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1.
Ethics Med Public Health ; 24: 100815, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35757376

RESUMEN

Background: The novel COVID-19 pandemic afforded public health leaders an opportunity to expedite vaccine development and dissemination. The United States found itself faced with the arduous task of ensuring swift and equitable distribution of limited resources, in the midst of often-competing priorities, including public health ethics, medical ethics, economic demands, and societal strains. Methodology: Using the American Public Health Association's (APHA) newly revised public health code of ethics, which provides a decision-making framework and guidance for ethical analysis, we analyzed how Pennsylvania's COVID-19 vaccine dissemination plan aligned with the four core functions of public health ethics inquiry. Results/Discussion: Upon investigation, the state's plan evidenced use of public health ethics in goal setting and design. However, the core public health value given the highest priority, promoting health and safety, competed with the other core public health values of inclusivity and engagement, health justice and equity, and professionalism and trust. Despite known social disparities and risk factors, the state plan for COVID-19 vaccine dissemination aligned closely with federal guidance and prioritized all healthcare personnel and long-term care facility populations over high-risk individuals residing in the community. Conclusion/Perspectives: Should another pandemic necessitate allocation of scarce resources, especially preventative measures such as vaccines, decision-making agencies must consider disparate populations in planning and dissemination of material to the public. Any anticipated limitations in the ability to fulfill public health ethical principles should be clearly communicated to the public prior to implementation, thereby increasing trust.

2.
Sci Rep ; 7(1): 12061, 2017 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-28935891

RESUMEN

We present a comprehensive study of the crystal structure of the thin-film, ferromagnetic topological insulator (Bi, Sb)2-x V x Te3. The dissipationless quantum anomalous Hall edge states it manifests are of particular interest for spintronics, as a natural spin filter or pure spin source, and as qubits for topological quantum computing. For ranges typically used in experiments, we investigate the effect of doping, substrate choice and film thickness on the (Bi, Sb)2Te3 unit cell using high-resolution X-ray diffractometry. Scanning transmission electron microscopy and energy-dispersive X-ray spectroscopy measurements provide local structural and interfacial information. We find that the unit cell is unaffected in-plane by vanadium doping changes, and remains unchanged over a thickness range of 4-10 quintuple layers (1 QL ≈ 1 nm). The in-plane lattice parameter (a) also remains the same in films grown on different substrate materials. However, out-of-plane the c-axis increases with the doping level and thicknesses >10 QL, and is potentially reduced in films grown on Si (1 1 1).

3.
Chest ; 104(4): 1304-5, 1993 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8404222

RESUMEN

A prevalent clinical perception is that thoracic restriction in patients with morphea or scleroderma should not result from cutaneous sclerosis alone; that there must be some underlying parenchymal lung disease or respiratory muscle weakness. But herein we describe a patient with morphea and severe thoracic restriction that appears to result mainly from cutaneous sclerosis.


Asunto(s)
Disnea/etiología , Esclerodermia Localizada/complicaciones , Tórax , Humanos , Enfermedades Pulmonares/diagnóstico , Mediciones del Volumen Pulmonar , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria , Músculos Respiratorios/fisiología
4.
Neuroscience ; 56(3): 717-27, 1993 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8255430

RESUMEN

The duration of long-term potentiation in the dentate gyrus of awake rats was examined following systematic manipulation of the number of stimulus trains delivered. This was correlated with the induction of immediate early genes in separate groups of animals given identical stimulus regimes. Following 10 trains of stimulation, long-term potentiation decayed with a time constant of up to several days (long-term potentiation 2), and this correlated with the appearance of an increase in the messenger RNA and protein levels of zif/268. Increasing the number of stimulus trains resulted in a greater probability of eliciting long-term potentiation with a time constant of several weeks (long-term potentiation 3), as well as increasing the induction of zif/268, c-Jun, Jun-B, Jun-D and Fos-related proteins. When 10 trains were delivered repeatedly on up to five consecutive days, only the zif/268 protein levels showed associated changes. These data provide support for the hypothesis that long-term potentiation 3 involves mechanisms additional to those for long-term potentiation 2. One possible mechanism is altered gene expression, initiated by immediate early gene transcription factors such as zif/268 and possibly homo- or heterodimers of Fos and Jun family members, that then contributes to the stabilization or maintenance of long-term potentiation 3.


