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Biomedical subjects

Masatoshi Takeda

Publications and source records attributed to Masatoshi Takeda.

At least 19 recordsLinked to original sources
PubMed2005

Association between cognitive impairment and gait disturbance in patients with idiopathic normal pressure hydrocephalus.

We compared the scores of the Frontal Assessment Battery (FAB), initial fluency subtest, category fluency subtest and subtests of the Mini-Mental State Examination (MMSE) between patients with idiopathic normal pressure hydrocephalus (iNPH) and age-, sex- and MMSE-matched patients with Alzheimer's disease (AD). In patients with iNPH, the time and number of steps required to go and come back a 10-meter distance were measured (Walking test) and the associations between the scores of the cognitive tests and the performance of the Walking test were evaluated. The scores of the FAB and initial fluency subtest in patients with iNPH were significantly lower than those in patients with AD. The scores of the FAB, initial fluency subtest and serial 7 subtest of the MMSE significantly correlated with the two scores of the Walking test in patients with iNPH. The present results indicate that frontal lobe functions were impaired in patients with iNPH and that cognitive impairment was closely associated with gait disturbance in patients with iNPH.

Aged↗
PubMed2005

Interaction of presenilins with FKBP38 promotes apoptosis by reducing mitochondrial Bcl-2.

Presenilins 1 and 2 (PS1/2), causative molecules for familial Alzheimer's disease (FAD), are multipass transmembrane proteins localized predominantly in the endoplasmic reticulum (ER) and Golgi apparatus. Heteromeric protein complexes containing PS1/2 are thought to participate in several functions, including intramembrane proteolysis mediated by their gamma-secretase activities. Previous studies have shown that PS1/2 are also involved in the regulation of apoptotic cell death, although the underlying mechanism remains unknown. Here, we demonstrate that FKBP38, an immunophilin family member residing in the mitochondrial membrane, is an authentic PS1/2-interacting protein. PS1/2 and FKBP38 form macromolecular complexes together with anti-apoptotic Bcl-2. PS1/2 promote the degradation of FKBP38 and Bcl-2 and sequester these proteins in the ER/Golgi compartments, thereby inhibiting FKBP38-mediated mitochondrial targeting of Bcl-2 via a gamma-secretase-independent mechanism. Thus, PS1/2 increase the susceptibility to apoptosis by antagonizing the anti-apoptotic function of FKBP38. In contrast, C-terminal fragments of caspase-processed PS1/2 redistribute Bcl-2 to the mitochondria by abrogating the activity of full-length PS1/2, resulting in a dominant-negative anti-apoptotic effect. In cultured cells and mutant PS1-knockin mice brains, FAD-linked PS1/2 mutants enhance the pro-apoptotic activity by causing a more efficient reduction in mitochondrial Bcl-2 than wild-type PS1/2. These results suggest a novel molecular mechanism for the regulation of mitochondria-mediated apoptosis by competition between PS1/2 and FKBP38 for subcellular targeting of Bcl-2. Excessive pro-apoptotic activity of PS1/2 may play a role in the pathogenesis of FAD.

Alzheimer Disease↗
PubMed2005

Information processing flow and neural activations in the dorsolateral prefrontal cortex in the Stroop task in schizophrenic patients. A spatially filtered MEG analysis with high temporal and spatial resolution.

Using a spatially filtered magnetoencephalography analysis (synthetic aperture magnetometry), we estimated neural activations in the Stroop task in nearly real time for schizophrenic patients with/without auditory hallucinations and for normal control subjects. In addition, auditory hallucinations were examined through the information processing flow of the brain neural network, including the frontal regions. One hundred unaveraged magnetoencephalography signals during the incongruent stimulus responses were analyzed with a time window of 200 ms in steps of 50 ms. In the 25-60-Hz band, cortical regions that showed significant current source density changes were examined for each time window. The three groups showed significantly decreased current source density, corresponding to neural activation, with temporal overlap along the fundamental cognitive information processing flow: sensory input system, executive control system, motor output system. Transient neural activations in the dorsolateral prefrontal cortex were bilateral with left-side dominancy for normal controls, left-lateralized for nonhallucinators and right-lateralized for hallucinators. Our results suggest that the dysfunction in the left dorsolateral prefrontal cortex was related to auditory hallucinations, while the information processing flow was unaffected in the schizophrenic subjects in the Stroop task.

