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1.
Dev Biol (Basel) ; 123: 251-63; discussion 265-6, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16566451

RESUMEN

PER.C6, a cell line derived from human embryonic retinal cells transformed with the Adenovirus Type 5 (Ad5) E1A and E1B genes, is used to produce E1-deleted Ad5 vectors such as the MRKAd5 HIV-1 gag vaccine. While whole, live PER.C6 cells are capable of growing as tumours when transplanted subcutaneously into immunodeficient nude mice at a high dosage, the process for vaccine production includes filtration steps and other methods which effectively preclude contamination by intact viable substrate cells. However, because of the neoplastic nature of this cell line, we carried out a series of investigations to assess the tumorigenic risk posed by residuals from the cell substrate in a vaccine. To address concerns about transmission of oncogenic DNA, we demonstrated that purified PER.C6 cellular DNA does not induce tumours in newborn hamsters or nude mice. To address concerns about other potential residuals, including hypothetical adventitious tumour viruses, we demonstrated that a PER.C6 cell lysate and a MRKAd5 HIV-1 gag vaccine produced on PER.C6 cells do not induce tumours in newborn hamsters or newborn rats. These results, in conjunction with the wide panel of viral safety tests performed on these cells, support the safety of the PER.C6 as a cell substrate for vaccine production.


Asunto(s)
Vacunas contra el SIDA/biosíntesis , Adenovirus Humanos/genética , Vacunas contra el SIDA/normas , Animales , Animales Recién Nacidos , Secuencia de Bases , Pruebas de Carcinogenicidad , Línea Celular Transformada , Cricetinae , Cartilla de ADN , Vectores Genéticos , Células HeLa , Humanos , Ratones , Ratones Desnudos , Neoplasias/epidemiología , Neoplasias/etiología , Reacción en Cadena de la Polimerasa , Ratas , Retina/virología
2.
Mol Pharmacol ; 58(3): 470-6, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10953038

RESUMEN

Peroxisome proliferators are a diverse group of compounds that cause hepatic hypertrophy and hyperplasia, increase peroxisome number, and on chronic high-dose administration, lead to rodent liver tumorigenesis. Various lines of evidence have led to the conclusion that these agents induce their pleiotropic effects exclusively via agonism of peroxisome proliferator-activated receptor (PPAR)alpha, a member of the steroid receptor superfamily involved in the regulation of fatty acid metabolism. Recently, agonists of two other members of this receptor family have been identified. PPARgamma is predominantly expressed in adipocytes where it mediates differentiation; PPARdelta is a widely expressed orphan receptor with yet unresolved physiologic functions. In the course of characterizing newer PPAR ligands, we noted that highly selective PPARgamma agonists or dual PPARgamma/PPARdelta agonists, lacking apparent murine PPARalpha agonist activity, cause peroxisome proliferation in CD-1 mice. We therefore made use of PPARalpha knockout mice to investigate whether these effects resulted from agonism of PPARalpha by these agents at very high dose levels or whether PPARgamma (or PPARdelta) agonism alone can result in peroxisome proliferation. We report here that several parameters linked to the hepatic peroxisome proliferation response in mice that were seen with these agents resulted from PPARalpha-independent effects.


Asunto(s)
Proliferadores de Peroxisomas/farmacología , Peroxisomas/efectos de los fármacos , Pirimidinas/farmacología , Receptores Citoplasmáticos y Nucleares/metabolismo , Tiazoles/farmacología , Tiazolidinedionas , Factores de Transcripción/metabolismo , Animales , Femenino , Regulación de la Expresión Génica , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Masculino , Ratones , Ratones Endogámicos ICR , Tamaño de los Órganos/efectos de los fármacos , Peroxisomas/fisiología , Receptores Citoplasmáticos y Nucleares/agonistas , Receptores Citoplasmáticos y Nucleares/deficiencia , Receptores Citoplasmáticos y Nucleares/genética , Factores de Transcripción/agonistas , Factores de Transcripción/deficiencia , Factores de Transcripción/genética
3.
Prostate ; 44(1): 8-18, 2000 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-10861752