Asunto(s)
Expresión Génica/fisiología , Genes Inmediatos-Precoces/fisiología , Potenciación a Largo Plazo/fisiología , Animales , Secuencia de Bases , Northern Blotting , Estimulación Eléctrica , Potenciales Evocados/efectos de los fármacos , Potenciales Evocados/fisiología , Hipocampo/fisiología , Inmunohistoquímica , Masculino , Datos de Secuencia Molecular , Oligonucleótidos , Biosíntesis de Proteínas , Sondas ARN , Ratas , Ratas Sprague-Dawley
5.
Brain Res ; 580(1-2): 147-54, 1992 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-1504794

RESUMEN

Expression of the immediate early gene zif/268 (also termed NGFI-A, Krox 24, TIS8 and Egr-1) was investigated in awake rats following various long-term potentiation (LTP) induction protocols. zif/268 mRNA (Northern blots) and protein (immunohistochemistry) levels sharply increased following LTP, and followed a time course characteristic of other immediate early genes. When measured across 3 tetanization protocols known to produce differing degrees of LTP persistence, zif/268 induction was found to be more highly correlated with LTP duration than with the magnitude of initial LTP. These data support the hypothesis that the immediate early gene zif/268 plays a role as a third messenger in the cascade of cellular and nuclear events that govern the persistence of LTP.


Asunto(s)
Expresión Génica/fisiología , Hipocampo/fisiología , Proteínas del Tejido Nervioso/genética , ARN Mensajero/biosíntesis , Animales , Secuencia de Bases , Northern Blotting , Potenciales Evocados/fisiología , Inmunohistoquímica , Masculino , Datos de Secuencia Molecular , Sondas de Oligonucleótidos , Ratas , Ratas Endogámicas , Factores de Tiempo
6.
Biochem J ; 267(3): 815-9, 1990 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-2339991

RESUMEN

Transferrin mRNA concentrations were measured in total RNA isolated from liver and mammary tissue of lactating rats at different stages of lactation. The mammary transferrin mRNA concentration varied in a biphasic manner, increasing up to parturition and then decreasing to undetectable levels at days 5 and 10 of lactation before increasing again markedly in late lactation. The values obtained at day 20 of lactation were double those found in livers of lactating rats. The concentrations of total RNA and mRNA for alpha-casein and alpha-lactalbumin did not change between days 5 and 20 of lactation. Transferrin concentrations were measured in milk from rats fed on an iron-free, a control and an iron-supplemented diet. Although there was a 5-fold difference in the transferrin concentration of samples taken between day 5 and day 20 of lactation, the dietary treatments did not result in significant changes. Maternal serum transferrin concentrations were, however, elevated, and pup haemoglobin concentrations were suppressed for the rats receiving the iron-free diet, indicating an alteration of the iron status of these rats.


Asunto(s)
Hierro/metabolismo , Glándulas Mamarias Animales/metabolismo , ARN Mensajero/análisis , Transferrina/genética , Animales , Dieta , Femenino , Regulación de la Expresión Génica , Embarazo , Ratas , Ratas Endogámicas
8.
Cancer Res ; 45(5): 2201-5, 1985 May.
Artículo en Inglés | MEDLINE | ID: mdl-3986769

RESUMEN

The oncogene N-ras has been found to be amplified (congruent to 20 copies) in the human breast carcinoma cell line MCF-7. The amplified sequences have been localized to a marker chromosome by in situ hybridization. Sublines of MCF-7, serially passaged in different laboratories, have marked variation in the degree of N-ras amplification. The differing degrees of amplification of N-ras are further evidence of heterogeneity within MCF-7 subclones. The phenomenon may not have general relevance for breast cancer, since other breast cancer cell lines and DNA from patient biopsies failed to show evidence of N-ras amplification.


