Baculovirus is Identified as Morgellons

[jeany]

[jeany]

[jeany]

Very informative site!

anatomy.iupui.edu/courses/histo_D502/D502f04/lecture.f04/cell.f04/cellf04.html

[kammy]

morgellons.org/case_definition.htm

From Morgellons.org - "abnormalities: elevated blood glucose, insulin, calcium, and (elevated) serum Homocysteine, and low serum potassium and magnesium."

lpi.oregonstate.edu/f-w99/vascular.html

Vascular Toxicity of Homocysteine and How to Control It

" Controlling Homocysteine with Vitamins and Betaine

Several groups of investigators have reported the impact of supplementation with vitamins B6, B12, and folic acid, administered alone or jointly, in patients with homocystinuria, resulting from an excess of homocysteine. Folic acid appears to be useful in most subjects; very high doses of B6 (100 mg or more daily) also seem to have broad utility, whereas lower doses may benefit only those whose baseline B6 status is poor. The efficacy of supplemental B12 may likewise hinge on baseline B12 status.

Not surprisingly, serum homocysteine levels tend to correlate inversely with serum levels or dietary intakes of these vitamins in the general population, indicating that vitamin nutriture is an important determinant of serum homocysteine in people who don't take B vitamin supplements. This may explain why low serum levels of folic acid or vitamin B6 have been shown to be cardiovascular disease risk factors.

Genetic abnormalities in the enzyme whose product is MTHF have also been found to be a common cause of increased homocysteine. One particular genetic defect in this enzyme is quite common in the general population, affecting about 12% of us. These people have serum homocysteine levels approximately 25% higher than people who do not have the defective gene.

Fortunately, ample supplemental intakes of folic acid can compensate for the diminished activity of the enzyme and thus reduce homocysteine levels. However, this strategy will not work in those who have a severe deficiency of the enzyme that generates MTHF."

**Has anyone noticed an improvement after taking a B supplement?

We're seeing from Jeany's posted video above where it is better to eat natural foods to get our vitamins, that supplements are synthesized chemicals and may not be as effective as eating food the way God intended.

Foods rich in folic acid

liver (best source) dried beans wholegrain breads spinach
chicken
giblets lentils wheat flour beetroot
kidney spilt peas potato brussel sprouts
egg yolk soya products sweet potato broccoli
almonds cabbage
nutz asparagus
banana
oranges
peaches

Betaine

www.nowfoods.com/M042772.htm

"In humans, betaine is normally made in the liver and kidneys; however, most of the betaine in our bodies comes from the food we eat. Betaine and its related compound choline, are present in variable amounts in our food. Also, plants and animals that live in high salt concentrations, like the ocean, have large amounts of betaine present within their cells. Examples of foods high in betaine are shellfish, wheat, spinach and sugar beets."

[kammy]

I have what is called a heart 'murmur'... I was tested years ago, my heart was fine, how many others are having irregular heartbeat? According to the case study - we supposedly have "low serum potassium and magnesium" levels.


journals.lww.com/cardiovascularpharm/Abstract/1987/10011/Potassium__Its_Relevance_for_Arrhythmias.5.aspx

"Summary: Potassium plays a critical role in cellular electrophysiology. Clinically, serious cardiac rhythm disturbances are a well-recognised complication of profound hypokalaemia. Recent research has focussed on the possibility that serious ventricular arrhythmias, particularly ventricular fibrillation, might be caused by the hypokalaemia that occurs in the acute phase of myocardial infarction."

www.chemocare.com/managing/hypomagnesemia-low-magnesium.asp

Hypomagnesemia (Low Magnesium)

What Is Hypomagnesemia?

Hypomagnesemia is an electrolyte imbalance and is indicated by a low level of magnesium in the blood. The normal adult value for magnesium is 1.5-2.5 mEq/L.

Magnesium is one of many electrolytes in your body and normal levels of magnesium are important for the maintenance of heart and nervous system function.

Foods with the highest concentrations of potassium and magnesium:

www.nutritiondata.com/foods-000122120118123000000-w.html

[jeany]

Kam you've been talking about Endocytosis and mineral imbalance such as magnesium. Lysosomes are also involved. It reminded me of a blog entry I wrote a while back where it shows a possible connection to the Baculovirus and where I am stating that I believe a mineral imbalance leads to susceptibility in causing M.

“Entry of baculovirus to mammalian cells has been thought to be similar to that found in insect cells. Cell surface molecule interactions with baculovirus during uptake in mammalian cells are unclear; however, the virus has been suggested to use rather widely distributed and heterogeneous cell surface motifs."

“In conclusion, these data indicate that baculovirus uses at least clathrin-mediated endocytosis as one of its entry pathways to HepG2 cells. However, baculovirus attachment to clathrin-coated pits seemed to be a relatively rare phenomenon, and therefore other internalization mechanisms could also coexist.”

“Clathrin-mediated endocytosis is known to lead to early and late endosomes, and finally to lysosomes (35). So far, many different viruses have been shown to utilize this pathway for release of the viral capsid to the cytoplasm from the early or late endosomes in mammalian cells.”

