Biomedical subjects
Publications and source records attributed to T Okada.
We report a rare cause of trigger finger related to an anatomical variation of an intertendinous connection between the flexor digitorum superficialis and flexor digitorum profundus tendons in the palmar region.
CNS activity is generally coupled to the vigilance state, being primarily active during wakefulness and primarily inactive during deep sleep. During periods of high neuronal activity, a significant volume of oxygen is used to maintain neuronal membrane potentials, which subsequently produces cytotoxic reactive oxygen species (ROS). Glutathione, a major endogenous antioxidant, is an important factor protecting against ROS-mediated neuronal degeneration. Glutathione has also been proposed to be a sleep-promoting substance, yet the relationship between sleep and cerebral oxidation remains unclear. Here we report that i.c.v. infusion of the organic peroxide t-butyl-hydroperoxide at a concentration below that triggering neurodegeneration (0.1 micromol/100 microl/10 h) promotes sleep in rats. Also, microinjection (2 nmol, 2 microl) or microdialysis (100 microM, 20 min) of t-butyl-hydroperoxide into the preoptic/anterior hypothalamus (POAH) induces the release of the sleep-inducing neuromodulators, nitric oxide and adenosine, without causing neurodegeneration. Nitric oxide and adenosine release was inhibited by co-dialysis of the N-methyl-D-aspartate receptor antagonist, d(-)-2-amino-5-phosphonopentanoic acid (D-AP5; 1 mM), suggesting that glutamate-induced neuronal excitation mediates the peroxide-induced release of nitric oxide and adenosine. Indeed, Ca2+ release from mitochondria and delayed-onset Ca2+ influx via N-methyl-D-aspartate receptors was visualized during peroxide exposure using Ca2+ indicator proteins (YC-2.1 and mitochondrial-targeted Pericam) expressed in organotypic cultures of the POAH. In the in vitro models, t-butyl-hydroperoxide (50 microM) causes dendritic swelling followed by the intracellular Ca2+ mobilization, and D-AP5 (100 microM) or glutathione (500 microM) inhibited t-butyl-hydroperoxide-induced intracellular Ca2+ mobilization and protected POAH neurons from oxidative stress. These data suggest that low-level subcortical oxidation under the control of an antioxidant system may trigger sleep via the Ca(2+)-dependent release of sleep-inducing neuromodulators in the POAH, and thus we propose that a moderate increase of ROS during wakefulness in the neuronal circuits regulating sleep may be an initial trigger in sleep induction.
Efficient gene transfer and regulated transgene expression in primate embryonic stem (ES) cells are highly desirable for future applications of the cells. In the present study, we have examined using the nonintegrating Sendai virus (SeV) vector to introduce the green fluorescent protein (GFP) gene into non-human primate cynomolgus ES cells. The GFP gene was vigorously and stably expressed in the cynomolgus ES cells for a year. The cells were able to form fluorescent teratomas when transplanted into immunodeficient mice. They were also able to differentiate into fluorescent embryoid bodies, neurons, and mature blood cells. In addition, the GFP expression levels were reduced dose-dependently by the addition of an anti-RNA virus drug, ribavirin, to the culture. Thus, SeV vector will be a useful tool for efficient gene transfer into primate ES cells and the method of using antiviral drugs should allow further investigation for regulated SeV-mediated gene expression.
Delayed gastric emptying often occurs in patients, including children, with gastroesophageal reflux (GER) due to neurological impairment (NI). The aim of this study was to evaluate gastric emptying of liquids in children with symptomatic GER using the (13)C- acetate breath test (ABT), and to compare the gastric emptying rates between children without and with NI. Thirteen patients were divided into 2 groups: group I without NI (5 patients) and group II with NI (8 patients). The liquid test meal consisted of Racoltrade mark (5 ml/kg) mixed with (13)C- acetate (50 mg for infants, 100 mg for children, and 150 mg for adolescents). Breath samples were collected for (13)CO (2) measurement before the intake of the meal, every 15 minutes during the first 2 hours after the meal and every 30 minutes thereafter to assess the ingestion of (13)C- acetate and Racoltrade mark. (13)CO (2) was measured using a gas chromatograph-isotope ratio mass spectrometer. The results were expressed as % of (13)C expired per hour and cumulative (13)C excretion over a 3-hour period. The half excretion time in (13)C- ABT(t (1/2) ex) was 1.095 hour for group I and 1.817 hour for group II (p = 0.0045). The lag time (t lag), which reflected the initial delay of gastric emptying, was 0.666 h for group I and 1.002 h for group II (p = 0.0045). Gastric emptying studies can be easily and reliably carried out in children with NI using (13)C- ABT. We showed that we were able to determine the gastric emptying rate by (13)C- ABT in patients with GER due to NI.
