RESUMEN
Defense systems against free radicals and reactive oxygen species minimize the lethal and mutagenic consequences of these destructive agents. To investigate the genetic response to oxidative stress in a eukaryote, we cloned and characterized oxidative stress-responsive genes by comparing gene expression in the free-living nematode Caenorhabditis elegans under atmospheric conditions and high oxygen concentrations using a method of RNA arbitrarily primed polymerase chain reaction method (RAP-PCR). We identified four genes whose expression levels increase under high oxygen. These encoded 18 s, 5.8 s and 26 s rRNAs, 16 kDa heat shock proteins (hsp16-1 and 16-48) and a vacuolar ATPase G subunit. In addition, we also established that oxi-1, an oxidative stress-responsive gene we previously cloned, encodes a family of proteins related to human E6-AP ubiquitin-protein ligase. The similarity between human and nematode was 54% in one conserved amino acid region.
Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans/genética , Clonación Molecular , Genes de Helminto , Proteínas del Helminto/genética , Estrés Oxidativo , Secuencia de Aminoácidos , Animales , Caenorhabditis elegans/metabolismo , Proteínas del Helminto/química , Humanos , Datos de Secuencia MolecularRESUMEN
DNA vaccines have the potential of giving rise to a potent cell-mediated immune response by inducing intracellular synthesis and subsequent antigenic presentation of encoded antigens. We have tested a DNA vaccine specific for human immunodeficiency virus type 1 (HIV-1) by the injection of animals with expression plasmids encoding the HIV-1 envelope protein and the Rev regulatory protein. Injection of both plasmids into mice, rabbits, or macaques was found to induce high levels of specific antibodies capable of efficiently inhibiting both HIV-1 infection and envelope-mediated cell fusion. A readily detectable delayed-type hypersensitivity (DTH) response was demonstrable in injected mice and lymphocytes derived from these proliferated in response to an HIV-1 envelope V3 loop-specific peptide. Interestingly, the injected mice or macaques also developed a strong cytotoxic T lymphocyte (CTL) response against target cells pulsed with the V3 peptide. Taken together, these data demonstrate that injection of HIV-1 gene expression plasmids can induce potent humoral and cell-mediated immune responses and suggest that DNA vaccines may prove to be significantly beneficial as a means of immunizing against HIV-1.
Asunto(s)
Formación de Anticuerpos/inmunología , ADN Viral/farmacología , Productos del Gen rev/inmunología , Genes env/inmunología , Inmunidad Celular/inmunología , Animales , Secuencia de Bases , ADN Viral/inmunología , Productos del Gen rev/genética , Genes env/genética , Infecciones por VIH/prevención & control , Humanos , Macaca , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Plásmidos/farmacología , Conejos , Vacunación , Productos del Gen rev del Virus de la Inmunodeficiencia HumanaRESUMEN
A mutant of rad-8, originally isolated on the basis of its hypersensitivity to ultraviolet radiation, is also hypersensitive to oxygen and methyl viologen, a superoxide-anion generator. Oxygen also retarded development and reduced fecundity in a concentration-dependent fashion in rad-8 but not in wild type. In addition, the mean life span of rad-8 (but not wild type) was progressively shortened when animals incubated in increasing oxygen concentrations. This cross hypersensitivity to both UV radiation and free radicals provides further evidence that DNA damage may be important in the aging process.
Asunto(s)
Envejecimiento/efectos de los fármacos , Caenorhabditis elegans/genética , Oxígeno/toxicidad , Tolerancia a Radiación/genética , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/crecimiento & desarrollo , Caenorhabditis elegans/efectos de la radiación , Fertilidad/efectos de los fármacos , Longevidad/efectos de los fármacos , Mutación , Paraquat/toxicidad , Tasa de SupervivenciaRESUMEN
Median sternotomy was used in 30 cases of lung surgery; (1) lung cancer with impaired pulmonary function or local invasion to the mediastinum-12 cases. An average FEV1.0, 960ml, 38% FVC was only reduced to 890ml one month after lobectomy. (2) concomitant heart disease-2 cases. A 5 year old boy, with tracheal stricture and tetralogy of Fallot, was successfully treated by one stage operation. Stenotic cartilage trachea, 2mm in diameter, was resected 15mm in length and anastomosed end to end under total extracorporeal circulation after cardiac operation. A left upper lobectomy for lung cancer was performed under partial extracorporeal circulation after mitral valve replacement and valvoplasty of tricuspid valve on a 62 year old man. Both patients are well two years after operation. (3) bilateral pulmonary lesions--11 cases. (4) others--5 cases. Median sternotomy provides less operative loss of lung function, and excellent exposure for selected cases. But these advantages may be lost in some cases in No. (3) when fragile metastatic nodules must be gently manipulated and when an autosuture must be used in different direction for bullae. Whether or not the median sternotomy or posterolateral skin incision is favorable, may be decided by CT findings preoperatively.