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The visual system uses the physical laws of nature as constraints for perceiving objects and events. Images violating natural laws would therefore tend to be perceived as unnatural. To understand vision’s implicit knowledge of natural speed in the real world, we examined visual tolerance to artificial speed deviations in 22 natural movies. For most movies, perception could tolerate deviations from original speed by as much as a factor 2×. However, for movies including human body movements or falling objects, perception only tolerated a significantly narrower range of speed deviations. In general, human observers are poor at judging the naturalness of speed in natural scenes except for events involving gravitational or biological motions.

Tin-free Giese reactions, employing primary, secondary, and tertiary alkyl iodides as radical precursors, ethyl acrylate as a radical trap, and sodium cyanoborohydride as a radical mediator, were examined in a continuous flow system. With the use of an automated flow microreactor, flow reaction conditions for the Giese reaction were quickly optimized, and it was found that a reaction temperature of 70 °C in combination with a residence time of 10–15 minutes gave good yields of the desired addition products.

The concentration of calcium in the cerebrospinal fluid (CSF) affects systemic blood pressure; an increase in calcium concentration lowers blood pressure, whereas a decrease raises it. Although this phenomenon has been known for more than 50 years, the precise mechanism is not completely understood. We examined whether the extracellular calcium-sensing receptor (CaSR), which was originally cloned from the parathyroid cells and later found in the brain, contributes to blood pressure regulation by calcium in the CSF. In urethane-anesthetized and artificially ventilated Wistar–Kyoto rats, an intracisternal injection of NPS R-467, an allosteric CaSR activator, decreased blood pressure associated with sympathoinhibition in a dose-dependent manner. Treatment with an inactivator of the CaSR elicited an increase in blood pressure. Similar results were observed in awake and freely moving animals. In contrast, when the CaSR activator/inactivator was administered into the lateral ventricle, the cardiovascular changes were minimal. These results indicate that the CaSR in the brain contributes, at least in part, to the hypotensive effect of centrally administered calcium and suggests that the CaSR in the lower brainstem participates in tonic regulation of blood pressure by sensing a change in the CSF Ca 2+ concentration.

A nanoscale thermal system design, especially for the precise measurement of the temperature distribution in microfabricated devices using novel nanomaterials such as carbon nanotubes and fullerene has become increasingly important along with the development of nanotechnology. A new approach has been proposed toward an optical nanoscale temperature measurement method using near-field optics and fluorescence thermometry, namely, Fluor-NOTN (fluorescent near-field optics thermal nanoscopy). The topographic image and temperature dependence of a fluorescently modified sample, excited by near-field light, are simultaneously monitored. In this article, the temperature dependence of Cy3 fluorescent dye is verified near room temperature (298–308 K). A Cy3 mono-dispersed sample of a permalloy (Ni81Fe19) wire heater, 500 nm in width and 100 nm in thickness, is designed and fabricated. A localized temperature gradient of ΔT = 4 K within a submicron distance from the heater was successfully detected by near-field fluorescence with 100 nm spatial resolution.

To assess the mechanism of gastrointestinal disorders by mycophenolate mofetil (MMF), the intestinal absorption and enterohepatic circulation of mycophenolic acid (MPA), an active metabolite of MMF, and its 7-O-glucuronide (MPAG) were investigated using rat intestinal loops and a linked-rat model. The stability of MPAG in the intestinal fluids, the toxicity of MPA and MPAG to intestinal mucosa, and biliary excretion of MPAG in rats with acute renal failure (ARF) were also characterized. MPA was rapidly and extensively absorbed from the rat intestine whereas MPAG was much less absorbable. When MPA was administered intravenously to bile-donor rats, 1.2% of dose was excreted in bile of receiver rats exclusively as MPAG during 4 h. MPAG was minimally deconjugated in the intestinal fluids. MPAG, but not MPA, significantly enhanced the release of lactate dehydrogenase from intestinal mucosa. When MPA was intravenously administered to ARF rats, the biliary excretion of MPAG significantly increased, compared with that in normal rats. These results demonstrated that MPAG accumulated in the intestinal lumen following biliary excretion and exerted some toxic effect on the intestinal mucosa. It was also suggested that enterohepatic circulation of MPAG under renal dysfunction increased the risk of gastrointestinal disorders due to MPAG.

Theiler's murine encephalomyelitis virus (TMEV) causes a demyelinating disease in infected mice which has similarities to multiple sclerosis. Spleen cells from TMEV-infected SJL/J mice stimulated with antigen-presenting cells infected with TMEV resulted in a population of autoreactive CD8+cytotoxic T cells that kill uninfected syngeneic cells. We established CD8+T cell clones that could kill both TMEV-infected and uninfected syngeneic targets, although infected target cells were killed more efficiently. The CD8+T-cell clones produced gamma interferon when incubated with either infected or uninfected syngeneic target cells. Intracerebral injection of the clones into naïve mice induced degeneration, not only in the brain, but also in the spinal cord. This suggests that CD8+Tc1 cells could play a pathogenic role in central nervous system inflammation.

Although the idea that energy metabolism of rats decreases with age has been widely accepted, few studies with regard to the diurnal rhythm of energy expenditure have been reported. Whether age alone altered the diurnal rhythm of energy expenditure was examined in Sprague-Dawley (SD) rats. The same determination was conducted in Otsuka Long Evans Tokushima Fatty (OLETF) rats to examine the effect of insulin resistance and diabetes. OLETF rats were developed as a model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity. The characteristic features of OLETF rats are late onset of hyperglycemia at about 18 weeks of age, followed by insulin deficiency at about 65 weeks. Age-associated changes in diurnal rhythm of energy expenditure were not observed in SD rats. In OLETF rats, the diurnal rhythm of energy expenditure with two peaks was observed at 8 weeks of age, while these two peaks disappeared at 24 weeks of age (with NIDDM). Then, the pattern of diurnal rhythm at 44 weeks of age (with advanced NIDDM) was resembled to that of 62 weeks of age (with insulin deficiency). In conclusion, we clarified the changes in diurnal rhythm of energy expenditure associated with the progress of diabetes, while age alone did not alter the diurnal rhythm.

