Date: Mon, 22 Nov 1999 21:03:34 -0500
From: "Eddie Bollenbach"
Subject: New Models PPS
Professor Bollenbach also explains RNA/Viruses/Polio
"... I think there are a million scenarios we could construct to explain PPS without evidence. They may sound nice but they aren't worth a lot. Statements like "We lose 1% of our neurons per year" I'm always skeptical of (but it may be true)."
I've always felt that the idea of PPS being "caused" by overuse is too simplistic and convenient. It's too simplistic because the assertion that motor units that recovered from early disease are not durable beyond 30 years isn't seen in everyone with a history of paralytic polio. Any model of the origin of PPS must account for them too. The overuse theory does not. There are many who do not have PPS who are going about their lives with the same degree of atrophy and compensation they've always had. No new symptoms for them. And It's too convenient a theory because giant motor units are the first thing you see when you look closely, with technology, at a person with the stigmata of polio. This idea has been presented as the whole enchilada without evidence but because it sounds nice.
So why do some people who've had polio lose a whole bunch of function? Why do some who never had an ache, a limp, or anything but a memory of polio now experience mind numbing fatigue, the use of ambulatory aids, and the loss of a little more function every year? There are some nice microscopic pictures in the polio literature supporting the idea that end fibers disengage from their muscles in PPS. I guess the supposition is that the pathogenesis in PPS is through the loss of end fibers (as if the entire neuron were not involved in this process) which results from overuse. I've even read about people saying not to massage muscles because the delicate end fibers can be knocked off by the stimulation. I don't think so. Muscle contraction results in a lot more stimulation than a rub and even if we have PPS they just don't all drop off that quickly.
And what about the cognitive stuff. I've always been confused as to the pathogenesis there. What causes it? If we accept the overuse idea we have to develop a whole new theory to account for this at the same time. The one thing both mental and physical have in common are neurons.
I know that if a muscle has become weaker than the load it can bear it gets sore and fatigued. I know that soreness, weakness, and fatigue are hallmarks of PPS. Wouldn't it be tempting to say overuse "causes" PPS if every time you did something you got sore? But you are sore because the muscles needed for the activity you are doing are inadequate to the task and the evidence for overuse causing that problem eludes me. One caveat: even if a normal muscle is overused regularly it will get weaker. So weak muscles, which we have will get weaker if they are overused. This is not the same thing as "overuse causes PPS". So overuse can be damaging if you have weak muscles.
Any cause of disordered function within a neuron will result in faulty transmission to its effector. Another way of saying this for our problem is that if there is screwed up metabolism (biochemistry) inside the body of a nerve cell it won't work properly. If the nerve doesn't work properly it will lose end fibers and not transmit impulses properly. The point of all this is that there can be a gazillion "causes" of PPS and we have to develop evidence that points toward a cause before we embrace it.
This year, out of France, comes a hint of something. The French, utilizing a biotechnological technique called Polymerase Chain Reaction have been able to detect polio virus genes (defective genes) which are obviously persisting in the spinal cords of those of us with PPS. Polio virus mutates like a son of a bitch when it infects cells. If a cell bursts releasing 10,000 new virus particles it is likely that only 10 percent of those (1000) will be able to infect new nerve cells. The other nine thousand are mutated and defective. The virus must be very frugal with its RNA genome. The amount of RNA that will code for one amino acid weighs about 1,000 daltons while the amino acid it codes for weighs only 100 daltons. Polio has to make 4 or so proteins with about 300 amino acids each. So it doesn't have the freedom to produce proteins that can correct mistakes when it reproduces, like our cells do. It leaves them out. The result is a lot of mutations. Some mutants hang out in the cells and are able to persistently infect without bursting cells or even moving over to adjacent cells.
Postpolio syndrome: poliovirus persistence is involved in the pathogenesis - 1999 Julien et al ABSTRACT
I don't know how big a part of the PPS pie is due to viral RNA but it is surely involved in the pathogenesis of this disease. I also know that the polio virus genome is a single strand of RNA and that we have the technology, right now, to produce the complementary strand that will combine with it. This could jam the whole process, or it could lead to more trouble. In any event, I'm not on line waiting for any therapy, but, as always, I find the discovery of new parts to puzzles like this irresistibly fascinating.
