Johnson & Johnson, Explanations for Clotting ? – Part 5

To the specialist:  This article attempts to make some very inaccessible material accessible. The simplifications are abbreviations for what the specialist already knows.  Plain language is used even when concise language is available. The innate and adaptive systems are now known to be so intermingled, they aren’t really separate systems, just different types of responses.

3.5 billion years ago, the first living organism successfully closed its “self” off from a  ancient ocean, with a stockade in the form of a fatty membrane. This captured, for all descendants, including you, the salty chemical balance of that ocean: the chloride salts of sodium and potassium. As the ancient sea was less salty than it is now, so your blood is less salty. This is your most ancient inheritance, from a time before time.  DNA may have come a little later.

In your salty inner sea, some molecules gain or lose electrons to other molecules, acquiring an electric charge. The cell walls of many bacteria are covered with polyanions, long chains of molecules that have gained electrons. This is used as a danger signal by oldest part of the immune system, the innate, which came about  with evolution of multicellular life,about 1.5 billion years ago. Heparin has an extremely high negative charge.

Without training or prior exposure, the innate immune response uses the bacterial polyanions to identify bacteria as pathogens. This is called a danger pattern or signal, one of many, for which the innate immune response has a repertoire of responses. Some  of these responses involve recruitment of the adaptive immune system.

Unlike the ancient innate response, the newer adaptive immune response has no immediate defense against a novel pathogen. It requires a sample of possibly alien substance, which it compares to a huge library of patterns, called epitopes. If found in the library, and detailed tests show it isn’t a legitimate part of you, production of antibodies commences. When in a normal state of vigilance, the immune system does not attack “self”tissue. This is called tolerance.

Burnet’s  1957 theory of clonal selection , still foundational, implies:

  • A mistake occurs when antibodies are generated that respond to “self”. This failure of tolerance results in an autoimmune disorder.
  • This mistake is  a binary outcome: it happened, or it didn’t.
  • The above is now known to be too simple.  There is a legitimate need, on occasion, for the immune system to  attack “self” tissue. A failure of tolerance can be induced for good purpose.

In wars of the 20th century, the final, desperate tactic of a trapped unit with some fortification was to call for artillery on top of its own position. So it is when the pathogen is adept at mimicking the body’s own tissue. When  lesser responses fail, pathogen and tissue are marked for destruction by the same antibody.

From (Blood) Heparin-Induced Thrombocytopenia,

Several theories have been advanced to explain this unusually high frequency of anti-PF4/heparin antibodies. PF4 binds effectively to bacterial walls of gram-positive and gram-negative bacteria,42-44  and bacterial infection, if accompanied by platelet activation and PF4 release, may provide a sufficient priming stimulus for an immune response upon subsequent heparin exposure.42 

This is a passive note, peripheral to the subject of the paper, which is low platelet count.  Implication: Platelets are adapters from the innate to the adaptive immune system. Binding with bacteria creates a narrow class of antigen, which includes heparin/PF4, from an innate danger signal. This allows the adaptive immune response to participate without requiring a specific antibody.

For a more active voice, see (PMC) Thrombocytopenia in Virus Infections. Quoting,

3.1.3. Sequestration and Intravascular Destruction – …Furthermore, platelets can bind to neutrophils, forming platelet-neutrophil aggregates, which in turn triggers the phagocytosis of platelets [,]…Implication: Platelets actively participate in the innate immune response.

3.1.4. Platelet Expression of Pattern Recognition Receptors  – …can identify pathogen associated molecular patterns (PAMPs) from viruses and many are expressed by platelets []… This enhances … activation of leucocytes []. … may have both an immune protective mechanism, [] or be injurious to the host. Implication: Strong coupling exists between innate and adaptive immune responses.

3.1.6. Platelets Act as Antigen Presenting Cells — APCs require MHC-I molecules to present antigen to CD8+ T cells. There is evidence now that platelets…contain all the MHC-I and co-stimulatory molecules necessary for antigen presentations. ….Implication: As well as innate, platelets are part of the adaptive immune response.

