Dec 19, 2005
http://www.nih.gov/news/pr/dec2005/nci-13a.htm NIH & Genome Ressearch Group Join Forces
The Cancer Genome Atlas Project (TCGA)
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Monday, December 19, 2005
9:38AM – What’s New in MDS Research Links
NIH & Genome Ressearch Group Join Forces
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Beware of Drugs!
The Cancer Genome Atlas Project (TCGA)
8:50AM – My Questions
How do I get the full article from pubmed – Loansome.doc? Infotrieve?
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Pub Med Central Looks Good so Far
Also Medline Plus http
8:29AM – BLOGS I Like and Use
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7:56AM – NIH Launches Comprehensive Effort to Explore Cancer Genomics
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December 13, 2005
The Cancer Genome Atlas Begins With Three-Year, $100 Million Pilot
The National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of the National Institutes of Health (NIH), today launched a comprehensive effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, especially large-scale genome sequencing. The overall effort, called Th Cancer Genome Atlas (TCGA), will begin with a pilot project to determine the feasibility of a full-scale effort to systematically explore the universe of genomic changes involved in all types of human cancer.
“Now is the time to move forward with this pioneering initiative. Thanks to the tools and technologies developed by the Huma Genome Project and recent advances in using genetic information to improve cancer diagnosis and treatment, it is now possible to envision a systematic effort to map the changes in the human genetic blueprint associated with all known forms of cancer,” sai NIH Director Elias A. Zerhouni, M.D. “This atlas of genomic changes will provide new insights into the biological basis of cancer, which in turn will lead to new tests to detect cancer in its early, most treatable stages; new therapies to target cancer at its most vulnerable points; and, ultimately, new strategies to prevent cancer.”
7:39AM – Research Sources and Links
Suppression of hematopoiesis (formation and development of blood cells) likely is mediated by an expanded population of cytotoxic T lymphocytes: cluster of differentiation 8, HLA-DR+ (CTLs: CD8, HLA-DR+), which are detectable in both the blood and bone marrow of patients with aplastic anemia. These cells produce inhibitory cytokines, such as gamma interferon and tumor necrosis factor, which are capable of suppressing progenitor cell growth. (The T lymphocytes are killing the progenitors!) These cytokines suppress hematopoiesis by affecting the mitotic cycle (cell division) and cell killing (apotosis) through induction Fas (Fas is a known inducer of apoptosis and is important in the regulation of several aspects of the immune system, including cytotoxic killing of cells potentially harmful to the organism such as virus-infected or tumor cells.)-mediated apoptosis (Programmed cell death) It also has been shown that these cytokines induce nitric oxide synthase and nitric oxide production by marrow cells, which contributes to immune-mediated cytotoxicity (The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitised T-lymphocytes or by lymphoid or myeloid “killer” cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement) and elimination of hematopoietic cells.
Anemia is a disorder that results in a decrease in the ability of the blood to carry oxygen. Anemia is itself not a diagnosis but merely a sign of underlying disease. The initial classification of anemia is best accomplished by examination of the data from a hematology analyzer and by an examination of the peripheral blood smear. The physician most commonly classifies anemias initially by the instrument’s red cell indicies, especially the mean corpuscular volume (MCV). On newer counters, the red cell distribution width (RDW) or red cell morphology index (RCMI) is another useful measurement. The anemia may be microcytic, normocytic, or macrocytic.
There is a relationship between CD34 and low amino acids. CD34 is a glycoprotein (protein that contains a part that is a carb) that spans the outer membrane of cells. Proteins (and glycoproteins are made up of constituent groups called amino acids. These amino acids are linked by peptide bonds (chemical bonds between the carboxyl and amino groups of amino acids) the low levels of both may be related.
It appears from a chemical structure of cd34 that it may made up primarily of the amino acids of which I am deficient (Threonine, Arginine and Cystine). Maybe my low levels of cd34 are due to low levels of amino acids and my body cannot synthesize the protein because of this but I believe it more likely that the low levels of amino acids are due to low levels of cd34. I don’t believe that my body is having problems producing cells with cd34. It is possible that the cd34 protein or something that binds to the protein is marking the cells for destruction. Thus destroying the amino acids.
Increasing intake of amino acids is worth a shot, but it may be detrimental to kidneys (excess protein). Most of the amino acids that are low are non-essential. My body should be able to produce these by itself. If my body was having problems producing these amino acids I would expect more health problems than anemia. The other essential amino acids are brought in from extraneous sources. Since I am low in both essential and non-essential I should look in other areas for the problem.
