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Antiinflamatorios/administración & dosificación , Prednisona/administración & dosificación , Accidente Cerebrovascular/diagnóstico , Arteritis de Takayasu/diagnóstico , Arteritis de Takayasu/tratamiento farmacológico , Anciano , Proteína C-Reactiva/análisis , Humanos , Imagen por Resonancia Magnética , Masculino , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: In x Ga1-x Sb is an important material that has tunable properties in the infrared (IR) region and is suitable for IR-device applications. Since the quality of crystals relies on growth conditions, the growth process of alloy semiconductors can be examined better under microgravity (µG) conditions where convection is suppressed. AIMS: To investigate the dissolution and growth process of In x Ga1-x Sb alloy semiconductors via a sandwiched structure of GaSb(seed)/InSb/GaSb(feed) under normal and µG conditions. METHODS: In x Ga1-x Sb crystals were grown at the International Space Station (ISS) under µG conditions, and a similar experiment was conducted under terrestrial conditions (1G) using the vertical gradient freezing (VGF) method. The grown crystals were cut along the growth direction and its growth properties were studied. The indium composition and growth rate of grown crystals were calculated. RESULTS: The shape of the growth interface was nearly flat under µG, whereas under 1G, it was highly concave with the initial seed interface being nearly flat and having facets at the peripheries. The quality of the µG crystals was better than that of the 1G samples, as the etch pit density was low in the µG sample. The growth rate was higher under µG compared with 1G. Moreover, the growth started at the peripheries under 1G, whereas it started throughout the seed interface under µG. CONCLUSIONS: Kinetics played a dominant role under 1G. The suppressed convection under µG affected the dissolution and growth process of the In x Ga1-x Sb alloy semiconductor.
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Mitotic catastrophe, which refers to cell death or its prologue triggered by aberrant mitosis, can be induced by a heterogeneous group of stimuli, including chromosome damage or perturbation of the mitotic apparatus. We investigated the mechanism of mitotic catastrophe and cell death induced by depletion of centrosomal proteins that perturbs microtubule organization. We transfected cells harboring wild-type or mutated p53 with siRNAs targeting Aurora A, ninein, TOG, TACC3, γ-tubulin, or pericentriolar material-1, and monitored the effects on cell death. Knockdown of Aurora A, ninein, TOG, and TACC3 led to cell death, regardless of p53 status. Knockdown of Aurora A, ninein, and TOG, led to aberrant spindle formation and subsequent cell death, which was accompanied by several features of apoptosis, including nuclear condensation and Annexin V binding in HeLa cells. During this process, cleavage of poly(ADP-ribose) polymerase-1, caspase-3, and caspase-9 was detected, but cleavage of caspase-8 was not. Cell death, monitored by time-lapse imaging, occurred during both interphase and M phase. In cells depleted of a centrosomal protein (Aurora A, ninein, or TOG), the rate of cell death was higher if the cells were cotransfected with siRNA against BubR1 or Mad2 than if they were transfected with siRNA against Bub1 or a control siRNA. These results suggest that metaphase arrest is necessary for the mitotic catastrophe and cell death caused by depletion of centrosomal proteins. Knockdown of centrosomal proteins led to increased phosphorylation of Chk2. Enhanced p-Chk2 localization was also observed at the centrosome in cells arrested in M phase, as well as in the nuclei of dying cells. Cotransfection of siRNAs against Chk2, in combination with depletion of a centrosomal protein, decreased the amount of cell death. Thus, Chk2 activity is indispensable for apoptosis after mitotic catastrophe induced by depletion of centrosomal proteins that perturbs microtubule organization.
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Apoptosis , Centrosoma/metabolismo , Mitosis , Aurora Quinasas , Autoantígenos/genética , Autoantígenos/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , División Celular , Línea Celular Tumoral , Quinasa de Punto de Control 2 , Proteínas del Citoesqueleto/antagonistas & inhibidores , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Células HCT116 , Células HeLa , Humanos , Interfase , Proteínas Asociadas a Microtúbulos/antagonistas & inhibidores , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Huso Acromático/metabolismo , Imagen de Lapso de Tiempo , Tubulina (Proteína)/química , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
X-ray line spectra ranging from 17 to 77 keV were quantitatively measured with a Laue spectrometer, composed of a cylindrically curved crystal and a detector. Either a visible CCD detector coupled with a CsI phosphor screen or an imaging plate can be chosen, depending on the signal intensities and exposure times. The absolute sensitivity of the spectrometer system was calibrated using pre-characterized laser-produced x-ray sources and radioisotopes. The integrated reflectivity for the crystal is in good agreement with predictions by an open code for x-ray diffraction. The energy transfer efficiency from incident laser beams to hot electrons, as the energy transfer agency for specific x-ray line emissions, is derived as a consequence of this work.
