Asunto(s)
Anticuerpos Antivirales/sangre , Fiebre del Nilo Occidental/epidemiología , Virus del Nilo Occidental/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brotes de Enfermedades , Susceptibilidad a Enfermedades/epidemiología , Femenino , Humanos , Israel/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estudios SeroepidemiológicosRESUMEN
The clinical significance of and the risk factors for persistent bacteremia were assessed in 299 episodes. Persistent bacteremia was defined as at least two positive blood cultures obtained on different calendar days during the same infectious episode. Short-term bacteremia was defined as positive blood cultures solely on the first day of the infectious episode. A total of 4,277 episodes of bloodstream infections were detected, of which 299 episodes (7%) were persistent bacteremia. The following were independent risk factors were for persistent bacteremia: burns, presence of a central vascular catheter, cirrhosis, infections caused by Salmonella spp., polymicrobial infections, and inappropriate empirical antibiotic treatment. Irrespective of the source of infection, the presence of a central vascular catheter was correlated with an increased risk for persistent bacteremia. Mortality among patients with persistent bacteremia was 50%, compared to 35% among patients with short-term bacteremia. Because of the high mortality associated with persistent bacteremia, a thorough search for the source of infection is essential to ensure timely and appropriate therapy.
Asunto(s)
Bacteriemia/diagnóstico , Bacteriemia/epidemiología , Patógenos Transmitidos por la Sangre/aislamiento & purificación , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Estudios de Cohortes , Intervalos de Confianza , Femenino , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/epidemiología , Humanos , Incidencia , Israel/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Probabilidad , Pronóstico , Factores de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Tasa de Supervivencia , Factores de TiempoRESUMEN
West Nile (WN) virus is endemic in Israel. The last reported outbreak had occurred in 1981. From August to October 2000, a large-scale epidemic of WN fever occurred in Israel; 417 cases were confirmed, with 326 hospitalizations. The main clinical presentations were encephalitis (57.9%), febrile disease (24.4%), and meningitis (15.9%). Within the study group, 33 (14.1%) hospitalized patients died. Mortality was higher among patients >70 years (29.3%). On multivariate regressional analysis, independent predictors of death were age >70 years (odds ratio [OR] 7.7), change in level of consciousness (OR 9.0), and anemia (OR 2.7). In contrast to prior reports, WN fever appears to be a severe illness with high rate of central nervous system involvement and a particularly grim outcome in the elderly.
Asunto(s)
Brotes de Enfermedades , Fiebre del Nilo Occidental/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Niño , Preescolar , Femenino , Fiebre/fisiopatología , Hospitalización , Humanos , Israel/epidemiología , Masculino , Meningitis Viral/mortalidad , Meningitis Viral/fisiopatología , Persona de Mediana Edad , Fiebre del Nilo Occidental/epidemiología , Fiebre del Nilo Occidental/inmunología , Fiebre del Nilo Occidental/mortalidadRESUMEN
BACKGROUND & AIMS: Helicobacter pylori resides within the gastric mucosa, a niche hostile to other microorganisms. Human gastrin levels are elevated after infection and return to normal after eradication. The aim of this study was to test the direct effect of gastrin on the growth of H. pylori. METHODS: H. pylori and control bacteria were grown with gastrin or control peptides and growth rate was determined. (125)I-labeled gastrin was used to determine uptake. RESULTS: Human gastrin stimulated H. pylori growth in a specific, dose-dependent manner. Gastrin shortened the lag time, increased growth rate in the logarithmic phase, and increased final bacterial concentration at the stationary phase. These effects were shown over a wide concentration range, including physiological luminal and serum levels. Labeled gastrin uptake was inhibited by unlabeled gastrin. Controls consisting of cholecystokinin and pentagastrin inhibited gastrin uptake but did not stimulate growth. In contrast, somatostatin and epidermal growth factor had no effect on either gastrin uptake or bacterial growth. These results suggest a structurally restricted, receptor-mediated, gastrin-specific effect. CONCLUSIONS: Human gastrin is a specific growth factor for H. pylori and may have a role in the adaptation of H. pylori to its unique habitat.
