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1.
Sci Adv ; 5(11): eaax8720, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31763453

RESUMO

The concept of topology has been widely applied in condensed matter physics, leading to the identification of peculiar electronic states on three-dimensional (3D) surfaces or 2D lines separating topologically distinctive regions. In the systems explored so far, the topological boundaries are built-in walls; thus, their motional degrees of freedom, which potentially bring about new paradigms, have been experimentally inaccessible. Here, working with a quasi-1D organic material with a charge-transfer instability, we show that mobile neutral-ionic (dielectric-ferroelectric) domain boundaries with topological charges carry strongly 1D-confined and anomalously large electrical conduction with an energy gap much smaller than the one-particle excitation gap. This consequence is further supported by nuclear magnetic resonance detection of spin solitons, which are required for steady current of topological charges. The present observation of topological charge transport may open a new channel for broad charge transport-related phenomena such as thermoelectric effects.

2.
Sci Adv ; 4(11): eaau7725, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30515457

RESUMO

Topological defects have been explored in different fields ranging from condensed matter physics and particle physics to cosmology. In condensed matter, strong coupling between charge, spin, and lattice degrees of freedom brings about emergent excitations with topological characteristics at low energies. One-dimensional (1D) systems with degenerate dimerization patterns are typical stages for the generation of topological defects, dubbed "solitons"; for instance, charged solitons are responsible for high electrical conductivity in doped trans-polyacetylene. Here, we provide evidence based on a nuclear magnetic resonance (NMR) study for mobile spin solitons deconfined from a strongly charge-lattice-coupled spin-singlet ferroelectric order in a quasi-1D organic charge-transfer complex. The NMR spectral shift and relaxation rate associated with static and dynamic spin susceptibilities indicate that the ferroelectric order is violated by dilute solitonic spin excitations, which were further demonstrated to move diffusively by the frequency dependence of the relaxation rate. The traveling solitons revealed here may promise the emergence of anomalous electrical and thermal transport.

3.
Sci Rep ; 8(1): 15014, 2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30301914

RESUMO

Rapid polarization control by an electric field in ferroelectrics is important to realize high-frequency modulation of light, which has potential applications in optical communications. To achieve this, a key strategy is to use an electronic part of ferroelectric polarization. A hydrogen-bonded molecular ferroelectric, croconic acid, is a good candidate, since π-electron polarization within each molecule is theoretically predicted to play a significant role in the ferroelectric-state formation, as well as the proton displacements. Here, we show that a sub-picosecond polarization modulation is possible in croconic acid using a terahertz pulse. The terahertz-pulse-pump second-harmonic-generation-probe and optical-reflectivity-probe spectroscopy reveal that the amplitude of polarization modulation reaches 10% via the electric-field-induced modifications of π-electron wavefunctions. Moreover, the measurement of electric-field-induced changes in the infrared molecular vibrational spectrum elucidates that the contribution of proton displacements to the polarization modulation is negligibly small. These results demonstrate the electronic nature of polarization in hydrogen-bonded molecular ferroelectrics. The ultrafast polarization control via π-electron systems observed in croconic acid is expected to be possible in many other hydrogen-bonded molecular ferroelectrics and utilized for future high-speed optical-modulation devices.

4.
Chem Sci ; 9(2): 425-432, 2018 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-29629113

RESUMO

The electric-field-induced phase transition from antipolar to polar structures is at the heart of antiferroelectricity. We demonstrate direct evidence of antiferroelectricity by applying a strong electric field to two antipolar crystals of squaric acid (SQA) and 5,5'-dimethyl-2,2'-bipyridinium chloranilate. The field-induced polarization of SQA is quite large and reasonably explained by the theoretically calculated polarization on the hydrogen-bonded sheet sublattice. The pseudo-tetragonal lattice of SQA permits unique switching topologies that produce two different ferroelectric phases of low and high polarizations. By tilting the applied field direction, the electrical switching mechanism can be attributed to a 90° rotation of the sheet polarization. From the viewpoint of applications, the strong polarization, high switching field, and quite slim hysteresis observed in the polarization versus electric field curve for SQA are advantageous for excellent-efficiency energy storage devices.