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The incidence of fibrous dysplasia (FD) is not frequent in the case of benign bone tumors of the chest wall, and differential diagnosis between FD and the malignancy on the basis of imaging findings is difficult. We report a case of a painful FD lesion (size, 9×8 cm) that originated from the 5th rib of a 52-year-old man and was surgically resected. His symptoms improved after the operation. Painful and large FD lesions should be resected because of a difficulty in differential diagnosis from malignant tumors.
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Displasia Fibrosa Ósea/cirugía , Costillas , Displasia Fibrosa Ósea/patología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Aurora kinases and cyclin-dependent kinases, which play critical roles in the cell cycle and are frequently overexpressed in a variety of tumors, have been suggested as attractive targets for cancer therapy. JNJ-7706621, a recently identified dual inhibitor of these kinases, is reported to induce cell cycle arrest, endoreduplication, and apoptosis. In the present study, we further investigated the molecular mechanisms underlying these effects. The inhibitor arrested various cells at G2 phase at low concentration, and at both G1 and G2 phases at high concentration. JNJ-7706621 did not prevent localization of Aurora A to the spindle poles, but did inhibit other centrosomal proteins such as TOG, Nek2, and TACC3 in early mitotic phase. Similarly, the drug did not prevent localization of Aurora B to the kinetochore, but did inhibit other chromosomal passenger proteins such as Survivin and INCENP. In the cells exposed to JNJ-7706621 after nocodazole release, Aurora B, INCENP, and Survivin became relocated to the peripheral region of chromosomes, but Plk1 and Prc1 were localized on microtubules in later mitotic phase. Treatment of nocodazole-synchronized cells with JNJ-7706621 was able to override mitotic arrest by preventing spindle checkpoint signaling, resulting in failure of chromosome alignment and segregation. Injection of the drug significantly inhibited the growth of TC135 Ewing's sarcoma cells transplanted into athymic mice by cell cycle arrest and apoptosis. JNJ-7706621 is a unique inhibitor regulating cell cycle progression at multiple points, suggesting that it could be useful for cell cycle analysis and therapy of various cancers, including Ewing's sarcoma.
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Antineoplásicos/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Mitosis/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Triazoles/farmacología , Animales , Aurora Quinasa A , Aurora Quinasa B , Aurora Quinasas , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/enzimología , Neoplasias Óseas/patología , Proliferación Celular/efectos de los fármacos , Quinasas Ciclina-Dependientes/metabolismo , Citocinesis/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , Ratones , Ratones Desnudos , Neoplasias/enzimología , Neoplasias/patología , Nocodazol/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Transporte de Proteínas , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/enzimología , Sarcoma de Ewing/patología , Huso Acromático/efectos de los fármacos , Huso Acromático/enzimología , Factores de Tiempo , Moduladores de Tubulina/farmacología , Carga Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Many researchers have studied differences in conditions of ethnic skin using biophysical measurements. However, few studies to date have focused on the antioxidative capacity of the skin. METHODS: We measured two parameters of oxidative stress in the stratum corneum, catalase activity and protein carbonylation of the stratum corneum (SCCP), in two ethnic groups, Japanese and French subjects, to characterize the susceptibility to oxidative stress. We also measured several physiological parameters at three different skin sites, two sun-exposed sites (cheek and dorsal aspect of the hand) and a sun-protected site (inner upper arm), in both ethnic groups. RESULTS: Transepidermal water loss (TEWL), the size of corneocytes and skin color showed differences between sun-exposed and sun-protected sites regardless of ethnicity. Regarding ethnic differences, catalase activities and parameters of skin hydration and barrier function of Japanese subjects were higher than those of French subjects. However, SCCP values showed a trend contrary to catalase activity. The difference in the b* value indicated that the melanin content of Japanese skin was higher than that of French skin. Pearson's correlation analyses showed that catalase activity and SCCP values had weak relationships with water content, TEWL and skin color in both ethnic groups. CONCLUSION: Differences in susceptibility to oxidative stress, namely melanin content and catalase activity in the skin, induce the better skin condition of Japanese compared with French subjects.
