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1.
J Synchrotron Radiat ; 29(Pt 5): 1251-1257, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-36073884

RESUMEN

X-ray topography exerting the super-Borrmann effect has been performed using synchrotron radiation to display dislocation images with a high-speed and high-resolution CMOS camera. Forward-transmitted X-rays are positively employed instead of reflected X-rays to reveal dislocations in relatively thick crystals by simultaneously exciting a pair of adjacent {111} planes owing to the super-Borrmann effect. Before the experiment, minimum values of the attenuation coefficients AminP for σ and π polarizations of the incident X-rays in the three-beam case are calculated. Results demonstrate that AminP for both polarizations are almost 20 times larger than those in the two-beam (usual Borrmann effect) case. The transmitted X-rays can be used to confirm the efficacy of taking topographs under the super-Borrmann conditions, as well as under multiple-diffraction conditions. Furthermore, super-Borrmann topographs can be considered for relatively thick crystals, where a conventional Lang X-ray topography technique is difficult to apply.

2.
Br J Cancer ; 110(6): 1497-505, 2014 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-24569463

RESUMEN

BACKGROUND: Eribulin mesilate (eribulin), a non-taxane microtubule dynamics inhibitor, has shown trends towards greater overall survival (OS) compared with progression-free survival in late-stage metastatic breast cancer patients in the clinic. This finding suggests that eribulin may have additional, previously unrecognised antitumour mechanisms beyond its established antimitotic activity. To investigate this possibility, eribulin's effects on the balance between epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) in human breast cancer cells were investigated. METHODS: Triple negative breast cancer (TNBC) cells, which are oestrogen receptor (ER-)/progesterone receptor (PR-)/human epithelial growth receptor 2 (HER2-) and have a mesenchymal phenotype, were treated with eribulin for 7 days, followed by measurement of EMT-related gene and protein expression changes in the surviving cells by quantitative real-time PCR (qPCR) and immunoblot, respectively. In addition, proliferation, migration, and invasion assays were also conducted in eribulin-treated cells. To investigate the effects of eribulin on TGF-ß/Smad signalling, the phosphorylation status of Smad proteins was analysed. In vivo, the EMT/MET status of TNBC xenografts in mice treated with eribulin was examined by qPCR, immunoblot, and immunohistochemical analysis. Finally, an experimental lung metastasis model was utilised to gauge the metastatic activity of eribulin-treated TNBC in the in vivo setting. RESULTS: Treatment of TNBC cells with eribulin in vitro led to morphological changes consistent with transition from a mesenchymal to an epithelial phenotype. Expression analyses of EMT markers showed that eribulin treatment led to decreased expression of several mesenchymal marker genes, together with increased expression of several epithelial markers. In the TGF-ß induced EMT model, eribulin treatment reversed EMT, coincident with inhibition of Smad2 and Smad3 phosphorylation. Consistent with these changes, TNBC cells treated with eribulin for 7 days showed decreased capacity for in vitro migration and invasiveness. In in vivo xenograft models, eribulin treatment reversed EMT and induced MET as assessed by qPCR, immunoblot, and immunohistochemical analyses of epithelial and mesenchymal marker proteins. Finally, surviving TNBC cells pretreated in vitro with eribulin for 7 days led to decreased numbers of lung metastasis when assessed in an in vivo experimental metastasis model. CONCLUSIONS: Eribulin exerted significant effects on EMT/MET-related pathway components in human breast cancer cells in vitro and in vivo, consistent with a phenotypic switch from mesenchymal to epithelial states, and corresponding to observed decreases in migration and invasiveness in vitro as well as experimental metastasis in vivo. These preclinical findings may provide a plausible scientific basis for clinical observations of prolonged OS by suppression of further spread of metastasis in breast cancer patients treated with eribulin.