5.
Transbound Emerg Dis ; 65(2): e434-e443, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29193771

RESUMO

Akabane virus (AKAV) is teratogenic to the foetus of domestic ruminants and causes a significant reproduction loss in cattle in Japan. In several past epizootics in cattle, AKAV was also associated with post-natal encephalomyelitis, mainly in calves and young stock. Previously analysed AKAV isolates in East Asia form two major clusters, genogroups I and II, with isolates involved in encephalomyelitis belonging mainly to the former. Between 2007 and 2013, AKAV epizootics were regularly observed in Japan during the summer/autumn season, and abnormal deliveries and post-natal encephalomyelitis caused by the virus in cattle were reported. During this period, 30 AKAV isolates were obtained from diseased and sentinel cattle, a piglet and Culicoides biting midges throughout Japan and were subjected to genetic comparison and phylogenetic analysis with previous isolates. In 2007, 2011 and 2013, AKAV belonging to genogroup I was identified in the central nervous systems of calves showing neurological disorders. Notably, a total of 165 cases of bovine encephalomyelitis were reported in 2011 and the isolated viruses from affected animals shared high genetic identities with a South Korean isolate that was associated with a large outbreak in 2010, suggesting some epidemiological linkage between these epizootics. Epizootics of genogroup II were observed in 2008 and 2010, but bovine post-natal encephalomyelitis cases rarely occurred. Our findings suggest that the frequent incursion of genogroup I isolates has increased the frequency of post-natal encephalomyelitis cases in Japan in recent years. Infection by genogroup I virus was also identified in piglets with neurological disorders or congenital malformations in 2011 and 2013. The aetiological role of AKAV in pigs should be elucidated in the future.


Assuntos
Infecções por Bunyaviridae/veterinária , Doenças dos Bovinos/virologia , Ceratopogonidae/virologia , Encefalomielite/veterinária , Orthobunyavirus/genética , Orthobunyavirus/isolamento & purificação , Doenças dos Suínos/virologia , Animais , Infecções por Bunyaviridae/epidemiologia , Infecções por Bunyaviridae/virologia , Bovinos , Doenças dos Bovinos/epidemiologia , Surtos de Doenças/veterinária , Encefalomielite/virologia , Feminino , Genótipo , Insetos Vetores/virologia , Japão/epidemiologia , Filogenia , Gravidez , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Suínos , Doenças dos Suínos/epidemiologia
6.
Nat Commun ; 8(1): 281, 2017 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-28819286

RESUMO

Shift current is a steady-state photocurrent generated in non-centrosymmetric single crystals and has been considered to be one of the major origins of the bulk photovoltaic effect. The mechanism of this effect is the transfer of photogenerated charges by the shift of the wave functions, and its amplitude is closely related to the polarization of the electronic origin. Here, we report the photovoltaic effect in an organic molecular crystal tetrathiafulvalene-p-chloranil with a large ferroelectric polarization mostly induced by the intermolecular charge transfer. We observe a fairly large zero-bias photocurrent with visible-light irradiation and switching of the current direction by the reversal of the polarization. Furthermore, we reveal that the travel distance of photocarriers exceeds 200 µm. These results unveil distinct features of the shift current and the potential application of ferroelectric organic molecular compounds for novel optoelectric devices.The bulk photovoltaics refers to an effect whereby electrons move directionally in non-centrosymmetric crystals upon light radiation. Here, Nakamura et al. observe this effect in a ferroelectric organic charge-transfer complex, which shows large diffusion distance of photogenerated electrons over 200 µm.


