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INTRODUCTION: Thinner slices are more susceptible in detecting small lesions but suffer from higher statistical fluctuation. This work aimed to reduce image noise in multiphase contrast-enhanced CT reconstructed with slice thickness thinner than the clinical setting (i.e., 5 mm) using convolutional neural network (CNN) for enabling better detection of hypo-vascular liver metastasis. METHODS: A DenseNet model was used to generate noise map for multiphase CT reconstructed with slice thickness of 2.5 mm and 1.25 mm. Image denoising was conducted by subtracting the CNN-generated noise map from CT images with reduced photon flux due to thinner slice thickness. The performance of DenseNet was evaluated on CT scans of electron density phantoms and patients with hypovascular liver metastases less than 1.5 cm in terms of Hounsfield Unit (HU) variation, statistical fluctuation, and contrast-to-noise ratio (CNR). RESULTS: The phantom study demonstrated that the CNN-based denoising method was able to reduce statistical fluctuation in CT images reconstructed with slice thickness of 2.5 mm and 1.25 mm without causing significant edge blurring or variation in HU values. With regards to patient study, it was found that the denoised 2.5-mm and 1.25-mm slices had higher CNR than the conventional 5-mm slices for hypo-vascular liver metastases in all 4 phases of multiphase CT. CONCLUSION: Our results demonstrated that the detection of hypo-vascular liver metastases in multiphase contrast-enhanced CT with slice thickness less than 5 mm could be improved by using the CNN-based denoising method. IMPLICATIONS FOR PRACTICE: Reconstruction slice thickness has a strong influence on the image quality of CT imaging. A CNN-based denoising method was used in this work to reduce the image noise in multiphase contrast-enhanced CT reconstructed with slice thickness less than 5 mm.
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Medios de Contraste , Neoplasias Hepáticas , Redes Neurales de la Computación , Fantasmas de Imagen , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Tomografía Computarizada por Rayos X/métodos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Relación Señal-Ruido , Hígado/diagnóstico por imagen , Hígado/irrigación sanguíneaRESUMEN
The growth, composition and structure of sandwich structures (Fe-rich layer/Si-rich layer/Fe-rich silicide layer) grown on a Si(111) surface were studied by a few complementary microscopic and spectroscopic techniques with high spatial resolution. Intermixing at the Fe/Si and Si/Fe interfaces is demonstrated. Fe-rich layers grown directly on the Si(111) surface are crystalline and have abrupt but rough interfaces at both sides. The succeeding layers are disordered and their interfaces are fuzzy. The distributions of Fe and Si within the layers are laterally non-uniform. The reproducible fabrication of thin non-magnetic silicide spacers of predetermined thickness is demonstrated. Sandwich structures with such spacers exhibit exchange coupling between ferromagnetic Fe-rich layers.
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The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphomas (PTCLs). Here, we report a robust anti-CD5 CAR (CD5CAR) transduced into a human NK cell line NK-92 that can undergo stable expansion ex vivo. We found that CD5CAR NK-92 cells possessed consistent, specific, and potent anti-tumor activity against a variety of T-cell leukemia and lymphoma cell lines as well as primary tumor cells. Furthermore, we were able to demonstrate significant inhibition and control of disease progression in xenograft mouse models of T-ALL. The data suggest that CAR redirected targeting for T-cell malignancies using NK cells may be a viable method for new and complementary therapeutic approaches that could improve the current outcome for patients.
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Antígenos de Neoplasias/inmunología , Antígenos CD5/inmunología , Inmunoterapia Adoptiva/métodos , Células Asesinas Naturales/inmunología , Linfoma de Células T Periférico/terapia , Terapia Molecular Dirigida , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Proteínas Recombinantes de Fusión/inmunología , Ligando 4-1BB/genética , Ligando 4-1BB/inmunología , Animales , Antígenos CD28/inmunología , Complejo CD3/genética , Complejo CD3/inmunología , Antígenos CD8/inmunología , Línea Celular Tumoral , Técnicas de Cocultivo , Citotoxicidad Inmunológica , Humanos , Células Asesinas Naturales/trasplante , Linfoma de Células T Periférico/patología , Ratones , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Terapia Recuperativa , Anticuerpos de Cadena Única/genética , Anticuerpos de Cadena Única/inmunología , Transducción Genética , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Exchange bias and interlayer exchange coupling are interface driven phenomena. Since an ideal interface is very challenging to achieve, a clear understanding of the chemical and magnetic natures of interfaces is pivotal to identify their influence on the magnetism. We have chosen Ni80Fe20/CoO(t CoO)/Co trilayers as a model system, and identified non-stoichiometric Ni-ferrite and Co-ferrite at the surface and interface, respectively. These ferrites, being ferrimagnets typically, should influence the exchange coupling. However, in our trilayers the interface ferrites were found not to be ferro- or ferri-magnetic; thus having no observable influence on the exchange coupling. Our analysis also revealed that (i) interlayer exchange coupling was present between Ni80Fe20 and Co even though the interlayer thickness was significantly larger than expected for this phenomenon to happen, and (ii) the majority of the CoO layer (except some portion near the interface) did not contribute to the observed exchange bias. We also identified that the interlayer exchange coupling and the exchange bias properties were not interdependent.
