Elevated TSH levels among California newborns after Fukushima.

Well, something is going on. Yesterday I went to two stores, and I actually went for a walk halfway around the shopping mall. I have not walked that much in two months. In fact, I hardly have been going out of the house at all more than once a week. I did pay for it today, with increased neurological symptoms.

But I decided the hell with it, I was going to do an analysis. I haven’t done any programming for four months, ever since the flu/M.E. nightmare started.

Let me tell you how important computer programming is to me. I started programming in 1971, when me and my friend Joel would sneak into the computer lab after hours in high school. They had a phone modem thingy. My first program was a computer baseball program written in BASIC. I picked up the language as I went along.

When I went to college, I learned FORTRAN by using punchcards. This ain’t easy. Punchcards are hardcore. They teach you to not make mistakes. This isn’t the touchy-feely BS they teach nowadays. I am a scientific programmer. I need speed and control.

I bought the original IBM PC in 1982. One of my first programs was an astrology program. I programmed the movement of the planets, any day for 1,000 years. I had to learn Bessel functions and that kind of stuff.

I have developed large database-driven systems for corporations. I have been invited to organize two major conference sessions in academic systems engineering. I have been wined and dined by corporate executives for a printing press scheduling program I wrote. (There is a story behind this. It goes into the inexplicable-things-that-have-happened-to-Bobby1 category. Not right now.)

So I have been always programming, for work, or for my own enjoyment or interests. Till I got sick.

Today, after four months, I was able to do an analysis. It just involved programming in VBA, nothing special. Though the data set was so large I had to expand MegaODA, so I had to find the program, expand its limits to 3 million observations, and recompile it in FORTRAN. I forgot if my computer had SSE4.1 on it, so I had to find and run CPU-Z to verify this.

This is like a marathon runner who suffers a devastating injury, and four months later, is able to take a few halting steps, while everyone applauds. Except nobody is applauding. I have a warm feeling in my heart, that’s all.


Oh, and by the way, this is the most significant result yet on American patients’ health in relation to Fukushima. It is more significant than my 2011 mortality study.

The data came from the Genetic Disease Screening Program at the California Department of Public Health. These are TSH (thyroid stimulating hormone) levels of California newborns for the period 2009-2012. Mangano, Sherman, and Busby used this same dataset for their paper on congenital hypothyroidism which was incomprehensibly botched. Dr. Yarnold and I made comments on this paper here.

While Mangano et al. created arbitrary classifications of hypothyroidism, which are not used in practice, these results reflect TSH levels before and after Fuku. TSH is implicated in many diseases, not just hypothyroidism. It affects the entire hypothalamus-pituitary-thyroid axis. For one thing, increased TSH levels cause the newborn to absorb more iodine-131 than average TSH newborns would.

This is also important because it involves the effect of all species of radioisotopes, I-131, Cs-137, Pu-239, etc. etc. We don’t know if only I-131 affects newborns, in fact Dr. Bandazhevsky has shown that Cs-137 affects thyroids too.

The data have been split up into three seasons:

1. January 1 – March 16
2. March 17 – June 30
3. July 1 – December 31

It involves virtually the entire population of California newborns for the years 2009-2012.

AFTERFUK is an indicator variable, which equals 1 if the birth was after Fukushima, and 0 otherwise. “IF 4.5 < TSH THEN AFTERFUK = 1" means than if TSH is greater than 4.5 (actually 4.99 in the original data), then the newborn is classified as being born after Fukushima. ODA uses maximum-accuracy classification - no model of this form achieves higher classification accuracy. No distributional assumptions are involved. All three seasons, and the combined data also, show increased TSH levels after Fukushima, and all are statistically significant by two-tailed UniODA at the p<.01 level. The ESS levels vary from 3.90% to 8.02%. The effect is weak, but I am not a thyroid doctor. Since over two million newborns are involved, even a small effect has consequences for many newborns. I would think that something that would affect even 100 newborns is a big huge deal.

Analysis for January 1 – March 16.

Analysis for March 17 – June 30.

Analysis for July 1 – December 31.

Analysis for the combined seasons.

How ME and radiation sickness has altered my mechanism of thinking.

