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Biomedical subjects

S Ueno

Publications and source records attributed to S Ueno.

At least 37 records · Page 2Linked to original sources

Magnetic resonance imaging of mean values and anisotropy of electrical conductivity in the human brain.

The conductivity distribution in the human brain is difficult to obtain by conventional impedance tomography methods, in which currents are applied via surface electrodes. In this study, we obtained images of anisotropic conductivity in the human brain using diffusion magnetic resonance imaging (MRI). Diffusion-weighted images of the brain were acquired by a 1.5 T MRI system using an echo planar imaging sequence. Motion-probing gradients (MPGs) were applied with 25 arrayed b-factors up to 5000 s/mm2. The fast and slow diffusion components were estimated by fitting a biexponential attenuation function to the measured signals. The effective conductivities in each direction were calculated from the fast diffusion components. The mean conductivities of the cortex, the corpus callosum, and the internal capsule were 0.10 +/- 0.03 S/m, 0.12 +/- 0.02 S/m, and 0.08 +/- 0.01 S/m, respectively. Tissues with highly anisotropic cellular structures, such as the corpus callosum and the internal capsule, exhibited high anisotropy in conductivity. The anisotropy indices in the cortex, the corpus callosum, and the internal capsule were 0.07 +/- 0.03, 0.60 +/- 0.07, and 0.65 +/- 0.05, respectively.

Anisotropy↗

Diffuse neurodeficits in intravascular lymphomatosis with ADAMTS13 inhibitor.

Inhibitory antibody to von Willebrand factor (vWF)-cleaving protease (ADAMTS13) was detected in a patient with intravascular lymphomatosis. The increased serum level of the antibody paralleled an increase in the expression of uncleaved vWF, which might cause microvascular thrombosis and platelet consumption. Malignant cell proliferations with superimposed thrombosis within the lumina throughout the entire vasculature account for diffuse neurodeficits observed in the patient.

ADAM Proteins↗

Identification and characterization of novel developmentally regulated neural-specific proteins, BRINP family.

Processes of neuronal differentiation involve activation of a set of neuronal specific genes and cessation of cell proliferation in postmitotic neurons. Previous studies revealed that bone morphogenetic protein (BMP) and retinoic acid (RA) play important roles in the differentiation of peripheral sympathetic neurons such as the synergistic induction of responsiveness to specific neurotrophic factors. In the present study, while trying to clarify the mechanism of the BMP/RA-actions, we identified a novel neural-specific protein, BMP/RA-inducible neural-specific protein-1 (BRINP1) which shows no similarity to other known proteins. Subsequently, two homologous proteins, BRINP2 and BRINP3, making up the BRINP family, are identified. Individual BRINP genes have distinct regulatory mechanisms of expression within the nervous system. In rodent brain, BRINP1 is expressed from earlier developmental stage, i.e. E9.5, and widely expressed in various neuronal layers and nuclei of the adult animal, while BRINP2 and BRINP3 were detectable from E11.5 and expressed in rather limited regions in a complementary manner. During the course of perinatal development of sympathetic neurons, BRINP1 is induced from earlier embryonic stage and further increased toward adult stage, while BRINP3 expressed from earlier stage is replaced by BRINP2 expression which increases postnatally in accordance with the action of BMP2 and RA. Furthermore, when expressed in nonneuronal cells, all three BRINP family proteins suppressed the cell cycle progression. Possible physiological functions of BRINP family members in the development of the nervous system are discussed.

Amino Acid Sequence↗

Detection of intracellular macromolecule behavior under strong magnetic fields by linearly polarized light.

Strong static magnetic fields on the order of 10 T have a diamagnetic force on cell components and generate a clear alignment of a smooth muscle cell assembly, parallel to the direction of the magnetic fields within an exposure period of 3 days. This work shows the effects of diamagnetic torque forces on cell component motion. Linearly polarized light was utilized to detect the displacement of intracellular macromolecules. The polarized light passed through a mass of cells in a magnetic field, and transmission of the light increased and reached a plateau 2 h after the beginning of magnetic field exposure at 14 T. However, no distinct change was observed in transmission of the light under zero magnetic field exposure. The change in polarized light intensity through the lamellar cell assembly under magnetic fields corresponds to behavioral changes in cell components. It was speculated that intracellular macromolecules rotated and showed a displacement due to diamagnetic torque forces during 2-3 h of magnetic field exposure at 14 T.

Animals↗

Frequency of spinocerebellar ataxia mutations in the Kinki district of Japan.