"In confocal microscopy and nanogold preembedding electron microscopy, the baculovirus particles were shown to colocalize with early and late endosomal/lysosomal markers. These results suggest that baculovirus may enter mammalian cells by both clathrin-mediated endocytosis and macropinocytosis.”

“Lysosomes are used for the digestion of macromolecules from phagocytosis (ingestion of other dying cells or larger extracellular material, like foreign invading microbes), endocytosis (where receptor proteins are recycled from the cell surface), and autophagy (wherein old or unneeded organelles or proteins, or microbes that have invaded the cytoplasm are delivered to the lysosome). Autophagy may also lead to autophagic cell death, a form of programmed self-destruction, or autolysis, of the cell, which means that the cell is digesting itself.

Other functions include digesting foreign bacteria (or other forms of waste) that invade a cell and helping repair damage to the plasma membrane by serving as a membrane patch, sealing the wound.

Magnesium thus acts as a major cellular and subcellular stabilizing agent which is necessary for the stability of plasma membranes, for the integrity of mitochondria, lysosomes, polysomes, and chromosomes as well as for the integrity of the helix of DNA and of messenger RNA and of RNA complexes.”

“The effects of magnesium on leucocytes — enhancing phagocytosis and the production of lymphocytes and their transformation into blast cells while moderating the inflammatory reaction.

“Magnesium deficiency produces low magnesium levels in the extra-cellular compartment and a reduction of levels in the cell along with hyperpermeability of the cell membrane. This depolarisation finally causes a lowered level of cellular potassium and a calcium overload (increase of intracellular Ca), in conjunction with a lowering of phosphorus levels and an increase in intracellular Na+. The increased influx of calcium into the cell produces lower blood levels of calcium and the release of potassium from the cell raises blood levels of potassium. Moreover, if the deficiency is prolonged, the cellular calcium overload may cause calcinosis, due to mixed apatite crystals which combine Ca, P and Mg.”

“Magnesium in general is essential for the survival of our cells but takes on further importance in the age of toxicity where our bodies are being bombarded on a daily basis with heavy metals. Magnesium thus protects the brain from toxic effects of chemicals.”

“Glutathione synthetase requires γ-glutamyl cysteine, glycine, ATP, and magnesium ions to form glutathione.

In magnesium deficiency, the enzyme y-glutamyl transpeptidase is lowered.

Data demonstrates a direct action of glutathione both in vivo and in vitro to enhance intracellular magnesium and a clinical linkage between cellular magnesium, GSH/GSSG ratios, and tissue glucose metabolism.[ix] Magnesium deficiency causes glutathione loss.”

“Magnesium deficiency (MgD) has been associated with production of reactive oxygen species, cytokines, and eicosanoids, as well as vascular compromise in vivo.”

Possible manifestations of magnesium deficiency include:

Low energy
Fatigue
Weakness
Confusion
Nervousness
Anxiousness
Irritability
Seizures (and tantrums)
Poor digestion
PMS and hormonal imbalances
Inability to sleep
Muscle tension, spasm and cramps
Calcification of organs
Weakening of the bones
Abnormal heart rhythm


morgellons2.wordpress.com/2009/09/15/lysosomes-magnesium-potassium-calcium-beneficial-for-morgellons-sufferers/

Jeany

[jeany]

Jan 14, 2010 8:46:47 GMT -5 kammy said:

Betaine

www.nowfoods.com/M042772.htm

"In humans, betaine is normally made in the liver and kidneys; however, most of the betaine in our bodies comes from the food we eat. Betaine and its related compound choline, are present in variable amounts in our food. Also, plants and animals that live in high salt concentrations, like the ocean, have large amounts of betaine present within their cells. Examples of foods high in betaine are shellfish, wheat, spinach and sugar beets."

I'm assuming that due to the high salt concentrations it might be the connection to the ADH/electrolyte levels I've been talking about in my post according Adenocarcinoma.

Jeany

[kammy]

morgellons.org/case_definition.htm

"Agents identified serologically... most herpes viruses, some strongly activated such as VZV and HHV-6"

HHV-6

www.hhv-6foundation.org/testing.html

"Nearly 100% of us have been infected with the HHV-6 virus by early childhood and have antibodies to it, and at least a 30% of us have small but detectable levels of latent virus in our blood1 2, so the relevant questions are not whether you have the virus, but rather how much virus do you have, and is it active or latent?"

"Human Herpesvirus Six (HHV-6) is one of the eight known viruses that are members of the human herpesvirus family.

Likewise in HIV/AIDS, HHV-6 re-activations cause disseminated infections leading to end organ disease and death. Although up to 100% of the population are exposed (seropositive) to HHV-6, most by 3 years of age, there are rare cases of primary infections in adults. In the United States, these have been linked more with HHV-6A, which is thought to be more pathogenic and more neurotropic and has been linked to several central nervous system-related disorders.

HHV-6 has been reported in multiple sclerosis patients.[4] and has been implicated as a co-factor in several other diseases, including chronic fatigue syndrome,[5] fibromyalgia, AIDS,[6] and temporal lobe epilepsy[7] but no definitive link has been established."