Yablokov et al. in their Chernobyl book demonstrated how radiation exposure affected the brains of liquidators and others at Chernobyl. The brain and central nervous system are some of prominent organs affected by radiation.

Profound cognitive changes have occurred since I came down with ME (myalgic encephalomyelitis) in April. It has affected the way I think, it has affected this blog, it has destroyed my career.

The first image below is a lattice. It reflects the way I used to think, in my previous 59 years. In developing large scientific computer programs, I would sit in a state of concentration for 7 hours at a time. “347 is related to 13, which is related to 3, which is related to 1245” etc. I was able to visualize the entire thing in my head at once, and move up and down, changing something at the bottom, then moving to the middle or the top, and conceptualize how the small changes affected the entire system. This is also the way I digested information by reading, and how I was able to present it in writing. This whole blog deals with unifying disparate pieces of information on Fukushima and other issues, and combining them into an argument. This is why there is a unique perspective here, as I discover new things by seeing patterns.

Nonlinear lattice thinking.

Linear thinking.

Lattice thinking has gone away. This is difficult to adjust to. It is impossible to multitask in the slightest.

The other image describes linear thinking. “A leads to B, B leads to C, C leads to D”, etc. It’s a chain, not a lattice. I have never been good at this kind of thinking.

But it seems that, while I am now incapable of lattice thinking, the alterations in neurotransmitter functions of serotonin, glutamate, and GABA have IMPROVED linear thinking.

The slightest distraction or exertion will cause me to forget what I was just thinking a second before. Or it will simply go away, POOF. With linear thinking, that means I forget what B is. What I do is simply go back to A and start over. It doesn’t affect this type of thinking like it does the lattice. The only thing I have to do is remember A.

In fact, since I no longer have to remember the entire lattice, this condition has streamlined things, making it easier.

I made a post on Facebook extolling the virtues of fat, for my own health, and ME patients in general.

FAT IS GOOD (for me at least)…

I should go back to the redneck diet I had years ago. I want to have grease dripping out of my mouth. I want pulled pork in my teeth.

Fat increases lymphotoxin, which increases IL-22, which provides immunity to bacteria, and repairs gut tissues, and alters the balance of gut microbiota.

This was without reading any testimonials whatever from ME (ME/CFS) sufferers. It is a product of the thought process behind this blog post I recently published.

1. I had read from UNSCEAR and the National CFIDS Foundation that radiation exposure impairs STAT-1 functions in the JAK/STAT pathway.

2. When I suddenly came down with ME, my plaque and guttate psoriasis suddenly disappeared. This NEVER happens like this to anyone. The inverse psoriasis remained, but that really isn’t psoriasis of the same kind, it’s due to skin damage from uranium and fluoride, some from Fuku, but mostly from Honeywell.

3. I knew from my previous research in psoriasis that there are two mechanisms for psoriasis, one based on IL-17, the other based on IFN-γ and IL-22. It was obvious that the inverse was based on IL-17, and the plaque and guttate were based on IFN-γ and IL-22.

4. Since STAT-1 contains the genes that produce IFN-γ, and this cytokine had suddenly dramatically decreased, I started a chain of reasoning, A -> B -> C etc.

The lack of IFN-γ causes a lack of SMAD7. The lack of SMAD7 causes an increase in TGF-β. The increase in TGF-β causes Th22 cells to not be differentiated. The lack of Th22 cells causes a lack of IL-22.

See, it explains why the psoriasis suddenly disappeared. It’s all about STAT-1 impairment.

Also, IFN-γ is expressed in group 1 innate lymphoid cells (ILC1). ILC’s are located in Peyer’s patches of the intestines, and other lymphoid nodules. ILC3, or group3 cells, express IL-22. The damage to ILC1 causes damage to ILC3. This causes tissue damage to the gut, and bacterial translocation from the gut to other parts of the body.

I was able to predict that eating fat would repair ILC3, and cause improvement in symptoms. I mentioned this is an ME group, and found that others already do this. In fact, ketogenic diets are popular in treatment of this condition. I had not known this.

So I was able to reason, starting from a particular kind of radiation damage, and presented a hypothesis, which was confirmed. This is what science is all about.

