243-1246 (1990).

68. Kim, H. and Haley, B. Synthesis and Properties of 2-Azido-NAD+: A Study of Interactions with Glutamate Dehydrogenase. J. Biol. Chem. 265, 3636-3641 (1990).

69. Drake, R., Palamarczyk, G., Haley, B. and Lennarz, W.J. Evidence for the Involvement of a 35-kDa Membrane Protein in the Synthesis of Glucosylphosphoryldolichol. Bioscience Reports 10, 61-68 (1990).

70. Marchase, R.B., Richardson, K.L., Srisomsap, C., Drake, R. and Haley, B.E. Resolution of Phosphoglucomutase and the 62 kDa Acceptor for the Glucosylphosphotransferase. Arch. Biochim. Biophys. 280, 122-129. (1990).

71. Salvucci, M.E. and Haley, B.E. Photoaffinity Labeling of Ribulose Bisphosphate Carboxylase/Oxygenase With 8-Azidoadenosine 5'-Triphosphate. Planta 181, 287-295 (1990).

72. Salvucci, M.E., Drake, R., Broadbent, K.P., Haley, B.E., Hanson, K.R. and McHale, N.A. Identification of the 64 Kilodalton Chloroplast Stromal Phosphoprotein as Phosphoglucomutase. Plant Physiology 93, 105-109 (1990).

73. Frost, D.J., Read, S.M., Drake, R., Haley, B.E. and Wasserman, B.P. Identification of the UDPG Binding Polypeptide of (1,3)-b-Glucan Synthase From A Higher Plant by Photoaffinity Labeling with 5-AzidoUDP-Glucose. J. Biol. Chem. 265, 2162-2167 (1990).

74. Lin, F.C., Brown, R.M. Jr., Drake, R.R. and Haley, B.E. Characterization of Cellulose Synthase Catalytic Subunit of Acetobacter xylinum Using 5-Azido-UDP-glc, A Photoaffinity Probe. J. Biol. Chem. 265, 4782-4784 (1990).

75. Salvucci, M.E., Drake, R.R., and Haley, B.E. Purification and Photoaffinity Labeling of Sucrose Phosphate Synthase from Spinach Leaves. Arch. Biochem. Biophys. 281, 212-218 (1990).

76. Chavan, A.J., Kim, H., Haley, B.E., and Watt, D.S. A Photoactive Phosphonamide Derivative of GTP for the Identification of the GTP Binding Domain of b-Tubulin. Bioconjugate Chemistry, 1, No. 5, 337-344 (1990).

77. Kwiatkowski, S., Crocker, P.J., Chavan, A.J., Nobuyuki, I., Haley, B.E. and Watt, D.S. Thiazolidine and Thiazoline Derivatives of 3-Aryl 3-Trifluormethyl Diazirines for the Preparation of Fluorescent or 35S-Radiolabeled Photoaffinity Probes. Tetrahedron Lett, 31, 2093-2096 (1990).

78. Palamarczyk, G., Drake, R., Haley, B. and Lennarz, W.J. Evidence that the Synthesis of Glucosylphosphoryl Dolichol in Yeast Involves a 35 kDa Membrane Protein. Proc. Natl. Acad. Sci. 87, 2666-2670 (1990).

79. King, S., Kim, H., and Haley, B. Strategies and Reagents for Photoaffinity Labeling of Mechanochemical Proteins. Meth. Enzymol. 196, 449-466 (1991).

80. Kim, H. and Haley, B. Identification of Peptides in the Adenine Ring Binding Domain of Glutamate and Lactate Dehydrogenase Using 2-AzidoNAD+. Bioconjugate Chemistry 2, 1142-147 (1991).

81. Mann, D., Haley, B., and Greenberg, R. Photoaffinity Labeling of Atrial Natriurtic Factor Analog Atriopeptin III woith [g32P]8N3GTP. Peptide Research 4, #2, 79-83 (1991).

82. Drake, R.R., Zimniak, P., Haley, B.E., Lester, R., Elbein, A.D. and Radominska, A. Synthesis and Characterization of5-Azido-UDP-Glucuronic Acid. J. Biol. Chem., 266, 23257-23260 (1991).

83. Drake, R.R., Zimniak, P., Haley, B.E., Lester, R., Elbein, A.D. and Radominska, A. Synthesis and Characterization of5-Azido-UDP-Glucuronic Acid. J. Biol. Chem., 266, 23257-23260 (1991).

84. Hiestand, D., Haley, B., and Kindy, M. Role of Calcium inInactivation of Calcium/Calmodulin Dependent Protein Kinase II After Cerebral Ischemia. Journal of the Neurological Sciences, 113, 31-37 (1992).

85. Salvucci, M., Chavan, A. and Haley, B. Identification of Peptides for the Adenine Binding Domains of ATP and AMP in Adenylate Kinase: Isolation of Photoaffinity Labeled Peptides by Metal Chelate Chromatography. Biochemistry 31 4479-4487 (1992).

86. Shoemaker, M., Lin, P.C., and Haley, B. Identification of the Guanine Binding Domain Peptide of the GTP Binding Site of Glucagon. Protein Science 1, 884-891 (1992).

87. Doukas, M., Chavan, A., Gass, C., Boone, T. and Haley, B. Identification and charaterization of a Nucleotide Binding Site on Recombinant Murine Granulocyte/Macrophage-Colony Stimulating Factor. Bioconjugate Chemistry 3, 484-492 (1992).

88. Segal, A., West, I., Wientjes, F., Nugent, J., Chavan, A., Haley, B., Garcia, R., Rosen, H. and Scrace, G. Cytochrome b-245 is a Flavocytochrome Containing FAD and the NADPH Binding Site of the Microbicidal Oxidase of Phagocytes. Biochem. J. 284, 781-788 (1992).

89. Hammond, D., Haley, B. and Lesnaw, J. Identification and Characterization of Serine/Threonine Protein Kinase ActivityIntrinsic to the L Protein of Vesicular Stomatitis Virus New Jersey. Journal of General Virology 73, 67-75 (1992)

90. Chavan, A., Nemoto, Y., Narumiya, S., Kozaki, S., and Haley, B. NAD+ Binding Site of Clostridium botulinum C3 ADP-ribosyltransferase: Identification of Peptide in the Adenine Ring Binding Domain using 2-Azido NAD+. J. Biol. Chem. 267, 14866-14870 (1992).

