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Biomedical subjects

T Tatsuno

Publications and source records attributed to T Tatsuno.

At least 19 recordsLinked to original sources

Statistical characterization of the interchange-instability spectrum of a separable ideal-magnetohydrodynamic model system.

A Suydam-unstable circular cylinder of plasma with periodic boundary conditions in the axial direction is studied within the approximation of linearized ideal magnetohydrodynamics (MHD). The normal mode equations are completely separable, so both the toroidal Fourier harmonic index n and the poloidal index m are good quantum numbers. The full spectrum of eigenvalues in the range 1< or = m < or = m(max) is analyzed quantitatively, using asymptotics for large m, numerics for all m, and graphics for qualitative understanding. The density of eigenvalues scales like m(2)(max) as m(max) -->infinity . Because finite-m corrections scale as 1/ m(2)(max) , their inclusion is essential in order to obtain the correct statistics for the distribution of eigenvalues. Near the largest growth rate, only a single radial eigenmode contributes to the spectrum, so the eigenvalues there depend only on m and n as in a two-dimensional system. However, unlike the generic separable two-dimensional system, the statistics of the ideal-MHD spectrum departs somewhat from the Poisson distribution, even for arbitrarily large m(max) . This departure from Poissonian statistics may be understood qualitatively from the nature of the distribution of rational numbers in the rotational transform profile.

Journal Article↗

Angular momenta creation in relativistic electron-positron plasma.

Creation of angular momentum in a relativistic electron-positron plasma is explored. It is shown that a chain of angular momentum carrying vortices is a robust asymptotic state sustained by the generalized nonlinear Schrödinger equation characteristic to the system. The results may suggest a possible electromagnetic origin of angular momenta when it is applied to the MeV epoch of the early Universe.

Journal Article↗

Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis.

In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-gamma (IFN-gamma) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-gamma. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.

Analysis of Variance↗

Analysis of effects and pharmacokinetics of subcutaneously administered BDNF.

Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family and has been shown to be a potent and effective trophic factor for motor neurons and other neurons of the peripheral and central nervous. Little is known, however, about the relationship between the efficacy and pharmacokinetics of s.c. administered BDNF. In this study, the efficacy of BDNF on motor neuron protection in sciatic or facial nerve axotomy models was examined and compared with the concommitant concentrations of BDNF in plasma. Delayed treatment (started at 1 week after surgery) of BDNF was also shown to retard choline acetyltransferase reduction in sciatic nerve axotomy models.

Animals↗

Vortex solitons: mass, energy, and angular momentum bunching in relativistic electron-positron plasmas.

It is shown that the interaction of large amplitude electromagnetic waves with a hot electron-positron (e-p) plasma (a principal constituent of the universe in the MeV epoch) leads to a bunching of mass, energy, and angular momentum in stable, long-lived structures. Electromagnetism in the MeV epoch, then, could provide a possible route for seeding the observed large-scale structure of the universe.

Journal Article↗

IL-12 and IL-18 are increased and stimulate IFN-gamma production in sarcoid lungs.

Sarcoidosis is a systemic chronic granulomatous disease of unknown cause. Recent investigations revealed that the cytokine profile in inflamed lesions of sarcoidosis is Th1 dominant. To obtain better immunopathologic understanding of sarcoidosis, we examined the expression of IL-12 and IL-18 and their roles in IFN-gamma production in pulmonary sarcoidosis. Sarcoid cases had significantly elevated levels of IL-12 (p40 and p70) and IL-18 in bronchoalveolar lavage (BAL) fluids compared with healthy subjects. IL-12 p70 and IL-18 were immunohistochemically expressed in the epithelioid cells and giant cells of sarcoid granulomas. Significant induction of IFN-gamma, IL-12 p70, and IL-18 was observed from sarcoid BAL fluid cells with LPS stimulation, whereas LPS tended to induce only IL-12 p70 in BAL fluid cells from healthy subjects. Sarcoid cases had significantly greater IFN-gamma induction with LPS stimulation than healthy subjects did. IL-18 mRNA expression was observed in freshly isolated sarcoid BAL fluid cells as well as in LPS-stimulated sarcoid BAL fluid cells, but IFN-gamma and IL-12 mRNA expression was observed only in LPS-stimulated BAL fluid cells. Treatment with anti-IL-12- and anti-IL-18-neutralizing Abs significantly inhibited IFN-gamma production from LPS-stimulated BAL fluid cells of sarcoid cases. Coadministration of rIL-12 or rIL-18 induced greater IFN-gamma production in sarcoid BAL fluid cells than in normal BAL fluid cells. We concluded that bioactive IL-12 and IL-18 were produced in sarcoid BAL fluid cells and synergistically induced IFN-gamma production, indicating important cytokines in the Th1 response of sarcoidosis.

