Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although L-carnitine is not considered as an essential nutrient, endogenous synthesis may fail to ensure adequate L-carnitine levels in neonates, especially those born prematurely. Free L-carnitine is found in many foods, mainly those from animal sources. Absorption of free L-carnitine is virtually complete. Lysine and methionine are necessary ingredients for the biosynthesis of L-carnitine. All tissues in the body can produce deoxy-carnitine but, in humans, the enzyme that enables hydroxylation of deoxy-carnitine to carnitine is found only in the liver, brain and kidneys. Complex exchanges of carnitine and its precursors occur between tissues. Muscles take up carnitine from the bloodstream and contain most of the body carnitine stores. L-carnitine and L-carnitine esters are eliminated mainly through the kidneys, which may play a central role in the homeostasis of this compound. Thyroid hormones adrenocorticotrophin (ACTH), and diet all influence urinary excretion of L-carnitine. Free L-carnitine can be assayed in plasma and urine and is occasionally measured in muscle biopsy specimens. Plasma L-carnitine levels may not accurately reflect L-carnitine body stores. L-carnitine ensures transfer of fatty acids to the mitochondria where they undergo oxidation. This process is associated with production of short-chain acylcarnitine which exit from the mitochondria or peroxisomes. L-carnitine ensures regeneration of coenzyme A and is thus involved in energy metabolism. L-carnitine also ensures elimination of xenobiotic substances. Carnitine deficiencies are common. Currently, these deficiencies are classified into two groups. In deficiencies with myopathy, only the muscles are deficient in L-carnitine, perhaps as a result of a primary anomaly of the L-carnitine transport system in muscles. In systemic deficiencies, L-carnitine levels are low in the plasma and in all body tissues. Systemic L-carnitine deficiencies are usually the result of a variety of disease states including deficient intake in premature infants or long-term parenteral nutrition; renal failure; organic acidemias; and Reye's syndrome. Modifications in L-carnitine metabolism have also been reported in patients with diabetes mellitus, malignancies, myocardial ischemia, and alcohol abuse. A large number of supplementation trials have been carried out.
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PMID:[L-carnitine: metabolism, functions and value in pathology]. 129 65

Interest in the role that activated granulocytes play in C5a-induced myocardial ischemia prompted us to investigate and compare activation responses of pig and human neutrophils. The responses of Hypaque-Ficoll purified porcine (P-PMN) and human neutrophils (H-PMN) to stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP), C5a, phorbol myristate acetate (PMA), and calcium ionophore A23187 (A23187) were compared by flow cytometrically measured changes in the cells' forward (FWD-SC) (a measure of shape/volume change) and right angle (90 degrees-SC) light scatter (a measure of secretion), and in the distribution of the membrane potential sensitive fluorescent probe di-O-C (3). FMLP, C5a, and Zymosan-activated serum (ZAS stimulated chemotaxis and FMLP vs. PMA-stimulated adherence to plastic were also compared. Unstimulated P-PMN had lower FWD-SC and 90 degrees-SC than H-PMN (39.4 +/- 1.4 vs. 48.4 +/- 2.0 P less than 0.05, and 32.7 +/- 2.7 vs. 52.4 +/- 1.5 units, P less than 0.005, for FWD-SC and 90 degrees-SC of P-PMN vs. H-PMN, respectively). P-PMN selectively failed to increase their FWD-SC upon stimulation with FMLP (0.0 +/- 0.5% vs. 26.1 +/- 6.8%, P-PMN vs. H-PMN), or decrease their 90 degrees-SC when treated with cytochalasin B + FMLP (secretion) (2.4 +/- 0.1% vs. -35.8 +/- 4.6% change in 90 degrees-SC, P-PMN vs. H-PMN), while responding comparably to C5a, PMA, and A23187. P-PMN failed to depolarize in response to FMLP but responded similarly to H-PMN when activated by C5a, A23187, and PMA. P-PMN's chemotactic response to FMLP was selectively absent since the cells responded well to purified pig C5a. FMLP stimulated significant increases in H-PMN adherence to bovine serum albumin-coated plastic (44.1 +/- 6.7% vs. 12.6 +/- 3.7%, FMLP vs. buffer, P less than 0.025), but failed to increase adherence of P-PMN above baseline 0.68 +/- 0.20% vs. 2.12 +/- 1.90%, FMLP vs. buffer, P greater than 0.05. PMA (100 ng/ml) stimulated comparable increases in adherence in both PMN types (48.6 +/- 5.2% vs. 58.7 +/- 4.9%, P-PMN vs. H-PMN, P less than 0.025). Binding studies using the fluoresceinated N-formyl peptide f-met-leu-phe-lysine-fluorescein-isothiocyanate (FMLPL-FITC) in the absence and presence of excess non-fluoresceinated FMLPL indicated that P-PMN lack specific binding sites for the N-formyl peptides.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vivo and in vitro assessment of porcine neutrophil activation responses to chemoattractants: flow cytometric evidence for the selective absence of formyl peptide receptors. 210 28

