Population Control Bioweapon? Medical Accident? What is Fibromuscular Dysplasia (FMD)?

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posted on Jan, 16 2005 @ 12:47 PM
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Fibromuscular dysplasia (FMD) is a disease that has all the characteristics of a long term population control stealth bioweapon, designed to destabilize society. Alternately, it might be the result of an accidental contamination of the first vaccines mass-produced for American soldiers in World War I: the disease first appeared in the early 1900's. Whatever its source, FMD is being used to help destroy democracy.

FMD is now epidemic – nearly 100% of the US population is infected by adulthood. FMD can incubate silently in the body for decades before striking. It is progressive, degenerative and incurable, and is always eventually fatal. It is seldom diagnosed and treated before it becomes life threatening. Early diagnosis and treatment are not covered by insurance. Victims may be disabled mentally or physically for decades before death comes. The FMD epidemic’s effects are far-reaching, impacting individual productivity, the GDP, costs of health care, elder care, Social Security, disability, unemployment, insurance and more.

The disease's origins and effects are being covered up, and nothing is being done to warn the public or deal with the epidemic. The current administration is positioning to lay the blame on today's bioterrorists.

Methods and means are now available to prevent FMD’s spread and transmission, and to prevent disease progression – but implementing these new methods would cut into big business profits. So instead of focussing on prevention, new policies protect business at the expense of ordinary peoples’ lives and rights.
Ie., See: www.atsnn.com...

Public health policies blame the victims, saying FMD and its various secondary effects are either genetic or self-inflicted. Laws are used to remove the afflicted from society, and new legislation is planned to offload responsibility for the disabled and dysfunctional. Other plans are in development to take away victims’ civil rights and rights of citizenship in later stages of disease progression, including the right to vote.
Ie., See: www.atsnn.com...

In short: FMD is epidemic but ordinary Americans cannot access early diagnosis or preventive medical treatments; available methods are not being implemented to stop FMD’s spread and transmission, or to remove contaminants that cause disease progression. Americans are left with no way out, unable to avoid infection or exposure to contaminants that promote and speed disease progression, and unable to find treatment. Many will become physically disabled or mentally dysfunctional long before retirement age – but will not have access to funds or other supports. Many, likely the majority, will lose their voting rights along with their ability to work, think and love.

*************************

FMD was acknowledged officially as a new but rare disease in 1938. Today, most Americans are infected by adulthood. FMD usually incubates silently in the body for decades before striking. It is progressive, degenerative and incurable. It is always eventually fatal, and is seldom diagnosed and treated before it becomes life threatening. Early diagnosis and treatment are not covered by insurance. In order to survive socially and professionally without medical help, victims are forced to try and hide their symptoms from the world and often, themselves.

65% of reported FMD cases in the USA are diagnosed in autopsy, and the disease is found in almost 100% of reported deaths.



www.emedicine.com...

“FMD frequency in the USA: incidence of new cases in adults diagnosed by angiography – 0.6%; diagnosed in autopsy – 1.1%.”

NOTE: Incidence means new cases found yearly, presented as a % of the total population. Also see “Population and Incidence” table below.


Death in patients diagnosed with FMD results mainly from heart attack (44.4%), cancer (33.3%) and stroke (22.2%) – now the three leading causes of death in the USA. FMD also causes arterial dissections, kidney failure, ruptured aneurysms, ruptured spleen and congestive heart failure.


Ie., see:
“Fibromuscular dysplasia of the internal carotid artery: long-term surgical results.” J Cardiovasc Surg (Torino). 1993 Dec;34(6):465-72. Moreau P, Albat B, Thevenet A. Service de Chirurgie Thoracique et Cardio-Vasculaire, Centre Hospitalier Universitaire, Montpellier, France. PMID: 8300709


Before death comes dysfunction and disability. In the past, FMD was seldom disabling before a victim reached their 60’s or 70’s – today, it is not uncommon for diagnosed FMD patients to be disabled by their 40’s or 50’s. FMD-caused dysfunction and disability may be physical or mental. The most common early symptoms are headaches and body pain, which result from spasms in blood vessels called “vasospasms.” In later stages, symptoms may include impotence, urinary problems, digestive problems, allergies and asthma, or joint or muscle pain. FMD can affect virtually any part of the body including the brain. It’s progressive effects on the brain were well-documented by Mettinger in the early 1980’s, and explained more simply by Dr. William Hammesfahr in 1996.


Hammesfahr:

“Vasospasm is a narrowing of the artery which bring blood to your brain, heart, and other organs. Vasospasm may occur in all of the parts of the body at the same time or in only certain parts of your body at specific times. Although everybody is different, there is a typical progession of symptoms that occurs with vasospasm. In the early stages, there is usually seen concentration problems, attention deficit type disorders, and mild memory disturbances. ...As the problem progresses, patients may develop headaches, then black-out spells, seizures, psuedo-seizures, strokes, transient ischemic attacks, and psychosis. The symptoms frquently wax and wane, or vary in level of severity or presence.”
www.medforum.com...

* “Fibromuscular dysplasia and the brain. I. Observations on angiographic, clinical and genetic characteristics.” Stroke. 1982 Jan-Feb;13(1):46-52. Mettinger KL, Ericson K. PMID: 7064180
* “Fibromuscular dysplasia and the brain. II. Current concept of the disease.” Stroke. 1982 Jan-Feb; 13(1): 53-8. Mettinger KL. PMID: 7039003


The FMD epidemic has far-reaching effects on individual Americans’ lives, and on society as a whole. High level decision-makers in politics and industry know about the epidemic and understand the nature of the disease. They factor the information into actuarial reports, business development plans, health insurance terms, unemployment and disability policy terms, mortgage and loan policies, retirement programs and more. Business protects itself. The goal is to profit, whatever the other costs may be.

Unlike scientists, businessmen don’t need unassailable proof. Business simply identifies patterns and trends, then acts to protect profits. At the same time though, business sends scientists off to chase their tails in circles, demanding unquestionable scientific “proof” on every minute detail. So in the interim, the public is not informed, corporate leaders run the show and business interests dominate.

Ordinary Americans are kept ignorant, and are blind-sided when the disease and reality finally strike – forced to make important life decisions without access to critical information.

This thread will debunk common medical myths about FMD, and investigate the science of the disease and the various impacts and implications of the epidemic to society, policy and the legal system. It is here to deny ignorance, and reveal truth – so we can protect ourselves and make informed decisions in our personal lives and as responsible citizens in a functioning democracy – so we can defend our nation.


From the international FMD Coalition:

It’s not your fault if you’re sick, and it’s not your fault if you don’t get better. But you do have some power. Learn what it is and how to use it.




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posted on Jan, 29 2005 @ 09:58 AM
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What is Fibromuscular dysplasia (FMD), and How Common is It?

Fibromuscular dysplasia (FMD) appears to be the original infectious prion strain introduced into the human population. The disease involves actin proteins mis-folding into "a-smooth muscle actin" (a-SMA). The presence of mis-folded a-SMA protein indicates that FMD almost certainly is caused by an infectious prion.

FMD is seldom diagnosed before a life threatening "event" and 65% of reported cases in the USA are diagnosed in autopsy, with an incidence rate of 1.1% in adults.



www.emedicine.com...

“FMD frequency in the USA: incidence of new cases in adults diagnosed by angiography – 0.6%; diagnosed in autopsy – 1.1%.”

NOTE: Incidence means new cases found yearly, presented as a % of the total population.
Also see Puri, PMID: 10334397.


Here's a table that puts together the stats for FMD incidence in autopsy with reported death stats:




YEAR - DEATHS - TOTAL POP - EST ADULT POP (75%) - 1.1% ADULT POP: FMD incid in autopsy

1999 - 2,391,399 - 279,295,000 - 209,471,250 - 2,304,184
1998 - 2,337,256 - 276,115,000 - 207,086,250 - 2,277,949
1997 - 2,314,245 - 272,912,000 - 204,684,000 - 2,251,524
1996 - 2,314,690 - 269,667,000 - 202,250,250 - 2,224,750
1995 - 2,312,132 - 266,557,000 - 199,917,750 - 2,199,095

Source: Population: Census; Reported Deaths; World Health Organization.



As shown above, nearly 100% of the American population is infected with FMD by adulthood.


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posted on Feb, 12 2005 @ 04:35 PM
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Originally posted by ADVISOR
unless you read French that is. However it also documents fibromuscular dysplasia, so here is another source. It is pdf format, in advance warning.

2002 doc

[edit on 31-1-2005 by ADVISOR]



FYI - your link has disappeared, and mine above referring to incidence was revised on Feb 7, 2005.

"Last Updated: February 7, 2005"

..IMO - not an update, but censorship. I learned long ago to copy all files - info on FMD tends to disappear when the links are posted publicly.



posted on Feb, 13 2005 @ 07:59 PM
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here is what i can do so far:

i got these when i searched "prions" at www.webmd.com:


Oct. 11, 2001 -- Mad cow disease strikes fear into the hearts of meat lovers everywhere, and with good reason. Although slightly more than 100 deaths have been attributed to eating contaminated beef, some researchers speculate that millions of people may one day fall victim to the fatal human form of the disease as a result of eating a single tainted burger or steak


my.webmd.com...


Aug. 13, 2001 -- Old drugs for malaria and psychiatric disease might get a new twist in treating the human form of mad cow disease, known as new variant Creutzfeldt-Jakob disease.


Like mad cow disease, this devastating brain condition is thought to be caused by infectious proteins called prions, discovered by Nobel Prize winner Stanley Prusiner. Only 1% of prion diseases are contracted by infection, which new variant Creutzfeldt-Jakob disease would fall under, about 5%-15% are inherited, and the rest have no known cause. Though prion diseases are relatively rare in humans, more than 100 young Europeans may have contracted new variant Creutzfeldt-Jakob disease by eating beef from so-called mad cows.


Now, a new study has found that the antimalarial drug quinacrine and the antipsychotic drug chlorpromazine can effectively treat mouse cells infected with prions, according to research described in the Aug. 14 issue of Proceedings of the National Academy of Science.


my.webmd.com...

Mad Cow Disease: Know the Basics

my.webmd.com...

The Official Mad Cow Disease Home Page

www.mad-cow.org...

Fibromuscular Dysplasia (Carotid Artery) Information

www.emedicine.com...

www.med.uc.edu...

www.westsubcardiology.com...

scienceweek.com...

Smooth Muscle Actin Information

www.researchd.com...

www.uic.edu...

biomeda.com... (PDF)

web.indstate.edu...

Myofibroblasts Information

ajp.amjpathol.org...

Actin Information

www.ks.uiuc.edu...

Prion Information

www-micro.msb.le.ac.uk...

en.wikipedia.org...

www.cjdsurveillance.com...

Useful Sites

www.webmd.com


i hope this helps. i am not an expert on this but this should be good information.





posted on Feb, 14 2005 @ 03:23 PM
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Thanks they see ALL - you have pulled the main spin showing what the official cover up stories say.

...Always good to have on file.


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posted on Feb, 20 2005 @ 07:19 PM
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So-called "shaken baby syndrome" has all the earmarks fibromuscular dysplasia (FMD). FMD is caused by a misfolded protein called a-smooth muscle actin (a-SMA), which appears to be an infectious prion.

FMD causes mutations in connective tissue stem cells and smooth muscle cells in the lymph and blood vessel walls, destroying vessel integrity. ...The disease is transmitted congenitally about 10% of the time and may cause a variety of different birth defects. Many of these defects are invisible, like those inside blood vessel walls.

What is Fibromuscular Dysplasia (FMD)?

The main diagnostic problem with protein misfolding and prion-related disorders is that there are no standardized tests to identify the diseases - they are diagnosed solely by their effects on tissue, called "pathology." The pathology focuses on late stage and acute effects; with FMD, acute effects include protein deposits that create blockages or "stenosis," and vacuoles that result in aneurysms.



For example,

"A 32-day-old boy died of recurring cerebral hemorrhages starting on the 4th day of life. Autopsy disclosed a remittingly ruptured saccular aneurysm of the anterior communicating artery. A 7-day-old brother of his had previously died of recurring subarachnoid hemorrhages as well. Nonaneurysmatic basal cerebral arteries showed remarkable histological changes partly resembling those seen in fibromuscular dysplasia…"

* A probably familial saccular aneurysm of the anterior communicating artery in a neonate. Childs Nerv Syst. 1993 Aug;9(5):302-5 Kuchelmeister K, Schulz R, Bergmann M, Schwuchow R, Vollmer E. Institut fur Neuropathologie, Universitat, Munster, Germany. PMID: 8252525




A significant difficulty in diagnosing FMD is that the pathology is often microscopic - finding the characteristic lesions, and thus evidence of disease, might require a nano-meter by nano-meter biopsy of the brain's blood vessels, with spectroscopic analysis. This is time consuming, VERY costly - and NOT in the budget for dealing with throwaway poor single mothers with "mental problems."





"A detailed post-mortem examination revealed FMD involvement of the intracranial vessels, not demonstrated by arteriography."

* "Fibromuscular dysplasia of cervico-cephalic arteries with multiple dissections and a carotid-cavernous fistula. A pathological study." Stroke. 1985 Mar-Apr;16(2):255-61. Bellot J, Gherardi R, Poirier J, Lacour P, Debrun G, Barbizet J. PMID: 3975964




Another difficulty in diagnosing FMD is that many fatal disease effects are dynamic, and can be observed only in living, functioning tissue. This limitation currently is documented with respect to the heart's electrical conduction system, but may be applied to the brain as well.





"Fibromuscular dysplasia of small coronary arteries has been described in several conditions: hypertrophic cardiomyopathy, Friedreich's ataxia, scleroderma, prolonged QT interval, Marfan's syndrome, progressive muscular dystrophy, tunnel aortic stenosis, mitral valve prolapse, and in the sinus node artery in sudden death."

* Sudden death and regional left ventricular fibrosis with fibromuscular dysplasia of small intramyocardial coronary arteries. Heart. 2000 Jan;83(1):101-2. Lee AH, Gray PB, Gallagher PJ. Department of Histopathology, Southampton General Hospital, Southampton, UK. PMID: 10618348
heart.bmjjournals.com...





Since SIDS first appeared in the 1960's, many parents have been charged wrongfully with murder when their babies died suddenly. However, unless the parents are wealthy and have the resources to force a full medical review, the cases are NOT reviewed or looked at differently. The anguish created by wrongful charges in SIDS is fairly well documented, yet the situation remains unresolved.





12 January 2005. Angela Cannings, who spent 18 months in prison for killing her infant sons, had her conviction quashed a year ago after judges ruled that expert evidence given by Professor Sir Roy Meadow had been flawed. (Sir Roy Meadow is a paediatrician and a former President of the Royal College of Paediatrics and Child Health.)
...Campaigners and legal experts accused the Home Office yesterday of flouting human rights laws over its refusal to pay compensation..."
Cannings' compensation claim is rejected

....

Oct 18, 1999. NEW YORK, PRNewswire/ -- Researchers at Harvard Medical School have documented a physical abnormality in the brain stem that renders some infants more susceptible to Sudden Infant Death Syndrome (SIDS), while researchers at the University of North Carolina have been developing new diagnostic tools and techniques that should ultimately allow physicians to identify infants during the fetal stage who are most at risk for SIDS and other developmental problems.
..."We have now identified a specific physical abnormality in this site," explains Dr. Kinney. "This abnormality can range from a complete absence of critical nerve cells in a small number of cases to a significant decrease in neurotransmitter receptor binding."
SIDS Risk Prevention Research Begins to Define Physical Abnormality in Brain Stem, Points to Possible Diagnostic/Screening Tools
Press Release

...

June 27 2003. "A group of Australian forensic experts and pathologists will join forces next year in a bid to set national standards for infant autopsies and a uniform definition of sudden infant death syndrome. ..."In Australia, we don't have a single definition of SIDS that everybody uses, we don't have a standard autopsy protocol to follow," Professor Byard said. "That means that everybody, particularly in smaller centres, is really following his own guidelines, and that's not a very good situation." ...If the workshop achieved a consensus, he said, it could lead to Australia becoming the first country to have an accepted national SIDS definition and standard infant autopsy procedures, which would ensure the accurate investigation of all infant deaths."
Experts to meet in bid to define SIDS

....