I know that I am on the right track, I know that ME is really radiation sickness, and I know that ME is not an autoimmune disease, but an immune deficiency disease, characterized by a loss of cellular immunity. But I’ll be damned if I can organize something which would demonstrate or prove this. That requires lattice thinking.

But maybe I am still good for something, maybe I can work again, but I don’t know just at what yet.

Latest Fukushima plume. Worst since Sept. 2013?

Lots of alarm bells ringing. Fukushima Diary has a story about a spike in radiation after a small earthquake. This is corroborated by many other monitors nearby Fukushima. Majia has been reporting on increased webcam activity. I saw on Facebook that radiation levels in Taiwan have risen, and there are high readings in the Midwest US. And there is this reading from a rain sample in Alberta, Canada:

Radioactive Rain – July 17 2014 – 11:20pm

4.98 μSv is pretty bad. Probably 25-40 times normal background. There were previous spikes this year in January and May, but this might be worse. The Aug-Sept 2013 release was really bad. It remains to be seen if this new one is worse. I haven’t looked at sludge data yet.

I can’t tell anymore from my own health. The ME swamps everything with its own signals. Autoimmune disease was so easy then.. relatively.

Origin of M.E. disease process in the immune system.

The sudden onset of M.E. (myalgic encephalomyelitis, ME/CFS) 3 months ago occurred when I when I was experiencing a flare of psoriatic arthritis, an autoimmune disease. The virus infection caused an huge amount of inflammation. Everything suddenly changed virtually overnight… so I have a personal insight into the ME disease process that doctors and other patients may not have.

Internal radiation exposure causes damage to the JAK/STAT pathway.

The JAK-STAT signaling pathway transmits information from chemical signals outside the cell, through the cell membrane, and into gene promoters on the DNA in the cell nucleus, which causes DNA transcription and activity in the cell. The JAK-STAT system is a major signaling alternative to the second messenger system.

The JAK-STAT system consists of three main components: (1) a receptor (2) Janus kinase (JAK) and (3) Signal Transducer and Activator of Transcription (STAT).[1]

Many JAK-STAT pathways are expressed in white blood cells, and are therefore involved in regulation of the immune system.

The receptor is activated by a signal from interferon, interleukin, growth factors, or other chemical messengers. This activates the kinase function of JAK, which autophosphorylates itself (phosphate groups act as “on” and “off” switches on proteins). The STAT protein then binds to the phosphorylated receptor, where STAT is phosphorylated by JAK.The phosphorylated STAT protein binds to another phosphorylated STAT protein (dimerizes) and translocates into the cell nucleus. In the nucleus, it binds to DNA and promotes transcription of genes responsive to STAT… (link)

The STAT protein (Signal Transducer and Activator of Transcription, or Signal Transduction And transcription) regulates many aspects of growth, survival and differentiation in cells. The transcription factors of this family are activated by Janus kinase (or ‘Just Another Kinase’, JAK) and dysregulation of this pathway is frequently observed in primary tumours and leads to increased angiogenesis, enhanced survival of tumours and immunosuppression. (link)

Specifically, radiation impairs the activity of STAT-1 protein, which is required for IFN-γ signalling. (link) IFN-γ is the hallmark Th1 cytokine, which is involved with cellular immunity.

We have recently characterized different mutations responsible for partial STAT1 functional deficiency. STAT1 is an essential protein for the signal transduction induced by IFNγ, under its homodimeric form (STAT1/STAT1, known as GAF) as well as its heterotrimeric form (STAT1/STAT2/p48, of ISGF3)… As a result, these observations prove that IFNγ-mediated anti-mycobacterial immunity depends on STAT1 and GAF. The characterization of patients with a STAT1 complete deficit and showing severe viral infections demonstrates that type I IFNs-mediated antiviral immunity is STAT1-dependent and ISGF3-dependent, at least for Herpes viruses. (link)

ME/CFS is usually linked to herpes viruses, Epstein-Barr viruses, or enteroviruses. Degradation of the STAT-1 pathway reduces immunity to these viruses. Herpes viruses hide in the immune system. They can become reactivated at any time. Everyone has these viruses latent in their systems since childhood. They are just waiting for a trigger to come back.

