Recently there seems to have been an incident in which several patients contracted Creutzfeldt-Jakob Disease from contaminated surgical equipment. http://www.medpagetoday.com/...
“Surgical instruments used on a patient later given a tentative diagnosis of sporadic CJD were subsequently used in at least eight other patients after ordinary sterilization which is not adequate to reliably eliminate the prion proteins responsible for CJD.”
What is CJD? Why would I be digging out my class research paper of 7 years ago on Mad Cow Disease to discuss CJD.
I have updated the material, but not much has changed since the paper was originally written. I feel sure it is not for lack of medical research but the PrP nut is a hard one to crack, much less to find a treatment for, much, much less find a cure.
Step over the sleeping kitties.
Creutzfeldt-Jakob Disease is a rare disease so why
does this occurrence matter anyway?
A protein that is normally found in the membranes of certain healthy cells.
A protein molecule normally occurring in certain cells in the brain and some other tissues that can alter its form which leads to apotheosis and encephalic deterioration, muscular dysfunction and death.
Spongiform Encephalopathy aka Prion Disease includes several diseases that cause cell death in the brain.
Stained slides of the diseased tissue are characterized by holes and fibrous mats and plaques of debris from dead brain tissue.
Prion Diseases do not include Alzheimer's or Parkinson’s though physical symptoms are very similar.
The abnormal pathogenic isomer of a Prion molecule
A naturally spontaneously occurring Prion Disease in some breeds of sheep.
It is characterized by compulsive, injurious rubbing.
Creutzfeldt-Jakob Disease a PrP to be discussed after some background
Variant CJD A name for the human version for BSE
Bovine Spongiform Encephalopathy or Mad Cow Disease, which is the name for the
bovine version of sheep Scrapie Both are PrP diseases.
Symptoms of Creutzfeldt-Jakob Disease
The most characteristic feature of CJD is the rapid progression of symptoms from what may initially resemble fatigue, Alzheimer’s Disease, or simply getting older, progressing to complete loss of mental and physical function, and to death.
CJD usually results in death within 6 - 18 months of early symptoms, though a few patients may survive up to two years, and may, very rarely, live for many years.
There are four types or causes for CJD: Sporadic, Familial, Variant and Iatrogenic.
Sporadic CJD: The source of sporadic CJD is unknown. The disease affects mainly those over 50. Sporadic CJD is marked by rapid onset of dementia and death, usually within months.
Familial CJD: As the name implies, CJD or the predisposition to produce the abnormal form of PrP, runs in families. Individuals show symptoms at an earlier age than Sporadic CJD, and tend to live longer.
Variant CJD; is linked to BSE. The average age of death for individuals with vCJD is 29 years. Unfortunately, there is no way to determine the length of incubation for this variety of CJD. In the meantime, individuals, who are infected may transmit the abnormal PrP through donated blood or tissues.
Iatrogenic CJD: This form of CJD is contracted by direct contact with human tissue or body fluids from an infected person. Exposure can come from corneal transplants, dural grafts or the use of human Growth Hormone (hGH) or gonadotropin. Neurosurgical instruments that had earlier been used on CJD infected patients have transmitted the disease.
Other PrP Diseases:
Gerstmann-Sträussler: an inherited PrP has a slower progression than, but is otherwise characteristic of, CJD. Individuals may survive for 3-5 years.
FFI or Fatal Familial Insomnia is also a PrP disease. is an inherited autosomal dominant mutation. The signature symptom is an almost total inability to achieve normal sleep. Other symptoms are characteristic of excessive loss of sleep, including hallucinations, leading to dysautonomia similar to other Prion Diseases. When the patient attempts sleep EEGs patterns are wildly abnormal. Even if the REM stage is achieved EEG patterns are abnormal. Symptoms characteristic of extreme stress like high pulse and blood pressure, and sweating may also be present. Characteristic PrP mental and physical deterioration progress and death occurs between 6 and 32 months after symptoms appear
What the ... is a Prion, Anyway?
How, Now Brown Cow? The Sheep Did It First.