Asunto(s)
Transición Epitelial-Mesenquimal/efectos de los fármacos , Furanos/farmacología , Cetonas/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia sin Enfermedad , Femenino , Expresión Génica , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Ratones , Ratones Desnudos , Metástasis de la Neoplasia , Fenotipo , Neoplasias de la Mama Triple Negativas/patología , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Integr Comp Biol ; 61(5): 1966-1980, 2021 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-34459487

RESUMEN

The goal of our Eyes Toward Tomorrow Program is to enrich the future workforce with STEM by providing students with an early, inspirational, interdisciplinary experience fostering inclusive excellence. We attempt to open the eyes of students who never realized how much their voice is urgently needed by providing an opportunity for involvement, imagination, invention, and innovation. Students see how what they are learning, designing, and building matters to their own life, community, and society. Our program embodies convergence by obliterating artificially created, disciplinary boundaries to go far beyond STEM or even STEAM by including artists, designers, social scientists, and entrepreneurs collaborating in diverse teams using scientific discoveries to create inventions that could shape our future. Our program connects two recent revolutions by amplifying Bioinspired Design with the Maker Movement and its democratizing effects empowering anyone to innovate and change the world. Our course is founded in original discovery. We explain the process of biological discovery and the importance of scaling, constraints, and complexity in selecting systems for bioinspired design. By spotlighting scientific writing and publishing, students become more science literate, learn how to decompose a biology research paper, extract the principles, and then propose a novel design by analogy. Using careful, early scaffolding of individual design efforts, students build the confidence to interact in teams. Team building exercises increase self-efficacy and reveal the advantages of a diverse set of minds. Final team video and poster project designs are presented in a public showcase. Our program forms a student-centered creative action community comprised of a large-scale course, student-led classes, and a student-created university organization. The program structure facilitates a community of learners that shifts the students' role from passive knowledge recipients to active co-constructors of knowledge being responsible for their own learning, discovery, and inventions. Students build their own shared database of discoveries, classes, organizations, research openings, internships, and public service options. Students find next step opportunities so they can see future careers. Description of our program here provides the necessary context for our future publications on assessment that examine 21st century skills, persistence in STEM, and creativity.


Asunto(s)
Aprendizaje , Ciencia/educación , Humanos , Estudios Interdisciplinarios , Estudiantes
4.
Diabetes Obes Metab ; 10(9): 772-9, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17970759

RESUMEN

AIM: We investigated the effects of the combined therapy of PPARgamma and PPARalpha agonists on HDL metabolism, especially concerning reverse cholesterol transport (RCT), using Zucker diabetic fatty rats (ZDF/Crl-Lepr fa rats) that are the rodent model for type 2 diabetes with obesity, hyperlipidaemia and insulin resistance. METHODS: The ZDF rats were divided into four medicated groups as follows: pioglitazone as a PPARgamma agonist (5 mg/kg/day; P group, n = 6), fenofibrate as a PPARalpha agonist (30 mg/kg/day; F group, n = 6), both these medications (P + F group, n = 6) and no treatment (UNT group, n = 6). Non-diabetic rats (ZDF/GmiCrl-lean, CON group, n = 6) served as controls. We evaluated HDL particle size and messenger RNA (mRNA) levels of the following factors: liver X receptor alpha (L x R alpha), ATP-binding cassette A1 (ABCA1) and ABCG1 which are regulated by PPARs and are related to early stage RCT. RESULTS: The significant increase in HDL particle size was demonstrated in rats of the F and P + F groups, although changes in plasma HDL-cholesterol levels were not significant. In accordance with this finding, mRNA levels of ABCG1 in the liver increased significantly. CONCLUSIONS: These findings suggest the efficacy of combined therapy with PPARgamma and PPARalpha in improving lipid metabolism, partly through the enhanced RCT, and insulin resistance in type 2 diabetes mellitus.


Asunto(s)
HDL-Colesterol/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fenofibrato/administración & dosificación , Hiperlipidemias/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Tiazolidinedionas/administración & dosificación , Transportador 1 de Casete de Unión a ATP , Transportadoras de Casetes de Unión a ATP/análisis , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Proteínas de Unión al ADN/análisis , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/metabolismo , Hiperlipidemias/metabolismo , Hipoglucemiantes/agonistas , Resistencia a la Insulina , Metabolismo de los Lípidos , Receptores X del Hígado , Masculino , Obesidad/metabolismo , Receptores Nucleares Huérfanos , PPAR alfa/agonistas , PPAR gamma/agonistas , Pioglitazona , Ratas , Ratas Zucker , Receptores Citoplasmáticos y Nucleares/análisis
5.
Mol Cell Biol ; 21(7): 2521-32, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11259600

