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Shunsuke Kobayashi

Publications and source records attributed to Shunsuke Kobayashi.

17 recordsLinked to original sources
PubMed2007

Functional differences between macaque prefrontal cortex and caudate nucleus during eye movements with and without reward.

The prefrontal cortex and the basal ganglia form mutually connected networks and are thought to play essential roles together in guiding goal-directed behaviors. Yet, these structures seem to have independent pathways to motor outputs as well, suggesting differential contributions to goal-directed behaviors. We hypothesized that the prefrontal cortex guides actions to a direction required by external demands and the basal ganglia guide actions to an internally motivated direction. To test this hypothesis, we used a task in which monkeys were required to make a memory-guided saccade to a direction indicated by a visual cue while only one direction was associated with reward. We observed a functional dissociation between the lateral prefrontal cortex (LPFC), which commonly represented the cue direction, and the caudate nucleus (CD), which commonly represented the reward-associated direction. Furthermore, cue-directed and reward-directed signals were integrated differently in the two areas; when the cue direction and the reward direction were opposite, LPFC neurons maintained tuning to the cue direction, whereas CD neurons lost the tuning. Different types of spatial tuning in the two brain areas may contribute to different types of goal-directed behavior.

Analysis of Variance↗
PubMed2006

Influences of rewarding and aversive outcomes on activity in macaque lateral prefrontal cortex.

Both appetitive and aversive outcomes can reinforce animal behavior. It is not clear, however, whether the opposing kinds of reinforcers are processed by specific or common neural mechanisms. To investigate this issue, we studied macaque monkeys that performed a memory-guided saccade task for three different outcomes, namely delivery of liquid reward, avoidance of air puff, and feedback sound only. Animals performed the task best in rewarded trials, intermediately in aversive trials, and worst in sound-only trials. Most task-related activity in lateral prefrontal cortex was differentially influenced by the reinforcers. Aversive avoidance had clear effects on some prefrontal neurons, although the effects of rewards were more common. We also observed neurons modulated by both positive and negative reinforcers, reflecting reinforcement or attentional processes. Our results demonstrate that information about positive and negative reinforcers is processed differentially in prefrontal cortex, which could contribute to the role of this structure in goal-directed behavior.

Analysis of Variance↗
PubMed2006

Expression and polysome association of YB-1 in various tissues at different stages in the lifespan of mice.

Tissue-specific translational regulation is important for gene expression. YB-1 binds to mRNAs to form mRNPs and affects translation. In this study we investigated expression and polysome association of YB-1 in various tissues at different stages in the lifespan of mice. YB-1 levels decreased markedly with growth in brain, heart and muscle, but increased in the spleen. In lung, kidney and testis, the levels of YB-1 diminished with aging. In liver, no significant change in the level of YB-1 was observed throughout life. We further showed that the distribution pattern of YB-1 on a sucrose gradient differed according to tissue. Moreover, the distribution pattern of YB-1 changed drastically with growth in the liver. In 5-day-old liver, YB-1 was distributed almost exclusively in nonpolysomal fractions, whereas in 4-week-old liver, it was associated with heavy-sedimenting polysomes, as was the case in 5-day-old brain. Immunohistochemical analysis revealed that YB-1 is mainly a cytoplasmic protein in these tissues. Our results indicate that the expression and polysome association of YB-1 are regulated with growth or aging in a tissue-specific manner, presumably to control gene expression at the translational level in each tissue.

Animals↗
PubMed2006

New-onset demyelination induced by infliximab therapy in two rheumatoid arthritis patients.

Therapies aimed at inhibiting tumor necrosis factor, a proinflammatory cytokine implicated in autoimmune disease, are effective for rheumatoid arthritis (RA) and Crohn's disease. We report two patients who newly developed multiple demyelinating lesions in the central nervous system in the course of infliximab therapy for active RA. Neurological symptoms and the number of gadolinium-diethylenetriamine pentaacetic acid-enhanced lesions in magnetic resonance imaging gradually diminished with steroid treatment.

Aged↗
PubMed2005

Retrograde degeneration of the corticospinal tract associated with pontine infarction.

