Re: Questions on chelation, etc.-Moria

[Guest guest]

Current scientific abstracts point towards a genetic predisposition to

immune/autoimmune disorders. (multiple triggers-not causation) The research

below appears to be coming from many reputable sources.

Cheryl

------------------------------------------------------------------------

Hum Immunol 2002 Apr;63(4):311-6 Related Articles, Links

The transmission disequilibrium test suggests that HLA-DR4 and DR13 are

linked to autism spectrum disorder.

AR, Maciulis A, Stubbs EG, Cutler A, Odell D.

Center for Persons with Disabilities (A.R.T., A.M., D.O.), Utah State

University, Logan, UT, USA

We have evaluated possible contributions of HLA-DRB1 alleles to autism

spectrum disorder (ASD) in 103 families of Caucasian descent. The DR4 allele

occurred more often in probands than controls (0.007), whereas the DR13,14

alleles occurred less often in probands than controls (p = 0.003). The

transmission disequilibrium test (TDT) indicated that the ASD probands

inherited the DR4 allele more frequently than expected (p = 0.026) from the

fathers. The TDT also revealed that fewer DR13 alleles than expected were

inherited from the mother by ASD probands (p = 0.006). We conclude that the

TDT results suggest that DR4 and DR13 are linked to ASD. Reasons for the

parental inheritance of specific alleles are poorly understood but coincide

with current genetic research noting possible parent-of-origin effects in

autism.

PMID: 12039413 [PubMed - in process]

J Immunol 2002 Aug 15;169(4):1729-34 Related Articles, Links

Editing autoreactive TCR enables efficient positive selection.

Santori FR, Arsov I, Lili M, Vukmanovic S.

Heidelberger Division of Immunology, Department of Pathology and

Kaplan Cancer Center, New York University School of Medicine, New York, NY

10016, USA.

Allelic exclusion is inefficient at the TCRalpha locus, allowing a sizeable

portion of T cells to carry two functional TCRs. The potential danger of

dual TCR expression is a rescue of autoreactive TCRs during selection in the

thymus and subsequent development of autoimmunity. In this study, we examine

the reason(s) for replacing an autoreactive TCR and for allowing the

survival of cells carrying two TCRs. We compared development of TCR

transgenic CD4(+)CD8(-) thymocytes in the presence or absence of MHC class

II autoantigen that does not induce deletion of thymocytes. Contrary to the

expected negative effect of the presence of autoantigen, approximately 100%

more CD4(+)CD8(-) thymocytes were found in the presence of MHC class II

autoantigen than in the neutral background. A further increase in the

strength of autoantigenic signal via expression of a human CD4 transgene led

to an additional increase in the numbers of CD4(+)CD8(-) thymocytes. Thus,

editing autoreactive TCR results in more efficient positive selection, and

this may be both a reason and a reward for risking autoimmunity.

PMID: 12165493 [PubMed - indexed for MEDLINE]

J Neuroimmunol 2002 Aug;129(1-2):125-32 Related Articles, Links

Dendritic cells and dendritic-like microglia in focal cortical ischemia of

the mouse brain.

Reichmann G, Schroeter M, Jander S, Fischer HG.

Institute for Medical Microbiology and Virology, Heinrich-Heine-University,

Universitatsstrasse 1, D-40225, Dusseldorf, Germany.

Intracerebral dendritic cells (DC) have recently been identified in

neuroinflammation initiated peripherally by brain-targeted autoimmunity or

infection. The present study detects DC in photochemically induced cortical

ischemia of the mouse brain, a brain-intrinsic lesion model characterized by

the lack of an overt T cell response. Concomitant to leukocyte infiltration

of the infarcted area, cells expressing the pan-DC surface marker CD11c

appeared at the lesion and persisted for weeks. These DC were located at the

border zone of the infarct and remote from the lesion in degenerating

corticothalamic fibre tracts and subcortical nuclei. All CD11c+ brain cells

displayed a uniform CD11b+/CD8alpha-/CD205- surface phenotype, indicating a

myeloid origin, and were immature DC based on their MHC class

II+/CD40-/CD80+/CD86+/- profile. By expressing high levels of CD45, most DC

from ischemic brain seemed to be blood-derived while a minority were

CD45(low), thus corresponding to resident microglia. Consistently,

round-shaped CD11c+ cells were found at the lesion whereas CD11c+ cells at

subcortical sites were ramified like parenchymal microglia. These findings

evidence a recruitment of myeloid DC to ischemic brain lesions and suggest

that reactive microglia in remote areas transform into dendritic-like cells.

Brain-infiltrating DC and their microglial counterparts may play a role in

the inflammatory response to cerebral ischemia independently of T cells.

PMID: 12161028 [PubMed - indexed for MEDLINE]

Immunity 2002 Jul;17(1):83-94 Related Articles, Links

Structural snapshot of aberrant antigen presentation linked to autoimmunity:

the immunodominant epitope of MBP complexed with I-Au.

He XL, Radu C, Sidney J, Sette A, Ward ES, KC.

Department of Microbiology and Immunology, Stanford University School of

Medicine, CA 94305, USA.

Murine experimental allergic encephalomyelitis (EAE) is a useful model for

the demyelinating, autoimmune disease multiple sclerosis. In the EAE system,

the immunodominant N-terminal epitope of myelin basic protein (MBP) is an

unusually short, weakly binding peptide antigen which elicits highly biased

TCR chain usage. In the 2.2 A crystal structure of I-A(u)/MBP1-11 complex,

only MBP residues 1-7 are bound toward one end of the peptide binding cleft.

The fourth residue of MBP1-11 is located in an incompatible p6 pocket of

I-A(u), thus explaining the short half-life of I-A(u) complexed with Ac1-11.

MBP peptides extended at the C terminus of Ac1-11 result in dramatic

affinity increases, likely attributed to register shifting to a higher

affinity cryptic epitope, which could potentially mask the presentation of

the immunodominant MBP1-11 peptide during thymic education.

PMID: 12150894 [PubMed - indexed for MEDLINE]

Exp Mol Pathol 2002 Aug;73(1):35-45 Related Articles, Links

Parenchymal microglia of naive adult C57BL/6J mice express high levels of

B7.1, B7.2, and MHC class II.

Zhang GX, Li J, Ventura E, Rostami A.

Department of Neurology, University of Pennsylvania Medical Center,

Philadelphia 19104-4283, USA.

In this study, we addressed B7.1, B7.2, and MHC class II expression on

microglia of normal adult C57BL/6J mice, which are susceptible to MOG35-55

peptide-induced experimental autoimmune encephalomyelitis (EAE). We showed

that there are two distinct major populations of CD11b(+) cells in the

central nervous system (CNS) of naive mice: CD45 low (CD45(lo); parenchymal

microglia) and CD45 intermediate (CD45(int); CNS-associated macrophages).