Child abuse is not a major cause of sudden infant death, according to a study.
...Previous research has suggested that as many as 40% of cases of sudden infant or cot death may be a result of deliberate abuse.
...However, a new study by a doctor in the north of England suggests the true figure may be much lower.
...Her study estimates that between 3% and 10% of sudden infant deaths may be murder.

Few cot deaths 'are murder'
...

"A radical overhaul of the way suspicious cot deaths are investigated is needed to avoid miscarriages of justice and torment for bereaved mothers, according to experts in the field. ...In the wake of the Trupti Patel case, where a mother was cleared of murdering her three babies, children's charities and pathologists said the investigations needed to be carried out initially by expert panels of doctors, before a decision is made to prosecute."

Call for an end to cot death court anguish

...

"An expert said there was a one in 73 million chance Sally Clark's babies died naturally - and a jury agreed. Sally Clark was ...condemned to life inside for murdering her two babies because - among other evidence - there was only 'one chance in 73 million' of the babies, born a year apart, both dying of natural causes.
But the discovery of a cot death gene means that the odds for a second death could have been as high as one in four - and that by hearing 'one in 73 million' the jury was presented with a simple, but false, probability.
...The new genetic research raises the possibility that Clark - and other women - have been the victims of an appalling series of miscarriages of justice in multiple cot death cases.
...A joint investigation by BBC's Five Live Report and The Observer has revealed a climate of suspicion against mothers who suffer two or more cot deaths, based on the 'crude aphorism' of top paediatrician Professor Sir Roy Meadow that, unless proven otherwise, 'two is suspicious and three is murder'. Sometimes known as 'Meadow's Law', it has been adopted by doctors, lawyers and the police.
...Microbiologist Dr David Drucker, who helped to identify the cot death gene, said of Meadow's Law: 'It's scientifically illiterate.' His is not a lone voice.

Gene find casts doubt on double 'cot death' murders




Three things stand out in cases of sudden infant death, 1) there are no standard autopsy procedures, 2) medical discoveries and scientific advances are not integrated into investigations, 3) new discoveries are still forthcoming which might explain natural causes, and 4) prion-related diseases are not recognized as a possible cause of death.

Despite the fact that SIDS has been around for more than 30 years - and parents are known to have been wrongly charged with murder - the flaws remain in the legal system. The situation with "shaken baby syndrome" is much worse.

Following the mini-epidemic of SIDS in the 1980s and early 1990s, "shaken baby syndrome" emerged as an all-new cause of baby deaths. There is good reason to suspect the true cause of this emerging mini-epidemic is a new form of an underlying and evolving infectious disease rather than an upsurge in violent abuse, most likely FMD or another prion-related disease.





"In the 1980s and early 1990s SIDS incidence rose considerably. ..."It is much more plausible that the rise was related to a changing epidemiology of an infectious agent or agents, i.e. natural variation," "
* "Research "Flawed" and Clues Ignored" Arch Dis Child 2003;88:1031,1095-1100.

...

"Arterial angiodysplasias constitute an ill-defined entity comprising conditions of apparently very variable natures. Apart from arterial fibrodysplasia, the clinical features of which, if not the etiology, are well established, there exists a number of different arterial abnormalities, stenotic or aneurysmal, the significance of which remains unclear (dolicho-arteries, the Moya-Moya syndrome, etc.). However, the role of genetic factors and metabolic abnormalities in these conditions is uncontestable. They demonstrate both the authenticity of this group of diseases and the importance of metabolic disorders of the interstitial tissues in the majority of these vascular abnormalities."
[Anatomopathological aspects of arterial angiodysplasias] Ann Med Interne (Paris). 1983;134(5):444-50. Chomette G, Auriol M, Tranbaloc P, de Saint-Maur PP. PMID: 6651065




"Shaken baby syndrome" likely represents a changing epidemiology of FMD or another prion-related congenital disorder, NOT an upsurge in parental abuse. As it stands, we don't know because the appropriate tests and medical examinations are not made.


FMD and the prion disease epidemics are not acknowledged officially, so changing epidemiology with respect to neonates is unrecognized.

The whole mess should be thoroughly investigated, and the gag oders on our scientists should be removed. Mad Cow-like prion diseases are epidemic and clearly the extent of the epidemics is being covered up to protect corporations from liability, and to preserve future profits. Parents being wrongfully charged with murder is only one of the cover-up's impacts.

US Still Silencing Scientists
Mad Cow Madness



Further reading:

* Conduction tissue and SIDS. Ann N Y Acad Sci. 1988;533:176-90. Ho SY, Anderson RH. PMID: 3421625

* Morphology, immunohistochemistry and morphometry of the thyroid gland in cases of sudden infant death syndrome (SIDS). Int J Legal Med. 1995;107(4):187-92. Rothfuchs D, Saeger W, Bajanowski T, Freislederer A. PMID: 7599094

* [Comparative histologic and hormonal studies of the thyroid gland with special reference to sudden infant death (SIDS)]
Z Rechtsmed. 1986;96(1):31-8. Risse M, Weiler G, Benker G. PMID: 3716646

* Pulmonary vessels in SIDS. N Engl J Med. 1975 Feb 27;292(9):479. Mason JM, Mason LH, Jackson M, Bell JS, Francisco JT, Jennings BR. PMID: 1113831

* Prevalence of the factor V leiden mutation in children and neonates with thromboembolic disease. J. Peds. 133:777-781, 1998. Hagstrom JN, Walter J, Amatniek J, Bluebond-Langner R, Manno CS, High KA.

* Reversible serous retinal detachments in two patients with thrombotic thrombocytopenic purpura. Arch Ophthalmol 103:1172-1174, 1985. Lambert SR, High KA, Cotlier C, and Benz EJ Jr:



posted on Feb, 28 2005 @ 11:40 AM
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...For those who don't know: Proteins are the building blocks of life - there are millions of different proteins and the body creates each one on order, tailored to do a very specific job. Proteins build cells by using a lock and key principle - proteins are 'coded' genetically - every protein key fits a specific protein lock in a particular way, first to build cells, then tissues, organs and other body parts. Kind of like a biological puzzle, where the pieces are created exactly and only when they're needed.

Prions are "misfolded proteins" - they muck up the works because they weasel in where they don't belong, hijack the protein-building and cell-building processes, and take over the works by causing mutations first in the proteins, and then down the line.


FYI - even before prions were identified officially, their role in mucking up the immune system was well known. ...One of the main difficulties was that there were so many different ways that the muck up occurred, no one could sort it out. ...The big hold-up was that genetic dogma said the only thing that could determine protein production and formation was "genes." To even suggest anything is was tantamount to heresy. ...But wrong. Prions can and do determine protein formation - they hijack gene function and often, cause genetic mutations.

...Now it's known that prions adapt to new cells and particles by mutating and shape-shifting - into whatever form or "key" will fit a particular lock. ...Researchers keep finding new and different infected proteins - enzymes, proteases, kineases and peptides. ...and the list keeps growing.


The "HLA-DR" system was identified very early on as the main pathway that prions use to access the immune system - and how they 'get in' to cause genetic mutations. ...Biologists, nephrologists and transplant doctors had world conferences in the early 1980's about HLA-DRw6


A few references from one of my HLA-DR files:

The genetics of the HLA system. McDevitt HO. J Rheumatol Suppl. 1983 Nov;10:50-3. PMID: 6319697

Reanalysis of the HLA-DRw6 complex. Schreuder GM, Parlevliet J, Termijtelen A, van Rood JJ. Tissue Antigens. 1983 Jan;21(1):62-74. PMID: 6601316

Monoclonal antibody identifies a new Ia-like (p29,34) polymorphic system linked to the HLA-D/DR region. Nature. 1981 Apr 16;290(5807):591-3. Nadler LM, Stashenko P, Hardy R, Tomaselli KJ, Yunis EJ, Schlossman SF, Pesando JM. PMID: 6163992

An HLA-D region restriction fragment length polymorphism associated with celiac disease. J Exp Med. 1986 Jul 1;164(1):333-8. Howell MD, Austin RK, Kelleher D, Nepom GT, Kagnoff MF. PMID: 3014038

DNA polymorphism of HLA class II genes in systemic lupus erythematosus. Tissue Antigens. 1994 Jan;43(1):34-7. Cowland JB, Andersen V, Halberg P, Morling N. Institute of Forensic Genetics, University of Copenhagen, Denmark. PMID: 7912858

HLA-DO polymorphism associated with resistance to type I diabetes detected with monoclonal antibodies, isoelectric point differences, and restriction fragment length polymorphism. J Exp Med. 1986 Sep 1;164(3):938-43. Schreuder GM, Tilanus MG, Bontrop RE, Bruining GJ, Giphart MJ, van Rood JJ, de Vries RR. PMID: 3462303

The new HLA-DRw6- and 8- associated HLA-Dw HAG specificity defined by homozygous typing cell 9W 1802. Analysis with primed lymphocyte typing clones. Tissue Antigens. 1984 Nov;24(5):292-301. Pawelec G, Muller C, Rehbein A, Balko I, Schunter F, Wernet P. PMID: 6085195

Different specificities of an HLA-DRw6 haplotype detected by alloreactive T lymphocytes. Hum Immunol. 1984 Dec;11(4):193-205. Myers LK, Ball EJ, Stastny P. PMID: 6210279

HLA-A, B, DR, and DQ antigens in black patients with severe chronic rheumatic heart disease. Circulation. 1987 Aug;76(2):259-61. Maharaj B, Hammond MG, Appadoo B, Leary WP, Pudifin DJ. PMID: 3475188

Analysis of the sheep MHC using HLA class I, II, and C4 cDNA probes. Immunogenetics. 1985;22(4):349-58. Chardon P, Kirszenbaum M, Cullen PR, Geffrotin C, Auffray C, Strominger JL, Cohen D, Vaiman M. PMID: 2997030

Human influenza virus-specific T helper cell clones can be restricted by MHC products different from serologically defined HLA-DR antigens. Tissue Antigens. 1983 Mar;21(3):238-45. Fleischer B. PMID: 6190261

The origin of HLA-DR"Br": exon 2 nucleotide sequence implicates possible gene conversion of DR1 by DR4-Dw10, DR5, or DRw6-Dw18. Hum Immunol. 1989 Nov;26(3):191-7. Bidwell JL, Bidwell EA, Sansom DM, Klouda PT, Bradley BA. PMID: 2575090

Analysis by molecular cloning of the human class II genes. Fed Proc. 1984 Dec;43(15):3025-30. Erlich H, Stetler D, Sheng-Dong R, Saiki R. PMID: 6094260

HLA-DRw6 as a risk factor for active cytomegalovirus but not for herpes simplex virus infection after renal allograft transplantation. Br Med J (Clin Res Ed). 1985 Sep 7;291(6496):619-22. Roenhorst HW, Tegzess AM, Beelen JM, Middeldorp JM, The TH. PMID: 2992676

Glycoprotein B from strain 17 of herpes simplex virus type I contains an invariant chain homologous sequence that binds to MHC class II molecules. Immunology. 2002 Sep;107(1):129-35. Sievers E, Neumann J, Raftery M, SchOnrich G, Eis-Hubinger AM, Koch N. Division of Immunobiology, Institute of Zoophysiology, University of Bonn, Germany. PMID: 12225371

Polymorphisms within the HLA-DRw6 haplotype. I. Restriction fragment length variation and its correlation with serology. The Journal of Immunology, Vol 134, Issue 5 3212-3217, Copyright © 1985 by American Association of Immunologists. ML Bosch, GM Schreuder, H Spits, A Termijtelen, MG Tilanus and MJ Giphart PMID: 2984285

HLA-DR2, -DR5, and DRw6 associated Dw subtypes correlate with HLA-DR beta and -DQ beta restriction fragment length polymorphisms. Proc Natl Acad Sci U S A. 1986 May;83(10):3361-5. Font MP, Gebuhrer L, Betuel H, Freidel C, Dausset J, Cohen D. PMID: 3010292

Biochemistry of HLA-DRw6: evidence for seven distinct haplotypes. J Immunol. 1986 May 15;136(10):3767-72. Haziot A, Lepage V, Freidel AC, Betuel H, Degos L, Charron DJ. PMID: 3486222

Hypoxia inhibits human bladder smooth muscle cell proliferation: A potential mechanism of bladder dysfunction. Neurourol Urodyn. 2004;23(4):342-8. Galvin DJ, Watson RW, O'Neill A, Coffey RN, Taylor C, Gillespie JI, Fitzpatrick JM. Department of Surgery, Mater Misericordiae University Hospital, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland. PMID: 15227652


And of course, the ever-present fibromuscular dysplasia (FMD):

"Fibro-muscular dysplasia is known to be more frequently associated with ... the presence of HLA-DRW6 antigen."
hyper.ahajournals.org... (1989)
medind.nic.in/jac/t03/i2/jact03i2p139.pdf (2003)
www.indegene.com/Car/FeatArt/indCarFeatArt25.html (2003)

Etiologic factors in renovascular fibromuscular dysplasia. A case- control study. Hypertension, Vol 14, 472-479, Copyright © 1989 by American Heart Association CN Sang, PK Whelton, UM Hamper, M Connolly, S Kadir, RI White, R Sanders, KY Liang and W Bias Outpatient Clinical Research Center, Johns Hopkins Medical Institutions, Baltimore, MD 21205.
MeSH terms: HLA-DR6 Antigen
HLA-DRw6; HLA-DR6; Antigen, HLA-DR6; HLA DR6 Antigen
Human immune-response, D-related antigen encoded by the D locus on chromosome 6 and found on lymphoid cells.


Also see:

"Mad Cow" Disease Uses Immune System to Spread in Body


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posted on Apr, 3 2005 @ 11:19 AM
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According to public health campaigns, infectious disease in the developed world was conquered decades ago. Other campaigns say bioterrorists are responsible for new disease threats. Neither claim is true, but microbiologists who speak out are silenced.

The truth: We have changed our world, biochemically and fundamentally - inside our own bodies and in the environment - and microbes are adapting to this synthetic new world much faster than we are. Bioterrorists are NOT required - "nature" has taken over, and now is creating virulent new incurable diseases without any help at all. Today, our world is teeming with new disease mutations that cause a range of often unrecognized and undignosed mild, chronic, and acute infectious diseases.

The evolutionary process now is coming to a peak. This process no longer can be prevented, but with appropriate measures, it still is possible to lessen the impact. However, only public education and demand will influence political directions and reverse current trends.


Super Bugs

"Super Bugs" are highly contagious and lethal bacteria. They can't be treated with antibiotics - in fact, antibiotics now cause previously benign bacteria to mutate into lethal forms - most "Super Bugs" mutate into highly contagious and lethal forms on exposure to antibiotics inside the host's body.

"Doctors know C. difficile flourish after patients take certain antibiotics. Now it seems any antibiotic can bring on the disease. ..."Something happened 18 to 24 months ago, ..." said Dr. Mark Miller, chief of infectious diseases at Montreal's Jewish General Hospital."
Clostridium difficile FAQs
Officials say c. difficile virtually impossible to eradicate.


Five lethal and virulent super bugs currently are recognized in North America - C. difficile, MRSA, VRE, flesh eating disease (necrotizing fasciitis), and ESBL-producing bacteria. Several common chronic debilitating infections fall under the VRE and ESBL categories.

What are ESBL-producing bacteria?
"ESBL stands for extended spectrum beta-lactamase, which are enzymes that have developed a resistance to antibiotics like penicillin. ...Enzymes are proteins produced by living organisms. The proteins speed up biochemical reactions. ...ESBL enzymes can also spread by passing from one bacterium to another."

Vancomycin-resistant enterococci (VRE)
"Enterococcus is a normally benign bacterium that lives in the intestine. Enterococcus infections can occur in the urinary tract, in the blood and in wounds, including surgical wounds. ...While these infections can usually be treated with antibiotics such as ampcillin and vancomycin, a strain that is resistant to both was first discovered in France in 1986. Similar strains can now be found all over the world. ...the bacteria sit dormant in the person's gut until they come into contact with an antibiotic. At that point the VRE can spread to the rest of the body."

