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)

The protein kinase activity in cytosol was similar in control, ischemic, and reperfused hearts; however, a 1.5-fold increase in membrane protein kinase activity was induced by ischemia and reperfusion. The H-7 inhibitable cytosolic protein kinase activity decreased by 40% with 30 min ischemia, while that of membrane fraction increased 1.8-fold. However, the CGS9343B inhibitable protein kinase activity in cytosolic fractions was unaffected by ischemia, while that of membrane increased by about 1.7-fold. These results suggest that myocardial ischemia is associated with enhanced protein kinase C and calmodulin-dependent kinase activities in membrane fraction. Furthermore, the results also suggest a translocation of protein kinase C activity from the cytosol to the membrane. Reperfusion of ischemic myocardium did not result in any further increase of protein kinase C and calmodulin-dependent kinase activities in the membrane. These enhanced protein kinase activities also resulted in an enhanced phosphorylation of endogenous membrane proteins. The creatine kinase released from the heart was increased by both ischemia and reperfusion. Therefore, these results suggest that biochemical cascades of reactions caused by enhanced membrane protein kinase C and calmodulin-dependent kinase activities may contribute to ischemic-reperfusion injury.
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PMID:Enhanced membrane protein kinase C activity in myocardial ischemia. 131 57

The immune cytotoxic mechanism of myocardial lesion was studied in 15 patients with non-specific myocarditis (NM) and in 10 patients with idiopathic congestive cardiomyopathy (ICC). In addition, 10 control patients having ischaemic heart disease (IHD) with congestive heart failure (CHF) and a control group of blood donors were examined. The following parameters were examined: anti-heart antibodies (by indirect enzyme-linked immunosorbent assay), lymphocyte sensibilization (by leucocyte migration inhibition test; the antigen used was cardiomyocyte membrane protein), and killer cells (K-cells) activity in the course of antibody-dependent cell-mediated cytotoxicity. Anti-heart antibodies were found in 73% of patients with NM, 50% patients with ICC and 33% patients with CHF. Lymphocyte sensibilization to the myocardium was found in 87% of patients with NM, and in more than half of the patients with ICC. Cardiospecific cytotoxic immune reaction was reproduced in vitro in 9 patients with NM and in 4 patients with ICC. It is assumed that an analogical mechanism of myocardial lesion functions in vivo.
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PMID:Immune cytotoxic mechanism of myocardial lesion in non-specific myocarditis and idiopathic congestive cardiomyopathy. 339 Oct 36

The levels of alpha-granule membrane protein (GMP-140) on the surface of platelet and serum TXB2 were determined in 55 patients with coronary heart disease (CHD) and 20 healthy individuals before and after exercise test. Among the 55 CHD patients, 36 had positive and 19 had negative results. The number of GMP-140 molecules on the platelet surface and serum TXB2 level were significantly increased in the patients with positive exercise test, P < 0.05. The increase was transient and GMP-140 returned to the preexercise level 15 minutes after the exercise test. In contrast, GMP-140 and TXB2 levels were not elevated in CHD patients with negative exercise test and also in normal subjects after exercise. The result indicates that platelet activation may be related to the exercise-induced myocardial ischemia in CHD patients.
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PMID:[The clinical significance of platelet activation during exercise-induced myocardial ischemia]. 752 Aug 51

Anticoagulant and antiplatelet function of NICM is weak, thereby presenting a hazard of coronary thrombus growth in patients subjected to coronary angiography. Similar antiplatelet effect was demonstrated for verapamil (V). The present study was designed to determine iopromide induced modifications in blood platelet membrane structure and aggregation in patients with primary hypertension and ischaemic heart disease receiving V compared to non-receivers of V. The blood for examinations was collected by Judkins' catheter placed in the vicinity of the coronary vessel ostium, and next centrifuged to obtain platelet-rich plasma. The ADP- and ristocetin (R)-induced blood platelet aggregation was determined by means of an aggregometer while their membrane structure was studied by electron paramagnetic resonance. The spin-label used, 4-maleimide-2, 2, 6, 6-tetramethyl-piperidine-1-oxyl (MSL) binds covalently to the -SH and -NH2 groups of platelet membrane proteins. The modifications in various spectral components, examined by means of a spectrometer, reflect conformational changes in these proteins. In non-receivers of V, iopromide diminished the aggregation, significantly in the case of ADP (p = 0.05), whereas in the receivers of V the iopromide-induced platelet aggregation examined with ADP did not change while with R was even enhanced (p = 0.05, Fig. 2). The platelet membrane protein conformation also changed due to iopromide: in non-receivers of V the accessibility of the above named groups for MSL was significantly reduced, p < 0.05, but in the receivers of V--inversely--significantly increased, p < 0.05. The results obtained confirm that in non-receivers of V, iopromide modifies the conformation of platelet membrane proteins which, in turn, may result in the lessening of the aggregation rate, favourable as regards the conditions of coronary thrombus growth. The tendency in the receivers of V was reverse and, however its nature remains obscure, this effect should be an indication for discontinuing the use of V several days before subjection the patient to coronary angiography.
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PMID:Verapamil influences the effect of nonionic contrast agent on platelet membrane structure and aggregation. 872 70

