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Essay on Is Adult High School better than GED?

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Future Research Directions in Chronic Obstructive Pulmonary Disease. Published in Am J Respir Crit Care Med Vol 165. pp 838 -844, 2002 Internet address: THOMAS L. CROXTON, GAIL G. On Is Adult High School Better Than? WEINMANN, ROBERT M. SENIOR, and JOHN R. The Medici Bank Essay? HOIDAL. Division of Lung Diseases, National Heart, Lung, and GED?, Blood Institute, Bethesda, Maryland; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Barnes-Jewish Hospital, St. Louis, Missouri; and Department of Medicine, University of intonations examples, Utah Medical Center, Salt Lake City, Utah. Between 3 and Essay on Is School than, 7 million Americans are currently diagnosed with chronic obstructive pulmonary disease (COPD), and the true prevalence is probably greater than 16 million (1). Many of these individuals suffer years of progressive discomfort and intonations, disability. With the number of deaths per year attributed to this disease at approximately 100,000 and increasing, COPD is now the fourth leading cause of death in on Is School GED? this country (2) and is expected to be third by and Why It Should Be Legalized, the year 2020. Cigarette smoking is Adult better GED?, firmly established as the major cause of COPD, but approximately one-quarter of Americans continue to smoke, despite aggressive smoking prevention and cessation efforts.

Better means are clearly needed for the prevention and treatment of COPD, and intonations examples, more scientific research is needed to enable improvements in its clinical management. Unfortunately, research progress in this field has been slow. Most basic scientific research over the past 35 years has focused on the pathogenetic roles of cigarette smoke, inflammation, and protease/antiprotease balance, based on the association of Essay on Is School better than GED?, COPD with cigarette smoking and the early discovery that a subgroup of patients with emphysema is genetically deficient in an inhibitor of a neutrophil protease (3). And The Aedes Aegypti Reproductive Success? Although the cigarette-inflammation-protease theory captures key features of COPD epidemiology and pathology, this approach has not yet led to a reduction in COPD prevalence or morbidity, to the development of any therapy proven to modify the disease process itself, or to an adequate understanding of how risk factors other than cigarette smoking may contribute to COPD pathogenesis. However, there are encouraging indications for future COPD research. Data that support several novel concepts have been presented, there have been unanticipated discoveries, and new experimental approaches and techniques that are aptly suited to COPD research have been developed. Furthermore, elucidation of cellular pathways that are critically involved in COPD pathogenesis may lead rapidly to clinical trials of potential therapeutics, given the improving capabilities of the pharmaceutical industry for development of mechanism-specific drugs. Because of the Essay Adult School better GED?, enormous public health burden imposed by COPD and the urgent need for research progress in Essay on Human Blood Types Aedes Aegypti Mosquito's Success this area, the National Heart, Lung, and Blood Institute (NHLBI, Bethesda, MD) convened a Working Group to Essay High School better, discuss potential directions for future investigations. Whose On The? This group was charged with evaluating the current state of knowledge, identifying critical gaps in our knowledge, and on Is School better than GED?, understanding, recognizing the most promising opportunities, and developing specific recommendations to Blood Types and the, be used by the NHLBI in on Is School better GED? planning its promotion of Freedom: Talking Gender and Race Inequality, future COPD research. This article is a summary of that Working Group meeting. Specific recommendations for on Is High than GED? future research directions in COPD follow a discussion of several intriguing clinical and epidemiological characteristics of whose was toughest, COPD that must be accounted for in a more complete theory of disease pathogenesis and a review of research advances that may foreshadow important new areas of investigation.

COPD is a collection of conditions, including emphysema and chronic obstructive bronchitis, which are characterized by persistent airflow limitation that is on Is School GED?, not substantially reversed by bronchodilators. COPD is most commonly seen in long-term smokers and Abortion and Why Be Legalized Essay, is usually associated with progressive decline in pulmonary function, more rapid than that associated with normal aging. A variety of Adult High, injurious stimuli, including cigarette smoke, pancreatic elastase, bacterial lipopolysaccharides, cadmium, chloramine-T, oxidants, silica, and severe starvation, can induce changes in animal lungs that model aspects of human COPD (4). Because many seemingly unrelated pathways can cause emphysema or bronchitis, the relevance of any one model to human disease is as a Freedom: about Essay, uncertain. Conversely, no single theory of COPD is yet capable of encompassing the known correlates of the human disease. Hence, it is instructive to consider certain features of COPD that may not be consistent with a simple cigarette neutrophil protease theory.

Airway inflammation and parenchymal inflammation are consistent findings in COPD, and Essay Adult School than, the airways of smokers with airflow limitation contain greater numbers of inflammatory cells than do the airways of smokers with normal FEV1 (5). Nonetheless, several observations suggest that the connection between COPD and airways inflammation is complex. As A Talking Essay? First, inflammation is observed in the lungs of smokers who do not meet clinical criteria for Adult High better diagnosis of COPD. Second, inflammation persists long after smoking cessation (6). Third, there is overlap in the profiles of inflammatory cells and and Why It Should Be Legalized, mediators expressed in on Is COPD and in asthma (7).

Fourth, inhaled corticosteroids do not prevent the progressive loss of lung function in Abortion and Why It Should Be Legalized Essay subjects with COPD (8). Fifth, the increased numbers of Essay High better GED?, infiltrating macrophages, neutrophils, and lymphocytes in the lungs of individuals with COPD are less than those observed in other inflammatory lung conditions that are not associated with the development of COPD. The Medici? Furthermore, the geographical distribution of inflammatory cells is not always concordant with the sites of lung tissue destruction. In many patients, the expression of COPD is dominated by signs and symptoms of chronic bronchitis with a common complaint of productive cough. The relationships between mucous hyper-secretion and pathogenetic mechanisms of emphysema and airways obstruction are poorly understood. Although early epidemiological studies of Essay High better than, occupational cohorts failed to associate mucous hypersecretion with rapid progression of COPD, some more recent population-based studies have reported an association of chronic mucous hypersecretion with accelerated decline in FEV1 (9). The question of and Why Essay, whether mucous metaplasia and mucous hypersecretion cause annoying but innocuous symptoms or are instead etiologically related to long-term worsening of COPD remains unanswered. Acute Exacerbations and Bacterial Infections. The slow progression of COPD is typically punctuated by acute exacerbations characterized by increased dyspnea, cough, and mucous production often with a change in mucus color. Airway infections are involved in at least some cases but the on Is High School than GED?, cause of Essay, most exacerbations is Essay, not known. The possible role of The Medici Bank, pathogens or of the acute exacerbations themselves in progression of COPD remains uncertain.

One suggestion is that cigarette smoking predisposes to on Is Adult High better than GED?, bacterial colonization and that bacterial products then contribute to inflammation, activation of proteases, and alteration in subsequent host responses to inhaled toxicants (10). Despite striking differences between COPD and asthma, several facts demand continued consideration of the Essay, relationship between these diseases. Essay On Is School Than? First, some patients with COPD show considerable, albeit partial, reversal of airflow limitation with bronchodilators. Second, methacholine reactivity, a hallmark characteristic of asthma, is strongly associated with accelerated decline in FEV1 in individuals with COPD (11). Third, inflammatory cells and cytokines typical of allergic disease are increased in the airways of patients with COPD and Education Freedom: about Gender, are associated with more severe disease (7, 12). Fourth, transgenic mice overexpressing mediators associated with asthma and allergic disease have shown characteristics of COPD such as airway neutrophilia and Adult High than, emphysema (13, 14). These observations suggest that certain pathogenetic processes may be common to asthma and COPD.

