There's no problem with questioning science as long as you make a satisfactory effort to understand it first. It's apparent you don't. In order for the alleged link between thimerosal and autism "to be possible", there would have to be sound science showing it is so. Where is this science? All we saw were unfounded conspiracy theories and allegations.
Did Dr. Christina Moellering really say thimerosal was in the MMR vaccine? This is wrong. MMR has never contained thimerosal. Did you misquote Moellering? Why didn't your reporters, who tell us they spent six months investigating the science of autism, catch that error? It's pretty basic. Moellering is right when she says your report was "misleading and biased and a poor example of journalism."
Enabling viewers with information "so they could make their own educated decisions about vaccines" only works when the information is accurate. There's more to accuracy than just showing both sides of a story. A journalist also filters information and exposes flawed arguments. Instead we get wide eyed credulity and cheap voyeurism.
It's no wonder the CDC didn't respond to your questions. They've all been answered, ad nauseum. The best available science is plain for all to see. But first is has to be understood.
ANB, An ombudsman project is a viewer advocate... A middle man that has ties to the newsroom...but not directly. The team wasn't involved in the selection process or responses to the emails.
A convenient excuse. You certainly know (by now at least)that MMR never contained Mercury or anything else as a Preservative. It is a live virus vaccine. A preservative would kill an attenuated live virus. Case closed on MMR, oral polio and Varicella vaccines. That KOMU allowed you to hijack its facilities for what is obviously a personal agenda, is disgraceful. You seem so proud of your work...it is sad. Were you to publish a "hard hitting thorough investigation" that proved the twin towers were destroyed by the Bush administration, you would also get hundreds... nay...thousands of emails and letters of congratulations from he 9/11 Truth people. A big viewer response is not a sign you are engaged in good journalism...unless your goal is to eventually work for the Enquirer (or Fox) By the way... I do not see my blog posts listed in viewer responses...why is that?
Dr. Julia Whiting has an active VICP claim. She subjects her daughter to Lupron, a powerful chemical castration drug, so she's hardly the unbiased voice of reason that she wants KOMU to believe she is. You can't complain about government scientists with drug company ties without objecting to vaccine suit plaintiffs posing as experts. At least the CDC is honest about past associations.
Stan Stanfield of Scotland is an anti-vaccinationist, and a cheerleader for the Geiers and Wakefield. I wouldn't be surprised if he were involved in the UK MMR litigation:
I feel for Dr. Miles. She's the only evidence-based professional interviewed at length for your series. That's not balance. It's one rational voice against a half dozen extremists. It's as if you interviewed a klavern of Klansman for a series on civil rights, then counted on Halle Barry for balance.
Why no context? Why no mention of the Geiers' fishy "studies", or Wakefield's bogus MMR research, or Ayoub's loony conspiracies? Why no explanation of the CDDS data or the blood brain barrier, or why there are no studies of children "cured" of autism through chelation"? You make passing reference to the scientists who dispute a vaccine link to autism but you never tell us why. Do you even know?
I don't expect anyone at KOMU to be embarrassed over this trainwreck. To fully comprehend the awfulness of this series, you would first need to understand the subject. It's apparent you don't.
I will now yield the floor to ad hominem attacks that have nothing to do with anything I've said.
It's as if you interviewed a klavern of Klansman for a series on civil rights, then counted on Halle Barry for balance.
Priceless, ANB.
Unfortunately these kids probably honestly think what they do is for the "greater good" and that in itself justifies throwing journalistic standards and intellectual integrity out the window.
Your PS: that thimerosal has not been used for sometime now, does not effect anyone older than 9 months of age. Below is a copy of the effective date of the law as April 1, 2007.
HCS/SS/SCS/SBs 74 & 49 - This act modifies and creates new provisions with respect to the Department of Health and Senior Services.
Missouri Law MERCURY IMMUNIZATIONS - Under the act, after April 1, 2007, any immunizations administered to knowingly pregnant women or children under three years of age shall not contain more than 1 microgram of mercury per 0.5-milliliter dose.
