[Prevention of cerebral infarction].
Explore the source record for details and available documents.
Cerebral Infarction↗
Biomedical subjects
N Tanahashi
Publications and source records attributed to N Tanahashi.
Nin1p, a regulatory subunit of the 26S proteasome, is necessary for activation of Cdc28p kinase of Saccharomyces cerevisiae.
The nin1-1 mutant of Saccharomyces cerevisiae cannot perform the G1/S and G2/M transitions at restrictive temperatures. At such temperatures, nin1-1 strains fail to activate histone H1 kinase after release from alpha factor-imposed G1 block and after release from hydroxyurea-imposed S block. The nin1-1 mutation shows synthetic lethality with certain cdc28 mutant alleles such as cdc28-IN. Two lines of evidence indicate that Nin1p is a component of the 26S proteasome complex: (i) Nin1p, as well as the known component of the 26S proteasome, shifted to the 26S proteasome peak in the glycerol density gradient after preincubation of crude extract with ATP-Mg2+, and (ii) nin1-1 cells accumulated polyubiquitinated proteins under restrictive conditions. These results suggest that activation of Cdc28p kinase requires proteolysis. We have cloned a human cDNA encoding a regulatory subunit of the 26S proteasome, p31, which was found to be a homolog of Nin1p.
Amino Acid Sequence↗
Non-amoeboid locomotion of cultured microglia obtained from newborn rat brain.
The movements of cultured microglia obtained from newborn rat brain were examined by video enhanced-differential interference contrast (VEC-DIC) microscopy. Active microglia measured 9.03 +/- 1.06 microns in diameter (mean +/- SD, n = 33; range, 7.03-10.36 microns). The microglia appeared to become smaller with spread of lamellipodia. The short axis of actively moving microglia measured 7.03 +/- 0.49 microns (n = 7). The lamellipodia were thin, transparent and developed rapidly around the cell body (maximal speed of extension, 4 or 5 microns/s). When shear stress from the medium was applied to the surface of cultured cells, the microglia swam with flat lamellipodia serving as sails in the stream. Spontaneous non-amoeboid movements of microglia were observed: they pivoted, circled and marched in various directions using their lamellipodia. The angular speed of rotation was maximally 3 degrees/s. In 5 marching cells, the average speed (distance/s) was calculated at 1.01 +/- 0.54 microns/s (ca. 60 microns/min or 3.6 microns/h).
Animals↗
Primary structures of two homologous subunits of PA28, a gamma-interferon-inducible protein activator of the 20S proteasome.
The primary structures of two proteins that comprise PA28, an activator of the 20S proteasome, have been determined by cDNA cloning and sequencing. These protein subunits, termed PA28 alpha and PA28 beta, are about 50% identical to one another and are highly conserved between rat and human. PA28 alpha and PA28 beta are homologous to a previously described protein, Ki antigen, whose function is unknown. PA28 alpha, but neither PA28 beta nor Ki antigen, contains a 'KEKE motif', which has been postulated to promote the binding of proteins having this structural feature. PA28 alpha and PA28 beta were coordinately regulated by gamma-interferon, which greatly induced mRNA levels of both proteins in cultured cells. The mRNA level of the Ki antigen also increased in response to gamma-interferon treatment, but the magnitude of the increase was less than that for the PA28s, and the effect was transient. These results demonstrate the existence of a new protein family, at least two of whose members are involved in proteasome activation. They also provide the basis for future structure/function studies of PA28 subunits and the determination of their relative physiological roles in the regulation of proteasome activity.
Amino Acid Sequence↗
Pentoxifylline ameliorates postischemic delayed hypoperfusion of the cerebral cortex following cardiac arrest in cats.