Date: Wed, 24 Nov 1999 10:44:10 -0500
From: "Eddie Bollenbach" <email@example.com>
Subject: New Models PPS
In my opinion, for what its worth, the polio virus genes found in the spinal fluid of PPS patients probably came from intact virus (whole virus particles). I believe this because I cannot understand how such fragile molecules can exist unprotected, without being destroyed, for all these years. Researchers have found polio virus genes in the spinal fluid, in the blood (in white blood cells) and post mortem in the spinal cords of PPS patients who have died of other causes. To my knowledge these genes have not been found in anyone with stable polio absent PPS.
The reason only genes are found and not the intact virus is because the sensitive technique used to detect them is specific for RNA (the molecule the genes are composed of) and not protein which comprises the rest of the virus. However, in addition to the RNA we find antibodies in PPS patients against polio virus proteins so the logic is clear that at least some of the proteins are there too.
Recently we learned that polio virus does not get released from cells after it infects them in the way we thought they did. We believed that polio was a lytic virus which meant that the cell ripped apart in response to polio virus activity and, consequently, thousands of virus particles were released in the process. That is why we believed that polio virus could not persist. We thought it killed all the cells it infected. But with the discovery and study of programmed cell death, called apoptosis, (which happens when a cell is damaged in certain areas). The cell proceeds through a process whereby it self destructs. Changes in the cells infected by polio in experimental animals show apoptosis is the way death and release of virus particles occurs, and not by lysis.
Many cells were infected but did not undergo apoptosis. They survived. So there would be, trapped inside these cells, intact polio virus--most of which are mutated. So there is an answer as to how polio virus could survive all these years. There is also no doubt that most of these viruses are mutated and defective and therefore do not have the ability to go through their normal life cycle. They exist inside cells and undoubtedly have the ability to cause metabolic problems inside those cells. It is possible that the free RNA genome is just the result of apoptosis which may begin occuring, for some reason, in many of us with PPS. As always we will be learning more in the years that come. I must admit though, that because of this new information, it sounds like there is some niche that polio virus has in what may be a very complicated cascade of events that lead to PPS.
Date: Wed, 24 Nov 1999 15:54:55 -0500
From: "Eddie Bollenbach" <firstname.lastname@example.org>
Subject: Re: Opinion
Margaret asked about viruses and DNA:
When you and I went to school, Margaret, it was thought that DNA was needed for everything to reproduce. I think this goes along with a lot of over generalization that we find in the history of science. A little more than a hundred years ago a German scientist named Robert Koch isolated the anthrax bacillus and showed it caused disease. This was the first time a microbe was proven to cause disease. Soon Koch constructed his famous Postulates, the first of which says: "All disease is caused by microorganisms." That is a famous over generalization. We know there are genetic diseases, developmental diseases, and degenerative diseases (eg cirrhosis). What often happens is we find something out, eg. DNA divides and replicates, and then we say it is always that way with every process we can ever know. As a matter of fact we were so enraptured with DNA duplicating that it became part of what was called "The central dogma of biology". But one shouldn't look for dogma in any principle because most of the time we are proven wrong later when more information becomes available.
Viruses can have genes made out of double stranded DNA, single stranded DNA, it can be the positive strand if its single stranded---(this is the strand that codes genetic information), or it can be the negative sense strand---(this is the strand the positive sense strand is homologous to and combines with and makes it easier for the entire molecule to reproduce)----or we can have RNA viruses, both single stranded or double stranded with the sense strand in a single stranded RNA virus or with the negative sense strand. Examples of RNA viruses run the gamut from Influenza, hoof and mouth disease, HIV, and polio. Polio is a positive sense strand virus so it can be mischievous easily. The strand can direct the production of protein from itself without going through a replication so it is no surprise that we find immune reactions in the CSF of post-polio patients.
Contact Professor Edward P. Bollenbach
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