Re: Question about complement C3

[Guest guest]

Did anyone have any info about the C3a and C4a. I think an elevated C4a

shows recent exposure.

Hi Guys: I dont know if any of you that have see Dr.S can help me with

this. I got some more labs back and my C3 is low but C4 is normal.

Quite awhile back someone here mentioned that one of those was mold and

one was Lyme. Does anyone know what a low C3 means and which of those

conditions it is pointing to? I am trying to figure out which one to

treat first. I could not find any info on his web sight about those

specific levels. Anyone remember that post? Thanks alot- D

**************AOL Search: Your one stop for directions, recipes and all other

Holiday needs. Search Now.

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[Guest guest]

All I remember about it was that at certain levels it was serious and the higher

the worse the releasse of cytokines. He has a chart in the Mold warriors book of

the pathwar that sort of explains it. Mine is (C4a), or was last year 22, 23000

(I cant remember off the top of my head)  and that was long after exposure. I

was told it was recwent exposure, or colonization. Depending on which C3a, He

said there are 2 different ones or something.

 

That is about as much help as I know how to be.

       

        " We The People "   

        If we dont pay attention " we " will loose our rights to our freedom.

From: ssr3351@... <ssr3351@...>

Subject: Re: [] Question about complement C3

Date: Wednesday, November 5, 2008, 7:42 PM

Did anyone have any info about the C3a and C4a. I think an elevated C4a

shows recent exposure.

Hi Guys: I dont know if any of you that have see Dr.S can help me with

this. I got some more labs back and my C3 is low but C4 is normal.

Quite awhile back someone here mentioned that one of those was mold and

one was Lyme. Does anyone know what a low C3 means and which of those

conditions it is pointing to? I am trying to figure out which one to

treat first. I could not find any info on his web sight about those

specific levels. Anyone remember that post? Thanks alot- D

[Guest guest]

Dr Shoemaker discusses the bloodwork results that are most meaningful

to him with mold patients in the presentation he made to the NTP last

year.

Its got a wealth of information in it, definitely worth downloading.

You have to scroll down to get to the tests..

http://ntp.niehs.nih.gov/files/ShoeNTP_12_06_07w_attach.pdf

also he has a lot of other stuff on biotoxin.info . Look under

Research and also Resources..

stuff like this..

http://www.biotoxin.info/docs/NTP_12_6_07_Understanding%20mold%20illness_2.pdf

On Tue, Nov 4, 2008 at 4:12 PM, dianebolton52 <dianebolton@...> wrote:

> Hi Guys: I dont know if any of you that have see Dr.S can help me with

> this. I got some more labs back and my C3 is low but C4 is normal.

> Quite awhile back someone here mentioned that one of those was mold and

> one was Lyme. Does anyone know what a low C3 means and which of those

> conditions it is pointing to? I am trying to figure out which one to

> treat first. I could not find any info on his web sight about those

> specific levels. Anyone remember that post? Thanks alot- D

>

>

[Guest guest]

Diane,

These are the relevant parts from Dr. Shoemaker's NTP presentation,

Scroll *way* down for the most specific info on C4a, etc.

(I'm including his preface- the long part at the beginning) because

it gives an additional executive summary of the labs that show mold

illness.

Barbara Shane, PhD

Executive Secretary

National Toxicology Program

NIEHS/NIH

PO Box 12233-MD A3-01

111 T.W. Dr.

Research Triangle Park, NC

27709 11/20/07

Dear Dr. Shane,

Thank you for the opportunity to address the NTP panel on the subject

of human illness

acquired following exposure to water-damaged buildings (WDB). It is my

understanding

that your group seeks to bring an objective, scientific approach to

public health concerns

regarding exposure to " mold " using tools of modern toxicology and

molecular biology. I

feel that my experience as a treating primary care physician, treating

over 6600 patients

exposed to biologically produced neurotoxins, including over 4500

people made ill

following exposure to water-damaged indoor environments, is pertinent to your

deliberations today. I have an extensive data base on those patients

that our group has

used to publish a series of academic papers on the subject of human

illness acquired

following exposure to WDB (1, 2, 3).

