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 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MR spectroscopy opens a window to the non-invasive evaluation of various aspects of cardiac metabolism. Experimentally, the method has extensively been used since 1970's. 31P-MR allows the registration of cardiac high-energy phosphate metabolism to non-invasively estimate the energetic state of the heart: ATP, phosphocreatine, inorganic phosphate, monophosphate esters and intracellular pH can all be quantitated. In conjunction with extracellular shift reagents such as [DyTTHA]3- or [TmDOTP]5-, 23Na- and 39K-MR allow the measurement of intra- and extra-cellular cation pools. 1H-MR spectroscopy allows the detection of a large number of metabolites such as, e.g. creatine, lactate, or carnitine. Human cardiac spectrocsopy has so far been confined to the 31P nucleus. Localization techniques (DRESS, ISIS, 3D-CSI etc.) are required to confine the acquired signal to the heart region. Relative quantification is straightforward (phosphocreatine/ATP ratio), absolute quantification (mM) is under development. Cardiac 31P-MR spectroscopy has research application in at least three clinical areas: (1) Coronary artery disease: A biochemical stress test for non-invasive ischemia detection (decrease of phosphocreatine with exercise) and viability assessment via quantification of ATP may become feasible. (2) Heart failure: The phosphocreatine/ATP ratio may provide an independent index for grading of heart failure, allow to monitor the longterm effects of different forms of drug therapy on cardiac energy metabolism in heart failure, and may also hold prognostic information on survival. (3) Valve disease: It is possible that the decrease of phosphocreatine/ATP can be used to guide the timing for the valve replacement. At the present time, no routine clinical applications can be defined for the use of human cardiac spectroscopy in patients with cardiac disease. However, the technique holds great potential for the future as a non-invasive approach to cardiac metabolism, and in coming years routine applications may become reality.
Mol Cell Biochem 1998 Jul
PMID:Clinical cardiac magnetic resonance spectroscopy--present state and future directions. 974 38

Myocardial hibernation, as first defined by Rahimtoola, is a state of chronic contractile dysfunction in patients with coronary artery disease which is fully reversible upon reperfusion. Clinical conditions consistent with the existence of myocardial hibernation include unstable and stable angina, myocardial infarction heart failure, and anomalous origin of coronary arteries. The mechanisms of hibernation are not known. Morphological alterations have been described in the hibernating area of patients, but these information are strongly affected by the diagnostic criteria utilized to screen patients. It has been postulated that hibernation is an adaptive phenomenon occurring during ischemia. In this context, downregulation of contraction is not regarded as a consequence of energetic deficit, but as a regulatory event aimed at reducing energy expenditure, thereby maintaining integrity and viability. Thus, hibernation might bear a relationship to the phenomenon of low-flow perfusion-contraction matching, or repetitive stunning or preconditioning. Clear-cut evidence for the mechanism of hibernation in the clinical setting seems likely to remain elusive, because of the nature of the studies needed to document it. Current experimental evidence supports the view that hibernation, stunning, preconditioning, or their coexistence can be responsible for regional myocardial contractile dysfunction which is reversible upon reperfusion. These are all adaptive and protective phenomena independent of their terminology and strict definitions and do not always apply to the extremely complex situation of myocardial ischemia in man.
Mol Cell Biochem 1998 Sep
PMID:Hibernating myocardium: its pathophysiology and clinical role. 977 1

Fibrinolysis is essential for maintaining the fluency of blood flow. Attenuated fibrinolytic activity has been frequently detected in coronary artery disease, peripheral vascular diseases, diabetes, hyperlipidaemia and obesity. The biologically active product of fibrinolytic system is plasmin. Generation of plasmin is regulated by plasminogen activators (PA) and their inhibitors (PAI). Vascular endothelial and smooth muscle cells synthesize tissue-type and urokinase-type PA (tPA and uPA) and their major physiological inhibitor, PAI-1. The production of fibrinolytic regulators is modulated by a number of biological factors related to thrombosis and atherosclerosis, including coagulation factors, hormones, growth factors, inflammatory mediators and lipoproteins. Several anticoagulants, including heparin, hirudin and hirulog-1, affect the production of fibrinolytic regulators in vascular cells. Studies in knockout mice demonstrated that mice deficient in PA or plasminogen are susceptible to thrombosis during inflammation or injury. Overexpression of uPA or deficiency of PAI-1 promotes neointima and aneurysm formation, which is probably due to active remodelling of extracellular matrix in vascular wall caused by excess plasmin. Long-term effect of treatment with thrombolytic agents or in atheroscleronic cardiovascular diseases remains to be defined. Future studies on determination of the role of PA and PAI in vascular remodelling may help understand the mechanism for neointima formation and orient the prevention of restenosis following vascular procedures.
Int J Mol Med 1998 Feb
PMID:Vascular cell-derived fibrinolytic regulators and atherothrombotic vascular disorders (Review). 985 42

