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Norio Tanahashi

Publications and source records attributed to Norio Tanahashi.

At least 19 recordsLinked to original sources
PubMed2006

G501C polymorphism of oxidized LDL receptor gene (OLR1) and ischemic stroke.

The human lectin-like oxidized low-density lipoprotein receptor 1 (OLR1/LOX-1) is the major endothelial scavenger receptor against oxidized low-density lipoprotein (Ox-LDL), which has been implicated in the pathogenesis of atherosclerosis. We investigated the G501C mutation in the OLR1 gene in 235 Japanese patients with ischemic cerebrovascular disease (CVD) and 274 age- and sex-matched healthy controls using single nucleotide primer extension analysis (SNuPe). There was no significant difference in the polymorphism between patients with ischemic CVD and controls (GC+CC versus GG, p=0.48). The C allele was not significantly different between the patients and controls (C versus G, p=0.91). Our results show that the OLR1 gene polymorphism has little effect on an increased risk for ischemic CVD in the Japanese population.

Brain Ischemia↗
PubMed2006

A561C polymorphism of E-selectin is associated with ischemic cerebrovascular disease in the Japanese population without diabetes mellitus and hypercholesterolemia.

E-selectin, which is a member of the selectin superfamily of adhesion molecules, contributes to the leukocyte-endothelial cell attachments and is involved in the pathogenesis of thrombovascular diseases as a consequence. We investigated the A561C mutation in the E-selectin gene in 235 Japanese patients with ischemic cerebrovascular disease (CVD) and 301 age- and sex-matched healthy controls. Excluding the subjects with diabetes mellitus and hypercholesterolemia, the AC genotype frequencies of patients with ischemic CVD were higher than those of controls: 12.7% vs. 5.8% (P=0.04). Our results show that E-selectin gene polymorphisms represent an increased risk for ischemic CVD in the Japanese population without diabetes mellitus and hypercholesterolemia.

Aged↗
PubMed2006

Capillo-venous flow in the brain: significance of intravascular RBC aggregation for venous flow regulation.

Despite numerous reports on the regulation of cerebral arterial blood flow, little work has been done on that of the capillary and venous system. We have examined capillo-venous blood flow in the rat intraparenchymal cerebral cortex, employing a high-speed video confocal fluorescence microscope and our own software (KEIOIS-2) to track individual RBCs and to document velocity changes in single capillaries and veins. We found temporal and spatial heterogeneous changes in capillary RBC density (hematocrit), RBC recruitment, oscillation of capillary flow or vasomotion, and capillary density unrelated to arteriolar diametric changes. In veins, blood flow was also quite variable in time and space, and at a high frame rate venous blood per se was observed as a moving column of amorphous RBC aggregates with irregular edges; we believe this is the first report of such an observation under physiological conditions. The formation of such intravascular RBC aggregates would enforce slowing of blood flow and vice versa: RBC aggregation was in turn entirely flow-dependent. In rapid venous flow, RBCs appeared as a straight gathering of individually separated and dispersed cells. At capillo-venous junctions, an "RBC pouring" process appeared to occur, with RBCs either being sucked up from the capillary, merging, or being held back in the capillary. Changes in venous blood viscosity due to RBC aggregation are likely to be involved in this process. These findings suggest that the capillo-venous junction somehow participates in the regulation of appropriate tissue capillary flow in toto.

Animals↗
PubMed2006

Reactive oxygen species generated by mitochondrial injury in human brain microvessel endothelial cells.

Generation of reactive oxygen species (ROS) and their detrimental effects on the brain after transient ischemia are widely recognized. We studied ROS production from mitochondria in human brain microvessel endothelial cells (HBEC) under chemical hypoxia. HBEC in confluent conditions were incubated for 30 min with 10 microM 5-(and-6)-carboxy-2',7'-dichlorodihydrofluorescein (DCF) diacetate, which was hydrolyzed and trapped inside the cells. ROS were measured with a fluorescent microscope, a CCD camera and an image analyzing system. Injury to mitochondrial respiratory chain was induced either with rotenone (an inhibitor of mitochondrial complex I) or with m-chlorocarbonyl cyanide phenylhydrazone (CCCP) (an uncoupler of ATP synthetase). Shortly after application of 10 microM rotenone, fluorescent intensity started to increase and the gradual increase continued for 10 min. Similarly, CCCP (10, 50 and 100 microM) dose-dependently increased the fluorescent intensity (p<0.01). Edaravone, a free radical scavenger widely used for treatment of cerebral infarction in Japan, at 100 microM successfully suppressed this ROS production (p<0.05). These data show that chemical hypoxia with normal concentration of oxygen in the medium induced free radicals generation in HBEC. Importance of endothelial mitochondria as a source of free radicals after reperfusion is suggested.

