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T Okubo

Publications and source records attributed to T Okubo.

At least 55 records · Page 3Linked to original sources

[Cytomegalovirus antigenemia assay as a useful tool for early diagnosis and therapy for cytomegalovirus infections in three cases with collagen diseases].

We report here three cases of collagen diseases with cytomegalovirus infections. (1) A 21-year-old female, who had been diagnosed as systemic lupus erythematosus, lupus nephritis and lupus peritonitis, had fever. Cytomegalovirus antigenemia (CMV-Ag) assay was 10/8 positive. (2) A 33-year-old female, who had been diagnosed as Wegener glanulomatosis, had fever and liver dysfunction. CMV-Ag assay was 933/896 positive. (3) A 64-year-old female, who had been diagnosed as microscopic polyangitis, had fever, liver dysfunction and pneumonia. CMV-Ag assay was 6/2 positive. They were considered to be complicated with CMV infections. We could make early diagnoses of CMV infection by using CMV-Ag assay and treat them with anti-CMV therapy effectively.

Adult↗

Changes in the apparent diffusion coefficient of water and T2 relaxation time in gerbil hippocampus after mild ischemia.

Selective neuronal death of the hippocampal CA1 area after mild ischemia is known as delayed neuronal death (DND). Progression of DND was evaluated using 7T MRI in gerbils. In the CA1, the T2 relaxation time started to increase on day 3 and was significantly higher on day 4 than that of the control gerbils. However, the apparent diffusion coefficient of water (ADC) was significantly lower on day 1 than in the control and continued to decline up to day 4. Changes in T2 coincided with loss of MAP2 immunoreactivity, while the ADC decrease preceded these changes. After 1 month, the ADC had returned to within the normal range, while T2 had decreased to below the control level. These results suggest that MRI is useful for monitoring DND.

Animals↗

Kinetic Analyses of Colloidal Crystallization in a Wide Range of Sphere Concentrations as Studied by Reflection Spectroscopy.

The nucleation and growth rates in the colloidal crystallization of silica spheres (103 nm in diameter) from 0.006 to 0.04 in volume fraction (straight phi) have been measured by reflection spectroscopy. Kinetics of the crystallization has been discussed in a wide sphere concentration range (from straight phi=0.0005 to straight phi=0.04) using the data of this work and the previous work (110 nm in diameter) in exhaustively deionized aqueous suspensions. The induction period for nucleation decreases sharply as the sphere concentration increases. The nucleation rate increases substantially from 1x10(-3) to 1x10(7) mm(-3) s(-1) when straight phi increases from 0.0005 to 0.04. The crystal growth process consists of the fast growing step toward metastable crystals (rate v(1)) and slow growth accompanied with the reorientation toward stable ones (rate v(2)). The v(1) values increase first from 5 to 20 µm/s and then turn back to 5 µm/s after passing a maximum. v(1) above straight phi=0.01 remains at 5 µm/s and is insensitive to sphere concentration. The slow step is observed in the high-sphere concentrations only, and v(2) decreases sharply from 3 µm/s to 0.7 nm/s when sphere concentration increases from 0.004 to 0.04 in volume fraction. Importance of the electrostatic intersphere repulsion by overlapping of the electrical double layers and the cooperative and synchronized fluctuation of colloidal spheres in the crystallization processes are supported strongly. Copyright 2000 Academic Press.

Journal Article↗

LiV2O4 spinel as a heavy-mass fermi liquid: anomalous transport and role of geometrical frustration

Transport and specific heat measurements on hydrothermally grown single crystals reveal the formation of a heavy-mass Fermi liquid in the LiV2O4 spinel, below a coherence temperature of T* = 20-30 K. A few observations which illustrate the uniqueness of this spinel are discussed in connection with the origin of the heavy mass, such as the anomalous absence of resistivity saturation above T* and the close proximity to a spin glass phase where the influence of the magnetic frustration is evident.

Journal Article↗

Sphingosine-1-phosphate and lysophosphatidic acid trigger invasion of primitive hematopoietic cells into stromal cell layers.

A new primitive hematopoietic cell line (THS119), exhibiting Lin(-)/Sca-1(+)/c-Kit(+) a surface phenotype, grew and survived underneath stromal cells (TBR59). The ability of the THS119 cells to invade these stromal cell layers was dependent on the inclusion of serum in the culture medium. This was apparently due to a requirement for lipids contained in serum. Their invasion of the stromal cell layers in serum-free cultures could be triggered by addition of sphingosine-1-phosphate (S1P) or lysophosphatidic acid (LPA) and was dependent on both Rho- and Ras-signaling pathways. Between the 2 possible receptors of S1P and LPA, edg-1 and edg-2, expression of edg-2 only was found to be correlated with immaturity and/or invasive activity of the primitive hematopoietic cells. These results suggest the importance of specific lipids and their specific receptors on the invasive activity of primitive hematopoietic cells in the hematopoietic microenvironment.