RESUMEN

To investigate the role of insulin receptor substrate 1 (IRS-1) and IRS-2, the two ubiquitously expressed IRS proteins, in adipocyte differentiation, we established embryonic fibroblast cells with four different genotypes, i.e., wild-type, IRS-1 deficient (IRS-1(-/-)), IRS-2 deficient (IRS-2(-/-)), and IRS-1 IRS-2 double deficient (IRS-1(-/-) IRS-2(-/-)), from mouse embryos of the corresponding genotypes. The abilities of IRS-1(-/-) cells and IRS-2(-/-) cells to differentiate into adipocytes are approximately 60 and 15%, respectively, lower than that of wild-type cells, at day 8 after induction and, surprisingly, IRS-1(-/-) IRS-2(-/-) cells have no ability to differentiate into adipocytes. The expression of CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) is severely decreased in IRS-1(-/-) IRS-2(-/-) cells at both the mRNA and the protein level, and the mRNAs of lipoprotein lipase and adipocyte fatty acid binding protein are severely decreased in IRS-1(-/-) IRS-2(-/-) cells. Phosphatidylinositol 3-kinase (PI 3-kinase) activity that increases during adipocyte differentiation is almost completely abolished in IRS-1(-/-) IRS-2(-/-) cells. Treatment of wild-type cells with a PI 3-kinase inhibitor, LY294002, markedly decreases the expression of C/EBPalpha and PPARgamma, a result which is associated with a complete block of adipocyte differentiation. Moreover, histologic analysis of IRS-1(-/-) IRS-2(-/-) double-knockout mice 8 h after birth reveals severe reduction in white adipose tissue mass. Our results suggest that IRS-1 and IRS-2 play a crucial role in the upregulation of the C/EBPalpha and PPARgamma expression and adipocyte differentiation.


Asunto(s)
Adipocitos/citología , Adipocitos/fisiología , Fosfoproteínas/fisiología , Animales , Diferenciación Celular/fisiología , Células Cultivadas , Proteínas Sustrato del Receptor de Insulina , Péptidos y Proteínas de Señalización Intracelular , Ratones , Ratones Noqueados
6.
Rev Sci Instrum ; 87(2): 023701, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26931854

RESUMEN

X-ray topographs are taken for a sapphire wafer with the [0001] surface normal, as an example, by forward transmitted synchrotron x-ray beams combined with two-dimensional electronic arrays in the x-ray detector having a spatial resolution of 1 µm. They exhibit no shape deformation and no position shift of the dislocation lines on the topographs. Since the topography is performed under multiple-beam diffraction conditions, the topographic images of a single diffraction (two-wave approximation condition) or plural diffractions (six-wave approximation condition) can be recorded without large specimen position changes. As usual Lang topographs, it is possible to determine the Burgers vector of each dislocation line. Because of high parallelism of the incoming x-rays and linear sensitivity of the electronic arrays to the incident x-rays, the present technique can be used to visualize individual dislocations in single crystals of the dislocation density as high as 1 × 10(5) cm(-2).

7.
Biochim Biophys Acta ; 1531(3): 178-87, 2001 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-11325610

RESUMEN

Treatment of human umbilical vein endothelial cells (HUVECs) with 7-ketocholesterol resulted in an increased release of soluble vascular cell adhesion molecule-1 (VCAM-1) into culture medium. 7-Ketocholesterol did not enhance the expression of mRNA for VCAM-1. 7 beta-Hydroxy- or 25-hydroxycholesterol had no effect on soluble VCAM-1 levels. Western blot analysis revealed that soluble VCAM-1, in the conditioned medium of both 7-ketocholesterol-stimulated and control cells, had a molecular size of 100 kDa. Stimulation of the TNF-alpha-treated HUVECs with 7-ketocholesterol further increased the levels of soluble VCAM-1 in the culture medium. Again, 7-ketocholesterol did not affect the VCAM-1 mRNA level, which was enhanced by TNF-alpha. Pretreatment of the cells with tissue inhibitor of membrane metalloproteinase-2 (TIMP-2) completely inhibited the release of VCAM-1 in response to 7-ketocholesterol but TIMP-1 had no effect. Adherence of mononuclear cells to TNF-stimulated HUVEC monolayers was slightly inhibited by 7-ketocholesterol, but this oxysterol did not affect the basal adherence to non-stimulated HUVECs. Immunofluorescent staining of the cells confirmed diffuse perinuclear distribution of VCAM-1 in HUVECs treated with TNF-alpha, but 7-ketocholesterol did not affect the intensity or distribution of immunofluorescence. We conclude that 7-ketocholesterol releases VCAM-1 from the endothelium probably by a proteolytic process.