These two populations compose CNS microglia. There is a rare CD45 high

(CD45(hi)) population. By contrast, splenic CD11b(+) cells (macrophages) are

CD45(int) and CD45(hi), but rarely CD45(lo). CD45(lo)CD11b(+) cells

constitutively express much higher levels of B7.1, B7.2, and MHC class II

compared to CD45(int) CD11b(+) cells. A shift of CD11b(+) cells from

CD45(lo) to CD45(int) was observed in the CNS of EAE mice. Our study

provides evidence that (1) CD45(lo) and CD45(hi), but not CD45(int), could

be unique markers to differentiate parenchymal microglia from infiltrating

macrophages in EAE; (2) the level of CD45 expression on parenchymal

microglia (CD45(lo)) was upregulated in EAE; and (3) parenchymal microglia

in normal CNS could be potent APCs by expressing high levels of B7.1, B7.2,

and MHC class II molecules and could therefore play an important role in

inflammation and autoimmunity in the CNS.

PMID: 12127052 [PubMed - indexed for MEDLINE]

J Immunol 2002 Jul 1;169(1):587-94 Related Articles, Links

Erratum in:

J Immunol 2002 Aug 1;169(3):1647

Induction of autoantibody production is limited in nonautoimmune mice.

Singh RR, Ebling FM, Albuquerque DA, Saxena V, Kumar V, Giannini EH, n

TN, Finkelman FD, Hahn BH.

Department of Internal Medicine, University of Cincinnati College of

Medicine and Veterans Affairs Medical Center, Cincinnati, OH 45220, USA.

singhrm@...

Many individuals develop a single or a few brief episodes of autoimmunity

from which they recover. Mechanisms that quell pathologic autoimmunity

following such a breakdown of self-tolerance are not clearly understood. In

this study, we show that in nonautoimmune mice, dsDNA-specific autoreactive

B cells exist but remain inactive. This state of inactivation in

dsDNA-specific B cells could be disrupted by autoreactive Th cells; in this

case T cells that react with peptides from the V(H) region of anti-DNA Abs

(hereafter called anti-V(H) T cells). Immunization with anti-DNA mAb, its

gamma-chain or peptides derived from its V(H) region induced anti-V(H) Th

cells, IgG anti-dsDNA Ab, and proteinuria. The breakdown of B cell tolerance

in nonautoimmune mice, however, was short-lived: anti-DNA Ab and nephritis

subsided despite subsequent immunizations. The recovery from autoimmunity

temporally correlated with the appearance of T cells that inhibited anti-DNA

Ab production. Such inhibitory T cells secreted TGFbeta; the inhibition of

anti-DNA Ab production by these cells was partly abolished by anti-TGFbeta

Ab. Even without immunization, nonautoimmune mice possess T cells that can

inhibit autoantibody production. Thus, inhibitory T cells in nonautoimmune

mice may normally inhibit T-dependent activation of autoreactive B cells

and/or reverse such activation following stimulation by Th cells. The

induction of such inhibitory T cells may play a role in protecting

nonautoimmune mice from developing chronic autoimmunity.

PMID: 12077292 [PubMed - indexed for MEDLINE]

Immunology 2002 Mar;105(3):252-62 Related Articles, Links

Diversity in MHC class II antigen presentation.

JH, Delvig AA.

Department of Microbiology and Immunology, The Medical School, University of

Newcastle upon Tyne, Newcastle upon Tyne, UK. j.h.robinson@...

Processing exogenous and endogenous proteins for presentation by major

histocompatibility complex (MHC) molecules to T cells is the defining

function of antigen-presenting cells (APC) as major regulatory cells in the

acquired immune response. MHC class II-restricted antigen presentation to

CD4 T cells is achieved by an essentially common pathway that is subject to

variation with regard to the location and extent of degradation of protein

antigens and the site of peptide binding to MHC class II molecules. These

subtle variations reveal a surprising flexibility in the ways a diverse

peptide repertoire is displayed on the APC surface. This diversity may have

profound consequences for the induction of immunity to infection and

tumours, as well as autoimmunity and tolerance.

Publication Types:

Review

Review, Tutorial

PMID: 11918686 [PubMed - indexed for MEDLINE]

Acta Crystallogr D Biol Crystallogr 2002 Oct;58(Pt 10 Pt 1):1749-51 Related

Articles, Links

Crystallization of HLA-DR4 fused to an immunodominant collagen II peptide

implicated in rheumatoid arthritis.

Hurlbert J, Izard T.

Department of Structural Biology, St. Jude Children's Research Hospital, 332

North Lauderdale Street, Memphis, TN 38105, USA.

Major histocompatibility complex (MHC) class II molecules are key players in

antigen-specific CD4(+) T cell stimulation, despite their lack of

discrimination between " self " and foreign antigens. The susceptibility of

many individuals to autoimmune diseases is directly attributed to this lack

of specificity, as well as to the expression of subclasses of MHC class II

molecules. Increased susceptibility to the autoimmune disease rheumatoid

arthritis (RA) has been attributed to the expression of the MHC class II

alleles HLA-DR1 and HLA-DR4. To define the structural requirements of the

HLA-DR4 protein in the autoimmune response of RA, we have crystallized

HLA-DR4 with the immunodominant peptide from human collagen II, covalently

linked to the N-terminus of the beta-chain [HLA-DR4/hCII(257-273)].

Crystallization time, crystal size, and reproducibility were greatly

improved by macroseeding into microdialysis buttons.

PMID: 12351899 [PubMed - in process]

Epilepsia 2002 Mar;43(3):236-9 Related Articles, Links

Erratum in:

Epilepsia 2002 Jul;43(7):777

An association between mesial temporal lobe epilepsy with hippocampal

sclerosis and human leukocyte antigens.

Ozkara C, Altintas A, Yilmaz E, Eskazan E, Erkol G, Ozyurt E, Erdogan E,

Kuday C.

Institute of Neurological Sciences, University of Istanbul, Turkey.

cigdemoz@...

PURPOSE: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS)

is one of the medically intractable epilepsies that may be remediable with

surgery. Although the pathogenesis of HS still remains obscure, genetics may

play a role as a predisposing factor, with the genetically controlled immune

system as one of its aspects. Our aim in this study was to investigate

whether there is any association between human leukocyte antigens (HLAs)

that are related to chromosome 6 and this specific type of epilepsy.

METHODS: HLA class I and II typing were performed with the

microlymphocytotoxicity method on 65 Turkish patients with MTLE-HS and on

184 healthy controls. RESULTS: Our study revealed a significantly high

frequency of class II antigens HLA-DQ2, -DR4, and -DR7 alleles and the

combination of HLA-DR4-DQ2, and DR7-DQ2 alleles. CONCLUSIONS: The HLA

alleles that occur with increased frequency in many HLA- associated

conditions appear to serve as risk factors that increase susceptibility but

are not essential for disease expression. Our data support the role of

genetic factors in the development of HS, possibly related to early

childhood events that may act as a trigger factor to initiate the cascade in

genetically prone patients with specific HLA types to give rise to MTLE

eventually.

PMID: 11906507 [PubMed - indexed for MEDLINE]

J Immunol 2001 Sep 15;167(6):3250-6 Related Articles, Links

T cell selection and differential activation on structurally related HLA-DR4

ligands.

