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A Role for Protein Misfolding in Immunogenicity of Biopharmaceuticals
…..misfolding of therapeutic proteins is an immunogenic signal and a risk factor for immunogenicity. ……Over the past decades, the use of therapeutic proteins has become common practice in medicine ……
Protein misfolding is an intrinsic and problematic property of proteins, which underlies a variety of degenerative diseases, such as Alzheimer disease. These diseases are characterized by the occurrence of fibrillar deposits, classically termed amyloid, containing aggregates of misfolded proteins.
……experiments pointed out that biopharmaceuticals, like any other protein, are amyloidogenic and that misfolding, detected by amyloid markers, takes place in several preparations. These markers, however, are not necessarily specific for fibrillar amyloid, but also for smaller misfolded protein species.
….. Various Biopharmaceuticals Display Amyloid-like Properties upon Exposure to Conditions of Stress, Indicating Protein Misfolding — During manufacturing and storage, biopharmaceuticals may also become exposed to various conditions of stress that can potentially underlie protein misfolding and the formation of amyloid-like properties.
…….Our results point to a common mechanism by which the immune system perceives misfolded proteins. We hypothesize that this lies in the changed conformation of the protein backbone itself. This implies that the innate immune system may be activated by recognition of the amyloid-like properties of misfolded protein. …
Originally posted by marg6043
reply to post by soficrow
I guess all we can do is get our bodies stronger to be able to fight what comes our way, we are surrounded by all kind of dangers we breath them, eat them, bath ourselves with it even our babies are been born polluted already.
Its going to take generations to undo what we have been done to ours and even that could be impossible.
Proteins are the building blocks of life - and our bodies are constantly creating new ones for repair, maintenance and replacement parts. These proteins don't just need the right chemistry - they need to be folded into exactly the right shape to work. Problem is, proteins misfold easily, in response to "environmental perturbations" - including temperature changes, or exposure to chemicals, heavy metals, oxygen or radiation.
A Role for Protein Misfolding in Immunogenicity of Biopharmaceuticals
…..misfolding of therapeutic proteins is an immunogenic signal and a risk factor for immunogenicity. ……Over the past decades, the use of therapeutic proteins has become common practice in medicine ……
Protein misfolding is an intrinsic and problematic property of proteins, which underlies a variety of degenerative diseases, such as Alzheimer disease. These diseases are characterized by the occurrence of fibrillar deposits, classically termed amyloid, containing aggregates of misfolded proteins.
……experiments pointed out that biopharmaceuticals, like any other protein, are amyloidogenic and that misfolding, detected by amyloid markers, takes place in several preparations. These markers, however, are not necessarily specific for fibrillar amyloid, but also for smaller misfolded protein species.
….. Various Biopharmaceuticals Display Amyloid-like Properties upon Exposure to Conditions of Stress, Indicating Protein Misfolding — During manufacturing and storage, biopharmaceuticals may also become exposed to various conditions of stress that can potentially underlie protein misfolding and the formation of amyloid-like properties.
…….Our results point to a common mechanism by which the immune system perceives misfolded proteins. We hypothesize that this lies in the changed conformation of the protein backbone itself. This implies that the innate immune system may be activated by recognition of the amyloid-like properties of misfolded protein. …
Time to fight the new global pandemic of chronic diseases
New cases of chronic noncommunicable diseases (NCDs) such as heart disease, stroke, cancer, diabetes and chronic lung disease are exploding throughout the world, even in the poorest countries. These conditions account for 63 percent of deaths globally, and 80 percent of those deaths are occurring in low- and middle-income countries. Chronic diseases are also incredibly disabling and have a major negative impact on economic development, as they occur at a much earlier age and rob families of their breadwinners.
Chronic disease to cost $47 trillion by 2030: WEF
"This is not a health issue, this is an economic issue…"
What's killing us? Diseases that will kill 9 of 10 Americans
…..cancer, heart disease, diabetes, and a variety of other chronic ailments. And worse, unlike some infectious diseases, they're quite preventable.