Asunto(s)
Endotelio Vascular/metabolismo , Hidroxicolesteroles/farmacología , Cetocolesteroles/farmacología , Molécula 1 de Adhesión Celular Vascular/metabolismo , Western Blotting , Células Cultivadas , Medios de Cultivo Condicionados , Ensayo de Inmunoadsorción Enzimática , Humanos , ARN Mensajero/análisis , Inhibidor Tisular de Metaloproteinasa-2/farmacología , Factor de Necrosis Tumoral alfa , Venas Umbilicales , Molécula 1 de Adhesión Celular Vascular/análisis
8.
Vet Immunol Immunopathol ; 103(1-2): 113-27, 2005 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-15626467

RESUMEN

A battery of mouse monoclonal antibodies (mAbs) reactive with porcine peripheral blood (PB) leukocytes was generated. Among the mAbs, 6F10 was found to react probably with cluster of differentiation (CD)8 alpha-chain, while 7G3 and 3E12 were found to recognize gammadelta T-cells, as revealed by two-color flow cytometric and immunoprecipitation studies. 7G3 was shown to react with the constant (C) region of the T-cell receptor (TCR) delta-chain by the following facts: (1) 7G3 immunoprecipitated full-length TCR delta-chain protein fused with glutathione S-transferase (GST) produced by Esherichia coli and (2) 7G3 reacted with TCR delta-chain expressing Cos-7 cells transfected with either full-length or N-terminal deleted mutant cDNA, but did not react with Cos-7 cells transfected with C-terminal deleted mutant TCR delta-chain cDNA. All three mAbs produced high-quality immunostaining results on frozen sections, revealing a distinct distribution of gammadelta T-cells and CD8(+) cells. This report precisely characterizes mAbs against porcine TCR for the first time, facilitating molecular biological investigations of the porcine immune system.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Linfocitos/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Porcinos/inmunología , Secuencia de Aminoácidos , Animales , Citometría de Flujo , Inmunohistoquímica , Inmunoprecipitación , Datos de Secuencia Molecular , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Receptores de Antígenos de Linfocitos T gamma-delta/genética
9.
Diabetes Care ; 17(9): 1059-61, 1994 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7988307

RESUMEN

OBJECTIVE: To evaluate change both in lipoprotein(a) [Lp(a)] and lipid levels in other lipoproteins in non-insulin-dependent diabetes mellitus (NIDDM) after short-term improvement of glycemic control. RESEARCH DESIGN AND METHODS: We compared Lp(a) levels in 210 NIDDM patients with those in 46 control subjects and evaluated the relationship between glycemic control and Lp(a) levels in diabetic patients. In addition, changes in Lp(a) levels and lipid levels were assessed after the improvement of glycemic control in 54 poorly controlled NIDDM patients. RESULTS: In NIDDM, Lp(a) levels in all patients, 62 patients with HbA1c < 6.0%, and 75 patients with HbA1c between 6.0 and 8.0%, were significantly higher than those in control subjects (19.1 [1.7-106.6], 19.2 [6.0-106.6], and 20.3 [2.7-75.3] vs. 15.4 [2.0-61.7] mg/dl, median [range], P < 0.05). Lp(a) levels in 73 patients with HbA1c of > or = 8.0% (18.7 [1.7-58.8] mg/dl) were not significantly different from those in control subjects. After glycemic control, lipid levels in plasma and in other lipoproteins fell significantly, but Lp(a) did not change (from 18.3 [1.7-58.8] to 18.4 [6.6-95.3] mg/dl). Changes in lipid levels, including Lp(a), did not correlate with those in fasting plasma glucose or HbA1c. CONCLUSIONS: These results suggest that elevated Lp(a) levels do not reflect poor glycemic control and that Lp(a) levels are independent of lipid levels in other lipoproteins after improved glycemic control in NIDDM.


Asunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Lipoproteína(a)/sangre , Lipoproteínas/sangre , Terapia Combinada , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ejercicio Físico/fisiología , Gliburida/uso terapéutico , Hemoglobina Glucada/análisis , Humanos , Insulina
10.
Am J Clin Nutr ; 71(3): 835-43, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10702181

RESUMEN

BACKGROUND: Animals treated with tumor necrosis factor alpha (TNF-alpha) developed severe metabolic abnormalities despite receiving sufficient protein and energy by total parenteral nutrition (TPN). OBJECTIVE: We sought to investigate the nutritional and metabolic effects of bacterial lipopolysaccharide (LPS) in rats. DESIGN: Rats were randomly allocated to 5 groups: oral nutrition (ON control; n = 7), TPN control (n = 7), ON+LPS (n = 6), TPN+LPS (n = 9), and pair fed (PF) in relation to ON+LPS (n = 6). RESULTS: Body weight decreased significantly as diet consumption decreased in the ON+LPS and PF groups compared with the ON control group. Relative carcass weights were significantly lower in the TPN+LPS and ON+LPS groups than in their respective control groups. Diaphragm and extensor digitorum longus weights were significantly lower in the ON+LPS and PF rats, but not in the TPN+LPS rats, compared with their respective controls. Biochemical abnormalities and plasma corticosterone concentrations were greater in the TPN+LPS group than in the other groups. CONCLUSIONS: These data suggest that provision of sufficient protein and energy by TPN does not prevent general carcass wasting induced by LPS but may protect individual muscles. However, compared with an oral ad libitum diet, TPN providing sufficient protein and energy worsens the biochemical abnormalities induced by LPS. More rapid clearance of TNF-alpha and low corticosterone concentrations in weight-losing animals may help reduce the severity of the metabolic effects of LPS.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales , Lipopolisacáridos/farmacología , Animales , Corticosterona/sangre , ADN/análisis , Ingestión de Alimentos , Escherichia coli , Masculino , Músculos/anatomía & histología , Tamaño de los Órganos , Nutrición Parenteral Total , Proteínas/análisis , Ratas , Ratas Wistar , Pérdida de Peso
11.
Anal Chem ; 72(8): 1810-3, 2000 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-10784146

RESUMEN

Synthetic polymer receptors selective for atrazine have been prepared by molecular imprinting using trialkylmelamines as template molecules in place of atrazine. Trialkylmelamines were shown to be useful as templates for introducing affinity for atrazine into ethylene glycol dimethacrylate-methacrylic acid copolymers. The polymers showed the selective binding capacity for triazine herbicides including atrazine, whereas agrochemicals in other categories were not adsorbed to the imprinted polymers. The group selectivity demonstrated was comparable with that of the original atrazine imprinted polymers. Use of the nonagrochemical template molecules as a substitution to atrazine has made it possible to synthesize herbicide-receptor polymers free from troubles caused by analyte contaminants, which are desired for analytical applications.

12.
Atherosclerosis ; 131(2): 237-42, 1997 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9199277

RESUMEN

Cholesterol regulates hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity by feedback inhibition. It has been suggested that oxidized derivatives of cholesterol (oxysterols) play an important role, as an intracellular mediator, in the feedback inhibition of cholesterol biosynthesis. We, therefore, investigated the role of intracellular oxysterols in the regulation of HMG-CoA reductase activity. Rats were fed with food (control), cholesterol, clofibrate as a potentiator of the microsomal monooxygenase cytochrome P-450 enzyme system, ketoconazole as a strong inhibitor of the system, or butylated hydroxytoluene (BHT) as an antioxidant. We analyzed and compared hepatic microsomal oxysterol levels among the groups. The results of this study indicated that the oxysterol level, especially 7beta-hydroxycholesterol and 7-ketocholestrol, in the liver was lowered by the administration of ketoconazole and BHT, and HMG-CoA reductase activity was increased in response to these agents. However, there was no change in the HMG-CoA reductase activity, after the administration of clofibrate. We conclude that reduced levels of oxysterol may release the inhibitory effect on the HMG-CoA reductase enzyme and lead to up-regulation of the enzyme.