91. Gunnersen, D.J. and Haley, B.E. Detection of Glutamine Synthetase in the Cerebrospinal Fluid of Alzheimer's Diseased Patients: A Potential Diagnostic Biochemical Marker. Proc. Natl. Acad. Sci. USA, 89 pp. 11949-11953 (1992).

92. Shoemaker, M., and Haley, B. Identification of a Guanine Binding Domain Peptide of the GTP Binding Site of Glutamate Dehydrogenase: Isolation with Metal-Chelate Affinity Chromatography. Biochemistry 32, 1883-1890 (1993).

93. Churn, S.B., Sankaran, B., Haley, B.E. and Delorenzo, R.J. Ischemic Brain Injury Selectively Alters ATP Binding of Calcium and Calmodulin-Dependent Protein Kinase-II. Biochem. Biophys. Res. Comm. 193:3, 934-940 (1993).

94. Salvucci, M., Rajagopalan, K., Sievert, G., Haley, B. and Watt, D. Photoaffinity Labeling of Rubisco Activase with ATP-g-benzophenone: Identification of the ATP g-Phosphate Binding Domain J. Biol. Chem. 268, 14239-14244 (1993).

95. Rajagopalan, K., Chavan, A., Haley, B. and Watt, D. Bidentate Cross-Linking Reagents: Non-Hydrolyzable Nucleotide Photoaffinity Probes with Two Photoactive Groups J. Biol. Chem. 268, 14245-14253 (1993).

96. Trad, C., Chavan, A., Clemens, J., and Haley, B. Identification and Characterization of an NADH Binding Site of Prolactin with 2-Azido-NAD+ Arch. Biochem. Biophys. 304, 58-64 (1993).

97. Chavan, A., Ensor, C., Wu, P., Haley, B. and Tai, H. Photoaffinity Labeling of Human Placental NAD+-Linked 15-Hydroxyprostaglandin Dehydrogenase with [a32P]-2N3NAD+: Identification of a Peptide in the Adenine Ring Binding Domain J. Biol. Chem. 268, 16437-16442 (1993).

98. Chavan, A., Richardson, S., Kim, H., Haley, B. and Watt, D. Forskolin Photoaffinity Probes for the Evaluation of Tubulin Binding Sites Bioconjugate Chem. 4, 268-274 (1993).

99. Duhr, E.F., Pendergrass, J. C., Slevin, J.T., and Haley, B. HgEDTA Complex Inhibits GTP Interactions With The E-Site of Brain b-Tubulin Toxicology and Applied Pharmacology 122, 273-288 (1993).

100. Jayaram, B. and Haley, B. Identification of Peptides Within the Base Binding Domains of the GTP and ATP Specific Binding Sites of Tubulin. J. Biol. Chem. 269 (5) 3233-3242 (1994).

101. A. Chavan, B. Haley, D. Volkin, K. Marfia, A. Verticelli, M. Bruner, J. Draper, C. Burke and R. Middaugh. Interaction of Nucleotides with Acidic Fibroblast Growth Factor (FGF-1). Biochemistry 33,7193-7202 (1994).

102. Logan, J., Hiestand, D., Daram, P., Huang, Z., Muccio, D., Hartman, J., Haley, B., Cook, W., and Sorscher, E. Cystic Fibrosis Transmembrane Conductance Regulator Mutations That Disrupt Nucleotide Binding. J. Clin. Invest. 94, 228-236 (1994).

103. Olcott, M. and Haley, B. Identification of Two Peptides From the ATP-Binding Domain of Creatine Kinase. Biochemistry, 33, 11935-11941 (1994).

104. Bhattacharyya, A., Chavan, A., Shuffett, M., Haley, B. and Collins, D. Photoaffinity Labeling of Rat Liver Microsomal 5a-Reductase by 2-Azido-NADP+. Steroids 59, 634-641 (1994).

105. Salvucci, M., Chavan, A., Klein, R., Rajagopalan, K. and Haley, B. Photoaffinity Labeling of the ATP Binding Domain of Rubisco Activase and a Separate Domain Involved in the Activation of Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase. Biochemistry 33, 14879-14886 (1994).

106. Pendergrass, J.C. and Haley, B.E. Mercury-EDTA Complex Specifically Blocks Brain b-Tubulin-GTP Interactions: Similarity to Observations in Alzheimer"s Disease. pp98-105 in Status Quo and Perspective of Amalgam and Other Dental Materials (International Symposium Proceedings ed. by L. T. Friberg and G. N. Schrauzer) Georg Thieme Verlag, Stuttgart-New York (1995).

107. Doukas, M., Chavan, A., Gass, C., Nickel, P., Boone, T. and Haley, B. Inhibition of GM-CSF Activity by Suramine and Suramin Analogues is Correlated to Interaction with the GM-CSF Nucleotide Binding Site. Cancer Research 55:5161-5163 (1995).

108. Bhattacharyya, A. K., Chavan, A.J., Haley, B., Taylor, M.F., and Collins, D.C. Identification of the NADP(H) Binding Site of Rat Liver Microsomal 5a-Reductase (Isozyme-1): Purification of a Photolabeled Peptide Corresponding to the Adenine Binding Domain. Biochemistry 34, 3663-3669 (1995)

109. Chavan, A., Gass, C., Haley, B., Boone, T. and Doukas, M. A. Identification of N-Terminus Peptide of Human Granulocyte/Macrophage Colony Stimulating Factor as the Site of Nucleotide Interaction. Biochem. Biophys. Res. Commun. 208,#1 390-396 (1995).

110. Shoemaker, M., and Haley, B. Identification of the Adenine Binding Domain Peptides of the ADP Binding Site of Glutamate Dehydrogenase. Bioconjugate Chemistry 7, 302-310 (1996).

111. Rajagopalan, K., Pavlinkova, G., Levy, S., Pokkuluri, R., Schiffer, M., Haley, B., and Kohler, H. Novel Unconventional Binding Site in the Variable Region of Immunoglobulins. Proc. Natl. Acad. Sci. 93, 6019-6024 (1996).

