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Biomedical subjects

Noriko Sato

Publications and source records attributed to Noriko Sato.

At least 19 recordsLinked to original sources
PubMed2007

The IL-15/IL-15Ralpha on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells.

We previously described unique features of the IL-15 receptor (IL-15R)alpha. IL-15Ralpha by itself forms stable complexes with IL-15 on cell surfaces and presents IL-15 in trans to neighboring natural killer/T cells. Moreover, the membrane IL-15/IL-15Ralpha complexes (membIL-15) undergo endosomal internalization but survive lysosomal degradation, allowing the complexes to recycle back to the cell surface. Here, we show that membIL-15+ cells act as a persistent source of IL-15 for the surrounding microenvironment (intercellular reservoir effect). Additionally, membIL-15+ cells give rise to augmented retention of IL-15 in the circulation as well as in tissues. Curiously, IL-15 retention was particularly associated with lungs, rather than with lymph nodes, in normal unstimulated mice, which correlated with the preferential homing of antigen-specific CD8 T cells to lungs during their contraction phase in an IL-15Ralpha-dependent manner. Furthermore, membIL-15, unlike soluble IL-15, caused sustained IL-15 signal transduction in the target cells. Collectively, these characteristics define IL-15 as a unique cytokine with prolonged in vivo survival and sustained biological action on the target cells, which may account for the proposed persistent action of IL-15 that helps the long-term survival of functional CD8 memory T cells in vivo.

Animals↗
PubMed2007

[A case of Möbius syndrome presenting with symptoms of severe infantile form of congenital muscular disorder].

Möbius syndrome is a rare disorder characterized by congenital bilateral facial nerve palsy. Abducent palsy or other cranial nerve palsy, facial malformations, limb malformations, and skeletal malformations are common features associated with this syndrome. We report a 9-month-old infant in whom congenital muscular disorder was previously suspected because of facial muscle involvement (mask-like face), respiratory and swallowing disturbances, and hypotonia since birth. After an improvement in the respiratory infection, she showed slightly exaggerated deep tendon reflexes and an improvement in muscle tone. The occurrence of combined facial nerve palsy, glossopharyngeal nerve palsy, vagus nerve palsy, and hypoglossal nerve palsy strongly suggested that she had Möbius syndrome. Finally, the absence of the roots of bilateral facial nerves on an MRI confirmed that the disorder was Möbius syndrome. We propose that a thin slice MRI should be obtained to observe the cranial nerves around the brain stem if patients show symptoms of congenital myopathy or congenital myotonic dystrophy as well as facial nerve and other cranial nerve paralyses.

Brain Stem↗
PubMed2006

DBC2 is essential for transporting vesicular stomatitis virus glycoprotein.

DBC2 is a tumor suppressor gene linked to breast and lung cancers. Although DBC2 belongs to the RHO GTPase family, it has a unique structure that contains a Broad-Complex/Tramtrack/Bric a Brac (BTB) domain at the C terminus instead of a typical CAAX motif. A limited number of functional studies on DBC2 have indicated its participation in diverse cellular activities, such as ubiquitination, cell-cycle control, cytoskeleton organization and protein transport. In this study, the role of DBC2 in protein transport was analyzed using vesicular stomatitis virus glycoprotein (VSVG) fused with green fluorescent protein. We discovered that DBC2 knockdown hinders the VSVG transport system in 293 cells. Previous studies have demonstrated that VSVG is transported via the microtubule motor complex. We demonstrate that DBC2 mobility depends also on an intact microtubule network. We conclude that DBC2 plays an essential role in microtubule-mediated VSVG transport from the endoplasmic reticulum to the Golgi apparatus.

Amino Acid Motifs↗
PubMed2006

Relationship between diffusion tensor imaging and brain morphology in patients with myotonic dystrophy.

