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AIM: To evaluate whether deep learning reconstruction (DLR) can accelerate the acquisition of magnetic resonance imaging (MRI) sequences of the knee for clinical use. MATERIALS AND METHODS: Using a 1.5-T MRI scanner, sagittal fat-suppressed T2-weighted imaging (fs-T2WI), coronal proton density-weighted imaging (PDWI), and coronal T1-weighted imaging (T1WI) were performed. DLR was applied to images with a number of signal averages (NSA) of 1 to obtain 1DLR images. Then 1NSA, 1DLR, and 4NSA images were compared subjectively, and by noise (standard deviation of intra-articular water or medial meniscus) and contrast-to-noise ratio between two anatomical structures or between an anatomical structure and intra-articular water. RESULTS: Twenty-seven healthy volunteers (age: 40.6 ± 11.9 years) were enrolled. Three 1DLR image sequences were obtained within 200 s (approximately 12 minutes for 4NSA image). According to objective evaluations, PDWI 1DLR images showed the smallest noise and significantly higher contrast than 1NSA and 4NSA images. For fs-T2WI, smaller noise and higher contrast were observed in the order of 4NSA, 1DLR, and 1NSA images. According to the subjective analysis, structure visibility, image noise, and overall image quality were significantly better for PDWI 1DLR than 1NSA images; moreover, the visibility of the meniscus and bone, image noise, and overall image quality were significantly better for 1DLR than 4NSA images. Fs-T2WI and T1WI 1DLR images showed no difference between 1DLR and 4NSA images. CONCLUSION: Compared to PDWI 4NSA images, PDWI 1DLR images were of higher quality, while the quality of fs-T2WI and T1WI 1DLR images was similar to that of 4NSA images.
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Aprendizaje Profundo , Articulación de la Rodilla , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Adulto , Femenino , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/anatomía & histología , Voluntarios Sanos , Persona de Mediana Edad , Relación Señal-Ruido , Interpretación de Imagen Asistida por Computador/métodosRESUMEN
AIM: To evaluate 1.5 T magnetic resonance imaging (MRI) brain images with denoising procedures using deep learning-based reconstruction (dDLR) relative to the original 1.5 and 3 T images. MATERIALS AND METHODS: Eleven volunteers underwent MRI at 3 and 1.5 T. Two-dimensional fast spin-echo T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR) imaging and diffusion-weighted imaging (DWI) sequences were performed. The dDLR method was applied to the 1.5 T data (dDLR-1.5 T), then the image quality of the dDLR-1.5 T data relative to the original 1.5 T and 3 T data was qualitatively and quantitatively assessed based on the structure similarity (SSIM) index; the signal-to-noise ratios (SNRs) of the grey matter (GM) and white matter (WM); and the contrast-to-noise ratios (CNRs) between the GM and WM (CNRgm-wm) and between the striatum (ST) and WM (CNRst-wm). RESULTS: The perceived image quality, and SNRs and CNRs were significantly higher for the dDLR-1.5 T images versus the 1.5 T images for all sequences and almost comparable or even superior to those of the 3 T images. For DWI, the SNRs and CNRst-wm were significantly higher for the dDLR-1.5 T images versus the 3 T images. CONCLUSION: The dDLR technique improved the image quality of 1.5 T brain MRI images. With respect to qualitative and quantitative measurements, the denoised 1.5 T brain images were almost equivalent or even superior to the 3 T brain images.
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Neoplasias Encefálicas , Aprendizaje Profundo , Humanos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias Encefálicas/patologíaRESUMEN
The surface magnetism of Fe(001) was studied in an atomic layer-by-layer fashion by using the in situ iron-57 probe layer method with a synchrotron Mössbauer source. The observed internal hyperfine field H_{int} exhibits a marked decrease at the surface and an oscillatory behavior with increasing depth in the individual upper four layers below the surface. The calculated layer-depth dependencies of the effective hyperfine field |H_{eff}|, isomer shift δ, and quadrupole shift 2ϵ agree well with the observed experimental parameters. These results provide the first experimental evidence for the magnetic Friedel oscillations, which penetrate several layers from the Fe(001) surface.