Assuntos
Cloranila/análogos & derivados , Eletricidade , Elétrons , Luz , Radiação
7.
Clin Radiol ; 72(10): 904.e1-904.e10, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28522258

RESUMO

AIM: To investigate the usefulness of high-resolution 3 T magnetic resonance imaging (MRI) for the evaluation of traumatic and degenerative triangular fibrocartilage complex (TFCC) abnormalities among three groups: patients presenting with wrist pain who were (a) younger than age 50 years or (b) age 50 or older (PT<50 and PT≥50, respectively), and (c) asymptomatic controls who were younger than age 50 years (AC). MATERIALS AND METHODS: High-resolution 3 T MRI was evaluated retrospectively in 96 patients, including 47 PT<50, 38 PT≥50, and 11 AC. Two board-certified radiologists reviewed the MRI images independently. MRI features of TFCC injury were analysed according to the Palmer classification, and cartilage degeneration around the TFCC was evaluated using the Outerbridge classification. Differences in MRI findings among these groups were detected using chi-square test. Cohen's kappa was calculated to assess interobserver and intra-observer reliability. RESULTS: The incidence of Palmer class 1A, 1C and 1D traumatic TFCC injury was significantly (p<0.05) higher in PT≥50 than in PT<50 (class 1A: 47.4% versus 27.7%, class 1C: 31.6% versus 12.8%, and class 1D: 21.1% versus 2.1%). Likewise, MRI findings of TFCC degeneration were observed more frequently in PT≥50 than in PT<50 (p<0.01). Outerbridge grade 2 or higher cartilage degeneration was significantly (p<0.01) more frequently seen in PT≥50 than in PT<50 (55.3% versus 17% in the lunate, 28.9% versus 4.3% in the triquetrum, 73.7% versus 12.8% in the ulna). CONCLUSION: High-resolution wrist MRI at 3 T enables detailed evaluation of TFCC traumatic injury and degenerative changes using the Palmer and Outerbridge classifications, with good or excellent interobserver and intra-observer reliability.


Assuntos
Doenças das Cartilagens/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Fibrocartilagem Triangular/diagnóstico por imagem , Adulto , Fatores Etários , Idoso , Doenças das Cartilagens/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Fibrocartilagem Triangular/lesões , Fibrocartilagem Triangular/patologia , Traumatismos do Punho/diagnóstico por imagem , Traumatismos do Punho/patologia , Articulação do Punho/patologia , Adulto Jovem
8.
Phys Rev Lett ; 118(10): 107404, 2017 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-28339275

RESUMO

Croconic acid crystals show proton displacive-type ferroelectricity with a large spontaneous polarization reaching 20 µC/cm^{2}, which originates from the strong coupling of proton and π-electron degrees of freedom. Such a coupling makes us expect a large polarization change by photoirradiations. Optical-pump second-harmonic-generation-probe experiments reveal that a photoexcited croconic-acid crystal loses the ferroelectricity substantially with a maximum quantum efficiency of more than 30 molecules per one absorbed photon. Based on density functional calculations, we theoretically discuss possible pathways toward the formation of a one-dimensional domain with polarization inversion and its recovery process to the ground state by referring to the dynamics of experimentally obtained polarization changes.

9.
J Dent Res ; 93(3): 245-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24436340

RESUMO

PAX9 is a transcription factor expressed in the tooth mesenchyme during tooth morphogenesis. In Pax9-null mice, tooth development is arrested at the bud stage. In humans, heterozygous mutations in PAX9 have been associated with non-syndromic tooth agenesis, predominantly in the molars. Here, we report 2 novel mutations in the paired domain of PAX9, a three-nucleotide deletion (73-75 delATC) and a missense mutation (C146T), in two unrelated Japanese patients with non-syndromic tooth agenesis. The individual with the 73-75del ATC mutation was missing all maxillary molars and mandibular second and third molars. The individual with the C146T mutation was missing the mandibular central incisors, maxillary second premolars, and first molars, along with all second and third molars. Both mutations affected amino acids that are highly conserved among different species and are critical for DNA binding. When both mutants were transfected to COS7 cells, nuclear localization of PAX9 proteins was not affected. However, reduced expression of the mutant proteins and almost no transcriptional activity of the target BMP4 gene were observed, suggesting haploinsufficiency of PAX9 as the cause of non-syndromic tooth agenesis.