Vaccinia virus IHD-J strain induces hemagglutinin (HA) on the surface membrane of infected cells and does not elicit cell-cell fusion (F-). We isolated 21 independent hemadsorption-negative (HAD-) mutant viruses from IHD-J and five HAD+ revertants from one of these mutants. Of the 21 mutants, 19 that synthesized either no or little HA at the cell surface caused cell-cell fusion (F+), whereas none of the five revertants that synthesized HA at the cell surface induced cell-cell fusion. Furthermore, anti-HA monoclonal antibody B2D10 induced extensive polykaryocytosis of IHD-J-infected cells and suppressed the ability of the IHD-J-infected cell extract to inhibit the polykaryocytosis induced by IHD-W. The other 2 of the 21 HAD- mutants, B1 and A2, which induced HAs at the cell surface, showed F- and F+ phenotype, respectively. The HA molecule of mutant B1 had a single amino acid substitution of Lys for Glu-121 in its extracellular domain, whereas that of mutant A2 had a single substitution mutation of Tyr for Cys-103. We conclude that the vaccinia HA is a fusion inhibition protein, that the active sites for the two activities reside separately in its extracellular domain, and that cysteine-103 is important in forming the proper tertiary structure of the protein to exert both activities.
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PMID:Hemadsorption and fusion inhibition activities of hemagglutinin analyzed by vaccinia virus mutants. 218 66

We analyzed serum lipoproteins and apolipoprotein E (apo E) from 199 patients in CCU, having ischemic heart disease, and from 211 healthy subjects. It was suggested that serum lipoprotein abnormalities, especially elevated low density lipoprotein (LDL) levels, are closely related to atherogenesis in relatively young patients and subjects with severe coronary lesions. The frequency of apo E-4 was higher and that of E-2 was lower in the CCU group than in the control group. Apo E mutants, E-7 (Glu244----Lys, Glu245----Lys) and E-5 (Glu3 (Glu3----Lys), were also frequent in the CCU group. Apo E isoproteins have higher pI in the order E-2, E-3, E-4, and we observed that LDL-cholesterol levels increased in the same order. The apo E mutants, E-5 and E-7, are also more basic than E-4. These findings suggest that basic apo Es were associated with the development of atherosclerosis. The prevalence of familial hypercholesterolemia (FH) in the CCU group was more than 10 times higher than the reported frequency of FH heterozygotes in normal population. The persistence of marked hypercholesterolemia from infancy probably makes FH patients susceptible to atherosclerosis. Based on the analysis of LDL-receptor protein synthesis, various types of mutations were observed even in phenotypically homozygous FH patients. FH homozygotes were divided into 2 groups, a receptor-negative group and a receptor-defective group. We found a great difference in the frequency of coronary heart disease depending on whether even a small number of receptors were present or not.
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PMID:Hyperlipoproteinemia as a risk factor for ischemic heart disease. 239 26

