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1.
Circ J ; 88(6): 876-884, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38569870

RESUMO

BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain.Methods and Results: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.


Assuntos
Implantes Absorvíveis , Clopidogrel , Stents Farmacológicos , Terapia Antiplaquetária Dupla , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Antagonistas do Receptor Purinérgico P2Y , Sistema de Registros , Humanos , Masculino , Idoso , Feminino , Intervenção Coronária Percutânea/efeitos adversos , Pessoa de Meia-Idade , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/administração & dosagem , Clopidogrel/uso terapêutico , Clopidogrel/efeitos adversos , Clopidogrel/administração & dosagem , Estudos Prospectivos , Japão , Terapia Antiplaquetária Dupla/métodos , Hemorragia/induzido quimicamente , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/uso terapêutico , Cloridrato de Prasugrel/efeitos adversos , Polímeros , Resultado do Tratamento
2.
Transfusion ; 63(3): 463-469, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36597800

RESUMO

BACKGROUND: Flow cytometry (FC) has proven its utility in scrutinizing AB antigen expression in red blood cells (RBCs), cooperating with serological tests for accurate blood group typing. However, technical difficulties may impair the characterization of weak ABO subtypes when background noises appear at non-negligible levels. STUDY DESIGN AND METHODS: We sought to establish an FC method that could prevent antibody-induced hemagglutination and an increase in cellular autofluorescence, two major issues inherent to RBC-FC analysis of AB expression. We optimized fixatives, multicolor-staining protocols, and sequential gating strategies. Blood samples from weak ABO subtype cases, Bm and Ael , were analyzed with the established protocol. RESULTS: The optimized mixture of glutaraldehyde and formaldehyde successfully generated fixed RBCs resistant to agglutination while maintaining low autofluorescence. These features allowed co-staining of leukocyte- and erythrocyte-markers, which enabled sequential gating strategies facilitating the precise AB antigen analysis in purely single RBCs with minimum background noises. By the established FC analysis, we could detect in the Bm sample a small RBC population exhibiting weak B antigen expression. The assay also proved it feasible to identify a small population (0.04%) of RBCs weakly expressing the A antigen in the Ael sample confirmed as harboring a rare c.816dupG ABO variant allele. CONCLUSION: The RBC-FC analysis described here allows the detection of AB antigens weakly expressed in RBCs while achieving minimum background noise levels in negative control samples. Overall, the modified protocol provides a quick and reliable assay valuable in transfusion medicine and is potentially applicable to the characterization of rare weak ABO variants.


Assuntos
Sistema ABO de Grupos Sanguíneos , Eritrócitos , Humanos , Citometria de Fluxo/métodos , Eritrócitos/metabolismo , Anticorpos/metabolismo , Tipagem e Reações Cruzadas Sanguíneas , Antígenos/metabolismo
3.
Mod Rheumatol ; 32(3): 641-649, 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-34910187

RESUMO

OBJECTIVES: To clarify the longitudinal changes in patients with preoperative Stage-3 locomotive syndrome (LS) according to different types of surgeries, we investigated the changes in the LS stage in patients who underwent surgery for degenerative musculoskeletal diseases. METHODS: A prospective cohort study was conducted on 168 patients with degenerative diseases [46 spinal deformities treated with thoracolumbar interbody fusion (T/LIF), 86 hips with osteoarthritis treated with total hip arthroplasty (THA), and 36 knees with osteoarthritis treated with total knee arthroplasty (TKA)]. The results for the LS stage, stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale (GLFS-25) were evaluated preoperatively and at 6 months, 1 year, and 2 years postoperatively. RESULTS: Preoperatively, most patients had Stage-3 LS (89.1, 90.8, and 80.6% in the T/LIF, THA, and TKA groups, respectively). At 2 years postoperatively, the Stage-3 LS improved in 41.5, 75.6, and 55.2% of patients in the T/LIF, THA, and TKA groups, respectively. All groups showed similar improvements in the two-step test. The THA group showed the best result in the GLFS-25. CONCLUSIONS: LS stage improved in different patterns over 2 years postoperatively and the LS risk test revealed differences in postoperative movement ability according to the type of surgery.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Osteoartrite , Idoso , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Humanos , Osteoartrite/etiologia , Estudos Prospectivos , Síndrome
4.
Mod Rheumatol ; 31(5): 1050-1058, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32924686