The short and sweet version is that Prion is the name given to a particular protein that normally occurs in several tissues in the body including the brain. Some times by heredity, or spontaneous mutation that molecule can reconform or change shape and become pathogenic. In that form it can be transmitted to other animals through food, direct contact with affected tissue or with contaminated surfaces like surgical instruments.
BSE, Bovine Spongiform Encephalopathy, or Mad Cow Disease is the Prion Disease that was transmitted to humans though contaminated beef products in Britain. In humans it is referred to as vCJD because the symptoms were similar to CJD.
Prions and Spongiform Encephalopathies
Aren’t brains supposed to be Spongiform, like, to soak up knowledge?
The cause of various diseases diagnosable as Spongiform Encephalopathies (SEs), also called Prion Diseases, is accepted to be the abnormally folded or reconformed form of a normally occurring non-infective, non-pathogenic cellular glycoprotein molecule. Prion molecules occur normally in brain tissue, leucocytes, platelets, erythrocytes, in tonsils and lymphocytic tissues, and in pituitary tissue containing human grown hormone Unfortunately all these can transmit PrP Disease if introduced directly into the body.
The abnormal prion, PrP, molecule is now recognized as the cause of neurodegenerative diseases, in humans, such as Creutzfeldt-Jakob Disease, new variant CJD, Gerstmann-Sträussler-Scheinker disease (GSS), Fatal Familial Insomnia (FFI), and Kuru.
Human Prion Diseases occur worldwide with about one case per two million of population, with men and women being equally affected. The disease generally strikes between the ages of 50 and 70. However, the inherited or transmitted forms can occur at much earlier ages. Generally in younger patients the disease progresses more slowly than in adults. All Prion Diseases are untreatable and are always fatal.
An outbreak of new variant CJD (vCJD, nvCJD) in humans in Britain during the 1990's is thought to have been the result of infection by the same agent that causes BSE in cattle. Goats also have scrapie, and cats, deer, zoo animals and domestic mink also have been diagnosed with SEs. (All of these animals have been exposed to feed products that contain flesh/tissues of other animals who might have had the PrP in their tissue. Deer and other wild animals were exposed through deer.bait.
A genetic mutation controlling the production of the Prion molecule can also cause formation of the reconformed protein.
An actual mystery disease from a remote primitive mountain people on a Pacific Island
In the highlands of Papua, New Guinea, in the 1950s, an epidemic of a transmittable disease called Kuru, occurred in 169 villages occupied by the Fore peoples.
Transmission of the disease occurred during a rite of mourning in which the tissues of a revered deceased person was consumed.
Women and children ate the brain and soft tissues and adolescent males and men the muscle. A small amount of the cooked brain tissue was also fed to infants. Kuru occurred most frequently in adult women and adolescents, but was never seen in very young children, and was rarely seen in adult men.
The funerary ritual was stopped in the late 1950's, and the occurrence of Kuru, is now very rare. The incubation period for Kuru is commonly around 15 years but can be longer than 30 years. Kuru occurs only in those who participated in the funerary rites more than thirty years ago.
Kuru was the first human Spongiform Encephalopathy to be investigated. Tissue examination from the brains of individuals, who had died of Kuru, showed a spongiform appearance. The brain tissue had holes left by dead cells and plaques of cellular debris and fibers.
A Short History of “Prion”
Wasn’t Prion the King of Troy who sacked Paris?
In 1965, Carleton Gajdusek extracted material from the brain of a Kuru victim and injected it directly into the brains of chimpanzees. Within a year and a half the chimps had developed Kuru. In 1968 Gajdusek applied the same procedure with Creutzfeldt-Jakob Disease brain tissue. Again the chimpanzees were infected.
Scrapie from affected sheep tissue also is transmissible by injection from diseased brains into the brains of healthy mammals.
Notice please this is direct tissue to tissue contamination. The Brits and their cattle got Prion Disease indirectly by eating affected tissue.
The pathogenic material has to cross the intestinal barrier and make it intact through the blood-brain barrier.
In 1967, the idea that proteins could act as infectious agents was proposed. This ran contrary to the existing CW. Until the discovery of PrP in victims of Kuru an hypothesis existed that no organic matter which did not contain DNA or RNA could function as a disease causing and/or a transmittable infectious agent.
