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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in human mitochondrial tRNA genes are associated with a number of multisystemic disorders. Using an assay that combines tRNA oxidation and circularization we have determined the relative amounts and states of aminoacylation of mutant and wild-type tRNAs in tissue samples from patients with MELAS syndrome (mito- chondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) and MERRF syndrome (myoclonus epilepsy with ragged red fibers), respectively. In most, but not all, biopsies from MELAS patients carrying the A3243G substitution in the mitochondrial tRNA(Leu(UUR))gene, the mutant tRNA is under-represented among processed and/or aminoacylated tRNAs. In contrast, in biopsies from MERRF patients harboring the A8344G substitution in the tRNA(Lys)gene neither the relative abundance nor the aminoacylation of the mutated tRNA is affected. Thus, whereas the A3243G mutation may contribute to the pathogenesis of MELAS by reducing the amount of aminoacylated tRNA(Leu), the A8344G mutation does not affect tRNA(Lys)function in the same way.
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PMID:Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients. 1069 70

We studied a patient with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes who had morphologically and biochemically abnormal muscle mitochondria. Molecular analysis revealed a T8316C transition in the mitochondrial DNA tRNA(Lys) gene. The mutation was homoplasmic in muscle from the proposita, heteroplasmic in her blood, and still less abundant in blood from her asymptomatic maternal relatives. The T8316C mutation affects a highly conserved base pair and was not found in controls, thus satisfying the accepted criteria for pathogenicity. Our data document the genetic heterogeneity in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome, underlining that the same syndrome may be associated with mutations of different genes.
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PMID:A mitochondrial tRNA(Lys) gene mutation (T8316C) in a patient with mitochondrial myopathy, lactic acidosis, and stroke-like episodes. 1099 80

The peptide nucleic acid (PNA)-directed PCR clamping technique was modified and applied to the detection of mitochondrial DNA mutations with low heteroplasmy. This method is extremely specific, eliminating false positives in the absence of mutant molecules, and highly sensitive, being capable of detecting mutations at the level of 0.1% of total molecules. Moreover, the reaction can be multiplexed to identify more than one mutation per reaction. Using this technique, the levels of three point mutations, the tRNA(Leu(UUA)) 3243 mutation causing mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS); the tRNA(Lys) 8344 mutation causing myoclonic epilepsy and ragged red fibers (MERRF); and the nucleotide position 414 mutation adjacent to the control region promoters, were evaluated in human brain and muscle from individuals of various ages. While none of the mutations were detected in brain samples from individuals ranging in age from 23 to 93, the 414 mutation could be detected in muscle from individuals 30 years and older. These data demonstrate that the 3243 and 8344 mutations do not accumulate with age to levels greater than 0.1% in brain and muscle. By contrast, the 414 mutation accumulates with age in normal human muscle, though not in brain. The reason for the striking absence of the 414 mutation in aging brain is unknown.
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PMID:The age-related accumulation of a mitochondrial DNA control region mutation in muscle, but not brain, detected by a sensitive PNA-directed PCR clamping based method. 1105 35

Although atherosclerosis progresses in an indolent state for decades, the rupture of plaques creates acute ischemic syndromes that may culminate in myocardial infarction and stroke. Mechanical forces and matrix metalloproteinase activity initiate plaque rupture, whereas tissue inhibitors of metalloproteinases have an important (albeit indirect) role in plaque stabilization. In this paper, an enzyme that could directly stabilize the plaque is described. Tissue transglutaminase (TG) catalyzes the formation of epsilon(gamma-glutamyl)lysine isopeptide bonds that are resistant to enzymatic, mechanical, and chemical degradation. We performed immunohistochemistry for TG in atherosclerotic human coronary and carotid arteries. TG was most prominent along the luminal endothelium and in the medium of the vessels with a distribution mirroring that of smooth muscle cells. Variable, often prominent, immunoreactivity for TG was also seen in the intima, especially in regions with significant neovascularization. Additionally, TG was detected in fibrous caps and near the "shoulder regions" of some plaques. A monoclonal antibody to the transglutaminase product epsilon(gamma-glutamyl)lysine isopeptide demonstrated co-localization with TG antigen. Transglutaminase activity was found in 6 of 14 coronary artery atherectomy samples. Cross-linking of TG substrates such as fibrinogen, fibronectin, vitronectin, collagen type I, and protease inhibitors stabilized the plaque. Furthermore, the activation of transforming growth factor-beta-1 by TG might be an additional mechanism for the promotion of plaque stabilization and progression by increasing the synthesis of extracellular matrix components.
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PMID:Localization of tissue transglutaminase in human carotid and coronary artery atherosclerosis: implications for plaque stability and progression. 1120 77