For a basic overview of microbial evolution and adaptation, see: Paul Ewald: Infectious Disease and the Evolution of Virulence


Like super bugs, bird flu mutates rapidly, and like ESBL and VRE, also has the ability to acquire proteins from other microbes infecting different animal species. See: The next pandemic?

"Super Bugs" and bird flu are just the tip of the iceberg. New mutations are becoming more deadly and virulent, much more rapidly. The two keys to rapid mutation are widespread environmental contaminations and infectious misfolded proteins like Mad Cow prions (misfolded proteins).

Misfolded proteins are created by common industrial processes and environmental contaminations, and can become infectious. FMD is the grandaddy of infectious misfolded proteins - and it's the worst, because it's an actin protein (a-smooth muscle actin or a-SMA).

Proteins work on a kind of "lock and key" mechanism, and only the right key can open the lock - misfolded actin proteins are like a "master key." Virtually every lifeform on this planet contains actin proteins - an open door for misfolded actin proteins and new diseases that can cross species barriers AND kingdom barriers. And once they're "in," misfolded actin proteins mutate again and again to create new strains that work better to take over different host cells.

Scientists and governments recognized the importance of misfolded actin proteins and the resultant trends in microbial mutation decades ago, and issued warnings regularly. Then, between 2 and 4 years ago something changed. Mutation rates shot up abruptly and rapidly - but the scientists recommending intervention and prevention suddenly were silenced. At the same time, public health campaigns and health insurance policies were modified to say disease is a "personal responsibility" and "genetic." Now, decision-makers totally dismiss the reality of rampantly mutating infectious disease.

Rather than modernizing clean-up technologies to prevent the spread and evolution of new disease mutations, the EPA budget was cut - rather than ordering vaccines or stockpiling antivirals, new policies establish parameters for "population triage" designed to "cull" the already sick, aged and vulnerable.

Many of these epidemics can be hidden from public view - and bioterrorists are set up to take the blame for new epidemics that can't be hidden.



Super Bugs Overview

NOTE: This section synopsizes a series of articles from the CBC about super bugs in non-profit Canadian hospitals - the situation is the USA likely is much worse, because most US hospitals are run for profit. The problem certainly is present in the USA, and has been evolving for a long time as this article indicates:
* Methicillin-resistant Staphylococcus aureus outbreak at a Veterans' Affairs Medical Center : importance of carriage of the organism by hospital personnel. Infect Control Hosp Epidemiol. 1990 Jun;11(6):291-6. PMID: 2373851


Invisible Dangers: Canadian hospitals
"Patients admitted to Canadian hospitals expect that their stay will make them healthier, yet a record number of Canadians are taking an infection home with them. And often those infections are resistant to many antibiotics, requiring people to take powerful medicine to fight the infection.

Methicillin-resistant staphlycoccus aureus (MRSA), vancomycin-resistant enterococci (VRE) and Clostridium difficle are the most common hospital-acquired infections.

An estimated 8,000 people die from antibiotic-resistant infections each year. ...According to Dr. Michael Rachlis, nursing staff and cleaners are often the first to be cut when hospitals have a budget crunch. Yet studies show hospitals are spending $100 million a year treating patients with antibiotic resistant infections they contracted in the hospital."



Clostridium difficile FAQs
"......C. difficile is not an uncommon bacterium – but it had some infectious disease specialists worrying that it has become the most dangerous superbug to hit North American hospitals in a decade. In October 2004, researchers found that 7,000 people had been infected with C. difficile in Montreal since 2003, and at least 600 of them died. Hospitals in Ottawa and Calgary have also experienced periodic outbreaks.

Why are health care officials concerned?

The experts investigating the outbreak say the bacterium appears to have mutated into a (new lethal) strain – and they don't know why. It has caused almost four times the usual number of cases of severe diarrhea in hospitals, and can persist in the body for months despite repeated antibiotic treatments.

Doctors know C. difficile flourish after patients take certain antibiotics. Now it seems any antibiotic can bring on the disease.

"Something happened 18 to 24 months ago, where the use of particular antibiotics didn't seem to matter anymore," said Dr. Mark Miller, chief of infectious diseases at Montreal's Jewish General Hospital.

How do I get it?

The bacteria are almost exclusively picked up in hospital. Infections tend to arise when a hospitalized patient – who has been unwittingly colonized by the bug – is given antibiotics for another condition.

Your risk of contracting the bacteria rises if you're undergoing chemotherapy, have abdominal surgery or have other stomach or intestine problems.

C. difficile bacteria also make spores that can be found in the environment – on toilet seats or doorknobs, for instance."

Also see: C. Difficile in Saskatchewan
Officials say c. difficile virtually impossible to eradicate.
Toronto hospital reports C. difficile strain



What are ESBL-producing bacteria?
"ESBL stands for extended spectrum beta-lactamase, which are enzymes that have developed a resistance to antibiotics like penicillin. ...Enzymes are proteins produced by living organisms. The proteins speed up biochemical reactions. ...ESBL enzymes can also spread by passing from one bacterium to another."

Also see Bibliography: NIH Research Proves Prions Can Be Enzymes


Vancomycin-resistant enterococci (VRE)
"Enterococcus is a normally benign bacterium that lives in the intestine. Enterococcus infections can occur in the urinary tract, in the blood and in wounds, including surgical wounds. ...While these infections can usually be treated with antibiotics such as ampcillin and vancomycin, a strain that is resistant to both was first discovered in France in 1986. Similar strains can now be found all over the world. ...the bacteria sit dormant in the person's gut until they come into contact with an antibiotic. At that point the VRE can spread to the rest of the body."

Flesh-eating disease: Necrotizing fasciitis
"Necrotizing fasciitis, or flesh-eating disease, is a fast-spreading infection caused by streptococcus bacteria that themselves have been infected with a virus. ...The infection sometimes starts at the site of a minor injury, such as a cut or bruise, but sometimes there is no obvious source of infection."

February 2005: Surveillance for MRSA in Canadian Hospitals
"Between 1995 and 2003, MRSA rates increased in CNISP hospitals from 0.46 cases per 1,000 admissions to 5.10 per 1,000 admissions (p = 0.002) (Table 1 and Figure 1). Most of the increase in MRSA cases occurred in central Canada (Ontario and Quebec), although there were also increases elsewhere in the country (Figure 2).

...Surveillance for MRSA in CNISP hospitals has shown that MRSA rates continue to climb in Canadian hospitals. Rates of MRSA are now 10 times higher than they were when surveillance started in 1995. Increases have occurred across the country, although the highest rates are seen in hospitals in Quebec and Ontario. Rates in the Atlantic Provinces remain low, but appear to have increased significantly in the past year. Although much of the observed increase in MRSA detection may be attributed to screening programs in hospitals, there has also been a five-fold increase in MRSA infection rates. MRSA infections are associated with increased morbidity and mortality, prolonged hospitalization, and increased costs(9,10).

In the past few years, community-acquired MRSA has emerged as a major problem in many parts of the United States, associated with the transmission of a strain of the organism possessing a specific staphylococcal chromosomal cassette (SCCmec type IV), and the Panton-Valentine leukocidin (PVL) genetic determinant(11). In Canada, most (approximately 85%) MRSA remains hospital-acquired, but these community-acquired strains have occasionally been seen in CNISP hospitals, particularly in aboriginals residing in western provinces (data not shown). In these patients, MRSA was associated with the development of skin and soft tissue infections.

...MRSA is typically resistant to multiple classes of antibiotics. Therefore treatment options for the management of serious MRSA infections are limited. ...It is noteworthy that the number of reported bacteremias due to MRSA has increased in Ontario, such that in 2003, 11% of S. aureus isolates from blood cultures in the province were MRSA(13).

...there has been an increase in high-level resistance to mupirocin (6% in 2002), an agent that is potentially useful for decolonization of MRSA carriers.

...Hospitals should make prevention of the emergence and transmission of antibiotic-resistant organisms and other hospital-acquired infections a patient safety priority, and should commit adequate resources to screening and implementation of other preventative measures. Ongoing surveillance is also essential in order to monitor the constantly evolving epidemiology of antibiotic-resistant organisms such as MRSA."



UK MRSA Surveillance April 2001-September 2004
"The number of MRSA bacteraemias in the first three complete years of the mandatory recording system rose from 7249 in 2001/02 to 7373 in 2002/03 and 7684 in 2003/04. ...The ...figures reflect the burden of serious infections associated with MRSA bacteraemia (or blood stream infections) and not all MRSA infection or carriage."

Also see: CACMID: There are serious gaps in infection control in Canadian hospitals.
The Economic Impact of Methicillin-Resistant Staphylococcus aureus in Canadian Hospitals




BIBLIOGRAPHY

Misfolded Actin Proteins: At Once Disease, Path and Doorway

Most modern diseases involve misfolded proteins causing connective tissue stem cells ("fibroblasts") to mutate into "myofibroblasts" - via actin proteins. The disease process also interferes with genetic transcription. These articles help explain actin's role, and how the disease process and genetic alterations work to develop new strains and diseases.


* Actin' like actin? Trends Cell Biol. 1996 Jun;6(6):208-212. Mullins RD, Kelleher JF, Pollard TD. The authors are at the Dept of Cell Biology and Anatomy, Johns Hopkins University School of Medicine, 725 N. Wolfe St, Baltimore, MD 21205, USA. PMID: 15157457

The most biologically significant property of actin is its ability to self-associate and form two-stranded polymeric microfilaments. In living cells, these micro filaments form the actin cytoskeleton, essential for maintenance of the shape, passive mechanical properties and active motility of eukaryotic cells. Recently discovered actin-related proteins (ARPs) appear to share a common ancestor with conventional actin. At present, six classes of ARPs have been discovered, three of which have representatives in diverse species across eukaryotic phyla and may share functional characteristics with conventional actin. The three most ubiquitous ARPs are predicted to share a common core structure with actin and contain all the residues required for ATP binding. Surface residues involved in protein protein interactions, however, have diverged. Models of these proteins based on the atomic structure of actin provide some clues about how ARPs interact with each other, with conventional actin and with conventional actin-binding proteins.


2004 – study “suggests a new paradigm for considering the cellular processes that regulate the dynamic organization of the actin cytoskeleton.”
* Actions by actin: reciprocal regulation of cortactin activity by tyrosine kinases and F-actin. Biochem J. 2004 Jun 1;380(Pt 2):E7-8. Gunst SJ. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202-5120, U.S.A. PMID: 15154835

The polymerization of actin is catalysed by the Arp (actin-related protein) 2/3 complex, which acts downstream of a variety of receptors and signalling cascades. Intermediary molecules such as cortactin bind to the Arp2/3 complex and stimulate its activity, thus promoting actin polymerization and actin filament stabilization. New data in this issue of the Biochemical Journal by the Kapus group suggest that cortactin is reciprocally regulated by filamentous (F) actin and tyrosine kinases. This suggests a new paradigm for considering the cellular processes that regulate the dynamic organization of the actin cytoskeleton.


* Actin-related protein 1 and cytoplasmic dynein-based motility - what's the connection? Trends Cell Biol. 1996 Jun;6(6):212-215. Schroer TA, Bingham JB, Gill SR. The authors are at the Dept of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA. PMID: 15157458

The actin-related protein Arp1 works in conjunction with the microtubule-based motor cytoplasmic dynein to drive many types of intracellular motility. In vertebrate cells, Arp1 is present exclusively in the form of a 37-nm filament that constitutes the backbone of dynactin, a 1.2-MDa macromolecular complex containing nine other polypeptides. Dynactin has been proposed to function as the link between dynein and its cargo. Recent work indicates that the dynactin subunit p150(Glued) mediates the interaction of the dynactin molecule with dynein and microtubules, leaving the Arp1 filament as a possible cargo-binding domain. Mechanisms for binding of F-actin to membranes are discussed as models of the Arp1-membrane interaction.


2004 – “various macromolecular entities possessing polyanionic character such as proteoglycans, lipid bilayer surfaces, microtubules, microfilaments and polynucleotides may provide a functional network which mediates a variety of cellular phenomena. The interaction of proteins with this array of polyanions is characterized by a lower degree of specificity than seen with most commonly recognized macromolecular interactions. …, potential roles for this polyanion network in diverse functions such as protein/protein interactions, protein folding and stabilization, macromolecular transport and various disease processes are all considered as well as the use of polyanions as therapeutic agents. … many hundreds to thousands of such interactions are present in cells and argue that future understanding of the proteome will require that the polyanion world be taken into account.”
* Polyanions and the proteome. Mol Cell Proteomics. 2004 May 13 [Epub ahead of print] Jones LS, Yazzie B, Middaugh CR. Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047. PMID: 15143156

* Protein misfolding and disease: Principles and protocols. Methods in molecular biology, Vol. 232, edited by P. Bross and N. Gregersen.: 2003. Protein Sci. 2004 Jun;13(6):1704-5. Totowa, New Jersey, USA: Human Press, Inc. 318 pp. $99.50. Sunde M. PMID: 15152098
Protein Science -- Sunde 13 (6): 1704
... These include cystic fibrosis with preventative degradation of variant proteins, and aggregation-associated problems such as Parkinson’s disease (PD) and 1 ...
www.proteinscience.org...

"Fibrosis occurs in multiple organs and tissues ...and is characterized by the accumulation of connective tissue (myofibroblasts and misfolded a-smooth muscle actin). ...Although fibrosis severely affects the functioning of organ or tissue and is often life-threatening, no effective therapy is currently available to attenuate the process."
pdf - TNO Pharma - part of the Netherlands Organization for Applied Scientific Research



Some Early Research

“Mutation and evolution at the molecular level.” Kimura M, Ota T. Genetics. 1973 Apr;73:Suppl 73:19-35. PMID: 4711555

“Regulation of gene expression by actinomycin D and other compounds which change the conformation of DNA.” Schwochau ME, Hadwiger LA. Arch Biochem Biophys. 1969 Oct;134(1):34-41. PMID: 5345595
“The interaction of actinomycin with DNA.” Goldberg IH. “The interaction of actinomycin with DNA.” Antibiot Chemother. 1971;17:67-86. PMID: 4142574

“Conformational changes induced by the interaction of sodium dodecyl sulfate with bovine plasma albumin.” Sogami M, Uyeda M, Ogura S. Biochim Biophys Acta. 1973 Jun 15;310(2):487-94. PMID: 4737020
“A model compound of actinomycin. Conformation of dimethyl actinocynilbis (L-threonate).”Anastasi B, Ascoli F, Costantino P, de Santis P, Savino M, Rizzo R.
Biochemistry. 1973 Apr 24;12(9):1834-7. PMID: 4121542

“The interaction of myosin, actin and ATP in the intact muscle.” Barany M, Barany K. J Mechanochem Cell Motil. 1973 May;2(1):51-9. PMID: 4780819

“Natural F-actin. VI. Degeneration of natural F-actin and its protection by ATP.” Suzuki S, Noda H, Maruyama K. J Biochem (Tokyo). 1973 Apr;73(4):695-703. PMID: 4720054

1965 - a-actinin, a new structural protein from striated muscle. J. Biochem. (Tokyo), 58:7-12, 1965. EBASHI, S. & EBASHI, F.
1984 - Microfilament-organizing centers in areas of cytoskeletal cell contact. J. Cell Biol., 99:83-91, 1984. GEIGER, B.; AVNUR, Z.; RINNERTHALER, G.; MINSSEN, M. & SMALL, K.J.
1984 - Isolation of brain a-actinin. Its characterization and a comparison of its properties with those of muscle a-actinins. Biochemistry, 23:1600-8, 1984. DUHAIMAN, A. S. & BAMBURG, J. R.

2000 - "Mammalian cells contain at least 8 actin isoforms. ...all astroglia in tissue culture express beta-actin isoform and about 86% of astroglia express alpha-smooth muscle actin isoform. ...astroglia have different mechanisms in regulating the expression of different actin isoforms and the alpha-sm actin isoform is important in migration of astroglia." - PMID: 11202154
astroglia -->astrocytes - The largest and most numerous neuroglial cells in the brain and spinal cord.

2003 - "there appears to be a specific skeletal/cardiac actin ratio in a normal heart that may vary in a compromised or diseased heart." - www3.interscience.wiley.com...

