Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial ischemia is associated with profound electrophysiologic derangements which occur within minutes and are rapidly reversible with reperfusion, suggesting that subtle and reversible biochemical alterations within or near the sarcolemma contribute. Our efforts have concentrated on two structurally similar amphipathic metabolites, long-chain acylcarnitine and lysophosphatidylcholine. Studies performed in vitro in isolated tissue indicate that incorporation of either metabolite into the sarcolemma at concentrations of 1-2 mole %, as verified using electron microscopic (EM) autoradiography, elicits profound electrophysiologic derangements analogous to those seen in the ischemic heart in vivo. In isolated myocytes in vitro, the electrophysiologic derangements elicited by hypoxia are associated with a marked 70-fold increase in the endogenous sarcolemmal accumulation of long-chain acylcarnitine. Inhibition of carnitine acyltransferase I (CAT-I) not only prevents the accumulation of long-chain acylcarnitine in isolated myocytes exposed to severe hypoxia, but also markedly attenuates the electrophysiologic alterations. Several lines of experimental evidence, including measurements in venous effluents as well as cardiac lymph, indicate that lysophosphatidylcholine (LPC) accumulates to a large extent in the extracellular space during ischemia. This extracellular accumulation may be secondary to release from vascular endothelium, smooth muscle or blood cell elements. In crude homogenates of myocardial tissue, the total enzymic activity for catabolism of LPC far exceeds the total activity for synthesis of LPC mediated by phospholipase A2 (PLA2) catalyzed hydrolysis of phosphatidylcholine (PC). Therefore, inhibition of catabolism would be required for net accumulation of LPC to occur. Three enzymes responsible for the catabolism of LPC are inhibited by either long-chain acylcarnitine or acidic pH. Thus, accumulation of long-chain acylcarnitine and acidosis contribute to the increase in LPC observed in ischemic tissue. In this report, we provide evidence that accumulation of long-chain acylcarnitine occurs very rapidly in ischemic myocardium in vivo, coincident with the development of electrophysiologic alterations leading to malignant arrhythmias as verified using 3-dimensional cardiac mapping procedures. Following a brief, 2-min period of ischemia, long-chain acylcarnitine content increased four-fold in the ischemic region, concomitant with the development of electrophysiologic abnormalities observed during this period. Additionally, we demonstrate that modification of intracellular lipolysis by beta-adrenergic receptor stimulation or blockade does not influence long-chain acylcarnitine accumulation following this 2-min interval of ischemia. These results suggest that production of long-chain acylcarnitine is not limited by the intracellular free fatty acid concentration early in ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Amphipathic lipid metabolites and their relation to arrhythmogenesis in the ischemic heart. 203 71

So-called pseudovascular spaces, said to occur in 10% of benign pigmented nevi, are presumed to be shrinkage artifacts of tissue processing. In an attempt to characterize the cells lining these spaces, three benign pigmented nevi were studied with immunoperoxidase techniques. It was found that they stained positively with an anti-melanoma antibody, P97a (gamma-2a), but negatively with an antibody against an antigen-related factor VIII, which is a marker for vascular endothelium. We conclude that these spaces are lined by melanocytes of nevi and that the spaces are not truly vascular. In one specimen, the spaces were filled with erythrocytes, which suggest that the spaces were present before fixation. It has been suggested, though, that altered collagen and elastic tissue and the nevi themselves may diminish the resistance of the dermis to the mechanical stress of the biopsy procedure, which results in the formation of these spaces.
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PMID:Identification of cells lining pseudovascular spaces of benign pigmented nevi. 608 57

Both beta 1- and beta 2-adrenergic receptors have been previously described in normal human placental homogenates; the cells upon whose surface membranes these receptors reside have not been identified. In order to show that a beta 1-adrenergic receptor is present on trophoblastic cells, the cells which mediate maternal-fetal transport and produce placental hormones, beta-adrenergic receptors were demonstrated in membrane fractions of human hydatidiform mole. Microscopic sections of the mole samples used demonstrated edematous villi lined by trophoblastic cells with minimal nontrophoblastic (stromal or vascular) contamination compared with placenta. (--)-[3H]Dihydroalprenolol [(--)-[3H]DHA] binding to molar membranes was reversible and saturable to a single class of sites (Kd = 0.97 +/- 0.12 nM; n = 7; maximum binding capacity, 72.9 +/- 6.4 fmol/mg protein). (--)-[3H]DHA binding was associated with catecholamine-stimulated adenylate cyclase activity. Agonist competition for the molar beta-adrenergic receptor showed the order of potency to be (--)isoproterenol much greater than norepinephrine = epinephrine, characteristic of a beta 1-adrenergic receptor subtype. Competition for (--)-[3H]DHA binding to trophoblastic membranes by the beta-adrenergic receptor subtype-specific agents metoprolol (beta 1 selective) and zinterol (beta 2 selective) was also characteristic of a homogeneous subtype of beta 1-adrenergic receptors. Because beta 1-adrenergic receptors alone were seen on trophoblast cells, the beta 2-adrenergic receptor in placenta must reside on nontrophoblastic elements (stromal or vascular endothelium). No differences in beta-adrenergic receptor binding were seen related with ploidy (2 or 3 N), the presence or absence of a fetus, or the progression of the mole to choriocarcinoma. Two choriocarcinoma cell lines, BeWo and JEG-3, however, showed no specific (--)-[3H]DHA binding. Human trophoblast contains beta 1-adrenergic receptors coupled to catecholamine-sensitive adenylate cyclase, supporting a role for catecholamines in the regulation of placental metabolism.
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PMID:Trophoblastic cells of the hydatidiform mole contain a beta 1-subtype adrenergic receptor. 628 22