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Currently, cardiovascular disease affects a relatively high proportion of the world's population. Thus, developing simple and effective methods for monitoring patients with cardiovascular disease is critical for research. Monitoring the heart rate of patients is a relatively simple and effective method for managing patients with this condition. For patients, the desired heart rate monitoring equipment should be portable, instantaneous, and accurate. Because smartphones have become the most prevalent mobile device, we utilized this technology as a platform for developing a novel heart-rate measurement system. Catering to the phenomenon of people using the front camera of their smartphones as a mirror, the proposed system was designed to analyze facial-image sequences captured using the front camera. A spatiotemporal alpha-trimmed mean filter was developed to estimate a user's heart rate quickly and accurately. The experimental results show that in addition to achieving these objectives, the developed system outperforms a similar personal computer-based system. In addition, the system performs effectively even when users are wearing glasses. Hence, the proposed system demonstrates practical value for people who must monitor their heart rate daily.
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Cara , Frecuencia Cardíaca/fisiología , Fotopletismografía , Teléfono Inteligente , Humanos , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodosRESUMEN
We studied peripheral leukocyte telomere length (LTL) as a predictor of antidepressant response to PPAR-γ agonist in patients with unremitted depression. In addition we examined correlation between LTL and the insulin resistance (IR) status in these subjects. Forty-two medically stable men and women ages 23-71 with non-remitted depression participated in double-blind placebo-controlled add-on of Pioglitazone to treatment-as-usual. Oral glucose tolerance tests were administered at baseline and at 12 weeks. Diagnostic evaluation of psychiatric disorders was performed at baseline and mood severity was followed weekly throughout the duration of the trial. At baseline, no differences in LTL were detected by depression severity, duration or chronicity. LTL was also not significantly different between insulin-resistant and insulin-sensitive subjects at baseline. Subjects with longer telomeres exhibited greater declines in depression severity in the active arm, but not in a placebo arm, P=0.005, r=-0.63, 95% confidence interval (95% CI)=(-0.84,-0.21). In addition, LTL predicted improvement in insulin sensitivity in the group overall and did not differ between intervention arms, P=0.036, r=-0.44, 95% CI=(-0.74,0.02) for the active arm, and P=0.026, r=-0.50, 95% CI=(-0.78,-0.03) for the placebo arm. LTL may emerge as a viable predictor of antidepressant response. An association between insulin sensitization and LTL regardless of the baseline IR status points to potential role of LTL as a non-specific moderator of metabolic improvement in these patients.
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Trastorno Depresivo/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Telómero , Tiazolidinedionas/uso terapéutico , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Pioglitazona , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The clinical manifestations of acute kidney injury (AKI) range from mild to fatal in cats; however, prognosis factors have been rarely studied. HYPOTHESIS/OBJECTIVES: To find the clinical factors significantly correlated with the outcome among cats with AKI and to develop a simple prognostic index. ANIMALS: Seventy cats with AKI were recruited. METHODS: Demographic and clinicopathological data obtained from 70 cats with AKI were retrospectively collected. Student's t-test or Mann-Whitney U-test and Pearson chi-square test or Fisher's exact were applied to determine the factors associated with survival in cats with AKI. Using logistic regression, the statistically significant factors associated with prognosis were identified and a new prediction model was generated. RESULTS: The overall case fatality rate was 64% (45/70). The results showed that nonsurviving cats had significantly lower levels of PCV, WBC, RBC, LDH and albumin, a lower albumin/globulin ratio, lower blood glucose, and a reduced body temperature, as well as being older. Serum urea and creatinine concentrations were not statistically significant as prognostic factors, but a decrease in these 2 variables in 3 days was significantly related to a reduction in death. A summary prognostic index including body temperature and LDH and albumin concentrations had area under the receiver-operating characteristic curve (AUROC) for predicting death of 0.86 (P < .05) and a cut-off value of 0.82, a sensitivity of 77% and a specificity of 90%. CONCLUSIONS: The prognosis in cats with AKI is quite different from that found for human and dogs.