Asunto(s)
Hidroximetilglutaril-CoA Reductasas/metabolismo , Microsomas Hepáticos/enzimología , Receptores de Esteroides/metabolismo , Animales , Antifúngicos/farmacología , Antioxidantes/farmacología , Hidroxitolueno Butilado/farmacología , Colesterol/biosíntesis , Cromatografía de Gases , Hidroxicolesteroles/metabolismo , Líquido Intracelular/enzimología , Cetocolesteroles/metabolismo , Cetoconazol/farmacología , Hígado/citología , Hígado/efectos de los fármacos , Hígado/enzimología , Masculino , Microsomas Hepáticos/efectos de los fármacos , Ratas , Ratas Wistar , Receptores de Esteroides/efectos de los fármacos , Regulación hacia Arriba
13.
J Histochem Cytochem ; 42(10): 1377-81, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7930520

RESUMEN

We studied the distribution of immunoreactive elements for [D-Ala2] deltorphin I (DADTI), a delta-opioid receptor ligand, in fetal and postnatal rat small intestine. DADTI-like immunoreactive cells were detected transiently on embryonic Days 20 and 21. Electron microscopic examination revealed that positive staining occurred in mucous epithelial cells, either mature goblet cells or undifferentiated cells containing only a few mucous granules. Positive immunoreaction products in mature goblet cells were confined in their apical cytoplasm to the luminal parts of mucous granule aggregates. The result suggests that a DADTI-like molecule(s) is synthesized in rat intestinal goblet cells and is secreted in a diacrine fashion into the intestinal lumen at a late fetal period. The molecule(s) thus secreted may be important for the intestine of rats just before birth, because DADTI-like immunopositive goblet cells are no longer seen at any postnatal period.


Asunto(s)
Intestino Delgado/química , Oligopéptidos/análisis , Secuencia de Aminoácidos , Animales , Animales Recién Nacidos , Feto/química , Inmunohistoquímica , Intestino Delgado/embriología , Datos de Secuencia Molecular , Ratas , Ratas Wistar
14.
J Assoc Res Otolaryngol ; 1(1): 46-63, 2000 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11548237

RESUMEN

Hair cell regeneration occurs spontaneously throughout life and following hair cell injury in the vestibular epithelia of mature birds and other nonmammalian vertebrates. We examined hair cell regeneration in post-hatch chick utricles that were cultured in media with or without the ototoxin, streptomycin, for various periods. The goal of our study was to characterize the dose- and time-dependent effects of streptomycin on hair cell loss and regeneration in vitro. Utricles that were cultured with streptomycin for 1 day displayed a dose-dependent loss of hair cells in spatial patterns and levels that were consistent with those observed in comparable experimental paradigms in vivo. Incorporation of the nucleotide analog bromodeoxyuridine (BrdU) demonstrated that supporting cell proliferation is decreased during the first day of culture in the presence of streptomycin, but it increases over time when cultures are subsequently placed in streptomycin-free media. Utricles cultured for 1 day with streptomycin followed by 2-4 more days without streptomycin had numerous bundles of immature stereocilia, suggesting that new hair cells were generated in vitro. We tested this hypothesis by culturing utricles with BrdU for 3 or 5 days and double-labeling them to detect BrdU and the hair cell-specific antigen, TuJ1. Numerous BrdU-positive/TuJ1-positive cells with phenotypic characteristics of immature hair cells were present in the cultures, and the number of such cells increased between 3 and 5 days in vitro, in a dose-dependent manner.


Asunto(s)
Pollos/fisiología , Regeneración , Sáculo y Utrículo/patología , Sáculo y Utrículo/fisiopatología , Animales , Animales Recién Nacidos/fisiología , Diferenciación Celular , División Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Ciliadas Vestibulares/efectos de los fármacos , Células Ciliadas Vestibulares/fisiología , Microscopía Electrónica de Rastreo , Técnicas de Cultivo de Órganos , Regeneración/efectos de los fármacos , Estreptomicina/farmacología , Factores de Tiempo
15.
Phys Rev Lett ; 85(20): 4293-6, 2000 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-11060621

RESUMEN

We report an investigation of the heterogeneity in supercooled liquids and glasses using the non-Gaussianity parameter. We simulate selenium and a binary Lennard-Jones system by molecular dynamics. In the non-Gaussianity three time domains can be distinguished: an increase on the ps scale due to the vibrational (ballistic) motion of the atoms, followed by a growth, due to local relaxations ( beta relaxation) at not too high temperatures, and finally a slow drop at long times. The non-Gaussianity follows in the intermediate time domain a sqrt[t] law. This is explained by collective hopping and dynamic heterogeneity. We support this finding by a model calculation.

