RESUMEN
Different treatment outcomes and prognoses in patients with breast cancer can be observed with similar clinical predictors; this is because the biology of breast cancer is complex and heterogenous, involving multiple unknown contributing factors. We looked for plasma human mammaglobin (hMAM) mRNA by RT-PCR in 82 Korean patients with breast cancer to determine if there is an association between the presence of plasma hMAM mRNA in these patients and known prognostic factors. The prognostic usefulness of detection of plasma hMAM mRNA expression in these patients was also evaluated by determining overall survival and event-free survival. A significant difference was observed in the rate of positivity of plasma hMAM mRNA between the early stages of cancer (stages I-II, 23.4%) and advanced stages (stages III-IV, 82.9%). The expression rates of estrogen receptor, progesterone receptor, and HER-2/neu in the breast tissue of these patients, by immunohistochemistry, were 69.5, 75.6, and 20.7%, respectively. In the univariate analysis, plasma hMAM expression was significantly correlated with high histological and nuclear grades, nodal metastasis, and negative estrogen receptor and progesterone receptor status. Patients negative for plasma hMAM mRNA had significantly higher rates of event-free survival compared to the patients positive for plasma hMAM mRNA. However, no significant association with overall survival was observed for expression of plasma hMAM mRNA (P = 0.16). Qualitative detection of plasma hMAM mRNA appears to be associated with unfavorable prognostic factors and lower rates of event-free survival in patients with breast cancer.
Asunto(s)
Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , Mamoglobina A/sangre , Mamoglobina A/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Células MCF-7 , Persona de Mediana Edad , ARN Mensajero/sangre , ARN Mensajero/genéticaRESUMEN
As part of a comprehensive study on the ecology of arthropod-borne viruses in the Amazon Basin region of Peru, we assayed 539,694 mosquitoes captured in Loreto Department, Peru, for arboviruses. Mosquitoes were captured either by dry ice-baited miniature light traps or with aspirators while mosquitoes were landing on human collectors, identified to species, and later tested on Vero cells for virus. In total, 164 virus isolations were made and included members of the Alphavirus (eastern equine encephalomyelitis, Trocara, Una, Venezuelan equine encephalomyelitis, and western equine encephalomyelitis viruses), Flavivirus (Ilheus and St. Louis encephalitis), and Orthobunyavirus (Caraparu, Itaqui, Mirim, Murutucu, and Wyeomyia viruses) genera. In addition, several viruses distinct from the above-mentioned genera were identified to the serogroup level. Eastern equine encephalomyelitis virus was associated primarily with Culex pedroi Sirivanakarn & Belkin, whereas Venezuelan equine encephalomyelitis virus was associated primarily with Culex gnomatos Sallum, Huchings & Ferreira. Most isolations of Ilheus virus were made from Psorophora ferox (Von Humboldt). Although species of the Culex subgenus Melanoconion accounted for only 45% of the mosquitoes collected, 85% of the virus isolations were made from this subgenus. Knowledge of the viruses that are being transmitted in the Amazon Basin region of Peru will enable the development of more effective diagnostic assays, more efficient and rapid diagnoses of clinical illnesses caused by these pathogens, risk analysis for military/civilian operations, and development of potential disease control measures.
Asunto(s)
Arbovirus/aislamiento & purificación , Culicidae/virología , Ambiente , Animales , Arbovirus/clasificación , Arbovirus/genética , Chlorocebus aethiops , Técnica del Anticuerpo Fluorescente Directa , Perú , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estaciones del Año , Especificidad de la Especie , Células VeroRESUMEN
A candidate vaccine against botulinum neurotoxin serotype A (BoNT/A) was developed by using a Venezuelan equine encephalitis (VEE) virus replicon vector. This vaccine vector is composed of a self-replicating RNA containing all of the VEE nonstructural genes and cis-acting elements and also a heterologous immunogen gene placed downstream of the subgenomic 26S promoter in place of the viral structural genes. In this study, the nontoxic 50-kDa carboxy-terminal fragment (H(C)) of the BoNT/A heavy chain was cloned into the replicon vector (H(C)-replicon). Cotransfection of BHK cells in vitro with the H(C)-replicon and two helper RNA molecules, the latter encoding all of the VEE structural proteins, resulted in the assembly and release of propagation-deficient, H(C) VEE replicon particles (H(C)-VRP). Cells infected with H(C)-VRP efficiently expressed this protein when analyzed by either immunofluorescence or by Western blot. To evaluate the immunogenicity of H(C)-VRP, mice were vaccinated with various doses of H(C)-VRP at different intervals. Mice inoculated subcutaneously with H(C)-VRP were protected from an intraperitoneal challenge of up to 100,000 50% lethal dose units of BoNT/A. Protection correlated directly with serum enzyme-linked immunosorbent assay titers to BoNT/A. The duration of the immunity achieved was tested at 6 months and at 1 year postvaccination, and mice challenged at these times remained refractory to challenge with BoNT/A.
