Maggie S Rough Draft

Chronic diseases are a serious problem in the U.S., disabling 1 in 10 and claiming the lives of nearly 1.7 million every year. ** REWORD These devastating numbers however have no reason to be this high.** maybe just move "however" to the beginning of the sentence With the exception of a few illnesses, many can be prevented through healthier life choices. While symptoms vary from disease to disease, there are criteria that fit every chronic disease. Diseases that are considered chronic are either long lasting or recurrent in the course of the illness. Recurrent courses relapse repeatedly with periods of remission betweenbetween what? and chronic courses are persisting conditions. Some head way has been made in the medical world in terms of vaccinating against diseases, but for many it still remains a matter of treating the symptoms rather than eliminating them. This unfortunate truth is a result of the fast paced life styles of most Americans that has led them to put their health in the back seat and forcing medical researchers to find more effective treatment methods. (Maybe connect in some of the diseases you will be covering or mention neurological, respiratory, etc)
Neurological diseases can be one diseases is plural, one is singular?? of the most taxing ailments not only on the patient, but the family as well. A well known disease of this kind is Alzheimer’s disease, affecting more than 18 million people and, with increased life expectancy, this number is expected to climb (15). Previous studies have lead researchers to believe that Alzheimer’s pathogenesis is concurrent with the accumulation of amyloid β (Aβ) in the brain (4). The Aβ comes in the form of compact senile plaques that are associated with pathological changes in surrounding brain neurons leading to their death (15). However, Initial studies to target Aβ were halted however because of the development of encephalitis. In a mouse model it was found that the use of Aβ1-42 prevented Aβ from depositing and improved cognition. These promising results encouraged researchers to find the cause of the encephalitis and develop a plausible vaccine for humans. The encephalitis was likely caused by the immunogen (Aβ1-42) and excessive cell-mediated immunity (4). To prevent this less than desirable side effect, studies have proposed the use of nonfibrillogenic, nontoxic Aβ homologous peptides and an adjuvant, such as alum, that is suitable to humans (4). The use of alum is still under investigation as to whether it is effective with Aβ1-42. Another possible side effect is cerebral bleeding in the form of micro-hemorrhages. Currently the goal of most studies is to reduce side effects while still efficiently removing the deposits of Aβ. In most clinical trials it has been found that immunization with Aβ1-42 must be done early in the course of the disease. This means that finding Aβ deposits before the onset of symptoms is crucial to an effective treatment (4). New ParagraphMultiple sclerosis (MS) is also a neurological disease. Affecting the central nervous system (CNS) white matter as a chronic inflammatory disease, it demyelinates neurons (10). this was very awkward consider rewording While the exact mechanism of disease initiation is unknown, it is thought that CD4+ T cells can target components of myelin sheaths, such as myelin basic protein, proteolipid protein and myelin oligodendrocyte glycoprotein (10). This theory leads many to believe that MS is actually an autoimmune disease; because of these findings the use of a T-cell vaccination may hold promise to halting MS (33). Another theory is modulation of CCR2 and CCL2 at the blood barrier.this again is really awkward-reword These chemokine and receptor pair plays- this is not in agreement a key role in the migration of leukocytes across the blood brain barrier (26). In MS patients it has been found that there is a lower level of CCL2, a potent monocyte and T cell chemo-attractant (26). Many of these findings have been concluded based off of the animal model known as experimental autoimmune encephalomyelitis (24, 30). new paragraph Another ailment of the nervous system is amyotrophic lateral sclerosis (ALS). A progressive disease of the upper and lower motor neurons, it essentially destroys the neurons verses the demylination that occurs in MS (2). Incapable of repairing the damaged neurons, the body continues to lose function generally starting with the limbs and speech. Death usually results in respiratory failure (2). wouldn't respiratory failure result in death? Not the other way around? Several factors have been examined as causes of the disease ,including gene mutations involving the body’s ability to reduce the amount of free radicals that cause damage to DNA. Other causes including oxidative stress, excitotoxicity, deprivation of trophic support and ionic imbalance have been known to contribute to other chronic degenerative disorders of the CNS (2). While reversal of ALS is improbable, vaccinations to protect surviving motor neurons could slow or even halt the progression of the disease. With the use of copolymer-1 (Cop-1), an anti-self T cell mediated response, can be generated with out the risk of autoimmune disease development (2). Currently Cop-1 is an effective treatment method towards MS and glaucoma have you talked at all about glaucoma at all in this paper, i don't see the significance of it; this is due to its ability to bypass tissue specificity barriers imposed by antigens that reside in the damaged tissue.