In 1982, the name PrP, for “proteinaceous infectious particle,” was given by Stanley B. Prusiner to the infectious agent that causes Scrapie in sheep, Creutzfeldt-Jakob Disease in humans and Bovine Spongiform Encephalopathy in cattle.
The Prion hypothesis of SEs postulated that these diseases are caused not by a conventional virus or bacterium but by a protein that has adopted an abnormal form.
Making the PrP even more pernicious, it cannot be degraded, destroyed or removed by a normal metabolic process. It is a very stable protein molecule that does not denature even in laboratory processes normally used for lysing or degrading proteins or routine means of decontamination or sterilization.
While DNA or RNA from non-Scrapie infected brain tissue was destroyed by ultraviolet or ionizing radiation, as they normally would be, the brain material from infected sheep was still able to transmit scrapie.
In 1974 Prusiner began tying to isolate the infectious agent. He was able to confirm the absence of DNA and RNA from the transmitting agent in 1982.
After isolating the gene for the Prion molecule, Prusiner found the gene in the chromosomes of other mammals not known to exhibit SEs. Prusiner hypothesized that the normal isomer of the Prion molecule is not infective. Therefore, there must be two isomers of the Prion protein.
In further research Prusiner showed that protease (any agent that lyses or cuts a protein), did degrade normal Prion molecules, but did not break down the PrP found in SE diseased brains.
Prusiner’s discovery of and research on the Prion molecule received a Nobel Prize in Physiology or Medicine in 1997.
Ok, So What is a Prion? I’m Waiting For An Answer
Thank Ceiling Cat we finally are getting to the point.
A prion is a protein that is normally found in the membranes of certain healthy cells, but in Prion Diseases, the Prion protein has an altered or reconformed shape, causing it to become pathogenic.
Infectious PrP molecules have the same amino acid sequence as the normal noninfectious prion molecule. A normal Prion is a folded molecule made of mostly α helices. However, in some prion molecules the α helices in the core of the molecule reconform into β strands that form sheets. The prion molecules with the altered strand/sheet, PrP form are apparently the cause of Prion diseases, causing encephalic dysfunction and eventual apotheosis of the cell that results in SEs.
Not All Prions Are In Great Shape
Is a Reconform anything like a Neocon Republican?
Mutation can insert incorrect amino acids at certain positions within or adjacent to key structural elements in the α helix that can cause the helix to become unstable and the influence the normal Prion α helix to reconform into the β sheet configuration. Additionally, it is hypothesized that when a reconformed PrP contacts a normal Prion molecule, the normal protein reforms from the α helix to β sheet form.
Trust me, you don’t want to know
The only certain way of diagnosing any of the SEs is postmortem tissue examination. Cerebral biopsy is possible but rarely performed.
vCJD can be detected by tonsil biopsy. The presumption is that after consumption of affected tissue the molecules travel through the lymphatic system into the brain.
Like Alzheimer’s and Parkinson Disease all the forms of Prion Diseases, human and animal, have characteristic behaviors that eventually distinguish them, from other motor and mental degenerative diseases, but that is after the disease is well advanced.
How Now Prion? You Didn’t Fold Your Sheets Right
The normal Prion molecule is a large molecule made with 209 amino acids of 35-39 kDa’s that, like most large proteins,is twisted or folded to form a three dimensional molecule. The protein carbon chain is in a mostly α helix configuration. In the PrP or pathogenic molecule the internal α helix reconforms to a β sheet configuration, also referred to as a misfolded protein. This reshaping makes the molecule dysfunctional and also causes a very stable non biodegradable configuration.
The going theory is that the ends of the amloid fibers that form the β sheets act as templates that allow the fibers to grow and brake. The broken pieces may also bond to the normal proteins and catalyze them into the pathogenic form. Dead cell debris and fibers are visible in a stained biopsy slide of a SE patient.
Some evidence sustaining this β strand theory is the empirical rate with which the disease progresses in lab mice being consistent with the square root of the concentration of normal Prion molecules.
In other words the quantifiable data seem to agree with the observation that Prion diseases once initiated progresses exponentially.