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Antioxidantes/metabolismo , Estrés Oxidativo/fisiología , Piel/metabolismo , Luz Solar/efectos adversos , Adolescente , Adulto , Pueblo Asiatico , Catalasa/metabolismo , Etnicidad , Femenino , Francia , Humanos , Japón , Masculino , Melaninas/metabolismo , Persona de Mediana Edad , Carbonilación Proteica/fisiología , Pigmentación de la Piel/fisiología , Pérdida Insensible de Agua/fisiología , Población Blanca , Adulto JovenRESUMEN
Kα line emissions from Mo and Ag plates were experimentally studied using clean, ultrahigh-intensity femtosecond laser pulses. The absolute yields of Kα x-rays at 17 keV from Mo and 22 keV from Ag were measured as a function of the laser pulse contrast ratio and irradiation intensity. Significantly enhanced Kα yields were obtained for both Mo and Ag by employing high contrast ratios and irradiances. Conversion efficiencies of 4.28×10â»5/sr for Mo and 4.84×10â»5/sr for Ag, the highest values obtained to date, were demonstrated with contrast ratios in the range 10⻹° to 10⻹¹.
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Rayos Láser , Rayos X , Diseño de Equipo , Análisis de Falla de Equipo , Dosis de RadiaciónRESUMEN
Recent studies have demonstrated that lysophospholipids (LPL) play critical roles in several biological signal transduction pathways to maintain the homoeostasis of cells, tissues and organs. Among them, lysophosphatidic acid (LPA) has been identified as a lipid mediator that induces morphological improvement in the epidermis in mice. In this study, we examined the effects of LPL (soybean-derived phospholipids modified with phospholipase A2 and C) compared with LPA. We initially examined the effects of LPA on normal human epidermal keratinocytes (NHEK) focusing on the expression of profilaggrin and serine palmitoyltransferase (SPT) mRNAs. LPA enhanced the expression of profilaggrin and SPT mRNAs via the modulation of Ca(2+) influx. Based on those results, the influence of LPL on NHEK was examined and was expanded to analyse the expression of two tight junction-related proteins, occludin and claudin-1. LPL had similar effects to increase profilaggrin and SPT mRNA expression and also stimulated the expression of occludin and claudin-1 at the mRNA and protein levels. In accordance with these results, LPL elicited significant improvements in surface water content in human skin. These findings indicate that LPL has the potential to strengthen the skin moisturizing capability by up-regulating the expression of mRNAs encoding components important to skin barrier function and skin hydration.
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Calcio/metabolismo , Diferenciación Celular/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Lisofosfolípidos/farmacología , Piel/efectos de los fármacos , Piel/metabolismo , Adulto , Western Blotting , Diferenciación Celular/fisiología , Claudina-1 , Método Doble Ciego , Células Epidérmicas , Epidermis/efectos de los fármacos , Epidermis/metabolismo , Humanos , Queratinocitos/citología , Queratinocitos/metabolismo , Lisofosfolípidos/administración & dosificación , Masculino , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/genética , Microscopía de Contraste de Fase , Persona de Mediana Edad , Ocludina , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serina C-Palmitoiltransferasa/biosíntesis , Serina C-Palmitoiltransferasa/genética , Piel/citología , Regulación hacia ArribaRESUMEN
Hydrogen-sorption isotherms of alkali metal-doped carbons at 77 K were determined for promoting application of these materials as hydrogen-recovery and isotope-separation agent. The hydrogen-sorption behavior of rubidium-doped Grafoil, with composition of RbC24, showed high sorption ability against hydrogen at low pressure. Taking into account the fact that sorption-desorption was fast and reversible, and the equilibrium pressure at half coverage was very low, i.e., 40 Pa, RbC24 prepared from Grafoil is promising as a recovery agent for hydrogen gas at low pressure. The hydrogen (H2)/deuterium(D2)-sorption isotherms of potassium-doped carbons with composition of KC10, prepared from multi wall carbon nanotube (MWCNT) and carbons derived from petroleum cokes with heat-treatment temperatures of 1000 and 1500 degrees C, were also determined. Isotope separation coefficient was estimated from those isotherms. A very large isotope effect was found for KC10 prepared from MWCNT, comparable to those prepared from carbons with heat-treatment temperatures of 1000 or 1500 degrees C. However, a severe problem was found for KC10 (MWCNT) that repetition of the sorption-desorption cycles resulted in the decrease of the sorbed amount of H2 and D2.
