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Biomedical subjects

Y Fujikawa

Publications and source records attributed to Y Fujikawa.

At least 19 recordsLinked to original sources

Surface and interface studies of GaN epitaxy on Si(111) via buffer layers.

Gallium nitride films, epitaxially grown on Si(111) via a lattice-matched ZrB(2) buffer layer by plasma-assisted molecular beam epitaxy, have been studied in situ by noncontact atomic force microscopy and also in real time by reflection high-energy electron diffraction. The grown films were determined to be always N-polar. First-principles theoretical calculations modeling the interface structure between GaN(0001) and ZrB(2)(0001) clarify the origin of the N polarity.

Journal Article↗

Imaging of all dangling bonds and their potential on the Ge/Si105 surface by noncontact atomic force microscopy.

High-resolution noncontact atomic force microscope (AFM) images were successfully taken on the Ge105-(1 x 2) structure formed on the Si105 substrate and revealed all dangling bonds of the surface regardless of their electronic situation, surpassing scanning tunneling microscopy, whose images strongly deviated from the atomic structure by the electronic states involved. An atomically resolved electrostatic potential profile by a Kelvin-probe method with AFM shows potential variations among the dangling bond states, directly observing a charge transfer between them. These results clearly demonstrate that high-resolution noncontact AFM with a Kelvin-probe method is an ideal tool for analysis of atomic structures and electronic properties of surfaces.

Journal Article↗

Nanofilm allotrope and phase transformation of ultrathin Bi film on Si(111)-7x7.

Our scanning tunneling microscopy and electron diffraction experiments revealed that a new two-dimensional allotrope of Bi forms on the Si(111)-7x7 surface. This pseudocubic [012]-oriented allotrope is stable up to four atomic layers at room temperature. Above this critical thickness, the entire volume of the film starts to transform into a bulk single-crystal (001) phase, as the bulk contribution in the cohesion becomes dominant. Based on ab initio calculations, we propose that the new allotrope consists of black phosphorus-like puckered layers stabilized by saturating all the p(z) dangling bonds in the film.

Journal Article↗

Transforming growth factor-beta induces osteoclast formation in the absence of RANKL.

Transforming growth factor beta (TGFbeta) is a multifunctional growth factor that is produced by many cells in bone and is abundant in the bone matrix. TGFbeta is known to regulate RANKL-induced osteoclast formation and bone resorbing activity. In this study we sought to determine whether TGFbeta could directly induce osteoclast formation by a RANKL-independent mechanism. We found that the addition of TGFbeta to cultures of human monocytes and RAW 264.7 cells (in the presence of M-CSF and the absence of RANKL, TNFalpha or IL-6/IL-11) was sufficient to induce the formation of TRAP+ and VNR+ cells, which formed actin rings and were capable of extensive lacunar resorption. The addition of osteoprotegerin or antibodies to TNFalpha and its receptors, as well as antibodies to gp130, did not inhibit lacunar resorption, indicating that TGFbeta did not act by stimulating RANKL, TNF or IL-6 production by monocytes. TGFbeta-induced osteoclast formation was qualitatively different from that induced by RANKL with numerous TRAP+/VNR+ mononuclear and small multinucleated cells being formed; these cells produced many small resorption lacunae. Our results indicate that TGFbeta, which is abundant in the bone matrix, can, in the presence of M-CSF, directly induce mononuclear phagocyte osteoclast precursors to differentiate into osteoclastic cells capable of lacunar resorption.

Actins↗

Re-evaluation and reconstruction of water purification system using soil. I. Assessment of soil as a sorbent of humic substances and phosphate ion.

The purpose of our study is to develop a treatment procedure for humic substances (HS hereafter) and phosphate ion in wastewater and environmental water by percolation of the water through a constructed soil layer at the hydraulic loading of a few metres per day. In the present work, batch sorption tests were conducted for more than 80 samples of soil, sludge, mineral and organic materials in order to find good sorbents for fulvic acid (FA hereafter) and phosphate ion. The results showed that the sorption of FA was high for some charcoal, and apatite and goethite minerals. Comparatively high sorption of FA was found for some Andosols and volcanic ash soil. Significant sorption of phosphate ion, on the other hand, was found for various types of soil, sludge from water treatment plants and some waste materials. The linear isotherm was obtained for the sorption of FA to a charcoal, apatite and goethite minerals, and Andosols.

Absorption↗

Re-evaluation and re-construction of water purification system using soil. II. Removal of pollutants from infiltrating water.

