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Biomedical subjects

Yoshitomo Takahashi

Publications and source records attributed to Yoshitomo Takahashi.

At least 19 recordsLinked to original sources
PubMed2006

Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher disease patient and a carrier.

A clinical association between Gaucher disease and parkinsonism has been demonstrated. We herein report a Japanese patient with type 3 Gaucher disease who was compound heterozygous for F213I and L444P mutations in the glucocerebrosidase gene while his father was heterozygous for the L444P mutation. They both presented with parkinsonism characterized by a predominance of akinetic-rigid signs and a favorable response to anti-Parkinson therapies. We investigated the dopaminergic neuronal function using positron emission tomography (PET) with radioligands, [(11)C] CFT and [(11)C] raclopride. PET studies of both patients demonstrated the [(11)C] CFT uptake to be severely decreased in the putamen and the caudate nucleus, however, the [(11)C] raclopride uptake was normal in the basal ganglia. Although the majority of Gaucher disease patients with parkinsonism tend to be refractory to anti-Parkinson therapies. The clinical features and the findings of the PET studies suggest that patients with parkinsonism associated with the mutation in the glucocerebrosidase gene, even in heterozygosis, may be related to the presynaptic dopaminergic neuronal dysfunction reported in Parkinson's disease. A PET study to evaluate the dopaminergic neuronal function in Gaucher disease would provide both a better understanding of the effects of anti-Parkinson therapies and a help to improve our ability to make an early diagnosis of parkinsonism associated with Gaucher disease.

Adult↗
PubMed2006

Autonomic arousal in cognitive conflict resolution.

Although cognitive efforts were reported to elicit global autonomic arousal, which cognitive processes associate with autonomic arousal has not been clear. We investigated autonomic arousal using event-related skin conductance responses (SCRs) during the Stroop color-word task. After baseline SCR deflections were determined in each trial block, SCRs were compared between cognitive conflict conditions (incongruent vs. congruent stimuli), between tasks assigned (word reading vs. color naming), and between erroneous and correct responses. Baseline SCRs were significantly greater at the beginning of each trial block. SCRs were significantly greater with incongruent than congruent stimuli while SCRs differed little between word reading and color naming. SCRs were greater when responses were incorrect. The results suggested that autonomic arousal occurs during cognitive conflict resolution in addition to mental set adoption for a task and in error awareness.

Adult↗
PubMed2006

Intronic mutation in the PGK1 gene may cause recurrent myoglobinuria by aberrant splicing.

A 33-year-old man with mental retardation and recurrent myoglobinuria demonstrated a deficiency in the phosphoglycerate kinase 1 (PGK1) activity of his muscles and erythrocytes. His PGK1 gene had intronic G-to-A substitution 5 nucleotides downstream from the normal exon 7 5' splice site (IVS7 + 5 G>A). This novel mutation results in a frame shift due to the insertion of 52 bp of intron 7 in the mature mRNA by aberrant splicing.

Adult↗
PubMed2006

Activation time course of responses to illusory contours and salient region: a high-density electrical mapping comparison.

Until recently, early visual areas (V1/V2) were believed to respond mainly to illusory contours (ICs). At present, however, functional neuroimaging suggests that the human lateral occipital complex (LOC), a higher tier than V2, responds strongly to ICs and that IC-related activation in V1/V2 in fact might be driven by feedback input from the LOC. When Kanizsa-type ICs are modified by rounding the corners of the inducers and misaligning them slightly, the impression of an enclosed salient region (SR) remains, although ICs no longer are perceived. Stanley and Rubin (Stanley, D.A., Rubin, N., 2003. fMRI activation in response to illusory contours and salient regions in the human lateral occipital complex. Neuron, 37, 323-331) found that the LOC responded to SR, suggesting that the LOC subserves a rapid but crude region-based segmentation process preceding boundary completion in V1/V2. The present study compared the time course of cortical responses to ICs with those to SR using high-density (74-channel) event-related potentials (ERPs). Scalp mapping and statistical analysis indicated that shared negative modulation for ICs and SR was distributed bilaterally over the lateral occipital scalp at a latency of 70 to 180 ms. Slightly later, a weak negative modulation occurred with ICs but not SR at the occipital pole scalp from 170 to 180 ms. Dipoles for early and late modulations were fitted optimally in the LOC and occipital pole, respectively. The present results suggested that IC-related cortical activation could be separated into region-based segmentation and subsequent boundary completion.

Adult↗
PubMed2006

Hepatic iron overload associated with a decreased serum ceruloplasmin level in a novel clinical type of aceruloplasminemia.