Asunto(s)
Gastrinas/fisiología , Helicobacter pylori/crecimiento & desarrollo , Campylobacter jejuni/efectos de los fármacos , Campylobacter jejuni/genética , Campylobacter jejuni/metabolismo , Relación Dosis-Respuesta a Droga , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Escherichia coli/metabolismo , Gastrinas/antagonistas & inhibidores , Gastrinas/farmacocinética , Gastrinas/farmacología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/metabolismo , Humanos , Cinética , Concentración Osmolar , Pentagastrina/farmacología , Sincalida/farmacología , Factores de TiempoRESUMEN
Recent data on the phenotype of nef-defective HIV-1 in vitro indicate a new function of the Nef gene product: enhancement of viral infectivity. Single-cycle replication studies have suggested that Nef enhances the efficiency of an early step during viral replication, a step that leads to the establishment of viral DNA. To test this interpretation, the accumulation of low-molecular-weight (unintegrated) viral DNA was measured in cells following exposure to wild-type and nef-defective viruses. nef-defective virus accumulated less DNA than the wild type. This difference was observed after as little as 5 hr of exposure to virus. However, the reverse transcriptase activities of wild-type and nef-defective viruses were equal when measured in cell-free assays using either exogenous or endogenous templates. In addition, the abilities of these viruses to bind and enter cells were not significantly different. Together, these data suggest that Nef optimizes postentry events that are required for efficient synthesis of viral DNA. To determine if these effects were related to the property of Nef-mediated downregulation of CD4, growth curves of these viruses were determined using cells that express a CD4 molecule unable to respond to Nef. nef-defective virus remained attenuated in these cells, indicating that Nef-mediated downregulation of CD4 is not required for Nef-mediated enhancement of viral propagation in vitro.
Asunto(s)
Antígenos CD4/fisiología , ADN Viral/biosíntesis , Productos del Gen nef/fisiología , VIH-1/crecimiento & desarrollo , Línea Celular , Regulación hacia Abajo , Proteína p24 del Núcleo del VIH/biosíntesis , Transcriptasa Inversa del VIH , VIH-1/metabolismo , Humanos , ADN Polimerasa Dirigida por ARN/metabolismo , Replicación Viral , Productos del Gen nef del Virus de la Inmunodeficiencia HumanaRESUMEN
Proviral sequences encoding defective HIV-1 regulatory genes have been detected previously in infected individuals; however, the role of these defective genomes in pathogenesis is unclear. The hypothesis that such replication-defective genomes might induce downregulation of the cellular receptor for HIV-1 (CD4) was tested. CEM cells were stably transfected with a provirus that contains a mutation in the splice site immediately 5' of the rev coding sequence. This mutant expresses early HIV-1 mRNAs but is defective for replication. Cells expressing this defective provirus displayed markedly reduced surface CD4. This downregulation of CD4 was dependent on an intact nef gene and was sufficient to cause resistance to superinfection by wild-type virus. These findings indicate that Nef as expressed by replication-defective HIV-1 can downregulate CD4. This perturbation of the T lymphocyte cell membrane is a potential basis for pathogenicity of defective HIV-1.
Asunto(s)
Antígenos CD4/biosíntesis , Virus Defectuosos/fisiología , Productos del Gen nef/fisiología , VIH-1/fisiología , Provirus/fisiología , Línea Celular , Virus Defectuosos/genética , Regulación hacia Abajo , VIH-1/genética , Mutación , Provirus/genética , Interferencia Viral/fisiología , Replicación Viral/genética , Productos del Gen nef del Virus de la Inmunodeficiencia HumanaRESUMEN
A 49-year-old woman with diabetes mellitus rapidly developed necrotizing cellulitis with fat necrosis and vasculitis after minor trauma to the right arm. Zygomycosis was diagnosed histologically. The lesion responded to aggressive debridement, amphotericin B, and normalization of blood glucose. Cultures yielded structures characteristic of Saksenaea vasiformis only after transfer to saline agar.
