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Biomedical subjects

Y Takano

Publications and source records attributed to Y Takano.

At least 19 recordsLinked to original sources

Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis.

Tumour growth depends on angiogenesis, which is closely associated with vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Extracellular MMP inducer (EMMPRIN) was reported to involve in the progression of malignancies by regulating expression of VEGF and MMPs in stromal cells. To clarify the role of EMMPRIN in progression and angiogenesis of gastric carcinoma, expression of EMMPRIN, ki-67, MMP-2, MMP-9 and VEGF was examined on tissue microarray containing gastric carcinomas (n=234) and non-cancerous mucosa adjacent to carcinoma (n=85) by immunohistochemistry. Additionally, microvessel density (MVD) was assessed after labelling with anti-CD34 antibody. Extracellular MMP inducer expression was compared with clinicopathological parameters of tumours, including levels of ki-67, MMP-2, MMP-9 and vascular endothelial growth factor (VEGF), MVD as well as survival time of carcinoma patients. Gastric carcinoma cell lines (HGC-27, MKN28 and MKN45) were studied for EMMPRIN expression by immunohistochemistry and Western blot. Extracellular MMP inducer expression was gradually increased from normal mucosa to carcinomas through hyperplastic or metaplastic mucosa of the stomach (P<0.05). There was strong EMMPRIN expression in all gastric carcinoma cell lines despite different levels of glycosylation. Extracellular MMP inducer expression was positively correlated with tumour size, depth of invasion, lymphatic invasion, expression of ki-67, MMP-2, MMP-9 and VEGF of tumours (P<0.05), but not with lymph node metastasis, UICC staging or differentiation (P>0.05). Interestingly, there was a significantly positive relationship between EMMPRIN expression and MVD in gastric carcinomas (P<0.05). Survival analysis indicated EMMPRIN expression to be negatively linked to favourable prognosis (P<0.05), but not be independent factor for prognosis (P>0.05). Further analysis showed three independent prognostic factors, depth of invasion, lymphatic and venous invasion, to influence the relationship between EMMPRIN expression and prognosis. Upregulated expression of EMMPRIN possibly contributes to genesis, growth and local invasion of gastric carcinomas. Altered EMMPRIN expression might enhance growth, invasion and angiogenesis of gastric carcinoma via upregulating MMP expression of both stromal fibroblasts and gastric cancer cells and could be considered as an objective and effective marker to predict invasion and prognosis.

Adenocarcinoma↗

Low-energy charge-density excitations in MgB2: Striking interplay between single-particle and collective behavior for large momenta.

A sharp feature in the charge-density excitation spectra of single-crystal MgB2, displaying a remarkable cosinelike, periodic energy dispersion with momentum transfer (q) along the c* axis, has been observed for the first time by high-resolution nonresonant inelastic x-ray scattering (NIXS). Time-dependent density-functional theory calculations show that the physics underlying the NIXS data is strong coupling between single-particle and collective degrees of freedom, mediated by large crystal local-field effects. As a result, the small-q collective mode residing in the single-particle excitation gap of the B pi bands reappears periodically in higher Brillouin zones. The NIXS data thus embody a novel signature of the layered electronic structure of MgB2.

Journal Article↗

Low-energy electrodynamics of superconducting diamond.

Heavily boron-doped, diamond films can become superconducting with critical temperatures Tc well above 4 K. Here we first measure the reflectivity of such a film down to 5 cm(-1), by also using coherent synchrotron radiation. We thus determine the optical gap 2Delta, the field penetration depth lambda, the range of action of the Ferrell-Glover-Tinkham sum rule, and the electron-phonon spectral function alpha2F(omega). We conclude that diamond behaves as a dirty BCS superconductor.

Journal Article↗

Screening and identification of substances that regulate nephrin gene expression using engineered reporter podocytes.