Assuntos
Anodontia/genética , Mutação/genética , Fator de Transcrição PAX9/genética , Adenina , Animais , Dente Pré-Molar/anormalidades , Proteína Morfogenética Óssea 4/genética , Células COS , Chlorocebus aethiops , Sequência Conservada/genética , Citosina , Éxons/genética , Vetores Genéticos/genética , Haploinsuficiência/genética , Heterozigoto , Humanos , Incisivo/anormalidades , Dente Molar/anormalidades , Dente Serotino/anormalidades , Mutação de Sentido Incorreto/genética , Odontogênese/genética , Linhagem , Plasmídeos/genética , Deleção de Sequência/genética , Timina , Germe de Dente/embriologia , Transfecção
10.
J Appl Microbiol ; 114(4): 1147-57, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23311468

RESUMO

AIMS: The oral administration of a compost produced by the fermentation of marine animals with thermophiles confers health benefits for fish and pigs. This study aimed to isolate the beneficial bacteria from this compost that would modulate the physiological conditions of host animals. METHODS AND RESULTS: The compost extract was orally administrated to germ-free mice for 21 days, and thereafter, the culturable bacterial population within the caeca was surveyed. Sequence analyses of the 16S rRNA gene from the two predominant thermophilic isolates revealed organisms that were closely related to Bacillus thermoamylovorans and Bacillus coagulans. These bacteria could grow at 37°C, but more abundantly at 50-55°C, and they were minor components of the original compost extract. When an individual bacterial strain or a mixture of strains was administered to the conventionally maintained mice, their levels of faecal immunoglobulin A, an indicator of the gut immune response, were markedly raised. In addition, their feeding efficiency also changed among the tested mouse groups. CONCLUSIONS: These two kinds of thermophilic bacterial species, isolated from the caeca after compost ingestion to the germ-free mice, are candidate probiotics that could function in the mammalian gut. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed that the compost used in agriculture can contain potential probiotic thermophiles.


Assuntos
Bactérias/isolamento & purificação , Ceco/microbiologia , Probióticos , Microbiologia do Solo , Animais , Bacillus/genética , Bacillus/isolamento & purificação , Bactérias/genética , Fezes/microbiologia , Fermentação , Vida Livre de Germes , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RNA Ribossômico 16S/genética , Solo
11.
Phys Rev Lett ; 104(22): 227602, 2010 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-20867204

RESUMO

The role of solitons in transport, dielectric, and magnetic properties has been revealed for the quasi-one-dimensional organic charge-transfer salt, TTF-QBrCl3 [tetrathiafulvalene (TTF)-2-bromo-3,5,6-trichloro-p-benzoquinone (QBrCl3)]. The material was found to be ferroelectric and hence the solitons should be located at the boundary of the segments with opposite electric polarization. This feature enabled the electric-field control of soliton density and hence the clear-cut detection of soliton contributions. The gigantic dielectric response in the ferroelectric phase is ascribed to the dynamical bound and creeping motions of spinless solitons.