Biliary atresia (BA) is occasionally diagnosed in infants whose first symptom is a bleeding disorder, such as intracranial bleeding, nasal bleeding or gastrointestinal bleeding. The authors describe 3 cases in which a bleeding disorder was the first symptom of BA. The presenting symptom was intracranial bleeding in a male on day 55 after birth, nasal bleeding in a female at 65 days, and gastrointestinal bleeding in a female at 25 days. Coagulation studies revealed a vitamin K deficiency in all patients. After the administration of vitamin K, the results of coagulation tests normalized and the bleeding tendency of the infants ceased. Subsequently, BA was suspected to be the cause of these bleeding disorders based on imaging findings. BA should therefore be considered in all infants with sudden onset of a tendency to bleed.
In flow cytometry using two detecting methods, we have found that amyloid-beta-protein(1-40) [Abeta(1-40)] has high affinity to IMR-32 neuroblastoma cell membrane when it is aggregated to form beta-sheet conformation, whereas random coil small Abeta-species has low affinity. The difference in the binding ability to the cell membranes well accounts for the cytotoxicity of Abeta(1-40); namely, aggregated beta-sheet Abeta(1-40) gives cytotoxicity higher than random coil Abeta(1-40). Specific binding between Abeta(1-40) and ganglioside GM1 of the raft-like domain in lipid membrane is suggested from a surface plasmon resonance (SPR) experiment.
UNLABELLED: We examined age- and sex-specific body compositions of Chinese children by the bioelectrical impedance method. The subjects were a total of 587 children aged 6-14 y who had normal relative weight. In all ages, boys had larger fat-free mass and lower percent body fat (%BF) than girls did. Even in the subjects with BMI <20 kg/m2, more than one quarter of them had high %BF. CONCLUSION: Chinese children may have higher %BF than that predicted by BMI.
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Optimized pulse shaping experiments were carried out on the control of two-photon excitation efficiency of an alpha-perylene crystal in the temperature region from 30 to 290 K. It was found that a pulse train with a pulse interval of 90 fs and an alternately reversing phase relation increased the excitation efficiency by a factor of 2 for the whole temperature region. The pulse shape characteristic for effective efficiency increase was reduced by double pulse experiments in which the dependence of the emission intensity on the pulse interval and relative phase between pulses were measured. The mechanism of the efficiency increase is briefly discussed using a sliding-window Fourier transform of the pulse shape.
The swallowing of sharp glass splinters is rare due to the difficulty of swallowing such objects, and perforation of the piriform recessus and mediastinitis are unusual complications. Perforation of the piriform recessus due to a swallowed sharp glass splinter requires prompt treatment. This report describes a child who was operated on immediately after the diagnosis of perforation of the piriform recessus and was managed successfully. Light-guided pharyngoscopy was very useful for detecting the region of perforation. The literature on such injuries is reviewed here, and the problems associated with treating children with perforation of the piriform recessus and mediastinitis caused by swallowed glass splinters are discussed.
Normal state bubble patterns in type I superconducting indium and lead slabs are studied by the high resolution magneto-optical imaging technique. The size of bubbles is found to be independent of the long-range interaction between the normal state domains. Under bubble diameter and slab thickness proper scaling, the results gather onto a single master curve. We calculate the equilibrium diameter of an isolated bubble resulting from the competition between the Biot-and-Savart interaction of the Meissner current encircling the bubble and the superconductor-normal interface energy. A good quantitative agreement with the master curve is found over two decades of the magnetic Bond number. The isolation of each bubble in the superconductor and the interface energy are shown to preclude any continuous size variation of the bubbles after their formation, contrary to the prediction of mean-field models.