BACKGROUND & AIMS: Aceruloplasminemia is a novel hereditary iron overload disease caused by a mutation in the ceruloplasmin gene and characterized by a complete deficiency of serum ceruloplasmin and iron accumulation in the liver and brain. METHODS: We herein studied a novel clinical type of aceruloplasminemia in which a low amount of ceruloplasmin was detected in the serum of a patient. The patient presented with an asymptomatic hepatic iron overload, retinal degeneration, and diabetes mellitus. Magnetic resonance imaging of the liver and basal ganglia showed T2-hypointensity signals associated with parenchymal iron accumulation because of an absence of the ferroxidase activity in ceruloplasmin. RESULTS: A gene analysis showed a novel G969S mutation in the ceruloplasmin gene. A biochemical analysis of the patients' serum and a biogenesis study of G969S mutant ceruloplasmin using mammalian cell culture system resulted in the synthesis and secretion of only apoceruloplasmin without any ferroxidase activity. CONCLUSIONS: This novel clinical type of aceruloplasminemia should therefore be considered in the differential diagnosis of unexplained hemochromatosis, which is associated with a decrease in the serum ceruloplasmin level.

Aged↗
PubMed2006

Autopsy case of neuro-Behçet's disease with multifocal neutrophilic perivascular inflammation.

We report here an autopsy case of neuro-Behçet's disease. The patient was a 28-year-old man, who developed a slight fever, right uveitis, and right sensory neural hearing loss at the age of 25. These symptoms relapsed repeatedly despite treatment. Eventually he was admitted to hospital because of progressing neurological deficits such as pyramidal symptoms, somatic sensorial and autonomic disorders, and bulbar palsy. The patient's condition deteriorated and he died of heart failure. Total clinical course was about three years. In postmortem examination, various-sized necrotic foci, often accompanied by gliosis and foamy macrophage infiltration, were scattered in the diencephalic region and brain stem. Meningitis was observed on the ventral side of the brain stem as well as inferior cerebral surface. Nonbacterial or non-fungal acute perivascular inflammatory foci were also present in the brain stem and cerebellar parenchyma. These histopathological findings suggest that a destructive multifocal neutrophilic inflammation might have caused the neurological deficits. Perivascular inflammation might be important to understanding the pathogenesis of neuro-Behçet's disease.

Adult↗
PubMed2006

Biochemical features of ceruloplasmin gene mutations linked to aceruloplasminemia.

Aceruloplasminemia is a neurodegenerative disease characterized by parenchymal iron accumulation owing to mutations in the ceruloplasmin gene. Ceruloplasmin is expressed in the central nervous system in which most of the ceruloplasmin is located on the surface of astrocytes in a glycosylphosphatidylinositol (GPI)-anchored form. We herein describe the biochemical features of wild-type and mutant GPI-anchored ceruloplasmin. An overexpression of wild-type GPI-anchored ceruloplasmin in Chinese hamster ovary cells led to the formation of aggresome-like inclusions, especially in the presence of proteasome inhibitors. As expected from the properties of aggresomes, the inclusions were colocalized with gamma-tubulin and a disruption of microtubules using nocodazole blocked the formation of such inclusions. Aceruloplasminemia-linked mutant proteins failed to form such inclusions even after treatment with proteasomal inhibitors. An immunofluorescent analysis indicated that the mutant proteins were thus retained in the endoplasmic reticulum (ER), whereas the transfected cells showed a decreased viability. The expression of glucose-regulated protein 78 that is one of the ER stress sensor proteins, and the activity of glucose-regulated protein 78 promoter was upregulated in the cells transfected with the mutants. These findings indicated that when the overexpressed cytoplasmic wild-type ceruloplasmin was not subjected to degradation by the proteasome-ubiquitin system, then the wild-type protein was transported along the microtubules, thus forming inclusions at the microtubule organizing center, whereas the mutant ceruloplasmin failed to form any such inclusions, because the mutant protein might not have been translocated across the ER into the cytoplasm. Therefore, the mutant protein was considered to have accumulated in the ER thus leading to the ER stress, which resulted in cell death.

Animals↗
PubMed2006

[An animal model of posttraumatic stress disorder in rats using a shuttle box].

