Yu Sato

Nano-scaled particles of titanium dioxide convert benign mouse fibrosarcoma cells into aggressive tumor cells.

Nanoparticles are prevalent in both commercial and medicinal products; however, the contribution of nanomaterials to carcinogenesis remains unclear. We therefore examined the effects of nano-sized titanium dioxide (TiO(2)) on poorly tumorigenic and nonmetastatic QR-32 fibrosarcoma cells. We found that mice that were cotransplanted subcutaneously with QR-32 cells and nano-sized TiO(2), either uncoated (TiO(2)-1, hydrophilic) or coated with stearic acid (TiO(2)-2, hydrophobic), did not form tumors. However, QR-32 cells became tumorigenic after injection into sites previously implanted with TiO(2)-1, but not TiO(2)-2, and these developing tumors acquired metastatic phenotypes. No differences were observed either histologically or in inflammatory cytokine mRNA expression between TiO(2)-1 and TiO(2)-2 treatments. However, TiO(2)-2, but not TiO(2)-1, generated high levels of reactive oxygen species (ROS) in cell-free conditions. Although both TiO(2)-1 and TiO(2)-2 resulted in intracellular ROS formation, TiO(2)-2 elicited a stronger response, resulting in cytotoxicity to the QR-32 cells. Moreover, TiO(2)-2, but not TiO(2)-1, led to the development of nuclear interstices and multinucleate cells. Cells that survived the TiO(2) toxicity acquired a tumorigenic phenotype. TiO(2)-induced ROS formation and its related cell injury were inhibited by the addition of antioxidant N-acetyl-l-cysteine. These results indicate that nano-sized TiO(2) has the potential to convert benign tumor cells into malignant ones through the generation of ROS in the target cells.

Role of the nucleus reticularis tegmenti pontis on visually induced eye movements

Abstract Optokinetic nystagmus (OKN) and visual suppression of caloric nystagmus were tested in cats with electrolytic lesions in the nucleus reticularis tegmenti pontis (NRT) or with hemicerebellectomies. The animals with a NRT lesion could follow higher stimulus velocities, but the eye movement output saturated at 10°/s. In the hemicerebellectomized cats, on the other hand, slow-phase OKN velocity was normal at stimulus velocities less than 30°/s. In addition, OKN impairment was more transient in the cats with hemicerebellectomies than in those with NRT lesions. In the cats with a NRT lesion, loss of visual suppression of caloric nystagmus was apparent in nystagmus with the slow phase toward the lesion side, whereas in cats with hemicerebellectomies, it was toward the contralateral side to the lesion. These findings suggest that the NRT may be a part of the relay nuclei mediating optokinetic signals responsible for OKN at all optokinetic stimulus velocities and the flocculus may be responsible for OKN at higher optokinetic stimulus velocities. In addition, the NRT may also be one of the prefloccular nuclei conveying visual input signals responsible for visual suppression of caloric nystagmus to the contralateral flocculus.

Visual Suppression of Caloric Nystagmus and Optokinetic Responses in Cats

Previously it was reported that loss of visual suppression (VS) was accompanied by disturbance of optokinetic nystagmus (OKN) in monkeys with lesions at the flocculus. In the present experiment with cats, OKN was investigated after inflicting lesions on either superior colliculus (SC) or inferior olive (IO), both of which are considered to be the main prefloccular relay nuclei to mediate visual signals to the flocculus. VS of caloric nystagmus was recognized in all the IO-lesioned cats and OKN remained normal except in one cat. After the left SC lesions, loss of VS was evidently revealed and optokinetic stimuli produced directional preponderance to the left with diminished responses to the right in 7 of 9 cats. The present findings suggest that the SC may be an important relay nucleus to the flocculus in conveying visual signals responsible for VOR gain.

