Creative Results of Brain Damage

http://www.sciam.com/article.cfm?chanID=sa011&articleID=7EAB47BF3A57DB8E440E5A788467C37F

The artlicle I have chosen to research deals with the "creative" outcome of a certain type of brain damage. Patients who have had certain kinds of injuries have developed severe mental problems, but on the other hand certain skills have greatly improved. This article deals with the before and after look concerning this issue.

This certain condition is known as frontotemporal lobar degeneration (FTLD). It is caused when the front part of the brain deteriorates away. The result of this corrotion is the demention. People who have developed this condition have seen a dramatic inhancement in their artistic ability. Even those who have never even been artistic are now able to paint these amazing pistures. People must understand that this is a rare condition and that getting knocked out by a baseball will not turn you into the next Picaso. The question doctors and scientists are trieng to figure out is if the brain is relaeasing this talent somehow or if the disease is causing it. To investigate this doctors studied the work of a lady who was an artist before she developed FTLD and then watched the values of her work as the disease progressed. They discovered that her techniques improved overall but she was putting less emotion into the paintings. Basically she was a better painter but she didnt really care about what she painted.

Researchers concluded that the disease doesn't affect the area of the brain that accounts for the painting, drawling, and writing. What it does affect is the surrounding area of the brain, so that the articstic area has more room to expand with information since the other areas are brain dead. This disease also damages the emotional area, so that the victims don't have the same feelings that they once did. Therefore they can paint the pictures very well but there's no emotion in the them.

My response to this article is filled with a couple emotions. First off i feal a little bit sorry for the patients who have to experience this terrible disease, because no disease is really a good one. On the other hand i think it's pretty amazing that even through the tragedy of it they come out a little bit on top. It's strange to think a talent could arise from a disease. Don't get me wrong i wouldn't want to develope this tommorow just so I could be a better painter. Who knows, I've seen other instances of this on the news where kids develope brain conditions and then become masters at music. It's crazy how the mind all works and all the detail that was put into creating it. In the end i just think its tight to see how a positive could come from such a negative as this disease.

Yours Truly,

Ryan Sells

Peacekeepers of the Immune System

doc10172006115507.pdf

The idea of an immune system attacking its own tissues began about a hundred years ago by a bacteriologist named Paul Ehrlich. He gave it the name autoimmunity. Many medical experts believed that this was not possible until evidence was found, identifying several unsolved sicknesses as having this autoimmunity. The scientists discovered that these diseases are usually caused by rebellious white blood cells called CD4+ T lymphocytes, which mature in the thymus. Normally these cells fight off bacteria, but occasionally they mutiny against the other parts of the body. Cells that are specifically designed to stop this irregular behavior were also discovered. They are called regulatory T cells, and necessary for keeping the immune system in agreement with the body. These cells also affect the responses of the immune system to various things like cancer and organ transplants. The hope of the scientists is to find ways to control regulatory T cells in order to solve medical problems like diabetes, multiple sclerosis, and several others.

Researchers found that when proteins from an animal’s central nervous system were injected into the animal, along with a generalized immune system stimulus called an adjuvant, an awful reaction occurs. Other autoimmune diseases can occur by changing the source of the injected protein. This shows the large variety of tissue types that can be affected by autoimmunity. Researchers began to wonder why most animals and humans are not affected by autoimmunity and, after more tests, found many defense mechanisms that the immune system uses to prevent self-destruction. The first of these includes the development of T cells. In the thymus, all immature T cells are rigorously trained not to react harmfully to any of the body’s tissues. However, a few of these autoaggressive T cells manage to break out and escape into the bloodstream. The second defense deals with blood and lymph vessels. A small amount of these vessels penetrating deep into tissues helps to isolate cells that could cause autoimmunity. A third way involves healthy immune system cells targeting these cells and destroying them or causing them to become inactive.