Gebe JA, Novak EJ, Kwok WW, Farr AG, Nepom GT, Buckner JH.

Benaroya Research Institute, Virginia Mason Research Center, Seattle, WA

98101, USA.

Plasticity of TCR interactions during CD4(+) T cell activation by an

MHC-peptide complex accommodates variation in the peptide or MHC contact

sites in which recognition of an altered ligand by the T cell can modify the

T cell response. To explore the contribution of this form of TCR

cross-recognition in the context of T cell selection on disease-associated

HLA molecules, we have analyzed the relationship between TCR recognition of

the DRB1*0401- and DRB1*0404-encoded HLA class II molecules associated with

rheumatoid arthritis. Thymic reaggregation cultures demonstrated that CD4(+)

T cells selected on either DRB1*0401 or DRB1*0404 could be subsequently

activated by the other MHC molecule. Using HLA tetramer technology we

identify hemagglutinin residue 307-319-specific T cells restricted by

DRB1*0401, but activated by hemagglutinin residues 307-319, in the context

of DRB1*0404. One such clone exhibits an altered cytokine profile upon

activation with the alternative MHC ligand. This altered phenotype persists

when both class II molecules are present. These findings directly

demonstrate that T cells selected on an MHC class II molecule carry the

potential for activation on altered self ligands when encountering Ags

presented on a related class II molecule. In individuals heterozygous for

these alleles the possibility of TCR cross-recognition could lead to an

aberrant immune response.

PMID: 11544312 [PubMed - indexed for MEDLINE]

Nat Immunol 2002 Oct;3(10):940-3 Related Articles, Links

A functional and structural basis for TCR cross-reactivity in multiple

sclerosis.

Lang HL, sen H, Ikemizu S, Andersson C, Harlos K, Madsen L, Hjorth P,

Sondergaard L, Svejgaard A, Wucherpfennig K, Stuart DI, Bell JI, EY,

Fugger L.

[1] Nuffield Department of Clinical Medicine, Radcliffe Hospital,

Headington, Oxford OX3 9DU, UK. [2] These authors contributed equally to

this work.

The multiple sclerosis (MS)-associated HLA major histocompatibility complex

(MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in strong

linkage disequilibrium, making it difficult to determine which is the

principal MS risk gene. Here we show that together the DRB1 and DRB5 loci

may influence susceptibility to MS. We demonstrate that a T cell receptor

(TCR) from an MS patient recognized both a DRB1*1501-restricted myelin basic

protein (MBP) and DRB5*0101-restricted Epstein-Barr virus (EBV) peptide.

Crystal structure determination of the DRB5*0101-EBV peptide complex

revealed a marked degree of structural equivalence to the DRB1*1501-MBP

peptide complex at the surface presented for TCR recognition. This provides

structural evidence for molecular mimicry involving HLA molecules. The

structural details suggest an explanation for the preponderance of MHC class

II associations in HLA-associated diseases.

PMID: 12244309 [PubMed - in process]

Mult Scler 2002 Aug;8(4):278-83 Related Articles, Links

Autoreactivity to myelin antigens related to HLA associations with multiple

sclerosis.

Yentur SP, Akman-Demir G, Eraksoy M, Saruhan-Direskeneli G.

Department of Immunology, Istanbul University DETAE, Capa-Istanbul, Turkey.

Multiple sclerosis (MS) is considered as an immune process influenced by

genetic and environmental factors. HLA-DR2 and -DR4 have been documented to

be associated with MS. The HLA-dependent differences of immune response to

myelin and other antigens might point out some relevant mechanisms in MS

development The responses to myelin antigens and to PPD have been compared

in 21 MS patients and 25 healthy controls (HCs) by primary proliferation and

by short-term T-cell lines. There was a significantly higher response to MBP

in DR2+ HCs compared to MS patients (SI: 5.9 versus 1.5, p = 0.02). In

short-term T-cell lines, we observed a higher response to PLP30-49 in both

DR4+ HCs and MS patients This response was significantly more frequent in

DR4+ MS patients (34.6%) than both DR2+ MS patients (0%, p = 0.0001) and

DR4+ HCs (7.7%, p = 0.001). The comparison between DR2+ and DR4+ MS patients

has revealed that the response to MBP was also increased in DR4+ (p = 0.02).

Among DR4+ groups, an increased PPD response was detected in HCs compared to

MS (65.2% versus 33.3%, p = 0.01). These results may indicate that

HLA-related differences to specific and recall antigens are detectable in MS

and these differences may have implications in the disease pathogenesis.

PMID: 12166496 [PubMed - in process]

J Immunol 2002 Jul 1;169(1):548-56 Related Articles, Links

High immunogenicity of intracellular myelin oligodendrocyte glycoprotein

epitopes.

Weissert R, Kuhle J, de Graaf KL, Wienhold W, Herrmann MM, Muller C,

Forsthuber TG, Wiesmuller KH, Melms A.

Department of Neurology, University of Tubingen, Tubingen, Germany.

robert.weissert@...

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the

CNS with associated axonal loss. There is strong evidence for an autoimmune

pathogenesis driven by myelin-specific T cells. Myelin oligodendrocyte

glycoprotein (MOG) induces a type of experimental autoimmune

encephalomyelitis in animals which is very MS-like since there are

demyelinating CNS lesions and axonal loss. This underscores the potential

role of MOG in MS pathogenesis. We performed a T cell reactivity pattern

analysis of MS patients at the onset of relapse or progression of

neurological deficits and controls that were stratified for the genetic risk

factor HLA-DRB1*1501. For the first time, we show that there is an

HLA-DR-restricted promiscuous dominant epitope for CD4(+) T cells within the

transmembrane/intracellular part of MOG comprising aa 146-154 (FLCLQYRLR).

Surprisingly, controls had broader T cell reactivity patterns toward MOG

peptides compared with MS patients, and the transmembrane and intracellular

parts of MOG were much more immunogenic compared with the extracellular

part. Measurements of in vitro binding affinities revealed that

HLA-DRB1*1501 molecules bound MOG 146-154 with intermediate and

HLA-DRB1*0401 molecules with weak affinities. The binding of MOG 146-154 was

comparable or better than myelin basic protein 85-99, which is the dominant

myelin basic protein epitope in context with HLA-DRB1*1501 molecules in MS

patients. This is the first study in which the data underscore the need to

investigate the pathogenic or regulatory role of the transmembrane and

intracellular part of MOG for MS in more detail.

PMID: 12077287 [PubMed - indexed for MEDLINE]

Hum Immunol 2001 Dec;62(12):1371-81 Related Articles, Links

The major histocompatibility complex influences the ethiopathogenesis of

MS-like disease in primates at multiple levels.

't Hart BA, Brok HP, Amor S, Bontrop RE.

Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk,

The Netherlands. hart@...