OBJECTIVES: To determine the frequencies of spinocerebellar ataxias (SCAs) in the Kinki district, the western part of the main island of Japan. MATERIAL AND METHODS: One hundred and forty-three families with dominantly inherited ataxia and 220 patients with apparently sporadic cerebellar ataxia were examined for the SCA1, SCA2, SCA3/Machado-Joseph disease (MJD), SCA6, SCA7, SCA8, SCA12 and dentatorubral-pallidoluysian atrophy (DRPLA) mutations. RESULTS: Among the dominant families, SCA1 accounted for 3%, SCA2 for 4%, SCA3/MJD for 24%, SCA6 for 31% and DRPLA for 12%. Neither SCA7 nor SCA12 mutations were detected. Among the apparently sporadic patients, 15% were found to have expanded triplet repeats. Of these, the SCA6 mutation was most frequently detected. CONCLUSION: SCA6 is the most common SCA in the Kinki district of Japan. Comparison of our results with those from other regions of Japan and different countries shows geographic and ethnic variation in the frequency of SCAs.

Adult↗

DNA microarray analysis of hematopoietic stem cell-like fractions from individuals with the M2 subtype of acute myeloid leukemia.

Acute myeloid leukemia (AML) may develop de novo or secondarily to myelodysplastic syndrome (MDS). Although the clinical outcome of MDS-related AML is worse than that of de novo AML, it is not easy to differentiate between these two clinical courses without a record of prior MDS. Large-scale profiling of gene expression by DNA microarray analysis is a promising approach with which to identify molecular markers specific to de novo or MDS-related AML. This approach has now been adopted with AC133-positive hematopoietic stem cell-like fractions purified from 10 individuals, each with either de novo or MDS-related AML of the M2 subtype. Sets of genes whose activity was associated with either disease course were identified. Furthermore, on the basis of the expression profiles of these genes, it was possible to predict correctly the clinical diagnosis for 17 (85%) of the 20 cases in a cross-validation trial. Similarly, different sets of genes were identified whose expression level was associated with clinical outcome after induction chemotherapy. These data suggest that, at least in terms of gene expression profiles, de novo AML and MDS-related AML are distinct clinical entities.

Antigens, CD↗

Eosinophilic major basic protein and interleukin-5 in eosinophilic myositis.

To determine whether eosinophils play a critical role in muscle fiber damage in patients with eosinophilic myositis (EM). We investigated expression of eosinophilic major basic protein (MBP) and interleukin (IL)-5 at the protein and mRNA levels in muscle biopsies from three patients with idiopathic EM. MBP deposits were found on the surface of eosinophils and muscle fibers surrounded by the eosinophils. Reverse transcriptase-polymerase chain reaction analysis showed increased IL-5 expression in EM muscle but not in control muscle. These results suggest that IL-5 induces local accumulation of eosinophils and their release of MBP. The secreted proteins adhere to the muscle fiber membrane, resulting in muscle damage.

Adult↗

Microbial community changes during organic solid waste treatment analyzed by double gradient-denaturing gradient gel electrophoresis and fluorescence in situ hybridization.

The bacterial community present during semicontinuous treatment of organic solid waste under alkaline and high-temperature conditions was studied. PCR-amplified 16S rDNA fragments were analyzed by double gradient-denaturing gradient gel electrophoresis (DGGE). The band pattern was stable during the steady state of the treatment phase, and the major bands resulting from individual treatments had the same DNA sequence with good reproducibility. No sequence in the DNA database of isolated bacteria showed close similarity to this sequence, the closest relative being Bacillus licheniformis with less than 97% similarity. The conditions for fluorescence in situ hybridization (FISH) were determined without the need to obtain extracts of the bacterial cells. An oligonucleotide probe was designed to detect the microorganisms found in the DGGE analysis. FISH analysis showed that the bacterium corresponding to the major bands accounted for 30% of the total eubacterial cell count at the steady state. These results indicate that this bacterium is a key microorganism in the biodegradation process.

Bacteria↗

Size-class differences in genetic structure and individual distribution of Camellia japonica L. in a Japanese old-growth evergreen forest.

Size-class differences in genetic structure and individual spatial distribution were investigated for Camellia japonica within a 1-ha plot in a Japanese old-growth evergreen forest using microsatellite markers. Three size-classes were considered containing plants that were: 30-32.5 cm tall, 103.8 cm-200 cm tall and those that had a diameter at breast height > or =5 cm, designated JV1, JV2, and ADL, respectively. Each size-class contained 174 individuals. Morisita's index of dispersion indicated clumping of individuals was present within all size-classes, with JV2 displaying the highest level. The clumped distribution of JV1 individuals may be a result of limited seed dispersal, while that of JV2 may be attributed to heterogenieties of favourable microsites, such as canopy gaps. There were no significant differences in allele frequencies among size-classes. There were, however, some differences in spatial genetic structure among them. Moran's I spatial autocorrelation analysis revealed clear spatial genetic structure in class JV1 probably due to limited seed dispersal. In class JV2, genetic structure was not observed. Overlapping seed shadows, probably in canopy gaps, may lead to blurred genetic structure in JV2.