Downregulation of nephrin in podocytes leads to development of proteinuria in human and experimental kidney diseases. However, little is understood about pathophysiologic substances that regulate nephrin expression. In this report, we established conditionally immortalized reporter podocytes REPON for sensitive, continuous monitoring of nephrin gene expression. A murine podocyte cell line harboring a temperature-sensitive simian virus 40 large T antigen was stably transfected with a gene encoding secreted alkaline phosphatase (SEAP) under the control of the 5.4 or 8.3 kb nephrin gene promoter. The established reporter cells REPON5.4 and REPON8.3 were exposed to various pathophysiologic substances, and culture media were subjected to SEAP assay to identify regulators of nephrin gene expression. Among the bioactive substances tested, three physiological ligands of nuclear receptors including all-trans-retinoic acid, 1,25-dihydroxyvitamin D3, and dexamethasone significantly activated the nephrin gene promoter in a dose-dependent manner. These effects were observed in both REPON5.4 and REPON8.3 and were associated with upregulation of nephrin mRNA. The effects of these substances were synergistic, and the maximum effect was observed by combination of three agents. In contrast, inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha as well as phorbol ester significantly downregulated the activity of the nephrin promoter as well as nephrin gene expression. These results elucidated the bidirectional regulation of nephrin by distinct pathophysiologic substances and may provide molecular bases for explaining how proteinuria is induced under pathologic situations and why some ligands for nuclear receptors have the anti-proteinuric potential.

Alkaline Phosphatase↗

Procyanidin oligomers counteract TGF-beta1- and TGF-beta2-induced apoptosis in hair epithelial cells: an insight into their mechanisms.

Procyanidin oligomers are polyphenol compounds we have identified in apples and barley which have hair growth stimulant effects, and which are able to promote hair epithelial cell growth and induce anagen induction of the hair cycle in the in vivo murine model. For the purpose of examining the hair-growing mechanisms of procyanidin oligomers, we examined their relationship to the TGF-beta signal pathway, known to be a regulator of catagen induction, and the mitogen-activated protein kinase cascade linked to cell proliferation. Addition of TGF-beta(1) or TGF-beta(2) to hair epithelial cell cultures dose-dependently decreased cell growth and induced apoptosis; however, addition of procyanidin B-2 to the culture neutralized the growth-inhibiting effects of both TGF-beta(1) and TGF-beta(2) and protected the cells from apoptosis. The same effects were observed with procyanidin B-3. We confirmed that procyanidin B-2 upregulates the expression of MEK-1/2 in cultured murine hair epithelial cells. We speculate that the hair-growing activity of procyanidin oligomers is at least linked to their growth-promoting effects on hair epithelial cells that follow MEK activation and their protective action on TGF-beta(1)- or TGF-beta(2)-induced apoptosis that is assumed to trigger catagen induction in the hair cycle.

Animals↗

Tomonaga-Luttinger liquid in a quasi-one-dimensional S = 1 antiferromagnet observed by specific heat measurements.

Specific-heat experiments on single crystals of the S = 1 quasi-one-dimensional bond-alternating antiferromagnet Ni(C9H24N4)(NO2)ClO2 (NTENP) have been performed in magnetic fields applied both parallel and perpendicular to the spin chains. We have found for the parallel field configuration that the magnetic specific heat (C(mag)) is proportional to temperature (T) above a critical field H(c), at which the energy gap vanishes, in a temperature region above that of the long-range ordered state. The ratio C(mag)/T increases as the magnetic field approaches H(c) from above. The data are in good quantitative agreement with the prediction of the c= 1 conformal field theory in conjunction with the velocity of the excitations calculated by a numerical diagonalization, providing conclusive evidence for a Tomonaga-Luttinger liquid.

Journal Article↗

Disrupted galectin-3 causes non-alcoholic fatty liver disease in male mice.