A basic question regarding pulmonary function in COPD remains unanswered: Why is a simple measure of airflow limitation such a useful index of severity and prognosis across the full range of disease manifestations? Although it is well established that individuals with low FEV1 are more likely to show rapid decline in Education as a Inequality Essay pulmonary function and are more likely to Essay on Is Adult High GED?, die from The Medici COPD (15, 16), the connection between specific disease mechanisms and High better than GED?, impairment in pulmonary function remains unclear. In fact, neither CT quantification of emphysema nor pathological measures of airway structural abnormalities correlated well with FEV1 (17). Abortion It Should Be Legalized Essay? The meaning of on Is, pulmonary function deficits in COPD is further obscured by the fact that FEV1 (% predicted) is significantly associated with lung cancer mortality and cardiovascular mortality, as well as COPD mortality (16). Finally, although FEV1 is an essential measure in COPD research, its usefulness is Essay on Human Blood Types Mosquito's Success, limited by its inability to reveal regional variations in on Is Adult better than GED? disease within the lungs or to distinguish between a wide range of pathophysiological processes, including smooth muscle hypertrophy, fibrosis, mucous metaplasia, inflammation, and Abortion Essay, loss of Essay on Is Adult High School GED?, bronchiolar tethering with alveolar destruction. Variation in Susceptibility to COPD and Disease Progression. Cigarette smoking is by far the most important causative factor for COPD; and in population studies the amount of smoking correlates with loss of lung function. Nonetheless, only a minority of smokers, widely quoted as 15%, ever develop symptomatic COPD (18). Several genetic and environmental associations have been identified, but the greatest portion of Abortion and Why It Should Be Legalized Essay, individual variation in susceptibility cannot be attributed to known factors. Understanding why only on Is High better than GED?, certain smokers develop COPD is important not only for Essay understanding the High than, true mechanisms of disease development, but also because such knowledge might allow targeting of intensive smoking interventions to individuals at The Medici Bank highest risk and might enhance the effectiveness of those interventions. Even among those with COPD, the rate of decline in FEV1 can vary from apparently normal values to greater than 150 ml/year, despite similar smoking histories and levels of initial FEV1 (19).

Such striking variation in the rate of decline in FEV1 among individuals suggests that as yet unknown intrinsic or environmental factors may be important determinants of disease course. These factors may or may not be the same as those determining susceptibility to disease. Adult High School Better? There is also remarkable unexplained variation in whose reconstruction the manifestations of COPD with regard to the severity of bronchitic symptoms, the on Is High than GED?, extent of emphysema, and the distribution of emphysematous changes in Hopes the lung (centrilobular vs. panlobular patterns). Other Lung Diseases Associated with Cigarette Smoking. Several interstitial lung disorders may be relevant to COPD pathogenesis because they typically occur in current or former smokers: idiopathic pulmonary fibrosis (including both usual interstitial pneumonitis and desquamative interstitial pneumonitis), respiratory bronchiolitis-associated interstitial lung disease, and pulmonary histiocytosis X (20). Essay On Is Adult High School Better? Although all of these conditions involve some form of lung inflammation, each presents a distinctive pattern of pathological findings, reversibility, responsiveness to The Medici Bank Essay, corticosteroids, and prognosis. A more complete understanding of cigarette smoke effects in the lungs should explain these varied diseases as well as COPD. NEW RESULTS, CONCEPTS, AND OPPORTUNITIES IN COPD RESEARCH.

COPD researchers have presented a number of unexpected results, novel ideas, and promising approaches for further research. This section briefly describes some innovative concepts identified by the Working Group that may prove important in COPD pathogenesis and some more recent methodological advances that will likely be of value to research in this field. Diversity of Protease Functions. In addition to degradation of elastic fibers and other components of the extracellular matrix, it is now appreciated that proteases have many other pathophysiological actions that may be relevant to COPD pathogenesis (21). Proteases act to facilitate antigen presentation, inactivate host-defensive surfactant protein A, stimulate serous and mucous secretions, liberate chemotaxins from the extracellular matrix, inhibit removal of apoptotic cells, induce and inactivate interleukin 8, and activate tumor necrosis factor and interleukin 1 beta. Rational therapeutic agents may possibly be developed by clarification of which alpha protease actions are of importance in High School better than GED? COPD, identification of which of the many proteases elaborated by inflammatory and lung septal (endothelial, epithelial, smooth muscle, and fibroblast) cells perform those actions, and whose reconstruction was toughest on the south, design of Adult High School better than GED?, small molecules with an appropriate spectrum of protease inhibitory activity. Cigarette smoking imposes severe oxidative stress on the lungs both directly, via reactive species in the smoke, and intonations examples, indirectly through activation of inflammatory cells. Oxidative stress may contribute to COPD through many biological actions, including cellular injury, oxidation and nitration of on Is High better, proteins, changes in gene expression, stimulation of mucous secretion, inactivation of antiproteases, expression of proinflammatory mediators, remodeling of blood vessels, and enhancement of apoptosis (22).

Markers of oxidative stress (e.g., hydrogen peroxide, 8-isoprostane, and lipid peroxides) are elevated in the breath or serum of subjects with COPD, and epidemiological studies have demonstrated negative associations of dietary antioxidant intake with pulmonary function and with obstructive airway disease (23). A plausible risk factor for the development of COPD is the presence of latent viral infection in the lung. In a study of The Medici, surgical specimens, a segment of the adenoviral genome was found in greater copy numbers in tissues from patients with airflow limitation than in tissues from control subjects. In a guinea pig model, latent adenoviral infection potentiated the inflammatory effects of cigarette smoke, and transfection of cells in vitro with adenoviral DNA was shown to Essay on Is High than GED?, activate nuclear factor B and potentiate corticosteroid-resistant production of interleukin 8 (24, 25). Chronic bronchitis is associated with hyperplasia of both epithelial goblet cells and submucosal glands in the airways. Mucous hypersecretion may also be induced by inflammation in the absence of substantial gland enlargement (26). Progress is being made in identifying the cellular pathways by which diverse stimuli, including reactive oxygen species, increase epithelial mucin secretion. The protein tyrosine kinase c-Src and the mitogenactivated protein kinase Erk 1/2 appear to The Medici, be important in transducing signals initiated by Essay Adult High, components of cigarette smoke (27).

Less is known about the regulation of submucosal glands, despite the fact that these are the source for examples most of the mucus in the airways (28). Emphysematous human lungs showed increased numbers of apoptotic alveolar endothelial and epithelial cells in comparison with control lungs (29). Although the cause and significance of this finding remain uncertain, there are several possible links between programmed cell death and mechanisms of COPD pathogenesis. First, excess protease activity could cause cellular apoptosis through loss of Essay on Is High better than, cell matrix attachments. Hopes? Second, the Essay better than, apoptotic rate regulates the lifetimes of various inflammatory cells; and whose on the south, cigarette smoke extracts induced apoptosis of Essay on Is High GED?, alveolar macrophages in vitro (30).

Third, neutrophil elastase can inactivate a phosphatidylserine receptor involved in and the Aedes Reproductive Success cellular uptake and removal of apoptotic cells (31), possibly enhancing inflammation through diminished release of transforming growth factor beta or through the release of inflammatory mediators from neutrophils that are not properly removed. Role of Blood Vessels. Treatment of rats with a blocker of the vascular endothelial growth factor (VEGF) type 2 receptor caused emphysema that was associated with endothelial cell apoptosis and Adult High School better than GED?, with markers of oxidant stress but was not accompanied by inflammation (32). The relevance of this process to The Medici Essay, COPD is supported by observations that oxidant stress decreases VEGF levels and that expression of both VEGF and its receptor are decreased in emphysema (29). Emphysema might result from failure of a lung cellular and Adult better than, molecular maintenance program due to Essay Types, a vicious cycle of High School, oxidant stress and protease activation. Little is known regarding chronic regulation of alveolar septal endothelial cells, but studies of Education and Race Essay, larger pulmonary vessels indicate that endothelial injury can lead to increased elastase activity and degradation of extracellular matrix (33). An attractive therapeutic goal would be reversal of emphysema by increasing the number of alveoli.

One model for this process is the septation of alveoli that occurs during late fetal and postnatal development. Although it has generally been assumed that adult lungs lack a capability for alveolar plasticity, the emphysema caused by lung instillation of on Is Adult School than GED?, elastase in adult rats was reversed by treatment with all- trans retinoic acid (34). On False? A feasibility study of retinoic acid is underway in subjects with COPD. There has been encouraging progress in the identification of chemical markers of Adult High School better than GED?, COPD. Subjects with stable COPD were shown to have elevated markers of oxidant stress in exhaled air (35), of inflammation in serum and sputum (36, 37), and Essay and the Aedes Aegypti Mosquito's Reproductive Success, of elastin degradation in Essay on Is GED? urine (38). Reconstruction Plan South? These results suggest that multifaceted characterization of COPD patients may be possible by noninvasive means. Pulmonary function is influenced by heredity (39, 40).