Transplant coronary artery disease (TxCAD) is manifest as a diffuse, concentric intimal proliferation which results in occlusion of the allograft vessel lumen, and is responsible for limiting the long-term success of cardiac transplantation. The recent discovery of high circulating levels of anti-endothelial antibodies (AEAs) in patients with TxCAD has resulted in increased clinical and experimental research interests in understanding their patho-physiological roles in TxCAD. Increasing evidence suggests that AEAs are cross-reactive towards an endothelial protein doublet of 56-58 kDa which has now been characterised and identified as the cytoskeletal protein vimentin. Despite this recent progress the immunopathogenesis of TxCAD remains unclear. In this review recent developments and mechanisms of the involvement of AEAs in the immunopathogenesis of TxCAD are discussed.
Int J Mol Med 1998 Feb
PMID:The role of anti-endothelial antibodies in the immunopathogenesis of transplant associated coronary artery disease (Review). 985 48

Accelerated transplant coronary artery disease (TxCAD) results in increased expression of antiendothelial antibodies whose target antigens remain largely unidentified. One of these endothelial antigens has been identified as vimentin, a cytoskeletal protein present in cells of the blood vessel walls. In the present study, SDS-PAGE and Western blot analysis of human endothelial cell (EAHy 926) lysates probed with sera from a TxCAD patient were used to confirm immunoreactivity of antiendothelial antibodies towards several endothelial proteins. To further elucidate the identity of these putative antigens, a human endothelial cell (EAHy 926) cDNA expression library was immunoscreened with serum obtained from a TxCAD patient. Two positive cDNA clones were identified by partial nucleotide sequence analysis and GenBank/EMBL database searches for homology as the 85 kDa human CD36 antigen (a cell surface glycoprotein expressed in various cells including epithelial and endothelial cells) and a 50 kDa keratin-like protein (a member of the intermediate filament protein expressed in epithelial cells). These results are the first to demonstrate that human CD36 antigen and a keratin-like protein may be additional target proteins for the anti-endothelial antibodies associated with TxCAD.
Int J Mol Med 1998 Jun
PMID:Identification of endothelial antigens relevant to transplant coronary artery disease from a human endothelial cell cDNA expression library. 985 39

Hypoxia is thought to be a common precursor of coronary artery disease and malignant tumors, both diseases representing the leading causes of death in industrial nations. So far, investigations of oxygen-regulated erythropoietin (EPO) gene expression in the human hepatoma cell lines Hep3B and HepG2 allowed many important insights into the mechanisms of oxygen-sensing, signalling and regulation of an increasing number of oxygen-responsive genes. To differentiate the various signalling pathways involved in EPO production by these two cell lines, we examined several factors that positively influenced EPO expression. The results demonstrate a keen differential effect of cell density and oxygen concentration on EPO induction in Hep3B compared to HepG2 cells. Using optimized cell culture conditions, EPO production rates as high as 1 U EPO per 10(6) Hep3B cells in 24 h could be achieved. We also found a moderate but reproducible positive effect of CoCl2 on hypoxia-induced EPO expression in Hep3B but a negative CoCl2 effect on hypoxic induction in HepG2 cells. CoCl2 inhibited cell growth in a concentration-dependent manner. Interleukin-6 was synergistic with hypoxia on EPO induction in Hep3B as well as HepG2 cells, and dexamethasone enhanced this effect in Hep3B but not in HepG2 cells. The moderate CoCl2-dependent increase of EPO production observed in hypoxic Hep3B cells might indicate that CoCl2 and hypoxia do not necessarily act via, identical signalling pathways.
Int J Mol Med 1998 Sep
PMID:Optimal erythropoietin expression in human hepatoma cell lines requires activation of multiple signalling pathways. 985 4