RESUMEN

BACKGROUND: Previous studies have shown that chronic treatment of castrate dogs with androgen and estrogen results in significant prostate growth. Estrogen treatment of castrate dogs in the absence of androgen has resulted in conflicting data as reported by several authors. The purpose of this experiment was to evaluate the effect of a physiological dose of estradiol on prostate growth in dogs, using ultrasound to study size changes over time. METHODS: Dogs (n = 25) were randomly divided into groups (n = 5) and treated as follows: castration alone (CC), castration plus low dose estradiol (E(2) low), castration plus high estradiol (E(2) high), castration plus estradiol and androstanediol (E(2)A), or no treatment (normal controls, NC). Silastic implants containing 5alpha-androstan-3alpha-17beta-diol (3alphadiol), and/or 17beta-estradiol were used for continous delivery of steroids. Prostate volume was measured by transrectal ultrasonography, and blood was drawn for hormone and sex hormone binding globulin (SHBG) determinations. RESULTS: Results show that serum estradiol and SHBG levels were fairly constant over 12 weeks in all groups. Estradiol-treated groups had mean serum estradiol values of approximately 40 and 60 pg/ml, respectively. Initially, all groups had similar prostate volumes. Over 12 weeks the castrate dogs had a decline in prostate volume, whereas the intact dogs and those treated with E(2) and 3alpha-diol maintained a constant prostate volume. Estradiol treatment caused a large, late onset (week 7), dose-dependent increase in prostate volume relative to the intact group (P < 0.01). At 12 weeks, animals were euthanized and prostates weighed. The mean prostate weights in each group were: NC 14.8 +/- 2. 9, CC 2.4 +/- 0.5, E(2)A 9.7 +/- 2.0, E(2) low 21.7 +/- 4.3, and E(2) high 63.6 +/- 12.6 g (geometric mean +/- SEM). Histologically, prostates of estrogen-treated dogs showed metaplastic squamous epithelium. CONCLUSIONS: These results demonstrate that estradiol causes marked dose-dependent stimulation of prostate growth in the castrate dog.


Asunto(s)
Anabolizantes/farmacología , Androstano-3,17-diol/farmacología , Estradiol/farmacología , Próstata/efectos de los fármacos , Anabolizantes/administración & dosificación , Anabolizantes/sangre , Androstano-3,17-diol/administración & dosificación , Androstano-3,17-diol/sangre , Animales , Cromatografía Líquida de Alta Presión/veterinaria , Dihidrotestosterona/sangre , Perros , Relación Dosis-Respuesta a Droga , Implantes de Medicamentos , Estradiol/administración & dosificación , Estradiol/sangre , Histocitoquímica , Masculino , Orquiectomía/veterinaria , Próstata/diagnóstico por imagen , Próstata/crecimiento & desarrollo , Distribución Aleatoria , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangre , Ultrasonografía
4.
Vaccine ; 18(13): 1282-7, 2000 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-10649630

RESUMEN

Four Saanen goats were immunized with affinity purified gp135 surface glycoprotein (SU) of caprine arthritis-encephalitis virus isolate 79-63 (CAEV-63) and evaluated for homologous and crossreactive serum neutralizing antibodies. CAEV-63 neutralizing antibodies were detected in all goats after seven immunizations with SU in Quil A adjuvant. Sera from three goats neutralized an independent CAEV isolate (CAEV-Co). However, serum from one goat did not detectably neutralize heterologous CAEV-Co and inhibited CAEV-Co neutralization by another serum.


Asunto(s)
Anticuerpos Monoclonales/metabolismo , Anticuerpos Antivirales/biosíntesis , Anticuerpos Antivirales/metabolismo , Virus de la Artritis-Encefalitis Caprina/inmunología , Glicoproteínas de Membrana/inmunología , Proteínas del Tejido Nervioso/inmunología , Adyuvantes Inmunológicos/farmacología , Animales , Anticuerpos Antivirales/sangre , Especificidad de Anticuerpos , Virus de la Artritis-Encefalitis Caprina/química , Virus de la Artritis-Encefalitis Caprina/aislamiento & purificación , Contactina 1 , Reacciones Cruzadas , Electroforesis en Gel de Poliacrilamida , Cabras , Immunoblotting , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Glicoproteínas de Membrana/aislamiento & purificación , Proteínas del Tejido Nervioso/aislamiento & purificación , Pruebas de Neutralización , Vacunas Virales/inmunología
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