Asunto(s)
Neoplasias de la Mama/genética , Amplificación de Genes , Oncogenes , Línea Celular , Femenino , Humanos
11.
Life Sci ; 31(1): 25-30, 1982 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-7109851

RESUMEN

1,4-dihydroxy-5-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione one (NSC 287836) and 1,4-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione diacetate (NSC 287513) have shown activity against solid tumors and are now in Phase I clinical trials. Fluorescence polarization was used to determine the extent of inhibition of the binding of acridine orange to DNA (Richardson, Boboz, Holland, Res. Comm. Chem. Pathol. Pharmac. 27, 497, 1980). Displacement of 50% of acridine orange from calf thymus DNA was obtained with 0.18 micro M of NSC 287836 while 0.52 micro M of NSC 287513 was needed to displace an equivalent amount of acridine orange. NSC 287513 showed preference for polynucleotides of high adenine + thymine content while NSC 287836 did not. Analogs lacking both hydroxyethylaminoethyl-amino side chains did not displace acridine orange.


Asunto(s)
Antraquinonas , Antibióticos Antineoplásicos , ADN , Naranja de Acridina , Polarización de Fluorescencia , Mitoxantrona
12.
Cancer Res ; 42(1): 117-21, 1982 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-7053840

RESUMEN

The semisynthetic anthracycline, 5-iminodaunorubicin (IM), was investigated to see whether modification of the benzoquinone moiety to produce a drug with low free radical potential would alter the cytotoxic and biochemical characteristics of this drug in comparison to Adriamycin (ADR), an agent with high free radical potential. Cell viability was measured in human colon carcinoma (HT-29) cells by soft-agar cloning. Upon exposure to either log-phase or early plateau-phase cells for 2 hr to IM or ADR, a threshold exponential cell lethality curve was obtained. Prolonging during exposure to 24 hr produced an exponential decline in cell survival and a marked reduction in viability of both log-phase and early plateau-phase cells. Inhibition of DNA synthesis in log-phase cells after 2 and 24 hr of exposure to IM and ADR paralleled the increased cell lethality produced by the drugs. In contrast, total RNA synthesis was not inhibited by IM, whereas ADR impaired both RNA and DNA synthesis. Nuclear rRNA, synthesis was not significantly inhibited following 24 hr of exposure to 10(-7) M ADR or IM but was inhibited by 85 and 35% at 10(-6) M ADR or IM, respectively. The affinity of IM and ADR for HT-29 DNA was measured in vitro by displacement of acridine orange binding and was found to be similar for both analogs. These studies suggest that the cytotoxicity of IM and ADR results from the interactions of these drugs with DNA.


Asunto(s)
Neoplasias del Colon/tratamiento farmacológico , Daunorrubicina/análogos & derivados , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , ADN de Neoplasias/biosíntesis , Daunorrubicina/farmacología , Daunorrubicina/uso terapéutico , Doxorrubicina/farmacología , Humanos , Peso Molecular , Neoplasias Experimentales/tratamiento farmacológico , ARN Neoplásico/biosíntesis
13.
Cancer Res ; 41(6): 2235-40, 1981 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7237423

RESUMEN

Nogalamycin, an anthracycline antibiotic, interacts with DNA. This interaction is measured by a competitive fluorescence polarization assay in which nogalamycin displaces acridine orange. The amount of acridine orange displaced is dependent upon the concentration and DNA-binding capability of the drug. The relative DNA-binding capacities of several nogalamycin analogs are also determined by this method. A comparison of these results with circular dichroism and thermal denaturation yields a positive correlation. The base-pair specificities of these compounds are also evaluated by competitive fluorescence polarization using DNA's of differing base composition. These results indicate that compounds containing the nogalose moiety generally prefer adenine and thymine. On the other hand, some of the 7-O-alkyl analogs appear to interact similarly with DNA's of differing base composition, and others show a preference for DNA's with high guanine and cytosine content. Specificities obtained with this method are compared with DNA thermal denaturation and polymerase inhibition studies. The potential value of this relatively new competitive method for the study of DNA-reactive antitumor compounds is discussed.