HHV-6 is not the virus that causes cold sores, genital herpes, chicken pox, shingles, or infectious mononucleosis.

I'm looking at 100% having... HHV-6A & B, 7?, 8?, 3? and 1... and 2 for some... VZV, EBV, CMV... and no telling what else... a heavy herpes and viral load.

[jeany]

Homocysteine, Genetics & Vitamins - Homocysteine Levels - Find out if you are at risk

www.besthomebasedbusinessforyou.com/healthblog/2009/09/homocysteine-levels-find-out-if-you-are-at-risk/

High HCY in your blood is linked to serious illness. Helping your body reduce high HCY may greatly reduce your risk for serious illness. So what can you do? Here are several things you can do to help:

* Eat fruits and vegetables high in antioxidants - 5 servings daily for children, 7 servings for women, and 9 servings for men.
* Reduce your stress load.
* Get at least 30 minutes of vigorous activity every day.
* Supplement your diet with nutrients such as TriVita’s HCY Guard and Energy Now!.
* Defeat stress by nurturing your spirit with healthy relationships and a healthy sense of purpose.

Remember, genes are not fate; you have as much control over your genes (through nutrients and nurturing) as they have over you. Build a healthy foundation for your future by balancing your homocysteine.

Be sure to have your homocysteine levels tested if:
You have a family history of:
Heart disease
Stroke
Alzheimer’s disease
Osteoporosis
Cancer
You experience gastric disturbances, breathing difficulties, or kidney issues
You are over 50
You are pregnant
You are experiencing high stress levels
You eat a poor diet
You don’t exercise regularly

[kammy]

Jeany and I are having a discussion about eating food vs. taking supplements. The people in America have to eat even if we suspect that the food might be contaminated? This is a heck of a position to be in - we're needing to call on our foods to help us get well - and yet, the food could be the source or adding to our illness? And, also due to modern day food processing methods, environmental conditions the natural nutrients are being removed from our foods. When our immune systems are deficient in the nutrients it needs - this leads to disease. We have to boost our immune systems to fight Morgellons, we cannot do it with food alone.

I'm seeing Glutathione as a key player, it is the most important healing agent and antioxidant. I went out to look Gluthathione supplements and it appears that these supplements are not as effective as a supplement, they don't cross the blood-brain barrier. I looked at a product called MAXGLE, it sounds good, but - it is expensive and I can't get it here... the Government doesn't allow certain supplements to be sent in the mail... so, I started looking at the foods that contain Gluthathione:

www.ehow.com/how_2265914_raise-ones-glutathione-level.html

"Eat foods rich in glutathione such as avocados, watermelon, walnuts, asparagus and broccoli.

Increase your intake of foods containing cysteine such as cottage and ricotta cheese, yogurt, poultry, wheat germ and oak flakes.

Take in foods that contain whey protein such as milk and milk products.

Drink Immunicol--a patented whey product similar to mothers' milk.

Add the herbal extract milk thistle that stimulates and regenerates liver cells and increases the body's production of glutathione.

Increase your intake of foods containing selenium such as Brazil nuts, button and shiitake mushrooms, tuna, shrimp and salmon."


**A thought just occurred seeing the 'mother's milk' reference above. I wasn't breast fed - I'm a "bottle baby" of the 50's... how many others here are also - "bottle babies"?

[kammy]

We know that stress can cause many diseases... From M.org - "Medical histories clearly support that most symptoms of Morgellons disease "precede" emotional effects."

Distress, stress, emotional upheaval, etc. - could be a catalyst? Is an overload of normal everyday pathogens, adding man-made chemicals/pathogens, other environmental conditions, causing latent viruses to become active, and by having a missing or defective immunity enzyme(s)... = evident Morgellons?

We've heard many say that stress seems to feed our Morgellons? We possibly need to look closer at stress and calming techniques?

[kammy]

morgellons.org/case_definition.htm

"Common physical findings include abnormal Romberg, peripheral neuropathy in ALL (feet, and in some cases fingers)"

Romberg's Test:

en.wikipedia.org/wiki/Romberg%27s_test

At the onset of Morgellons - I started having fear of heights, getting on a roof was terrifying, I felt as if I was going to topple off head first. I also became 'paranoid' in speeding traffic - anxious - as if the cars were speeding past me at a rate that my brain couldn't tolerate, kind of like a motion sickness.

At first I noticed that I couldn't ride on the back of a motorbike without the feeling that I was going to come off, felt as if I couldn't hold on. Then, as the driver... I also became 'dizzy' and would have to pull over and stopped riding motorbikes all together.

[jeany]

I did that Romberg test once and failed. I fell over. Another thing I have, is tremor in both hands, especially while handling with small objects such as while sewing for example.
Restless legs at night with sudden twitching also.
As a child I had severe problems with motion sickness and this kept on. I cannot sit in the back seat of the car for a longer period of time or I get an upset stomach, but I can ride and drive a motorcycle without problems and with huge enjoyment!..
Even riding backwards in a train makes me feel dizzy. I've noticed that I need to 'follow' and see the traffic in the right direction to prevent this.
Also riding on carousels and such you can see at fairs is another problem. Everything that moves in circles or back and forth gives me that strange feeling of dizziness.
Funny is though, I can ride the wildest roller coaster, even up and down with curves. It has to be in one direction only and I'm fine. Climbing up a ladder is ok, but I feel highly insecure when climbing back down. It's like I have a problem with the distance I need to reach the ground.

