Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Bedside measurements of a somatosensory-evoked response, of hemispheral blood flow, and of Doppler flow velocity, therefore, add objective criteria to the other available means of assessment of the condition of an aneurysm patient. Angiography can never be superseded; CT scan with the assessment of the density and distribution of subarachnoid blood has been shown to be of considerable value in relation to spasm, and the fundamental analysis, the view from the foot of the bed by an experienced clinician, can, therefore, be expanded in a variety of collateral ways, all of which will lead over the next few years, to fresh and increased understanding of the vexing question of vasospasm.
Mol Chem Neuropathol 1990 Jan
PMID:Bedside monitoring in subarachnoid hemorrhage. Evoked responses, hemispheral blood flow, and flow-velocity measurements. 227 3

Arterial sensitivity to vasospasm was assessed prior to and 2 weeks following a 15-min period of external compression of the superficial femoral artery in dogs. Compression was achieved by placing a plastic cuff around the artery to produce a 40-60% reduction in the artery cross-sectional area. An additional six dogs were used to assess morphologic changes produced in the artery immediately and at 2 weeks after compression. Angiography following intraarterial infusions of serotonin (10 and 30 micrograms/min), norepinephrine (0.1 microgram/min), ergonovine (20 micrograms/min), and the thromboxane mimic U-46,619 (0.1 microgram/min) demonstrated a specific sensitivity to serotonin 2 weeks after the 15-min application of external arterial compression. The serotonin response was antagonized by the specific serotonin (5-HT2) receptor antagonist, ketanserin. Scanning electron microscopy of the acutely injured luminal surface revealed loss of endothelium and deposition of platelets. Patchy areas with intact endothelium and migrating leukocytes were located within the denuded sites. Two weeks after constrictor placement, the compressed area appeared as a raised or semiraised lesion in which the orientation and shape of the luminal cells were distinctly delineated from the adjacent noninjured segments. However, the luminal cells appeared to be endothelium that had regrown over the previously denuded area. The results of this study demonstrate, in an in vivo model, an enhancement in serotonin-mediated vasoconstriction following intimal injury and repair and support the suggestion that endothelial damage or dysfunction may play a role in the pathophysiology of arterial spasm.
Exp Mol Pathol 1990 Apr
PMID:In vivo demonstration of enhanced arterial constrictor response to serotonin following focal endothelial cell loss. 233 36

Intimal injury and atherosclerotic change seem to be causative factors linked to spasm of the coronary artery. Intimal thickening was produced by mechanical injury to the endothelium of the canine coronary artery and we investigated the distribution of adrenergic, cholinergic, and peptidergic nerves in the coronary arteries. Although adrenergic and cholinergic nerves were not altered in density, neuron specific enolase positive nerve fibers were increased in number in dogs killed 1 and 3 months after injury. Substance P-containing fibers were also increased at 3 months after the induced injury.
Exp Mol Pathol 1986 Apr
PMID:Intimal thickening and the distribution of vasomotor nerves in the mechanically injured dog coronary artery. 242 54

Apart from the generally known functions, the heart has also an endocrine function. Atrial cardiocytes, being typical secretory cells, release peptide hormones into the blood stream: atrial natriuretic peptide containing 28 amino acids and cardiodilatin. The structure of atrial peptides was determined. It was shown that both peptides were derived from their common precursor, a protein containing 151 amino acids. The presence of specific receptors is demonstrated on plasmatic membranes of cells of kidney epithelium, arterial smooth muscle, arterial endothelium, kidney cortex and hypophysis. The interaction of atrial peptides with these receptors activates the guanylate cyclase system. The biological action of atrial peptides manifests itself in the quick, massive and instantaneous increase of diuresis and electrolyte excretion, elevated clearance of creatinine, decrease of kidney vascular resistance, intensification of glomerular filtration, inhibition of stimulated secretion of aldosterone, relaxation of blood vessels, elimination of arterial and intestinal spasm induced by various endogenous and exogenous vasoconstrictors and in correction of kidney hypertension. Various radioimmunoassays for the presence of atrial peptides in human plasma were developed; it was shown that in patients with congestive heart failure the content of atrial peptides is increased.
Mol Biol (Mosk)
PMID:[Endocrine function of the heart. Structure and biological properties of peptides secreted by the heart atrium]. 295 15

