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)

Alpha 1-acid glycoprotein (AAG) concentrations and propranolol binding were investigated in the serum of elderly hospitalized patients with acute illness, and healthy elderly and young subjects. Significantly greater AAG concentrations and reduced unbound propranolol fraction were observed in the elderly with acute disease compared to the elderly controls. The greatest changes (up to five-fold) occurred with cancer, with lesser changes associated with myocardial infarction and ischaemic heart disease, acute infection, heart failure, chronic obstructive respiratory disease, and cerebrovascular accident. Various miscellaneous conditions were also associated with high AAG concentrations and enhanced propranolol binding. The healthy elderly had higher AAG concentrations and lower unbound propranolol fractions than the healthy young group. Overall there was a highly significant correlation between the propranolol binding ratio (bound/free) and the serum AAG concentration. These results suggest that the elderly population may be particularly susceptible to changes in AAG concentrations, and that during acute illness interpretation of serum concentrations of drugs which bind mainly to AAG, may require knowledge of their free fractions.
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PMID:Alpha 1-acid glycoprotein concentrations and propranolol binding in elderly patients with acute illness. 650 90

Scanning electron microscopy and transmission electron microscopy were used together with tannic acid and ruthenium-red staining to examine connective tissue damage caused by acute myocardial ischemia for 20, 40 and 120 min in pig hearts. The microsphere blood flow technique revealed that blood flow was approximately 0.02 ml/min/g in inner, middle and outer thirds of the ischemic zone. After 20 min of occlusion of the left anterior descending coronary artery, the collagen network and microfilaments became irregularly arranged. After 40 min of occlusion, ruthenium-red positive glycoprotein material around the collagen fibrils and elastin began to disappear. After 2 h occlusion, the collagen fibrils and microfilaments had separated from the basement membrane. Collagen fibrils, elastic fibers, and microfilaments were broken down and were found in decreased quantities. These results have revealed that the connective tissue remains intact during the first 20 min of coronary occlusion despite zero blood flow and mild cellular changes but does undergo prominent alterations after 40 min of occlusion.
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PMID:Connective tissue changes in early ischemia of porcine myocardium: an ultrastructural study. 687 83

Lipoprotein(a) or Lp(a) is similar to low density lipoproteins (LDL), but also contains a large glycoprotein molecule called apo-lipoprotein(a) or apo(a). The lipid composition of Lp(a) is nearly identical to that of LDL. The structure of apo(a) is similar to that of plasminogen. Several genetic polymorphisms have been described for apo(a). The increasing interest in Lp(a) is due to the positive correlation which exists between the plasma level of Lp(a) and the incidence of ischaemic heart disease. Plasma Lp(a) level varies greatly from one individual to another and is basically dependent on genetic factors, especially for the isoforms of apo(a). A level above 30 mg.dl is associated with increased risk of atherosclerosis-related diseases. There are few treatments which are effective in significantly reducing raised levels of Lp(a).
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PMID:[Lipoprotein (a)]. 782 70

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

The structure, formation, and function of the virion membranes are among the least well understood aspects of vaccinia virus replication. In this study, we investigated the role of gp42, a glycoprotein component of the extracellular enveloped form of vaccinia virus (EEV) encoded by the B5R gene. The B5R gene was deleted by homologous recombination from vaccinia virus strains IHD-J and WR, which produce high and low levels of EEV, respectively. Isolation of recombinant viruses was facilitated by the insertion into the genome of a cassette containing the Escherichia coli gpt and lacZ genes flanked by the ends of the B5R gene to provide simultaneous antibiotic selection and color screening. Deletion mutant viruses of both strains formed tiny plaques, and those of the IHD-J mutant lacked the characteristic comet shape caused by release of EEV. Nevertheless, similar yields of intracellular infectious virus were obtained whether cells were infected with the B5R deletion mutants or their parental strains. In the case of IHD-J, however, this deletion severely reduced the amount of infectious extracellular virus. Metabolic labeling studies demonstrated that the low extracellular infectivity corresponded with a decrease in EEV particles in the medium. Electron microscopic examination revealed that mature intracellular naked virions (INV) were present in cells infected with mutant virus, but neither membrane-wrapped INV nor significant amounts of plasma membrane-associated virus were observed. Syncytium formation, which occurs in cells infected with wild-type WR and IHD-J virus after brief low-pH treatment, did not occur in cells infected with the B5R deletion mutants. By contrast, syncytium formation induced by antibody to the viral hemagglutinin occurred, suggesting that different mechanisms are involved. When assayed by intracranial injection into weanling mice, both IHD-J and WR mutant viruses were found to be significantly attenuated. These findings demonstrate that the 42-kDa glycoprotein of the EEV is required for efficient membrane enwrapment of INV, externalization of the virus, and transmission and that gp42 contributes to viral virulence in strains producing both low and high levels of EEV.
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PMID:Deletion of the vaccinia virus B5R gene encoding a 42-kilodalton membrane glycoprotein inhibits extracellular virus envelope formation and dissemination. 833 27