Early research dealing with the genetic impacts of environmental poisons, with reference to actin:
froglab.biology.utah.edu...

* HeLa cell adherence, actin aggregation, and invasion by nonenteropathogenic Escherichia coli possessing the eae gene. Infect Immun. 1991 Nov;59(11):3924-9. Cantey JR, Moseley SL. Veterans Affairs Medical Center, Charleston, South Carolina 29403. PMID: 1682254
www.pubmedcentral.nih.gov...
* HEp-2 cell adherence, actin aggregation, and intimin types of attaching and effacing Escherichia coli strains isolated from healthy infants in Germany and Australia. Infect Immun. 2003 Jul;71(7):3995-4002. Beutin L, Marches O, Bettelheim KA, Gleier K, Zimmermann S, Schmidt H, Oswald E. Division of Emerging Bacterial Pathogens, Department of Biological Safety, Robert Koch Institute, 13353 Berlin, Germany. BeutinL@rki.de PMID: 12819087
iai.asm.org...

* Actin control over microtubules suggested by DISTORTED2 encoding the Arabidopsis ARPC2 subunit homolog. Plant Cell Physiol. 2004 Jul;45(7):813-22. Saedler R, Mathur N, Srinivas BP, Kernebeck B, Hulskamp M, Mathur J. Botanical Institute III, University of Koln, Gyrhofstrasse 13, D-50931 Koln, Germany. PMID: 15295064


Actin Muscles In On DNA Transcription
"Overturning a scientific stereotype, researchers at the University of Illinois at Chicago have discovered a new role for a key protein involved in muscle contraction and shown it is present not just in the cytoplasm of cells but in the nucleus as well.
"...in the nucleus, ...actin acts instead like a binding protein. It recruits other proteins in the very complicated process our bodies use to transcribe DNA segments into messages made of RNA." These messages travel out to the cytoplasm, where they serve as templates for building proteins, including actin itself."
"Learning about the precise components and sequence of events in DNA transcription is important because the process is essential to all cellular activity, whether in normal healthy tissues or in diseases like cancer, ...The knowledge we gain will one day open up opportunities for intervening when genetic transcription goes awry." "
"If actin is blocked, transcription can't begin," "

Original Press Release from U of Illinois


Cell Biology of Filamentous Influenza Virus (5/6/2002)
"...spherical virus production predominates in fibroblasts and non-polarized epithelial cell lines, filamentous virus production requires a polarized epithelial cell type ...a viral component may be interacting with the actin cytoskeletal network to promote filamentous particle formation. Thus, filamentous influenza virus formation requires the interaction of viral specific components with host cell components, presumably actin or actin-associated proteins."


The first experimental vaccine for H5N1 bird flu developed in 1999:
"Influenza virus genes and expression vectors. ...A full-length cDNA copy of the HA gene of HK97 was cloned into the EcoRI and BglII sites of pCAGGS/MCS (18), a vector that contains a chicken beta -actin promoter.
The plasmid DNA encoding TyIr83 HA is under the control of the CMV promoter, and the plasmid vector encoding HK97 HA is under the control of the chicken beta -actin promoter. "
DNA vaccine encoding hemagglutinin provides protective immunity against H5N1 influenza virus infection in mice. J Virol. 1999 Mar;73(3):2094-8. Kodihalli S, Goto H, Kobasa DL, Krauss S, Kawaoka Y, Webster RG. Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. PMID: 9971791
jvi.asm.org...

VIRUSES ARE VECTORS for misfolded proteins, COMMONLY USED IN GENE THERAPY - scientists got the idea from nature.....
"...certain viruses invade animal or plant cells without completing a destructive cycle and ...can be used as gene vectors. Generally they can carry larger portions of DNA than can plasmids."
web.ukonline.co.uk...


Background Re: RNA interference, viruses used as vehicles of transmission (1983?)
Pdf. RNA interference, viruses used as vehicles of transmission

Bellett, A.J.D. et al. (1989). "Functions of the Two Adenovirus Early E1A Proteins and Their Conserved Domains in Cell Cycle Alteration, Actin Reorganization, and Gene Activation in Rat Cells," J. Virol. 63(1):303-310.


More on Actin in viruses

* Filamentous forms associated with newly isolated influenza virus. Lancet 1949; 1:602. Chu, C.M., Dawson, I.M. and Elford, W.J.
* Biological and physical properties of the Ryan strain of filamentous influenza virus. J Gen Micro 1958;19:23. Ada, G.L., Perry, B.T. and Abbot, A.
* Studies of two kinds of virus particles which comprise influenza A virus strains. III. Morphological and functional traits. J Exp Med 1960;112:945. Choppin, P.W., Murphy, J.S. and Tamm, I.
* Genetic studies of influenza virus. I. Viral morphology and growth capacity as exchangeable genetic traits. Rapid in ovo adaptation of early passage Avian strain isolated by combination with PR8. J Exp Med 1960;111:387-405. Kilbourne, E.D. and Murphy, J.S.

* "Functions of the Two Adenovirus Early E1A Proteins and Their Conserved Domains in Cell Cycle Alteration, Actin Reorganization, and Gene Activation in Rat Cells," J. Virol. 63(1):303-310. Bellett, A.J.D. et al. (1989).


An Introduction to the Actin Cytoskeleton (pdf)

* Interactions between the plasma membrane and cytoskeleton of cultured fibroblasts. Prog Clin Biol Res. 1980;41:925-30. Ash JF, Louvard D, Singer SJ. PMID: 7005909
* The organization of actin in spreading macrophages. The actin-cytoskeleton of peritoneal macrophages is linked to the substratum via transmembrane connections. Exp Cell Res. 1981 Apr;132(2):235-48. Trotter JA. PMID: 7011822

…possible parallels between the cell-to-cell transport of endosomes and intracellular pathogens.
* Getting connected: actin-based cell-to-cell channels in plants and animals. Trends Cell Biol. 2004 Aug;14(8):404-8. Baluska F, Hlavacka A, Volkmann D, Menzel D. Institute of Cellular and Molecular Botany, University of Bonn, D-53115 Bonn, Germany. PMID: 15308205

“Cytoskeletal integrity appears important for maintaining cerebral arterial diameter during changing intravascular pressure. In addition, the process of actin polymerization may be a significant contributor to development of myogenic tone after forced dilatation.”
* Vascular smooth muscle actin cytoskeleton in cerebral artery forced dilatation. Stroke. 1998 Jun;29(6):1223-8. Cipolla MJ, Osol G. Department of Surgery, Oregon Health Sciences University, Portland 97201, USA. cipollam@ohsu.edu PMID: 9626298. stroke.ahajournals.org...

“…actin assembly plays an important role in the establishment of an intracellular niche that sustains bacterial growth.”
* Remodelling of the actin cytoskeleton is essential for replication of intravacuolar Salmonella. Cell Microbiol. 2001 Aug;3(8):567-77. Meresse S, Unsworth KE, Habermann A, Griffiths G, Fang F, Martinez-Lorenzo MJ, Waterman SR, Gorvel JP, Holden DW. Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Univ.Med., Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. PMID: 11488817

“…actin assembly plays an important role in the establishment of an intracellular niche that sustains bacterial growth.”
* Remodelling of the actin cytoskeleton is essential for replication of intravacuolar Salmonella. Cell Microbiol. 2001 Aug;3(8):567-77. Meresse S, Unsworth KE, Habermann A, Griffiths G, Fang F, Martinez-Lorenzo MJ, Waterman SR, Gorvel JP, Holden DW. Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Univ.Med., Campus de Luminy, Case 906, 13288 Marseille Cedex 09, France. PMID: 11488817


ACTIN MISFOLDING and CONFORMATION CHANGES

"stress fibers are an organelle present in endothelial cells in vivo and that they reorganize during endothelial cell adaptation to unfavorable or pathological situations."
* Organization of actin cytoskeleton in normal and regenerating arterial endothelial cells. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2361-4. Gabbiani G, Gabbiani F, Lombardi D, Schwartz SM. PMID: 6340120

"areas of membrane-cytoskeletal interaction may be involved in the aberrant cell-cell communication as well as the aggressive behavior often seen in transformed cells." Cell Motil. 1983;3(5-6):383-90. F-actin aggregates may activate transformed cell surfaces. Carley WW, Webb WW. PMID: 6661766

“In tumor cells, arising from transformed epithelium with A-type of actin pattern alteration, a secondary redistribution of actin bundles towards B-type occurred. Histochemical staining of such cells revealed a high activity of gamma-glutamyltranspeptidase, a marker enzyme for transformed cultures. The complete loss of actin bundles was observed in soft agar clone originated from cells with B-type alteration of actin pattern.”
* Changes in the actin cytoskeleton during transformation and tumor progression in liver epithelium in culture] Tsitologiia. 1982 Feb;24(2):195-9. Troianovskii SM, Bannikov GA. PMID: 7071937

“The actin cytoskeleton was examined in cultured skin fibroblasts of control individuals and patients with adenomatosis of colon and rectum ...the actin distribution pattern differs significantly between the group(S).”
* Actin distribution patterns in patients with adenomatosis of colon and rectum. Mol Biol Rep. 1986;11(4):225-30. Goos CM, Vermeesch-Markslag AM, Vermorken AJ. PMID: 3543653

CELL-CELL CONTACT, AMOEBA
Rapid polymerization of Entamoeba histolytica actin induced by interaction with target cells. J Exp Med. 1985 Aug 1;162(2):546-58. Bailey GB, Day DB, Gasque JW. PMID: 2862217

CELL-CELL CONTACT, KERATINOCYTES
J Invest Dermatol. 1983 Jul;81(1 Suppl):131s-6s. Transformation and immortalization of human keratinocytes by SV40. Steinberg ML, Defendi V. PMID: 6306114


Actin and AIDS

NOTE: HLA-DR is part of the immune system and is associated with FMD.

“…on antigen presenting cells, such as B cells and fibroblasts, actin microfilaments acts as a regulator of the movement and capping of HLA-DR receptors.”
Interaction of HLA-DR with actin microfilaments. Hum Immunol. 2003 Mar;64(3):327-37. Fernandez EM, O'Toole PJ, Morrison IE, Cherry RJ, Fernandez N. Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, UK. PMID: 12590977

* Actin, troponin C, Alzheimer amyloid precursor protein and pro-interleukin 1 beta as substrates of the protease from human immunodeficiency virus. J Biol Chem. 1991 Aug 5;266(22):14548-53. Tomasselli AG, Hui JO, Adams L, Chosay J, Lowery D, Greenberg B, Yem A, Deibel MR, Zurcher-Neely H, Heinrikson RL. Upjohn Laboratories, Upjohn Company, Kalamazoo, Michigan 49001. PMID: 1907279

* Disruption of the actin cytoskeleton can complement the ability of nef to enhance human immunodeficiency virus type 1 infectivity. J Virol. 2004 Jun;78(11):5745-55. Campbell EM, Nunez R, Hope TJ. Department of Microbiology and Immunology, University of Illinois at Chicago, 835 S. Wolcott, Chicago, IL 60612. thope@uic.edu PMID: 15140972

The human immunodeficiency virus (HIV) protein Nef has been shown to increase the infectivity of HIV at an early point during infection. Since Nef is known to interact with proteins involved in actin cytoskeleton rearrangements, we tested the possibility that Nef may enhance HIV infectivity via a mechanism that involves the actin cytoskeleton. We find that disruption of the actin cytoskeleton complements the Nef infectivity defect. The ability of disruption of the actin cytoskeleton to complement the Nef defect was specific to envelopes that fuse at the cell surface, including a variety of HIV envelopes and the murine leukemia virus amphotropic envelope. In contrast, the infectivity of HIV virions pseudotyped to enter cells via endocytosis, which is known to complement the HIV Nef infectivity defect and can naturally penetrate the cortical actin barrier, was not altered by actin cytoskeleton disruption. The results presented here suggest that Nef functions to allow the HIV genome to penetrate the cortical actin network, a known barrier for intracellular parasitic organisms.




Actin, FMD and Cancer

* Bcl-2-related proteins, alpha-smooth muscle actin and amyloid deposits in aggressive and non-aggressive basal cell carcinomas. Acta Derm Venereol. 2002;82(6):423-7. Bozdogan O, Erkek E, Atasoy P, Kocak M, Birol A, Caydere M. Department of Pathology, Kirikkale University, Faculty of Medicine, Turkey. PMID: 12575847
* (Study of skin fibroblasts in mice) "...disruption of the PrP gene resulted in an aberrant regulation of a battery of genes important for cell proliferation, differentiation, and survival, including those located in the Ras and Rac signaling pathways."
Am J Pathol. 2000 Jul;157(1):59-68. Gene expression profile in prion protein-deficient fibroblasts in culture. Satoh J, Kuroda Y, Katamine S. Division of Neurology, Department of Internal Medicine, Saga Medical School, Japan. satoj1@post.saga-med.ac.jp PMID: 10880376
ajp.amjpathol.org...
* Mandibular osteosarcoma with unusual expression of alpha-actin smooth muscle antibody. Pathol Res Pract. 1996 Feb;192(2):148-53. Remadi S, Samson J, Sando Z, Kuffer R. PMID: 8692715
* [Immunohistochemical differentiation of leiomyocellular tumors and tumors with myogenic differentiation] Cesk Patol. 2003 Apr;39(2):64-8. Povysil C, Ciprova V, Dundr P, Horakova M. Ustav patologie 1. LF UK a VFN, Praha. PMID: 12874903



* Arrhythmic sudden cardiac death in a 3-year-old child with intimal fibroplasia of coronary arteries, aorta, and its branches. Cardiovasc Pathol. 2001 Jan-Feb;10(1):43-8. Maresi E, Becchina G, Ottoveggio G, Orlando E, Midulla R, Passantino R. Department of Pathology, University of Palermo, Via Gustavo Rocella 61, 90128 Palermo, Italy. emilianomaresi@hotmail.com PMID: 11343995

We report an unusual case of "arrhythmic" sudden cardiac death in a 3-year-old child who died of ischemic myocardial lesions as a result of intimal fibroplasia of the coronary arteries. Also affected were the aorta and its major branches, whereas renal and mesenteric arteries, celiac trunk, and systemic veins were normal. Histopathologic examination showed severe concentric thickening of intima because of a proliferation of spindle-shaped cells (mesenchymal cells) set in an abundant extracellular matrix. In some vascular segments the intima was densely fibrotic and hyalinized. No significant inflammation, foam cells, cholesterol clefts, or other evidence of atheroma were present. The intimal lesions did not involve the media and/or the adventitia. Immunohistochemical staining of intima showed the proliferating mesenchimal cells to be myofibroblastic. Reactions for vimentin and smooth muscle actin were positive, while those for desmin, myosin, CD34, and Factor VIII were negative.



* Relaxin modulates cardiac fibroblast proliferation, differentiation and collagen production and reverses cardiac fibrosis in vivo. Endocrinology. 2004 May 20 Samuel CS, Unemori EN, Mookerjee I, Bathgate RA, Layfield SL, Mak J, Tregear GW, Du XJ. Howard Florey Institute of Experimental Physiology and Medicine (C.S.S., I.M., R.A.D.B., S.L.L., G.W.T.), University of Melbourne, Victoria 3010, Australia; Connetics Corporation (E.N.U., J.M.), Palo Alto, CA 94303; and Baker Heart Research Institute (X.D.), Melbourne, Victoria 8008, Australia. PMID: 15155573

Cardiac fibrosis is a key component of heart disease, and involves the proliferation and differentiation of matrix-producing fibroblasts. The effects of an anti-fibrotic peptide hormone, relaxin, in inhibiting this process were investigated. We used rat atrial and ventricular fibroblasts, which respond to pro-fibrotic stimuli and express the relaxin receptor (LGR7), in addition to two in vivo models of cardiac fibrosis. Cardiac fibroblasts when plated at low-density or stimulated with transforming growth factor-beta (TGF-beta) or Angiotensin II (Ang II) accelerated fibroblast differentiation into myofibroblasts, as demonstrated by significantly increased alpha-smooth muscle actin (alpha-SMA) expression, collagen synthesis and collagen deposition (by up to 95% with TGF-beta and 40% with Ang II; all P < 0.05). …findings indicate that relaxin regulates fibroblast proliferation, differentiation and collagen deposition and may have therapeutic potential in diseased states characterized by cardiac fibrosis.