Adolescent↗
PubMed2005

Everyday memory impairment of patients with mild cognitive impairment.

We evaluated everyday memory impairment in 24 patients with mild cognitive impairment (MCI) with the Rivermead Behavioral Memory Test (RBMT) and compared the scores with those of 48 age-, sex- and education-matched normal controls (NC) and 48 age-, sex- and education-matched Alzheimer disease (AD) patients. Overall everyday memory was impaired in MCI patients but the severity was milder than that in AD patients. The MCI patients showed impairment of everyday memory tasks requiring delayed recall. But they could normally perform tasks immediately after memorizing, except for recalling and retracing a simple new route. The total Profile score correctly classified 100% of the MCI patients and 91.7% of NC, thus demonstrating the usefulness of the RBMT for diagnosing MCI patients. Prospective memory tasks were not useful for detecting the patients with MCI.

Aged↗
PubMed2005

Identification of hippocampus-related candidate genes for Alzheimer's disease.

Alzheimer's disease (AD) is a complex multifactorial disease in which many genetic and environmental factors are involved. We performed an association study using 376 AD patients and 376 control subjects. We studied 35 single nucleotide polymorphisms in 35 genes that were significantly downregulated or upregulated only in the AD hippocampus compared with control and found that 9 single nucleotide polymorphisms were associated with AD. Our data indicated that single nucleotide polymorphisms could highly reflect differences in gene expression. Furthermore, an intronic polymorphism (+9943T/C) in POU2F1 was most significantly associated with AD (p = 0.0007). Our results suggest that POU2F1 is a candidate gene for AD.

Aged↗
PubMed2005

A stress-induced, superoxide-mediated caspase-1 activation pathway causes plasma IL-18 upregulation.

Psychological/physical stresses are known to cause relapses of autoimmune and inflammatory diseases. To reveal a mechanism by which noninflammatory stresses affect host defenses, responses to immobilization stress in mice were investigated, focusing on the role of a multifunctional cytokine, interleukin-18 (IL-18). In the adrenal cortex, the stress induced IL-18 precursor proteins (pro-IL-18) via adrenocorticotropic hormone (ACTH) and a superoxide-mediated caspase-1 activation pathway, resulting in conversion of pro-IL-18 to the mature form, which was released into plasma. Inhibitors of caspase-1, reactive oxygen species, and P38 mitogen-activated protein kinase (MAPK) suppressed stress-induced accumulation of plasma IL-18. These inhibitors also blocked stress-induced IL-6 expression. This, together with the observation that IL-6 was not induced in IL-18-deficient mice, showed that IL-6 induction by stress is dependent on IL-18. In stressed organisms, IL-18 may influence pathological and physiological processes. Controlling the caspase-1 activating pathway to suppress IL-18 levels may provide preventative means against stress-related disruption of host defenses.

Adrenal Cortex↗
PubMed2005

Event-related potentials in panic disorder and generalized anxiety disorder.

To evaluate the neurophysiological differences between panic disorder (PD) and generalized anxiety disorder (GAD), 52 patients with PD and 34 with GAD were investigated using event-related potentials (ERP). The ERP were recorded using a tone discrimination task, and peak latencies for N1, P2, N2, and P3 at a Pz electrode site were measured. In addition to analyzing the peak latencies of the ERP, the interpeak latencies (IPL; N1-P2, P2-N2, and N2-P3) were also analyzed. The same analysis was performed in 28 age-matched healthy volunteers (controls). When compared to those of the GAD and control groups, the mean latencies of P2, N2, and P3 were shorter in the PD patients. With regard to the IPL in the PD patients, the N1-P2 IPL was shorter than that in the other groups, and no individual with PD had a longer N1-P2 IPL than 1 SD above the mean of the controls. These findings suggest that certain attention-related processes in the cerebrum that affect ERP data are accelerated in PD patients. These findings demonstrate that it may be useful to neurophysiologically distinguish PD from GAD by measuring ERP peak latencies and IPL.