12.
Proc Inst Mech Eng H ; 223(6): 739-48, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19743639

RESUMO

Parafunctional habits, such as bruxism and prolonged clenching, have been associated with functional overloading in the temporomandibular joint (TMJ), which may result in internal derangement and osteoarthrosis of the TMJ. In this study, the distributions of stress on the mandibular condylar surface during prolonged clenching were examined with TMJ mathematical models. Finite element models were developed on the basis of magnetic resonance images from two subjects with or without anterior disc displacement of the TMJ. Masticatory muscle forces were used as a loading condition for stress analysis during a 10 min clenching. In the asymptomatic model, the stress values in the anterior area (0.100 MPa) and lateral area (0.074 MPa) were relatively high among the five areas at 10 min. In the middle and posterior areas, stress relaxation occurred during the first 2 min. In contrast, the stress value in the lateral area was markedly lower (0.020 MPa) than in other areas in the symptomatic model at 10 min. The largest stress (0.050 MPa) was located in the posterior area. All except the anterior area revealed an increase in stress during the first 2 min. The present result indicates that the displacement of the disc could affect the stress distribution on the condylar articular surface during prolonged clenching, especially in the posterior area, probably leading to the cartilage breakdown on the condylar articular surface.


Assuntos
Força de Mordida , Bruxismo/fisiopatologia , Análise do Estresse Dentário/métodos , Côndilo Mandibular/fisiopatologia , Modelos Biológicos , Simulação por Computador , Módulo de Elasticidade , Análise de Elementos Finitos , Humanos , Estresse Mecânico
13.
Phys Rev Lett ; 102(19): 197601, 2009 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-19518994

RESUMO

We have investigated the optical response resulting from the proton-pi-electron-molecular-skeleton coupled dynamics in an organic ferroelectric 55DMBP-Hia. Upon the ferroelectric-to-paraelectric transition, almost all of the vibrational modes below 500 cm;{-1} are anomalously blurred and amalgamated into the high-frequency tail of the polarization-relaxation mode. This indicates that the constituent molecular shape is no more well defined around T_{C} due to the dynamical disorder of the pi-conjugated structure originating from proton delocalization on the intermolecular bifurcated hydrogen bond.

14.
Eur J Clin Nutr ; 62(1): 60-7, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17299464

RESUMO

OBJECTIVE: To examine the effect of purple sweet potato (PSP) beverage rich in acylated anthocyanins on serum hepatic biomarkers in healthy Japanese men. DESIGN: A randomized, double-blind, placebo-controlled, parallel study. SETTING: Kumamoto in Japan. SUBJECTS: Healthy adult men (30-60 years) with borderline hepatitis who had one or more of serum gamma-glutamyl transferase (GGT), aspertate aminotransferase (AST) and alanine aminotransferase (ALT) levels over normal ranges, and who were negative for hepatitis virus were openly recruited by an advertisement. Of the 48 persons enrolled, 38 (mean age 43.0 years (30-54 years)) completed the study. METHODS: The subjects were randomly assigned to the PSP group and the placebo group. During the 8-week intervention, the subjects in the PSP group consumed two bottles of the PSP beverage with acylated anthocyanins (200.3 mg anthocyanins per 125 ml per bottle) per day, and the subjects in the placebo group, two bottles of a placebo beverage (1.7 mg anthocyanins per 125 ml per bottle). All of the data measured were analyzed by two-way repeated measures analysis of variance (ANOVA) with groups and times. The data of the hepatic markers were analyzed using the Dunnett multiple comparison among the time points and t-test between groups at the same time point. Two-sided P<0.05 were defined as the level of significance. RESULTS: Serum GGT, AST and ALT levels showed interactions (P<0.05) between the beverage groups and time; the others were not affected. The PSP beverage group showed lower hepatic marker levels than the placebo group during the ingestion period, particularly the GGT level (-14.1 IU/l, 95% Confidence intervel (CI) -25.4 to -2.7, P=0.017 at 2 weeks; -16.8 IU/l, 95% CI -36.2 to 2.5, P=0.081 at 4 weeks; -26.7 IU/l, 95% CI -47.6 to -5.7, P=0.014 at 6 weeks and -27.9 IU/l, 95% CI -49.9 to -5.9; P=0.014 at 8 weeks). No correlation between alcohol consumption and each hepatic biomarker level before and after the ingestion was observed. CONCLUSION: The intake of the PSP beverage significantly decreased the serum levels of hepatic biomarkers, particularly the GGT level, in healthy men with borderline hepatitis.


