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Biomedical subjects

Norio Tanahashi

Publications and source records attributed to Norio Tanahashi.

14 recordsLinked to original sources
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↗
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↗
PubMed2002

Moment analysis of microflow histogram in focal ischemic lesion to evaluate microvascular derangement after small pial arterial occlusion in rats.

The authors' high-spatial-resolution optical method was used to examine microvascular derangement in a focal cerebral cortex lesion in 12 Sprague-Dawley rats anesthetized with alpha-chloralose-urethane. A pial artery (approximately 40- to 50 microm diameter) was occluded by laser-beam cauterization (n = 6). Diluted carbon black suspension was injected into the internal carotid artery, and images in a 2-mm x 2-mm region of interest during tissue dye-dilution were recorded. Sequential frames were analyzed with Matlab software to evaluate blood distribution and mean transit time, affording a two-dimensional microflow map and histogram with first, second, third, and fourth moments. In the early phase of ischemia, blood distribution and average flow decreased (both P < 0.01), and the second moment (microflow heterogeneity) and third moment (skew to the left owing to increase in low-flow components) increased (P < 0.05 and P < 0.01, respectively). At approximately 2 hours, blood distribution decreased further in 3 cases, apparently because capillary stasis prevented carbon black filling. However, average microflow unexpectedly increased in 4 of 5 rats, presumably due to exclusion of unperfused (low flow at the earlier stage) channels from the calculation. The authors conclude that flow in ischemic tissue is quite heterogeneous and that an averaged flow value tends to smear important information about ischemic microvascular derangement.

Animals↗
PubMed2002

Thrombolysis candidates for the treatment of stroke at an emergency department in Japan.

OBJECTIVES: To study the proportion and characteristics of potential candidates for the intravenous administration of tissue plasminogen activator (IV-tPA) among patients with cerebral infarction in a Japanese emergency department (ED). METHODS: A retrospective observational study was performed using patients who had been transported by ambulance between August 1988 and April 2000 to an urban ED of a university hospital located in the Tokyo metropolitan area. Potential candidates for IV-tPA were identified using the criteria of the National Institute of Neurological Disorders and Stroke (NINDS) study. RESULTS: Of all 30,064 patients transported by ambulance, 526 were diagnosed as having cerebral infarction. Among them, 190 patients arrived at the ED within two hours of symptom onset (early ED arrivers). In comparison of their demographics with late ED arrivers (n = 319), atrial fibrillation, male gender, and consciousness disturbance were related with early ED arrivers, while aging and diabetes were related with late ED arrivers. As to the stroke subtype, patients with an embolic infarction accounted for 76.8% among early ED arrivers. Application of exclusion criteria identified 114 patients, who were suitable for the thrombolysis treatment, indicating that the proportion of potential IV-tPA candidates was 21.7% among all cerebral infarction patients and 0.38% among all ED patients. CONCLUSIONS: The number of potential IV-tPA candidates among patients transported to the ED by ambulance in Japan was substantial, where the proportion of embolic infarction cases was extremely high.

Aged↗
PubMed2002

Treatment of acute ischemic stroke: recent progress.

Intravenous thrombolysis with tissue plasminogen activator is currently the most effective treatment of acute ischemic stroke if administerd within 3 hours after symptom onset. Intraarterial thrombolysis by prourokinase is the another choise if the middle cerebral artery is occluded and within less than 6 hours after onset. Although heparin especially a moderate dose is not proved to be effective, a randomized, placebo-controlled trial to determine the safety and efficacy of argatroban (a selective thrombin inhibitor) in patients with acute ischemic stroke was started in USA. Aspirin provides some benefit to patients with acute stroke. However, its effect is not fully satisfactory. Although reports of numerous trials for neuroprotective drugs have been disappointing, edaravone (free radical scavenger) was approved for the treatment of acute ischemic stroke in Japan. In the future, thrombolytic and neuroprotective drugs will be used in combination.

Anticoagulants↗
PubMed2002

[Study of genotype frequencies of ANP 664G/A polymorphism in normal subjects and CVD patients, and its association with plasma ANP levels].

Atrial natriuretic peptide (ANP) plays a crucial role in regulating body fluid volume and blood pressure, by promoting natriuresis and vasodilatation and by inhibiting the renin-angiotensin system. Plasma levels of ANP are elevated in heart failure and hypertension, and ANP is thus believed to be involved in the pathogenesis of cardiovascular disorders. Previous case-control studies have shown that a single nucleotide polymorphism in the first exon of ANP gene, 664G/A, is associated with a risk of cerebrovascular disease (CVD) in white populations. Plasma ANP levels, however, were not evaluated in these studies in relation to the 664G/A, although the nucleotide substitution causes an amino-acid change in the propeptide of ANP. In this study, we analyzed the genotype frequencies of the 664G/A in Japanese patients with CVD (n = 199) and age- and gender-matched control subjects(n = 176). Genotypes with the 664A allele in the Japanese control subjects (G/A and A/A 12.5%) were apparently more frequent compared to the published frequency of the white control population (G/A and A/A 6.6%, p = 0.0437). Genotypes with the 664A allele, however, were not significantly different between our CVD patients(15.1%) and controls (12.5% p = 0.4714). In the control group (n = 137), the mean plasma ANP levels were not different between the 664G/G (15.7 +/- 10.7 pg/ml) and 664G/A genotypes (15.6 +/- 6.8 pg/ml, p = 0.9708). These results suggest that there is a racial difference in the allele frequency of 664G/A, and that this polymorphism may not be a major risk factor for CVD in the Japanese, nor is it a major determinant of plasma ANP level.

Atrial Natriuretic Factor↗