We administered inescapable footshocks (IS) to male Wistar rats in a shuttle box, and after 2 weeks, an avoidance/escape task was performed in the same box. The rats exposed to IS 2 weeks beforehand exhibited PTSD-like bi-directional changes similar to symptoms of "avoidance/ numbing" and "hyperarousal". That is, in the relatively calm period just before the avoidance/escape task, spontaneous locomotor activities decreased. On the other hand, in the stressful situation after starting the task, not only responses to external stimuli but also locomotor activities increased. Thus, the paradigm we have used until now could serve as a useful PTSD model because of its "face validity". To demonstrate the greater validity, we administered paroxetine (PRX), which is effective for PTSD, to rats to examine its chronic effect on our model. We also substituted F344 rats, which are vulnerable to various stressors, for the Wistar rats to investigate the difference between the strains. Two weeks of PRX treatment significantly reduced hyperarousal-like behavior, and its ameliorating effect on avoidance/numbing-like behavior was also significant. F344 showed more significant 'bi-directional changes' than Wistar rats. These findings demonstrate that our paradigm is sufficiently valid for an animal model of PTSD, especially in "predictive validity" and "construct validity."

Animals↗
PubMed2006

[Present status and prospects about an animal model of post-traumatic stress disorder in rats using a shuttle box].

Wistar rats exposed to inescapable foot shocks (IS) for 2 wk exhibited PTSD-like bi-directional changes similar to avoidance/numbing and hyperarousal symptoms when placed in a shuttle box. Paroxetine administration after IS reduced the hyperarousal-like behavior, and its therapeutic effect on avoidance/numbing-like behavior was also significant. Further, F344 rats, which were more vulnerable to various kinds of stressors, showed more significant 'bi-directional changes' than Wistar rats. Thus, the paradigm we have developed could serve as a useful PTSD model because of its face, predictive, and construct validity. Moreover, the intensity of IS dose-dependently induced PTSD-like behaviors and hypo-activity in a shuttle box, similar to the 'avoidance/numbing' that reappeared in a square open field. These findings further support the construct validity of this paradigm. Both electro-convulsive shock treatment before and after IS ameliorated the PTSD-like behaviors in this model, so electro-convulsive therapy may be an effective method for prevention and medical treatment of PTSD in the future. On the other hand, pretreatment with fluvoxamine before IS did not have a significant effect, and its improving effect after IS was only observed for 'hyperarousal' behavior. Lastly, we recently developed a useful criterion, which is represented as a 'bi-directional index', for separating real PTSD rats from those exposed to IS.

Animals↗
PubMed2005

Suicide prevention strategies: a systematic review.

CONTEXT: In 2002, an estimated 877,000 lives were lost worldwide through suicide. Some developed nations have implemented national suicide prevention plans. Although these plans generally propose multiple interventions, their effectiveness is rarely evaluated. OBJECTIVES: To examine evidence for the effectiveness of specific suicide-preventive interventions and to make recommendations for future prevention programs and research. DATA SOURCES AND STUDY SELECTION: Relevant publications were identified via electronic searches of MEDLINE, the Cochrane Library, and PsychINFO databases using multiple search terms related to suicide prevention. Studies, published between 1966 and June 2005, included those that evaluated preventative interventions in major domains; education and awareness for the general public and for professionals; screening tools for at-risk individuals; treatment of psychiatric disorders; restricting access to lethal means; and responsible media reporting of suicide. DATA EXTRACTION: Data were extracted on primary outcomes of interest: suicidal behavior (completion, attempt, ideation), intermediary or secondary outcomes (treatment seeking, identification of at-risk individuals, antidepressant prescription/use rates, referrals), or both. Experts from 15 countries reviewed all studies. Included articles were those that reported on completed and attempted suicide and suicidal ideation; or, where applicable, intermediate outcomes, including help-seeking behavior, identification of at-risk individuals, entry into treatment, and antidepressant prescription rates. We included 3 major types of studies for which the research question was clearly defined: systematic reviews and meta-analyses (n = 10); quantitative studies, either randomized controlled trials (n = 18) or cohort studies (n = 24); and ecological, or population- based studies (n = 41). Heterogeneity of study populations and methodology did not permit formal meta-analysis; thus, a narrative synthesis is presented. DATA SYNTHESIS: Education of physicians and restricting access to lethal means were found to prevent suicide. Other methods including public education, screening programs, and media education need more testing. CONCLUSIONS: Physician education in depression recognition and treatment and restricting access to lethal methods reduce suicide rates. Other interventions need more evidence of efficacy. Ascertaining which components of suicide prevention programs are effective in reducing rates of suicide and suicide attempt is essential in order to optimize use of limited resources.

Antipsychotic Agents↗
PubMed2005

Relationships between temperament dimensions in personality and unconscious emotional responses.