These peer-reviewed papers present a case definition of " mold

illness; " a case control

study; a roster of symptoms and lab abnormalities seen in affected

patients; a double

blinded, placebo controlled trial confirming benefit of treatment with

cholestyramine

(CSM); and assessment of sequential changes in inflammatory elements seen during

treatment, re-exposure and re-treatment. These studies employ a

5-step, repetitive

exposure study design (ABB`AB, see appendix 4) that includes prospective

documentation of acquisition of illness. In the second paper in

Neurotoxicology and

Teratology (3), peer reviewers permitted us to say that the data

presented were consistent

with the hypothesis that exposure to WDB caused the illness.

My request to NTP is to investigate " mold illness " by recognizing that

the illness is

multi-factorial and that no single agent, especially mycotoxins, is

the source of illness

symptoms. We already have a large database collected prospectively (following

informed consent) that demonstrates that the acute and chronic illness

acquired following

exposure to WDB is indeed caused by such exposure. We also know that the illness

physiology can be demonstrated such that an organized approach to

treatment can follow

delineation of the abnormalities in innate immune response these patients have.

I have organized my presentation according to the following categories:

1) What do we know about symptoms seen in cases versus controls?

2) What objective parameters are present in all cases and found in no controls?

3) Treatment should correct parameters found in cases to equal those

found in controls.

4) Hypothesis testing: prospective acquisition of illness after

re-exposure in successfully

treated patients will re-create baseline symptoms and objective

parameters rapidly and

reproducibly, independent of type of organisms found in the WDB (appendix 4).

5) Serial recording of objective parameters in blood (appendix 3) from

innate immune

responses will show differences according to a time course that is

paralleled by gene

activation (genomics work underway).

6) Presence or absence of particular haplotypes of HLA DR account for nearly all

differences in individual susceptibility, given the same exposure.

7) Prior abnormalities in innate immune responses change the rate of

response when

previously affected patients are re-exposed.

8) First order or monotonic dose-response relationships do not apply

to illnesses when

differential activation of immune cascades is present and multiple

potential toxigenic

organisms and inflammagens are present simultaneously in a WDB.

9) Assessing the effects of one-time, massive exposures of rats or

mice to a single type of

inflammagen found in WDB to assess the potential for human illness

acquisition is

illogical. Given that WDB contain many different kinds of potential sources of

inflammation, each must be looked at in an inhalant model of illness.

Studies must be

done in people.

10) Use of a case definition (appendix 1) and visual contrast testing

(appendix 2) presents

a rapid, inexpensive and reproducibly reliable method of screening

exposed populations

before lab testing is performed.

11) Defining problems for further research begins with an unbiased

assessment of the

potential human health risk given the number of buildings in the US

with current or

future water intrusion problems.

I will use the term, " mold illness, " in this summary to save time:

what I mean by the

term " mold illness " is a chronic, biotoxin associated illness acquired

following exposure

to interior environments of WDB with resident toxigenic organisms,

including but not

limited to fungi, bacteria, mycobacteria and actinomycetes; as well as

inflammagens such

as beta glucans, VOCs, proteinases, hemolysins and particulates made by those

organisms, and others as yet identified. Solely focusing on molds as a

source of public

health concern would be a serious error in assessment. Please look at

WDB as the unit of

exposure and not just molds!

BACKGROUND: I have attached a current CV. I continue to practice in a

rural area of

the Eastern Shore of land, beginning in a NHSC clinic site at Pocomoke City,

land, 1980. My training was in molecular biology as Duke,

including work here at

NIEHS in the lab of Dr. Jud Spaulding in the early 1970's looking at

the effects of

pesticides on membrane-bound phospholipids. I chose Family Practice as a career,

feeling that the union of primary care and clinical research in a

medically underserved

area was an ideal match for me.

My involvement with biotoxin associated illnesses was not due to

choice but was instead

due the unexpected outbreak of human illness in patients exposed to

estuaries, beginning

with the Pocomoke River, a tributary of the Chesapeake that flows past

my office, that

harbored resident toxigenic dinoflagellates, including Pfiesteria,

beginning in 1997.