Intracoronary thrombi resulting in acute myocardial ischemia can often be lysed by thrombolytic agents. We examined the potential of a fibrin(ogen)-degradation product pentapeptide 6A (Ala-Arg-Pro-Ala-Lys), which increases coronary blood flow partly by stimulation of prostacyclin release, in reestablishing coronary blood flow in dogs with experimentally induced thrombus. An occlusive thrombus in the circumflex coronary artery was created by electrical stimulation of the endothelial surface. After the occlusive thrombus was stable without electrical current for at least 15 min, peptide 6A (5 mumol/min for 20 min intracoronary) or tissue-plasminogen activator (t-PA) [10 micrograms/kg/min for 20 min intravenously (i.v.)] was randomly administered. Peptide 6A administration reestablished coronary blood flow (peak 16 +/- 2 ml/min, mean +/- SE) in 6 of 12 animals with occlusive coronary thrombus. Mean time to blood flow reestablishment was 5.3 +/- 2.2 min, but the reflow was short lived (mean duration of reflow: 15.7 +/- 1.6 min). t-PA reestablished coronary blood flow (peak 19 +/- 3 ml/min) in 4 of 10 animals. The time of flow reestablishment was 12.0 +/- 3.9 min and the reflow persisted for 22.0 +/- 3.1 min. Peptide 6A administration was associated with an increase in coronary venous plasma 6-keto-PGF1 alpha, indicating stimulation of prostacyclin release. This study demonstrates the potential of peptide 6A in reestablishing coronary blood flow in a canine model of coronary thrombosis. This transient effect is associated with release of prostacyclin, which may be beneficial because of its vasodilator and platelet inhibitory effects.
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PMID:Effects of peptide 6A on coronary blood flow dynamics in canine coronary thrombosis. 248 73

Vaccinia virus strains vary considerably in the amounts of extracellular enveloped virus (EEV) that they release from infected cells. The IHD-J strain produces up to 40 times more EEV than does the related WR strain and consequently generates elongated comet-shaped virus plaques instead of sharply defined round ones in susceptible monolayer cells under liquid medium. The difference in EEV formation is due to the retention of enveloped WR virions on the cell surface (R. Blasco and B. Moss, J. Virol. 66:4170-4179, 1992). By using WR and IHD-J DNA fragments for marker transfer and analyzing the progeny virus by the comet formation assay, we determined that gene A34R and at least one other gene regulate the release of cell-associated virions. Replacement of the A34R gene of WR with the corresponding gene from IHD-J increased the amount of EEV produced by 10-fold and conferred the ability to form distinctive comet-shaped plaques. Gene A34R encodes an EEV-specific glycoprotein with homology to C-type animal lectins (S.A. Duncan and G.L. Smith, J. Virol. 66:1610-1621, 1992). The nucleotide sequences of the A34R genes of WR and IHD-J strains differed in six positions, of which four were silent. One of the codon mutations (Lys-151-->Glu), which is located in the putative carbohydrate recognition domain, was sufficient to transfer a comet-forming phenotype to WR virus. These data indicate that the A34R-encoded glycoprotein is involved, through its lectin homology domain, in the retention of progeny virus on the surface of parental cells and raise the possibility that the protein also has a role in virus attachment to uninfected cells.
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PMID:Dissociation of progeny vaccinia virus from the cell membrane is regulated by a viral envelope glycoprotein: effect of a point mutation in the lectin homology domain of the A34R gene. 849 53

Perfusion of the isolated rabbit heart with 5 x 10(6) human polymorphonuclear leukocytes (PMNL), under recirculating conditions (50 ml) and challenge with A-23187 (0.5 mu M) increased coronary perfusion pressure (CPP) sixfold, accompanied by increased levels of sulfidopeptide leukotrienes (CY-SLT), which had previously shown to correlate linearly with the increase in CPP. Pretreatment (20 min) of isolated rabbit hearts with the prostacyclin (PGI(2)) analogue iloprost (3 nM) resulted in significant protection against the increase in CPP and in almost complete inhibition of 5-lipoxygenase (5-LO) product synthesis. Similarly, pretreatment of isolated rabbit heart with defibrotide (200 mu g/ml), a polydeoxyribonucleotide derivative known to inhibit PMNL activation and enhance PGI(2) production by heart endothelial cells, produced significant protection against the increase in CPP and almost complete inhibition of 5-LO product synthesis. Neither iloprost nor defibrotide affected the A-23187-induced arachidonic acid (AA) metabolism in isolated PMNL alone. Inhibition of rabbit cyclooxygenase by intravenous (i.v.) administration of lysine-acetylsalicylate (60 mg/kg) 2 h before the animals were killed significantly reduced the protection provided by defibrotide, with a parallel fivefold increase in sulfidopeptide LT levels, returning to values in the range observed in control hearts. Control of endogenous modulators of leukocyte-vascular wall interactions such as PGI(2) results in significant changes in sulfidopeptide LT production in an organ model of transcellular metabolism of LT A(4), suggesting a novel mechanism of action for cardioprotective drugs in myocardial ischemia.
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PMID:Vasoconstriction to polymorphonuclear leukocytes in the isolated, perfused rabbit heart: inhibition by prostacyclin mimetics. 885 38

