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)

The effect of cerebral hypoxia on protein synthesis was investigated by exposing rats to 5% O2, and examining polypeptide synthesis and size distribution profiles of ribosomes. The findings were compared with the results from cerebral anoxia (decapitation) and hypoglycemia. In cerebral hypoxia there was suppression of polypeptide synthesis, though to a lesser extent than in cerebral anoxia, while no effect was detected in hypoglycemia. Among 4 different ribosomal fractions used for polypeptide synthesis, the microsome was the most sensitive for hypoxia and anoxia, and the polyribosome after short centrifugation was the least sensitive. The size distribution profiles of 3 different ribosomes revealed an increase in the size of the monomere-dimer complex and a decrease of the polysome peak both in cerebral hypoxia and anoxia. Comparison of the energy state and the extent of lactic acidosis in cerebral hypoxia, anoxia and hypoglycemia available in the literature and the functional and structural state of polyribosomes in the present investigation suggests that intracellular acidosis may be the main cause of the suppression of polypeptide synthesis and disaggregation of polyribosomes in hypoxia, and the depletion of energy reserve may be the main cause in anoxia-ischemia.
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PMID:Protein synthesis in rat brain in hypoxia, anoxia and hypoglycemia. 42 Nov 33

Twenty patients with peripheral arterial disease and 10 normal controls were submitted to i.v. injection of aprotinin, polypeptide (mol.wt. 6512) extracted from bovine lung, in order to examine its effects on: (a) lower limbs pain, (b) lower limbs sensibility, (c) calf blood flow. Aprotinin (100,000 Ku i.v. diluted in NaCl 0.9%) was given in a single dose or twice a day for a week; for control the same subject received, before or after aprotinin, an equivalent volume of diluent (0.9% NaCl). The results demonstrate that aprotinin is able to increase the initial pain limit walking tolerance and to decrease the intensity of pain at rest and of myalgic or "trigger" areas. No variation was observed on skin sensibility and on calf blood flow, both basal resting and hyperemic. The favorable effect of examined polypeptide on ischemic pain can be attributed neither to increase of calf blood flow nor to influence on perception of painful stimuli. It seems therefore to suggest that aprotinin acts on biochemical mechanisms that cause the ischemic pain. Presumably it inhibits kininogenases and tissue protein-hydrolyzine enzymes activated in the course of ischemia.
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PMID:Effect of a proteinase inhibitor on intermittent claudication or on pain at rest in patients with peripheral arterial disease. 108 49

Previous studies have shown degradation of cardiac structural proteins and disruption of the sarcolemma as a result of acute myocardial infarction. However, there is no evidence to date on changes in sarcolemmal membrane proteins induced by experimental subacute myocardial infarction. We studied subepicardial layers overlying myocardial infarct 4 days following ligation of the left anterior descending coronary artery in 12 dog hearts. We first demonstrated that this layer provides the anatomic-electrophysiologic substrate for reentrant arrhythmias using activation mapping techniques and histologic correlations. The makeup of membrane proteins was studied using SDS polyacrylamide gel electrophoresis, peptide mapping, and laser densitometry. Sarcolemmal membrane proteins were isolated by ultracentrifugation through a sucrose gradient. We found that a sarcolemmal polypeptide (MW 126,000; n = 12) in the normal tissues has a different mobility than the corresponding protein (MW 124,000; n = 12) of the ischemic tissues although their peptide analysis appeared similar, suggesting that the protein undergoes a post-translational modification. In addition, two proteins (MW 75,000; n = 12 and MW 88,000; n = 12) were present in greater amount in the ischemic than in the control tissues suggesting either acceleration in protein synthesis or slow down of degradation turnover. These results demonstrate that specific changes occur in membrane proteins subjected to ischemic insults which might be responsible for membrane alterations following ischemia and may contribute to the abnormal electrophysiologic properties and arrhythmia seen in vivo at this stage.
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PMID:Changes in sarcolemmal proteins in subacute myocardial infarction in the dog. 130 6