RESUMO

OBJECTIVES: Patients requiring total hip arthroplasty (THA) may possibly have locomotive syndrome (LS). Therefore, we investigated changes of LS in patients undergoing THA and clarified key factors that affected LS stage. METHODS: A prospective cohort study was conducted with 88 patients undergoing THA (74 females, 14 males, mean age: 67.6 years). Data collected using LS stage, stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale results were evaluated before THA, and 6 months, 1 year, and 2 years after THA. Key factors were determined using multivariate analysis and receiver operating characteristic (ROC) curve analysis. RESULTS: Before THA, all patients had fallen LS (stage1: 3.4% and stage2: 96.6%). Overall, 56.8% patients improved their LS stage, and 17.0% of patients overcame LS at 2 years after THA. The key factors that affected LS stage were preoperative two-step test and age. ROC analyses showed a preoperative two-step test score of 0.988 and an age of 67.5 years as a cut-off value for the change of LS stage. CONCLUSIONS: Patients experiencing LS due to hip disorders have the potential to recover after THA. Additional postoperative training may be beneficial for patients with low preoperative two-step test scores to improve their LS stage.


Assuntos
Artroplastia de Quadril , Idoso , Artroplastia de Quadril/efeitos adversos , Feminino , Humanos , Locomoção , Estudos Longitudinais , Masculino , Estudos Prospectivos , Resultado do Tratamento
5.
Biosci Biotechnol Biochem ; 84(12): 2440-2447, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32841581

RESUMO

The anticancer effects of curcumin are based on the induction of apoptosis, but the specific mechanisms have not yet been fully elucidated. To address this issue, we investigated the effects of curcumin on the intrinsic apoptosis pathway using mitochondria from A549 cells. Curcumin decreased the levels of 14-3-3 proteins, key molecules that inhibit the activation of proapoptotic factors known as BH3-only proteins (e.g. Bad). Curcumin-induced suppression of 14-3-3 protein levels was associated with reduced cytosolic Bad and elevation of mitochondrial Bad, leading to a drop in the mitochondrial membrane potential. 14-3-3 proteins generally interact with Bad phosphorylated by AKT, thus preventing its translocation to the mitochondria where it can promote cell death. Curcumin not only decreased the expression of 14-3-3 proteins but also promoted Bad dephosphorylation in an AKT-dependent fashion. Our results provide novel evidence for the induction of apoptosis by curcumin at multiple stages of the mitochondrial cascade.


Assuntos
Proteínas 14-3-3/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Neoplasias Pulmonares/patologia , Proteína de Morte Celular Associada a bcl/metabolismo , Células A549 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos
6.
Sensors (Basel) ; 20(24)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33321954

RESUMO

It is known that humans experience a haptic illusion, such as the sensation of being pulled in a particular direction, when asymmetric vibrations are presented. A pulling illusion has been used to provide a force feedback for a virtual reality (VR) system and a pedestrian navigation system, and the asymmetric vibrations can be implemented in any small non-grounded device. However, the design methodology of asymmetric vibration stimuli to induce the pulling illusion has not been fully demonstrated. Although the frequency of the asymmetric vibration is important, findings on the frequency have not been reported. In this study, we clarified the influences of the effects on the pulling illusion based on the investigation of asymmetric vibration frequency differences. Two psychophysical experiments that related to the frequency of asymmetric vibration were performed. Experiment I showed that the illusion occurs for specific vibration waveforms at 40 Hz and 75 Hz. As a result of Experiment II, the threshold was the lowest when the frequency was 40 Hz, and highest when the frequency was 110 Hz. This result supports the previous hypothesis that the Meissner corpuscles and the Ruffini endings contribute to the illusion, while the Pacinian corpuscles do not.

