Search PubMed⌕ Search

Biomedical subjects

S Tsuji

Publications and source records attributed to S Tsuji.

At least 19 recordsLinked to original sources
PubMed2006

Prolactin-releasing peptide is a potent mediator of stress responses in the brain through the hypothalamic paraventricular nucleus.

The effects of i.c.v. administration of prolactin-releasing peptide on neurons in the paraventricular nucleus of rats and plasma corticosterone levels were examined by measuring changes in Fos-like immunoreactivity, c-fos mRNA using in situ hybridization histochemistry, and plasma corticosterone using a specific radioimmunoassay. Approximately 80% of corticotropin-releasing hormone immunoreactive cells exhibited Fos-like immunoreactivity in the parvocellular division of the paraventricular nucleus 90 min after i.c.v. administration of prolactin-releasing peptide. The greatest induction of the c-fos mRNA expression in the paraventricular nucleus was observed 30 min after administration of prolactin-releasing peptide, and occurred in a dose-related manner. Plasma corticosterone levels were also significantly increased 30 min after administration of prolactin-releasing peptide. Next, the effects of restraint stress, nociceptive stimulus and acute inflammatory stress on the expression of the prolactin-releasing peptide mRNA in the dorsomedial hypothalamic nucleus, nucleus of the solitary tract and ventrolateral medulla were examined using in situ hybridization histochemistry for prolactin-releasing peptide mRNA. Restraint stress and acute inflammatory stress upregulated the prolactin-releasing peptide mRNA expression in the nucleus of the solitary tract and ventrolateral medulla. Nociceptive stimulus upregulated the prolactin-releasing peptide mRNA expression in the ventrolateral medulla. Finally, we observed that pretreatment (i.c.v. administration) with an anti-prolactin-releasing peptide antibody significantly attenuated nociceptive stimulus-induced c-fos mRNA expression in the paraventricular nucleus. These results suggest that prolactin-releasing peptide is a potent and important mediator of the stress response in the brain through the hypothalamic paraventricular nucleus.

Analysis of Variance↗
PubMed2006

Regulation of STAT3-mediated signaling by LMW-DSP2.

Signal transducer and activator of transcription 3 (STAT3), which mediates biological actions in many physiological processes, is activated by cytokines and growth factors, and has been reported to be constitutively activated in numerous cancer cells. In this study, we examined whether low molecular weight-dual specificity phosphatase two (LMW-DSP2) is involved in the regulation of the interleukin 6 (IL-6)/leukemia inhibitory factor (LIF)/STAT3-mediated signaling pathway. IL-6/LIF-induced LMW-DSP2 expression in murine testicular or hepatoma cell lines, while LMW-DSP2 overexpression in 293T cells suppressed IL-6-induced phosphorylation and activation of STAT3. Furthermore, LMW-DSP2 suppressed the expression of IL-6-induced endogenous genes. In contrast, small-interfering RNA-mediated reduction of LMW-DSP2 expression enhanced IL-6-induced STAT3-dependent transcription. In fact, LMW-DSP2 interacted with STAT3 in vivo and endogenous LMW-DSP2 bound to STAT3 in murine testicular GC-1 cells. These results strongly suggest that LMW-DSP2 acts as a negative regulator of the IL-6/LIF/STAT3-mediated signaling pathway.

Animals↗
PubMed2006

High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and easily tolerated method of altering cortical physiology. To date, numerous open and sham controlled clinical trials have explored the antidepressant potential of rTMS. In the present study, we investigated clinical trials of high-frequency rTMS (20 Hz) for treatment of refractory depression, and also examined the effect of rTMS on plasma levels of catecholamine metabolites and brain-derived neurotropic factor (BDNF). METHODS: Twenty-six depressed inpatients who met the DSM-IV criteria for major depressive disorder and had failed to respond to treatment with at least two antidepressant drugs given at adequate doses (above 150 mg/day in an equivalent dose of imipramine) and durations (at least 4 weeks for each drug) were enrolled in this study. Eleven were males, 15 females. The ages of the subjects ranged from 19 to 78 years old (mean +/- SD = 52.9 +/- 17.8). All patients were administered left prefrontal 20 Hz rTMS at 80 % MT (total 800 pulses a day) over ten daily sessions. The plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed by high-performance liquid chromatography. The plasma levels of BDNF were also measured with the sandwich ELISA method. RESULTS: The mean 17-item Hamilton Rating Scale for Depression (Ham-D) score of 20.5 +/- 5.2 before rTMS was significantly decreased to 15.6 +/- 7.3 after rTMS. Nine of 26 patients (35 %) demonstrated some improvement (Ham-D > or = 25 %) by rTMS. The levels of plasma MHPG, but not those of HVA, were significantly reduced after rTMS treatment, and a negative correlation was observed between the change in plasma MHPG levels and the change in scores of agitation. In addition, the plasma levels of BDNF were significantly increased by 23 % in responders and partial responders, but not in nonresponders, after rTMS treatment, and a trend for association was found between the changes in Ham-D scores and changes in plasma BDNF levels in all patients after rTMS treatment. CONCLUSION: These results suggest that rTMS treatment brings about some improvement in refractory depression, especially for symptoms such as agitation, by influencing MHPG and BDNF, which is in accordance with previous reports showing that BDNF was increased by various antidepressants treatments.