16.
Ann N Y Acad Sci ; 942: 34-45, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11710476

RESUMEN

Hair cells in the vestibular organs of birds have a relatively short life span. Mature hair cells appear to die spontaneously and are then quickly replaced by new hair cells that arise from the division of epithelial supporting cells. A similar regenerative mechanism also results in hair cell replacement after ototoxic damage. The cellular basis of hair cell turnover in the avian ear is not understood. We are investigating the signaling pathways that lead to hair cell death and the relationship between ongoing cell death and cell production. In addition, work from our lab and others has demonstrated that the avian inner ear contains a resident population of macrophages and that enhanced numbers of macrophages are recruited to sites of hair cells lesions. Those observations suggest that macrophages and their secretory products (cytokines) may be involved in hair cell regeneration. Consistent with that suggestion, we have found that treatment with the anti-inflammatory drug dexamethasone reduces regenerative cell proliferation in the avian ear, and that certain macrophage-secreted cytokines can influence the proliferation of vestibular supporting cells and the survival of statoacoustic neurons. Those results suggest a role for the immune system in the process of sensory regeneration in the inner ear.


Asunto(s)
Apoptosis , División Celular/inmunología , Células Ciliadas Vestibulares/fisiología , Animales , Aves , División Celular/efectos de los fármacos , Dexametasona/farmacología , Células Ciliadas Vestibulares/citología , Células Ciliadas Vestibulares/inmunología , Macrófagos/citología , Neomicina/farmacología , Sáculo y Utrículo/citología , Sáculo y Utrículo/efectos de los fármacos
17.
J Atheroscler Thromb ; 8(1): 21-4, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11686311

RESUMEN

Functional impairment of the vascular endothelium is an early event in the development of atherosclerosis, and soluble adhesion molecules in plasma are regarded as an indicator of the endothelial damage in diabetes mellitus. We compared the soluble vascular adhesion molecule levels in the patients with diabetic nephropathy in concerning with plasma 7-ketocholesterol levels, which is major cholesterol auto-oxidation products. Average value of plasma VCAM-1 in 31 patients with type 2 diabetes mellitus was 297.6+/-10.2 ng/ml (mean+/-SE), and the value was significantly higher than that in 8 age-matched healthy controls (231.9+/-15.0 ng/ml). Among the 31 diabetic patients, the group with macroalbuminuria (n = 8) had the higher levels of plasma VCAM-1 (349.5+/-26.0 ng/ml) than the levels in the group with normoalbuminuria (n=15; 280.6+/-12.3 ng/ml). The levels of plasma 7-ketocholesterol in diabetes (26.9+/-1.5 ng/ml) or the patients with macroalbuminuria (31.4+/-3.3 ng/ml) were significantly higher than the control (22.5+/-1.8 ng/ml). The level of soluble VCAM-1 showed significant correlation between the values of 7-ketocholesterol (r=0.42, p=0.024), TC (r=0.42, p=0.014) and LDL-C (r=0.38, p=0.044). However no correlation was demonstrated with HbA1c nor creatinine level. We conclude that soluble VCAM-1 in plasma may be an indicator of oxidative stress and vascular injury in diabetic nephropathy.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Nefropatías Diabéticas/sangre , Cetocolesteroles/sangre , Molécula 1 de Adhesión Celular Vascular/sangre , Anciano , Estudios de Casos y Controles , Colesterol/metabolismo , Femenino , Hemoglobina Glucada/análisis , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Oxidación-Reducción
18.
J Control Release ; 68(3): 335-41, 2000 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-10974387

