Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pathogenesis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 955 records · Page 53Linked to original sources
PubMed2002

Pathogenesis of asthma.

There is now strong evidence that airway inflammation is a predominant underlying problem in patients with asthma, and it has been suggested that ongoing inflammation may lead to airway injury and remodeling. There is also recent evidence that longstanding asthma could be associated with loss of elastic recoil, which can enhance airway obstruction and worsen asthma control [82,83]. Therefore, the use of anti-inflammatory therapy has been advocated in all guidelines, including the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report [84] and its recent update [85] that recommended inhaled steroids as a first mode of therapy for patients with mild, moderate, or severe, persistent asthma. There is preliminary evidence that early institution of anti-inflammatory therapy might lead to disease modification and limit the progression of subepithelial fibrosis and airway remodeling. The pathogenesis of asthma clearly involves many cells and mediators, although the contribution of each individual factor is probably different from patient to patient depending on the setting and stimulus. Although currently available therapies are highly effective in controlling asthma symptoms and limiting exacerbations in the majority of patients, there is still a subset of patients that proceed to develop severe asthma with decreased lung function, lack of responsiveness to therapy, or frequent exacerbations. It is hoped that rapid progress in the area of asthma genetics and pharmacogenetics will yield a more precise and patient-specific understanding of asthma pathogenesis and allow practitioners to prescribe therapies that are designed for a particular patient or exacerbation. That will undoubtedly help to improve the care of asthma, limit its morbidity, and reduce the side effect of medications.

Asthma↗
PubMed1982

Familial dysbetalipoproteinemia. New aspects of pathogenesis and diagnosis.

New aspects in the pathogenesis and diagnosis of familial dysbetalipoproteinemia are discussed, including the clarification of the chemical basis of the polymorphism of apoprotein E, the allelic nature of the primary isoforms of the protein, the relationship of the abnormality of apoprotein E to the accumulation of remnant lipoproteins in dysbetalipoproteinemia and in persons carrying the trait for abnormal apoprotein E, and the pathogenesis of hyperlipidemia in this disorder. The related clinical features of dysbetalipoproteinemia are included in the discussion.

Apolipoproteins↗
PubMed1980

Aplastic anemia: recent advances in pathogenesis and treatment.

Successful bone marrow transplantation and bone marrow culturing techniques have generated a large body of research into the pathogenesis and treatment of aplastic anemia. Most prominent has been the emphasis on autoimmune mechanisms. Several etiologic types and diagnostic criteria are discussed, the evidence supporting immune and other mechanisms of pathogenesis is examined, and results of current therapeutic trials are addressed.

Adrenal Cortex Hormones↗
PubMed1993

Necrotizing enterocolitis. New thoughts about pathogenesis and potential treatments.

Necrotizing enterocolitis (NEC) remains a major cause of morbidity and mortality in premature infants. An incomplete understanding of its pathogenesis has hampered efforts to devise an effective preventative strategy. New insights into the pathogenesis of NEC, particularly at the cellular and biochemical level, however, offer a rational basis for the development of new approaches to this disease.

Adrenal Cortex Hormones↗
PubMed2002

Pathogenesis of colorectal cancer.

It is frequently stated that all but a few colorectal cancers arise in adenomatous polyps, in turn initiated by APC mutation. Moderation of this view is now required. The proportion of colorectal cancers that arises in a polypoid adenoma is likely to be around 70% [39,61]. The pre-eminence of the adenoma-carcinoma model has been influenced by two factors: (1) the need to avoid overtreatment of innocent lesions, and (2) the absence of a convincing alternative mechanism. The latter position has changed in recent years. Collectively, the alternative pathways may account for the pathogenesis of up to 30% of colorectal cancers. The alternative pathways are difficult to observe in clinical practice because the precursors may be either inconspicuous or show rapid evolution following the establishment of genetic instability. As a concept, the polyp-cancer sequence is entrenched in both specialized and student texts. This is unfortunate, because progress in prevention and early cancer detection will be delayed by the failure to adopt a critical and nondogmatic approach to the pathogenesis of colorectal cancer. The advent of DNA chip technology will catalyze the development of revised paradigms. Specifically, modern genomics will allow polyps and cancers to be grouped within pathogenic pathways on the basis of shared gene expression profiles. The era of molecular medicine has dawned for colorectal cancer.

Adenomatous Polyposis Coli↗
PubMed2003

Masking of the contribution of V protein to Sendai virus pathogenesis in an infection model with a highly virulent field isolate.