In mammalian myocardium, muscle contraction is regulated by the rapid release of Ca2+ ions through ryanodine-sensitive Ca2+ release channels present in the intracellular membrane compartment, sarcoplasmic reticulum (SR). In this study, the effects of regional ischemia on intrinsic SR Ca2+ release channel function were determined by studying the Ca2+ transport and release, and [3H]ryanodine binding properties of whole muscle homogenates and SR-enriched membrane fractions from normal and ischemic myocardium. Measurement of oxalate-supported 45Ca(2+)-uptake rates before and after pretreatment with 1 mM ryanodine, indicated that the SR Ca2+ release channel retained its ability to be effectively closed by the channel-specific probe ryanodine after 15 and 60 min of ischemia. 45Ca2+ efflux from, and high-affinity [3H]ryanodine binding to SR-enriched vesicle fractions indicated retention of regulation of Ca2+ release channel activity by Ca2+, Mg2+ and adenine nucleotide in 15 and 60 min ischemic samples. Further, sodium dodecylsulfate polyacrylamide gel and immunoblot analysis revealed no proteolytic degradation of the M(r) 565,000 SR Ca2+ release channel polypeptide after 15 and 60 min of ischemia. These results suggested a minimal, if any, loss of intrinsic SR Ca2+ release channel function in ischemic hearts.
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PMID:Effects of regional ischemia on the ryanodine-sensitive Ca2+ release channel of canine cardiac sarcoplasmic reticulum. 133 60

Inflammation, metastasis and ischemia are processes that require lymphocyte or leukocyte cell recognition and adherence to endothelial counter receptors such as ICAM-1. Mapping the sites of interaction of ICAM-1 with LFA-1, the receptor for ICAM-1 on lymphocytes, may lead to the design of novel inhibitors of inflammation or metastasis. To this end, recombinant soluble ICAM-1 cDNA was engineered into the baculovirus expression system, which is capable of expressing large amounts of proteins. These constructs were designed to contain a protein leader sequence so that the transfected insect cells would secrete the recombinant polypeptide into the culture media for ease of isolation. We engineered four constructs of ICAM-1 into the baculovirus system and obtained relatively high expression of two soluble forms of ICAM-1, a two domain and a five domain form. These truncated proteins were isolated and shown to promote adherence of HL-60 cells and Molt-4 cells. These recombinant soluble proteins also inhibited cell adherence to purified intact ICAM-1 isolated from K562 cells.
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PMID:Functional expression of soluble ICAM-1 by baculovirus-infected Sf9 cells. 135 79

We have isolated, from newborn rats, heart cultures enriched in contractile muscle cells (M) and cultures of fibroblast-like cells (F). M cultures respond to simulated ischemia by an arrest of beating activity, by a decrease in beta oxydation rate, ATP and phosphocreatine content and by a loss of membrane phospholipids associated with neutral lipids accumulation. F cells in contrast do not respond to oxygen deprivation. Firstly, we observed that cocultures of M and F cells respond to oxygen deprivation by an arrest of beating activity and a decrease in cellular ATP content, but failed to exhibit any significant loss of membrane phospholipids. Secondly, we demonstrated that culture medium conditioned by F cells is able to inhibit the reaction of M cells to simulated ischemia thus suggesting that fibroblasts produce a diffusible factor able to block phospholipase activation. Heat treatment and trypsinisation failed to abolish this activity, indicating that the phospholipase inhibitory factor is probably not a polypeptide.
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PMID:Regulation of membrane phospholipid metabolism in heart cell culture. 163 76

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.
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PMID:Neurochemical characterization of excitotoxin lesions in the cerebral cortex. 167 Jul 82

Histochemical changes in peptidergic and catecholaminergic neurons during ischemia were investigated in the cerebral neocortex of the gerbil. Catecholaminergic fibers were observed by catecholamine histofluorescence with glyoxylic acid solution, and peptidergic neuron systems such as vasoactive intestinal polypeptide (VIP), somatostatin (SOM), and neuropeptide Y (NPY) were observed by immunohistochemistry. Two hours after unilateral occlusion of the internal carotid artery, catecholaminergic fibers disappeared in the neocortex on the occlusion side, while peptidergic nerve fibers except for NPY fibers were intact after 2 hours of ischemia. NPY fibers had decreased in number on the occlusion side 2 hours after ischemia. VIP-, SOM-, and NPY-immunoreactive neurons showed a decrease of 60% six hours after ischemia, and these neurons completely disappeared in the cerebral neocortex 24 hours after ischemia. These results suggest that catecholaminergic neuron system is more vulnerable than the peptidergic one in ischemic event.
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PMID:[Selective vulnerability of peptide-containing neurons in cerebral ischemia; immunohistochemical study]. 168 33