The clinical use of calcium antagonist drugs in coronary artery disease preceded knowledge of the mechanism of their action. Basic research into their pharmacological actions and development of a wide range of compounds which block calcium entry into cells enabled clinicians to greatly expand the indications for their use. Thus the calcium antagonists were rediscovered and found to be potent anti-anginal drugs when used in adequate dosage for effort related angina. Knowledge of their potent relaxing action on vascular smooth muscle led to their use in coronary artery spasm. The exact trigger mechanism/s for spasm and the reason for enhanced vascular reactivity remain unclear, perhaps explaining the failure of specific antagonist therapy. Calcium antagonists acting nonspecifically inhibit both induced and spontaneous attacks of vasospastic angina. They may favourably influence the prognosis and are now drugs of first choice for this condition. The vasodilator action of these drugs has most recently been utilized to treat hypertension, with efficacy confirmed in many controlled trials. Unlike other vasodilators, the calcium antagonists reduce blood pressure without salt and water retention, and with mild or no stimulation of renin, aldosterone, or sympathetic nervous overactivity, and without postural effects. This spectrum of action makes them ideal therapeutic agents, and current guidelines are changing to include calcium antagonists as first or second line therapy.
J Mol Cell Cardiol 1987 May
PMID:Calcium antagonist drugs in the treatment of coronary spasm, effort angina and hypertension. 330 67

A model is described which permits the study of localized and generalized arterial spasm in the intact working perfused rabbit heart with a perfluorochemical (FC-43) as perfusate. Coronary arteries were visualized by intraatrial injection of Patent Blue Dye with gated photography. Localized spasm resulted from topical spray of histamine (40 mumols) on the epicardial surface overlying an obtuse marginal artery. Before and following topical administration of histamine, regional coronary flow was determined using radioisotope-labeled microspheres. Generalized arterial spasm was initiated by intraatrial injection of histamine (10 mumols). After topical administration, abtuse marginal artery diameter decreased by 57%; large vessel resistance rose 32 fold; 20% rise of total coronary resistance resulted in a slight reduction of total coronary flow (16%). Heart rate, cardiac output, dP/dtmax and myocardial oxygen consumption did not change. However, regional coronary flow in the myocardium supplied by the affected artery diminished 21% resulting in ischemic changes in redox pairs. After intraatrial injection of histamine, changes were more pronounced. Obtuse marginal artery diameter declined by 88% resulting in 3300-fold rise of large vessel resistance. Total coronary resistance increased 150%, coronary flow and cardiac output diminished (56% and 24%). Both heart rate and dP/dtmax increased (16% and 17%). Generalized coronary spasm after intraatrial histamine injection resulted in severe metabolic effects: Myocardial oxygen consumption (-48%); ATP (-29%); creatine phosphate (-34%); redox ratios, alpha-glycerophosphate/dihydroxyacetone phosphate and lactate/pyruvate, increased by 449% and 114%, respectively. The findings illustrate that localized and generalized coronary spasm can be produced and quantitated in a working heart model.
J Mol Cell Cardiol 1985 Sep
PMID:A model for the study of coronary spasm induced changes in cardiac metabolism. 404 51

Arterial spasm was induced by application of calcium chloride to the adventitial surface of the rabbit common carotid artery in vivo. Sodium chloride (NaCl) was applied to the contralateral vessel as control. Vessels were fixed in situ by intravascular perfusion after 15 min, 1 hr, or 24 hr and prepared for light and scanning electron microscopy (SEM). With SEM, the luminal surface at the site of calcium application showed severe longitudinal folding accompanied by endothelial desquamation with extensive platelet deposition on exposed subendothelium. The luminal cross-sectional area was reduced by 53 +/- 19.5% after 15 min and by 44 +/- 12% after 1 hr as compared with the contralateral control. Furthermore, the luminal area at the site of calcium application was found to be reduced by 42 +/- 8% after 1 hr when compared with segments of the same vessel distal to the site of calcium application. Blood flow rate, as measured by electromagnetic flow probe, was not reduced. Vessels examined after 24 hr showed a significant increase in luminal cross-sectional area as compared with contralateral control vessels (136 +/- 70%). Control vessels (NaCl) showed no significant change in luminal cross-sectional area and no endothelial desquamation or platelet deposition after 15 min, 1 hr, or 24 hr. Examination of histologic sections showed calcium precipitation within the attached thrombus after 15 min with calcium deposits also adherent to the adjacent luminal aspect of the internal elastic lamina (IEL). By 24 hr, this precipitation extended throughout the media. Marked deposition of leukocytes was seen after 24 hr which showed a preferential attachment for areas of endothelial damage and discontinuity of IEL.
Exp Mol Pathol 1983 Oct
PMID:Intimal changes associated with arterial spasm induced by periarterial application of calcium chloride. 661 26