It’s tempting to leap to this conclusion: COVID-19 causes clotting, so COVID holds the smoking gun.  But there isn’t enough logical glue. You might find your leap is actually a dive, and there isn’t any water in the pool.

To be continued shortly.

 

 

 

 

 

 

 

 

 

I am Pro Vaccine; Misuse of Blog Content

From extensive conversation with an antivaxer, I discovered a curious overlap between some of this person’s beliefs, and statements of this blog, which have been taken out of context to support irrational anti-vaxer beliefs. This person is not a reader of this blog, but relies on many sources, some of whom may be readers.

I don’t know the specifics of who  the readers are, but the blog is written for an elite readership. To some extent, I feel free of the responsibilities of a public health steward, or “influencer.” Still, some readers may appropriate content for  purposes markedly different from mine.

I am pro-vaccine. That doesn’t mean that, in presentations to a sophisticated audience, I have to be pro every vaccine . Early in 2020, we were as desperate as India is now. Every effort started then, including AstraZeneca, was justified. In August 2020, I expressed doubts about adenovirus vectors. We are not as desperate now, so criticism is within the context of safer alternatives.

In  early spring 2021, vaccines were not yet available in my area. I decided I would take whatever shot showed up, including J&J. I am not fond of adenovirus technology, but I know how to play the numbers.  I did not have to make that choice.

A vaccine is not a health cocktail. It swaps a major risk for a minor one. To appreciate the difference, one has to have mathematical sense of proportion, and appreciation and trust in the science that trades these risks.

That so many Americans lack both sense of proportion and trust in the scientists who work for our benefit is a grave problem of society, for which there is no easy answer.

The AstraZeneca/J&J analysis will continue shortly.

 

Johnson & Johnson, Explanations for Clotting ? – Part 4

My annotations in blue.

We’ve looked at how an adenovirus vector, by migration away from the injection site,  could challenge the  immune system in ways not intended by vaccine design. It would not be surprising, since many challenges, even absent infection, such as sterile surgical inflammation, can cause immune system dysregulation.

Dysregulation is a term used a lot in the literature. It occurs when the immune system becomes too active, as with autoimmunity, or is suppressed, as caused by many viruses. It covers a mountain of ignorance. While specific feedback/control mechanisms have been studied in detail,   there is no unified theory of the whole thing. As part of our hypothesis, the adenovirus vector causes dysregulation by liver toxicity.

Once  you get out of comfy Middleton’s Allergy (which old-used is like $20), immune system literature  is like leaving your cozy house out to a blinding blizzard. Facts,  statistics, associations,  implications, and hunches  hit your eyes and crust your glasses, while icicles grow down to your keyboard. Even something as simple as a platelet becomes the research of someone’s lifetime, while someone else spends years trying to fit that work to a broader context.

Clotting disorders are a feature of many virus infections. Have virologists acquired anything useful on why an adenovirus vector would cause a clotting disorder?  (PMC) Thrombocytopenia in Virus Infections, is a meta-study, which winnows 413 PubMed search results into 203 papers that were actually read. Results are presented in tables. HIT is not referenced; PF4 gets a single mention with Zika fever. The sought-after secret, a relation between virus, dysregulation and clotting, is not in plain view.

In high school biology, we learned that platelets are simple plug-the-hole pellets, fragments of other cells, without a nucleus, maybe not even alive. Wrong! Quoting from (PMC) Thrombocytopenia in Virus Infections,

Conversely, platelets also affect the inflammatory response to viral infection and can even internalize [engulf] several viruses [and bacteria] directly. In response to infection, platelets interact with leukocytes [white blood cells] and vascular endothelial cells [lining of blood vessels] before activating and secreting soluble prothrombotic [causing clots] and…

Platelets do some  things similar to the functions of white blood cells, but with differences of style. Their roots are different: the innate and adaptive immune systems. which were formerly thought to be separate. The innate system goes back to the dawn of life;  its logic was thought to be “shoot on sight.”  The adaptive system, thinking as much as something without a brain can, crafts an individual response to each challenge.

