RESUMEN
This study characterized the current epidemiology of vibrio infections in Florida and examined cases reported from 1998 to 2007. Logistic regression was used to determine risk of death. There were 834 vibrio infections in 825 individuals (average annual incidence rate 4·8/1,000,000). Common Vibrio species reported were Vibrio vulnificus (33%), V. parahaemolyticus (29%), and V. alginolyticus (16%). Most exposures were attributed to wounds (42%), and the most common clinical syndromes were wound infections (45%) and gastroenteritis (42%). Almost half of individuals reported an underlying health condition. Risk of death was associated with any underlying condition and increased with the number of conditions (P<0·0001). In Florida, incidence of vibriosis associated with raw oyster consumption has decreased while incidence associated with wound infections has increased. Most prevention efforts to date have focused on oyster consumption. New educational messages focusing on the risk of vibriosis from wound infections should target high-risk populations.
Asunto(s)
Vibriosis/epidemiología , Vibriosis/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Conducta Alimentaria , Femenino , Florida/epidemiología , Gastroenteritis/epidemiología , Gastroenteritis/microbiología , Gastroenteritis/mortalidad , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Vibriosis/mortalidad , Vibrio alginolyticus/aislamiento & purificación , Vibrio parahaemolyticus/aislamiento & purificación , Vibrio vulnificus/aislamiento & purificación , Infección de Heridas/epidemiología , Infección de Heridas/microbiología , Infección de Heridas/mortalidad , Adulto JovenRESUMEN
Multidrug transporters mediate the extrusion of structurally unrelated drugs from prokaryotic and eukaryotic cells. As a result of this efflux activity, the cytoplasmic drug concentration in the cell is lowered to subtoxic levels and, hence, cells become multidrug resistant. The activity of multidrug transporters interferes with the drug-based control of tumours and infectious pathogenic microorganisms. There is an urgent need to understand the structure-function relationships in multidrug transporters that underlie their drug specificity and transport mechanism. Knowledge about the architecture of drug and modulator binding sites and the link between energy-generating and drug translocating functions of multidrug transporters may allow one to rationally design new drugs that can poison or circumvent the activity of these transport proteins. Furthermore, if one is to inhibit multidrug transporters in human cells, one should know more about their physiological substrates and functions. This review will summarize important new insights into the role that multidrug transporters in general, and P-glycoprotein and its bacterial homologue LmrA in particular, play in the physiology of the cell. In addition, the molecular basis of drug transport by these proteins will be discussed.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Resistencia a Múltiples Medicamentos , Animales , Sitios de Unión , Transporte Biológico , Humanos , Modelos Biológicos , Relación Estructura-ActividadRESUMEN
1. The acidic interior of neuroendocrine secretory vesicles provides both an energy gradient for amine-proton exchangers (VMATs) to concentrate small transmitter molecules, for example catecholamines, and an optimal pH for the prohormone convertases which cleave hormone precursors. There is evidence that VMAT activity modulates prohormone cleavage, but in the absence of measurements of pH in secretory vesicles in intact cells, it has not been possible to establish whether these effects are attributable to raised intravesicular pH due to proton transport through VMATs. 2. Clones were generated of the hamster insulinoma cell line HIT-T15 expressing a pH-sensitive form of green fluorescent protein (GFP-F64L/S65T) targeted to secretory vesicles, with and without co-expression of VMAT2. In order to study prohormone cleavage, further clones were generated that expressed preprogastrin with and without co-expression of VMAT2. 3. Confocal microscopy of GFP fluorescence indicated that the pH in the secretory vesicles was 5.6 in control cells, compared with 6.6 in cells expressing VMAT2; the latter was reduced to 5.8 by the VMAT inhibitor reserpine. 4. Using a pulse-chase labelling protocol, cleavage of 34-residue gastrin (G34) was found to be inhibited by co-expression with VMAT2, and this was reversed by reserpine. Similar effects on vesicle pH and G34 cleavage were produced by ammonium chloride. 5. We conclude that VMAT expression confers the linked abilities to store biogenic amines and modulate secretory vesicle pH over a range influencing prohormone cleavage and therefore determining the identity of regulatory peptide secretory products.
