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The aim of this study was to evaluate the dose-dependent effects of a hydroxy-analog of selenomethionine (HMSeBA) on rumen fermentation, apparent nutrient digestibility, and total selenium absorption in mid-lactation dairy cows, and to compare the effects with those of sodium selenite (SS). Fifty mid-lactation dairy cows with similar milk yields, days in milk, and parity were randomly assigned to 1 of 5 treatments according to a randomized complete block design. The cows were fed a basal diet containing 0.06 mg/kg dry matter (DM) of Se (control) or the same basal diet supplemented with SS, yielding 0.3 mg of Se/kg of DM (SS-0.3), or HMSeBA, yielding 0.1, 0.3, or 0.5 mg of Se/kg of DM (SO-0.1, SO-0.3, and SO-0.5, respectively), during the experimental period. The final content of Se in control, SS-0.3, SO-0.1, SO-0.3, and SO-0.5 was 0.06, 0.34, 0.15, 0.33, and 0.52 mg of Se/kg of DM. The experiment lasted for 10 wk, with a pretrial period of 2 wk. Supplementation with HMSeBA altered rumen fermentation by linearly increasing total volatile fatty acids and the molar proportions of propionate and butyrate but decreasing rumen pH, ammonia content, and the ratio of acetate to propionate. Compared with SS, HMSeBA enhanced the molar proportion of propionate in the rumen and the apparent digestibility of crude protein, neutral detergent fiber, acid detergent fiber, and selenium. We demonstrated that HMSeBA promoted rumen fermentation, apparent nutrient digestibility, and selenium absorption, implying that HMSeBA has a greater apparent absorption than SS.
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Bovinos/metabolismo , Suplementos Dietéticos/análisis , Nutrientes/metabolismo , Rumen/metabolismo , Compuestos de Selenio/metabolismo , Alimentación Animal/análisis , Animales , Lactancia Materna , Dieta , Digestión , Ácidos Grasos Volátiles/metabolismo , Femenino , Fermentación , Lactancia , Leche/metabolismo , Paridad , Embarazo , Distribución AleatoriaRESUMEN
This study aimed to evaluate the effect of hydroxy-selenomethionine (HMSeBA), a novel organic selenium (Se) source, on milk performance, antioxidative status, and Se concentrations in the milk and plasma of mid-lactation dairy cows compared with that of sodium selenite (SS). Fifty mid-lactation dairy cows with similar days in milk, milk yield, and parity received the same basal diet containing 0.06 mg of Se/kg of DM. They were assigned to 1 of 5 treatments according to a randomized complete block design: negative control (without Se supplementation), SS supplementation (0.3 mg of Se/kg of DM; SS-0.3) or HMSeBA supplementation (0.1, 0.3, or 0.5 mg of Se/kg of DM: SO-0.1, SO-0.3, and SO-0.5, respectively). The experiment lasted for 10 wk, including a pretrial period of 2 wk. The results indicated that neither Se supplementation nor Se source affected dry matter intake, milk yield, milk composition, or blood biochemical parameters, except for milk fat percentage. Simultaneously, milk fat percentage and milk fat yield increased linearly as the quantity of HMSeBA supplementation was increased. Production of 4% FCM and ECM was elevated linearly as dietary HMSeBA increased. The SO-0.3 group showed higher serum activity of glutathione peroxidase, total antioxidant capacity, and superoxide dismutase than the SS-0.3 group, but malondialdehyde content was not affected by Se source. Furthermore, HMSeBA supplementation linearly increased the activities of serum glutathione peroxidase and superoxide dismutase, but decreased malondialdehyde content. Compared with the SS-0.3 group, the SO-0.3 group showed augmented concentrations of total Se in milk and plasma, and total Se milk-to-plasma concentration ratio. In addition, increasing doses of HMSeBA linearly increased the concentrations of total Se in the milk and plasma. This study demonstrates that HMSeBA improves antioxidant status and increases milk and plasma Se concentrations more effectively than SS, indicating that HMSeBA could replace SS as an effective organic Se source for lactating dairy cows.
