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Disease Specificity (disease + specificity)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Disease-specific Helicobacter pylori Virulence Factors: The Unfulfilled Promise

HELICOBACTER, Issue S1 2000
David Y. Graham
A number of putative virulence factors for Helicobacter pylori have been identified including cagA, vacA and iceA. The criteria for a true virulence factor includes meeting the tests of biologically plausibility with the associations being both experimentally and epidemiologically consistent. Although disease-specific associations have been hypothesized/claimed, there are now sufficient data to conclusively state that none of these putative virulence factors have disease specificity. CagA has been claimed to be associated with increased mucosal IL-8 and inflammation, increased density of H. pylori in the antrum, duodenal ulcer (DU), gastric cancer, and protection against Barrett's cancer. Only the increase in IL-8/inflammation is direct and substantiated. Different H. pylori strains with functional cag pathogenicity islands do not vary in virulance as it has been shown that mucosal IL-8 levels are proportional to the number of cagA +H. pylori independent of the disease from which the H. pylori were obtained. It is now known that the density of either cagA + and cagA,H. pylori in the antrum of patients with H. pylori gastritis is the same. In contrast, the mean density of H. pylori in the antrum in DU is greater than in the antrum of patients with H. pylori gastritis. Of interest, the density of H. pylori is higher in the corpus of patients with H. pylori gastritis than those with DU, suggesting that acid secretion plays a critical role in these phenomena. The presence of a functional cag pathogenicity island increases inflammation and it is likely that any factor that results in an increase in inflammation also increases the risk of a symptomatic outcome. Nevertheless, the presence of a functional cag pathogenicity island has no predictive value for the presence, or the future development of a clinically significant outcome. The hypothesis that iceA has disease specificity has not been confirmed and there is currently no known biological or epidemiological evidence for a role for iceA as a virulence factor in H. pylori -related disease. The claim that vacA genotyping might prove clinically useful, e.g. to predict presentation such as duodenal ulcer, has been proven wrong. Analysis of the worldwide data show that vacA genotype s1 is actually a surrogate for the cag pathogenicity island. There is now evidence to suggest that virulence is a host-dependent factor. The pattern of gastritis has withstood the test of time for its relation to different H. pylori -related diseases (e.g. antral predominant gastritis with duodenal ulcer disease). The primary factors responsible for the different patterns of gastritis in response to an H. pylori infection are environmental (e.g. diet), with the H. pylori strain playing a lesser role. Future studies should work to eliminate potential bias before claiming disease associations. Controls must exclude regional or geographic associations related to the common strain circulation and not to the outcome. The authors must also control for both the presence of the factor and for the disease association. The study should be sufficiently large and employ different diseases and ethnic groups for the results to be robust. The findings in the initial sample (data derived hypothesis) should be tested in a new group (hypothesis testing), preferably from another area, before making claims. Finally, it is important to ask whether the results are actually a surrogate for another marker (e.g. vacA s1 for cagA) masquerading for a new finding. Only the cag pathogenicity island has passed the tests of biological plausibility (increased inflammation) and experimental and epidemiological consistency. [source]

The Tyranny of Diagnosis: Specific Entities and Individual Experience

THE MILBANK QUARTERLY, Issue 2 2002
Charles E. Rosenberg
Diagnosis has always played a pivotal role in medical practice, but in the past two centuries, that role has been reconfigured and has become more central as medicine,like Western society in general,has become increasingly technical, specialized, and bureaucratized. Disease explanations and clinical practices have incorporated, paralleled, and, in some measure, constituted these larger structural changes. This modern history of diagnosis is inextricably related to disease specificity, to the notion that diseases can and should be thought of as entities existing outside the unique manifestations of illness in particular men and women. During the past century especially, diagnosis, prognosis, and treatment have been linked ever more tightly to specific, agreed-upon disease categories, in both concept and everyday practice. In fact, this essay might have been entitled "Diagnosis Mediates an Invisible Revolution: The Social and Intellectual Significance of Specific Disease Concepts." It would have been even more precise, if rather less arresting. The articulation and acceptance of specific disease entities constitute one of the most important intellectual and cultural events of the past two centuries. This notion is central to how we organize health care delivery, think about ourselves, debate and formulate social policy, and define and manage deviance. Diagnosis is indispensable to linking specific disease concepts with doctor and patient and the social and economic institutions shaping such clinical interactions. Disease is a social entity, not an array of ideal types. The history of medicine is partly the story of how disease entities have become social entities, accumulating the flesh of diagnostic and therapeutic practice, social expectation, and bureaucratic reification. Despite criticism of reductionist medicine in the West and less focus on disease entities and mechanisms, our social response still depends on this concept of sickness. But this concept can no longer remain invisible if we are to understand contemporary medicine as both a social and a technological system. The articulation and acceptance of specific disease entities constitute one of the most important intellectual and cultural events of the past two centuries. This notion is central to how we organize health care delivery, think about ourselves, debate and formulate social policy, and define and manage deviance. Diagnosis is indispensable to linking specific disease concepts with doctor and patient and the social and economic institutions shaping such clinical interactions. Disease is a social entity, not an array of ideal types. The history of medicine is partly the story of how disease entities have become social entities, accumulating the flesh of diagnostic and therapeutic practice, social expectation, and bureaucratic reification. Despite criticism of reductionist medicine in the West and less focus on disease entities and mechanisms, our social response still depends on this concept of sickness. But this concept can no longer remain invisible if we are to understand contemporary medicine as both a social and a technological system. The articulation and acceptance of specific disease entities constitute one of the most important intellectual and cultural events of the past two centuries. This notion is central to how we organize health care delivery, think about ourselves, debate and formulate social policy, and define and manage deviance. Diagnosis is indispensable to linking specific disease concepts with doctor and patient and the social and economic institutions shaping such clinical interactions. Disease is a social entity, not an array of ideal types. The history of medicine is partly the story of how disease entities have become social entities, accumulating the flesh of diagnostic and therapeutic practice, social expectation, and bureaucratic reification. Despite criticism of reductionist medicine in the West and less focus on disease entities and mechanisms, our social response still depends on this concept of sickness. But this concept can no longer remain invisible if we are to understand contemporary medicine as both a social and a technological system. The articulation and acceptance of specific disease entities constitute one of the most important intellectual and cultural events of the past two centuries. This notion is central to how we organize health care delivery, think about ourselves, debate and formulate social policy, and define and manage deviance. Diagnosis is indispensable to linking specific disease concepts with doctor and patient and the social and economic institutions shaping such clinical interactions. Disease is a social entity, not an array of ideal types. The history of medicine is partly the story of how disease entities have become social entities, accumulating the flesh of diagnostic and therapeutic practice, social expectation, and bureaucratic reification. Despite criticism of reductionist medicine in the West and less focus on disease entities and mechanisms, our social response still depends on this concept of sickness. But this concept can no longer remain invisible if we are to understand contemporary medicine as both a social and a technological system. [source]