Sendai virus V protein is not essential for virus replication in cultured cells but is essential for efficient virus replication and pathogenesis in mice, indicating that the V protein has a luxury function to facilitate virus propagation in mice. This was discovered in the Z strain, an egg-adapted avirulent laboratory strain. In the present study, we reexamined the function of Sendai virus V protein by generating a V-knockout Sendai virus derived from the Hamamatsu strain, a virulent field isolate, which is an appropriate model for studying the natural course of Sendai virus infection in mice. We unexpectedly found that the V-knockout virus propagated efficiently in mice and was as virulent as the wild-type virus. Switching of the functionally important V unique region demonstrated that this region of the Hamamatsu strain was also functional in a Z strain background. It thus appears that the V protein is nonsense in a field isolate of Sendai virus. However, the V protein was required for virus growth and pathogenesis of the Hamamatsu strain in mice when the virulence of the virus was attenuated by introducing mutations that had been found in an egg-adapted, avirulent virus. The V protein therefore seems to be potentially functional in the highly virulent Hamamatsu strain and to be prominent if virus replication is restricted.

Animals↗
PubMed1981

Multiple juvenile polyposis. A study of the pathogenesis of juvenile polyps and their relationship to colonic adenomas.

Solitary juvenile polyps are common lesions whose pathogenesis is poorly understood. Multiple juvenile polyposis is characterized by large numbers of these lesions either confined to the colon or throughout the gastrointestinal tract. A study of two cases of multiple juvenile polyposis provided fresh insight into the pathogenesis of juvenile polyps and their relationship to colonic adenomas. Mucosal ulceration in very early lesions, together with glandular epithelial calcification, suggested that impaired cell renewal resulting from disturbed regenerative kinetics may predispose to surface epithelial erosion, setting in motion a cycle of ulceration, inflammation, and granulation tissue formation. We postulate that a dyskinetic continuum may link juvenile, "metaplastic," and adenomatous polyps. The finding in our second case of multiple adenomatous lesions, including a villoglandular polyp, emphasizes the neoplastic potential of juvenile polyposis.

Adenoma↗
PubMed1985

Pathogenesis of "fibrosis" in interstitial pneumonia: an electron microscopic study.

Seven cases in which interstitial fibrosis developed in patients who had acute interstitial pneumonia were studied ultrastructurally to elucidate the pathogenesis of the interstitial thickening seen by light microscopy. Interstitial fibrosis is generally thought to result from fibroblast proliferation and collagen deposition, and this mechanism was confirmed. However, two additional mechanisms that also contributed to the interstitial thickening were identified. One, which was not described previously, involves folding of portions of alveolar septa or collapse of entire alveoli and permanent apposition of their walls. This process occurred in areas that had been denuded of alveolar lining epithelium. Granular pneumocytes attempting to re-epithelialize the denuded basal lamina proliferated over the surface of apposed septa, thereby combining the folded or collapsed alveoli and forming a single thickened septum. The second mechanism involves incorporation of intra-alveolar exudates into alveolar septa. It occurred when granular pneumocytes re-epithelialized along the luminal surface of intra-alveolar debris overlying denuded alveolar epithelial basal laminae. The relative importance of each of these mechanisms in the pathogenesis of interstitial fibrosis and their role in the more common chronic interstitial pneumonias are unknown. However, their recognition may inspire new approaches for the prevention and treatment of interstitial fibrosis.

Basement Membrane↗
PubMed1999

Rarity of genomic instability in pathogenesis of systemic anaplastic large cell lymphoma (ALCL) in immunocompetent patients.

Microsatellite instability (MSI) is a recently described type of genetic alteration resulting from defects in the DNA mismatch repair genes that appears to play an integral role in neoplastic transformation. MSI has been described in a wide variety of malignancies; however, data regarding the role of MSI in the pathogenesis of non-Hodgkin's lymphoma (NHL) are limited. MSI appears to be important in some T-cell lymphomas, including ALCL arising in immunocompromised patients. In addition, MSI has recently been identified in CD30+ cutaneous lymphoproliferative processes and lymphoblastic lymphoma. In this study, we have analyzed five well-characterized cases of systemic T-cell ALCL arising in immunocompetent patients for the presence of MSI. Genomic DNA isolated from paired normal and tumor tissue was analyzed at seven microsatellite loci by polymerase chain reaction. We were unable to identify MSI or loss of heterozygosity (LOH) in our cases, suggesting that abnormalities in the DNA mismatch repair system do not play a major role in the pathogenesis of most systemic ALCL. Our data provide additional molecular evidence that the various subgroups of lymphoma with ALCL morphology are biologically distinct processes.

