"Noel Fragment" Disease
in DNA Damage and Cell Mutation

"Noel Fragment Disease in DNA Damage and Cell Mutation" discusses a new theory for DNA mutation, cell growth and replication abnormalities. Mutagenesis by segment substitution causes much faster DNA and chromosomal damage, than current point mutation models. This phenomenon may be relevant to cancer cell growth. Viruses involved include herpes, EBV, CMV. DNA Polymerase (multiple sources), promotes replication of the "Noel Fragments" leading to chromosomal damage.

"Noel Fragment" Disease

(Pronounced No-elle Fragment)

A theory to explain advanced mutagenesis in cells, but by a "segment substitution", not a "point mutation" model. The significance lies in the extreme rapidity with which normal cell functions can be altered and with which normal cell controls are lost, allowing uncontrolled cell replication and growth.

Noel (Pronounced No-elle) Fragment Disease occurs when DNA remnants found within human cells replicate using persistent intracellular viral DNA polymerase, or replicate perhaps directly or indirectly via remnant Paill Spectrum organism sourced DNA polymerase.

(A range of viruses may be responsible for the presence of viral DNA polymerase, but the most common viruses would be expected to be from the Herpes family of viruses, notably CMV (Cytomegalovirus), EBV (Epstein Barr Virus, also known as glandular fever), and Human Herpes 6 virus. It is likely that other less well known viruses such as JC virus may also play a role in the development of Noelle Fragment disease). Clinically, EBV appears to be a very significant organism. The Paill Spectrum disease model would explain why clinically many Paill related symptoms and signs including fatigue, intensify after the development of EBV infection.

The suggestion, clinically is that EBV and other intracellular viruses produce a DNA polymerase enzyme (or otherwise remnant DNA polymerase from other sources), and this enzyme supports a cascade of DNA replication that interferes with cell growth and replication mechanisms.

These DNA fragments or remnants are heretofore called "Noel Fragments". They form the final disease arm of the Paill Spectrum illness.

These DNA fragments or remnants are able to replicate using this non human DNA polymerase. This results in the long-term presence of abnormal DNA and its by-products such as RNA and proteins. These by-products (proteins, RNA or DNA fragments) or simple bacterial action (i.e. intracellular penetration, of the intracellular environment as a consequence of the Paill organisms' normal life cycle), are likely to cross the nuclear membrane and may cause host cell DNA strand damage.

As the quantity of Paill or viral DNA increases, the DNA (perhaps predominantly Paill DNA), spreads intracellularly, including to within the host cell nuclear membrane and may attach to existing host DNA. Damaged host cell DNA strands, may be improperly repaired resulting in “segmental mutations” of cell DNA. The presence of damaged host cell DNA strands would also complicate the repair of DNA injury, allowing segment substitution. This would be expected in the Paill Spectrum model to result in substantial alteration in cellular control mechanisms in a much more rapid and immunogenic fashion than would be explained by the current theory of cellular “point” mutation caused by external agents such as radiation or chemical agents. (Note, the Paill Spectrum model predicts that there are multiple sources of the DNA strands, both intrinsic and extrinsic).

In short, big changes occur very fast, with the potential for repeated cascades of injury then repair. In the Paill Spectrum model cf. “usual” models (point mutation models) of cell dysfunction, recurrent segmental DNA damage and repair results in a rapid distortion of the DNA and chromosomal structure of affected cells. Furthermore, in the Paill Spectrum model, the conditions exist in the intracellular environment for repeated injury. This injury process is not random, but is in fact directed at the most vulnerable point in the host. I.e. “Most” damage occurs in the cells that are “most” affected, while other cells may be hardly affected at all.

This process is likely to be lethal for many cells, due to simple critical systems damage. Alternately, if sufficient alteration of cellular protein synthesis occurs, these cells will be exterminated by the immune system. Because the new proteins are very different, they are easily identified by the immune system and recognized as “foreign”. These cells would then be destroyed by cell mediated and perhaps even antibody mediated immune processes. The Paill Spectrum model would predict that immune suppression would increase substantially, the risk of abnormal "cell growth" syndromes, (so called CPE events). This theory would be consistent with the observation of an increased incidence of lymphoma in long term immunosuppressed patients, such as transplant patients. Abnormal cells in the Paill Spectrum model would have substantially and variably altered DNA and chromosomal structure not consistent with the standard “point mutation” model of these cell growth dysfunction syndromes. The Noel Fragments as well as damaged host DNA may both be re-incorporated into repairing cells.