Camellia↗

Characterization of stage progression in chronic myeloid leukemia by DNA microarray with purified hematopoietic stem cells.

Chronic myeloid leukemia (CML) is characterized by the clonal expansion of hematopoietic stem cells (HSCs). Without effective treatment, individuals in the indolent, chronic phase (CP) of CML undergo blast crisis (BC), the prognosis for which is poor. It is therefore important to clarify the mechanism underlying stage progression in CML. DNA microarray is a versatile tool for such a purpose. However, simple comparison of bone marrow mononuclear cells from individuals at different disease stages is likely to result in the identification of pseudo-positive genes whose change in expression only reflects the different proportions of leukemic blasts in bone marrow. We have therefore compared with DNA microarray the expression profiles of 3456 genes in the purified HSC-like fractions that had been isolated from 13 CML patients and healthy volunteers. Interestingly, expression of the gene for PIASy, a potential inhibitor of STAT (signal transducer and activator of transcription) proteins, was down-regulated in association with stage progression in CML. Furthermore, forced expression of PIASy has induced apoptosis in a CML cell line. These data suggest that microarray analysis with background-matched samples is an efficient approach to identify molecular events underlying the stage progression in CML.

AC133 Antigen↗

Brain lateralization for mismatch response to across- and within-category change of vowels.

Differences in hemispheric predominance between across- and within-category change perception of vowels were assessed using a whole-head magnetoencephalography. The magnetic mismatch responses (MMNm) to pure-tone and vowel within-category changes were significantly predominant in the right hemisphere; on the other hand, vowel across-category MMNm did not differ in power between hemispheres. The results suggest that both hemispheres are symmetrically activated in the preattentive across-category change perception of vowels, while the within-category change of a vowel is analyzed as the change in physical features of the stimuli, thus predominantly activating the right hemisphere. Thus, the relative contribution of the left auditory cortex in the preattentive speech processing may occur only at the level of perception of the vowel across-category change.

Acoustic Stimulation↗

Sak serine-threonine kinase acts as an effector of Tec tyrosine kinase.

The murine sak gene encodes a putative serine-threonine kinase which is homologous to the members of the Plk/Polo family. Although Sak protein is presumed to be involved in cell growth mechanism, efforts have failed to demonstrate its kinase activity. Little has been, therefore, elucidated how Sak is regulated and how Sak contributes to cell proliferation. Tec is a cytoplasmic protein-tyrosine kinase (PTK) which becomes activated by the stimulation of cytokine receptors, lymphocyte surface antigens, heterotrimeric G protein-linked receptors, and integrins. To clarify the in vivo function of Tec, we have tried to isolate the second messengers of Tec by using the yeast two-hybrid screening. One of such Tec-binding proteins turned out to be Sak. In human kidney 293 cells, Sak became tyrosine-phosphorylated by Tec, and the serine-threonine kinase activity of Sak was detected only under the presence of Tec, suggesting Sak to be an effector molecule of Tec. In addition, Tec activity efficiently protects Sak from the "PEST" sequence-dependent proteolysis. Internal deletion of the PEST sequences led to the stabilization of Sak proteins, and expression of these mutants acted suppressive to cell growth. Our data collectively supports a novel role of Sak acting in the PTK-mediated signaling pathway.

Amino Acid Sequence↗

Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cell fraction.

Myelodysplastic syndrome (MDS) is a slowly progressing hematologic malignancy associated with a poor outcome. Despite the relatively high incidence of MDS in the elderly, differentiation of MDS from de novo acute myeloid leukemia (AML) still remains problematic. Identification of genes expressed in an MDS-specific manner would allow the molecular diagnosis of MDS. Toward this goal, AC133 surface marker-positive hematopoietic stem cell (HSC)-like fractions have been collected from a variety of leukemias in a large-scale and long-term genomics project, referred to as "Blast Bank," and transcriptome of these purified blasts from the patients with MDS were then compared with those from AML through the use of oligonucleotide microarrays. A number of genes were shown to be expressed in a disease-specific manner either to MDS or AML. Among the former found was the gene encoding the protein Delta-like (Dlk) that is distantly related to the Delta-Notch family of signaling proteins. Because overexpression of Dlk may play a role in the pathogenesis of MDS, the disease specificity of Dlk expression was tested by a quantitative "real-time" polymerase chain reaction analysis. Examination of the Blast Bank samples from 22 patients with MDS, 31 with AML, and 8 with chronic myeloid leukemia confirmed the highly selective expression of the Dlk gene in the individuals with MDS. Dlk could be the first candidate molecule to differentiate MDS from AML. The proposal is made that microarray analysis with the Blast Bank samples is an efficient approach to extract transcriptome data of clinical relevance for a wide range of hematologic disorders.

