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)

Tenascin (TN), a large oligomeric glycoprotein, is a recently described component of the extracellular matrix (ECM). Previous reports focusing largely on the role of TN in nephrogenesis have documented the strong expression of TN in embryonic kidney tissue and implied an important role for TN in nephrogenesis. However, the expression of TN in normal and pathologic kidneys in adults has not been systematically evaluated. In this study immunohistochemical staining for TN was applied to 184 renal specimens diagnosed as: normal kidney (23 cases); minimal change disease and its variants (8); mesangial proliferative glomerulonephritis (GN) including IgA nephropathy and mesangial proliferative lupus nephritis (9); endocapillary proliferative GN including membranoproliferative GN, lupus nephritis, and post-infectious GN (25); crescentic GN (11); membranous GN (19); focal segmental sclerosis (15); thrombotic microangiopathy (8); amyloidosis (5); diabetic nephropathy (9); primary tubulointerstitial nephritis (14); transplant rejection (14); and ischemia (24). It was found that: (a) there was unequivocal global diffuse staining limited to the mesangium in normal kidney; (b) regardless of the etiologies and the morphologic types of glomerular disease, whenever there was expansion of the ECM, whether in the mesangial, endocapillary, or extracapillary spaces, there was a concomitant and proportional in situ increase in the TN staining; (c) globally sclerotic glomeruli, regardless of causes, showed diffuse, strong staining, especially in the subcapsular fibrous deposition seen in ischemic sclerosis; (d) non-sclerotic glomeruli showing early ischemic change uniformly displayed a marked decrease or complete loss of staining; (e) in cases of thrombotic microangiopathy, there was segmental or global staining of the capillary wall, probably corresponding to the enlarged lamina rara interna; (f) all nodular lesions in diabetic glomerulosclerosis showed strong staining, but in several of them this staining was much more pronounced in the periphery than in the center of the lesion. Our study proves that TN is probably a component of the normal mesangial matrix, that TN is an ubiquitous component of the expanded glomerular ECM in pathologic conditions regardless of morphologic subtypes, and that further studies on the cell types and mechanisms responsible for TN synthesis may provide a new venue for the understanding of the process of glomerular sclerosis.
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PMID:Tenascin is an important component of the glomerular extracellular matrix in normal and pathologic conditions. 751 Mar 49

The effects of the exposure of hippocampal slices to brief periods of ischemic-like conditions on the tyrosine phosphorylation of proteins and glycoproteins were investigated. Freshly prepared hippocampal slices contained a range of tyrosine-phosphorylated proteins and two prominent tyrosine-phosphorylated glycoproteins of apparent M(r) 110,000 (GP110) and 180,000, which we have previously shown to correspond to the postsynaptic density (PSD)-associated glycoprotein PSD-GP180. When hippocampal slices were incubated in oxygenated Krebs-Ringer buffer containing 10 mM glucose (KRB), there was a transient increase in the tyrosine phosphorylation of a protein of M(r) 42,000 (p42) and a pronounced increase in the tyrosine phosphorylation of GP110. After these initial changes, the tyrosine phosphorylation of all proteins remained constant for at least 60 min. In vitro "ischemia" was achieved by transferring slices that had been preincubated for 60 min in KRB to KRB that had been equilibrated with N2 instead of O2 and that did not contain glucose. Tyrosine-phosphorylated GP110 and PSD-GP180 could no longer be detected after 10 min of exposure of the slices to ischemic-like conditions. GP110 was rapidly rephosphorylated on tyrosine after transfer of slices back to oxygenated, glucose-containing buffer. In contrast, short periods of ischemia (5 or 10 min) resulted in the long-term loss of phosphotyrosine [Tyr(P)]-PSD-GP180 so that it was not detected even after 60 min of reincubation in oxygenated KRB. The sustained decrease in tyrosine phosphorylation of PSD-GP180 after ischemia was Ca2+ dependent, the levels of Tyr(P)-PSD-GP180 slowly increasing to preischemic values if Ca2+ was omitted from the incubation media.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tyrosine phosphorylation in a model of ischemia using the rat hippocampal slice: specific, long-term decrease in the tyrosine phosphorylation of the postsynaptic glycoprotein PSD-GP180. 756 82

The extracellular matrix plays an important role in biological processes, for example cellular adhesion, proliferation, migration and differentiation. Many of the cell-cell and cell-matrix interactions are mediated by extracellular matrix components and by their respective membrane receptors. Important pathophysiological processes occur through these interactions of which ontogenesis tissue differentiation and reconstruction, many inflammatory and immunological events and metastatic processes and invasion. The myocardium is made of muscular, vascular and connective components that exist in a state of equilibrium based on their relative proportions, integral structures, and on their physical and chemical characteristics. The Authors have described molecular events that lead to the organization of the cardiac tissue in physiological conditions and to its reorganization in pathological situation. Furthermore they have evaluated the role of fibronectin, a glycoprotein of the extracellular matrix in the initial phase of cardiac ischemia.
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PMID:[Anatomical and functional characteristics of the myocardial interstitial space]. 763 98