Assuntos
Antocianinas/uso terapêutico , Ipomoea batatas/química , Testes de Função Hepática , Fígado/efeitos dos fármacos , Fígado/enzimologia , Adulto , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Bebidas , Biomarcadores/sangue , Método Duplo-Cego , Hepatite/sangue , Hepatite/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , gama-Glutamiltransferase/metabolismo
15.
J Pathol ; 211(5): 516-523, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17318812

RESUMO

Gastric cancers with and without high-frequency microsatellite instability (MSI-H) represent distinctive pathways of carcinogenesis. The aim of this study was to clarify if human leukocyte antigen (HLA) class I antigen subunits and antigen processing machinery (APM) components are differentially downregulated in these two groups of tumours. Using reverse transcription PCR (RT-PCR), loss of heterozygosity (LOH) analysis, methylation-specific PCR (MSP), DNA sequencing, immunohistochemistry, and flow cytometry, we analysed expression and/or alteration of HLA class I antigen subunits and APM components, including low molecular weight polypeptide proteasome subunit (LMP)2, LMP7, LMP10, transporter associated with antigen processing (TAP)1, TAP2, tapasin, proteasome activator (PA) 28alpha, and PA28beta in two stage-matched panels of 30 MSI-H and 30 microsatellite stable (MSS) gastric cancers. Mutations at coding microsatellites (cMS) located within beta2-microglobulin (beta2m) and genes encoding APM components, including endoplasmic reticulum (ER) chaperone protein genes, such as calnexin, SEC63, SEC31, and P4HB (p55), were also analysed. HLA class Ia transcripts were totally downregulated in 18.3% of cancer cases. Locus-specific downexpression of HLA-A, -B, and -C was detected in 41.7%, 45.0%, and 31.7% of cases. Loss of HLA-A was significantly more frequent in MSI-H cancers. The LOH ratios of the HLA-A, -B, and -C loci microsatellite markers were relatively low: 5/32 (15.6%) for D6S306, 4/32 (12.5%) for D6S258, 4/33 (12.1%) for D6S273, and 4/30 (13.3%) for D6S1666. Methylation of HLA-A, -B, and -C was detected in 38.3%, 40.0%, and 28.3% of cases. A significant association between methylation and reduction in expression was observed in gastric cancer tissues. Mutations at cMS of beta2m and APM components were detected in 3.3-46.7% of MSI-H cancers but in none of MSS cancers. These data show that gastric cancers have various defects in HLA class I antigen subunits and APM components and that the MSI phenotype is associated with frequent HLA-A inactivation and frameshift mutations of the beta2m and APM genes.


Assuntos
Antígenos de Neoplasias/imunologia , Antígenos HLA/genética , Instabilidade de Microssatélites , Neoplasias Gástricas/genética , Análise Mutacional de DNA/métodos , DNA de Neoplasias/genética , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Mutação da Fase de Leitura/genética , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Humanos , Imuno-Histoquímica/métodos , Interferons/genética , Perda de Heterozigosidade/genética , Metilação , Fenótipo , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro/genética , Neoplasias Gástricas/imunologia , Regulação para Cima/genética
16.
Scand J Clin Lab Invest ; 65(4): 263-71, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16076681