Myotonic dystrophy type 1 (MyD) is a common inherited neuromuscular disorder. In addition to neuromuscular symptoms, many MyD patients show central nervous system neuropathology. This study evaluated whether MyD patients display diffusion tensor (DT) abnormalities associated with regional cortical atrophy and clinical features. Three-dimensional T1-weighted and DT magnetic resonance images of the brain were obtained in 11 MyD patients and 13 age- and sex-matched healthy subjects. Fractional anisotropy (FA) and mean diffusivity (MD) values were calculated in corpus callosum subregions with DT imaging (DTI) along with volumetric changes, and correlations with clinical features were examined. Differences between MyD patients and healthy subjects were analyzed statistically. Significantly lower FA and higher MD values were found in the genu, rostral body, anterior midbody, posterior midbody and splenium in MyD patients than in control subjects (p<0.05, corrected; lower FA in the splenium was at a trend level). These corpus callosum subregions were the areas connected to cortical areas where significantly lower volumes were found in MyD patients. No significant decrease in volumes was noted in the parietal cortex, where connecting fibers pass through the isthmus in which DTI abnormalities were not detected in MyD patients. Significant negative correlations to volumes of frontal areas were noted, particularly bilateral motor areas, with cytosine thymine guanidine (CTG) triplet expansion. DTI results in corpus callosum may reflect morphological changes in the connecting cortical areas of MyD patients.

Brain↗
PubMed2006

Interleukin-2-dependent mechanisms of tolerance and immunity in vivo.

IL-2 is a critical T cell growth factor in vitro, but predominantly mediates tolerance in vivo. IL-2 is mainly produced by CD4(+) Th cells, but the role of Th cell-derived IL-2 in vivo is controversial. We demonstrate that during immunity to a tumor/self-Ag, the predominant role of Th cell-derived IL-2 was to maintain IL-2Ralpha (CD25) on CD4(+) T regulatory cells (T(reg)), which resulted in their maintenance of the T(reg) cell lineage factor, Forkhead/winged helix transcription factor (Foxp3), and tolerance. However, in the absence of T(reg) cells, Th cell-derived IL-2 maintained effector T cells and caused autoimmunity. IL-2R signaling was indispensable for T(reg) cell homeostasis and efficient suppressor function in vivo, but, surprisingly, was not required for their generation, because IL-2(-/-) and CD25(-/-) mice both contained Foxp3(+) T cells in the periphery. IL-2R signaling was also important for CD8(+) T cell immunity, because CD25(-/-) tumor-reactive CD8(+) T cells failed to affect established tumors. Conversely, IL-2R signaling was not required for Th cell function. Lastly, administration of anti-IL-2 plus exogenous IL-15 to tumor-bearing mice enhanced the adoptive immunotherapy of cancer. Therefore, Th cell-derived IL-2 paradoxically controls both tolerance and immunity to a tumor/self-Ag in vivo.

Animals↗
PubMed2006

The orphan nuclear receptor GCNF recruits DNA methyltransferase for Oct-3/4 silencing.

Somatic DNA methylation patterns are determined in part by the de novo methylation that occurs after early embryonic demethylation. Oct-3/4, a pluripotency gene, is unmethylated in the blastocyst, but undergoes de novo methylation and silencing during gastrulation. Here we show that the transcriptional repressor GCNF recruits DNA methyltransferase to the Oct-3/4 promoter and facilitates its methylation. Although acetylation of histone H3 at lysine 9 (K9) and/or 14 (K14) and methylation of H3 at lysine 4 (K4) decrease during this period, as do Oct-3/4 transcript levels, H3K9 and H3K27 methylation levels remain constant, indicating that DNA methylation does not require repressive histone modifications. We found that GCNF interacts directly with Dnmt3 molecule(s) and verified that this interaction induces the methylation of the Oct-3/4 promoter. Our finding suggests a model in which differentiation-induced GCNF recruits de novo DNA methyltransferase and facilitates the silencing of a pluripotency gene.

Animals↗
PubMed2006

MR signal of the solid portion of pilocytic astrocytoma on T2-weighted images: is it useful for differentiation from medulloblastoma?