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease

primarily affecting the central nervous system. Of the many candidate

polymorphic major histocompatibility complex (MHC) and non-MHC genes

contributing to disease susceptibility, including those encoding effector

(cytokines and chemokines) or receptor molecules within the immune system

(MHC, TCR, Ig or FcR), human leukocyte antigen (HLA) class II genes have the

most significant influence. In this article we put forward the hypothesis

that the influence of HLA genes on the risk to develop MS is actually the

sum of multiple antigen presenting cell (APC) and T-cell interactions

involving HLA class I and class II molecules. This article will also discuss

that, because of the genetic and immunologic similarity to humans,

autoimmune models of MS in non-human primates are the experimental models

" par excellence " to test this hypothesis.

Publication Types:

Review

Review, Tutorial

PMID: 11756006 [PubMed - indexed for MEDLINE]

J Immunol 2001 Dec 15;167(12):7119-25 Related Articles, Links

T cell epitopes of human myelin oligodendrocyte glycoprotein identified in

HLA-DR4 (DRB1*0401) transgenic mice are encephalitogenic and are presented

by human B cells.

Forsthuber TG, Shive CL, Wienhold W, de Graaf K, Spack EG, Sublett R, Melms

A, Kort J, Racke MK, Weissert R.

Institute of Pathology, School of Medicine, Case Western Reserve University,

Cleveland, OH 44106, USA. tgf2@...

Myelin oligodendrocyte glycoprotein (MOG) is an Ag present in the myelin

sheath of the CNS thought to be targeted by the autoimmune T cell response

in multiple sclerosis (MS). In this study, we have for the first time

characterized the T cell epitopes of human MOG restricted by HLA-DR4

(DRB1*0401), an MHC class II allele associated with MS in a subpopulation of

patients. Using MHC binding algorithms, we have predicted MOG peptide

binding to HLA-DR4 (DRB1*0401) and subsequently defined the in vivo T cell

reactivity to overlapping MOG peptides by testing HLA-DR4 (DRB1*0401)

transgenic mice immunized with recombinant human (rh)MOG. The data indicated

that MOG peptide 97-108 (core 99-107, FFRDHSYQE) was the immunodominant

HLA-DR4-restricted T cell epitope in vivo. This peptide has a high in vitro

binding affinity for HLA-DR4 (DRB1*0401) and upon immunization induced

severe experimental autoimmune encephalomyelitis in the HLA-DR4 transgenic

mice. Interestingly, the same peptide was presented by human B cells

expressing HLA-DR4 (DRB1*0401), suggesting a role for the identified MOG

epitopes in the pathogenesis of human MS.

PMID: 11739534 [PubMed - indexed for MEDLINE]

J Neurovirol 2000 May;6 Suppl 2:S67-75 Related Articles, Links

Particle-associated retroviral RNA and tandem RGH/HERV-W copies on human

chromosome 7q: possible components of a 'chain-reaction' triggered by

infectious agents in multiple sclerosis?

Perron H, Perin JP, Rieger F, Alliel PM.

BioMerieux STELHYS, Chemin de l'Orme, 69280 Marcy l'Etoile, France.

Different groups have observed retrovirus particle (RVP) production in cell

cultures from patients with multiple sclerosis (MS). This in vitro

production appeared relatively specific for MS versus healthy controls, but

was likely to be enhanced or activated by infectious triggers such as

Herpesviruses (e.g. HSV, EBV). Independent molecular analysis of retroviral

RNA associated with RVP revealed two different genetic families of

endogenous retroviral elements (HERV): MSRV/HERV-W and RGH/HERV-H.

Interestingly, these sequences were detected by mutually exclusive primers

in RT - PCR amplifications. Surprisingly, these two HERV families both

contain an ancestral proviral copy inserted in chromosome 7q21-22 region at

about 1 kb of distance of each other. Another HERV-W proviral sequence is

located within a T-cell alpha-delta receptor (TCR) gene in chromosome

14q11.2 region. Interestingly, these two regions correspond to genetic loci

previously identified as potentially associated with 'multigenic'

susceptibility to MS and TCR alpha chain genetic determinants have been

reported to be statistically associated with MS. A plausible role for

infectious agents triggering a co-activation of the chromosome 7q HERV

tandem (replicative retrovirus and/or other virus and/or intracellular

bacteria) and, eventually, other HERV copies, is discussed. The role of

particular HERV polymorphism and the production of pathogenic molecules

(gliotoxin and superantigen) possibly associated with retroviral expression

are also evoked. An integrative concept of pathogenic 'chain-reaction' in MS

involving several step-specific pathogenic 'agents' and 'products' somewhat

interacting with particular genetic elements would federate most partial

data obtained on MS, including retroviral expression.

Publication Types:

Review

Review Literature

PMID: 10871789 [PubMed - indexed for MEDLINE]

Badner JA, Gershon ES. Related Articles, Links

Regional meta-analysis of published data supports linkage of autism with

markers on chromosome 7.

Mol Psychiatry. 2002;7(1):56-66.

PMID: 11803446 [PubMed - indexed for MEDLINE]

Deb-Rinker P, Klempan TA, O'Reilly RL, Torrey EF, Singh SM. Related

Articles, Links

Molecular characterization of a MSRV-like sequence identified by RDA from

monozygotic twin pairs discordant for schizophrenia.

Genomics. 1999 Oct 15;61(2):133-44.

PMID: 10534399 [PubMed - indexed for MEDLINE]

Diabetologia 2002 Sep;45(9):1340-3 Related Articles, Links

Non-transmitted maternal HLA DQ2 or DQ8 alleles and risk of Type I diabetes

in offspring: the importance of foetal or post partum exposure to

diabetogenic molecules.

Pani MA, Van Autreve J, Van Der Auwera BJ, Gorus FK, Badenhoop K.

University Hospital furt am Main, Department of Internal Medicine I,

Division of Endocrinology, furt am Main, Germany.

AIMS/HYPOTHESIS. Type I (insulin-dependent) diabetes mellitus results from

an immune-mediated destruction of pancreatic beta cells for which HLA

haplotypes DR3-DQ2 and DR4-DQ8 represent the strongest genetic risk markers.

Mothers of patients with rheumatoid arthritis carry more frequently the HLA

DR4-DQ8 haplotype as non-transmitted haplotype than mothers of healthy

control subjects. As maternal cells have been shown to persist in their

offspring up to 30 years after birth, we investigated whether the

association of HLA DR3-DQ2 and DR4-DQ8 with Type I diabetes is purely a

genetic effect acting through inheritance or whether it can also act as an

environmental factor, for example through foetal exposure in utero to

maternal circulating cells. METHODS. We analysed the non-transmitted

parental HLA DQ alleles of 464 families (1367 subjects) with a Type I

diabetic offspring. HLA DQ alleles were assessed using sequence-specific

primers and allele-specific oligonucleotides hybridisation. A chi-square

test was done to compare allele and transmission frequencies in the

respective subsets of families. RESULTS. The non-transmitted HLA DR3-DQ2 and

DR4-DQ8 were more frequent in mothers than in fathers of all non- DQ2/DQ8

heterozygous diabetic offspring ( p=0.0001) as well as in offspring not

carrying any HLA high-risk allele ( p=0.0243). In patients with either risk

allele alone, more maternal than paternal non-transmitted risk alleles

complemented the constellation to DQ2/DQ8 ( p<0.0099).