112. Pavlinkova, G., Rajagopalan, K., Muller, S., Chavan, A., Sievert, G., Lou, D., O'Tolle, C., Haley, B., and Kohler, H. Site-Specific Photobiotinylation of Immunoglobins, Fragments and Light Chain Dimers. J. Immunological Methods 201, 77-88 (1997).

113. Pendergrass, J.C. and Haley, B.E. Inhibition of Brain Tubulin-Guanosine 5'-Triphosphate Interactions by Mercury: Similarity to Observations in Alzheimer's Diseased Brain. In Metal Ions in Biological Systems V34, Mercury and Its Effects on Environment and Biology, Chapter 16. Edited by H. Sigel and A. Sigel. Marcel Dekker, Inc. 270 Madison Ave., N.Y., N.Y. 10016 (1996).

114. McGuire, M., Carroll, L. J., Yankie, L., Thrall, S. H., Dunaway-Mariano, D., Hertzberg, O., Jayaram, B. and Haley, B. Determination of the Nucleotide Binding Site within Clostridium symbiosum Pyruvate Phosphate Dikinase by Photoaffinity Labeling, Site-Directed Mutagenesis, and Structural Analysis. Biochemistry 35, 8544-8552 (1996).

115. Kohler, H., Pavlinkova, G., and Haley, B. Immunoglobulin Nucleotide Binding Site: A Possible Superantigen Receptor. In Human B Cell Superantigens, edited by Moncei Zouali, Chapter 13, pp 189-194 (1996).

116. Sankaran, B., Chavan, A. and Haley, B. Identification of Adenine Binding Domain Peptides of the NADP+ Active Site within Porcine Heart NADP+-Dependent Isocitrate Dehydrogenase. Biochemistry 35, 13501-13510 (1996).

117. Sankaran, B., Clemens, J., and Haley, B. A Comparison of Changes in Nucleotide-Protein Interactions in the Striatal, Hippocampus and Paramedian Cortex After Cerebral Ischemia and Reperfusion: Correlations to Regional Vulnerability. Molecular Brain Research 47, 237-250 (1997).

118. Hensley, K., Cole, P. ,Aksenov, M., Aksenova, M., Bummer, P.E., Carney, J.M., Haley, B.E., and Butterfield, D.A. Oxidatively-Induced Structural Alteration of Glutamine Synthetase Assessed by Analysis of Spin Label Incorporation Kinetics. J. of Neurochemistry 68, 2451-2457 (1997).

119. Pendergrass, J. C., Haley, B.E., Vimy, M. J., Winfield, S.A. and Lorscheider, F.L. Mercury Vapor Inhalation Inhibits Binding of GTP to Tubulin in Rat Brain: Similarity to a Molecular Lesion in Alzheimer's Disease Brain. Neurotoxicology 18(2), 315-324 (1997).

120. Olcott, M.C. and Haley, B.E. Identification of an Adenine-nucleotide Binding Site on Interferon-a2. Eur. J. Biochem. 247/3, 762-769 (1997).

121. David, S., Shoemaker, M., and Haley, B. Abnormal Properties of Creatine kinase in Alzheimer's Disease Brain: Correlation of Reduced Enzyme Activity and Active Site Photolabeling with Aberrant Cytosol-Membrane Partitioning. Molecular Brain Research accepted (1997).

RESEARCH PAPERS (ABSTRACTS)