Two major events occurring in the cerebral hemodynamics after successful resuscitation from cardiac arrest are reactive hyperemia and postischemic hypoperfusion. We examined the effect of pentoxifylline on the feline cerebral hemodynamics following cardiac arrest. Fifteen cats were anesthetized and artificially ventilated. Using our photoelectric method, the local cerebral blood volume (CBV), mean transit time of blood (MTT), and cerebral blood flow (CBF) in the parietotemporal region were measured. Thoracotomy was performed, and cardiac arrest (ventricular fibrillation) was induced by direct application of a 2-V DC countershock. The heart was resuscitated with a DC countershock at 30 sec after cardiac arrest. In 9 cats, pentoxifylline (25 mg/kg) was infused into the femoral vein at 5 min before cardiac arrest (PTX group). The other 6 cats served as controls (control group). In both groups, the CBV, CBF and mean arterial blood pressure (MABP) overshot the control levels just after resuscitation, whereas the MTT was decreased. In the control group, postischemic hypoperfusion was detected at 30-180 min after resuscitation from cardiac arrest (CBF (ml/100 g/min): 51 +/- 4 (control), 38 +/- 4 (30 min, p < 0.05), and 23 +/- 3 (180 min, p < 0.05)). However, the postischemic hypoperfusion was not observed in the PTX group. Pentoxifylline ameliorated postischemic delayed hypoperfusion in the cerebral cortex after a short period of cardiac arrest. Pentoxifylline may be useful in the emergency situations following cardiac arrest.
Animals↗
Effects of ventricular arrhythmia on the cerebral microcirculation in cats.
To test the widely believed but poorly proved hypothesis that the cerebral symptoms observed during ventricular arrhythmia are caused by a reduced cerebral blood supply, we examined the effects of single and multiple ectopic ventricular beats (or ventricular tachycardia of short duration) on the cerebral microcirculation. Six anesthetized cats were used. Ectopic ventricular systoles of various sequences were produced by electrically stimulating the ventricle through a bipolar needle-type electrode for 1 to 50 times at a rate of 300/min. The local cerebral blood volume (CBV) and blood flow (CBFLD) in the cortex were measured continuously employing the photoelectric and laser Doppler methods. CBV reflects the cumulative dimensions of the cerebrocortical microvessels. Ectopic ventricular contractions, as confirmed by electrocardiograms, always reduced the CBV and arterial blood pressure in a total of 104 attempts. The CBV reductions ranged from 0.20 +/- 0.03 vol% for a single ectopic beat to approximately 0.6-0.8 vol% for runs of 8 or more beats. The CBFLD reductions measured with the laser Doppler flowmeter were 10-35%. The reductions in CBV and CBFLD during the ventricular arrhythmia could be attributed to the abrupt and marked reductions in arterial blood pressure. Runs of ectopic ventricular beats have significant effects on the cerebral microcirculation, whether clinically apparent or not.
Animals↗
Ordered structure of the crystallized bovine 20S proteasome.
Eukaryotic proteasomes are multicatalytic proteinase complexes with a molecular weight of 750 kDa, containing, respectively, two copies of a hetero-heptamer of alpha-type subunits and one of beta-type subunits, (alpha 1-7 beta 1-7)2. Proteasome was purified from bovine liver and crystallized into a hexagonal system with cell dimensions of a = b = 121.83(2) A, c = 930.68(6) A. A cylindrical particle size of 122 A diameter and 155 A height was determined from the molecular packing in a unit cell. The crystal gave diffraction spots up to at least 4.4 A resolution, which was the minimum spacing of the camera used. The overall temperature factor of the enzyme was estimated to be in the range of 36.2 to 25.8 A2. These results imply that the enzyme complex has a unique ordered structure comprising multisubunits with two types of hetero-heptamer. This ordered structure may facilitate highly organized cooperation of individual functions of subunits within the enzyme complex.
Amino Acid Sequence↗
Activated leukocytes, endothelial cells, and effects of pentoxifylline: observations by VEC-DIC microscopy.