BACKGROUND AND PURPOSE: Although imaging features of cerebellar pilocytic astrocytoma and medulloblastoma have been described in many texts, original comparisons of magnetic resonance intensity between these two tumours are limited. In the present study the results of magnetic resonance imaging (MRI) were reviewed, focusing especially on the signal intensity of the solid portion of these neoplasms. METHODS: MR images of ten cerebellar pilocytic astrocytomas and ten medulloblastomas were reviewed. The signal intensities of the solid components were graded on a scale of 1 to 5, with higher scores indicating a signal intensity closer to that of water. The degree of enhancement, tumour cysts and peripheral oedema were evaluated on MR images. When the solid portion was heterogeneous (i.e. mixed signal intensity or degree of enhancement), the dominant area was selected for evaluation. RESULTS: On T2-weighted images, the signal intensity of the solid portion was equal to that of cerebrospinal fluid (CSF) in 50% of pilocytic astrocytomas. No medulloblastomas showed such hyperintensity. Most medulloblastomas (80%) were isointense to grey matter. On T1-weighted images, the signal intensity varied widely in pilocytic astrocytomas; however, all medulloblastomas were iso- or hypointense to grey matter. The MR enhancement pattern, cystic component and peripheral oedema all varied in both tumour types and no specific features were identified. CONCLUSION: A signal intensity of the solid portion isointense to CSF on T2-weighted images was characteristic of cerebellar pilocytic astrocytomas; this was not observed in medulloblastomas. Attention to T2-weighted imaging of the solid portions of a tumour is easy and helpful in differentiating between cerebellar pilocytic astrocytoma and medulloblastoma.

Adolescent↗
PubMed2006

Confirmation of the anomeric structure of galacturonic acid in the galacturonosyl-ceramide of Sphingomonas yanoikuyae.

The anomeric structure of glycosphingolipids significantly influences their activity to stimulate natural killer T cells. In this study the chemical structure of the galacturonosyl-ceramide in Sphingomonas yanoikuyae, designated GSL-1'sy, was re-examined to prove the anomeric structure of the Dgalacturonic acid (GalA) in the lipid, which was reported as beta-configuration by Naka et al., but was suggested as alpha-configuration in our preliminary study. GSL-1'sy was purified from the bacterial cells with the same procedure as Naka et al. The 1H-NMR analysis of GSL-1'sy revealed that the coupling constant of the anomeric proton of GalA was 3.0 Hz, indicating that GalA in GSL-1'sy is alpha-anomer, the configuration active for the stimulation of natural killer T cells.

Glycosphingolipids↗
PubMed2006

Function and practice of public health nursing in Japan: a trial to develop the Japanese Purpose-Focused Public Health Nursing Model.

AIM: To clarify the significance of public health nurses' practice, we introduced the activities of Japanese public health nurses and tried to develop a model based on the purpose of their work. BACKGROUND: Despite international efforts toward clarifying public health nurses' practice, earlier models based on the purpose of their activities were underdeveloped. METHOD: Japanese terms describing public health nurses' activities were gathered from the literature, nine researchers analysed and brainstormed the activities to develop a model. Seven municipality public health nurses and three researchers in both Japan and the USA validated the model. RESULTS: The model includes three categories: creating the basis for support; working with individuals, families to enhance their health; and enhancing the health of individuals, families, groups, communities/regions by working with the community. CONCLUSION: The Japanese Purpose-Focused Public Health Nursing Model was based on the purpose of public health nurses' practice which was considered significant for assisting public health nurses to explain the meaning of their work.

Attitude of Health Personnel↗
PubMed2006

Prepulse inhibition of acoustic startle response in mild cognitive impairment and mild dementia of Alzheimer type.