The disturbance in cellular control mechanisms would be substantially exacerbated by faulty “segmental” DNA repair. These would affect typical cell activities such as cell growth, cell death and cell replication.

In Noel Fragment Disease, changes occur in cell structure
with the addition of strings of useful ingredients (functional genes),
resulting in large rapid changes in cellular appearance and function.
This face would take millennia to evolve
from its ingredients, being added to the genetic mix one point mutation at a time,
but only a single generation to produce this face,
in the Paill Spectrum model of Noel Fragment disease.

Noel Fragments cause weird rapid changes in cells growth and control systems. Cells change what they are and how they work.

The presence of Noel Fragments provides a separate mechanism for DNA mutations. These mutations are segmental not point mutations and the Paill Spectrum model would suggest that the mutations occur secondarily to DNA mis-reads or substitutions during replication / repair. This mechanism would be expected to produce a disseminated form of cell injury, affecting a diverse range of genes in many different body systems with many diverse cell replication, growth and cell death abnormalities occurring, in many different and perhaps unrelated body tissues.

Faulty repair of multiple damage points on DNA strands in the host cell nucleus would exacerbate this tendency for DNA damage via segment substitution.

Inflammatory reactions may also be triggered by the DNA fragments (of a diverse range) causing a wide variety of inflammatory diseases under general group banners, but with an extreme range of disease severity and of disease markers being present.  Abnormal protein markers may be present variably within the family of Paill Related autoimmune or inflammatory diseases.

The existence of Noel Fragment disease in the Paill Spectrum model suggests that there may be two phases to many Paill illnesses. Also that the symptoms and signs of the Paill Spectrum illnesses caused by Noel Fragment Disease would show a diverse range of symptoms dependent on the genetic / enzymatic makeup of the individual. This would result in disease symptoms in multiple organs at multiple ages or stages or life with variable immune component or disturbance where an immune process has been triggered.

The existence of Noel Fragment disease in the Paill Spectrum model is based on the theoretical projection that there may be two phases to many Paill illnesses. Also that the symptoms and signs of the Paill Spectrum illnesses secondary to Noel Fragment disease, would show a diverse range of symptoms dependent on the genetic / enzymatic makeup of the individual. This would result in disease symptoms in multiple organs at multiple ages or stages or life with variable immune disturbance where an immune process has been triggered.

Perhaps it may suggest an answer to the age old question

Cell longevity and telomerase effects may

Discusses a new theory for DNA mutation, cell growth and replication abnormalities. Mutagenesis by segment substitution causes much faster DNA and chromosomal damage than current point mutation models. May be relevant to abnormal cell growth. Abnormal cell growth occurs when chromosomal damage is faultily repaired incorporating Noel fragments into host cell DNA, by a segment substitution mechanism.

Prerequisites for Cell Proliferation Events,
under the Paill Spectrum Model: "Noel Fragments"

• “Double Strand” Damaged Host DNA:

DNA that has complete avulsion of continuous double helix DNA strands. Such damage would typically affect one chromosomal arm, but not necessarily both chromosomal arms. Where more than one chromosomal arm is affected, the damage is unlikely to be symmetrical, (due to the mechanism of injury).

• Presence of a “Foreign” DNA Donor: for DNA “segment substitution”

Paill is the most likely source of foreign DNA due to its chronicity and immune evading modus operandi, its importance being amplified by its intracellular lifecycle and persistent chronic replication. Intranuclear invasion is likely the most important CPE disease precipitant, when the Paill organism is present.
Other Typical DNA donors include viruses. Well known culprits include: EBV or CMV. Other possible culprits include: herpes 6 virus and other DNA viruses such as for example JC virus. Any Viruses with a “DNA phase” in replication could be another possible source of Foreign DNA.
Any intracellular infecting organism could act as a foreign DNA source. Possibly in some circumstances including extracellular infecting bacteria or unusual infections such as anti-bacterial viral phages, superinfecting bacterial infecting organisms of bacterially contaminated sites, could act as mammalian “segment substitution” DNA donors.