Adjuvants, Immunologic↗

[Method-performance studies of notified analytical method for fenbutatin oxide and cyhexatin].

Method-performance studies were conducted for the notified revised analytical method of fenbutatin oxide (FBTO) and cyhexatin (CHT). FBTO and CHT spiked into rice, soybeans, spinach, orange, tea powder and tea extract at the level of 0.5 microgram/g for FBTO and 0.1 microgram/g for CHT were analyzed in replicate in 6 laboratories. Means recoveries of FBTO were 85.2-96.5% and those of CHT were 83.5-89.2% except from soybeans (46.5%). Repeatability relative standard deviation values of FBTO and CHT in each crop were in the ranges of 2.3-9.4% and 3.2-6.3%, respectively. Reproducibility relative standard deviations were 3.9-12.6% for FBTO and 8.3-12.9% for CHT. Detection limits were 0.015-0.05 microgram/g for FBTO and 0.005-0.02 microgram/g for CHT.

Food Analysis↗

[Method-performance studies of notified analytical method for inabenfide].

Method-performance studies were conducted for the notified revised analytical method of inabenfide in unpolished rice. Six laboratories analyzed unpolished rice spiked with 0.05 microgram/g of inabenfide in replicate. Mean recovery from rice was 85.0%. Repeatability relative standard deviation value was 4.2% and reproducibility relative standard deviation value was 8.1%. The detection limits were 0.002-0.01 microgram/g.

Isonicotinic Acids↗

[Method-performance studies of notified analytical method for chinomethionat].

Method-performance studies were conducted for the notified revised analytical method of chinomethionat in agricultural products by interlaboratory study. Six laboratories analyzed unpolished rice, cabbage, squash, lettuce and orange spiked with 0.1 microgram/g of chinomethionat in replicate. Mean values of recovery from the 5 crops ranged from 90.2 to 100.5%. Repeatability relative standard deviations ranged from 4.4 to 7.7% and reproducibility relative standard deviations ranged from 10.9 to 17.1%. The detection limits were 0.003-0.012 microgram/g.

Brassica↗

[Method-performance studies of notified analytical method for clofentezine].

Method-performance studies were conducted for the notified revised analytical method of clofentezine. Clofentezine spiked in azuki beans, apple, orange, banana, grape, tea powder and tea extract at the level of 0.2 microgram/g (2 micrograms/g for tea) was analyzed in replicate in 6 laboratories. Mean values of recovery from 7 crops ranged from 78.4 to 85.2%. Repeatability relative standard deviation values ranged from 2.2 to 4.6% and reproducibility standard deviation values ranged from 4.8 to 10.3%. The detection limits were 0.005-0.01 microgram/g. These results show the notified analytical method has good performance.

Chlorobenzenes↗

Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death.

PURPOSE: To determine if brain-derived neurotrophic factor (BDNF) has a neuroprotective effect against N-methyl-D-aspartate (NMDA)-induced cell death in retina. METHODS: NMDA was injected into the vitreous of rat eyes. NMDA-induced neuronal death was measured by morphometric analyses on cell counts of ganglion cell layer cells and thickness of retinal layers. Also, we conducted additional experiment using retrograde labeling with a fluorescent tracer (Fluoro-Gold) for exact counting of retinal ganglion cells (RGCs). In addition, intravitreal glutamate levels were measured with the use of a high-performance liquid chromatography (HPLC) system. RESULTS: Morphometric analysis of retinal damage in NMDA-injected eyes showed that BDNF could protect inner retinal cells from glutamate receptor-mediated neuronal death. Also, counts of RGCs labeled with a fluorescent tracer showed that BDNF could protect RGCs from glutamate receptor-mediated neuronal death. Furthermore, measurements of intravitreal glutamate levels indicated an increase in this excitatory amino acid in the vitreous after NMDA injection. CONCLUSIONS: Exogenous BDNF can protect inner retinal cells (possible RGCs and amacrine cells) from NMDA-induced neuronal death. However, increased intravitreal glutamate levels in response to NMDA-mediated neurotoxicity may augment retinal degeneration.

Animals↗

Increased levels of interleukin-18 in patients with pulmonary sarcoidosis.