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Vacunas Bacterianas/inmunología , Toxinas Botulínicas Tipo A/inmunología , Botulismo/prevención & control , Encefalomielitis Equina Venezolana/genética , Replicón/genética , Animales , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/genética , Toxinas Botulínicas Tipo A/genética , Línea Celular , Clostridium botulinum/inmunología , Clostridium botulinum/metabolismo , Encefalomielitis Equina Venezolana/metabolismo , Vectores Genéticos , Ratones , Ratones Endogámicos BALB C , Vacunación , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/inmunologíaRESUMEN
To investigate the roles of type I interferon (IFN-alpha/beta) and other mediators of innate immune responses (e.g., inducible nitric oxide synthase [iNOS]) in early dissemination of Venezuelan equine encephalitis virus (VEE) infection, we used mice with targeted deletions in either their IFN-alpha/beta-receptor (IFNAR-1-/-) or interferon regulatory factor 2 (IRF-2-/-) genes. Following footpad infection, both IFNAR-1-/- and IRF-2-/- mice were more susceptible than control mice to VEE. The IFNAR-1-/- mice also exhibit accelerated VEE dissemination to serum, spleen, and brain, and compared with control mice, they evidenced faster kinetics in the upregulation of proinflammatory genes. In contrast, in IRF-2-/- mice, iNOS gene induction was completely absent following peripheral virulent VEE infection. In evaluating the role of cells involved in iNOS production, primary microglial cell cultures were found to be highly permissive to VEE infection. Moreover, VEE infection increased levels of nitric oxide (NO) in resting microglial cultures but decreased NO production in IFN-gamma-stimulated microglia. Thus, these findings suggest that reactive nitrogen species play an important contributory role in VEE dissemination and survival of the host. Our results further suggest the necessity for a carefully balanced host response that follows a middle course between immunopathology and insufficient inflammatory response to VEE infection.
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Encéfalo/enzimología , Encéfalo/inmunología , Encefalomielitis Equina Venezolana/enzimología , Encefalomielitis Equina Venezolana/inmunología , Interferón Tipo I/genética , Óxido Nítrico Sintasa/genética , Proteínas Represoras , Factores de Transcripción , Animales , Encéfalo/virología , Células Cultivadas , Cricetinae , Proteínas de Unión al ADN/genética , Virus de la Encefalitis Equina Venezolana/patogenicidad , Virus de la Encefalitis Equina Venezolana/fisiología , Encefalomielitis Equina Venezolana/genética , Factor 2 Regulador del Interferón , Proteínas de la Membrana , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/inmunología , Microglía/virología , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Receptor de Interferón alfa y beta , Receptores de Interferón/genética , Regulación hacia Arriba , Virulencia , Replicación ViralRESUMEN
An alkaliphilic, endospore-forming bacterium isolated from Brazilian soil was taxonomically studied and is proposed as a new Paenibacillus species. This organism (strain 324T) was particularly distinguishable from other Paenibacillus species by its ability to grow optimally at pH 10 and 40 degrees C. The DNA G+C content was 5.0 mol%. The diamine acid of the cell-wall peptidoglycan was meso-diaminopimelic acid. MK-7 was the predominant menaquinone and anteiso-C15:0 was the major fatty acid. Levels of 16S rDNA similarity between strain 324T and other Paenibacillus species were 90.6-95.9%. Phylogenetically, strain 324T formed an evolutionary lineage distinct from other species within the evolutionary radiation encompassing the genus Paenibacillus. Based on phenotyic and chemotaxonomic properties, and phylogenetic inference, it is proposed that strain 324T should be placed in the genus Paenibacillus as a new species is strain 324T should be placed in the genus Paenibacilus as a new species, Paenibacillus campinasensis. This type strain of the new species is strain 325T (= KCTC 0364BP).