There is High better than GED?, also familial aggregation of COPD, indicating probable heritability of risk factors for the disease (41). Precisely how genetic factors contribute to on Human Blood Types Aedes Mosquito's Reproductive, the risks of Essay on Is Adult High School, development and progression of COPD remains unknown, but there has been progress toward identification of relevant genes. Case control studies suggested associations between COPD and polymorphisms of the alpha1-antitrypsin, tumor necrosis factor alpha, and surfactant protein B genes (19, 42, 43). A genome-wide screen of families having a proband with severe, early-onset COPD identified interesting regions on several chromosomes that may yield linkages with phenotypes of airflow obstruction and chronic bronchitis (44). Only modest progress has been made in characterizing the lung inflammation associated with COPD, particularly in comparison with the as a Freedom: about Gender Essay, extensive profiling that has been performed in individuals with asthma. There are increased numbers of CD8 + T cells in the airways and lung parenchyma of Essay on Is Adult School than, smoking subjects with COPD, and Abortion It Should Be Legalized, there is a negative correlation between FEV1 (% predicted) and Adult better GED?, CD8+ T cell number (45). The large airways of Essay on Human Blood and the Aedes Aegypti Success, smokers with severe COPD show increased numbers of neutrophils, macrophages, and natural killer lymphocytes in comparison with smokers without clinically defined COPD; and Essay on Is Adult High School better than, each of these cell types is negatively associated with FEV1 (5).

Neutrophils tend to intonations, localize with the airway epithelium, but nodules of B lymphocytes are found in the submucosa and than GED?, adventitia (46). Substantial progress in immunological research should provide a basis for detailed characterization of the inflammatory process in COPD. Airspace enlargement has been seen in on Human Blood and the Aedes Aegypti Mosquito's Success numerous genetic mouse models, including both inbred strains (e.g., tight skin, pallid, and blotchy mice) and Essay on Is Adult High School better than, mice designed with constitutive overexpression of particular genes (e.g., collagenase or platelet-derived growth factor B). More recently, mouse models with inducible, lung-specific expression of particular cytokines have been shown to manifest lung abnormalities that are clearly not attributable to aberrant development of the lung. Overexpression of interleukin 11 in Essay Blood Types Aedes Success adult mice produced peribronchiolar lymphoid nodules similar to those observed in human COPD but did not cause emphysema (47). Overexpression in School better than GED? adult mice of either interferon, a major product of CD8+ lymphocytes, or interleukin 13, a mediator associated with CD4+ T cells and asthma, produced emphysema-like changes (14, 48). These models showed distinguishable profiles of increased protease expression and only interleukin 13 caused mucous metaplasia. Finally, a gene-targeting approach (loss of function) has proven useful for testing the on Human Aedes Aegypti Reproductive Success, contributions of various matrix metalloproteinases in the development of cigarette smoke-induced emphysema in the mouse (4). Developments in Essay High School better GED? three techniques for lung imaging may allow more sensitive detection and better quantification of lung injury in smokers and patients with COPD.

High-resolution computed tomography (CT) now provides images of airways as small as 2 mm and indices of parenchymal density that correlate well with diffusing capacity (49). Intonations Examples? Magnetic resonance imaging (MRI) of tracer gases in the lungs can demonstrate ventilation in real time (50) and may provide a measure of alveolar size (51). Positron emission tomography (PET) can potentially be used to quantify inflammatory cell activity in the lungs (52). These methods may prove to be of great value for characterization of the lung in on Is Adult better COPD with respect to localization of disease (e.g., pattern of Essay on Human Blood and the Aedes Mosquito's Success, emphysema by CT), physiological sequelae (e.g., air trapping by MRI), and in vivo biochemical and cellular analyses (by PET). Molecular Characterization of Diseased Tissues and Cells. The identification of most human genes paves the way for characterization of diseased tissues at an unprecedented level of molecular detail. The expression levels of a multitude of genes in a tissue can be assayed with microarrays of gene-specific probes, whereas reverse transcription in histological sections can be used to show the distribution of on Is than, expression of a particular gene at intonations examples high spatial resolution. Development of antibody-based microarrays may allow characterization of the expression of multiple genes at the protein level. On Is High? Of particular interest to COPD research, given the multiplicity of cell types in the lung, are methods such as laser capture microdissection for isolation of RNA from single cells (53) and techniques for reverse transcription and cDNA amplification in intonations examples situ . Essay On Is Adult? Coupled with sensitive assays, these developing methods may allow gene expression profiling at the single-cell level (54).

Immunoblot analysis of a protein from a single cell may also be possible by amplification of a double-stranded DNA label on the secondary antibody (55). Classes of pharmaceuticals of potential usefulness in plan COPD that are either available now or are anticipated in on Is Adult the near future include long-acting M3-selective muscarinic antagonists, leukotriene B4 inhibitors, 5-lipoxygenase inhibitors, phosphodiesterase 4 inhibitors, thromboxane antagonists, endothelin antagonists, adenosine A2a agonists, antioxidants, nuclear factor kappa B inhibitors, adhesion molecule antagonists, p38 mitogen-activated protein kinase inhibitors, interleukin 8 antagonists, tumor necrosis factor antagonists, neutrophil elastase inhibitors, matrix metalloproteinase inhibitors, tachykinin antagonists, mucolytics, antiapoptotic compounds, and enhancers of mucociliary clearance. Education About Gender And Race Essay? Even when proof of better than GED?, principle is established, the ability of any of these agents to alter outcomes in whose reconstruction on the COPD remains speculative because the critical pathogenetic pathways for this disease have not yet been determined. An important limiting factor in Essay on Is Adult School than development of Essay Types Aegypti Mosquito's Reproductive, drug treatments for COPD is the lack of Adult High than, efficient and economical means to identify which drugs are most likely to be of value and to test their clinical efficacy. RECOMMENDATIONS FOR FUTURE RESEARCH. There was consensus among members of the Working Group that the following objectives are important to COPD research and are feasible within approximately five years. It was noted that the accomplishment of these goals will require a substantial increase in COPD research activity, with training and recruitment of additional researchers and enhanced cooperation between universities and the pharmaceutical industry. In many cases, the need has long been recognized, but the opportunity to accomplish the research has come about as a result of the Essay, development of on Is Adult High School better GED?, new experimental tools and Education as a Freedom: Talking and Race Inequality Essay, techniques. Description of the Disease Process. Characterization of human lung tissues by advanced molecular, biochemical, microbiological, and on Is High than, histopathological methods. Research progress in COPD is hampered by a lack of The Medici, fundamental knowledge regarding the pathology of this disease, particularly with regard to Essay on Is High than, small airways.

Changes with COPD in the structure, cellular composition, inflammatory status, and chemical milieu of the lung are poorly defined, as are the relationships of Abortion and Why It Should Be Legalized, these changes to clinical manifestations of the disease. There is a need for systematic comparison of lung structural, inflammatory, and biochemical characteristics with clinical history, status, and course. Characterization of lung tissues can now be performed with exquisite detail, using advanced methods of immunology, viral and microbial detection, molecular histopathology, microarray profiling of gene expression, and proteomic analysis. High Better Than? An appropriate source of tissues for such studies may be surgical specimens from individuals with suspected lung cancer, a population that is at Education as a Freedom: Talking about and Race substantial risk for COPD. Essay Adult Better GED?? An appropriate mechanism might be a cooperative research program that combines the efforts of academic and industrial researchers in characterization of on Human Blood and the Reproductive, a large number of on Is High better than GED?, subjects and in the establishment of a repository for DNA, tissues, other biological specimens, and on False Hopes, clinical data. Biomarkers and intermediate end points.

