RESUMO
We investigate the crystallographic and electronic properties of wurtzite Cr-doped AlN (AlCrN) films (Cr ≤12.0%) that absorb visible light. We confirmed that the films consist of wurtzite columnar single crystals that are densely packed, c-axis oriented, and exhibit a random rotation along the a-axis in plane by using transmission electron microscopy. The oxidation state of Cr was found to be 3+ using Cr K-edge X-ray absorption near edge structure, which implies that Cr can be a substitute for Al3+ in AlN. The first nearest neighbor distances estimated using Cr K-edge extended X-ray absorption fine structure (EXAFS) were found to be nearly isotropic for incident light with electric fields that are parallel and perpendicular to the plane. The results of ab initio lattice relaxation calculations for the model of wurtzite Al1-xCrxN supercell where Cr replaces Al support the EXAFS results. The calculations for the model showed that additional energy bands are formed in the band gap of AlN, in which the Fermi energy (EF ) is present. As expected from the calculation results, the electrical conductivity increases with increase in the Cr concentration, implying that the density of states at EF increases monotonically. From these results, we can conclude that AlCrN films are an intermediate band material with respect to their crystallographic and electric properties.
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TiO(2) nanocrystals were synthesized by a hydrolysis method combined with a thermal treatment. TiO(2) nanocrystals with rutile and anatase structure were selectively synthesized by controlling the pH level in the precursor solution, and the crystallite size was controlled by changing the reaction temperature. Moreover, Co-doped TiO(2) nanocrystals with rutile structure were also synthesized by means of the addition of Co to the precursor solution. Secondary phases such as Co precipitates and Co oxide were not present in the sample tested, with [Co]<10 mol%. With an increase in the Co doping level, the E(g)-phonon signal at 447 cm(-1) was broadened and shifted to a lower frequency, indicating the incorporation of Co into the rutile TiO(2) host lattice and lattice expansion. Optical absorption spectra showed that the absorption edge at â¼3.0 eV corresponded to the band gap of rutile TiO(2) and shifted to the lower energy side upon Co doping. These results indicated the possibility of band gap engineering of rutile TiO(2) via Co doping. On the other hand, the charge transfer gap between O 2p and Co 3d orbitals was also observed for samples with Co, suggesting the possibility of photo-induced magnetism in rutile TiO(2) nanocrystals, obtained by visible light irradiation.
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Zn(1-x)Co(x)O samples were prepared by a standard solid-state reaction method. Zn(1-x)Co(x)O crystals in the wurtzite structure were obtained with a Co composition of up to 22.1%. The a- and c-axis lengths increased and decreased, respectively, with an increase in Co composition. Raman spectra showed systematic broadening of the E(2) (high) phonon mode associated with the increase in Co composition, and electronic transitions of Co in the oxygen tetrahedron were observed in optical absorption measurement. These results indicated systematic substitution of Co into the Zn sites. Furthermore, an additional broad absorption band at 2.4-3.3 eV corresponding to the charge transfer (CT) process [Formula: see text] was also observed. The Raman spectra showed strong enhancement of the LO phonon due to a resonant Raman process induced with the coupling of the LO phonon and a photo-excited carriers mediated CT gap. These results suggest the possibility of carrier-induced ferromagnetism based on double exchange interaction in Zn(1-x)Co(x)O by visible light irradiation.
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Nanometre-sized ZnO crystals doped with Co were synthesized by a co-precipitation method combined with a thermal treatment. By changing the reaction temperature, we can control the crystallite size from roughly 10 nm particles to 20 nm × 200 nm nm rods grown along the hexagonal c-direction. X-ray diffraction and Raman scattering showed growth of high-quality wurtzite ZnO crystals incorporating Co systematically in the ZnO host lattice in the tested range of [Co]<3.0 mol%. Electronic transitions of Co in the oxygen tetrahedron were also observed in optical absorption, giving supporting evidence for systematic substitution of Co into the Zn site.
