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Biomedical subjects

Takashi Seki

Publications and source records attributed to Takashi Seki.

16 recordsLinked to original sources
PubMed2006

Uncaria rhynchophylla, a Chinese medicinal herb, has potent antiaggregation effects on Alzheimer's beta-amyloid proteins.

Because the deposition of beta-amyloid protein (Abeta) is a consistent pathological hallmark of Alzheimer's disease (AD) brains, inhibition of Abeta generation, prevention of Abeta fibril formation, or destabilization of preformed Abeta fibrils would be attractive therapeutic strategies for the treatment of AD. We examined the effects of several medicinal herbs used in traditional Chinese medical formulae on the formation and destabilization of Abeta fibrils by using the thioflavin T binding assay, atomic force microscopic imaging, and electrophoresis. Our study demonstrates that several of these herbs have potent inhibitory effects on fibril formation of both Abeta(1-40) and Abeta(1-42) in concentration-dependent manners; in particular, Uncaria rhynchophylla inhibited Abeta aggregation most intensively. Significant destabilization of preformed Abeta(1-40) and Abeta(1-42) fibrils was also induced by Uncaria rhynchophylla as well as some other herb extracts. Three-dimensional HPLC analysis indicated that the water extract of this herb contains several different chemical compounds, including oxindole and indol alkaloids, which have been regarded as neuroprotective. Our results suggest that Uncaria rhynchophylla has remarkably inhibitory effects on the regulation of Abeta fibrils, and we conclude that this medicinal herb could have the potency to be a novel therapeutic agent to prevent and/or cure AD.

Alzheimer Disease↗
PubMed2006

GINS is a DNA polymerase epsilon accessory factor during chromosomal DNA replication in budding yeast.

GINS is a protein complex found in eukaryotic cells that is composed of Sld5p, Psf1p, Psf2p, and Psf3p. GINS polypeptides are highly conserved in eukaryotes, and the GINS complex is required for chromosomal DNA replication in yeasts and Xenopus egg. This study reports purification and biochemical characterization of GINS from Saccharomyces cerevisiae. The results presented here demonstrate that GINS forms a 1:1 complex with DNA polymerase epsilon (Pol epsilon) holoenzyme and greatly stimulates its catalytic activity in vitro. In the presence of GINS, Pol epsilon is more processive and dissociates more readily from replicated DNA, while under identical conditions, proliferating cell nuclear antigen slightly stimulates Pol epsilon in vitro. These results strongly suggest that GINS is a Pol epsilon accessory protein during chromosomal DNA replication in budding yeast. Based on these results, we propose a model for molecular dynamics at eukaryotic chromosomal replication fork.

Base Sequence↗
PubMed2006

Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro.

The assembly of the prereplicative complex (pre-RC) at the origin of replication in eukaryotes is a highly regulated and highly conserved process that plays a critical role in preventing multiple rounds of DNA replication per cell division cycle. This study analyzes the molecular dynamics of the assembly of Saccharomyces cerevisiae pre-RC in vitro using ARS1 plasmid DNA and yeast whole cell extracts. In addition, pre-RC assembly was reconstituted in vitro using ARS1 DNA and purified origin-recognition complex (ORC), Cdc6p and Cdt1p-Mcm2-7p. The results reveal sequential recruitment of ORC, Cdc6p, Cdt1p and Mcm2-7p on to ARS1 DNA. When Mcm2-7p is maximally loaded, Cdc6p and Cdt1p are released, suggesting that these two proteins are co-ordinately regulated during pre-RC assembly. In extracts from sid2-21 mutant cells that are deficient in CDT1, ORC and Cdc6p bind to ARS1 but Cdt1p and Mcm2-7p do not. However, Mcm2-7p does bind in the presence of exogenous Cdt1p or Cdt1p-Mcm2-7p complex. Cdt1p-Mcm2-7p complex, which was purified from G1-, early S or G2/M-arrested cells, exhibits structure-specific DNA binding, interacting only with bubble- or Y-shape-DNA, but the biological significance of this observation is not yet known.

Cell Cycle Proteins↗
PubMed2006

Visual function with acupuncture tested by visual evoked potential.