Asunto(s)
Naranja de Acridina/metabolismo , ADN/metabolismo , Daunorrubicina/análogos & derivados , Nogalamicina/metabolismo , Animales , Composición de Base , Unión Competitiva , Bovinos , Dicroismo Circular , ADN Polimerasa Dirigida por ADN/metabolismo , Polarización de Fluorescencia , Métodos , Nogalamicina/análogos & derivados , Desnaturalización de Ácido Nucleico , Moldes Genéticos
14.
Ann N Y Acad Sci ; 359: 367-82, 1981 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-6942682

RESUMEN

The ability of retinoids to prevent or alter the course of experimental tumorigenesis is well established. We have extended these observations to include effects on establishment of tumors and tumor metastases. A diet containing excess retinyl acetate fed to rats prior to injection of a metastatic line of transplantable hepatoma, prevented establishment of secondary tumor foci while 75% of the animals fed adequate retinyl acetate showed pulmonary metastases. Metastatic ability may be related to the ability to bind fibronectins, proteins that link cells to an underlying stroma. Findings suggest involvement of higher gangliosides in the attachment of cells to a fibronectin-collagen complex. Prior to metastasis, hepatoma lines become depleted in the putative fibronectin receptor gangliosides as an end result of a complex cascade of altered glycosyltransferase activities. After metastasis, fibronectin receptors are apparently restored in those secondary tumor foci that become established. Analyses suggest that excess vitamin A may prevent the reappearance of fibronectin receptor gangliosides so that secondary tumor foci do not establish.


Asunto(s)
Gangliósidos/biosíntesis , Glicósidos/metabolismo , Neoplasias Hepáticas Experimentales/fisiopatología , Vitamina A/farmacología , Animales , Adhesión Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Metástasis de la Neoplasia , Ratas , Tretinoina/farmacología
15.
Environ Mutagen ; 3(5): 545-53, 1981.
Artículo en Inglés | MEDLINE | ID: mdl-6793355

RESUMEN

Several metals are known mutagens and carcinogens. These metals effectively displace acridine orange from DNA when measured by fluorescence polarization. Displacement of 50% of the acridine orange is obtained with less than 0.5 mM concentrations of lead, manganese, cobalt, zinc, cadmium, nickel, iron, copper, and cis-platinum. In contrast, greater than 80 mM concentrations of lithium, sodium, and potassium are required to displace an equivalent amount of acridine orange from calf thymus DNA. Although cis-platinum shows the best DNA reactivity in this assay, the interaction between this metal and DNA does not occur immediately, as it does for the other metals tested. These results indicate the acridine orange displacement assay provides a relative measure of the interaction of metals with DNA, and this DNA reactivity shows a positive correlation with mutagenic/carcinogenic potential.


Asunto(s)
Naranja de Acridina/metabolismo , Carcinógenos/metabolismo , ADN/metabolismo , Metales/metabolismo , Mutágenos/metabolismo , Animales , Unión Competitiva , Bovinos , Cisplatino/metabolismo , ADN/biosíntesis , Polarización de Fluorescencia , Tiourea/farmacología
16.
Biochim Biophys Acta ; 652(1): 55-63, 1981 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-7213736

RESUMEN

The increase in the fluorescence polarization of acridine orange upon binding to DNA molecules is used as the basis of a competitive method to study the interaction of a variety of fluorescent and non-fluorescent compounds with DNA. Test compounds that interact with DNA inhibit both the binding of acridine orange to DNA and the accompanying increase in fluorescence polarization. Actinomycin D exhibits a dose-dependent inhibition of acridine orange-DNA binding with Micrococcus luteus DNA, calf thymus DNA, and poly(dG-dC); no detectable inhibition of acridine orange intercalation into poly(dA-dT) is observed. In contrast, proflavine shows similar acridine orange inhibition for poly(dA-dT), calf thymus DNA and M. luteus DNA.


