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Biomedical subjects

Satoru Kawai

Publications and source records attributed to Satoru Kawai.

16 recordsLinked to original sources

A reexamination of the size-weight illusion induced by visual size cues.

The size-weight illusion induced by visually perceived sizes was reexamined to investigate whether this illusion is a sensory based or cognitive-based phenomenon. A computer-augmented environment was utilized to manipulate visual size information of target objects independently of their haptic information. Two physical cubes of equal mass (30.0 g) and size (3.0 x 3.0 x 3.0 cm) were suspended in parallel by wires attached to small graspable rings, in order to keep haptically obtained information constant between lifts. Instead of directly seeing each physical cube, subjects viewed 3D graphics of a cube with a wire and a ring that were precisely superimposed onto each physical cube. Seventeen subjects vertically lifted these augmented cubes, one after the other, by grasping the attached rings, and then reported their perception of cube heaviness. The graphical size of a comparison cube pseudo randomly varied for every comparison from 1.0 x 1.0 x 1.0 to 9.0 x 9.0 x 9.0 cm, while that of a standard cube remained constant (5.0 x 5.0 x 5.0 cm). Results indicated that the size-weight illusion frequently and systematically occurred for all the subjects such that when the comparison cube was relatively smaller than the standard cube, it was perceived to be heavier, and vice versa. As the size difference increased between the standard cube and the comparison cube, more subjects experienced the illusion, and vice versa. Follow-up tests showed occurrence of the size-weight illusion was significantly correlated with subject's sensitivity to discriminate weight, but not with sensitivity to discriminate visual size. Results suggest that the size-weight illusion induced by only visual size cues in an augmented environment is sensory based, and depends on an individual's integrated perception based on multimodal sensory information.

Adult↗

Does estrogen contribute to the hepatic regeneration following portal branch ligation in rats?

The aim of this study was to determine whether estrogen plays any role in the hepatic regeneration of nonligated lobe following portal branch ligation (PBL). Male rats were subjected to PBL on the left and middle lobes. Two and 7 days after PBL, the rats were killed and blood and liver samples were analyzed. Sham animals underwent only laparotomy. The serum estradiol levels were significantly elevated on day 2 following PBL and returned to normal levels on day 7. The expression of estrogen receptors (ER) in the liver evaluated by Western blotting did not show any change in the nonligated lobe compared with shams. Immunohistochemical study for ER showed a predominant ER expression in the hepatocyte nucleus in periportal area (zone 1), although there was no apparent difference in the amount and expression pattern between sham and PBL. However, chronic inhibition of ER by an ER antagonist (ICI 182,780) showed a significantly lower regeneration rate of the nonligated lobe compared with vehicle treatment. Liver regeneration-associated genes also were less activated in the ICI group. Moreover, portal venous flow, determined by fluorescent microsphere injection, was significantly lower in the ICI group compared with vehicle group. These changes correlated with the attenuated expression of endothelial nitric oxide synthase mRNA in both superior mesenteric arteries and veins. In conclusion, these results indicate that the estrogen's contribution on hepatic regeneration following PBL is at least partly mediated through maintaining mesenteric blood flow by mesenteric endothelial nitric oxide synthase upregulation rather than directly activating liver regeneration in the liver.

Alanine Transaminase↗

PbGCbeta is essential for Plasmodium ookinete motility to invade midgut cell and for successful completion of parasite life cycle in mosquitoes.

When malaria parasites enter to mosquitoes, they fertilize and differentiate to zygotes and ookinetes. The motile ookinetes cross the midgut cells and arrive to the basement membranes where they differentiate into oocysts. The midgut epithelium is thus a barrier for ookinetes to complete their life cycle in the mosquitoes. The ookinetes develop gliding motility to invade midgut cells successfully, but the molecular mechanisms behind are poorly understood. Here, we identified a single molecule with guanylate cyclase domain and N-terminal P-type ATPase like domain in the rodent malaria parasite Plasmodium berghei and named it PbGCbeta. We demonstrated that transgenic parasites in which the PbGCbeta gene was disrupted formed normal ookinetes but failed to produce oocyst. Confocal microscopic analysis showed that the disruptant ookinetes remained on the surface of the microvilli. The disruptant ookinetes showed severe defect in motility, resulting in failure of parasite invasion of the midgut epithelium. When the disruptant ookinetes were cultured in vitro, they transformed into oocysts and sporozoites. These results demonstrate that PbGCbeta is essential for ookinete motility when passing through the midgut cells, but not for further development of the parasites.