Who else has these symptoms? I think we should take a closer look at the inner ear and neurological effects.

Jeany

[kammy]

Back to the mysterious German "wood critter"... I really didn't know what was making those footsteps up to the sliding glass door... I think I figured it out... today's footprints:



Today's meanderings:

my-stuff-dot-com.com/Heidenheim/Jan1510.htm

[kammy]

I wanted to finish looking at the Morgellons.org Case Definition Study before I moved back to our "Mystery Spheres"... it seems like we're jumping around and we are, but - that's ok, that's the nature of 'thread' postings and researching - what am I trying to accomplish here? I'm trying to give the doctors/scientists that we're about to see in our upcoming appointments educated guesses of places to look and to begin to 'see' what our disease is.

What do we believe to be true from what has been scientifically or reliably reported? We know that our disease is 'invisible'... our immune systems do not recognize it as a serious pathogen even though it is, we do not have a normal immune response to the pathogen(s). This logically indicates that the Morgellons pathogens must be partially created from within our own system(s) or were artificially created from human body functioning cells/systems. Our pathogens do not show up in modern-day pathology lab testing. Our lesions are cancer-like, in that they are sores that do not heal and/or stay with us for long periods of time. Our lesions resemble skin cancer lesions. There is a 'sand-like/granular' material coming out of our lesions. Carnicom is finding human hemoglobin in the "Morgellons Mystery Sphere".

Carnicom is testing for hemoglobin and that normal white blood cells do NOT contain hemoglobin:

wiki.answers.com/Q/Do_white_blood_cells_contain_hemoglobin

However, in the name of finding cures for diseases - scientists have manipulated various cells so that the human body does not reject them, so that the immune system does not see them as 'foreign', and they have even coated some of these cells with human hemoglobin, creating "hybrid" hemoglobin.

www.encyclopedia.com/doc/1P2-8135893.html

"scientists have created laboratory mice whose blood cells make human hemoglobin"...

www.jstor.org/pss/3973658

(**I just noted to Jeany because of the reference to sickle cell in the above article, and I don't know if this has any significance at all? - that my neighbor in Atlanta, with whom we share the same water source, was Afro-American and had a long battle with sickle-cell anemia and passed away a couple of years ago. She had been in that particular home for many years.)

I was curious as to what sickle cell looks like microscopically:

Sickle Cell

[kammy]

From what little bit I can tell that has happened in disease research, I can see where cells were taken from humans and put into vaccines, they were assumed/considered to be safe there and were added to other things... and eventually into pesticides.

I just put in a wide range search on "history of cells in disease research"... we don't know what all has happened in cell research for the past 50 years? I want to look at the history of it to see what has transpired and to see what has been documented?

tinyurl.com/yg5jwqb

In studying disease research, we can also look at Stem Cells:

Stem Cell Research Basics: Early Stem Cells

www.kumc.edu/stemcell/early.html

The blastocyst fits in size to the Morgellons Spheres:

"How big is a blastocyst?

A blastocyst is a microscopic group of cells — smaller than Roosevelt’s eye on the face of a U.S. dime."

If you scroll down in the above article you see the patient in the hospital bed and out to the side you see that the pancreas makes its own cell, called a pancreatic cell - I decided to look at this a little closer since some have and are reporting pancreas involvement with their Morgellons:

en.wikipedia.org/wiki/Pancreatic_stellate_cell

en.wikipedia.org/wiki/Pancreas

[kammy]

To get a better idea of how human cells initially started being manipulated, let's go back to the 50's... scientists were looking for cells that the body wouldn't reject, that reproduced heartily and quickly, could not be easily destroyed - for polio research... in fact, the polio vaccine that we all received contained HeLa cells - cells from a woman who died of "an aggressive adenocarcinoma of the cervix". Her cancer cells were harvested without her nor her family's knowledge and used in future vaccines and research. 14 years after the polio vaccine was created, her family found out and sued and tried to stop the production of her cells being used without permission nor consent in research and lost the case in court.

WHAT THE HELA HAPPENED HERE?:

Henrietta Lacks - HeLa Cells

en.wikipedia.org/wiki/Henrietta_Lacks

"Henrietta Lacks (August 18 (?), 1920 – October 4, 1951) was the involuntary donor of cells from her cancerous tumor, which were cultured by George Otto Gey to create an immortal cell line for medical research. This is now known as the HeLa cell line.

The new book, The Immortal Life of Henrietta Lacks tells the story of Henrietta Lacks and her amazing cells.