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Nonlinear optical frequency conversion has been challenged to move down to the extreme ultraviolet and x-ray region. However, the extremely low signals have allowed researchers to only perform transmission experiments of the gas phase or ultrathin films. Here, we report second harmonic generation (SHG) of the reflected beam of a soft x-ray free-electron laser from a solid, which is enhanced by the resonant effect. The observation revealed that the double resonance condition can be met by absorption edges for transition metal oxides in the soft x-ray range, and this suggests that the resonant SHG technique can be applicable to a wide range of materials. We discuss the possibility of element-selective SHG spectroscopy measurements in the soft x-ray range.
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Half-metallic fully compensated ferrimagnets (HM-FCFMs) constitute a special class of half-metals exhibiting zero magnetization at zero temperature. While there have been a number of theoretical studies predicting the existence of such materials over the last 25 years, very few of those have been synthesized and observed that they exhibit expected properties. Herein, we demonstrate that a NiAs-type hexagonal-structured (CrFe)S compound could serve as an HM-FCFM material. It has a half-metallic nature of 100% spin-polarised Fermi surfaces and yet zero magnetisation at the ground state. The magnetisation shows linear behaviour as a function of the magnetic field at temperatures below the compensation temperature (~ 190 K). In addition, it shows a high magnetic coercivity of 3.8 T at 300 K. These magnetic features contribute to a significant development in the application of HM-FCFMs for spintronics devices.
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A new virus-like particle has been found in Drosophila. Thus far it has been detected only in electron micrographs of certain cells capable of division, such as those in larval imaginal disks, cell lines derived from imaginal disks, cells from a genetically controlled brain tumor, and adult gut cells. It appears to be slightly elliptical in shape, about 37 millimicrons by 45 millimicrons, and occurs in both the nucleus and cytoplasm. From the evidence it is suggested that the particle is a new virus.
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The electronic structures of transition metal pnictides ABX(2), where A and B are the transition metal elements and X = N, P, As, Sb, and Bi, with the total valence d-electron number of the transition metal ions being ten, are investigated in the framework of the first-principles KKR Green's function method. Some possible crystal structures such as NiAs-type, NaCl-type, chalcopyrite, zinc-blende, wurtzite, and MnP-type structures are assumed. Similarly to chalcogenides, a new type of spin-compensated half-metallic ferrimagnet is found for the case of nitrides. The stability and magnetic transition temperature of these nitrides indicate that they are good candidates for spintronics materials. For other cases of pnictides such as P, As, Sb, and Bi, the half-metallicity seems not to be realized.
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We present a relativistic formulation of the optimized effective potential method (ROEP) and its implementation within the Korringa-Kohn-Rostoker multiple scattering formalism. The scheme is an all-electron approach, treating core and band states formally on the same footing. We use exact exchange (EXX) as an approximation to the exchange correlation functional. Numerical four-component wavefunctions for the description of core and valence electrons and the corresponding ingredients of the ROEP integral equation are employed. The exact exchange expression for the valence states is reformulated in terms of the electronic Green's function that in turn is evaluated by making use of multiple scattering formalism. We present and discuss the application of the formalism to non-magnetic alkali metals.
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Co doped ZnO (Zn(1-x)Co(x)O) is studied as a prototype material for transition metal doped II-VI diluted magnetic semiconductors (DMSs) from first-principles and Monte Carlo simulations. The exchange interactions are calculated using the Korringa-Kohn-Rostoker (KKR) Green's function method. The exchange coupling constants thus obtained are treated in the classical Heisenberg model and the magnetic phase transitions are studied by the Monte Carlo technique. Our results show that the defect free substitutional DMSs of Zn(1-x)Co(x)O do not sustain magnetization at low concentration. At high concentration, we find layered magnetic structures. Ferromagnetism, with Curie temperature below room temperature, is stable at intermediate Co concentrations. First-principles studies with the generalized gradient approximation (GGA) and the GGA together with the Hubbard U are discussed with respect to structural and electronic properties of ZnO.