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Lesión Renal Aguda/veterinaria , Enfermedades de los Gatos/patología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/patología , Animales , Análisis Químico de la Sangre/veterinaria , Nitrógeno de la Urea Sanguínea , Enfermedades de los Gatos/sangre , Gatos , Creatinina/sangre , Femenino , Hematócrito/veterinaria , Hemoglobinas/análisis , Recuento de Leucocitos/veterinaria , Masculino , Pronóstico , Curva ROC , Estudios RetrospectivosRESUMEN
Magnetic iron oxide nanoparticles (MIONPs) must be biocompatible, and a thorough knowledge on their potential cytotoxicity is crucial for their biomedical applications. However, the detailed study about the effects of iron oxide nanoparticles on cell viability, cell morphology, and cellular uptake of different mammalian cells is still insufficient. In this paper, comparative cytotoxicity study of uncoated magnetite nanoparticles at different concentrations was performed on human cervical cancer cell line (HeLa) and immortalized normal human retinal pigment epithelial cell line (RPE). The size, structure, and magnetic behavior of the MIONPs were characterized using transmission electron microscopy (TEM), X-ray diffractometry (XRD), and vibrating sample magnetometry (VSM) respectively. After 24-hour incubation with the MIONPs, the cell viability was determined by live/dead assay, the cell morphology at high magnification was observed under scanning electron microscopy (SEM), and the cellular uptake of MIONPs was measured under TEM and verified by energy-dispersive X-ray spectroscopy (EDX) analysis. Our results indicate that the uncoated MIONPs at a high concentration (0.40 mg/ml) were toxic to both HeLa and RPE cells. However, the cytotoxicity of uncoated MIONPs at low concentrations was cell-type specific, and RPE cells were more susceptible to these MIONPs than HeLa cells. The effects of the MIONPs on cell morphology and the nanoparticles uptake also showed different features between these two cell lines. Hence cell type should be taken into consideration in the in vitro cytotoxicity study of uncoated MIONPs. Additionally, it should be noticed that the cell morphological changes and the uptake of nanoparticles can take place even though no toxic effect of these MIONPs at low concentrations was reflected in the traditional cell viability assay.
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Supervivencia Celular/efectos de los fármacos , Magnetismo , Nanopartículas , Células HeLa , Humanos , Técnicas In Vitro , Microscopía Electrónica de Rastreo , Microscopía Electrónica de Transmisión , Microscopía Fluorescente , Espectrometría por Rayos X , Difracción de Rayos XRESUMEN
A retrospective case-series study evaluated the prognosis of 853 dogs with acute kidney injury (AKI) based on the RIFLE (Risk, Injury, Failure, Loss and End-stage renal failure) criteria, derived from human medicine. The 30-day mortality of dogs with AKI in each class was found to be 23.8 per cent (40 of 168) dogs for Risk, 41.0 per cent (107 of 261) dogs for Injury and 78.5 per cent (333 of 424) dogs for Failure. Using the dogs in the Risk class as the reference, the mortality of dogs in either the Injury or Failure class was significantly higher than that of dogs in the Risk class (P<0.05). The longest median survival time was observed in the Risk class (nine days) and the shortest median survival time was observed in the Failure class (three days). Using a multiple logistic regression model, a new score that simultaneously considered RIFLE class, diarrhoea status and serum phosphorus level was calculated to predict prognosis. Evaluation using the area under the receiver-operating characteristic curve (AUROC) indicated that the new scoring method (AUROC 0.80) was a better prognostic indicator than using RIFLE criteria alone (AUROC 0.73).