Actin, the Brain, Mad Cow and Other Prion Related Diseases

Description of actin proteins' various roles in body and disease, how targeted by drugs (pdf)

"The mRNAs of two cytoskeletal components, glial fibrillary acidic protein (GFAP) and beta actin, varied significantly, and differently, during brain development ...The beta actin mRNAs peaked at day 1 after a slight increase, then dropped rapidly during the first 15 days postnatal, and thereafter remained at a level which was strictly maintained throughout development and adulthood."
* Brain Res Mol Brain Res. 1991 Jul;10(4):343-6. Regulation of the glial fibrillary acidic protein, beta actin and prion protein mRNAs during brain development in mouse. Lazarini F, Deslys JP, Dormont D. Laboratoire de Neuropathologie Experimentale et Neurovirologie, CRSSA, Commissariat a l'Energie Atomique, DPTE/DSV, Fontenay-aux Roses, France. PMID: 1681406

...The antiprion drug latrunculin works by disrupting the actin cytoskeleton and research shows that "yeast cells are efficiently cured of the [PSI] prion by prolonged incubation with latrunculin (and) ...points to the possible relationships between prions and (actin) cytoskeletal networks." Methods Enzymol 2002;351:499-538.
* An antiprion effect of the anticytoskeletal drug latrunculin A in yeast. Gene Expr 2000;9(3):145-56. An antiprion effect of the anticytoskeletal drug latrunculin A in yeast. Bailleul-Winslett PA, Newnam GP, Wegrzyn RD, Chernoff YO. School of Biology, Georgia Institute of Technology, Atlanta, Georgia 30332-0230

"Expression of PrP was well correlated with that of SM {alpha}-actin, a well known marker for stellate cell activation. ...These results indicate that PrP expression is closely related to stellate cell activation associated with fibrogenic stimuli. ...This study demonstrated that expression of PrP mRNA and its protein was negligible in normal liver tissue, a finding consistent with previous studies. However, it was found to increase dramatically in diseased livers associated with stellate cell activation. ...It has been also suggested that PrPc may function as a neural cell receptor or a cell adhesion molecule, directing and/or maintaining the architecture of the nervous system.26,27 The demonstration by immunoelectron microscopy that PrPc localizes on the surface of activated stellate cells is consistent with this view. ...the present finding of the restricted expression of PrP mRNA and protein in activated stellate cells both in vitro and in vivo suggests that PrP expression could be involved in the development of liver fibrosis."
Am J Pathol. 1998 Dec;153(6):1695-700. Expression of cellular prion protein in activated hepatic stellate cells. Ikeda K, Kawada N, Wang YQ, Kadoya H, Nakatani K, Sato M, Kaneda K. Department of Anatomy, Osaka City University Medical School, Osaka, Japan. ikeda@med.osaka-cu.ac.jp PMID: 9846959
ajp.amjpathol.org...

"These results indicate that the disruption of the PrP gene resulted in an aberrant regulation of a battery of genes important for cell proliferation, differentiation, and survival, including those located in the Ras and Rac signaling pathways. ...PrPC might play a role in the organization of signaling complexes in CLDs (rafts), and the deficiency of its function might disturb the CLD- (raft-) associated signal transduction that is pivotal for protection against oxidative stress and apoptosis, or for synaptic transmission..."
* Gene expression profile in prion protein-deficient fibroblasts in culture. Am J Pathol. 2000 Jul;157(1):59-68. Satoh J, Kuroda Y, Katamine S. Division of Neurology, Department of Internal Medicine, Saga Medical School, Japan. satoj1@post.saga-med.ac.jp PMID: 10880376
ajp.amjpathol.org...

* Expression of unglycosylated mutated prion protein facilitates PrP(Sc) formation in neuroblastoma cells infected with different prion strains. J Gen Virol. 2000 Oct;81(Pt 10):2555-63. Korth C, Kaneko K, Prusiner SB. Institute for Neurodegenerative Diseases and Departments of Neurology and Biochemistry and Biophysics, Box 0518, University of California, San Francisco, CA 94143-0518, USA. PMID: 10993946
vir.sgmjournals.org...

* Interaction of D-lactate dehydrogenase protein 2 (Dld2p) with F-actin: Implication for an alternative function of Dld2p. Biochem Biophys Res Commun. Hachiya NS, Sakasegawa Y, Jozuka A, Tsukita S, Kaneko K: [PubMed]
* Stimulation of Cellular Prion Protein (PrPc) Expression by Thyroid Stimulating Hormone in Human Thyroid Follicles. Biochem Biophys Res Commun, 305: 1034-1039,2003 Yamazaki K, Yamada E, Kanaji Y, Yanagisawa T, Kato Y, Sato S, Takano K, Sakasegawa Y, Kaneko K. [PubMed]
* Stimulation of cellular prion protein expression by TSH in human thyrocytes. Biochem Biophys Res Commun. 2003 Jun 13;305(4):1034-9. Yamazaki K, Yamada E, Kanaji Y, Yanagisawa T, Kato Y, Sato K, Takano K, Sakasegawa Y, Kaneko K. Thyroid Disease Institute, Kanaji Hospital, Kita-ku, Tokyo 114-0015, Japan. PMID: 12767934
* Interaction of D-lactate dehydrogenase protein 2 (Dld2p) with F-actin: implication for an alternative function of Dld2p. Biochem Biophys Res Commun. 2004 Jun 18;319(1):78-82. Hachiya NS, Sakasegawa Y, Jozuka A, Tsukita S, Kaneko K. Department of Cortical Function Disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. PMID: 15158445
* Ecm10p localizes in yeast mitochondrial nucleoids and its overexpression induces extensive mitochondrial DNA aggregations. Biochem Biophys Res Commun. 2003 Sep 12;309(1):217-21. Sakasegawa Y, Hachiya NS, Tsukita S, Kaneko K. Department of Cortical Function Disorders, National Institute of Neuroscience (NIN), National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi Kodaira, Tokyo, Japan. PMID: 12943685

Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature. 2001 Aug 16;412(6848):739-43. Peretz D, Williamson RA, Kaneko K, Vergara J, Leclerc E, Schmitt-Ulms G, Mehlhorn IR, Legname G, Wormald MR, Rudd PM, Dwek RA, Burton DR, Prusiner SB. Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94143-0518, USA. PMID: 11507642

“…the actin cytoskeleton plays a central role in the physiology and diseases of the intrahepatic bile duct.”
Emerging roles of the actin cytoskeleton in cholangiocyte function and disease. Semin Liver Dis. 2002 Aug;22(3):263-76. Doctor RB, Fouassier L. Division of Gastroenterology and Hepatology, University of Colorado Health Sciences Center, Denver, Colorado, USA. brian.doctor@uchsc.edu PMID: 12360420

RE: SICK BUILDING SYNDROME?
* Involvement of Secreted Aspergillus fumigatus Proteases in Disruption of the Actin Fiber Cytoskeleton and Loss of Focal Adhesion Sites in Infected A549 Lung Pneumocytes. J Infect Dis. 2004 Jun 1;189(11):1965-73. Epub 2004 May 11. Kogan TV, Jadoun J, Mittelman L, Hirschberg K, Osherov N. Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. PMID: 15143461

Aspergillus fumigatus is an opportunistic pathogenic fungus that predominantly infects the respiratory system. Penetration of the lung alveolar epithelium is a key step in the infectious process. The cytoskeleton of alveolar epithelial cells forms the cellular basis for the formation of a physical barrier between the cells and their surroundings. This study focused on the distinct effects of A. fumigatus on the actin cytoskeleton of A549 lung pneumocytes. Of the 3 major classes of cytoskeletal fibers--actin microfilaments, microtubules, and intermediate filaments--only the actin cytoskeleton was found to undergo major structural changes in response to infection, including loss of actin stress fibers, formation of actin aggregates, disruption of focal adhesion sites, and cell blebbing. These changes could be specifically blocked in wild-type strains of A. fumigatus by the addition of antipain, a serine and cysteine protease inhibitor, and were not induced by an alkaline serine protease-deficient strain of A. fumigatus. Antipain also reduced, by ~50%, fungal-induced A549 cell detachment from the plates and reduction in viability. Our findings suggest that A. fumigatus breaches the alveolar epithelial cell barrier by secreting proteases that act together to disorganize the actin cytoskeleton and destroy cell attachment to the substrate by disrupting focal adhesions.


"Unique vasculopathy following herpes virus infection might be a more severe and extensive disease. We speculate that sustained viral infection, repetitive activation of virus related antigens, and suppressed immune state might contribute to formation of peculiar vascular alterations."
(J Rheumatol 2004;31:925-30) Department of Medicine, the Japan Self Defense Forces Central Hospital, Tokyo, Japan. J. Shimizu, MD; A. Inatsu, MD; S. Oshima, MD; T. Kubota, MD.
Unique Angiopathy After Herpes Virus Infection


Other notes

IMPORTANT re actin filament chain
Synopses of Research Articles
File Format: PDF/Adobe Acrobat - View as HTML
... sequences,such as those found in the human prion protein responsible for ... the protein
complex that initiates actin polymerization.Called actin-related protein 2 ...
www.bioengineering.ucsf.edu...

Interesting - evolutionary analysis of metabolism

Trafficking of prion proteins through a caveolae-mediated pathway
describes role of actin in caveolae...
File Format: PDF/Adobe Acrobat - View as HTML
... JCB Article 703 Trafficking of prion proteins through a caveolae-mediated endosomal
pathway ... Introduction Prion diseases are fatal neurodegenerative disorders. ...
www.nki.nl...
caveolae = plasma membrane anchored by actin cytoskeleton
NOTE - refers to SV40 infected cells, creation of caveosomes


More on Misfolded Actin - Cross-Kingdom Impacts

"At the subcellular level, cell shape changes are linked to severe filamentous actin aggregation and compromised vacuole fusion."
* Mutations in actin-related proteins 2 and 3 affect cell shape development in Arabidopsis. Plant Cell. 2003 Jul;15(7):1632-45. Mathur J, Mathur N, Kernebeck B, Hulskamp M. Botanical Institute III, University of Koln, D 50931 Koln, Germany. jaideep.mathur@uni-koeln.de PMID: 12837952
www.plantcell.org...

Dutch Elm Disease - Actin
...integrins also facilitate adhesion and cause reorganization of actin filaments

* Surface attachment and pre-penetration stage development by plant pathogenic fungi. Annu Rev Phytopathol. 2001;39:385-417. Tucker SL, Talbot NJ. School of Biological Sciences, University of Exeter, Washington Singer Laboratories, Perry Road, Exeter, EX4 4QG, United Kingdom. PMID: 11701871



"... of an immature myocardium; for example, smooth muscle a-actin and ß ... studies point
to a specific role of atrial loading conditions in fibrosis accumulation. ..."
pdf - Atrial Fibrillation: the Tip of the Iceberg

"Renal interstitial fibrosis is the final common pathway leading to end stage renal disease in various nephropathies including renal amyloidosis. ...Abstract : Renal interstitial fibrosis is the final common ... of anti a smooth uscle
cell actin SMA stained ... and the fractional area of a SMA positive interstitium ..."
pdf - Interstitial Mast Cell Accumulation in AA type Renal Amyloidosis

"Diabetes Care: Accumulation of N[H.sub.2]-terminal fragment of ... was predominantly localized to smooth muscle actin-positive myofibroblasts ... for induction of fibrosis and neovascularization ..."
Myofibroblasts and Diabetic Retinopathy

Of Interest: How a Slime Mold Came to the Aid of Alzheimer's Research



More Background/History

Detection of Kaposi's sarcoma(KS)-associated herpesvirus-like DNA sequence(KSHV) in vascular lesions: A reliable diagnostic marker for KS. Am. J. Clin. Pathol. 105:360~363,1996. Jin, Y.T., S.T. Tsai., J.J. Yan., J.H. Hsiao., Y.Y. Lee. and I.J. Su.

1978 - Actin filaments in paramyxovirus-infected human fibroblasts studied by indirect immunofluorescence. PMID: 356824
1983 - Fate of microfilaments in vero cells infected with measles virus and herpes simplex virus type 1. PMID: 6343843
1985 - Interaction of frog virus 3 with the cytomatrix. III. Role of microfilaments in virus release. PMID: 4060576
1986 - Use of indirect immunofluorescence to show changes in liver actin microfilament staining in inbred mice strains exposed to the mycotoxin sporidesmin. PMID: 3526071
1986 - HERPES - Involvement of actin-containing microfilaments in HSV-induced cytopathology and the influence of inhibitors of glycosylation. PMID: 3022680
1987 - Distribution by immunofluorescence of viral products and actin-containing cytoskeletal filaments in rubella virus-infected cells. PMID: 3545151

1988 - Changes in cellular microfilaments in viral infection. PMID: 2854678
1989 - Aggregation of membrane-associated actin filaments following localized adherence of enteropathogenic Escherichia coli to HeLa cells. PMID: 2691516
1989 - Opposing microtubule- and actin-dependent forces in the development and maintenance of structural polarity in retinal photoreceptors. PMID: 2642427
1980 - Accumulation of actin microfilaments in adult rat hepatocytes cultured on collagen gel/nylon mesh. PMID: 6893678
1990 - Actin filament nucleation by the bacterial pathogen, Listeria monocytogenes. PMID: 2125302

1990 - Actin gene expression in murine erythroleukemia cells treated with cytochalasin D. PMID: 2347376
1990 - The role of microfilaments and microtubules in apical growth and dimorphism of Candida albicans. PMID: 2200842
1991 - Requirement of microfilaments in sorting of actin messenger RNA. PMID: 1891715
1991 - Sequential rearrangement and nuclear polymerization of actin in baculovirus-infected Spodoptera frugiperda cells.
PMID: 1995943
1993 - Directional actin polymerization associated with spotted fever group Rickettsia infection of Vero cells. PMID: 8478082
1993 - Actin microfilaments dynamics in African green monkey renal cell line (Vero) during cultivation. PMID: 8186459
1993 - Dissociation of actin microfilament organization from acquisition and maintenance of elongated shape of human dermal fibroblasts in three-dimensional collagen gel. PMID: 8309424
1994 - Characterization of a monoclonal antibody prepared against plant actin. PMID: 7859296
1994 - Effects of thymosin beta 4 and thymosin beta 10 on actin structures in living cells. PMID: 8194107
1994 - Concentration-dependent effects of cytochalasin D on tight junctions and actin filaments in MDCK epithelial cells. PMID: 8006058
1995 - Myosin-actin interaction plays an important role in human immunodeficiency virus type 1 release from host cells. PMID: 7892219
1995 - Proteolysis of p6.9 induced by cytochalasin D in Autographa californica M nuclear polyhedrosis virus-infected cells.PMID: 7871717
1996 - HIV-1 Gag protein associates with F-actin present in microfilaments. PMID: 8661406
1996 - Plant and animal profilins are functionally equivalent and stabilize microfilaments in living animal cells. PMID: 8834793
1996 - Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton of the parasite. PMID: 8601316