Chance brought me an opportunity to treat some of my index patients with

cholestyramine (CSM), with subsequent rapid reduction of symptoms and clinical

improvement. I published the first papers in the world's literature on

acquisition and

treatment of Pfiesteria human illness acquired in the wild in

1997-1998 (4, 5), followed

by papers in EHP in 2001 (6, 7). Application of the method of trial

and error led to

similar successful use of CSM in patients made ill by ciguatera,

cyanobacteria, Borrelia

species, apicomplexans and more, with no differences in lab

abnormalities seen by

location or duration of illness (see CV). My first " mold patients "

were treated in 1998.

Thanks to the pioneering work and teaching of Dr. Ken Hudnell (US EPA, NHEERL,

RTP), who first used visual contrast sensitivity (VCS) testing in

patients with biotoxin

illnesses, I have been using VCS since 7/1998. Just like the symptoms

and abnormalities

in innate immune responses, the diagnostic deficits seen on VCS

testing are essentially

identical in all biotoxin-formers.

I define a biotoxin as a biologically produced, low molecular weight

toxin, usually an

ionophore that creates a molecular dipole or anion ring in three

dimensions. These

compounds have the potential to elicit a pro-inflammatory cytokine

response by binding

to membrane receptors, independent of their possible intracellular

effects. These effects

can be seen in isolated cell systems. We identify the illness from

exposure to a biotoxin

by the inflammatory effects of such exposures seen in affected

patient. Not all patients

exposed to biotoxins become ill: Individual susceptibility is not part

of the definition of a

biotoxin but is part of the definition of the illnesses caused by biotoxins.

My clinical research is accomplished through my private practice and a

non-profit 501-c-

3 organization, the Center for Research on Biotoxin Associated

Illnesses (CRBAI).

Early in our group's work, we established that a series of illnesses,

each of which would

be present in a thorough differential diagnosis of symptoms acquired

following exposure

to WDB, do not cause the particular grouping of illness symptoms

(identified by cluster

analysis); do not cause abnormalities in innate immune responses; and

do not cause VCS

deficits. Combining these modalities in logistic regression provides

an ability to classify

patients with biotoxin illness compared to control with an extremely

high degree of

accuracy. Moreover, use of CSM does not correct other symptoms of

systemic illnesses

such as depression, stress, diabetes, high blood pressure, menopause,

use of medications,

lupus, asthma, nasal allergy, sensitivity to dust mites, sleep apnea

and states such as

deconditioning and obesity, among many others. Successful therapy with CSM in

illnesses that don't self-heal, with say, removal from exposure,

suggests that the

mechanism of illness causation, corrected by CSM, involves the effects

of a substance

that is bound and removed by CSM.

I have included a lengthy list of references that reflect the

explosion of publications that

support the hypothesis that inflammatory processes are initiated in

susceptible patients

following exposure to WDB (see attachment, Current References). The

recent papers

from the CDC (8) and EPA (9) show an evolution of opinion from Federal

agencies on

the potential for human illness and exposure to WDB. The comments of

Bob Weinhold

in EHP (10) regarding a mini-monograph on inhalational effects of mold

also reflect a

significant shift in opinion regarding the health effects of WDB. He

concludes that,

" …the overall recommendations of many organizations and agencies worldwide are

reaching a common conclusion: Don't mess with mold. If you can see it

or smell it-and

especially if health problems are occurring (emphasis added)-clean it

out, throw it out or

get out. "

Our data supports that conclusion. We want you to know that mold

illness is readily

identifiable, readily treatable and is a preventable cause of human misery.

1) SYMPTOMS: Biotoxin illnesses are typified by multiple acute and chronic

symptoms from multiple organ systems. One would expect that more than one

organ symptoms would be involved if a systemic inflammatory illness were

present. Presence of one symptom compared to another has little significance, as

the commonality of symptoms across the board in biotoxin illnesses is invariably

found. Fatigue, cognitive effects, especially in executive cognitive

functioning,

respiratory effects, gastrointestinal symptoms, musculoskeletal symptoms,

neurologic effects, headache and eye symptoms are routinely seen. In an average

biotoxin illness patient, approximately 15-20 of 37 symptoms are the norm.

