RESUMEN
Bighorn sheep (BHS, Ovis canadensis) are much more susceptible than domestic sheep (DS, Ovis aries) to pneumonia caused by leukotoxin (Lkt)-producing members of the Family Pasteurellaceae, particularly Mannheimia haemolytica and Bibersteinia trehalosi. Leukotoxin is widely accepted as the critical virulence factor of these bacteria since Lkt-negative mutants do not cause death of BHS. Typically, DS carry Lkt-positive M. haemolytica and/or B. trehalosi as commensal bacteria in their nasopharynx. In contrast, most BHS do not carry Lkt-positive M. haemolytica or B. trehalosi, or carry Lkt-negative strains in their nasopharynx. In previous studies, we demonstrated that unimmunized DS resist M. haemolytica challenge while BHS succumb to it. We hypothesized that Lkt-neutralizing antibodies, induced by Lkt-positive M. haemolytica and/or B. trehalosi innately carried by DS in their nasopharynx, render them less susceptible to infection by these bacteria. In this study we developed BHS×DS F1 hybrids by artificial insemination of domestic ewes with BHS semen. F1 hybrids were fertile, and produced F2 hybrids and back-crosses. The F1, F2, and back-crosses were raised together with domestic ewes. All these animals acquired Lkt-positive M. haemolytica and/or B. trehalosi, and developed high titers of Lkt-neutralizing antibodies in the absence of vaccination. Furthermore, all of these animals resisted challenge with lethal dose of M. haemolytica. These results suggest that lack of previous exposure to Lkt is at least partially responsible for fatal pneumonia in BHS when they acquire Lkt-positive M. haemolytica and/or B. trehalosi from DS when the two species commingle.
Asunto(s)
Susceptibilidad a Enfermedades/veterinaria , Hibridación Genética/inmunología , Mannheimia haemolytica , Infecciones por Pasteurellaceae/veterinaria , Enfermedades de las Ovejas/inmunología , Animales , Anticuerpos Antibacterianos/sangre , Anticuerpos Neutralizantes/sangre , Susceptibilidad a Enfermedades/inmunología , Exotoxinas/inmunología , Femenino , Nasofaringe/microbiología , Infecciones por Pasteurellaceae/inmunología , Ovinos , Enfermedades de las Ovejas/microbiología , Borrego Cimarrón/inmunología , Oveja Doméstica/inmunología , VacunaciónRESUMEN
Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P(4)) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P(4), we compared early (6-h), intermediate (48-h), and late (14-Day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESF) from women with endometriosis (hESF(endo)) with hESF from women without endometriosis (hESF(nonendo)). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESF were isolated and treated with P(4) (1 µM) plus estradiol (E(2)) (10 nM), E(2) alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P(4) in both hESF(nonendo) and hESF(endo), although a blunted response to P(4) was observed in the latter. The normal response of hESF to P(4) involves a tightly regulated kinetic cascade involving key components in the P(4) receptor and MAPK signaling pathways that results in inhibition of E(2)-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESF(endo) early response to P(4). The abnormal response of this cell type to P(4) may contribute to compromised embryonic implantation and infertility in women with endometriosis.
Asunto(s)
Endometriosis/genética , Endometriosis/metabolismo , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Progesterona/farmacología , Adulto , Secuencia de Bases , Estudios de Casos y Controles , Cartilla de ADN/genética , Resistencia a Medicamentos/genética , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Expresión Génica/efectos de los fármacos , Perfilación de la Expresión Génica , Redes Reguladoras de Genes/efectos de los fármacos , Humanos , Técnicas In Vitro , Persona de Mediana Edad , Enfermedades Peritoneales/genética , Enfermedades Peritoneales/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacosRESUMEN
A large family with X-linked mental retardation, originally reported in 1944 by Allan, Herndon, and Dudley, has been reinvestigated. Twenty-nine males have been affected in seven generations. Clinical features include severe mental retardation, dysarthria, ataxia, athetoid movements, muscle hypoplasia, and spastic paraplegia with hyperreflexia, clonus, and Babinski reflexes. The facies appear elongated with normal head circumference, bitemporal narrowing, and large, simple ears. Contractures develop at both small and large joint. Statural growth is normal and macroorchidism does not occur. Longevity is not impaired. High-resolution chromosomes, serum creatine kinase, and amino acids are normal. This condition, termed the Allan-Herndon syndrome, appears distinct from other X-linked disorders having mental retardation, muscle hypoplasia, and spastic paraplegia.
Asunto(s)
Anomalías Múltiples/genética , Ligamiento Genético , Discapacidad Intelectual/genética , Cromosoma X , Adulto , Anciano , Cara/anomalías , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Musculares/genética , Linaje , SíndromeAsunto(s)
Acidosis Tubular Renal/genética , Calcio/orina , Acidosis Tubular Renal/etiología , Acidosis Tubular Renal/fisiopatología , Adolescente , Adulto , Análisis Químico de la Sangre , Niño , Preescolar , Femenino , Tasa de Filtración Glomerular , Humanos , Concentración de Iones de Hidrógeno , Inmunoglobulinas/orina , Capacidad de Concentración Renal , Túbulos Renales Proximales/fisiopatología , Masculino , Peso Molecular , Muramidasa/orina , Nefrocalcinosis/etiología , Nefrocalcinosis/genética , Linaje , Proteínas/análisis , Proteinuria/etiología , Aminoacidurias Renales/etiología , Cálculos Urinarios/genética , Infecciones Urinarias/genética , OrinaRESUMEN
Hemoglobin A(2) (alpha(2)delta(2)) in New World primates represents about 1/160 to 1/16 of total hemoglobin and, by virtue of this low proportion, is presumed to be functionally unimportant. Nonetheless, A(2) exhibits genetic polymorphism by electrophoresis in three out of five genera, whereas the major component, hemoglobin A (alpha(2)beta(2)), is electrophoretically invariant. Moreover, in four genera, including man, the evolutionary accumulation of mutations has been greater in delta than in beta Such findings suggest that both polymorphism and evolutionary changes can accrue to an effectively functionless and thus selectively nearly netutral gene.