1997 - Microtubule-associated protein 2c reorganizes both microtubules and microfilaments into distinct cytological structures in an actin-binding protein-280-deficient melanoma cell line. PMID: 9049250
1997 - Pasteurella multocida enters polarized epithelial cells by interacting with host F-actin. PMID: 9100334
1997 - Both microtubules and actin filaments are required for efficient postendocytotic traffic of the polymeric immunoglobulin receptor in polarized Madin-Darby canine kidney cells. PMID: 9045707
1998 - Involvement of actin microfilaments in the replication of human parainfluenza virus type 3. PMID: 9525582
1998 - Role of cellular actin in the gene expression and morphogenesis of human respiratory syncytial virus. PMID: 9875324
1998 - Disruption of actin microfilaments by cytochalasin D leads to activation of p53. PMID: 9688570
1998 - Cytochalasin D alters kinetics of Ca2+ transient in rat ventricular cardiomyocytes: an effect of altered actin cytoskeleton? PMID: 9737950
1998 - Actin binding and nucleation by Autographa california M nucleopolyhedrovirus. PMID: 9527926
1999 - Involvement of actin microfilaments in the transcription/replication of human parainfluenza virus type 3: possible role of actin in other viruses. PMID: 10523790
1999 - Organized F-actin is essential for normal trichome morphogenesis in Arabidopsis. PMID: 10590162
1999 - Actinobacillus actinomycetemcomitans may utilize either actin-dependent or actin-independent mechanisms of invasion. PMID: 10495707
1999 - The role of actin microfilaments in the down-regulation of the degranulation response in RBL-2H3 mast cells. PMID: 9973500
1999 - Distribution of cytoskeletal structures and organelles of the host cell during evolution of the intracellular parasitism by Trypanosoma cruzi. PMID: 10626001
1999 - Role of actin filaments in the hatching process of mouse blastocyst. PMID: 10418105
1999 - "HIV-1 NCp7 can bind F-actin directly and ...interaction between HIV-1 Gag and the actin cytoskeleton through the NC domain may play an important role in HIV-1 assembly and/or other steps of the viral life cycle." PMID: 10074138
2000 - Filamentous actin is required for lepidopteran nucleopolyhedrovirus progeny production. PMID: 10859396
2000 - Enhancement of herpes simplex virus-induced polykaryocyte formation by 12-O-tetradecanoyl phorbol 13-acetate: association with the reorganization of actin filaments and cell motility. PMID: 11044806
2001 - "A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization." PMID:11136447
2001 - Hantavirus nucleocapsid protein is expressed as a membrane-associated protein in the perinuclear region. PMID: 11160679
2001 - Actin microfilaments facilitate the retrograde transport from the Golgi complex to the endoplasmic reticulum in mammalian cells. PMID: 11576448
2001 - Actin cytoskeleton role in the structural response of epithelial (MDCK) cells to low extracellular Ca2+. PMID: 11763195
2002 - Participation of host cell actin filaments during interaction of trypomastigote forms of Trypanosoma cruzi with host cells. PMID: 12207050
2002 - A functional link between the actin cytoskeleton and lipid rafts during budding of filamentous influenza virions.
PMID: 12359424
2002 - Cytoskeletal changes during poliovirus infection in an intestinal cell line. PMID: 12138662
2002 - Microinjected anti-actin antibodies decrease gap junctional intercellular commmunication in cultured astrocytes. PMID: 12460650
2002 - Chlamydia trachomatis induces remodeling of the actin cytoskeleton during attachment and entry into HeLa cells.
PMID: 12065523
2003 - Actin filaments participate in West Nile (Sarafend) virus maturation process. PMID: 12966555
***2003 - Interaction of HLA-DR with actin microfilaments. PMID: 12590977***
2003 - Effects of cytochalasin D on the actin cytoskeleton: association of neoformed actin aggregates with proteins involved in signaling and endocytosis. PMID: 12827288
2003 - Disruption of F-actin stimulates hypertonic activation of the BGT1 transporter in MDCK cells. PMID: 12527556
2004 - Role of actin microfilaments in canine distemper virus replication in vero cells. PMID: 15133271
2004 - Role of actin filaments in targeting of Crimean Congo hemorrhagic fever virus nucleocapsid protein to perinuclear regions of mammalian cells. PMID: 14635015
2004 - Actin filaments play an essential role for transport of nascent HIV-1 proteins in host cells. PMID: 15020258
2004 - Role of cytoskeleton components in measles virus replication. PMID: 15098105


MECHANICS
ACTIN - IN ALL LIVING CYTOSKELETONS - MEMBRANES (INSIDE OUTSIDE)
1990 - Microinjection of covalently cross-linked actin oligomers causes disruption of existing actin filament architecture in PtK2 cells. PMID: 2277094
1992 - Distribution of F-actin during mouse facial morphogenesis and its perturbation with cytochalasin D using whole embryo culture. PMID: 1517392
1994 - Differences in the G/total actin ratio and microfilament stability between normal and malignant human keratinocytes.PMID: 7834816
1998 - Actin microfilaments are essential for the cytological positioning and morphology of the Golgi complex. PMID: 9650778
1999 - Expression and characterization of Cys374 mutated human beta-actin in two different mammalian cell lines: impaired microfilament organization and stability. PMID: 10428484
2000 - Cytochalasin D reduces Ca2+ sensitivity and maximum tension via interactions with myofilaments in skinned rat cardiac myocytes. PMID: 11101650
2000 - Optimal development of Chlamydophila psittaci in L929 fibroblast and BGM epithelial cells requires the participation of microfilaments and microtubule-motor proteins. PMID: 10839969
2002 - Endoplasmic reticulum calcium release is modulated by actin polymerization. PMID: 12358800
2000 - Actin filament disruption inhibits L-type Ca(2+) channel current in cultured vascular smooth muscle cells. PMID: 10913014
2000 - Changes in actin network during calcium-induced exocytosis in permeabilized GH3 cells: calcium directly regulates F-actin disassembly. PMID: 10974661
2000 - Actin depolymerization and polymerization are required during apoptosis in endothelial cells. PMID: 10867649
2000 - Specific types of prosomes distribute differentially between intermediate and actin filaments in epithelial, fibroblastic and muscle cells. PMID: 10928458
2000 - Effects of cross-linked profilin:beta/gamma-actin on the dynamics of the microfilament system in cultured cells. PMID: 10739658
2001 - Actin filament nucleation by endosomes, lysosomes and secretory vesicles. PMID: 11163138
2001 - Actin filaments and myosin I alpha cooperate with microtubules for the movement of lysosomes. PMID: 11739797


1998 - Stable expression of nucleocapsid proteins of Puumala and Hantaan virus in mammalian cells. PMID: 9857992
1997 - Modification of cytoskeleton and prosome networks in relation to protein synthesis in influenza A virus-infected LLC-MK2 cells. PMID: 9381792
2004 - Tula hantavirus L protein is a 250 kDa perinuclear membrane-associated protein. PMID: 15105534
1994 - The role of microfilaments and microtubules during pH-regulated morphological transition in Candida albicans. PMID: 8180693
2002 - Involvement of SipA in modulating actin dynamics during Salmonella invasion into cultured epithelial cells. PMID: 2116966
1999 - Induction of an acrosomal process in Toxoplasma gondii: visualization of actin filaments in a protozoan parasite. PMID: 10430901
2003 - A role for glycoprotein C in pseudorabies virus entry that is independent of virus attachment to heparan sulfate and which involves the actin cytoskeleton. PMID: 12667810

IMMUNE
2002 - Actin mediates secretory immunoglobulin A transport: effect of ethanol. PMID: 12356147

PLANTS
1987 - Effects of microfilament disrupters on microfilament distribution and morphology in maize root cells. PMID: 3623996
2001 - Actin polymerization is essential for pollen tube growth. PMID: 11514633
2002



posted on Apr, 3 2005 @ 11:28 AM
link   
continued from above:

PLANTS
2002 - Microtubules and microfilaments in cell morphogenesis in higher plants. PMID: 12361589

CHEMICAL TOXINS AND ACTIN
1990 - The effects of delta-9-tetrahydrocannabinol on actin microfilaments. PMID: 2175259

GENETICS
2000 - Polymerization of nonfilamentous actin into microfilaments is an important process for porcine oocyte maturation and early embryo development. PMID: 10775164



posted on Apr, 3 2005 @ 11:32 AM
link   
1982
"The host's immune system may play both a protective and a pathogenic role."
Rev Infect Dis. 1982 Jul-Aug;4(4):851-8. Giardiasis: host-pathogen biology. Stevens DP. PMID: 6750749

1997
"Only recently recognized as human pathogens, ...Cryptosporidium and Cyclospora have been shown to be transmitted through fecally contaminated food and water. The mode of transmission for microsporidia is still unclear. The laboratory diagnosis of these protozoa is difficult. The routine ova and parasites screen does not include screening for them."
Clin Lab Sci. 1997 Sep-Oct;10(5):273-8. Emerging intestinal protozoa: a diagnostic dilemma. Collins PA, Wright MS. University of Kentucky, Lexington 40536-0080, USA. PMID: 10177205

Brasseur P. Waterborne cryptosporidiosis: a major environmental risk. J Eukaryot Microbiol. 1997 Nov-Dec;44(6):67S-68S. PMID: 9508449

1998
"...disease associated with exposure to low levels of waterborne protozoa are of increasing concern. Current methodologies may not be sensitive enough to define these low levels of disease. ...Single microbial exposures (non-threshold) are capable of causing symptomatic illness unlike traditional chemical exposures, which require a threshold to be reached. Due to the lack of efficient recovery and detection methods for protozoa, we may be underestimating the occurrence, concentration and distribution of these pathogenic micro-organisms."
Parasitology. 1998;117 Suppl:S205-12. Risk assessment of waterborne protozoa: current status and future trends. Gibson CJ 3rd, Haas CN, Rose JB. Department of Marine Science, University of South Florida, St. Petersburg 33701, USA. PMID: 10660941

"The initial cases were not diagnosed as cryptosporidiosis by the health-care system despite patients seeking care, underscoring the need for increased awareness of cryptosporidiosis and routine laboratory diagnostic practices among health-care providers."
MMWR Morb Mortal Wkly Rep. 1998 Oct 16;47(40):856-60. Outbreak of cryptosporidiosis associated with a water sprinkler fountain--Minnesota, 1997. PMID: 9790661

"The signs are that the growing strength of molecular epidemiology on the one side, and of a global epidemiology based on information systems on the other, will come to dominate epidemiology and segregate it into separate disciplines. At the same time, the links with public health interests grow weaker. A multilevel ecoepidemiology has the potential to bind these strands together."
J Epidemiol Community Health. 1998 Oct;52(10):608-11. Does risk factor epidemiology put epidemiology at risk? Peering into the future. Susser M. Columbia University, Sergievsky Center, New York, NY 10032, USA. PMID: 10023453

1999
"Recognized as waterborne parasites, Giardia, Cryptosporidium, and Cyclospora have now been associated with several foodborne outbreaks. The oocysts and cysts of these organisms can persist and survive for long periods of time both in water and on foods. As a result, these parasites have emerged as public health risks and have become a concern to the food industry. Control and prevention of protozoan foodborne disease depends upon our ability to prevent, remove, or kill protozoan contaminants. This review will address the biology, foodborne and waterborne transmission, survival, and methods for detection and control ...."
J Food Prot. 1999 Sep;62(9):1059-70. Giardia, Cryptosporidium, and Cyclospora and their impact on foods: a review. Rose JB, Slifko TR. Department of Marine Science, University of South Florida, St. Petersburg 33701, USA. PMID: 10492484

2000
"The environmental route of transmission is important for many protozoan and helminth parasites, with water, soil and food being particularly significant. Both the potential for producing large numbers of transmissive stages and their environmental robustness, being able to survive in moist microclimates for prolonged periods of time, pose a persistent threat to public and veterinary health. Global sourcing of food, coupled with changing consumer vogues, including the consumption of raw vegetables and undercooking to retain the natural taste and preserve heat-labile nutrients, can increase the risk of foodborne transmission. Robust, efficient detection, viability and typing methods are required to assess risks and to further epidemiological understanding."
Int J Parasitol. 2000 Nov;30(12-13):1379-93. Emerging parasite zoonoses associated with water and food. Slifko TR, Smith HV, Rose JB. College of Marine Science, University of South Florida, 140 7th Avenue South, FL 33701, St. Petersburg, USA. PMID: 11113263

"Various disinfection processes ...produce certain types and amounts of disinfection by-products (DBPs), including trihalomethanes (THM), haloacetic acids, haloacetonitriles, and bromate, among others. Human health risks from the ubiquitous exposure to complex mixtures of DBPs are of concern because existing epidemiologic and toxicologic studies suggest the existence of systemic or carcinogenic effects."
Drug Chem Toxicol. 2000 Feb;23(1):307-21. A multiple-purpose design approach to the evaluation of risks from mixtures of disinfection by-products. Teuschler LK, Gennings C, Stiteler WM, Hertzberg RC, Colman JT, Thiyagarajah A, Lipscomb JC, Hartley WR, Simmons JE. NCEA, U.S. EPA, Cincinnati, OH, USA. PMID: 10711404

"The measures needed to prevent food-borne protozoa causing disease require clear assessments of the risks of contamination and the effectiveness of processes to inactivate them. The globalisation of food production can allow new routes of transmission, and advances in diagnostic detection methods and surveillance systems have extended the range of protozoa that may be linked to food."
Br Med Bull. 2000;56(1):209-35. Food-borne protozoa. Nichols GL. Environmental Surveillance Unit, Communicable Disease Surveillance Centre, London, UK. PMID: 10885117

"These findings, ...clearly demonstrate the presence of low level, asymptomatic infections in post-weaned and adult cattle in the United States and indicate the potential role of such cattle as reservoirs of infectious parasites."
Vet Parasitol. 2000 Nov 10;93(2):103-12. Prevalence of Cryptosporidium, Giardia and Eimeria infections in post-weaned and adult cattle on three Maryland farms. Fayer R, Trout JM, Graczyk TK, Lewis EJ. United States Department of Agriculture, Agricultural Research Service, 10300 Baltimore Avenue, Building 1040, Beltsville, MD 20705, USA. PMID: 11035228

"Waterborne diseases, such as cryptosporidiosis, cause many cases of serious illness in the United States annually. Recommendations are made for government actions that would increase the efficiency of efforts to ensure water quality; protect watersheds; strengthen waterborne disease surveillance; and protect the health of vulnerable populations."
Am J Public Health. 2000 Jun;90(6):847-53. Water quality laws and waterborne diseases: Cryptosporidium and other emerging pathogens. Gostin LO, Lazzarini Z, Neslund VS, Osterholm MT. Georgetown/Johns Hopkins Program on Law and Public Health, Washington, DC, USA. PMID: 10846499

"During the last 30 years, our concept of cryptosporidiosis has changed from that of a rare, largely asymptomatic disease, to an important cause of diarrhea in animals and humans worldwide. Cryptosporidium are now ubiquitous and disease has been described in over 79 host species. "
Ann N Y Acad Sci. 2000;916:102-11. Cryptosporidiosis. A global challenge. Mosier DA, Oberst RD. Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas 66506, USA. PMID: 11193609

2001
"...waterborne infections from agents such as Cryptosporidium parvum and Escherichia coli: O157:H7 might be transmitted from contaminated water to humans through drinking water; from interpersonal contact; or from infected individuals to the environment, and back to other susceptible individuals. These multiple pathways and the dependency of exposure on the prevalence of infection in a population suggest that epidemiological models are required to complement standard risk assessments in order to quantify the risk of infection. This paper presents new models of infection transmission systems that ...are designed to help inform water treatment system design decisions."
Sci Total Environ. 2001 Jul 2;274(1-3):197-207. Infection transmission system models for microbial risk assessment. Chick SE, Koopman JS, Soorapanth S, Brown ME. Department of Industrial and Operations Engineering, The University of Michigan, Ann Arbor 48109-2117, USA. PMID: 11453296

"Unusual findings included two enteroinvasive E. coli strains, one Shigella dysenteriae 2 isolate, and a non-O:1 Vibrio cholerae culture. EPEC bacteria and S. flexneri (but not Salmonella) showed unusually frequent antimicrobial resistance, especially towards beta-lactam antibiotics..."
J Clin Microbiol. 2001 Jun;39(6):2134-9. Etiology of children's diarrhea in Montevideo, Uruguay: associated pathogens and unusual isolates. Torres ME, Pirez MC, Schelotto F, Varela G, Parodi V, Allende F, Falconi E, Dell'Acqua L, Gaione P, Mendez MV, Ferrari AM, Montano A, Zanetta E, Acuna AM, Chiparelli H, Ingold E. Bacteriology and Virology Department, Institute of Hygiene, School of Medicine, Universidad de la Republica, CP 11600, Montevideo, Uruguay. PMID: 11376047
jcm.asm.org...

"This is the first time that parasites have been detected on vegetables and fruit obtained in a highly developed. wealthy country, without there being an outbreak situation. These findings may have important implications for global food safety."
J Food Prot. 2001 Nov;64(11):1793-8. Occurrence of parasites on fruits and vegetables in Norway. Robertson LJ, Gjerde B. Department of Pharmacology, Microbiology and Food Hygiene, The Norwegian School of Veterinary Science, Oslo. PMID: 11726161

2002
RE: CHRONICALLY INFECTED BUT ASYMPTOMATIC: "asymptomatic" means that the disease does not show up on standard tests - it does not mean that the disease is not progressive, or that infected people don't feel pain or other degenerative effects.

