Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acid-sensing ion channels (ASICs) are ion channels activated by extracellular protons. They are involved in higher brain functions and perception of pain, taste, and mechanical stimuli. Homomeric ASIC1a is potently inhibited by the tarantula toxin psalmotoxin 1. The mechanism of this inhibition is unknown. Here we show that psalmotoxin 1 inhibits ASIC1a by a unique mechanism: the toxin increases the apparent affinity for H(+) of ASIC1a. Since ASIC1a is activated by H(+) concentrations that are only slightly larger than the resting H(+) concentration, this increase in H(+) affinity is sufficient to shift ASIC1a channels into the desensitized state. As activation of ASIC1a has recently been linked to neurodegeneration associated with stroke, our results suggest chronic desensitization of ASIC1a by a slight increase of its H(+) affinity as a possible way of therapeutic intervention in stroke.
J Gen Physiol 2005 Jul
PMID:The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by increasing its apparent H+ affinity. 1595 77

During vertebrate evolution there has been a shift in the way in which the heart varies cardiac output (the product of heart rate and stroke volume). While mammals, birds, and amphibians increase cardiac output through large increases in heart rate and only modest increases (approximately 30%) in stroke volume, fish and some reptiles use modest increases in heart rate and very large increases in stroke volume (up to 300%). The cellular mechanisms underlying these fundamentally different approaches to cardiac output modulation are unknown. We hypothesized that the divergence between volume modulation and frequency modulation lies in the response of different vertebrate myocardium to stretch. We tested this by progressively stretching individual cardiac myocytes from the fish heart while measuring sarcomere length (SL), developed tension, and intracellular Ca2+ ([Ca2+]i) transients. We show that in fish cardiac myocytes, active tension increases at SLs greater than those previously demonstrated for intact mammalian myocytes, representing a twofold increase in the functional ascending limb of the length-tension relationship. The mechanism of action is a length-dependent increase in myofilament Ca2+ sensitivity, rather than changes in the [Ca2+]i transient or actin filament length in the fish cell. The capacity for greater sarcomere extension in fish myocardium may be linked to the low resting tension that is developed during stretch. These adaptations allow the fish heart to volume modulate and thus underpin the fundamental difference between the way fish and higher vertebrates vary cardiac output.
J Gen Physiol 2006 Jul
PMID:The cellular basis for enhanced volume-modulated cardiac output in fish hearts. 1676 95

Acid-sensing ion channels (ASICs) are thought to trigger some forms of acid-induced pain and taste, and to contribute to stroke-induced neural damage. After activation by low extracellular pH, different ASICs undergo desensitization on time scales from 0.1 to 10 s. Consistent with a substantial conformation change, desensitization slows dramatically when temperature drops (Askwith, C.C., C.J. Benson, M.J. Welsh, and P.M. Snyder. 2001. PNAS. 98:6459-6463). The nature of this conformation change is unknown, but two studies showed that desensitization rate is altered by mutations on or near the first transmembrane domain (TM1) (Coric, T., P. Zhang, N. Todorovic, and C.M. Canessa. 2003. J. Biol. Chem. 278:45240-45247; Pfister, Y., I. Gautschi, A.-N. Takeda, M. van Bemmelen, S. Kellenberger, and L. Schild. 2006. J. Biol. Chem. 281:11787-11791). Here we show evidence of a specific conformation change associated with desensitization. When mutated from glutamate to cysteine, residue 79, which is some 20 amino acids extracellular to TM1, can be altered by cysteine-modifying reagents when the channel is closed, but not when it is desensitized; thus, desensitization appears to conceal the residue from the extracellular medium. D78 and E79 are a pair of adjacent acidic amino acids that are highly conserved in ASICs yet absent from epithelial Na(+) channels, their acid-insensitive relatives. Despite large effects on desensitization by mutations at positions 78 and 79-including a shift to 10-fold lower proton concentration with the E79A mutant-there are not significant effects on activation.
J Gen Physiol 2007 Apr
PMID:A conformation change in the extracellular domain that accompanies desensitization of acid-sensing ion channel (ASIC) 3. 1738 50