In view of the clinical importance of lipoprotein(a) [(Lp(a)] in coronary artery disease (CAD), we investigated the apo(a) size polymorphism, sequence polymorphisms of five base repeats [(TTTTA)n] in the noncoding region, and of Met/Thr in the coding region of the apolipoprotein(a) [apo(a)] gene. The apo(a) polymorphisms were examined in 184 Korean patients with CAD and 121 healthy subjects. In size polymorphism, there was an inverse association between plasma Lp(a) levels and the apo(a) isoforms in the CAD group (p < 0.005). For (TTTTA)n sequence polymorphism, subjects with the 8/8 genotype were most frequently observed in the two groups. Plasma Lp(a) levels showed a significant difference between the 8/5 versus the 8/8 genotype in the CAD group. On the other hand, Lp(a) levels varied significantly among the genotypes of a Met/Thr polymorphism in normal controls (P < 0.01). The heterozygous genotype had an intermediate level of Lp(a) between the two homozygous genotypes, thereby showing gene dosage effect. Thus, it is possible that the apo(a) polymorphisms are responsible for variations in the Lp(a) levels.
Mol Cells 1998 Oct 31
PMID:Association between apolipoprotein(a) polymorphism and Lp(a) levels in Koreans. 985 41

Familial hypercholesterolemia (FH), a monogenic disease known to be caused by low-density lipoprotein receptor (LDLR) gene mutations, results in the development of premature atherosclerosis and coronary artery disease in affected individuals. The spectrum of LDLR gene mutations in Russia is poorly known. Using polymerase chain reaction (PCR)-single-strand conformational polymorphism (SSCP) analysis, followed by DNA sequencing, we have screened selected exons of the LDLR gene in 80 unrelated St. Petersburg FH patients for the presence of mutations. Two new LDLR gene mutations, 347delGCC and E397X, were characterized among individuals with familial hypercholesterolemia in St. Petersburg. The carriers of both mutations possessed highly elevated blood serum cholesterol. Cosegregation of E397X mutation and LDLR gene RFLP haplotypes with hyperlipidemia was demonstrated by family study. Both mutations seem to be specific to Slavic patients.
Mol Genet Metab 1998 Dec
PMID:Two novel low-density lipoprotein receptor gene mutations (E397X and 347delGCC) in St. Petersburg familial hypercholesterolemia. 988 19

Cultured human endometrial stromal cells respond to the gonadal steroids, progesterone and 17beta-estradiol, with morphological and biochemical changes that are characteristic of decidualization in vivo. To date, the cellular mechanisms involved in the terminal differentiation of human endometrial stromal cells into decidual cells remain poorly understood. We have recently determined that the novel cadherin subtype, known as cadherin-11, is expressed by endometrial stromal cells undergoing decidualization during the luteal phase of the menstrual cycle and the decidua of pregnancy. In these studies, we have examined cadherin-11 mRNA and protein expression levels in human endometrial stromal cells undergoing steroid-mediated decidualization in vitro. Progesterone or a combination of progesterone and 17beta-estradiol increased stromal cadherin-11 mRNA and protein expression levels with time in culture. Maximum levels of cadherin-11 expression in these cell cultures correlated with a marked increase in IGFBP-1 mRNA levels, a biochemical marker of decidualization. In contrast, 17beta-estradiol had no effect on stromal cad-11 mRNA and protein expression or the levels of the IGFBP-1 mRNA transcript. Taken together, these observations demonstrate that cadherin-11 mRNA and protein expression levels are up-regulated during the terminal differentiation of endometrial stromal cells-suggesting that this cell adhesion molecule may serve as a useful cellular marker for decidualization.
Mol Reprod Dev 1999 Feb
PMID:Cadherin-11 is a hormonally regulated cellular marker of decidualization in human endometrial stromal cells. 989 Jul 46

Advancing age is associated with increased risk of coronary artery disease. Changes in fatty acid metabolism affect important cellular membrane properties and functions which may contribute to the vascular pathophysiology of aging. This study was designed to investigate the effects of aging on the fatty acid composition of the plasma, liver, aorta, and renal artery in 4-, 15-, and 24-month old Fischer 344 rats, an animal model for aging. With aging, the levels of total polyunsaturated fatty acids (PUFA) increased in the plasma, aorta, and renal artery. The major changes in the liver fatty acid profile were increases in the levels of 18:2n6 and 18:3n3 and a decrease in the levels of 20:3n6 and 20:5n3. The results indicate that significant shifts occur in the levels of n6 and n3 PUFA in the plasma, liver, and vasculature with aging. The alterations in the fatty acid composition may be a pathogenetic mechanism of the vascular changes associated with aging.
Biochem Mol Biol Int 1998 Dec
PMID:Age-related changes in plasma and tissue fatty acid composition in Fischer 344 rats. 989 44


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