Animals↗

Novel polymorphisms of the human cholecystokinin A receptor gene: an association analysis with schizophrenia.

The cholecystokinin A receptor (CCK-AR) modulates CCK-stimulated dopamine release in the posterior nucleus accumbens, and its gene is mapped to 4p15.2-15.1 with the dopamine receptor 5 (DR5) gene. We speculated that alterations in the CCK-AR lead to an increase in dopamine release, which may in turn constitute a predisposition in schizophrenia. We investigated genetic variations in the promoter region and the coding region of the CCK-AR gene. An association analysis was conducted between 83 unrelated schizophrenic patients and 80 healthy controls. Novel polymorphisms (201A-->G, 246G-->A in the promoter region, 1260T-->A, 1266T-->C in intron 1 within the 3' mRNA splice acceptor site consensus sequence, and Leu306Leu in exon 5) were found in addition to the variants (608G-->A in intron 1, 3849C-->T [Ile296Ile] in exon 5) reported previously. Significant differences were found in the allele frequencies of the 201A-->G nucleotide substitution in the promoter region between patients and controls (P = 0.0181, odds ratio: 1.972, after Bonferroni correction: P = 0.0543). These differences were also found between the patients with paranoid type and controls (P = 0.0274, odds ratio = 3.667, after Bonferroni correction: P = 0.0822). Our analyses suggest that the 201A allele frequency was higher in the schizophrenic group, especially in the paranoid type, than in the control group at a rate that was not quite significant after Bonferroni correction. Am J. Med Genet. (Neuropsychiatr. Genet.) 96:141-145, 2000.

Adult↗

Long-term remission in an elderly patient with mantle cell leukemia treated with low-dose cyclophosphamide.

We present an elderly patient with mantle cell leukemia who was successfully treated with low-dose cyclophosphamide (CY). A 76-year-old female was diagnosed as mantle cell leukemia based on abnormal lymphocytosis and splenomegaly without lymphadenopathy. She was orally treated with 50 mg of CY daily and had continuous remission over 4 years. Rearrangements of BCL1 and immunoglobulin heavy chain genes in the peripheral blood lymphocytes were detected at diagnosis, but not 1 or 4 years later. Further studies are required to confirm the role of low-dose CY therapy for patients with mantle cell leukemia and lymphoma.

Aged↗

Dendritic cells are associated with augmentation of antigen sensitization by influenza A virus infection in mice.

To study the mechanisms responsible for enhanced sensitization of inhaled antigen in respiratory viral infections, we examined the contribution of dendritic cells (DC) and T lymphocytes to the development of inhalation sensitization during infection with influenza A virus in mice. BALB/c mice were sensitized by inhalation of ovalbumin (OA) from 3 to 7 days after the inoculation with influenza A virus, and were challenged with OA 3 weeks later. Airway responsiveness and serum OA-specific IgE were increased. The numbers of eosinophils and CD4(+) and CD8(+) T cells in bronchoalveolar lavage fluid were also increased. These changes were not observed in animals only sensitized with OA or only inoculated with the virus. In animals only inoculated with the virus, DC were immunohistochemically detected on the bronchial epithelium on days 2-5. With OA inhalation after virus inoculation, DC with high expression of MHC class II were retained for 5 weeks. These results show that influenza virus infection induces the migration of DC to the bronchial epithelium, and that simultaneous inhalation of antigen causes the loading of antigen-peptide / class II molecule complex on DC. Thus, the migration of DC in viral infection may play some role in the augmentation of antigen sensitization.

Animals↗

IL-12-encoding plasmid has a beneficial effect on spontaneous autoimmune disease in MRL/MP-lpr/lpr mice.

Systemic lupus erythematosus (SLE) is characterized by immune abnormalities explained by the overproduction of Th(2)cytokines such as autoantibody production and polyclonal B cell activation. We examined the effect of administering a DNA plasmid encoding IL-12 on the lupus-like disease of MRL/MP-lpr/lpr (MRL/lpr) mice. Treatments were delivered intramuscularly every 4 weeks, starting at 4 weeks of age. This intervention significantly inhibited the accumulation of CD4(-)CD8(-)T cells, and reduced lymphadenopathy and splenomegaly. A significant decrease in serum IgG anti-DNA autoantibody titers was observed, and plasmid IL-12 therapy was also associated with a reduction in the proteinuria and glomerulonephritis characteristic of this disease. Serum IFN-gamma level was increased by inoculating IL-12 encoding plasmid, suggesting that the cytokine balance was skewed towards Th(1). The clinical implications of this suppression of autoimmune disease are also discussed.