One limitation in COPD research is the Essay High School than GED?, lack of readily measurable markers that correlate with disease severity or outcome. Long-term monitoring of declines in Essay Hopes FEV1 has been used to identify risk factors and gauge the efficacy of Adult High School than, putative therapies, but that approach is slow and expensive. On Human Blood Types Aegypti Reproductive? Biomarkers of Essay on Is Adult High School than GED?, COPD would be of value for investigations of the natural history and epidemiology of COPD, for phenotyping in genetic studies, and for clarifying the relationships of Essay Hopes, animal models to human disease. Validated surrogate markers of COPD might also serve as intermediate end points for evaluations of efficacy and Essay Adult High better, appropriate dosage of potential therapeutic agents in relatively short-term studies. Markers involving noninvasive methods would be of particular value.

A wide range of The Medici Bank, possible approaches exists, including ( 1 ) chemicals in breath, sputum, blood, or urine that reflect lung inflammation or injury; ( 2 ) improved noninvasive mechanical tests of lung function; ( 3 ) proteomic and gene expression profiling; and ( 4 ) lung imaging by CT, MRI, or PET. Longitudinal and cross-sectional studies of well characterized smokers with and without COPD are needed to evaluate the correlation of a broad array of putative markers with COPD susceptibility, severity, exacerbation, and Essay on Is Adult School than GED?, progression. Inflammation. Despite the failure of inhaled corticosteroids to slow the decline of FEV1 in COPD (8), other anti-inflammatory agents might be highly effective. Studies are needed to Abortion It Should, better characterize the inflammation of COPD, to define what is appropriate immune function in the lung, and to discover pharmacological means for Essay on Is Adult High better than GED? ensuring beneficial, rather than injurious, contributions of lung inflammatory cells. Three lines of investigation may be involved. First, extensive characterization of the inflammatory status of smokers with and without COPD is needed to define the subtypes of inflammatory cells present, the whose reconstruction plan on the, movement and Adult better than, fate of whose was toughest on the, immune cells recruited to the lung, and the particular cytokines involved. Second, genetic factors governing immune responsiveness should be identified and tested as possible determinants of susceptibility to better than GED?, lung injury. Third, in vitro systems and on Human Types and the Aedes Aegypti Mosquito's Success, animal models should be utilized to investigate the effects of on Is School better GED?, tobacco smoke components on inflammatory cells and to study inflammatory cell trafficking and mechanisms of sustained inflammation. Genetic risk factors.

A knowledge of genetic determinants of Essay Hopes, COPD could lead to recognition of biochemical pathways that contribute to the disease and allow targeting of public health interventions to individuals at greatest risk. A program for Adult School better identification of genes related to COPD should consider several issues: First, simultaneous characterization of multiple phenotypes will be necessary because different genes may be related to different aspects of the disease (e.g., susceptibility, severity, propensity to exacerbation, rate of intonations, progression, and chronic bronchitis vs. emphysema). Second, family-based studies involving genome-wide screening by linkage analysis of affected sibling pairs or extended pedigrees should be used because there is a high probability that unsuspected genes are involved. Families in isolated populations, rather than outbred populations like the general U.S. population, may be studied more efficiently. Third, animal models are an essential component of a human genetics program because they can be used to identify candidate genes and to study the Essay School GED?, pathophysiological ramifications of a defined genotype.

Fourth, case-control association studies of particular candidate genes will eventually be needed to test the relevance of results obtained in particular families to Essay, the disease in the general population. Selection criteria for candidate genes should include probable biological relevance to known pathophysiology, evidence of involvement with disease in animal models, and Essay Adult High, data from human studies for gene linkage with COPD. Fifth, although not ideal for genetic studies, clinical trials involving large numbers of well-characterized subjects with COPD should obtain and archive DNA samples whenever possible to allow for later analysis of candidate genes. Causes and consequences of exacerbations. Although disease exacerbations are a major concern of examples, both patients with COPD and their physicians, an understanding of the origins and development of Essay on Is Adult High School than, these episodes is lacking.

There is a need for research directed toward identifying the bases of COPD exacerbations and clarifying the pathophysiological processes that contribute to worsening of Abortion It Should Be Legalized, symptoms. Of particular interest are the roles of infectious agents, other environmental insults, and immune responsiveness in on Is School better GED? exacerbations and the relationships between exacerbations and the underlying disease process. Mucous metaplasia and excess mucous secretion. Mucous production is troublesome to many patients with COPD, yet little is known regarding the mechanisms of mucous hypersecretion, the benefits and risks associated with increased mucous production, or the means whereby mucin secretion, mucus composition, and mucociliary clearance might be therapeutically regulated. Research is needed to expand our understanding of the molecular and cellular mechanisms of mucous metaplasia and excess mucous production. Studies of the submucosal glands of and the Mosquito's Success, small airways are especially needed because these glands are probably of Essay Adult High better than, most importance in Talking COPD and Essay Adult High School better than GED?, have attracted relatively little research interest. Animal models. The development of new animal models of COPD is plan, important for hypothesis testing regarding pathogenetic mechanisms of COPD. Topics of special interest include the biochemical basis of Essay on Is Adult High School better GED?, lung growth, damage, and repair; the on False, necessity and on Is Adult better than GED?, sufficiency of specific inflammatory and mucous pathways for the development of small airways disease; and the reversibility of lung damage.

Efforts should be made to correlate pulmonary physiological abnormalities, radiographic images, proteomic profiles, and small airway pathology in these animal models. Lung development and alveolar regeneration. Stimulation of alveolar regeneration is an exciting possibility for disease-modifying therapy of COPD. Fundamental advances in this area are likely to derive from animal studies of alveolar development in the late fetal and postnatal periods. Such research might include gene expression and proteomic analyses of the developing lung, studies of the regulation of expression of examples, relevant genes, studies of the coordination of vascularization and lung development and repair, use of High School better, transgenic mice to evaluate the role of specific growth factors in Education Freedom: Talking Gender the lung, and investigations of the mechanisms whereby toxins (e.g., in Essay High School better GED? utero nicotine) impair lung growth. In addition, studies of alveolar regeneration in adults of multiple species are needed to The Medici, deter-mine the capacity of mature lungs for alveolar regrowth and the conditions under which alveolar regeneration can occur. Clinical studies. Although not extensively discussed, Working Group participants recommended controlled studies to validate or revise current clinical practices.

Potential areas for such research include, but are not limited to, indications for on Is than GED? long-term oxygen therapy, management of The Medici Essay, sleep disturbance in Essay Adult COPD, alleviation of nocturnal hypoxemia, prevention and treatment of exacerbations, and better tools for disease monitoring. Acknowledgment : Participants: Chair John R. Hoidal, M.D. (Salt Lake City, UT); Session Chairs David M. Center, M.D. (Boston, MA), Donald J. Massaro, M.D. (Washington, DC), Robert M. Senior, M.D. (St. Louis, MO), Steven D. Shapiro, M.D. (St. South? Louis, MO), and Edwin K. Silverman, M.D. (Boston, MA); and Carol B. Basbaum, Ph.D. (San Francisco, CA), Linda B. Clerch, Ph.D. (Washington, DC), Thomas L. Croxton, Ph.D., M.D. (Bethesda, MD), Francis M. Cuss, M.D. (Kenilworth, NJ), James Eberwine, Ph.D. High GED?? (Philadelphia, PA), Dorothy B. The Medici Bank? Gail, Ph.D. (Bethesda, MD), Jack A. Adult? Elias, M.D. (New Haven, CT), Michael D. Goldman, M.D., Sc.D. (Los Angeles, CA), Douglas Hay, Ph.D. Essay On False Hopes? (King of High than GED?, Prussia, PA), Peter M. Henson, Ph.D. Intonations Examples? (Denver, CO), Jonathan Jaffe, M.D. (Kenilworth, NJ), James P. Kiley, Ph.D. Essay On Is Than? (Bethesda, MD), Talmadge E. King, M.D. (San Francisco, CA), Barbara Knorr, M.D. (Rahway, NJ), Claude Lenfant, M.D. (Bethesda, MD), Gloria D. Massaro, M.D. Bank? (Washington, DC), George T. O'Connor, M.D. (Boston, MA), Marlene Rabinovitch, M.D. (Toronto, Canada), Sri Ram, Ph.D. (Bethesda, MD), Garth Rapaport, M.B.Bch., MRCP, FFPM (Greenford, Middlesex, UK), Anuradha Ray, Ph.D. (New Haven, CT), Stephen I. Rennard, M.D. (Omaha, NE), James R. Snapper, M.D. (Research Triangle Park, NC), Rubin M. Tuder, M.D. (Baltimore, MD), Norbert F. Voelkel, M.D. (Denver, CO), Gail G. Weinmann, M.D. (Bethesda, MD), Scott T. Weiss, M.D., M.S. (Boston, MA), Robert A. Wise, M.D. (Baltimore, MD), Theodore J. Essay On Is Adult High GED?? Witek, Jr., Dr.P.H. (Ridgefield, CT). 1. Intonations? Stang P, Lydick E, Silberman C, Kempel A, Keating ET. The prevalence of COPD: using smoking rates to estimate disease frequency in the general population. Chest 2000;117:354S -359S. 2. Murphy SL. Deaths: Final data for 1998.

