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Tomoyuki Okada

Publications and source records attributed to Tomoyuki Okada.

17 recordsLinked to original sources

Posttranscriptional regulation by the upstream open reading frame of the phosphoethanolamine N-methyltransferase gene.

Phosphoethanolamine N-methyltransferase (PEAMT) is involved in choline biosynthesis in plants. The 5' untranslated region (UTR) of several PEAMT genes was found to contain an upstream open reading frame (uORF). We generated transgenic Arabidopsis calli that expressed a chimeric gene constructed by fusing the 5' UTR of the Arabidopsis PEAMT gene (AtNMT1) upstream of the beta-glucuronidase gene. The AtNMT1 uORF was found to be involved in declining levels of the chimeric gene mRNA and repression of downstream beta-glucuronidase gene translation in the calli when the cells were treated with choline. Further, we discuss the role of the uORF.

5' Untranslated Regions↗

Sevelamer hydrochloride and calcium bicarbonate reduce serum fibroblast growth factor 23 levels in dialysis patients.

Fibroblast growth factor 23 (FGF23) is a member of the fibroblast growth factor superfamily which displays a strong phosphaturic action and an inhibition of vitamin D 1-alpha hydroxylase activity. Fourty-six patients undergoing maintenance hemodialysis therapy participated in the study. They were randomly divided into 2 groups, and treated with either 3 g sevelamer hydrochloride+3 g of calcium bicarbonate (CaCO3), or 3 g of CaCO3 alone. Serum FGF23 levels were determined by a sandwich enzyme-linked immunosorbent assay (ELISA) system that detects the intact form of FGF23 molecules. Although the serum inorganic phosphate (Pi) levels were comparable before treatment, the levels were significantly lower in the patients treated with sevelamer hydrochloride+CaCO3 than those with CaCO3 alone after 4 weeks of treatment (P<0.05). Serum FGF23 levels significantly decreased after 4 weeks of the treatment with sevelamer hydrochloride+CaCO3 from the pretreatment levels (P<0.05), while no changes were found in the patients treated with CaCO3 alone. Thus, the use of sevelamer hydrochloride and CaCO3 reduced serum FGF23 levels in dialysis patients presumably through inhibiting phosphate load into the intestine.

Bicarbonates↗

Prospective randomized multicenter trial of sevelamer hydrochloride and calcium carbonate for the treatment of hyperphosphatemia in hemodialysis patients in Japan.

A prospective, randomized open-label trial of sevelamer hydrochloride with or without calcium carbonate (CC) involved 86 hemodialysis patients in Japan. The dosage of CC was fixed at 3.0 g/day for the 12-week study. After the first 4 weeks all subjects were changed from CC to sevelamer 3.0 g/day for another 4 weeks, then allocated randomly to three groups for the final 4 weeks: group A, sevelamer 6.0 g/day; group B, sevelamer 3.0 g/day and CC 3.0 g/day; group C, CC 3.0 g/day. The target serum phosphorous concentration (P)=5.5 mg/dL and the corrected calcium concentration (Ca) was 9.0-10.0 mg/dL. Of the 86 patients, 62 finished the study without a change of dosage and their data were analyzed (group A, N=16; group B, N=26; group C, N=20). At week 8 compared with week 4, the concentration of P increased from 5.7+/-1.4 to 6.4+/-1.7 mg/dL in group A, and decreased significantly in groups B and C, and in group B compared with groups A and C; groups A and C had similar concentrations at week 8. The Ca concentration decreased significantly from 9.7+/-1.0 to 9.1+/-0.7 mg/dL after the change to sevelamer. At week 8 Ca was not significantly changed in group A, whereas a significant increase occurred in groups B and C. Side-effects with sevelamer administration occurred in 34 of the 86 patients and 24 dropped out of the study, with a high frequency in group A (13/29; 44.8%). In conclusion, there was an additive effect of sevelamer for the treatment of hyperphosphatemia with CC. The combination therapy was better tolerated and showed higher patient compliance than CC or sevelamer monotherapy.