We report a 40-year-old man with myotonic dystrophy who survived for 5 years after pontine infarction. Serial MRI detected abnormal T2 elongation of the corticospinal tract at the cerebral peduncle 4 years after the infarction. An autopsy confirmed the existence of retrograde degeneration extending from the pons to the internal capsule, evidence that retrograde degeneration in the corticospinal tract occurs above the pontine level. MRI was suggested to be useful for detection of the degenerative process.

Adult↗
PubMed2005

Application of the BC1 RNA gene promoter for short hairpin RNA expression in cultured neuronal cells.

BC1 RNA is a neuronal cell-specific non-messenger RNA transcribed by RNA polymerase III (Pol III). We previously reported that the transcription of BC1 RNA is controlled both by intragenic promoters for Pol III and by a 5'-flanking region containing several unique cis-elements that are possible members of the Pol II transcription system. In this study, we chose beta-secretase (BACE1) as a target and applied the promoter to produce a short hairpin RNA (shRNA) for RNA interference (RNAi) in cultured neuronal cells. A plasmid vector in which the promoter was linked to a target sequence functioned in rodent NG108-15 cells and suppressed BACE1 protein expression, but did not function in non-neuronal NIH3T3 cells. It was also effective in rat primary hippocampal neurons. We further showed that the promoter can be active in human neuroblastoma SH-SY5Y cells and reduced expression of targeted protein, although the BC1 RNA gene is a rodent-specific gene. The use of this vector-based system for shRNA expression may be an important component of future development of neuronal cell-selective RNAi in both transgenic and therapeutic applications.

Amyloid Precursor Protein Secretases↗
PubMed2005

Vocal amusia in a professional tango singer due to a right superior temporal cortex infarction.

We describe the psychophysical features of vocal amusia in a professional tango singer caused by an infarction mainly involving the superior temporal cortex of the right hemisphere. The lesion also extended to the supramarginal gyrus, the posterior aspect of the postcentral gyrus and the posterior insula. She presented with impairment of musical perception that was especially pronounced in discriminating timbre and loudness but also in discriminating pitch, and a severely impaired ability to reproduce the pitch just presented. In contrast, language and motor disturbances were almost entirely absent. By comparing her pre- and post-stroke singing, we were able to show that her singing after the stroke lacked the fine control of the subtle stress and pitch changes that characterized her pre-stroke singing. Such impairment could not be explained by the impairment of pitch perception. The findings suggest that damage to the right temporoparietal cortex is enough to produce both perceptive and expressive deficits in music.

Aged↗
PubMed2004

Interhemispheric transmission of visuomotor information for motor implementation.

Using transcranial magnetic stimulation (TMS), we addressed the contribution of both hemispheres to the visuomotor control of each hand. The subjects had to press one of two buttons as quickly as possible after the go-signal. A precue preceding this conveyed full, partial or no advance information (hand and/or button), such that reaction time (RT) shortened with increasing amount of information. We gave TMS over each hemisphere at various time intervals (100-350 ms) after the go-signal and before the expected onset of response, and measured its effect on RT, movement time (MT) and error rate. At short intervals (100-200 ms), left hemisphere TMS delayed RT and prolonged MT of both hands, while right hemisphere TMS delayed RT only of the right hand, without affecting error rates. At long intervals (250-350 ms), TMS produced slightly more pronounced RT delays of the contralateral hand. RT was delayed more if the precues were less informative. The results suggest the importance of interhemispheric transmission of visuomotor information for motor implementation. The right hemisphere may play a role mainly in calculating target and effector information, determining RT, while the left hemisphere may play a role in elaborating the motor program and determining MT.

Adult↗
PubMed2003

Isolation and characterization of brain Y-box protein: developmentally regulated expression, polyribosomal association and dendritic localization.