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The anisotropy of the hot-electron velocity distribution in ultra-high-intensity laser produced plasma was studied with x-ray polarization spectroscopy using multilayer planar targets including x-ray emission tracer in the middle layer. This measurement serves as a diagnostic for hot-electron transport from the laser-plasma interaction region to the overdense region where drastic changes in the isotropy of the electron velocity distribution are observed. These polarization degrees are consistent with analysis of a three-dimensional polarization spectroscopy model coupled with particle-in-cell simulations. Electron velocity distribution in the underdense region is affected by the electric field of the laser and that in the overdense region becomes wider with increase in the tracer depth. A full-angular spread in the overdense region of 22.4 degrees -2.4+5.4 was obtained from the measured polarization degree.
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Dose verification of intensity-modulated arc therapy using an ERGO++ treatment planning system and Elekta internal multileaf collimators is described. Prostate intensity-modulated arc therapy was planned using the arc modulation optimization algorithm inverse planning module of ERGO++. After transferring the plan to Elekta Synergy's controller (Elekta Ltd, Crawley, UK), the isocentre dose was measured and compared with a calculated dose using a pinpoint chamber and a water phantom in a cylindrical acrylic enclosure. Subsequently, an EDR2 film was placed inside a multilayer plastic phantom, and total dose distributions were measured in three axial planes as well as in the coronal and sagittal planes to compare the actual dose with the calculated dose. The dose discrepancy at the isocentre was 1.7%. The calculated gamma indices were less than 1 over 90% of the three axial planes, as well as in the coronal and sagittal planes, having a dose greater than 50% of the maximum target dose.
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Interpretación de Imagen Asistida por Computador/instrumentación , Neoplasias de la Próstata/radioterapia , Planificación de la Radioterapia Asistida por Computador/instrumentación , Radioterapia de Intensidad Modulada/métodos , Algoritmos , Humanos , Masculino , Dosis de Radiación , Dosificación Radioterapéutica , RotaciónRESUMEN
Oxidative stress caused by ultraviolet (UV) radiation generates reactive oxygen species (ROS) in the skin, induces the secretion of melanocyte growth and activating factors from keratinocytes, which results in the formation of cutaneous hyper-pigmentation. Thus, increasing the anti-oxidative ability of skin cells is expected to be a good strategy for skin-lightening cosmetics. Metallothionein (MT) is one of the stress-induced proteins and is known to exhibit a strong anti-oxidative property. We previously reported that a zinc(II) complex with glycine (Zn(II)(Gly)(2)) effectively induces MT expression in cultured human keratinocytes. To determine its potential as a new skin lightening active, we examined whether Zn(II)(Gly)(2) regulates the release of melanocyte-activating factors from UVB-irradiated keratinocytes and affects melanin production in a reconstructed human epidermal equivalent. Conditioned medium from UVB-irradiated keratinocytes accelerated melanocyte proliferation to 110%, and that increase could be prevented by pre-treatment with Zn(II)(Gly)(2). In addition, Zn(II)(Gly)(2) significantly reduced both the production of prostaglandin E(2) and proopiomelanocortin expression in UVB-irradiated keratinocytes. Zn(II)(Gly)(2) also decreased melanin production in a reconstructed human epidermal equivalent. These results indicate that MT-induction in the epidermis effectively up-regulates tolerance against oxidative stress and inhibits the secretion of melanocyte growth and activating factors from keratinocytes. Thus, Zn(II)(Gly)(2) is a good candidate as a new skin-lightening active.
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Glicina/análogos & derivados , Melaninas/biosíntesis , Metalotioneína/biosíntesis , Compuestos Organometálicos/farmacología , Piel/efectos de los fármacos , Rayos Ultravioleta , Compuestos de Zinc/farmacología , Cationes Bivalentes , Línea Celular , Dinoprostona/metabolismo , Glicina/farmacología , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Queratinocitos/efectos de la radiación , Melanocitos/efectos de los fármacos , Melanocitos/metabolismo , Melanocitos/efectos de la radiación , Metalotioneína/genética , Proopiomelanocortina/biosíntesis , Proopiomelanocortina/genética , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Piel/citología , Piel/metabolismo , Piel/efectos de la radiaciónRESUMEN
Citrin is the liver-type aspartate-glutamate carrier that resides within the inner mitochondrial membrane. Citrin deficiency (due to homozygous or compound heterozygous mutations in the gene SLC25A13) causes both adult-onset type II citrullinaemia (CTLN2) and neonatal intrahepatic cholestasis (NICCD). Clinically, CTLN2 is characterized by hyperammonaemia and citrullinaemia, whereas NICCD has a much more varied and transient presentation that can include multiple aminoacidaemias, hypoproteinaemia, galactosaemia, hypoglycaemia, and jaundice. Personal histories from CTLN2 patients have repeatedly described an aversion to carbohydrate-rich foods, and clinical observations of dietary and therapeutic outcomes have suggested that their unusual food preferences may be directly related to their pathophysiology. In the present study, we monitored the food intake of 18 Japanese citrin-deficient subjects whose ages ranged from 1 to 33 years, comparing them against published values for the general Japanese population. Our survey confirmed a marked decrease in carbohydrate intake, which accounts for a smaller proportion of carbohydrates contributing to the total energy intake (PFC ratio) as well as a shift towards a lower centile distribution for carbohydrate intake relative to age- and sex-matched controls. These results strongly support an avoidance of carbohydrate-rich foods by citrin-deficient patients that may lead to worsening of symptoms.
