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

HeLa, SIRC, and RK-13 cells were compared as to their production of intracellular naked vaccinia virus (INV) and extracellular enveloped vaccinia virus (EEV) after infection with vaccinia strains WR and IHD-J. IHD-J produced more EEV from all three cell lines than did WR, although both strains produced approximately the same quantity of INV. The most efficient EEV release was from RK-13 cells infected with IHD-J, which was 200 times more than from WR-infected SIRC cells. This permitted for the first time the purification of milligram quantities of EEV that contained much fewer cell protein contaminants than could be obtained from HeLa or SIRC cells. The INV surface proteins 200K, 95K, 65K, and 13K were present in both HeLa and RK-13 cell-derived INV but were absent in SIRC cell INV. These proteins were absent in EEV from all three cell lines. Four glycoproteins of molecular weights 210 x 10(3) (210K), 110K, 89K, and 42K and five glycoproteins in the 23K to 20K range plus a nonglycosylated protein of 37K were detected in EEV from the hemagglutinin-positive IHD-J vaccinia strain. The 89K glycoprotein was not present in EEV or membranes from cells infected with the hemagglutinin-negative vaccinia strain IHD-W. Antisera to IHD-W lacking hemagglutinin-inhibiting antibodies did not precipitate the 89K glycoprotein of IHD-J. The only glycoprotein that specifically attached to rooster erythrocytes was the 89K glycoprotein. This evidence indicates that the 89K glycoprotein is the vaccinia hemagglutinin.
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PMID:Identification of the vaccinia hemagglutinin polypeptide from a cell system yielding large amounts of extracellular enveloped virus. 50 96

Insulin-dependent diabetic patients with diabetic nephropathy have a highly increased morbidity and mortality from cardiovascular diseases. To determine whether altered levels of apolipoprotein(a) (apo(a)), the glycoprotein of the potentially atherogenic lipoprotein(a) (Lp(a)), contribute to the increased risk of ischaemic heart disease, apo(a) was determined in 50 insulin-dependent diabetic patients with diabetic nephropathy (group 1), in 50 insulin-dependent diabetic patients with microalbuminuria (group 2), in 50 insulin-dependent diabetic patients with normoalbuminuria (group 3), and in 50 healthy subjects (group 4). The groups were matched with regard to sex, age and body mass index. The diabetic groups were also matched with regard to diabetes duration. The level of apo(a) was approximately the same in the four groups, being: 122 (x/ divided by 4.2) U l-1, 63 (x/ divided by 4.4) U l-1, 128 (x/ divided by 3.5) U l-1 and 126 (x/ divided by 3.7) U l-1 (geometric mean (x/ divided by antilog SD)) in group 1, 2, 3 and 4, respectively. 1 U l-1 apo(a) approximates 0.7 mg l-1 Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoprotein(a) in insulin-dependent diabetic patients with and without diabetic nephropathy. 141 Dec 63

Nucleotide sequence analysis of a 42-kb region of the vaccinia virus (strain Western Reserve) genome identified a gene with the potential to encode a 35.1-kDa polypeptide with properties of a membrane glycoprotein (Smith et al., J. Gen. Virol. 72, 1349-1376, 1991). The 317 amino acid open reading frame (ORF) has similarity with complement control proteins and a secretory vaccinia virus protein (C28K) which interferes with complement function. The predicted B5R gene product differs from the latter protein in that it contains a C-terminal hydrophobic sequence and may be membrane-associated rather than secretory. Transcriptional mapping by Northern blotting and S1 nuclease protection showed that the gene is transcribed both early and late during infection, with the early RNA start site located 60 bp upstream of the late start site that is present at -9 to -5 bp relative to the ORF. Nevertheless, translation of early and late mRNAs are predicted to produce the same polypeptide. A rabbit antiserum was raised to the predicted external hydrophilic domain of B5R expressed in Escherichia coli and used to immunoprecipitate a M(r) 42 K protein from vaccinia-infected cells. This protein was synthesized throughout infection, with a peak from 6 to 7 hr, and its production was inhibited by tunicamycin but not monensin. Western blotting of proteins from purified extracellular enveloped virus (EEV) or intracellular naked virus with anti-B5R serum showed that this M(r) 42 K protein and two higher molecular weight forms (Mr82 and 87 K) were present only in EEV. Anti-B5R serum inhibited comet formation by the IHD-J strain of virus on RK13 cells. B5R is the third vaccinia gene shown to encode an EEV glycoprotein, the others being the virus hemagglutinin gene, and gene SalL4R which encodes a group of lectin-like glycoproteins of M(r) 22-24 K.
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PMID:A constitutively expressed vaccinia gene encodes a 42-kDa glycoprotein related to complement control factors that forms part of the extracellular virus envelope. 158 49