Presented in this paper are the results of a series of column experiments and a pilot scale test conducted to develop the treatment system of freshwater and wastewater by their percolation through soil and the other materials at the rate of a few metres per day. Materials that had high ability to sorb fulvic acid (FA hereafter) and phosphate ion were selected based on the results of the batch sorption tests and were processed into beads before subjecting them to the column test. The results of the column experiment suggested that the reagents added to increase the strength of the beads reduced the sorption of FA, thus causing the early breakthrough of the FA injected into the column. Less effect from the bead processing was observed for the removal of phosphate ion. Pilot scale test showed that the removal of particulate fraction of phosphorus differed among the materials used. The bead processing technique that can ensure the high water permeability while maintaining the sorption capacity of the material was required for further development of the treatment system.

Benzopyrans↗

Na adsorption on the Si111-(7 x 7) surface: from two-dimensional gas to nanocluster array.

We have systematically investigated Na adsorption on the Si(111)-(7 x 7) surface at room temperature using scanning tunneling microscopy (STM). Below the critical coverage of 0.08 monolayer, we find intriguing contrast modulation instead of localized Na adsorbates, coupled with streaky noise in the STM images, which is accompanied by monotonic work function drop. Above the critical coverage, Na clusters emerge and form a self-assembled array. Combined with first-principles theoretical simulations, we conclude that the Na atoms on the (7 x 7) surface are, while strongly bound ( approximately 2.2 eV) to the surface, highly mobile in "basins" around the Si rest atoms, forming a two-dimensional gas phase at the initial coverage, and that the cluster at the higher coverage consists of six Na atoms together with three Si adatoms.

Journal Article↗

Menatetrenone (vitamin K2) acts directly on circulating human osteoclast precursors.

It is still not certain what the direct effect of menatetrenone is on osteoclast precursors. In the present study, we investigated whether menatetrenone has a direct effect on circulating osteoclast precursors to influence osteoclast differentiation. Monocytes isolated from human peripheral blood were cultured with receptor-activated NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Menatetrenone or vitamin K1 was then added to the cultures. Geranylgeraniol or phytol (the respective side chain) was also added to the cultures instead of menatetrenone or vitamin K1, respectively. After 7 and 14 days incubation, cultures were evaluated for cytochemical and functional evidence of osteoclast formation. The number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) and the percentage area of lacunar resorption induced by RANKL and M-CSF were decreased when menatetrenone or geranylgeraniol was added to the cultures. Dose-dependent inhibition of osteoclast formation and lacunar resorption was seen when the cultures were treated with menatetrenone or geranylgeraniol. In contrast, vitamin K1 or phytol did not affect the number of TRAP-positive MNCs nor the percentage area of lacunar resorption. These results indicate that menatetrenone not only influences osteoclast formation via bone stromal cells but also acts directly on circulating osteoclast precursors to influence osteoclast differentiation. These findings also suggest that geranylgeraniol, the side chain of menatetrenone, plays an important role in this inhibitory effect.

Acid Phosphatase↗

Interleukin-6 and interleukin-11 support human osteoclast formation by a RANKL-independent mechanism.

Interleukin-6 (IL-6) and interleukin-11 (IL-11) are known to influence osteoclast formation and bone resorption. In order to determine whether IL-6 and IL-11 could independently support human osteoclast formation, these factors were added to cultures of human peripheral blood mononuclear cells of the monocyte (CD14(+)) fraction in the presence of macrophage colony-stimulating factor (M-CSF). Under these conditions, IL-6 and IL-11 induced the formation of multinucleated cells which were positive for TRAP, VNR, and calcitonin receptor and capable of lacunar resorption. Osteoclastogenesis induced by IL-6 and IL-11 was inhibited by the addition of an anti-gp130 antibody but not by osteoprotegerin. These results indicate that IL-6 and IL-11, which are thought to play a role in several osteolytic bone disorders, are directly capable of inducing osteoclast formation by a RANKL-independent mechanism.

Acid Phosphatase↗

Long-term response to zonisamide in patients with West syndrome.

The long-term effectiveness of zonisamide (ZNS) was evaluated in 11 patients with West syndrome (7 symptomatic) who had cessation of spasms with ZNS monotherapy. During the follow-up period (24 to 79 months, mean = 53 months), this response was maintained in 7 patients (3 symptomatic, relapse rate = 36%), including 2 children in whom ZNS was successfully discontinued. No serious adverse reactions were noted. ZNS may be both effective and well tolerated for the treatment of West syndrome.

