An experimental setup for creating and imaging 4He2 * excimer cluster tracers in superfluid helium-4 via neutron-3He absorption reaction.

For the purpose of future visualization of the flow field in superfluid helium-4, clusters of the triplet state excimer 4He2 * are generated along the micro-scale recoil tracks of the neutron-absorption reaction n + 3He → 3T + p. This reaction is induced by neutron irradiation of the 3He fraction contained in natural isotopic abundance liquid helium with neutron beams either from the Japan Proton Accelerator Research Complex, Materials and Life Science Experimental Facility (JPARC)/Materials and Life Science Experimental Facility or from the Kyoto University Institute for Integrated Radiation and Nuclear Science. These 4He2 * clusters are expected to be ideal tracers of the normal-fluid component in superfluid helium with several advantageous properties. Evidence of the excimer generation is inferred by detection of laser induced fluorescence emitted from the 4He2 * clusters excited by a purpose-built short pulse gain-switched titanium:sapphire (Ti:sa) laser operating at a wavelength of 905 nm. The setup and performance characteristics of the laser system including the Ti:sa and two continuous wave re-pumping lasers are described. Detection at the fluorescence wavelength of 640 nm is performed by using optical bandpass filtered photomultiplier tubes (PMT). Electrical noise in the PMT acquisition traces could successfully be suppressed by post-processing with a simple algorithm. Despite other laser-related backgrounds, the excimer was clearly identified by its fluorescence decay characteristics. Production of the excimer was found to be proportional to the neutron flux, adjusted via insertion of different collimators into the neutron beam. These observations suggest that the apparatus we constructed does function in the expected manner and, therefore, has the potential for groundbreaking turbulence research with superfluid helium.

Relativistic jet activity from the tidal disruption of a star by a massive black hole.

Supermassive black holes have powerful gravitational fields with strong gradients that can destroy stars that get too close, producing a bright flare in ultraviolet and X-ray spectral regions from stellar debris that forms an accretion disk around the black hole. The aftermath of this process may have been seen several times over the past two decades in the form of sparsely sampled, slowly fading emission from distant galaxies, but the onset of the stellar disruption event has not hitherto been observed. Here we report observations of a bright X-ray flare from the extragalactic transient Swift J164449.3+573451. This source increased in brightness in the X-ray band by a factor of at least 10,000 since 1990 and by a factor of at least 100 since early 2010. We conclude that we have captured the onset of relativistic jet activity from a supermassive black hole. A companion paper comes to similar conclusions on the basis of radio observations. This event is probably due to the tidal disruption of a star falling into a supermassive black hole, but the detailed behaviour differs from current theoretical models of such events.

[Organometal-catalyzed asymmetric synthesis stereocontrolled by organosulfur functionality].

Our recent studies on asymmetric synthesis with the assistance of organometal catalysts stereocontrolled by organosulfur functionality involved in reaction substrates or ligands are reviewed. The studies focused on asymmetric synthesis via chiral pi-allylmetal complexes derived from (S)-proline allyl ester, olefinic cyclopropanes, chiral 2-alkynyl sulfinates, and chiral new ligands, and also focused on asymmetric cycloaddition reactions with chiral sulfoxides and sulfinates, such as intramolecular ene, metallo-type ene, and hetero Diels-Alder reactions. Participation of organosulfur functionality in organometal-catalyzed asymmetric reactions was unveiled on the basis of the stereochemical outcomes obtained.

Studies on Lewis acid-mediated intramolecular cyclization reactions of allene-ene systems.

The Lewis acid-mediated reactions of allene-ene compounds, derived from 3-methylcitronellal or dimethyl malonate, were carried out using various Lewis acids such as ethylaluminum dichloride, diethylaluminum chloride, titanium chloride, zinc chloride etherate, or boron trifluoride etherate, affording unexpectedly intramolecular [2+2]cycloaddition products under some particular reaction conditions without any formation of intramolecular ene reaction products.

Roles of constitutive nitric oxide synthase in postischemic rat retina.