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Proteínas de Unión al Calcio/deficiencia , Colestasis Intrahepática/etiología , Citrulinemia/etiología , Carbohidratos de la Dieta/administración & dosificación , Preferencias Alimentarias , Transportadores de Anión Orgánico/deficiencia , Adolescente , Adulto , Niño , Preescolar , Grasas de la Dieta/administración & dosificación , Ingestión de Energía , Femenino , Glucosa/metabolismo , Humanos , Lactante , Masculino , Persona de Mediana Edad , NAD/metabolismoRESUMEN
There are many reports indicating that night time blood pressure (BP) is closely associated with target organ damage. However, BP in the waking period is influenced by physical activity and also by the psychological status. Recently, base BP (BP0: minimum and stable BP during sleep) has been reported to correlate with organ damage in hypertensives. However, little is known about the implications of BP0. We examined how BP0 is associated with BP, heart rate variability and health-related quality of life (HRQOL) in healthy subjects. One hundred and thirty-five participants, composed of 88 male and 47 female (age: 21-33 years) underwent a 24-h ambulatory BP monitoring (ABPM). Sympathetic nervous activity (ratio of low-frequency to high-frequency component: LF/HF) and parasympathetic nervous activity (high-frequency component: HF) were calculated by electrocardiogram monitoring. BP0 was calculated as previously reported. HRQOL was assessed by Medical Outcome Study Short-Forum 36-Item Health Survey. Base systolic BP (SBP0) positively correlated with 24-h systolic BP (SBP) (r=0.662, P<0.0001) and night time SBP (r=0.810, P<0.0001). SBP0 positively correlated with 24-h LF/HF (r=0.214, P<0.02) and night time LF/HF (r=0.326, P<0.001). Moreover, SBP0 negatively correlated with the scores of body pain (r=-0.223, P<0.02). Multiple linear regression analysis showed that SBP0 correlated with gender (P<0.01), night time LF/HF (P<0.04) and the scores of body pain (P<0.04). In conclusion, SBP0 correlated with BP, LF/HF and the scores of body pain (HRQOL). SBP0 may be a useful indicator for assessing 24-h BP, sympathetic nervous functions and HRQOL in healthy subjects.
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Presión Sanguínea , Calidad de Vida , Sueño/fisiología , Adulto , Monitoreo Ambulatorio de la Presión Arterial , Femenino , Humanos , Masculino , Análisis Multivariante , Dolor/fisiopatología , Sistema Nervioso Simpático/fisiologíaRESUMEN
There is a concern on the part of public health community that adverse health consequence by thimerosal, a preservative in vaccines for infants, may occur among infants during immunization schedule. Therefore, the cytotoxic action of thimerosal was examined on lymphocytes dissociated from thymic glands of young rats using a flow cytometer and respective fluorescent probes for monitoring changes in intracellular Ca2+ concentration ([Ca2+]i) and membrane potential, and for discriminating intact living cells, apoptotic living cells and dead cells. Incubation with thimerosal at 3 microM or more (up to 30 microM) for 60 min depolarized the membranes, associated with increasing the [Ca2+]i. Thimerosal at 30 microM induced an apoptotic change in membranes of almost all living cells. Furthermore, the prolonged incubation with 30 microM thimerosal induced a loss of membrane integrity, leading to cell death. Since the blood concentration of thimerosal after receiving vaccines is theoretically submicromolar, it may be unlikely that thimerosal affects lymphocytes of infants.