This new, ultra-deadly pandemic threat is caused by we, ourselves. Sedentary lifestyles, poor eating habits, smoking, and other high-risk behavior causes most of these diseases. ….
More than anything, the root causes are apathy and sloth.
A generation ago, people trusted their doctors blindly and implicitly. There seemed to be a personal bond with one's doctor which has eroded with the emphasis on medicine as a business, CPT codes, HMOs and iatrogeny, among other things. The health care market place is not kind and people have lost trust. Iatrogeny plays a large and ugly role in this.
A recent study published in The Joumal of The American Medical Association 2000:284:94); by Barbara Starfield, MD, MPH showed that in the US, this data was found:
12,000 deaths/year from unnecessary surgery
7,000 deaths/year from medication errors in hospitals
20,000 deaths/year from other errors in hospitals
80,000 deaths/year from nosocomial infections in hospitals
106,000 deaths/year from adverse effects of medications
This totals 225,000 deaths per year from iatrogenic causes, placing iatrogeny as the third leading cause of death in the US, second only to heart disease and cancer.
The protein in question was a retroviral protease of the Mason-Pfizer monkey virus, which causes an AIDS-like disease in monkeys. Over the last decade, many researchers had tried a variety of techniques to determine the protein’s structure, but kept coming up empty handed. “This viral protein…has really evaded the efforts of expert crystallographers and the very best automated tools,” Das said.
April 23, U.S. Health and Human Services Secretary Margaret Heckler announces at a press conference that an American scientist, Dr. Robert Gallo, has discovered the probable cause of AIDS: the retrovirus subsequently named human immunodeficiency virus or HIV in 1986. She also declares that a vaccine will be available within two years.
Robert Gallo (continued) Allegations Overshadow Scientific Accomplishments Almost a year before Gallo announced his findings, Montagnier at the Pasteur Institute had identified a virus he called LAV, though he was not able to prove that it caused AIDS. The two laboratories were cooperating with each other in the race to find the cause of AIDS and several samples of this virus had been sent to Gallo at the National Cancer Institute. The controversy which would embroil the American scientist's career for almost the next decade began when the United States government denied the French scientists a patent for the AIDS test and awarded one to his team instead. The Pasteur Institute believed their contribution was not recognized in this decision, and they challenged it in court. Gallo did not deny that they had preceded him in isolating the virus, but he argued that it was proof of the causal relationship and the development of the blood test which were most important, and he maintained that these advances had been accomplished using a virus which had been independently isolated in his laboratory.
For twenty years, all AIDS research has been based on the HIV hypothesis. Do we now have reasons to question this hypothesis? Yes, because there is a major problem with isolation and purification of HIV. The major problem being that, in spite of innumerable claims to the contrary, this retrovirus has never been isolated nor purified in a scientifically acceptable manner that would satisfy the classic requirements of virology.
This first stage of the controversy ended in a legal settlement that was highly unusual for the scientific community: Gallo and Montagnier agreed out of court to share equal credit for their discovery. This settlement followed a review of records from Gallo's laboratory and rested on the assumption that the virus Gallo had discovered was different from the one Montagnier had sent him. An international committee renamed the virus HIV, and in what Specter calls "the first such negotiated history of a scientific enterprise ever published," the American and French groups published an agreement about their contributions in NATURE in 1987. In 1988, Gallo and Montagnier jointly related the story of the discoveries in SCIENTIFIC AMERICAN.
HIV (human immunodeficiency virus) is adopted as name of the retrovirus that was first proposed as the cause of AIDS by Luc Montagnier of France, who named it 'LAV (lymphadenopathy associated virus) and Robert Gallo of the United States, who named it HTLV-III (human T-lymphotropic virus type III)
In 1983, Luc Montagnier, a French scientist at the Pasteur Institute, claimed to have found a new retrovirus in AIDS patients. But nobody paid attention, because he hadn't isolated a virus, and he hadn't found a single viral particle in the blood - remember the titer was zero, undetectable. Seeking some academic support, Montagnier sent a cell sample to Robert Gallo at the NIH. Gallo took the cell-line Montagnier sent him and modified it slightly. Then he did something strange. He stole it.