Do you really think it is better to have 1 in every 150 child being vaccine injured and diagnosed with autism? According to the CDC, 1 in 6 has a behavioral disorder and/or a neuro developmental disorder. History shows the rates of diphtheria, tetanus and rubella were never that high even prior to vaccines. As reported by Dr. Engley, thimerosal is toxic to human cells at a nanomolar level so a micro gram in vaccines is still a toxic level 1000 times over.
(μg, μgs) The prefix "micro" means 1/1,000,000 = 1e-6. Therefore, 1 microgram = 0.001 milligram = 0.000001 grams, or 1,000,000 μg = 1 g. 1 μg = 1e-9 kg. Nanogram (ng, ngs) The prefix "nano" means 1/1,000,000,000 = 1e-9, so 1,000,000,000 ng = 1e+09 1000 ng = 1 microgram.
This is the most balanced report. KOMU interviewed 5 different parents with children diagnosed with autism exposing viewers to different therapies and beliefs. 2 scientist and 2 MD's. One of the scientists was even Dr. Miles teacher and Assistant Dean of the School of Medicine at MU.
Ken,
Of course all the view points were biased on one side or the other, just like the biased science paid for by pharmaceutical companies. The conflict centers around MONEY and who is going to pay for the damage done to a generation of kids.
Thimerosal in any amount causes mercury poisoning.
Linda,Your comment about my "PS" makes no sense. THe law you quote clearly states that Thimerosol as a preservative is not allowed for children under the age of 3 (When most vaccines are given) Children do not usually get vaccines after age two until age 4 or 5 (Except those children who have parents convinced by series like this that there is a problem getting more than one vaccine at a time...thus dragging out the process. here is your quote: "Your PS: that thimerosal has not been used for sometime now, does not effect anyone older than 9 months of age." Whaaa? The "Doctors" you quote are not physicians and their "Science" on Mercury is bogus. Sorry. Have you considered plastic as a cause? What about Electromagnetic waves from power lines and appliances? It is most unfortunate that children are being diagnosed more often now with Autism. Autism is indeed terrible. Definitely more study is needed. Attacking vaccinations which have prevented thousands of deaths and birth defects since their introduction may fulfill some kind of odd religious or political motivation, but I believe it to be incredibly exploitative of folks with Autism and their parents.
Linda, you said "according to the CDC, 1 in 6 has a behavioral disorder and/or a neuro developmental disorder." This is a fatuous interpretation of normally distributed data on a bell curve. It's like saying that half of all children are below average, yet another example of cherry picked data and quote mining disguised as science.
Pharmacogenomics shows that the dose at which a poisonious effect is achieve varies greatly in a genetically heterogenous population.
Small doses of Xrays in young girls across their chests in their teens who are BRCA carriers leads to a huge risk event for cancer 20 years later.
It is unfortunate that this debate is not happening between many MDs, JDs, PhDs and Journalism School faculty on UM campus in a live format instead of here with lay people who comprehend less of the science on both ends of this debate than do many others in medicine and science who know whats going on.
TO KOMU I AM AVAILABLE TO HAVE SUCH A DEBATE AT THE J SCHOOL ANYTIME YOU WANT.
Looking bad again ANB, what was it about science that you were saying above on this thread? Maybe you should try to understand this series:
Arch Toxicol. 2003 Jan;77(1):50-5. Epub 2002 Nov 6. Related Articles, Links Click here to read Click here to read Click here to read Thimerosal induces micronuclei in the cytochalasin B block micronucleus test with human lymphocytes.
Westphal GA, Asgari S, Schulz TG, Bünger J, Müller M, Hallier E.