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We report unusual evolution of the conduction-electron state in the localized f electron system CexLa1-xB6 from normal electron state to heavy Fermi liquid (FL) state through local FL and non-FL states with increasing Ce concentration and/or with increasing magnetic field. The effective mass of quasiparticle or the coefficient A of T2 term of resistivity is found to increase divergently near the boundary between FL state and non-FL state. The features of the non-FL state are also different from those of the typical non-FL systems previously observed or theoretically predicted.
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Betanodaviruses are the causative agents of viral nervous necrosis (VNN) or viral encephalopathy and retinopathy (VER) in cultured marine fish. A total of 131 apparently healthy fish from 30 species were collected in two geographically remote aquaculture areas, Yashima Bay (Kagawa Prefecture) and Tamanoura Bay (Nagasaki Prefecture), in Japan. The brains of fish were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR to detect the coat protein gene of betanodavirus. In Yashima Bay, two and 13 of 20 cultured fish were positive for nodavirus in RT-PCR and nested PCR, respectively, and four of five wild fish were positive only in nested PCR. In Tamanoura Bay, 28 and 99 of 106 wild fish were positive for the virus in RT-PCR and nested PCR, respectively. All the sequences of the nested PCR products (177 nt) from 27 fish species (10 cultured and 17 wild) were highly homologous to each other (99-100%) and were closely related to that of the known betanodavirus, redspotted grouper nervous necrosis virus (RGNNV). These results illustrate that large populations of cultured and wild marine fish in aquaculture areas are subclinically infected with genetically closely related betanodaviruses, suggesting an importance of such infected fish as a carrier or reservoir of betanodaviruses.
Assuntos
Doenças dos Peixes/virologia , Nodaviridae/genética , Reação em Cadeia da Polimerase/métodos , Infecções por Vírus de RNA/veterinária , Animais , Aquicultura , Encéfalo/virologia , Proteínas do Capsídeo/genética , Primers do DNA , Peixes , Japão , Filogenia , Infecções por Vírus de RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Análise de Sequência de DNA/veterináriaRESUMO
We report measurements of the de Haas-van Alphen effect in ZrZn2 under hydrostatic pressures up to 21 kbar where the Curie temperature vanishes. The exchange splitting of a Fermi surface changes in behavior with increasing magnetic field, which is qualitatively consistent with the behavior of the high-field magnetization, suggesting the existence of a crossover between two distinct magnetic states. These and previously unexplained findings may be understood in terms of a p-T-B phase diagram qualitatively similar to that of the ferromagnetic superconductor UGe2.
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To determine the distribution of marine birnavirus (MABV) in cultured populations of different marine fish species, 1291 pooled tissue samples from 2672 fish belonging to 22 species and one hybrid were collected from Kagawa Prefecture, Japan, during 1999-2001. Using cell-culture MABV was isolated from three species: yellowtail, Seriola quinqueradiata Temminck & Schlegel (positive number/sample number, 10/419), amberjack, S. dumerili (Risso) (4/72), and Japanese flounder, Paralichthys olivaceus (Temminck & Schlegel) (41/481). Using PCR on MABV-negative samples, the MABV genome was detected in the same three species [yellowtail (9/409), amberjack (4/68) and Japanese flounder (93/440)] and two additional species, spotted halibut, Verasper variegatus (Temminck & Schlegel) (5/11), and goldstriped amberjack, S. lalandi Valenciennes (1/5). These MABV-positive species can be taxonomically divided into two groups: the genus Seriola and flatfish. In Japanese flounder, MABV was detected during all seasons, and the infection rate was correlated with water temperature. Aquaculture sites with MABV-positive fish were evenly distributed over the surveyed area, suggesting that MABV is widely distributed at aquaculture sites in Kagawa Prefecture. The nucleotide sequence at the variable region, the VP2/NS junction, revealed that the 39th base mutation occurs host-specifically for flatfish. Flatfish are suspected to be the main reservoir of MABV and might be responsible for establishing the infection cycle in aquaculture environments.