Antipyrine↗
PubMed2006

Astroglial swelling for removed rat brain enlargement incubated in deoxygenated mock cerebrospinal fluid.

The source and target of edema fluid for ischemic brain swelling clinically often observed in "malignant infarction" was examined in ex vivo. Wister rat brain hemispheres were removed and incubated air-tightly in a deoxygenated artificial cerebrospinal fluid at 37 degrees for 30 min. Ionic movement into the brain tissue was calculated from their concentration changes in the incubation fluid. We found a weight increase by 11.3+/-2.5% (p<0.01) and a decrease in Na+ from 148.0 to 139.0 +/- 8.2 mEq/l (p<0.01) and an increase in K+ from 4.3 to 11.2 +/- 1.2 mEq/l. Video tape recording revealed that the brain swelling started immediately upon the incubation, and the electronmicroscopical investigation of the swollen cortical tissue revealed that the fluid moved mainly into astroglial cells. The astroglial swelling was quite similar to that of specimen taken from clinical cases at autopsy. The driving force of the water shift can be explained by discharge of thermodynamic potential, i.e., a coupled transport of water with Na+ across the cell membrane (anomalous osmosis). The swelling was not affected by addition of aquaporin blocker, mercuric chloride. It is concluded that cerebrospinal fluid bathing the brain in situ can be the source of edema fluid for ischemic brain swelling.

Animals↗
PubMed2006

[Stroke and renin-angiotensin system].

Angiotensin II is a key mediator in the mechanism of hypertension and plays a pathophysiological role for the development of ischemic stroke. Activation of AT1 receptors by angiotensin II initiates a complex signaling cascade via in part reactive oxygen species produced by the enzyme NADPH oxidase in blood vessels and induces vasoconstriction, vascular proliferation, and inflammation leading to cerebrovascular insufficiency. On the other hand, AT2 receptors are potentially protective. Recently, many clinical trials showed inhibition of renin-angiotensin system(AT1 receptor blockers and ACE inhibitors) has beneficial effect on stroke prevention independent of blood pressure lowering. Inhibition of renin-angiotensin system is a new promising strategy for stroke prevention.

Angiotensin II↗
PubMed2005

T280M and V249I polymorphisms of fractalkine receptor CX3CR1 and ischemic cerebrovascular disease.

The contribution to atherosclerosis of two CX3CR1 single nucleotide polymorphisms, V249I and T280M has been recently reported. The atherosclerosis of intracranial vessels is thought to be the major pathological mechanism of ischemic stroke. In this study, we investigated the risk of ischemic stroke associated with fractalkine receptor CX3CR1 polymorphisms. We investigated the T280M and V249I mutations in the CX3CR1 gene in 235 Japanese patients with ischemic cerebrovascular disease (CVD) and 306 age- and sex-matched healthy controls. Polymerase chain reaction and restriction fragment length polymorphism were used for genotyping. There was no significant difference in both polymorphisms between patients with ischemic CVD and controls (VV versus II+VI, p=0.83; TT versus MM+TM, p=0.66). The I and M allele frequencies were not significantly different between CVD patients and controls: odds ratio (OR)=0.89 (95% confidence interval (CI)=0.50-1.60, p=0.70) and OR=1.19 (95% CI=0.71-2.00, p=0.51), respectively. We found eight of nine possible combined genotypes, including a new haplotype V249-M280, in Japanese. Our results show that these CX3CR1 gene polymorphisms are not associated with an increased risk for ischemic CVD in the Japanese population.

CX3C Chemokine Receptor 1↗
PubMed2005

Initial oligemia with capillary flow stop followed by hyperemia during K+-induced cortical spreading depression in rats.