1. Haley, B. and Yount, R. Inhibition of Myosin by Gamma-Fluoroadenosine Triphosphate, Abstracts Pacific Slope Biochemistry Conference, Seattle, Washington (1969).
2. Haley, B. Synthesis of Photoaffinity Analogs of ATP and AMP and Their Use as Membrane Probes. Mount Sinai School of Medicine & Rockefeller University School of Medicine, (Invited paper)(1974)
3. Haley, B. and Hoffman, J. Photoaffinity Labeling of ATP Binding Sites of Human Erythrocyte Membrane, FASEB Meeting, Atlantic City (1974).
4. Haley, B. Photoaffinity Labeling of cAMP Binding Sites of Human Erythrocyte Membranes, Abstracts 1975 ICN-UCLA Biochemistry Conference on Energy Transduction (1975).
5. Haley, B. Photoaffinity Labeling of Human Red Cell Membrane Binding Sites Using 8-Azido-cAMP, Abstracts 1975 FASEB Meeting, Atlantic City (1975).
6. Owens, J.R. and Haley, B. A Study of cAMP Stimulated Phosphorylation and cAMP Binding Sites of Human Erythrocyte Membrane Proteins using 32P-8-Azido-cAMP, a Photoaffinity Probe. ICN-UCLA Conference on Molecular and Cellular Biology (1975).
7. Owens, J. and Haley, B. Properties of cAMP Binding Proteins of the Human Erythrocyte Membrane, Abstracts 1976 ICN-UCLA Biochemistry Conference on Cell Shape and Surface Architecture (1976).
8. Seery, V. and Haley, B. Activation of Glycogen Phosphorylase by 8-Azidoadenosine 5'-Monophosphate, Abstracts ASBC Meeting, San Francisco (1976).
9. Waterson, R. and Haley, B. Interactions of Photoaffinity AMP and ATP Analogs with E. coli Aminoacyl-tRNA Synthetases, Abstracts ASBC Meeting, San Francisco (1976).
10. Fletcher, P., Kaltenback, C. and Haley, B. Photoaffinity Labeling of Adenosine-3', 5' Cyclic Monophosphate Binding Sites in Ovine Corpus Lutea. Abstracts, Society for the Study of Reproduction, Philadelphia, Pennsylvania (1976).
11. Geahlen, R.L., Moore, V.G., Kaiser, I.I. and Haley, B.E. Synthesis and Biological Activity of Photoactive 8-Azidoguanosine Nucleotide Analogs. Abstracts, 1977 FASEB Meeting, Chicago (1977).
12. Owens, J. and Haley, B. Mechanism of Action of Membrane Bound cAMP Activated Protein Kinase. 1977 ICN-UCLA Conference on Molecular Aspects of Membrane Transport (1977).
13. Hahn, G.L., Metz, K.W., Atherton, R.W. and Haley, B.E. Labeling of a Surface Cyclic-AMP Receptor Site on Rabbit Sperm Utilizing a Photoaffinity Analog. American Society of Andrology, Nashville, Tennessee (1978).
14. Owens, J. and Haley, B.E. Mechanism of Mg-ATP Regulation of Membrane Bound Type 1 cAMP Activated Protein Kinase, Transmembrane Signaling, ICN-UCLA Symposia (1978).
15. Czarnecki, J. and Haley, B. Interaction of 8-Azido-2'-Deoxyadenosine-5'-Triphosphate, A Photoaffinity Label, with a DNA-Dependent DNA Polymerase. ASBC Meeting, Atlanta (1978).
16. Hoyer, P.B. and Haley, B.E. Partial Characterization of Rat Brain cAMP Binding Proteins: Cellular Location, Molecular Weights, and Nucleotide Effects. 1979 ICN-UCLA Conference on Covalent Modification of Proteins (1979).
17. Schoff, P., Atherton, R.W. and Haley, B.E. A Study of the cAMP Receptor Proteins of Human Ejaculated Sperm Using a Photoaffinity Analog. 1979 Soc. Study of Reproduction (1979).
18. Briggs, F.N., Al-Jumaily, W. and Haley, B.E. Interactions of the Photoaffinity Analog of ATP, 8-Azido-ATP, 8-Azido-ATP, with Vesicles of Skeletal and Cardiac Sarcoplasmic Reticulum (1980).
19. Hoyer, P.B. and Haley, B.E. Use of Photoaffinity Probes to Study cAMP Dependent Membrane Partitioning of ATP Binding and Phosphorylated Proteins (1980).
20. Owens, J.R. and Haley, B.E. Photoaffinity Labeling of Guanosine Polyphosphate (Magic Spot) Binding Proteins. Fed. Proc. 40, St. Louis, Missouri (1981).
21. Khatoon, S., Schoff, P.L., Haley, B.E. and Atherton, R.W. A Comparative Study of Sperm cAMP Dependent Protein Kinases by a Photoaffinity Analysis. American Society of Andrology Meeting, New Orleans, Louisiana (1981).
22. Woody, A-Young, M., Vader, C.R., Reisbig, R.R., Woody, R.W. and Haley, B.E. Photoaffinity Labeling of DNA-dependent RNA Polymerase from E. coli with 8-Azido-Adenosine 5'-Triphosphate. Biophysical Society Meeting, Denver, Colorado (1981).
23. Schoff, P.K., Khatoon, S., Haley, B.E. and Atherton, R.W. Protein Kinases: Control by Ca and cAMP in Rat Caudal Epididymal Sperm. American Society of Andrology Meeting, New Orleans, Louisiana (1981).
24. Kaiser, I.I., Moore, V.G., Van Kirk, E. and Haley, B.E. The Enzymatic Synthesis of an 8-Azido-Adenosine-Containing Analog of OS-adenosylmethionine. Fed. Proc. 40, St. Louis, Missouri (1981).
25. Hoyer, P.B. Phosphorylation of the cAMP Dependent Protein Kinases Catalytic Subunit Inhibits Phosphorylation of Endogenous Substrates. Fed. Proc. 40, St. Louis, Missouri (1981).
26. Haley, B.E. and Al-Jumaily, W. Utilization of Nucleotide Probes to Study Adenylyl Cyclase in Biological Membranes. 1982 UCLA Symposium: "Evolution of Hormone-Receptor Systems", Squaw Valley, California (1982).
27. Khatoon, S., Haley, B.E. and Atherton, R.W. A Photolabeling Analysis of the cAMP-Dependent Protein Kinase Regulatory Subunits in Sea Urchin and Rat Sperm. Society for the Study of Reproduction, Madison, Wisconsin (1982).
28. Owens, J.R. and Haley, B.E. Labeling of Nucleotide Binding Sites in E. coli and B. subtilis with "Magic Spot" Photoaffinity Analogs. FASEB Meeting, New Orleans, Louisiana (1982).
29. Owens, M., Haley, B.E. and Barden, R.E. Photolibile Multisubstrate Analogues as Photoaffinity Probes for Adenylate Kinase: Synthesis and Kinetic Studies. FASEB Meeting, New Orleans, Louisiana (1982).
30. Haley, Boyd. Utilization of Nucleotide Photoaffinity Probes to Study Adenylyl Cyclase and Protein Kinases in Biological Systems. 12th International Congress of Biochemistry. Perth, Australia (1982).
31. Khatoon, S., Atherton, R. and Haley, B. Studies on Rat Epidimal Sperm Phosphorylating Systems Using Nucleotide Photoaffinity Analogs. ASBC Meetings, San Francisco, California (1983).
32. Haley, B., Hoyer, P. and Middaugh, C.R. Studies on Adenylyl Cyclase Using Fluorescent and Photoaffinity GTP Analogs. ASBC Meeting, San Francisco, California (1983).