RESUMO

BACKGROUND: Kidney failure is a common complication in familial amyloidotic polyneuropathy (FAP). It has been suggested that advanced glycation end products (AGEs) play an important role in the development and pathogenesis of FAP. MATERIAL AND METHODS: To evaluate the impact of AGEs on FAP patients' kidney dysfunction, we measured AGE in serum and urine of 28 FAP patients and 18 healthy controls by AGE-specific enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry utilizing antibodies to AGE and the receptor for AGE (RAGE) were used on kidney tissue from 3 FAP patients and 3 diabetic patients to disclose a correlation between amyloid deposits and AGE-RAGE. RESULTS: The glomeruli of FAP patients were heavily deposited with amyloid and the glomerular size was enlarged. The space between Bowman's capsule and glomerulus was totally covered by the enlarged glomerulus. AGE and RAGE were deposited in glomeruli and tubuli and correlated with amyloid deposits. Decreased AGE levels in the liver-transplanted FAP patients' serum compared with that of non-transplanted patients were noted, and AGE concentration in serum tended to be higher in non-transplanted FAP patients compared with normal control subjects. There were no differences in the AGE urine levels in FAP patients compared with controls. No correlation could be found between AGE in urine and serum compared with serum albumin, serum creatinine and creatinine clearance. CONCLUSIONS: The accumulation of AGE, RAGE and amyloid in the kidney of FAP patients suggests that these molecules play an important role in the origin and pathogenesis of renal failure in FAP patients.


Assuntos
Neuropatias Amiloides Familiares/metabolismo , Neuropatias Amiloides Familiares/patologia , Produtos Finais de Glicação Avançada/metabolismo , Insuficiência Renal/metabolismo , Insuficiência Renal/patologia , Neuropatias Amiloides Familiares/complicações , Amiloidose/complicações , Amiloidose/metabolismo , Amiloidose/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Pré-Albumina/metabolismo , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/metabolismo , Insuficiência Renal/etiologia
17.
Br J Cancer ; 92(6): 1098-103, 2005 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-15756272

RESUMO

The putative presence of a mutation in codon 12 of the K-ras gene was investigated in the endometrium of tamoxifen (TAM) and toremifene (TOR)-treated breast cancer patients. DNA was extracted from fresh cytologic samples of the endometrium in 86 TAM and 21 TOR-treated breast cancer patients. Mutations were detected by enriched PCR and an enzyme-linked mini-sequence assay (ELMA). K-ras mutation was found in 35 TAM-treated endometrial samples, and in only one TOR-treated endometrium (P<0.003). In 24 premenopausal patients, K-ras mutation was found in seven (43.8%) of 16 patients with less than 47 months of TAM treatment, while none was found in eight patients with more than 48 months of TAM treatment (P<0.03). In 62 postmenopausal-amenorrheic patients, K-ras mutation was found in three (15.8%) of 19 patients with less than 23 months of TAM treatment, while it was found in 16 (61.5%) of 26 patients with 24-47 months of TAM treatment and nine (52.9%) of 17 patients with more than 48 months of TAM treatment (P=0.002). The presence of K-ras mutation is significantly influenced by the duration of TAM treatment and menstrual status of the patients. TOR may have a lower potential genotoxicity than TAM.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Endométrio/metabolismo , Genes ras , Mutação , Tamoxifeno/uso terapêutico , Toremifeno/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Códon , Endométrio/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Ultrassonografia
18.
Diabetologia ; 48(2): 317-27, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15654600

RESUMO

AIMS/HYPOTHESIS: Glomerular mesangial expansion is a characteristic feature of diabetic nephropathy, and the accumulation of AGE in the mesangial lesion has been implicated as one of its potential causes. However, the route for the AGE accumulation in mesangial lesions in diabetic patients is poorly established. METHODS: Glycolaldehyde-modified BSA (GA-BSA) and methylglyoxal-modified BSA (MG-BSA) were prepared as model AGE proteins, and their in vivo plasma clearance was examined in mice, and renal uptake by in vitro studies with isolated renal mesangial cells. RESULTS: Both (111)In-GA-BSA and (111)In-MG-BSA were rapidly cleared from the circulation mainly by both the liver and kidney. Immunohistochemical studies with an anti-GA-BSA antibody demonstrated that intravenously injected GA-BSA accumulated in mesangial cells, suggesting that such cells play an important role in the renal clearance of circulating AGE proteins. Binding experiments at 4 degrees C using mesangial cells isolated from mice showed that (125)I-GA-BSA and (125)I-MG-BSA exhibited specific and saturable binding. Upon incubation at 37 degrees C, (125)I-GA-BSA and (125)I-MG-BSA underwent endocytic degradation by these cells. The binding of the ligands to these cells was inhibited by several ligands for scavenger receptors. The endocytic degradation of GA-BSA by mesangial cells from class A scavenger receptor (SR-A) knock-out mice was reduced by 80% when compared with that of wild-type cells. The glomerular accumulation of GA-BSA after its intravenous administration was attenuated in SR-A knock-out mice, as evidenced by immunohistochemical observations. CONCLUSIONS/INTERPRETATION: These results raise the possibility that circulating AGE-modified proteins are subjected to renal clearance by mesangial cells, mainly via SR-A. This pathway may contribute to the pathogenesis of AGE-induced diabetic nephropathy.