Galectin-3, a beta-galactoside-binding animal lectin, is a multifunctional protein. Previous studies have suggested that galectin-3 may play an important role in inflammatory responses. Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a liver condition that may progress to end-stage liver disease and based on the known functions of galectin-3, it was hypothesized that galectin-3 might play a role in the development of NAFLD. Thus, this study investigated the role of galectin-3 in NAFLD by comparing galectin-3 knockout (gal3(-/-)) mice and wild-type (gal3(+/+)) mice. The livers of gal3(-/-) male mice at 6 months of age histologically displayed mild to severe fatty change. The liver weight per body weight ratio, serum alanine aminotransferase levels, liver triglyceride levels, and liver lipid peroxide in gal3(-/-) mice were significantly increased compared with those in gal3(+/+) mice. Furthermore, the hepatic protein levels of advanced glycation end-products (AGE), receptor for AGE (RAGE), and peroxisome proliferator-activated receptor gamma (PPARgamma) were increased in gal3(-/-) mice relative to gal3(+/+) mice. In conclusion, this study suggests that the absence of gal3 can cause clinico-pathological features in male mice similar to those of NAFLD.

Alanine Transaminase↗

Assignment of 117 genes from HSA5 to the porcine IMpRH map and generation of a dense human-pig comparative map.

Twenty-two and eight significant quantitative trait loci for economically important traits have been located on porcine chromosomes (SSC) 2q and SSC16 respectively, both of which have been shown to correspond to human chromosome 5 (HSA5) by chromosome painting. To provide a comprehensive comparative map for efficient selection of candidate genes, we assigned 117 genes from HSA5 using a porcine radiation hybrid (IMpRH) panel. Sixty-six genes were assigned to SSC2 and 48 to SSC16. One gene was suggested to link to SSC2 markers and another to SSC6. One gene did not link to any gene, expressed sequence tag or marker in the map, including those in the present investigation. This study demonstrated the following: (1) SSC2q21-q28 corresponds to the region ranging from 74.0 to 148.2 Mb on HSA5q13-q32 and the region from 176.0 to 179.3 Mb on HSA5q35; (2) SSC16 corresponds to the region from 1.4 to 68.7 Mb on HSA5p-q13 and to the region from 150.4 to 169.1 Mb on HSA5q32-q35 and (3) the conserved synteny between HSA5 and SSC2q21-q28 is interrupted by at least two sites and the synteny between HSA5 and SSC16 is also interrupted by at least two sites.

Animals↗

Assignment of 204 genes localized on HSA17 to a porcine RH (IMpRH) map to generate a dense comparative map between pig and human/mouse.

Bi- and uni-directional chromosome painting (ZOO-FISH) and gene mapping have revealed correspondences between human chromosome (HSA) 17 and porcine chromosome (SSC) 12 harboring economically important quantitative trait loci. In the present study, we have assigned 204 genes localized on HSA17 to SSC12 to generate a comprehensive comparative map between HSA17 and SSC12. Two hundred fifty-five primer pairs were designed using porcine sequences orthologous with human genes. Of the 255 primer pairs, 208 (81.6%) were used to assign the corresponding genes to porcine chromosomes using the INRA-Minnesota 7000-rad porcine x Chinese hamster whole genome radiation hybrid (IMpRH) panel. Two hundred three genes were integrated into the SSC12 IMpRH linkage maps; and one gene, PPARBP, was found to link to THRA1 located in SSC12 but not incorporated into the linkage maps. Three genes (GIT1, SLC25A11, and HT008) were suggested to link to SSC12 markers, and the remaining gene (RPL26) did not link to any genes/expressed sequence tags/markers registered, including those in the present study. A comparison of the gene orders among SSC12, HSA17, and mouse chromosome 11 indicates that intra-chromosomal rearrangements occurred frequently in this ancestral mammalian chromosome during speciation.

Acetyltransferases↗

Origin of the metallic properties of heavily boron-doped superconducting diamond.