Adolescent↗
PubMed2002

The molecular pathogenesis of collagen-induced arthritis in mice--a model for rheumatoid arthritis.

The most widely used model for rheumatoid arthritis is the collagen-induced arthritis (CIA) in mice. This model has gained acceptance since it is reproducible, well defined and has proven useful for development of new therapies for rheumatoid arthritis, as exemplified by the most recent advancement using TNFalpha neutralization treatment. The collagen-induced arthritis model, however, represents only certain pathways leading to arthritis and there is no consensus on how they operate. Nevertheless, we are beginning to understand the immune recognition structures, such as MHC molecules, lymphocyte receptors and type II collagen epitopes, which are of crucial importance for the development of this disease. These provide useful tools for further investigations of the pathogenesis of CIA as well as for understanding the pathogenesis of rheumatoid arthritis.

Animals↗
PubMed2003

Pathogenesis and pathophysiology of yellow fever.

It will be apparent to the reader that there is much to learn about the pathogenesis of YF. The role of specific genes and molecular determinants of neurotropism and viscerotropism has been defined only partially. The availability of infectious clones and a small animal (hamster) model should allow dissection of virulence factors, which can then be tested in the more difficult monkey model. The marked differences between wild-type YF strains should be evaluated by evaluating the relationships between virulence and genome sequence. The role of cytokine dysregulation and endothelial injury in YF will be elucidated as access to patients and of patients to more sophisticated medical care improves. The number of cases of YF in unvaccinated travelers hospitalized after return from the tropics has unfortunately increased, but such cases afford unique opportunities to study the pathogenesis of renal failure, coagulopathy, vascular instability, and shock, as well as new treatment modalities. At the cellular level, there are also important opportunities for research on YF virus-cell receptor interactions, the control of apoptotic cell death, and the predilection for cells of the midzone of the liver lobule. The role of dendritic cells in the early stage of YF infection is deserving of study. Finally, the role of the immune response to infection, particularly cellular immunity, is poorly characterized, and the suggestion that immune clearance may aggravate the condition of the host during the period of intoxication should be evaluated in appropriate animal models.

Animals↗
PubMed2002

Neuropathology and pathogenesis of diabetic autonomic neuropathy.

Autonomic neuropathy is a significant complication of diabetes resulting in increased patient morbidity and mortality. A number of studies, which have shown correspondence between neuropathologic findings in experimental animals and human subjects, have demonstrated that axonal and dendritic pathology in sympathetic ganglia in the absence of significant neuron loss represents a neuropathologic hallmark of diabetic autonomic neuropathy. A recurring theme in sympathetic ganglia, as well as in the pot-ganglionic autonomic innervation of various end organs, is the involvement of distal portions of axons and nerve terminals by degenerative or dystrophic changes. In both animals and humans, there is a surprising selectivity of the diabetic process for subpopulations of autonomic ganglia, nerve terminals within sympathetic ganglia and end organs, from end organ to end organ, and between vascular and other targets within individual end organs. Although the involvement or autonomic axons in somatic nerves may reflect an ischemic pathogenesis, the selectivity of the diabetic process confounds simple global explanations of diabetic autonomic neuropathy as the result of diminished blood flow with resultant tissue hypoxia. A single unifying pathogenetic hypothesis has not yet emerged from clinical and experimental animal studies, and it is likely that diabetic autonomic neuropathy will be shown to have multiple causative mechanisms, which will interact to result in the variety of presentations of autonomic injury in diabetes. Some of these mechanisms will be shared with aging changes in the autonomic nervous system. The role of various neurotrophic substances and the polyol pathway in the pathogenesis and treatment of diabetic neuropathy likely represents a two-edged sword with both salutary and exacerbating effects. The basic neurobiologic process underlying the diabetes-induced development of neuroaxonal dystrophy, synaptic dysplasia, defective axonal regeneration, and alterations in neurotrophic substance may be mechanistically related.

Animals↗
PubMed1999

Giant fusiform aneurysm of the basilar artery: consideration of its pathogenesis.