The existence of regulatory T cells dates back to the 1960’s, when removing the thymus from young female mice resulted in the mice losing their ovaries. The researchers first believed the idea of some hormone that was secreted from the thymus and necessary in order for the ovaries to develop. Then it was discovered that immune system cells were attacking the ovaries. When the mice received a vaccine of normal T cells, the disease was repressed.
A few years later, it was proposed that these T cells might be able to diminish immune responses. Scientists began looking for a “marker” in order to distinguish T cells that could prevent autoimmunity. In 1995, Sakaguchi experimented with a molecule called CD25, and proved it to be a dependable marker. When CD4+ T cells exhibiting the molecule were removed from mice, inflammation occurred in the stomach, thyroid, pancreas, gonads, and salivary glands, confirming that the body was under an autoimmune attack. Also depriving certain mice without immune systems of their CD4+ T cells containing CD25 caused autoimmunity, and the greater the depletion, the worse the diseases that resulted. These cells are now being called CD 25+ regulatory T cells, or T-regs.

How T-regs function and develop is still somewhat of a mystery. Recently, it was revealed that T-regs contain a large amount of a molecule called Foxp3. Foxp3 regulates the activity of specific genes, basically controlling the system of the protein production, and modifying proteins can affect how a cell functions. Foxp3 has been reported to transform T cells into T-regs by the changes it brings in gene activity. Foxp3 was studied in rodents, but it is also present in great amounts in human T-reg cells. One major indication that Foxp3 is crucial for human health comes from a rare genetic disorder known as IPEX. IPEX involves a mutation in a gene on the X chromosome and is seen in male children who only have one X chromosome and do not have a normal duplicate. This mutation causes severe autoimmune disease leading to very early death. New proof states that this is a mutation in Foxp3.

Evidence shows that T-regs do not prevent autoimmune disease in people, but they do seem to aid health in other ways. One study involved transferring T cells not containing T-regs into mice without immune systems. Some mice received a deadly form of inflammatory bowel disease, but the immune system’s activity was not primarily focused upon the bowel tissue. The bowels of animals and humans contain huge amounts of foreign bacteria, which actually prove to be helpful, aiding in the digestion of food and take the place of harmful bacteria that would try to invade the intestines. In these mice, the immune system attacked the harmful bacteria, causing the bowel to become swollen. Yet when T-regs were transferred with the other T cells, the bowel disease was avoided.

T-regs may also affect responses to dangerous foreign cells. It is possible that they could prevent an invader from being fully destroyed, allowing it to break out again. However this may not altogether be a bad thing. When the immune system was left unharmed in the mice, the response to the reinfection was quick and efficient. When the immune system was deprived of its T-regs, the body rid itself completely of the invader, yet reinfection was not swift or efficient. Therefore we see how T-regs contribute to keeping immunological memory, a process that the success of vaccination depends on. T-regs are useful in protecting pregnancies. The baby is basically considered to be an organ transplant to the immune system because half of its genes come from its father. Placental tissue called the trophoblast protects the baby from autoimmunity by way of the mother’s blood and produces molecules to suppress autoimmune disease. It has also been reported that T-regs become more active in women during pregnancy. Scientists contemplate if a great enough decrease in T-reg activity could cause the reappearance of unexpected abortion.

Medicine that changes the activity of T-regs has strong potential for being used to help regulate immune responses in the future. Experiments are being conducted and scientists are trying to find ways to solve diseases by altering the actions of T-regs as well as the number of T-regs. Increasing T-reg activity may eventually be used to cure allergies, avert organ transplant rejection, and even allow grafts to be tolerated better. Decreasing T-reg activity could perhaps help in diseases, like AIDS and tuberculosis, where the immune system cannot fight effectively by itself. A treatment for cancer could also be discovered by T-reg depletion. T-regs are believed to hinder immune cells that would destroy cancerous cells, and in a way inadvertently help the cancer spread. Research implies that cancer patients have unusually high levels of active T-regs, and that some cancerous cells secrete signals that draw T-regs to them and even transform non T-regs into T-regs.

Scientists are having many challenges trying to create medicines that would make a change in T-regs, mainly because they do not know which T-regs to pursue. T-regs are very rare cells; so obtaining millions of them needed to prevent autoimmune disease could be impossible. By treating regular T cells with certain biochemical signals, researchers have created what they call Tr1 cells, that are thought to be identical to T-regs. These Tr1 cells are definitely immunosuppressive. Foxp3 is also being examined, since it was discovered to be a main component for managing the development and function of T-regs. Researchers are also trying to figure out ways to transfer Foxp3 into more easily accessible T cells, so T-reg cells could be developed. Methods of distinguishing molecular events that trigger the production of Foxp3 are also being investigated. In regard to organ transplants, T-regs could be taken from the patient who will receive the transplant and cultivated with cells from the organ donor, causing T-regs that will help restrain the rejection to multiply. This has been accomplished in rodents and is expected to work for humans also.