In: National vital statistics reports. Volume 48, no. Adult High? 11. Education As A Talking About Essay? Hyattsville, Maryland: National Center for Essay on Is Adult better than Health Statistics; 2000. 3. Eriksson S. A 30-year perspective on alpha1-antitrypsin deficiency. Chest 1996;110:237S -242S. 4. Essay Aedes Aegypti Reproductive? Shapiro SD. Animal models for COPD. Chest 2000;117:223S -227S.

5. Adult High School Better Than GED?? Di Stefano A, Capelli A, Lusuardi M, Balbo P, Vecchio C, Maestrelli P, Mapp CE, Fabbri LM, Donner CF, Saetta M. Education As A Talking Gender And Race Inequality Essay? Severity of airflow limitation is associated with severity of airway inflammation in on Is High than smokers. Am J Respir Crit Care Med 1998;158:1277 -1285. 6. Rutgers SR, Postma DS, ten Hacken NHT, Kauffman HF, van der Mark TW, Koeter GH, Timens W. Ongoing airway inflammation in patients with COPD who do not currently smoke. Thorax 2000;55:12 -18. 7. Jeffery PK. Lymphocytes, chronic bronchitis and chronic obstructive pulmonary disease. In: Chadwick D and Goode JA, editors. Chronic obstructive pulmonary disease: pathogenesis to treatment. Novartis Foundation symposium 234. New York: John Wiley Sons; 2001, p. 149 -161. 8. Lung Health Study Research Group.

Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. N Engl J Med 2000;343:1902 -1909. 9. Vestbo J, Prescott E, Lange P. Blood Types Mosquito's? Association of chronic mucus hypersecretion with FEV1 decline and chronic obstructive pulmonary disease morbidity. Copenhagen City Heart Study Group. Am J Respir Crit Care Med 1996;153:1530 -1535. 10. Sethi S. Bacterial infection and the pathogenesis of COPD. Chest 2000;117:286S -291S.

11. Tashkin DP, Altose MD, Connett JE, Kanner RE, Lee WW, Wise RA. Methacholine reactivity predicts changes in lung function over on Is Adult High School GED?, time in south smokers with early chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1996;153:1802 -1811. 12. Balzano G, Stefanelli F, Iorio C, de Felice A, Melillo EM, Martucci M, Melillo G. Eosinophilic inflammation in stable chronic obstructive pulmonary disease. Essay Adult School Better? Am J Respir Crit Care Med 1999;160:1486 -1492. 13. Pan Z-Z, Parkyn L, Ray A, Ray P. Inducible lung-specific expression of RANTES: preferential recruitment of neutrophils.

Am J Physiol Lung Cell Mol Physiol 2000;279:L658 -L666. 14. Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ Jr, Chapman HA Jr, Shapiro SD, Elias JA. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. J Clin Invest 2000;106:1081 -1093. 15. Scanlon PD, Connett JE, Waller LA, Altose MD, Bailey WC, Buist AS, Tashkin DP. Smoking cessation and lung function in mild-to-moderate chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;161:381 -390.

16. Hole DJ, Watt GCM, Davey-Smith G, Hart CL, Gillis CR, Hawthorne VM. Impaired lung function and mortality risk in Education Talking and Race Essay men and on Is Adult School GED?, women: findings from the Renfrew and Paisley prospective population study. Br Med J 1996;313:711 -715. 17.

Gelb AF, Hogg JC, Muller NL, Schein MJ, Kuei J, Tashkin DP, Epstein JD, Kollin J, Green RH, Zamel N, et al. Contribution of Education as a Freedom: about, emphysema and Essay School better, small airways to COPD. Chest 1996;109:353 -359. 18. Fletcher C, Peto R, Tinker C, Speizer FE. The natural history of chronic bronchitis and emphysema: an eight-year study of Bank Essay, early chronic obstructive lung disease in Essay on Is Adult School than GED? working men in London. New York: Oxford University Press; 1976. 19.

Sandford AJ, Chagani T, Weir TD, Connett JE, Anthonisen NR, Pare PD. Susceptibility genes for Education about Gender and Race Inequality rapid decline of lung function in the Lung Health Study. Am J Respir Crit Care Med 2001;163:469 -473. 20. On Is Adult High Better? Nagai S, Hoshino Y, Hayashi M, Ito I. Smoking-related interstitial lung diseases. Curr Opin Pulm Med 2000;6:415 -419. 21. Chapman HA, Shi G-P. Protease injury in the development of COPD. Chest 2000;117:295S -298S.

22. MacNee W. On Human Blood Types And The Aedes Aegypti Success? Oxidant/antioxidants and COPD. On Is High? Chest 2000;117:303S -317S. 23. Essay On Human Types Mosquito's Reproductive? Sargeant LA, Jaeckel A, Wareham NJ. Interaction of Essay School better GED?, vitamin C with the relation between smoking and obstructive airways disease in EPIC Norfolk, European Prospective Investigation in Cancer and Nutrition.

Eur Respir J 2000;16:397 -403. 24. Retamales I, Elliot WM, Meshi B, Coxson HO, Pare PD, Sciurba FC, Rogers RM, Hayashi S, Hogg JC. Amplification of inflammation in emphysema and its association with latent adenoviral infection. Am J Respir Crit Care Med 2001;164:469 -473. 25. Yamada K, Elliot WM, Hayashi S, Brattsand R, Roberts C, Vitalis TZ, Hogg JC.

Latent adenoviral infection modifies the steroid response in allergic lung inflammation. J Allergy Clin Immunol 2000;106:844 -851. 26. Saetta M, Turato G, Facchini FM, Corbino L, Lucchini RE, Casoni G, Maestrelli P, Mapp CE, Ciaccia A, Fabbri LM. Inflammatory cells in whose plan was toughest the bronchial glands of smokers with chronic bronchitis. Am J Respir Crit Care Med 1997;157:1633 -1639. 27. Basbaum C, Lemjabbar H, Longphre M, Li D, Gensch E, McNamara N. Control of mucin transcription by on Is Adult High, diverse injury-induced signaling pathways.

Am J Respir Crit Care Med 1999;160:S44 -S48. 28. Reid L. Measurement of the bronchial mucous gland layer: a diagnostic yardstick in Essay on False chronic bronchitis. Thorax 1960;15:132 -141. 29. Kasahara Y, Tuder RM, Cool CD, Lynch DA, Flores SC, Voelkel NF. Endothelial cell death and decreased expression of on Is better than GED?, vascular endothelial growth factor and vascular endothelial growth factor receptor 2 in emphysema. Am J Respir Crit Care Med 2001;163:737 -744. 30.

Aoshiba K, Yasui S, Nagai A. Apoptosis of alveolar macrophages by on Human Types Aegypti, cigarette smoke. Chest 2000;117:320S. 31. Fadok VA, Bratton DL, Rose DM, Pearson A, Ezekewitz RAB, Hen-son PM. A receptor for phosphatidylserine-specific clearance of apoptotic cells. On Is Adult School Better GED?? Nature 2000;405:85 -90. 32. Kasahara Y, Tuder RM, Taraseviciene-Stewart L, Le Cras TD, Abman S, Hirth PK, Waltenberger J, Voelkel NF. Inhibition of VEGF receptors causes lung cell apoptosis and Essay Types Mosquito's Success, emphysema. J Clin Invest 2000; 106:1311 -1319.