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RATIONALE AND OBJECTIVES: To investigate the impact of random survival forest (RSF) classifier trained by radiomics features over the prediction of the overall survival of patients with resectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The dynamic computed tomography data of 127 patients (97 men, 30 women; mean age, 68 years) newly diagnosed with resectable HCC were retrospectively analyzed. After manually setting the region of interest to include the tumor within the slice at its maximum diameter, texture analyses were performed with or without a Laplacian of Gaussian filter. Using the extracted 96 histogram based texture features, RSFs were trained using 5-fold cross-validation to predict the individual risk for each patient on disease free survival (DFS) and overall survival (OS). The associations between individual risk and DFS or OS were evaluated using Kaplan-Meier analysis. The effects of the predicted individual risk and clinical variables upon OS were analyzed using a multivariate Cox proportional hazards model. RESULTS: Among the 96 histogram based texture features, RSF extracted 8 of high importance for DFS and 15 for OS. The RSF trained by these features distinguished two patient groups with high and low predicted individual risk (P=1.1×10-4 for DFS, 4.8×10-7 for OS). Based on the multivariate Cox proportional hazards model, high predicted individual risk (hazard ratio=1.06 per 1% increase, P=8.4×10-8) and vascular invasion (hazard ratio=1.74, P=0.039) were the only unfavorable prognostic factors. CONCLUSIONS: The combination of radiomics analysis and RSF might be useful in predicting the prognosis of patients with resectable HCC.
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Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Tomografía Computarizada por Rayos X , Anciano , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Neoplasias Hepáticas/patología , Masculino , Invasividad Neoplásica , Pronóstico , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
Phorbol esters activate the expression of a variety of early-response genes through protein kinase C-dependent pathways. In addition, phorbol esters may promote cell growth by the inhibition of expression of cellular gene products regulated by antiproliferative agents such as interferons (IFN)s. In human diploid fibroblasts, phorbol 12-myristate 13-acetate (PMA) selectively inhibits the IFN-alpha-induced cellular gene ISG54. Using transient transfection assays, we have delineated two elements in the promoter of this gene that are necessary for the inhibitory actions of PMA. These elements include (i) the IFN-stimulated response element (ISRE) which is necessary for IFN-alpha-induced cellular gene expression, and (ii) an element located near the site of transcription initiation. IFN-alpha treatment resulted in the rapid induction of ISGF3, a multisubunit transcription factor which binds to the ISRE. PMA caused a substantial reduction in IFN alpha-induced ISGF3 in both nuclear and cytoplasmic extracts, as determined by electrophoretic mobility shift assays with the ISRE as a probe. In vitro reconstitution experiments revealed that IFN-alpha activation of the ISGF3 alpha component of ISGF3 was not affected by PMA. Further experiments were consistent with the possibility that PMA regulated the activity of a cellular factor which competed with ISGF3 gamma for binding of the activated ISGF3 alpha polypeptides. Electrophoretic mobility shift assays using the cap site of ISG54 as a probe demonstrated the formation of a specific complex whose DNA binding activity was not affected by treatment of cells with PMA or IFN-alpha. Competitive inhibition studies were consistent with the DNA-protein complex at the cap site of ISG54 containing proteins with DNA binding sites in common with those which also interact with the ISRE. These data suggest a unique regulatory mechanism by which phorbol esters can modulate IFN signaling.
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Interferón-alfa/antagonistas & inhibidores , Regiones Promotoras Genéticas , Transducción de Señal/efectos de los fármacos , Acetato de Tetradecanoilforbol/farmacología , Secuencia de Bases , Línea Celular , Colforsina/farmacología , ADN , Proteínas de Unión al ADN/metabolismo , Fibroblastos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interferón-alfa/fisiología , Datos de Secuencia Molecular , Transducción de Señal/fisiología , TransfecciónRESUMEN
The electronic and magnetic properties of pyrite-type mixed crystals M(1-x)M(x)(')S(2) (M, M(') = Fe,Co,Ni) were investigated by use of the full-potential Korringa-Kohn-Rostoker (KKR) method combined with the coherent potential approximation (CPA). The results well explain the systematic behaviour of these systems as long as they are in a metallic phase. It is also concluded that the full-potential treatment is necessary to describe these anisotropic systems.