Visual evoked potential (VEP) testing is used frequently and is an important ophthalmologic physiological test to examine visual functions objectively. The VEP is a complicated waveform consisting of negative waveform named N75 and N135, and positive waveform named P100. Delayed P100 latency and greatly attenuated amplitude on VEP are known characteristics for diagnosing optic nerve disease. Acupuncture has been used to treat wide clinical symptoms with minimal side effects. The confirmation of the efficacy of acupuncture generally relies on subjective symptoms. There is not much scientific evidence supporting the acupuncture treatments for eye diseases up to today. However, the VEP test can evaluate objectively and numerically the efficacy of the treatment by the acupuncture. We analyzed 19 healthy subjects (38 eyes). The P100 latencies in the group of less than 101.7 msec (total average) before acupuncture stimulations were not different than those after treatment (98.2 +/- 3.0 msec, 98.2 +/- 4.0 msec, respectively, p = 0.88, n = 17), but the latencies in those subjects with longer or equal to 101.7 msec were statistically different after acupuncture (104.6 +/- 2.8 msec, 101.9 +/- 3.7 msec, respectively, p = 0.006, n = 21). These results show that the acupuncture stimulation contributes to the P100 latencies of pattern reversal (PR)-VEP to some subjects who have delayed latencies, and this electrophysiological method is a valuable technique in monitoring the effectiveness of acupuncture therapy in the improvements of visual functions. The purpose of this study is to evaluate the physiological effects by acupuncture stimulations using PR-VEP in normal subjects.

Acupuncture Therapy↗
PubMed2005

Acupuncture for patients with glaucoma.

CONTEXT: Research of the effects of one acupuncture method for patients with glaucoma, focusing on intraocular pressure (IOP) and visual acuity. OBJECTIVE: To explore the possibility of using acupuncture for patients with glaucoma. DESIGN: Pilot study utilizing a one-group preintervention, postintervention design. SETTING: Eleven patients with glaucoma were recruited through advertisement at the clinic for glaucoma. INTERVENTION: Acupuncture was carried out twice a week over 5 weeks. OUTCOME MEASURES: IOP, visual acuity, and subjective symptoms were observed at 15 minutes before and after acupuncture once a week and in a four-week follow-up. RESULTS: IOP was significantly improved at 15 minutes after acupuncture, at one week, two weeks, and five weeks and tended to be lower weekly. Uncorrected visual acuity was significantly improved at three weeks, four weeks, and five weeks, and best corrected visual acuity was significantly improved at five weeks. However at the four-week follow-up, significance remained only in uncorrected visual acuity. CONCLUSIONS: Although these results should be interpreted cautiously, acupuncture can be used to supplement the conventional therapy for glaucoma.

Acupuncture Therapy↗
PubMed2005

Plasma homocysteine and risk of coexisting silent brain infarction in Alzheimer's disease.

BACKGROUND: Cerebrovascular disease is common in Alzheimer's disease (AD). Elevated plasma homocysteine (pHcy) levels are reported to be associated with an increased risk of poor cognition and dementia. OBJECTIVE: To determine whether high pHcy levels are associated with an increased risk of coexisting silent brain infarctions (SBIs) in AD. METHODS: Study population comprising 143 outpatients with clinical diagnosis of probable AD (73.3 +/- 7.0 years) were classified into 2 groups according to the presence or absence of SBIs on magnetic resonance imaging. RESULTS: SBIs were noted in 32.9% (47/143) of the AD patients. The pHcy levels in the AD with SBIs (14.0 +/- 4.5 micromol/l) were significant ly elevated compared with the AD without SBIs (11.7 +/- 4.7 micromol/l, p = 0.007). After adjusting for age and gender, high pHcy (>12.4 micromol/l), but not hypertension, was associated with an increased risk of developing SBIs in AD (OR = 4.61, 95% CI = 1.74-12.2, p = 0.002). However, age at onset, cognitive function, cerebrospinal tau or amyloid beta-peptide(1-42) levels were not significantly correlated with pHcy levels in AD. CONCLUSION: SBIs commonly coexist with AD, and may be a unique vascular condition in which homocysteine plays an important role. Homocysteine-lowering therapy rather than antihypertensive medication might be an appropriate strategy to prevent stroke associated with AD.

Aged↗
PubMed2005

Risk of falls in Alzheimer's disease: a prospective study.

OBJECTIVE: Falls are common in patients with Alzheimer's disease (AD). Identification of the potential risk factors and developing preventive strategies for falls will have a significant impact in maintaining the quality of life in AD. PATIENTS: Clinical follow-up of 124 (74.1+/-6.1 years, range 62-88) mild to moderate AD patients in an outpatient memory clinic. METHODS: Postural sway, cognitive function, use of neuroleptics, severity of periventricular and deep white matter lesions, and the presence or absence of silent brain infarctions on magnetic resonance imaging were assessed at baseline. RESULTS: A total of 104 patients (84%) completed the study. Fall events were confirmed in 42.3% (44/104). After adjustment for age, gender, and cognitive status, a high grade of periventricular white matter lesions (odds ratio 8.7 [95%CI 1.5 to 51.8], p = 0.017) and neuroleptic drug use (odds ratio 3.5 [95%CI 1.2 to 10.5], p = 0.027) were significantly associated with an increased risk of falls. CONCLUSION: Our results suggest that periventricular white matter lesions and the use of neuroleptics may be related to falls in mild to moderate AD. A comprehensive risk management of brain ischemia as well as the use of the smallest efficacious dose of neuroleptics in the treatment of behavioral and psychiatric symptoms of AD should be recommended to help reduce the risk of unexpected falls.