Increased platelet activation has been suggested as a possible reason for the increased vulnerability of depressed patients to ischemic heart disease (IHD). Translocation of P-selectin, an integral alpha-granule membrane protein, to the platelet surface is a measure of platelet activation. Herein, western blots of platelet plasma membranes containing P-selectin were quantified in patients with major depression (n=19; mean age=39 +/- 2 years) and healthy comparison subjects (n=17; mean age=36 +/- 2 years). None evidenced clinical signs of IHD, and only two patients had a lifestyle IHD risk factor (smoking). Blood was obtained from all 19 depressed patients before treatment, and 15 returned after 6-8 weeks of open-label bupropion treatment. Bupropion was chosen as the antidepressant because it did not elevate plasma norepinephrine or serotonin, endogenous agonists that can induce platelet degranulation. Western blotting revealed more P-selectin immunoreactivity (75 kD band) in depressed patients compared to healthy controls (P=0.003). After bupropion treatment, P-selectin remained high in depressed patients. beta3-Integrin, a reference plasma membrane protein that does not translocate during activation, was of equivalent density in depressed patients and healthy control subjects, and was unchanged after treatment with bupropion. P-Selectin failed to correlate with severity of illness based on the Hamilton Depression scale, or with the post-treatment plasma concentration of bupropion. The results suggest an elevation in P-selectin on platelet plasma membranes might be a trait marker for depression.
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PMID:Elevated P-selectin on platelets in depression: response to bupropion. 1116 7

To investigate the humoral immune response to the major outer membrane protein (MOMP) of Chlamydia pneumoniae, a fusion protein, thioredoxin-(His)6-MOMP (rMOMP) was produced in Escherichia coli and purified; this served as an antigen to establish an enzyme-linked immunosorbent assay (ELISA). Specific IgG and IgA antibodies against rMOMP were determined in sera from patients with ischemic heart disease. The findings were compared with those obtained by ELISA using the outer membrane protein complex (Hitazyme). The positivity rates for IgG antibody by rMOMP-ELISA were low (28%) compared with those by Hitazyme (72%). However, the positivity rates of IgA antibody by rMOMP-ELISA were similar to those by Hitazyme (76%). Interestingly, antigen positivity by immunohistochemical staining in the atherosclerotic lesions of coronary arteries was high in the groups with a high IgA titer of rMOMP-ELISA.
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PMID:Analysis of the serological response to Chlamydia pneumoniae in patients with ischemic heart disease by recombinant MOMP-ELISA. 1181 May 81

In HeLa cells the assembly of modified vaccinia virus Ankara (MVA), an attenuated vaccinia virus (VV) strain, is blocked. No intracellular mature viruses (IMVs) are made and instead, immature viruses accumulate, some of which undergo condensation and are released from the cell. The condensed particles may undergo wrapping by membranes of the trans-Golgi network and fusion with the plasma membrane prior to their release (M. W. Carroll and B. Moss, Virology 238:198-211, 1997). The present study shows by electron microscopy (EM), however, that the dense particles made in HeLa cells are also released by a budding process at the plasma membrane. By labeling the plasma membrane with antibodies to B5R, a membrane protein of the extracellular enveloped virus, we show that budding occurs at sites that concentrate this protein. EM quantitation revealed that the cell surface around a budding profile was as strongly labeled with anti-B5R antibody as were the extracellular particles, whereas the remainder of the plasma membrane was significantly less labeled. To test whether budding was a characteristic of MVA infection, HeLa cells were infected with the replication competent VV strains Western Reserve strain (WR) and International Health Department strain-J (IHD-J) and also prepared for EM. EM analyses, surprisingly, revealed for both virus strains IMVs that evidently budded at the cell surface at sites that were significantly labeled with anti-B5R. EM also indicated that budding of MVA dense particles was more efficient than budding of IMVs from WR- or IHD-J-infected cells. This was confirmed by semipurifying [(35)S]methionine-labeled dense particles or extracellular enveloped virus (EEVs) from the culture supernatant of MVA- or IHD-J-infected HeLa cells, respectively, showing that threefold more labeled dense particles were secreted than EEVs. Finally, although the released MVA dense particles contain some DNA, they are not infectious, as assessed by plaque assays.
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PMID:Plasma membrane budding as an alternative release mechanism of the extracellular enveloped form of vaccinia virus from HeLa cells. 1294 3