The above picture is obsolete; the innate and adaptive systems are highly interdependent. The next steps of our hypothesis:

  • The platelet is a bridge between the innate and adaptive immune systems.
  • Dysregulation of either system results in dysregulation of the other.
  • The  antibodies of HIT (heparin induced thrombosis) are not inherently pathological. They are a normal occurrence, observed in normal individuals. They exist as a necessary part of the bridge between the innate and adaptive systems.
  • HIT antibodies, when amplified by immune dysregulation, are pathological.

Support from literature will be provided. To be continued shortly.

Johnson & Johnson, Explanations for Clotting ? – Part 3

We continue from Johnson & Johnson, Explanations for Clotting ? – Part 2, where the liver is described as a kind of jail for viruses. It is also an EPA Superfund site,  where many of the features of the blood-borne immune response are replicated as stationary recycling operations. In goes a shiny virus with a blown motor; out comes scrap metal. This operation looks like a typical by-the-side-of-the-railroad-tracks recycler. Awaiting their fate, pathogens are stuck to walls with glue, or stored inside cells, sorted in special sacks, called endosomes.

The liver does all this while metabolizing myriad small-molecule poisons, such as the ethanol in the fine Chablis you just had.

Adenoviruses are natively toxic to the liver, just by being themselves. But what about the inner genome, which is activated when a virus successfully enters a cell? A competent virus hijacks a cell to make more of itself, frequently destroying the cell.  An adenovirus vector does not have the ability to reproduce. It still frequently destroys the transfected cell, which in measured degree is thought to be a good thing.

It might not be such a good thing if the transfected cell is in the liver. Nota bene: While specific features of the immune system are understood in great detail, the overall regulation of immune response remains a mystery. The  most viable theory has a huge hole.  In place of this, piecemeal ideas fill the gap. The immune system responds more reliably to a possible pathogen  if there is also some  damage, indicated by the signals of a dying cell.

Spike protein has been found to be toxic, even when not formed into a complete spike:

Quoting from the last,

Evidence provided suggests that the SARS-CoV-2 spike proteins trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function. Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells; thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients.

From the sum of three papers, a suspicion arises that might otherwise be dismissed: Even short peptide sub units of spike protein  may cause harm  if sufficient quantities end up in the wrong places.

The quantity of spike protein that ends up in the wrong place depends on  mobility (how well it travels). There is a crucial difference between traditional  vaccines that contain antigen, and the new technologies: mRNA, and adenovirus-vector, which cause cells of the recipient to make antigen.

A vaccine which contains antigen usually contains an adjuvant substance. How adjuvants improve vaccines is frequently revised, but there is one constant. Whether an adjuvant consists of microscopic oily droplets of squalene, or tiny crystals of alum, it binds the small antigen molecule to a much larger one. This reduces the mobility of the antigen, so it sticks near the injection site.

  • When the spike antigen produced by a new vaccine leaves the cell, it is bound to nothing larger. Compared to spike protein bound to adjuvant, it can travel fast and far.
  • This is mitigated with mRNA vaccines by the fragility of mRNA, so the producing cells remain clustered.
  • This is exacerbated by adenovirus vectors, which are stable.

To be continued.

 

(CNN) US investigating possible mysterious directed energy attack near White House

(CNN) US investigating possible mysterious directed energy attack near White House. Quoting CNN,

Federal agencies are investigating at least two possible incidents on US soil, including one near the White House in November of last year, that appear similar to mysterious, invisible attacks that have led to debilitating symptoms for dozens of US personnel abroad.

A bookmark with links to 16 articles: (CNN)’Sonic attacks’ suffered by US diplomats likely caused by microwave energy, government study says. I am one of the dissenters to the microwave theory.  The White House is a particularly unlikely locale for a microwave attack.