PURPOSE: Nitric oxide is a reactive species that could be protective or destructive to the retina depending on the stage of the evolving ischemic process. This study was conducted to obtain a better understanding of the roles of constitutive nitric oxide synthase (cNOS) during reperfusion after ischemia in rat retina. METHODS: Retinal ischemia was induced for 60 minutes in Sprague-Dawley rats by ligating the optic nerve. Gene expression for endothelial and neuronal nitric oxide synthases (eNOS and nNOS) was studied by reverse transcription-polymerase chain reaction (RT-PCR). To inhibit cNOS, NG-nitro-L-arginine (L-NNA) was injected intraperitoneally four times (every 6 hours) beginning 2 hours after reperfusion, for a total dose of 80 mg/kg. Retinal damage was assessed by the rate of a- and b-wave recovery on electroretinograms and by the thickness of the retinal layers. Retinal circulation and vessel diameter were evaluated by the dye-dilution technique. RESULTS: After ischemia ended, eNOS mRNA initially decreased until 6 hours, then increased to a peak at 12 hours, and decreased progressively beyond 24 hours until the final measurement at 96 hours of reperfusion. nNOS mRNA decreased to nearly undetectable levels during the same measurement periods. L-NNA treatment enhanced reduction of a- and b-wave amplitudes and increased thinning of the inner retina in postischemic eyes. Retinal mean circulation time was markedly prolonged in L-NNA-treated postischemic eyes. Arterial mean transit times were 2.1-fold and 4.5-fold longer in L-NNA-treated postischemic eyes than in L-NNA-treated nonischemic eyes and in D-NNA-treated postischemic eyes, respectively. CONCLUSIONS: This study shows that postischemic inhibition of NOS worsens retinal damage after ischemia-reperfusion and alters postischemic retinal circulation. Nitric oxide may play an important role in protecting the retina from ischemic injury, possibly by preventing postischemic hypoperfusion.

Role of nitric oxide during the initial phase of reperfusion after retinal ischemia in the rat.

The onset of reperfusion and the recovery of the ERG b-wave following retinal ischemia was examined among three groups of rats: group 1 (n = 12) and group 2 (n = 6) received pretreatment with NG-nitro-L-arginine (20 mg/kg, i.p., 2 h before ischemia) followed by intravenous injection of saline (group 1) or of 200 mg/kg L-arginine (group 2) 5 min before the end of ischemia; group 3 (n = 7) received saline pretreatment followed by intravenous injection of saline as a control. Group 1 showed delayed onset of reperfusion compared to the other two groups and a reduction in the rate of the b-wave recovery compared to the control on the 1st day after reperfusion (group 1 vs. group 3; p = 0.0357). The L-arginine posttreatment significantly increased the b-wave recovery (group 2 vs. group 1; p = 0.0005 on day 1 and p < 0.0006 on day 3). The rate of the b-wave recovery in group 1 was inversely proportional to the time to establish complete reperfusion. Inhibition of nitric oxide synthase during the initial phase of reperfusion may worsen the recovery of the b-wave following retinal ischemia, at least in part, by inhibiting establishment of reperfusion.

Prognostic factors for hypotensive effects of isopropyl unoprostone in eyes with primary open-angle glaucoma.

It has been reported that isopropyl unoprostone, a prostaglandin-related compound, has potent effects in lowering intraocular pressure and that its hypotensive effect is an increase of uveoscleral outflow. In the present study, we investigated the clinical characteristics of the hypotensive effects of this novel antiglaucoma drug in 115 primary open-angle glaucoma (POAG) eyes. The mean intraocular pressure (+/- standard deviation) before the addition of isopropyl unoprostone to the current regimens was 21.3 +/- 4.4 mmHg. The values at 1 month, 3 months, and 6 months after treatment were, respectively, 20.2 +/- 3.9 mmHg, 19.4 +/- 3.4 mmHg, and 18.4 +/- 2.5 mmHg. In POAG, the outflow pressure difference (delta OP), which is determined as (pretreatment pressure - posttreatment pressure)/(pretreatment pressure - 10) x 100 (%), was reduced by more than 20% in 36 (31%) of 115 eyes, 35 (36%) of 97 eyes, and 33 (53%) of 62 eyes, respectively at 1, 3, and 6 months. We defined the "early success" group as eyes with a significant reduction in delta OP (> or = 20%) at 1-month posttreatment. To identify the prognostic factors related to the significant reduction in intraocular pressure occurring after the administration of this drug, we carried out a statistical analysis by logistic regression analysis. Statistical analysis revealed significant prognostic factors: history of cataract surgery (P = 0.0084) and pretreatment pressure levels (P = 0.0105) at 1-month posttreatment. Also, further statistical analysis showed a significant influence of pretreatment pressure levels (P = 0.0010) at 3 months posttreatment. Our study shows an interindividual difference in the responsiveness of hypotensive effects on POAG eyes and some prognostic factors (history of cataract surgery and pretreatment pressure levels) prior to the use of this drug.