CD 34 is a membrane protein. It has a part that extends well outside of the cell and a part that extends inside of the cell. Many membrane proteins are transport proteins that act to bring “stuff” inside or outside of cells. Seems like the actual structure of cd34 is in dispute. Can’t seem to find anything definitive. I do see that there are possible phosphorylation sights for all of the amino acids I am deficient in. (Phosphorylation is an energy favorable reaction) not important but in the fact that it shows me that the extra cellular tail probably is made up of a lot of the aminos I specified. (Only one definitive though) Cd34 is also possibly related in allot of cell-to-cell binding. Found primarily in hematopoietic cell lines. Cell to cell binding such as clotting (platelets may have an unusually high number of cd34 binding sites or more active cd34 binding sites.
Something is destroying my hematopoeitic cells before they mature. Interesting that L-selectin binds cd34 and is seen as a homing receptor for lymphocytes. It is only supposed to bind endothelial cells (possibly for destruction) and it is not supposed to bind to hematopoietic cd34. Maybe it is binding hema cd34 in my system.
All right cd34 and threonine. Okay let’s start from the beginning. Again, cd34 is a protein. Proteins are made up of amino acids.
Amino acids share a similar chemical structure, most notably that they all have two “ends” one carboxyl end and one amino end (that’s where they get their name from).
Chemically I do not have to know what constitutes these groups as long as I recognize that they both have differences in charge (think magnets likes repel opposites attract) These amino acids are linked (bonded) together by peptide bonds between the two chemical groups of different amino acids.
Amino acids linked by peptide bonds. These linked amino acids are proteins. These proteins can actually include chemical structures that are not altogether protein in nature. We are going to focus on glycoproteins. Glycoproteins have somewhere within their structure a chemical component that is carbohydrate in nature (not an amino acid but a structure that is organic in nature (primarily Carbon)and is usually made up of Carbon Oxygen and Hydrogen.
They are usually primary energy sources for cells.) In other words this protein has been attached to a carbohydrate and has formed a stable product. (Not predisposed to being broken apart into its constituent amino acid and carbohydrate groups) This is cd34. A glycoprotein. CD34 is a membrane protein. This means that it is found attached to the outer membrane of cells.
They are usually attached between the two phosholipid bilayers of the cells. Cells have many membrane proteins. Some only extend above the membrane (in contact only with stuff outside of the cell). Others extend only into the inside of the cells. Others extend both inside AND outside of the cell. These are transmembrane proteins. (they extend across the cellular membrane) This is the type of protein that is cd34. I would guess that the carbohydrate portion of this glycoprotein is the section that actually spans the membrane (the charge of the amino acids would not bond there very well.
A phospolipid does not like charge. It has a charge on its phosphate end but this is attached to a long hydrocarbon tail that lacks charge. Because this tail does not like the charges of the amino acid it would not want the amino acid to be located very close to the tails. This is where the neutral (more or less) carbohydrate section could come into place. It acts as a bridge that connects to proteins on each side of the cell membrane. Because this is stable it is labeled a glycoprotein.
Many membrane proteins allow particles (charged particles (ions etc.) that would normally not be allowed across) into the cells. Others actually just send signals into the cell when the proper receptor is stimulated. I’m not sure what cd34 is used for yet but I do have some ideas. Funny thing is that the exact structure of cd34 is in dispute. There are definitely two conformations. One has a section that extends into the cell only a short distance. The other extends into the cell a much longer distance. It sounds like the extracellular portion of the protein is the same for both conformations (structures). Because of the similar structure of cell membranes between all cells it could be very difficult to differentiate between the cells.
This is where proteins come into play. Each cell has a different membrane protein profile. This is the mechanism that the immune system uses to attack invading cells. If it does not have proteins that are seen as being the same as the organism the cell is marked for destruction. Okay that’s it for now but I still have to explain threonines potential role in this.
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6:57AM – My Alternative Stance
What follows is a guide to healing yourself using an approach that is an alternative to the drug based protocols being recommended by conventional medicine. I am not a medical professional but my wife and I have read countless books on nutrition and alternative healing strategies. The first thing we recommend is a radical change in diet and lifestyle. My full regimen is documented at http://aplasticcentral.com/Holistic_Medicine/Holistic.htm.
Contrary to what we have come to expect in our society, there are no quick and easy answers. Since adopting my alternative/holistic regimen, I have returned to 90% of my formal self. In the interest of full disclosure, as of November, 2005 after over three years of feeling great I am currently in a bit of a relapse but am still able to carry on a fairly normal lifestyle.