Pediatric patients have fewer symptoms, averaging 10-12. Control patients will

have fewer than 4 of the same symptom roster.

2) OBJECTIVE PARAMETERS: Standard lab testing is normal. CBC, CMP,

TSH, ESR, CRP, ANA, immunoglobulin profiles, and more are not different in

cases compared to controls. Testing of innate immune responses (see appendices

of lab parameters) however is incredibly different. MSH deficiency, elevated

MMP9, dysregulation of simultaneously measured ADH/osmolality and

ACTH/cortisol jump off the page. VEGF deficiency, elevation of C4a and

evidence of abnormalities of T-regulatory cell function are no less

important: not

found in controls with statistical significance, these abnormalities are nearly

always present in cases. VCS deficits are found in 92% of cases and in 1% of

controls, with errors in sensitivity and specificity that are less than 1.5%.

3) TREATMENT EFFECTS: As presented in multiple studies from our group and

mirrored by multiple physicians employing our protocols across the country show

that therapy with CSM, eradication of biofilm-forming commensals (11) found in

case but not controls and correction of excessive cytokine responses as initial

steps of treatment returns symptoms, labs and VCS found in cases to control

values. Newer data, obtained in clinical trials (12, 13) with those not improved

with the above protocols, show that reduction of refractory elevation

of C4a with

low-dose erythropoietin (epo) is of paramount importance in correcting central

nervous system metabolic abnormalities of elevated lactate and depressed ratios

of glutamate to lactate seen on magnetic resonance spectroscopy,

cognitive effects

and peripheral symptoms. With re-exposure the CNS metabolic effects, symptoms

and C4a elevation all rise within 24 hours.

4) HYPOTHESIS TESTING: We use a model of illness acquisition derived by

treating and monitoring hundreds of patients. Much of this data is unpublished,

but is mostly presented at academic conferences. If a sequential cascade of gene

activation and gene product effects on downstream pathways is a player in human

illness caused by exposure to WDB, then we should be able to re-create

a longterm

illness in an incredibly short period of time. Our repetitive exposure clinical

trails confirm that essentially 95% of a long-term illness re-appears

within three

days or re-exposure. The " SAIIE index " presentation (14)), attached to this

summary was the result of collation of a series of 50 cases and

controls in which

we could use the lab results of patients, previously affected,

undergoing reexposure,

to create an index of illness that maintained a close correlation with the

recent EPA index, ERMI, named for a building summary of fungal DNA. To

date, we see a clear uniformity, within biological variation of the hyperacute

markers of illness, including C4a, VEGF, MMP9, leptin, factor VIII, von

Willebrand's' factor and ristocetin-associated antigen. While we feel that the

bleeding, usually profuse epistaxis and hemoptysis seen in re-exposure

trials and

in mold illness patients, particularly children, is due to acquired on

Willebrand's

disease, our data sets are still building to assess statistical

significance later.

5) GENOMICS RULES THE WORLD!: We feel that the genomic changes of

hyperacute activation of genes predicted to be activated by our models, and

shown by Dr at NOAA in his ciguatoxin experiments (15), will be

confirmed by ongoing testing using PAXgene testing. These data should be ready

by 12/6/07 in an initial cohort. Costs of the 124-gene microarray are

difficult to

bear for a tiny, privately-funded non-profit group. We will be able to

correlate lab

results with gene activation in this ambitious project.

6) HLA DR SAYS A LOT: Each of us has two haplotypes of the immune response

genes HLA DR found on chromosome 6. Large population studies (over 4000

patients, cases and controls) have shown a consistent increased presence of

particular haplotypes in cases compared to controls. There are six separate

haplotypes with an increased relative risk in cases of mold illness compared to

controls. These haplotypes are in turn sub-divided by relative risk of

development of profound, disabling chronic fatigue, with two uncommon

haplotypes (DRB1-4, DQ-3, DRB4-53 and DRB1-11, DQ-3- DRB3-52B), found

in 4% of the population actually representing 88% of cases of refractory CFS

(16).

