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)

Limitation on infarct size, using propionyl-L-carnitine (Sigma-Tau) by itself and with the calcium entry blocker, tiapamil (Hoffmann-LaRoche), was evaluated in two groups of ten dogs each, during chronic (9 days) myocardial infarction. There were eight dogs that served as the control group. A closed-chest model was used to produce the thrombus by placing a helically shaped copper wire in the LAD by catheter technique, under x-ray visualization. Necrotic tissue in serial transventricular sections were delineated by triphenyltetrazolium chloride and measured by computer technique, using an IBM PC interfaced with a digitizing pad, 9 days following occlusion. The mean total amount of necrosis in the propionyl-L-carnitine (7.4%) and the propionyl-L-carnitine/tiapamil (6.7%) groups were significantly less (p less than .01) than found in the control (14.1%) group, reflecting a difference of 50 and 58%, respectively, between the treated groups and control. A number of significant between-group comparisons (p less than .05 to p less than .001), under the same conditions, were found for various ischemia, hemodynamic, and hematologic variables followed before and at 30, 60, 90, 120, and 180 minutes after occlusion, as well as on the second and ninth day. The results of this study strongly suggest that propionyl-L-carnitine and propionyl-L-carnitine with tiapamil has a protective effect on myocardial function, following thrombotic occlusion of the LAD, as well as limiting the resulting infarct size.
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PMID:Effect of propionyl-L-carnitine on experimental myocardial infarction in dogs. 203 76

PM, IBM, and DM represent the commonly occurring inflammatory myopathies. In DM, the effector response appears to be predominantly humoral and directed against intramuscular blood vessels; a local humoral response may occur in muscle itself. Capillary lysis precedes other pathologic changes, suggesting that the capillary endothelium is an early and possibly primary target of the immune response. Questions remain about the role of immune complexes versus circulating antibodies, whether the muscle fiber injury can be explained by ischemia alone, and the possible role of endomysial CD8+ T cells. In PM and IBM, there is evidence for T-cell mediated cytotoxicity against the muscle fibers; however, muscle fiber destruction also could result from antibody-dependent complement-mediated lysis of the sarcolemma. Questions remain about the identity of the muscle fiber surface antigen(s) recognized by T cells and the molecular mechanisms of T-cell-mediated muscle fiber destruction.
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PMID:Immune effector mechanisms in inflammatory myopathies. 215 32

A computer model simulating both excitation and recovery processes within a block of heart muscle tissue has been developed and implemented on different IBM PC AT compatible computers. The model incorporates blocks of tissue consisting of several thousand elements and introduces phenomena which are completely or partly omitted in other existing cardiac electrophysiology models. These phenomena include the electric anisotropy of the tissue, different durations of repolarization in different layers of tissue, and the different shapes of action potential which correspond to cells excited when not fully recovered. Implementation of the model on small personal computers requires the use of a special data structure management and an effective algorithmic background. The program of the model is written in PASCAL and uses dynamically allocated data structures and the asynchronous simulation technique of event planing. These techniques are described in detail. The model has been used in various experiments. Results of simulation studies are presented in the form of modeled three-lead electrocardiographic records. The experimental series which are described include basic patterns of regular activation sequences, modeling of premature beats, simulation of effects due to fast pacing, models of ischemia and infarction, simulation of reentry mechanisms with a special reference to the initiation of ventricular fibrillation, and models of late potentials. The future development of more realistic models of the cardiac recovery process is also discussed.
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PMID:Computer model of cardiac repolarization processes and of the recovery sequence. 272 Nov 68

Immunoreactive class 1 and class 2 major histocompatibility complex gene products (MHCP) and beta 2 microglobulin (beta 2 MG) were demonstrated by microscopic immunocytochemistry in cryostat sections of skeletal muscle biopsies of 67 patients with various neuromuscular diseases. Diagnoses included normal muscle, chronic partial denervation, Duchenne dystrophy, polymyositis, dermatomyositis, inclusion body myositis, and miscellaneous neuromuscular diseases. Normal mature muscle fibers did not express MHCP, but blood vessels showed both class 1 and 2 MHCP and beta 2 MG. Regenerating muscle fibers showed consistent sarcolemmal class 1 MHCP expression irrespective of the disease. In polymyositis, the majority of extrafusal muscle fibers of most patients showed strong sarcolemmal class 1 MHCP expression. In dermatomyositis, muscle fibers situated either in perifascicular or in randomly clustered distribution revealed strong class 1 MHCP reactivity. In inclusion body myositis, scattered small clusters of muscle fibers were positive for class 1 MHCP. In polymyositis and inclusion body myositis, particularly strong class 1 MHCP expression was invariably seen in nonnecrotic muscle fibers partially invaded by lymphocytes whose cytotoxic effects are believed to be class 1 MHCP restricted. Factors or agents that trigger class 1 MHCP expression are presumed also to sensitize lymphocytes to muscle fibers in these diseases, but their identity remains obscure at this time. In dermatomyositis, the expression of MHCP in perifascicular muscle fibers and in areas of capillary loss may represent the triggering of MHCP expression by a nonspecific cellular stress reaction, in this case probably low-grade ischemia.
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PMID:Expression of immunoreactive major histocompatibility complex products in human skeletal muscles. 327 73