Asunto(s)
Dermatomicosis/microbiología , Diabetes Mellitus Tipo 1/complicaciones , Mucorales/aislamiento & purificación , Mucormicosis/microbiología , Femenino , Humanos , Persona de Mediana EdadRESUMEN
The replication competence of human immunodeficiency virus type 1 genomes containing mutations in the nef open reading frame was evaluated in continuous cell lines. Mutants that contained a deletion in the nef open reading frame, premature termination codons, or missense mutations in the N-terminal myristoylation signal were constructed. The replication of these mutants was tested in three ways. First, plasmid genomes were used to transfect T-lymphoblastoid cells. Second, low-passage posttransfection supernatants were used to infect cells with a relatively low virus input. Third, high-titer virus stocks were used to infect cells with a relatively high virus input. These experiments demonstrated a 100- to 10,000-fold decrement in p24 production by the nef mutants compared with that by the wild-type virus. The greatest difference was obtained after infection with the lowest virus input. The myristoylation signal was critical for this positive effect of nef. To investigate the mechanism of the positive influence of nef, nef-positive and nef-minus viruses were compared during a single cycle of replication. These single-cycle experiments were initiated both by infection with high-titer virus stocks and by transfection with viral DNA. Single-cycle infection yielded a three- to fivefold decrement in p24 production by nef-minus virus. Single-cycle transfection yielded equal amounts of p24 production. These results implied that nef does not affect replication after the provirus is established. In support of these results, viral production from cells chronically infected with nef-positive or nef-minus viruses was similar over time. To determine whether the effect of nef was due to infectivity, end point titrations of nef-positive and nef-minus viruses were performed. nef-positive virus had a greater infectivity per picogram of HIV p24 antigen than nef-minus virus. These data indicated that the positive influence of nef on viral growth rate is due to an infectivity advantage of virus produced with an intact nef gene.
Asunto(s)
ADN Viral/biosíntesis , Genes nef/genética , VIH-1/crecimiento & desarrollo , VIH-1/genética , Secuencia de Aminoácidos , Secuencia de Bases , Fusión Celular , Proteína p24 del Núcleo del VIH/genética , Células Madre Hematopoyéticas/microbiología , Humanos , Datos de Secuencia Molecular , Mutación , Ácido Mirístico , Ácidos Mirísticos/metabolismo , Procesamiento Proteico-Postraduccional , Linfocitos T/microbiología , Regiones Terminadoras Genéticas/genética , Transfección , Replicación ViralRESUMEN
The viral regulatory gene, nef, is unique to the human immunodeficiency viruses (HIV) and their related primate lentiviruses. Expression of the nef gene has been shown to be essential to the maintenance of high levels of virus replication and the development of pathogenesis in the animal model of simian immunodeficiency virus (SIV) infection. In contrast to this in vivo model, the use of standard T cell culture systems to study nef function in vitro has produced a spectrum of contradictory results, and has failed to demonstrate a significant positive influence of nef on viral life cycle. We have developed a cell model to study regulation of HIV-1 replication that we believe reflects more accurately virus-cell interactions as they occur in vivo. Our experimental system used acute virus infection of purified, quiescent CD4 lymphocytes and subsequent induction of viral replication through T cell activation. With this cell model, NL4-3 virus clones with open and mutated nef reading frames were compared for replication competence. The clones with nef mutations showed reproducible and significant reductions in both rates of growth and maximal titers achieved. The degree of reduced replication was dependent on initial virus inoculum and the timing of T cell activation. The influence of nef was highly significant for induction of virus replication from a latent state within resting CD4 cells. Its effect was less apparent for virus infection of fully proliferating CD4 cells. This study demonstrates that nef confers a positive growth advantage to HIV-1 that becomes readily discernable in the primary cell setting of virus induction through T cell activation. The experimental cell model, which we describe here, provides not only a means to study nef function in vitro, but also provides important clues to the function of nef in HIV infection in vivo.