Animals↗

Cardiac metastatic liposarcoma.

Metastatic cardiac liposarcoma is extremely rare, with only 2 cases previously reported, to our knowledge; of those, only 5 involved surgical resection of right ventricular liposarcoma. The first such case in Japan involved a 61-year-old woman with metastatic liposarcoma of the right ventricle. Despite emergency resection, the patient died of severe congestive heart failure 6 days after operation. Her history included surgery for liposarcoma in the right knee 11 years previously, although it is very difficult to predict that metastasis would proceed thereafter to the cardiac cavity. This rare case suggests, however, that follow-up including examination for cardiac lesions is necessary long after resection of the primary lesion.

Female↗

Novel polymorphisms of the AP-2 gene (6p24): analysis of association with schizophrenia.

The transcription factor activator protein 2 (AP-2) gene is a possible candidate gene for schizophrenia, since it maps near D6S470, a marker on chromosome 6p24 that provided evidence of linkage to schizophrenia. In the present study we analyzed the promoter region and the whole coding region of the human AP-2 gene in order to identify genetic variations that may lead to the modification of AP-2 expression or the alteration of protein function, contributing to schizophrenia or particular schizophrenic phenotypes. Genomic DNA was isolated from the whole blood samples of 87 unrelated schizophrenics and 100 healthy controls. Polymerase chain reaction (PCR) was performed, using 15 primer sets that spanned the promoter region and the whole coding region, and amplified products were screened by single-strand conformational polymorphism (SSCP) analysis. Aberrant SSCP patterns were analyzed by direct sequencing. Three novel polymorphisms were found in the promoter region; two relatively common (-90G-->C, -803G-->T) and one rare (-1769G-->A). Polymorphic status at both loci suggested strong linkage disequilibrium between the -90G and -803G alleles, and between the -90C and -803T alleles. Although no significant differences in genotypic and allelic frequencies at the -90 and -803 loci were found between patients and controls, significant differences in the distribution of genotypes at the -90 (P = 0.008) and -803 (P = 0.037) loci were observed in patients with an episodic course compared with controls. However, the difference for the -803 locus was not significant after Bonferroni correction for multiple comparisons. Our data provided no direct evidence of an association between schizophrenia and the polymorphisms of the AP-2 gene, although the positive result at the -90 locus in schizophrenics with an episodic course is potentially interesting.

Adult↗

Self-renewal and differentiation of a novel bipotent myeloid progenitor clone in the stroma-dependent culture.

To understand regulation of myeloid development, it is necessary to obtain the myeloid progenitor cell lines with self-renewal and differentiation capacities. Because prolonged hematopoiesis occurs with the production of myeloid cells at all stages of differentiation in the Dexter-type long-term bone marrow cultures, we tried to obtain stroma-dependent myeloid progenitor cells starting from the long-term bone marrow culture. Murine cobblestone areas generated in long-term bone marrow cultures were serially passaged every 10 days. After 4 months, the resultant hematopoietic cells, designated as DFC, were passaged on a monolayer of established spleen stromal cell line, MSS62. After 10-12 passages of DFC cells on MSS62, several clones were obtained by colony formation on MSS62 cell layer. Among these clones, DFC-a cells could be maintained for a long period by coculturing with the established stromal cell line, MSS62.DFC-a cells proliferated by forming cobblestones and contained blast cells, granulocytes, and macrophages. Cell sorting and coculture experiments indicated that the blast type cells exhibiting c-Kit(+) Gr-1(-) Mac-1(-), stroma-dependently self-renewed, and spontaneously differentiated toward granulocytes (c-Kit(+) Gr-1(+) Mac-1(+)) and macrophages (c-Kit(low/+) Gr-1(-) Mac-1(high)). Although most of DFC-a cells expressed c-Kit, SCF-c-Kit interaction was not always necessary for their growth. In the presence of stromal cells, growth and differentiation of DFC-a cells were stimulated by GM-CSF or IL-3. Without stromal cells, DFC-a was transiently expanded by GM-CSF or IL-3 but could not be maintained constantly by these cytokines. The present study demonstrated that DFC-a is a novel bipotent myeloid progenitor cell clone as a simple model system of stroma-dependent myeloid development. It may reflect distinct properties for the earliest myeloid progenitor cells in vivo. It is of interest to know what signals are provided by MSS62 stromal cells to maintain the myeloid progenitor cells.

