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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drawing on data from a previously published literature survey on the clinical and experimental epidemiology of the Mallory body, we discuss current theories on its development in a pro et contra manner. Conclusions have been largely left open to the interpretations of the reader because many are still speculative. The main results of this study characterize Mallory bodies as stereotypical histological byproducts to diverse hepatic injuries (mostly alcohol associated) of questionable pathogenic importance. The temporal characteristics of Mallory bodies cast doubt on their role in hepatic neoplasia both as a disease marker and a causative agent, and prognosis studies suggest that they may be considered preterminal markers in some nonalcoholic liver diseases but remain prognostically unimportant in most studies on alcoholic patients. By similar line of inquiry, no consistent relationships may be found with disease severity or duration in alcoholic liver diseases. The roles of vitamin A deficiency and protein-calorie malnutrition are circumstantial. Drugs known to have calcium-antagonist properties and the physiological characteristics of the stress-response protein ubiquitin support the concept of defective protein systems in Mallory body pathogenesis. Disproportionate hepatic copper accumulation seems both epidemiologically and topographically associated with Mallory bodies, but these connections are largely unsupported by exposure studies. Many arguments still downplay the importance of uncoordinated changes in hepatic oxygen delivery and consumption, but ischemia-reperfusion studies suggest a role of oxygen-derived free radicals in the liver injuries under scrutiny. Finally, the role of Mallory bodies in the control system of hepatocyte function is addressed, and indirect evidence lends credence to a cybernetic approach in future study designs. It is reasonable to assume that different elements of a multifactorial setting operate with varying intensity over time as this may account for some of the controversies that exist. In conclusion, the biological significance of Mallory bodies is still mystery. It is not known whether Mallory bodies represent an epiphenomenon or play a role themselves in the initiation and continuation of liver damage.
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PMID:The Mallory body: theories on development and pathological significance (Part 2 of a literature survey). 792 69

The heat shock (HS) response is remarkably conserved during evolution and is evoked under many conditions of stress. There are a number of ways in which this ubiquitous response may be important for the understanding of renal pathophysiology. Ischemia, toxin exposure, and oxidative stress induce this response. Several models of hypertension are associated with increased susceptibility to environmental stress and increased accumulation of heat shock protein mRNA. HSP70 polymorphism has been demonstrated when comparing normotensive and hypertensive rats. Heat shock proteins may play a role in renal diseases through their important involvement in immunological processes. Several observations point to a role of the heat shock response in systemic lupus erythematosus (SLE). Autoantibodies against HSP70 and ubiquitin are found in many patients with this disease. Autoantibodies against ubiquitin and ubiquitinated histone H2A are localized to the kidney glomerular basement membrane of SLE patients with active disease. A better understanding of the HS response may thus provide important insight into renal pathophysiology and may suggest paradigms for therapeutic interventions.
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PMID:Heat shock proteins and the kidney. 804 58

Excessive stimulation of glutamate receptors and elevation of intracellular calcium levels initiate the neurodegenerative process resulting from cerebral ischemia. However, the subsequent cascade of molecular changes which are of pathogenic significance is less well understood. Breakdown of the cytoskeleton may be involved in the progression from compromise of neuronal viability to irreversible damage. Alteration of the microtubule-associated protein tau, as reflected by increased Alz-50 immunoreactivity, was induced by permanent focal cerebral ischemia in vivo but only in a proportion of neurones. Alz-50 immunoreactive neurones did not exhibit the characteristics of irreversible ischemic cell damage. Increased immunoreactivity to the stress response protein ubiquitin was also induced by ischemia in a proportion of neurones. Both proteins are components of neurofibrillary tangles in Alzheimer's disease. Alterations of the microtubule-associated protein tau may be a feature of the early stages of the ischemia-induced degeneration and the ubiquitin response may be an attempt by compromised neurones to deal with the presence of abnormal proteins.
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PMID:Cerebral ischemia induces alterations in tau and ubiquitin proteins. 808 73