7) SICKER, QUICKER: Patients undergoing repetitive exposure protocols must

not be those with any C4a that exceeds 20,000 (normal < 2830 ng/ml by RIA in

Complement Lab, Dr. P. Giclas, at NJC, Denver, Colorado). They do poorly with

re-exposure, with a correction rate following second treatment that is

far less than

those with C4a of < 20,000. In our data sets of C4a that exceed 2000 patients,

C4a elevation of this magnitude is not uncommon, found in over 10% of patients.

Finding a C4a of over 20,000 in a screening sample of patients with

exposure to a

WDB should create a call for immediate action.

8) WHAT DOES IT TAKE TO MAKE SOMEONE SICK? Dose response

relationships seen in illness caused by exposure of genetically

susceptible patients

to interior environments of water-damaged buildings (WDB) are not linear: there

are so many variables of exposure and response that postulating a 1:1

relationship

of total mass or number of spores required for a threshold exposure is

nonsensical.

Consider that an effect or response (X) is related in a linear fashion

to dose. (X)

will then be equal to the sum of routes of exposure (A) plus

contaminants ( plus

length of time of exposure © plus individual genetic susceptibility (D) plus

individual prior exposure and change of susceptibility from that

exposure (E) plus

amounts/types of microbial organisms, each potentially acting

synergistically with

another (F) plus the amount of inflammagens causing potentially exponential

changes in c-type lectin receptors, especially dectin-1 and dectin-2

receptors (G).

X then is equal to the combined effects of A through G, each of which can cause

amplification, not additional, effects of innate immune responses. Moreover, the

elements A through G are each themselves variable. It gets worse for the linear

dose-response advocates: there are interactions of A through G, some of which

are synergistic and some involve differential gene activation as well

as epigenetic

phenomena. It is impossible to assume that response or effect X will be linearly

related to variables, each simultaneously expressed A through G. We cannot

analyze one component of exposure, namely mold spores, and come to any

meaningful conclusions from classical monotonic dose-response relationships.

9) IS ONE SINGLE DOSE RAT STUDY ENOUGH TO BE ACCEPTED AS

DEFINITIVE SCIENCE FOR ALL LOW DOSE EXPOSURES IN

HUMANS? I am aware that there are older consensus statements (17) about

mold illness that relied on a single study of a single application of an unknown

numbers of toxins on unknown number of spores into trachea of rats. The rats

were seriously ill from this exposure, but the ACOEM statement authors

concluded that the number of mycotoxins required to cause illness in people were

insurmountably high. Some people actually think this bizarre mathematical

speculation is good science. Our group presented an argument (3) that

refutes the

ACOEM position. Mold illness involves so many inflammagens and toxins, that

trying to study the unique ecological niche that is a WDB with just

one parameter

doesn't make sense. Just two years ago, no one talked about mycolactoneforming

mycobacteria and, quite frankly, mentions of c-type lectin receptors were

discussed in just a small branch of immunology. Now c-type lectins, especially

dectin-1 (and now dectin-2, how many others?!) receptors are recognized as

critically important in generating an inflammatory response to beta glucans (see

section in Current References). Even more important, the response of c-type

lectins, recognizing glycoproteins, remains critical to understanding

how lowdose

erythropoietin (epo) reverses the ongoing activation of production of the

short-lived anaphylatoxin C4a. Epo lowers C4a and stops its regeneration. Does

epo affect/stabilize c-type lectins?