Assuntos
Aquabirnavirus/genética , Infecções por Birnaviridae/veterinária , Doenças dos Peixes/virologia , Variação Genética , Animais , Aquicultura , Sequência de Bases , Infecções por Birnaviridae/genética , Primers do DNA , Eletroforese em Gel de Ágar , Doenças dos Peixes/genética , Peixes , Japão , Dados de Sequência Molecular , Mutação Puntual/genética , Reação em Cadeia da Polimerase , Água do Mar , Análise de Sequência de DNA , TemperaturaRESUMO
Molecular virological analyses of 8 Japanese VHSV (viral hemorrhagic septicemia virus) isolates from wild and farmed Japanese flounder Paralichthys olivaceus were performed to investigate their genetic relatedness to American and European isolates of VHSV. Phylogenetic analyses based on the partial nucleotide sequences of G and P genes revealed that there are 2 genogroups of VHSV in Japan. The first one represented by the Obama25 isolate is closely related to the American isolates (Genogroup I) while the other, the KRRV9601 isolate, is closely related to the traditional European isolates (Genogroup III). The 2 types of Japanese VHSV showed differences in the relative mobility of the G protein and intensity of the antibody reaction on the P and M proteins. The Obama25 type of VHSV is widely distributed as a native virus in the coastal areas of western Japan and has been responsible for the occurrence of VHSV infection in farmed Japanese flounder while the KRRV9601 isolate is considered to have been introduced from a foreign country.
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Doenças dos Peixes/virologia , Linguado , Novirhabdovirus/classificação , Novirhabdovirus/genética , Infecções por Rhabdoviridae/veterinária , Proteínas do Envelope Viral/genética , Animais , Sequência de Bases , Western Blotting/veterinária , Eletroforese em Gel de Poliacrilamida/veterinária , Europa (Continente) , Genes Virais , Japão , Filogenia , RNA Viral/química , Infecções por Rhabdoviridae/virologia , Análise de Sequência de RNA/veterinária , Estados UnidosRESUMO
OBJECTIVES: Natural angiogenesis has been shown to be impaired in spontaneously hypertensive rats (SHR). The purpose of this study was to determine whether pathological angiogenesis in the setting of tissue ischemia is also impaired in SHR, and to what extent it is modified by angiotensin-converting enzyme (ACE) inhibition. METHODS: Ischemia was induced in the hindlimb of SHR by excision of the femoral artery, after which the animals were randomly assigned to receive low-dose perindopril (sub-antihypertensive, 0.2 mg/kg/day), high-dose perindopril (antihypertensive, 2.0 mg/kg/day), or vehicle for 3 weeks. Wistar-Kyoto rats (WKY) with femoral artery excision served as a control group. RESULTS: Tissue ACE activity in SHR was significantly increased compared to WKY (49.4+/-6.2 vs. 34.0+/-14.2 IU/mg, P<0.01). Administration of perindopril significantly reduced ACE activity in SHR (low dose: 12.4+/-2.3; high dose: 11.0+/-2.1 IU/mg, P<0.005). Angiogenesis of the ischemic limb muscles was significantly impaired at 4 weeks in SHR versus WKY as indicated by the lower capillary density in the former (364.5+/-43.0 vs. 463.8+/-63.0/mm(2), P<0.05) as well as the reduced hindlimb perfusion assessed by laser Doppler imaging (0.86+/-0.08 vs. 1.03+/-0.09, P<0.05). Administration of perindopril significantly augmented both the capillary density (low dose: 494.3+/-69.8; high dose: 543.9+/-76.9/mm(2), P<0.005) and the limb perfusion (low dose: 1.06+/-0.15; high dose: 1.05+/-0.12, P<0.05) of the ischemic limb in SHR. CONCLUSIONS: These findings indicate that pathological angiogenesis in the setting of tissue ischemia is impaired in SHR compared with WKY, and that this impairment can be reversed by ACE inhibition. The angiogenic properties of an ACE inhibitor may benefit patients with essential hypertension presenting with lower limb vascular insufficiency.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Hipertensão/tratamento farmacológico , Isquemia/tratamento farmacológico , Perindopril/uso terapêutico , Análise de Variância , Animais , Capilares/patologia , Membro Posterior/irrigação sanguínea , Hipertensão/enzimologia , Hipertensão/patologia , Isquemia/enzimologia , Isquemia/patologia , Masculino , Modelos Animais , Músculo Esquelético/enzimologia , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Fluxo Sanguíneo Regional/efeitos dos fármacosRESUMO
To determine the infectivity of marine birnavirus (MABV) in various marine fish species, experimental infection was performed in combination groups of 5 fish species with 7 strains of MABV and 1 strain of infectious pancreatic necrosis virus (IPNV). Mortality was observed in yellowtail Seriola quinqueradiata and amberjack S. dumerili infected with MABV strains Y-6, Y-10K and H-1, but not in other infected species. MABV was reisolated from most combination groups, but the virus isolation rate and virus infectivity titer were often significantly different among groups with the same fish species or with the same virus strain. All MABV strains replicated well in makogarei Limanda yokohamae, but only slightly in tiger puffer Takifugu rubiipes. IPNV also replicated in all fish species without causing death. The isolation rate and infectivity titer of IPNV were similar to or higher than those of non-virulent strains of MABV. In conclusion, the infectivity of MABV for different fish species is considered to change, which is an important factor in the development of the infection cycle of this virus among marine organisms.