Analysis of Variance↗

Oxy-peptide nucleic acid with a pyrrolidine ring that is configurationally optimized for hybridization with DNA.

Four stereoisomers of oxy-peptide nucleic acids containing ether linkages in the main chain and conformationally-restricted pyrrolidine rings (pyrrolidine-based oxy-PNA = POPNA) were newly synthesized and investigated for binding to DNA. cis-l-POPNA with 9 adenine bases formed the most stable hybrid with dT(9). The POPNA showed high sequence specificity similar to that of the Nielsen-type PNA and sharper melting behavior in hybridization with DNA than the Nielsen-type PNA.

DNA↗

Abnormalities of the electrogastrogram in globus pharyngeus.

There appear to be multiple indicators for the presence of globus pharyngeus. We have assumed that patients with abnormal gastric motility can be included among those suffering from globus pharyngeus. Gastric motility can be examined non-invasively using the electrogastrogram (EGG). In this study, 32 patients (22 females, 10 males; mean age 55+/-13 years) with symptoms of globus pharyngeus consented to EGG recording. The EGGs of asymptomatic healthy adults (6 females, 10 males; mean age 28+/-5 years) were obtained as controls. No significant statistical difference was found in any of the measurement parameters between the two groups. However, we found that 9.4% of patients with globus pharyngeus exhibited abnormal gastric myoelectrical activity as measured by the EGG. This suggests that a small proportion of patients who complain of globus pharyngeus have abnormal gastric motility.

Adult↗

Heterogeneity of dendritic cells in the mouse liver: identification and characterization of four distinct populations.

Liver dendritic cells (DC) are believed to play important roles in liver immunity, autoimmunity, and in the regulation of hepatic allograft acceptance. However, limited information is available on the phenotypes and functions of DC in the liver. To address this issue, we isolated DC from murine liver using procedures that do not involve collagenase, and characterized the freshly isolated DC population that had not been subjected to in vitro expansion. Thence, based on the expression of CD4, B220, and CD11b, four subsets or groups of hepatic NK1.1(-)CD11c(+) DC were identified with the following phenotypes: B220(+)CD4(+), B220(+)CD4(-), B220(-)CD11b(+), and B220(-)CD11b(-). Each subset was further characterized both phenotypically and functionally. In addition to unique phenotypic expression, each subset displayed different allostimulation capability in mixed lymphocyte reaction assays. All four groups developed DC morphology following in vitro culture with activation agents and synthesized distinct patterns of cytokines in response to different stimuli. Taken together, our results suggest that groups I and II are IFN-alpha-producing plasmacytoid DC, group III cells are myeloid-related DC, while group IV is a heterogeneous population containing both myeloid- and lymphoid-related DC. Our results demonstrate the highly heterogeneous nature of hepatic DC, which is in agreement with the unique requirements for APC in the complex liver environment.

Animals↗

Murine thymic plasmacytoid dendritic cells.

We report herein heterogeneous murine thymic cell subsets expressing CD11c and B220 (CD45R). The CD11c(+)B220(+) subset expresses Ly6C(high) and MHC class II(low) in contrast with previously described thymic DC (CD11c(+)B220(-) cells). Freshly isolated thymic CD11c(+)B220(+) cells show typical plasmacytoid morphology which differentiates to mature DC, in vitro with CpG oligodeoxynucleotides (ODN) 2216; we term this subset thymic plasmacytoid DC (pDC). These thymic pDC are highly sensitive to spontaneous apoptosis in vitro and induce low T cell allo-proliferation activity. Thymic pDC express low TLR2, TLR3 and TLR4 mRNA, normally found on human immature DC, and high TLR7 and TLR9 mRNA, normally found on human pDC. Thymic pDC also produce high amounts of IFN-alpha following culture with CpG ODN 2216 (TLR9 ligands) as compared with the previously defined thymic DC lineage which expresses low TLR9 mRNA and produce high IL-12 (p40) with CpG ODN 2216. These results indicate that thymic pDC are similar to IFN-producing cells as well as human pDC. The TLR and cytokine production profiles are consistent with a nomenclature of pDC. The repertoire of this cell lineage to TLR9 ligands demonstrate that such responses are determined not only by the quantity of expression, but also cell lineage.