10) SCREENING: This point is the thrust of my concerns for public health. In my

experience, early case identification leads to far better outcomes from early

intervention. Find the sick kid in school because the nurse does symptom

recording and VCS testing on all third graders and that kid will be

able to access

definitive care more quickly. Find a bunch of sick kids from dry homes and the

school gets evaluated for water intrusion and microbial growth. Early case

finding leads to early remediation. No moisture, no mold and no more new cases

of sick patients. As our data sets on MR spectroscopy grow (we have over 300

cases and 50 controls), we will be able to show statistical certainty

of the presence

of distinctive increases in lactate (i.e. lack of oxygen delivery from capillary

hypoperfusion) that correlate with reduced production of the excitatory

neurotransmitter glutamate compared to glutamine in long-standing cases, but

increased glutamate to glutamine in shorter duration cases. MRS, however, isn't

a good screening tool: VCS and symptoms screening take 5 minutes, yielding

incredibly accurate results quickly (18). MR spectroscopy costs $1500 and

requires 90 minutes of tech and machine time. While I am not suggesting routine

measurements of HLA DR by PCR, MMP9, MSH and C4a in all people exposed

to a WDB, we have used that approach at the request of employers in the past.

11) FUTURE RESEARCH NEEDS: NTP can best define its investigation by a

multi-site, case/control study, adding treatment/outcome studies as

their data set;

small as it will be at onset, reaches statistical significance. Labs

that reflect the

basic disease mechanisms should be collected in all patients. PAXgene samples

for mRNA analysis should be drawn and saved for future microarray assays.

Investigation into the mechanism of C4a regeneration needs a prime position in

analysis, as does the role of IL-4, IL-8 and IL-10, each of which

could account for

the reduced antigen recognition mechanism seen in previously affected patients

(reduced presentation of HLA on monocytes??). Population studies of controls

and cases need to be collated using a standard set of answers to

questions obtained

by a trained professional (not a checklist), with VCS testing, as performed

currently according to a standard protocol by NIOSH, perhaps correlated with

ERMI. Most importantly, NTP needs to support rigorous academic data

collection by series of coordinated practices across the country.

These practices

are already identified.

Sincerely,

Ritchie C. Shoemaker, MD

.......

Then he has a bunch of references and describes the VCS,

Then he has the description of the labwork that shows mold illness

(the part you were asking about):

...................

3. Laboratory studies

LabCorp, Inc. and Quest Diagnostics, each CLIA approved, high

complexity, national

laboratory facilities. Factors analyzed included:

MSH: Alpha melanocyte stimulating hormone (MSH) is a 13 amino acid compound

formed in the ventromedial nucleus (VMN) of the hypothalamus, solitary

nucleus and

arcuate nucleus by cleavage of proopiomelanocortin (POMC) to yield

beta-endorphin and

MSH. MSH exerts inductive regulatory effects on production of hypothalamic

endorphins and melatonin. MSH has multiple anti-inflammatory and neurohormonal

regulatory functions, exerting regulatory control on peripheral

cytokine release as well as

on both anterior and posterior pituitary function. Deficiency of MSH,

commonly seen in

biotoxin-associated illnesses, is associated with impairment of

multiple regulatory

functions and dysregulation of pituitary hormone release. Symptoms

associated with

MSH deficiency include chronic fatigue and chronic, unusual pain

syndromes. Normal

values of MSH established in research labs and in commercial labs are

35-81 pg/ml. I

note that the recent shift in normal range for MSH from LabCorp to

0-40 pg/ml was made

following the receipt of so many low values of MSH. I have questioned

both Dr. Andre

Valcour and Dr. Marsella of LabCorp about this change; they

have received

case/control data sets from me and assure me that they will review the

adjustment of

normal ranges that were made only after lumping values for cases and

control together.

No lab, including LabCorp, can logically equate a case value of a test

with a control value

for a test.

Leptin: Leptin is a 146 amino acid adipocytokine produced by fat cells

in response to

rising levels of fatty acids. Leptin has peripheral metabolic effects,

promoting storage of

fatty acids, as well as central effects in the hypothalamus. Following

binding by leptin to

a long isoform of the leptin receptor in the VMN, a primordial gp-130

cytokine receptor,

a JAK signal causes transcription of the gene for POMC, which is in

turned cleaved to

make MSH. Peripheral cytokine responses can cause phosphorylation of a

serine moiety

(instead of threonine) on the Leptin receptor, creating leptin

resistance and relative

deficiency of MSH production. Normal values in commercial labs show differences

between males (5-8 ng/ml) and females (8-18 ng/ml), with levels of

leptin correlated with

BMI. In the presence of MSH deficiency, the relationship between body weight and

leptin changes, as leptin elevation becomes disproportionate to weight.