Assuntos
Aquabirnavirus/patogenicidade , Infecções por Birnaviridae/veterinária , Doenças dos Peixes/virologia , Animais , Aquabirnavirus/isolamento & purificação , Infecções por Birnaviridae/mortalidade , Infecções por Birnaviridae/virologia , Linhagem Celular , Suscetibilidade a Doenças/veterinária , Doenças dos Peixes/mortalidade , Peixes , Vírus da Necrose Pancreática Infecciosa/isolamento & purificação , Vírus da Necrose Pancreática Infecciosa/patogenicidade , Frutos do Mar , Replicação ViralRESUMO
Myocardial ischemia initiates an acute inflammatory response, in which polymorphonuclear leukocytes (PMNs) are major participants. We investigated whether increased PMN activity in the peripheral blood is a marker for high-grade coronary artery stenosis in patients with angina pectoris. PMN activity was examined in 45 patients by measuring the luminol-dependent chemiluminescence (CL) response of the peripheral blood upon addition of phorbol myristate acetate (PMA). The CL of patients with angiographic filling delay was 1.6-fold higher than in patients without delay (480+/-54 vs. 302+/-33 counts/PMN, P<0.01). The CL of patients with a filling delay of the left anterior descending artery (LAD) was 1.7-fold higher than in patients without an LAD filling delay (537+/-79 vs. 317+/-27 counts/PMN, P<0.01). With the CL cut-off at 400 counts/PMN, the sensitivity and specificity for detecting an angiographic filling delay of the LAD were 69 and 75%, respectively. These data indicate that PMN activity in the peripheral blood is increased with the presence of a flow-limiting coronary lesion showing an angiographic filling delay. Measuring PMN activity may be a useful approach to assess indications for and timing of angiography and/or adjunctive invasive therapies in patients with angina pectoris.
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Angina Pectoris/fisiopatologia , Circulação Coronária , Estenose Coronária/fisiopatologia , Ativação de Neutrófilo , Angina Pectoris/sangue , Angina Pectoris/complicações , Angina Pectoris/diagnóstico por imagem , Angiografia Coronária , Estenose Coronária/sangue , Estenose Coronária/complicações , Estenose Coronária/diagnóstico por imagem , Feminino , Humanos , Medições Luminescentes , Luminol/farmacologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Neural precursors often generate distinct cell types in a specific order, but the intrinsic or extrinsic cues regulating the timing of cell fate specification are poorly understood. Here we show that Drosophila neural precursors (neuroblasts) sequentially express the transcription factors Hunchback --> Krüppel --> Pdm --> Castor, with differentiated progeny maintaining the transcription factor profile present at their birth. Hunchback is necessary and sufficient for first-born cell fates, whereas Krüppel is necessary and sufficient for second-born cell fates; this is observed in multiple lineages and is independent of the cell type involved. We propose that Hunchback and Krüppel control early-born temporal identity in neuroblast cell lineages.