Specific Some diseases target the respiratory system, ranging such as from asthma toand chronic obstructive pulmonary disease. Allergy induced asthma is a chronic airway inflammatory disorder associated with Th2-type lymphocytes, eosinophils and mast cells (23). Currently the most used treatment modality is immunotherapy with protein allergens, which reduces the symptoms.Are you sure about this? I have asthma and I know alot of people with asthma and most people have bronchdialators or something to that sort that I know of However this method must be limited because of reduced forced expiratory volume in 1 second (FEV 1) and safety concerns. The newest strategy is to down regulate the allergic response through the use of a DNA vaccine. The vaccine encodes for Dermatophagoides pteronyssinus group 2 allergen (Der p 2), which has been shown to generate immunologic protection in Der p 2 allergen induced allergic airway inflammation in a mouse model (23). Current studies have shown that the vaccination of mice with the DNA vaccine inhibited the development of airway inflammation and was also effective in treating allergen-induced allergic airway inflammation.does this protect against all allergen induced asthma or only der p allergen incided?? Specifically, the vaccination inhibits the production of Der p 2-specific IgE antibody. Suppression of the synthesis of IgE was also associated with the decrease in levels of Th2-derived cytokines, IL-4 and IL-13 in BAL what does this Stand for? fluid, a key factor to reducing inflammation of the airway and finding an effective vaccination for allergy induced asthma.once again will this vaccine work for all asthma or only der p induced asthma Possible New Paragraph?? Another disease affecting the respiratory path is chronic obstructive pulmonary disease, also known as COPD. Air flow is restricted into and out of lungs by several factors; loss of elasticity in alveoli and bronchioles, destruction of the walls of the alveoli, airways become inflamed and swollen, and cells of the airway secrete more mucous clogging air flow. It is thought that the disease can be caused by cigarette smoking and prolonged exposure to other lung irritants. While COPD currently has no vaccination due to its causes, treatments are available to avoid infections that seem to concur with it. The vaccination under debate is that of Streptococcus pneumoniae, a leading cause of mortality especially among elderly with chronic conditions. An effective vaccine called pneumococcal polysaccharide (PPS) has been found to be effective at what? in healthy adults, but has shown little promise in high risk groups (20). To increase the immunogenicity, protein conjugated PPS vaccines have been created and have been successful atwhat, killing the disease? stoping the disease from entering the body? against invasive diseases of children that were unresponsive to PPS (20). One of these protein conjugated PPS vaccines is type 6B tetanus toxoid conjugate (Pn6B-TT). Studies compared the two vaccines in the sera of COPD elderly patients to see if there was an increased immunological response in one vaccine over the other (20). Both vaccines proved to increase the antibody levels and therefore increase the protection against pneumonia. However,** more research is required to find the most effective carrier protein for PPS to be conjugated to and a vaccination schedule must be devised.** - ** I would explain this thought more, i don't know if i fully understand it.
While most think of common ailments of the cardiovascular system as heart disease or heart attacks, another serious problem can lead to these conditions is atherosclerosis.reword** Targeting the arteries, plaque that is composed of fat, cholesterol, calcium and other substances in the blood builds up in the walls of the arteries and causes them to narrow. This narrowing restricts blood flow to organs reducing the amount of oxygen and nutrients that reach them. Oxidized LDL (ox-LDL) has been found to be one of the immunogenes that plays an important role in the pathogenesis of atherosclerosis (3). LDL or low density lipoprotein is cholesterol found in the blood. Under normal LDL conditions it is harmless, but the oxidized version presents a problem in plaque build up. Generally, macrophages assist in the clean up of ox-LDL, when the levels of ox-LDL are high the-omit macrophages become fatty streaks, a symptom of atherosclerosis. This condition is often caused by a high cholesterol diet and can be treated through a change in diet. However there are cases where this does not work and studies are investigating whether immunization with Cu2+-LDL and MDA-LDL can induce antibodies against ox-LDL (3). It was found that the immunization did work in the case of a high cholesterol diet, but was not successful for a normal diet (3). Further investigation of this vaccine is needed in order to develop the most effective treatment.