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Antioxidantes/análisis , Bovinos/fisiología , Lactancia/fisiología , Leche/química , Selenio/análisis , Selenometionina/administración & dosificación , Animales , Dieta/veterinaria , Suplementos Dietéticos , Femenino , Glutatión Peroxidasa/sangre , Malondialdehído/análisis , Embarazo , Selenio/administración & dosificación , Selenio/sangre , Compuestos de Selenio/administración & dosificación , Selenito de Sodio/administración & dosificación , Superóxido Dismutasa/sangreRESUMEN
Physical activity has been shown to suppress tumor initiation and progression. The neurotransmitter dopamine (DA) is closely related to movement and exhibits antitumor properties. However, whether the suppressive effects of physical activity on tumors was mediated by the nervous system via increased DA level remains unknowns. Here we show that regular moderate swimming (8 min/day, 9 weeks) raised DA levels in the prefrontal cortex, serum and tumor tissue, suppressed growth, reduced lung metastasis of transplanted liver cancer, and prolonged survival in a C57BL/6 mouse model, while overload swimming (16 and 32 min/day, 9 weeks) had the opposite effect. In nude mice that were orthotopically implanted with human liver cancer cell lines, DA treatment significantly suppressed growth and lung metastasis by acting on the D2 receptor (DR2). Furthermore, DR2 blockade attenuated the suppressive effect of moderate swimming on liver cancer. Both moderate swimming and DA treatment suppressed the transforming growth factor-beta (TGF-ß1)-induced epithelial-mesenchymal transition of transplanted liver cancer cells. At the molecular level, DR2 signaling inhibited extracellular signal-regulated kinase phosphorylation and expression of TGF-ß1 in vitro. Together, these findings demonstrated a novel mechanism by which the moderate exercise suppressed liver cancer through boosting DR2 activity, while overload exercise had the opposite effect, highlighting the possible importance of the dopaminergic system in tumor growth and metastasis of liver cancer.
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Neoplasias Hepáticas Experimentales/patología , Receptores de Dopamina D2/fisiología , Natación , Animales , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal , Quinasas MAP Reguladas por Señal Extracelular/fisiología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Factores de Tiempo , Factor de Crecimiento Transformador beta1/fisiología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The cold-cathode Penning ion gauge (PIG) type ion source has been used for generation of negative hydrogen (H(-)) ions as the internal ion source of a compact cyclotron. A novel method called electrical shielding box dc beam measurement is described in this paper, and the beam intensity was measured under dc extraction inside an electrical shielding box. The results of the trajectory simulation and dc H(-) beam extraction measurement were presented. The effect of gas flow rate, magnetic field strength, arc current, and extraction voltage were also discussed. In conclusion, the dc H(-) beam current of about 4 mA from the PIG ion source with the puller voltage of 40 kV and arc current of 1.31 A was extrapolated from the measurement at low extraction dc voltages.
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Aniones/química , Ciclotrones/instrumentación , Hidrógeno/química , ElectrodosRESUMEN
The Bcr-Abl fusion gene encodes for the p210(Bcr-Abl) or p185(Bcr-Abl) tyrosine kinase (TK) implicated in the pathogenesis of chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia, respectively. Because Bcr-Abl TK is chaperoned by Hsp90 (90 kDa heat-shock protein), we investigated the effects of novobiocin (NB), an Hsp90 C-terminal inhibitor, on the viability of the Bcr-Abl-positive human leukemia cells HL-60/Bcr-Abl and K562, the expression of Bcr-Abl protein and the interaction between Hsp90 and Bcr-Abl TK. Present studies demonstrate that NB is a potent inhibitor of the growth of Bcr-Abl-positive human leukemia cells. NB induces cytosolic accumulation of cytochrome c and activation of caspase-9 and caspase-3, triggering apoptosis of HL-60/Bcr-Abl and K562 cells. Treatment of cell lines with NB disrupts Bcr-Abl /Hsp90 and Bcr-Abl /Hsp70 interactions, resulting in a decreased amount of intracellular Bcr-Abl protein levels. Co-treatment with the proteasome inhibitor N-acetyl leucyl-leucyl norlucinal increases NB-mediated accumulation of Bcr-Abl in the detergent-insoluble cellular fraction, which demonstrates that NB promotes proteasomal degradation of Bcr-Abl. Moreover, both imatinib-resistant K562/G01 and primary CML CD34(+) cells are sensitive to NB.