CONCLUSION/INTERPRETATION. HLA high risk alleles were more frequent among

maternal non-inherited (but possibly exposed) alleles than among paternal

non-inherited alleles. These results indicate that HLA DR-DQ is an

environmental risk factor for Type I diabetes.

PMID: 12242468 [PubMed - in process]

Hereditas 1997;127(1-2):113-24 Related Articles, Links

Presence of retroelements reveal the evolutionary history of the human DR

haplotypes.

Svensson AC, Andersson G.

Department of Cell Research, Uppsala Genetic Center, Swedish University of

Agricultural Sciences, Sweden.

Comparison of intron sequences has been a successful tool for drawing major

conclusions about the evolutionary relationship of DRB genes. This complex

family of genes is discussed in this review as well as a proposed model for

the evolution of HLA-DR haplotypes. The model is based both on phylogenetic

analysis of intron sequences as well as presence of ERV9 LTR elements

located at identical position in intron 5 of a number of DRB genes.

According to this model, two main evolutionary branches of DR haplotypes

exist. The DR53 haplotype represents one branch, and the second branch

contains the DR51, DR52, DR1, and DR8 haplotypes. After the divergence of

the DR53 haplotype, an ERV9 LTR element was inserted in a primordial gene.

Consequently, all DRB1 genes as well as the DRB3 gene within haplotypes of

the second branch, contain this LTR element. In addition, conserved

regulatory sequence motifs are found present within these LTR elements that

might regulate DRB gene expression. Novel haplotypes are generated by

recombinations and the maintenance of the DR haplotype variation as well as

the frequent genetic rearrangements observed might be evolutionary

advantageous.

Publication Types:

Review

Review, Tutorial

PMID: 9420477 [PubMed - indexed for MEDLINE]

Di Cristofano A, Strazullo M, Longo L, La Mantia G. Related Articles,

Links

Characterization and genomic mapping of the ZNF80 locus: expression of this

zinc-finger gene is driven by a solitary LTR of ERV9 endogenous retroviral

family.

Nucleic Acids Res. 1995 Aug 11;23(15):2823-30.

PMID: 7659503 [PubMed - indexed for MEDLINE]

Clin Endocrinol (Oxf) 2002 Jun;56(6):773-7 Related Articles, Links

Preliminary evidence that an endogenous retroviral long-terminal repeat

(LTR13) at the HLA-DQB1 gene locus confers susceptibility to 's

disease.

Pani MA, Seidl C, Bieda K, Seissler J, Krause M, Seifried E, Usadel KH,

Badenhoop K.

Department of Internal Medicine I, University Hospital, furt am Main,

Germany.

OBJECTIVE: 's disease is associated with particular haplotypes of the

human leucocyte antigen (HLA) region [DQA1*0501-DQB1*0201 (DQ2) and

DQA1*0301-DQB1*0302 (DQ8)]. This locus harbours several human endogenous

retroviral (HERV) long-terminal repeats (LTR). LTRs within the HLA region

have been shown to confer additional susceptibility to type 1 diabetes and

rheumatoid arthritis. DESIGN: We investigated the role of LTR3 and LTR13,

both of which are located adjacent to the DQB1 gene, in 's disease.

PATIENTS: Eighty-seven patients and 160 controls were genotyped for HLA-DQA,

-DQB, and the presence or absence of LTR3 and LTR13. RESULTS: Significantly

more patients' HLA alleles than those of controls carried the LTR13

insertion (19.0% vs. 10.6%, P = 0.0143), whereas there was only a trend for

LTR3 (allele-wise chi-squared test: P = 0.0941). Both, LTR3 and LTR13 are in

strong linkage disequilibrium with DQ8, which itself was significantly more

frequent in patients than in controls (29.9% vs. 15.0%, P = 0.0089).

However, significantly more alleles of DQ8+ patients than of DQ8+ controls

carried the LTR13 insertion (44.2% vs. 18.8%, P = 0.0119), whereas we did

not observe any difference for LTR3 in the DQ8+ subset (30.5 vs. 23.1%, P =

0.9416). CONCLUSIONS: We have found preliminary evidence that the endogenous

retroviral element DQ-LTR13, but not LTR3, is associated with 's

disease. LTR13 appears to enhance HLA-DQ8 mediated disease risk. This

retroviral insertion therefore might represent a novel susceptibility factor

in 's disease, but these findings need to be confirmed in a larger

data set.

PMID: 12072047 [PubMed - indexed for MEDLINE]

Hum Immunol 1999 Jan;60(1):63-8 Related Articles, Links

An endogenous retroviral long terminal repeat at the HLA-DQB1 gene locus

confers susceptibility to rheumatoid arthritis.

Seidl C, Donner H, shofen E, Usadel KH, Seifried E, Kaltwasser JP,

Badenhoop K.

Institute of Transfusion Medicine and Immunohematology, Red Cross Blood

Donor Service Hessen, Johann Wolfgang Goethe University, furt, Germany.

Human endogenous retrovirus (HERV) long terminal repeat (LTR) elements

contain regulatory sequences that can influence the expression of adjacent

cellular genes, which may contribute to breakdowns of the immune function

leading to autoimmune disease. Rheumatoid arthritis (RA) is associated with

particular HLA-DR/DQ haplotypes that modulate the pathogenesis of this

autoimmune disease. We have therefore studied a solitary LTR element

(DQ-LTR3) of the HERV-K family at the HLA-DQB1 locus for a possible disease

association among 228 RA patients and 311 unrelated blood donors. The

DQ-LTR3 was significantly more frequent among patients (76% vs 33%, OR =

5.07,p < 0.0001), with the majority of patients being heterozygous for the

DQ-LTR3 (61% vs 22%, p < 0.0001). HLA-DRB1*04 positive patients did still

differ for the presence of the DQ-LTR3 (88% vs 70%, OR = 3.03, p < 0.001),

with an increase of both DQ-LTR3 homozygous and heterozygous patients, when

compared to DRB1*04 positive controls (p = 0.0015). HLA-DR/DQ genotype

analysis among HLA-DRB1*04 positive individuals revealed significantly more

DQ-LTR3 homozygotes among HLA-DRB1*04-DQBI*03 homozygous patients (72% vs

27%, P = 0.015), and the number of DQ-LTR3 homozygous (23% vs 19%) and

heterozygous (66% vs 53%) individuals was also increased among HLA-DRB1*04

heterozygous patients (p = 0.034). The presence of the DQ-LTR3 element

increased both the relative risk and the positive predictive value for

either DRB1*04-DQB1*03 positive/negative individuals when compared to the

presence of HLA-DRB1*04-DQB1*03 alone. In conclusion, these data suggest

that this DQ-LTR3 enhances susceptibility to RA.

PMID: 9952028 [PubMed - indexed for MEDLINE]

Front Biosci 2001 Aug 1;6:D936-43 Related Articles, Links

The association of MHC genes with autism.