Scientists’ understanding of the immune system has drastically changed over the past few years. They have discovered T cells and see their autodestructive and immunosuppressive capabilities. Learning more about how they develop and carry out their actions will help scientists find ways to used them for preventing certain diseases and disorders. T-regs may eventually be considered to be vital immunological peacekeepers.

This article contains very helpful and thorough information about T-cells and how they help against autoimmune disease. It provides proof for its statements by backing them up with experiments that were conducted. It also explains what makes T-regs so necessary and the certain markers that are seen in T cells. It talks about diseases that could be cured by altering T-regs, but it seems like much more investigation is needed before these treatments can be found. With time, research, and patience, more clues should eventually unfold.

Inside the Mind of a Savant

doc10172006115117.pdf


Savant syndrome was first coined in 1887 by J. Langdon Down, who described it as "astounding powers of memory" that is almost always linked to a specific domain, such as music, art or mathematics. Fifty-four-year-old Kim Peek, however, has a different story. Phenomenal memory is the skill in Peek, called "Kim-puter" by friends.

Kim began memorizing books the age of eighteen months, as they were read to him. So far he has memorized 9,000 books by heart and every page he reads in eight to ten seconds. One of Kim’s major interests is classical music. He can identify hundreds of compositions, tell when and where each was composed and first performed, give the name of the composer and many biographical details, and even discuss the formal and tonal components of the music. In light of his severe developmental problems, he is far out-reaching the average savant in that for the past two years, he’s actually been learning to play the classical music he’s so fascinated by. Kim was born with an enlarged head, on the back of which was an encephalocele, or a baseball-size "blister", which spontaneously resolved. Kim also had a malformed cerebellum, which may account for Kim’s problems with coordination and mobility. Something that is still a medical mystery is the absence of a corpus callosum, the stalk of nerve tissue connecting the left and right halves of the brain. Doctors suppose that the two hemispheres, in a way, function as one "under the same roof"; however, some people lacking a corpus callosum suffer no disabilities, whereas others have savant abilities. Another possibility is that when the left hemisphere cannot function properly (due perhaps to a high level of circulating testosterone in the womb), the right hemisphere compensates by developing new skills or recruiting brain tissue normally used for other purposes.

Although he generally has a limited capacity for abstract thinking, he does comprehend most of the material he has committed to memory, whereas many savants memories things without comprehension. Kim cannot explain many commonplace proverbs, such as the time his father asked him once in a restaurant to "lower his voice", and Kim merely slid lower in his chair, thus lowering his voice box. Other times his answers seem to be quite ingenious. Like a musician, Kim thinks quickly, so quickly that it can be difficult to keep up with his intricate associations. Though Kim is still physically awkward, his manual dexterity is increasing. When seated at the piano, he may play the piece he wishes to discuss, sing the passage of interest or describe the music verbally, shifting seamlessly from one mode to another. April Greenan, Kim’s music professor and a Mozart scholar, makes these observations: "Kim’s knowledge of music is considerable. His ability to recall every detail of a composition he has heard – in many cases only once and more than 40 years ago – is astonishing. The connections he draws between and weaves through compositions, composer’s lives, historical events, movie soundtracks, and thousands of facts stored in his database reveal enormous intellectual capacity."

Kim’s prodigious memory caught the attention of writer Barry Marrow in 1984 and inspired him to write the screenplay for Rain Man. The main character of this movie, played by Dustin Hoffman, is a savant but does not tell Kim’s life story. After the success of this movie, Kim’s life began to change. Before then, he had been reclusive; and afterward, the confidence he gained from his contacts with the filmmakers inspired him and his father to share Kim’s talents with many audiences. Over the years they have shared their story with over 2.6 million people.