Using video-enhanced contrast (VEC)-differential interference contrast (DIC) microscopy, ultrastructural observations were made of the activation of polymorphonuclear leukocytes (PMNLs), the interaction between activated PMNLs and endothelial cells (ECs), and the effects of pentoxifylline (PTX). The ECs were obtained from a commercial source as human umbilical cord vein endothelial cells (HUVECs) or were obtained from pig or rat brains. They were cultured on a coverglass with DMEM for about 1 week. The human PMNLs were obtained from the authors' venous blood. The control appearance of the PMNLs resembled an elastic ball covered with fine villi. The PMNL was activated spontaneously and became flattened on the glass surface within 10 min in the observation chamber. The activation of the PMNLs was estimated arbitrarily from the polymorphous changes in cell shape, agitation of the intracellular granules, and apparent increase in adhesiveness. Preadministered PTX prevented such PMNL activation, and the PMNLs remained round for more than 15 min. PMNL activation was accelerated by chemoattractants (PAF, fMLP, and PMA). In one case, a PMNL that had been activated by PMA tended to recover its round shape with PTX, but finally ended by swelling and bursting. When PMNLs were introduced into the EC-containing chamber, they became entrapped by the ECs and activated, with degranulation followed by release of a smoke-like material. After about 3 h, the EC with an attached PMNL shrank and fell into a state of coagulation necrosis. When PTX was introduced at the time of adhesion of the flattened PMNL, the PMNL appeared to be deactivated, becoming smaller and assuming its previous round shape, and detached from the EC. PTX prevented the spontaneous activation of PMNLs, and of deactivated PMNLs even after their adherence to the endothelium.
Animals↗
[A case of spontaneous arteriovenous fistula presenting as the partial oculomotor nerve palsy].
We report a case of partial oculomotor nerve palsy due to spontaneous arteriovenous fistula. A 62-year-old man noticed double vision on downward gaze and periorbital pain. Clinical examination revealed inability to move the left eye downwards and to the right, and also anisocoria. No conjunctival injection or proptosis was noted. Findings of computed tomographic scan, magnetic resonance imaging and magnetic resonance angiography of the orbits, cavernous sinus region and brainstem were all normal. Carotid angiography demonstrated arteriovenous fistula via the left ophthalmic artery, the dural branch of the left external carotid artery, and the dural branch of the right internal carotid artery. Partial oculomotor palsy in this case indicated that the left inferior branch of the oculomotor nerve was affected. Inferior branch palsy of the oculomotor nerve in spontaneous arteriovenous fistula has not been described in the literature, while it is reported in cases of trauma, tumor, or aneurysm of the cavernous sinus.
Arteriovenous Fistula↗
Role of nitric oxide in regulation of cerebral microvascular tone and autoregulation of cerebral blood flow in cats.
The role of nitric oxide in the regulation of cerebrocortical microvascular tone and autoregulation of cerebral blood flow (CBF) was examined in 24 anesthetized cats. The local cerebral blood volume (CBV), mean transit time of blood (MTT), and CBF in the cortex were measured by our photoelectric method. CBV represents the cumulative dimensions of the cerebral microvessels. Intravenous injection of 0.35-0.7 mg/kg/min NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, significantly increased mean arterial blood pressure (MABP; 8.4-14.1%, P < 0.01), decreased CBV (15.2-28.7%, P < 0.01), and decreased CBF (20.0-29.8%, P < 0.01) in a dose-related manner. The changes in MABP, CBV, and CBF elicited by L-NMMA were inhibited (P < 0.05) by simultaneous infusion of 35 mg/kg/min L-arginine. Autoregulation of CBF was examined during controlled hypotension of -30 to -40 mmHg (artificial bleeding) and recovery of blood pressure (reinfusion of blood). Although CBF remained constant with blood pressure changes in the control state (delta CBF/delta MABP of 0.037 +/- 0.155 with hypotension), CBF became dependent on blood pressure changes (delta CBF/delta MABP of 0.478 +/- 0.135, P < 0.05) during infusion of 0.35 mg/kg/min L-NMMA. It is concluded that nitric oxide participates in both the regulation of basal tone of cerebral microvessels and the autoregulation of CBF.
Animals↗
Purification and characterization of the 26 S proteasome from spinach leaves.