Adult↗
PubMed2006

Investigation of new cytogenetic biomarkers specific to high-LET radiation using in vivo and in vitro exposed human lymphocytes.

PURPOSE: To find detectable cytogenetic biomarkers that can offer information about the radiation quality of in vivo exposure retrospectively. MATERIALS AND METHODS: Chromosome-type aberrations of peripheral lymphocytes of uterine cancer patients that received internal gamma- and external X-ray therapy or carbon beam therapy and of victims severely exposed to neutrons and gamma-rays in a criticality accident that occurred in Tokai-mura, Japan were analysed. Data obtained from in vitro irradiation experiments using 60Co gamma-rays and 10 MeV neutrons were compared with the in vivo exposure data. RESULTS: The ratio of acentric rings to dicentric chromosomes (termed RaD ratio) and that of excess fragments to dicentrics (termed EfD ratio) showed significant (p < 0.05) differences between the two groups of cancer patients, and these ratios for accidental victims were in between the values of the two groups of cancer patients. The in vitro studies using doses equivalent to 1 - 3 Gy of gamma-rays have confirmed that the EfD ratios were increased with the high LET (linear energy transfer) and RaD ratios decreased. CONCLUSION: The present data show that the RaD and EfD ratios can be used as cytogenetic biomarkers of exposure to high-LET radiation at least within a few years of exposure.

Aged↗
PubMed2005

Er81 is expressed in a subpopulation of layer 5 neurons in rodent and primate neocortices.

Laminar organization is a fundamental cytoarchitecture in mammalian CNS and a striking feature of the neocortex. ER81, a transcription factor, has recently been utilized as a marker of cells in the layer 5 of the neocortex. We further pursued the distribution of ER81 to investigate the identity of the ER81-expressing cells in the brain. Er81 transcript was expressed in a subset of pyramidal cells that were scattered throughout the entire width of layer 5. In the rat cortex, Er81 transcripts were first detected in the ventricular zone at E15, remained expressed in putative prospective layer 5 neurons during infant and juvenile stages. The ER81-expressing subpopulation in adult layer 5 neurons did not segregate with the phenotypes of the projection targets. By retrograde labeling combined with immunohistochemistry or reverse transcription-polymerase chain reaction analysis, we found ER81 expression in nearly all of the layer 5 neurons projecting to the spinal cord or to the superior colliculus, while in only one-third of the layer 5 neurons projecting to the contralateral cortex. Er81 was also detected in layer 5 neurons in a P2 Japanese macaque monkey but not in adult monkey cortices. These findings suggest that a neuron class defined by a molecular criterion does not necessarily segregate with that defined by an anatomical criterion, that ER81 is involved in cell differentiation of a subset of layer 5 projection neurons and that this mechanism is conserved among rodents and primates.

Aging↗
PubMed2005

Three dimensional magnetic resonance imaging by magnetic resonance force microscopy with a sharp magnetic needle.

An electropolished magnetic needle made of Nd(2)Fe(14)B permanent magnet was used for obtaining better spatial resolution than that achieved in our previous work. We observed the magnetic field gradient |G(Z)|=80.0G/microm and the field strength B=1250G at Z approximately 8.8 microm from the top of the needle. The use of this needle for three dimensional magnetic resonance force microscopy at room temperature allowed us to achieve the voxel resolution to be 0.6 microm x 0.6 microm x 0.7 microm in the reconstructed image of DPPH phantom. The acquisition time spent for the whole data collection over 64 x 64 x 16 points, including an iterative signal average by six times per point, was about 10 days.