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Linhagem da Célula/fisiologia , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila , Drosophila melanogaster/crescimento & desenvolvimento , Proteínas de Homeodomínio/metabolismo , Neurônios/fisiologia , Proteínas Repressoras , Fatores de Transcrição/metabolismo , Animais , Linhagem da Célula/genética , Proteínas de Ligação a DNA/genética , Drosophila melanogaster/genética , Drosophila melanogaster/fisiologia , Regulação da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Hormônios Juvenis/genética , Hormônios Juvenis/metabolismo , Fatores de Transcrição Kruppel-Like , Morfogênese/genética , Morfogênese/fisiologia , Neurônios/citologia , Fatores do Domínio POU , Fatores de Tempo , Fatores de Transcrição/genéticaRESUMO
The mechanism of stent thrombosis was evaluated by a flow chamber model. A Palmaz-Schatz stent was placed on glass surfaces coated with type I collagen in a parallel-plate flow chamber. Platelets were rendered fluorescent with mepacrine and whole blood was perfused through the chamber. Platelet thrombi formed around the implanted stents were continuously recorded by epi-fluorescent video-microscopy. Platelet thrombi appeared on the collagen surface within a few minutes in the absence of function blocking monoclonal antibodies. Antibody blocking vWF interaction with GP Ib alpha completely inhibited the platelet thrombi around the stent, but had no effect on platelet thrombus formation in the space between the stents and collagen, while both were inhibited by anti-GP IIb/IIIa. Our results suggest that two distinct mechanisms, one mediated by vWF interaction with GP Ib alpha occurring at high shear rates, and the other mediated exclusively by GP IIb/IIIa occurring at low shear rates, are involved in the process of platelet thrombus formation in the presence of stents.
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Agregação Plaquetária , Stents , Animais , Células Cultivadas , Colágeno , Humanos , Camundongos , Complexo Glicoproteico GPIIb-IIIa de PlaquetasRESUMO
The study investigated whether patients hospitalized for unstable angina pectoris (UAP), who subsequently develop complete coronary thrombosis (acute transmural myocardial infarction (AMI)) despite medical treatment, exhibit platelet hyperaggregability in an assay system that does not employ agonist stimulation. The study comprised 89 patients with UAP (Braunwald type B). Unfractionated heparin and nitrate were administered to all patients via continuous intravenous drip together with aspirin taken orally. Citrated platelet-rich plasma (230-250x 10(3)/microl) was obtained on admission and again, in some patients, following the AMI. Platelet aggregability was measured in an optically modified cone-plate viscometer that enables the detection of platelet aggregation without agonist stimulation. A continuous shear rate of 1,200/s was employed. Of the 89 patients, 85 were finally stabilized, while 4 developed an AMI accompanied by persistent ST-segment elevation with increased levels of plasma creatine kinase within 3 h after starting the treatment. The extent of platelet aggregation on admission was significantly greater in these 4 patients compared with the 85 who were stabilized (87.8+/-6.8%, n=4 vs 26.8+/-9.1%, n=85; mean+/-SD). These data suggest that platelet hyperaggregability mediated mainly by fibrinogen binding to the activated glycoprotein IIb/IIIa complex occurs before a complete thrombotic occlusion and this evaluation may provide important information before the onset of myocardial infarction.
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Angina Instável/sangue , Trombose Coronária/sangue , Hemorreologia , Infarto do Miocárdio/sangue , Agregação Plaquetária , Testes de Função Plaquetária/métodos , Estresse Mecânico , Idoso , Angina Instável/complicações , Angina Instável/tratamento farmacológico , Angina Instável/epidemiologia , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Biomarcadores , Comorbidade , Trombose Coronária/complicações , Creatina Quinase/sangue , Creatina Quinase Forma MB , Eletrocardiografia , Feminino , Fibrinogênio/metabolismo , Heparina/uso terapêutico , Humanos , Isoenzimas/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Nitratos/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
To clarify the role of B-12 in the immunological function, serum C3, IgM, IgG, IgE contents, splenocytes expression of CD4, CD8, and CD4 positive intracellular IFN-gamma and IL-4 were examined in B-12-deficient mice, and the effect of the administration of CH3-B-12 was also studied. Serum C3, IgM and IgG contents were lower in B-12-deficient mice than in the control mice. On the other hand, serum IgE content was significantly higher in B-12-deficient mice, and the value in CH3-B-12 administered mice, administered CH3-B-12 to B-12-deficient mice for 48 h before the end of feeding period, showed a tendency to recovery. CD4+CD8- cells and CD4+CD8-/CD4-CD8+ ratio in splenocytes were significantly higher in B-12-deficient mice than in control mice. CD4+IFN-gamma+ cells was significantly lower in B-12-deficient mice than in control mice, and CD4+IL-4+ was significantly higher in B-12-deficient mice than in control mice. These results suggest that B-12-deficiency causes CD4+CD8-T cells shift from the T helper type 1 to the T helper type 2, which participate in the IgE production and elevates CD4+CD8-/CD4-CD8+ ratio. Thus, B-12 plays a role in maintaining the immune function in mice.
