Asunto(s)
Antineoplásicos/efectos adversos , Cladribina/efectos adversos , Inmunosupresores/efectos adversos , Leucemia de Células Pilosas/tratamiento farmacológico , Meningitis Criptocócica/etiología , Antineoplásicos/uso terapéutico , Cladribina/uso terapéutico , Humanos , Inmunosupresores/uso terapéutico , Masculino , Meningitis Criptocócica/fisiopatología , Persona de Mediana EdadRESUMEN
We have observed that plasmid pKH47, a pBR322-derivative containing a 100bp poly(dA)-poly(dT) insertion, causes growth inhibition of host E. coli cells harboring it. In this paper we show that this inhibitory effect is due to an increased copy number property of this plasmid, which is turn leads to an over expression of the plasmid-encoded tet gene. Our work also indicates that contrary to other pleiotropic effects caused by the tet gene product, which solely depend on the expression of the 5' end of the gene, growth inhibition requires an intact tet gene. In addition we present the isolation of an E. coli mutant that is refractive to the inhibitory effect of pKH47 and shares some properties with the parental bacteria containing plasmid pKH4.
Asunto(s)
Escherichia coli/crecimiento & desarrollo , Escherichia coli/genética , Plásmidos , Composición de Base , Secuencia de Bases , Southern Blotting , Sondas de ADN , Escherichia coli/efectos de los fármacos , Kanamicina/farmacología , Resistencia a la Kanamicina/genética , Cinética , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Mutagénesis Insercional , Poli dA-dT , Mapeo Restrictivo , Especificidad de la Especie , Transformación BacterianaRESUMEN
A unique deletion covering around 43% of the pBR322 genome was found after attempting to insert 100 or 200 bp poly(dA).poly(dT) into the EcoRV site of pBR322 DNA. This result was not observed if an equivalent size heterologous DNA or a larger poly(dA).poly(dT) fragment of 10-20,000 bp was introduced at the same site. DNA sequencing analysis at the junctions suggests that a specific intramolecular pairing may be involved in the formation of this deletion mutant.
Asunto(s)
Deleción Cromosómica , Plásmidos , Poli dA-dT/genética , Polidesoxirribonucleótidos/genética , Secuencia de Bases , Southern Blotting , Análisis Mutacional de ADN , ADN Bacteriano/genética , Datos de Secuencia Molecular , Mutación , Mapeo Restrictivo , Transformación GenéticaRESUMEN
Bone marrow transplantation represents the technical application of basic immunologic principles to the treatment of a variety of neoplastic and allied disorders that originate in the bone marrow. The results have improved during the past 15 years, being most striking for the treatment of the acute and chronic leukemias. The promise of autologous bone marrow transplantation for the treatment of leukemias and solid tumors is awaiting the perfection of techniques for the effective removal of residual neoplastic cells as well as more effective therapy. The use of this technique at its present stage of development for the treatment of benign hematologic disorders, which cause severe morbidity (ie, thalassemia or sickle cell anemia), is controversial, raises serious ethical issues, and cannot be recommended routinely at this time. Complications of bone marrow transplantation such as graft rejection, graft-versus-host disease, and opportunistic infections are discussed.