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Citometría de Flujo/métodos , Linfocitos/efectos de los fármacos , Conservadores Farmacéuticos/toxicidad , Timerosal/toxicidad , Vacunas/efectos adversos , Animales , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Separación Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Membranas Intracelulares/efectos de los fármacos , Linfocitos/metabolismo , Linfocitos/patología , Ratas , Ratas Wistar , Timo/citologíaRESUMEN
OBJECTIVES: To examine whether autoantibodies against bone morphogenetic protein receptor-II (BMPR-II) or activin receptor-like kinase 1 (ALK-1) are associated with pulmonary arterial hypertension (PAH) in patients with mixed connective tissue disease (MCTD). METHODS: We studied sera from 37 MCTD patients with or without PAH, six patients with idiopathic PAH, and 30 healthy controls. Circulating anti-BMPR-II and anti-ALK-1 antibodies were detected using immunoprecipitation of recombinant antigens generated by in vitro transcription/translation and indirect immunofluorescence of cultured cells that were induced to express these antigens by gene transfer. Anti-BMPR-II antibodies were further examined by immunoprecipitation and immunoblotting using a recombinant fragment of the extracellular domain of BMPR-II. RESULTS: Serum anti-BMPR-II and anti-ALK-1 autoantibodies were not detected in MCTD patients irrespective of the presence or absence of PAH, or in patients with idiopathic PAH. CONCLUSIONS: Our finding does not support the hypothesis that autoantibody-mediated dysregulation of signals through BMPR-II or ALK-1 contributes to the development of PAH in patients with connective tissue diseases.
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Receptores de Activinas Tipo I/inmunología , Autoanticuerpos/sangre , Hipertensión Pulmonar/inmunología , Enfermedad Mixta del Tejido Conjuntivo/inmunología , Proteínas Serina-Treonina Quinasas/inmunología , Receptores de Proteínas Morfogenéticas Óseas de Tipo II , Células Cultivadas , Técnica del Anticuerpo Fluorescente Indirecta/métodos , Humanos , Hipertensión Pulmonar/complicaciones , Immunoblotting/métodos , Enfermedad Mixta del Tejido Conjuntivo/complicaciones , Receptores de Superficie Celular/inmunología , Proteínas Recombinantes/inmunologíaRESUMEN
There is a concern on the part of public health community that adverse health consequences by thimerosal, a preservative in vaccines for infants, may occur among infants during immunization schedule. Therefore, the effect of thimerosal on cellular content of glutathione was examined on thymocytes obtained from 4-week-old rats using a flow cytometer and 5-chloromethylfluorescein diacetate. Thimerosal at concentrations ranging from 1 to 10 microM reduced the cellular content of glutathione in a concentration-dependent manner, and the complete depletion of cellular glutathione was observed when the cells were treated with 30 microM thimerosal. L-Cysteine significantly attenuated the actions of thimerosal to reduce the glutathione content and to increase the intracellular Ca2+ concentration. Prolonged incubation (24 h) with 1-3 microM thimerosal induced the apoptosis. The cytotoxic action of thimerosal was greatly augmented when the cells suffered oxidative stress induced by H2O2. It may be unlikely that thimerosal exerts potent cytotoxic action under the in vivo condition because the blood concentration of thimerosal after receiving vaccines does not seem to reach micromolar range and nonprotein thiols at micromolar concentrations are present in the blood.
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Citometría de Flujo/métodos , Glutatión/metabolismo , Conservadores Farmacéuticos/toxicidad , Timerosal/toxicidad , Timo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Fluoresceínas , Colorantes Fluorescentes , Peróxido de Hidrógeno/farmacología , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Linfocitos/patología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Timo/metabolismo , Timo/patologíaRESUMEN
Metallothionein (MT) is induced in the liver not only by heavy metals, but also by stress such as starvation. However, the meaning of the induced MT during starvation has never been clear. In this study, we investigated the relationship between changes in hepatic MT synthesis and the hepatic damage that occurs during starvation. MT synthesis was assessed by measuring MT contents and the expression of the MT gene in the liver. The hepatic damage was assessed by measuring glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) activities in the serum. MT synthesis in the liver increased over the normal level by starvation, but decreased under the normal level by refeeding after starvation. Both GPT and GOT activities of the refeeding group were higher than those of the control group. However, MT synthesis increased by a subcutaneous injection with CdCl(2) (1 mg Cd /kg) at the same time as refeeding after starvation. At this point, GOT activity decreased until it reached the normal level. MT synthesis decreased by refeeding after starvation, and from the results found in this study, we proposed the hypothesis that the liver damage caused by refeeding after starvation might be due to the decrease in the synthesis of a sufficient amount of MT induced by metals.