Y-box proteins are DNA- and RNA-binding proteins and control specific gene expression at both transcriptional and translational levels. Particularly in germ cells, it has been reported that Y-box proteins bind to paternal or maternal mRNAs to form mRNPs, mask them from translation and control cell maturation. In this study, we cloned cDNA for a Y-box protein from rat brain. A deduced amino acid sequence of the protein was very similar to that of several other Y-box proteins, and we termed the protein rBYB1 (rat brain Y-box protein 1). rBYB1 was found to be considerably expressed in the cytoplasm of pre- and early postnatal brains, and then decreased to adult levels with brain development. Further, we found rBYB1 to be distributed in both polyribosomal and nonpolyribosomal (mRNP) fractions on a sucrose density gradient, and to be associated with polyribosomes via RNA in the higher-density fractions. Moreover, rBYB1 was localized in dendrites of the primary hippocampal neurons. We compared these sucrose gradient and intracellular rBYB1 localization results with those for fragile X mental retardation protein (FMRP), which is known to be an mRNA-binding and polyribosome-associating translational regulator distributed in neuronal dendrites. Our results suggest that in the brain of prenatal and newborn animals, rBYB1 may function in storage and/or translational regulation of mRNAs involved in the rapid progress of the postnatal brain, and in mature neurons, it may also participate in the control of protein synthesis in dendrites.

Amino Acid Sequence↗
PubMed2003

Positive and negative regulators for neuronal BC1 RNA transcription by RNA polymerase III are possible members of the RNA polymerase II transcription system.

Neuronal cell-specific BC1 RNA is a unique RNA polymerase III (Pol III) transcript. The transcription is controlled by an activator E2 site and by BCRE, a repressor element, in response to neuronal activity. BC1 RNA is localized to dendritic domains as ribonucleoprotein particles, and it has been suggested to play a functional role in translational regulation of dendritic mRNAs. In the present study, using a luciferase assay in NG108-15 cells, we found that the positive and negative regulators for BC1 RNA transcription can also function in the Pol II transcription system. Our results suggest that the neuronal activity-dependent expression of BC1 RNA by Pol III and a subset of neuronal mRNAs by Pol II may be simultaneously controlled by the E2 site and BCRE, as well as their binding proteins.

Animals↗
PubMed2003

Progressive improvement of prognosis for patients with gastric cancer (dynamic stage grouping) with increasing survival interval from initial staging: how much longer can a given survivor expect to live?

BACKGROUND: The prognosis in gastric cancer is usually defined at the time of presentation. Prognosis, however, is a variable that alters with time. Once a patient has survived for 1 year, the prognosis will change. This study examines this variable in patients who have survived from 1 to 5 years after operation. METHODS: Of 1468 patients with gastric cancer, the next 5-year survival (5YS) of patients who already survived for 1, 2, 3, 4, and 5 years after the initial operation was examined, ie, for patients who have survived 1 year, the 5YS (the 6-year survival from operation) was calculated. Similar survival was determined for patients who had survived more than 2, 3, 4, or 5 years and reported according to stage. RESULTS: In patients who survived 2 years, the next 5YS from that time of patients in stage III a stage was similar to that in stage II, and was similar to the 5YS of patients in stage II at the time of diagnosis. In patients who survived 3, 4, or 5 years, the next 5YS from that time of patients in stage III b and stage III a was similar to that of stage II, and subsequently improved. Similarly, the relationship between stage and survival was disordered subsequently with the passage of time. Similar improvement in survival such that 5YS from the 3rd, 4th, and 5th postoperative year approximated that of the survival of patients at an earlier stage at the time of diagnosis. CONCLUSIONS: Survival is not only stage-dependent at the time of diagnosis but dependent on the length of survival from the initial operation. Progressive improvement in subsequent 5YS appears to approximate survival of lower-stage disease with the passage of time.

Adult↗
PubMed2002

Identification of mRNA/protein (mRNP) complexes containing Puralpha, mStaufen, fragile X protein, and myosin Va and their association with rough endoplasmic reticulum equipped with a kinesin motor.

Puralpha, which is involved in diverse aspects of cellular functions, is strongly expressed in neuronal cytoplasm. Previously, we have reported that this protein controls BC1 RNA expression and its subsequent distribution within dendrites and that Puralpha is associated with polyribosomes. Here, we report that, following treatment with EDTA, Puralpha was released from polyribosomes in mRNA/protein complexes (mRNPs), which also contained mStaufen, Fragile X Mental Retardation Protein (FMRP), myosin Va, and other proteins with unknown functions. As the coimmunoprecipitation of these proteins by an anti-Puralpha antibody was abolished by RNase treatment, Puralpha may assist mRNP assembly in an RNA-dependent manner and be involved in targeting mRNPs to polyribosomes in cooperation with other RNA-binding proteins. The immunoprecipitation of mStaufen- and FMRP-containing mRNPs provided additional evidence that the anti-Puralpha detected structurally or functionally related mRNA subsets, which are distributed in the somatodendritic compartment. Furthermore, mRNPs appear to reside on rough endoplasmic reticulum equipped with a kinesin motor. Based on our present findings, we propose that this rough endoplasmic reticulum structure may form the molecular machinery that mediates and regulates multistep transport of polyribosomes along microtubules and actin filaments, as well as localized translation in the somatodendritic compartment.