BACKGROUND: We tried to determine the pathogenesis of a fusiform aneurysm of the basilar artery based on the findings of two patients who had pontine infarctions due to thrombosis within the aneurysm. CASE REPORT: The patients were female, aged 75 and 62 years. At autopsy of the first case, the dilated basilar artery was filled with fresh and old thrombus. The wall was extremely thin on the left side, where a fresh red thrombus was evident, and thick on the right side, where an old white thrombus appeared. The thick wall had a thickened and hyalinized intima, and a deposition of atheromatous plaque disrupted both the internal elastic lamina and muscle layer. The left vertebral artery was atherosclerotic and its lumen was severely compromised, but the right vertebral artery was hypoplastic. On angiogram of the second case, the dilated basilar artery presumably was filled with thrombus on the left side, contralateral to the dilated and tortuous vertebral artery. The left vertebral artery was hypoplastic. CONCLUSION: Atherosclerosis may be the essential factor in the pathogenesis of a fusiform aneurysm of the basilar artery in elderly patients. The disrupted internal elastic lamina and muscle layer may be susceptible to mechanical injury by hemodynamic strain, causing progressive attenuation of the arterial wall. Stenosis of the vertebral artery on the dominant side probably produces a jet stream within the basilar artery on the stenotic side and a stagnant zone on the opposite side, promoting the initial thrombus formation.

Aged↗
PubMed1999

Is there a potential role for hyoid bone compression in pathogenesis of carotid artery stenosis?

BACKGROUND: Blood flow turbulence and increased shear stress, particularly at sites of sudden, marked arterial wall changes, are significant hemodynamic parameters in the pathogenesis of atherosclerosis. We present a case in which we found the hyoid bone protruding into the carotid vessels and may have been contributing, in part, to atherosclerotic carotid stenosis. CASE PRESENTATION: An 85-year-old woman presenting with left arm and leg weakness consistent with right hemispheric transient ischemic attack. Magnetic resonance arteriography (MRA) and carotid non-invasive studies revealed a 90% stenosis of the right internal carotid artery. At surgery, the hyoid bone on the right side was projecting into the internal carotid artery, causing indentation. There was associated rotation of the internal and external carotid arteries from their normal position. Right carotid endarterectomy was performed and the lateral one-third of the hyoid bone excised to alleviate the external compression. Postoperative spiral computerized tomography (CT) scan of the carotid vessels demonstrated the extent of hyoid resection as well as rotation of the external and internal carotid arteries. CONCLUSIONS: We suggest the possible contribution of hyoid bone compression to the pathogenesis of atherosclerotic carotid artery stenosis. This report also highlights the diagnostic value of CT angiography in the assessment of carotid artery occlusive disease.

Aged↗
PubMed2001

Myocyte apoptosis in the pathogenesis of ureteral damage in rats with obstructive uropathy.

OBJECTIVES: To elucidate the role of signal apoptosis in the pathogenesis of ureteral damage during the course of obstructive uropathy and to investigate the cell proliferation in the smooth muscle layer of ligated ureter. METHODS: The apoptotic cells were detected with the method of in situ end-labeling of DNA fragments. The expression of Fas, tumor necrosis factor receptor 1 (TNF-R1), and proliferation cell nuclear antigen (PCNA) was examined in 54 rats by immunohistochemistry. RESULTS: The severity of hydroureter and the histologic changes of ureteral smooth muscle were aggravated during the period of obstruction. The apoptotic cells and the expression of Fas and PCNA in the smooth muscle layer were present since day 14 after ligation. The percentages of apoptotic cells and the expression indexes of Fas and PCNA in the smooth muscle layer progressively increased, reaching a peak on day 21 after ligation, and then declined. The expression of TNF-R1 in the smooth muscle layer was only found on day 21 after ligation. The numbers of the apoptotic cells in the smooth muscle layer correlated significantly with the expression of PCNA, Fas, and TNF-R1. The expression of Fas and TNF-R1 in the smooth muscle layer also correlated significantly. The appearance of apoptotic cells and the expression of Fas and PCNA in the smooth muscle layer were associated with tissue damage and fibrosis in the smooth muscle layer. CONCLUSIONS: We conclude that cell apoptosis and the expression of Fas, TNF-R1, and PCNA might play important roles in the pathogenesis of ureteral damage in the smooth muscle layer of obstructed ureters.

Animals↗
PubMed1995

Atopic dermatitis: the skin as a window into the pathogenesis of chronic allergic diseases.