7.
J Oral Rehabil ; 47(11): 1358-1367, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32895952

RESUMO

BACKGROUND: Quantitative assessment of swallowing function is necessary to prevent swallowing impairment due to ageing. Though surface electromyography (EMG) has been widely used to measure swallowing activity, the relationship between EMG results and swallowing function is unclear. OBJECTIVE: This study examined the relationship between the temporal characteristics of muscle activity and laryngeal elevation (LE) during swallowing. METHODS: This study analysed 60 healthy volunteers in two age groups (young, between 20 and 38 years; old, between 65 and 75 years), each containing the same number of male and female participants. Surface EMG signals were recorded from the suprahyoid and infrahyoid muscle groups (SH-EMG and IH-EMG, respectively). LE was measured using an array of pressure sensors. The participants swallowed 3 mL of water under three swallowing speed conditions: fast, normal and slow swallowing. The EMG duration, EMG time intervals before and after the onset of LE (pre-LE and post-LE intervals, respectively), and the LE velocity were analysed. RESULTS: Both EMG duration and the post-LE interval of IH-EMG were significantly longer in the older group. As for the gender effect, the pre-LE interval of SH-EMG was significantly longer and the LE velocity was significantly higher in men than in women. Furthermore, there was a negative correlation between pre-LE interval and LE velocity in the fast swallowing condition. CONCLUSION: Though ageing slightly prolonged the muscle activity time, gender influenced swallowing activity in a more complex manner. Therefore, it is important to take gender into account when examining swallowing function with increasing age.


Assuntos
Transtornos de Deglutição , Deglutição , Eletromiografia , Feminino , Humanos , Masculino , Músculos do Pescoço
8.
Br J Haematol ; 181(6): 791-802, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29741776

RESUMO

Somatic mutations in the calreticulin (CALR) gene have been found in most patients with JAK2- and MPL-unmutated Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). It has recently been shown that mutant CALR constitutively activates the thrombopoietin receptor MPL and, thus, plays a causal role in the development of MPNs. However, the roles of mutant CALR in human haematopoietic cell differentiation remain predominantly elusive. To examine the impact of the 5-base insertion mutant CALR gene (Ins5) on haematopoietic cell differentiation, we generated induced pluripotent stem cells from an essential thrombocythaemia (ET) patient harbouring a CALR-Ins5 mutation and from a healthy individual (WT). Megakaryopoiesis was more prominent in Ins5-haematopoietic progenitor cells (Ins5-HPCs) than in WT-HPCs, implying that the system recapitulates megakaryocytosis observed in the bone marrow of CALR-mutant ET patients. Ins5-HPCs exhibited elevated expression levels of GATA1 and GATA2, suggesting a premature commitment to megakaryocytic differentiation in progenitor cells. We also demonstrated that 3-hydroxy anagrelide markedly perturbed megakaryopoiesis, but not erythropoiesis. Collectively, we established an in vitro model system that recapitulates megakaryopoiesis caused by mutant CALR. This system can be used to validate therapeutic compounds for MPN patients harbouring CALR mutations and in detailed studies on mutant CALR in human haematological cell differentiation.


Assuntos
Calreticulina/metabolismo , Diferenciação Celular , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Megacariócitos/metabolismo , Mutação , Mielopoese , Calreticulina/genética , Feminino , Fator de Transcrição GATA1/genética , Fator de Transcrição GATA1/metabolismo , Fator de Transcrição GATA2/genética , Fator de Transcrição GATA2/metabolismo , Células-Tronco Hematopoéticas/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Masculino , Megacariócitos/citologia
9.
Appetite ; 116: 493-501, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28572067

RESUMO

Because chewing sounds influence perceived food textures, unpleasant textures of texture-modified diets might be improved by chewing sound modulation. Additionally, since inhomogeneous food properties increase perceived sensory intensity, the effects of chewing sound modulation might depend on inhomogeneity. This study examined the influences of texture inhomogeneity on the effects of chewing sound modulation. Three kinds of nursing care foods in two food process types (minced-/puréed-like foods for inhomogeneous/homogeneous texture respectively) were used as sample foods. A pseudo-chewing sound presentation system, using electromyogram signals, was used to modulate chewing sounds. Thirty healthy elderly participants participated in the experiment. In two conditions with and without the pseudo-chewing sound, participants rated the taste, texture, and evoked feelings in response to sample foods. The results showed that inhomogeneity strongly influenced the perception of food texture. Regarding the effects of the pseudo-chewing sound, taste was less influenced, the perceived food texture tended to change in the minced-like foods, and evoked feelings changed in both food process types. Though there were some food-dependent differences in the effects of the pseudo-chewing sound, the presentation of the pseudo-chewing sounds was more effective in foods with an inhomogeneous texture. In addition, it was shown that the pseudo-chewing sound might have positively influenced feelings.