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that regulates the proliferation and maturation of hematopoietic progenitor cells and modulates the function of mature neutrophils. The responses to administration of G-CSF alone, and in combination with antimicrobials, were studied in an equine model of ascending colon ischemia. Complete segmental colonic ischemia (3.75 hours) with pelvic flexure enterotomy was created in four treatment groups. Group 1 horses received recombinant canine G-CSF (10 micrograms/kg, every 24 hours, intramuscularly), gentamicin sulfate (2.2 mg/kg, every 8 hours, intravenously), and potassium penicillin G (40,000 IU/kg, every 6 hours, intravenously). Group 2 horses were treated with the G-CSF vehicle and antimicrobials as for group 1. Group 3 horses received G-CSF and the antimicrobial drug vehicles, and group 4 horses served as the untreated control receiving G-CSF vehicle and antimicrobial vehicles. The results for 20 horses, five horses in each group, were compared. Treatment with G-CSF was associated with an increased concentration of white blood cells, band neutrophils, neutrophils, lymphocytes, and monocytes in the peripheral blood after surgery. Antimicrobial administration had no detectable effect on cell concentrations after surgery. Administration of G-CSF was associated with an increased concentration of nucleated cells in the peritoneal fluid including neutrophils, small mononuclear cells and large mononuclear cells. Horses that developed incisional infections had lower neutrophil concentrations in the peripheral blood on postoperative day 2 than horses without infected incisions. These results suggested that the prophylactic administration of G-CSF may be useful in the treatment of patients at risk for developing neutropenia after surgery.
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PMID:Effects of perioperative granulocyte colony-stimulating factor on horses with ascending colonic ischemia. 769 19

The progressive nature of dermal ischemia and subsequent tissue destruction within the "zone of stasis" is a central focus in burn research. To examine the role of neutrophils and neutrophil adherence within the zone of stasis, we utilized the monoclonal antibody (MAb) 60.3, directed to the human leukocyte adherence glycoprotein CD18 to block neutrophil adherence to endothelium and intravascular aggregation in a rabbit model of partial-thickness burn. Burns were created by applying an 80 degrees C brass template to the dorsal rabbit skin for 5 or 10 seconds. Animals treated with MAb 60.3 thirty minutes following a 5-second burn had less edema, thinner eschar, and earlier elevation of the eschar than control animals. Histologic analysis revealed an eightfold increase in live hair follicles (p < 0.05) and 43 percent greater reepithelialization at 8 days (p < 0.05) and a 15 percent reduction in burn surface area at 24 hours (p < 0.0001) in the antibody-treated group. There was no significant difference between treatment and control groups exposed to 10-second burns. We conclude that neutrophils and increased neutrophil adherence play important roles in the progressive tissue destruction within the zone of stasis in burns. Furthermore, moderate burn injury may be significantly attenuated by blocking neutrophil adherence functions with a CD18 MAb.
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PMID:Reduction of burn injury by inhibiting CD18-mediated leukocyte adherence in rabbits. 791 82

Paraplegia may occur after transient aortic occlusion as a consequence of primary ischemia to the spinal cord or injury during the reperfusion period. In animal models of ischemia/reperfusion there is evidence that reperfusion injury may be modulated partially by neutrophils. The efficacy of the neutrophil adherence blocking murine monoclonal antibody (MAb 60.3) was assessed in spinal cord ischemia/reperfusion in rabbits. Spinal cord ischemia was accomplished by balloon catheter occlusion of the infrarenal aorta. Neurologic assessment was graded as normal, partial neurologic deficit, or complete paralysis. Electrophysiologic monitoring with somatosensory evoked potentials was used to determine the optimal length of time of occlusion. Animals were treated randomly with 2 mg/kg of intravenous Mab 60.3 (n = 8) or saline solution (n = 9) with the investigator unaware of treatment. Mean occlusion times were no different between groups (control, 32.7 +/- 3.6 minutes versus MAb, 32.4 +/- 6.0 minutes). Five (55%) saline-treated and four (50%) MAb 60.3-treated animals became paraplegic. Animals with initial paraparesis all progressed to flaccid paraplegia within 24 hours. We conclude that spinal cord injury after transient aortic occlusion is independent of the CD11/CD18 glycoprotein complex of the neutrophil. Injury in this setting may occur during ischemia and thus may not be dependent on neutrophils or reperfusion.
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PMID:Inhibition of neutrophil adhesion does not prevent ischemic spinal cord injury. 794 51

Paroxysmal nocturnal hemoglobinuria is an acquired clonal expansion of bone marrow stem cells that are deficient in the decay-accelerating factor, which is a complement regulatory glycoprotein (CD55), as well as in the membrane inhibitor of reactive lysis (CD59) and the C8-binding protein. These proteins are deficient on the membranes of red blood cells, granulocytes, monocytes, and platelets. The disorder is associated with intermittent hemolytic anemia, hemoglobinuria, infection, a tendency toward bone marrow aplasia, and venous thromboses. The thromboses, on resolution, may give rise to endothelial proliferation that may cause ischemia and ulceration, or, alternatively, the thromboses may cause ulceration leading to a granulation tissue response with exaggerated endothelial proliferation. We report a second case of paroxysmal nocturnal hemoglobinuria that presented roentgenographically as an ulcerated circumferential duodenal mass secondary to venous thrombosis accompanied by florid papillary endothelial hyperplasia. We also review the literature concerning this phenomenon.
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PMID:Paroxysmal nocturnal hemoglobinuria associated with venous thrombosis and papillary endothelial hyperplasia presenting as ulcerated duodenal mass. 806 Feb 37