Journal Article↗
PubMed2005

Neuroprotective mechanisms of lidocaine against in vitro ischemic insult of the rat hippocampal CA1 pyramidal neurons.

To compare neuroprotective effects of lidocaine and procaine against ischemic insult, intracellular recordings were made from rat hippocampal CA1 pyramidal neurons in slice preparations. Superfusion of the slices with oxygen- and glucose-deprived medium (in vitro ischemia) produced a rapid depolarization 6 min from the onset. When oxygen and glucose were reintroduced, the membrane depolarized further until it reached 0 mV, and thereafter the membrane showed no functional recovery. Pretreatment with lidocaine (10 microM), but not procaine (50 microM), restored the membrane potential after the reintroduction of oxygen and glucose. Lidocaine, compared to procaine, significantly inhibited the reduction in both tissue ATP content and flavoprotein fluorescence during and after in vitro ischemia. Under electron microscopy, only lidocaine well preserved the structure of mitochondria in the CA1 pyramidal cell body. Extracellular recordings revealed that procaine reduced the field postsynaptic potential whereas lidocaine augmented it. Both drugs reduced the presynaptic volley dose-dependently. Neither lidocaine nor procaine significantly affected a rapid rise of the intracellular Ca2+ level produced by in vitro ischemia in the CA1 region. All the results suggest that the neuroprotective lidocaine action is due to the protection of the mitochondria to maintain the tissue ATP content during and after in vitro ischemia.

Adenosine Triphosphate↗
PubMed2005

Construction of a genetic linkage map of Japanese quail (Coturnix japonica) based on AFLP and microsatellite markers.

The Japanese quail (Coturnix japonica) is a notably valuable egg and meat producer but has also been used as a laboratory animal. In the present study, we constructed a Japanese quail linkage map with 1735 polymorphic amplified fragment length polymorphisms markers, and nine chicken microsatellite (MS) markers, as well as sex and phenotypes of two genetic diseases; a muscular disorder (LWC) and neurofilament-deficient mutant (Quv). Linkage analysis revealed 578 independent loci. The resulting linkage map contained 44 multipoint linkage groups covering 2597.8 cM and an additional 218.2 cM was contained in 21 two-point linkage groups. The total map was 2816 cM in length with an average marker interval of 5.5 cM. The Quv locus was located on linkage group 5, but linkage was not found between the LWC locus and any of the markers. Comparative mapping with chicken using orthologous markers revealed chromosomal assignments of the quail linkage group 1 to chicken chromosome 2 (GGA2), 5 to GGA22, 2 to GGA5, 8 to GGA7, 27 to GGA11, 29 to GGA1 and 45 to GGA4.

Animals↗
PubMed2005

Interference of CREB-dependent transcriptional activation by expanded polyglutamine stretches--augmentation of transcriptional activation as a potential therapeutic strategy for polyglutamine diseases.

On the basis of the hypothesis that the interaction of mutant proteins with expanded polyglutamine stretches with transcriptional co-activator, TAFII130, leads to transcriptional dysregulation, the transcriptional activation of c-Fos and its suppression by expanded polyglutamine stretches was investigated. The phosphorylation of cAMP-responsive element binding protein (CREB) and induction of c-Fos in response to cAMP were strongly suppressed in Neuro2a cells expressing expanded polyglutamine. The suppression of CREB-dependent transcriptional activation was reversibly rescued by increasing the concentration of cAMP. Expanded polyglutamine-induced cytotoxicity was also substantially suppressed by augmenting CREB-dependent transcriptional activation with a high concentration of cAMP. FR901228, a histone deacetylase inhibitor, was also demonstrated as rescuing the expanded polyglutamine-induced suppression of CREB phosphorylation and c-Fos expression. Furthermore, nuclear fragmentation was significantly suppressed by FR901228. The co-expression of dominant-negative CREB vectors considerably abrogated the suppressive effect of cAMP and FR901228 on the expanded polyglutamine-induced nuclear fragmentation, suggesting that these compounds suppress polyglutamine-induced cytotoxicity, largely, via the enhancement of CREB-dependent transcriptional activation. These findings suggest that the interference of CREB-dependent transcriptional activation by expanded polyglutamine stretches is involved in the pathogenetic mechanisms underlying neurodegeneration, and that the augmentation of CREB-dependent transcriptional activation is a potential strategy in treating polyglutamine diseases.

