RESUMEN
We report on two cases of patients who developed diabetes insipidus (DI) before acute erythroleukaemia (EL). A brain MRI showed an empty sella turcica in one case and hypothalamo-hypophyseal peduncle damage in the second case. Reduced levels of TGF-beta1 and Vitamin D3, with associated EVI-1 over-expression and karyotypic abnormalities were documented. These two cases show specific chromosomal/molecular alterations in EL with DI. The hypothesis of pituitary involvement in erythroleukemogenesis is discussed.
Asunto(s)
Diabetes Insípida/complicaciones , Síndrome de Silla Turca Vacía/inducido químicamente , Enfermedades Hipotalámicas/complicaciones , Leucemia Eritroblástica Aguda/complicaciones , Hipófisis/patología , Adulto , Colecalciferol/sangre , Aberraciones Cromosómicas , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Diabetes Insípida/diagnóstico , Diabetes Insípida/metabolismo , Síndrome de Silla Turca Vacía/diagnóstico , Síndrome de Silla Turca Vacía/metabolismo , Femenino , Humanos , Enfermedades Hipotalámicas/diagnóstico , Enfermedades Hipotalámicas/metabolismo , Leucemia Eritroblástica Aguda/diagnóstico , Leucemia Eritroblástica Aguda/metabolismo , Proteína del Locus del Complejo MDS1 y EV11 , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Proto-Oncogenes/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Transgenic animal models for neurocarcinogenesis have provided significant insights into the molecular mechanisms underlying carcinogenic processes, including those which affect the nervous system. In view of the very rapid pace of acquisition of knowledge, it is not possible to cover all transgenic mouse models for neural tumors. Instead, this article discusses some of the most important technical innovations for manipulation of the mammalian genome (notably the various methods for targeted genome modifications, as well as the technology for introducing large DNA fragments into the germ line of mice), and presents a selection of the transgenic mouse models which are proving most promising for furthering our understanding of the pathogenetic basis of cancer in the nervous system.
Asunto(s)
Modelos Animales de Enfermedad , Ratones Transgénicos/genética , Neoplasias del Sistema Nervioso , Animales , Humanos , Ratones , Ratones Noqueados , Neoplasias del Sistema Nervioso/genética , Neoplasias del Sistema Nervioso/fisiopatologíaRESUMEN
Infectious and transforming activity was obtained from cultures of a large kidney tumour with very high N-myc amplification. The patient belonged to a cluster of neuroblastoma cases diagnosed in Southern Louisiana in 1986-1988. Infection with ultra-filtered supernatants from neuroblastoma cultures caused the appearance of small foci of rounded cells with neural features and the presence of virus was indicated by electron microscopy: the virus was called Micro-Foci inducing virus or MFV. Infected young adult rats did not develop overt disease, but 11/11 of the litters from infected animals developed a very dramatic and highly lethal syndrome which could resemble neuroblastoma symptoms. N-myc amplification disappeared in very early cultures of the tumour, but it was subsequently detected in MFV-infected cell cultures.
Asunto(s)
Neoplasias Renales/microbiología , Neuroblastoma/microbiología , Virus Oncogénicos/aislamiento & purificación , Animales , Preescolar , Femenino , Amplificación de Genes , Genes myc/genética , Humanos , Virus Oncogénicos/genética , Ratas , Ratas Endogámicas F344RESUMEN
The natriuretic effects of atrial peptide hormones have been attributed, at least in part, to their stimulation of guanylate cyclase activity in renal cell membranes. The effects of atrial natriuretic factor (ANF) on stimulation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation were investigated in cloned human kidney tumor (hKT) cells and parent cells from a human renal tumor epithelial cell line (SK-NEP-1). Human ANF-(99-126) (10(-6)M) stimulated (p less than 0.001) cellular cGMP accumulation in a dose-dependent manner from a basal level of 0.26 +/- 0.04 to 3.73 +/- 0.81 pmol/mg protein/5 mi (mean +/- SEM, n = 13). ANF stimulation of cGMP accumulation was specific, in that high concentrations (10(-6)M) of atriopeptin I [rat ANF-(103-123)], angiotensin II, arginine vasopressin, and amiloride (10(-4)M) did not increase basal cGMP. Amiloride (10(-4)M) enhanced (p less than 0.01, n = 6) the ANF stimulation of cGMP accumulation (1.24 +/- 0.39 pmol/mg protein/5 min), particularly at low doses of ANF (10(-10)M) where stimulation by ANF without amiloride (0.34 +/- 0.08 pmol/mg protein/5 min) was barely distinguishable from a basal level (0.19 +/- 0.02 pmol/mg protein/5 min) of cGMP accumulation. The stimulatory effect of ANF (1.59 +/- 0.07 pmol/mg protein/5 min) was attenuated (0.75 +/- 0.06 pmol/mg protein/5 min, p less than 0.01, n = 6) by preincubation of the cells with pertussis toxin but not by cholera toxin. ANF (4.56 +/- 0.93 pmol/mg protein/5 min, n = 8) did not affect cAMP accumulation (4.32 +/- 0.98 pmol/mg protein/5 min) in hKT cells. This is the first report of an ANF responsive human renal cell line, and its use should facilitate investigation of ANF-receptor interactions.