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Lesión Renal Aguda/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades Renales/veterinaria , Enfermedad Aguda , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Animales , Área Bajo la Curva , Enfermedades de los Perros/mortalidad , Perros , Femenino , Indicadores de Salud , Enfermedades Renales/diagnóstico , Enfermedades Renales/mortalidad , Masculino , Fósforo/sangre , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
The dependence of the cooling field and the ion-beam bombardment on the exchange bias effects in NiFe/(Ni,Fe)O bilayers were investigated. The positive exchange bias was found in the zero-field-cooled (ZFC) process whereas a negative exchange bias occurred in the FC process. The increased exchange field, H(ex) with increasing (Ni,Fe)O thicknesses indicates the thicker the AF (Ni,Fe)O, the stronger the exchange coupling between the NiFe layer and the (Ni,Fe)O layer. In addition, the dependence of the H(ex) (ZFC vs. FC) on the (Ni,Fe)O thicknesses reflects the competition between the applied magnetic field and the (Ni,Fe)O surface layer exchange coupled to the NiFe layer. Further, an unusual oscillating exchange bias was observed in NiFe/(Ni,Fe)O bilayers that results from the surface of the (Ni,Fe)O layer being bombarded with different Ar-ion energies using End-Hall deposition voltages (V(EH)) from 0 to 150 V. The behavior of the H(ex) and the H(c) with the V(EH) is attributed to the surface spin reorientation that is due to moderate ion-beam bombardment effects on the surface of the (Ni,Fe)O layer. Whether the (Ni,Fe)O antiferromagnetic spins are coupled to the NiFe moments antiferromagnetically or ferromagnetically changes the sign of the exchange bias.
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The antioxidative ability, stability of storage protein dioscorin, and the quality of fried yam chips from different cultivars of Chinese yams influenced by various processing treatments were investigated. Total phenolic content and DPPH free radical scavenging effect were found to be the highest in Mingchien (MC) and the lowest in Keelung (KL) yam. Following processing, freeze-dried yams of all varieties showed the least decrease in total phenolic compounds and DPPH radical scavenging effect, while boiling caused the greatest decrease in both. Fresh yams of all varieties contained the highest dioscorin contents comparing with their counterparts. Boiling and deep-frying caused severe protein denaturation resulting in loss of dioscorin solubility after purification. Freeze-drying resulted in increase in protein surface hydrophobicity (So); nonetheless, it attained higher total phenol content, antioxidative capacity, and dioscorin stability of yams compared with other processing treatments. The peroxide values of all yam chips increased during the initial stage, then declined with advanced storage. Fracturability of all yam chips gradually decreased, due to the absorption of moisture, with increasing storage time.
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Antioxidantes/análisis , Dioscorea , Manipulación de Alimentos/métodos , Ipomoea batatas , Culinaria , Estabilidad de Medicamentos , Liofilización , Ipomoea batatas/clasificación , Peróxidos/análisis , Proteínas de Plantas/análisis , Especificidad de la EspecieRESUMEN
Adenocarcinoma of the duodenum is an exceedingly rare disorder. Its vague and non-specific symptoms often lead clinicians and patients to suspect other more benign differential diagnoses. Improved endoscopy and radiology have enabled more of these cases to be unearthed. Definitive surgery is the only means of potential cure, with the prognosis being significantly better for node-negative patients. We present a case of a 52-year-old man who underwent a Whipple's operation for this uncommon disease and a literature review of the subject.
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Adenocarcinoma/diagnóstico , Anorexia/etiología , Neoplasias Duodenales/diagnóstico , Adenocarcinoma/complicaciones , Adenocarcinoma/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Neoplasias Duodenales/complicaciones , Neoplasias Duodenales/cirugía , Humanos , Laparotomía/métodos , Masculino , Persona de Mediana Edad , Pérdida de PesoRESUMEN
We have investigated the structural and magnetic properties of ion-beam deposited polycrystalline NiFe (25 nm)/Fe-oxide (35 nm) bilayers. A film prepared with an assist beam O2 to Ar gas ratio of 0% during deposition had a bottom layer that consisted of pure b.c.c. Fe (a = 2.87 A) whereas films prepared with 19%O2/Ar and 35%O2/Ar had either Fe3O4 (a = 8.47 angstroms) or alpha-Fe2O3 (a = 5.04 angstroms, c = 13.86 angstroms) bottom layers, respectively. Cross-sectional transmission electron microscopy revealed a smooth interface between the top nano-columnar NiFe and bottom nano-columnar Fe-oxide layer for all films. At room temperature, the observed coercivity (Hc approximately 25 Oe) for a film prepared with 19% O2/Ar indicates the existence of a magnetically hard ferrimagnetic Fe3O4 phase that is enhancing the plain NiFe (Hc approximately 2 Oe) by way of exchange coupling. A significant amount of exchange bias is observed below 50 K, and at 10 K the size of exchange bias hysteresis loops shift increases with increasing oxygen in the films. Furthermore, the strongest exchange coupling (H(ex) approximately 135 Oe at 10 K) is with alpha-Fe2O3 (35% O2/Ar) as the bottom film layer. This indicates that the pure antiferromagnetic phases work better than ferrimagnetic phases when in contact with ferromagnetic NiFe. H(ex) (T) is well described by an effective AF domain wall energy that creates an exchange field with a (1 - T/T(crit)) temperature dependence. Hc (T) exhibits three distinct regimes of constant temperature that may indicate the existence of different AF spin populations that couple to the FM layer at different temperatures.
