Search PubMed⌕ Search

Biomedical subjects

Takao Takeshima

Publications and source records attributed to Takao Takeshima.

At least 19 recordsLinked to original sources
PubMed2006

Increased plasma substance P and CGRP levels, and high ACE activity in migraineurs during headache-free periods.

Substance P (SP), calcitonin gene-related peptide (CGRP), and angiotensin converting enzyme (ACE) may have roles in trigeminovascular nociceptive mechanisms. We investigated interictal levels of SP, CGRP, ACE activity, and their correlation, in a sample of migraineurs. Forty-one patients suffering from migraine with aura (MA), 54 without aura (MO), and 52 non-headache subjects (controls) participated in this study. Blood samples were collected from cubital veins. Plasma levels of SP and CGRP were measured by enzyme immunoassay. Plasma ACE activities were measured spectrophotometrically. SP levels in MA (6.6+/-3.7 pg/ml; mean+/-SD) and MO (6.6+/-3.2 pg/ml) were significantly higher than in controls (4.8+/-2.4 pg/ml) (P<0.01). CGRP levels in MA (18.8+/-8.8 pg/ml) and MO (19.1+/-9.4 pg/ml) were also significantly higher than in controls (13.4+/-4.4 pg/ml) (P<0.01). ACE activities in MA (34.6+/-19.0 U/l) were significantly higher than in MO (25.3+/-13.2 U/l) and controls (27.0+/-20.4 U/l) (P<0.05). There was a significant correlation between SP and CGRP levels (P<0.05). In MA, SP and CGRP showed a tendency toward positive correlation, which was not significant. There was a weak, but significant positive correlation between SP levels and ACE activities (P<0.01). However, a relationship between ACE activities and CGRP levels was not observed. The data suggest that SP, CGRP, and ACE are relevant to migraine pathophysiology, and that they may interact.

Adult↗
PubMed2006

D-beta-hydroxybutyrate protects dopaminergic SH-SY5Y cells in a rotenone model of Parkinson's disease.

It has been postulated that the pathogenesis of Parkinson's disease (PD) is associated with mitochondrial dysfunction. Rotenone, an inhibitor of mitochondrial complex I, provides models of PD both in vivo and in vitro. We investigated the neuroprotective effect of D-beta-hydroxybutyrate (bHB), a ketone body, against rotenone toxicity by using SH-SY5Y dopaminergic neuroblastoma cells. SH-SY5Y cells, differentiated by all-trans-retinoic acid, were exposed to rotenone at concentrations ranging from 0 to 1,000 nM. We evaluated cellular oxidation reduction by the alamarBlue assay, viability by lactate dehydrogenase (LDH) assay, and survival/death ratio by live/dead assays. Exposure to rotenone for 48 hr oxidized cells and decreased their viability and survival rate in a concentration-dependent manner. Pretreatment of cells with 8 mM bHB provided significant protection to SH-SY5Y cells. Whereas rotenone caused the loss of mitochondrial membrane potential, released cytochrome c into the cytosol, and reduced cytochrome c content in mitochondria, addition of bHB blocked this toxic effect. bHB also attenuated the rotenone-induced activation of caspase-9 and caspase-3. Administration of 0-10 mM 3-nitropropionic acid, a complex II inhibitor, also decreased the reducing power of SH-SY5Y cells measured by alamarBlue assay. Pretreatment with 8 mM bHB attenuated the decrease of alamarBlue fluorescence. These data demonstrated that bHB had a neuroprotective effect that supported the mitochondrial respiration system by reversing the inhibition of complex I or II. Ketone bodies, the alternative energy source in the mammalian brain, appear to have therapeutic potential in PD.

3-Hydroxybutyric Acid↗
PubMed2006

Familial limb pain in childhood: unusual manifestation of migraine?