Animals↗

Wallenberg's syndrome: neurotological classification.

OBJECTIVES: Visually induced eye movements were investigated in 26 patients with Wallenberg's syndrome. METHODS: Slow-phase optokinetic nystagmus (OKN) velocities, pursuit gains, and percentage fixation suppression (%FS) of caloric nystagmus were recorded by DC electrooculography (EOG), and stored directly onto FM magnetic tape. RESULTS: OKN velocities, pursuit gains, and %FS decreased toward the lesion side (group A), whereas OKN velocities and pursuit gains decreased toward the side contralateral to the lesion side. %FS decreased toward the lesion side (group B). MR images in group A showed that lesions were only in and near to the vestibular nuclei, and images in group B showed that lesions extended to the cerebellum. CONCLUSION: Visually guided eye movements allow classification of Wallenberg's syndrome into two types, one with brainstem lesions and one with both brainstem and cerebellar lesions. This demonstrates that assessing eye movements is helpful in supplementing MRI data.

Adult↗

Horizontal eye response to an abrupt lateral head drop in normal subjects and patients with Meniere's disease.

OBJECTIVE: To detect the endolymphatic hydrops by using the otolithic nature in patients with Meniere's disease and delayed hydrops. METHODS: We developed a new technique for measuring horizontal eye movements, corresponding to lateral head drop in total darkness, approximately 1g environment. Normal subjects (n=16, mean age: 27.3 years old) and patients (seven for pre-operative state, four for furosemide test at pre-operative state; two for post-operative state) were employed in the test. The principle of the test is to drop the head in a lateral position separately from the body with a rapid release exposing the head. Bitemporal EOG, accelometric and trigger signals for the releaser were recorded for processing at 1 KHz sampling time. RESULTS: The drop was performed five times in succession. The latency of horizontal eye response was of 40 ms order in normal subjects on both sides and were never beyond 60 ms. Eye response of the patients was in different patterns from normal subjects and the latencies delayed either to normal side or to the affected side. Following furosemide intravenous injection, more certain information was obtained. Three of four patients were recovered to normal range as to the latency. CONCLUSIONS: We emphasize that this test may provide a new measure sensitive to the hydrops and can underline this test to detect the hydrops in Meniere's disease.

Adult↗

Two cases of Aspergillus sinusitis with bone destruction.

We experienced the clinical courses of two cases of destructive Aspergillus in paranasal sinuses in which an Aspergillus fungus ball was formed, and which caused bony destruction are described. The case in which a nidus could not be completely surgically removed and with intervening diabetes had an unfavorable prognosis. It is recommend to perform an early expanded operation as well as to administer a sufficient amount of antifungal drugs for the treatment of destructive Aspergillus in paranasal sinuses.

Aged↗

Subcutaneous emphysema secondary to tonsillectomy: a case report.

We report a patient in whom subcutaneous emphysema developed shortly after a tonsillectomy. A 55-year-old female with a chronic tonsillitis underwent a tonsillectomy, and about 8 h after surgery complained of swelling to the left side of the face and neck. There was crepitus and local tenderness in the left side of the neck. A CT scan revealed subcutaneous emphysema. The mechanisms underlying emphysema after tonsillectomy are discussed.

Chronic Disease↗

A case of meningoencephalic herniation of the temporal bone.

A case of cerebrospinal fluid leakage from a meningoencephalic herniation of the temporal bone is presented. Computed tomography and magnetic resonance imaging were useful for a diagnosis of meningoencephalic herniation. After surgical treatment, no recurrence was observed during a 6-month follow-up period.

Cerebrospinal Fluid Otorrhea↗

Elevated C-met in thymic dendritic cells of New Zealand Black mice.