According to reporter Michael Rogers, the subsequent development of HeLa by a researcher at the hospital helped answer the demands of 10,000 who marched for a cure to polio just a few days before. By 1954, HeLa was used by Jonas Salk to develop a vaccine for polio.[6] As stated by reporter Van Smith in 2002 a demand for HeLa cells "quickly rose ... the cells were put into mass production and traveled around the globe- even into space, on an unmanned satellite to determine whether human tissues could survive zero gravity". Smith continued, "In the half-century since Henrietta Lacks' death, her ... cells ... have continually been used for research into cancer, AIDS, the effects of radiation and toxic substances, gene mapping, and countless other scientific pursuits". HeLa cells have been used to test human sensitivity to tape, glue, cosmetics, and many other products."

What do they look like? Here's a stock photo of a HeLa Cell -

[kammy]

There has been lots of controversy around HeLa Cells.

www.infobarrel.com/The_Origin_of_Hela_Cells

"Hela cells are the most widely used cell line in cell and tissue culture laboratories. It is this very cell line that was used to discover the polio vaccine.

Hela cells were first taken from Henrietta Lacks who died of cervical cancer. Henrietta Lacks was diagnosed with cancer of the cervix at Johns Hopkins Hospital in November 1950. The gynaecologist sent a cervical biopsy to the pathology lab for inspection. Unfortunately she died as the biopsy was being carried out. However, the scientist at the lab called George Otto Gey decided to grow cells extracted from the biopsy. He discovered that the cells where capable of growing indefinitely in cell culture flasks. He decided to call it HeLa cells after the 2 letters derived from Henrietta Lacks.

George decided to send the cells to various labs across the country. Today Hela cells are being used in almost all biological labs for scientific research. Its unique feature to divide abnormally makes it very useful as it can be easily maintained in incubators. The scientific reason for its immortality has been attributed to its active form of “Telomerase”. Telomerases have been implicated in aging the process. It is suggested that as cells divided telomeres at the end of chromosomes shortens and ultimately the cell dies. The active form of telomerase prevents the shortening of the chromosomes of Hela cells.

Today a lot of controversy has surrounded the Hela cell line. The cells taken from Henrietta Lacks were grown in flasks and even cultured to be sold to research labs around the world. Hela cells today are produced in large numbers from the very cell line taken in 1951 by various biological companies specialising in cells. The immediate family of Henrietta Lacks were unaware of the issue till a few years back. The demands are that she is given sainthood for her contribution to science."

www.ncbi.nlm.nih.gov/pubmed/19722756

"The cancer cells, now called HeLa cells, grew rapidly in cell culture and became the first human cell line. HeLa cells were used by researchers around the world. However, 20 years after Henrietta Lacks' death, mounting evidence suggested that HeLa cells contaminated and overgrew other cell lines. Cultures, supposedly of tissues such as breast cancer or mouse, proved to be HeLa cells. We describe the history behind the development of HeLa cells, including the first published description of Ms Lacks' autopsy, and the cell culture contamination that resulted. The debate over cell culture contamination began in the 1970s and was not harmonious. Ultimately, the problem was not resolved and it continues today. Finally, we discuss the philosophical implications of the immortal HeLa cell line."

[kammy]

www.archivesofpathology.org/doi/full/10.1043/1543-2165-133.9.1463

"Abstract

Henrietta Lacks died in 1951 of an aggressive adenocarcinoma of the cervix. A tissue biopsy obtained for diagnostic evaluation yielded additional tissue for Dr George O. Gey's tissue culture laboratory at Johns Hopkins (Baltimore, Maryland). The cancer cells, now called HeLa cells, grew rapidly in cell culture and became the first human cell line. HeLa cells were used by researchers around the world. However, 20 years after Henrietta Lacks' death, mounting evidence suggested that HeLa cells contaminated and overgrew other cell lines. Cultures, supposedly of tissues such as breast cancer or mouse, proved to be HeLa cells. We describe the history behind the development of HeLa cells, including the first published description of Ms Lacks' autopsy, and the cell culture contamination that resulted. The debate over cell culture contamination began in the 1970s and was not harmonious. Ultimately, the problem was not resolved and it continues today. Finally, we discuss the philosophical implications of the immortal HeLa cell line.

THE AUTOPSY

Ms Lacks' autopsy was performed at 10:30 am on the same day as her death. Examination of the body revealed a “well-developed, thin, colored female [with] deeply pigmented skin over the lower abdomen such as seen after x-ray treatment.”3 The peritoneal cavity contained a small amount of yellowish fluid and approximately 1 L of fluid was found in the pleural cavity, but the pericardium was devoid of fluid. The lungs were noted to have bibasilar lobar pneumonia with cheesy material in the bronchi. The mucosa of the bronchi was blood stained. The cranial cavity and neck organs were not examined because permission was not granted.

Small, white, and firm nodules were observed throughout both the thoracic and abdominal cavities, including the surfaces of the peritoneum, the entire length of the intestines, and the surface of the liver. Furthermore, both the pleural surface and the superior surface of the diaphragm (right side more than the left side) were covered with nodules, as were the lung, liver parenchyma, and the pericardium. The nodules varied slightly in size, measuring from 8 mm in diameter on the peritoneal surface to 1 cm in the lung parenchyma. However, the largest mesenteric lymph node infiltrated with tumor was 6 cm in length. Small tumor nodules, 3 mm in diameter, were seen in each adrenal gland. At the apex of the right ventricle, a tumor nodule approximately 1 cm in diameter protruded into the lumen. Relatively little necrosis was seen in any of the nodules.