Interleukin-18 (IL-18) has recently been identified as an interferon-gamma (IFN-gamma)-inducing factor, and it plays an important role in T helper 1 (Th1) response. We measured the serum levels of IL-18 and IFN- gamma in 37 patients with pulmonary sarcoidosis and 25 healthy control subjects. We also measured the levels of IL-18 and IFN-gamma in 10-fold concentrated bronchoalveolar lavage (BAL) fluids of 19 patients with pulmonary sarcoidosis and 9 healthy control subjects (all lifelong nonsmokers). The levels of serum IL-18 and IFN-gamma were significantly increased in patients with sarcoidosis. The levels of BAL fluid IL-18 were significantly elevated in patients with sarcoidosis, however, the IFN-gamma levels of the patients and control subjects were all below sensitivity. Serum IL-18 levels significantly correlated with serum IFN-gamma levels and lysozyme activity. The patients positive for gallium-67 ((67)Ga) scan had significantly elevated serum IL-18 levels as compared with those of the negative patients. BAL fluid IL-18 levels significantly correlated with serum IL-18 levels in patients with sarcoidosis, and there was a significant correlation between IL-18 levels and lymphocyte proportions in sarcoid BAL fluids. In patients with sarcoidosis, IL-18 seems to induce IFN-gamma production and IL-18 levels in sera may reflect disease activity of sarcoidosis.

Adult↗

Enhanced mRNA expression of Th1 cytokines and IL-12 in active pulmonary sarcoidosis.

BACKGROUND AND AIM OF THE WORK: Active sarcoidosis is considered to be a Th1 dominant condition. We examined whether Th1 cytokines are highly expressed at inflammed lesions of Japanese patients with sarcoidosis. METHODS: To investigate the mRNA expression of Th1 cytokines and IL-12 in sarcoid BAL cells, we used semiquantitative reverse transcription--polymerase chain reaction method. RESULTS: The mRNA expressions of Th1 cytokines (IFN-gamma and IL-2) in active sarcoid BAL cells were significantly elevated as compared with those in healthy volunteers. The proportion of positive IL-4 mRNA expression in sarcoid BAL cells was not significantly higher than that in healthy volunteers. Further, there was no significant difference in IFN-gamma mRNA levels between the groups positive and negative for IL-4 mRNA expression. Although the proportion of positive expression of IL-12 mRNA in active sarcoid BAL cells was not significantly higher than that in healthy volunteers, the group positive for IL-12 mRNA expression had significantly elevated levels of IFN-gamma mRNA than did the negative group. CONCLUSIONS: These results may indicate that IL-12 induces IFN-gamma expression and subsequent Th1 dominant condition in Japanese patients with sarcoidosis.

Adult↗

BDNF attenuates retinal cell death caused by chemically induced hypoxia in rats.

PURPOSE: To investigate the neuroprotective effects of brain-derived neurotrophic factor (BDNF) against potassium cyanide (KCN)-induced retinal damage. METHODS: Rats were injected intravitreally with iodinated BDNF. Two days later, eyeballs were dissected into various parts, and the level of radioactivity in each part was measured. Retinal damage was induced by incubating rat eyeballs with 5 mM KCN. BDNF was injected intravitreally 2 days before KCN treatment, and subsequent morphometric analysis was carried out to evaluate the retinal cell damage. To elucidate the mechanisms of BDNF's neuroprotective effects, the intravitreal concentrations of amino acids and the expression of calretinin were investigated. RESULTS: Intravitreally injected BDNF was distributed evenly throughout the eyes, and the incorporation of iodinated BDNF into the retina was three times higher than in other ocular tissues. Immunohistochemical analysis demonstrated that exogenous BDNF diffused throughout the retina and was especially concentrated in the inner (INL) and outer nuclear layer. Morphometric analysis showed that the number of INL cells of the posterior area, 880 microm from the optic nerve head, was 190 +/- 4 with KCN treatment and 284 +/- 9 in control animals. Cell death appeared to be necrotic. When eyes injected with either phosphate-buffered saline (PBS) or BDNF were subjected to treatment with KCN, the number of INL cells was 186 +/- 5 in the PBS-treated controls and 253 +/- 8 in eyes treated with BDNF. Also, BDNF increased the number of calretinin-positive cells in the INL and reduced the KCN-induced elevation of intravitreal glutamate levels. CONCLUSIONS: BDNF injected intravitreally reaches the retina and attenuates the INL cell death caused by KCN-induced metabolic insult. The neuroprotective effects of BDNF are partly ascribed to the upregulation of a calcium-binding protein and the attenuation of glutamate release into the vitreous body.

Animals↗

BDNF prevents and reverses adult rat motor neuron degeneration and induces axonal outgrowth.