New paragraphAutoimmune diabetes or type I diabetes has been found to be caused by the autoimmune destruction of insulin producing beta cells that are resident to pancreatic islets (13). The destruction is both necrotic and apoptotic. Both CD4+ and CD8+ T cells make up the effectors of this disease-wordy, as well as functional defects in antigen presenting cells such as macrophages, dendritic cells and B lymphocytes. Generally, T-cells infiltrate the pancreas and target against-omit multiple autoantigens including glutamic acid decarboxylase and insulin (17). The targeting of self may be caused by recognition of a processed peptide antigen that is presented by major histocompatibility complex class II molecules (13). To develop a vaccine for this disease, it is necessary to find a way to target autoreactive T cells. Two vaccines are being tested; one that uses a recombinant adenoassociated virus (rAAV) expressing glutamic acid decarboxylase 65 peptide GAD500-585 and the other using a T cell epitope of the human 65-kDa heat shock protein. The use of rAAV as a vector to express GAD500-585 was successful in reducing the pancreatic insulitis and prevented the development of type I diabetes (17). Prevention was marked by the inactivation of GAD500-585 responsive T lymphocytes. A functionally important peptide with in within is one word the sequence of the human variant of the 65-kDa heat shock protein has been found to be recognized by T cell clones that mediate insulitis and hyperglycemia (13). Administration of this peptide can down regulate immunity to the 65-kDa heat shock protein and prevent the development of diabetes (13). These findings in both studies have strongly encouraged the clinical use of these vaccines.
The increase in life expectancy has brought the prevalence of chronic conditions with it. Common ailments, especially among elderly, are bone conditions. Osteoporosis is among these. A metabolic disease targeting postmenopausal women and a few men, results in fractures from decreased bone mass (29).-maybe combine this to one sentence The decreased bone mass is thought to be caused by activation of bone resorbing osteoclasts. This osteoclastogensis is initiated by the interaction of TNF-related activation induced cytokine (TRANCE) and receptor activator NF-κB ligand (RANKL) that is expressed on stromal cells and RANK (29). Current therapies have been successful in reducing bone resorption, but not with out the risk of side effects affecting the gastrointestinal and circulatory systems. Not to mention its high cost and low availability, the need for a user friendly and cost effective treatment is becoming more prevalent. By using a decoy receptor for TRANCE/RANKL, the disease can be blocked. Covalently linking TRANCE/RANKL to virus like particles has been shown to overcome the natural tolerance of the immune system toward self proteins and produce high levels of antibodies with out the addition of adjuvant. This vaccine has been highly effective in treating osteoporosis (29). IL-6 has also been shown to be a mediator in postmenopausal osteoporosis (5). Neutralizing IL-6 therefore may also have therapeutic effects for osteoporosis (5). New paragraph
-Think about itAnother crippling bone disease is Rheumatoid Arthritis (RA). It is characterized by chronic inflammation of the articular synovial tissues (12).-I think if you combine this info with the first sentence it will flow better This is initiated by the infiltration of leukocytes such as neutrophils, macrophages and T cells. Also the secretion of inflammatory cytokines (TNF-α, IFN-γ, IL-1 and IL-6), chemokines and destructive enzymes such as matrix metalloproteases contributes to the pathogenesis of the disease (12). Several treatments have been examined including the use of T cells and mediation of pro-inflammatory cytokines. The use of T cells to induce a regulatory immune response appeared to work in experimental models, but showed little success as a treatment option for RA (8). The mediation of pro-inflammatory cytokines such as TNF-α is a much formore plausible treatment modality. An active anti-hTNF-α immunotherapy was developed using a keyhole limpet hemocyanin-hTNF-α heterocomplex immunogen (hTNF-α) (6). This vaccine has proven to be effective in many studies and could be used to treat RA. (did you mention what MTX was?) MTX is also a treatment for RA similar to that of TNF blockers, but recently it has shown to reduce the effects of pneumococcal vaccinations (21). As with many suffering from chronic diseases the prevalence of infection is increased and RA patients are no exception to this. Therefore the use of MTX is less desirable than that of the TNF blockers which showed no effect on the pneumococcal vaccination (21).
