RESUMEN
Airborne pathogens commonly trigger severe respiratory failure or death in smokers with lung disease. Cigarette smoking compromises the effectiveness of innate immunity against infections but the underlying mechanisms responsible for defective acquired immune responses in smokers remains less clear. We found that mice exposed to chronic cigarette smoke recovered poorly from primary Influenza A pneumonia with reduced type I and II interferons (IFNs) and viral-specific immunoglobulins, but recruited γδ T cells to the lungs that predominantly expressed interleukin 17A (IL-17A). Il-17a-/- mice exposed to smoke and infected with Influenza A also recruited γδ T cells to the lungs, but in contrast to wild-type mice, expressed increased IFNs, made protective influenza-specific antibodies, and recovered from infection. Depletion of IL-17A with blocking antibodies significantly increased T-bet expression in γδ T cells and improved recovery from acute Influenza A infection in air, but not smoke-exposed mice. In contrast, when exposed to smoke, γδ T cell deficient mice failed to mount an effective immune response to Influenza A and showed increased mortality. Our findings demonstrate a protective role for γδ T cells in smokers and suggest that smoke-induced increase in IL-17A inhibits the transcriptional programs required for their optimal anti-viral responses. Cigarette smoke induces IL-17A expression in the lungs and inhibits γδ T-cell-mediated protective anti-viral immune responses.
Asunto(s)
Virus de la Influenza A/inmunología , Pulmón/patología , Infecciones por Orthomyxoviridae/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Linfocitos T/fisiología , Animales , Anticuerpos Antivirales/sangre , Fumar Cigarrillos/efectos adversos , Progresión de la Enfermedad , Femenino , Genes Codificadores de la Cadena delta de los Receptores de Linfocito T , Inmunidad Celular , Inmunidad Innata , Interleucina-17/genética , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Antígenos de Linfocitos T gamma-delta/genéticaRESUMEN
Eighteen cases of Ewing's sarcoma are presented. The mean age was 13 years. The male to female ratio was 2:1. Tumor occurred frequently in the long bones, especially the femur. The average course was 7 months. The main symptoms were pain, moderate fever, tumor mass with tenderness and leucocytosis. Diagnosis was established according to the clinical, radiological and pathological findings. In this series, the major treatment was radiotherapy alone or radiotherapy combined with chemotherapy. The mean survival time was 16 months with 2- and 5-year survival rate of 31% and 20%, respectively. Misdiagnosis and failure or interruption of the combined treatment were the main factors for poor prognosis.
Asunto(s)
Neoplasias Óseas/radioterapia , Sarcoma de Ewing/radioterapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/mortalidad , Niño , Preescolar , Terapia Combinada , Femenino , Neoplasias Femorales/tratamiento farmacológico , Neoplasias Femorales/mortalidad , Neoplasias Femorales/radioterapia , Humanos , Masculino , Pronóstico , Sarcoma de Ewing/tratamiento farmacológico , Sarcoma de Ewing/mortalidad , Tasa de SupervivenciaRESUMEN
Complementation of Rhizobium leguminosarum dct mutants with a cosmid bank yielded Rhizobium meliloti homologs of the dctA, dctB, and dctD genes. The genes dctB and dctD are thought to form a two-component system which responds to the presence of C4-dicarboxylates to regulate expression of a transport protein encoded by dctA. DNA sequence analysis showed that dct coding and intergenic regions, including putative binding sites for the dctD protein and sigma 54-RNA polymerase, were highly conserved between these two Rhizobium species. Mutation of R. meliloti dctD showed that it was not essential for symbiotic nitrogen fixation but was needed for growth on succinate and the expression of a dctA-lacZ fusion gene in free-living cells. Hybridization of R. meliloti genomic DNA with probes representing the central portion of dctD potentially identified more than 20 similar regulatory genes, all of which are likely to depend upon the alternative sigma factor encoded by rpoN and stimulate transcription in a manner very similar to ntrC activation of glnA in enteric bacteria.
Asunto(s)
Regulación Bacteriana de la Expresión Génica , Genes Bacterianos , Genes Reguladores , Rhizobium/genética , Secuencia de Aminoácidos , Secuencia de Bases , ADN Bacteriano/genética , ARN Polimerasas Dirigidas por ADN/metabolismo , Datos de Secuencia Molecular , Secuencias Reguladoras de Ácidos Nucleicos , Succinatos/metabolismo , Transcripción GenéticaRESUMEN
Glycoprotein B (gB) of Herpes simplex virus type 1 (HSV-1) plays an essential role in viral entry. A set of more than 100 HpaI (GTTAAC) linker insertion mutations and their derivatives were isolated in plasmids specifying the gB coding and flanking sequences. Mutations including addition, deletion and nonsense mutations at 34 independent sites were identified by DNA sequence analysis of 48 plasmids. A map was constructed for the ability of addition mutants to complement a gB-null virus. The expression of gB activity for some plasmids was temperature-dependent. Many complementation-negative plasmids inhibited the complementation activity of a plasmid specifying wild-type gB, suggesting an interaction between active and inactive molecules to form oligomers. The interaction was localized to 328 of the total of 904 amino acids comprising gB. Partial Endo H digestion of nonsense polypeptides revealed that five of the six potential N-linked oligosaccharide sites are glycosylated; the most C-terminal site appears not to be glycosylated. A number of mutations, including some on the cytoplasmic side, were identified that blocked processing, transport and secretion. Addition mutations that blocked processing of membrane polypeptides also blocked processing and secretion when combined into a nonsense mutant that by itself was processed and secreted. The previously predicted membrane spanning domain and the membrane orientation of the N-terminal portion of gB were confirmed.
Asunto(s)
Plásmidos , Simplexvirus/análisis , Proteínas del Envoltorio Viral/análisis , Secuencia de Aminoácidos , Secuencia de Bases , ADN Viral , Técnica del Anticuerpo Fluorescente , Genes Virales , MutaciónRESUMEN
42 patients of midline malignant histiocytosis are reported. The differential diagnosis should be made carefully, for its clinical sign and pathologic picture are similar to some neoplasms, inflammatory or allergic diseases. The 3, 5 and 10 year survival rates are 52.4%, 38.1% and 21.4% respectively. The survival rate of those in the prodromal stage is the highest. The authors suggest that this disease probably belongs to the malignant tumor of mononuclear macrophage system and be a special type of malignant histiocytosis. It may be designated as the midline malignant histiocytosis.