A familial case of limb pain is described. Frequent vascular pain appeared during early childhood in affected individuals, often with predominance in the lower extremities. This pain subsided in patients during adolescence, when they began to suffer from typical migraine. The limb pain was moderate to severe, and refractory to analgesic and anti-migraine medications. Limb temperature was cold at the onset of pain, and became warm during the painful attacks. Plasma substance P and calcitonin gene-related peptide were elevated during the episodic pain. We propose this condition is a new precursor etiology of migraine, with possible autosomal dominant inheritance.

Analgesics↗
PubMed2006

[Three Japanese cases of hypnic headache].

We described three cases of hypnic headache with successful treatment by lithium carbonate or caffeine. This is the first detail report of Japanese cases. An endocrinological test and rhythm analyses of ambulatory blood pressure (ABP) and heart rate variability in a case suggested possible association between hypnic headache and hypothalamic-pituitary dysfunction. Case 1: A 48-year-old female migraineur complained of new-onset nocturnal headaches. Her headache awakened her from sleep between 1 AM and 2 AM. The headache occurred 3-4 times per week and lasted from 1 hour to 2 hours. The headache were moderate intensity and bilateral dull throbbing pain that located in the forehead to temples. There was no accompanying symptoms such as nausea, phonophobia, photophobia, nor the other autonomic features including conjunctival injection or tearing during the headache attacks. Physical and neurological examinations showed normal results except slight weakness and mild dysesthesia of the left arm due to a vertebral disk herniation at C5/6 level. In the pituitary endocrinological test, the prolactin level remarkably increased in response to the TRH loading. The single cosinor analysis demonstrated significant circadian rhythm of ABP parameters. However, the analysis did not demonstrate any significant circadian rhythm of Holter ECG parameters of time domain analysis and frequency analysis. Receiving 200 mg lithium bicarbonate before sleep, her nocturnal headache completely disappeared. Case 2: A 68-year-old woman had been followed up by her chronic tension-type headache since her forties. At her 66-years, she suffered from a new nocturnal headache. She awoke from sleep by the headache about 3 AM and the headache lasted 30 min. Moderate, dull headache located on her left temple to parietal head, 3-4 times/week. She was able to go back asleep without any medication after spontaneous headache cessation. She first complained the nocturnal headache at the 10 months later of the new headache appearance. She received 200 mg caffeine just before sleep and her headache has been disappeared. Case 3: 70-year-old women had been regularly visited our clinics for her migraine and chronic tension-type headache. She received amitriptyline and her headaches was well controlled. At her 69 years, she complained nocturnal headache. It occured every other day. The headache was moderate pulsative dull pain on the occipital region and lasted 90 minutes without any autonomic symptoms. Headache began between midnight and 1 AM. She told us her new nocturnal headache one year later of the onset. Oral caffeine (200 mg) just before sleep did not improve her headache and caused insomnia. Receiving 100 mg lithium before sleep, her hypnic headache disappeared completely. These three cases are compatible with the diagnostic criteria proposed in ICHD-II. There were some patients with hypnic headache in Japan and neurologists should pay attentions to this form of benign headache, because some beneficial treatments are currently available.

Aged↗
PubMed2005

Novel cytoprotective mechanism of anti-parkinsonian drug deprenyl: PI3K and Nrf2-derived induction of antioxidative proteins.

Neuroprotection has received considerable attention as a strategy for the treatment of Parkinson's disease (PD). Deprenyl (Selegiline) is a promising candidate for neuroprotection; however, its cytoprotective mechanism has not been fully clarified. Here, we report a novel cytoprotective mechanism of deprenyl involving PI3K and Nrf2-mediated induction of oxidative stress-related proteins. Deprenyl increased the expression of HO-1, PrxI, TrxI, TrxRxI, gammaGCS, and p62/A170 in SH-SY5Y cells. Deprenyl also induced the nuclear accumulation of Nrf2 and increased the binding activity of Nrf2 to the enhancer region of human genomic HO-1. The Nrf2-mediated induction of antioxidative molecules was controlled by PI3K. Indeed, furthermore, neurotrophin receptor TrkB was identified as an upstream signal for PI3K-Nrf2 activation by deprenyl. These results suggest that the cytoprotective effect of deprenyl is, in part, dependent on Nrf2-mediated induction of antioxidative proteins, suggesting that activation of the PI3K-Nrf2 system may be a useful therapeutic strategy for PD.