Department of Occupational Health, Georg-August-University Göttingen, Waldweg 37, 37073 Göttingen, Germany. gwestph@gwdg.de
Thimerosal is a widely used preservative in health care products, especially in vaccines. Due to possible adverse health effects, investigations on its metabolism and toxicity are urgently needed. An in vivo study on chronic toxicity of thimerosal in rats was inconclusive and reports on genotoxic effects in various in vitro systems were contradictory. Therefore, we reinvestigated thimerosal in the cytochalasin B block micronucleus test. Glutathione S-transferases were proposed to be involved in the detoxification of thimerosal or its decomposition products. Since the outcome of genotoxicity studies can be dependent on the metabolic competence of the cells used, we were additionally interested whether polymorphisms of glutathione S-transferases (GSTM1, GSTT1, or GSTP1) may influence the results of the micronucleus test with primary human lymphocytes. Blood samples of six healthy donors of different glutathione S-transferase genotypes were included in the study. At least two independent experiments were performed for each blood donor. Significant induction of micronuclei was seen at concentrations between 0.05-0.5 micro g/ml in 14 out of 16 experiments. Thus, genotoxic effects were seen even at concentrations which can occur at the injection site. Toxicity and toxicity-related elevation of micronuclei was seen at and above 0.6 micro g/ml thimerosal. Marked individual and intraindividual variations in the in vitro response to thimerosal among the different blood donors occurred. However, there was no association observed with any of the glutathione S-transferase polymorphism investigated. In conclusion, thimerosal is genotoxic in the cytochalasin B block micronucleus test with human lymphocytes. These data raise some concern on the widespread use of thimerosal.
Int J Hyg Environ Health. 2001 Jul;203(5-6):479-81.
Inhibition of the human erythrocytic glutathione-S-transferase T1 (GST T1) by thimerosal.
Müller M, Westphal G, Vesper A, Bünger J, Hallier E.
Department of Occupational and Social Medicine, Georg-August-University Göttingen, D-37073 Göttingen, Germany. mmuelle3@gwdg.de
We have investigated the interaction of thimerosal, a widely used antiseptic and preservative, with the human erythrocytic GST T1 (glutathione-S-transferase T1). This detoxifying enzyme is expressed in the erythrocytes of solely the human species and it displays a genetic polymorphism. Due to this polymorphism about 25% of the individuals of the caucasian population lack this activity ("non-conjugators"), while 75% show it ("conjugators") (Hallier, E., et al., 1993). Using our newly developed HPLC-fluorescence detection assay (Müller, M., et al., 2001) we have profiled the kinetics of enzyme inhibition in erythrocyte lysates of two individuals previously identified as "normal conjugator" (medium enzyme activity) and "super-conjugator" (very high activity). For the normal conjugator we have determined a 2.77 mM thimerosal concentration to inhibit 50% of the GST T1 activity. In the case of the super-conjugator a 2.3 mM thimerosal concentration causes a 50% inhibition of the enzyme activity. For both phenotypes a 14.8 mM thimerosal concentration results in residual enzyme activities equal to those typically detected in non-conjugator lysates. Thus, sufficiently high doses of thimerosal may be able to change the phenotypic status of an individual--at least in vitro--by inhibition of the GST T1 enzyme.
Am J Med Genet B Neuropsychiatr Genet. 2006 Dec 5;141(8):947-56.
Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism.
James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, Cutler P, Bock K, Boris M, Bradstreet JJ, Baker SM, Gaylor DW.
Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 72202, USA. jamesjill@uams.edu
Autism is a behaviorally defined neurodevelopmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal. Although both genetic and environmental factors are thought to be involved, none have been reproducibly identified. The metabolic phenotype of an individual reflects the influence of endogenous and exogenous factors on genotype. As such, it provides a window through which the interactive impact of genes and environment may be viewed and relevant susceptibility factors identified. Although abnormal methionine metabolism has been associated with other neurologic disorders, these pathways and related polymorphisms have not been evaluated in autistic children. Plasma levels of metabolites in methionine transmethylation and transsulfuration pathways were measured in 80 autistic and 73 control children. In addition, common polymorphic variants known to modulate these metabolic pathways were evaluated in 360 autistic children and 205 controls. The metabolic results indicated that plasma methionine and the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), an indicator of methylation capacity, were significantly decreased in the autistic children relative to age-matched controls. In addition, plasma levels of cysteine, glutathione, and the ratio of reduced to oxidized glutathione, an indication of antioxidant capacity and redox homeostasis, were significantly decreased. Differences in allele frequency and/or significant gene-gene interactions were found for relevant genes encoding the reduced folate carrier (RFC 80G > A), transcobalamin II (TCN2 776G > C), catechol-O-methyltransferase (COMT 472G > A), methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C), and glutathione-S-transferase (GST M1). We propose that an increased vulnerability to oxidative stress (endogenous or environmental) may contribute to the development and clinical manifestations of autism. (c) 2006 Wiley-Liss, Inc.