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The possibility of half-metallic diluted antiferromagnetic semiconductors of II-VI compounds is investigated on the basis of first-principles electronic structure calculation. The electronic structures of ZnS, ZnSe, ZnO, CdS and CdSe doped with two kinds of 3d transition metal ions are calculated using the Korringa-Kohn-Rostoker (KKR) method and their magnetic transition temperatures are determined using a cluster-type approximation. It is predicted that II-VI compound semiconductors doped with two kinds of magnetic ions might be good candidates for half-metallic antiferromagnets.
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The aim of this work is to develop the method of calculating atomic interactions in metals and semiconductors on the basis of first-principles electronic structure calculation. A new method to calculate the atomic interactions in the framework of KKR-CPA is proposed. In this approach two specific atoms embedded in a CPA medium are considered and the effects of both electron-electron interactions and multiple scattering, which are neglected in the generalized perturbation method (GPM), are fully taken into account. The calculated atomic interactions show that these effects are important for alloys containing transition-metal alloys such as FeAl. On the other hand, in the case of AuCu, where the d states lie considerably below the Fermi level, the effects are less important.
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It is well known that the magnetizations as a function of the valence electron number per atom of 3d transition metal substitutional alloys form the so-called Slater-Pauling curve. Similarly, the Curie temperatures of these alloys also show systematic behaviour against the valence electron number. Though this fact has long been known, no attempt has been made so far to explain this behaviour from first principles. In this paper we calculate T(C) of 3d transition metal alloys in the framework of first-principles electronic structure calculation based on the local density approximation.
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BACKGROUND: Growth factors can enhance the malignant potential of tumor cells. To examine the relationship between growth factors and tumor progression, we previously established a weakly malignant cell line, ER-1. We found that a 24-hour exposure of ER-1 cells to epidermal growth factor (EGF) induced malignant properties (tumor progression) that were reversible but that, after a 1-month exposure, these changes were irreversible. In this study, we investigated the irreversible changes induced in ER-1 cells by a 1-month exposure to EGF and the possible involvement of oxidative stress. METHODS: ER-1 cells were treated with EGF (100 ng/mL) for 1 month in the presence or absence of an antioxidant, N-acetylcysteine or selenium, and compared with untreated control ER-1 cells. We assessed tumor progression by measuring intracellular peroxide levels, 8-hydroxydeoxyguanosine (a marker for oxidative DNA damage) levels, in vitro invasiveness, and in vivo tumorigenicity and metastatic ability. All statistical tests are two-sided. RESULTS: After ER-1 cells were treated for 1 month with EGF, levels of intracellular peroxide and 8-hydroxyguanosine in the DNA of treated cells were higher than those in the DNA of control cells, and treated ER-1 cells were more tumorigenic and metastatic in vivo and more invasive in vitro than untreated control cells (all P<.001). Levels of 8-hydroxyguanosine in DNA increased as the length of the EGF treatment increased (P<.001). However, when N-acetylcysteine or selenium was added with EGF for 1 month, levels of intracellular peroxide and 8-hydroxyguanosine in DNA were comparable to those in control cells (r =.795). Both tumorigenicity (P =.008) and metastatic ability (P<.001) decreased after addition of N-acetylcysteine or selenium. CONCLUSION: The irreversible changes caused by continuous EGF stimulation of ER-1 cells result from increased oxidative damage in the DNA, which generates tumor cells with more malignant characteristics.