Local cerebral blood volume (CBV) and capillary flow changes in regions of depolarizing neurons during K(+)-induced cortical spreading depression (CSD) in the cerebral cortex of alpha-chloralose-urethane-anesthetized rats were examined employing a transillumination (550 nm) video system. Capillary flow was calculated as the reciprocal of mean transit times of blood in pixels of 40 microm x 40 microm, each of which contains a few capillaries. Potassium microinjection into the cortex evoked repetitive wave-ring spreads of oligemia at a speed of ca. 2.33 +/- 0.48 mm/min. During the spread of CSD, tracer (either saline or carbon black) was injected into the internal carotid artery. Colocated with the oligemic wave, we detected capillary flow stop as evidenced by disappearance of the hemodilution curves. At any location in the region of interest within the cerebral cortex, we observed cyclic changes of capillary flow stop/hyperperfusion in synchrony with oligemia/hyperemia fluctuations. The initial flow stop and oligemia were ascribed to capillary compression by astroglial cell swelling, presumably at the pericapillary endfeet, since the oligemia occurred before larger vessel changes. We conclude that local depolarizing neurons can decrease adjacent capillary flow directly and immediately, most likely via astroglial cell swelling, and that the flow stop triggers upstream arteriolar dilatation for capillary hyperperfusion.

Animals↗
PubMed2005

Clinical and laboratory features of in-patients with multiple sclerosis in a University Hospital in Tokyo from 1988-2002.

OBJECTIVE: The aim of this study was to analyze the clinical and laboratory features of each subtype of multiple sclerosis (MS) (relapsing-remitting, primary progressive, and secondary progressive) in the Tokyo metropolitan area. METHODS AND PATIENTS: We retrospectively analyzed the medical records of 104 consecutive patients with a diagnosis of MS, who had been admitted to our university hospital from 1988 to 2002. They all met criteria for definite MS, by clinical or laboratory standards. RESULTS: Eighty-four (80.8%) patients were classified as having relapsing-remitting MS, while 8 patients (7.7%) and 12 patients (11.5%) were classified as having primary progressive MS and secondary progressive MS, respectively. A significant female predominance existed in the relapse-remitting MS (female : male=2.4 : 1) cohort, but this ratio was 1 : 1 in both primary progressive and secondary progressive MS. The age at onset was older in the primary progressive MS (36.6+/-17.1 years of old) population than in either the relapsing-remitting MS (27.9+/-11.1) or the secondary progressive MS (27.8+/-11.5) subjects. Although the duration of illness was similar among the three types of MS, the number of exacerbations in the secondary progressive (5.9+/-4.6) cohort was significantly higher than that in the relapsing-remitting MS subjects (3.2+/-2.6). Patients with primary progressive MS showed a significantly higher rate of gait disturbance (87.5%) as the initial symptom than those with relapsing-remitting MS (23.8%), and this was thought to be due to the higher incidence of brainstem and spinal cord lesions. Visual disturbance as the initial symptom was frequently noted in those with secondary progressive MS (50.0%), while it was noted only in 29.8% and 12.5% in the relapsing-remitting and primary progressive patients, respectively. Primary progressive MS subjects had a higher propensity to be wheelchair-bound (75.0%) than those suffering from relapsing-remitting MS (1.2%). Increased total protein in the cerebrospinal fluid (CSF) of the secondary progressive cohort was statistically significant compared to the relapsing-remitting cohort. The frequency of oligoclonal IgG bands was rather low in each type of MS (17.1-33.3%). Gadolinium enhancement of plaques on MRI was more frequently present in secondary progressive MS (66.7%) than in either relapsing-remitting MS (32.1%) or primary progressive MS (50.0%). Of note, the opticospinal form was found in only 16.3% of the total MS patients, a proportion less than that in previous reports from southern Japan. CONCLUSION: The present study confirms that while the clinical and laboratory features of the MS patients in the Tokyo metropolitan area are similar to those in Western countries in most regards, features such as proportionally fewer primary and secondary progressive MS patients as well as less oligoclonal IgG bands on CSF analysis are different from those in Western countries.

Adult↗
PubMed2004

High throughput multiple combination extraction from large scale polymorphism data by exact tree method.

Single nucleotide polymorphisms (SNPs) are increasingly becoming important in clinical settings as useful genetic markers. For the evaluation of genetic risk factors of multifactorial diseases, it is not sufficient to focus on individual SNPs. It is preferable to evaluate combinations of multiple markers, because it allows us to examine the interactions between multiple factors. If all the combinations possible were evaluated round-robin, the number of calculations would rapidly explode as the number of markers analyzed increased. To overcome this limitation, we devised the exact tree method based on decision tree analysis and applied it to 14 SNP data from 68 Japanese stroke patients and 189 healthy controls. From the obtained tree models, we succeeded in extracting multiple statistically significant combinations that elevate the risk of stroke. From this result, we inferred that this method would work more efficiently in the whole genome study, which handles thousands of genetic markers. This exploratory data mining method will facilitate the extraction of combinations from large-scale genetic data and provide a good foothold for further verificatory research.