Publication Types:
* Comparative Study * Research Support, N.I.H., Extramural * Research Support, Non-U.S. Gov't
15 comments:
There's no problem with questioning science as long as you make a satisfactory effort to understand it first. It's apparent you don't. In order for the alleged link between thimerosal and autism "to be possible", there would have to be sound science showing it is so. Where is this science? All we saw were unfounded conspiracy theories and allegations.
Did Dr. Christina Moellering really say thimerosal was in the MMR vaccine? This is wrong. MMR has never contained thimerosal. Did you misquote Moellering? Why didn't your reporters, who tell us they spent six months investigating the science of autism, catch that error? It's pretty basic. Moellering is right when she says your report was "misleading and biased and a poor example of journalism."
Enabling viewers with information "so they could make their own educated decisions about vaccines" only works when the information is accurate. There's more to accuracy than just showing both sides of a story. A journalist also filters information and exposes flawed arguments. Instead we get wide eyed credulity and cheap voyeurism.
It's no wonder the CDC didn't respond to your questions. They've all been answered, ad nauseum. The best available science is plain for all to see. But first is has to be understood.
ANB,
An ombudsman project is a viewer advocate... A middle man that has ties to the newsroom...but not directly. The team wasn't involved in the selection process or responses to the emails.
A convenient excuse.
You certainly know (by now at least)that MMR never contained Mercury or anything else as a Preservative. It is a live virus vaccine. A preservative would kill an attenuated live virus. Case closed on MMR, oral polio and Varicella vaccines.
That KOMU allowed you to hijack its facilities for what is obviously a personal agenda, is disgraceful.
You seem so proud of your work...it is sad. Were you to publish a "hard hitting thorough investigation" that proved the twin towers were destroyed by the Bush administration, you would also get hundreds... nay...thousands of emails and letters of congratulations from he 9/11 Truth people. A big viewer response is not a sign you are engaged in good journalism...unless your goal is to eventually work for the Enquirer (or Fox)
By the way...
I do not see my blog posts listed in viewer responses...why is that?
Then your ombudsman has been played, too.
Dr. Julia Whiting has an active VICP claim. She subjects her daughter to Lupron, a powerful chemical castration drug, so she's hardly the unbiased voice of reason that she wants KOMU to believe she is. You can't complain about government scientists with drug company ties without objecting to vaccine suit plaintiffs posing as experts. At least the CDC is honest about past associations.
Stan Stanfield of Scotland is an anti-vaccinationist, and a cheerleader for the Geiers and Wakefield. I wouldn't be surprised if he were involved in the UK MMR litigation:
http://tinyurl.com/tvxi
http://tinyurl.com/2d6ft2
http://tinyurl.com/18r
I feel for Dr. Miles. She's the only evidence-based professional interviewed at length for your series. That's not balance. It's one rational voice against a half dozen extremists. It's as if you interviewed a klavern of Klansman for a series on civil rights, then counted on Halle Barry for balance.
Why no context? Why no mention of the Geiers' fishy "studies", or Wakefield's bogus MMR research, or Ayoub's loony conspiracies? Why no explanation of the CDDS data or the blood brain barrier, or why there are no studies of children "cured" of autism through chelation"? You make passing reference to the scientists who dispute a vaccine link to autism but you never tell us why. Do you even know?
I don't expect anyone at KOMU to be embarrassed over this trainwreck. To fully comprehend the awfulness of this series, you would first need to understand the subject. It's apparent you don't.
I will now yield the floor to ad hominem attacks that have nothing to do with anything I've said.
It's as if you interviewed a klavern of Klansman for a series on civil rights, then counted on Halle Barry for balance.
Priceless, ANB.
Unfortunately these kids probably honestly think what they do is for the "greater good" and that in itself justifies throwing journalistic standards and intellectual integrity out the window.
Bill,
Your PS: that thimerosal has not been used for sometime now, does not effect anyone older than 9 months of age. Below is a copy of the effective date of the law as April 1, 2007.
HCS/SS/SCS/SBs 74 & 49 - This act modifies and creates new provisions with respect to the Department of Health and Senior Services.