Adenosine Triphosphatases↗

Enhancement of splenic glucose metabolism during acute malarial infection: correlation of findings of FDG-PET imaging with pathological changes in a primate model of severe human malaria.

In the current study, to elucidate the clinical features of severe malaria, we performed whole-body positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) of Plasmodium coatneyi-infected acute-phase Japanese macaques. The infected monkeys clearly exhibited increase in splenic FDG uptake indicating marked enhancement of glucose metabolism. The standardized uptake values (SUVs) of the spleen in the infected monkeys were significantly higher than those in the uninfected monkey. At autopsy, splenomegaly was clearly present in all infected monkeys, and histopathologic findings included hyperplasia of lymphoid follicles in white pulp, a large number of activated macrophage, and congestion of parasitized red blood cells (PRBCs) and malaria pigments in red pulp. We suggest that increase in splenic glucose uptake may thus be closely related to activation of splenic clearance system against blood-stage malarial parasites.

Animals↗

SURFIN is a polymorphic antigen expressed on Plasmodium falciparum merozoites and infected erythrocytes.

The surfaces of the infected erythrocyte (IE) and the merozoite, two developmental stages of malaria parasites, expose antigenic determinants to the host immune system. We report on surface-associated interspersed genes (surf genes), which encode a novel polymorphic protein family, SURFINs, present on both IEs and merozoites. A SURFIN expressed in 3D7 parasites, SURFIN4.2, was identified by mass spectrometric analysis of peptides cleaved off the surface of live IEs with trypsin. SURFINs are encoded by a family of 10 surf genes, including three predicted pseudogenes, located within or close to the subtelomeres of five of the chromosomes. SURFINs show structural and sequence similarities with exported surface-exposed proteins (PvSTP1, PkSICAvar, PvVIR, Pf332, and PfEMP1) of several Plasmodium species. SURFIN4.2 of a parasite other than 3D7 (FCR3S1.2) showed polymorphisms in the extracellular domain, suggesting sequence variability between genotypes. SURFIN4.2 not only was found cotransported with PfEMP1 and RIFIN to the IE surface, but also accumulated in the parasitophorous vacuole. In released merozoites, SURFIN4.2 was present in an amorphous cap at the parasite apex, where it may be involved in the invasion of erythrocytes. By exposing shared polymorphic antigens on IEs and merozoites, the parasite may coordinate the antigenic composition of these attachment surfaces during growth in the bloodstream.

Animals↗

Cerebral metabolic reduction in severe malaria: fluorodeoxyglucose-positron emission tomography imaging in a primate model of severe human malaria with cerebral involvement.

Cerebral metabolic changes in Japanese macaques (Macaca fuscata) infected with Plasmodium coatneyi, a primate model of severe human malaria with cerebral involvement, were directly evaluated by fluorodeoxyglucose-positron emission tomography (FDG-PET). We observed diffuse and heterogeneous reduction of metabolism in the cerebral cortex in the acute phase of malaria infection. Neuropathologic examination showed preferential sequestration of parasitized red blood cells in the cerebral microvasculature. However, hemorrhagic change or necrosis was not observed in hematoxylin and eosin-stained and Nissl-stained brain tissues. This suggests that reduction of cerebral metabolism occurs before parenchymal changes appear in the brain. This may be one reason why more than half of the patients with cerebral malaria have no neurologic sequelae after recovery.

Animals↗

Heaviness perception. III. Weight/aperture in the discernment of heaviness in cubes haptically perceived by thumb-index finger grasp.