Asunto(s)
Factor Natriurético Atrial/farmacología , GMP Cíclico/metabolismo , Riñón/metabolismo , Línea Celular , Guanilato Ciclasa/metabolismo , Humanos , Riñón/citología , Riñón/enzimología , Toxina del Pertussis , Estimulación Química , Factores de Virulencia de Bordetella/farmacologíaRESUMEN
The neurobiology of aging continues to attract scientists and techniques from the more fundamental disciplines, as witness the great strides now being made from molecular genetic approaches to Alzheimer's disease. The present report is a commentary on reviews of immune mechanisms and tissue culture methods applied to investigations of aging and age-related cognitive dysfunction.
Asunto(s)
Envejecimiento/inmunología , Encéfalo/citología , Envejecimiento/fisiología , Animales , Encéfalo/crecimiento & desarrollo , Encéfalo/inmunología , Técnicas de CultivoRESUMEN
Recent findings suggest that the local renin-angiotensin systems, locally generated catecholamines, and possibly other locally generated peptides interact in a complex fashion to regulate the cellular biology of the myocardium, the vascular wall, and other tissues. New evidence indicates that the components of the renin-angiotensin system are synthesized in cardiovascular tissues, that the synthesis of these components can be modulated by pharmacologic agents, and that angiotensin II, the effector protein of the renin system, appears to be capable of producing hypertrophy or hyperplasia in specific tissues. In addition, recent studies suggest the participation of enhanced proto-oncogene transcriptional activity in the development of hyperplasia and hypertrophy in cardiovascular tissue. Taken together, these data raise the possibility that angiotensin and perhaps other components of the renin system can be viewed as locally active growth factors capable of acting in a fashion similar to that associated with cytokines in other systems.
Asunto(s)
Fenómenos Fisiológicos Cardiovasculares , Animales , Sistema Cardiovascular/citología , Sistema Cardiovascular/patología , Hiperplasia/etiología , Hiperplasia/fisiopatología , Hipertrofia/etiología , Hipertrofia/fisiopatología , Sistema Renina-AngiotensinaRESUMEN
The Hu-ets-1 oncogene was found to be rearranged and amplified 30-fold in one case of acute myelomonocytic leukemia in which a homogeneously staining region occurred on 11q23; the oncogene was rearranged and amplified approximately tenfold in a case of small lymphocytic cell lymphoma with an inverted insertion that also involved band 11q23. This work suggests that Hu-ets-1 is an unusual oncogene that can help explain the common involvement of chromosome band 11q23 in various subtypes of hematopoietic malignancies.