Adult↗
PubMed2004

Fluorometric determination of glucose utilization in neurons in vitro and in vivo.

Glucose is the major energy source the adult brain utilizes under physiologic conditions. Recent findings, however, have suggested that neurons obtain most of their energy from the oxidation of extracellular lactate derived from astroglial metabolism of glucose transported into the brain from the blood. In the present studies we have used 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), a fluorescent analogue of 2-deoxyglucose, which is often used to trace glucose utilization in neural tissues, to examine glucose metabolism in neurons in vitro and in vivo. Cultured neurons and astroglia were incubated with 2-NBDG for up to 15 minutes, and nonmetabolized 2-NBDG was washed out. We found that fluorescence intensity increased linearly with incubation time in both neurons and astroglia, indicating that both types of brain cells could utilize glucose as their energy source in vitro. To determine if the same were true in vivo, Sprague-Dawley rats were injected intravenously with a pulse bolus of 2-NBDG and decapitated 45 minutes later. Examination of brain sections demonstrated that phosphorylated 2-NBDG accumulated in hippocampal neurons and cerebellar Purkinje cells, indicating that neurons can utilize glucose in vivo as energy source.

4-Chloro-7-nitrobenzofurazan↗
PubMed2004

[Genetic risk factors for ischemic cerebrovascular disease--analysis on fifteen candidate prothrombotic gene polymorphisms in the Japanese population].

Accumulating evidence suggests that several polymorphisms in factors regulating blood coagulation, platelet function, and lipid metabolism are relevant for susceptibility to ischemic cerebrovascular diseases (CVD). The present study analyzed 15 genetic polymorphisms possibly associated with atherosclerosis and thrombosis in a case-control study involving a total of 200 genetically unrelated Japanese patients with ischemic CVD (mean age 58.3 +/- 7.6 y) and 281 age- and gender-matched control subjects (59.0 +/- 4.1 y). Control subjects were randomly selected from unrelated donors with no history of documented CVD or any type of cardiovascular disease with normal resting electrocardiograms. Among the factors genotyped, two factors, platelet glycoprotein (GP) Ib alpha (Thr145Met) and NADPH oxidase p22phox (His72Tyr), were significantly associated with CVD after adjustment for acquired risk factors including hypertension, diabetes mellitus, hyperlipidemia, and smoking. For those with age < 60 y, 10.6% of the CVD patients and 2.9% of the control subjects had both of the two risk genotypes (GPIb alpha 145Met and p22phox 72Tyr, p < 0.05). The mean onset-age of CVD was 58.6 +/- 7.7 y for those having no or only one risk genotype, while 53.3 +/- 5.5 y for those having both of the risk genotypes (p < 0.05). Thus, GPIb alpha 145Met and p22phox 72 Tyr are the genetic factors associated with the risk of ischemic CVD in the Japanese. Carrying both of the two mutations might be associated with developing CVD at a younger age.

Aged↗
PubMed2004

A case report of giant cell myocarditis and myositis observed during the clinical course of invasive thymoma associated with myasthenia gravis.

The patient is a 62-year-old man who was diagnosed with myasthenia gravis and invasive thymoma at the age of 45 years, and had received treatment by extended thymectomy and radiotherapy. At the age of 61, he had suffered from a myasthenic crisis, and been administered immunoadsorption therapy under managed ventilatory care. Treatment had then been continued with steroids; however, due to subsequent deterioration of his diabetic state, treatment was switched to the immunosuppressant drug tacrolimus. Three months after the commencement of tacrolimus administration, the patient developed generalized malaise and dyspnea. The serum creatine phosphokinase (CPK) level was abnormally elevated, and abnormal electrocardiographic findings were noted, including atrioventricular dissociation and ventricular escape contraction. Steroid pulse therapy was therefore initiated, however, 4 days later, the patient suddenly died. Autopsy examination revealed inflammatory cell infiltration with giant cells in the myocardium, diffuse myocardial degeneration, and polymyositis. The case was therefore considered as one with the syndrome of myasthenia gravis, polymyositis, giant cell myocarditis, and thymoma.

Alopecia↗
PubMed2003

Dynamic observation of oxygenation-induced contraction of and transient fiber-network formation-disassembly in cultured human brain microvascular endothelial cells.