Marked hyperemia accompanies reperfusion after ischemia in the brain, and may account for the propensity of cerebral hemorrhage to follow embolic stroke or carotid endarterectomy, and for the morbidity that follows head injury or the ligation of large arteriovenous malformations. To evaluate the contribution of trigeminal sensory fibers to the hyperemic response, CBF was determined in 12 symmetrical brain regions, using microspheres with up to five different isotopic labels, in four groups of cats. Measurements were made at 15-min intervals for up to 2 h of reperfusion after global cerebral ischemia induced by four-vessel occlusion combined with systemic hypotension of either 10- or 20-min duration. In normal animals, hyperemia in cortical gray matter 30 min after reperfusion was significantly greater after 20 min (n = 10) than after 10 min (n = 7) of ischemia (312 ml/100 g/min versus 245 ml/100 g/min; p less than 0.01). CBF returned to preischemic levels approximately 45 min after reperfusion and was reduced to approximately 65% of basal CBF for the remaining 75 min. In cats subjected to chronic trigeminal ganglionectomy (n = 15), postocclusive hyperemia in cortical gray matter was attenuated by up to 48% on the denervated side (249 versus 150 ml/100 g/min; p less than 0.01) after 10 min of ischemia. This effect was maximal in the middle cerebral artery (MCA) territory, and was confined to regions known to receive a trigeminal innervation. In these animals, substance P (SP) levels in the MCA were reduced by 64% (p less than 0.01), and the density of nerve fibers containing calcitonin gene-related peptide (but not vasoactive intestinal polypeptide or neuropeptide Y) was decreased markedly on the lesioned side. Topical application of capsaicin (100 nM; 50 microliters) to the middle or posterior temporal branch of the MCA 10-14 days before ischemia decreased SP levels by 36%. Postocclusive hyperemia in cortical gray matter was attenuated throughout the ipsilateral hemisphere by up to 58%, but the cerebral vascular response to hypercapnia (PaCO2 = 60 mm Hg) was unimpaired. The duration of hyperemia and the severity of the delayed hypoperfusion were not influenced by trigeminalectomy, capsaicin application, or the intravenous administration of ATP. These data demonstrate the importance of neurogenic mechanisms in the development of postischemic hyperperfusion, and suggest the potential utility of strategies aimed at blocking axon reflex-like mechanisms to reduce severe cortical hyperemia.
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PMID:Chronic trigeminal ganglionectomy or topical capsaicin application to pial vessels attenuates postocclusive cortical hyperemia but does not influence postischemic hypoperfusion. 170 54

We have used brain (dog, rat) and spinal cord (dog, rabbit) cell-free systems to study early postischaemic inhibition of protein synthesis. Ischaemia alone produced a relatively small decrease in activity of all subcellular systems used. When 15 min of normoxic reperfusion was used, more than 30% decrease (p less than 0.01) in [14C]-leucine incorporation was detected. A translational inhibitor that appeared in the postribosomal supernatant fraction at the early stage of reperfusion reduced translational capacity of an initiating cell-free system. It also phosphorylated the small (38 kDa) subunit of eukaryotic initiation factor 2 (eIF-2) in vitro. Effect of the inhibitor can be reversed by addition of partially purified intact eIF-2 and/or high concentration (2 mmol/l) of GTP. A prevention of postischaemic free oxygen radical formation by the reoxygenation with hypoxaemic blood, containing 37.5 mm Hg O2 at 0-5 min and 56 mm Hg O2 at 6-10 min of recirculation, that was followed by 5 min of normoxic reperfusion, resulted in a significant increase (p less than 0.02) of polypeptide chain synthesis in vitro when compared with normoxic reperfusion.
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PMID:Mechanism of protein synthesis inhibition in CNS during postischaemic reperfusion. 181 18


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