AR, Maciulis A, Odell D.

Center for Persons with Disabilities and Biology Dept., Utah State

University, Logan, Utah 84322-6895, USA. rtorres@...

Several immune abnormalities have been noted in autistic subjects. These

associations have been extended to the Major Histocompatibility Complex

(MHC), a section of DNA remarkable for the number of encoded proteins with

immunological functions. The strongest MHC association identified thus far

is for the null allele of C4B in the class III region. The complex allelic

composition of C4 as determined by immunoelectrophoresis is discussed. Low

levels of C4 resulting from the null allele may be important in disease

pathogenesis especially since C4 has been identified in developing brain

neurons. The DNA region just telomeric to C4 has several genes including

tumor necrosis factor which encode proteins with immunological functions.

These proteins may act in concert with C4 in disease contribution and the

genes should be more closely examined.

Publication Types:

Review

Review, Tutorial

PMID: 11487481 [PubMed - indexed for MEDLINE]

Int Immunopharmacol 2001 Mar;1(3):365-92 Related Articles, Links

Genetic, structural and functional diversities of human complement

components C4A and C4B and their mouse homologues, Slp and C4.

Blanchong CA, Chung EK, Rupert KL, Yang Y, Yang Z, Zhou B, Moulds JM, Yu CY.

Children's Research Institute, 700 Children's Drive, Columbus, OH

43205-2696, USA.

The complement protein C4 is a non-enzymatic component of the C3 and C5

convertases and thus essential for the propagation of the classical

complement pathway. The covalent binding of C4 to immunoglobulins and immune

complexes (IC) also enhances the solubilization of immune aggregates, and

the clearance of IC through complement receptor one (CR1) on erythrocytes.

Human C4 is the most polymorphic protein of the complement system. In this

review, we summarize the current concepts on the 1-2-3 loci model of C4A and

C4B genes in the population, factors affecting the expression levels of C4

transcripts and proteins, and the structural, functional and serological

diversities of the C4A and C4B proteins. The diversities and polymorphisms

of the mouse homologues Slp and C4 proteins are described and contrasted

with their human homologues. The human C4 genes are located in the MHC class

III region on chromosome 6. Each human C4 gene consists of 41 exons coding

for a 5.4-kb transcript. The long gene is 20.6 kb and the short gene is 14.2

kb. In the Caucasian population 55% of the MHC haplotypes have the 2-locus,

C4A-C4B configurations and 45% have an unequal number of C4A and C4B genes.

Moreover, three-quarters of C4 genes harbor the 6.4 kb endogenous retrovirus

HERV-K(C4) in the intron 9 of the long genes. Duplication of a C4 gene

always concurs with its adjacent genes RP, CYP21 and TNX, which together

form a genetic unit termed an RCCX module. Monomodular, bimodular and

trimodular RCCX structures with 1, 2 and 3 complement C4 genes have

frequencies of 17%, 69% and 14%, respectively. Partial deficiencies of C4A

and C4B, primarily due to the presence of monomodular haplotypes and

homo-expression of C4A proteins from bimodular structures, have a combined

frequency of 31.6%. Multiple structural isoforms of each C4A and C4B

allotype exist in the circulation because of the imperfect and incomplete

proteolytic processing of the precursor protein to form the beta-alpha-gamma

structures. Immunofixation experiments of C4A and C4B demonstrate > 41

allotypes in the two classes of proteins. A compilation of polymorphic sites

from limited C4 sequences revealed the presence of 24 polymophic residues,

mostly clustered C-terminal to the thioester bond within the C4d region of

the alpha-chain. The covalent binding affinities of the thioester carbonyl

group of C4A and C4B appear to be modulated by four isotypic residues at

positions 1101, 1102, 1105 and 1106. Site directed mutagenesis experiments

revealed that D1106 is responsible for the effective binding of C4A to form

amide bonds with immune aggregates or protein antigens, and H1106 of C4B

catalyzes the transacylation of the thioester carbonyl group to form ester

bonds with carbohydrate antigens. The expression of C4 is inducible or

enhanced by gamma-interferon. The liver is the main organ that synthesizes

and secretes C4A and C4B to the circulation but there are many extra-hepatic

sites producing moderate quantities of C4 for local defense. The plasma

protein levels of C4A and C4B are mainly determined by the corresponding

gene dosage. However, C4B proteins encoded by monomodular short genes may

have relatively higher concentrations than those from long C4A genes. The 5'

regulatory sequence of a C4 gene contains a Spl site, three E-boxes but no

TATA box. The sequences beyond--1524 nt may be completely different as the

C4 genes at RCCX module I have RPI-specific sequences, while those at

Modules II, III and IV have TNXA-specific sequences. The remarkable genetic

diversity of human C4A and C4B probably promotes the exchange of genetic

information to create and maintain the quantitative and qualitative

variations of C4A and C4B proteins in the population, as driven by the

selection pressure against a great variety of microbes. An undesirable

accompanying byproduct of this phenomenon is the inherent deleterious

recombinations among the RCCX constituents leading to autoimmune and genetic

disorders.

Publication Types:

Review

Review, Academic

PMID: 11367523 [PubMed - indexed for MEDLINE]

Lymphokine Cytokine Res 1994 Oct;13(5):303-8 Related Articles, Links

Identification of HLA-DRB1 and HLA-DQB1 identical individuals by a

cytokine-based mixed lymphocyte culture.

Danzer SG, A Campo C, Kunze B, Kirchner H, Rink L.

Institute of Immunology and Transfusion Medicine, University of Lubeck

School of Medicine, Germany.

Cytokine determination in MLC is under discussion as providing more

sensitive and specific information regarding host-graft compatibility, and

is therefore suggested to represent a new method for transplantation

medicine. Little is known, however, about the stimulatory influence of HLA

class II antigens and minor lymphocyte-stimulating antigens (Mls). Our

results demonstrate that cytokine determination in MLC is suitable to detect

identical alleles of HLA-DRB1 and HLA-DQB1. Among more than 100 random MLC

experiments, we observed one cytokine pattern similar to the cytokine

release detected in a control MLC of HLA-identical siblings, which showed

marginal or no secretion of IL-2, sIL-2R, IFN-gamma, TNF-alpha, and IL-6.

HLA-typing of these two nonreactive individuals elevated identical HLA-DRB1

and HLA-DQB1 regions, while they differed in the HLA-DP locus. This suggests

that HLA-DP has no stimulatory influence on cytokine release. Further

investigation of the stimulatory capacity of HLA-DR and DQ showed that

HLA-DR is more effective in inducing IFN-gamma release than HLA-DQ. To

evaluate the stimulatory influence of human Mls, i.e., human endogenous

retroviruses (HERV), we analyzed HERV sequences of nonreactive individuals.

Both individuals showed identical HERV patterns. A third individual, who had

shown distinct cytokine release in MLC with both nonreactive individuals,

differed in the HERV fragments. In conclusion, cytokine determination in MLC

is a new method of evaluating the biological relevance of stimulatory

antigens after allogeneic stimulation detecting all individual diversities

in one experiment.