"...most of the participant families were chronically infected but asymptomatic. Our findings highlighted differences in the transmission mode of these two pathogens..."
Am J Trop Med Hyg. 2002 Jun;66(6):794-8. Hyperendemic Cryptosporidium and Giardia in households lacking municipal sewer and water on the United States-Mexico border. Redlinger T, Corella-Barud V, Graham J, Galindo A, Avitia R, Cardenas V. Department of Biologic Sciences and Center for Environmental Resource Management, The University of Texas at El Paso, 79968, USA. PMID: 12224594
www.ajtmh.org...

"The presence of human pathogenic parasites in irrigation waters used in the production of crops traditionally consumed raw suggests that there may be a risk of infection to consumers who come in contact with or eat these products."
J Food Prot. 2002 Feb;65(2):378-82. Detection of protozoan parasites and microsporidia in irrigation waters used for crop production. Thurston-Enriquez JA, Watt P, Dowd SE, Enriquez R, Pepper IL, Gerba CP. US Department of Agriculture, Agricultural Research Service, University of Nebraska, Lincoln 68583-0934, USA. PMID: 11848571

"...a risk assessment framework must be based on a description of the exposure and disease processes. Regarding exposure to waterborne pathogens, the appropriate framework is one that explicitly models the disease transmission pathways of pathogens. This approach provides a crucial link between science and policy."
Environ Health Perspect. 2002 Aug;110(8):783-90. Disease transmission models for public health decision making: analysis of epidemic and endemic conditions caused by waterborne pathogens. Eisenberg JN, Brookhart MA, Rice G, Brown M, Colford JM Jr. Center for Occupational and Environmental Health and School of Public Health, University of California, Berkeley, California, USA. PMID: 12153759
ehp.niehs.nih.gov...

"As the epidemiology of waterborne diseases is changing, there is a growing global public health concern about new and reemerging infectious diseases that are occurring through a complex interaction of social, economic, evolutionary, and ecological factors."
Crit Rev Microbiol. 2002;28(1):1-26. Emerging waterborne infections: contributing factors, agents, and detection tools. Theron J, Cloete TE. Department of Microbiology and Plant Pathology, University of Pretoria, South Africa. PMID: 12003038

�Problems in the management of waterborne communicable disease outbreaks.� Commun Dis Public Health. 2002 Sep;5(3):183-4. Mayon-White R. PMID: 12434687

"The results confirm the resistance of Clostridium perfringens spores, enteroviruses and protozoa to chlorination and demonstrate the relative persistence of these organisms in the effluents even during the ultraviolet light treatment. The yields also emphasise the influence of the analytical method for the determination of protozoan parasites."
New Microbiol. 2002 Oct;25(4):413-20. Fate of bacterial indicators, viruses and protozoan parasites in a wastewater multi-component treatment system. Bonadonna L, Briancesco R, Cataldo C, Divizia M, Donia D, Pana A. Istituto Superiore di Sanita, Laboratorio di Igiene Ambientale, Roma, Italy. PMID: 12437220

"The transmission of Cryptosporidium and Giardia through treated water supplies that meet water quality standards demonstrates that water treatment technologies have become inadequate, and that a negative coliform no longer guarantees that water is free from all pathogens, especially from protozoan agents. Substantial concern persists that low levels of pathogen occurrence may be responsible for the endemic transmission of enteric disease. In addition to Giardia and Cryptosporidium, some species of genera Cyclospora, Isospora, and of family Microsporidia are emerging as opportunistic pathogens and may have waterborne routes of transmission. More than 15 different groups of viruses, encompassing more than 140 distinct types can be found in the human gut. Some cause illness unrelated with the gut epithelium, such as Hepatitis A virus (HAV) and Hepatitis E virus (HEV). The most striking concern is that enteric viruses such as caliciviruses and some protozoan agents, such as Cryptosporidium, are the best candidates to reach the highest levels of endemic transmission, because they are ubiquitous in water intended for drinking, being highly resistant to relevant environmental factors, including chemical disinfecting procedures."
Crit Rev Microbiol. 2002;28(4):371-409. Microbial agents associated with waterborne diseases. Leclerc H, Schwartzbrod L, Dei-Cas E. Faculte de Medecine de Lille, and Institut Pasteur de Lille, France. PMID: 12546197

2003
"The major protozoan species that affect humans are Entamoeba histolytica, Acanthamoeba sp., Neagleria sp. Giardia intestinalis, Cryptosporidium parvum, Cyclospora cayetanensis, Toxoplasma gondii, Isospora/Sarcocystis sp. Encephalitozoom intestinals and Enterocytozoon bieneuisi. These parasites exist in the environment as oocyst, cysts or spores, which are the transmissive stages in many environmental conditions, e.g. water, soil, food as well as being infective stages to subsequent generation of hosts. Global concern with parasitic contamination of our environment must influence development of better detection methods and of evaluation and risk assessment of these infections."
Acta Microbiol Pol. 2003;52 Suppl:97-107. Environmental contamination with protozoan parasite infective stages: biology and risk assessment. Sinski E. Department of Parasitology, Institute of Zoology, Miecznikowa 1 str., 02-096 Warsaw, Poland. PMID: 15058818

"The results of this study do not support the hypothesis that drinking water is an independent risk factor for cryptosporidiosis .... These findings should be used to design larger studies of endemic cryptosporidiosis to elucidate the precise mechanisms of transmission, whether waterborne or other."
BMC Public Health. 2003 Mar 07;3(1):11. Print 2003 Mar 7. Is drinking water a risk factor for endemic cryptosporidiosis? A case-control study in the immunocompetent general population of the San Francisco Bay Area. Khalakdina A, Vugia DJ, Nadle J, Rothrock GA, Colford JM Jr. Division of Public Health Biology and Epidemiology, Centers for Family & Community Health and Occupational & Environmental Health, School of Public Health, University of California, Berkeley, California, USA. PMID: 12689343

"Our study showed that these two protozoan exist in dairy farm soil at different rates, and this risk could be modified by manipulating the pH of the soil."
J Dairy Sci. 2003 Mar;86(3):784-91. Factors associated with the likelihood of Giardia spp. and Cryptosporidium spp. in soil from dairy farms. Barwick RS, Mohammed HO, White ME, Bryant RB. Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. PMID: 12703614

"Predation by free-living protozoa and rotifers was investigated as a possible mechanism for the removal of Cryptosporidium parvum oocysts in aquatic ecosystems including wastewater treatment plants. All organisms investigated ingested oocysts. Predation activity and rates of ingestion varied with predator species and prey density. The significance of predation on the fate of Cryptosporidium oocysts in the environment is discussed."
Water Sci Technol. 2003;47(3):77-83. Predation of Cryptosporidium oocysts by protozoa and rotifers: implications for water quality and public health. Stott R, May E, Ramirez E, Warren A. Dept of Civil Engineering, University of Portsmouth, Portsmouth PO1 3QL, UK . PMID: 12639009

"Because filth flies carry viable C. parvum oocysts and G. lamblia cysts acquired naturally from unhygienic sources, they can be involved in the epidemiology of cryptosporidiosis and giardiasis."
Am J Trop Med Hyg. 2003 Feb;68(2):228-32. Detection of Cryptosporidium parvum and Giardia lamblia carried by synanthropic flies by combined fluorescent in situ hybridization and a monoclonal antibody. Graczyk TK, Grimes BH, Knight R, Da Silva AJ, Pieniazek NJ, Veal DA. The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA. PMID: 12641416
www.ajtmh.org...

OF SPECIAL NOTE:

�Animal prion infections, such as scrapie (sheep) and "mad cow disease" (cattle), have shown a pattern of horizontal transmission in farm conditions and several ectoparasites have been shown to harbor prion rods in laboratory experiments. Fly larvae and mites were exposed to brain-infected material and were readily able to transmit scrapie to hamsters. New lines of evidence have confirmed that adult flies are also able to express prion proteins. � Several cell types found on the human skin, including keratinocytes, fibroblasts and lymphocytes, are susceptible to the abnormal infective isoform of the prion protein, which transforms the skin to produce a potential target for prion infection.�
Int J Dermatol. 2003 Jun;42(6):425-9. Could ectoparasites act as vectors for prion diseases? Lupi O. Center for Vaccine Development, University of Texas Medical Branch at Galveston, Galveston, TX, USA. PMID: 12786866

2004
"This article provides an overview of the waterborne disease (WBD) issue in developed countries (USA, Canada, UK and other European countries). The factors involved in the epidemiology of waterborne infection are analysed (microbial, social, environmental, etc.) and the main WBD etiological agents are described with particular interest to emerging pathogens (i.e. Cryptosporidium parvum, Legionella and Calicivirus)."
Ann Ist Super Sanita. 2004;40(1):117-40. [Drinking water microbiological risk in developed countries] Carraro E, Bonetta S, Palumbo F, Gilli G. Dipartimento di Scienze dell'Ambiente e della Vita, Universita del Piemonte Orientale "A. Avogadro", Alessandria. PMID: 15269459
www.iss.it...

"Scientists have evidence that bacteria dangerous to humans have begun evolving in insects, for reasons that are not clear.
The October edition of Nature Reviews: Microbiology reports that invertebrates such as worms and insects may have begun enabling a rapid evolution for bacteria normally not harmful to humans. Not only are insects capable of delivering disease through bites and stings, they now may be the breeding ground for strains of infectious bacteria never before seen in humans."
Dangerous Bacteria Evolving in Insects
www.unknowncountry.com...

"Washington -- Scientists are researching ways that genetically modified (GM) insects could be used to stop the spread of diseases that affect livestock and crops, reduce pesticide use and create pharmaceutical proteins, said speakers at a "Biotech Bugs" conference held September 20-21 in Washington. However, speakers said, more regulations need to be developed, and must be clear and coordinated among government agencies to ensure that the development of improved insects includes adequate risk assessments."
"Biotech Bugs" Could Stop Spread of Diseases, Scientists Say
www.allamericanpatriots.com...

[Right. And infectious prions only cause brain disease. Not.]



The Fascists Creed: "It is infinitely easier to suffer in obedience to a human command than to accept suffering as free, responsible men."
Dietrich Bonhoeffer



posted on Apr, 6 2005 @ 09:43 AM
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Fibromuscular dysplasia (FMD) is caused by a misfolded protein called a-smooth muscle actin (a-SMA) - obviously an infectious prion protein. a-SMA is likely "Mad Cow" in its early stages, before it affects the brain directly. ...More important, a-SMA is able to access/infect/take over virtually any cell in the human body - and any other lifeform - via actin proteins present in every cells' cytoskeleton, membrane and nucleus. ...Misfolded actin proteins are implicated in most new diseases in most species and kingdoms - from Dutch Elm disease and gall cancers to the new pseudorabies, airborne E. coli and super bugs (C. difficile, MRSA, VRE, flesh eating disease (necrotizing fasciitis), and ESBL-producing bacteria) to most human cancers.


From FMD to Bird Flu, Super Bugs, Psuedo-Rabies and Cancer: How it Works

Between the 1960's and 1980's, FMD often was described as an "angiopathy" - a disease of the blood vessels and lymph vessels - which means the disease moves through the body via the blood and lymphatic systems. At first, FMD only infects the connective tissue inside the vessel walls but eventually, the a-SMA infects the vessels' "smooth muscle" cells. Smooth muscle cells can be up to 1500 meters long and loop through the body from head to foot 5 or 6 times. Once smooth muscle cells are infected, the disease can "pop up" virtually anywhere in the body.

As more and more cells are infected, the (misfolded) a-SMA builds up to form "fibrosis" and create "vacuoles" or holes in tissue (where cells are missing), creating cold-sore-like lesions. In blood vessels for example, the fibrosis creates blockages called "stenosis" and the vacuoles become aneurysms.

Eventually the lesions break through the vessel walls and then, infect new cells on contact - this is how FMD spreads from the blood and lymph vessels to glands, bone, joints and other parts of the body. Prions adapt to new cells by changing their "conformation" - meaning they mutate so they can infect other cells more easily. So as the disease moves through the body infecting new cells, it literally morphs into new and different diseases as it travels.

FMD is particularly adaptable and able to evolve because it is an actin protein - there are actin proteins in virtually every cell in the body, and in every other lifeform on earth. ...So FMD's a-SMA is like a master key that can get into any cell, anywhere. For example, if an infectious microbe comes into contact with FMD lesions inside the body, the a-SMA can get into the microbe's cells through actins in the microbe's cytoskeleton or membrane, and take it over and make it mutate - without killing it. ...This process creates new diseases too, and a-SMA can infect people, animals, plants, insects, bacteria, viruses, spirochetes, molds, protozoa - anything.


FMD and Mad Cow were mysteries for a long time - the mutation process was confusing, and the path the disease takes through the body was difficult to confirm. Progression - and the time progression can take (decades) - was difficult to understand. ...Prion related diseases are normally very slowly progressive, with active and inactive phases - the damage is cumulative and hits a critical peak with 1) Age (time); or 2) Exposure to triggers (chemicals, toxins, hormones, physical trauma, other pathogens).



Why FMD, Cancer and Other Prion Diseases Progress Very Slowly at First, Then Suddenly Speed Up

It's basic arithmetic - 1) Prions require direct cell-cell contact to spread; and 2) It's the nature of the "doubling phenomenon."

Here is a (hypothetical) case study by the numbers:

A 2 year-old is exposed to 1000 prions - each prion takes one year to make one single cell mutate and then, takes one year to infect and take over another cell - or "double" inside his body (without re-infection or exposure to additional triggers). ...So it takes *time* for mutated cells to accumulate in the body.

AGE NUMBER of PRION INFECTED CELLS

2. 1,000*
3. 2,000
4. 4,000
5. 8,000
6. 16,000
7. 32,000
8. 64,000
9. 128,000
10. 256,000
11. 512,000
12. 1,024,000*
13. 2,048,000
14. 4,096,000
15. 8,192,000
16. 16,384,000
17. 32,768,000
18. 65,536,000
19. 131,072,000
20. 262,144,000
21. 524,288,000
22. 1,048,576,000*
23. 2,097,152,000
24. 4,194,304,000
25. 8,388,608,000
26. 16,777,216,000
27. 33,554,432,000
28. 67,108,864,000
29. 134,217,720,000 (134.2)
30. 268,600,000,000
31, 537,200,000,000
32. 1,074,400,000,000*
33. 2,148,800,000,000
34. 4,297,600,000,000
35. 8,595,200,000,000
36. 17,190,400,000,000
37. 34,380,800,000,000
38. 68,761,600,000,000
39. 137,523,200,000,000
40. 275,046,400,000,000
41. 550,092,800,000,000
42. 1,100,185,600,000,000*
43. 2,200,037,120,000,000
44. 4,400,742,400,000,000
45. 8,801,484,800,000,000
46. 17,602,969,000,000,000
47. 35,205,938,000,000,000
48. 70,411,876,000,000,000
49. 140,823,750,000,000,000
50. 281,647,500,000,000,000
51. 563,295,000,000,000,000
52. 11,265,900,000,000,000,000*

IMPORTANT NOTE: It took 49 years for our hypothetical patient to accumulate 563,295,000,000,000,000 mutated cells - but only one more year to double that to 11,265,900,000,000,000,000 mutated cells...

So the important questions become:

* What was the amount of the initial exposure? When did exposure occur, and how long has the disease been spreading in the body?
* What is the actual rate of doubling?
* What influences the rate of doubling - either causing it to speed up or to slow down?
* At what point does the impact become significant? Ie., How many mutated cells does it take to cause disease or symptoms, or to affect functioning of a body part or system?
* What was the 'point of entry' and what path is the disease taking to spread through the body? ...What cells, organs and systems are most seriously affected?
* ...And this is BEFORE we consider the impact of additional exposures to other pathogens, mutagens, carcinogens etc. or the question, What are the subsequent exposures that might create new diseases inside the body?