Using immunohistochemistry, we visualized the localization of ubiquitin in the gerbil hippocampus following 3 min of ischemia with or without pretreatment with 2 min of sublethal ischemia and 3 days of reperfusion. Ubiquitin immunoreactivity in the hippocampus disappeared 4 h after 3 min of ischemia both with and without pretreatment. The immunoreactivity in the CA3 and the dentate gyrus recovered by 24 h, but never recovered in the CA1, where delayed neuronal death takes place, without pretreatment. However, the pretreatment, which protects against CA1 neuronal damage, led to recovery of ubiquitin immunoreactivity in the CA1 by 48 h. Thus, recovery of ubiquitin may be a prerequisite to neuronal survival after ischemia and the role of ubiquitin in ischemic tolerance was suggested.
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PMID:Immunohistochemical localization of ubiquitin in gerbil hippocampus with induced tolerance to ischemia. 839 55

Insoluble ubiquitin conjugates (UC) in the mitochondrial fraction of the gerbil cortex were analyzed following transient forebrain ischemia. At 1 h of reperfusion after 2-10 min of ischemia, UC increased as the duration of ischemia was prolonged. Pre-treatment with pentobarbital, rather than post-treatment immediately after recirculation, reduced the increase of UC at 1 h of reperfusion following 5 min of ischemia. Pentobarbital had no effect on in vitro ubiquitination of heat-denatured lysozyme by the extract of gerbil cortex. These results suggest that increase in UC is dependent on ischemic damage and pentobarbital attenuates the increase of UC by relieving injury during ischemia.
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PMID:Increase in ubiquitin conjugates dependent on ischemic damage. 840 94

We investigated ubiquitin immunoreactivity in the post-ischemic gerbil hippocampus using a panel of ubiquitin antibodies. Immunostaining for ubiquitin in the hippocampus was strongly dependent on the antibodies used. With rabbit polyclonal antibody U-5379, immunoreactivity disappeared from the hippocampus in the early reperfusion period and reappeared in the dentate granule cells and CA3 pyramidal cells but never in the CA1 pyramidal cells. In contrast, rat monoclonal antibody DF2 and mouse monoclonal antibody MAB1510 showed sustained immunoreactivity in the CA1 during the 48-hour reperfusion period. On the immunoblots of gerbil brain homogenates, three antibodies, U-5379, DF2 and MAB1510, exhibited similar specificities; all three labeled free ubiquitin most strongly. Immunoprecipitation disclosed that, under nondenaturing conditions, U-5379 bound exclusively free ubiquitin, whereas DF2 and MAB1510 had little affinity for free ubiquitin but appeared to have more affinity for conjugated ubiquitin. Immunoabsorption of these antibodies with free ubiquitin confirmed the above result. It is most likely that U-5379 recognized free ubiquitin in the tissue, whereas DF2 and MAB1510 recognized preferentially conjugated ubiquitin. Thus, transient ischemia depletes free ubiquitin but not conjugated ubiquitin in the CA1. This depletion may be caused by impaired conversion from conjugated to free ubiquitin and/or failure of de novo ubiquitin synthesis.
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PMID:Transient ischemia depletes free ubiquitin in the gerbil hippocampal CA1 neurons. 854 12

Long lasting myocardial ischemia causes death of myocytes despite the restoration of coronary blood flow. Short period of ischemia and reperfusion transiently injures myocytes and is followed by the prolonged but reversible contractile dysfunction called myocardial stunning. Additionally, after a short time ischemia the postischemic myocardium shows enhanced tolerance towards subsequent, long time ischemia, so called ischemic preconditioning. The mechanisms responsible for both phenomena are not completely understood. Myocardial stunning is probably caused by injury to the heart at the molecular level (for example the transient inactivation or damage of proteins of the sarcoplasmic reticulum or the contractile machinery). Since contractility of stunned myocardium recovers, this injury is reversible. The presence of anti-oxidant enzymes system in the heart as well as endogenous protective substances like adenosine or bradykinin and synthesis of stress proteins like hsp 70, hsp 27 or ubiquitin might represent the molecular defense mechanisms against ischemia/reperfusion injury.
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PMID:[Molecular mechanisms for protecting the heart]. 858 24