The physical properties of lightly doped semiconductors are well described by electronic band-structure calculations and impurity energy levels. Such properties form the basis of present-day semiconductor technology. If the doping concentration n exceeds a critical value n(c), the system passes through an insulator-to-metal transition and exhibits metallic behaviour; this is widely accepted to occur as a consequence of the impurity levels merging to form energy bands. However, the electronic structure of semiconductors doped beyond n(c) have not been explored in detail. Therefore, the recent observation of superconductivity emerging near the insulator-to-metal transition in heavily boron-doped diamond has stimulated a discussion on the fundamental origin of the metallic states responsible for the superconductivity. Two approaches have been adopted for describing this metallic state: the introduction of charge carriers into either the impurity bands or the intrinsic diamond bands. Here we show experimentally that the doping-dependent occupied electronic structures are consistent with the diamond bands, indicating that holes in the diamond bands play an essential part in determining the metallic nature of the heavily boron-doped diamond superconductor. This supports the diamond band approach and related predictions, including the possibility of achieving dopant-induced superconductivity in silicon and germanium. It should also provide a foundation for the possible development of diamond-based devices.

Journal Article↗

Comparison of the University of California at Los Angeles Line-by-Line Equivalent Radiative Transfer Model and the Moderate-Resolution Transmission Model for accuracy assessment of the National Polar-Orbiting Operational Environmental Satellite System's Visible-Infrared Imager-Radiometer Suite cloud algorithms.

To support the verification and implementation of the National Polar-Orbiting Operational Environmental Satellite System's Visible-Infrared Imaging-Radiometric Suite (VIIRS) algorithms used for inferring cloud environmental data records, an intercomparison effort has been carried out to assess the consistency between the simulated cloudy radiances-reflectances from the University of California at Los Angeles Line-by-Line Equivalent Radiative Transfer Model and those from the Moderate-Resolution Transmission Model (MODTRAN) with the 16 stream Discrete Ordinate Radiative Transfer Model (DISORT) incorporated. For typical ice and water cloud optical depths and particle sizes, we found discrepancies in the visible and near-infrared reflectances from the two models, which presumably are due to the difference in phase function (nonspherical versus Henyey-Greenstein), different numbers of phase function expansion terms (16 versus 200 terms), and different treatment of forward peak truncation in each model. Using the MODTRAN4, we also found substantial differences in the infrared radiances for optically thick clouds. These differences led to the discovery by MODTRAN4 developers of an inconsistency in the MODTRAN4-DISORT interface. MODTRAN4 developers corrected the inconsistency, which provided dramatic reductions in the differences between the two radiative transfer models. The comparison not only affects the prospective test plan for the VIIRS cloud algorithms but also should lead to improvements in future MODTRAN releases.

Journal Article↗

Macroscopic quantum tunneling in a d-wave high-TC Bi2Sr2CaCu2O8 + delta superconductor.

While Josephson-junction-like structures intrinsic to the layered cuprate high temperature superconductors offer an attractive stage for exploiting possible applications to new quantum technologies, the low energy quasiparticle excitations characteristically present in these d-wave superconductors may easily destroy the coherence required. Here we demonstrate for the first time the feasibility of macroscopic quantum tunneling in the intrinsic Josephson junctions of a high temperature superconductor Bi(2)Sr(2)CaCu(2)O(8 + delta), and find it to be characterized by a high classic-to-quantum crossover temperature and a relatively weak quasiparticle dissipation.

Journal Article↗

Structure-activity relationship of neuropeptide gamma derived from mammalian and fish.