This article, I think, was very informative and thorough on the life of Kim Peek, but not necessarily on the disorder itself. I found myself in the end wondering what true savantism really was, and although every case is different, I felt somewhat uneducated on a common cause of this disorder. Hopefully with further technology and discoveries, doctors and medically prove a cause and effect of this disorder.ftp://ftp.tolcs.org/class/jforgrave/duns%20article

Kayla's article: Huntington's Disease

Huntington's disease, a dominant disease that causes people to lose control over voluntary movements, is soon to have a cure. Scientist have found the main gene that causes this disease, it is a neurodegeneration condition, and it affects thousands in the United States. Its protein is called huntingtin (Htt); when mutated, scientist found out that it malfuntions and kills neurons. Here are three of the many disruptions this mutant Htt causes: interfering with normal gene activity patterns, the transport of proteins needed for nerve cell maintenance, and overwhelming cells with toxic (calcium ions). Researchers everywhere are excited, they are finding drugs that have potential for this neuronal problem caused by Htt.

Researchers are using mice models to help find how mutant Htt causes the brain degeneration of this disease. At the beginning of the mutation there is a string of the amino acid glutamine that contains thirty-six or more glutamine. A normal version of Htt only contains from six to thirty-five. With that many glutamines in protein it produces up to nine genes and causes the neurodegenerative disease; scientist are still trying to get a better understanding of ths event. There are clumps or abnormal deposits of the mutant Htt near other protein being found in brain tissue of Huntington's patients that flow along the long axonal projectios which causes toxicity. Then there are enzymes splitting from protein that attaches to Htt and release another toxic (N-terminal fragments) into the brains of the Huntington's patients, but N-terminal fragments are not toxic in normal humans. Potential therapy is offered by the enzymes with its inhibitors because it can scientificly decrease the toxicity of mutant Htt in Huntington's patients (mice).

Scientists are all agreeing that N-terminal fragments of mutant Htt are toxic, there is then the aggregates that kill the neurons or protect other cells from the mutant Htt's toxic. But the aggregates can be harmful and it shows that to reduce toxicity of mutant Htt, the aggregates restrain their formation. Then there is a drug called rapamycin that decreases Htt aggregation, and the toxicity in cultured neurons by stimulating autophagy; which cells use to get rid of useless proteins. Lysosomes also help in the process and by clearing this does not keep it under control for long. All researchers have their opinion whether or not Htt aggregation is harmful because they have found that lab mice neurons die even with the lack of Htt inclusions. If the neurons have the inclusions there is a better chances of survival than those without it; with a lot of inclusions show no signs of neurodegeneration.

Ignoring the fact that all forms of mutant Htt is toxic, remember the extra glutamines that cause problems in the protein. An example would be in the nerve cells for the gene activity. This is because Htt joins protein that control gene expression which is part of the cell's gene regulatory machinery. Researchers say that the mutant N-terminal fragments of Htt affects the regulatoey machinery: by not letting the Htt to join with the transcription factor. When this happens it can not do its job, and prevent factors from using certian genes. Binding to and restraining a histone acetylase, which is an enzyme that marks genes for activity, happens indirectly to a genes expression from a mutant Htt, causing another way of decreasing Htt's toxicity.

Then there are treatments that restrain the enzymes that will remove acetyl groups from histone to slow down the the neurodegeneration called sodium butyrate. And researchers are also finding that the mitochondria, produces cell energy, will malfunction causing neuronal damage from the mutant Htt. There is also the p53 that controls several genes and the mutant Htt binds to the transcription factor which affects the mitochondria. Scientist showed that by inactivating the p53 gene prevents malfunctioning of the mitochondria. Molecules need to be found to block the p53 mutant Htt or slow down the energy produced from the mitochondria. Then there is the medium spiny neurons that are to be the first to degenerate in Huntington's disease, and these neuronsexperienced a greater take of calcium ions which cause them to die. These receptors where glutamine exerts are possible starts for the disease's therapies. Finally there is the normal Htt that needs protection because they supply brain-derived neurotrophic factors which cells need to survive. Usually Huntington's disease shows up in the patient's forties, and scientist are now closer to finding the most effective treatments.

