Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune-mediated mechanisms appear to play a primary role in the pathogenesis of polymyositis (PM) and dermatomyositis (DM). The serum of patients with active DM has high levels of circulating complement fragments C3b, C4b, and C5b-9 membranolytic attack complex (MAC) and demonstrates a very high C3 uptake in an vitro assay system. The MAC and the immune complex-specific C3bNEO fragment are deposited on the endomysial capillaries early in the disease and lead sequentially to loss of capillaries, muscle ischemia, muscle fiber necrosis, and perifascicular atrophy. In contrast, in PM the muscle fiber injury is initiated by sensitized CD8+ cytotoxic T cells that recognize heretofore unknown and probably endogenous muscle antigens in the context of major histocompatibility complex (MHC) class I expression. A restricted (oligoclonal) pattern of T-cell receptor with prominence of Va1, Vb6, and Vb15 genes is noted within the endomysial infiltrates suggesting that the T-cell response is antigen driven. In both PM and DM, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 are upregulated in the endomysial endothelial cells and function as ligands for the leukocyte integrins leukocyte function-associated antigen (LFA)-1 and very late activating antigen (VLA)-4, allowing activated lymphocytes to adhere to the endothelial cells and migrate to the muscle fibers. Among viruses, only the retroviruses human immunodeficiency virus (HIV) and human T-cell lymphotropic virus (HTLV)-1 have been convincingly shown to trigger PM, which is mediated by nonviral-specific, cytotoxic CD8+ cells. The treatment of inflammatory myopathies remains empirical. Many patients respond to steroids to some degree and for some period of time. Azathioprine, methotrexate, cyclosporine, cyclophosphamide, and plasmapheresis can be of mild to moderate benefit. High-dose intravenous immunoglobulin (IVIg) is a promising therapeutic modality for some patients resistant to therapies. In a controlled study, IVIg was effective in DM not only in improving the clinical symptoms but also in reversing the underlying immunopathology. The role of IVIg in PM and IBM is under study in control trials.
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PMID:Immunopathogenesis of inflammatory myopathies. 896 19

Immunopathology techniques are useful and sometimes indispensable tools to diagnose and/or define pathogenesis of disease processes in an organ allograft. Using immunostaining and/or in situ hybridization, cells and molecules can be identified and localized in organ grafts. Considered in this chapter are the "priming" of tissues by ischemia and infection, cell-mediated and antibody-mediated acute and chronic rejection in xenografts and allografts, graft infection, and recurrent or de novo immune disease in organ grafts. The chapter is designed to provide an overview, with illustrative examples of the contribution of immunopathology to analysis of solid organ allografts.
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PMID:Immunopathology of organ transplantation. 1295 64

Giant-cell arteritis is an immune-mediated disease characterized by granulomatous infiltrates in the wall of medium-size and large arteries. The immunopathology consists of 2 components. Excessive cytokine production (for example, of interleukin-1 and interleukin-6) induces systemic inflammation with an exuberant acute-phase response. In parallel, interferon-gamma, which is released by T cells captured in the arterial wall, activates tissue-injurious macrophages. In response to the immune injury, the artery generates hyperplasia of the intima that leads to luminal occlusion and subsequent tissue ischemia. Despite the systemic character of the disease, distinct vascular territories are preferentially affected. On the basis of the predominant involvement, clinical subtypes can be distinguished: cranial giant-cell arteritis with ischemic complications in the eye, the face, and the central nervous system; large-vessel giant-cell arteritis with occlusions in the subclavian or axillary vessels; aortic giant-cell arteritis; giant-cell arteritis presenting as an intense systemic inflammatory syndrome with nonstenosing vasculitis; and "isolated" polymyalgia rheumatica with myalgias, systemic inflammation, and subclinical vasculitis. Temporal artery biopsy remains the diagnostic procedure of choice to detect arteritis in cranial vessels. In other vascular territories, giant-cell arteritis is most commonly diagnosed by vascular imaging. Laboratory studies characteristically document the marked elevations of nonspecific acute-phase reactants, such as C-reactive protein and erythrocyte sedimentation rate. Cytokines, such as interleukin-6, that induce the acute-phase reaction are currently being explored as more sensitive biological markers of disease activity. Corticosteroids are highly effective in suppressing systemic inflammation, but they do not eliminate the immune responses in the vessel wall. In general, the clinical outcome of giant-cell arteritis is excellent, and efforts must now concentrate on tailoring therapies to the needs of the individual patient.
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PMID:Giant-cell arteritis and polymyalgia rheumatica. 1367 49