Antioxidants↗
PubMed2005

Association of the insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients of migraine with aura.

Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an angiotensin II receptor blocker were demonstrated to have a clinically important prophylactic effect in migraine. ACE is one of the key enzymes in the rennin-angiotensin-aldosterone system, which modulates vascular tension and blood pressure. In humans, serum ACE levels are strongly genetically determined. Individuals who were homozygous for the deletion (D) allele showed increased ACE activity levels. To investigate the role of ACE polymorphism in headache, we analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering from migraine with aura (MwA), 122 from migraine without aura, 78 from tension-type headache (TH), and 248 non-headache healthy controls. The ACE D allele were significantly more frequent in the MwA than controls (p<0.01). The incidence of the D/D genotype in MwA (25.9%) was significantly higher than that in controls (12.5%; p<0.01; odds ratio=5.26, 95% confidence interval: 1.69-16.34, adjusted for age and gender). No differences in the remaining groups were found. Our results support the conclusion that the D allele and the D/D genotype in the ACE gene is a genetic risk factor for Japanese MwA. There seems to be a possible relationship between ACE activity and the pathogenesis of migraine.

Adult↗
PubMed2005

Pro-apoptotic protein glyceraldehyde-3-phosphate dehydrogenase promotes the formation of Lewy body-like inclusions.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein; however, previous studies by our group and others have demonstrated that GAPDH is a general mediator initiating one or more apoptotic cascades. Our most recent findings have elucidated that an expression of a pro-apoptotic protein GAPDH is critically regulated at the promoter region of the gene. Apoptotic signals for its subsequent aggregate formation and nuclear translocation are controlled by the respective functional domains harboured within its cDNA component. In this study, coexpression of GAPDH with either wild-type or mutant (A53T) alpha-synuclein and less likely with beta-synuclein in transfected COS-7 cells was found to induce Lewy body-like cytoplasmic inclusions. Unlike its full-length construct, the deleted mutant GAPDH construct (C66) abolished these apoptotic signals, disfavouring the formation of inclusions. The generated inclusions were ubiquitin- and thioflavin S-positive appearing fibrils. Furthermore, GAPDH coimmunoprecipitated with wild-type alpha-synuclein in this paradigm. Importantly, immunohistochemical examinations of post mortem materials from patients with sporadic Parkinson's disease revealed the colocalized profiles immunoreactive against these two proteins in the peripheral zone of Lewy bodies from the affected brain regions (i.e. locus coeruleus). Moreover, a quantitative assessment showed that about 20% of Lewy bodies displayed both antigenicities. These results suggest that pro-apoptotic protein GAPDH may be involved in the Lewy body formation in vivo, probably associated with the apoptotic death pathway.

Acetates↗
PubMed2005

Increased plasma transforming growth factor-beta1 in migraine.

BACKGROUND AND OBJECTIVES: Migraine is characterized by the peripheral and central sensitization of pain perceptive neural systems, and neurogenic inflammation is a key step in the development of migraine headache. We focused on transforming growth factor-beta1 (TGF-beta1), which is a multifunctional proinflammatory cytokine. To address the possibility of TGF-beta1 involvement in migraine, we investigated the plasma level of TGF-beta1 in patients with migraine headache during headache-free periods. SUBJECTS AND METHODS: Sixty-eight subjects with migraine participated: 23 with migraine with aura (MWA) and 45 without aura (MWoA). We recruited 58 healthy subjects without headache as controls. In addition, we examined 12 subjects with episodic tension-type headache. Platelet poor plasma (PPP) was obtained from subjects during headache free-periods. TGF-beta1 levels in PPP were determined by enzyme-linked immunosorbent assay. RESULTS: The TGF-beta1 level in PPP was 2.62*+/- 0.23 (mean +/- SE) ng/mL in migraine, 2.08 +/- 0.20 ng/mL in tension-type headache, and 1.80 +/- 0.09 ng/mL in controls (P= .007, ANOVA; *P < .01, post hoc tests vs. the controls). CONCLUSION: TGF-beta1 in PPP was significantly increased in patients with migraine during headache-free periods. TGF-beta1 may play some role in the development of migraine headache.