Weight/aperture (W/A) and weight/square aperture (W/A2) rather than weight (W) previously emerged as possible heaviness models for when a cube is haptically held by thumb-index finger grasp. This is based on the convincing evidence that discernment of a cube's heaviness depends on the integration of sensory information about W and size of finger aperture (A). The present study, therefore, determined which model would be the best predictor for subject-perceived heaviness. Fifteen subjects were asked to judge whether the second of a pair of cubes was heavier, lighter, or identical to the first in 3 x 3 (density x weight) conditions. The subject responses were compared with the expected responses for each of the possible heaviness models as well as W. The percentage of consistent trials, i.e., subject response matched the expected response, was then compared among the three models and conditions within each model. The results indicated that subject responses were significantly more consistent with the expected responses determined from W/A compared with those determined from W or W/A2, suggesting W/A as a best predictor of perceived heaviness by finger-grasp perception. W/A2, however, reflected subject responses almost as accurately as W/A could and was, therefore, discussed as one of possible heaviness models when subjects perceive heaviness with different sensory modality.

Adolescent↗

Heaviness perception. IV. Weight x aperture -1 as a heaviness model in finger-grasp perception.

The present study verified that a simple division of Weight/Aperture (W/A) from information obtained from the individual cubes could describe perceived heaviness when pairs of cubic objects were haptically held one-by-one for comparison utilizing a thumb/index finger grasp. To test the effect of W/A, 15 subjects judged the heaviness between a pair of cubes in three experimental conditions with all visual and material input blocked: (1) cubes with similar ratios, but different weights; (2) cubes with different ratios, but of the same weight; and (3) cubes with dissimilar ratios and weights. The largest percentage of errors (67.4%) was made when objects with similar ratios but different weights were presented, because subjects tended to perceive these objects as being of equal weight. In the condition "equal weight and different ratio", the percentage of correct responses (17.7%) was relatively small, as the subjects tended to perceive the objects as being of different weights. These results strongly suggest that the W/A ratio is an authoritative model to explain human performance in the process of discriminating heaviness. The division model is proposed as Weight x Aperture(-1) on the basis of a recently expounded concept of multiplicative neural circuits.

Adolescent↗

Plasmodium coatneyi-infected erythrocytes bind to C32 amelanotic melanoma cells under static and flow conditions.

The ability of Plasmodium coatneyi-infected red blood cells (IRBCs) to bind to C32 amelanotic melanoma cells was examined under static and physiologic flow conditions in vitro. Six blood samples obtained from P. coatneyi-infected Japanese macaques (Macaca fuscata) with severe manifestations of disease were used in the static adhesion assay. All blood samples constantly exhibited binding of IRBCs to C32 cells under static conditions. Immunofluorescence staining with anti-CD36 mAb revealed a positive reaction at the surface of C32 cells with the infected erythrocytes, while the reaction with C32 cells without IRBCs was negative. To further examine the specificity of the interaction between P. coatneyi-infected erythrocytes and C32 cells, we carried out the binding assay under physiological flow conditions. In flow adhesion assay, three blood samples were used. Adhesion and rolling of IRBCs on C32 cells were detected at several rates of shear stress under flow conditions. At a shear stress of 1.0 dyne/cm(2), the number of IRBCs adherent to C32 cell averaged 5 to 6, and the number of IRBCs rolling on C32 cells averaged 6 to 11. The anti-CD36 mAb OKM5 inhibited 75-100% of IRBC adhesion and rolling, while the inhibitory effect of anti-ICAM-1 mAb 84H10 varied between 20-40%. The combination of anti-CD36 and anti-ICAM-1 mAb resulted in 83-100% inhibition of rolling and 100% inhibition of adhesion. These findings suggest that CD36 is one of the principal adhesion receptors of P. coatneyi-infected erythrocytes.

Animals↗

Increased plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell molecule-1 (sVCAM-1) associated with disease severity in a primate model for severe human malaria: Plasmodium coatneyi-Infected Japanese macaques (Macaca fuscata).