N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels that contribute to fundamental physiological processes such as learning and memory and, when dysfunctional, to pathophysiological conditions such as neurodegenerative diseases, stroke, and mental illness. NMDARs are obligate heteromultimers typically composed of NR1 and NR2 subunits with the different subunits underlying the functional versatility of NMDARs. To study the contribution of the different subunits to NMDAR channel structure and gating, we compared the effects of cysteine-reactive agents on cysteines substituted in and around the M1, M3, and M4 segments of the NR1 and NR2C subunits. Based on the voltage dependence of cysteine modification, we find that, both in NR1 and NR2C, M3 appears to be the only transmembrane segment that contributes to the deep (or voltage dependent) portion of the ion channel pore. This contribution, however, is subunit specific with more positions in NR1 than in NR2C facing the central pore. Complimentarily, NR2C makes a greater contribution than NR1 to the shallow (or voltage independent) portion of the pore with more NR2C positions in pre-M1 and M3-S2 linker lining the ion-conducting pathway. Substituted cysteines in the M3 segments in NR1 and NR2C showed strong, albeit different, state-dependent reactivity, suggesting that they play central but structurally distinct roles in gating. A weaker state dependence was observed for the pre-M1 regions in both subunits. Compared to M1 and M3, the M4 segments in both NR1 and NR2C subunits had limited accessibility and the weakest state dependence, suggesting that they are peripheral to the central pore. Finally, we propose that Lurcher mutation-like effects, which were identified in and around all three transmembrane segments, occur for positions located at dynamic protein-protein or protein-lipid interfaces that have state-dependent accessibility to methanethiosulfonate (MTS) reagents and therefore can affect the equilibrium between open and closed states following reactions with MTS reagents.
J Gen Physiol 2007 Jun
PMID:Subunit-specific contribution of pore-forming domains to NMDA receptor channel structure and gating. 1750 10

Aortic dissection masquerading as ischemic stroke is particularly challenging in the era of thrombolysis as a result of narrow diagnostic time window and severe hemorrhagic potential. We describe a case of a 77-year-old patient with a presumed ischemic cerebral infarct, in whom planned treatment with tissue plasminogen activator therapy (TPA) was withheld because of partial spontaneous improvement in his condition. Shortly afterwards, newly elicited clues in the medical history and physical examination led to timely diagnosis and treatment of ascending thoracic aorta dissection, which was the underlying disorder. Analysis of the features of this case and similar previously published cases illustrates the importance of using and mastering basic diagnostic skills.
J Gen Intern Med 2007 Sep
PMID:Ischemic stroke, aortic dissection, and thrombolytic therapy--the importance of basic clinical skills. 1761 33

Secondary erythrocytosis of cyanotic congenital heart disease (CCHD) is pathologically different from primary erythrocytosis of polycythemia vera (PV). An association between elevated hematocrit and thrombosis has been established in PV patients, and treatment guidelines recommend maintaining hematocrit <45%. Although an association between elevated hematocrit and thrombosis has not been established in CCHD and secondary erythrocytosis, the current clinical practice is to phlebotomize these patients to hematocrit <65%. We report a 21-year-old woman with CCHD who presented with symptomatic erythrocytosis with numbness and tingling with hemoglobin 25.2 g/dl and hematocrit 75.8%. Her symptoms resolved with IV hydration. Other factors, including dehydration and iron deficiency, may precipitate hyperviscosity symptoms. The treatment is volume replacement and low-dose iron therapy, not phlebotomy. Repeated phlebotomy causes iron deficiency with microcytic erythrocytes, which increases the whole blood viscosity and, therefore, can potentially accentuate rather than decrease the risk for a cerebrovascular accident.
J Gen Intern Med 2007 Dec
PMID:Cyanotic congenital heart disease (CCHD) with symptomatic erythrocytosis. 1791 83