Animals↗
PubMed2002

Feature-based anticipation of cues that predict reward in monkey caudate nucleus.

A subset of caudate neurons fires before cues that instruct the monkey what he should do. To test the hypothesis that the anticipatory activity of such neurons depends on the context of stimulus-reward mapping, we examined their activity while the monkeys performed a memory-guided saccade task in which either the position or the color of a cue indicated presence or absence of reward. Some neurons showed anticipatory activity only when a particular position was associated with reward, while others fired selectively for color-reward associations. The functional segregation suggests that caudate neurons participate in feature-based anticipation of visual information that predicts reward. This neuronal code influences the general activity level in response to visual features without improving the quality of visual discrimination.

Animals↗
PubMed2002

c-myc amplification and enhancement of sensitivity to cytosine arabinoside: an in vitro and in vivo study on four sublines established from a pulmonary adenocarcinoma.

PURPOSE: Meticulous treatment strategies taking tumor heterogeneity into account are considered essential to achieve breakthroughs in current cancer therapy. We analyzed tumor heterogeneity in the primary tumor of a patient with pulmonary adenocarcinoma characterized by a poor prognosis. METHODS: Four sublines with different growth characteristics in vitro were established from the tumor using a method for short-term selective cultivation. We examined the differences in morphological, biochemical, and genetic findings of these sublines. RESULTS: Differences in the histological features of the transplanted tumors were seen in the four sublines. The 88-2T and 88-2 tumors revealed a well-differentiated adenocarcinoma; the 88-2F tumor revealed a large cell-like carcinoma resembling the metastatic tumor in the lymph nodes; and the 88-2FA tumor was composed of signet-ring cells. There were differences in oncogenes, with the 88-2F line alone exhibiting 12-fold amplification of c-myc. Sensitivity to cytosine arabinoside (Ara C) was specifically increased in the 88-2F cell line, alone. CONCLUSIONS: These sublines demonstrate that human pulmonary adenocarcinoma has various types of heterogeneity within the primary tumor. Furthermore, c-myc amplification may play an important role in altering phenotype and growth characteristics in vitro and in vivo, and for increasing sensitivity to Ara C and the potential of cancer cells to metastasize to lymph nodes.

Adenocarcinoma↗
PubMed2002

Influence of reward expectation on visuospatial processing in macaque lateral prefrontal cortex.

The lateral prefrontal cortex (LPFC) has been implicated in visuospatial processing, especially when it is required to hold spatial information during a delay period. It has also been reported that the LPFC receives information about expected reward outcome. However, the interaction between visuospatial processing and reward processing is still unclear because the two types of processing could not be dissociated in conventional delayed response tasks. To examine this, we used a memory-guided saccade task with an asymmetric reward schedule and recorded 228 LPFC neurons. The position of the target cue indicated the spatial location for the following saccade and the color of the target cue indicated the reward outcome for a correct saccade. Activity of LPFC was classified into three main types: S-type activity carried only spatial signals, R-type activity carried only reward signals, and SR-type activity carried both. Therefore only SR-type cells were potentially involved in both visuospatial processing and reward processing. SR-type activity was enhanced (SR+) or depressed (SR-) by the reward expectation. The spatial discriminability as expressed by the transmitted information was improved by reward expectation in SR+ type. In contrast, when reward information was coded by an increase of activity in the reward-absent condition (SR- type), it did not improve the spatial representation. This activity appeared to be involved in gaze fixation. These results extend previous findings suggesting that the LPFC exerts dual influences based on predicted reward outcome: improvement of memory-guided saccades (when reward is expected) and suppression of inappropriate behavior (when reward is not expected).

Animals↗