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Electroquímica/métodos , Compuestos Férricos/química , Hierro/química , Nanotecnología/métodos , Níquel/química , Óxidos/química , Iones , Magnetismo , Microscopía Electrónica de Transmisión , Nanotecnología/instrumentación , Oxígeno/química , Temperatura , Difracción de Rayos XRESUMEN
A Ni80Fe20/(Ni,Fe)O thin film exhibits a positive exchange bias when cooled in a zero field and a negative exchange bias when field cooled. With transmission electron microscopy and electron energy loss spectrometry, the composition and magnetic structure has been ascertained and a distribution of magnetization easy axes about the interface extrapolated. The results indicate that the positive exchange bias is from antiferromagnetic interface moments perpendicular to their ferromagnetic counterparts. With field cooling the alignment is put into a parallel configuration resulting in a negative exchange bias.
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CONTEXT: An ethnobotanical study was carried out among the Jah Hut people who live in the central part of peninsular Malaysia. MATERIALS AND METHODS: The information on the medicinal plants was obtained from interview with a traditional medicinal man. The traditional uses and remedies were documented. The literature searches were carried out for the evaluation on the current status of investigations on these plants. RESULTS: In this study, we present 16 species of plants, which are commonly used among the Jah Hut people to cure some common diseases. DISCUSSION: This study is important to preserve the knowledge of medicinal plants used by Jah Hut people. The surveys of phytopharmacological literatures of these plants have great pharmacological and ethnobotanical significance.
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Fitoterapia , Preparaciones de Plantas/uso terapéutico , Plantas Medicinales , Ecología , Etnobotánica , Humanos , MalasiaRESUMEN
Microbiological and physicochemical characteristics of reduced-fat (approximately 22%) Chinese-style sausages containing 0.1% chitosan (in 1% lactic acid solution) with three different molecular weights [low molecular weight chitosan (CHL), MW= 150 kDa; medium molecular weight chitosan (CHM), MW=600 kDa; high molecular weight chitosan (CHH), MW=1250 kDa] were demonstrated. Sausages were also subject to oven heating or deep-fat frying for sensory evaluation. Treatments containing chitosan were lower in pH at any storage periods than the control (CONT). Generally speaking, total plate counts and lactic acid bacteria counts of all treatments slightly increased, with CHL being the lowest. However, all bacterial counts were lower than 7 [log colony forming unit (CFU)/g] at the end of storage. Results from sensory evaluation showed that deep-fat fried sausages from treatments CHL and CHM were higher in overall acceptability. This study demonstrated that the addition of chitosan to reduced-fat Chinese-style sausage resulted in no detrimental effect on textural properties.
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The aim of this present study was to investigate the effect of amount and degree of oxidation of dietary oil on type 2 T-helper cell (TH)-related immune responses. Four groups of BALB/c mice were fed either 50 g soyabean oil/kg (50-S), 50 g oxidized oil/kg (50-O), 150 g soyabean oil/kg (150-S) or 150 g oxidized oil/kg (150-O). After 14 weeks consuming the experimental diets, the mice were immunized with ovalbumin (OVA) plus Al and antigen-specific immunoglobulin (Ig)E, IgG1 and IgG2a, inflammatory mediators such as prostaglandin (PG) E2 and leukotriene (LT)B4 were determined. Higher hepatic microsomal cytochrome P450 was noted in mice fed 150 g oxidized oil/kg compared with those of other groups. OVA-specific IgG1 and IgE were higher in mice fed 150 g oxidized oil/kg compared with those of the other groups. The data suggested the interleukin (IL)-4: interferon (IFN)-gamma ratio was higher in mice fed 50 g dietary oxidized oil/kg compared with that of the 50-S group. The IL-5:IFN-gamma ratios were higher in the 150-S and 150-O groups than in the 50-S and 50-O groups. PGE2 and LTB4 produced by macrophages stimulated by lipopolysaccharide were highest in mice in the 150 g oxidized oil/kg group. The data suggested that an increased intake of oxidized oil might exert an unfavourable effect on the TH2 response involved in allergic disease.