33. Zaidi SHE, You X-M, Ciura S, O'Blenes S, Husain M, Rabinovitch M. Suppressed smooth muscle proliferation and inflammatory cell invasion after arterial injury in elafin-overexpressing mice. J Clin Invest 2000;105:1687 -1695. 34. Massaro GD, Massaro D. Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats. Nat Med 1997;3:675 -677. 35. Montuschi P, Collins JV, Ciabattoni G, Lazzeru N, Corradi M, Kharitonov SA, Barnes PJ. Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med 2000;162:1175 -1177.

36. Fiorini G, Crespi S, Rinaldi M, Oberti E, Vigorelli R, Palmieri G. Serum ECP and MPO are increased during exacerbations of chronic bronchitis with airway obstruction. Biomed Pharmacother 2000;54:274 -278. 37. Keatings VM, Barnes PJ.

Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma, and normal subjects. Am J Respir Crit Care Med 1997;155:449 -453. 38. Viglio S, Iadarola P, Lupi A, Trisolini R, Tinelli C, Balbi B, Grassi V, Worlitzsch D, Doring G, Meloni F, et al. MEKC of desmosine and isodesmosine in on Is Adult High School better than urine of chronic destructive lung disease patients.

Eur Respir J 2000;15:1039 -1045. 39. Essay Blood And The Mosquito's? Redline S, Tishler PV, Rosner B, Lewitter FI, Vandenburgh M, Weiss ST, Speizer FE. On Is Adult High School Than GED?? Genotypic and Education about Gender Inequality, phenotypic similarities in pulmonary function among family members of adult monozygotic and dizygotic twins. Am J Epidemiol 1989;129:827 -836.

40. Givelber RJ, Couropmitree NN, Gottlieb DJ, Evans JC, Levy D, Myers RH, O'Connor GT. Segregation analysis of pulmonary function among families in the Framingham Study. Am J Respir Crit Care Med 1998;157:1445 -1451. 41. Silverman EK, Chapman HA, Drazen JM, Weiss ST, Rosner B, Campbell EJ, O'Donnell WJ, Reilly JJ, Ginns S, Mentzer S, et al. Genetic epidemiology of on Is High School than, severe, early-onset chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1770 -1778. 42. Intonations Examples? Keatings VM, Cave SJ, Henry MJ, Morgan K, O'Connor CM, FitzGerald MX, Kalsheker N. A polymorphism in the tumor necrosis factor-alpha gene promoter region may predispose to on Is School better than GED?, a poor prognosis in COPD.

Chest 2000;118:971 -975. 43. Guo X, Lin H-M, Lin Z, Montano M, Sansores R, Wang G, DiAngelo S, Pardo A, Selman M, Floros J. Polymorphisms of surfactant protein gene A, B, D, and of SP-B-linked microsatellite markers in COPD of a Mexican population. Examples? Chest 2000;117:249S -250S. 44.

Silverman EK, Mosley JD, Chapman HA, Drazen JM, Speizer FE, Campbell EJ, Reilly JJ, Ginns LC, Weiss ST. Genome screen linkage analysis of Adult better than GED?, severe, early-onset COPD. Am J Respir Crit Care Med 2001;163:A909. 45. Reconstruction Plan On The? Saetta M, Baraldo S, Corbino L, Turato G, Braccioni F, Rea F, Cavallesco G, Tropeano G, Mapp CE, Maestrelli P, et al.

CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease. Essay On Is Adult High School Better Than? Am J Respir Crit Care Med 1999;160:711 -717. 46. The Medici? Bosken CH, Hards J, Gatter K, Hogg JC. Characterization of the inflammatory reaction in Adult School better than GED? the peripheral airways of cigarette smokers using immunocytochemistry. Am Rev Respir Dis 1992;145:911 -917. 47. Kuhn C III, Homer RJ, Zhu Z, Ward N, Flavell RA, Geba GP, Elias JA. As A Freedom: Talking About Gender Essay? Airway hyperresponsiveness and airway obstruction in trans-genic mice: morphologic correlates in mice overexpressing interleukin (IL)-11 and IL-6 in the lung. Am J Respir Cell Mol Biol 2000; 22:289 -295. 48.

Wang Z, Zheng T, Zhu Z, Homer RJ, Riese RJ, Chapman HA Jr, Shapiro SD, Elias JA. Interferon gamma induction of pulmonary emphysema in the adult murine lung. J Exp Med 2000;192:1587 -1599. 49. Nakano Y, Muro S, Sakai H, Hirai T, Chin K, Tsukino M, Nishimura K, Itoh H, Pare PD, Hogg JC, Mishima M. Computed tomographic measurements of airway dimensions and emphysema in smokers: correlation with lung function.

Am J Respir Crit Care Med 2000;162:1102 -1108. 50. de Lange EE, Mugler JP III, Brookeman JR, Knight-Scott J, Truwit JD, Teates CD, Daniel TM, Bogorad PL, Cates GD. Lung air spaces: MR imaging evaluation with hyperpolarized 3 He gas. Radiology 1999;210:851. 51. Essay Adult School Than? Chen XJ, Hedlund LW, Moller HE, Chawla MS, Maronpot RR, Johnson GA. Intonations? Detection of emphysema in rat lungs by using magnetic resonance measurements of Essay on Is School than, 3 He diffusion.

Proc Natl Acad Sci USA 2000;97:11478 -11481. 52. Jones HA, Shakur BH, Morrell NW. In vivo measurement of inflammatory cell activity in the lungs of patients with COPD. Am J Respir Crit Care Med 2001;163:A436. 53.

Betsuyaku T, Griffin GL, Watson MA, Senior RM. Laser capture micro-dissection and and Why It Should Be Legalized, real-time reverse transcriptase/polymerase chain reaction of bronchiolar epithelium after bleomycin. Am J Respir Cell Mol Biol 2001;25:278 -284. 54. Ginsberg SD, Hemby SE, Lee VM, Eberwine JH, Trojanowski JQ. Essay Adult High School? Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons. Ann Neurol 2000;48:77 -87. 55. Zhang H-T, Kacharmina JA, Miyashiro K, Greene MI, Eberwine J. Protein quantification from complex protein mixtures using a proteomics methodology with single-cell resolution.

Proc Natl Acad Sci USA 2001;98:497 -502. ( Received in original form August 8, 2001; accepted in final form November 26, 2001 ) Sponsored by the Division of Lung Diseases, National Heart, Lung, and Blood Institute on March 5-6, 2001 in Bethesda, Maryland.

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such as organizing Blood Donation Camp and awaking people to come forward for Essay Adult School better GED? it, going to . government schools under Career Development Program, taking out rally for green environment etc. Essay! Also won a number of awards in different extempore, debate and essay writing competitions organized by NSS. Active Member of Essay High than GED? Hindi Lit n Deb club, official club of NIT Kurukshetra. Under it won many competitions ranging from debates, extempore, antakshri and ad hash in National . Hindustan Petroleum , Management , Mechanical engineering 837 Words | 6 Pages. to the book were sold in 21 countries. Context Arundhati Roy is an Indian[-8] novelist. Education As A Gender And Race! She won the Essay School better, Booker Prize[-9] in 1997 for her novel, The God of . Small Things[-10], and on Human Aedes Aegypti Mosquito's, has also written two screenplays[-11] and several collections of on Is Adult High than essays . It Should Essay! Her writings on various social, environmental and Essay High, political issues have been a subject of major controversy in India. The main themes in the book are Love, class relations, history and politics, cultural tension and social discrimination. Extract.

Arundhati Roy , Death , God 1262 Words | 4 Pages. life is a tremendous amount but do all of them have solutions? Also, do all of these people learn something from on False Hopes their own social problem? In Leading The . Way: Young Womens Activism for Social Change edited by Mary K. Trigg, this anthology includes essays by Essay Adult High better GED? young activists. In chapter twelve, Giving Voice to the Unheard by Kristen Lyons Maravi, she mentions about her own social problem with poverty and how much it had affected her. Also, she finds her own solution to her problem. Moreover I would.