Amnestic mild cognitive impairment (MCI) describes the condition of memory-impaired individuals who otherwise function well and do not meet the clinical criteria for dementia. Such individuals are considered to represent a transitional stage between normal aging and dementia of Alzheimer type (DAT). Neurobiologic changes in amnestic MCI, and their significance for psychophysiologic function, are poorly understood. In this study, the authors compared acoustic prepulse inhibition (PPI) between subjects with amnestic MCI and mild DAT to characterize sensorimotor gating. The acoustic startle reflex, which the authors measured using an accelerometer and electromyogram, involves whole-body movement and eye blink in response to a sudden loud noise (115 dB). PPI is inhibition of this reflex by a softer noise (prepulse; 85 dB) preceding the startle stimulus by 30 ms. PPI was examined in 30 controls, 20 subjects with amnestic MCI, and 20 subjects with mild DAT. Neither amnestic MCI nor mild DAT affected startle movement amplitude. Subjects with amnestic MCI showed significantly enhanced PPI (gating facilitation), while subjects with mild DAT exhibited significantly less PPI than controls (gating deficit). This pattern of PPI changes suggests that neuropathologic changes in the limbic cortex, mainly the entorhinal cortex, at the earliest stage of DAT might be responsible for PPI abnormalities via disturbed regulation of the limbic cortico-striato-pallido-pontine circuitry. Startle PPI changes could be used as a biologic marker for amnestic MCI and mild DAT.

Acoustic Stimulation↗
PubMed2006

Increased number of subcortical hyperintensities on MRI in children and adolescents with Tourette's syndrome, obsessive-compulsive disorder, and attention deficit hyperactivity disorder.

OBJECTIVE: To investigate whether cerebral hyperintensities on T2-weighted magnetic resonance images (MRI) are associated with childhood neuropsychiatric disorders. METHOD: The authors compared the frequency of cortical and subcortical cerebral hyperintensities in 100 children and adolescents with Tourette's syndrome, obsessive-compulsive disorder (OCD), or attention deficit hyperactivity disorder (ADHD) and 32 healthy comparison subjects. RESULTS: The frequency of cerebral hyperintensities was significantly higher in subjects with Tourette's syndrome, OCD, or ADHD than in healthy comparison subjects; each diagnostic group seemed to contribute to this effect. Among the patient groups, the likelihood of detecting cerebral hyperintensities in the subcortex (primarily the basal ganglia and thalamus) was significantly greater than in the cortex. CONCLUSIONS: A childhood diagnosis of Tourette's syndrome, OCD, or ADHD significantly increased the likelihood of detecting cerebral hyperintensities, particularly in the subcortex, supporting the notion that subcortical injury may play a role in the pathophysiology of these conditions.

Adolescent↗
PubMed2005

Phosphorylation of threonine-265 in Zipper-interacting protein kinase plays an important role in its activity and is induced by IL-6 family cytokines.

Zipper-interacting protein kinase (ZIPK) is a widely expressed serine/threonine kinase that has been implicated in cell death and transcriptional regulation, but its mechanism of regulation remains unknown. Here, we identified threonine-265 (Thr265) in ZIPK as a major autophosphorylation site. Mutational analyses revealed that autophosphorylation of Thr265 were essential for its full catalytic activity toward an exogenous substrate as well as for cell death induction. Furthermore, leukemia inhibitory factor (LIF) stimulated Thr265 phosphorylation of ZIPK, thereby leading to phosphorylation and activation of signal transducer and activator of transcription (STAT3). Taken together, our findings demonstrate that ZIPK is positively regulated through Thr265 phosphorylation and that this phosphorylation is essential for its function.

Animals↗
PubMed2005

Nuclear retention of STAT3 through the coiled-coil domain regulates its activity.