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Citocinas/sangue , Imunoglobulinas/sangue , Deficiência de Vitamina B 12/imunologia , Vitamina B 12/uso terapêutico , Animais , Relação CD4-CD8 , Complemento C3/metabolismo , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Interferon gama , Interleucina-4 , Masculino , Camundongos , Camundongos Endogâmicos BALB C/imunologia , Vitamina B 12/administração & dosagem , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/terapiaRESUMO
A novel hemostatic device, Adapty (Medikit, Tokyo, Japan), was developed to achieve effective and comfortable hemostasis following transradial procedures. The device consists of a pad fixed to a transparent plastic plate and a self-adhesive strap. The catheter sheath is removed from the radial artery after the pad has been positioned precisely over the puncture site, with the strap attached to the plate. Compression pressure then is adjusted with the self-adhesive strap, as is required with occlusive clamps. Patients do not need to maintain hyperextension of the wrist after the procedure. The wrist can be mobilized immediately after application. The efficacy of Adapty was evaluated in prospective observations of 200 patients. The device was successfully applied in all patients immediately after sheath removal. No patient required interruption of compression because of pain, congestion or ischemia. Complete hemostasis was obtained in 199 patients (99.5%), and the device caused no vascular complications. This study demonstrates that Adapty is highly effective for achieving hemostasis after transradial procedures.
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Angiografia Coronária/instrumentação , Técnicas Hemostáticas/instrumentação , Revascularização Miocárdica/instrumentação , Artéria Radial , Idoso , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Automated 3-dimensional intravascular ultrasound (IVUS) analysis was used to assess status of the treated coronary artery immediately and 6 months after placement of a self-expanding Radius stent in 15 patients. Serial 3-dimensional IVUS analysis demonstrated gradual stent expansion that countered neointimal proliferation and preserved the lumen.
Assuntos
Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/cirurgia , Revascularização Miocárdica , Stents , Ultrassonografia de Intervenção , Idoso , Idoso de 80 Anos ou mais , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Components of the renin-angiotensin (R-A) system have been repeatedly investigated as candidate genes for essential hypertension. In particular, suggestive or significant association has been detected in some studies for the angiotensinogen M235T, angiotensin I-converting enzyme I/D, angiotensin II type 1 receptor A1166C, and aldosterone synthase C-344T polymorphisms, although the results remain inconclusive. OBJECTIVE AND METHODS: To evaluate the importance of these candidate genes for hypertension, we undertook an extensive association study in the Japanese. This case-control study was conducted in a total of 1476 individuals using the four R-A gene polymorphisms. In the assessment of genotyping data, 843 hypertensive subjects were divided into three case subgroups according to severity of hypertension, while 633 normotensive subjects divided into two control subgroups by the age of enrollment. Each subgroup was further divided by sex. Subsequently, the presence of synergy (or gene-gene interaction) was evaluated among four R-A gene polymorphisms. RESULTS: No significant association was observed between the individual R-A gene polymorphisms and hypertension status in our case-control study. The results were almost unchanged when severity of hypertension, sex-specificity, and synergy were taken into account CONCLUSIONS: Despite a relatively large number of subjects, we did not find significant evidence for disease association in the Japanese population. Given confounding factors in the case-control strategy, the lack of association does not exclude the relevance of the R-A genes to hypertension. Further investigation needs to be performed in large-scale populations, where the use of not only hypertension status, but also 'intermediate' phenotypes would be useful.