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Crisis Blástica/tratamiento farmacológico , Proteínas de Fusión bcr-abl/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Leucemia/tratamiento farmacológico , Novobiocina/farmacología , Apoptosis/efectos de los fármacos , Benzamidas , Benzoquinonas/farmacología , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Proliferación Celular/efectos de los fármacos , Citocromos c/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas de Fusión bcr-abl/análisis , Células HL-60 , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Humanos , Mesilato de Imatinib , Inmunoprecipitación , Células K562 , Lactamas Macrocíclicas/farmacología , Leucemia/metabolismo , Leucemia/patología , Piperazinas/farmacología , Complejo de la Endopetidasa Proteasomal/fisiología , Pirimidinas/farmacologíaRESUMEN
Stanniocalcin (STC) is a glycoprotein hormone originally found in bony fish, in which it regulates calcium/phosphate homeostasis and protects against hypercalcemia. The recently characterized human STC shows about 70% homology with fish STC. We previously reported a constitutive expression of STC in terminally differentiated neurons. Here, we show that exposure of human neural-crest-derived cell line Paju to hypercalcemic culture medium induced expression of STC. Treatment of Paju cells with recombinant human STC increased their uptake of inorganic phosphate. Paju cells expressing STC by cDNA transfection displayed increased resistance to ischemic challenge and to elevated intracellular free calcium induced by treatment with thapsigargin. An up-regulated and redistributed expression of STC was observed in neurons surrounding the core of acute infarcts in human and rat brains. Given that mobilization and influx of calcium is considered a main neurotoxic mechanism following ischemia, our results suggest that the altered expression of STC contributes to the protection of cerebral neurons against hypoxic/ischemic damage. Manipulation of the STC expression may therefore offer a therapeutic approach to limit the injury after ischemic brain insults.
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Isquemia Encefálica/patología , Glicoproteínas/fisiología , Hormonas/fisiología , Neuronas/fisiología , Adolescente , Animales , Isquemia Encefálica/metabolismo , Calcio/metabolismo , Muerte Celular , Hipoxia de la Célula , Línea Celular , Femenino , Glicoproteínas/genética , Glicoproteínas/metabolismo , Hormonas/genética , Hormonas/metabolismo , Humanos , Hipercalcemia/metabolismo , Hipercalcemia/fisiopatología , Inmunohistoquímica , Hibridación in Situ , Masculino , Neuronas/metabolismo , Neuronas/patología , Ratas , Ratas Wistar , Regulación hacia ArribaRESUMEN
Stanniocalcin (STC) is a 28 kD glycoprotein hormone originally found in bony fish in which it regulates calcium/phosphate homeostasis and protects against hypercalcemia. The recently characterized mammalian STC shows about 70% homology with fish STC. The epithelial cells of proximal tubuli in human and rat kidney and brain neurons have been found to express STC. Here we show that the epithelium of the choroid plexus, already at 16 weeks of fetal age, and of plexus papillomas, synthesize and express STC. Our findings suggest that STC may be of importance for the distribution of calcium and phosphate between the cerebrospinal fluid and blood.
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Plexo Coroideo/citología , Glicoproteínas/análisis , Hormonas/análisis , Adulto , Animales , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/secundario , Calcio/metabolismo , Preescolar , Plexo Coroideo/embriología , Plexo Coroideo/patología , Células Epiteliales/citología , Células Epiteliales/patología , Femenino , Feto , Peces , Edad Gestacional , Humanos , Lactante , Masculino , Persona de Mediana Edad , Papiloma/patología , RatasRESUMEN
Gelsolin belongs to a family of proteins that modulate the structural dynamics of cytoskeletal actin. Gelsolin activity is required for the redistribution of actin occurring during membrane ruffling, cell crawling, and platelet activation. A point mutation (G654A) in the gelsolin gene causes a dominantly inherited systemic amyloidosis called familial amyloidosis of the Finnish type (FAF). This disease is characterized by a cranial neuropathy that cannot be explained solely by amyloid deposits. To address the question of whether gelsolin has a specific role in neural cell development, we transfected cDNA for wild type and G654A point-mutated gelsolin into a neural cell line, Paju, which can be induced to differentiate by treatment with phorbol 12-myristate 13-acetate. Overexpressed wild type gelsolin inhibited neural differentiation whereas mutated gelsolin did not, indicating that appropriate gelsolin activity is essential for neural sprouting. The G654A mutant gelsolin induced stabilization of F-actin and reduced the plasticity of neural development. This provides a novel etiopathogenetic mechanism for the neuronal dysfunction in FAF.