In Japan, no pulsatile ventricular assist devices are available specifically for use in children. Pumps designed for adults are thus often used in children. We report herein a case of end-stage heart failure in a 3-year old girl (height 100.4 cm; body weight 16.2 kg; body surface area 0.66 m2) who underwent implantation with an adult-sized Toyobo-NCVC left ventricular assist device (Toyobo-National Cardiovascular Center, Osaka, Japan) in our unit. We started with the driving mode to "full-fill, full-empty" mode. The problem was difficult-to-treat hypertension due to excessive stroke volume induced by the left ventricular assist device. Aggressive administration of antihypertensive therapy was needed. Successful heart transplantation was performed in Germany 5 months after beginning support with the Toyobo-NCVC left ventricular assist device.
Gen Thorac Cardiovasc Surg 2008 Jul
PMID:Bridge to transplantation with a Toyobo-NCVC left ventricular assist device in a 3-year-old girl. 1860 86

Spontaneous dissection of the internal carotid artery usually presents with stroke-like symptoms secondary to ischemia in its vascular territory, as well as local signs and symptoms, which may include head, face or neck pain, Horner's syndrome, pulsatile tinnitus, and cranial nerve palsies. We report a case of a 44-year-old healthy white male who presented with tongue swelling mimicking angioedema as an unusual manifestation of spontaneous dissection of the internal carotid artery. Two weeks after the initial presentation, the patient returned with similar symptoms and slurred speech. Upon physical examination, he was noted to have isolated left-sided hypoglossal nerve palsy. Subsequent diagnostic imaging revealed segmental narrowing of the left internal carotid artery. The appearance was consistent with the presence of a spontaneous internal carotid artery dissection with associated pseudoaneurysm formation.
J Gen Intern Med 2009 Jan
PMID:Spontaneous dissection of internal carotid artery masquerading as angioedema. 1883 59

A-76-year-old woman consulted for open biopsy for a pulmonary mass. Thoracoscopic wedge resection was performed. The lesion was histologically diagnosed as nonspecific inflammation. On the first postoperative day (POD1), the patient lost consciousness transiently. Eleven hours after the first stroke, the patient experienced a second stroke together with hypoxia. Pulmonary perfusion scan on POD2 showed multiple perfusion defects, and the patient was diagnosed with pulmonary embolism (PE). Thrombolitic therapy was started. Neurological symptoms didn't improve, and cerebral angiography on POD3 showed delayed perfusion in superficial veins. The patient was diagnosed with cerebral venous thrombosis (CVT). Thrombolytic and anticoagulant therapy had been continued, and the patient was found to have hemorrhagic cerebral infarction on POD11. After persistent therapy, the patient was discharged on POD120. Although both PE and CVT are rare complications after thoracic surgery, we must consider these complications in patients undergoing thoracic operations including thoracoscopic surgery.
Gen Thorac Cardiovasc Surg 2008 Nov
PMID:Pulmonary embolism and cerebral venous thrombosis after thoracoscopic surgery for benign pulmonary disease. 1900 60

Effort angina of a 70-year-old man was diagnosed as due to triple coronary vessel disease, and he was scheduled to undergo coronary artery bypass surgery. Preoperative carotid duplex scan revealed more than 75% stenosis of the right internal carotid artery, which was functionally proven to be significantly ischemic on brain single photon emission computed tomography. Although he was neurologically asymptomatic, we chose staged surgery for fear of stroke during coronary artery bypass surgery. He had successful carotid artery stenting first by neurosurgeons; then, 2 months later he underwent uneventful coronary artery bypass surgery. This experience prompted us to report the case.
Gen Thorac Cardiovasc Surg 2009 Jan
PMID:Asymptomatic severe carotid stenosis undergoing staged carotid artery stent and coronary artery bypass grafting: decisive role of brain single photon emission computed tomography. 1916 11


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