The involvement of nitric oxide synthase (NOS) in ischemia was evaluated by detecting the expression of neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS) by the immunohistochemical method in the rat model of middle cerebral artery (MCA) occlusion. Transient MCA occlusion (2 hours) was induced in 32 male Wistar rats by extracranial insertion of a 3-0 nylon thread through the internal carotid artery into the MCA. Animals were killed at 0, 6, 24, 72, and 168 hours after MCA occlusion (n = 6, 6, 8, 6, and 6, respectively). The brains were fixed with periodate-lysine-paraformaldehyde, frozen, and sectioned. Sections were stained with polyclonal antibody against nNOS, eNOS, and iNOS. Each section was evaluated by microscopic observation (x100). The number of nNOS-positive neurons was 41.6 +/- 5.8 (mean +/- SD) in the control hemisphere. nNOS was upregulated in the ischemic hemisphere (88.3 +/- 18.9), especially in the border zone at 6 hours after MCA occlusion. However, the number decreased to 36.4 +/- 3.6 and 26.3 +/- 7.3 in the ischemic hemisphere after 72 and 168 hours, respectively. eNOS immunoreactivity was present in the endothelium of major vessels at each time point. eNOS was not detected in the microvessels before ischemia, but faint staining was found in the endothelium at 6 hours after MCA occlusion. Immunostaining became more intense thereafter. Faint iNOS immunoreactivity was seen in the microvessels at 6 hours after MCA occlusion. Macrophages in the ischemic core and astrocytes in the border zone showed immunoreactivity to iNOS at 72 and 168 hours after MCA occlusion. Three types of NOS must be related to different stages of ischemic brain damage. nNOS may be neurotoxic in ischemia in the early phase, like iNOS in the late phase. On the other hand, eNOS seemed to be neuroprotective in all stages. These observations suggest the necessity for tailored therapeutic intervention against NOS isoforms at each stage in patients with ischemic stroke.
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PMID:Time course of expression of three nitric oxide synthase isoforms after transient middle cerebral artery occlusion in rats. 1125 30

Myosin subfragment 1 (S1) is the ATP catalyzing motor protein in muscle. It consists of three domains that catalyze ATP and bind actin (catalytic), conduct energy transduction (converter), and transport the load (lever arm). These domains interface in two places identified as interface I, containing the reactive thiol (SH1) and ATP-sensitive tryptophan (Trp510), and interface II, containing the reactive lysine residue (RLR). Two crystal structures of S1 were extrapolated to working "in solution" or oriented "in tissue" forms, using structure-sensitive optical spectroscopic signals from extrinsic probes located in the interfaces. Observed signals included circular dichroism (CD) and absorption originating from S1 in solution in the presence and absence of actin and fluorescence polarization from cross-bridges in muscle fibers. Theoretical signals were calculated from S1 crystal structure models perturbed with lever arm movement from swiveling at three conserved glycines, 699, 703, and 710 (chicken skeletal myosin numbering). Structures giving the best agreement between the computed and observed signals were selected as the representative forms. Both interfaces undergo dramatic conformational change during ATPase and force development. Changes at interface I suggest the molecular basis for the collisional quenching sensitivity of Trp510 to nucleotide binding. The probe conformation at SH1 suggests how it alters S1 ATPases. At interface II, the spatial relationship of the lever arm and the extrinsic probe at RLR suggests how the probe alters S1 ATPases and that it should inhibit lever arm movement during the power stroke. The latter possibility, if true, establishes a part of the corridor through which the lever arm swings during the power stroke. Global structural changes in actomyosin are discussed in the accompanying paper [Burghardt et al. (2001) Biochemistry 40, 4821-4833].
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PMID:Conformation of myosin interdomain interactions during contraction: deductions from proteins in solution. 1129 51

A simple, sensitive and reproducible isocratic high-performance liquid chromatography (HPLC) method has been developed for the determination of amino acids in human serum. The method involves precipitation of the serum proteins with methanol followed by pre-column derivatization of amino acids with o-phthalaldehyde-2-mercaptoethanol or o-phthalaldehyde-sodium sulfite. HPLC separation of the derivatives was performed using an ODS column with an isocratic mobile phase system and electrochemical detection (+0.75 V). The response was linear over the range 5-300 microM for all amino acids. The method allows quantitative determination of glutamic acid, asparagine, serine, glutamine, histidine, taurine, alanine, arginine, methionine, isoleucine, ornithine, leucine, phenylalanine, lysine and tryptophan at concentrations as low as 0.5-5.0 pmol (signal-to-noise ratio=2). Using this method, the levels of amino acids in serum from healthy donors and patients with ischemic stroke were determined.
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PMID:Analysis of amino acids in human serum by isocratic reversed-phase high-performance liquid chromatography with electrochemical detection. 1135 26