A large subcapsular hematoma was present at the superior pole of the right kidney and a tumor nodule had grown into the capsule. Bilaterally, the ureters, calyces, and pelves were markedly dilated, consistent with severe hydronephrosis. The left ureter was involved in a mass of tumor just inside the brim of the pelvis, while a tumor mass near the posterior wall of the bladder entangled the right ureter. The bladder itself was adherent to the anterior abdominal wall. Many small nodules were seen on the bladder mucosa, and the external surface was nearly a solid mass of tumor.

The right ureter was dilated within 4 cm of the bladder, where the dilatation ceased abruptly. At this level, the circumference of the ureter was 14 mm; distally, the right ureter had been left intact and a probe passed with some difficulty down to the bladder. The probe could not be passed through the left ureter to the bladder, although both ureteral openings appeared patent from within the bladder. Closer examination revealed that the left ureter was dilated to the bladder wall, at which point a mass of tumor on the external surface caused the obstruction. The bladder was partially surrounded by nodular masses of tumor that penetrated the bladder wall, particularly in the trigone area. The bladder was not especially dilated. Tumor was seen infiltrating the wall of the vagina and friable masses of tumor replaced the cervix. The uterus was approximately normal in size and covered with tumor nodules, while the fallopian tubes and ovaries were obliterated by clusters of tumor nodules. A mass of tumor surrounded the iliac veins, and the area of the right iliac vein appeared to have tumor entering its lumen. Focal uremic diphtheritic colitis was also noted.

HeLa CELLS

Previous efforts to grow either normal cervical epithelium or cervical carcinoma in culture proved elusive9; however, efforts to grow cells from the aggressive adenocarcinoma of the cervix that had affected Henrietta Lacks were successful.

Recently, HeLa cells have been shown to contain human papillomavirus (HPV) 18 DNA11 and HPV18-positive HeLa cells have been linked to changes in microRNA expression.12 Since HPV18 has been associated with very aggressive adenocarcinomas, this finding may explain why Dr Gey was surprised by the prolific growth of HeLa cells in culture. Routine Papanicolaou smear screening may not detect rapidly progressive cervical carcinomas; the new HPV vaccine holds the promise of preventing these tumors.

TISSUE CULTURE CONTAMINATION

George Gey was generous with requests for HeLa cells. Since HeLa cells were a robust, immortal cell line, easily propagated over generations in culture, Dr Gey supplied samples to scientists in the United States and internationally who were interested in studying the first established human cancer cell line. HeLa cells proliferated in cultures around the world and, as the years passed, evidence accumulated that HeLa cells had contaminated other cell lines. Interspecies cross-contamination with HeLa, easier to detect than intraspecies contamination, was described in the early 1960s.

In 1974, 5 cell lines—reportedly of human lineage and infected with animal viruses—were sent to the United States from the Soviet Union. All of the cell lines were revealed to be HeLa in origin.22 In a story previously detailed,7 the realization that HeLa cells had contaminated cultures so far afield led to a reappraisal of tissue culture stocks by the American Type Culture Collection (ATCC; Manassas, Virginia) and the Cell Culture Laboratory at the Naval Biosciences Laboratory (Oakland, California).21–27 For instance, a follow-up study to the proper identification of the Soviet Union cell lines implicated HeLa cells as contaminants of several other cell lines.23 The ATCC found that 27 of 56 cell lines had G6PD type A variant.24 Further analysis revealed that several of these cell lines possessed some, but not all, HeLa markers. It was hypothesized that these variations could represent somatic cell hybridization between the original cell line and the contaminating HeLa cells.

During the previous quarter century, Dr Gey's samples of HeLa cells had multiplied in laboratories throughout the world, as they were transferred from researcher to researcher and across international borders. Several hypotheses were offered for HeLa cells' remarkable growth beyond what might be expected of a very aggressive cervical adenocarcinoma. As the first human cancer cell line, and a potent cell at baseline, it had been selected to survive in culture after countless passages, cell divisions, and viral infections.

In the battle for reproduction, HeLa was best selected to outcompete other cell lines and eventually overgrew other cultures it invaded. Another possible explanation was that cell lines often came from outside laboratories. Prior to their deposition in tissue culture collection banks, the cell lines had been subjected to variable laboratory techniques. Furthermore, these laboratories undoubtedly possessed other cell lines such as the ubiquitous HeLa. Since HeLa cell contamination has been reported from air droplets,28 poor laboratory technique would suffice to rapidly contaminate other cell lines, which would then be passed on to subsequent laboratories.24,29