New Zealand Black (NZB) mice are a well-known animal model of human autoimmune disease. Although the mechanism for development of autoimmunity is unclear, NZB mice are well known for severe thymic microarchitecture abnormalities. It is thought that thymic dendritic cells (DC) may play a role in thymic education and contribute to the autoimmune process. To address this issue and, in particular, that qualitative and/or quantitative differences exist in thymic DC, we took advantage of a novel restriction analysis system that allow definition of differences in the expression of tyrosine kinases using highly enriched populations of thymic DC from NZB compared to BALB/c and C57BL/6 mice. The method chosen, restriction analysis of gene expression, allowed the determination of protein tyrosine kinase transcription profiles. We report herein that NZB mice have a significant upregulation of C-met compared to the control strains. The abnormality of the C-met transcription was confined to thymic DC. We believe that its abnormal expression reflects the resistance of thymic cells to apoptosis, which will ultimately lead to defects and/or abnormal signaling by the interaction of thymic DC and thymocytes. Further studies involving such interactions are under way.

Animals↗

Increased frequency of pre-pro B cells in the bone marrow of New Zealand Black (NZB) mice: implications for a developmental block in B cell differentiation.

Reductions in populations of both Pre-B cell (Hardy fractions D) and Pro-B cells (Hardy fractions B-C) have been described in association with murine lupus. Recent studies of B cell populations, based on evaluation of B cell differentiation markers, now allow the enumeration and enrichment of other stage specific precursor cells. In this study we report detailed analysis of the ontogeny of B cell lineage subsets in New Zealand black (NZB) and control strains of mice. Our data suggest that B cell development in NZB mice is partially arrested at the fraction A Pre-Pro B cell stage. This arrest at the Pre-Pro B cell stage is secondary to prolonged lifespan and greater resistance to spontaneous apoptosis. In addition, expression of the gene encoding the critical B cell development transcription factor BSAP is reduced in the Pre-Pro B cell stage in NZB mice. This impairment may influence subsequent B cell development to later stages, and thereby accounts for the down-regulation of the B cell receptor component Ig alpha (mb-1). Furthermore, levels of expression of the Rug2, lambda5 and Ig beta (B29) genes are also reduced in Pre-Pro B cells of NZB mice. The decreased frequency of precursor B cells in the Pre-Pro B cell population occurs at the most primitive stage of B cell differentiation.

Animals↗

Thermodynamic analysis of hybridization between POPNA and DNA.

We have developed a new series of oxy-peptide nucleic acids with pyrrolidine rings of four different types of structural isomers (cis L, cis D, trans L, trans D configurations; POPNAs). Melting curves of adenine nanomers of POPNAs in the presence of the complementary DNA showed the highest Tm value for cis L-POPNA, but in the case of RNA, the highest Tm value was observed for trans L-POPNA. Thermodynamic parameters (delta H and delta S) of POPNA/DNA and POPNA/RNA hybridizations were evaluated from concentration dependence of Tm values. The POPNA/DNA and POPNA/RNA hybridizations were governed by entropy and enthalpy terms, respectively.

DNA↗

Age-related alterations in the lymphohematopoietic and B-lineage precursor populations in NZB mice.

Significant disturbances in B lineage populations of New Zealand Black (NZB) mice have been reported, both with respect to their phenotypes as well as to their function. Notably, there is a profound age-dependent decrease in B-cell precursors in this strain of lupus prone mice. In efforts to characterize the impact of this disturbance in disease, we performed an intensive phenotypic and B-cell population analysis in young and old NZB mice. Our results revealed that there was a significant age-dependent decrease in B cell precursors at all levels of the B-cell-lineage developmental pathway. Analysis of the proliferative capacity of these cell populations showed a comparative decrease in cycling activity in the B-cell-lineage populations of old NZB mice. Furthermore, these cell subsets were much more susceptible to spontaneous apoptosis when compared with similar populations from age-matched BALB/c or young NZB mice. Since the frequency of cells that express the interleukin-7 receptor (IL-7R) declines as NZB mice age, we hypothesize that impairment of IL-7R signal transduction pathways could contribute to severe perturbations of B-cell function in aged NZB mice.

Aging↗