Inducible nitric oxide synthase in retinal ischemia-reperfusion injury.

The purpose of this study was to determine whether inducible nitric oxide synthase (iNOS) was implicated in the pathogenesis of retinal ischemia-reperfusion injury. Semi-quantitative reverse transcription-polymerase chain reaction showed that the level of iNOS mRNA expression was markedly increased in rat retina following transient ischemia, with peak expression at 12 hr after reperfusion (15.7-fold increase over pre-ischemic levels). In situ hybridization showed that iNOS mRNA was expressed by resident retinal cells, most likely glial cells in the innermost retina, and also by the neutrophils that had infiltrated the retina. Intraperitoneal administration of NG-(1-iminoethyl)-L-ornithine (L-NIO), an inhibitor of iNOS, significantly increased the rate of b-wave recovery compared to that of control animals. The values (mean +/- S.E.M.) were 55.0 +/- 4.4% versus 40.1 +/- 5.1% (P < 0.05) at 1 day and 68.6 +/- 6.6% versus 45.8 +/- 3.5% (P < 0.05) at 3 days. This study shows that iNOS mRNA is highly expressed by non-neuronal cells of the inner retina during reperfusion following transient retinal ischemia. It also shows that L-NIO treatment provides some protection against ischemia-reperfusion injury. We suggest that nitric oxide produced by iNOS may mediate retinal ischemia-reperfusion injury.

[Stereochemistry of highly selective transition metal or Lewis acid-catalyzed asymmetric reactions].

Recent progress of our studies on catalytic asymmetric synthesis is reviewed focused on transition metal-catalyzed intramolecular asymmetric reactions using chiral organo-sulfur groups as main chiral auxiliaries such as asymmetric vinyl-cyclopropane-cyclopentene rearrangements and intramolecular asymmetric metallo-ene reactions, Lewis acid-catalyzed intramolecular asymmetric ene reactions with chiral sulfinyl groups, and palladium-catalyzed intramolecular asymmetric allylations via chiral enamines.

Effects of ornithine on the electroretinogram in cat retina.

PURPOSE: To study the acute effects of L-ornithine hydrochloride on the function of cat retina in vivo. METHODS: A small amount of ornithine was administered intravitreously or intravenously. Changes in retinal function were monitored by vitreal electroretinogram (ERG) and intraretinal ERG with K(+)-selective microelectrodes. RESULTS: Intravitreal injections (0.2 to 0.5 M; 15 microliters) of ornithine caused a decrease in the standing potential and the vitreal ERG c-wave amplitude. The ERG c-wave decreased continuously during a 5-hour period. Intravenous injection (0.2 M; 10 ml) of ornithine also diminished the c-wave. Intraretinal recording showed that the amplitudes of the retinal pigment epithelium (RPE) component and the Müller cell component of the ERG c-wave were reduced after intravitreal injection. The light-evoked [K+]o decrease in the subretinal space did not change. The change in transepithelial resistance contributed little to the decrease in the c-wave. CONCLUSION: These results demonstrated that ornithine selectively affects the c-wave and suggested that it affects RPE and Müller cells directly without affecting photoreceptors.

Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene.

Taking advantage of the restricted expression of metabotropic glutamate receptor subtype 6 (mGluR6) in retinal ON bipolar cells, we generated knockout mice lacking mGluR6 expression. The homozygous mutant mice showed a loss of ON responses but unchanged OFF responses to light. The mutant mice displayed no obvious changes in retinal cell organization nor in the projection of optic fibers to the brain. Furthermore, the mGluR6-deficient mice showed visual behavioral responses to light stimulation as examined by shuttle box avoidance behavior experiments using light exposure as a conditioned stimulus. The results demonstrate that mGluR6 is essential in synaptic transmission to the ON bipolar cell and that the OFF response provides an important means for transmitting visual information.

A case of beriberi accompanying short bowel.