Assuntos
Ingestão de Alimentos/psicologia , Potenciais Evocados/fisiologia , Serviços de Alimentação , Mastigação/fisiologia , Som , Percepção do Tato , Idoso , Eletromiografia , Feminino , Humanos , Masculino , Cuidados de Enfermagem , Inquéritos e Questionários , Paladar
10.
Proc Natl Acad Sci U S A ; 109(31): 12538-43, 2012 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-22802639

RESUMO

Hepatocytes generated from human induced pluripotent stem cells (hiPSCs) are unprecedented resources for pharmaceuticals and cell therapy. However, the in vitro directed differentiation of human pluripotent stem cells into mature hepatocytes remains challenging. Little attention has so far been paid to variations among hiPSC lines in terms of their hepatic differentiation. In the current study, we developed an improved hepatic differentiation protocol and compared 28 hiPSC lines originated from various somatic cells and derived using retroviruses, Sendai viruses, or episomal plasmids. This comparison indicated that the origins, but not the derivation methods, may be a major determinant of variation in hepatic differentiation. The hiPSC clones derived from peripheral blood cells consistently showed good differentiation efficiency, whereas many hiPSC clones from adult dermal fibroblasts showed poor differentiation. However, when we compared hiPSCs from peripheral blood and dermal fibroblasts from the same individuals, we found that variations in hepatic differentiation were largely attributable to donor differences, rather than to the types of the original cells. These data underscore the importance of donor differences when comparing the differentiation propensities of hiPSC clones.


Assuntos
Diferenciação Celular , Derme , Fibroblastos , Hepatócitos , Células-Tronco Pluripotentes Induzidas , Adulto , Células Cultivadas , Derme/citologia , Derme/metabolismo , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Células Hep G2 , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino
11.
Ergonomics ; 58(5): 736-47, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25434697

RESUMO

This study examined whether manipulability during smartphone thumb-based touch operations could be predicted by the following robotic manipulability indices: the volume and direction of the 'manipulability ellipsoid' (MEd), both of which evaluate the influence of kinematics on manipulability. Limits of the thumb's range of motion were considered in the MEd to improve predictability. Thumb postures at 25 key target locations were measured in 16 subjects. Though there was no correlation between subjective evaluation and the volume of the MEd, high correlation was obtained when motion range limits were taken into account. These limits changed the size of the MEd and improved the accuracy of the manipulability evaluation. Movement directions associated with higher performance could also be predicted. In conclusion, robotic manipulability indices with motion range limits were considered to be useful measures for quantitatively evaluating human hand operations.


Assuntos
Postura , Smartphone , Polegar , Interface Usuário-Computador , Fenômenos Biomecânicos , Ergonomia , Feminino , Humanos , Masculino , Movimento , Amplitude de Movimento Articular , Robótica , Análise e Desempenho de Tarefas , Adulto Jovem
12.
J Nanosci Nanotechnol ; 14(3): 2198-203, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24745212

RESUMO

An aqueous solution of sodium dodecylsulfate (SDS) was injected into a Langmuir monolayer of dioctadecyldimethylammonium chloride (DODAC) at the air-water interface. Infrared external spectra, atomic force microscopy (AFM), and quartz crystal microbalance (QCM) measurements revealed that the resulting surface monolayer was a multilayer structure consisting of a DODAC monolayer as the upper layer and an SDS bilayer as the underlayer. Furthermore, the SDS alkyl chain was in the all-trans conformation, and the molecular packing of the DODAC alkyl chains was hexagonal with the trans-zigzag plane of the methylene chain oriented randomly around the chain axis. We also discuss the structure of the multilayer obtained by injecting SDS into a mixed Langmuir monolayer of DODAC + SDS.