33. Owens, M., Barden, R. and Haley, B. Labeling of the Active Site of Adenylate Kinase Using a Multisubstrate Photoaffinity Probe. ASBC Meetings, San Francisco, California (1983).
34. Owens, J., Woody, A.-J. and Haley, B. Photoaffinity Labeling of RNA Polymerase with [5'-32P] 8-Azidoguanosine-3'-phosphate-5'-phosphate, A Transcriptional Inhibitor. ASBC Meeting, San Francisco, California (1983).
35. Middlebrook, J.L., Evans, G.R., Smith, L.A. and Haley, B.E. Interaction of Azido-ATP with Botulinum Neurotoxin. 3rd International Congress on Cell Biology (1984).
36. Khatoon, S. and Haley, B.E. Autophosphorylation of cAMP Dependent Protein Kinase Catalytic Subunit Inhibits its Ability to Bind Nucleotide Triphosphates. ASBC Meeting, St. Louis, Missouri (1984).
37. Karpel, R.L., Levin, V.Y. and Haley, B.E. Photoaffinity Labeling of a Nucleic Acid Helix-Destabilizing Protein. USLA Symposia on Protein Structure, Folding and Design (1985).
38. Haley, B.E., Evans, R.K. and Roth, D.A. Studies on Viral Induced Nucleotide Binding Proteins in Tobacco. ASBC Meetings, Anaheim, California (1985).
39. Evans, R.K., Johnson, J.D. and Haley, B.E. Synthesis of 5-azido-2'-deoxyuridine-5'-triphosphate: Enzymatic Incorporation into DNA. ASBC Meetings, Anaheim, California (1985).
40. Duhr, E., Leppla, S.H. and Haley, B. Studies on Bacillus anthracis and Staphyloccoccal Protein Toxins Using Nucleotide Photoaffinity Analogs. ASBC Meetings, Anaheim, California (1985).
41. Francis, B., Mackenzie, III, C.W. and Haley, B.E. Photoaffinity Labeling and Phosphorylation Studies of cGMP Dependent Protein Kinase. ASBC Meetings, Anaheim, California (1985).
42. Toner, J.A., Haley, B. and Taylor, S.J. Scoichiometric Autophosphoration of the Catalytic Subunit of cAMP-dependent Protein Kinase II. ASBC Meetings, Anaheim, California (1985).
43. Khatoon, S., Haley, B. and Coleman, M.S. Interactions of Deoxynucleotide Photoaffinity Analog with Terminal Deoxynucleotidyl Transferase (TdT). ASBC Meetings, Anaheim, California (1985).
44. Shi, Q.H., Ruiz, J., Ho, R.J. and Haley, B.E. Evaluation of Inhibition of Forskolin-activated Adenylate Cyclase by GDP or TNP-GTP. ASBC Meetings, Anaheim, California (1985).
45. Khatoon, S., Beach, C., Haley, B. and Coleman, M.S. Active Site Characterization of Terminal Deoxynucleotidyl Transferase (TdT): Modification with Deoxynucleotide Photoaffinity Analogs. ASBC Meetings, Washington, D.C. (1986).
46. Karpel, R.L., Levin, V.Y. and Haley, B. Characterization of a Crosslinked Nucleic Acid: Helix Destabilizing Protein Complex. ASBC Meetings, Washington, D.C. (1986).
47. Khatoon, S., Haley, B.E. and Slevin, J.T. Decreased Availability of the Exchangeable GTP Binding Site of the b-Subunit of Brain Tubulin in Alzheimer's Disease. AAN Scientific Program, New York, New York (1987).
48. Lewis, C., Haddad, R., Carlson, G.M. and Haley, B.E. Photoaffinity Labeling of Phosphoenolpyruvate Carboxykinase (GTP) by 8-Azido-GTP. ASBC Meetings, Philadelphia, Pennsylvania (1987).
49. Kim, H., Ponstingl, H. and Haley, B.E. Identification of the Guanosine Interacting Peptide of the GTP Binding Site of b-Tubulin Using 8N3GTP. ASBC Meetings, Philadelphia, Pennsylvania (1987).
50. Khatoon, S., Slevin, J.T. and Haley, B.E. GTP Binding to the b-Subunit of Tubulin is Greatly Reduced in Alzheimers Disease. ASBC Meetings, Philadelphia, Pennsylvania (1987).
51. Campbell, S.R., Khatoon, S., Haley, B.E. and Slevin, J.T. Inability of Brain Microtubules in Alzheimers Disease to Cold-Depolymerize. Neuroscience Meeting, New Orleans, Louisiana (1987).
52. Ho, L.T., Nie, Z.M., Mende, T.J., Richardson, S., Lee, H., Watt, D.S., Haley, B.E. and Ho, R.J. Photoaffinity-Analogs of Forskolin and their Effects on Adenylate Cyclase. APS Meeting, San Diego, California (1987).
53. Li, S.W., Sobol, R.W., Kariko, K., Haley, B.E. and Suhadolnik, R.J. Photoaffinity Labeling of 2-5A Synthetase by 2- and 8-azido-ATP. FASEB Meeting, Las Vegas, Nevada (1988).
54. Francis, B.R. and Haley, B.E. Regulation of Protein Phosphorylation in Colon Carcinoma Homogenates by Metabolic Products of Glycolysis and IP3. FASEB Meeting, Las Vegas, Nevada (1988).
55. Drake, R.R., Evans, R.K. and Haley, B.E. Synthesis and Properties of 5-azido-UDP-glucose, an Active Site-directed Photoaffinity Probe. FASEB Meeting, Las Vegas, Nevada (1988).
56. Nie, Z.M., Ho, L.T., Lee, D.S., Bowdan, J.B., Mende, T.M., Watt, D.S., Haley, B.E. and Ho, R.J. Photoaffinity Analogs of Adenylate Cyclase Activator, Forskolin. FASEB Meeting, Las Vegas, Nevada (1988).
57. Salvucci, M.E. and Haley, B.E. Photoaffinity Labeling of the Large and Small Subunits of Ribulose Bisphosphate Carboxylase with 8-Azido-ATP. Plant Physiology (1988).
58. Droms, K.A., Smith, G.J., Malkinson, A.M. and Haley, B.E. Gsa and Lung Epithelial Cell Growth. American Association for Cancer Research Meeting, Miami, Florida (1988).
59. Lewis, C.T., Haley, B.E. and Carlson, G.M. Evidence for Formation of a Transient Sulfenamide Bond During Photoaffinity Labeling by 8-Azido-GTP of Phosphoenolpyruvate Carboxykinase. American Chemical Society, San Diego, California (1988).
60. Chavan, A.J., Watt, A.J., Kim, H. and Haley, B.E. Synthesis and Application of GTP Phosphonamide Photoaffinity Reagents. American Chemical Society Meeting, Los Angeles, California (1988).
61. Lee, H., Watt, D.S., Kim, H. and Haley, B.E. Synthesis and Application of a Forskolin Photoaffinity Probe to a Tubulin Binding Site. American Chemical Society Meeting, Atlanta, Georgia (1988).
62. Drake, R.R. and Haley, B.E. Covalent Labeling of Phosphoglucomutase by [32P]UDP-GLC AND [32P]5N3UDP-GLC. ASBMB Meeting, Los Angeles, California (1989).
63. Watt, D.S., Lee, H.-W., Kim, H.-T. and Haley, B.E. Detection of a Forskolin Binding Site Using a Photoaffinity Probe. ASBMB Meeting, Los Angeles, California (1989).