ADH/osmolality: abnormalities in ADH/osmolality are recorded as

absolute if ADH is <

1.3 or > 8 pg/ml; or if osmolality is >295 or <275 mOsm/kg.

Abnormalities are recorded

as relative if simultaneous osmolality is 292-295 and ADH < 2.3; or if

osmo is 275-278

and ADH> 4.0. Symptoms associated with dysregulation of ADH include dehydration,

frequent urination, with urine showing low specific gravity; excessive

thirst and

sensitivity to static electrical shocks; as well as edema and rapid

weight gain due to fluid

retention during initial correction of ADH deficits.

ACTH/cortisol: abnormalities in ACTH/cortisol are absolute if AM

cortisol > 19 ug/ml

or < 8 ug/ml; or if AM ACTH is >60 pg/ml or < 10 pg/ml. Abnormalities

are recorded as

dysregulation if simultaneous cortisol is > 15 and ACTH is > 15, or if

cortisol is < 8 and

ACTH <40. Early in the illness, as MSH begins to fall, high ACTH is

associated with

few symptoms; a marked increase in symptoms is associated with a fall in ACTH.

Finding simultaneous high cortisol and high ACTH may prompt

consideration of ACTH

secreting tumors, but the reality is that the dysregulation usually

corrects with therapy.

Androgens: total testosterone, androstenedione and DHEA-S provide measurements

regarding the effectiveness of gonadotrophin secretion as influenced

adversely by MSH

deficiency. Normal ranges of these hormones in males are 75-205 ng/ml for

androstenedione, 350-1030 ng/ml for testosterone and 70-218 ug/ml for DHEA-S.

Normal values for pre-menopausal women are 60-245, 10-55 and 48-247,

respectively.

Post-menopausal normal ranges are 30-120, 7-40 and 48-247, respectively.

HLA DR by PCR: LabCorp offers a standard HLA DR typing assay of 10

alleles using a

PCR sequence specific chain reaction technique. As opposed to

serologic assays for the

HLA DR genotypes, the PCR gives far greater specificity in

distinguishing individual

allele polymorphisms. Linkage disequilibrium is strong in these

genotypes, with multiple

associations made to inflammatory and autoimmune disease. These genes

are part of the

human major histocompatibility complex (MHC), also called the HLA complex, and

located on the short arm of chromosome 6. Relative risk was

calculated, susceptible

genotypes identified, compared within each group to location and

exposure. The HLA

doesn't by itself say that mold makes a patient sick: the increased

relative risk in cases

versus controls shows the increased individual susceptibility

expressed as a statistical

ratio,

MMP9: matrix metalloproteinase 9 (gelatinase is an extracellular

zinc-dependent

enzyme produced by cytokine-stimulated neutrophils and macrophages. MMP9 is

involved in degradation of extracellular matrix; it has been

implicated in the pathogenesis

COPD by destruction of lung elastin, in rheumatoid arthritis, atherosclerosis,

cardiomyopathy, and abdominal aortic aneurysm. Cytokines that stimulate MMP9

production include IL-1, IL-2, TNF, IL-1B, interferons alpha and

gamma. MMP9 is felt

to play a role in central nervous system disease including

demyelination, by generation of

myelin peptides, as it can break down myelin basic protein. MMP9 " delivers "

inflammatory elements out of blood into subintimal spaces, where

further delivery into

solid organs (brain, lung, muscle, peripheral nerve and joint) is

initiated. Normal ranges

of MMP9 have a mean of 150, with range of 85-322 ng/ml.

C3a and C4a: Split products of complement activation, often called

anaphylatoxins.

Each activates inflammatory responses, with spillover of effect from

innate immune

response to acquired immune responses and hematologic parameters.