Despite the proven efficacy of current antithrombotic therapy in preventing ischemic heart disease (IHD), vascular events still occur. Our aims were i) to evaluate if combined oral treatment of clopidogrel and LA419, a novel nitric oxide donor with anti-ischemic and antiplatelet properties, provides additional antiplatelet effects to those of the blockade of P2Y(12) receptor; and ii) to gain insight into the mechanism behind LA419 antiplatelet effects. Pigs (n = 16) were randomized into four groups: 1) placebo-control; 2) LA419; 3) clopidogrel; and 4) LA419+clopidogrel. Both compounds were administered orally: LA419 0.9 mg kg(-1) twice daily for 10 days; clopidogrel 10 mg kg(-1) day the three last days. Antithrombotic effects were assessed by measuring platelet deposition (PD) triggered by denuded and disrupted vessel wall placed on the Badimon chamber. LA419 effects on platelet aggregation, hemodynamic parameters, and platelet protein expression upon in vitro thrombin stimulation were also evaluated. Total PD on denuded vessels was similarly reduced by all treatments with respect to placebo (p < 0.05). However, combination of LA419+clopidogrel largely reduced PD triggered by disrupted vessel wall by 80% versus placebo (p < 0.005), 15% versus clopidogrel alone (p < 0.01), and 30% versus LA419 alone (p < 0.005). All treatments inhibited collagen- and ADP-induced platelet aggregation, and no variations were detected in hemodynamic parameters. Proteomic analysis revealed that LA419 was associated with an increase in membrane protein disulphide isomerase (protein implicated in nitric oxide release). Treatment with LA419 may result in additional antiplatelet effect to that of clopidogrel in addition to restoring impaired endothelial dependent vasodilation without hemodynamic side effects. Further studies in IHD patients seem warranted.
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PMID:Protein disulphide isomerase-mediated LA419- NO release provides additional antithrombotic effects to the blockade of the ADP receptor. 1739 29

Sarcolipin (SLN) is a small molecular weight sarcoplasmic reticulum (SR) membrane protein expressed both in cardiac and skeletal muscle tissues. Recent studies using transgenic mouse models have demonstrated that SLN is an important regulator of cardiac SR Ca2+ ATPase 2a (SERCA2a). However, there is a paucity of information regarding the SLN protein expression in small versus larger mammals and its regulation during development and cardiac pathophysiology. Therefore, the major goal of this study was to generate an SLN specific antibody and perform detailed analyses of SLN protein expression during muscle development and in the diseased myocardium. The important findings of the present study are: (i) in small mammals, SLN expression is predominant in the atria but low in the ventricle and in skeletal muscle tissues, whereas in large mammals, SLN is quite abundant in skeletal muscle tissues than the atria, (ii) SLN and SERCA2a are co-expressed in all striated muscle tissues studied except ventricle and co-ordinately regulated during muscle development and (iii) SLN protein levels are approximately 3 fold upregulated in the atria of heart failure dogs and approximately 30% decreased in the atria of hearts prone to myocardial ischemia. In addition we found that in the phospholamban null atria, SLN protein levels are upregulated.
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PMID:Differential expression of sarcolipin protein during muscle development and cardiac pathophysiology. 1756 Nov 7

Obesity is endemic in many regions of the world and a forerunner of several serious and sometimes fatal diseases such as ischemic heart disease, stroke, kidney failure and neoplasia. Although we know its origin--it results when energy intake exceeds energy expenditure--at present, the only proven therapy is bariatric surgery. This is a major abdominal procedure that, for reasons that are largely unknown (it cannot be explained solely by a reduction in ventricular volume), significantly reduces energy intake, but because of cost and limited availability, it will most likely be reserved for only a small fraction of those who stand to gain from effective antiobesity treatment. Clearly, alternative ways to treat obesity are needed. Another way to combat excessive accumulation of white adipose tissue would be to increase energy expenditure. Rodents, hibernators and human infants all have a specialized tissue--brown adipose tissue (BAT)--with the unique capacity to regulate energy expenditure by a process called adaptive thermogenesis. This process depends on the expression of uncoupling protein-1 (UCP1), which is a unique marker for BAT. UCP1 is an inner mitochondrial membrane protein that short circuits the mitochondrial proton gradient, so that oxygen consumption is no longer coupled to adenosine triphosphate synthesis. As a consequence, heat is generated. Mice lacking ucp-1 are severely compromised in their ability to maintain normal body temperature when acutely exposed to cold and they are also prone to become obese. We have shown that, in mice, BAT protects against diet-induced obesity, insulin resistance and type 2 diabetes. This is based on prevention of excessive accumulation of triglyceride in non-adipose tissues such as muscle and liver. Ectopic triglyceride storage at these locations is associated with initiation of insulin resistance and, ultimately, development of type 2 diabetes.
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PMID:Brown adipose tissue in humans. 2093 66


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