Asunto(s)
Cromosomas Humanos 6-12 y X , Leucemia Mieloide Aguda/genética , Linfoma no Hodgkin/genética , Oncogenes , Aberraciones Cromosómicas/genética , Bandeo Cromosómico , Trastornos de los Cromosomas , Mapeo Cromosómico , Cromosomas Humanos 13-15/ultraestructura , Cromosomas Humanos 6-12 y X/ultraestructura , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , Humanos , Hibridación de Ácido Nucleico , Translocación GenéticaRESUMEN
We examined the arrangement of the mu heavy-chain immunoglobulin (Ig) genes in the leukemic blast cell DNA of 93 children with acute lymphoblastic leukemia (ALL). All cases met morphologic and cytochemical criteria for ALL, lacked detectable T cell surface antigens, and expressed HLA-DR (Ia) antigens. Eighty-three of the 93 patients (89%) were positive for the common acute lymphoblastic leukemia antigen (CALLA), and 20 of 91 (22%) tested had detectable cytoplasmic immunoglobulin. As expected, the heavy-chain lg gene was rearranged in all cases, and the pattern of rearrangements was variable; 23 had one allele rearranged and one in the germ line configuration; 15 had one rearranged and one deleted; and 37 had two rearranged. Unexpectedly, in 18 patients the presence of more than two mu gene-hybridizing bands was detected. Combinations of enzymes and heavy-chain gene probes were used to confirm that the extra bands were not the result of underdigestion of the DNA or DNA restriction site polymorphism. In eight of the 18 patients, we identified an extra chromosome 14 as a possible cause of the extra bands' hybridizing to the mu heavy-chain constant-region probe. In the remaining ten patients, the presence of three or four bands hybridizing with the mu probe suggests the presence of two populations of leukemic cells that may have arisen either by separate leukemic transformation events or by clonal evolution of one clone into two related lines. Although preliminary (2-year follow-up), our data suggest that childhood ALL of B lineage with more than two mu heavy-chain genes, but without extra copies of chromosome 14, may be more resistant to therapy.
Asunto(s)
Cadenas Pesadas de Inmunoglobulina/genética , Cadenas mu de Inmunoglobulina/genética , Leucemia Linfoide/inmunología , Adolescente , Antígenos de Neoplasias/análisis , Linfocitos B , Niño , Preescolar , Aberraciones Cromosómicas , Cromosomas Humanos 13-15 , Femenino , Humanos , Cadenas kappa de Inmunoglobulina/genética , Lactante , Cariotipificación , Leucemia Linfoide/genética , Masculino , Neprilisina , Pronóstico , Recombinación GenéticaRESUMEN
We studied the arrangement of the immunoglobulin heavy chain genes by Southern blot analysis of DNA freshly obtained from marrow blast cells of 14 children with T cell acute lymphoblastic leukemia (T-ALL) using probes to the C mu and JH gene segments: At least one of the C mu-gene alleles was rearranged in three cases. In two of these, one C mu gene had the germ-line configuration and one was rearranged, whereas both alleles were rearranged in the third case. In one case, a rearranged heavy chain gene hybridized to the C mu-region probe, but not to the JH probe, indicating that the entire JH region had been deleted. These results demonstrate that immunoglobulin heavy chain gene rearrangements are not restricted to B lineage lymphoproliferative diseases in humans.
Asunto(s)
Mapeo Cromosómico , Cadenas Pesadas de Inmunoglobulina/genética , Leucemia Linfoide/genética , Adolescente , Niño , Preescolar , Femenino , Genes , Humanos , Cadenas kappa de Inmunoglobulina/genética , Lactante , Masculino , Fenotipo , Formación de Roseta , Linfocitos TRESUMEN
The 5.2-kilobase (kb) RNA genome of avian carcinoma virus MH2 has the genetic structure 5' - delta gag (0.2 kb)-mht (1.2 kb)-myc (1.4 kb)-c(0.4 kb)-poly (A) (0.2 kb)-3'. delta gag is a partial retroviral core protein, mht and myc are cell-derived MH2-specific sequences, and c is the 3'-terminal retroviral vector sequence. the following results were obtained from the complete nucleotide sequences of the mht and myc genes in MH2. (i) delta gag-mht forms a hybrid gene with a contiguous reading frame of 2682 nucleotides that terminates with a stop codon near the 3' end of the mht gene. The 3' 969 nucleotides of mht up to the stop codon are 80% sequence related to the onc-specific raf sequence of murine sarcoma virus 3611 (MSV 3611) (94% homologous at the deduced amino acid level). (ii) The myc coding region in MH2 is preceded by 181 nucleotides derived from the intron immediately upstream from the second exon of the chicken cellular proto-myc gene, followed by an RNA splice acceptor site shared with the proto-myc gene, followed by an RNA splice acceptor site shared with the proto-myc, beyond which it is colinear up to a 3'-termination codon and 40 noncoding nucleotides with the myc sequences of avian retrovirus MC29 and chicken proto-myc. Thus, myc forms, together with a 5' retroviral exon, a second MH2-specific gene. It is concluded that MH2 contains two genes with oncogenic potential, the delta gag-mht gene, which is closely related to the delta gag-raf transforming gene of MSV 3611, and the myc gene, which is related to the transforming gene of MC29. Furthermore, it may be concluded that the cellular proto-onc genes, which on sequence transduction become viral onc genes, are a small group because among the 19 known onc sequences, 5 are shared by different taxonomic groups of viruses of which the mht/raf homology is the closest so far.