Adolescent↗
PubMed2005

Prediction of first episode of panic attack among white-collar workers.

The purpose of the present study was to elucidate a longitudinal matrix of the etiology for first-episode panic attack among white-collar workers. A path model was designed for this purpose. A 5-year, open-cohort study was carried out in a Japanese company. To evaluate the risk factors associated with the onset of a first episode of panic attack, the odds ratios of a new episode of panic attack were calculated by logistic regression. The path model contained five predictor variables: gender difference, overprotection, neuroticism, lifetime history of major depression, and recent stressful life events. The logistic regression analysis indicated that a person with a lifetime history of major depression and recent stressful life events had a fivefold and a threefold higher risk of panic attacks at follow up, respectively. The path model for the prediction of a first episode of panic attack fitted the data well. However, this model presented low accountability for the variance in the ultimate dependent variables, the first episode of panic attack. Three predictors (neuroticism, lifetime history of major depression, and recent stressful life events) had a direct effect on the risk for a first episode of panic attack, whereas gender difference and overprotection had no direct effect. The present model could not fully predict first episodes of panic attack in white-collar workers. To make a path model for the prediction of the first episode of panic attack, other strong predictor variables, which were not surveyed in the present study, are needed. It is suggested that genetic variables are among the other strong predictor variables. A new path model containing genetic variables (e.g. family history etc.) will be needed to predict the first episode of panic attack.

Adult↗
PubMed2005

Neural basis of fear conditioning induced by video clip: positron emission tomography study.

In patients with post-traumatic stress disorder (PTSD), re-experiencing the trauma is often induced by external cues in the environment. The cues, which were emotionally neutral for the patients before the traumatic event, become fearful ones after the event. This phenomenon is considered to be associated with fear conditioning. The paradigm was set up so that the emotionality changes in the patients with PTSD would be reproduced, and the regional cerebral blood flow (rCBF) measured with positron emission tomography (PET) was compared during exposure to the same stimuli before and after acquisition of fear conditioning. Ten healthy male subjects were asked to look at some emotionally neutral photos, then to watch a video with fearful content that also contained images similar to that presented in the photos, and afterwards to look at the photos again. Five of the 10 subjects felt that the object in the photos was more fearful after watching the video than before, and they were considered to have acquired fear conditioning. In those five subjects, the rCBF in the right amygdala and the left posterior cingulate gyrus after acquisition of fear conditioning significantly increased relative to the rCBF before conditioning. Thus, these regions seem to have a critical role in fear conditioning.

Adult↗
PubMed2005

Detection by radioligand assay of antibodies against Borna disease virus in patients with various psychiatric disorders.

Using a radioligand assay, which preserves the natural form of the antigen, antibodies against Borna disease virus nucleoprotein and phosphoprotein were detected in 11 and 19 sera of 171 psychiatric patients, respectively. Compared with results by Western blotting, three and nine sera were concordantly positive, respectively. The four sera showing the highest levels of antibodies by radioligand assay were all negative by Western blotting; however, dilution and inhibition tests supported the positive results. Our results suggest the importance of conformational structure to detect human anti-Borna disease virus antibodies.

Antibodies, Viral↗
PubMed2004

Amyloid-beta down-regulates XIAP expression in human SH-SY5Y neuroblastoma cells.