This study of relationship between structure and biologic activity was performed using five neuropeptide gammas [NPgamma; mammalian-NPgamma (M-NPgamma), trout-NPgamma (T-NPgamma), goldfish-NPgamma (G-NPgamma), bowfin-NPgamma (B-NPgamma), and shark-NPgamma (S-NPgamma)]. Circular dichroism (CD) spectra showed that all peptides took random structure in buffer solution. In neutral and acidic liposomes, M-NPgamma, T-NPgamma, B-NPgamma, and S-NPgamma still adopted random structure, while G-NPgamma had an alpha-helical structure. The biologic activity of NPgammas has been estimated by their effects on the intestinal motility and arterial relaxation. The intestinal motility was investigated with rat duodenum (RD), carp intestine (CI), and guinea-pig ileum (GPI). The arterial relaxing effect was tested with guinea-pig aorta (GPA) and rat mesenteric artery (RMA). In RD, the order of potency compared with the EC50 value was M-NPgamma >> S-NPgamma >> B-NPgamma >> G-NPgamma >> T-NPgamma. G-NPgamma was the most contractile agent in CI. S-NPgamma was the most contractile agent in GPI. Using an arterial relaxing test, the order of potency was G-NPgamma >> T-NPgamma >> B-NPgamma >> S-NPgamma >> M-NPgamma in GPA, and all NPgammas remarkably reduced relaxing activity in RMA. Despite their structural similarities to NPgammas, G-NPgamma has high affinity to tachykinin receptor-binding sites in GPA and CI, indicating an alpha-helical structure may have a critical role for receptor binding. However, an alpha-helical structure does not play a critical role in recognizing receptor-binding sites in RD and GPI.

Amino Acid Sequence↗

Site-specific effect of ascorbic acid deficiency on the structure and function of odontoblasts in the teeth of osteogenic disorder rat in vivo.

The influence of chronic L-ascorbic acid (AsA) deficiency on dentinogenesis was examined in Osteogenic Disorder Shionogi (ODS) rat, which bear inborn lack of L-gulonolactone oxidase. Weanling male rats were kept on AsA-free diet for 4 weeks until all suffered from scurvy. Control rats were given AsA in drinking water. The dentin of molars and incisors of the scorbutic rats was thinner than that in control, except for the crown-analogue (enamel-related) of incisors. Predentin in scorbutic molars showed irregular thickness, and was almost lacking in roots. In the root-analogue (cementum-related) region of scorbutic incisors, dentin displayed metachromatic incremental lines, and the thickened predentin contained collagen fibrils of irregular diameter. The odontoblasts facing the affected regions contained dilated rough endoplasmic reticulum cisternae. In the crown-analogue of scorbutic incisors, however, dentin, predentin, and odontoblasts were comparable to those of controls. These data indicate that AsA deficiency differentially affects the synthetic and/or secretory activity of odontoblasts in ODS rat teeth in a site-specific manner. The regional differences implicate the presence of putative local factor(s) in the crown-analogue of incisors that might have compensated for AsA deficiency. The odontoblasts in the crown-analogue of incisors may have different requirements for AsA from those in molars and the root-analogue of incisors.

Animals↗

Histochemical localization of cholinesterase activity in the dental epithelium of guinea pig teeth.

Cholinesterase is known for its remarkable diversity in distribution and function. An association of this enzyme with proliferative and morpho-differentiating tissues has been reported in several species. Here we report on the first evidence of the presence of cholinesterase in the enamel organ of continuously erupting incisors and molars of the guinea pig. Frozen sections of the incisors and molars of the guinea pig were incubated for histochemical demonstration of cholinesterase activity by means of the thiocholine method as described by Karnovsky and Root. The cholinesterase activity was observed in several types of cells of the dental epithelium; cells forming the basal portion of the enamel organ, outer enamel epithelium and maturation stage ameloblasts of both the incisors and molars. In the crown analogue side, the outer enamel epithelial cells gained strong reactions for cholinesterase and maintained the reaction throughout the secretory and maturation stages of amelogenesis. In contrast, cholinesterase reactions were lacking in the inner enamel epithelium, pre-ameloblasts, and secretory ameloblasts. In the early stage of enamel maturation, ameloblasts began to show positive reactions for cholinesterase, which was upregulated in the incisal direction. Although both tooth types showed similar reactive patterns for cholinesterase at the growing ends, maturation ameloblasts depicted a different pattern of staining displaying the reactions only sporadically in molars. These data indicate the role of cholinesterase in the enamel organ in tooth morphogenesis and function of guinea pig teeth.

Ameloblasts↗

High magnetic field phase diagram of PrOs4Sb12.