Animals↗
PubMed2004

Beta-synuclein gene alterations in dementia with Lewy bodies.

OBJECTIVE: To determine whether mutations in the genes for alpha-synuclein or beta-synuclein are responsible for dementia with Lewy bodies (DLB), a disorder closely related to Parkinson disease (PD). METHODS: The authors ascertained 33 sporadic cases of DLB and 10 kindreds segregating DLB. DNA samples from the 43 index cases were screened for alterations in the genes for alpha-synuclein and beta-synuclein, as alpha-synuclein alterations cause PD and beta-synuclein may modulate alpha-synuclein aggregation and neurotoxicity. RESULTS: Two amino acid alterations were identified in unrelated DLB index cases: a valine to methionine substitution at codon 70 (V70M) and a proline to histidine substitution at codon 123 (P123H), both in the beta-synuclein gene. These amino acid substitutions occur at conserved residues in highly conserved regions of the beta-synuclein protein. Screening of at least 660 chromosomes from control subjects matched to the patients' population groups failed to identify another V70M or P123H allele. Cosegregation analysis of an extended pedigree segregating the P123H beta-synuclein alteration suggested that it is a dominant trait with reduced penetrance or a risk factor polymorphism. Histopathology and immunohistochemistry analysis of index case brain sections revealed widespread Lewy body pathology and alpha-synuclein aggregation without evidence of beta-synuclein aggregation. CONCLUSION: Mutations in the beta-synuclein gene may predispose to DLB.

Aged↗
PubMed2004

A new cytochemical method for ultrastructural localization of Co2+ in rat hippocampal CA1 pyramidal neurons in vitro.

This paper describes new cytochemical method for the ultrastructural localization of Co(2+) following blockade of synaptic transmission. In the CA1 region of rat hippocampal slices, electrical stimulation of the Schaffer collaterals elicited field excitatory postsynaptic potentials (fEPSPs). The fEPSPs were completely blocked within 2 min after the addition of Co(2+) (2 mM). The slice was then fixed and precipitated Co(2+) was examined by means of a solution containing 2.5% glutaraldehyde and 10 mM K(3)[Fe(3+)(CN)(6)] in 90 mM NaCl. Electron spectroscopic imaging confirmed Co in the precipitate. The precipitates were found as clusters on the membranes of the fine apical dendrites and their spine heads of CA1 pyramidal neurons. No clustered precipitate was found when slices were treated: (1) without Co(2+); (2) after recovery from the Co(2+)-induced blockade of fEPSPs; (3) without electrical stimulation of the Schaffer collaterals; and (4) with dl-2-amino-5-phosphonopentanoate and 6-cyano-7-nitroquinoxaline-2,3-dione. After administrating glutamate (5 mM) in the presence of tetrodotoxin (1 microM) and Co(2+), precipitates were found on dendritic membranes and spine heads. These results indicate that the Schaffer collaterals stimulation induces the binding of Co(2+) on CA1 pyramidal neuron membrane.

2-Amino-5-phosphonovalerate↗
PubMed2004

Adult-onset leukoencephalopathy with vanishing white matter with a missense mutation in EIF2B5.

We report of a woman aged 52 years born to consanguineous parents and seeking treatment for progressive dementia and delusion. Neurologic examination revealed dementia and emotional instability, indifference, and confabulation. There was also mild spasticity of the bilateral lower limbs. MRI revealed diffuse white matter hyperintensity on T2-weighted images accompanied by hypointense areas on fluid-attenuated inversion recovery images. A homozygous missense mutation was identified in EIF2B5.

Adult↗
PubMed2004

Motor hand representation in cortical area 44.

OBJECTIVE: To elucidate whether area 44 of human frontal cortex is essential for the organization of voluntary hand movements or not, the authors examined effects of single transcranial magnetic stimulation (TMS) of human area 44 on voluntary hand movement and electromyography (EMG) activities in hand muscles. METHOD: Surface EMG responses were recorded from the thenar muscles of 10 normal subjects following TMS over area 44. Stimuli were applied 2 cm anterior to the primary tongue motor area. RESULTS: Single TMS over area 44 could easily interrupt target-oriented hand movements. Human area 44 has facilitatory and inhibitory effects over both tonic and phasic finger movements. It is shown that single TMS of area 44 produces motor evoked potential from hand muscles. CONCLUSION: Human area 44 is involved in voluntary hand movements and has direct fast-conducting corticospinal projections.