64. Dholakia, J.N., Francis, B.R., Haley, B.E. and Wahba, A.J. Characterization of the Guanine Nucleotide Exchange Factor as a GTP Binding Protein. ASBMB Meeting, Los Angeles, California (1989).
65. Parker, K.W., Drake, R.R., Haley, B.E. and Salvucci, M.E. Photoaffinity Labeling of Tobacco Subcellular Fractions with [32P]-Azido-UDP-Glucose. ASPP/CSPP Toronto, Ontario, Canada (1989).
66. Campbell, S., Kim, H., Haley, B.E. and Doukas, M. Photoaffinity Labeling of Nucleotide Binding Sites on Interleukin-2. Second International Workshop on Cytokines. Hilton Head, North Carolina (1989).
67. Wasserman, B.P., Frost, D.J., Wu, A., Read, S.M., Drake, R.R. and Haley, B.E. Identification of the UDPG-Binding Polypeptide of (1,3)-b-Glucan Synthase of Higher Plants by Photoaffinity Labeling with 5-Azido-UDPG. Fifth Cell Wall Meeting, Edinburgh (1989).
68. Gunnersen, D.J., Slevin, J.T. and Haley, B.E. Novel Proteins in Alzheimer's Diseased Brain May be Due to Pathological Modification of b-Tubulin. ASBMB Meeting, New Orleans, Louisiana (1990).
69. Drake, R., Hiestand, D., Sharp, J. and Haley, B. Nucleotide Binding and Autophosphorylation Properties of IL-1b. ASBMB Meeting, New Orleans, Louisiana (1990).
70. Kim, H. and Haley, B. Identification of Active Site Peptides of Glutamate and Lactate Dehydrogenases by Photoaffinity Labeling. ASBMB Meeting, New Orleans, Louisiana (1990).
71. Lin, P.P-C., Shoemaker, M.T. and Haley, B.E. Observation of a Specific Nucleotide Binding Site on Glucagon by Photoaffinity Labeling with Azido-GTP. ASBMB Meeting, New Orleans, Louisiana (1990).
72. Olcott, M. and Haley, B. Identification of a Nucleotide Binding Site on Interferon-a. ASBMB Meeting, New Orleans, Louisiana (1990).
73. Campbell, S., Kim, H., Hiestand, D. and Haley, B. Photoaffinity Labeling of Nucleotide Binding Sites on Tumor Necrosis Factor. ASBMB Meeting, New Orleans, Louisiana (1990).
74. Duhr, E., Slevin, J. and Haley, B. Low Level HgEDTA Complex Specifically Blocks [32P]8N3GTP Interaction with Human Brain Tubulin. ASBMB Meeting, New Orleans, Louisiana (1990).
75. Mann, D.M., Haley, B.E. and Greenberg, R.N. GTP Binding to Atrial Natriuretic Factor as Determined by Photoaffinity Labeling with [g-32P]8N3GTP. ASBMB Meeting, New Orleans, Louisiana (1990).
76. Droms, K.A., Haley, B.E. and Malkinson, A.M. Mechanism of Decreased b-Adrenergic Stimulation of Adenylate Cyclase in Neoplastic Mouse Lung Epithelial Cell Lines. FASEB Meeting, Washington, D.C. (1990).
77. Manning, E.L., Kim, H., Haley, B.E. and Jacobson, M.K. Utilization of 2-Azido-NAD for Studies of ADP-Ribose Polymer Metabolism. ASBMB Meeting, New Orleans, Louisiana (1990).
78. Watt, D.S., Chavan, A.J., Kim, H.-T. and Haley, B.E. A Novel GTP Photoaffinity Probe for the Identification of the Exchangeable GTP-Binding Domain in Tubulin. ASBMB Meeting, New Orleans, Louisiana (1990).
79. Doukas, M., Chavan, A.J., Campbell, S. and Haley, B.E.Photolabeling of the Granulocyte/Macrophage-Colony StimulatingFactor (GM-CSF) Eliminates Its Biological Activity. FASEBMeeting, Atlanta, Georgia (1991), FASEB J., 5 (4), A424.
80. Duhr, E., Pendergrass, C., Kasarskis, E., Slevin, J. and Haley, B.E. Hg2+ Induces GTP-Tubulin Interactions in Rat Brain Similar to those Observed in Alzheimer's Disease. FASEB Meeting, Atlanta, Georgia (1991), FASEB J., 5, (4), A456.
81. Trad, C.H., Chavan, A.J. and Haley, B.E. Detection of an NAD+/NADH Binding Site on Prolactin Using [32P]2N3NAD+. FASEB Meeting, Atlanta, Georgia (1991), FASEB J., 5, (4), A795.
82. Shoemaker, M.T., Jayaram, B. and Haley, B.E. Glucagon-GTP Interactions: Identification of a Binding Domain Peptide. FASEB Meeting, Atlanta, Georgia (1991), FASEB J., 5, (4), A795.
83. Jayaram, B., Sankaran, B., Watt, D.S. and Haley, B.E. Synthesis and Use of Radiolabeled, Non-Hydrolyzable GTP Photoaffinity Probes. FASEB Meeting, Atlanta, Georgia (1991), FASEB J., 5, (6), A1508.
84. Campbell, S., Doukas, M. and Haley, B.E. Identification of the [a-32P]8-Azido-ATP Photolabeled Peptides of rhIL-2. FASEB Meeting, Atlanta, Georgia (1991), FASEB J., 5, (6), A1521.
85. Gunnersen, D.J., Slevin, J.T. and Haley, B.E. Preliminary Characterization of a Novel Alzheimer's Disease Associated Protein. FASEB Meeting, Atlanta, Georgia (1991), FASEB J., 5, (4), A456.
86. Hiestand, D.M., Haley, B.E. and Kindy, M.S. Nucleotide Binding and Phosphorylation Properties of Proteins from Control and Ischemic Brains. FASEB Meeting, Atlanta, Georgia (1991), FASEB J., 5, (4), A458.
87. Rajagopalan, K., Chavan, A.J., Haley, B.E. and Watt, D.S. Bidentate GTP Photoaffinity Probes: Cross-Linking Agents with Two Photoactive Groups. FASEB Meeting, Atlanta, Georgia (1991), FASEB J., 5, (6), A1522.
88. Bradley, M., Olcott, M. and Haley, B. Characterizaton of the ATP Binding Domain of Creatine Kinase Using Photoaffinity Probes. ASBMB Meeting, Houston, Texas (1992)
89. Doukas, M., Chavan, A., Boone, T., Gass, C. and Haley, B. Nucleotide Binding Site of Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF) is Preserved Across Species Barriers. ASH Annual Meeting, Anaheim, California (1992)
90. Sankaran, B., Haley, B. and Clemens, J. Identification of Changes in Nucleotide Interacting Proteins in Control vs Ischemic Rat Brains. Society for Neuroscience Meeting, Anaheim, California (1992)
91. Gunnersen, D., and Haley, B. Detection of Glutamine Synthetase in the CSF of Alzheimer's Diseased Patients: A Potential Diagnostic Biochemical Marker. Society for Neuroscience Meeting, Anaheim, California (1992)
92. Hiestand, D., Cha]van, A. and Haley, B. Identification of a Nucleotide Binding Domain on Recombinant Human IL-1b. FASEB Meeting, New Orleans, Louisiana (1993)
93. Olcott, M., Haley, B. Identification of Two Peptides in the Adenine Binding Domain of Creatine Kinase Using Immobilized Al3+ Affinity Chromatography. FASEB Meeting, New Orleans, Louisiana (1993)
94. Rajagopalan, K., Chavan, A., Haley, B., and Watt, D. Synthesis and Application of Bidentate Nucleotide Photoaffinity Cross-linking Reagents with Two Photoactive Groups. FASEB Meeting, New Orleans, Louisiana (1993)