Numerous financial interests are fighting against the obvious - and the legitimate research - and have been for decades. But now, as shown above, nearly 100% of Americans are infected - and most older adults are reaching the critical point of super-infection. These people do not necessarily die - but they do become very sick, or disabled and dysfunctional. Which is what we are not being told...


.



posted on Jan, 3 2006 @ 04:25 PM
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Please go here to comment or contribute.

Electropollution and chemical contaminations have altered the structure and composition of the organic molecules that circulate in this planet's ecosphere. Much research describes these altered molecules' impact on non-living systems like the earth's carbon, nitrogen and hydrogen cycles - but the science is being buried by the "global warming debate." Similarly, the research investigating the effects of altered organic molecules on living cells and organisms is overshadowed and obscured by the so-called evolution/intelligent design "debates" that pit science against religion - another obviously orchestrated polarization.

This thread is not a forum for debate on whether or not humans mutate and evolve - the premise is that a) humans do mutate and evolve, and b) the mutation/evolutionary process is escalating. The goal is to explain exactly and simply how our electrobiochemically altered world is triggering mutation, and causing an evolutionary crisis.


Premises

1. Altered organic molecules circulating in the ecosphere cause mutations in living organisms;
2. The numbers of altered organic molecules present in the ecosphere have grown exponentially, reached the point of self-organizing criticality and besides affecting the functioning of non-living systems, now are rapidly altering the genetic composition of living organisms;
3. The electrobiochemical composition of the planet has changed sufficiently to trigger an evolutionary crisis affecting all life from the smallest microbes to the largest complex organisms, including humans.

Goal

To develop a simple explanation for the ATS Research Forum that describes how:

1. Electrochemical pollution and industrial activity alter organic molecules;
2. Altered organic molecules in turn alter living cells, organisms and their genes.

Questions: Can You Help?

Do you have any information, good quotes, or links to basic science sites that can help?

Feedback? Comments? Criticism? Questions?

Special Request: My research focuses on environmental proteins. I can show how electrochemical processes and contamination cause proteins to misfold and become prions, then cause cellular and genetic mutations. As far as I can tell - prions are by far the most important agent causing mutations and evolutionary change. The most important prion seems to be a misfolded isoform of a-smooth muscle actin (ASMA), simply because it is an actin protein, and therefor can access virtually every living cell in every species and kingdom.

BUT - huge amounts of DNA, fat (lipids), sugar (polysaccharrides), and carbohydrate molecules also circulate in the environment, likely are being altered - and also may be impacting cells and genes in living organisms, either directly or indirectly. ...Anyone know?


General Background

Organic molecules called
biomacromolecules are present in all life and non-living systems that make up our earth’s global ecosystem (the ecosphere or biosphere ).

These biomacromolecules cycle constantly through the earth’s air, soil and water; they are present in inorganic matter, and also are the "building blocks of life" that make up living organisms. Acting as both messenger and message, these molecules carry and exchange biochemical information between organisms, between organisms and the planet’s non-living systems, and around and back again. In effect, biomacromolecules continually adjust and balance the molecular composition of life and non-living systems, and act to keep the earth in harmony with itself at the most fundamental level: by standardizing the molecules that make up the planet and all its parts.

Today, pollution also is a defining part of this planet’s ecosphere. Contaminants interract with biomacromolecules, modify their structures, and change their biochemical properties. As a result, altered biomacromolecules change non-living systems like the planet's carbon, nitrogen, and water cycles. In addition, altered biomacromolecules trigger mutations in living organisms.



Glossary

Biogeochemistry: A science that deals with the relation of earth chemicals to plant and animal life in an area; of or relating to the partitioning and cycling of chemical elements and compounds between the living and nonliving parts of an ecosystem; study of microbially-mediated chemical transformations of geochemical interest, for example nitrogen or sulphur cycling.

Biogeochemical Cycles: Geological and biological processes that recycle chemicals vital to life; the circulation of chemical elements (e.g., oxygen, carbon, etc.) from the environment into plants and animals and back again into the environment. In ecology, a biogeochemical cycle is a circuit or pathway by which a chemical element or molecule moves through both biotic ("bio-") and abiotic ("geo-") compartments of an ecosystem. ...The most well-known and important biogeochemical cycles, for example, include the carbon cycle, the nitrogen cycle, the oxygen cycle, the phosphorus cycle, and the water cycle. ...Biogeochemical cycles always involve equilibrium states: a balance in the cycling of the element between compartments. However, overall balance may involve compartments distributed on a global scale.

Microbiology: The branch of biology that deals with microorganisms and their effects on other living organisms.

Molecular Biology: the study of the biochemistry of cells, it is closely linked to cell biology, in particular the biochemistry of DNA and cogeners.

More on Molecular Biology

Central Dogma of Molecular Biology: The central dogma of molecular biology deals with the detailed residue-by-residue transfer of sequential information. It states that such information cannot be transferred from protein to either protein or nucleic acid. ...Prions provide the only exception to the dogma so far known.




WHAT DO YOU THINK?



posted on Jan, 3 2006 @ 04:27 PM
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Mutation, Disease and Human Evolution: What Are the Options?

Please go here to comment or contribute.

Electropollution and chemical contaminations have altered the structure and composition of the organic molecules that circulate in this planet's ecosphere. In turn, these altered organic molecules, or biomacromolecules, cause mutations in living cells and organisms. The earth's electrobiogeochemical composition has changed so much that the process cannot be stopped, although it still might be possible to slow down the rate of change.

Many new mutations appear to be "disease," but likely represent essential steps in the evolutionary process. Whether we define new mutations as disease or an evolutionary step, they represent a conundrum, and our options to deal with them are limited.

This purpose of this thread is to identify and evaluate the options we have to deal with mutation, disease and humanity's escalating process of evolutionary change. The thread Mutation and Human Evolution is a companion to this one, created to develop a scientifically accurate description of the situation.

The Options

The thing is, we are in an evolutionary crisis - it's happening whether we like it or not. And it's not just happening to us, this crisis is occurring in every living thing from viruses and bacteria to mycoplasma and fungi, to plants and animals. Microbes are mutating, evolving and adapting quickly - and integrating altered biomacromolecules that give them better access to complex organisms. From a certain perspective, microbes are vehicles that transport biomacromolecules between living organisms and non-living systems, thus balancing and standardizing the planet's biogeochemical composition. In comparison to microbes, complex organisms like humans are evolving slowly - perhaps too slowly.

We seem to have four options:

1. Clean up the planet and everything it in so we can get back to normal.

Analysis: It's too late. Electrochemical contamination no longer is our biggest problem - we're facing widespread electrochemical alterations on circulating organic molecules. These altered biomacromolecules now are an integral part of the global ecosystem. We cannot even identify all the altered biomacromolecules, never mind find them and remove them from the environment. And we already are far past dealing with secondary and tertiary effects.

NOTE: Clean up is essential in the adaptation argument - not to restore the planet to its original balance and composition, which is now impossible, but rather to slow down the rate of change in hopes that we might keep up with it in an evolutionary sense.

2. Put our faith in medical technology and transhumanism.

Traditional medical interventions covered by insurance include medication and surgery; insurance does not cover transhumanism technologies like stem cell therapy, gene therapy, cloning, and tissue engineering.

Analysis:

a. Medication treats the symptoms, not the cause. Most modern medicines are targeted to proteins and cause protein misfolding as a "side effect." First stage effects are beneficial, but subsequent effects are not. Medication represents a destructive dead end that perpetuates and worsens the crisis.

b. Surgery treats the symptoms, not the cause - and generally is available only after symptoms become life threatening. Not a significant option IMO - and the writing is on the wall: enrollment in surgery has plummeted.

c. Transhumanism: Stem cell therapies, gene therapy, cloning, and tissue engineering for example go straight to the cause of disease - and deal with protein production in differentiating cells. Unlike medications, these therapies work and do not alter macromolecules in the body. However, unless the planet is cleaned up, individuals will be constantly re-exposed to altered biomacromolecules - and the contaminations that alter biomacromolecules - and will require ongoing treatment and genetic "tune-ups" throughout their lifetimes.

The two most apparent flaws in transhumanism therapies are: a) Accessibility. Insurance companies refuse to cover these technologies, which means that the individuals' ability to get treatment is determined by their economic status; and b) Non-adaptation. Beneficiaries of stem cell therapies and tissue engineering are not adapted to the planet's changed environment. Moreover, the treatments are designed to restore adaptations relevant to an ecosystem that no longer exists. The long term implications are difficult to assess but at the least, very likely will result in infertility.

Of interest:


Expanding the Genetic Code

What is amazing is that every form of life on Earth uses the same set of 20 amino acids to make all proteins. Indeed, this set of amino acids is the basis for the genetic code, the code that specifies the relationship between the nucleotide sequence of a gene and the amino acid sequence of a protein. This fact leads to the rather interesting question of why every form of life has the same set of building blocks. Why not 21 or more? Moreover, if we can add new amino acid building blocks to the genetic code, will we be able to create proteins or even new organisms with enhanced chemical, physical, or biological properties?

...Our goals for 2005 are to incorporate unnatural amino acids into multicellular organisms; show that amino acids with altered backbones can be incorporated; incorporate metal-binding amino acids, fluorescent amino acids, and posttranslationally modified amino acids; and determine x-ray crystal structures of mutant synthetases that encode heavy-atom, keto, and glycosylated amino acids.




3. Remove ourselves from the natural ecosystem to prevent altered biomacromolecules from affecting our cells and genes.

This involves creating totally synthetic environments - a possibility explored in synthetic bio-habitats, and much science fiction.

...A seriously dumb solution imo, when we had such a beautiful planet to start with. And it won't work anyway - synthetic biohabitats rely on elelctricity, which creates "alien" electromagnetic fields, and alters biomacromolecules inside the body and in the environment.

Of interest: One of my favorite sci-fi scenarios is Twilight of the Basilisks written by Jacob Transue (Joan Matheson), and published in 1973.

4. Go with the flow, trust to nature, adaptation, and the evolutionary process - and hope for the best.

Analysis: Successful species are adapted to their environments. It is not the "fittest" that survive environmental change - but rather, those species able to adapt to the changes.

For humans and other complex organisms, the main constraint is the speed of mutation required in the current environment. We are changing our environment far more quickly than we can adapt to the changes. Microbes can adapt rapidly - but humans and other animals are constrained by their rates of reproduction. As we already have seen, welfare programs designed to push reproduction rates and "breed for immunity" have not worked - proving that mutation, adaptation and evolution will not succeed without additional efforts.

With altered biomacromolecules like prions, the amount of exposure determines the speed of the effect - and at least superficially, the rate of change in the body determines individual survival. So on the surface at least, minimizing the amount of exposure will allow the individual - and species - more time to adapt and evolve. Clean up is essential - not to restore the planet to its original balance and composition, which is now impossible, but rather to slow down the rate of change in hopes that we might keep pace with it.


WHAT DO YOU THINK?

What's your analysis? Are there other options? Do you think we can change along with our world, and adapt? Should we trust to science and technology to change us, and modify our cells, organs and/or genes so we can live in this new world we have created? Is transhumanism the answer? Or should we hit space and find a cleaner place?



posted on Feb, 29 2012 @ 09:15 AM
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FMD has become more recognized over the years since this thread was started. Here is one of the latest news releases about current research.




Coronary dissection "not rare" in young females

Doctors in a Canadian hospital say spontaneous coronary artery dissection (SCAD) in young women under the age of 50 is not as rare as previously thought [1]. They believe it is the most commonly encountered form of nonatherosclerotic coronary artery disease in such patients, causing more than 25% of MIs, and is frequently missed because the angiographic findings are subtle. Furthermore, they propose that the majority of sufferers have underlying cardiac fibromuscular dysplasia (CFMD), which predisposes them to SCAD.

Lead author Dr Jacqueline Saw (Vancouver General Hospital, BC) told heartwire: "In April 2011, in the spate of two weeks, I saw three young women with coronary dissection, and these women didn't have traditional coronary disease risk factors. Upon screening, they were found to have fibromuscular dysplasia (FMD). In the intervening months I saw another three cases, so in six months I saw six cases in one hospital alone, so it's not that rare. Just imagine what the incidence is elsewhere."

Saw and colleagues now report these six cases in a paper in the February 2012 issue of Circulation: Cardiovascular Interventions, and at the TCT meeting last year, Saw presented a series of 99 women under the age of 50 who underwent coronary angiograms at the hospital: among 41 of these who had elevated troponin, a third—12 (29.3%)—had SCAD or FMD [2].


Hopefully, breakthroughs in proteomics and other disciplines will lead to a blood test soon - Early Blood Test in the Pike.



posted on Nov, 23 2013 @ 08:58 AM
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Prions are infectious misfolded proteins that can mutate to create new strains and infect a variety of cells. However, prion disease was re-defined during the last administration to acknowledge only prion infections in the brain. Now, a new prion disease has been discovered and acknowledged to involve abnormal prion proteins found all over the body; it is NOT associated with dementia. The main symptoms are "severe diarrhea; neuropathy, manifesting as loss of feelings in feet; and loss of bladder control and postural hypotension." This "new discovery" may open the door for more comprehensive prion disease research.


A Novel Prion Disease Associated with Diarrhea and Autonomic Neuropathy

BACKGROUND
Human prion diseases, although variable in clinicopathological phenotype, generally present as neurologic or neuropsychiatric conditions associated with rapid multifocal central nervous system degeneration that is usually dominated by dementia and cerebellar ataxia. Approximately 15% of cases of recognized prion disease are inherited and associated with coding mutations in the gene encoding prion protein (PRNP). The availability of genetic diagnosis has led to a progressive broadening of the recognized spectrum of disease.

CONCLUSIONS
Abnormal forms of prion protein that were found in multiple peripheral tissues were associated with diarrhea, autonomic failure, and neuropathy.

Novel Prion Disease With Peripheral Symptoms Identified

…the affected family presented with 11 members showing symptoms of this syndrome, with severe diarrhea; neuropathy, manifesting as loss of feelings in feet; and loss of bladder control and postural hypotension. The researchers studied 6 of the affected family members in detail, along with autopsy or biopsy samples obtained from 5 of them, and found abnormal prion protein deposits.

…Prion diseases have so far been confined to the brain, but in this condition, the abnormal prion proteins were found all over the body.

edit on 23/11/13 by soficrow because: (no reason given)



posted on Aug, 3 2014 @ 02:09 PM
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As predicted: epigenetic, not genetic. And supporting old research showing FMD is systemic, and involves connective tissue pathology.


Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-β expression and connective tissue features

....Extra-arterial pathology included low bone density (P



posted on Aug, 3 2014 @ 02:14 PM
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Trying again. As predicted: epigenetic, not genetic. And supporting old research showing FMD is systemic, and involves connective tissue pathology.


Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-β expression and connective tissue features

....Extra-arterial pathology included low bone density (P



posted on Oct, 16 2014 @ 07:10 AM
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Genetic studies aren't telling us much about FMD. This article helps explain why.





Proteogenomics: Integrating Proteomics and Genomics to Unlock Biological Function

Learn how a proteogenomics approach can improve your investigational power.
Mary F. Lopez, Ph.D.
A BRIMS scientist connects up an ion source, which is often used in proteomics experiments.
Combining genomic and proteomic techniques can reveal important insights to unlock complex biological function. The exploration of methods for integrating large genomic and proteomic data sets is gaining traction due to improved bioinformatics and the public availability of well-organized, searchable data. Also, by merging RNA sequencing with mass spectrometry and improving bioinformatics, scientists can strategically select from a much broader range of investigational techniques and take advantage of complementary information. When one avenue of investigation closes, another may offer a new route to discovery—either building on previously inconclusive results or offering altogether new insights. Multiple studies in the past several years have demonstrated that transcriptional profiling data do not necessarily correlate with protein expression data, confirming that the two types of information are not duplicates but, instead, may be synergistic in terms of broadening our understanding of basic biology.1

In this brief overview, three recent examples illustrate how a “proteogenomics” approach can improve investigational power by enabling a progression of approaches that lead to actionable conclusions. When it comes to translational medicine, proteogenomics may provide better prospects for revealing biomarkers, assessing disease states, and identifying the complex mechanisms behind biological function.





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