Assuntos
Cátions , Bicamadas Lipídicas/química , Membranas Artificiais , Compostos de Amônio Quaternário/química , Dodecilsulfato de Sódio/química , Tensoativos/química , Adsorção , Ar , Gases , Microscopia de Força Atômica , Quartzo , Soluções , Propriedades de Superfície , Fatores de Tempo , Água/química
13.
J Nanosci Nanotechnol ; 14(4): 3252-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24734763

RESUMO

We describe the bottom-up design of highly ordered free-standing nanofilms consisting of polymer Langmuir-Blodgett films (polymer nanosheets). Polymer nanosheets enable the incorporation of a wide variety of functional groups such as reactive components and chromophores, which serve as building blocks of free-standing nanofilms. We demonstrated a free-standing fluorescent hybrid nanofilm in which the separation between gold nanoparticles and fluorophores was tuned at the nanometer scale. Moreover, we prepared a free-standing nanofilm consisting of a two-dimensional homogeneous nickel zinc iron oxide (NiZnFe22O4) nanoparticle monolayer assembled on polymer nanosheets.

14.
Langmuir ; 29(48): 15058-64, 2013 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-24255947

RESUMO

We propose a general strategy for fabricating ultrasmall attoliter-sized (10(-18) L) one-dimensional (1D) aligned nanocup arrays embedded in poly(dimethylsiloxane) (PDMS) films based on a combination of colloidal soft-lithography and wrinkle processing. The nanocup consists of a metallic shell (silver-single or double-layer silver/gold type) with a thickness of several tens of nanometers and whose diameter was ca. 500 nm and cavity depth was ca. 250 nm. First, monodisperse polystyrene (PS) colloids (d = 500 nm) were arranged onto a sinusoidally wrinkled PDMS substrate. Then, the colloid particle arrays were transferred onto another flat PDMS substrate, and a metal film was vacuum deposited over the array to form a nanostructured surface consisting of half-shell metal-coated colloid particle arrays. After the metal-coated PS array was gently transferred onto another soft PDMS substrate prepared by nonthermal curing, the attached films were thermally cured. After that, both films were carefully separated to selectively transfer the metal-coated PS particle arrays, since the metallic shell on the PS surface can adhere to the soft PDMS. Finally, the PS colloids were removed by plasma etching, leaving behind the 1D hemispherical metallic shells, called here the "metallic nanocup array structure". This structure was evaluated by performing atomic force microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy measurements. We further demonstrate chemical modification of the inner nanocup surface through construction of a self-assembled monolayer, and we also fill them with nanomaterials (silica nanoparticles) to demonstrate their application to size-selecting devices. The obtained metallic nanocup arrays could be components in a new class of chemical and/or biological nanoreactors with small reaction vessels, surface-enhanced Raman scattering (SERS)-based sensors, and size separators for nanoparticles.

15.
Langmuir ; 29(24): 7239-48, 2013 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-23320820

RESUMO

In this article, we propose a novel methodology for the formation of monodisperse regularly sized disks of several nanometer thickness and with diameters of less than 100 nm using Langmuir monolayers as fabrication media. An amphiphilic triimide, tri-n-dodecylmellitic triimide (1), was spread as a monolayer at the air-water interface with a water-soluble macrocyclic oligoamine, 1,4,7,10-tetraazacyclododecane (cyclen), in the subphase. The imide moieties of 1 act as hydrogen bond acceptors and can interact weakly with the secondary amine moieties of cyclen as hydrogen bond donors. The monolayer behavior of 1 was investigated through π-A isotherm measurements and Brewster angle microscopy (BAM). The presence of cyclen in the subphase significantly shifted isotherms and induced the formation of starfish-like microstructures. Transferred monolayers on solid supports were analyzed by reflection absorption FT-IR (FT-IR-RAS) spectroscopy and atomic force microscopy (AFM). The Langmuir monolayer transferred onto freshly cleaved mica by a surface touching (i.e., Langmuir-Schaefer) method contained disk-shaped objects with a defined height of ca. 3 nm and tunable diameter in the tens of nanometers range. Several structural parameters such as the disk height, molecular aggregation numbers in disk units, and 2D disk density per unit surface area are further discussed on the basis of AFM observations together with aggregate structure estimation and thermodynamic calculations. It should be emphasized that these well-defined structures are produced through simple routine procedures such as solution spreading, mechanical compression, and touching a substrate at the surface. The controlled formation of defined nanostructures through easy macroscopic processes should lead to unique approaches for economical, energy-efficient nanofabrication.