Asunto(s)
Álcalis/metabolismo , Hidrógeno/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana , Neuropéptidos , Sistemas Neurosecretores/metabolismo , Vesículas Secretoras/metabolismo , Cloruro de Amonio/farmacología , Animales , Cricetinae , Gastrinas/antagonistas & inhibidores , Gastrinas/efectos de los fármacos , Gastrinas/metabolismo , Gastrinas/fisiología , Proteínas Fluorescentes Verdes , Concentración de Iones de Hidrógeno , Indicadores y Reactivos , Proteínas Luminiscentes , Glicoproteínas de Membrana/antagonistas & inhibidores , Microscopía Confocal , Sistemas Neurosecretores/citología , Precursores de Proteínas/antagonistas & inhibidores , Precursores de Proteínas/efectos de los fármacos , Precursores de Proteínas/metabolismo , Precursores de Proteínas/fisiología , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Reserpina/farmacología , Células Tumorales Cultivadas , Proteínas de Transporte Vesicular de Aminas Biógenas , Proteínas de Transporte Vesicular de MonoaminasRESUMEN
Captive great egret (Ardea albus) nestlings were maintained as controls or were dosed with methylmercury chloride at low (0.5), and high doses (5 mg/kg, wet weight) in fish. Low dosed birds were given methylmercury at concentrations comparable to current exposure of wild birds in the Everglades (Florida, USA). When compared with controls, low dosed birds had lower packed cell volumes, dingy feathers, increased lymphocytic cuffing in a skin test, increased bone marrow cellularity, decreased bursal wall thickness, decreased thymic lobule size, fewer lymphoid aggregates in lung, increased perivascular edema in lung, and decreased phagocytized carbon in lung. High dosed birds became severely ataxic and had severe hematologic, neurologic, and histologic changes. The most severe lesions were in immune and nervous system tissues. By comparing responses in captive and wild birds, we found that sublethal effects of mercury were detected at lower levels in captive than in wild birds, probably due to the reduced sources of variation characteristic of the highly controlled laboratory study. Conversely, thresholds for more severe changes (death, disease) occurred at lower concentrations in wild birds than in captive birds, probably because wild birds were exposed to multiple stressors. Thus caution should be used in applying lowest observed effect levels between captive and wild studies.
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Enfermedades de las Aves/inducido químicamente , Intoxicación por Mercurio/veterinaria , Compuestos de Metilmercurio/toxicidad , Análisis de Varianza , Animales , Enfermedades de las Aves/inmunología , Enfermedades de las Aves/patología , Enfermedades de las Aves/fisiopatología , Aves , Recuento de Células Sanguíneas/veterinaria , Proteínas Sanguíneas/efectos de los fármacos , Médula Ósea/patología , Cápsulas , Virus de la Encefalitis Equina del Este/inmunología , Femenino , Hematócrito/veterinaria , Sistema Inmunológico/patología , Pulmón/patología , Masculino , Intoxicación por Mercurio/inmunología , Intoxicación por Mercurio/patología , Intoxicación por Mercurio/fisiopatología , Compuestos de Metilmercurio/administración & dosificación , Sistema Nervioso/patología , Examen Neurológico/veterinaria , Albúmina Sérica Bovina/inmunología , Vacunas Virales/inmunologíaRESUMEN
BACKGROUND & AIMS: The RegIalpha gene (Reg) encodes a secretory protein proposed to regulate islet beta-cell and gastric mucous cell growth. Reg is expressed in rat gastric enterochromaffin-like (ECL) cells. The aim of this study was to examine Reg expression in human corpus and to determine the identity of Reg in ECL cell carcinoid tumors in hypergastrinemic patients. METHODS: Reg messenger RNA (mRNA) abundance was quantified by Northern blot in extracts of gastric corpus from patients with and without ECL cell tumors and in AR4-2J cells stimulated by gastrin; cellular origins were determined by immunocytochemistry. Mutations of Reg were determined by reverse-transcription polymerase chain reaction, cloning, and sequencing, and the mutated protein was expressed in HIT-T15 cells. RESULTS: Reg mRNA abundance was increased approximately threefold in the corpus of hypergastrinemic patients compared with controls, and was enriched in 3 of 7 ECL cell carcinoid tumors but not in non-endocrine cell gastric polyps. In AR4-2J cells, gastrin stimulated Reg mRNA abundance; this was eliminated by the gastrin/cholecystokinin B antagonist L-740,093 (10(-9) mol/L). Immunocytochemistry indicated that Reg was located in both chief cells and ECL cells in human corpus. Mutations of Reg were identified in 3 of 5 patients with ECL cell carcinoid tumors; in 2 cases, mutation of the initiator methionine residue led to exclusion of the protein from the secretory pathway. CONCLUSIONS: Gastrin regulates Reg mRNA abundance in human corpus. Mutations of Reg that prevent secretion are associated with ECL cell carcinoids, suggesting a function as an autocrine or paracrine tumor suppressor.