I rely on conventional medicine only for life saving therapies like blood and platelet transfusions, monitoring of blood counts, infection control, etc. I highly recommend contacting an environmental doctor in your area http://www.aaem.com Tel (316) 6845500, seeking a phone consult with either Dr. Rea http://ehcd.com Phone: 214.368.4132 or Dr. Sherry Rogers 315-488-2856 or get the books by Dr. Rogers at http://prestigepublishing.com
I do not believe in any quick fixes when it comes to healing the body. Unfortunately, we live in a “sound byte” society and are constantly bombarded with the latest “purple pill” designed to cure everything from eczema to “acid reflux disease” – in English that means you are eating too much of the wrong foods and drinking soda.
In the case of AA/MDS, the conventional approach is another “miracle drug” called cyclosporine and is often coupled with “ATG” (a serum extracted from a horse or a rabbit!). This drug based approach to healing almost killed me. See photo on the website.
My approach to healing is certainly no less bizarre than injecting someone with horse serum, but unfortunately most people are reluctant to recognize the value of an alternative approach and are unwilling to take the time and effort it requires. I am living proof (see photo on the right taken in November of 2005 with 2 of 3 grandchildren) that an alternative/holistic strategy works. It takes a lot of discipline and is not easy, but it works!
If after reading the website at http://aplasticcentral.com you would like a one stop source of how all this worked for me, you can preview my book “Aplastic Anemia and Autoimmune Diseases, for FREE at http://aplasticcentral.com/AA_Book_Preview.htm
Provide a Healthy Environment to Allow You Body to Heal Itself.
Take the time to read everything at my site because it chronicles my journey and many others with all the ups and downs http://aplasticcentral.com. My story is at http://aplasticcentral.com/AA_Members/bruce.htm. I tried ATG and the toxic drugs regimen; I was a candidate for Bone Marrow Transplant and decided against it. I was also very close to undergoing another toxic strategy using a drug called cytoxin. I decided against all of them and have taken a “Natural or Alternative Approach”. The good news is that it is not expensive – the bad news is you have to make radical changes in your lifestyle and diet and it took almost 6 months before I stabilized. I am now transfusion independent and have 85 % of my old life back!
Read the books by Dr. Sherry Rogers that can be found at either http://amazon.com or http://prestigepublishing.com. If possible, start with an environmental or chemical allergy doctor if you can find one. If not, maybe go online and start with http://www.macrobiotics.org/default.html and try to build from there using other links I provide at http://aplasticcentral.com/Alternative_Medicine/alternative.htm (bottom of page). Also check this website http://www.geocities.com/marlakins/index.html – Marla uses a vegetable based diet and is very knowledgeable on how virtually everything impacts our immune system. I use a vegetable and macrobiotic combination. Other very good sources that have been recommended by Marla http://www.gerson.org, http://www.godshealthplan.com/healthtips/healthtips.html.
Set a goal to become transfusion and drug independent. Maintain the transfusion regimen because it is necessary to keep you alive while you fight your fight, but set goals to lengthen the time between transfusion and then meet the goals (It takes time and there will be setbacks so also be patient with yourself). As of December 14, 2002 it has been nearly seven months since my last blood transfusion and nearly four months since my last platelet transfusion.
Make the necessary lifestyle changes based on the belief that AA is an autoimmune disorder and we need to help our body rebalance its immune system. Avoid the “quick fix” cures with herbs and shark oil or any “other one stop shop for a cure” Many of them may help but it is the understanding of a full program that will result in success.
Become at peace with your self and your illness – If you are a “Type A”, become a “Type B”. Dr. Bernie Siegel says that a positive attitude is perhaps the most important ingredient in combating illness and disease.
Give your body the rest it is asking for – Even if it means sleeping 10 hours a night – It is literally battling for your life and needs all the help you can give it. Take naps when you feel tired, but also push yourself to exercise as much as you can.
Get tested for toxins by the environmental or chemical allergist and take the antigens prescribed. Avoid people who smoke, use lots of perfumes, gasoline fumes, etc. After a while you will virtually smell and feel the things to avoid. Go for fresh air and sunlight. Get a good air cleaner (mine cost about $500) and use it to clean the air in your sleeping room. Keep the dusts and pollens down.