Smad7 is a protein, the expression of which is induced by STAT-1 and IFN-γ.

SMAD7 is a protein that, as its name describes, is a homolog of the Drosophila gene: “Mothers against decapentaplegic”. It belongs to the SMAD family of proteins, which belong to the TGFβ superfamily of ligands. Like many other TGFβ family members, SMAD7 is involved in cell signalling. It is a TGFβ type 1 receptor antagonist. It blocks TGFβ1 and activin associating with the receptor, blocking access to SMAD2. (link)

Here we present a basis for the integration of TGF-beta and IFN-gamma signals. IFN-gamma inhibits the TGF beta-induced phosphorylation of Smad3 and its attendant events, namely, the association of Smad3 with Smad4, the accumulation of Smad3 in the nucleus, and the activation of TGFbeta-responsive genes. Acting through Jak1 and Stat1, IFN-gamma induces the expression of Smad7, an antagonistic SMAD, which prevents the interaction of Smad3 with the TGF-beta receptor. (link)

So radiation damages the STAT-1 pathway, reducing IFN-γ, and reducing Smad7, which causes uncontrolled growth in TGF-β levels. This cytokine suppresses the immune system further, and causes the development of Treg cells, which regulate and suppress the immune system.

TGF-beta and CD4+CD25+ regulatory T cells (Treg) both play an important role in the control of immune responses and the maintenance of immune homeostasis. The mechanism of suppression induced by Treg and the factors which regulate Treg function and number, have only begun to be elucidated. TGF-beta seems to act as an effector cytokine involved in the immunosuppressive function of Treg in vitro and in vivo, although its origin and mechanism of action remains to be defined. In addition, TGF-beta signaling in peripheral Treg seems to be essential for the regulation of peripheral Treg numbers and for their immunosuppressive function in vivo. This review will focus on the role of TGF-beta for the generation and expansion of CD4+CD25+ Treg, as well as for their immunosuppressive function in vitro and in vivo. (link)

IL-22 (interleukin-22) is a cytokine that is produced by Th17 and Th22 cells. TGF-β counteracts IL-22 and reduces the differentiation of Th22 cells.

IL-22 a member of a group of cytokines called the IL-10 family or IL-10 superfamily (including IL-19, IL-20, IL-24, and IL-26),[4] a class of potent mediators of cellular inflammatory responses… IL-22 is produced by activated DC and T cells and initiates innate immune responses against bacterial pathogens especially in epithelial cells such as respiratory and gut epithelial cells. IL-22 along with IL-17 is rapidly produced by splenic LTi-like cells [6] and can be also produced by Th17 cells and likely plays a role in the coordinated response of both adaptive and innate immune systems. (link)

IL-22 is an important part of immune protection against enteropathogens. Depletion of Th22 cells depletes IL-22.

Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria…

Interleukin-22 (IL-22) is central to host protection against bacterial infections at barrier sites. Both innate lymphoid cells (ILCs) and T cells produce IL-22. However, the specific contributions of CD4(+) T cells and their developmental origins are unclear. We found that the enteric pathogen Citrobacter rodentium induced sequential waves of IL-22-producing ILCs and CD4(+) T cells that were each critical to host defense during a primary infection. Whereas IL-22 production by ILCs was strictly IL-23 dependent, development of IL-22-producing CD4(+) T cells occurred via an IL-6-dependent mechanism that was augmented by, but not dependent on, IL-23 and was dependent on both transcription factors T-bet and AhR. Transfer of CD4(+) T cells differentiated with IL-6 in the absence of TGF-β (“Th22” cells) conferred complete protection of infected IL-22-deficient mice whereas transferred Th17 cells did not. These findings establish Th22 cells as an important component of mucosal antimicrobial host defense. (link)

IL-22 suppresses bacterial translocation in the intestines, and promotes regeneration in the cells of the epithelial wall. It also activates STAT-3. IL-22 deficiency counteracts all this.