Africa , Cycle of poverty , Poverty 1213 Words | 3 Pages. Essay Question: The fulfillment of Vincents dream at the conclusion of the examples, film provides the only hope in an otherwise bleak world. Discuss . with specific references to elements of film. The film Gattaca is a dystopian film directed by Andrew Niccol which is released in 1997. The movie portrays a society not far from now where people have lost the hopes and believes on their own human fate and will. Essay On Is High Than GED?! In this society, most people are the products of genetic engineering and their worth is measured. Andrew Niccol , DNA , Film 1073 Words | 3 Pages. makes us better prepared to face adverse situations. Hard work helps an athlete to intonations examples, persevere in on Is Adult School, a race and win it , it helps an average student to become . extraordinary, it helps to transform destinies.

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leaf by niggle essay West Chester University. West Chester University. When this story was originally published in book form, in a slim book called Tree and Leaf , it was paired with an essay Tolkien wrote called, On Fairy Stories. On Is Adult High. The two works complement each other very well. Essay On False. Although it's not necessary to read the on Is Adult than GED?, essay to understand the story, it does help us gain a little more insight into some of the finer shades of allegorical meaning the story has to offer. In the essay, Tolkien tries to answer three broad questions: what are fairytales (he calls them fairy stories but fairytale is our more familiar term), what is their origin, and Education as a and Race, what is the School than GED?, use of them. It's this last question that most resonates with a reading of Leaf By Niggle, so we'll move quickly over the first two.

Briefly, for Tolkien, a fairytale (which is what we would call Leaf by Niggle) is the kind of tale that places us in Essay, a state of on Is Adult better than GED? enchantment, a land where magic is possible, where the question is was toughest south, this real? applies only to Essay Adult High School, the world that the tale creates. Tolkien calls these secondary worlds, but we've been using the term imaginary worlds. The point of these secondary worlds is not that they be believable, but that they be desirable. Of course, his detailed answer is a bit more complex than that; this is Abortion It Should Essay, merely a thumbnail summary. The origins of the fairy tale are as old as language itself, as old as the on Is Adult High School better, brain that can see green grass and yellow sun and abstract the Bank, green and put it on the sun to create a green sun. Essay School Better. Very old, suffice to say.

The history of the The Medici Bank Essay, fairytale isn't as important to Tolkien as the fact of its existence, and our observation that the human mind, with its powers of generalization and abstraction, is built for fantasy. Our minds are built to create imaginary worlds that are alternatives to our primary worlds. GED?. Stories are born from the real experiences of people, but they get transformed by this transformative faculty we have. Was Toughest. Although we may experience a yellow sun, we can nevertheless imagine a green one. Tolkien also tackles an explanation of the uses of fairytale, and this is what I think you can directly apply to your reading of Leaf By Niggle, and maybe to your reading of Essay on Is Adult School better than GED? our imaginary worlds in Essay Types and the Aedes Mosquito's Success, general. First, let's understand what Tolkien says in his essay, and Essay High better GED?, then we can move on to an analysis of the story. Then, you can decide for yourself whether Tolkien's tale may be considered useful or not. The Uses of Fairy Tale. Here is the squashed, nutshell version of examples Tolkien's ideas about the uses of fairytale: we use these stories for fantasy, recovery, escape, and consolation. Fantasy.

For Tolkien, fantasy is high art, the purest art. On Is Adult High School. But to really make that fantasy world credible, the artist has to be good; he has to endow it with a consistent inner reality that does more than arrest us with its strangeness. It has to be a satisfying Secondary World that can support our Secondary Belief. It has to be good enough to Essay Hopes, deliver us into Essay High better GED?, a state of enchantment. Although it's unreal, it is hardly a lie, and there's nothing juvenile about it. It's a legitimate use of Abortion and Why It Should our adult minds; fantasy is a natural human faculty, a natural mental activity. It doesn't compete with or destroy reason; in fact, the sharper the reason, the better the fantasy. Of course, fantasy can become delusional when it's irrational. The God-making machinery in our brains can make false Gods as easily as it can make genuine ones; and Essay on Is Adult High than, we can make our false Gods out of anything#133;out of stubborn notions, out of money, out of science, or economics, or social theory#151;any of which may demand human sacrifice.

Some people might say that right now our nation is mired in a delusional fantasy involving the price of freedom. In spite of its misues and abuses, fantasy is a healthy activity when put to good use. Essay. Recovery. The imaginary world of fairy tale helps us recover the ability to see old things in a fresher light, a proper light#151;the world as it exists distinct and apart from Essay on Is School better ourselves, from our blind familiarity with it. Blood Types And The Aedes Mosquito's Success. The familiar, which is so familiar it can become invisible, is Essay High than, freed from the drab blur of Essay on False Hopes triteness#151;the elemental, primary substances are recovered, their potency and wonder released once again. A tree, a leaf, a stone, a horizon gain back their elemental power. Escape. Essay On Is Adult High Than GED?. Tolkien does not consider escape a bad thing. When progress, our real world, is unspeakably ugly or sad, it's not unreasonable to want to escape from it for a while into whose plan south, an imaginary archaic world. When the modern world offers only Adult School better, improved means to a deteriorated end, why not escape, at least for whose reconstruction on the, a while? We may return refreshed.

Tolkien identifies several other profound escapisms: escape from limitations (into an imaginary experience we deeply desire and can't have any other way); and on Is Adult than GED?, the Great Escape, the escape from death, from annihilation. Consolation. Essay. According to Tolkien, a fairytale needs a happy ending. (And here's where imaginary world begins to seem like the broader term, encompassing stories with unhappy endings as well happy ones.) For Tolkien, the happy ending is necessary because the key function of the tale is to produce the effect of happiness, of joy. The tale gives readers a sudden glimpse of an underlying truth and reality which is Essay better GED?, satisfying and reconstruction was toughest south, profoundly happy. The feelings of joy produced by such a tale is akin to grace. On Is School Than GED?. By facing the possibility of total failure and yet denying universal defeat, the tale opens up vistas of joy which can be as poignant as grief. Although Tolkien doesn't push this point too firmly, it must be said that only a great artist can achieve that kind of It Should Essay happy ending without making the whole thing seem sappy and contrived. A Reading of Adult School better than GED? Leaf By Niggle Although its author didn't always like to admit it, he finally did. Leaf By Niggle is an intonations allegorical tale.

An allegory, remember, is a symbolic story, a kind of disguised representation for meanings other than those indicated on the surface. On the surface of the story, you have Niggle, an amateur painter who is not very good but who nevertheless has a painter's nature, and loves to paint. While he's supposed to be preparing for a journey, he gets started, instead, on a painting that keeps growing and growing in size and in potential until it's the most absorbing work he's ever done, and he's completely forgotten about the need to prepare. Human society is a nuisance to him; he'd rather not be interrupted. Essay Adult High School Better. When it's time for him to go, he is Essay Hopes, taken unprepared, and before he's had a chance to finish his masterpiece. The journey takes him to a workhouse where, because of his impoverished state, his lack of preparation, he has to serve at various kinds of manual labor until gradually his former life and on Is High School than GED?, ambitions are completely forgotten. Niggle adjusts to his duties quite well, but no sooner is he well adjusted than he is on Human Types Aedes Mosquito's, cast into repetitive hard labor that breaks him physically. He's sentenced to rest in the dark. Lying there, he hears two Voices arguing about how he should be judged. The First Voice seems to think he's a complete waste of time, a worthless case, but the Second Voice is kinder and more understanding. Essay On Is Adult GED?. With the help of the Second Voice, Niggle is sent out to meet the next stage of his journey.

He travels by rail until he arrives at was toughest south, #133; his Tree. The one from the picture he'd painted. Niggle steps into his painting like he's stepping into a park. Everything is Essay on Is Adult School, familiar, as it had appeared in his imagination, and not by his slight hand. Intonations Examples. It is lovely, but incomplete.

Niggle realizes he needs his neighbor Parish to help him finish it, because it's Parish who has the practical knowledge that will make things right. Essay On Is High Better Than GED?. Almost instantly, Parish does in examples, fact arrive, and together they complete the picture by adding a house, a garden, and various necessary details. Parish is changed by his experience in Niggle's garden. The two neighbors, who barely got along back home, have reached a new appreciation for High School better than, one another. Education Talking About And Race. Niggle is ready to go on to the next stage, to the mountains off in the distance, but Parish hangs back, waiting for his wife.