Adult↗
PubMed2005

Approximate entropy in the electroencephalogram during wake and sleep.

Entropy measurement can discriminate among complex systems, including deterministic, stochastic and composite systems. We evaluated the changes of approximate entropy (ApEn) in signals of the electroencephalogram (EEG) during sleep. EEG signals were recorded from eight healthy volunteers during nightly sleep. We estimated the values of ApEn in EEG signals in each sleep stage. The ApEn values for EEG signals (mean +/- SD) were 0.896 +/- 0.264 during eyes-closed waking state, 0.738 +/- 0.089 during Stage I, 0.615 +/- 0.107 during Stage II, 0.487 +/- 0.101 during Stage II, 0.397 +/- 0.078 during Stage IV and 0.789 +/- 0.182 during REM sleep. The ApEn values were found to differ with statistical significance among the six different stages of consciousness (ANOVA, p<0.001). ApEn of EEG was statistically significantly lower during Stage IV and higher during wake and REM sleep. We conclude that ApEn measurement can be useful to estimate sleep stages and the complexity in brain activity.

Adult↗
PubMed2005

[Genetic analysis of migraine headache: a review].

Recent advances in genetic analysis of migraine headache are reviewed. Point mutations of P/Q -type Ca2+ channel alpha1 subunit(CACNA1A) gene and Na-K ATPase, alpha2 (ATP1A2) gene have been identified in the familial hemiplegic migraine (FHM-1 and FHM-2, respectively). Mutations in notch-3 gene cause the cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is an autosomal dominant inherited disorder often accompanying with migraine like headache. Serotonin (5-HT) related genes, dopamine D2 receptors (DRD2) gene, methylenetetrahydrofolate reductase (MTHFR) gene, and angiotensin converting enzyme (ACE) gene have been noticed as the susceptible genes for migraine pathogenesis. Genetic study of migraine is promising and will provide further understanding of the migraine pathophysiology. Discovery of the responsible or susceptible genes will open an avenue to develop new therapeutic strategy.

CADASIL↗
PubMed2005

[Migraine update].

Migraine is one of the common diseases suffering 8.4 million patients in Japan. The pathophysiology of migraine remains unclear. The genetic and basic studies of the familial hemiplegic migraine, a specific subtype of migraine with aura, have demonstrated the dysfunction of mutant brain-expressed calcium ion channel and/or the Na+/K+ ion transporter and suggested the association between cortical spreading depression (CSD) and migraine with aura. It is suggested that the CSD, neurogenic inflammation and vasodilatation caused by unknown triggers may activate the 'brainstem migraine generator' and amplified back way. In consequence, headache and/or aura will be appeared and strengthened. Our etiological data of headache in Daisen located in Western Japan clarified as follows; 1) Overall prevalence of migraine in Daisen was 6.0%. Women observed a 5.9-fold higher risk of migraine than men. 2) Fatigue, mental stress, and lack of sleep were the main headache triggers. 3) Only 7.3% of those with migraine with aura and 5.3% of those with migraine without aura had consulted a physician. 4) Migraineurs consume significantly more fatty/oily foods, coffee, and tea than nonheadache subjects of the same community. Migraineurs consume significantly fewer fish than nonheadache residents. As a conclusion, only a few Japanese migraineurs receive benefits of medical services and recent advances of headache medicine. The Japanese guideline for chronic headache treatment has declared in 2002. The International Classification of headache disorders has reedited to the 2nd edition. Public education concerning headaches is one of the most urgent issues in Japan.