Electrooculographic evaluation of methylmercury intoxication in monkeys

Abstract Methylmercury chloride (MeHg) was administered to five monkeys. Electrooculography (EOG) was used as an objective measure of vestibular and oculomotor functions. Monkeys with acute and subacute exposures to MeHg exhibited spontaneous nystagmus and positional nystagmus of the apogeotropic type which were the earliest indications of dysfunction prior to the onset of clinical signs and symptoms. In these monkeys the slow-phase velocity of optokinetic nystagmus (OKN) waxed and waned with every test. At velocities of optokinetic stimuli greater than 50°/s, the slow-phase velocity of OKN fluctuated during every test and lagged behind the velocity of the optokinetic stimuli. The second and third phases of optokinetic after-nystagmus appeared at an early stage of the experiment, and were accompanied by the second and third phases of caloric nystagmus. Visual suppression (VS) of caloric nystagmus was normal for MeHg dosages up to 10 mg/kg. Larger dosages resulted in a loss of VS which was observed several days before severe neurological signs and symptoms appeared, and OKN was impaired. Monkeys which were administered minimum MeHg dosage equal to one-tenth of those in monkeys with acute and subacute exposures did not show any neurological or histological changes. The only significant positive signs were spontaneous nystagmus and positional nystagmus. Hence, the EOG is very sensitive to functional disturbances and can be utilized to detect dysfunction in MeHg intoxication.

Ionic Conductivity and Assembled Structures of Imidazolium Salt-Based Block Copolymers with Thermoresponsive Segments

Ionic liquid-based block copolymers composed of ionic (solubility tunable)–nonionic (water-soluble and thermoresponsive) segments were synthesized to explore the relationship between ionic conductivity and assembled structures. Three block copolymers, comprising poly(N-vinylimidazolium bromide) (poly(NVI-Br)) as a hydrophilic poly(ionic liquid) segment and thermoresponsive poly(N-isopropylacrylamide) (poly(NIPAM)), having different compositions, were initially prepared by RAFT polymerization. The anion-exchange reaction of the poly(NVI-Br) in the block copolymers with lithium bis(trifluoromethanesulfonyl)imide (LiNTf2) proceeded selectively to afford amphiphilic block copolymers composed of hydrophobic poly(NVI-NTf2) and hydrophilic poly(NIPAM). Resulting poly(NVI-NTf2)-b-poly(NIPAM) exhibited ionic conductivities greater than 10−3 S/cm at 90 °C and 10−4 S/cm at 25 °C, which can be tuned by the comonomer composition and addition of a molten salt. Temperature-dependent ionic conductivity and assembled structures of these block copolymers were investigated, in terms of the comonomer composition, nature of counter anion and sample preparation procedure.

On the role of the nucleus reticularis tegmenti pontis for visual suppression of caloric nystagmus

Loss of visual suppression (VS) of caloric nystagmus was produced after creating flocculus destruction. The flocculus receives visual signals through a climbing fiber pathway and also through a mossy fiber pathway. In the previous report, we stated that the inferior olive as a source of the climbing fiber might be unrelated to the immediate modification of the vestibuloocular reflex by visual stimuli. A mossy fiber pathway presumably via the superior colliculus is a likely candidate for visual suppression of caloric nystagmus. A very recent anatomical and physiological experiment has revealed that the nucleus pontis (NP) and the nucleus reticularis tegmenti pontis (NRT) project mossy fibers to the flocculus.In the present experiment, major concerns were to ascertain whether NP or NRT is the prefloccular relay nucleus responsible for the VS of caloric nystagmus. To achieve this goal, the VS of caloric nystagmus and optokinetic nystagmus (OKN) were investigated after making lesions in NP or NRT in 27 cats. After making the NP lesions, the VS of caloric nystagmus was revealed and OKN was normal in all the cats with the NP lesion. After making the NRT lesion, loss of VS was observed toward the side opposite to the lesion and OKN showed directional preponderence to the lesion site. These experimental findings are quite compatible with the fact that the early component of the field potentials in the flocculus induced by strobe flashes decreased markedly after making a lesion in the contralateral NRT. Together with the anatomical evidence that the superior colliculus sends its fibers to the NRT, the mossy fiber pathway via NRT is believed to be the final relay nuclei responsible for the VS of caloric nystagmus.

A Newly Devised Box for the Caloric Test in Cats

We devised a new animal box with which the caloric test can be easily performed in the awake cat.The animal box has the following advantages:1) This device is suitable for all adult cats of various sizes in which a steel bar could be passed through both the canines.2) With the animal box standing upright, the horizontal semicircular canal lay in an optimal position, and the caloric test could be easily performed in the awake cat.3) This device is suitable for the positional test. Any desired position is feasible.4) It was also advantageous for the optokinetic test, because bars or clamps do not interfere with movements of the cat.