The 26 S proteasome complex catalyzing ATP-dependent breakdown of ubiquitin-ligated proteins was purified from spinach leaves to near homogeneity by chromatography on DEAE-cellulose, gel filtration on Biogel A-1.5, and glycerol density gradient centrifugation. The purified enzyme was shown to degrade multi-ubiquitinated, but not unmodified, lysozymes in an ATP-dependent fashion coupled with ATPase activity supplying energy for proteolysis and isopeptidase activity to generate free ubiquitin. By nondenaturing electrophoresis, the purified enzyme was separated into two distinct forms of the 26 S complex, named 26 S alpha and 26 S beta proteasomes, with different electrophoretic mobilities. The 26 S proteasome was found to consist of multiple polypeptides with molecular masses of 23-35 and 39-115 kDa, which were thought to be those of a 20 S proteasome with multicatalytic proteinase activity and an associated regulatory part with ATPase and deubiquitinating activities, respectively. The subunit multiplicity of the spinach 26 S proteasome closely resembled that of rat liver with minor differences in certain components. No sulfhydryl bond was involved in the assembly of this multicomponent polypeptide complex. Electron microscopy showed that the 26 S proteasome complex had a "caterpillar"-like shape, consisting of four central protein layers, assumed to be the 20 S proteasome, with asymmetric V-shaped layers at each end. These structural and functional characteristics of the spinach 26 S proteasome showed marked similarity to those of the mammalian 26 S proteasomes reported recently, suggesting that the 26 S proteasome is widely distributed in eukaryotic cells and is of general importance for catalyzing the soluble energy- and ubiquitin-dependent proteolytic pathway.
Adenosine Triphosphate↗
Dilatation of cerebral microvessels mediated by endothelin ETB receptor and nitric oxide in cats.
The functional role of the endothelin (ET)B receptor in the cerebral microvessels was examined in seven anesthetized cats. The effects of intracarotidly injected IRL1620, a selective ETB receptor agonist, on the cerebral blood volume (CBV) in the cortex were examined by a photoelectric method. CBV reflects the cumulative dimensions of the cerebral microvessels. High doses of IRL1620 (0.1-1 nmol/kg) elicited a transient fall in CBV, followed by a marked and dose-related increase of CBV (P < 0.01). The CBV increase was significantly inhibited (P < 0.01) by simultaneous administration of 0.35 mg/kg/min NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis. The marked, but transient, depressor effect of IRL1620 was also attenuated (P < 0.01) by L-NMMA. The ETB receptor subtype and production of nitric oxide, probably in the endothelium, mediate the vasodilatory action of ET in the cerebral microvessels.
Animals↗
Cerebral vasodilatory effect of high-dose, intravascular endothelin-1: inhibition by NG-monomethyl-L-arginine.
The effects of intracarotid administration of endothelin-1 on the cerebral microvessels were examined in anesthetized cats. The local cerebral blood volume in the cortex, which reflects the cumulative dimensions of the cerebral microvessels, was measured by our photoelectric method. A low dose of endothelin-1 (0.1 nmol) elicited mild but significant declines in cerebral blood volume. Following a high dose of endothelin-1 (3 nmol), the cerebral blood volume was initially reduced, probably due to the marked fall in arterial blood pressure, but was subsequently increased significantly. The increase in cerebral blood volume was not secondary to the rise in blood pressure, since it was unaffected by inhibition of the blood pressure changes with BQ-123 (1 mg/kg), an endothelin antagonist. However, the cerebral blood volume increase was prevented by continuous administration of NG-monomethyl-L-arginine (0.35 mg/kg per min), an inhibitor of nitric oxide synthesis, plus BQ-123. BQ-123 itself had no significant effects on cerebral blood volume or blood pressure. We conclude that while a low dose of intravascular endothelin-1 steadily constricts the cerebral microvessels, a high dose dilates the cerebral microvessels through the induction of nitric oxide synthesis, probably in the endothelium.
Animals↗
Constriction/dilatation of the cerebral microvessels by intravascular endothelin-1 in cats.
The effects of intracarotidly injected endothelin (ET)-1 (0.01-3 nmol) on the local cerebral blood volume (CBV) in the parietotemporal cortex were examined by the photoelectric method in 17 anesthetized cats. CBV reflects the cumulative dimensions of the cerebral microvessels. Low doses of ET-1 (0.01 and 0.1 nmol) elicited mild but significant reductions in CBV without changes in the systemic arterial blood pressure (SABP). High doses of ET-1 (3 nmol) initially induced marked declines of CBV, which were attributable to the significant falls in SABP. CBV subsequently exhibited significant increases. The CBV increases were not secondary to the accompanying elevations of SABP, since they were unaffected by inhibition of the SABP changes after preinjection of BQ-123 (1 mg/kg), an ET antagonist specific to the ETA receptors. The CBV increases, however, were prevented by continuous administration of NG-mono-methyl-L-arginine (0.35 mg/kg/min), an inhibitor of nitric oxide synthesis, plus BQ-123. We conclude that while low doses of intravascular ET-1 constrict the cerebral microvessels, high doses of ET-1 dilate the cerebral microvessels through the induction of nitric oxide probably in the cerebrovascular endothelium.