In the present study, we investigated plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in seven Japanese macaques (Macaca fuscata) infected with Plasmodium coatneyi. Concentrations of sICAM-1 and sVCAM-1 were significantly elevated in the severe phase; the levels were maximally increased up to six times and three times those before infection, respectively. We subsequently examined kinetic profiles of sICAM-1 and sVCAM-1 concentration in plasma obtained from two infected monkeys. Both infected monkeys had markedly increased levels of these adhesion molecules when they exhibited severe clinical signs correlated with rapid increase in parasitemia. These results suggest that the elevation of levels of sICAM-1 and sVCAM-1 is a critical step in the pathogenesis of severe malaria in vivo.

Animals↗

Grasping an augmented object to analyse manipulative force control.

Augmented reality allows changes to be made to the visual perception of object size even while the tangible components remain completely unaltered. It was, therefore, utilized in a study whose results are being reported here to provide the proper environment required to thoroughly observe the exact effect that visual change to object size had on programming fingertip forces when objects were lifted with a precision grip. Twenty-one participants performed repeated lifts of an identical grip apparatus to a height of 20 mm, maintained each lift for 8 seconds, and then replaced the grip apparatus on the table. While all other factors of the grip apparatus remained unchanged, visual appearance was altered graphically in a 3-D augmented environment. The grip apparatus measured grip and load forces independently. Grip and load forces demonstrated significant rates of increase as well as peak forces as the size of graphical images increased; an aspect that occurred in spite of the fact that extraneous haptic information remained constant throughout the trials. By indicating a human tendency to rely - even unconsciously - on visual input to program the forces in the initial lifting phase, this finding provides further confirmation of previous research findings obtained in the physical environment; including the possibility of extraneous haptic effects (Gordon et al. 1991a, Mon-Williams and Murray 2000, Kawai et al. 2000). The present results also suggest that existing knowledge concerning human manipulation tasks in the physical world may be applied to an augmented environment where the physical objects are enhanced by computer generated visual components.

Adolescent↗

Heaviness perception. I. Constant involvement of haptically perceived size in weight discrimination.

With visual input blocked, subjects in this study utilized fingertips only to investigate the involvement of haptically perceived size in heaviness perception among humans. The objects used for testing consisted of three sets - copper (CP), aluminum (AL), and plastic (PL) - of ten cubes of various weights (0.05-0.98 N). All of the cubes were covered with a smooth vinyl material to eliminate any extraneous input concerning the actual composition. Screens enclosed the working space to eliminate any possible visual cues. Each comparison was between a pair of cubes of the same material to eliminate the effect of density. Fifteen subjects ( M=19.2, SD=0.68 years) attempted to judge differences in heaviness between the first and second cube in each trial that had been handed to them by the experimenter and were grasped between the thumb and the index finger. A total of 340 trials with 70 combinations of weight composed of 160 ascending trials (heavier), 160 descending trials (lighter), and 20 identical weight trials were pseudo-randomly presented to each subject for each material. Combinations of difference in weight and the number of trials were identical for all materials so that haptic size was regarded as the single independent factor. Accuracy of the subjects' responses for identical weight differences that resulted from placing a pair of cubes of the same combination was compared among the three materials. It was observed that a material like CP that had a lesser size effect facilitated significantly more accurate discrimination of the identical weight differences than PL with its greater size effect. This suggests that small changes in haptic size by the fingertips have a direct influence on heaviness perception when comparing objects of equal density. This finding, therefore, can be considered analogous to the size-weight illusion when comparing objects of unequal density. The findings of this study also suggest the constant involvement of haptic size in heaviness perception by humans along with the existence of a processing mechanism that integrates the factors of weight and haptic size in which heaviness increases either as weight increases or as size decreases, and vice versa.

Adolescent↗

Heaviness perception. II. Contributions of object weight, haptic size, and density to the accurate perception of heaviness or lightness.