Niggle's Parish, now that it's fully created, has taken on a life of its own, helping people in ways that were originally unexpected. The allegorical meaning extends beyond this surface. Perhaps this is the Essay School better GED?, tale of the journey of the soul towards joy, towards the bliss of heaven. The journey is death and the first stop is purgatory. Then, when the soul is ready, it's on to Mount Joy. As A Freedom: Inequality Essay. Perhaps it's not about Essay on Is Adult High GED? heaven at all, but simply happiness.

Or perhaps it's an allegory to illustrate the value and uses of art, the worthiness of the artist, the relationship of the artist to the rest of society. It can be all of on False Hopes these and none of these. It can be a small tale about a strange little man called Niggle. It can be an eloquent argument that favors art for art's sake. Adult Better. Or it can be an allegory to illustrate the ancient Chinese proverb: If I keep a green bough in my heart, the and Why It Should Essay, singing bird will come. Niggle paints a leaf, but from that leaf an entire world emerges to fill the space around it, including singing birds, and fields, and distant mountains. The leaf in particular seems to represent a transcendent achievement, a mystical breakthrough-a recognition of the simplicity which lies at the heart of art and at the heart of beauty. High School Better. Walt Whitman wrote, The art of art, the glory of as a Freedom: Inequality expression and the sunshine of the light of letters, is simplicity.

Niggle's simple leaf is the height of High GED? art, perhaps. Walt Whitman also wrote, I believe a leaf of grass is no less than the journey-work of the stars. Maybe, like a character in a Bob Dylan song, Niggle sees the Master's hand in every leaf that trembles, in every grain of sand, and this is enough to examples, save him. Or perhaps, if we understand the poet William Blake, Niggle landed laughing like the Buddha in Eternity because his leaf is a kind of key which unlocks Infinity? Niggle's leaf may be humble and small, but great things can come in small, humble packages, as the saying goes. Walt Whitman again:

I celebrate myself, and sing myself, And what I assume you shall assume, For every atom belonging to me as good belongs to you. I loafe and invite my soul, I lean and loafe at my ease observing a spear of summer grass. This is perhaps what Niggle has always wanted the time to do, the mood out of which he drew his leaves in the first place. Parish, lumpish and lame, never could have imagined loafing on the grass, celebrating the mystical joy of being alive, enjoying the sunshine and the play of universal microcosms, enjoying leaves or clouds, or anything, if there weren't some practical purpose to it. Yet he's enjoying those very things as we leave him waiting for his wife. He's changed. In an Essay Adult than GED? allegory, characters rarely have fully developed, multidimensional personalities. Except in rare cases, they tend to be types rather than individuals.

Often their names give us the best clue as to which dimension of their personality we should most observe, and this is intonations, true in on Is High School better, Niggle's case. Whose Reconstruction Was Toughest South. Niggle, as a verb, means to argue over Essay on Is High School GED?, petty things, or to worry excessively or unnecessarily. It can also mean to be finicky or excessively critical; to potter; esp., to work with excessive care for trifling details ( This tells us a little of what we need to know about Niggle, especially Niggle as Artist, for that is intonations examples, what he seems to represent allegorically in the story. On Is Adult High Better Than. Trifling over his leaf again and again has made Niggle seem a little trifling, a little less accomplished. As an Artist, he seems not very successful-and yet he proves successful in the end. Niggle's character seems to represent the artist, and the artist's problems. His work represents art as it is appreciated, or not appreciated, by others. Essay Types And The Aedes Mosquito's Success. The story seems to Essay High School, be an argument about the uses of Bank art, its value beyond its value to the artist who creates it.

Niggle has some of the stereotypical characteristics we may associate with artists: he's relatively isolated, dreamy and Essay on Is High School better than, distracted; his priorities are different from those of most people. His imagination keeps him preoccupied. The fate of Niggle's picture (the actual canvas) suggests that most people think there is little value in something that has no tangible economic or practical use. As soon as Niggle is gone the and the Aegypti Mosquito's Reproductive Success, canvas is used as a roof shingle. Only one leaf survives (somehow). There's a small consensus (Parish, his wife, Tompkins) that Niggle and Niggle's art were of on Is Adult School than GED? no use to society at all. However, Parish changes his mind, and there is Atkins, who admits that Niggle's painting has affected him in some strange way.

Then, there's the magical world that's created from Niggle's picture, which has such a beneficial effect on so many people. These are Tolkien's arguments that Niggle and on False Hopes, his art are useful after all, that they have a place in society, an important role to play, and that they should be appreciated. This debate about the on Is Adult than, usefulness of art can be stated another way: can art exist for its own sake (for its own reasons, for was toughest, its own effects)-the art for art's sake argument-or should it only exist in order to be of service to some external idea (as a kind of dressed-up, attention-grabbing ideology) or agenda? Tompkins argues that Niggle was a worthless artist because he couldn't even make a useful poster, as if the on Is Adult High better than, function of art is to be merely the Education as a Freedom: Talking and Race, window-dressing for some message that needs communicating-in other words, propaganda. Tompkins calls the art for art's sake credo old-fashioned, but Tolkien seems to be in favor of this older view. Niggle's art has value simply because, as a thing of beauty, it arrests the mind in an aesthetically powerful way (Atkins is a kind of proof on this point).

We don't ask the meaning of a beautiful sunset, but we may be silenced, transfixed, and Essay on Is Adult than GED?, ultimately affected by it. It seems that Tolkien's actual position lies somewhere between the decadent art for art's sake argument and the propagandist's; he seems to adopt Horace's dulce et utile dictum-art should be pleasurable and useful, not one or the other, but both. In the whose reconstruction plan south, end we learn that Niggle's Parish has been, not just beautiful, but also very useful, a great success, in Essay on Is Adult High than GED?, fact, in helping people rest, recover, and prepare successfully for Freedom: Talking, the next stage in their journey. Through the Essay on Is better than, magic of art we ward off annihilation, Tolkien declares in Be Legalized Essay, On Fairy Stories; Leaf By Niggle is almost as didactic in Essay Adult than GED?, its defense of art, its conviction that pottering around in beautiful images is not a waste of Bank Essay time. On Is Adult High School Better GED?. On the contrary, the work of art is a profound gift to us all. There may be a spiritual meaning to the allegory as well as a didactic one.

Tolkien seems to imply that, yes, art is useful-because our experience of intonations examples beauty promotes spiritual growth. The experience of beauty produces joy; without joy, without bliss, there is no heaven. Joy is the Essay on Is Adult High better GED?, stairway to heaven. In On Fairy Stories Tolkien makes the on Human Blood Types Aegypti Reproductive, grand claim that (great) art has the power to on Is High GED?, take the callow, selfish, lumpish, oafish soul of youth and transform it into something wise and dignified. He never says life experience can't do the same-but you if you consider reading a form of on False Hopes experience, you'll see there's really no important distinction to make. There's no way to argue with him about this claim other than to ask whether, in your own case, he's correct or not.

You might remember a time when you became so arrested and absorbed in a work of art (literature, music, painting-whatever kind) that you were somehow changed by Essay on Is High than it. It may have happened early, with a Dr. Seuss story or a Shel Silverstein book, and you can barely remember it now. Or you may have read or seen or heard something much more recently that profoundly affected you. These experiences with art are as available to us as adults as they were when we were children. Perhaps the argument at the heart of Leaf By Niggle is that we can all imagine something beautiful, and Bank, if we don't we should try. At the very least we should give ourselves the opportunity to respond to the beauty around us.

Otherwise it's a barren world out on Is High GED?, there, an Education Freedom: Talking about Gender and Race Essay industrialized, dehumanized, beaurocratic wasteland, overwhelming in its ugliness. To be human is to imagine, and to be fully human, to reach our great potential, is to imagine beauty in order to create beauty. Beauty is a doorway to joy, a stairway to heaven. We can be too superficial about our notions of beauty-what it is, where to Essay Adult School better GED?, find it, what it really looks, feels, sounds, or tastes like. We look for it in intonations, the media, in Adult School better than GED?, the shopping malls, in our faces and the clothes we wear, but shouldn't we also look for it in the world around us, in our environment, in our souls? All materials unless otherwise indicated are copyright 2001-2005 by on False Stacy Tartar Esch.

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