Fifty perfused cadaver kidneys transplanted in this institution were statistically analyzed with an IBM computer to determine the most important prognostic factors in long-term actual function, namely, the kidney donor warm ischemia, length of preservation, the perfusion characteristics (flow, pressure, perfusate gases, and occasionally electrolytes and osmolarity), and the recipient's response and clinical history (age, sex, race, original renal disease, HLA-antigen matching, number of transplants, number of rejection episodes, kidney function, final outcome, etc.). Although we found no significant (P greater than 0.05) correlation between graft survival and the parameters studied, high perfusate flow appeared to have an important beneficial effect on long-term graft function. Other prognostic indicators of posttransplantation renal function were not clearly seen in our study. It is important to mention that although no significant (P greater than 0.05) differences were seen, patients without diabetes mellitus, first cadaver kidney transplants, and more than two HLA-antigen matches did better than the group without these characteristics.
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PMID:Are there any important predicting factors of renal function during hypothermic pulsatile perfusion for transplantation? 699 29

We studied mitochondrial function in inflammatory myopathies, using cytochrome c oxidase (COX) reaction on muscle biopsy samples from 30 patients (15 with dermatomyositis, 12 with polymyositis, and 3 with inclusion body myositis) and 30 age-matched controls. We also performed immunocytochemistry for COX II and COX IV subunits in 7 of these patients who had COX deficiency. COX-deficient fibers were a constant finding in patients or controls older than 65 years and the percentage of COX-deficient fibers correlated with age in both patients and controls. Focal COX deficiency was found in 24 patients (13 of 15 with dermatomyositis, 8 of 12 with polymyositis, and 3 of 3 with inclusion body myositis) and 18 controls. The percentages of COX-deficient fibers were higher in patients with inflammatory myopathies (range: 0-4.7%; mean: 1.2%) than in age-matched controls (range: 0-1.9%; mean: 0.4%) (P < 0.01). In the subgroup of patients under age 65, COX-deficient fibers were more frequent in dermatomyositis than in polymyositis (mean: 0.8% vs 0.2%, P = 0.02). In patients with dermatomyositis, capillary loss correlated positively with COX deficiency (P < 0.02). Immunocytochemistry for COX II and IV showed that 82% of COX-negative fibers were COX II-negative and 26% were COX IV-negative, suggesting that proteins encoded by mitochondrial DNA are predominantly, but not exclusively, involved in COX deficiency. We conclude that mitochondrial dysfunction and COX deficiency can occur in inflammatory myopathies. Such a mitochondrial dysfunction is not solely related to the aging process. We suggest that muscle ischemia contributes to mitochondrial dysfunction in dermatomyositis.
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PMID:Cytochrome c oxidase deficiencies in the muscle of patients with inflammatory myopathies. 874 Feb 35

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

There are five major types of idiopathic inflammatory myopathies: dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), autoimmune necrotizing myopathy (AINM) and inflammatory myopathies associated with connective tissue diseases (overlap myositis). DM, PM and AINM are characterized by subacute, proximal and symmetrical weakness and respond to corticoids and immunosuppressants. Cutaneous involvement is specific for DM. IBM manifests by late onset, selective muscle weakness with early distal involvement and is unresponsive to immunosuppressants. PM is the rarest of these conditions. Histological features characterize each entity: perivascular inflammation, microangiopathy with reduced capillary density, ischemia, and perifascicular atrophy for DM; endomysial inflammation with invasion of non-necrotic fibers and diffuse expression of major histocompatibility complex class I antigens for PM; rimmed vacuoles in IBM coexisting with immunological features similar to PM; and necrosis is the prominent feature of AINM, without inflammation but associated with microangiopathy. The risk of malignant disease is increased in DM and AINM. Myopathy associated with anti-synthetase antibodies is characterized by frequent interstitial lung disease, perifascicular atrophy and prominent perimysial pathology. Myopathy associated with anti-SRP antibody is a necrotizing myopathy with rapid progression and partial resistance to corticoids. Inflammatory myopathies associated with connective tissue disease (CTD) are heterogeneous, involving all four major types (PM, DM, AINM, and IBM) and including additional pathological features. This category of myopathies has not yet been adequately characterized, because classification is usually replaced by the term "overlap myositis".
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PMID:[Inflammatory myopathies: diagnosis and classifications]. 1928 37