Dead Paill organisms are more likely to result in DNA damage, but continued cell survival. This DNA load arising from deceased Paill Organisms would typically be seen in Paill infection and would of course increase with infection chronicity.

• Presence of non-specific DNA polymerase:

A non-specific DNA polymerase is essential to allow replication of naked DNA strands in the nucleus or other sites in the cell.  As the number of these strands increases, the probability of their accidental incorporation into defectively repaired segments of damaged mammalian DNA increases. These foreign DNA strands may be incorporated into mammalian host cell DNA by segment substitution.

It would be expected that a natural defense to control intracytoplasmic or intranuclear foreign DNA strand replication, would be “specificity” of mammalian DNA Polymerase for initiation sequences of a specific type, (these initiation sequences are distinct and different to initiation codons)
Non-mammalian DNA polymerase would be expected to respond more acceptingly / more generally to initiation sequences, than mammalian DNA polymerase. I.e. Non mammalian DNA polymerase would likely recognize and accept a wider variety of initiation sequences resulting in a better probability to replicate any DNA strand whether a native DNA strand from the host cell or a “foreign” DNA strand from a foreign organism.

Once sufficient foreign DNA strands are present, this would increase the probability of accidental faulty repair of damaged DNA, by segment substitution methods.

• Accelerating Agents:

DNA damage by other sources would enhance the prevalence of defective DNA repair. Sources of DNA damage include:
Ionizing radiation
Chemical alkylating agents or other DNA cross-linking agents
Chemical mutagens e.g. aflatoxin, dioxins

• Genes of Host Mammalian Cells

This includes genes that are predisposed to increase cell proliferation. Another concept may include structures such as chromosomal DNA strand “crease points” creating a likely damage point for double strand DNA breakage. Currently, DNA supercoiling is poorly understood, but faults at this level would likely change the frequency of CPEs. A simple common model for DNA strand crease points is the fragile X syndrome, where long repetition sequences of DNA create bendy bits in the DNA, making the X chromosome look bent or as if “broken” under a light microscope. If a problem is going to occur and affect full gene sequences, it is most likely to affect the “weakest” link or the most fragile DNA sequence. DNA structure is likely to result in specific faults arising in characteristic locations in susceptible individuals, causing specific patterns of cell injury or specific types of CPEs.

• Accelerating circumstances:

• Immune Suppressing Agents.

By its nature DNA segment substitution mutation, can result in a wide variety of “new” cells. Where the DNA and the DNA products of the new cells differ substantially from the DNA and DNA products of the normal host population of cells, it is likely that the body would recognize these cells are foreign and mount an immune response to the new foreign cells, causing eradication of the cells. Only cells with DNA and DNA products largely similar to the normal cell population, would be likely to evade the immune response and therefore to successfully proliferate. The changes therefore grade towards changes in quantity and control sequences, rather than changes in quality within the mammalian cell DNA.

• Damage / Changes to cell growth control genes:

The predominant method of damage is segment substitution, not point mutation.
This may take the form of duplications of genes, loss of function of control segments of genes or addition of new control segments. Typically, some specific types of alteration in function are more likely to survive and thrive, causing identifiable patterns of CPEs in affected host cell populations. As mentioned above, the selection process initiated by the immune system, favors the replication of segment substitution sequences that do not produce “new” gene products.

• Active Transformation Sequences Present:

Viruses such as EBV have a capacity to transform specific mammalian cells in culture so that cell growth will bypass the Hayflick limit. Presence of transformation sequence genes would increase the probability of CPEs.

 

 

Changing the likelihood of progression of CPEs
would of course target the progression
of successive steps in the cycle of CPE development.

E.g.

• Control Paill:

Likely to produce effects at multiple levels such as removing a DNA donor, reducing DNA polymerase, reducing DNA cell damage. Even when killed, naked DNA strands from Paill would persist and are capable of initiating a number of medical conditions. Disease cannot be eliminated by killing Paill.