CELL CULTURE CONTROVERSY

The debate over cell culture contamination was not always harmonious.7,30 Contaminated cell lines went far beyond HeLa cells. In one study, human breast cancer cell lines were found to have both intraspecies and interspecies contamination. Other cell lines reported to be human cells were actually derived from hamster, rat, mouse, mongoose, or mink; gibbon cells were actually human cells; horse cells were dog cells.25 In total, 41 of 253 cell lines (16%) were not what they had been purported to be. Years of research and numerous academic careers were built on the presumed identity of various cell lines, and clarifying incorrect data required repudiating previously reported results.31 Alternative explanations for HeLa cell contamination were offered in some instances.32

Unfortunately, the impact of cell culture contamination extended far beyond the relatively narrow field of cytobiology and the researchers studying cell lines. For example, radiobiologists investigating the relation of radiation doses to cell death in human kidney cells were surprised to discover that the cells they thought were derived from human kidney were actually HeLa.26 Controversy erupted regarding the interpretation of their results: how did irradiating malignant cells translate to normal cells when evaluating cell death?33 The debate even ensnared Jonas Salk, MD, who stated at a conference in October 1978 that he had injected study subjects, enrolled in a vaccine trial, with HeLa cells that had contaminated his cultures7; however, any mention of HeLa failed to find its way into his published remarks regarding the “‘theoretical’ possibility of transmitting a neoplasia-inducing factor.”34

HeLa CELLS AND CELL CULTURE CONTAMINATION TODAY

Despite the passing of nearly 50 years since the problem first surfaced of HeLa cell contamination of tissue cultures and despite the explosive advances in molecular biology, cell culture contamination remains an important issue for the scientific community.35–38 The problem extends far beyond HeLa cells, although they remain a culprit.38 In one study, 45 of 252 human cell lines (18%) supplied by 27 of 93 originators (29%) were contaminated.39 Most of the contaminants were intraspecies cells, suggesting improved detection of interspecies contamination, but still concerning. New techniques, such as amplification of minisatellite-region DNA40 and short tandem repeat profiling,41 which are faster and more precise than older techniques such as chromosome banding, have not been widely adopted in a standardized, universal fashion. Fortunately, there was recently a call to action on preventing contaminated cell lines.42"

From above:

"The debate even ensnared Jonas Salk, MD, who stated at a conference in October 1978 that he had injected study subjects, enrolled in a vaccine trial, with HeLa cells that had contaminated his cultures7; however, any mention of HeLa failed to find its way into his published remarks regarding the “‘theoretical’ possibility of transmitting a neoplasia-inducing factor."

Neoplasm

en.wikipedia.org/wiki/Neoplasm

[kammy]

G6PD

Jan 12, 2010 20:00:29 GMT -5 kammy said:

Chronic granulomatous disease

en.wikipedia.org/wiki/Chronic_granulomatous_disease

"Chronic granulomatous disease (CGD) (also known as "Bridges–Good syndrome," "Chronic granulomatous disorder," and "Quie syndrome"[1]) is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds (most importantly, the superoxide radical) used to kill certain ingested pathogens.[2] This leads to the formation of granulomata in many organs.[3] CGD affects about 1 in 200,000 people in the United States, with about 20 new cases diagnosed each year.[4][5]

The underlying cellular mechanism that causes chronic granulomatous disease was discovered in 1967, and research since that time has further elucidated the molecular mechanisms underlying the disease.[8]

Chronic granulomatous disease is the name for a genetically heterogeneous group of immunodeficiencies. The core defect is a failure of phagocytic cells to kill organisms that they have engulfed because of defects in a system of enzymes that produce free radicals and other toxic small molecules. There are several types, including chronic X-linked disease, chronic b-negative disease, X-linked cytochrome b-positive disease, x-linked variant disease, and atypical granulomatous disease[9].

Symptoms

Classically, patients with chronic granulomatous disease will suffer from recurrent bouts of infection due to the decreased capacity of their immune system to fight off disease-causing organisms. The recurrent infections they acquire are specific and are, in decreasing order of frequency:

* pneumonia
* abscesses of the skin, tissues, and organs
* suppurative arthritis
* osteomyelitis
* bacteremia/fungemia
* superficial skin infections such as cellulitis or impetigo

Most people with CGD are diagnosed in childhood, usually before age 5.[10] Early diagnosis is important since these people can be placed on antibiotics to ward off infections before they occur.

Atypical infections

People with CGD are sometimes infected with organisms that usually do not cause disease in people with normal immune systems. Among the most common organisms that cause disease in CGD patients are:

* bacteria (particularly those that are catalase-positive)[11]
o Staphylococcus aureus.
o Serratia marcescens.
o Salmonella species.
o Klebsiella species.
o Pseudomonas cepacia, a.k.a. Burkholderia cepacia.[12]
o Nocardia.[13]
* fungi
o Aspergillus species. Aspergillus has a propensity to cause infection in people with CGD and of the Aspergillus species, Aspergillus fumigatus seems to be most common in CGD.
o Candida species.

Microscopic image of the fungus, Aspergillus fumigatus,
an organism that commonly causes disease in people
with chronic granulomatous disease.