Olfactory epithelium amyloid-, and paired helical filament-tau pathology in Alzheimer disease

ANNALS OF NEUROLOGY, Issue 4 2010
Steven E. Arnold MD
Objective Olfactory dysfunction is common in Alzheimer disease (AD) and other neurodegenerative diseases. Paired helical filament (PHF)-tau, ,-synuclein, and amyloid-, lesions occur early and severely in cerebral regions of the olfactory system, and they have also been observed in olfactory epithelium (OE). However, their frequency, abundance, and disease specificity, and the relationships of OE pathology to brain pathology have not been established. Methods We investigated the pathological expression of amyloid-,, PHFtau, ,-synuclein, and TDP-43 in postmortem OE of 79 cases with AD, 63 cases with various other neurodegenerative diseases, and 45 neuropathologically normal cases. Results Amyloid-, was present as punctate and small patchy aggregates in 71% of AD cases, compared with 22% of normal cases and 14% of cases with other diseases, and in greater amounts in AD than in either of the other 2 diagnostic categories. PHFtau was evident in dystrophic neurites in 55% of cases with AD, 34% with normal brains, and 39% with other neurodegenerative diseases, also at higher densities in AD. ,-Synuclein was present in dystrophic neurites in 7 cases, 6 of which also had cerebral Lewy bodies. Pathological TDP-43 inclusions were not observed in the OE in any cases. Amyloid-, and to a lesser degree, PHFtau ratings in OE significantly correlated with cortical A, and PHFtau lesion ratings in the brain. Interpretation These data demonstrate that AD pathology in the OE is present in the majority of cases with pathologically verified AD and correlates with brain pathology. Future work may assess the utility of amyloid-, and PHFtau measurement in OE as a biomarker for AD. ANN NEUROL 2010;67:462,469 [source]

PAN,DR-Binding Hsp60 self epitopes induce an interleukin-10,mediated immune response in rheumatoid arthritis

ARTHRITIS & RHEUMATISM, Issue 7 2009
Huib de Jong
Objective Human Hsp60 is expressed in the joints of patients with rheumatoid arthritis (RA) and can elicit a regulatory T cell response in the peripheral blood and synovial fluid. However, Hsp60 can also trigger strong proinflammatory pathways. Thus, to understand the nature of these Hsp60-directed responses in RA, it is necessary to study such responses at the molecular, epitope-specific level. This study was undertaken to characterize the disease specificity and function of pan,DR-binding Hsp60,derived epitopes as possible modulators of autoimmune inflammation in RA. Methods Lymphocyte proliferation assays (using 3H-thymidine incorporation and carboxyfluorescein diacetate succinimidyl ester [CFSE] staining) and measurement of cytokine production (using multiplex immunoassay and intracellular staining) were performed after in vitro activation of peripheral blood mononuclear cells from patients with RA, compared with healthy controls. Results A disease (RA),specific immune recognition, characterized by T cell proliferation as well as increased production of tumor necrosis factor , (TNF,), interleukin-1, (IL-1,), and IL-10, was found for 3 of the 8 selected peptides in patients with RA as compared with healthy controls (P < 0.05). Intracellular cytokine staining and CFSE labeling showed that CD4+ T cells were the subset primarily responsible for both the T cell proliferation and the cytokine production in RA. Interestingly, the human peptides had a remarkably different phenotype, with a 5,10-fold higher IL-10:TNF, ratio, compared with that of the microbial peptides. Conclusion These results suggest a disease-specific immune-modulatory role of epitope-specific T cells in the inflammatory processes of RA. Therefore, these pan,DR-binding epitopes could be used as a tool to study the autoreactive T cell response in RA and might be suitable candidates for use in immunotherapy. [source]