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Biomedical subjects

Hiroyuki Toda

Publications and source records attributed to Hiroyuki Toda.

10 recordsLinked to original sources
PubMed2006

Behavioral stress and activated serotonergic neurotransmission induce XBP-1 splicing in the rat brain.

The splicing of 26 nucleotides in the coding region of the X-box binding protein-1 (XBP-1) transcript to generate a mature active transcription factor is a part of the unfolded protein response to intracellular endoplasmic reticulum stress. In this study, we demonstrated that XBP-1 splicing is promptly induced in the rat brain including the hippocampus by both inescapable electric foot shock (IS) and pharmacologically manipulated activation of 5-hydroxytryptamine release in a dose-dependent manner. By administering ketanserin, a 5-hydroxytryptamine 2A antagonist, however, we could only partially block the increased splicing by IS and observed that the splicing was not influenced by lithium carbonate pretreatment. Although it is still unclear whether the enhanced unfolded protein response functions neuroprotectively by modulating the rate of general translation and increasing chaperone proteins or whether it eventually induces cellular damage by triggering apoptosis, the present results indicate the possible existence of a new adaptive intracellular signaling pathway in the brain that responds to environmentally challenged behavioral stress loading.

Analysis of Variance↗
PubMed2006

Three-repeat Tau 69 is a major tau isoform in laser-microdissected Pick bodies.

By utilizing a novel combinatorial method of a Laser Microdissection System and Western blot analysis, we demonstrate that a distinct isoform of abnormally phosphorylated tau (69 kDa, Tau 69) predominantly aggregated in laser-microdissected Pick bodies (PBs) in sporadic Pick's disease. By contrast, tau migrated as two major bands of 60 and 64 kDa (Tau 60 and 64) in total brain homogenates as previously reported. Comparative immunohistochemical analysis with anti-4-repeat antibody revealed that a major component of the abnormally phosphorylated tau in these PBs was 3-repeat tau (3R-tau). Whether 29 amino acid repeat encoded by exons 2 and 3 in the Tau 69 might accelerate the formation of PBs remains to be further investigated. Such a combination of morphological and biochemical techniques significantly complements the existing histopathological methods.

Aged↗
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

Relationship between plasma concentration levels of risperidone and clinical effects in the treatment of delirium.

The present study aimed to examine the relationship between plasma concentration levels of risperidone and clinical effects in the treatment of delirium. We conducted a prospective, open-label, flexible-dose study of risperidone oral solution. Ten patients with delirium were assessed using Delirium Rating Scales. Plasma concentration levels of risperidone were measured 30 min after the first administration of a 0.5 mg dose. Two patients with high plasma levels had adverse effects and one patient with the lowest plasma level did not achieve remission; the remaining seven patients achieved remission without any adverse effects. A highly significant negative correlation was observed in these responders without adverse effects between the plasma levels and durations of treatment until remission (r=-0.861, P=0.0095). The plasma concentration level of risperidone at 30 min after the first 0.5 mg dose may be a favourable response predictor in the treatment of delirium. Further studies in larger samples are needed to verify this preliminary finding.

Administration, Oral↗
PubMed2004

[Kuru].

Explore the source record for details and available documents.

Animals↗
PubMed2003

[Clinical aspects of abnormal eye movements].

This paper reviews a variety of abnormal eye movements which include abnormal ocular positions, restricted eye motions, impairment of conjugated eye movements, abnormal smooth pursuit, abnormal saccade, gaze-evoked nystagmus, down-beat nystagmus, internuclear ophthalmoplegia, supranuclear ophthalmoplegia, square wave jerks, roving eye movement, ocular bobbing, ocular dipping, reverse ocular bobbing, and ping-pong gaze. Abnormal eye movements occur from stroke, spinocerebellar degeneration, Parkinson disease, multiple system atrophy, progressive supranuclear palsy, multiple sclerosis, Miller Fisher syndrome, myasthenia gravis, opsoclonus-polymyoclonia syndrome, and Creutzfeldt-Jakob disease. In neurological practice, it is important to observe abnormal eye movements accurately and enthusiastically, to make appropriate anatomical and etiological diagnosis.

Adult↗
PubMed2002

In situ phage screening. A method for identification of subnanogram tissue components in situ.

We have established a novel method, in situ phage screening (ISPS), to identify proteins in tissue microstructures. The method is based on the selection of repertoires of phage-displayed antibody fragments with small samples of tissues microdissected using a laser. Using a human muscle frozen section with an area of 4800 microm2 as a model target, we successfully selected monoclonal antibody fragments directed against three major (myosin heavy chain, actin, and tropomyosin-alpha) and one minor (alpha-actinin 2) muscle constituent proteins. These proteins were present in the sample in amounts less than one nanogram, and the antibodies were used to visualize the proteins in situ. This shows that the use of ISPS can obtain monoclonal antibodies for histochemical and biochemical purposes against minute amounts of proteins from microstructures with no requirement for large amounts of samples or biochemical efforts.

Antigens↗