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1.
Nat Immunol ; 15(8): 727-37, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24952505

ABSTRACT

Microbes or danger signals trigger inflammasome sensors, which induce polymerization of the adaptor ASC and the assembly of ASC specks. ASC specks recruit and activate caspase-1, which induces maturation of the cytokine interleukin 1ß (IL-1ß) and pyroptotic cell death. Here we found that after pyroptosis, ASC specks accumulated in the extracellular space, where they promoted further maturation of IL-1ß. In addition, phagocytosis of ASC specks by macrophages induced lysosomal damage and nucleation of soluble ASC, as well as activation of IL-1ß in recipient cells. ASC specks appeared in bodily fluids from inflamed tissues, and autoantibodies to ASC specks developed in patients and mice with autoimmune pathologies. Together these findings reveal extracellular functions of ASC specks and a previously unknown form of cell-to-cell communication.


Subject(s)
Apoptosis/immunology , Caspase 1/immunology , Cytoskeletal Proteins/immunology , Inflammation/immunology , Interleukin-1beta/immunology , Amino Acid Chloromethyl Ketones/pharmacology , Animals , Antibodies/immunology , Apoptosis Regulatory Proteins , Autoantibodies/immunology , Autoimmune Diseases/immunology , CARD Signaling Adaptor Proteins , Carrier Proteins/genetics , Caspase 1/genetics , Caspase Inhibitors/pharmacology , Cell Communication/immunology , Cytoskeletal Proteins/genetics , Humans , Inflammasomes/immunology , Lysosomes/pathology , Macrophages/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , NLR Family, Pyrin Domain-Containing 3 Protein , Phagocytosis/immunology , Prions/chemistry , Pseudomonas Infections/immunology , Pseudomonas aeruginosa/immunology , Signal Transduction/immunology
2.
J Anat ; 212(5): 674-85, 2008 May.
Article in English | MEDLINE | ID: mdl-18410314

ABSTRACT

Incisional hernias represent one of the most common complications after laparotomy. Specific pre-operative risk factors have not yet been identified. Recent studies indicate that changes in extracellular matrix components such as collagen I and collagen III may be involved in hernia development. In the present study we have evaluated the significance of fibrillin-1 in hernia development as one of the main components of the extracellular matrix. Tissue samples from non-scar skin and muscle fascia of 12 patients with incisional hernias as well as from the respective scar tissues were obtained. Corresponding tissue samples of 10 patients with normal postoperative wound healing served as controls. Distribution of fibrillin-1 was evaluated immunohistochemically. Differences in fibrillin-1 distribution in the non-scar tissues of muscle fascia have been found in patients with incisional hernia, compared to those without hernia. In scar regions of both patient groups, slight differences in the pattern of fibrillin-1 were observed. A tendency to a differential deposition of fibrillin-1 in skin samples, although hardly quantifiable, was observed as well. Our results suggest that fibrillin-1 is a relevant factor contributing to tissue stability. Disturbances in its deposition, even before scar formation, may be an important factor to the development of incisional hernias.


Subject(s)
Cicatrix/metabolism , Fascia/chemistry , Hernia, Abdominal/metabolism , Microfilament Proteins/analysis , Postoperative Complications/metabolism , Skin/chemistry , Abdominal Wall , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Case-Control Studies , Collagen Type I/analysis , Collagen Type III/analysis , Female , Fibrillin-1 , Fibrillins , Humans , Immunohistochemistry , Laparotomy , Male , Middle Aged , Reoperation , Risk , Wound Healing
3.
Am J Med ; 118(2): 168-74, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15694903

ABSTRACT

PURPOSE: To identify indicators of accuracy for consumer health information on the Internet. METHODS: Several popular search engines were used to find websites on carpal tunnel syndrome. The accuracy and completeness of these sites were determined by orthopedic surgeons. It also was noted whether proposed indicators of accuracy were present. The correlation between proposed indicators of accuracy and the actual accuracy of the sites was calculated. RESULTS: A total of 116 websites and 29 candidate indicators were examined. A high Google toolbar rating of the main page of a site, many inlinks to the main page of a site, and an unbiased presentation of information on carpal tunnel syndrome were considered genuine indicators of accuracy. Many proposed indicators taken from published guidelines did not indicate accuracy (e.g., the author or sponsor having medical credentials). CONCLUSION: There are genuine indicators of the accuracy of health information on the Internet. Determining these indicators, and informing providers and consumers of health information about them, would be useful for public health care. Published guidelines have proposed many indicators that are obvious to unaided observation by the consumer. However, indicators that make use of the invisible link structure of the Internet are more reliable guides to accurate information on carpal tunnel syndrome.


Subject(s)
Carpal Tunnel Syndrome , Information Services/standards , Internet , Patient Education as Topic , Humans , Public Health , Quality Control
4.
J Am Med Inform Assoc ; 9(1): 73-9, 2002.
Article in English | MEDLINE | ID: mdl-11751805

ABSTRACT

OBJECTIVES: To identify indicators of accuracy for consumer health information on the Internet. The results will help lay people distinguish accurate from inaccurate health information on the Internet. DESIGN: Several popular search engines (Yahoo, AltaVista, and Google) were used to find Web pages on the treatment of fever in children. The accuracy and completeness of these Web pages was determined by comparing their content with that of an instrument developed from authoritative sources on treating fever in children. The presence on these Web pages of a number of proposed indicators of accuracy, taken from published guidelines for evaluating the quality of health information on the Internet, was noted. MAIN OUTCOME MEASURES: Correlation between the accuracy of Web pages on treating fever in children and the presence of proposed indicators of accuracy on these pages. Likelihood ratios for the presence (and absence) of these proposed indicators. RESULTS: One hundred Web pages were identified and characterized as "more accurate" or "less accurate." Three indicators correlated with accuracy: displaying the HONcode logo, having an organization domain, and displaying a copyright. Many proposed indicators taken from published guidelines did not correlate with accuracy (e.g., the author being identified and the author having medical credentials) or inaccuracy (e.g., lack of currency and advertising). CONCLUSIONS: This method provides a systematic way of identifying indicators that are correlated with the accuracy (or inaccuracy) of health information on the Internet. Three such indicators have been identified in this study. Identifying such indicators and informing the providers and consumers of health information about them would be valuable for public health care.


Subject(s)
Fever/therapy , Health Education/standards , Information Services/standards , Internet , Quality Indicators, Health Care , Child , Humans
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