The most significant progresses in the understanding of human brain functions have been possible due to the use of functional magnetic resonance imaging (fMRI), which when used in combination with other standard neuroimaging techniques (i.e., EEG) provides researchers with a potential tool to elucidate many biophysical principles, established previously by animal comparative studies. However, to date, most of the methods proposed in the literature seeking fMRI signs have been limited to the use of a top-down data analysis approach, thus ignoring a pool of physiological facts. In spite of the important contributions achieved by applying these methods to actual data, there is a disproportionate gap between theoretical models and data-analysis strategies while trying to focus on several new prospects, like for example fMRI/EEG data fusion, causality/connectivity patterns, and nonlinear BOLD signal dynamics. In this paper, we propose a new approach which will allow many of the abovementioned hot topics to be addressed in the near future with an underlying interpretability based on bottom-up modeling. In particular, the theta-MAP presented in the paper to test brain activation corresponds very well with the standardized t test of the SPM99 toolbox. Additionally, a new Impulse Response Function (IRF) has been formulated, directly related to the well-established concept of the hemodynamics response function (HRF). The model uses not only the information contained in the signal but also that in the structure of the background noise to simultaneously estimate the IRF and the autocorrelation function (ACF) by using an autoregressive (AR) model with a filtered Poisson process driving the dynamics. The short-range contributions of voxels within the near-neighborhood are also included, and the potential drift was characterized by a polynomial series. Since our model originated from an immediate extension of the hemodynamics approach [Friston, K.J., Mechelli, A., Turner, R., Price C.J. (2000a). Nonlinear responses in fMRI: the balloon model, volterra kernels, and other hemodynamics. NeuroImage 12, 466-477.], a natural interpretability of the results is feasible.
This study aimed to identify distribution of metals and the influential factors on metal concentrations in incineration residues. Bottom ash and fly ash were sampled from 19 stoker and seven fluidized bed incinerators, which were selected to have a variety of furnace capacity, furnace temperature, and input waste. In the results, shredded bulky waste in input waste increased the concentration of some metals, such as Cd and Pb, and the effect was confirmed by analysis of shredded bulky waste. During MSW incineration, lithophilic metals such as Fe, Cu, Cr, and Al remained mainly in the bottom ash while Cd volatilized from the furnace and condensed to the fly ash. About two thirds of Pb and Zn was found in the bottom ash despite their high volatility. Finally, based on the results obtained in this study, the amount of metal in incineration residues of MSW was calculated and the loss of metal was estimated in terms of mass and money. A considerable amount of metal was found to be lost as waste material by landfilling of incineration residues.
Classical phenylketonuria (PKU) is a metabolic disorder caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase (PAH). If untreated, accumulation of phenylalanine will damage the developing brain of affected individuals, leading to severe mental retardation. Here, we show that a liver-directed PAH gene transfer brought about long-term correction of hyperphenylalaninemia and behavioral improvement in a mouse model of PKU. A recombinant adeno-associated virus (AAV) vector carrying the murine PAH cDNA was constructed and administered to PAH-deficient mice (strain PAH(enu2)) via the portal vein. Within 2 weeks of treatment, the hyperphenylalaninemic phenotype improved and completely normalized in the animals treated with higher vector doses. The therapeutic effect persisted for 40 weeks in male mice, while serum phenylalanine concentrations in female animals gradually returned to pretreatment levels. Notably, this long-term correction of hyperphenylalaninemia was associated with a reversal of hypoactivity observed in PAH(enu2) mice. While locomotory activity over 24 h and exploratory behavior were significantly decreased in untreated PAH(enu2) mice compared with the age-matched controls, these indices were completely normalized in 12-month-old male PKU mice with lowered serum phenylalanine. These results demonstrate that AAV-mediated liver transduction ameliorated the PKU phenotype, including central nervous system dysfunctions.
Hematopoietic stem cell gene therapy has not provided clinical success in disorders such as chronic granulomatous disease (CGD), where genetically corrected cells do not show a selective advantage in vivo. To facilitate selective expansion of transduced cells, we have developed a fusion receptor system that confers drug-induced proliferation. Here, a 'selective amplifier gene (SAG)' encodes a chimeric receptor (GcRER) that generates a mitotic signal in response to estrogen. We evaluated the in vivo efficacy of SAG-mediated cell expansion in a mouse disease model of X-linked CGD (X-CGD) that is deficient in the NADPH oxidase gp91phox subunit. Bone marrow cells from X-CGD mice were transduced with a bicistronic retrovirus encoding GcRER and gp91phox, and transplanted to lethally irradiated X-CGD recipients. Estrogen was administered to a cohort of the transplants, and neutrophil superoxide production was monitored. A significant increase in oxidase-positive cells was observed in the estrogen-treated mice, and repeated estrogen administration maintained the elevation of transduced cells for 20 weeks. In addition, oxidase-positive neutrophils were increased in the X-CGD transplants given the first estrogen even at 9 months post-transplantation. These results showed that the SAG system would enhance the therapeutic effects by boosting genetically modified, functionally corrected cells in vivo.