A case of beriberi based on short bowel is reported. A 4 year old girl, who underwent a resection of the intestine when a neonate and has had a short bowel, manifested beriberi despite eating normal Japanese food. Considering that she has had no dislikes of foods, and her family members, who have eaten meals similar to hers have been healthy, beriberi is considered in this case to have developed mainly through hypoabsorption of vitamin B1. This patient has responded well to vitamin B1 therapy with a relatively slow recovery in neural functions. Although it has not been confirmed whether short bowel syndrome is prone to be accompanied by beriberi, special attention should be given to vitamin B1 in short bowel syndrome patients.

Intraretinal analysis of electroretinogram with K+ microelectrodes during acute intraocular pressure elevation.

We examined the effects of acute intraocular pressure elevation on the intraretinal electroretinogram in the cat dark-adapted eye. Perfusion pressure of the eye (mean arterial pressure minus intraocular pressure) was regulated within the range of 25-75 mm Hg by increasing the intraocular pressure, which was adjusted by changing the height of the reservoir of balanced salt solution perfused into the eye through a needle placed in the anterior chamber. The vitreal electroretinogram, transepithelial c-wave, slow PIII and light-evoked decrease in extracellular K+ concentration were recorded during intraocular pressure elevation in the dark-adapted retina. The c-wave increased in amplitude between 40 and 75 mm Hg of perfusion pressure and decreased below 40 mm Hg in some cases. These changes were unrelated to the standing potential. The transepithelial c-wave, slow PIII and light-evoked decrease in extracellular K+ concentration were larger in the range of perfusion pressure examined. These suggest that some factor induces electroretinographic changes that are not readily explained by hypoxia or pH changes alone.

Design of a new disposable ERG electrode.

A new electrode for electroretinography (ERG) has been produced. The new device made of gold filament was applied as corneal and noncorneal electrod. Flash ERG and pattern ERG were recorded in normal subjects using this new electrode and compared with those made by available electrodes. There were so significant differences in amplitude and latency between the new electrode placed on the cornea and the JET-type electrode. For pattern ERG there were no significant differences between the new electrode placed in the lower fornix and a gold-foil-type electrode. As this new electrode is less expensive and more comfortable than the available electrodes, it is clinically useful.

Analysis of electroretinogram during systemic hypercapnia with intraretinal K(+)-microelectrodes in cats.

PURPOSE: Systemic hypercapnia alters the intraretinal pH and metabolism and profoundly affects the vitreal electroretinogram (ERG). Using intraretinal K(+)-selective microelectrodes (ISMs), the authors examined the effects of systemic hypercapnia on ERG in the intact cat eye in vivo. METHODS: Double-barreled K(+)-ISMs were used to record intraretinal, light-evoked [K+]o decrease, intraretinal ERG, vitreal ERG, and standing potential (SP) in the dark-adapted retina. Hypercapnia was induced by adding CO2 to the inhaled mixture of gas (without significant hypoxia). RESULTS: The standing potential was elevated, and the vitreal ERG c-wave increased in amplitude whereas the b-wave decreased during hypercapnia. Intraretinal recordings showed that the amplitudes of slow PIII and the transepithelial (TEP) c-wave decreased. The slow PIII decreased more than the TEP c-wave. The light-evoked [K+]o decrease also was reduced, but no change was noted in the subretinal [K+]o. CONCLUSION: The neural retina was more sensitive than the retinal pigment epithelium to the intraretinal acidification caused by systemic hypercapnia. However, the change in the SP and b-wave suggested complicated effects other than acidosis.

[Detection of HTLV-1 provirus DNA in T-cell neoplasms].

Using polymerase chain reaction (PCR) amplification and Southern hybridization, gag, pol, env and pX region genes of HTLV-1 provirus were detected in T-cell malignancy such as adult T-cell leukemia/lymphoma (ATLL), mycosis fungoides in leukemic phase (MF) and, CD8-leukemia. The gag, pol, and/or env regions, were not amplified in some cases of ATLL, which was considered to be induced by mutation, but not deletion. However, the pX-1 and pX-2 regions could be amplified in all cases examined. As it is suggested that the pX gene plays an important role in leukemogenesis, the mutation may not occur in this region gene. Interestingly, the pX-2 was amplified in the cases with MF and CD8-leukemia as well. The amplified products were hybridized to the HTLV-1 pX sequence, even though the products contained DNA fragments with a size larger than expected as well as those of an expected size. These results indicated the possibility that the virus having sequence identical with HTLV-1 pX is integrated in the tumor cells of MF and CD8 leukemia.