In 1984 Gallo called an international press conference and together with Margaret Heckler, the head of the Department of Health and Human Services, announced that he'd discovered the "probable cause" of AIDS. It was a new retrovirus called HTLV-III, (later re-named HIV). Later that same day, he patented the modified cell-line he'd originally gotten from Montagnier. He hadn't published a single word of his research. Robert Gallo, a government-backed scientist, simply announced that a retroviral-epidemic was on its way.
He sold the cell-line to Abbot Labs, a pharmaceutical company that makes HIV tests. The French government demanded that all patent rights be returned to Montagnier. Gallo refused, claiming it was all his work. In 1987, Gallo and Montagnier were forced by President Reagan and French Prime Minister Chirac to meet in a hotel room to work out the HIV patent rights. In 1992, Gallo was officially convicted of theft by a federal scientific ethics committee. The AIDS Debate The Most Controversial Story You've Never Heard By Liam Scheff
Questions about the isolation of the AIDS virus were revived in 1989 by a long article in the CHICAGO TRIBUNE. The journalist, a Pulitzer Prize winner named John Crewdson, had spent three years investigating Gallo's laboratory, making over one hundred requests under the Freedom of Information Act. He directly questioned Gallo's integrity and implied he had stolen Montagnier's virus. The controversy intensified when it was established that the LAV virus which the French had isolated and the HTLV-3 virus were virtually identical. The genetic sequencing in the two were in fact so close that some believed they actually came from the same AIDS patient, and Gallo was accused of simply renaming the virus Montagnier had sent him. Gallo's claim to have independently isolated the virus was further damaged when it was discovered that in the 1984 SCIENCE article announcing his discovery of HTLV-3 he had accidently published a photograph of Montagnier's virus.
Finding of Scientic Misconduct Reversed on Appeal
In 1990, pressure from a congressional committee forced the NIH to undertake an investigation. In THE WASHINGTON POST, Malcolm Gladwell observed of this inquiry: "No other investigation has taken so long, dealt with a scientific discovery of such importance or directly implicated so distinguished a researcher." The NIH investigation found Popovic guilty of scientific misconduct but Gallo guilty only of misjudgment. A committee of scientists which oversaw the investigation was strongly critical of these conclusions, and the group expressed concern that Popovic had been assigned more than a fair share of the blame. In June 1992, the NIH investigation was superseded by the Office of Research Integrity (ORI) at the Department of Health and Human Services, and in December of that year ORI found both Gallo and Popovic guilty of scientific misconduct . Based largely on a single sentence in the 1984 SCIENCE article that described the isolation of the virus, the ORI report found Gallo guilty of misconduct for "falsely reporting that LAV had not been transmitted to a permanently growing cell line." This decision renewed the legal threat from the Pasteur Institute, whose lawyers moved to claim all the back royalties from the AIDS blood test, which then amounted to approximately $20 million.
ABSTRACT: The evidence that Robert Gallo and his colleagues presented on 4th May 1984 regarding HTLV-III (HIV) isolation and the role of HIV in the pathogenesis of AIDS is critically analysed. It is concluded that the evidence does not constitute proof of the isolation of a retrovirus, that the virus is exogenous or that the virus is causally related to AIDS.