Asunto(s)
Naranja de Acridina/metabolismo , ADN/metabolismo , Animales , Unión Competitiva , Bovinos , ADN Bacteriano/metabolismo , Dactinomicina/farmacología , Polarización de Fluorescencia , Micrococcus , Poli dA-dT/metabolismo , Polidesoxirribonucleótidos/metabolismo
17.
Fertil Steril ; 34(4): 379-85, 1980 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7418892

RESUMEN

A fluorescent derivative of human chorionic gonadotropin (hCG) for binding studies was prepared by conjugation of hightly purified hCG with fluorescein isothiocynate (FITC-hCG) in a molar ratio of 3:1. The resulting FITC-hCG conjugate retained full cross-reactivity with antibodies directed against intact hCG, the hCG beta-subunit, the carboxyl-terminal peptide sequence of beta-hCG. The fluorescent hormone retained binding activity similar to that of native hCG, and the capacity to induce progesterone production from primate corpora luteal cells in vitro. After intravenous administration to female rhesus monkeys, FITC-hCG was localized within the theca cell layer of certain antral follicles, including the dominant follicle, but no fluorescence was noted around preantral follicles. Areas of fluorescence were also localized to discrete groups of interstitial gland cells in the stroma. The degree of fluorescence associated with these cells was indistinguishable from that observed in the thecal cells. The development of a fluorescent derivative that is biologically and immunologically similar to native hCG has permitted differential microscopic localization of luteinizing hormone/hCG uptake in the preovulatory ovary.


Asunto(s)
Gonadotropina Coriónica/metabolismo , Hormona Luteinizante/metabolismo , Ovario/metabolismo , Ovulación , Animales , Gonadotropina Coriónica/inmunología , Femenino , Fluoresceínas , Polarización de Fluorescencia , Macaca fascicularis , Ratas
18.
Res Commun Chem Pathol Pharmacol ; 27(3): 497-506, 1980 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7384639

RESUMEN

The title compound is now undergoing Phase I clinical trials as an experimental antitumor agent. Fluorescent polarization was used to determine the extent of inhibition of the binding of acridine orange to DNA. Displacement of 50% of the acridine orange was achieved by 0.21 microM of the title compound, 0.32 microM daunorubicin, 0.41 microM doxorubicin, 0.61 microM dactinomycin, and 7.8 microM cis-platinum. Binding inhibition was essentially equivalent with natural DNAs (calf thymus and Micrococcus luteus) and synthetic polymers [poly d(A):d(T) and poly d(G):d(C)] of widely differing adenine plus thymidine content.


Asunto(s)
Antracenos/metabolismo , Antineoplásicos/metabolismo , ADN/metabolismo , Naranja de Acridina/metabolismo , Unión Competitiva , Fenómenos Químicos , Química , ADN Bacteriano/metabolismo , Dactinomicina/metabolismo , Daunorrubicina/metabolismo , Doxorrubicina/metabolismo , Polarización de Fluorescencia , Micrococcus/metabolismo , Mitoxantrona
19.
Lloydia ; 41(5): 450-2, 1978.
Artículo en Inglés | MEDLINE | ID: mdl-362106

RESUMEN

Shikimic acid, reported to cause tumors in mice, and its close structural analog, quinic acid, both ubiquitous constituents of higher plants, were found not be be mutagenic in the Ames assay when tested with and without the rat liver microsomal activation system.