When guinea pigs were exposed to sulfur dioxide (SO2) gas (800 ppm, 2 h), they showed hyperresponsiveness to intravenously administered serotonin (5-hydroxytryptamine (5-HT)). This hyperresponsiveness continued for over 24 h after the exposure to the gas. The degeneration, desquamation of epithelium, and edema of the lamina propria of the trachea and bronchi were observed in animals after a 2-h exposure of SO2 histopathologically. These changes seemed to be the early phase of acute bronchitis. Then, we examined the effect of clenbuterol, a selective beta-2 adrenoceptor agonist, on the SO2-induced bronchial hyperresponsiveness in these animals. Orally administered clenbuterol (1-10 micrograms/kg) suppressed the hyperresponsiveness to 5-HT in a dose-dependent manner. These results suggest that clenbuterol might inhibit the hyperresponsiveness that accompanies acute bronchitis and that this agent may be useful for remission of broncho-spasm.
Res Commun Mol Pathol Pharmacol 1995 Feb
PMID:Effect of clenbuterol on sulfur dioxide-induced acute bronchitis in guinea pigs. 774 57

As the structural database continues to expand, new methods are required to analyse and compare protein structures. Whereas the recognition, comparison, and classification of folds is now more or less a solved problem, tools for the study of constellations of small numbers of residues are few and far between. In this paper, two programs are described for the analysis of spatial motifs in protein structures. The first, SPASM, can be used to find the occurrence of a motif consisting of arbitrary main-chain and/or side-chains in a database of protein structures. The program also has a unique capability to carry out "fuzzy pattern matching" with relaxed requirements on the types of some or all of the matching residues. The second program, RIGOR, scans a single protein structure for the occurrence of any of a set of pre-defined motifs from a database. In one application, spatial motif recognition combined with profile analysis enabled the assignment of the structural and functional class of an uncharacterised hypothetical protein in the sequence database. In another application, the occurrence of short left-handed helical segments in protein structures was investigated, and such segments were found to be fairly common. Potential applications of the techniques presented here lie in the analysis of (newly determined) structures, in comparative structural analysis, in the design and engineering of novel functional sites, and in the prediction of structure and function of uncharacterised proteins.
J Mol Biol 1999 Jan 29
PMID:Recognition of spatial motifs in protein structures. 991 19

Stress alone is generally not sufficient to produce serious disease, but stress imposed upon pre-existing disease can contribute to disease progression. To explore this phenomenon, cold-immobilization stress was imposed on young 12.5 month, necrotic phase with small vessel coronary spasm) and older (5 month, quiescent phase, between necrosis and heart failure) cardiomyopathic hamsters. Our hypothesis was that changes in mitochondrial energy processes are involved in stress induced pathology. Polarographic and high performance liquid chromatography (HPLC) techniques were used to measure mitochondrial respiration and oxidative phosphorylation and concentrations of phosphocreatine and adenylates, respectively, in hearts from young and old cardiomyopathic hamsters (stressed and unstressed). No significant differences were found between the young (2.5 month) and old (5 month) age groups in unstressed and stressed healthy hamsters and between young (2.5 month) and old (5 month) unstressed cardiomyopathic hamsters with respect to different parameters of mitochondrial oxidative phosphorylation and with respect to concentration of bioenergetic metabolites, except that ADP concentration was higher in older cardiomyopathic hamsters. Application of stress uncovered differences between young and old cardiomyopathic hamsters: respiration control index was lower and State 4 respiration was higher in young compared to old cardiomyopathic hamsters; whereas the total concentration of ATP was decreased to the same level in both cardiomyopathic groups when compared to control. Mitochondrial oxidative phosphorylation in young cardiomyopathic hamsters was more sensitive to Ca2+, as evidenced by partial uncoupling of respiration and oxidative phosphorylation, than in older cardiomyopathic hamsters and controls. In conclusion, young cardiomyopathic hamsters, i.e. in the necrotic phase of disease, were more susceptible to stress induced changes in mitochondrial oxidative phosphorylation than older cardiomyopathic hamsters and controls.
J Mol Cell Cardiol 1999 Mar
PMID:Mitochondrial oxidative phosphorylation in heart from stressed cardiomyopathic hamsters. 1019 86


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