95. Shoemaker, M., and Haley, B. Identification of the Adenine Binding Domain of ADP Regulatory Site within GDH. FASEB Meeting, New Orleans, Louisiana (1993)
96. Chavan, A., Doukas, M., Gass, C., Haley, B. and Boone, T. Covalent Linkage of [a32P]ATP or [g32P]ATP to rmGM-CSF in the Absence of Light. FASEB Meeting, New Orleans, Louisiana (1993)
97. Doukas, M., Chavan, A., Gass, C., Boone, T. and Haley, B. Nucleotide Binding Sites of Human and Murine Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF) are Identical. FASEB Meeting, New Orleans, Louisiana (1993)
98. Pendergrass, J., Duhr, E., Slevin, J., and Haley, B. meso-2, 3-Dimercaptosuccinic (DMSA) Acid to both Alzheimer's Diseased (AD) Brains and to HgEDTA Treated Control Brains. FASEB Meeting, New Orleans, Louisiana (1993)
99. Sorscher, E.J., Daram, P., Hiestand, D., Huang, Z., Peng, S., Muccio, D., Haley, B., and Logan, J. Mutations in CFTR Nucleotide Binding Domains (NBD's) Disrupt Trinitrophemyl ATP Binding. FASEB Meeting, New Orleans, Louisiana (1993).
100. Logan, J., Hiestand, D., Huang, Z., Muccio, D., Haley, B., and Sorscher, E. 3-Isobutyl-1-methylxanthine (IBMX) Blocks Binding of ATP Analogs to the CFTR First Nucleotide Binding Domain (NBD-1). FASEB Meeting, New Orleans, Louisana (1993).
101. Rajagopalan, K., Chavan, A.J., Cockle, S., Haley, B. and Watt, D. Identification of ATP-g-Phosphate Binding Domain of Pertussis Toxin By Photoaffinity Labeling. FASEB Meeting, New Orleans, Louisiana (1993).
102. Kasarskis, E, Haley, B., and Gunnerson, D. GTP-binding Proteins in Amyotrophic Lateral Sclerosis Cerebrospinal Fluid. Abstracts American Neurological Assoc., Ann. Neurology 34, 297 (1993).
103. Pendergrass, J., Duhr, E., Haley, B., and Slevin, J. Effect of Chronic Ingestion of Micromolar HgCl2 and HgEDTA Complex on Rodent Neuronal Cytoskeleton. Society for Neuroscience 23rd Annual Meeting, Abstracts, p193, #81.6 Washington, DC (1993).
104. Haley, B., Duhr, E., and David, S. Identification of an 8-Hydroxyguanosine Nucleotide in CSF that Blocks GTP Binding to b-Tubulin. Abstracts Annual Meeting Soc. For Neuroscience (1994).
105. Shoemaker, M., and Haley, B. Creatine Kinase is Generally Depleted and Inactive in Alzheimer's Diseased Brain. ASBMB Abstracts, FASEB J. 8, #7 (1994)
106. Sankaran, B., and Haley, B. Identification of the Coenzyme Binding Site of NADP+-Dependent Isocitrate Dehydrogenase. ASBMB Abstracts, FASEB J. 8, #7 (1994).
107. Hiestand, D., Sorscher, E., and Haley, B. Use of 2N3ATP to Identify the Site of ATP Interaction on Nucleotide Binding Domain-2 From the Cystic Fibrosis Transmembrane Conductance Regulator. ASBMB Abstracts, FASEB J. 8, #7 (1994).
108. Hiestand, D., Sorscher, E., Huang, Z., Wang, Y., and Haley, B. Use of 2N3ATP to Identify the Site of ATP Interaction on Nucleotide Binding Domain-2 From the Cystic Fibrosis Transmembrane Conductance Regulator. Abstracts 8th Annual N. American Cystic Fibrosis Conference, Orlando, FL (1994).
109. Kohler, H., Pavlinkova, G., Rajagopalan, K., Wang, H-T., Chatterjee, S., and Haley, B. Specific Photoaffinity Labeling Locus on Antibodies: Use for Chelation, Protein Conjugation and Gene Delivery. Abstracts Annual meeting Exper. Biol., Anaheim, CA, FASEB J. 8, #4 pA236 (1994)
110. Lorscheider, F., Vimy, M., Pendergrass, J., and Haley, B. Toxicity of Ionic Mercury and Elemental Mercury Vapor on Brain Neuronal protein Metabolism. Abstracts 12th Intern. Neurotoxicology Conf. Univ. Arkansas Med. Ctr., Hot Springs, AR (1994).
111. Lorscheider, F., Vimy, M., Pendergrass, J. and Haley, B. Mercury Vapor Exposure Inhibits Tubulin Binding to GTP in Rat Brain: A Molecular Lesion Also Present in Alzheimer's Diseased Brain. Expt. Biol. Annual Meeting Abstracts, Atlanta, GA, FASEB J. 9, #4 pA663 (1995)
112. Chavan, A., Doukas, M., Gass, C., Haley, B., and Collins, D. Inhibition of Nucleotide Binding to Recombinant GM-CSF by Suramin and it's Analogs Correlates with Inhibition of Biological Activity. Annual ASBMB Meeting, San Francisco, CA FASEB J. 9, #6 pA1417 (1995).
113. Lorscheider, F., Vimy, M., Pendergrass, J., and Haley, B. Mercury Vapor Inhalation inhibits Binding of GTP to Tubulin in Rat Brain: A Molecular Lesion Present in Alzheimer's Diseased Brain. 25th Annual meeting of Society for Neuroscience, San Diego, CA Soc. Neurosci. 21, #3, p1723 (1995).
114. Hicks, R., Pendergrass, J. and Haley, B. Identification of the Guanine Binding Domain Peptide of Myelin Basic Protein Using [32P]8N3GTP. Abstracts PGSRM Meeting, Madison, WI (1995).
115. Pendergrass, J., Israel, M., and Haley, B. Use of Photoaffinity Labeling and 2-D Electrophoresis to Identify Changes in Nucleotide Binding Proteins in Brain and CSF: A Potential Diagnostic Technique for Neurological Diseases. Annual Meeting AAPS Miami, FL (1995)
116. Hicks, R., Pendergrass, J., and Haley, B. Identification of the Guanine Binding Domain peptide of Myelin Basic Protein Using [32P]8N3GTP. Annual Meeting AAPS Miami, Fl. (1995).
117. Pendergrass, J., Isarel, M., Borths, C., Chavan, A., and haley, B. Detection of Multiple Cytodines and Growth Factors in Human CSF Using Photochemistry. 6th International Congress on Cell Biology & 36th Amer. Soc. Cell Biol. Annual Meeting, San Francisco, CA (1996).
118. Kohler, H., Pavlinkova, G., Sievert, G., Freeman, J., and Haley, B. Tumor-Targeting of Oligonucleotides Using Affinity Linked Antibodies. Abstracts FASEB Meeting, New Orleans, Louisiana, FASEB J. 10, #6 pA1350 (1996).
119. Chavan, A., Doukas, M., Gass, C., Boone, T., and Haley, B. Probing Anti-Growth Factor Activity of Suramin Using Azido Nucleotides. 6th International Congress on Cell Biology & 36th Amer. Soc. Cell Biol. Annual Meeting, San Francisco, CA (1996).
120. Doukas, M., Chavan, A., Gass, C., Boone, T., Nickel, P., and Haley, B. Suramin and Suramin Analog Activity Against Leukemic Cell Lines: Correlation to Interaction with the Granulocyte/Macrophage Colony Stimulating Factor Nucleotide-Binding Site. Abstracts AACR Meeting (1996).