Inflammation is a major contributor to atherosclerosis by its effects on arterial wall biology and lipoprotein metabolism. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may modulate the atherosclerotic disease process. We investigated the effects of adeno-associated virus (AAV) vector-mediated gene transfer of IL-10 on atherogenesis in apolipoprotein E (ApoE)-deficient mice. A murine myoblast cell line, C2C12, transduced with AAV encoding murine IL-10 (AAV2-mIL10) secreted substantial amounts of IL-10 into conditioned medium. The production of monocyte chemoattractant protein-1 (MCP-1) by the murine macrophage cell line, J774, was significantly inhibited by conditioned medium from AAV2-mIL10-transduced C2C12 cells. ApoE-deficient mice were injected with AAV5-mIL10 into their anterior tibial muscle at 8 weeks of age. The expression of MCP-1 in the vascular wall of the ascending aorta and serum MCP-1 concentration were decreased in AAV5-mIL10-transduced mice compared with AAV5-LacZ-transduced mice. Oil red-O staining of the ascending aorta revealed that IL-10 gene transfer resulted in a 31% reduction in plaque surface area. Serum cholesterol concentrations were also significantly reduced in AAV5-mIL10-transduced mice. To understand the cholesterol-lowering mechanism of IL-10, we measured the cellular cholesterol level in HepG2 cells, resulting in its significant decrease by the addition of IL-10 in a dose-dependent manner. Furthermore, IL-10 suppressed HMG-CoA reductase expression in the HepG2 cells. These observations suggest that intramuscular injection of AAV5-mIL10 into ApoE-deficient mice inhibits atherogenesis through anti-inflammatory and cholesterol-lowering effects.
G-protein-coupled receptors constitute the largest transmembrane receptor family in human. They are generally activated on binding their specific ligands at the extracellular side of membranes. The signal carried by an agonist is then transmitted to the intracellular side through a conformational change of the receptor, which becomes competent to catalyse GDP/GTP exchange in the alpha-subunit of heterotrimeric G-protein. Since most of the G-protein-coupled receptors (rhodopsin-like subfamily) share a set of conserved amino acid residues in the transmembrane domain, it is probable that the ligand-triggered activation process involves a common mechanism of rearrangement of the hepta-helical transmembrane bundle. For understanding the nature of this event that is not yet characterized sufficiently, X-ray crystallographic studies of rhodopsin with or without light stimulation can provide valuable information. In rhodopsin, the initial cis-trans photoisomerization of retinal chromophore triggers the structural changes of transmembrane helices. This activation process has been characterized with some spectroscopically distinct photoreaction intermediates (batho, lumi, Meta I and Meta II). With recent advances in the conditions for crystallographic experiments, the diffraction limit of the rhodopsin crystals has been substantially extended. As a result, it becomes possible to detect small structural changes evoked after photoactivation under cryogenic conditions.
We hypothesized that hyperbaric oxygenation (HBO) combined with a long tube (LT) [HBO + LT] would be more effective than HBO combined with a short tube (ST) [HBO + ST] for simple adhesive postoperative intestinal obstruction (APIO) in children, assuming that there is synergism between HBO and LT. The objective of this study was to determine retrospectively the effect of HBO + LT compared to HBO + ST for simple APIO in children. Seventy-three patients were diagnosed with simple APIO, and 51 of these patients were treated with HBO + LT during 104 HBO sessions, while 22 were treated with HBO + ST during 34 HBO sessions. HBO was performed at a pressure of 2 atmospheres for 60 minutes once daily. The recovery rates after HBO therapy were 87.5 % for the HBO + LT group and 82.4 % for the HBO + ST group (p = 0.4496). HBO was performed 5 +/- 3 (range 1 to 15) times for the HBO + LT group and 4 +/- 2 (range 1 to 8) times for the HBO + ST group (p = 0.9847) for ultimate recovery from simple APIO. The recovery rate after HBO therapy of up to 6 sessions was 78.2 % for HBO + LT and 92.1 % for HBO + ST (p = 0.0360) among the cases that recovered ultimately. The effect of HBO + LT did not significantly differ from that of HBO + ST, but the insertion of an LT is more intricate and the cost is higher than that of an ST. Therefore, we conclude that the use of an LT is not necessarily required for HBO therapy for simple APIO.