PMID: 7858063 [PubMed - indexed for MEDLINE]

_________________________________________________________________

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[Guest guest]

Hello Cheryl,

> I guess you've lost me. Why would I consider it?

It is fine if you don't consider it. You are under no

obligation. My point was that a statement

of NOT being metal toxic is questionable, and, since we

are discussing metal toxicity, and since we are presumably

interested in how it might apply for real people (us

and/or our kids) then this may be a good thing for

some readers to know. If you are not interested in

it that is okay.

> I can't validate

it with

> tests and I don't have the symptoms of mercury poisoning.

Mercury poisoning has a ***very*** wide range of symptoms.

I don't have MS but MS is often eliminated by amalgam

removal. And in actual real people has been eliminated

AND THEN RETURNED after getting [thimerosal containing]

shots. [3 adults I'm aware of.] BUT, MS doesn't seem

terribly related to autism.....well, mercury has pervasive

effects on many body systems, so there is also a range

of symptoms. To illustrate this idea, here is a list

of diseases which CAN be caused by mercury:

http://www.noamalgam.com/#diseases

(My sons

symptoms

> don't match either) Is there research somewhere that would validate

this?

> (The type that would stand up to peer review?) I've read

theories..or things

> on mineral levels...that's about it.

I'm on the " mineral level " theory myself

/files/HOW_TO_hair_test

[note that I am coauthor of this page. I am NOT coauthor of

the IDEA regarding disordered mineral transport: that is

Andy's work. I just helped with writing/organizing this info.]

Urine porphyrins test is probably more mainstream, BUT it can

only tell you there is toxicity -- not what TYPE. It won't

narrow it down to mercury.

I'm not sure what (if anything) is peer reviewed regarding

tests, since that is not my particular slant on life.

Everyone has their own standards and ideas of what is convincing

and what should be ignored. If you want to look into testing

options further, I'd suggest Andy's book (same URL as the

list of diseases). He covers a number of different tests.

In the end, my 2 cents says that mercury is tricky stuff,

and NOT easy to measure in neat & tidy ways.

best wishes,

Moria

========================================================

the following is quoted from:

Autism: a Novel Form of Mercury Poisoning

S. Bernard, B.A., A. Enayati, M.S.M.E., L. Redwood, M.S.N., H. ,

B.A., T. Binstock

Sallie Bernard, ARC Research, 14 Commerce Drive, Cranford, NJ 07901

USA, 908 276-6300, fax 908 276-1301

=================================================

[this is a table in the original: sorry the formatting doesn't

come out If you want to look at it with formatting intact:

http://www.cureautismnow.org/sciwatch/invest.cfm

It is a WORD [.doc] file. ]

===================================================

Table I: Summary Comparison of Traits

of Autism & Mercury Poisoning

(ASD references in bold; HgP references in italics)

Psychiatric Disturbances

Social deficits, shyness, social withdrawal (1,2,130,131;

21,31,45,53,132)

Repetitive, perseverative, stereotypic behaviors; obsessive-compulsive

tendencies (1,2,43,48,133; 20,33-35,132)

Depression/depressive traits, mood swings, flat affect; impaired face

recognition (14,15,17,103, 134,135; 19,21,24,26,31)

Anxiety; schizoid tendencies; irrational fears (2,15,16; 21,27,29,31)

Irritability, aggression, temper tantrums (12,13,43; 18,21,22,25)

Lacks eye contact; impaired visual fixation (HgP)/ problems in joint

attention (ASD) (3,36,136,137; 18,19,34)

Speech and Language Deficits

Loss of speech, delayed language, failure to develop speech

(1-3,138,139; 11,23,24,27,30,37)

Dysarthria; articulation problems (3; 21,25,27,39)

Speech comprehension deficits (3,4,140; 9,25,34,38)

Verbalizing and word retrieval problems (HgP); echolalia, word use and

pragmatic errors (ASD) (1,3,36; 21,27,70)

Sensory Abnormalities

Abnormal sensation in mouth and extremities (2,49; 25,28,34,39)

Sound sensitivity; mild to profound hearing loss (2,47,48;

19,23-25,39,40)

Abnormal touch sensations; touch aversion (2,49; 23,24,45,53)

Over-sensitivity to light; blurred vision (2,50,51; 18,23,31,34,45)

Motor Disorders

Flapping, myoclonal jerks, choreiform movements, circling, rocking,

toe walking, unusual postures (2,3,43,44; 11,19,27,30,31,34,39)

Deficits in eye-hand coordination; limb apraxia; intention tremors

(HgP)/problems with intentional movement or imitation (ASD)

(2,3,36,181; 25,29,32,38,70,87)

Abnormal gait and posture, clumsiness and incoordination; difficulties

sitting, lying, crawling, and walking; problem on one side of body

(4,41,42,123; 18,25,31,34,39,45)

Cognitive Impairments

Borderline intelligence, mental retardation - some cases reversible

(2,3,151,152; 19,25,31,39,70)

Poor concentration, attention, response inhibition (HgP)/shifting

attention (ASD) (4,36,153; 21,25,31,38,141)

Uneven performance on IQ subtests; verbal IQ higher than performance

IQ (3,4,36; 31,38)

Poor short term, verbal, and auditory memory (36,140;

21,29,31,35,38,87,141)

Poor visual and perceptual motor skills; impairment in simple reaction

time (HgP)/ lower performance on timed tests (ASD) (4,140,181;

21,29,142)

Deficits in understanding abstract ideas & symbolism; degeneration of

higher mental powers (HgP)/sequencing, planning & organizing (ASD);

difficulty carrying out complex commands (3,4,36,153; 9,18,37,57,142)

Unusual Behaviors

Self injurious behavior, e.g. head banging (3,154; 11,18,53)

ADHD traits (2,36,155; 35,70)

Agitation, unprovoked crying, grimacing, staring spells (3,154;

11,23,37,88)

Sleep difficulties (2,156,157; 11,22,31)

Physical Disturbances

Hyper- or hypotonia; abnormal reflexes; decreased muscle strength,

especially upper body; incontinence; problems chewing, swallowing

(3,42,145,181; 19,27,31,32,39)

Rashes, dermatitis, eczema, itching (107,146; 22,26,143)

Diarrhea; abdominal pain/discomfort, constipation, " colitis "

(107,147-149; 18,23,26,27,31,32)

Anorexia; nausea (HgP)/vomiting (ASD); poor appetite (HgP)/restricted

diet (ASD) (2,123; 18,22)

Lesions of ileum and colon; increased gut permeability (147,150;

57,144)

Table II: Summary Comparison of Biological Abnormalities

in Autism & Mercury Exposure

Mercury Exposure Autism

Biochemistry

Binds -SH groups; blocks sulfate transporter in intestines, kidneys

(40,93) Low sulfate levels (91,92)

Reduces glutathione availability; inhibits enzymes of glutathione

metabolism; glutathione needed in neurons, cells, and liver to

detoxify heavy metals; reduces glutathione peroxidase and reductase

(97,100,161,162) Low levels of glutathione; decreased ability

of liver to detoxify xenobiotics; abnormal glutathione peroxidase

activity in erythrocytes (91,94,95)