Near the White House, the radio spectrum is subject to intense monitoring, in search of electronic espionage bugs that might communicate with nearby controllers. The surveillance receivers are very sensitive, because bugs transmit weak signals. At least some information from these receivers is recorded.

A microwave attack near the White House would inevitably leave a trace in the record of a surveillance receiver, either through direct detection, or inter modulation products. The microwave power levels required of a weapon tend to leak into  monitoring receivers,  leaving  traces, even if not by design.

A decade ago, it might have been possible, if the adversary had detailed knowledge of the monitoring equipment. But in the ’90’s, a chip innovation, the flash A/D converter, combined with software radio allowed monitoring, and recording the entire radio/microwave spectrum simultaneously, with no tuning required. This technology is now widely deployed.The equipment is surprisingly compact.

The electronic records of the surveillance receivers should indicate anomalies simultaneous with the presumed attacks — unless the discrimination software discards them as noise.

If you’d like to get started with detecting microwave weapons, you need 32 bucks:  NooElec USB Stick. It tunes up to 2.3 gHz, but should be sensitive to overload/intermod birdies at much higher frequencies. If one had been operating near the Ellipse, it would have blown the whistle.

If there are no indications, ultrasound might be worth another look.

 

Johnson & Johnson, Explanations for Clotting ? – Part 2

We continue from Johnson & Johnson, Explanations for Clotting ?

Most immunizations are into the deltoid muscle of the upper arm.  In recent years, there has been increased interest in subcutaneous injection. This can result in more immune response with less antigen, or the reverse.  That tissue is more delicate, more susceptible to damage.  And there have been some tragic failures, when the immunization did not “take”. So whatever site is used in the clinical trials is baked into the usage.

The deltoid muscle is resistant to damage, and there is a simple “finger rule” to avoid hitting a nerve with the needle. Some muscle fibers die as a result of the injection, but they are replaced in days. The muscle has strong blood supply and high metabolic rate, which protects it from occasional bacterial pathogens.

A fraction of active material of the injection stays in muscle to “transfect” muscle cells, causing them to produce spike protein, which in turn induces immunity. Most of the injected material does not remain in place.  Muscle is so well supplied with circulation that most of the active material drains out. Another fraction drains through the lymphatic system, reaching the axial lymph nodes, in the armpit, where it may still make a contribution to immunity, if it can find suitable cells to transfect.

The remaining fraction enters the blood circulation. With a classical vaccine, consisting of inert materials, this fraction is lost; it makes no contribution to developing immunity and has no further effect on the body. The bulk of it is caught by the liver, degraded into less suspicious substances, and excreted.

We are going to accumulate Tinkertoy pieces that may be useful in building a hypothesis bridge from a place called Mystery,  to another called Prospect, spanning the River Doubt. If and when the bridge is complete, it will be a theory that can be tested. Cast a wide net at first. Keep  Occam’s Razor always within sight. Back in August 2020, I had some suspicion. There are some Tinkertoys in (CNN) More European nations pause AstraZeneca vaccine use as blood clot reports investigated, but I’m not eager to pick them up. If in the future, they make an Occam contribution, well and good; let them lie for now.

An adenovirus vaccine is not inert. Even though the vector cannot reproduce, it pries its way into cells. The fraction that enters the blood may not be benign. Adenoviruses are generally toxic to the liver; (BMJ) The promise and potential hazards of adenovirus gene therapy. Quoting,

What’s toxic about adenovirus vectors?

Much concern has focused on the direct toxic effects of adenoviruses, particularly as intravenous administration of the virus can induce acute liver injury, as shown in animal models. It is this effect which may have triggered the cascade of events leading to the death of the patient with OTC deficiency—

AstraZeneca/J&J know this well, and think they have their bases covered, with a comparatively minute quantity of vaccine reaching the liver. Maybe, maybe not. It may depend upon prior infections, which often leave live viruses, jailed, in the liver. Until something comes along with the key.

You’re probably wondering what this has to do with CVST.  We’ll get to that. To be continued shortly.

 

 

Johnson & Johnson, Explanations for Clotting ?