(Not interesting topic sentence)Parasitic infections are a major cause of disease. In particular, Chagas Disease which is caused by the Trypanosoma cruzi insect derived metacyclic trypomastigotes (19). It can infect through breaks in the skin or mucosal routes, this makes finding a vaccine to protect both of these infection sites very difficult. Explain Chagas a little more, right now I don't see how this helps support your paper at all and therefore should be cut.
Among chronic diseases are a category of diseases that are known as autoimmune diseases. Systemic lupus erythematosus (SLE) is one of these diseases. SLE is characterized by a wide spectrum of multi-organ manifestations and genetic, hormonal, environmental and immuno-regulatory factors that have been known to contribute to the disease (16). What makes this an autoimmune disease is the presence of autoantibodies to nuclear antigens (16).Isn't the definition of an autoimmune disease a disease that makes antigens to own body parts- reword sentece or cut Occurring in episodes, flares cause increased disability and organ damage (11). maybe explain what a flar is or how it occurs Another possible contributing factor is human cytomegalovirus (HCMV). This virus has been known to induce autoimmunity through molecular interaction with the immune system and concurrently shows up in many SLE patients (7). do you know the exact molecular interaction? As a result of HCMV infection the presence of circulating auto-antibodies to erythrocytes, nuclear components or smooth muscles is apparent (7). Present treatment methods have proven to be effective, but are poorly tolerated. Side effects such as bone marrow depression, ovarian failure and enhanced risk of bladder cancer occur with the use of cyclophosphamide (11). These side effects have led researchers to find a less toxic therapy. It has also been observed that mitochondrial hyper-polarization and enhanced Ca2+ fluxing in T cells occurs in SLE patients (14). A treatment that has been found to be effective in regulating mitochondrial membrane potential and Ca2+ is Rapamycin (14). This treatment has also been shown to ameliorate T cell function and prolong survival in lupus-prone mice (14).
maybe add a sentence to lead into this paragraph Human immunodeficiency virus type one (HIV) is a virus that attacks the immune system, specifically the helper T cells, macrophages and dendritic cells. Eventually leading to AIDS and death, this virus has proven to be tricky to treat. Its diversity in sequencing allows it to evolve with in an individual during the course of infection (1). This means that targeting highly conserved regions and identifying ways to exploit the limitations of sequence evolution is needed to find a permanent treatment method. Using an animal model called simian immunodeficiency virus (SIV) found in the rhesus macaque, treatments are being investigated that could help boost the immune system prolonging the life of a patient. Studies have shown that using CpG-C ISS-ODN C274 can stimulate dendritic cells and the use of C274 can stimulate B cells (31). This overall improves the mucosal and systemic immunity (31).
Many diseases have a target organ or system that they affect; this however is not the case with cancer. Cancer can affect any part of the body and has the capabilities to spread to different organs. Cancer gets its start from cells with damaged DNA that replicate rapidly. Damage to DNA can occur in several ways; smoking, environment, viruses, pollution and several other factors. Current treatments include chemotherapy, radiation and radical surgery, most having side effects and drastically changing the patient’s life style (18). With advances in medicine, more viable treatments are becoming available. One of the most promising of these is the use of dendritic cells. Dendritic cells are antigen presenting cells (APCs) that initiate and modulate the immune response or amplify existing cytotoxic anti-tumor T-cell responses (18, 25). They engulf antigens and present them to T cells so an immune response can be generated. Dendritic cells are unable to recognize cancer cells because the cancer cells are derived from your-avoid 2nd person own cells and your body will not attack itself except in the case of autoimmune diseases. This requires that each vaccine must be tailored to each individual patient.Last sentence feels like it could be broken up. Presently studies have using "presently" implies present tense and "have been conducted" implies past tense. make your tenses agree been conducted to see whether a vaccine with dendritic cells engineered to express IL-12 by adenovirus mediated gene transfer can enhance anti-tumor immunity (18). Speculation has been made to further the development by using cells of the adaptive immune system, while continuing to use dendritic cells as the central role. ** i'm confused, you talked about how dendridic cells could be used to treat cancer, then you go into exlpaining why they can't, then you say it's possible. Could you exlpain this more
Currently chronic diseases affect millions of people world wide and are on the rise. These devastating illnesses however are becoming more manageable through medical research. With advanced treatment for symptoms, hope is on the horizon for more permanent vaccinations. This is not to say, however that more time and research is necessary to develop these vaccines. **last sentence is not what i got out of the paper, change it to reflect the overall theme of your paper

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