To assess the therapeutic potential of brain-derived neurotrophic factor (BDNF) in clinics, we extensively investigated the effects of BDNF on adult motor neurons in a rat spinal root avulsion model. Intrathecal administration of BDNF immediately after the spinal root avulsion greatly protected against the motor neuron cell death. BDNF also showed a protective effect on the atrophy of soma and on the reduction of transmitter-related enzymes such as choline acetyl transferase and acetylcholine esterase. Very interestingly, BDNF induced axonal outgrowth of severely damaged motor neurons at the avulsion site. The BDNF administration following 2-week treatment with phosphate-buffered saline after avulsion prevented further augmentation of cell death and reversed cholinergic transmitter-related enzyme deficiency. BDNF was demonstrated to possess a wide variety of biological effects on survival, soma size, cholinergic enzymes, and axonal outgrowth of adult motor neurons. These results provide a rationale for BDNF treatment in motor neuron diseases such as spinal cord injury and amyotrophic lateral sclerosis.

Acetylcholinesterase↗

Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain.

1. We studied the effects of tandospirone, a novel serotonin (5-HT)1A receptor-related anxiolytic, on the intracellular second messenger systems and neurotransmitter release. 2. Tandospirone inhibited forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes by activation of 5-HT1A receptors and had high efficacy comparable to 5-HT1A receptor agonists such as 5-HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 3. Tandospirone suppressed carbachol-stimulated phosphatidyl-inositol metabolism (PI response), which was shown to be a 5-HT1A receptor-mediated event. 4. Tandospirone did not affect the release of 5-HT, norepinephrine (NE), dopamine (DA) and acetylcholine (ACh) from rat brain slice preparations. 5. These findings suggested that tandospirone shows high agonistic efficacy on the postsynaptic 5-HT1A receptors but does not affect the presynaptic autoreceptors located on nerve endings. The modulation of the second messenger system via postsynaptic 5-HT1A receptors might be involved in the anxiolytic efficacy of tandospirone.

Acetylcholine↗

Tricyclic quinoxalinediones: 5,6-dihydro-1H-pyrrolo[1,2,3-de] quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de] quinoxaline-2,3-diones as potent antagonists for the glycine binding site of the NMDA receptor.

A series of tricyclic quinoxalinediones, 5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones, were synthesized and was evaluated for their affinity for the glycine binding site of the NMDA receptor using a [3H]-5,7-dichlorokynurenic acid binding assay. The six-membered ring-fused tricyclic quinoxalinedione 18g (Ki = 9.9 nM) displayed high affinity for the glycine site. The anilide derivative 20g (Ki = 2.6 nM) was 4-fold more potent than 18g and as potent as L-689,560, one of the most potent glycine antagonists so far prepared. Although the carboxylic acid derivative of the corresponding five-membered ring-fused tricyclic quinoxalinedione 18e (Ki = 7.3 nM) had affinity comparable to that of 18g, the anilide derivative 20e largely decreased in the affinity in contrast to 20g. Enantiomers 23g, 24g, 25g, and 26g were prepared and tested. Only the S enantiomer 25g (Ki = 0.96 nM) retained the affinity among the anilide derivatives, whereas both enantiomers 23g (Ki = 2.3 nM) and 24g (Ki = 9.6 nM) were active among the carboxylic acid derivatives. The origin of the high affinity of carboxylic acid derivatives such as 18e and 18g would be a charge-charge interaction between the anionic carboxylate residues of the compounds and the cationic proton-donor site in the receptor.

Animals↗

Regulation of nerve growth factor secretion in L-M cells by catechol derivatives.

We investigated the mechanism responsible for the stimulation of nerve growth factor (NGF) secretion by catechol derivatives in L-M cells, using L-threo-3,4-dihydroxyphenylserine (L-DOPS). Treatment of the cells with L-DOPS increased the NGF content in the L-M cell medium by approximately 3-fold. This stimulatory effect was not blocked by a decarboxylase inhibitor, or by alpha- or beta-adrenergic blockers. Intracellular cAMP levels were not changed by exposure to L-DOPS. The antioxidants, ascorbic acid and sodium pyrosulfite, completely prevented the stimulatory effect of L-DOPS, and radical scavengers (superoxide dismutase plus catalase) caused a significant partial inhibition of the response to L-DOPS. Quinone derivatives (adrenochrome, 4-n-propyl-1,2-benzoquinone), which are the oxidative products of the catechol derivatives, increased the NGF content in the medium, and their potency was greater than that of the catechol derivatives themselves. These findings suggest that L-DOPS and other catechol derivatives might be oxidized in the medium to form quinone derivatives, and that it is these which predominantly express a stimulatory effect on NGF secretion by a novel cAMP-independent mechanism in L-M cells.

Animals↗