In what follows, J&J and Astrazeneca are considered identical. The eventual explanation may fork into separate ones for each vaccine, but nothing’s showing now.

Let’s define some terms. The scientific method names two classes of explanation:

  • Theory –an explanation that has a test, and can be proven false.
  • Hypothesis — a good idea, with clues that point in a direction, with plenty of imagined glue to tie it together.

(BioSpace) COVID-19 Brief: Theories on the COVID-19 Blood Clotting and More Top Stories blurbs an incomplete theory, first described for  AstraZeneca  in this paper: Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. It’s  better than a hypothesis but not a complete explanation either. Quoting from the blurb:

The leading theory appears to be an unusual and rare immune response similar to heparin-induced thrombocytopenia (HIT), where the immune system makes antibodies to a complex of heparin and a protein known as platelet factor 4 (PF4). This causes platelets to form dangerous clots throughout the body. Some research has found that patients with clots had antibodies to PF4.

Antibodies were observed. They were created by the immune system in response to antigen which mimics portions of PF4 with pathological features. This antigen remains unidentified.

It was almost a complete theory. If part of the spike antigen made by these vaccines were shown to be the antigen by cross-reaction with PF4, it would be complete. An unreviewed preprint with good methodology, (ResearchSquare, pdf) Anti-SARS-CoV-2 Spike Protein and Anti-Platelet Factor 4 Antibody Responses Induced by COVID-19 Disease and ChAdOx1 nCov-19 vaccination, shows that it does not cross-react.

So to be complete,  this “leading theory” requires that some other antigen, made by some other action of the vaccine, reacts with PF4. The BioSpace blurb offers this:

A research team out of the University of Griefswal…Their theory is that there are about 50 billion virus particles in each dose of the vaccine, and some might break apart and release their DNA. Like heparin, DNA has a negative charge that might help bind it to PF4, which has a positive charge. That bound complex might trigger antibodies’ production, which could signal the body to increase blood coagulation.

This is not a theory. It’s a completely legitimate hypothesis.  To describe it as a theory in a specialty website does no service to the subject. It erodes clear thinking.

Next: A few more hypotheses, which you may elaborate with your own imaginative, well-founded logic.

 

 

 

 

Conviction of Derek Chauvin — Black Lives Matter

The law is a blunt instrument, but sometimes, justice is done. The problem of Black Lives Matter runs so  deep that the guilty verdict serves as an admission and a statement — but not as a solution. Previous articles:

Police brutality and racial discrimination have ample precedent in U.S. history, though we thought we had banished the worst of the past. Why has the social climate in the U.S. has deteriorated so much since 9/11?

  • Delayed effect of external pressure from terrorism?
  • Modest expansions of liberality by the Obama presidency, or awakening of latent racism by a Black president?
  • Decline of the standard of living, bringing illegal immigration to the fore?
  • Or is it the Web, which has spawned millions of tiny hate channels?

How much has changed!, since JFK’s inaugural (YouTube):

(click for full text) And so, my fellow Americans: ask not what your country can do for you — ask what you can do for your country. My fellow citizens of the world: ask not what America will do for you, but what together we can do for the freedom of man.

The U.S. is not a failed state. It is a troubled state, with generosity and compassion under siege.

 

Biden: Leaving Afghanistan

The argument for leaving is laid out in Trump Wants to Fire U.S. Commander in Afghanistan, in which I explained that the unsolvable part of the Afghan problem is civil, not military. Quoting,

The bare-bones boiled-down essence of modern government is just a few things:

    • Raise revenue by taxation.
    • Use at least some of the taxes to provide services.
    • Facilitate commerce.
    • The services provided justify the taxes enough for popular acquiescence.

You can add all the bells and whistles. But it’s the irreducible minimum. Anything less, and it becomes a protection racket.

Afghanistan has no legitimate economy.

Hence there is no way for the legitimate government to differentiate itself from the Taliban, save social values, which are not enough. We could stay there forever, as Lindsay Graham advised Trump. But when forever is over, the result would be the same. Liza Minnelli: Money makes the world go around.