16.
Phys Chem Chem Phys ; 15(23): 8890-901, 2013 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-23552643

RESUMO

Calcitonin (CT) is an amyloid fibril forming peptide. Since salmon calcitonin (sCT), having Leu residues (Leu12, Leu16 or Leu19) instead of Tyr12, Phe16 or Phe19 for human calcitonin (hCT), is known to form the fibrils much slower than hCT, hCTs mutated to Leu residues at the position of 16 (F16L-hCT), 19 (F19L-hCT), and 12, 16 and 19 (TL-hCT) were examined to reveal the role of aromatic side-chains on amyloid fibrillation using solid-state (13)C NMR. The detailed kinetics were analyzed using a two-step reaction mechanism such as nucleation and fibril elongation with the rate constants of k1 and k2, respectively. The k2 values of hCT mutants were significantly slower than that of hCT at a neutral pH, although they were almost the same at an acidic pH. The (13)C chemical shifts of the labeled sites showed that the conformations of monomeric hCT mutants take α-helices as viewed from the Gly10 moiety. The hCT mutants formed fibrils and during the fibril formation, the α-helix around Gly10-Phe22 changed to the ß-sheet, and the major structures around Ala26-Ala31 were random coil in the fibrils. Molecular dynamics simulation was performed for the ß-sheet system of hCT9-23 and its mutants F16L-hCT9-23, F19L-hCT9-23 and TL-hCT9-23. In one of the stable fibril structures, Phe16 of hCT interacts with Phe19 of the next strand alternatively. In the hCT mutants, lack of Phe16 and Phe19 interaction causes significant instability as compared with the hCT fibril, leading to the reduction of k2 values, as observed experimentally in the hCT mutants at a neutral pH.


Assuntos
Amiloide/química , Amiloide/metabolismo , Calcitonina/química , Calcitonina/metabolismo , Amiloide/genética , Amiloide/ultraestrutura , Calcitonina/genética , Humanos , Simulação de Dinâmica Molecular , Ressonância Magnética Nuclear Biomolecular , Mutação Puntual , Estrutura Secundária de Proteína
17.
J Stroke Cerebrovasc Dis ; 22(4): 349-57, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22051352

RESUMO

BACKGROUND: To investigate stroke incidence and rate of thrombolytic therapy in an urban city of around 500,000 residents. METHODS: Patients suffering acute stroke in Kurashiki City (population 474,415) between March 2009 and February 2010 (inclusive) and admitted to 1 of 10 hospitals throughout the city were prospectively enrolled. RESULTS: We enrolled patients with first-ever stroke (n = 763; men 415; median age 72 years) and first-ever/recurrent stroke (n = 1009; men 552; median age 73 years). Among first-ever strokes, 68% were cerebral infarctions, 23% were intracerebral hemorrhages, and 8% were subarachnoid hemorrhages. Crude incidences for first-ever stroke per 100,000 residents were 159.8 (95% confidence interval [CI] 148.4-171.1) for all strokes, 108.8 (95% CI 99.4-118.1) for cerebral infarction, and 36.5 (95% CI 31.0-41.9) for intracerebral hemorrhage. After adjustment using the world population model, age-adjusted incidences were 60.7 (95% CI 45.4-75.9) for all strokes, 38.4 (95% CI 26.3-50.5) for cerebral infarction, and 16.1 (95% CI 8.3-24.0) for intracerebral hemorrhage. Among 698 cases with first-ever and recurrent cerebral infarction, thrombolysis was administered for 31 (5%). Of 197 cerebral infarction patients admitted within 3 hours of onset, the thrombolysis rate was 16%. CONCLUSION: In this urban Japanese city, the age-adjusted incidence of first-ever stroke between March 2009 and February 2010 was 60.7 per 100,000 residents, which was relatively low compared with findings for other countries. Thrombolysis was given to approximately 5% of patients with acute ischemic stroke.