Bone morphogenetic protein-7 (BMP-7) has been shown to enhance dendritic growth and improve functional recovery after experimental stroke. In this study, we examined the effect of BMP-7 on functional recovery, local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu) following transient middle cerebral artery occlusion. Sprague--Dawley rats (n=29) were anesthetized with halothane/nitrous oxide and received 2-h middle cerebral artery occlusion (MCAo) by poly-L-lysine-coated intraluminal suture. Rectal and cranial temperatures were regulated at 37.0--37.5 degrees C. BMP-7 or vehicle (volume, 25 microl) was administered intracisternally in a blinded fashion at 24 h after MCAo. Neurological status was evaluated during occlusion (60 min) and daily for 2 days after MCAo. In matched animal groups, LCMRglu was measured autoradiographically with [(14)C]2-deoxyglucose (2-DG) and LCBF with [(14)C]iodoantipyrine 48 h after MCAo. Four animals groups were studied: LCMRglu series (BMP-7, n=7; vehicle, n=8); LCBF series (BMP-7, n=6; vehicle, n=8). Average three-dimensional image data sets were constructed for each group and were compared by pixel-based statistical methods. Rectal and cranial temperatures, mean blood pressure, plasma glucose and blood gases were similar among groups. BMP-7 significantly improved the total neurological score compared to vehicle at 48 h after MCAo (7.3+/-0.4 vs. 9.0+/-0.2, respectively; P<0.0003). Compared to vehicle-rats, BMP-7 enhanced glucose utilization in the basal ganglia ipsilateral to stroke and improved LCBF in ipsilateral subthalamus, but decreased LCBF and LCMRglu in contralateral cortical regions.
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PMID:The effect of bone morphogenetic protein-7 (BMP-7) on functional recovery, local cerebral glucose utilization and blood flow after transient focal cerebral ischemia in rats. 1142 82

The KIF1 subfamily members are monomeric and contain a number of amino acid inserts in surface loops. A particularly striking insertion of several lysine/arginine residues occurs in L12 and is called the K-loop. Two recent studies have employed both kinetic and single-molecule methods to investigate KIF1 motor properties and have produced very different conclusions about how these motors generate motility. Here we show that a hitherto unstudied member of this group, KIF1D, is not chemically processive and drives fast motility despite demonstrating a slow ATPase. The K-loop of KIF1D was analysed by deletion and insertion mutagenesis coupled with characterization by steady state and transient kinetics. Together, the results indicate that the K-loop not only increases the affinity of the motor for the MT, but crucially also inhibits its subsequent isomerization from weak to strong binding, with coupled ADP release. By stabilizing the weak binding, the K-loop establishes a pool of motors primed to undergo their power stroke.
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PMID:KIF1D is a fast non-processive kinesin that demonstrates novel K-loop-dependent mechanochemistry. 1156 75

Using high performance liquid chromatography, we measured the Asp, Glu, Ser, Gly, Thr, Arg, Ala, Tyr, Met, Val, Phe, Ile, Ley, Lys, GABA concentrations in cerebrospinal fluid(CSF) of 15 patients with ischemic cerebral infarction and 10 control subjects. The severity of the neurological deficit was assessed with Chinese stroke scale; infarct volume was determined by Zhang's method. The concentration of Asp, Glu, Ala, Leu were higher significantly in the infarct group than that in control(P < 0.01; P < 0.05); however, the concentration of GABA in the infarct group was lower than that in control(P < 0.05). The concentrations of Asp and Glu were positively correlated with infarct volume(rAsp = 0.56, P < 0.05; rGlu = 0.52, P < 0.05). The other amino acids were not correlated with infarct volume. All of the amino acids determined were not correlated with severity of neurological deficit. The results support the excitoxic activity of Asp and Glu in patients with ischemic cerebral infarction. Whether GABA protects neuronal tissue from ischemic cerebral damage needs to be studied further.
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PMID:[Changes of amino acids in cerebrospinal fluid of patients with cerebral infarction]. 1221 63


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