Adult↗
PubMed2004

Transcriptional activation of p62/A170/ZIP during the formation of the aggregates: possible mechanisms and the role in Lewy body formation in Parkinson's disease.

Formation of intracellular inclusion bodies due to defects in the protein degradation machinery is associated with the pathogenesis of neurodegenerative diseases. Sequestosomal protein p62/A170/ZIP, which is an oxidative stress-related protein and a ubiquitin-binding protein, is a component protein of Lewy bodies that are observed in patients with Parkinson's disease. The association of p62 with poly-ubiquitinated proteins may be an important step in the formation of intracellular protein aggregates like Lewy bodies. To study the role of p62 in the formation of protein aggregates in PC12 cells, we monitored the intracellular localizations of p62 and ubiquitinated proteins and the levels of both components during treatment with MG132, a proteasome inhibitor. In the early stage of aggregate formation, p62 did not always co-localize with ubiquitin. In contrast, these proteins were always co-localized in later stages. After the treatment of the cells with MG132, we found that the expression level of p62 increased due to the transcriptional activation of the gene and that higher molecular sizes of p62, corresponding to mono- and di-ubiquitinated formes, were also formed. Both the transcriptional inhibitor actinomycin D and an antisense oligonucleotide of p62 inhibited the MG132-mediated increase of p62, the sequestration of ubiquitinated proteins, and the enlargement of the aggregates. Furthermore, p62-positive aggregates were observed primarily in surviving cells. Together, these results suggest that p62 plays an important role in the protection of cells from the toxicity of misfolded proteins by enhancing aggregate formation especially in the later stages.

Animals↗
PubMed2004

The regulatory region polymorphisms of the MTHFR gene are not associated with Alzheimer's disease.

Recent epidemiological studies have emphasized the impact of elevated blood homocysteine levels on the pathogenesis of Alzheimer's disease (AD). In spite of a significant impact of a MTHFR C677T polymorphism on the blood homocysteine levels, the association between the C677T polymorphism and AD remains controversial. Therefore, other unidentified genetic factor(s) that regulate blood homocysteine levels may exist. Here, we have analyzed the 5'-upstream region of the MTHFR gene and examined AD patients (n = 223) and nondemented individuals (n = 323) for polymorphisms in the 5'-upstream region of the MTHFR gene. We identified two polymorphisms (-713G/A and -393C/A, upstream of the start codon). We found no significant relationship between AD and the 5'-upstream region polymorphisms of the MTHFR gene. Thus, our study does not reinforce the hypothesis of an independent involvement of the MTHFR gene upstream region polymorphisms in AD risk.

Aged↗
PubMed2004

p53-mediated mitochondrial dysfunction by proteasome inhibition in dopaminergic SH-SY5Y cells.

Decreased proteasome activity is an important pathology in Parkinson's disease (PD), which is related to cell death and Lewy body formation. In this study, we show that p53-activity may correlate with neuronal death via the mitochondrial pathway in PD model. The proteasome inhibitor, MG132, induced the accumulation of p53 in human dopaminergic neuroblastoma SH-SY5Y cells. The increased stabilization of p53 upregulated the level of Bax and mitochondrial depolarization. These events were inhibited by the p53 inhibitor, pifithrin-alpha (PFT). Cell viability analyzes demonstrated that PFT partially prevented MG132-induced cell death. These results suggest that p53 is a candidate as an intermediary between the proteasome system and mitochondria-related neuronal death in PD.

Benzimidazoles↗
PubMed2004

Somatosensory evoked high-frequency oscillations in migraine patients.