Oxygenation-induced contraction of nonconfluent cultured human brain microvascular endothelial cells (HBECs, n = 30) was examined by video-enhanced contrast-differential interferential contrast microscopy. After administering a continuous gentle blow of pure oxygen gas to the surface of the medium just above the flattened HBEC, the plasma membrane exhibited tensioning and wrinkling, resulting in a strong contraction of the cell body by 14 +/- 7% (P < 0.001). When the cell stopped contracting, transient formation of a fiber network starting from certain spots (possibly adhesion plaques, though these were not visible in the majority of cases) and expanding to the whole cell was observed. The occurrence of fiber network formation was statistically significant (26 of 30 separate cells, P < 0.05). After cessation of oxygen delivery, the observed network of fibers broke up rapidly (in a period of 3.3 +/- 1.2 seconds) into small particles of <0.5 microm in diameter, which subsequently fused into the cellular structure. The HBEC completely recovered the control appearance. The sequential process was completed within 30 seconds and was reproduced in individual cells each time that oxygen gas was supplied. The authors conclude that the HBEC strongly contracts in response to a transient oxygenation stimulus, followed by rapid formation/disassembly of a network structure.

Brain↗
PubMed2003

[Problems in development and use of guidelines for clinical practice].

According to the Agency for Healthcare Research and Quality in the USA, the characteristics to be fulfilled by clinical guidelines are validity, reproducibility, reliability, clinical flexibility, clarity and scheduled review. However, most clinical guidelines do not necessarily fully satisfy these factors. I have been engaged in the development of evidence-based guidelines for the management of stroke in Japan. Problems in development of guidelines are as follows. The first is the lack of high level evidence such as randomized controlled trials, which influences recommendation grade. In the case of clinical guidelines for treatment of cerebral hemorrhage in the acute stage, the recommendation grade (C1, C2), which means a lack of sufficient scientific evidence, covered 86% of all recommendation items. The second is ease of clinical application. Evidence based clinical guidelines are not likely to be easy to use if sufficient high-level scientific evidence is not available. It must be realized that guidelines can only be applied to 60 to 95% of patients. Depending on the patient, setting, and other factors, guidelines can and should be tailored to fit individual needs. Deviations from guidelines will be fairly common and can be justified by differences in individual circumstances.

Bibliography of Medicine↗
PubMed2002

Repetitive concentric wave-ring spread of oligemia/hyperemia in the sensorimotor cortex accompanying K(+)-induced spreading depression in rats and cats.

Vascular changes accompanying spreading depression (SD) remain controversial. We examined dynamic alterations of local cerebral blood volume (CBV) during SD by observing light transmission at an isosbestic point of hemoglobin (550 nm) in seven rats and five cats under alpha-chloralose/urethane anesthesia. The two species were used for comparison between the lissencephalic and gyrencephalic brains. We found that a concentrated K(+) solution microinjected into the sensorimotor cortex provoked CBV changes that appeared as a repetitive propagation of concentric wave-rings of ischemia followed by hyperemia expanding peripherally from the injection site at speeds of 1.9-3.2 mm/min. The dynamic CBV changes continued repeatedly every 1-5 min for more than 30 min in three rats, ceased within 30 min in three rats and remained at the site of K(+) injection in one rat. Similar repeated CBV changes occurred in two out of five cats.

Animals↗
PubMed2002

Dilatation of cerebral parenchymal vessels mediated by angiotensin type 1 receptor in cats.

We report the effects of angiotensin II (ANG-II), as well as angiotensin II type 1 (AT1) and type 2 receptor antagonists (CV-11974 and PD-123319, respectively) on the cerebral parenchymal microvessels in cats using the photoelectric method. ANG-II continuously and dose-dependently increased the cerebral blood volume (CBV) for 15 min. Maximum CBV increases were +0.36+or-0.11 vol% for 0.01 nmol/kg (P<0.05), +0.51+or-0.24 vol% for 0.1 nmol/kg (P<0.05), +1.87+or-0.55 vol% for 1 nmol/kg (P<0.05), and +2.14+or-0.77 vol% for 10 nmol/kg (P<0.05). Systemic arterial blood pressure increased at only 1 min following ANG-II infusion (1 and 10 nmol/kg). CV-11974 and PD-123319 per se did not change the resting CBV. CV-11974 completely inhibited the vasodilatory action of ANG-II, however, PD-123319 did not block it. We conclude that ANG-II directly dilates the parenchymal vessels through the AT1 receptor without increasing systemic blood pressure, and that intrinsic ANG-II may not be associated with maintenance of resting vascular tone.

Angiotensin II↗