The nanoscale thermal properties are becoming increasingly important for the thermal design of electronic devises as the MEMS technology makes progress. The thermal conductivity of nanoscale thin film is remarkably lower than that of bulk materials because of its various size effects. In addition, the nano-materials will have pointing defects or lattice imperfections during the production process. Therefore, nanoscale thermal properties measurement technique, which can be applied in-situ or in-process, is required. We have developed a new thermal properties measurement technique by using near-field optics, which targets spatial resolution better than 100nm (up to 10nm) and is applicable to measure the thermal properties of nanoscale materials in-situ. In this article, in order to check the validity of the control system, the topographic image of diffraction grating is monitored. Moreover, the temperature change of Al thin film is detected as a thermoreflectance signal. Finally, the capability of our present work, to measure the thermal properties of nanostructures, is discussed.

There are increasing concerns about the diarrhea caused by mycophenolate mofetil (MMF), a potent immunosuppressive agent, in transplant recipients. In this study, the incidence rates of diarrhea with or without MMF administration were investigated in patients who had undergone a renal transplantation in Sapporo City General Hospital. MMF administration was normally started 3 days before operation and diarrhea occurred in approximately 20% of patients every day immediately after MMF administration to 5 days after operation. The incidence rate dropped sharply after 6 days from operation. There was no evidence of gender differences in the incidence rates of diarrhea among MMF-treated patients. When the incident rates were evaluated during a period from 3 days before operation to 7 days post transplantation, the rate was significantly greater in the MMF-treated patients than in the MMF-non-treated patients. Moreover, diarrhea was more severe in MMF-treated patients. Accordingly, it was obvious that the MMF administration made the diarrhea in the renal transplant recipients much worse. Therefore, it is very important for pharmacists to monitor the occurrence of diarrhea in the early stages of MMF administration and provide suitable information about any adverse reactions to patients.

From mice infected with the DA strain of Theiler’s murine encephalomyelitis virus (TMEV), CD8 + cytotoxic T lymphocytes (CTLs) could be detected after stimulation with TMEV infected antigen presenting cells (APCs). These CTLs killed not only TMEV infected but also uninfected syngeneic cells. Killing was associated with interferon (IFN)-g production in ELISPOTassays. The CTLs were efficiently induced by vaccinia virus encoding DA virus capsid proteins, but not by APCs infected with the GDVII strain of TMEV. The CTLs produced IFN-g in response to TMEV infected, but not uninfected, astrocytes. The CTLs could be maintained in the presence of interleukin (IL)-2. We hypothesized that, in DA virus infection, CD8 + CTLs specific for viral capsid protein could recognize self protein on oligodendrocytes by molecular mimicry, leading to demyelination. D 2005 Elsevier B.V. All rights reserved.

The significance of intestinal P-glycoprotein (P-gp) in determining the oral bioavailability of tacrolimus has been still controversial. In this study, we reevaluated the interaction of tacrolimus with P-gp in the rat small intestine, by evaluating its absorption from the rat small intestine and its modulating effect on the absorption of known P-gp substrates (digoxin, methylprednisolone, and vinblastine). Intestinal absorption of tacrolimus itself was as extensive as other P-gp modulators such as cyclosporine and verapamil. While cyclosporine and verapamil significantly increased the absorption of methylprednisolone and vinblastine through potent inhibition of intestinal P-gp, tacrolimus failed to achieve this. When cyclosporine and tacrolimus were intravenously administered to rats, digoxin absorption was significantly increased by cyclosporine but not by tacrolimus. When tacrolimus was coadministered with clotrimazole, a specific CYP3A inhibitor, into the rat small intestine, the area under the curve of tacrolimus blood concentrations increased more than seven-fold compared with that of tacrolimus alone. Our present results strongly suggest that the interaction between tacrolimus and P-gp is limited in the rat small intestine and that extensive metabolism by CYP3A enzymes is more responsible for the low oral bioavailability of tacrolimus. It was considered that the extensive absorption of cyclosporine and verapamil was closely associated with their potent ability to inhibit intestinal P-gp.

Otsuka Long Evans Tokushima Fatty (OLETF) rats were developed as a model of non-insulin-dependent diabetes mellitus (NIDDM) with mild obesity. We reported that the daily profiles of energy expenditure associated with two peaks (one between 05:00 and 08:00 and the other between 20:00 and 22:00) were observed at 8 weeks of age (without NIDDM), while these two peaks disappeared at 24 weeks of age with NIDDM. As a new anti-diabetic drug, a peroxisome proliferator-activated receptor g agonist pioglitazone hydrochloride has been developed, we examined whether pioglitazone normalized daily profiles of energy expenditure at 24 weeks of age. A control diet and pioglitazone (0.1%)-containing diet were fed from 6 weeks of age. The two peaks of daily profiles of energy expenditure, which disappeared in OLETF rats with the control diet at 24 weeks of age, were reproduced by administration of pioglitazone. The respiratory quotient was lower and fat derived energy used for combustion was increased by pioglitazone at both ages. The body weight, daily food intake, plasma levels of fat, insulin, leptin and the wet weight of visceral fat were not influenced, but the levels of blood hemoglobin A1c and plasma tumor necrosis factor α were decreased by pioglitazone. Administration of pioglitazone improved daily profiles of energy expenditure via affecting glucose and fat metabolisms.