RESUMEN
Heterozygous germ-line mutations in the DNA mismatch repair genes lead to hereditary nonpolyposis colorectal cancer. The disease susceptibility of individuals who constitutionally lack both wild-type alleles is unknown. We have identified three offspring in a hereditary nonpolyposis colorectal cancer family who developed hematological malignancy at a very early age, and at least two of them displayed signs of neurofibromatosis type 1 (NF1). DNA sequence analysis and allele-specific amplification in two siblings revealed a homozygous MLH1 mutation (C676T-->Arg226Stop). Thus, a homozygous germ-line MLH1 mutation and consequent mismatch repair deficiency results in a mutator phenotype characterized by leukemia and/or lymphoma associated with neurofibromatosis type 1.
Asunto(s)
Reparación del ADN , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Neoplasias Hematológicas/genética , Proteínas de Neoplasias/genética , Neurofibromatosis 1/genética , Proteínas Adaptadoras Transductoras de Señales , Proteínas Portadoras , ADN/química , Femenino , Humanos , Masculino , Homólogo 1 de la Proteína MutL , Proteínas de Neoplasias/deficiencia , Proteínas NuclearesRESUMEN
Short tandem repeat (STR) loci are ideal markers for personal identification and for genomic mapping. Two fluorescent multiplex systems, each designed for simultaneous PCR amplification of four polymorphic STR loci (HUMCSF1PO, HUMTPOX, HUMTH01 and HUMVWFA31, and HUMF13A01, HUMFESFPS, HUMBFXIII and HUMLIPOL), were evaluated on three laser fluorescence detection instruments. Concordant DNA typing results were obtained with all three detection methods. These fluorescent multiplex STR systems offer an accurate, reproducible and versatile method of DNA profiling that is well-suited for forensic identity testing and other genetic analyses.
Asunto(s)
ADN/análisis , Fluorometría/métodos , Rayos Láser , Reacción en Cadena de la Polimerasa , Secuencias Repetitivas de Ácidos Nucleicos , Análisis de Secuencia de ADN/métodos , Alelos , Electroforesis en Gel de Poliacrilamida/métodos , Colorantes Fluorescentes , Control de Calidad , Sensibilidad y Especificidad , Análisis de Secuencia de ADN/instrumentaciónRESUMEN
C57BL/6 and Balb/c mice were immunized with ultraviolet-irradiated cercariae of Egyptian strains of Schistosoma mansoni and S. haematobium, challenged with nonirradiated cercariae of the homologous or heterologous species, and assayed for protection against challenge infection by comparing the adult worm burdens of immunized and non-immunized mice. Homologous protection (per cent reduction in worm recovery) ranged from 56% to 69% for S. mansoni and 88% to 99% for S. haematobium. Significant heterologous protection was consistently induced against S. haematobium by immunization with S. mansoni, but not against S. mansoni by immunization with S. haematobium. These results are discussed in relation to those of previous studies and in terms of implications for vaccine development.
Asunto(s)
Schistosoma haematobium/inmunología , Schistosoma mansoni/inmunología , Animales , Egipto , Femenino , Interacciones Huésped-Parásitos/inmunología , Inmunización , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Schistosoma haematobium/crecimiento & desarrollo , Schistosoma haematobium/efectos de la radiación , Schistosoma mansoni/crecimiento & desarrollo , Schistosoma mansoni/efectos de la radiación , Esquistosomiasis Urinaria/inmunología , Esquistosomiasis Urinaria/parasitología , Esquistosomiasis Urinaria/prevención & control , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/parasitología , Esquistosomiasis mansoni/prevención & control , Especificidad de la Especie , Vacunas/aislamiento & purificaciónRESUMEN
Subcutaneous implantation of demineralized diaphyseal rat bone matrix in ACI rats initiates a developmental cascade that results in the formation of new endochondral bone and an associated hematopoietic bone marrow differentiation. Irradiation (1500 rad, 60Co) of the implantation site 24 h prior to implantation suppresses the formation of endochondral bone and bone marrow. All phases of the developmental cascade, including chemotaxis, proliferation, and differentiation, are arrested by the irradiation. Simultaneous implantation with the extracellular matrix of bone marrow, bone, pieces of a four-day-old implant or of thoracic muscle--but not of brain, liver, or spleen tissue--results in the development of endochondral bone and bone marrow at the irradiated site. Concurrent implantation with the extracellular matrix of in vitro growing fibroblasts of marrow or ossicle origin does not restore the developmental cascade.
Asunto(s)
Desarrollo Óseo/efectos de la radiación , Células de la Médula Ósea , Matriz Ósea/fisiología , Hematopoyesis/efectos de la radiación , Fosfatasa Alcalina/metabolismo , Animales , Encéfalo/citología , Calcio/metabolismo , Fibroblastos/citología , Hígado/citología , Músculos/citología , Ratas , Ratas Endogámicas ACI , Factores de TiempoRESUMEN
The regulation of dihydrofolate reductase (DHFR) gene expression was studied in gene-amplified, estrogen-responsive human breast cancer cells (MTX MCF-7). Previous studies have shown that estrogen increases, whereas tamoxifen decreases the rate of DHFR enzyme synthesis resulting in corresponding changes in the level of this enzyme. DHFR levels also increase following incubation with methotrexate (MTX), an effect which is dependent on both the concentration of extracellular drug and the duration of exposure and which occurs at concentrations that are insufficient to inhibit cell growth. MTX, like estrogen and tamoxifen, has no apparent effect on the rate of DHFR enzyme degradation. The increase in DHFR in response to MTX is additive with that of estrogen and is not prevented by tamoxifen. Whereas hormone-mediated changes in DHFR are associated with changes in the level of DHFR mRNA, there is no apparent change in DHFR mRNA concentrations in cells exposed to MTX. The regulation of DHFR enzyme levels was also studied in gene-deleted Chinese hamster ovary cells which were transfected with a functional human DHFR minigene constructed from human DHFR genomic and cDNA sequences. Incubation with MTX increases DHFR levels in Chinese hamster ovary cells transfected with the human DHFR minigene but has no effect in cells transfected with a DHFR minigene which uses a viral promotor and polyadenylation signal. Thus, the human DHFR minigene contains sequences other than the protein coding region which effect the regulation of this gene by MTX.