Dermal microvascular endothelial cells (DMEC) exposed to hypoxic conditions show a rapid induction of several proteins that do not increase in other cell types placed in a similar environment. These DMEC proteins differ from the well-characterized stress proteins that have been observed in a wide variety of cultured cell types. The DMEC proteins are induced rapidly, within 2-4 h, and are expressed transiently. They include a group of acidic proteins (pI approximately 5-5.2) with molecular weights in the range 100,000-120,000 and at least one glycoprotein (pI 5.1, M(r) 57,000) that is probably expressed on the cell surface. In some primary DMEC cell strains, this response is accompanied by a transient overall increase in protein synthesis. The oxygen-regulated proteins (ORP) that are induced in most other cell types under hypoxic conditions show little variation in their rate of synthesis in DMEC within the first 24 h. The response of DMEC differs from that of umbilical vein endothelial cells (UVEC) and from spindle-shaped cells derived from DMEC, that show a response to hypoxia that is similar to most other cell types. The changes seen in DMEC proteins take place in the same time scale as ischemia-reperfusion injury and may reflect the specialized change of functions of the microvasculature observed under conditions of hypoxic stress in vivo.
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PMID:The response of human dermal microvascular endothelial cells to hypoxia. 808 90

The aim of this study was to determine whether immunoneutralization of the common beta-subunit of the neutrophil CD11/CD18 glycoprotein adherence complex with monoclonal antibody IB4 (mAb IB4) or neutrophil depletion with a specific canine polyclonal antineutrophil serum (ANS) would reduce the extent of no-reflow in postischemic skeletal muscle. Microvascular patency was assessed by infusion of india ink contrast media and quantified by counting ink-containing microvessels < 15 microns diameter in histological sections obtained from isolated canine gracilis muscles subjected to 4.5 h of continuous perfusion (nonischemic control), 4 h of ischemia and 30 min of reperfusion [ischemia/reperfusion (I/R)] alone, I/R plus ANS, and I/R plus mAb IB4. I/R was associated with a marked reduction in microvascular patency compared with nonischemic controls (0.9 +/- 0.1 vs. 2.3 +/- 0.1 ink-containing microvessels per muscle fiber, respectively). Neutrophil depletion or prevention of neutrophil adherence attenuated the I/R-induced reduction in the number of ink-containing capillaries (1.6 +/- 0.1 and 2.2 +/- 0.2 ink-containing microvessels per muscle fiber, respectively). These data indicate that neutrophils play an important role in the genesis of no-reflow in postischemic skeletal muscle by a mechanism that appears to involve CD18-dependent neutrophil adhesion to the endothelium.
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PMID:CD18-dependent adherence reactions play an important role in the development of the no-reflow phenomenon. 809 75

Myocardial ischemia of sufficient duration produces irreversible myocardial injury and cell death. Associated with the direct ischemic insult, there is the indirect attack on the jeopardized tissue through activation of the complement system. The latter, occurring in response to ischemia, facilitates neutrophil-endothelial cell interactions, neutrophil migration into and across the vascular wall, along with the formation of cytotoxic oxygen metabolites and release of proteolytic enzymes. The neutrophil dependent actions participate in extending the tissue injury beyond that due to ischemia alone. The invading neutrophils injure the myocardial vasculature and sarcolemma through the generation of oxygen free radicals. Components of the complement system can damage tissue indirectly through formation of neutrophil chemoattractants as well as directly through assembly of the "membrane attack complex." Pharmacologic interventions that prevent complement activation, modulate neutrophil function or scavenge oxygen radicals, can reduce the extent of myocardial injury associated with ischemia reperfusion. The inflammatory reaction of cell injury mediated by neutrophil invasion of the affected tissue is an important site for pharmacologic intervention. Specific adhesive glycoprotein receptors are expressed on the neutrophil in conjunction with corresponding endothelial cell ligands. Recognition of these events has led to the development of specific antibodies having the potential to prevent cell-cell interactions essential for promoting and maintaining the inflammatory response. Therefore, neutrophil-independent extension of irreversible cell death that occurs upon reperfusion, is additive to the component of cell death attributed to the ischemic interval. As is the situation with any organ, function and cellular viability are dependent upon a blood supply, which if interrupted for a sufficiently long period, will lead to irreversible cellular changes and necrosis. Reperfusion is essential for arresting the otherwise progressive injury due to ischemia. The accelerated inflammatory response upon reperfusion contributes to an extension of the injury, a phenomenon known as "reperfusion" or "reoxygenation" injury.
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PMID:Complement, neutrophils and free radicals: mediators of reperfusion injury. 818 17


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