Boyd Haley
CURRICULUM VITAE

The basic research interest of our laboratory centers on biochemical and biomedical problems involving control at the molecular level. Specifically, we are most interested in biological systems regulated by protein-nucleotide interactions where the bioenergetics involved are expressed through site-specific nucleotide binding of high affinity or through protein substrate phosphorylation. Our approach to the study of this general phenomenon is to synthesize novel nucleotide analogs that are photoactive or fluorescent, or both. The analogs are then used to study various aspects of protein-nucleotide interactions which regulate enzyme activity. Analogs used may be modifications of the commonly known nucleotides such as ATP, cAMP, GTP, dUTP, NAD+, UDP-Glc, etc. or probes of the more unusual nucleotides such as the proposed alarmones guanosine-3'-phosphate-5'phosphate (magic spot compounds) and diadenosine-P1, P4-tetraphosphate.
These nucleotide analogs are used to study a wide variety of enzymes that either use or are regulated by nucleotides including cyclases, kinases, and polymerases. Certain of these probes have proven useful in the study of the differences between normal and diseased tissues as observed through changes in nucleotide binding proteins. Alzheimer's disease, Amyotrophic Lateral Sclerosis and Multiple Sclerosis are some of the diseases we are currently investigating. I am currently interested in the several low molecular weight nucleotide binding proteins that we have detected in human cerebrolspinal fluid that seem to vary in presence and concentration with various disease states. One of these is aFGF (binds ATP) and another is myelin basic protein (binds GTP, is phosphorylated and ADP-ribosylated).
We have also done studies that implicate low levels of Hg as being capable of being involved in certain neurological diseases. This is based on our observation that Hg2+ chelated with EDTA is a more potent inhibitor of tubulin polymerization than is free Hg2+. Addition of Hg-EDTA complex to non-demented human brain homogenates renders the photolabeling profile to be identical to that of Alzheimer's diseased brain homogenates. Further, exposure of rats to low level mercury vapor causes a great increase in rat brain mercury levels and a marked decrease in brain tubulin photolabeling as is observed in Alzheimer's diseased brain. These results support the contention that mercury vapor would exacerbate the symptoms associated with Alzheimer's disease. This is a major concern since substantial levels of mercury vapor is known to be released from dental amalgams and EDTA is a common food additive.
Additionally, we have found that several of the large polypeptide hormones (or biological response modifiers) have nucleotide binding sites. These include GM-CSF, aFGF,IL-1, IL-2, Interferon-alpha, TNF (tumor necrosis factor), glucagon and GH (growth hormone). We therefore feel that the transmembrane signaling effected by these proteins may, at least be expressed partially by an activity associated with the "hormone" itself. This is supported by the observation that IL-1 and IL-2 also autophosphorylate using ATP.


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