Assuntos
Padrões de Prática Médica/estatística & dados numéricos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Terapia Trombolítica/estatística & dados numéricos , Saúde da População Urbana/estatística & dados numéricos , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Hemorragia Cerebral/tratamento farmacológico , Hemorragia Cerebral/epidemiologia , Distribuição de Qui-Quadrado , Criança , Feminino , Fibrinolíticos/administração & dosagem , Fidelidade a Diretrizes , Humanos , Incidência , Japão/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Sistema de Registros , Acidente Vascular Cerebral/diagnóstico , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/epidemiologia , Fatores de Tempo , Ativador de Plasminogênio Tecidual/administração & dosagem , Adulto Jovem
18.
Hematol Oncol ; 30(2): 82-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21692099

RESUMO

Patients with aplastic anemia (AA) or myelodysplastic syndrome (MDS) often have persistent severe neutropenia and are susceptible to infectious complications. We retrospectively reviewed the clinical course of patients with AA or MDS who had neutropenia (neutrophil count < 500/µl) for more than 25 days. A total of 46 patients, 11 with AA and 35 with MDS, were included. Twenty-three patients had infectious events (IE), and the cumulative incidence of IE was 30% at 6 months and 51% at 1 year. The cumulative incidence of IE was 67% at 1 year in 30 patients who experienced very severe neutropenia of less than 200/µl. Overall survival in all patients was 76% at 6 months and 65% at 1 year. In a multivariate analysis, male sex, underlying diseases, and a neutrophil count of less than 200/µl as a time-dependent covariate significantly affected IE. In analyses that excluded patients with AA, male sex was the only factor. In conclusion, severe neutropenia was significantly associated with IE in patients with AA or MDS, and IE might be lethal. When we only considered patients with MDS, the neutrophil count alone could not be used to predict the prognosis.


Assuntos
Anemia Aplástica/complicações , Síndromes Mielodisplásicas/complicações , Neutropenia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Aplástica/mortalidade , Feminino , Humanos , Incidência , Infecções/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Síndromes Mielodisplásicas/mortalidade , Neutropenia/complicações , Estudos Retrospectivos
19.
J Nanosci Nanotechnol ; 12(1): 451-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22524001

RESUMO

Three types of Au shells, an isolated half-shell, one-dimensional strings of shells, and two-dimensional films, were fabricated by using a monolayer of polystyrene (PS) particles with diameters of 213, 560, and 1360 nm. The three types of Au shells that were removed from the PS particle monolayer and the as-deposited Au shells that adhered to PS particles were modified with 4-mercaptopyridine for use as platforms for surface-enhanced Raman scattering (SERS). We examined the effects of the shapes and sizes of Au shells on their SERS efficiency and found that the Au shells exhibited strong SERS signals and that Au shells prepared by using 560-nm PS particles were the most suitable platform for SERS at both 632.8- and 785-nm excitations. Further, we found that SERS enhancements depended on the shape of Au shells and on whether Au shells adhered to PS particles or not.


Assuntos
Coloides/química , Cristalização/métodos , Ouro/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Ressonância de Plasmônio de Superfície/métodos , Luz , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Espalhamento de Radiação , Propriedades de Superfície
20.
J Nanosci Nanotechnol ; 12(1): 648-55, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22524034

RESUMO

Ag2S nanoparticles (NPs) of 3.1 +/- 0.6, 8.1 +/- 1.0, and 10.2 +/- 1.6 nm in diameter capped with a long-chain amidoamine derivative (C18AA) were synthesized by a modified Brust method. Ag2S NPs capped with two types of azobenzene-derivatized alkanethiol differing in chain length (2AM10SH and 8AM5SH) were obtained by the ligand exchange method. The trans to cis photoisomerization conversion of 2AM10SH and 8AM5SH on Ag2S NPs dispersed in toluene was above 95%. 2AM10SH-capped Ag2S NPs of 8.1 nm or more in toluene were found to show reversible dispersion-aggregation behavior under alternating irradiation with UV and visible lights, i.e., Ag2S NPs capped with trans- and cis-2AM10SH were in dispersed and aggregated states, respectively. However, Ag2S NPs of 3.1 nm capped with 2AM10SH and Ag2S NPs of 8.1 nm capped with 8AM5SH were always in a dispersed state regardless of whether 2AM10SH and 8AM5SH were in the trans or cis conformation.


Assuntos
Alcanos/química , Compostos Azo/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Compostos de Prata/química , Compostos de Sulfidrila/química , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Propriedades de Superfície
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