Recent observations suggest that amyloid-beta (Abeta), a major constituent of senile plaques, induces apoptosis in cultured neuronal cells. However, the concentration of Abeta that leads to neuronal cell death is much higher (10-25 microM) than that in the cerebrospinal fluid of normal controls or AD patients (nM order). As reported here, we found that subtoxic concentrations (100-500 nM) of Abeta(1-42) can down-regulate the expression of the X-linked inhibitor of apoptosis (XIAP) in human SH-SY5Y neuroblastoma cells, and that vulnerability to oxidative stress caused by Abeta(1-42) is attenuated by over-expression of XIAP. These results suggest that down-regulation of XIAP expression in response to subtoxic, more physiological concentrations (100-500 nM) of Abeta(1-42) increases vulnerability to oxidative stress.

Amyloid beta-Peptides↗
PubMed2004

Slow repetitive transcranial magnetic stimulation increases somatosensory high-frequency oscillations in humans.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a possible treatment for psychiatric and neurological disorders characterized by focal brain excitability, such as major depression and action myoclonus. However, the mechanism of modulating excitability by rTMS is unclear. We examined the changes in high frequency oscillations (HFOs) of somatosensory evoked potentials (SEPs) before and after slow rTMS over the right primary somatosensory cortex (0.5 Hz, 50 pulses, 80% motor threshold intensity). The HFOs, which represent a localized activity of intracortical inhibitory interneurons, were significantly increased after slow rTMS, while the SEPs were not changed. Our results suggest that slow rTMS affects cortical excitability by modulating the activity of the intracortical inhibitory interneurons beyond the time of the stimulation and that rTMS may have therapeutic effects on such disorders.

Adult↗
PubMed2004

Effectiveness of a clinical pathway for the diagnosis and treatment of dementia and for the education of families.

AIMS: Clinical pathways (CPs) are rarely used in the treatment of dementia. We established a CP for a series of medical practices (diagnosis, treatment, establishment of a care system, and caregiver education) for patients with dementia hospitalized for a three-week period, and evaluated its usefulness. METHODS: The length of hospital stay and hospital costs were compared between 23 consecutive patients with dementia hospitalized and treated using a CP and 20 controls treated by conventional medical practice without using a CP in a special ward for dementia patients. In the CP group, at the time of discharge, primary caregivers, physicians, and nurses were given a questionnaire to obtain their comments about the impression of treatment with the CP. RESULTS: The questionnaire survey indicated that the CP deepened the caregiver's understanding of the sequence of medical practices for the inpatient, the disorders of the inpatient, the treatment methods, and the methods for coping with the disorder. The CP was also useful for facilitating inpatient medical practice and promoting the establishment of a care system after discharge. The use of the CP significantly shortened the length of hospital stay and decreased hospital costs during hospitalization but increased the amount of work per day and made the medical staff feel that their freedom to choose medical procedures had been restricted. CONCLUSIONS: The CP was useful for execution of inpatient medical practices for patients with dementia.

Aged↗
PubMed2004

Treatment of typical Charles Bonnet syndrome with donepezil.

Charles Bonnet syndrome (CBS) is characterized by the presence of complex visual hallucinations in psychologically normal people. Although visual hallucinations in the elderly are often associated with dementia with Lewy body (DLB), Alzheimer's disease and delirium, they are excluded from the diagnosis of typical CBS, as are cognitive or psychiatric disturbances, sleep disorders and focal neurological lesions. Here, we describe a patient with typical CBS, who responded to donepezil, a cholinesterase inhibitor, and has not shown any symptoms suggestive of Alzheimer's disease or DLB for approximately the past 40 months. However, follow-up examination of her clinical symptoms is necessary for a definite exclusion of Alzheimer's disease and DLB. The effectiveness of donepezil indicates that the patient's visual hallucinations might be related to dysfunction of cholinergic neurones, although she did not exhibit any cognitive decline, or morphological and physiological brain pathology. Because donepezil has fewer adverse effects than anticonvulsants and neuroleptic drugs, it may be a safer option for the treatment of CBS in the elderly.