BACKGROUND: In addition to character dimensions, personality includes temperament dimensions, defined as individual differences in implicit associative learning responses to environmental stimuli processed by unconscious memories. We examined whether temperament dimensions were associated with patterns of unconscious emotional responses of an autonomic nature. METHODS: From 70 healthy men, high and low novelty-seeking (NS) groups and high and low harm-avoidance (HA) groups were selected using scores on the Tridimensional Personality Questionnaire measuring temperament dimensions. Emotionally negative, neutral, and positive visual stimuli were presented subliminally using backward masking, and skin conductance responses (SCRs) were measured as an autonomic index of emotional responses. Skin conductance responses to the three emotional stimulus conditions were compared between groups. RESULTS: Skin conductance responses in the high NS group were significantly greater than in the low NS group when positive or negative emotional stimuli were presented but not neutral stimuli. Skin conductance responses in the high HA group were significantly greater than in the low HA group for stimuli of all three valences. CONCLUSIONS: Autonomic response patterns to unconscious emotional perception differed between NS and HA, suggesting that different dimensions of temperament may be associated with different patterns of unconscious emotional responses. Novelty seeking and HA may be associated with specificity and susceptibility of preattentive emotional perception, respectively.

Adult↗
PubMed2005

Karojisatsu in Japan: characteristics of 22 cases of work-related suicide.

With the rapidly increasing number of work-related suicides in Japan (Karojisatsu, in Japanese), both applications for worker's compensation insurance and civil suits are proliferating. The phenomenon of work-related suicide is examined along with the process and related factors. With informed consent from bereaved families, two certified psychiatrists independently reviewed and summarized 22 insurance and legal reports filed by psychiatrists on employee suicides that were related to heavy workloads. A clinical epidemiologist participated in discussions with psychiatrists to reach a consensus concerning the cause of the suicides. Only one case involved a female. Seventeen had experienced personnel changes, such as a promotion or transfer. Low social support was recognized in 18, high psychological demand in 18, low decision latitude in 17, and long working hours in 19 cases (more than 11 hours per day for 3 months or more, and without a day off in 9). The subjects had depressive episodes by the ICD-10 criteria and showed suicidal signs. Ten of them saw a general practitioner because of unspecified somatic complaints, but no effective measures were taken. None of them had a history of psychiatric consultation or had received mental health education dealing with job stress management. Although causality cannot be made from this case series report, we hypothesize that long working hours, heavy workloads, and low social support may cause depression, which can lead to suicide. Appropriate countermeasures are urgently needed and the present findings suggest some of them are possible.

Adult↗
PubMed2004

Interhemispheric difference in emotional response without awareness.

To investigate interhemispheric differences concerning unconscious human emotional responses processed, we measured human skin conductance responses (SCRs) to masked (unseen) emotional stimuli presented to left or right visual fields. Backward masking was used to preclude conscious processing of emotional stimuli. Masked negative or neutral emotional pictures from the International Affective Picture System (IAPS) were presented to 11 right-handed male volunteers. Mean SCR for negative emotional stimuli presented to the left visual field was significantly greater than mean SCRs for negative emotional stimuli to the right visual field and for neutral stimuli to the left or right visual fields. Thus, the right rather than the left hemisphere appears to respond to preattentive negative emotional stimuli.

Adult↗
PubMed2004

Effect of paroxetine on a model of posttraumatic stress disorder in rats.

To better understand neurochemical and psychopharmacological aspects of post-traumatic stress disorder (PTSD), it is necessary to establish an animal model of PTSD in which behavioral changes persist after the initial traumatization. We administered inescapable electric foot-shock (IS) to male Wistar rats in a shuttle-box with the gate closed. With or without paroxetine (PRX; belonging to selective serotonin reuptake inhibitors) treatment for 2 weeks after IS, we performed an avoidance/escape task session in the shuttle-box using signal lights as non-specific anxiogenic stimulants. Locomotor activity decreased before the task session and avoidance behavior increased during the session. Two weeks of PRX administration reduced hypervigilant behavior during the task session. We considered these behavioral changes as representative of numbing/avoidance and hypervigilance, referred to as bi-directional changes in PTSD.

Animals↗
PubMed2004

Perception of apparent motion in depth: a high-density electrical mapping study in humans.

We evaluated brain activity using 64-channel visual evoked potentials (VEPs) while subjects perceived apparent motion in depth. Checkerboard patterns (CBPs) within small and large circles were presented in turn as experimental conditions. Motion in depth was perceived when the CBP in the large circle was coarser than in the small circle; when coarseness did not change, no motion in depth was perceived. As control conditions only fine or coarse CBPs were presented. We used ANOVA to compare VEPs associated with experimental vs. control conditions and with coarse vs. fine CBPs. Negative potentials at a latency near 190 ms showed statistically significant interactions between these comparisons in the right lateral occipital and posterior parietal areas when apparent motion in depth was perceived. This suggests that higher tiers of the dorsal stream mediate this motion perception.

Adult↗