Adult↗
PubMed2004

Japanese SCA families with an unusual phenotype linked to a locus overlapping with SCA15 locus.

The authors identified two Japanese spinocerebellar ataxia (SCA) families characterized by postural and action tremor and a very slow progression rate. A genome-wide linkage analysis revealed linkage to chromosome 3p26.1-25.3 with the highest multipoint lod score at D3S3728 (Zmax = 3.31 at theta = 0.00). The candidate region was 14.7 cM flanked by D3S1620 and D3S3691, which was partly overlapping with the locus of SCA15 characterized by pure cerebellar ataxia. Despite the difference in phenotypes, there remains a possibility that the causative gene for these Japanese SCA is allelic to SCA15.

Adult↗
PubMed2004

Magnetic resonance imaging of isolated single liposome by magnetic resonance force microscopy.

Magnetic resonance imaging (MRI) is very useful spectroscopy to visualize a three-dimensional (3D) real structure inside the sample without physical destruction. The spatial resolution of the readily available MRI spectrometer is, however, limited by a few ten to hundreds of microns due to a technological boundary of generating larger magnetic field gradient and to the insensitivity inherent to the inductive signal detection. Magnetic resonance force microscopy (MRFM) is new alternative MRI spectroscopy which is anticipated to significantly surpass the conventional MRI in both resolution and sensitivity. We report two imaging experiments on our MRFM spectrometer operated at room temperature and in vacuum approximately 10(-3)Pa. One is for approximately 20 microm liposome membrane labeled entirely by a nitroxide imaging agent and the other for approximately 15 microm DPPH particles, both are nearly the same size as that of human cell. The reconstructed images at spatial resolution approximately 1 microm were in satisfactory agreement with the scanning electron microscope images. The potential capability of visualizing intrinsic radicals in the cell is suggested to investigate redox process from a microscopic point of view.

Biphenyl Compounds↗
PubMed2004

Reduction in levels of amphiphysin 1 mRNA in the hippocampus of aged rats subjected to repeated variable stress.

Various neurobiological studies of aging indicate that elevated levels of circulating glucocorticoids lead to hippocampal vulnerability to stress, though little is known about the molecular mechanism underlying stress vulnerability in the elderly. We have compared the gene expression profiles in the hippocampus of aged (20 months) and adult (3 months) rats in response to repeated variable stress (RVS) for 4 days, using a cDNA array technique and real-time quantitative PCR, to identify putative genes involved in the mechanism of stress vulnerability in the elderly. We found a significant decrease in the levels of amphiphysin 1 mRNA in aged rats subjected to RVS compared with treated and untreated adult rats or to untreated aged rats. Similarly, we found a significant decrease in hippocampal levels of amphiphysin 1 mRNA in aged rats subjected to RVS for 8 days, but not in those subjected to a single VS. These findings suggest that the decrease in the hippocampal levels of amphiphysin 1 mRNA in response to repeated stress may be involved in the stress vulnerability in the elderly, and may lead to the disturbance of learning and memory under stressful conditions in the elderly.

Aging↗
PubMed2004

Independent mitochondrial origin and historical genetic differentiation in North Eastern Asian cattle.

In order to clarify the origin and genetic diversity of cattle in North Eastern Asia, this study examined mitochondrial displacement loop sequence variation and frequencies of Bos taurus and Bos indicus Y chromosome haplotypes in Japanese, Mongolian, and Korean native cattle. In mitochondrial analyses, 20% of Mongolian cattle carried B. indicus mitochondrial haplotypes, but Japanese and Korean cattle carried only B. taurus haplotypes. In contrast, all samples revealed B. taurus Y chromosome haplotypes. This may be due to the import of zebu and other cattle during the Mongol Empire era with subsequent crossing with native taurine cattle. B. taurus mtDNA sequences fall into several geographically distributed haplogroups and one of these, termed here T4, is described in each of the test samples, but has not been observed in Near Eastern, European or African cattle. This may have been locally domesticated from an East Eurasian strain of Bos primigenius.

Animals↗