DNA↗

Elicitation of N400m in sentence comprehension due to lexical prosody incongruity.

The role of lexical prosody in the semantic integration of spoken sentences consisting of a quiz stem and an answer word was investigated analyzing the event-related magnetic response, N400m. Three conditions regarding the relations between the quiz and the answer word were prepared: pitch-accent violation, phonemic violation and no violation. Both the pitch-accent and phonemic violations elicited significant N400m without any significant differences in the peak latency and magnitude of the equivalent current dipoles, suggesting that the role of pitch-accent in semantic integration is equivalent to that of phonemes. However, the rate of violation detection and the successful N400m source estimation were lower for the pitch-accent violation than for the phonemic violation, suggesting differential neural processes for the phonemic and prosodic cues.

Adult↗

Allosteric modulation in spontaneously active mutant gamma-aminobutyric acidA receptors.

Tryptophan substitutions were made in the second transmembrane domain of the gamma-aminobutyric acid(A) (GABAA) receptor alpha and beta subunits and the resulting mutant receptors, containing alpha2(S270W) and/or beta1 (S265W), were expressed in Xenopus oocytes. Mutation of either or both subunits resulted in receptors that exhibited enhanced sensitivity to agonist and were spontaneously active in the absence of GABA. The spontaneous activity was blocked by picrotoxin or bicuculline. The enhancement of GABA-induced currents by pentobarbital, by the neurosteroid 5alpha-pregnan-3alpha-ol-20-one, and by the benzodiazepine flunitrazepam was dramatically reduced in the mutant receptors. These results are consistent with the idea that a mutation that promotes gating behavior in a ligand-gated ion channel will also show reduced effects of all positive allosteric modulators in a generalized manner, even when these modulators act at distinct sites on the receptor.

Allosteric Regulation↗

Detection of dichromate (VI)-induced DNA strand breaks and formation of paramagnetic chromium in multiple mouse organs.

DNA single-strand breaks (and/or alkali-labile sites) induced by Cr(VI) were evaluated with the alkaline single cell gel electrophoresis (SCG) (Comet) assay in five organs (liver, kidney, spleen, lung, and brain) of male mice dosed with K(2)Cr(2)O(7) (20 mg Cr/kg) by a single ip injection in vivo, and the formation of paramagnetic Cr(V) in these organs was investigated by electron spin resonance (ESR) spectrometry. Furthermore, the in vivo effects of deferoxamine (DFO), an iron chelator, and dimethylthiourea (DMTU), a hydroxyl radical scavenger, on the formation of Cr(V) and DNA strand breaks induced by the metal in the liver and kidney were examined. SCG assay detected DNA strand breaks were detected in the liver and kidney at 15 min and showed that they were being repaired at 3 h after Cr(VI) injection. The ESR spectra of paramagnetic Cr(V) were also observed in the liver and kidney for 15 min to 24 h after Cr(VI) injection. In contrast, there were no significant levels of DNA strand breaks and Cr(V) in the spleen, lung, or brain. The pretreatment of mice with DFO reduced the formation of Cr(VI)-induced DNA strand breaks and Cr(V) complexes as well as the total contents of Cr in the liver and kidney at 15 min after the metal injection. In the case of the pretreatment with DMTU, DNA strand breaks induced by Cr(VI) were suppressed in the liver and kidney at 15 min, without any influence on the levels of Cr(V) complexes and total Cr contents in the organs. The in vitro study showed that DFO decreased the levels of Cr(V)-GSH complexes and Cr(V)-mediated hydroxyl radicals, while DMTU reduced only the levels of Cr(V)-mediated hydroxyl radicals without affecting the formation of Cr(V)-GSH complexes. These results demonstrated that the SCG assay may be useful for detecting DNA strand breaks and/or alkali-labile sites caused by Cr(VI) in vivo. The results also indicated that the in vivo formation of hydroxyl radicals during the reduction of Cr(VI) may play an important role in the induction of the DNA strand breaks caused by this metal and implied that the levels of Cr(V) inside the cells may not always be related to the induction of DNA strand breaks.

Animals↗