Find a regimen that will help eliminate harmful toxins from your system (I take a daily sauna). Clean up your personal environment. Get rid of carpets (I moved to a different house with hardwood floors). Avoid chemicals in your house and environment. Pay very careful attention to your physical environment – Clean air? (get a good quality air filter – $500) Mine is an Austin Health mate (Search on Austin Health mate at http://google.com and you’ll find lots of places to by one) Avoid toxic substances (gas, cleaning fumes, etc)
Exercise at least 45-60 minutes per day You will likely have to build up to this as I could barely walk when I started)
What you eat is critically important and we all seem to be constantly experimenting with this facet. The one clear theme is what NOT to eat, i.e. processed foods, fast foods, “enriched” flours, etc. I personally subscribe to what I call a”rotational mostly macrobiotic diet”. As much as is humanly possible, I eat Grains (30-60% of each meal), Greens (25-30%) and Beans (10-15%). This means I eat lots of Healthy Brown Rice, Oats, Barley, etc. I also try to eat only organically grown fresh vegetables and many say you should not even cook the vegetables (strictly raw fruits and vegetables) and I eat beans prepared from scratch (black, red, navy and a few others). I also eat a limited amount of meat including turkey, chicken and fish. (Once in a while I have pork even though I know it is not good for me, but it is a serious weakness.) I have successfully gotten off beef. I am quite sure that everyone’s situation is a bit different and you probably need to experiment with different wholesome foods to see what it is your body needs. After a while you can actually feel what is good and what is not. Obviously avoid smoking, caffeine, drugs or any kind, processed foods (especially sugar), fast foods – All the things your mother told you would be bad for you!
I drink only fresh spring water courtesy of my In Laws. They have a natural spring on their property and we make a weekly trip to their property and then refrigerate the water. I strenuously avoid soda, caffeine drinks, sweetened drinks, etc.
I also must tell you that I do a daily colon cleansing routine using a coffee enema as prescribed by Dr. Sherry Rogers in her books “Tired or Toxic.” Yuk, Ugh, etc. but it works. Here is the procedure and history.
Research and read everything you can find that discusses these alternative approaches and decides what will work best for you and be willing to a make the necessary changes. Keep a journal so you can refer back to it. You will definitely feel overwhelmed and confused at times. That is one of the reasons I keep this website active and chronicle all my successes and failures. If you falter, regroup and start over.
Do not lose hope or become discouraged because your outlook is critical. Maintain a positive attitude – When you lose you way, come back and read the success stories and words of hope at my site.
Find spiritual peace – I became active in church and strengthened my faith in God after drifting away for a long time. Every one of us needs three things: Someone to love, something to do and something to hope for.
Do a personal fund raiser – I had a golf tournament and raised the money I needed to attend the treatment center in Dallas (EHCD) and cover expenses not covered by insurance. My wife, daughters and friends organized it and it was very successful. I had a second one primarily to let people know that their kindness worked. It was hundreds of people giving small amounts but added up to a big enough number to cover my expenses.
Keep up with the forum and become an active participant. Surround yourself with positive people and bombard yourself with positive thoughts.
Seek God’s Blessing and Good Luck in Your Endeavor!
As Dr. Kenneth Bock states in his book “The Road to Immunity”, No one therapy works all the time, just as nothing is 100 percent preventive. When my patients start out with an attitude of “This is it”, I counsel them that healing is the result of hard work at many levels, and their healing regimen may involve many different treatments and approaches used simultaneously.
Diagnosed with SAA 1/2001 2X ATG (Failed)
Now 90% healthy using Alternative/Holistic Methods
Webmaster of http://aplasticcentral.com
NOT A MEDICAL PROFESSIONAL – PLEASE CONSULT YOUR CARETAKERS
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6:47AM – Genetic Level Research
From Erin, Genetic Counselor
In every cell of our bodies, we have 46 chromosomes, having inherited 23 from each parent. Chromosomes are packages of genes, which are your body’s “blueprints” or sets of instructions for how you grow, develop, function, learn, what you look like, etc. DNA is one of the chemicals that makes up the genes. The other chemical is RNA which will be discussed later. Imagine that each cell of your body has a set of instruction books for how to function. The actual books are the chromosomes, the instructions inside are the genes, and the letters which make up the words is the DNA. Our DNA is 6 billion letters long, in each cell of the body!
As a cell grows and divides into two daughter cells (this process is called mitosis), it has to replicate it’s DNA in order to have two copies for each daughter cell. Remember that DNA is 6 billion letters….so imagine you had to take a 6 billion page book to the photocopier, you may make a mistake somewhere along the line. Well, our cells make mistakes too…a “spelling” mistake that occurs in the DNA of our genes is called a mutation. Mutations in a gene can affect the function of the gene. We have genes that regulate cell growth and proliferation. We have genes for apoptosis. Apoptosis is a fancy word for “programmed cell death.” Our cells are “programmed” to die after a period of time; this helps to regulate cell growth. If aplastic anemia is thought to be caused by more cells undergoing programmed cell death, then there is probably a trigger that is inducing this death earlier. This may be due to a faulty gene instruction.