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Adenocarcinoma/metabolismo , Daño del ADN , Desoxiguanosina/análogos & derivados , Factor de Crecimiento Epidérmico/efectos adversos , Depuradores de Radicales Libres/farmacología , Neoplasias Mamarias Experimentales/metabolismo , Estrés Oxidativo , 8-Hidroxi-2'-Desoxicoguanosina , Acetilcisteína/farmacología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Animales , Antioxidantes/farmacología , Daño del ADN/efectos de los fármacos , Desoxiguanosina/metabolismo , Progresión de la Enfermedad , Femenino , Glutatión Peroxidasa/metabolismo , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/genética , Microscopía Confocal , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Selenio/farmacología , Células Tumorales CultivadasRESUMEN
The question of whether 8-hydroxyguanine (8-OHG) formation is involved in initiation by low dose levels of N-nitrosodiethylamine (DEN) was addressed using a rat liver model. Male Fischer 344 rats, 6 weeks of age, were administered single i.p. doses of DEN between 0.001 and 100 mg/kg body weight. The 8-OHG levels in liver DNA were measured within 72 h thereafter in randomly selected rats. The remaining rats were given either no further treatment, partial hepatectomy (PH) at hour 4, or PH with i.p. administration of 500 mg/kg body weight of colchicine on days 1 and 3. A selection procedure was performed between weeks 2 and 4, and the initiating activity of DEN was assessed in terms of development of gamma-glutamyltransferase-positive foci at week 5. The 8-OHG levels in the liver DNA were significantly elevated between hours 6 and 72 in a manner dependent on the DEN dose. Dose-dependent induction of foci was similarly noted with doses of 1-100 and 0.001-100 mg/kg body weight in the non-PH and the PH rats, respectively. The sizes of the foci were also significantly increased in a manner dependent on the DEN doses of 1-100 and 0.001-100 mg/kg body weight in the non-colchicine-treated and the colchicine-treated rats, respectively. Statistically, linear trends of 8-OHG formation due to DEN were different at 0.001-0.1 and 1-100 mg/kg body weight, but the total adducts formed within 72 h of the administration proved to be closely related to the development of foci at the termination. These results indicate that 8-OHG formation in the liver DNA may be involved in DEN initiation of hepatocarcinogenesis even at low dose levels, and that single i.p. doses of 0.001-0.1 and 1-100 mg/kg body weight might exert different effects.
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Dietilnitrosamina/administración & dosificación , Guanina/análogos & derivados , Neoplasias Hepáticas/inducido químicamente , Neoplasias Hepáticas/metabolismo , 2-Acetilaminofluoreno/farmacología , Animales , Tetracloruro de Carbono/farmacología , Colchicina/farmacología , Relación Dosis-Respuesta a Droga , Guanina/metabolismo , Riñón/metabolismo , Modelos Lineales , Neoplasias Hepáticas/terapia , Pulmón/metabolismo , Masculino , Miocardio/metabolismo , Páncreas/metabolismo , Ratas , Ratas Endogámicas F344 , Medición de Riesgo , Factores de Tiempo , gamma-Glutamiltransferasa/metabolismoRESUMEN
The chemopreventive potential of a selective cyclooxygenase-2 inhibitor, nimesulide (NIM), against the development of rat superficial urinary bladder carcinomas after initiation with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. Six-week-old Fischer 344 male rats were given 0.05% BBN in their drinking water for 8 weeks, followed by diets supplemented with 0, 100, 200, or 400 ppm NIM for 12 weeks, and they were then sacrificed. NIM decreased, in a dose-dependent manner, the incidence of transitional cell carcinoma (TCC) to 12 of 20 (60.0%), 8 of 16 (50.0%), and 5 of 19 (26.3%) and the multiplicity of TCCs to 0.75 +/- 0.79, 0.56 +/- 0.63, and 0.37 +/- 0.78 per rat at 100, 200, and 400 ppm, respectively, as compared with the BBN alone group values of 18 of 20 (90.0%) and 2.35 +/- 1.23. NIM did not significantly affect the cell differentiation or invasiveness of TCCs. These results indicate clear chemopreventive potential of a selective cyclooxygenase-2 inhibitor against postinitiation development of superficial rat urinary bladder carcinomas.