RESUMEN

Functional polyvinylpyrrolidone (PVP) was synthesized as a novel polymeric modifier for polymer-conjugated cytokines, and its efficiency and applicability as a drug delivery system (DDS) were evaluated. PVP with a carboxyl group at one end of the main chain was prepared by radical polymerization (M(n): 6000, M(w)/M(n): 1.14) with the aid of 4,4'-azobis(4-cyanovaleric acid) as a radical initiator and 3-mercaptopropionic acid as a transfer agent. Interleukin-6 (IL-6) was covalently conjugated via the formation of amino bonds between the lysine amino groups of IL-6 and PVP. PVP-conjugated IL-6, in which 60% of the fourteen lysine amino groups of IL-6 were estimated to be coupled with PVP (M-PVP-IL-6), showed more than 50-fold greater thrombopoietic potency in vivo than native IL-6. No side effects, such as body weight loss, were observed in the M-PVP-IL-6 treated mice. These results indicate that PVP as a polymeric modifier is a promising DDS for clinical application of cytokines and other therapeutic agents.


Asunto(s)
Plaquetas/efectos de los fármacos , Interleucina-6/administración & dosificación , Interleucina-6/farmacología , Excipientes Farmacéuticos/química , Povidona/química , Animales , Peso Corporal/efectos de los fármacos , Interleucina-6/química , Ratones , Ratones Endogámicos C3H , Peso Molecular , Recuento de Plaquetas , Estimulación Química , Relación Estructura-Actividad
19.
J Am Coll Surg ; 186(1): 10-6, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9449595

RESUMEN

BACKGROUND: Pylorus-preserving pancreatoduodenectomies (PPPDs) have been performed for disorders of the pancreatic head and periampullary region. The most commonly used reconstructive technique anastomoses the duodenum end-to-side to the jejunum, with pancreatic and biliary anastomoses placed proximally to the end-to-side duodenojejunostomy. In contrast, we have favored PPPD with gastrointestinal reconstruction by the Imanaga method (PPPD-Imanaga), which consists of end-to-end duodenojejunostomy, end-to-side pancreatojejunostomy, and choledochojejunostomy, performed in that order, because the PPPD-Imanaga provides a physiologic mixture of food, pancreatic juice, and bile in the upper portion of the jejunum. STUDY DESIGN: To identify their postoperative complications, we retrospectively reviewed the cases of 55 patients who underwent a PPPD-Imanaga between December 1986 and December 1996. In all cases, the right gastric artery was divided and the pancreatic duct was sewn directly to a small opening in the jejunal mucosa. Twenty patients with malignancy received adjuvant radiotherapy. RESULTS: Five patients died without being discharged, including one who died of cancer progression, for a postoperative mortality rate of 9%. These deaths were limited to patients who had received adjuvant radiotherapy, with only two deaths being procedure related. Delayed gastric emptying, pancreatic leak, and marginal ulcer were observed in 25 (45%), 3 (5%), and 3 (5%) patients, respectively. The delay in gastric emptying was transient and resolved spontaneously, with no patients undergoing reoperation. Only one patient required a reoperation, for the control of intraabdominal bleeding. CONCLUSIONS: A PPPD-Imanaga can be performed with acceptable morbidity and mortality risks. We conclude that the Imanaga method is a favorable complement to PPPD.


Asunto(s)
Pancreaticoduodenectomía/métodos , Complicaciones Posoperatorias/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Duodenostomía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatoyeyunostomía , Complicaciones Posoperatorias/mortalidad , Píloro , Estudios Retrospectivos
20.
J Chromatogr A ; 889(1-2): 25-31, 2000 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-10985532

RESUMEN

Triazine herbicide-selective polymer spheres were prepared by molecular imprinting using dibutylmelamine (DBM) as a template in suspension polymerization, and were utilized in solid-phase extraction (SPE) of atrazine. Atrazine-selective SPE was successfully demonstrated with a recovery of ca. 97% and an enrichment factor of 50, proving the good aptitude of DBM as the template species for developing a specific sorbent for triazine herbicides. It is also noteworthy that DBM-imprinted polymers have no possibility of disturbance in agrochemical analyses even if DBM remained in the polymer, which may occur by insufficient washing at the stage of removing the template to yield the binding sites, increasing the availability of imprinted polymers for practical applications.


Asunto(s)
Herbicidas/aislamiento & purificación , Triazinas/química , Técnicas de Química Analítica/métodos , Herbicidas/química , Microesferas , Polímeros/química
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