Ischemia reperfusion (IR) activates TLRs causing subsequent sterile inflammation, for example in postischemic acute renal failure. Unexpectedly, TLR signaling predominates in intrinsic renal cells and not in intrarenal APCs in the postischemic kidney. We hypothesized that certain factors suppress APC activation and thereby limit sterile renal inflammation, for example, IFN regulatory factor 4 (IRF-4), an inducible inhibitor of LPS signaling. Oxidative stress was a trigger for IRF4 induction in myeloid cells in vitro as well as in CD45(+)/CD11c+ cells in the postischemic kidney. Lack of IRF4 aggravated acute renal failure 24 h after renal artery clamping together with increased intrarenal expression of TNF-alpha, IL-6, CXCL2, and CCL2 as well as excessive tubular necrosis and peritubular neutrophil influx as compared with wild-type IR kidneys. This effect almost entirely depended on the role of IRF4 to suppress TNF-alpha release by intrarenal APCs because either clodronate liposome depletion of these cells or TNF-alpha blockade with etanercept entirely abrogated the aggravation of cytokine expression and acute renal failure in Irf4-deficient mice. Thus, loss-of-function mutations in the IRF4 gene predispose to IR injury because the postischemic induction of IRF4 in resident APCs like CD11c(+) dendritic cells, suppresses them to secrete TNF-alpha, and thereby limits inappropriate immunopathology.
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PMID:Ischemia reperfusion induces IFN regulatory factor 4 in renal dendritic cells, which suppresses postischemic inflammation and prevents acute renal failure. 2060 97

Acute traumatic injury is a complex disease that has remained a leading cause of death, which affects all ages in our society. Direct mechanical insult to tissues may result in physiological and immunologic disturbances brought about by blood loss, coagulopathy, as well as ischemia and reperfusion insults. This inappropriate response leads to an abnormal release of endogenous mediators of inflammation that synergistically contribute to the incidence of morbidity and mortality. This aberrant activation and suppression of the immune system follows a bimodal pattern, wherein activation of the innate immune responses is followed by an anti-inflammatory response with suppression of the adaptive immunity, which can subsequently lead secondary insults and multiple organ dysfunction. Traumatic injury rodent and swine models have been used to describe many of the underlying pathologic mechanisms, which have led to an improved understanding of the morbidity and mortality associated with critically ill trauma patients. The enigmatic immunopathology of the human immunologic response after severe trauma, however, has never more been apparent and there grows a need for a clinically relevant animal model, which mimics this immune physiology to enhance the care of the most severely injured. This has necessitated preclinical studies in a more closely related model system, the nonhuman primate. In this review article, we summarize animal models of trauma that have provided insight into the clinical response and understanding of cellular mechanisms involved in the onset and progression of ischemia-reperfusion injury as well as describe future treatment options using immunomodulation-based strategies.
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PMID:Modeling acute traumatic injury. 2548 28

Hepatocytes are targeted for infection by a number of major human pathogens, including hepatitis B virus, hepatitis C virus, and malaria. However, hepatocytes are also immunological agents in their own right. In systemic immunity, they are central in the acute-phase response, which floods the circulation with defensive proteins during diverse stresses, including ischemia, physical trauma, and sepsis. Hepatocytes express a variety of innate immune receptors and, when challenged with pathogen- or damage-associated molecular patterns, can deliver cell-autonomous innate immune responses that may result in host defense or in immunopathology. Important human pathogens have evolved mechanisms to subvert these responses. Finally, hepatocytes talk directly to T cells, resulting in a bias toward immune tolerance.
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PMID:Hepatocytes as Immunological Agents. 2668 14

This article provides a brief overview of the second scientific session of the 37th Annual Symposium of the Society of Toxicologic Pathology in Indianapolis, Indiana, on June 18, 2018. The session was entitled "Acute Kidney Injury (AKI): The Toxicologic Pathologist's Constant Companion" and was co-chaired by Drs. Zaher Radi and Torrie Crabbs. The fundamentals of tubule and interstitial anatomy were covered by Dr. Kevin McDorman, followed by a review of International Harmonization of Nomenclature and Diagnostic Criteria, Standard for Exchange of Nonclinical Data, and Drug-Induced Kidney Injury terminology, which was presented by Dr. Torrie Crabbs. Dr. Bruce Molitoris gave a talk on renal hemodynamics, microcirculation, and ischemia. Advances and challenges on new therapies and clinical targets of AKI were presented by Dr. Brad Rovin, and the session ended with a review from Dr. Zaher Radi on immunopathology of AKI.
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PMID:Acute Kidney Injury (AKI)-The Toxicologic Pathologist's Constant Companion. 3018 97