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Carcinoma/prevención & control , Inhibidores de la Ciclooxigenasa/uso terapéutico , Sulfonamidas/uso terapéutico , Neoplasias de la Vejiga Urinaria/prevención & control , Animales , Peso Corporal/efectos de los fármacos , Butilhidroxibutilnitrosamina , Carcinógenos , Carcinoma/inducido químicamente , Carcinoma/patología , Ingestión de Alimentos/efectos de los fármacos , Incidencia , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas F344 , Neoplasias de la Vejiga Urinaria/inducido químicamente , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
The neural plasticity associated with behavioral sensitization following repeated administration of a psychostimulant methamphetamine (METH) is thought to require synthesis of new proteins. The aim of the present study was to investigate the role of p70-S6 kinase (p70-S6K) phosphorylation, which contributes to the selective translation of a unique family of mRNA, in mediating both the METH-induced rewarding effect and its sensitization. An intra-nucleus accumbens (N.Acc.) pre-injection with 0.025 pmol/rat of a selective p70-S6K inhibitor rapamycin failed to affect the METH-induced conditioned place preference. However, this treatment clearly abolished the development of sensitization of the METH-induced conditioned place preference. Consistent with the behavioral assay, the level of the immunoreactivity of phosporylated-p70-S6K was not changed in the cytosolic fraction of the N.Acc. obtained from rats that had revealed the METH-induced rewarding effect. In contrast, the immunoreactivities in the cytosolic preparation for Western blotting and immunohistochemical density of phosphorylated-p70-S6K were significantly increased in the N.Acc. obtained from METH-sensitized rats as compared with those with chronic saline treatment. However, the immunoreactivities of phosphorylated-extracellular signal-regulated kinase and phosphorylated-ribosomal S6 protein were not significantly altered in the N.Acc. under the same condition. The present data provide evidence for the change in the translation rate, which can be regulated by S6K phosphorylation, in the N.Acc. during the development of sensitization to METH-induced rewarding effects in rats.
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Estimulantes del Sistema Nervioso Central/farmacología , Condicionamiento Operante/efectos de los fármacos , Metanfetamina/farmacología , Recompensa , Proteínas Quinasas S6 Ribosómicas 70-kDa/fisiología , Animales , Conducta Animal/efectos de los fármacos , Western Blotting/métodos , Vías de Administración de Medicamentos , Interacciones Farmacológicas , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Inmunohistoquímica/métodos , Masculino , Microinyecciones/métodos , Núcleo Accumbens/efectos de los fármacos , Fosforilación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Sirolimus/farmacologíaRESUMEN
OBJECTIVE: To solve a possible relationship between mtDNA mutation of tRNALYS(8344) and diabetes, we have surveyed the tRNALYS mutation, glucose intolerance, and insulin secretory capacity in a Japanese family with diabetes and myoclonic epilepsy with ragged-red fiber disease. Several lines of evidence suggested possible linkage between mtDNA mutation and diabetes (1-4). RESEARCH DESIGN AND METHODS: DNA was isolated from peripheral lymphocytes. The polymerase chain reaction analysis for the tRNA(LYS)(8344) mutation of the mtDNA was conducted as described by Larsson (5). Insulin secretory capacity was assessed by 24-h urinary C-peptide immunoreactivity response (CPR) excretion and plasma CPR to glucagon administration. RESULTS: We identified seven subjects with the tRNA(LYS) mutation as well as seven non-mutated members in the pedigrees. Oral glucose tolerance tests in the pedigree indicated that five of the mutated subjects were diabetic, one had impaired glucose tolerance, and one had normal glucose tolerance (NGT), whereas all nonmutated family members had NGT. The pedigree shows maternal transmission of diabetes and the tRNA(LYS) mutation over three generations. Twenty-four-hour urinary excretion of CPR was significantly reduced in the mutant subjects (mean +/- SD, 67.8 +/- 79.2 nmol/day, n = 6, P < 0.001) compared with the nonmutant members (276.6 +/- 41.8 nmol/day, n = 5) and the age-matched normal control subjects (263 +/- 64.3 nmol/day, n = 12). Plasma CPR 6 min after glucagon injection demonstrated a marked reduction in the mutant subjects (3.68 +/- 3.45 nmol/l, n = 5, P < 0.001) compared with the nonmutant members (19.4 +/- 1.17 nmol/l, n = 5) and the normal control subjects (15.8 +/- 3.81 nmol/l, n = 12). Bilateral neurosensory deafness was demonstrated in five of seven (71.4%) mutant subjects (five of five [100%] mutated diabetic patients), but not detected in six nonmutant members. CONCLUSIONS: This observation is the first report of association of diabetes with the mitochondrial tRNA(LYS) mutation. Insulin secretory capacity was significantly lower in the mutant members than in the nonmutated members. These findings suggest that the pancreatic beta-cell secretory defect of insulin might be one of the phenotypes of the mitochondrial tRNA(LYS) mutation.