The aim was to examine the expression of ubiquitin (Ub), 27 kDa heat shock protein (hsp 27) and hsp 60 mRNA in normal and briefly ischemic and reperfused porcine myocardium. The left anterior descending coronary artery was occluded for two periods of 10 min, separated by 30 min of reperfusion. After the second occlusion the myocardium was reperfused up to 210 min. Tissue from ischemic, ischemic-reperfused and nonischemic regions of the heart were analysed by Northern and slot blot hybridization and nuclear run-on transcription assays employing radiolabelled cDNA probes for Ub, hsp 27 and hsp 60 as well as by Western blot using monoclonal antibodies recognizing Ub protein conjugates and antiserum recognizing hsp 27. Systolic wall thickening was significantly decreased at 30 min reperfusion after both occlusions and remained depressed at longer periods of reperfusion. Using Northern blot hybridizations several mRNAs encoding Ub, 0.9 kb mRNA encoding hsp 27, and 2.2 kb mRNA encoding hsp 60 were detected in sham-operated, nonischemic and ischemic myocardial tissues. Densitometric analysis of Northern and slot blot hybridization signals showed the significant increase of the basal tissue levels of Ub mRNA in stunned regions only during the 30 min of the second reperfusion period. Increased levels of hsp 27 mRNA in stunned tissue were already noted at the first ischemic period and were sustained during the subsequent periods of reperfusion as compared to the control region of the heart. Changes in hsp 60 mRNA tissue levels were not observed during ischemia and subsequent reperfusions. Transcription of the Ub and hsp 27 genes was increased during 30 and 120 min of the second reperfusion period. The transient enhancement of tissue levels of Ub mRNA was associated with the temporary formation of new Ub-protein conjugates. However, the increased synthesis of mRNA encoding hsp 27 was not followed by changes of hsp 27 protein content in the myocardial tissue.
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PMID:[Expression of heat shock proteins in the normal and acutely stunned myocardium]. 858 25

For the study of ischemia-related adaptations we employed DDRT-PCR on mRNA obtained from heart regions undergoing brief (10') occlusions/reperfusions. We found and sequenced 52 differentially expressed clones that we further characterized using Northern analysis with RNA from a wide variety of tissues. We selected only clones (1) with a new sequence, (2) that showed a Northern signal, and (3) that exhibited organ-specific (heart, muscle) or (4) situation-specific (ischemia, non-specific stress) expression. We found two new heart-specific transcripts and three new stress-inducible genes. The transcripts with known sequences showed an expression pattern typical for repair processes after ischemia-reperfusion (ubiquitin, ATPases). About 20% of clones were truly differentially expressed.
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PMID:Characterization of differentially expressed genes following brief cardiac ischemia. 861 68

Succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide (Suc-LLVY-MCA) hydrolyzing activities of the 20S and 26S proteasomes in the gerbil cortex following transient forebrain ischemia were examined. Using extraction solutions without ATP, only 20S proteasome activity was noted after separation with glycerol gradient centrifugation. When these extracts were incubated with ATP and an ATP-regenerating system prior to glycerol gradient separation, both 20S and 26S proteasome activities were detected. Following 10 min of ischemia, the activity of the 26S proteasomes decreased, whereas the 20S proteasome activity increased after 30 min of reperfusion. These changes returned to the control level after 1 h. The active 26S proteasomes were formed with ATP-dependent association with the 20S proteasomes and several subunits and the 26S proteasomes degraded ubiquitin-protein conjugates. These results indicate that proteasome activity might not be irreversibly impaired after transient ischemia. However, transient inhibition of ATP-dependent conversion of 20S to 26S proteasomes in vitro must be one of the causes of the accumulation of the ubiquitin-protein conjugates in the early reperfusion period.
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PMID:Changes in proteasome activity following transient ischemia. 871 10


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