Aged↗
PubMed2004

TAFI polymorphisms at amino acids 147 and 325 are not risk factors for cerebral infarction.

Thrombin-activatable fibrinolysis inhibitor (TAFI) was reported as an anaphylatoxin-inactivating enzyme generated by proteolytic cleavage of its zymogen, and is the same enzyme as that first designated by our group as procarboxypeptidase R (proCPR). Its level in plasma appears to influence vascular disease. In addition, TAFI activity is strongly influenced by genetic polymorphism, especially at amino acids 147 and 325. We investigated whether these TAFI polymorphisms would act as a risk factor for cerebral infarction (CI) by examining 253 samples in which the diagnosis was cliniconeuropathologically confirmed. We found little that was statistically significant in terms of these polymorphisms among patients with no vascular problems or in a population-based control group. In the present study of an elderly Japanese group, our samples revealed a lower percentage of the Ile allele at Thr/Ile-325 compared with western counterparts. Although patients with severe infarcts had a lower percentage of the Ile allele (10%) at amino acid position 325 compared with the slightly and moderately affected patients and the population-based control group (15-18%), no statistical significance was found. None of our results showed any statistical correlation between TAFI polymorphisms and CI.

Aged↗
PubMed2004

Sleep characteristics of menopausal insomnia: a polysomnographic study.

Although menopausal insomnia is of clinical significance, the essential features of this form of disrupted sleep are poorly understood. The aim of the present study was to identify the sleep characteristics of menopausal insomnia by using overnight polysomnography (PSG). Twenty-one subjects with menopausal insomnia (MI) and 13 sex- and age-matched normal control (NC) subjects without sleep complaints took part in the present study. All MI and NC subjects underwent PSG on two consecutive nights. In comparison with NC, MI subjects had non-specific findings such as significantly shorter total sleep time, longer sleep latency, higher wake time after sleep onset, and lower sleep efficiency. As for rapid eye movement (REM) sleep variables, MI subjects had significantly shorter total REM sleep time, fewer numbers of REM sleep periods, longer REM latency, and higher REM density than did the NC subjects. As for the time course of REM density, REM density during the first 3 h period of nocturnal sleep was significantly higher for MI than for NC subjects. Unlike NC subjects, REM density for MI subjects did not tend to rise progressively during nocturnal sleep. The MI subjects had objective evidence of disrupted sleep and the most striking characteristics of this dysfunction were observed in REM sleep variables. The sleep characteristics of MI subjects were found to differ in REM sleep variables from those of patients with major depression (except for REM density). Menopausal insomnia patients appear to be similar to patients with generalized anxiety disorder accompanied by severe sleep disruption. These data lend support to the clinical distinction between menopausal insomnia and insomnia associated with major psychiatric disorders.

Adult↗
PubMed2004

Electrogastrography abnormality in eating disorders.

Eating disorders are common psychiatric disorders in young women. The aim of the present study was to evaluate the gastric electrical activity of patients with eating disorders and its relation to their symptoms. The electrogastrography (EGG) was performed before and after a water load test for outpatients with eating disorders (n = 36; 14 anorexia nervosa, 14 bulimia nervosa, eight eating disorder not otherwise specified) and healthy women (n = 19). A structured interview (Eating Disorder Examination) was used to assess clinical symptoms. The percentage of normal gastric myoelectrical power was significantly smaller in the eating disorder patients (44.5% vs 74.2%; P < 0.05), while the percentage of bradygastric power was significantly greater, both before and after the water load test compared with the control subjects (30.4% vs 10.4%; P < 0.05). In addition, moderate correlation was found between the duration of illness and the percentage of bradygastria (P < 0.05). In conclusion, it is suggested that longstanding abnormal eating in patients with eating disorders may induce disturbances to gastric motor function, resulting in their abnormal, eating-related behavior, and form a symptomatic vicious circle. The EGG may be a promising method for determining the pathophysiology of eating disorders and for developing effective therapeutic approaches.

Adolescent↗