Animals↗
Interferon-gamma induces different subunit organizations and functional diversity of proteasomes.
To obtain information on the role of proteasomes in the immune system, we examined the effect of a major immunomodulatory cytokine, gamma interferon (IFN-gamma), on the expressions, structures, and functions of proteasomes. IFN-gamma greatly increased the levels of the mRNAs encoding LMP2 and LMP7, putative immuno-proteasome subunits encoded by genes within the class II MHC region, and these two subunits synthesized were assembled completely into the proteasomal multi-subunit complex in various types of human cells. The subunit organization of proteasome changed in response to IFN-gamma stimulation, due to assembly of newly synthesized subunits through up- and down-expressions of at least 6 proteasome genes including LMP2/LMP7 without change in the structure of pre-existing proteasomes. Interestingly, IFN-gamma dramatically stimulated the trypsin-like and chymotrypsin-like activities of the multifunctional proteasome and depressed the peptidylglutamyl-peptide-hydrolyzing activity, without affecting the activity for ATP-, ubiquitin-dependent proteolysis. These results indicate that IFN-gamma modifies not only the structural organization of the proteasome, but also its functions. Based on these findings, we discuss the role in the antigen processing/presentation pathway of proteasomes with functional diversity acquired through alteration of their subunit assembly in response to IFN-gamma stimulation.
Adenosine Triphosphate↗
Midpontine tegmentum infarction with "one-and-a-half syndrome" demonstrated by magnetic resonance imaging.
Magnetic resonance imaging (MRI) revealed a small midpontine tegmentum infarction in a patient with Fisher's one-and-a-half syndrome. The lesion was extremely restricted to the unilateral paramedian area of the midpontine tegmentum involving both the paramedian pontine reticular formation and medial longitudinal fasciculus. The typical form of this syndrome, that is, a combination of lateral gaze palsy and unilateral internuclear ophthalmoplegia, can be caused by a midpontine lesion.
Aged↗
[Creutzfeldt-Jakob disease with a point mutation at codon 232 of prion protein--a case report].
We report a 50-year-old female with sporadic Creutzfeldt-Jakob disease who revealed a point mutation at codon 232 of prion protein (Met to Arg). The initial symptom was visual disturbance. The patient then developed progressive dementia, cerebellar ataxia and myoclous. About eight months after the onset, the patient went into the state of akinetic mutism. The electroencephalogram showed periodic synchronous discharges. From the prion protein's DNA sequencing of the patient's family members, the 84-year-old father without any neurological symptoms was also detected to have a point mutation at codon 232. These findings which, have not been reported before, are interesting when considering the relation between the pathogenesis of Creutzfeldt-Jakob disease and mutations of prion protein gene.
Aged↗
Transient cerebral vasodilatory effect of neuropeptide Y mediated by nitric oxide.
The effects of intracarotidly injected neuropeptide Y (NPY; 0.1 micrograms/kg) on the local cerebral blood volume (CBV) and blood flow (CBF) in the parieto-temporal cortex were examined by the photoelectric method in 17 anesthetized cats. CBV reflects the cumulative crosssectional area of the cerebral microvascular beds. NPY immediately caused transient but significant increases in CBV and CBF, which lasted for less than 5 min. Thereafter, CBV returned to and remained at the control level, although CBF was decreased by 30-40% for 60 min during the monitoring period. The CBV increases after NPY were prevented by a 15-min preinjection of 0.35 mg/kg/min of NG-monomethyl-L-arginine (L-NMMA), which is a competitive blocker of nitric oxide synthesis. The CBV increases after NPY reappeared following a 15-min administration of 0.25 mg/kg/min of L-arginine, which is a precursor of nitric oxide. We conclude that NPY administered in vivo exerts a previously unreported effect of transient vasodilatation on the cerebral microvessels. This action appears to be mediated by nitric oxide, which is a major candidate as an endothelium-derived relaxing factor (EDRF).
Animals↗