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Diferenciación Celular/fisiología , Gelsolina/genética , Gelsolina/fisiología , Neuronas/citología , Adolescente , Neuropatías Amiloides/genética , Neuropatías Amiloides/patología , Diferenciación Celular/efectos de los fármacos , Línea Celular , Femenino , Humanos , Neuronas/efectos de los fármacos , Mutación Puntual , Proteínas Recombinantes/metabolismo , Acetato de Tetradecanoilforbol/farmacología , TransfecciónRESUMEN
Stanniocalcin (STC) is a glycoprotein hormone first found in fish, in which it regulates calcium homeostasis and protects against hypercalcemia. Human and mouse stc cDNA were recently cloned. We found a dramatically upregulated expression of STC during induced neural differentiation in a human neural crest-derived cell line, Paju. Immunohistochemical staining of sections from human and adult mouse brain revealed abundant presence of STC in the neurons with no activity in the glial cells. STC expression was not seen in immature brain neurons of fetal or newborn mice. Given that STC has been found to regulate calcium/phosphate metabolism in some mammalian epithelia, we suggest that STC may act as a regulator of calcium homeostasis in terminally differentiated brain neurons.
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Encéfalo/metabolismo , Glicoproteínas/biosíntesis , Hormonas/biosíntesis , Neuronas/metabolismo , Animales , Animales Recién Nacidos , Northern Blotting , Western Blotting , Diferenciación Celular , Glicoproteínas/genética , Hormonas/genética , Humanos , Inmunohistoquímica , Ratones , Neuronas/efectos de los fármacos , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , Acetato de Tetradecanoilforbol/farmacología , Factores de Tiempo , Células Tumorales Cultivadas , Regulación hacia ArribaRESUMEN
We studied gene expression in relation to induced neural differentiation in a human neural crest-derived cell line, Paju. Messenger RNA isolated before and after treatment with phorbol 12-myristate 13-acetate was analyzed by differential display reverse transcription PCR. A strongly up-regulated expression of decay-accelerating factor (DAF, CD55) was found to parallel the induced neural sprouting while the expression of two other complement regulatory proteins (CD59/protectin, CD46/membrane cofactor protein) remained unaltered during neural differentiation. The increased membrane expression of DAF, which was also seen on neural processes and growth cones, conferred elevated resistance to complement-mediated lysis. Our findings suggest that in sprouting neurons DAF expression is up-regulated to provide additional complement resistance to pathfinding axons/dendrites invading new environment. It is also suggested that membrane expression of DAF may constitute a marker of growing and regenerating neurons.
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Antígenos CD55/genética , Regulación del Desarrollo de la Expresión Génica , Cresta Neural/citología , Neuronas/citología , Antígenos CD55/biosíntesis , Antígenos CD55/inmunología , Carcinógenos/farmacología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/genética , Línea Celular , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Humanos , Cresta Neural/inmunología , Neuronas/inmunología , Acetato de Tetradecanoilforbol/farmacología , Regulación hacia ArribaRESUMEN
A main function attributed to the BCL2 protein is its ability to confer resistance against apoptosis. In addition to the constitutively high expression of BCL2, caused by gene rearrangement in follicular lymphomas, elevated expression of the BCL2 gene has been found in differentiating hematopoietic, neural, and epithelial tissues. To address the question of whether the expression of BCL2 is a cause or consequence of cell differentiation, we used a human neural-crest-derived tumor cell line, Paju, that undergoes spontaneous neural differentiation in vitro. The Paju cell line displays moderate expression of BCL2, the level of which increases in parallel with further neural differentiation induced by treatment with phorbol 12-myristate 13-acetate. Transfection of normal human BCL2 cDNA in sense and antisense orientations had a dramatic impact on the differentiation of the Paju cells. Overexpression of BCL2 cDNA induced extensive neurite outgrowth, even in low serum concentrations, together with an increased expression of neuron-specific enolase. Paju cells expressing the anti-sense BCL2 cDNA construct, which reduced the endogenous levels of BCL2, did not undergo spontaneous neural differentiation. These cells acquired an epithelioid morphology and up-regulated the intermediate filament protein nestin, typically present in primitive neuroectodermal cells. The manipulated levels of BCL2 did not have appreciable impact on cell survival in normal culture. Our findings demonstrate that the BCL2 gene product participates in the regulation of neural differentiation.