Missouri Law
MERCURY IMMUNIZATIONS - Under the act, after April 1, 2007, any immunizations administered to knowingly pregnant women or children under three years of age shall not contain more than 1 microgram of mercury per 0.5-milliliter dose.
Do you really think it is better to have 1 in every 150 child being vaccine injured and diagnosed with autism? According to the CDC, 1 in 6 has a behavioral disorder and/or a neuro developmental disorder. History shows the rates of diphtheria, tetanus and rubella were never that high even prior to vaccines. As reported by Dr. Engley, thimerosal is toxic to human cells at a nanomolar level so a micro gram in vaccines is still a toxic level 1000 times over.
(μg, μgs) The prefix "micro" means 1/1,000,000 = 1e-6. Therefore, 1 microgram = 0.001 milligram = 0.000001 grams, or 1,000,000 μg = 1 g. 1 μg = 1e-9 kg. Nanogram
(ng, ngs) The prefix "nano" means 1/1,000,000,000 = 1e-9, so 1,000,000,000 ng = 1e+09 1000 ng = 1 microgram.
This is the most balanced report. KOMU interviewed 5 different parents with children diagnosed with autism exposing viewers to different therapies and beliefs. 2 scientist and 2 MD's. One of the scientists was even Dr. Miles teacher and Assistant Dean of the School of Medicine at MU.
Ken,
Of course all the view points were biased on one side or the other, just like the biased science paid for by pharmaceutical companies. The conflict centers around MONEY and who is going to pay for the damage done to a generation of kids.
Thimerosal in any amount causes mercury poisoning.
I am with Bill and Ken on this one. I live in the UK. We have different vaccine schedules, different thimerosal exposure, the same autism. Go figure.
According to the CDC, 1 in 6 has a behavioral disorder and/or a neuro developmental disorder.
Yes, and half of all children are below average.
You might want to read up on bell curves and standard deviation.
Ken,
Why did the CDC, HHS, and AAP sound the autism ALARM in 2004?
Do you think they wanted to draw attention to the state of children's poor health under their leadership and medical care?
Linda,Your comment about my "PS" makes no sense. THe law you quote clearly states that Thimerosol as a preservative is not allowed for children under the age of 3 (When most vaccines are given) Children do not usually get vaccines after age two until age 4 or 5 (Except those children who have parents convinced by series like this that there is a problem getting more than one vaccine at a time...thus dragging out the process. here is your quote:
"Your PS: that thimerosal has not been used for sometime now, does not effect anyone older than 9 months of age."
Whaaa?
The "Doctors" you quote are not physicians and their "Science" on Mercury is bogus. Sorry.
Have you considered plastic as a cause? What about Electromagnetic waves from power lines and appliances? It is most unfortunate that children are being diagnosed more often now with Autism. Autism is indeed terrible. Definitely more study is needed.
Attacking vaccinations which have prevented thousands of deaths and birth defects since their introduction may fulfill some kind of odd religious or political motivation, but I believe it to be incredibly exploitative of folks with Autism and their parents.
Linda, you said "according to the CDC, 1 in 6 has a behavioral disorder and/or a neuro developmental disorder." This is a fatuous interpretation of normally distributed data on a bell curve. It's like saying that half of all children are below average, yet another example of cherry picked data and quote mining disguised as science.
Congrats - you fooled KOMU.
Thimerosal in any amount causes mercury poisoning.
Are you kidding? Can one microgram cause mercury poisoning? If this were the case, then everybody is severely mercury poisoned.
Pharmacogenomics shows that the dose at which a poisonious effect is achieve varies greatly in a genetically heterogenous population.
Small doses of Xrays in young girls across their chests in their teens who are BRCA carriers leads to a huge risk event for cancer 20 years later.
It is unfortunate that this debate is not happening between many MDs, JDs, PhDs and Journalism School faculty on UM campus in a live format instead of here with lay people who comprehend less of the science on both ends of this debate than do many others in medicine and science who know whats going on.
TO KOMU I AM AVAILABLE TO HAVE SUCH A DEBATE AT THE J SCHOOL ANYTIME YOU WANT.