And in my case, there is a strong possibility that I am “predisposed” to having a problem with the gene responsible for creating healthy blood cells? (My father had Hodgkin’s)
So, there are 46 chromosomes – 23 pairs (is this the double helix?) in every cell in our body (except red blood cells – what is this about?) and they look like this:
The male has an x and y. The male has 2 x’s. The chromosome are made up of Genes
The very first cell (Mother’s fertilized egg) begins to divide (mitosis), becomes an embryo and from there on, each cell is told what it is supposed to become and do. You – become a brain cell. You – become a blood cell. You – become part of the lung, and so on. All cells are derived from stem cells which are the primitive types of cells from which a given organ or tissue arise.
Stem cells are unspecialized cells that have two important characteristics that distinguish them from other cells in the body. First, they can replenish their numbers for long periods through cell division. Second, after receiving certain chemical signals, they can differentiate, or transform into specialized cells with specific functions, such as a heart cell or nerve cell.
Stem cells can be classified by the extent to which they can differentiate into different cell types:
· Totipotent stem cells can differentiate into any cell type in the body plus the placenta, which nourishes the embryo. A fertilized egg is a type of totipotent stem cell. Cells produced in the first few divisions of the fertilized egg are also totipotent.
· Pluripotent stem cells are descendants of the totipotent stem cells of the embryo. These cells, which develop about four days after fertilization, can differentiate into any cell type, except for totipotent stem cells and the cells of the placenta.
· Multipotent stem cells are descendents of pluripotent stem cells and antecedents of specialized cells in particular tissues. For example, hematopoietic stem cells, which are found primarily in the bone marrow, give rise to all of the cells found in the blood, including red blood cells, white blood cells, and platelets. Another example is neural stem cells, which can differentiate into nerve cells and neural support cells called glia.
· Progenitor cells (or unipotent stem cells) can produce only one cell type. For example, erythroid progenitor cells differentiate into only red blood cells.
At the end of the long chain of cell divisions are “terminally differentiated” cells, such as a liver cell or lung cell, which are permanently committed to specific functions. These cells stay committed to their functions for the life of the organism or until a tumor develops. In the case of a tumor, the cells dedifferentiate, or return to a less mature state.
Haemopoietic stem cell
Cell that gives rise to distinct daughter cells, one a replica of the stem cell, one a cell that will further proliferate and differentiate into a mature blood cell.
Megakaryocytes – Giant polyploid cell of bone marrow that gives rise to 3-4,000 platelets.
Karyocyte – Any cell with a nucleus
Chromosomes – Chromosomes are the instructions resident in every cell
We have a set of instruction books in our cells 46 of them – 23 pairs
23 different instruction books but in pairs – 2 strands
One pair or strand is the “sense” and the other pair or strand is the “antisense”
Every single cell has this set of instructions
Each chromosome has short arms and long arms and kinks (the separator between the two arms and this kink is technically called the centromere
The two ends of the chromosomes are called the telomeres
Over time with multiple cell divisions (mitosis) these telomeres (tell-o-mears) become frayed (aging) In the case of some MDS and AA patients they are also prematurely shortened. There is current research at the NIH trying to understand why this occurs and what if anything can be done about it.
Pluripotent stem cells can give rise to all lineages, committed stem cells (derived from the pluripotent stem cell) only to some.
RBC’s do not have a nucleus and therefore do not have chromosomes, genes or DNA?
Each chromosome or book of instructions has a predetermined responsibility, e.g. Book number 1 or chromosome number 1 may be responsible creating brain cells, liver cells, skin cells and multiple other cells (100’s – 1000’s for each chromosome); book number 2 or chromosome number 2 may be responsible for creating bone cells, and hair and kidneys, etc. The stem cells are the karyocytes that
Each book may have 100’s of 1000’s of genes and each gene has a specific responsibility
Others have specific responsibilities and the human genome project was about trying to understand what each gene does – this was accomplished by “sequencing the genes because we can’t really see the genes yet.
Some of the genes are termed “junk” which probably means we don’t know what they do
Others have been sequenced so we know what they do.
The DNA are the words that make up the instructions
DNA Building block of the gene – the letters and the words
Another way to think of it:
Rope is the chromosome
Fiber is the Genes
Chemicals that make up the fiber are the DNA
DNA is the basic building block
DNA’s together make up the Gene
Bunch of genes and junk DNA make up the chromosome
Human Genome Project
Sequence of DNA _ Read all the letters
Much of it is junk
Now we’re trying to better understand what makes up the Genes
Humans have 25,000 genes (Same as a worm!)