Signal transducer and activator of transcription 3 (STAT3), which mediates biological actions in many physiological processes, is activated by cytokines and growth factors via specific tyrosine phosphorylation, dimerization, and nuclear translocation. However, the mechanism involved in its nuclear translocation remains unclear. A previous study demonstrated that STAT3 with Arg-214/215 mutations in the coiled-coil domain (R214A/R215A; STAT3 RA) failed to undergo nuclear translocation. Here, we re-examined the nature of the STAT3 RA mutant and found that it showed higher and more extensive tyrosine-phosphorylation as well as much higher STAT3 transcriptional activity in response to stimuli. Furthermore, STAT3 RA showed nuclear translocation and faster nuclear export than wild-type STAT3 after stimulation. Moreover, nuclear retention of STAT3 RA by a chromosomal region maintenance 1 (CRM1) inhibitor, leptomycin B, decreased the enhanced STAT3 activation by stimuli. These data demonstrate that Arg-214/215 are involved in CRM1-mediated STAT3 nuclear export and the regulation of STAT3 activity.

Active Transport, Cell Nucleus↗
PubMed2005

Physical and functional interactions between STAT3 and ZIP kinase.

Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor that can be activated by cytokines and growth factors. It plays important roles in cell growth, apoptosis and cell transformation, and is constitutively active in a variety of tumor cells. In this study, we provide evidence that zipper-interacting protein kinase (ZIPK) interacts physically with STAT3. ZIPK specifically interacted with STAT3, and did not bind to STAT1, STAT4, STAT5a, STAT5b or STAT6. ZIPK phosphorylated STAT3 on serine 727 (Ser727) and enhanced STAT3 transcriptional activity. Small interfering RNA-mediated reduction of ZIPK expression decreased leukemia inhibitory factor (LIF)- and IL-6-induced STAT3-dependent transcription. Furthermore, LIF- and IL-6-mediated STAT3 activation stimulated ZIPK activity. Taken together, our data suggest that ZIPK interacts with STAT3 within the nucleus to regulate the transcriptional activity of STAT3 via phosphorylation of Ser727.

Apoptosis Regulatory Proteins↗
PubMed2005

Synthesis and pharmacological evaluation of benzamide derivatives as selective 5-HT(4) receptor agonists.

It is thought that selective 5-HT(4) receptor agonists-such as 4-amino-5-chloro-2-methoxy-N-[1-(6-oxo-6-phenylhexyl)piperidin-4ylmethyl]benzamide (2)-have the ability to enhance both upper and lower gastrointestinal motility without any significant adverse effects. Modification of 2 was performed. Variation of the piperidin-4ylmethyl moiety of 2 led to a decrease in the binding affinity for the 5-HT(4) receptor. Following conversion of the carbonyl group on the benzoyl part to a hydroxyl or sulfoxide group, the binding affinity for the 5-HT(4) receptor was retained although the effect on defecation was reduced. Many of the 4-amino-5-chloro-2-methoxy-N-(piperidin-4ylmethyl)benzamides that had a ether or sulfide moiety in the side-chain part at the 1-position of the piperidine exhibited high affinity for the 5-HT(4) receptor. Among these, phenylthio 41c and benzylthio derivative 44 were selective 5-HT(4) receptor agonists, and had a similar effect on defecation to compound 2.

Animals↗
PubMed2005

Asymmetric synthesis and biological evaluation of the enantiomeric isomers of the immunosuppressive FTY720-phosphate.

A practical asymmetric synthesis of both enantiomers of the immunosuppressive FTY720-phosphate (2) was accomplished, and the enantiomers were pharmacologically evaluated. Several lipases showed considerable activity and enantioselectivity for O-acylation of N-acetyl FTY720 (3) or N-benzyloxycarbonyl FTY720 (7) in combination with vinyl acetate or benzyl vinyl carbonate as the acyl donors. The synthesis using the lipase-catalyzed acylation as the key step produced the enantiomerically pure (>99.5% ee) enantiomers of 2 in multigram quantities. (S)-Isomer of 2 had more potent binding affinities to S1P(1,3,4,5) and inhibitory activity on lymphocyte migration toward S1P than (R)-2, suggesting that (S)-isomer of 2 is responsible for the immunosuppressive activity after administration of 1. Severe bradycardia was observed in anesthetized rats when (S)-2 was administered intravenously, while (R)-2 had no clear effect on heart rate up to 0.3 mg/kg.

Animals↗