Introduction In 1982, Robert Gallo from the National Cancer Institute in the USA, put forward the hypothesis that the cause of AIDS is a retrovirus. One year later, Myron Essex and his colleagues (1) found that AIDS patients had antibodies to the Human T-cell Leukemia virus Type-1 (HTLV-I), a virus discovered by Gallo a few years earlier. At the same time, Gallo and his colleagues (2) reported the isolation of HTLV-I from AIDS patients and advocated a role for this retrovirus in the pathogenesis of AIDS. This hypothesis however, was not without a few problems: 1. While HTLV-I was accepted to induce T4-cell proliferation and cause adult T-cell leukaemia,(3) the "hallmark" of AIDS was T4-cell depletion, and the incidence of leukaemia in AIDS patients was no higher than in the general population;
On the basis of his experience with retroviruses, Duesberg has challenged the virus-AIDS hypothesis in the pages of such journals as Cancer Research, Lancet, Proceedings of the National Academy of Sciences, Science, Nature, Journal of AIDS, AIDS Forschung, Biomedicine and Pharmacotherapeutics, New England Journal of Medicine and Research in Immunology. He has instead proposed the hypothesis that the various American/European AIDS diseases are brought on by the long-term consumption of recreational drugs and/or AZT itself, which is prescribed to prevent or treat AIDS. See The AIDS Dilemma: Drug diseases blamed on a passenger virus.
But even if HIV was found to cause these previously known conditions, a problem remains. The HIV-antibody tests do not diagnose actual HIV-infection. Instead, they look for non-specific antibody reactions in your blood to proteins in the HIV-test. The test manufacturers claim that the proteins stand in for HIV, but in reality, none of the test proteins have been proven to be specific to HIV. These tests are, in fact, so nonspecific that they cross-react with nearly 70 other documented conditions, including the flu, previous vaccinations, blood transfusions, arthritis, alcoholic hepatitis, drug use, yeast infections and even pregnancy, as well as conditions endemic in Africa: tuberculosis, parasitic infection, leprosy and malaria. Because no HIV test can actually find HIV, not a single HIV-test has been approved by the FDA for diagnosing HIV-infection.
Your readers may be surprised to learn that AIDS in Africa is diagnosed completely differently than in Europe or the US. In Africa, an AIDS diagnosis can be made based on commonly occurring physical symptoms alone. This is ironic, because AIDS is a collection of diseases, and has no uniform symptoms. Even the co-founder of HIV theory, Luc Montagnier, admits that AIDS has no specific clinical symptoms.
I have had it with the character limitations for today.
Suffice it to say that this microcosmic historical timeline and data sets I have offered only demonstrate how much trouble we are in regarding Western "medicine", particularly since so much of that is controlled by government.
I hope I didn't stray too much from the topic, I just want to share the tragic devolution of science in the Western world.
Well you did strictly speaking but the detailed information is important to the larger discussion. ...I just don't want you to conclude by saying prions aren't relevant.
Originally posted by soficrow
reply to post by SpartanKingLeonidas
Gotcha - but did you see this post?
Could you please read it and comment on it? ...Point being, it's not just our food that's contaminated - prions are a natural byproduct of any 'process' involving proteins, the whole world is already contaminated, and there's really no way to get rid of them... The upside is that prions are clearly an evolutionary mechanism and we could conceivably benefit if we are not totally overwhelmed by their negative effects first.
Originally posted by SpartanKingLeonidas
Originally posted by soficrow
reply to post by SpartanKingLeonidas
Gotcha - but did you see this post?
Could you please read it and comment on it? ...Point being, it's not just our food that's contaminated - prions are a natural byproduct of any 'process' involving proteins, the whole world is already contaminated, and there's really no way to get rid of them... The upside is that prions are clearly an evolutionary mechanism and we could conceivably benefit if we are not totally overwhelmed by their negative effects first.
No disrespect meant to you, soficrow, but what's the point?
Agreeing, disagreeing, opening up others minds, and all of that.
But after a certain point it is all an empty gesture.
Because no one is actually doing a damn thing to change the status quo.
Well, I take that back, I am, but I see no proof of anyone else.
You, not you specifically, cannot sit around discussing things, and getting others to learn.
Without a specific goal of attempting to change that status quo than through more than knowledge.
If nothing is done with that knowledge then nothing is gained it is useless.
Words without actions to follow behind them are but a hollow gesture and living a lie.
....I need more out of the conspiracy theory community.
I have been a conspiracy theorist now for 32 years, since I was 6, and I've been making efforts.
I have been driving towards changing those things no one else gives a damn about.
I have talked the talk, and walked the walk, and now I'm challenging all conspiracy theorists.
Step up or shut up.