How many genes do we have – Completed in 2001
Figured out the order of the letters
What do all the genes do?
Know what some do, others are still being researched.
Chromosomes are the packaged set of instructions
Some of the DNA is wound around proteins
A chromosome is made up of genes and proteins
Proteins are what your body is made up of
The instructions are how to make a protein
We have proteins that make skin color
We have proteins that make blood vessels
Proteins are part of a blood cell
Proteins do different things
Enzyme is a particular type of protein that helps chemical reactions occur
In biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific target molecules (substrates); the process is termed “phosphorylation”. An enzyme that removes phosphate groups from targets is known as a phosphatase.
Generally, the purpose of phosphorylation is to “activate” or “energize” a molecule, increasing its energy so it is able to participate in a subsequent reaction with a negative free energy change. All kinases require a divalent metal ion such as Mg2+ or Mn2+ to be present, which stabilizes the high-energy bonds of the donor molecule and allows phosphorylation to occur.
The largest group of kinases is Protein kinases, which act on and modify the activity of specific proteins. These are used extensively to transmit signals and control complex processes in cells. Various other kinases act on small molecules (lipids, carbohydrates, aminio acids, nucleotides and more), either for signaling or to prime them for biochemical reactions in metabolism. These are named after their substrates and include:
Some proteins are in the membrane of the cell
Amino acids are the building block of the protein
They are the chemicals that form together to make a protein
Amino acid levels can change dramatically
We do amino acids on children and they change dramatically and taken by themselves are not very meaningful.
Metabolic physician should read those reports
PATTERNS of amino acids and that may reveal something
CD34 is a protein made up of amino acids
There are 20 amino acids in our body each protein is made up of various combinations of proteins.
Protein 1 may consist of amino acids 1, 3 ,5 , 7
Protein 2 could be 3, 3, 4, 3, 6
An antigen is simply another type of protein
There are thousands of classes of proteins – antigens, enzymes, antibodies
An antigen is a protein that sits on the surface of a cell and acts like a name tag for a cell
CD34 is a tag saying something is wrong with me – kill me
A Genotype is the actual instruction that is provide by DNA –and the phenotype is the physical characteristic or trait. So the DNA says give me blue eyes that’s the instruction The resulting blue eyes is the phenotype.
Phenotype The physical trait that you get as a result of the genotype
Some people with MDS have different genotypes (-5, -7) but have the same phenotype which is MDS.
Telomere – the tip of the chromosome – Prevents the chromosome from unraveling
The kink is the centromere ( in the middle)
Telomere is the aging process
Everytime a cell divides the telomere gets frayed
Telomorase is a little enzyme (protein) that rebuilds the telomere
If you have low amounts of telomorase you may end up with shortened telomeres
Current research at DNA is discovering that many people with AA have shortened telemeres.
Have known about telmorase for a long time but did not know how they related to various diseases
Scientists experiment with manipulating mice DNA and get predictable results – then go to clinical studies.
MDS – Treatment
Methylation – compounds (chemicals) in the body that surround DNA – bind to the gene and block them from working – Black piece of paper in front
People who have MDS, have too many Methyl groups – they are preventing the genes from doing what they are supposed to.
Is there a less invasive or more natural way to accomplish this methylation process than using invasive toxic drugs.
Herbal therapy? Chinese Medicines?
RNA is the intermediate between DNA and the protein
DNA makes RNA and RNA makes protein
Anti-sense therapy (From Leukemia Book)
Two strings – RNA Is one string
2 stranded DNA
1 strand codes for one
Sense and Antisense
When DNA makes RNA the 2 strands separate
Strand A makes RNA type 1
The sense strand is the strand that actually makes the protein
With antisense therapy – If someone is making a faulty protein, the antinsense strand can bind to the sense strand and prevent it from making the protein altogether.
Gene Therapy (From Leukemia Book)
Has not been as successful as had been hoped
Trying to correct the spelling errors
Whoever perfects the art of gene therapy will be the owner of the universe
Minor success on kids with metabolic diseases – missing certain chemical
Not sure about progress with Leukemia
Antigens block the name tag that says I am allergic to grass
The double helix of DNA has these features: View articel and picture here:
It contains two polynucleotide strands wound around each other.
The backbone of each consists of alternating deoxyribose and phosphate groups.
The phosphate group bonded to the 5′ carbon atom of one deoxyribose is covalently bonded to the 3′ carbon of the next.