Adolescent↗

Origin of the stability of Ge(105) on si: a new structure model and surface strain relaxation.

The structure of Ge(105)-(1 x 2) grown on Si(105) is examined by scanning tunneling microscopy (STM) and first-principles calculations. The morphology evolution with an increasing amount of Ge deposited documents the existence of a tensile surface strain in Si(105) and its relaxation with increasing coverage of Ge. A detailed analysis of high-resolution STM images and first-principles calculations produce a new stable model for the Ge(105)-(1 x 2) structure formed on the Si(105) surface that includes the existence of surface strain. It corrects the model developed from early observations of the facets of "hut" clusters grown on Si(001).

Journal Article↗

Localization of group IB phospholipase A(2) isoform in the gills of the red sea bream, Pagrus (Chrysophrys) major.

We previously reported that PLA(2) activity in the gills is higher than that in other tissues in red sea bream and purified PLA(2) from the gills belongs to the group IB PLA(2) as well as other red sea bream PLA(2)s. In this study, we reconfirmed that the level of PLA(2) activity is extremely high in the gills compared with other tissues, and gill PLA(2) was detected only in the gills by immunoblotting and inhibition test using anti-gill PLA(2) monoclonal antibody. The level of PLA(2) activity and protein expression in the gills are well correlated. Fish can be roughly divided into high and low groups based on the level of PLA(2) activity. Gill PLA(2) was detected in the gills of the high group, but not the low group by immunoblotting. In the gills of the high group, gill PLA(2) was detected in the mucous cells and pavement cells located on the surface of gill epithelia by immunohistochemistry. On the other hand, positive signals were observed only in the mucous cells by in situ hybridization. We also isolated inactive proPLA(2), having AR propeptide, preceding the mature enzyme from the gill extract. These results suggest that gill PLA(2) is synthesized as an inactive proPLA(2) in the mucous cells and is secreted to the surface of gill epithelia.

Animals↗

Gender- and age-related differences in osteoclast formation from circulating precursors.

A number of bone diseases characterised by excessive osteolysis (e.g. osteoporosis and Paget's disease) exhibit a marked gender difference in prevalence and are more common in the elderly population. Bone resorption is carried out by osteoclasts, which are formed by fusion of circulating mononuclear precursor cells of haematopoietic origin. In this study, we have determined whether there are gender- and age-related differences in osteoclast formation from circulating precursors. Peripheral blood mononuclear cells (PBMCs) were co-cultured with UMR106 osteoblast-like cells in the presence of macrophage-colony stimulating factor (M-CSF) and 1,25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) or cultured alone in the presence of sRANKL (soluble receptor activator of nuclear factor kappa B ligand) and M-CSF. As assessed by the formation of tartrate resistant acid phosphatase (TRAP)-positive (TRAP(+)) and vitronectin receptor-positive (VNR(+)) multinucleated cells (MNCs), there was no difference in the number of circulating osteoclast precursors in males and females. Lacunar resorption carried out by osteoclasts formed from these precursors was generally increased in males compared with females (P=0.03). An increase in the number of TRAP(+) and VNR(+) MNCs formed from male PBMCs was noted in response to 1,25(OH)(2)D(3) (P<0.005). An increase in lacunar resorption in cultures of PBMCs (10(5) per well) from males was also noted in response to 10(-9) M 1,25(OH)(2)D(3) (P<0.05) and sRANKL (P=0.05), but not M-CSF. The addition of dexamethasone resulted in a marked increase in osteoclast formation and lacunar resorption in both males and females. Post-menopausal females and males of comparable age showed similar levels of osteoclastogenesis. Pre-menopausal women showed similar levels of osteoclastogenesis but less resorption (P=0.01) compared with males of comparable age. These results show that there are specific gender/age-related differences in osteoclast formation and bone resorption and have implications for evaluating osteoclastogenesis in skeletal diseases such as primary osteoporosis and Paget's disease.

Adult↗

Cellular mechanisms of bone resorption in breast carcinoma.