Intraretinal study of cat electroretinogram during retinal ischemia-reperfusion with extracellular K+ concentration microelectrodes.

PURPOSE: Intraretinal electroretinograms (ERG) during retinal ischemia-reperfusion were analyzed to clarify which cells are affected in the cat dark-adapted eye. METHODS: Ischemia was induced by raising the intraocular pressure above arterial systolic pressure in vivo. Double-barreled microelectrodes were used to record the intraretinal ERGs and the light-evoked [K+]o decrease in the subretinal space. Vitreal ERGs, the standing potential and the transepithelial resistance were also recorded. RESULTS: After 10 minutes of ischemia, vitreal ERG b- and c-waves had recovered fully in 2 hours, and after 30 minutes of ischemia, recovered approximately 85% and 77% of their control amplitudes in 4 hours, respectively. At the early period of reperfusion after 10 minutes of ischemia we observed the supernormal c-wave (124% of its control amplitude, n = 10) with an elevated standing potential. The transepithelial potential (TEP) c-wave increased without changes of slow PIII and transepithelial resistance when the supernormal amplitudes occurred. The light-evoked [K+]o decrease in the subretinal space (90% retinal depth) in the area centralis recovered to about 90% of the control amplitude in 2 hours, and after 30 minutes of ischemia recovered to about 70% of the control amplitudes in 4 hours. The recovery courses of the slow PIII and TEP c-wave were almost the same as that of the light-evoked [K+]o decrease. CONCLUSIONS: The temporary supernormal amplitude of the ERG c-wave was originated from the retinal pigment epithelium (RPE) during the early period of reperfusion after 10 minutes of ischemia. The photoreceptors, Muller cell and RPE are responsible for the changes in the light-evoked [K+]o decrease, a slow PIII and TEP c-wave, respectively. Intraretinal recordings suggested that after ischemia of 10 to 30 minutes duration, the responses of photoreceptors, Muller cells and the RPE recovered with a similar time course. These findings suggest that in all cases, primarily photoreceptors were damaged.

Effects of intravenous superoxide dismutase and catalase on electroretinogram in the cat postischemic retina.

We examined the effects of the antioxidant enzymes, 10,000 U/kg of superoxide dismutase (SOD) and 50,000 U/kg of catalase (CAT) on cat electroretinograms during the reperfusion after retinal ischemia. The intravenous administrations of SOD and CAT promoted the recovery of the c-wave after 30 min of ischemia but not the b-wave. At 5 min after onset of reperfusion, SOD- and CAT-treated eyes showed 90 and 110% recovery of the c-wave amplitude respectively, against 50% recovery in the untreated eyes. These results suggested that the oxygen-derived free radicals affected the retinal pigment epithelium at the early period of reperfusion.

Ascorbic acid phosphate ester and wound healing in rabbit corneal alkali burns: epithelial basement membrane and stroma.

We examined the effect of L-ascorbic acid 2-phosphate (P-Asc) on the healing of alkali-burned corneas in rabbits. Round filter paper containing 1 N NaOH was applied to the central cornea for 60 or 120 s to produce the alkali burn. Animals were treated with topical saline, 10% ascorbate, or 6.5% P-Asc applied on the cornea. The corneas were then examined histologically. Burned stroma showed no toluidine blue staining, indicating a loss of glycosaminoglycan. In the 60-s burn group, P-Asc reduced the size of the unstained area as compared with the control. Transmission electron microscopy showed basal lamina under new epithelia in the corneas treated with ascorbate or P-Asc, but not in controls. These observations support the theory that P-Asc may have a therapeutic role in the repair of corneal alkali burns.

Effects of iodate on intraretinal b and c waves of the cat electroretinogram.

In 12 cats, the intravenous and intravitreal administrations of sodium iodate (SI) were performed to examine the effects on b and c waves of electroretinogram in the dark-adapted retina. The intravitreal SI (0.5-3.5 mM) produced the complete suppression of intraretinal b waves without remarkable changes of slow PIII and light-evoked [K+]o decrease in the subretinal space. Intravenous SI (30 mg/kg) also showed the suppression of intraretinal b waves. SI not only acted as a poison to the retinal pigment epithelium but also might block the post-synaptic response.