This review has attempted to highlight several important advances in our understanding of the immunopathogenesis of AD. These include the observation that IgE has a multifunctional role in the pathogenesis of allergic inflammation. Aside from its involvement in IgE-mediated degranulation of mast cells and basophils, it is also involved in the activation of macrophage/monocytes and the stimulation of TH2 cells. Recent data also suggest that the pattern of cytokine expression in AD depends on the acuity or duration of the skin lesion. The acute onset of skin inflammation in AD is associated with a predominance of T lymphocytes and IL-4 gene expression. In chronic AD, macrophage and eosinophil activation dominate. These effector cells overexpress IL-5, IL-10, GM-CSF, and PGE2, all of which may contribute to the persistence of this disease. Although AD is not simply "asthma of the skin," similar principles may be operative in these associated atopic diseases. Both involve local infiltration of IL-4--and IL-5--secreting TH2-like cells, and both show pathologic evidence of epithelial damage, which likely serves to amplify tissue inflammation. In the case of AD, keratinocyte damage caused by scratching or microbial agents (e.g., S. aureus) is accompanied by the release of proinflammatory cytokines. In the case of asthma, bronchial epithelial damage (e.g., damage caused by viruses or eosinophil cationic proteins) and cytokine release from airway epithelium are believed to play an important role in the pathogenesis of airway inflammation. The observation that chronic AD is associated with lichenification and dermal fibrosis, which are only slowly responsive to topical corticosteroids, is somewhat analogous to the recent concerns over airway remodeling (e.g., subepithelial airway fibrosis) is asthma and the finding that early intervention with inhaled corticosteroids is needed for optimal responses. Differences in the clinical manifestations of disease in these important target organs are likely to lie in their distinct resident cells, environment exposures that occur in the skin but not the lung, and the immune response to allergen sensitization of specialized lymphoid systems. Although the major focus of research in allergy to date has been on understanding of generic mechanisms underlying IgE regulation and action, it is well known that although IgE responses are necessary, they are not sufficient to account for the chronicity or tissue specificity of different allergic diseases.(ABSTRACT TRUNCATED AT 400 WORDS)

Allergens↗
PubMed1998

A murine model of allergic rhinitis: studies on the role of IgE in pathogenesis and analysis of the eosinophil influx elicited by allergen and eotaxin.

BACKGROUND: Allergic rhinitis is a prevalent disease with significant morbidity. Studies of its pathophysiology in human subjects have been limited. Nasal biopsy specimens are difficult to obtain, and nasal secretions incompletely reflect the cellular and molecular events in the mucosa. IgE-mediated mast cell activation and the elaboration of factors promoting eosinophil development and chemotaxis are likely to participate in pathogenesis. OBJECTIVES: We sought to develop a murine model of allergic rhinitis, to use it to assess the role of IgE in pathogenesis, and to study the effects of IL-5 and eotaxin in the nasal mucosa. METHODS: A protein extract of Aspergillus fumigatus (Af) was instilled intranasally in mice. Histologic changes were examined in wild-type and IgE-deficient (IgE-/-) animals. The effect of eotaxin administration was assessed in wild-type and IL-5 transgenic mice. RESULTS: Af-treated mice developed a nasal mucosal eosinophil influx comparable to that described for humans. This histology was distinct from that observed in a murine model of Af-induced asthma. The pathology appeared over a time course similar to that reported for human subjects. There was no difference in the intensity of the mucosal inflammatory infiltrate of Af-treated IgE-/- mice compared with wild-type mice. Eotaxin was able to recruit eosinophils to the mucosa but only in IL-5 transgenic animals. CONCLUSION: We describe a murine model for allergic rhinitis with an eosinophilic infiltrate comparable to that found in human disease and have demonstrated that rhinitis can arise in the absence of IgE. We have shown that the eosinophil influx can be induced by eotaxin in the presence of IL-5.

Allergens↗
PubMed1999

Chemical mediators in atopic dermatitis: involvement of leukotriene B4 released by a type I allergic reaction in the pathogenesis of atopic dermatitis.

BACKGROUND: The mediators produced from a type I allergic reaction have not yet been able to explain the pathogenesis of atopic dermatitis (AD). OBJECTIVE: The purpose of this study was to elucidate the involvement of leukotriene (LT) B4 produced from a type I allergic reaction in the pathogenesis of AD. METHOD: The release of LTB4 was measured both in vitro, in passively sensitized and antigen-challenged human skin slices, as well as in vivo, in skin chambers on patients with AD. RESULTS: LTB4 was released from in vitro human skin by stimulation of the antigen (54.9 +/- 14.6 pg/g wet weight of skin by antigen challenge and 28.0 +/- 11.1 pg/g in control skin, P <.002). Antigen-specific release of LTB4 and histamine was also observed in vivo in nonlesional skin from the patients with AD by using the skin chamber technique. CONCLUSION: LTB4 release during type I allergic reaction in human skin has been determined in vitro. The released LTB4 possibly contributes to cellular response at the acute inflammatory lesion of AD.

Adolescent↗