The two strands are “antiparallel”; that is, one strand runs 5′ to 3′ while the other runs 3′ to 5′.
The DNA strands are assembled in the 5′ to 3′ direction and, by convention, we “read” them the same way.
The purine or pyrimidine attached to each deoxyribose projects in toward the axis of the helix.
Each base forms hydrogen bonds with the one directly opposite it, forming base pairs (also called nucleotide pairs).
Discussion of base pairing in DNA
3.4 Å separate the planes in which adjacent base pairs are located.
The double helix makes a complete turn in just over 10 nucleotide pairs, so each turn takes a little more (35.7 Å to be exact) than the 34 Å shown in the diagram.
There is an average of 25 hydrogen bonds within each complete turn of the double helix providing a stability of binding about as strong as what a covalent bond would provide.
The diameter of the helix is 20 Å.
The helix can be virtually any length; when fully stretched, some DNA molecules are as much as 5 cm (2 inches!) long. The path taken by the two backbones forms a major (wider) groove (from “34 A” to the top of the arrow) and a minor (narrower) groove (the one below).
Link to John Kyrk’s animations showing the structure of DNA.
Please let me know by e-mail if you find a broken link in my pages.)
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6:46AM – Cord Bloodstem Cell Bill Passed
This is NOT the embryonic stem cell research bill – that will be debated in early 2006
Contact: J.P. Duffy of Family Research Council, 202-679-6800
WASHINGTON, Dec. 16 /U.S. Newswire/ — This evening, Senator Frist called up and the Senate passed the bi-partisan lifesaving cord blood stem cell bill, sponsored by Rep. Chris Smith. The Stem Cell Therapeutic and Research Act of 2005 (H.R. 2520) already passed the House in May by an overwhelming bipartisan vote of 431-1. However, because the Senate-passed bill has modest changes, the House must pass the amended version before sending it to for his signature.
Tony Perkins, President of the Family Research Council, released the following statement: “Though proponents of embryonic stem cell research previously objected to passage of this life-saving bipartisan bill, I applaud the Senate for now passing the cord blood stem cell bill.
“Cord blood stem cells are currently being used to treat patients for a variety of diseases and this bill will increase the number of patients who receive life-saving cures. Senator Frist, Representative Chris Smith, Senator Brownback, and Senator Hatch deserve special praise for their hard work on this bill, as well as members of the Congressional Black Caucus who actively support this bill because cord blood stem cells have treated sickle cell anemia, a condition that largely affects the African American community. The House must now pass this bill immediately and send it to the president’s desk.”
Studies continue to show, cord blood stem cells have also effectively treated a variety of diseases such as leukemia, lymphoma, myelodysplasia, severe aplastic anemia, genetic diseases of the blood and immune system as well as certain genetic metabolic diseases like adrenoleukodystrophy (“Lorenzo’s oil disease”), as well as Krabbe disease and Hurler’s disease, genetic neurological diseases that kill infants by the age of 2.
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6:39AM – Antisense Therapy
Article fomr 2001 – According to Erin, this type of therpy is not yet delivering on its promise.
The use of short spans of nucleic acid–DNA or RNA–to disrupt the expression of disease-related genetic code is an idea vast number ofillnesses, including most neoplasms. On several fronts, including hematologic
malignancies, the concept has reached clinical trials–where appreciation of the in vivo hurdles is leading to new approaches for
The perturbing, or even silencing, of disease-related genes is an idea that seems applicable to a vast number of illnesses, perhaps especially to complex ones, including most neoplasms. The idea also seems straightforward. Having chosen a target, one prepares its genetic complement. Applied to cells, the antisense enters, hybridizes, and the abnormal function is stopped. This seeming simplicity makes the actual hurdles all the more vexing. In theory, antisense is a new magic bullet. In practice, the bullet may fail to cross cell membrane. It may fall short of a needed intracellular compartment. Its target may lie shielded in molecular tangles. Yet such hurdles are unexpected only if one persists in naive, simplistic assumptions about how nucleic acids function within the complexity of living cells. Many hematologic and other malignancies are currently incurable, and are treated only by highly toxic interventions. With their prospect of exquisite specificity, nucleic-acid therapeutics continue, therefore, to be highly desirable. If the problems are now becoming clear, so are potential strategies for overcoming them.
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ALAN M. GEWIRTZ
University of Pennsylvania
potentially applicable to a
delivery of this new magic bullet.