(The Hill) Top general: Counterterrorism strikes in Afghanistan after withdrawal ‘harder’ but ‘not impossible’ Quoting ,

On Tuesday, [Gen. Frank] McKenzie also said he continues to have “grave doubts” about the Taliban’s reliability in upholding its commitments under the deal signed last year.

I have grave certainty that they won’t uphold. This will be a slaughter of the good. The   future reeks of the fall of Saigon, when our friends were falling off helicopter skids as they begged for rescue. I suspect that the slaughter of innocents bothers H.R. McMaster even more than the strategic retreat.

To remain would only delay the inevitable. Afghanistan is caught in the gyre of a primitive cultural ocean.  Eventually, China, and perhaps India will, in exploitation, bring some measure of humanity.

A legacy of attitude promotes Indefinite commitment. In 2001, the U.S. was the unchallenged superpower. Now it is challenged. We are not quite through that era, but we can see the sunset. Now, we must prioritize.

With the withdrawals, ceding large territories to the Taliban, costs are down. The cost of regaining control of the country approximates the $100BN/ year peak costs. But the budget bleed is not the deciding factor.

Afghanistan is not supplied by a sustainable air bridge. For gross tonnage, we rely on Pakistan, which has strong ties to China. The other bordering states are potential, if not actual, adversaries. U.S. troops could be isolated as hostages if hostilities occur elsewhere. Our presence in Afghanistan interferes with credible deterrence elsewhere.

This is not hawk versus dove. Most military, particularly those who are familiar with the hard truths of simulations, know this: A superior military can be destroyed by over-extension.

To those who idealize the U.S. posture without thought of strategic balance, there’s always common sense:

You don’t go into a gunfight with your nuts hanging out.

 

 

 

CNN takes on CDC and FDA! “These unlikely events are still more likely than a blood clot after the J&J vaccine

John Avlon takes on the medical establishment in video: These unlikely events are still more likely than a blood clot after the J&J vaccine.

All news teams encounter a  universal problem when the issue goes beyond the general competence implied by a modern, liberal education. Avlon’s team has grabbed statistics for a way into the problem. But as I wrote in AstraZeneca, What to Do?,

Statistics needs mechanisms. If peculiarities of cases are not correctly weighted, the statistical  threshold, surpassing chance, could be missed. Mechanisms  focus statistics.

Without the mechanism of these clots, the stats of the video are useless as reassurance. The FDA and CDC are concerned about adverse effects that are buried in noise of the unknown future. With mechanisms, you know what you are looking for. With knowledge of mechanisms, you can rule things out, like future mass casualties.

If you were to time travel back 60 years, to the time of dark ignorance preceding molecular biology,  to a med school class in tropical diseases, the prof might remark, if not in writing,  “Eventually, if an individual receives enough immunizations, the recipient will probably die.”

The current state of knowledge is vastly greater. Nevertheless, it might surprise that it is still  not possible to predict with certainty whether a particular virus, for which the genome is completely known, can reproduce in a particular host. The viral landscape remains shrouded in twilight, with at least the possibility of long term effects that must be ruled out by rigorous investigation. Statistics  by itself does not suffice.

The chance of widespread harm, from a vaccine administered to a mass population, is the nightmare of vaccinology. Here presents a hazard, on a scale Hippocrates could not have imagined, which reminds us of the first principle of bioethics: “First, do no harm.”

News teams cannot be expected to have specialist knowledge. They may rely on individuals who have been misqualified as competent on the issue. What systematic could a news team find useful to plug this gap? It’s worth taking a look at the (Wikipedia) Delphi method. Quoting,

Delphi is based on the principle that forecasts (or decisions) from a structured group of individuals are more accurate than those from unstructured groups.[6]

CNN, you might find it fascinating to assemble a group to address John Avlon’s question, and watch them work. Just by watching, you get insights into the structure of knowledge of the field in question.

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