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Inmunoglobulina E/biosíntesis , Mediadores de Inflamación/metabolismo , Aceite de Soja/farmacología , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Animales , Asma/etiología , División Celular/inmunología , Citocinas/biosíntesis , Dinoprostona/biosíntesis , Ingestión de Energía , Femenino , Inmunoglobulina G/biosíntesis , Leucotrieno B4/biosíntesis , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Oxidación-Reducción , Aceite de Soja/química , Bazo/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Aumento de Peso/efectos de los fármacosRESUMEN
In the liver, most insulin-like growth factor I (IGF-I) transcripts originate in exon 1, where important cis-regulatory regions are located downstream from the major transcription initiation sites. Within these regions, we have attempted to identify sequences which are involved in the decrease in IGF-I gene transcription associated with diabetes mellitus. The function of different genomic templates was assessed by in vitro transcription, which revealed a consistent 50-80% decrease in the activity of nuclear extracts from streptozotocin-diabetic as compared with normal rats. The disparity in transcriptional activity between normal and diabetic nuclear extracts was reduced with templates containing 11-bp mutations within DNase I protected regions III or V (+42 and +129 bp, respectively, from the major transcription initiation site), but a mutation between regions IV and V had little effect. Within region III, gel mobility shift analysis and methylation interference studies indicated that DNA-protein interactions involve a GCGC core sequence. In region V, gel mobility shift studies and uracil interference analysis revealed interactions involving a TTAT core. While gel mobility shift analysis and transient transfection studies indicate that the GCGC core sequence in region III recognizes C/EBP, the AT-rich sequence in region V is likely to recognize a protein with homeodomain characteristics. Identification of the nuclear factor(s) interacting with regions III and V, downstream from exon 1 initiation sites, will be important for understanding the mechanism of reduced IGF-I gene transcription due to diabetes mellitus.
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Factor I del Crecimiento Similar a la Insulina/genética , Proteínas Nucleares/metabolismo , Animales , Secuencia de Bases/genética , Sitios de Unión/fisiología , Extractos Celulares/fisiología , Núcleo Celular/química , Diabetes Mellitus Experimental/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Mutación/fisiología , Ratas , Ratas Sprague-Dawley , Valores de Referencia , Transcripción Genética/fisiologíaRESUMEN
The present investigation showed that microinjection of substance P (SP) into dorsal vagal nucleus inhibited gastric myoelectric fast wave and gastric motility. The effect could be blocked by SP antiserum or SP antagonist [Arg6, D-Trp7,9, N-Me-Phe8]-SP6-11 or vagotomy. Depletion of sympathetic transmitters by reserpine did not affect induction of the inhibition. The results indicate that both exogenous and endogenous SP of dorsal vagal nucleus decrease the gastric myoelectric fast wave and motility, which is mediated by vagus nerve.
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Motilidad Gastrointestinal/efectos de los fármacos , Hipotálamo/fisiología , Estómago/fisiología , Sustancia P/farmacología , Nervio Vago/fisiología , Animales , Electromiografía/efectos de los fármacos , Masculino , Microinyecciones , Ratas , Ratas Sprague-DawleyRESUMEN
Arsenic is ubiquitous in the environment and the toxicological response of various organisms to it is dependent on the particular chemical form involved. In general, methylation of inorganic arsenic is considered to be a detoxification reaction. While this transformation is known to be mediated by methyltransferases in several species of mammals, less is known about the fate of arsenic in invertebrates. As part of a continuing interest in heavy metals and metalloid toxicology, the alkylating activity of cytosol prepared from the common earthworm, Lumbricus terrestris, towards sodium arsenite has now been investigated. Thus, S-adenosyl-l-[(14)C]methionine ([(14)C-methyl]SAM) fortified earthworm cytosol was incubated with sodium arsenite at 37 degrees C for 90 min. Initial TLC analysis of the incubation mixture suggested incorporation of radiolabel into dimethylarsinic acid. This was subsequently proven by isolation of the metabolite through radiodilution followed by recrystallization of the recovered material to constant specific activity. This result suggests that earthworm cytosol has the same methylating reactivity towards arsenite as do similar preparations from various tissues of several species of mammals.