Genetics

Most cases of chronic granulomatous disease are transmitted as a mutation on the X chromosome and are thus called an "X-linked trait".[10] The affected gene on the X chromosome codes for the gp91 protein p91-PHOX (p is the weight of the protein in kDa; the g means glycoprotein). CGD can also be transmitted in an autosomal recessive fashion (via CYBA and NCF1) (*??) and affects other PHOX proteins. The type of mutation that causes both types of CGD are varied and may be deletions, frame-shift, nonsense, and missense.(*??)[14][15]

A low level of NADPH, the cofactor required for superoxide synthesis, can lead to CGD. This has been reported in women who are homozygous for the genetic defect causing glucose-6-phosphate dehydrogenase deficiency (G6PD), which is characterised by reduced NADPH levels.

Pathophysiology

Phagocytes (i.e., neutrophils, monocytes, and macrophages) require an enzyme to produce reactive oxygen species to destroy bacteria after they ingest the bacteria in a process called phagocytosis, a process known as the respiratory burst. This enzyme is termed "phagocyte NADPH oxidase" (PHOX). The initial step in this process involves the one-electron reduction of molecular oxygen to produce superoxide anion, a free radical.

Superoxide then undergoes a further series of reactions to produce products such as hydrogen peroxide, hydroxyl radical and hypochlorite (bleach). The reactive oxygen species this enzyme produces are toxic to bacteria and help the phagocyte kill them once they are ingested. In particular, individuals are vulnerable to infections with catalase positive organisms.

Defects in one of the four essential subunits of this enzyme can all cause CGD of varying severity, dependent on the defect. There are over 410 known possible defects in the PHOX enzyme complex that can lead to chronic granulomatous disease[3].

Diagnosis

The nitroblue-tetrazolium (NBT) test is the original and most widely-known test for chronic granulomatous disease.[16] It is negative in CGD, and positive in normal individuals.

This test depends upon the direct reduction of NBT by superoxide free radical to form an insoluble formazan. This test is simple to perform and gives rapid results, but only tells whether or not there is a problem with the PHOX enzymes, not how much they are affected. A similar test uses dihydrorhodamine (DHR); whole blood is stained with DHR, incubated, and stimulated produce superoxide radicals which reduce DHR to rhodamin in cells with normal function.

An advanced test called the cytochrome C reduction assay tells physicians how much superoxide a patient's phagocytes can produce. Once the diagnosis of CGD is established, a genetic analysis may be used to determine exactly which mutation is the underlying cause.

Antibiotics

Physicians often prescribe the antibiotic trimethoprim-sulfamethoxazole to prevent bacterial infections.[17] This drug also has the benefit of sparing the normal bacteria of the digestive tract. Fungal infection is commonly prevented with itraconazole,[18] although a newer drug of the same type called voriconazole may be more effective.[19] The use of this drug for this purpose is still under scientific investigation.

Immunomodulation

Interferon, in the form of interferon gamma-1b (Actimmune) is approved by the Food and Drug Administration for the prevention of infection in CGD. It has been shown to prevent infections in CGD patients by 70% and to reduce their severity. Although its exact mechanism is still not entirely understood, it has the ability to give CGD patients more immune function and therefore, greater ability to fight off infections. This therapy has been standard treatment for CGD for several years.[20]

Hematopoietic stem cell transplantation (HSCT)

Hematopoietic stem cell transplantation from a matched donor is potentially curative. The procedure is controversial, and not without significant risk [21]

Prognosis

There are currently no studies detailing the long term outcome of chronic granulomatous disease with modern treatment. Without treatment children often die in the first decade of life. Available data indicates that X linked CGD is more severe, with most treated patients dying in the third or fourth decade of life [22].

Epidemiology

CGD affects about 1 in 200,000 people in the United States, with about 20 new cases diagnosed each year.[4][5]

Chronic granulomatous disease affects all people of all races, however, little information on prevalence outside of the United States is available. One survey in Sweden reported an incidence of 1 in 220,000 people [22].

Research

Gene therapy is currently being studied as a possible treatment for chronic granulomatous disease. CGD is well-suited for gene therapy since it is caused by a mutation in single gene which only affects one body system (the hematopoietic system). Viruses have been used to deliver a normal gp91 gene to rats with a mutation in this gene, and subsequently the phagocytes in these rats were able to produce oxygen radicals.[24]

In 2006, two human patients with X-linked chronic granulomatous disease underwent gene therapy and blood cell precursor stem cell transplantation to their bone marrow. Both patients recovered from their CGD, clearing pre-existing infections and demonstrating increased oxidase activity in their neutrophils. However, long-term complications and efficacy of this therapy are unknown.[25]"

web.mit.edu/sts/pubs/pdfs/MIT_STS_WorkingPaper_25_Landecker.pdf

On page 8 in the above .pdf, (we are not permitted to reprint) -

It mentions that so many cross-contaminations had occurred (1966) that it a bank of cell lines had to be established to be able to distinguish cell lines. A geneticist, Stanley Gartler, tested 18 supposedly different human cell lines and all of them came back with the G6PD enzyme A band that is only present in blacks.

All of the cell lines had become contaminated with HeLa, which has the G6PD A band.

From 1986-1996, it was internationally realized that the variances in the G6PD is the cause of haemolytic diseases.