Low-density lipoprotein (LDL) and oxidized low-density lipoprotein (OxyLDL) have previously been shown to inhibit vasorelaxation caused by endothelium-derived relaxing factor (EDRF). The purpose of the present study was to directly determine the effects of LDL and OxyLDL on EDRF bioactivity and nitric oxide (NO) production in vascular endothelium to further understand the mechanism whereby lipoprotein alters vascular reactivity. Cultured bovine aortic endothelial cells were incubated with either LDL or OxyLDL for 1 hour. After washing the cells free of lipoprotein, agonist-stimulated (bradykinin; BK) EDRF bioactivity and NO content of the effluent were quantitated. These results were compared with control cells not exposed to lipoprotein. In a second series of experiments, the effects of LDL and OxyLDL on EDRF-mediated increases in cyclic guanosine monophosphate (cGMP) in a reporter fibroblast cell line were determined. Last, the direct effects of LDL on NO-induced vasodilation of isolated coronary artery rings were determined by using standard in vitro isometric recording methods. LDL and OxyLDL significantly decreased EDRF bioactivity but not NO production by endothelial cells. When expressed as percent relaxation of the biodetector per mole of NO produced, both LDL and OxyLDL resulted in the release of a significantly less-potent vasodilator than that derived from control cells. In the reporter fibroblast experiments, there was no significant difference in the amount of cGMP generated by fibroblasts in response to medium from control and lipoprotein-treated cells. In isolated ring experiments, LDL did not directly alter NO vasorelaxation. We conclude that both LDL and OxyLDL inhibit EDRF-induced vasorelaxation by complex mechanisms other than the direct inhibition of NO synthesis by endothelial cells or extracellular inactivation of EDRF. LDL and OxyLDL may result in the release of a less potent NO-containing relaxing factor by altering the metabolism of an endogenous nitrosovasodilator.
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PMID:The effects of native LDL and oxidized LDL on EDRF bioactivity and nitric oxide production in vascular endothelium. 796 25

The University of Wisconsin's (UW) solution has been used commonly for current liver transplantation. However, its effect on the vascular endothelium remains unclear. Experiments were designed to study the effects. Human hepatic arteries harvested from patients with hepatocellular carcinoma undergoing liver resection were preserved in 4 degree C physiological solution (group 1, the content showed on the text) and UW solution (group 2) for 1 hr. Segments of preserved and control (group 3) hepatic arteries were suspended in organ chamber to measure the isometric force. The relaxations to acetylcholine (ACH) and adenosine diphosphate in segments of hepatic artery with endothelium were significantly greater than those segments without endothelium. The maximal relaxation to ACH in arterial segments with endothelium of group 2 was significantly different from those of group 1 and 3 (group 1 to group 3, 82 +/- 2%, 57 +/- 6%, and 83 +/- 4% of the initial tension contracted by neoepinephrine (3 X 10-7 mole/l, P < 0.05). The maximal relaxation to adenosine diphosphate was similar to the response to ACH. Perfusate hypoxia (oxygen tension 30 +/- 5 mmHG) caused endothelium-dependent contraction of the arterial segments (group 1 to group 3, 233 +/- 32%, 276 +/- 35%, and 251 +/- 40% of the initial tension, P < 0.05). Endothelium-independent relaxation and contraction of human hepatic artery to sodium nitroprusside and norepinephrine were not altered by UW solution. In summary, the impaired endothelium-dependent relaxation by UW solution and prominent endothelium-dependent contraction to hypoxia of human hepatic artery would favor vasospasm and thrombus formation after liver transplantation.
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PMID:The endothelium-dependent response of human hepatic artery after preservation with the UW solution. 865 29