OBJECTIVE: To explore additional evidence concerning generators of somatosensory evoked high-frequency oscillations (HFOs). METHODS: We recorded HFOs in migraine patients. Subjects were 19 healthy normal subjects and 19 migraineurs. Electrical stimuli were delivered alternately to the right and left median nerves at their wrists. EEGs were recorded from C3'-Fz, C4'-Fz, Erb1-Erb2, Erb2-Erb1 and Cv6-Fz using a 0.3 Hz low-frequency filter and a 3000 Hz high-frequency filter. Responses to 5000 stimuli were averaged. For separation of HFOs from underlying N20, the digitized wide-band signals were digitally bandpass filtered (400-800 Hz) and averaged. RESULTS: There were no significant differences in peak latencies and amplitudes for N9, N13, N20 and P25 components between normal controls and migraineurs. Root-mean-square amplitudes for HFOs in migraineurs were significantly diminished compared with normal controls. CONCLUSIONS: A diminished inhibitory mechanism in the somatosensory system may exist in migraineurs. It remains to determine what cell populations contribute to generating HFOs. SIGNIFICANCE: This indicates that there is a dysfunction in cortical information processing in the somatosensory cortex of migraineurs.

Adolescent↗
PubMed2004

A haplotype of the methylenetetrahydrofolate reductase gene is protective against late-onset Alzheimer's disease.

Epidemiological studies have shown that elevated plasma homocysteine (Hcy) levels play an important role in the pathogenesis of Alzheimer's disease (AD). In spite of the evidence that a C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene elevates plasma Hcy levels, the impact of the C677T polymorphism on the development of AD is controversial. Here, we performed a genetic case-control study in a Japanese population to investigate whether three polymorphisms of the MTHFR gene, C677T (Ala222Val), A1298C (Glu429Ala), and A1793G (Arg594Gln), are associated with the development of late-onset AD (LOAD). In our study, the MTHFR gene had four major regional haplotypes: Haplotype A (677C-1298A-1793G), Haplotype B (677T-1298A-1793G), Haplotype C (677C-1298C-1793G), and Haplotype D (677C-1298C-1793A). The frequency of Haplotype C in LOAD was significantly lower than that in control group. Furthermore, the benefit conferred by the presence of at least one Haplotype C was stronger in LOAD patients who lacked the ApoE 4 allele (OR=0.293; 95% CI=0.115-0.744; P=0.010). The results indicate that Haplotype C of the MTHFR gene is protective against the development of LOAD.

Aged↗
PubMed2004

Population-based door-to-door survey of migraine in Japan: the Daisen study.

OBJECTIVES: To determine prevalence and characteristics of migraine in Japan, and to investigate use of medical care and whether food preference is associated with risk of migraine. METHODS: Structured questionnaires were given to all adult residents (N = 5758; 2681 men and 3077 women) in Daisen, a rural community in western Japan. Second questionnaires, specific to headache, were given to 1628 residents with headache. A telephone survey was also carried out. Statistical Packages for the Social Sciences analyzed the data. RESULTS: The 1-year prevalence of migraine was 2.3% (migraine with aura, 0.4% and without aura, 1.9%) in men and 9.1% (migraine with aura, 1.0% and migraine without aura, 8.1%) in women. Overall prevalence of migraine in Daisen was 6.0% (95% confidence interval [CI], 5.4% to 6.6%). Women observed a 5.9-fold higher risk of migraine than men (odds ratio, 5.9; 95% CI, 4.5 to 8.0; P <.0001, after age adjustment, by logistic analysis). Fatigue and loss of vigor were predominant premonitory symptoms of migraine. Fatigue, mental stress, and lack of sleep were the main headache triggers. Over a 3-month period, 20.3% of migraineurs experienced time or days off work due to headache. Only 7.3% of those with migraine with aura and 5.3% of those with migraine without aura had consulted a physician, and of those with migraine, 61.0% with aura and 71.8% without aura had never visited a medical doctor for their headache. Consumption of alcohol and cigarette smoking did not influence the risk for migraine or tension-type headache, after age and gender adjustment (logistic analysis). Migraineurs consume significantly more fatty/oily foods, coffee, and tea than nonheadache subjects of the same community. Migraineurs consume significantly fewer fish than nonheadache residents. CONCLUSIONS: Only a few Japanese migraineurs receive benefits of medical services and recent advances of headache medicine. Public education concerning headaches is one of the most urgent issues in Japan.

Adult↗