EFFIIIMD
Maybe you and Dr. Ayoub can talk about the World Health Organization plot to depopulated the earth with vaccines. Or would that be too off-topic?
Looking bad again ANB, what was it about science that you were saying above on this thread? Maybe you should try to understand this series:
Arch Toxicol. 2003 Jan;77(1):50-5. Epub 2002 Nov 6.
Related Articles, Links
Click here to read Click here to read Click here to read
Thimerosal induces micronuclei in the cytochalasin B block micronucleus test with human lymphocytes.
Westphal GA, Asgari S, Schulz TG, Bünger J, Müller M, Hallier E.
Department of Occupational Health, Georg-August-University Göttingen, Waldweg 37, 37073 Göttingen, Germany. gwestph@gwdg.de
Thimerosal is a widely used preservative in health care products, especially in vaccines. Due to possible adverse health effects, investigations on its metabolism and toxicity are urgently needed. An in vivo study on chronic toxicity of thimerosal in rats was inconclusive and reports on genotoxic effects in various in vitro systems were contradictory. Therefore, we reinvestigated thimerosal in the cytochalasin B block micronucleus test. Glutathione S-transferases were proposed to be involved in the detoxification of thimerosal or its decomposition products. Since the outcome of genotoxicity studies can be dependent on the metabolic competence of the cells used, we were additionally interested whether polymorphisms of glutathione S-transferases (GSTM1, GSTT1, or GSTP1) may influence the results of the micronucleus test with primary human lymphocytes. Blood samples of six healthy donors of different glutathione S-transferase genotypes were included in the study. At least two independent experiments were performed for each blood donor. Significant induction of micronuclei was seen at concentrations between 0.05-0.5 micro g/ml in 14 out of 16 experiments. Thus, genotoxic effects were seen even at concentrations which can occur at the injection site. Toxicity and toxicity-related elevation of micronuclei was seen at and above 0.6 micro g/ml thimerosal. Marked individual and intraindividual variations in the in vitro response to thimerosal among the different blood donors occurred. However, there was no association observed with any of the glutathione S-transferase polymorphism investigated. In conclusion, thimerosal is genotoxic in the cytochalasin B block micronucleus test with human lymphocytes. These data raise some concern on the widespread use of thimerosal.
MeSH Terms:
* Cell Division/drug effects
* Cytochalasin B/toxicity*
* Dose-Response Relationship, Drug
* Drug Antagonism
* Genotype
* Glutathione Transferase/blood
* Glutathione Transferase/classification
* Glutathione Transferase/genetics
* Humans
* Lymphocytes/drug effects*
* Lymphocytes/enzymology
* Microfilaments/drug effects
* Micronucleus Tests/methods*
* Mutagens/toxicity*
* Polymorphism, Genetic
* Preservatives, Pharmaceutical/toxicity*
* Thimerosal/toxicity*
Substances:
* Mutagens
* Preservatives, Pharmaceutical
* Cytochalasin B
* Thimerosal
* Glutathione Transferase
PMID: 12491041 [PubMed - indexed for MEDLINE]
Int J Hyg Environ Health. 2001 Jul;203(5-6):479-81.
Inhibition of the human erythrocytic glutathione-S-transferase T1 (GST T1) by thimerosal.
Müller M, Westphal G, Vesper A, Bünger J, Hallier E.
Department of Occupational and Social Medicine, Georg-August-University Göttingen, D-37073 Göttingen, Germany. mmuelle3@gwdg.de
We have investigated the interaction of thimerosal, a widely used antiseptic and preservative, with the human erythrocytic GST T1 (glutathione-S-transferase T1). This detoxifying enzyme is expressed in the erythrocytes of solely the human species and it displays a genetic polymorphism. Due to this polymorphism about 25% of the individuals of the caucasian population lack this activity ("non-conjugators"), while 75% show it ("conjugators") (Hallier, E., et al., 1993). Using our newly developed HPLC-fluorescence detection assay (Müller, M., et al., 2001) we have profiled the kinetics of enzyme inhibition in erythrocyte lysates of two individuals previously identified as "normal conjugator" (medium enzyme activity) and "super-conjugator" (very high activity). For the normal conjugator we have determined a 2.77 mM thimerosal concentration to inhibit 50% of the GST T1 activity. In the case of the super-conjugator a 2.3 mM thimerosal concentration causes a 50% inhibition of the enzyme activity. For both phenotypes a 14.8 mM thimerosal concentration results in residual enzyme activities equal to those typically detected in non-conjugator lysates. Thus, sufficiently high doses of thimerosal may be able to change the phenotypic status of an individual--at least in vitro--by inhibition of the GST T1 enzyme.