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

Vaccinia virus gene B5R encodes a M(r) 42K glycoprotein that is expressed throughout infection and forms part of the envelope of extracellular virus. In this paper deletion mutants (delta B5R) lacking the B5R open reading frame (ORF) from the Western Reserve (WR) and IHD-J strains of vaccinia virus have been constructed and shown to form very small plaques compared with the wild-type viruses. This phenotype was directly attributable to loss of the B5R gene since re-insertion of this gene from WR or IHD-J into the WR mutant lacking B5R (W-delta B5R) restored a normal plaque phenotype. In the latter case the failure of the revertant to form comets indicated that the nine amino acid differences in the B5R ORF between the IHD-J and WR strains of virus are not responsible for comet formation by IHD-J virus. Furthermore, the B5R deletion mutant of IHD-J (I-delta B5R) still formed small comets. Despite the small plaque phenotype of the deletion mutants, normal yields of intracellular naked virus (INV) were produced. In contrast, deletion of B5R had a profound affect on the formation of the extracellular enveloped virus (EEV). Transmission electron microscopy indicated that INV particles were not wrapped by a double layer of Golgi-derived membrane and enveloped particles were not detected within the cell or on the cell surface without expression of the B5R protein. Biochemical measurement of EEV formation, by labeling infected cells with [3H]thymidine followed by cesium chloride density gradient centrifugation of particles released from the cells 24 hr postinfection, showed that only 10% of WT levels of EEV were produced by I-delta B5R. The loss of the B5R ORF caused severe attenuation in intranasally infected mice. At doses between 10(4) and 3 x 10(7) plaque-forming units there were no signs of disease in animals infected with W-delta B5R, whereas at comparable doses the WR parent virus caused significant mortalities. Finally, an ORF with 93.4% amino acid identity to vaccinia WR B5R is present in variola major virus strain Harvey and the B5R protein was shown by Western blotting to be expressed by all orthopoxviruses tested.
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PMID:The vaccinia virus 42-kDa envelope protein is required for the envelopment and egress of extracellular virus and for virus virulence. 850 78

The vaccinia virus strain Western Reserve (WR) A34R gene encodes a C-type lectin-like glycoprotein, gp22-24, that is present in the outer membrane of extracellular enveloped virus (EEV) with type II membrane topology (S.A. Duncan and G.L. Smith, J. Virol. 66:1610-1621, 1992). Here we that a WR A34R deletion mutant (WR delta A34R) released 19- to 24-fold more EEV from infected cells than did WR virus, but the specific infectivity of the released virions was reduced 5- to 6-fold. Rupture of the WR delta A34R EEV outer envelope by freeze-thawing increased virus infectivity by five- to sixfold, because of the release of infectious intracellular mature virus. All other known EEV-specific proteins are incorporated into WR delta A34R EEV, and thus the loss of gp22-24 is solely responsible for the reduction of EEV specific infectivity. The WR delta A34R virus is highly attenuated in vivo compared with WR or a revertant virus in which the A34R gene was reinserted into WR delta A34R. This attenuation is consistent with the known important role of EEV in virus dissemination and virulence. Vaccinia virus strain International Health Department-J (IHD-J) produces large amounts of EEV and forms comets because of an amino acid substitution within the A34R protein (R. Blasco, R. Sisler, and B. Moss, J. Virol. 67:3319-3325, 1993), but despite this, IHD-J EEV has a specific infectivity equivalent to that of WR EEV. Substitution of the IHD-J A34R gene into the WR strain induced comet formation and greater release of EEV, while coexpression of both genes did not; hence, the WR phenotype is dominant. All orthopoxviruses tested express the A34R protein, but most viruses, including variola virus, have the WR rather than the IHD-J A34R genotype. The A34R protein affects plaque formation, EEV release, EEV infectivity, and virus virulence.
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PMID:Vaccinia virus glycoprotein A34R is required for infectivity of extracellular enveloped virus. 852 36

Factor VII (FVII) is a plasma vitamin K-dependent glycoprotein that plays an important role in the initiation of tissue factor-induced coagulation (extrinsic pathway of blood coagulation). An increase in FVII coagulant activity (FVIIc) has been proposed as an independent risk factor for coronary artery disease. Recently, the coagulation assay using soluble tissue factor(sTF) enables us to measure the plasma levels of the activated form of factor VII(FVIIa) without the effect of the FVII zymogen form. We have developed the fluorogenic assay for FVIIa using sTF and measured the plasma FVIIa in atherosclerotic diseases. The FVIIa level in the Japanese was lower than that reported in Caucasians, suggesting that the incidence of ishemic heart disease is lower in the former. The FVIIa level was higher in the patients with cardiovascular diseases (ischemic heart disease and cerebral infarction), non-insulin-dependent diabetic mellitus, hypertension with microalbuminuria, and renal failure than in the healthy controls. The FVIIa levels were also increased in non-insulin-dependent diabetic patients, and this FVIIa increase was positively correlated with urinary albumin excretion. Furthermore, FVIIa levels were not correlated with the levels of lipids and the activity of hepatic synthesis, indicating that FVIIa may be an independent risk factor for cardiovascular disease.
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PMID:[Activated factor VII as a new cardiovascular risk factor of atherothrombotic disease]. 856 29

Protein C is a circulating glycoprotein with anticoagulant properties. Functional and immunological levels of protein C were determined in 34 cases of ischaemic heart disease and 12 healthy age-matched controls. The sensitive colorimetric assay was used to determine the functional levels and ELISA for antigenic levels. Mean protein C activity and antigenic levels were found to be elevated in these patients as compared to controls. Protein C levels in the three individual subgroups-acute myocardial infarction, previous myocardial infarction and chronic stable angina pectoris-were also raised as compared to controls. The elevation was significant in the case of the acute myocardial infarction group. These results further support the hypothesis that the body synthesises increased amounts of protein C in ischaemic heart disease to compensate for the hypercoagulable state that exists in this disorder, thus playing a protective role.
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PMID:Protein C levels in ischaemic heart disease. 868 50


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