Asunto(s)
Oncogenes , Retroviridae/genética , Alpharetrovirus/genética , Animales , Secuencia de Bases , Pollos/genética , Mapeo Cromosómico , Clonación Molecular , Codón , Humanos , Especificidad de la EspecieAsunto(s)
Virus de la Leucosis Aviar/genética , Genes , Oncogenes , Animales , Virus de la Mieloblastosis Aviar/genética , Secuencia de Bases , Pollos , Clonación Molecular , Enzimas de Restricción del ADN , Humanos , Hibridación de Ácido Nucleico , Especificidad de la Especie , Transducción GenéticaRESUMEN
The presence of greater than 3% Sudan black B (SBB) positivity in leukaemic blasts has been considered diagnostic of acute non-lymphocytic leukaemia (ANLL). A rare report has indicated that this finding may not be specific for ANLL. In order to determine whether SBB could be found in acute lymphoblastic leukaemia (ALL) the data on 350 patients with newly diagnosed ALL were reviewed. Six patients (1.6%) were found to have 5% or greater SBB positive blasts. The diagnosis of ALL was supported by morphology, cytochemistries, immunologic markers, therapeutic response, and in one case immunoglobulin gene rearrangement. It is important to recognize the fact that SBB is not specific for AML and may be found in the blasts of patients with ALL.
Asunto(s)
Leucemia Linfoide/diagnóstico , Adolescente , Antígenos de Neoplasias/análisis , Compuestos Azo , Médula Ósea/patología , Preescolar , Gránulos Citoplasmáticos/patología , Femenino , Genes MHC Clase II , Histocitoquímica , Humanos , Lactante , Leucemia Linfoide/inmunología , Leucemia Linfoide/patología , Masculino , Naftalenos , Coloración y EtiquetadoRESUMEN
c-myc is the cellular gene homologous to the transforming sequence of MC29, an acute avian retrovirus. The human c-myc gene was cloned and used to study the structure and expression of c-myc in a variety of human hematopoietic malignancies. In a careful study of 106 patients, c-myc RNA was found to be expressed at elevated levels in tumor cells of 17 leukemia patients and five lymphoma patients. The c-myc gene was found to be rearranged in two lymphomas, an African Burkitt's lymphoma and a non-Hodgkins lymphoma in leukemic phase. The Burkitt's rearrangement involved the insertion of new DNA sequences upstream from the c-myc 5' coding region, presumably replacing the normal c-myc transcriptional promoter. None of the other 104 patients, including 20 with elevated myc expression, exhibited any evidence of a genetic rearrangement involving the c-myc gene. Our results show that there is a subset of hematopoietic malignancies characterized by elevated expression of c-myc. This elevated expression in most cases is not due to obvious genetic changes (rearrangement, amplification) at the c-myc locus nor to chromosomal translocations in the vicinity of this gene.
Asunto(s)
Clonación Molecular , Leucemia/genética , Linfoma/genética , Oncogenes , Secuencia de Bases , Linfoma de Burkitt/genética , Enzimas de Restricción del ADN , Humanos , Hibridación de Ácido Nucleico , Valores de ReferenciaRESUMEN
Samples of leukemic cell DNA from 14 children with acute nonlymphocytic leukemia (ANLL) and 4 human myeloid leukemia cell lines were analyzed for rearrangement in the heavy chain region of the immunoglobulin gene. The diagnosis of ANLL was confirmed in all patients by morphological, cytochemical, and immunologic studies. By restriction endonuclease digestion and hybridization with cloned heavy chain immunoglobulin gene probes for the constant (Cmu) and joining (JH) regions, the DNA of 2 patients and 1 cell line (ML-1) was found to contain rearrangements. The DNA from the remaining 12 patients and 3 cell lines was not rearranged (germline configuration). Both patients with apparent immunoglobulin gene rearrangement achieved complete remission on therapy for ANLL. Immunoglobulin gene rearrangement in phenotypically defined ANLL suggests (1) that such changes may not be limited to lymphoid leukemia of B cell lineage, or (2) that, in some patients, the leukemic transforming event may involve stem cells capable of both B cell and myeloid differentiation.