Assuntos
Acetaldeído/análogos & derivados , Acetaldeído/farmacocinética , Mesângio Glomerular/fisiologia , Proteínas/metabolismo , Aldeído Pirúvico/farmacocinética , Receptores Imunológicos/fisiologia , Actinas/metabolismo , Animais , Área Sob a Curva , Fator VIII/metabolismo , Imuno-Histoquímica , Queratinas/metabolismo , Taxa de Depuração Metabólica , Camundongos , Receptores Depuradores , Receptores Depuradores Classe A , Soroalbumina Bovina/metabolismo , Vimentina/metabolismo
19.
J Microsc ; 213(2): 135-9, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14731295

RESUMO

A novel method for forming dye-containing nano-domains in thin films using a polymer alloy system has been developed. The polymer alloy system (PS-b-PMMA), which consists of polystyrene (PS) and polymethyl methacrylate (PMMA), forms microphase separation in thin films. The film was treated using a previously reported technique under vacuum conditions, and an organic dye was selectively dispersed into the PS. Selective association of the dye (diarylethene; cis-1, 2-dicyano-1, 2-bis (2,4,5-trimethyl-3-thienyl) ethene) with the PS nano-domains was then observed, with both transmission electron microscopy and scanning near-field optical microscopy with an absorption spectrum.

20.
Amino Acids ; 25(3-4): 283-92, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14661091

RESUMO

Our present knowledge on chemically modified proteins and their receptor systems is originated from a proposal by Goldstein and Brown in 1979 for the receptor for acetylated LDL which is involved in foam cell formation, one of critical steps in atherogenesis. Subsequent extensive studies using oxidized LDL (OxLDL) as a representative ligand disclosed at least 11 different scavenger receptors which are collectively categorized as "scavenger receptor family". Advanced glycation endproducts (AGE) and their receptor systems have been studied independently until recent findings that AGE-proteins are also recognized as active ligands by scavenger receptors including class A scavenger receptor (SR-A), class B scavenger receptors such as CD36 and SR-BI, type D scavenger receptor (LOX-1) and FEEL-1/FEEL-2. Three messages can be summarized from these experiments; (i) endocytic uptake of OxLDL and AGE-proteins by macrophages or macrophage-derived cells is mainly mediated by SR-A and CD36, which is an important step for foam cell formation in the early stage of atherosclerosis, (ii) selective uptake of cholesteryl esters of high density lipoprotein (HDL) mediated by SR-BI is inhibited by AGE-proteins, suggesting a potential pathological role of AGE in a HDL-mediated reverse cholesterol transport system, (iii) a novel scavenger receptor is involved in hepatic clearance of plasma OxLDL and AGE-proteins.


Assuntos
Proteínas/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores Imunológicos/metabolismo , Animais , Antígenos CD36 , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Ligantes , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/metabolismo , Modelos Biológicos , Oxirredução , Proteínas/química , Receptores Imunológicos/classificação , Receptores Depuradores , Receptores Depuradores Classe A , Receptores Depuradores Classe B , Receptores Depuradores Classe D , Receptores Depuradores Classe E
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