The present study investigated the contributions of object weight, haptic size, and density to the accurate perception of heaviness or lightness in the process of discriminating differences in weight between pairs of cubes with cue conflicts such as that resulting from the size-weight illusion. Fifteen subjects, with visual input blocked and relying on the input gained by grasping the cubes with only their fingertips, attempted to accurately discriminate possible differences in weight factor between the two respective cubes in each step of the trials. Three sets - one set each of copper (CP), aluminum (AL), and plastic (PL) - of seven cubes of various weight (0.10-0.74 N) were used. All of the cubes were covered with smooth, thin vinyl to eliminate possible input concerning density or material per se. Screens were strategically placed to eliminate any visual cues. One hundred and ninety-six trials with 37 combinations were pseudorandomly presented to subjects in the following conditions: PL versus AL, AL versus CP, and CP versus PL. Trials included 2 x 3 combinations on the basis of density (98 trials for higher and 98 for lower conditions) and weight (84 ascending trials for heavier, 28 for identical, and 84 descending for lighter conditions). The response for each trial given by each subject was regarded as correct when it accurately identified the weight relationship between the first and second cube. It was found that the subjects fairly accurately identified the weight relationship when density and weight both increased for the second cube (95.6% for given trials), and when density and weight both decreased (94.6%). The current results were markedly greater than those in the constant-density conditions obtained previously, suggesting that changes in density may be as much of an aid in the perception of heaviness and lightness as is weight. Whenever two cues conflicted directionally with each other, however, accuracy fell dramatically to 33.6% for lower density/ascending weight, and to 22.7% for higher density/descending weight. These results indicate the possibility of two different cues contributing to the perception of heaviness and lightness. Cue conflict such as the size-weight illusion naturally occurs when discriminating weight between objects. The present results, however, suggest that a person may perceive heaviness on the basis of the well-regulated relations between changes of density, size, and weight. The way in which these two cues are related through the haptic size is discussed.

Adolescent↗

Effect of jasplakinolide on the growth, invasion, and actin cytoskeleton of Plasmodium falciparum.

The effect of jasplakinolide (JAS), an actin-polymerizing and filament-stabilizing drug, on the growth, invasion, and actin cytoskeleton of Plasmodium falciparum was examined. Jasplakinolide markedly decreased the parasitemia in a synchronized culture of P. falciparum strain FCR-3 in a time- and concentration-dependent manner. The decrease became evident at day 2 at concentrations of 0.3 micro M and above, and parasites finally disappeared at day 4. Giemsa-stained smears of P. falciparum-infected erythrocytes demonstrated that there was no effect on the development of schizonts from ring forms. Merozoites were released from the infected erythrocytes in a normal manner with and without JAS. However, there were no ring form-infected erythrocytes when JAS was administered, even after the release of merozoites. This indicates that the merozoites exposed to JAS failed to invade erythrocytes. The inhibitory effect of JAS on the parasitemia was reversed by the removal of the drug after exposure to 1 micro M of JAS for 1 day. Electron microscopy revealed that the merozoites treated with JAS showed a protrusion of the apical end which contained the microfilament structure. Immunoblot analysis indicated that the JAS treatment increased F-actin filaments of merozoites but had no effect on those of the trophozoites and schizonts. Therefore, this study demonstrated that JAS has an antimalarial activity.

Actin Cytoskeleton↗

Chimeric recombinant hepatitis E virus-like particles as an oral vaccine vehicle presenting foreign epitopes.

Many viral and bacterial pathogens establish infections through mucosal surfaces in their initial stage. However, only a few nonreplicating molecules successfully induce strong mucosal immune reaction without the addition of adjuvants by oral administration. To overcome this difficulty, we investigated whether hepatitis E virus-like particles (HEV-VLPs) could be utilized as a carrier molecule for foreign antigenic epitopes and to stimulate mucosal immunity without the need for adjuvants. To accomplish this goal, we incorporated a B cell epitope tag, consisting of 11 amino acids at the C-terminal of HEV-VLP. The chimeric VLP showed morphology similar to that of the mature HEV virion and VLP. The inserted epitope was reactive with a specific monoclonal antibody in the VLP form, suggesting that it was exposed on the surface of the VLP. After oral administration without adjuvant, this chimeric HEV induced significant levels of specific IgG and IgA to both the inserted epitope and HEV-VLP in intestinal secretions. These humoral immune responses were observed as early as 2 weeks after the first immunization. These results suggest the potential of HEV-VLP as a mucosal vaccine carrier vehicle for the presentation of antigenic epitopes through oral administration.

Administration, Oral↗