These short-lived

products are re-manufactured rapidly, such that an initial rise of

plasma levels is seen

within 12 hours of exposure and sustained elevation is seen until

definitive therapy is

initiated. The components increase vascular permeability, release

inflammatory elements

from macrophages, neutrophils and monocytes, stimulate smooth muscle

spasm in small

blood vessels and disrupt normal apoptosis. They also recruit

additional inflammatory

generators, such as chemokines, into action.

Anticardiolipins IgA, IgM and IgG: autoantibodies often identified in collagen

vascular diseases such as lupus and scleroderma; often called

anti-phospholipids. These

antibodies in high titers are associated with increased intravascular

coagulation requiring

treatment with heparin and coumadin. Lower level titers are associated with

hypercoagulability. An increased risk of spontaneous fetal loss in the

first trimester of

pregnancy is not uncommonly seen in women with presence of cardiolipin

antibodies.

This problem does not have the same " dose-response " relationship seen

with levels of

autoantibodies and illness, as does the antiphospholipid syndrome.

Anticardiolipins are

found in over 33% of children with biotoxin-associated illnesses.

Antigliadin IgA and IgG: Antibodies thought at one time to be specific

for celiac

disease. With the advent of testing for IgA antibodies to tissue

transglutaminase (TTGIgA),

gliadin antibodies are most often seen in patients with low levels of MSH.

Ingestion of gliadin, the 22-amino acid protein found in gluten (found

in wheat, oats,

barley and rye; often added to processed foods) will initiate a

release of pro-inflammatory

cytokines in the tissues lining the intestinal tract. This cytokine

effect will often cause

symptoms within 30 minutes of ingestion that mimic attention deficit

disorder, often

leading to an incorrect diagnosis. Antigliadin antibodies are found in

over 58% of

children with biotoxin-associated illnesses.

Vasoactive intestinal polypeptide (VIP): neuroregulatory hormone with

receptors in

suprachiasmatic nucleus of hypothalamus. This hormone/cytokine

regulates peripheral

cytokine responses, pulmonary artery pressures and inflammatory

responses throughout

the body. VIP raises intracellular levels of cAMP, a vital secondary

messenger of cell

signaling. Deficiency is commonly seen in mold illness patients,

particularly those with

dyspnea on exertion.

.....

There you have it...

HTH.

[Guest guest]

The first video of biotoxin.info has alot about C4a. Live did not specify this

well because he has not been treated by Dr. Shoemaker. Dr. Shoemaker says that

C4a and MSH are two of the most important markers he uses.

       

        " We The People "   

        If we dont pay attention " we " will loose our rights to our freedom.

From: LiveSimply <quackadillian@...>

Subject: Re: [] Question about complement C3

Date: Thursday, November 6, 2008, 1:18 PM

Dr Shoemaker discusses the bloodwork results that are most meaningful

to him with mold patients in the presentation he made to the NTP last

year.

Its got a wealth of information in it, definitely worth downloading.

You have to scroll down to get to the tests..

http://ntp.niehs. nih.gov/files/ ShoeNTP_12_ 06_07w_attach. pdf

also he has a lot of other stuff on biotoxin.info . Look under

Research and also Resources..

stuff like this..

http://www.biotoxin .info/docs/ NTP_12_6_ 07_Understanding %20mold%20illnes

s_2.pdf

[Guest guest]

D, to be specific here are the markers you need

C3 should be 90-180 mg/dl (Shoemaker does not use this test)

C3d-IC should be 0-8 mcg/ml (Shoemaker does not use this test)

C3a should be <940ng/ml (this might be lime?? It looks like he uses it but did

not test         me for it. A doctor that did, he said it was the wronf test.)

C4a should be <2830 ng/ml but higher than 20000 is dangerous

MSH should be 35-81 pg/ml

 

Any other questions just let me know.

 

 

       

        " We The People "   

        If we dont pay attention " we " will loose our rights to our freedom.

From: dianebolton52 <dianebolton@...>

Subject: [] Question about complement C3

Date: Tuesday, November 4, 2008, 4:12 PM

Hi Guys: I dont know if any of you that have see Dr.S can help me with

this.