What I think is interesting is how far and close the scientist are to finding a treatment, they have practically found what causes this disease. Now they just need to put all the little pieces together and find the right drug. It is all most like cancer in a way because it takes awhile to develop and when it does it is very hard to control. It is also amazing that there is a list of so many potential drugs for this disease that you would think that if you could just mix a little of each together and find the cure. But it is not that simple it's comlpex just like God who allowed this disease to exist.

Taming Lupus

Systemic lupus erythematosus or commonly known as just lupus is a disorder that we don't commonly hear about. However it affects over 1.4 million Americans. It has a variety of symptoms ranging from the skin, joints, heart, lungs, blood vessels or even the brain. One common symptom is the butterfly shaped rash across the face. Lupus is a disease of the immune system. What happens is the antibodies that are supposed to attack and kill foreign invaders attack the healthy cells. This "self-attack" is known as autoimmunity which includes other diseases such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, and maybe even psoriasis. Lupus is more severe than these other diseases because the antibodies are known to and sometimes even target the DNA in the cells. These attacks can cause immolation which can cause disruption of the normal functions of cells. In laboratory studies the auto antibodies have attached themselves to healthy cells and destroyed or penetrated them to disrupt normal cell function.
The specific cause of lupus is currently unknown, however there is currently extensive research being done. It has been discovered that lupus can be passed by genetics; about 10% of people effected have close blood relatives how are infected with this disease. However genetics only accounts for a small percentage of cases, therefore the environmental contributors must have some part in this disease. Many of the patients exhibit sensitivity to rays from the sun and receive rashes. The common belief is that the ultraviolet light changes the DNA in the skin cells causing the cells not to recognize each other. Therefore the lupus cells attack the skin cells. Some medications and vaccines have been known to cause flares in lupus patients also. Despite all the research being done in this area a specific virus or bacteria has never been brought forth as the main cause of the disease.
Another characteristic of Lupus is apoptosis or "cell suicide". Apoptosis is a normal cell function and in people without lupus does not cause any problems. However in lupus patients this happens in excessive amount especially in B and T cells. In normal bodies the cells have a way of discarding the old cells remains, but in lupus the system seems to be broken. This creates a double problem with the extra cell remains and with no way to get rid of them. This causes the auto antibodies to attack the remains that are left over because they don't recognize the material as their own. The material that comes from the apoptotic cells in people with lupus is abnormal, especially the DNA fragments. Some of these fragments have methyl groups that control gene activity. In people with lupus these immune complexes are undermethylated. These fragments can affect the B lymphocytes as they mature which cause them to attack these strands. In short the mechanisms that are supposed to ensure self vs. non-self recognition go wrong.
The problem lies mostly on these B cells which function as the antibody-secreting agent. They bind themselves to foreign agents in order to destroy them. What leads these B cells astray are the signaling devices called T cells. If there is a slight imbalance in these sensors then the B cells are likely to be confused and attack its own body. Lupus is also 10 times more likely in women and than men and develops earlier in their life. This is because women tend to produce more immune fighting agents then men. Estrogen can make to body create more lymphocytes than needed which can impair self tolerance.
There are currently drugs that treat lupus, but they work by weakening the immune system as a whole. The current drug research is to create drugs that prevent autoimmune bodies without disabling the body’s entire immune system. One method that the drug researchers are exploring is finding a way to mimic the shut off molecule that tells the body that danger has passed and it can stop making antibodies. Another method that has been explored is impeding the work between B and T cells, therefore making them unable to create the antibodies. Testing in mice with disease was positive; however human testing has been inconclusive.
In order to find a cure for lupus or how to prevent it, scientists need to answer some tough questions. Such as, what causes lupus and how much wrong signaling actually leads to this autoimmunity? Hopefully they will be able to answer these in the very near future.

I found this article very interesting because prior to reading it I didn't know anything about lupus. I also didn't know much about autoimmune diseases. I think it is interesting that the body can attack itself and destroy itself from the inside out. I also found this article interesting because I would like to be a pharmacist and in this article discusses what they test to figure out what the drugs need to do. It's amazing how they can create drugs to treat a specific detail in a cell. Maybe they will have a better drug to help lupus patients by the time I'm behind the counter.

taming lupus