• Control existence of Foreign DNA:

Inactive anti-viral vaccines are an easy and obvious step, but would need to target a range of common DNA phase viruses to make an epidemiological impact. Even common and apparently harmless vaccinations may be associated with long-term illness. Note, for example, in medical school a number of textbooks noted that measles virus fragments have been found in a number of conditions such as Paget’s disease and some tumors. Therapy targeted towards unique control sequences genes may be beneficial, but the problem is to deliver this agent into the intracellular environment and to enable the agent to work there.

• Minimize exposure to DNA damage:

Standard Workplace health and Safety type protocols: most of these agents are already well known and recognized.

• Agents to inhibit replication of intracellular DNA strands. A number of natural remedies have this pleasant and desirable side effect.
• Vaccination against the gene products of active transformation sequences would be expected to reduce CPEs.

However, because the likely sources of active transformation sequences have no single source, any vaccine would need to be very polyvalent indeed. Additionally, where no gene product inn terms of a protein or polysaccharide is produced, successful effects are likely to be limited.

 

The challenge in such a process would of course be not only to achieve control of CPEs but also to quantify any anti-agathic effect of such a treatment program.

 

Characteristics of CPEs as explained by this Model

• CPEs would form medical problems with no single cause and no single cure (by this model). Even problems with technically the same name, would have slightly different gene sequences and would not necessarily respond to the same immunotherapy, where such a therapy may be possible,
• Once a sustaining CPE has occurred, by definition the variant cells would be sufficiently similar to normal cells, to evade immune response.
• Events arise in any susceptible tissue type, in any organ of the body in the context of a large number of normal cells being present, not generally in the context of a large population of abnormal cells. Segment substitution causes changes to develop in a single cell replication cycle giving rise to a proliferating stable cell population. There would of course be many failed events but these could not be detected against the background of normal cell apoptosis.
• Chromosomal and gene sequence abnormalities would be found, not in keeping with a point mutation model of pathogenesis. The extent of the abnormalities found in the stable CPE cell line would have required substantial affected cell populations to allow the evolution of the substantially altered DNA of the CPE cell line.
• CPE events would vary widely in aggressiveness, growth and invasiveness, even amongst conditions where the diagnosis is technically the same. This would make the prognosis often unpredictable.
•  Foreign DNA segments should be able to be located, typically related to viruses or Paill.
• Genetic predisposition would give a faint familial preponderance, but CPE events could affect different tissue types in different hosts over the generations. The likely finding is that there is predisposition to CPE of many sorts rather than a predisposition to many different sorts of CPEs.
  
  
  
  
• Paill treatment will not totally eradicate the risk of a CPE, as the remaining DNA strands may exist in a self-replicating form in the presence of non-specific DNA polymerase, typically from a non-mammalian source. Dead Paill organisms are in fact the probable mainstay of Noel Fragment disease and probably also of a number of autoimmune diseases.
• The selection of cell lines by the immune system results in successful CPE cell lines being substantially similar to normal cells in terms of DNA, structure. There are very few fingerprints remaining in affected CPE cells to give much of a clue as to the pathogenesis of the new DNA / chromosomal variants existing in the CPE cell lines. Only viral gene fragments may be found, often to a variable extent in a number of affected CPE individuals, providing little consistent evidence of which causative DNA donor e.g. virus was involved. It would be possible to arrive at a variant of the same disease by in fact incorporating DNA segments from a number of different viruses, if the genes involved belonged to the same “Class” and cause similar replication anomalies in host cell lines. A library approach to intracellular DNA cell damage may show surprising results.
• CPE changes may involve a number of foreign DNA donors, not just one organism. Isolation of a causative agent would be difficult under these circumstances.
• Cell Line studies would be compromised by contamination.
  
  
  
  

Cell line study may involve “transformation of normal or abnormal cell lines with an agent such as EBV, as may be typically used in a laboratory. This practice would complicate isolation of foreign DNA donor agents. Then cells we need to study to find a cause may not tell us a cause because in the study process, the scientists have needed to deliberately contaminate the cell lines with a “causative agent”, to transform the cells being studied into a stable population that is able to be studied..

• Where Paill in involved, the timeline for problems would span decades and would naturally show age based clusters of occurrence, but generally increasing over time.