RESUMO
The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they or their contacts have increased susceptibility to severe vaccine side effects. As vaccines can no longer be tested for their ability to prevent smallpox, licensing will necessarily include comparative immunogenicity and protection studies in non-human primates. Here we compare the highly attenuated modified vaccinia virus Ankara (MVA) with the licensed Dryvax vaccine in a monkey model. After two doses of MVA or one dose of MVA followed by Dryvax, antibody binding and neutralizing titres and T-cell responses were equivalent or higher than those induced by Dryvax alone. After challenge with monkeypox virus, unimmunized animals developed more than 500 pustular skin lesions and became gravely ill or died, whereas vaccinated animals were healthy and asymptomatic, except for a small number of transient skin lesions in animals immunized only with MVA.
Assuntos
Macaca fascicularis/imunologia , Macaca fascicularis/virologia , Mpox/imunologia , Mpox/prevenção & controle , Vacina Antivariólica/imunologia , Vacinas Atenuadas/imunologia , Vaccinia virus/genética , Animais , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Embrião de Galinha , DNA Viral/sangue , Fibroblastos , Humanos , Interferon gama/imunologia , Modelos Animais , Mpox/patologia , Mpox/fisiopatologia , Monkeypox virus/genética , Monkeypox virus/imunologia , Monkeypox virus/fisiologia , Vacina Antivariólica/administração & dosagem , Vacina Antivariólica/genética , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética , Vaccinia virus/classificação , Carga ViralRESUMO
Serrated adenoma is a recently described entity characterized by the presence of a hyperplastic (serrated) growth pattern combined with cytologic features of dysplasia. In contrast to conventional (nonserrated) adenomas, the molecular features of serrated adenomas have been poorly studied. Thus, it remains unclear if serrated adenomas are simply a morphologic variant of conventional adenomas or represent a different biologic entity. In this study, 46 serrated adenomas from 39 patients, 32 conventional (nonserrated) adenomas from 31 patients, and 18 hyperplastic polyps from 16 patients were evaluated for loss of heterozygosity (LOH) of APC, p53, p16, and 3p and for K-ras mutations of codons 12, 13, and 61 by polymerase chain reaction (PCR) analysis. Serrated adenomas demonstrated LOH of at least one genetic locus in 32.6% of cases. LOH of the APC gene, 3p, p53, and p16 was seen in 19.4%, 14.2%, 9.3%, and 13.8% of cases, respectively. K-ras mutations were observed in 18% of cases. Similar to serrated adenomas, conventional adenomas demonstrated at least one LOH event in 37.5% of cases and K-ras mutations in another 19% of cases. LOH of APC, 3p, p53, and p16 was observed in 22%, 33%, 5.8%, and 13.4% of cases, respectively. There were no significant differences in either the total number of genetic events or the presence of LOH of any of the individual markers between serrated adenomas and conventional adenomas. However, hyperplastic polyps showed LOH in 22% of cases and a single K-ras mutation (11%). The prevalence of LOH in hyperplastic polyps was lower than both serrated adenomas and conventional adenomas (P < .05). These results support the hypothesis that serrated adenomas represent a biologically similar morphologic variant of conventional adenomas.
Assuntos
Adenoma/genética , Neoplasias do Colo/genética , Pólipos do Colo/genética , Perda de Heterozigosidade , Adenoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 3 , Neoplasias do Colo/patologia , Pólipos do Colo/patologia , Primers do DNA/química , DNA de Neoplasias/análise , Dissecação , Feminino , Genes APC , Genes p16 , Genes p53 , Genes ras , Marcadores Genéticos/genética , Humanos , Hiperplasia/genética , Hiperplasia/patologia , Masculino , Micromanipulação , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
Cardiac myxomas are the most frequent cardiac tumors and cause for significant morbidity and mortality. Recent evidence indicates that cardiac myxomas are, in fact, neoplasms rather than organized thrombi. Cardiac myxomas may present as solitary lesions or in association with the Carney complex. Carney complex has been linked to chromosome 2p16 and the PRKAR1A gene at 17q22-24. In this study, we analyzed sporadic cardiac myxomas to evaluate whether the genetic alterations seen in Carney complex are present in non Carney complex associated cardiac myxomas as well. We analyzed microdissected material from 13 patients with cardiac myxomas for the markers PRKAR1 9CA, D2S2153, D2S2251 and D2S123. None of the cases demonstrated loss of heterozygosity or definite band changes suggestive of microsatellite instability for any of the markers used. We conclude that sporadic cardiac myxomas are genetically not related to Carney complex and most likely do not represent an incomplete form of Carney complex.