Although previous studies have demonstrated that complement (C)5a causes myocardial ischemia and mechanical dysfunction, the cardiac response of endogenously produced C5a and C5a des-Arg in zymosan-activated serum (ZAS) and the critical role of granulocytes in this process are poorly understood. Therefore, we compared the coronary and cardiac effects of ZAS and purified C5a and investigated the role of leukocyte adhesion-promoting receptors (i.e., CD11/CD18). Like purified C5a, ZAS (0.5 ml) significantly reduced coronary artery blood flow and regional segment shortening, whereas coronary venous granulocyte concentration and myocardial lactate extraction were significantly decreased. A monoclonal antibody (MoAb) to C5a/C5a des-Arg attenuated ZAS-induced cardiac alterations. Three minutes of continuous infusion of C5a or ZAS induced sustained decreases in coronary venous granulocyte concentrations, although coronary flow and segment shortening returned to control levels after 2 min. Another MoAb, IB4, directed against CD18, significantly inhibited ZAS-induced granulocyte extraction and associated cardiac effects. Thus, cardiac dysfunction occurs after activation of the complement cascade with zymosan resulting in extraction of granulocytes mediated by the CD18 adherence glycoprotein. Furthermore, intramyocardial retention of granulocytes appears necessary for the initial and full ZAS-induced cardiac dysfunction.
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PMID:Role of granulocytes and C5a in myocardial response to zymosan-activated serum. 167 37

As a result of their ability to transport oxygen, PFC emulsions are being investigated for possible use in a wide variety of conditions. The recent FDA approval of F-DA to diminish myocardial ischemia during angioplasty is the first marketing approval for such a product in the world. The many potential uses of such products may result in their common application in the future, especially as new and better products are developed. The elimination, distribution, and tissue retention of PFC emulsions as well as the physiological changes that occur upon their administration have been the subject of many investigations. The results indicate that these agents may influence the pharmacokinetic properties of other drugs by a wide variety of mechanisms. Several studies have shown significant, but not necessarily consistent, changes in drug elimination and distribution following PFC emulsion infusion. Changes appear dependent on the drug examined, emulsion utilized, degree of blood exchange, species utilized, and the controls chosen for comparison. Often, the changes are time dependent indicating the importance of conducting long-term studies. While PFC emulsions do not appear to alter renal elimination of drugs, several studies have demonstrated that these agents have the potential to induce drug metabolism from several days to possibly months after exposure. Observed changes in drug volumes of distribution, which are often time dependent, may be due to changes in normal drug transport throughout the circulation and/or changes in membrane permeability and cell transport mechanisms. Changes in drug transport may result from depletion of plasma proteins or increases in alpha 1-acid glycoprotein levels due to trauma or PFC emulsion effects. The binding of drugs by PFC emulsion droplets varies greatly and PFC emulsion components displace some plasma protein bound drugs. The wide variability in the results and conclusions of the pharmacokinetic studies conducted to date emphasize the importance of utilizing adequate controls to identify which alterations are PFC emulsion specific.
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PMID:Perfluorochemical erythrocyte substitutes: disposition and effects on drug distribution and elimination. 193 77

The activation and accumulation of leukocytes during inflammatory processes such as that initiated by myocardial ischemia and reflow appear to be major determinants of irreversible tissue injury. Myocardial salvage by dual cyclooxygenase/lipoxygenase inhibitors and selective 5-lipoxygenase inhibitors has suggested a role for lipoxygenase (LOX) products, such as the potent chemotactic factor leukotriene B4, in ischemia-reflow injury. However, many LOX inhibitors are antioxidants and several have been shown to directly inhibit neutrophil function in vitro, thereby questioning the role of LOX products in reperfusion injury. To clarify further the protective mechanism of lipoxygenase inhibitors, we have examined the effects of two nonantioxidant inhibitors, SK&F 86002 and REV-5901, on human neutrophil activation and function in vitro. The antioxidant LOX inhibitor nordihydroguiaretic acid, which served as a positive control, exhibited a concentration-dependent inhibition of N-formyl-methionyl-leucyl-phenylalanine (fMLP) and recombinant C5a-induced neutrophil bipolarization, fMLP-induced upregulation of the adherence glycoprotein Mac-1 (CD11b/CD18), fMLP-induced aggregation and neutrophil adherence to and migration through interleukin-1-stimulated human endothelial monolayers. In contrast, neither SK&F 86002 nor REV-5901 (in concentrations up to 50 microM) had any effect on these functions, nor did they inhibit neutrophil oxidative metabolism (phorbol myristate acetate-induced chemiluminescence). Inasmuch as both of these agents have been observed to reduce myocardial ischemia-reflow injury in vivo, their failure to directly inhibit neutrophil function further supports an important role for chemotactic LOX products in the pathogenesis of reperfusion injury.
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PMID:Comparison of antioxidant and nonantioxidant lipoxygenase inhibitors on neutrophil function. Implications for pathogenesis of myocardial reperfusion injury. 215 49