The magnetic phase diagram of PrOs4Sb12 has been investigated by specific heat measurements between 8 and 32 T. A new Schottky anomaly, due to excitations between two lowest crystalline-electric-field (CEF) singlets, has been found for both H parallel (100) and H parallel (110) above the field where the field-induced ordered phase (FIOP) is suppressed. The constructed H-T phase diagram shows weak magnetic anisotropy and implies a crossing of the two CEF levels at about 8-9 T for both field directions. These results provide an unambiguous evidence for the Gamma(1) singlet being the CEF ground state and suggest the level crossing (involving lowest CEF levels) as the driving mechanism of FIOP.

Journal Article↗

Accelerated bone formation and increased osteoblast number contribute to the abnormal tooth germ development in parathyroid hormone-related protein knockout mice.

Our previous study showed that tooth germs at late embryonic stage [later than embryonic day 17.5 (E17.5)] and neonatal homozygous parathyroid hormone-related protein (PTHrP)-knockout mice are compressed or penetrated by the surrounding alveolar bone tissue. In vivo and in vitro studies have shown that the development of the tooth germ proper is not disturbed, but insufficient alveolar bone resorption, due to the decreased number and hypofunction of osteoclasts, is the main cause of this abnormality. In addition to the insufficient alveolar bone resorption, progressive bone formation toward tooth germs was observed in homozygous mice, suggesting that accelerated bone formation also contributes to this abnormality. To further investigate this, homozygous mice at E14.0 and E15.5, when alveolar bone is forming, were used for histochemical and bone histomorphometric analyses. In contrast to the late embryonic stage, the alveolar bone did not yet compress developing tooth germs in homozygous mice on E14.0, but a larger amount of bone tissue was seen compared to wild-type littermates. Histomorphometric analysis of bone at E14.0 revealed that the osteoblast numbers and surfaces in the mandibles and in the bone collar of femora of homozygous mice were significantly higher than those of wild-type mice. However, unlike our previous study showing the osteoclast surface on E18.5 in homozygous mice to be significantly lower than that of wild-type mice, this study at E14.0 showed no significant difference between the two genotypes. To evaluate the amount of calcification around tooth germs, 3D images of mandibles were reconstructed from the calcein-labeled sections of the wild-type and mutant mice. Labeling was performed at E14.0, and the mice were sacrificed 1 h after the calcein injection to minimize the effect of bone resorption. Comparison of the 3D images revealed that the labeled surface was larger around developing tooth germs in homozygous mouse than in wild-type mouse. On day E15.5, osteoblasts approached the enamel organ of homozygous mice but this was not observed in wild-type mice. In this study, we report a systemic increase in osteoblast number and accelerated bone formation in homozygous PTHrP-knockout mice, both of which contribute to the abnormal tooth development.

Acid Phosphatase↗

Inflammatory cells in brush cytology samples correlate with the severity of corneal lesions in atopic keratoconjunctivitis.

BACKGROUND: Inflammatory cells infiltrating to the tarsal conjunctiva are thought to be involved in the pathogenesis of corneal lesions in severe allergic conjunctival diseases. The relation between such cells and the severity of corneal lesions was studied. METHODS: Six patients with atopic keratoconjunctivitis (AKC) were enrolled in this study. Tarsal brush cytology findings and the severity of corneal damage at that point were recorded and analysed for correlation. RESULTS: Four out of six patients exhibited correlation between eosinophils and corneal damage. Three out of six patients exhibited correlation between neutrophils and corneal damage. Two out of six patients exhibited correlation between both eosinophils and neutrophils and corneal damage. Analysis of all data from all patients taken together revealed that both eosinophils and neutrophils in brush cytology samples significantly correlated with corneal damage. CONCLUSIONS: Inflammatory cells in brush cytology samples correlated with corneal damage. Evaluation of the relative percentages of inflammatory cells in brush cytology samples is a useful method of assessing disease activity in allergic conjunctival disease.

Adolescent↗