Asunto(s)
Mutágenos , Ácido Quínico/farmacología , Salmonella typhimurium/efectos de los fármacos , Ácido Shikímico/farmacología , Animales , Técnicas In Vitro , Microsomas Hepáticos/fisiología , Ratas , Salmonella typhimurium/genética
20.
J Natl Cancer Inst ; 60(6): 1313-27, 1978 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-206706

RESUMEN

Hyperplastic nodules and hepatocellular carcinomas were induced in livers of rats by a low-protein diet containing 0.05% of the carcinogen N-2-fluorenylacetamide. Ganglioside amounts and composition were determined for histologically different hepatocellular carcinomas and compared with those for control livers, hyperplastic nodules, and liver tissue surrounding hepatomas and nodules as well as those for livers of fetal, newborn, 1-week-old, weanling, and adult Sprague-Dawley rats. Ganglioside sialic acid levels were elevated above those of normal adult liver in all liver tissues following the carcinogen treatment regimen. Livers of fetal and newborn rats contained nearly twice the amount of ganglioside sialic acid on a protein or DNA basis as did livers of adult rats. Analyses of individual nodules and hepatomas revealed two populations of tumors in which the levels of ganglioside sialic acid were 2.3 and 3.8 times normal. Ganglioside sialic acid content was at hepatoma levels in small nodules. Individual gangliosides were evenly distributed between products of the monosialoganglioside and disialoganglioside pathways in normal liver with a ratio of [N-acetylneuraminic acid (sialic acid)] (NAN)-galactose (Gal)-N-acetylgalactosamine (GalNAc)-(NAN)-Gal-glucose (Glc)-ceramide (Cer) (GD1a) to Gal-GalNAc-(NAN)2-Gal-Glc-Cer (GD1b) of about one. In contrast, the monosialogangliosides predominated in liver tissues following administration of the carcinogen. Increased levels of specific monosialogangliosides were present in nodules, in liver of carcinogen-treated animals prior to the appearance of tumors, and in the liver tissues surrounding nodules and hepatomas. In single hepatomas, ganglioside patterns correlated with tumorigenicity. A well-differentiated hepatoma had a normal complement of most gangliosides but was deficient in trisialogangliosides. In a poorly diferentiated but well-circumscribed hepatoma, the relative levels of all higher gangliosides were reduced. The monosialoganglioside Gal-GalNAc-(NAN)-Gal-Glc-Cer (GM1) accounted for 80% of the total ganglioside in a poorly circumscribed and poorly differentiated hepatoma. The ganglioside pattern of fetal livers most closely resembled that of a poorly differentiated hepatoma. During the first week post natum, levels of all higher monosialogangliosides and disialogangliosides declined, but the decline was most pronounced for gangliosides GM1 and GD1a. The ratio of GM1 + GD1a to GD1b + NAN-Gal-GalNAc-(NAN)2-Gal-Glc-Cer or (NAN)3-Gal-Glc-Cer (GT), used as an index of the relative predominance of the monoslaloganglioside and disialoganglioside pathways, fell from 2.7 for fetal liver to 0.4 for adult liver. Pools of precursor gangliosides increased during development, transiently for GalNAc-(NAN)-Gal-Glc-Cer and for more than 3 weeks for NAN-Gal-Glc-Cer. When hyperplastic nodules and hepatocellular carcinomas were compared, a reverse pattern was observed. The ratio of GM1 + GD1a to GD1b + GT rose steadily to values of 2.7 and 11...


Asunto(s)
2-Acetilaminofluoreno , Carcinoma Hepatocelular/metabolismo , Fluorenos , Gangliósidos/metabolismo , Neoplasias Hepáticas/metabolismo , Animales , Animales Recién Nacidos/metabolismo , Carcinoma Hepatocelular/inducido químicamente , Gangliósido G(M1)/aislamiento & purificación , Gangliósido G(M1)/metabolismo , Gangliósido G(M2)/aislamiento & purificación , Gangliósido G(M2)/metabolismo , Gangliósido G(M3)/aislamiento & purificación , Gangliósido G(M3)/metabolismo , Hiperplasia/metabolismo , Hígado/embriología , Hígado/metabolismo , Neoplasias Hepáticas/inducido químicamente , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/metabolismo , Lesiones Precancerosas/metabolismo , Ratas , Ácidos Siálicos/metabolismo
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