Efforts in Finland to implement the recommended non-pharmacological and pharmacological principles for the control of hypertension, stroke and ischaemic heart disease have been accompanied by an approximately 10 mm Hg fall in the population average of diastolic blood pressure, and about 60% decrease in deaths from both stroke and ischaemic heart disease among 30-59-year-old men and women from 1972 to 1992. Adherence to antihypertensive drug therapy has been quite good. However, the drug treatment does not seem to account for more than 5-6% of the observed fall of blood pressure, and 10-15% of the decrease in deaths from strokes and ischaemic heart disease. There has been no overall adherence to several non-pharmacological recommendations, and marked increases in the intake of alcohol, obesity among men, and smoking among women have been observed. However, the population adherence to recommendations to decrease the intakes of sodium and saturated fats, and to reduce the sodium-to-potassium ratio and the saturated-to-unsaturated fat ratio, has been good. These dietary changes appear to account for a major part of the fall of blood pressure and the decrease in the cardiovascular diseases. Currently a rapid further population-wide decrease in the dietary sodium-to-potassium ratio is taking place, due to a decrease in the use of salt and replacement of common salt by a novel sodium-reduced, potassium-, magnesium-, and l-lysine HCI-enriched salt, both in home kitchens and in the food industry.
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PMID:Adherence to and population impact of non-pharmacological and pharmacological antihypertensive therapy. 896 92

Selective troponin I (TnI) modification has been demonstrated to be in part responsible for the contractile dysfunction observed with myocardial ischemia/reperfusion injury. We have isolated and characterized modified TnI products in isolated rat hearts after 0, 15, or 60 minutes of ischemia followed by 45 minutes of reperfusion using affinity chromatography with cardiac troponin C (TnC) and an anti-TnI antibody, immunological mapping, reversed-phase high-performance liquid chromatography, and mass spectrometry. Rat cardiac TnI becomes progressively degraded from 210 amino acid residues to residues 1-193, 63-193, and 73-193 with increased severity of injury. Degradation is accompanied by formation of covalent complexes between TnI 1-193 and, respectively, TnC residues 1-94 and troponin T (TnT) residues 191-298. The covalent complexes are likely a result of isopeptide bond formation between lysine 193 of TnI and glutamine 191 of TnT by the cross-linking enzyme transglutaminase. With severe ischemia, cellular necrosis results in specific release of TnI 1-193 into the reperfusion effluent and TnT degradation in the myocardium (25-, 27-, and 33-kDa products). Two-dimensional electrophoresis demonstrated that phosphorylation of TnI prevents ischemia-induced degradation. This study characterized the modified TnI products in isolated rat hearts reperfused after a brief or severe period of ischemia, revealing the progressive nature of TnI degradation, changes in phosphorylation, and covalent complexes with ischemia/reperfusion injury. Finally, we propose a model for ischemia/reperfusion injury in which the extent of proteolytic and transglutaminase activities ultimately determines whether apoptosis or necrosis is achieved.
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PMID:Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury. 991 81

Patients suffering from myocardial ischemia reportedly exhibit reduced in vitro binding of exogenous Co(2+) to the N-terminal of human serum albumin (HSA). The purpose of our investigation was to simulate changes in the N-terminus of HSA that may account for these ischemia-induced modifications to the cobalt binding site. HPLC, LC-MS and (1)H NMR analyses have shown that the N-terminal region of HSA Asp-Ala-His-Lys binds the transition metals Co(2+) and Ni(2+). Synthetic peptides with the first 2-12 amino acids of the HSA sequence demonstrated that the first three amino acids, Asp-Ala-His, are essential for strong binding of cobalt. Modification of the N-terminus peptide of HSA by way of N-acetylation or the deletion of one or more amino acid resulted in no binding of cobalt. Because the degradation of the susceptible, specific transition metal binding site of HSA may account for the decreased cobalt binding observed during ischemic events, an assay that detects this reduced binding could be useful in the diagnosis of ischemia.
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PMID:Characterization of the Co(2+) and Ni(2+) binding amino-acid residues of the N-terminus of human albumin. An insight into the mechanism of a new assay for myocardial ischemia. 1112 Nov


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