Accidental Falls↗
PubMed2005

A randomized, observer-blind, controlled trial of the traditional Chinese medicine Yi-Gan San for improvement of behavioral and psychological symptoms and activities of daily living in dementia patients.

OBJECTIVE: This randomized, observer-blind, controlled trial examined the efficacy and safety of the traditional Chinese herbal medicine Yi-Gan San (YGS, Yokukan-San in Japanese) in the improvement of behavioral and psychological symptoms of dementia (BPSD) and activities of daily living (ADL). METHOD: Fifty-two patients with mild-to-severe dementia (24 men and 28 women, mean +/- SD age = 80.3 +/- 9.0 years) according to DSM-IV criteria were investigated. Participants were randomly assigned to the YGS group (N = 27) or control (drug-free) group (N = 25) and treated for 4 weeks. The Neuropsychiatric Inventory (NPI) for the assessment of BPSD, the Mini-Mental State Examination (MMSE) for cognitive function, and the Barthel Index for ADL were administered at baseline and the end of the treatment. The frequency of extrapyramidal symptoms (EPS) and other adverse events was recorded. If patients showed insufficient response to treatment after 1 week, tiapride hydrochloride, a dopamine D(1) selective neuroleptic, was added to the regimen. Data were collected from January 2004 to March 2004. RESULTS: All participants in both groups completed the trial. In the control group, 11 patients required treatment with tiapride hydrochloride. Significant improvements in mean +/- SD NPI (from 37.9 +/- 16.1 to 19.5 +/- 15.6) and Barthel Index (from 56.4 +/- 34.2 to 62.9 +/- 35.2) scores were observed in the YGS group, but not in the control group. MMSE results were unchanged in both groups. EPS were not observed in either group, but dizziness and impaired postural sway were observed in 6 patients treated with tiapride hydrochloride. CONCLUSION: Yi-Gan San improves BPSD and ADL. Follow-up studies using a double-blinded, placebo-controlled design are recommended.

Activities of Daily Living↗
PubMed2004

Phosphorylation-dependent binding of mitotic cyclins to Cdc6 contributes to DNA replication control.

Cyclin-dependent kinases (CDKs) limit the activation of DNA replication origins to once per cell cycle by preventing the assembly of pre-replicative complexes (pre-RCs) during S, G2 and M phases of the cell cycle in the budding yeast Saccharomyces cerevisiae. CDKs inhibit each pre-RC component (ORC, Cdc6, Cdt1/Mcm2-7) by different mechanisms. We show here that the mitotic CDK, Clb2/Cdc28, binds tightly to an amino-terminal domain (NTD) of Cdc6, and that Cdc6 in this complex is unable to assemble pre-RCs. We present evidence indicating that this Clb2-dependent mechanism contributes to preventing re-replication in vivo. CDK interaction with the NTD of Cdc6 is mediated by the cyclin subunit Clb2, and could be reconstituted with recombinant Clb2 protein and synthetic NTD peptides. Tight Clb2 binding occurred only when the NTD was phosphorylated on CDK consensus sites. Human CDKs containing cyclins A, B and E also bound specifically to phospho-NTD peptides. We propose that direct binding of cyclins to phosphopeptide motifs may be a widespread phenomenon contributing to the targeting of CDKs to substrates.

Amino Acid Motifs↗
PubMed2002

Combined Analysis of CSF Tau Levels and [(123)I]Iodoamphetamine SPECT in Mild Cognitive Impairment: Implications for a Novel Predictor of Alzheimer's Disease.

OBJECTIVE: The aim of this study was to establish an objective and reliable index to predict the development of Alzheimer's disease in a large pool of elderly patients with mild cognitive impairment. METHOD: Twenty-three patients with probable Alzheimer's disease, 22 patients with mild cognitive impairment who eventually developed Alzheimer's disease, eight patients with mild cognitive impairment who did not develop dementia, and 19 cognitively normal subjects were included in the study. The authors constructed a new diagnostic index, the CSF-CBF index, based on CSF tau levels divided by regional cerebral blood flow (CBF) in the posterior cingulate cortex. RESULTS: Receiver operating characteristic analysis showed that applying a cutoff value for the CSF-CBF index of 296.0 achieved a sensitivity of 88.5% and a specificity of 90.0% in discriminating mild cognitive impairment that progressed to Alzheimer's disease from mild cognitive impairment that did not progress to Alzheimer's disease. CONCLUSIONS: The CSF-CBF index is useful in predicting Alzheimer's disease in subjects with mild cognitive impairment.

Aged↗