Disrupts purine and pyrimidine metabolism (10,97,158,159) Purine

and pyrimidine metabolism errors lead to autistic features (2,101,102)

Disrupts mitochondrial activities, especially in brain (160,163,164)

Mitochondrial dysfunction, especially in brain (76,172)

Immune System

Sensitive individuals more likely to have allergies, asthma,

autoimmune-like symptoms, especially rheumatoid-like ones

(8,11,18,24,28,31,111,113) More likely to have allergies and

asthma; familial presence of autoimmune diseases, especially

rheumatoid arthritis; IgA deficiencies (103,106-109,115)

Can produce an immune response in CNS; causes brain/MBP autoantibodies

(18,111,165) On-going immune response in CNS; brain/MBP

autoantibodies present (104,105,109,110)

Causes overproduction of Th2 subset; kills/inhibits lymphocytes,

T-cells, and monocytes; decreases NK T-cell activity; induces or

suppresses IFNg & IL-2 (100,112,117-120,166) Skewed immune-cell

subset in the Th2 direction; decreased responses to T-cell mitogens;

reduced NK T-cell function; increased IFNg & IL-12

(103,108,114-116,173,174)

CNS Structure

Selectively targets brain areas unable to detoxify or reduce

Hg-induced oxidative stress (40,56,161) Specific areas of brain

pathology; many functions spared (36)

Accummulates in amygdala, hippocampus, basal ganglia, cerebral cortex;

damages Purkinje and granule cells in cerebellum; brain stem defects

in some cases (10,34,40,70-73) Pathology in amygdala, hippocampus,

basal ganglia, cerebral cortex; damage to Purkinje and granule cells

in cerebellum; brain stem defects in some cases (36,60-69)

Causes abnormal neuronal cytoarchitecture; disrupts neuronal

migration, microtubules, and cell division; reduces NCAMs

(10,28,57-59,161) Neuronal disorganization; increased neuronal

cell replication, increased glial cells; depressed expression of NCAMs

(4,54,55)

Progressive microcephaly (24) Progressive microcephaly and

macrocephaly (175)

Neuro-chemistry

Prevents presynaptic serotonin release and inhibits serotonin

transport; causes calcium disruptions (78,79,163,167,168)

Decreased serotonin synthesis in children; abnormal calcium

metabolism (76,77,103,179)

Alters dopamine systems; peroxidine deficiency in rats resembles

mercurialism in humans (8,80) Either high or low dopamine levels;

positive response to peroxidine, which lowers dopamine levels

(2,177,178)

Elevates epinephrine and norepinephrine levels by blocking enzyme that

degrades epinephrine (81,160) Elevated norepinephrine and

epinephrine (2)

Elevates glutamate (21,171) Elevated glutamate and aspartate

(82,176)

Leads to cortical acetylcholine deficiency; increases muscarinic

receptor density in hippocampus and cerebellum (57,170) Cortical

acetylcholine deficiency; reduced muscarinic receptor binding in

hippocampus (83)

Causes demyelinating neuropathy (22,169) Demyelination in brain

(105)

Neurophysiology

Causes abnormal EEGs, epileptiform activity, variable patterns, e.g.,

subtle, low amplitude seizure activities (27,31,34,86-89)

Abnormal EEGs, epileptiform activity, variable patterns, including

subtle, low amplitude seizure activities (2,4,84,85)

Causes abnormal vestibular nystagmus responses; loss of sense of

position in space (9,19,34,70) Abnormal vestibular nystagmus

responses; loss of sense of position in space (27,180)

Results in autonomic disturbance: excessive sweating, poor

circulation, elevated heart rate (11,18,31,45) Autonomic disturbance:

unusual sweating, poor circulation, elevated heart rate (17,180)

[Guest guest]

Hi Moria,

Could you point me to research that links MS to mercury poisoning?

All the research I've seen from around the world is pointing towards

certain HLA halotypes, viruses, genetic retroviruses and other

infectious/immune triggers.

You might find this hard to believe but I began my journey in the

alternative world. I actually had a hair analysis done on my son.

(thankfully I didn't do treatments based on the results)

I've read the things that you mention. What my question was is

there anything that scientifically validates what is written. There

are alot of references on the immune system. I guess I missed the

research that shows a link with mercury and all the disorders

mentioned. Could you point those out to me? I think there was

something on mineral transport in the viral research I just posted.

I also recently read research on some of the mineral transporters

also serving as retrovirus transporters...some have a multiple

purpose.

My best advice to people is not to believe anyones opinion/

beliefs...not mine or yours. Learn how to do your own research

before believing in , mercury poisoning or anything else. Do

some research on the substances being used. There are several

things I've found that concerns about products like MSM, ALA, etc.

Also consider research that may show an alternative reason for

reports of improvement that are not related to metals. Check the

source, is it a respected publication, is there some type of review

or do that print anything sent in? I try to help in that way by

showing that there is tons of research that relates to . (that

isn't coming from us) If you can show me anything that is coming

from a neutral source, based on current knowledge (not stuff 20-

30yrs old) then I'd be willing to consider it.

There is so much that has changed with the genome work that many

things in the old literature have been invalidated. Many genes that

were looked at in different areas of medicine were actually found to

be the same. In some instances one gene might have had 3, 4, 5

different names. I've noticed that some of the old names, or

descriptions are used in papers I've read. In other cases like ones

on gluten and caseine, they discuss things that are from the

body/immune system as if they originate from the foods.

Cheryl

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi

there are also various search engines that can be used

> Hello Cheryl,

>

>>

> Mercury poisoning has a ***very*** wide range of symptoms.

> I don't have MS but MS is often eliminated by amalgam

> removal. And in actual real people has been eliminated

> AND THEN RETURNED after getting [thimerosal containing]

> shots. [3 adults I'm aware of.] BUT, MS doesn't seem

> terribly related to autism.....well, mercury has pervasive

> effects on many body systems, so there is also a range

> of symptoms. To illustrate this idea, here is a list

> of diseases which CAN be caused by mercury:

> http://www.noamalgam.com/#diseases

>

>

> I'm on the " mineral level " theory myself

> /files/HOW_TO_hair_test

> [note that I am coauthor of this page. I am NOT coauthor of

> the IDEA regarding disordered mineral transport: that is

> Andy's work. I just helped with writing/organizing this info.]

>

> Urine porphyrins test is probably more mainstream, BUT it can

> only tell you there is toxicity -- not what TYPE. It won't

> narrow it down to mercury.

>

> I'm not sure what (if anything) is peer reviewed regarding

> tests, since that is not my particular slant on life.

> Everyone has their own standards and ideas of what is convincing

> and what should be ignored. If you want to look into testing

> options further, I'd suggest Andy's book (same URL as the

> list of diseases). He covers a number of different tests.

> In the end, my 2 cents says that mercury is tricky stuff,

> and NOT easy to measure in neat & tidy ways.

>

> best wishes,

> Moria