Animals↗

Design, synthesis and structure-affinity relationships of 4-methylidenepiperidine and 4-aryl-1,2,3,6-tetrahydropyridine derivatives as corticotropin-releasing factor1 receptor antagonists.

Recently, various non-peptide corticotropin-releasing factor1 (CRF1) receptor antagonists have been reported. Structure-affinity relationships (SARs) of non-peptide CRF antagonists suggest that such antagonists can be constructed of three units: a hydrophobic unit (Up-Area), a proton accepting unit (Central-Area), and an aromatic unit (Down-Area). Our interest focused on the Up-Area in deriving the novel methylidenepiperidine derivatives 8-10 and 4-aryl-1,2,3,6-tetrahydropyridine derivatives 11-13 as non-peptide CRF1 receptor antagonists. Compounds 8a and 11a had moderate affinity for CRF1 receptor, but compounds 9, 10, 12 and 13 did not exhibit CRF1 receptor affinity. Modification of derivatives 11 afforded compounds 11i (CRA1001) and 11x (CRA1000), which had high affinity and selectivity for CRF1 receptors with potent anxiolytic-like and antidepressant-like properties in some experimental animal models. These findings suggest that the hydrophonic unit (Up-Area) may be useful for design of CRF1 antagonists. We report here the design, synthesis and SARs of the derivatives 8 and 11 and isosteres 9, 10, 12 and 13.

Animals↗

Catalytic differences between porcine blastocyst and placental aromatase isozymes.

Two isozymes of porcine aromatase, the placental and the blastocyst forms, were expressed in CHO cells using the mammalian cell transfection method. Using an 'in-cell' assay (a 3H-water release method), catalytic parameters of the porcine placental aromatase were found to be very similar to those of the human enzyme; however, the activity of the blastocyst isozyme was found to be one-thirtieth that of the placental isozyme. Product isolation assay (using testosterone as the substrate) revealed that the major steroid products were 17beta-estradiol and 19-nortestosterone. The product ratio of estradiol/19-nortestosterone was found to be 94 : 6 for the porcine placental form, 6 : 94 for the porcine blastocyst form, and 92 : 8 for the human wild-type aromatase. Therefore, the porcine blastocyst aromatase isozyme catalyzes mainly androgen 19-desmethylation rather than aromatization. In addition, inhibition profile analyses on the placental and blastocyst isozymes were performed using three steroidal inhibitors [4-hydroxyandro-stenedione (4-OHA), 7alpha-(4'-amino)phenylthio-1, 4-androstandiene-3,17-dione (7alpha-APTADD), and bridge (2, 19-methyleneoxy) androstene-3,17-dione (MDL 101,003)], and four nonsteroidal inhibitors [aminoglutethimide (AG), CGS 20267, ICI D1033, and vorozole (R83842)]. While the two isozymes of porcine aromatase share 93% amino-acid sequence identity, our results indicate that the two porcine aromatase isozymes have distinct responses to various aromatase inhibitors.

Animals↗

Contrast-enhanced magnetic resonance imaging of the cranial nerves in patients with acoustic schwannoma: correlation with surgical findings.

Eighteen patients with acoustic schwannoma were examined on a 1.5-T magnetic resonance imaging (MRI) unit with precontrast and postcontrast T1-weighted spin-echo sequences. Each abnormality was assessed in terms of the size, location, extensions and signal intensity of the lesions. If a nerve was enhanced and was involved by the tumor around the fundus of the internal auditory canal (IAC), the nerve was interpreted to be the originating nerve. The postcontrast T1-weighted images revealed enhanced masses of the cerebellopontine angle and/or the IAC in all cases. In 11 of the 19 operated patients with shwannomas, the site of tumor origin (or origin nerve) was confirmed by surgery. In 2 of the 11 cases (18%), surgical findings coincided with the T1-weighted image findings. Facial nerve enhancement on the ipsilateral side of the tumor was noted in 10 cases (53%) and the contralateral facial nerve enhancement was demonstrated in 7 (70%). The enhancement of facial nerve associated with acoustic schwannoma was not correlated to the degree of nerve compression by the tumor. These results demonstrate that it was possible, although infrequent, to predict the site of origin of acoustic schwannoma before surgery in some patients. Improvement of the imaging matrix or multiplanar reconstruction techniques with three-dimensional data acquisition may make it possible to overcome the limitations of MRI.

Adult↗