Intestinal mucus functions as a lubricant and a physiological barrier between luminal contents and mucosal surface (59). Mucin (Muc) 1, which is a heavily O-glycosylated membrane-bound mucin, represents one of the major components in the intestinal mucus (59)… Interestingly, a recent study proposes the ability of Muc1 to suppress the expansion of both Th17 cells and IL-17-producing ILCs presumably by blocking the translocation of bacterial products from intestinal lumen into intestinal lamina propria (62)… Interestingly, the ability of IL-22 to promote the production of functional Muc1 through activation of STAT3, but not STAT1, has been demonstrated using human colonic cancer cell lines (T84 and HT29) and primary colonic epithelial cells from mice (9,67)… IL-22 has been demonstrated to promote the epithelial cell regeneration with goblet cell restitution under intestinal inflammatory condition, but it may play no obvious role innormal colonic epithelial homeostasis in the healthy state (9,21). (link)

Cinnabarinic acid is a product of tryptophan metabolism, activates the aryl hydrocarbon receptor (AHR), and is an important source of IL-22.

The aryl hydrocarbon receptor (AHR) binds to environmental toxicants including synthetic halogenated aromatic hydrocarbons and is involved in a diverse array of biological processes. Recently, the AHR was shown to control host immunity by affecting the balance between inflammatory T cells that produce IL-17 (Th17) and IL-22 versus regulatory T cells (Treg) involved in tolerance. While environmental AHR ligands can mediate this effect, endogenous ligands are likely to be more relevant in host immune responses. We investigated downstream metabolites of tryptophan as potential AHR ligands because (1) tryptophan metabolites have been implicated in regulating the balance between Th17 and Treg cells and (2) many of the AHR ligands identified thus far are derivatives of tryptophan. We characterized the ability of tryptophan metabolites to bind and activate the AHR and to increase IL-22 production in human T cells. We report that the tryptophan metabolite, cinnabarinic acid (CA), is an AHR ligand that stimulates the differentiation of human and mouse T cells producing IL-22…

Although the AHR was initially proposed to affect Treg and Th17 development, a Th17-associated cytokine, IL-22, is even more specifically dependent upon AHR activation [13]. Ahr -/- mice retain the ability to generate some Th17 cells but are compromised in terms of IL-22 production [13,17]. Human T cell differentiation also exhibits distinct requirements for the AHR: activation of the AHR in stimulated human T cells was found to inhibit Th17 differentiation and to promote the differentiation of CD4+ T cells that produce IL-22 [18]…

Potential enzymatic modulators that can regulate the generation of CA from 3-HAA would predictably affect the resolution of inflammation. Such enzymes include ceruloplasmin [39], super-oxide dismutase [33], catalase [33], and the fungal virulence factor, laccase [39]…

We have shown previously that tryptophan catabolism can result in a loss of Th17 cells in the context of HIV disease through generation of 3-HAA [30]. We hypothesize that this loss, particularly within the gut mucosa, allows for ongoing inflammation due to continued microbial translocation. Conversion of 3-HAA into CA could reverse the effects of 3-HAA within immune cells, and thereby restore IL-22-producing cells in the context of increased IDO activity. This would allow for the resolution of the inflammatory signaling cascade by strengthening the mucosal barrier, thus stopping a vicious cycle that might otherwise drive disease progression [30]. Although IL-22 was initially linked to IL-17 as a pro-inflammatory cytokine, recent evidence suggests that it probably plays an independent immunoregulatory role in the context of non-hematopoietic cells, maintaining epithelial cell homeostasis in the mucosal tissues [50,57,58]. If so, the pathways that lead to the generation of CA may operate in tandem with the immunosuppressive mechanisms linked to tryptophan metabolism to generate a population of IL-22 producing cells that plays a specific role in tissue repair following inflammation [58]. (link)

So the initial insult of the disease that triggers ME causes massive inflammation, but the lack of IL-22 causes the damage from this inflammation to not be healed, which results in bacterial and viral translocation from the gut. Consequently, the patient is repeatedly re-infected with these pathogens. The lack of IFN-γ and IL-22 reduces innate and adaptive immunity to these pathogens. Tryptophan metabolism is also affected, and its normal function in healing of the gut is abrogated by excessive amounts of TGF-β.

This immune process begins a dysfunctional process that affects the entire body. But it begins with STAT-1 impairment. An effective treatment for M.E. would target the source. Everything else has to do with reducing symptoms.