In patients with various forms of ischemic heart disease the following indices were examined by radial immunodiffusion: alpha-1-acid glycoprotein, alpha-1-antitrypsin, haptoglobin, alpha-2-glycoprotein, beta-2-glycoprotein, immunoglobulin, C3 and C4 complement fractions. The changes in the serum glycoproteins during the acute phase of myocardial infarction are pointed out. The changes in the immunoglobulins and the complement fractions in patients with ischemic heart disease are discussed. Their determination in patients with stenocardia and past myocardial infarction is of no diagnostic value.
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PMID:[Ischemic heart disease--clinical, biochemical and immunobiological parallels]. 321 29

A monoclonal antibody (904) that binds to a leukocyte cell adhesion-promoting glycoprotein, (Mo1; CD11b/CD18) was administered (1 mg/kg, iv.) to open chest anesthetized dogs 45 min after the induction of regional myocardial ischemia. Ischemia was produced by occluding the left circumflex coronary artery (LCX) for 90 min and then reperfusing for 6 h. There was no difference between control and antibody treated groups with respect to arterial blood pressure, heart rate, or LCX blood flow. Administration of antibody produced no observable effect on circulating neutrophil counts, suggesting that antibody-bound neutrophils were not cleared from the circulation. The mean size of myocardial infarct expressed as percentage of the area at risk of infarction that resulted was reduced by 46% with anti-Mo1 treatment (25.8 +/- 4.7%, n = 8) compared to control (47.6 +/- 5.7%, n = 8; P less than 0.01). The area at risk of infarction was similar between groups. Circulating (serum) antibody excess was confirmed in all 8 anti-Mo1 treated dogs by immunofluorescence analysis. Analysis of ST segment elevation on the electrocardiogram as an indicator of the severity of ischemia suggests that the anti-Mo1 reduces infarct size independent of the severity of ischemia. An additional group of dogs (n = 5) was tested with a control monoclonal antibody of the same subtype (murine IgG1) and was found to produce no significant reduction in myocardial infarct size. Accumulation of neutrophils within the myocardium was significantly attenuated with 904 treatment when analyzed by histological methods. These data demonstrate that administration of anti-Mo1 monoclonal antibody after the induction of regional myocardial ischemia results in reduced myocardial reperfusion injury as measured by ultimate infarct size.
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PMID:Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. 333 35

The elimination kinetics of disopyramide was studied in 9 patients with decreased hepatic function (DHF) due to histologically verified cirrhosis of the liver, and in 11 patients with ischaemic heart disease (IHD). Disopyramide 100 and 150 mg was given intravenously as a bolus to the patients with IHD and DHF, respectively, followed by a continuous infusion of disopyramide 0.3 (DHF group) and 0.4 mg X min-1 (IHD group) until steady-state was achieved. A significant (p less than 0.001) positive correlation between the percentage unbound and total serum concentration of disopyramide was demonstrated in both groups. The percentage of unbound disopyramide at a total serum concentration of 5.9 mumol X l-1 was 45.5% and 19.4% in the DHF and IHD groups, respectively. A negative correlation (r = -0,751, p less than 0.05, and r = -0.827, p less than 0.01 in the IHD and DHF patients, respectively) between the free fraction of disopyramide and alpha 1-acid glycoprotein was observed. The serum concentration of alpha 1-acid glycoprotein, the major binding protein of disopyramide, was significantly lower in the patients with DHF. The clearance of unbound disopyramide and its total volume of distribution and half-life were significantly lower in the DHF patients. No difference in total elimination clearance could be demonstrated. The clinical implication of the present findings appear to be that the dosage of disopyramide should be reduced by 25% when it is given intravenously to patients with decreased hepatic function.
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PMID:Kinetics of disopyramide in decreased hepatic function. 378 Aug 31

Protein binding of disopyramide, binding capacities, affinity constants and serum concentrations of alpha 1-acid glycoprotein (AAG) were studied in five groups of patients. A: young healthy volunteers (n = 8); B: elderly patients with minor symptoms of ischaemic heart disease (n = 9); C: patients with cirrhosis of the liver and normal values of coagulation factors (II, VII and X), albumin and immunoglobulin G (n = 8); D: patients with cirrhosis and at least two abnormal of the previously mentioned values (n = 9) and E: eleven patients with severely impaired renal function. Subfractions of AAG (Fr1, Fr2 and Fr3) were determined by affinoimmunoelectrophoresis. AAG concentration was significantly (P less than 0.005) elevated in group E patients and decreased (P less than 0.025) in group D patients. Fr2 is probably associated with the high affinity, first binding site of disopyramide to AAG. Earlier observations of a reduced qualitative binding of disopyramide in patients with cirrhosis can be explained by a significant decrease in Fr2 (P less than 0.001) in group D patients. The protein binding of disopyramide in patients with uraemia was significantly increased due to a significant (P less than 0.005) increase in AAG concentration in spite of a smaller (P less than 0.025) affinity constant. Suggestions for therapeutic drug monitoring based on total serum concentrations are given.
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PMID:Quantitative and qualitative binding characteristics of disopyramide in serum from patients with decreased renal and hepatic function. 381 61


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