MeSH Terms:
* Anti-Infective Agents, Local/adverse effects*
* Chromatography, High Pressure Liquid
* Erythrocytes/enzymology*
* European Continental Ancestry Group/genetics
* Fluorescence
* Glutathione Transferase/drug effects*
* Glutathione Transferase/metabolism*
* Humans
* Phenotype
* Polymorphism, Genetic
* Thimerosal/adverse effects*
Substances:
* Anti-Infective Agents, Local
* Thimerosal
* glutathione S-transferase T1
* Glutathione Transferase
PMID: 11556154 [PubMed - indexed for MEDLINE]
Am J Med Genet B Neuropsychiatr Genet. 2006 Dec 5;141(8):947-56.
Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism.
James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, Cutler P, Bock K, Boris M, Bradstreet JJ, Baker SM, Gaylor DW.
Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas 72202, USA. jamesjill@uams.edu
Autism is a behaviorally defined neurodevelopmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal. Although both genetic and environmental factors are thought to be involved, none have been reproducibly identified. The metabolic phenotype of an individual reflects the influence of endogenous and exogenous factors on genotype. As such, it provides a window through which the interactive impact of genes and environment may be viewed and relevant susceptibility factors identified. Although abnormal methionine metabolism has been associated with other neurologic disorders, these pathways and related polymorphisms have not been evaluated in autistic children. Plasma levels of metabolites in methionine transmethylation and transsulfuration pathways were measured in 80 autistic and 73 control children. In addition, common polymorphic variants known to modulate these metabolic pathways were evaluated in 360 autistic children and 205 controls. The metabolic results indicated that plasma methionine and the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), an indicator of methylation capacity, were significantly decreased in the autistic children relative to age-matched controls. In addition, plasma levels of cysteine, glutathione, and the ratio of reduced to oxidized glutathione, an indication of antioxidant capacity and redox homeostasis, were significantly decreased. Differences in allele frequency and/or significant gene-gene interactions were found for relevant genes encoding the reduced folate carrier (RFC 80G > A), transcobalamin II (TCN2 776G > C), catechol-O-methyltransferase (COMT 472G > A), methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C), and glutathione-S-transferase (GST M1). We propose that an increased vulnerability to oxidative stress (endogenous or environmental) may contribute to the development and clinical manifestations of autism. (c) 2006 Wiley-Liss, Inc.
Publication Types:
* Comparative Study
* Research Support, N.I.H., Extramural
* Research Support, Non-U.S. Gov't
MeSH Terms:
* Adolescent
* Autistic Disorder/blood
* Autistic Disorder/genetics*
* Autistic Disorder/metabolism*
* Catechol O-Methyltransferase/genetics
* Child
* Child, Preschool
* DNA Primers
* Female
* Gene Frequency
* Glutathione Transferase/genetics
* Humans
* Male
* Membrane Transport Proteins/genetics
* Methionine/blood*
* Methionine/metabolism
* Methylation
* Methylenetetrahydrofolate Reductase (NADPH2)/genetics
* Oxidative Stress/genetics*
* S-Adenosylhomocysteine/blood
* S-Adenosylmethionine/blood
* Transcobalamins/genetics
Substances:
* DNA Primers
* Membrane Transport Proteins
* Transcobalamins
* reduced folate carrier
* S-Adenosylmethionine
* Methionine
* S-Adenosylhomocysteine
* Methylenetetrahydrofolate Reductase (NADPH2)
* Catechol O-Methyltransferase
* Glutathione Transferase
Grant Support:
* 1C06 RR16517-01/RR/United States NCRR
* 3C06 RR16517-01S1/RR/United States NCRR
* 5R01 HD39054-05/HD/United States NICHD
PMID: 16917939 [PubMed - indexed for MEDLINE]
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