The cellular mechanisms that account for the increase in osteoclast numbers and bone resorption in skeletal breast cancer metastasis are unclear. Osteoclasts are marrow-derived cells which form by fusion of mononuclear phagocyte precursors that circulate in the monocyte fraction. In this study we have determined whether circulating osteoclast precursors are increased in number or have an increased sensitivity to humoral factors for osteoclastogenesis in breast cancer patients with skeletal metastases (+/- hypercalcaemia) compared to patients with primary breast cancer and age-matched normal controls. Monocytes were isolated and cocultured with UMR 106 osteoblastic cells in the presence of 1,25 dihydroxyvitamin D3[1,25(OH)2D3] and human macrophage colony stimulating factor (M-CSF) on coverslips and dentine slices. Limiting dilution experiments showed that there was no increase in the number of circulating osteoclast precursors in breast cancer patients with skeletal metastases (+/- hypercalcaemia) compared to controls. Osteoclast precursors in these patients also did not exhibit increased sensitivity to 1,25(OH)2D3or M-CSF in terms of osteoclast formation. The addition of parathyroid hormone-related protein and interleukin-6 did not increase osteoclast formation. The addition of the supernatant of cultured breast cancer cell lines (MCF-7 and MDA-MB-435), however, significantly increased monocyte-osteoclast formation in a dose-dependent fashion. These results indicate that the increase in osteoclast formation in breast cancer is not due to an increase in the number/nature of circulating osteoclast precursors. They also suggest that tumour cells promote osteoclast formation in the bone microenvironment by secreting soluble osteoclastogenic factor(s).

Aged↗

Synthesis and biological evaluations of condensed pyridine and condensed pyrimidine-based HMG-CoA reductase inhibitors.

A series of 3,5-dihydroxyheptenoic acid derivatives containing pyrazolopyridine, isoxazolopyridine, thienopyridine, and pyrazolopyrimidine as a key scaffold was synthesized from condensed pyridine and condensed pyrimidine carboxylic acid esters by homologation, aldol condensation with ethyl acetoacetate dianion, and stereoselective reduction of the 5-hydroxyketone. Several compounds in the series were found to have potent HMG-CoA reductase inhibitory activities in vitro and marked cholesterol biosynthesis inhibitory activities in vivo. It has been shown that these scaffolds can be used as a suitable replacement for the hexahydronaphthalene ring present in naturally occurring HMG-CoA reductase inhibitors.

Administration, Oral↗

Effect of particle size on macrophage-osteoclast differentiation in vitro.

To determine whether particle size affects macrophage-osteoclast differentiation in vitro, latex beads of 0.1, 1, and 10 microm in diameter were added to a murine macrophage-UMR106 osteoblast-like cell coculture system. The extent of osteoclast differentiation was determined by assessing the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells on glass coverslips and the extent of lacunar resorption on dentine slices. The addition of particles, 1 and 10microm in size, to the cocultures resulted in a significant increase in the number of TRAP-positive osteoclast-like cells and in the resorption pit surface area compared with findings in control cultures to which no particles had been added. Particles 0.1 microm in size also stimulated osteoclast formation relative to the control; however, the difference was not significant. These results indicate that particles, particularly these 1 and 10microm in size, sizes which were phagocytosable, significantly enhanced the process of macrophage-osteoclast differentiation and suggest that particle size plays an important role in periprosthetic osteolysis.

Acid Phosphatase↗

Cloning and expression of group IB phospholipase A2 isoforms in the red sea bream, Pagrus major.

Two cDNA encoding red sea bream DE-1 and DE-2 phospholipases A2 (PLA2) were cloned from the hepatopancreas of red sea bream, Pagrus (Chrysophrys) major. The cDNA of DE-1 PLA2 encoded a mature protein of 125 amino acid residues with an apparent signal peptide of 20 residues and propeptide of 5 residues, and that of DE-2 PLA2, a mature protein of 126 amino acid residues with an apparent signal peptide of 17 residues and propeptide of 6 residues. Comparison of the predicted amino acid sequences for mature DE-1 and DE-2 PLA2 showed that both proteins contain 14 cysteines including Cys 11 and 77 and a pancreatic loop, which are commonly conserved in group IB PLA2; however, the identity in amino acid sequence between DE-1 and DE-2 PLA2 was low (47%). A previous report concerning the cDNA cloning of red sea bream gill G-3 PLA2 and the present results represent the first cloning and sequencing of three distinct isoforms of group IB PLA2 in a single fish species, red sea bream. Reverse transcription-polymerase chain reaction analysis showed that DE-1 PLA2 mRNA was expressed in the hepatopancreas, pyloric ceca, intestine, spleen, gonad, stomach, and kidney, whereas gill G-3 PLA2 mRNA was expressed only in the gills and gonad. The expression of DE-2 PLA2 mRNA was detected in all of the tissues analyzed. These results indicate that three distinct isoforms of group IB PLA2, DE-1 and DE-2 PLA2 in hepatopanceas and gill G-3 PLA2, are expressed in a tissue-specific manner in red sea bream.

Amino Acid Sequence↗