Posted: 5:54 PM, 12/18/2005 in Alternative Therapies
Sunday, December 18, 2005
12:01AM – Introduction
Welcome to my Bone Marrow Disorder BLOG. My name is Bruce Lande and I was first diagnosed with Aplastic Anemia in January of 2001 and began hosting a website at http://aplasticcentral.com to store research (before BLOGS).
I was doing well with the illness until September of 2005 when my blood counts began to fall off again and my diagnosis was changed to Myelodysplasia so I am aggressively researching again to better understand BMD’s and get back on my original treatment regimen plus understand what else can be done to avoid these reoccurances.
Those of you who followed my story know that I felt quite fortunate to be alive to see grandson number one born. As of May, 2006, Sue and I are proud grandparents of 5 (Joshua Riley Torres, Zachary Tyler Torres, Ryan Patrick O’Connor, Hannah Jessica Torres and Lauren Hope O’Connor) and we want to be around to see them grow into adults with children of their own!
This format may lend itself to easier collection of research (publishing to the website is cumbersome and the forum only allow about 2800 characters per post so will be trying this out for a while as an online repository for my research. Fell free to add comments, articles etc as we build this into the online resource I had envisioned so long ago.
In the interest of simplicity, I will report progress, thoughts and strategies here rather than multiple places so this in essence will become my new journal. I have now been on my new regimen for about three weeks having taken it back up in earnest after counts dropped for the third successive visit on October 28, 2005. I had been through an aggressive purge fast and was prepping for the new regimen beginning on October 18th but had my last “good meal” of pot roast, potatoes and carrots on Sunday October 30th followed my beef stew on Monday. So as of November 18th, I am 18 days and counting on a very restrictive diet, diligent sauna & “treatment”, daily exercise, stress reduction and spiritual focus (My old Holistic approach revived!) but will be looking to add what I can glean from Marla, John and others as well as Sue and I re-reading everything from last time and trying to not only recapture previous success but seek better results. This could be the start of a sequel book!
If I am successful in getting my counts up to where Marla is now, I will shout success from the hilltops and will raise funds to to encourage others to develop and implement a natural and alternative approach to healing because I am still absolutely convinced that this is the correct strategy. I am continuing to put in pretty full days and weeks with the consulting business which is really getting traction so hope to continue that activity as I fight this new battle.
Our family and friends have continued to be very patient with all my ups and downs and crazy ideas and will go on record once again to thank Sue; Michelle & Richard; Melanie, Fred, Joshua & Zachary; Melissa, Mike & Ryan; Jack & Liz; Sue’s Family; My family; Tom; Mark; Rich; Ray and Pastor Derron. Good spirits and frequent laughter are a big part of the healing process and I thank them all for standing by me through thick and thin. So… here we go again.
This time I have an attack plan which is a take off on what my business partner Tom and I call a Strategic Growth Plan. It will include a Vision, Mission, Goals & Objectives and Tasks. This approach has worked very well in the formation of our business and is beginning to pay dividends for many of our clients as well.
Bruce’s New Attack Plan
Vision – Updated May 1, 2006
Create a patient based Bone Marrow Research Group dedicated to the prevention and treatment of Bone Marrow Disorders.
Clearly understand and document what treatment protocols are actually working today and develop a foundation to fund further reserach into targeted strategies which may include targeted biomedical research, nutritional strategies and other meaningful approaches. Create a public awareness of the Bone Marrow Disorders, publish and disseminate information to current patients and their families and to the public at large. When possible, work within existing organizations to avoid duplicaiton of effot and to gain leveage from current initiatives. As appropriate, raise money to clearly document what is currently working combat the illnesses, find new and better ways to prevent and treat them and then communicate success.
Goals and Objectives – Updated May 2006
Focus my energy beyond a personal treatment protocol to an effort to develop ways for everyone who suffers from BMD’s to beat their illness and to develop ways to prevent the illnesses from happening in the first place or progressing to the level of life threatneing diseases.
Wipe out Bone Marrow Disorders by 2010.
Refocus myself to battling my illness as the number one priority again DONE
Get a new Bone Marrow Biopsy done and discuss results with Jeff May 2006
Get a cardio/ion panel done and interpret the results – Panel done waiting for appt with Dr. Rogers
Get a blood transfusion DONE (Unfortunatley 2 of them already as of May 2006)
Further my understanding of Bone Marrow Disorders and MDS – WIP (Probably forever)
Create a new journal for this stage of the battle – DONE
Carefully evaluate and calmly discuss with Sue the value of each supplement vs natural foods WIP
Clearly document all vitamins, minerals, natural sources with efficacy – Done
Get the Bone Marrow Research Group started – Kickoff meeting May 23, 2006
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