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

Extramedullary hematopoiesis (EMH) after fetal development is uncommon and is most often seen in patients who have hematologic disorders. EMH unassociated with hematologic disease is rare. After the recent observation of EMH in a myocardial infarct, we sought to determine the frequency and clinicopathologic setting of EMH in myocardial tissues submitted for pathologic examination. Hematoxylin and eosin (H&E)-stained sections from 805 consecutive myocardial samples (207 surgical specimens, 598 autopsy specimens) were examined retrospectively. The presence of immature erythroid or myeloid cell clusters in intramyocardial capillaries or stroma was considered sufficient for the diagnosis of EMH. Immunoperoxidase studies confirming the nature of the hematopoietic cell infiltrate were performed in selected cases. Foci of EMH (often multiple) were identified in 15 of 207 surgical hearts (7.2%) and in 22 of 598 autopsy hearts (3.7%). Patient ages (exclusive of premature infants) ranged from 2 weeks to 73 years (median, 13 years). Twenty-four of 37 (65%) EMH-positive cases were associated with infarcts in various stages of repair (accounting for 11 of 68 [16.2%] of all infarcts in surgical specimens and 13 of 86 [15.1%] of infarcts in autopsy specimens). Acute infarcts less than 72 hours old, excluding those with acute extension, were not associated with EMH. Viral myocarditis and myocardial hypertrophy with fibrosis accounted for primary diagnoses in the nonischemic, EMH-positive surgical cases, whereas seven of nine nonischemic, EMH-positive autopsy cases involved premature or term infants with no obvious myocardial disease. Another autopsy patient had sarcoidosis with myelophthisic involvement of her bone marrow and represented one of only two cases overall in which a hematopoietic disorder was coexistent or suspected. Myocardial EMH is relatively common after myocardial infarct but is rarely encountered in normal or nonischemic myocardium. Its presence in healing but not early acute stages of infarct suggests that EMH results from inflammation- or repair-associated trophic factors, not from ischemia itself.
 ...
PMID:Myocardial extramedullary hematopoiesis: a clinicopathologic study. 1091 38

Viral myocarditis is a disease with a high morbidity and mortality. The pathogenesis of this disease remains poorly characterized, with components of both direct virus-mediated and secondary inflammatory and immune responses contributing to disease. Apoptosis has increasingly been viewed as an important mechanism of myocardial injury in noninfectious models of cardiac disease, including ischemia and failure. Using a reovirus murine model of viral myocarditis, we characterized and targeted apoptosis as a key mechanism of virus-associated myocardial injury in vitro and in vivo. We demonstrated caspase-3 activation, in conjunction with terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling and annexin binding, in cardiac myocytes after myocarditic viral infection in vitro. We also demonstrated a tight temporal and geographical correlation between caspase-3 activation, histologic injury, and viral load in cardiac tissue after myocarditic viral infection in vivo. Two pharmacologic agents that broadly inhibit caspase activity, Q-VD-OPH and Z-VAD(OMe)-FMK, effectively inhibited virus-induced cellular death in vitro. The inhibition of caspase activity in vivo by the use of pharmacologic agents as well as genetic manipulation reduced virus-induced myocardial injury by 40 to 60% and dramatically improved survival in infected caspase-3-deficient animals. This study indicates that apoptosis plays a critical role in mediating cardiac injury in the setting of viral myocarditis and is the first demonstration that caspase inhibition may serve as a novel therapeutic strategy for this devastating disease.
 ...
PMID:Caspase inhibition protects against reovirus-induced myocardial injury in vitro and in vivo. 1545 24