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Diferenciación Celular , Neuronas/citología , Proteínas Proto-Oncogénicas/fisiología , Adolescente , Northern Blotting , Diferenciación Celular/efectos de los fármacos , División Celular , Línea Celular , ADN Complementario , Femenino , Humanos , Cinética , Neuritas/efectos de los fármacos , Neuritas/fisiología , Tumores Neuroectodérmicos Primitivos , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas c-bcl-2 , Proto-Oncogenes , Proteínas Recombinantes/biosíntesis , Acetato de Tetradecanoilforbol/farmacología , Transfección , Células Tumorales CultivadasRESUMEN
This is a collective review of 564 patients with Marfan syndrome among 98 pedigrees reported from 18 provinces and cities in China over a 37-year period from 1951 to 1987. A positive family history of Marfan syndrome was found in 74.3% of the patients: the mode of inheritance was dominant in 73.8% and recessive in 0.5%. Sporadic cases occurred in 25.7%. A screening of 29,067 children found five children with Marfan syndrome, giving a prevalence of 17.2 per 100,000 of the population, a gene frequency of 8.61 per 100,000 genes, and a penetrance of 71.69%. Pleiotropy was clear in these cases: arachnodactyly in 77%, ectopia lentis in 86.8%, and dilated aortic root in 80.1%. Chromosome examination showed no regular aberrations except in a family of five in whom a giant-satellited chromosome 14 was found in three afflicted members but not in the two unaffected relatives. The high prevalence of aortic root dilation in Marfan syndrome makes echocardiography the most useful and practical means of diagnosis. Close follow-up and regular echocardiographic evaluation are indicated not only in patients with Marfan syndrome but also in their families, for both diagnostic and therapeutic purposes.
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Síndrome de Marfan/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Masculino , Síndrome de Marfan/complicaciones , Síndrome de Marfan/genética , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
In a previous paper, an algorithm was presented for analyzing multiple RNA secondary structures utilizing a multiple string alignment algorithm. In this paper we present another approach to the problem of comparing many secondary structures by utilizing a very efficient tree-matching algorithm that will compare two trees in O([T1] X [T2] X L1 X L2) in the worst case and very close to O([T1] X [T2]) for average trees representing secondary structures. The result of the pairwise comparison algorithm is then used with a cluster algorithm to produce a multiple structure clustering which can be displayed in a taxonomy tree to show related structures.
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Algoritmos , Conformación de Ácido Nucleico , ARN/ultraestructura , Secuencia de Bases , Cómputos Matemáticos , Datos de Secuencia Molecular , ARN/química , Programas InformáticosRESUMEN
Peripheral T lymphocyte subsets in 60 cases of Graves' disease (GD) and 16 cases of Hashimoto's thyroiditis (HT) were determined by the use of OKT monoclonal antibodies (McAb). The results showed that in both diseases OKT3 cells (total T cells) and OKT8 cells (suppressor T cells, TS cells) were lower and the ratio of OKT4 cells (helper T cells, TH cells) OKT8 cells was much higher than those in normal controls. GD patients who were treated with antithyroid drugs (ATD) and whose serum T3, T4 recovered to normal, could be further divided into subgroups of high OKT4/OKT8 cell ratio and of normal ratio. The pathogenesis, treatment and relapse of autoimmune thyroid diseases (AITD) were discussed in this paper on the basis of the results.
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Enfermedad de Graves/inmunología , Linfocitos T/inmunología , Tiroiditis Autoinmune/inmunología , Adulto , Anticuerpos Monoclonales/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Reguladores/inmunología , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
One member of a Chinese family with Holt-Oram syndrome also had high myopia, which is a hitherto unreported feature. The genetic background of this unusual association is discussed.
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Anomalías Múltiples/genética , Cardiopatías Congénitas/genética , Miopía/genética , Radio (Anatomía)/anomalías , Adulto , Defectos del Tabique Interatrial/genética , Humanos , Masculino , Linaje , SíndromeRESUMEN
This is a collective review of all cases of HOS reported from China. Of the 24 total cases, 18 are living and are included in this report. The clinical features, including previously undescribed associated anomalies, mode of transmission in the family, genetic characteristics, and dermatoglyphics of this familial upper limb-cardiovascular syndrome, are presented. A practical classification of the syndrome is proposed based on the relative preponderance of either upper limb deformities or cardiovascular anomalies.