Asunto(s)
Proteínas de Unión al Calcio/genética , Tumor Carcinoide/genética , Tumor Carcinoide/patología , Células Enterocromafines/patología , Gastrinas/sangre , Mutación/fisiología , Proteínas del Tejido Nervioso , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Proteínas de Unión al Calcio/metabolismo , Tumor Carcinoide/sangre , Tumor Carcinoide/metabolismo , Neoplasias de las Glándulas Endocrinas/sangre , Femenino , Mucosa Gástrica/metabolismo , Gastrinas/fisiología , Humanos , Litostatina , Masculino , Metionina/genética , Persona de Mediana Edad , Biosíntesis de Proteínas/fisiología , ARN Mensajero/sangre , Neoplasias Gástricas/sangre , Neoplasias Gástricas/metabolismo , Distribución Tisular/fisiologíaRESUMEN
Cache Valley virus (CVV) and Potosi virus (POTV) are two closely related mosquito-borne viruses (Bunyaviridae: Bunyamwera group) that appear to circulate in several regions of the United States, especially the Midwest. We determined the prevalence of specific neutralizing antibodies to both viruses in Indiana white-tailed deer and conducted infection experiments to assess whether deer could serve as an vertebrate-amplifying host. Cross-infection experiments also were carried out to investigate the level of antibody cross-reactivity and cross-protection between the two viruses. The seroprevalence rate was high for both CVV (> 66%) and POTV (> 43%) in adult deer statewide. Antibodies neutralizing CVV were more common among deer harvested in the northern part of Indiana whereas the prevalence of POTV antibodies suggested a more southern distribution for this virus. Experimental infections of captive deer showed that they may serve as amplifying hosts for either virus. Deer infected with CVV or POTV developed a 1-3-day viremia with 3.0 and 4.1 log10 plaque-forming units/ml mean peak titers, respectively. However, significant levels of antibody cross-reactivity between the two viruses were observed. Viremia was lower and shorter when animals immune to either CVV or POTV were cross-infected with the alternate virus and antibody responses following cross-infections resembled original antigenic sin with higher titers of antibodies against the primary agent.
Asunto(s)
Anticuerpos Antivirales/sangre , Virus Bunyamwera/inmunología , Virus Bunyamwera/aislamiento & purificación , Infecciones por Bunyaviridae/veterinaria , Ciervos/inmunología , Ciervos/virología , Animales , Virus Bunyamwera/patogenicidad , Infecciones por Bunyaviridae/epidemiología , Infecciones por Bunyaviridae/inmunología , Reacciones Cruzadas , Femenino , Indiana/epidemiología , Masculino , Pruebas de Neutralización , Estudios SeroepidemiológicosRESUMEN
Midwestern populations of Coquillettidia perturbans (Walker) and Anopheles quadrimaculatus (Say) were tested for their ability to transmit Cache Valley virus (CV), a recognized human and animal pathogen. Field-collected mosquitoes were fed artificial blood meals containing 5.2-6.2 log10 pfu/ml of CV. After 9-23 d at 28 degrees C, 75-93% of blood-fed Cq. perturbans had disseminated infections and 6-62% transmitted the virus to suckling mice. However, when infected with a lower virus titer (3.3 log10 pfu/ml), only 10-36% of the mosquitoes had disseminated infections and 0-10% transmitted the virus to suckling mice. A similar infection rate (21%) was observed in Cq. perturbans fed on viremic (3.2 log10 pfu/ml) hamsters. An. quadrimaculatus were infected (81-100%) by both doses used, with transmission rates ranging from 13-67% after 16-23 d of incubation. Transmission rates for the laboratory strain An. quadrimaculatus SAVANNAH ranged from 20 to 33% after 7-14 d of incubation. Our data show that although An. quadrimaculatus is more susceptible to CV infections than Cq. perturbans, both mosquito species could be involved in the midwestern transmission cycle of the virus.
Asunto(s)
Anopheles/virología , Virus Bunyamwera/fisiología , Infecciones por Bunyaviridae/transmisión , Culicidae/virología , Animales , Infecciones por Bunyaviridae/fisiopatología , Cricetinae , Geografía , Humanos , Ratones , Medio Oeste de Estados Unidos , Viremia/fisiopatologíaRESUMEN
One group of sequence variants of Epstein-Barr virus is characterized by a 10-amino-acid deletion within the CTAR-2 functional domain of the latent membrane protein, LMP1. A role for this deletion in enhancing the tumorigenicity of the viral oncogene in rodent fibroblasts was recently demonstrated. We examined the effect of this deletion upon LMP1 function in four human lymphoid cell lines by using three natural variants of LMP1: the prototype B95.8 gene and the CAO and AG876 genes, both of which have codons 343 to 352 of the B95.8-LMP1 deleted. These experiments revealed that LMP1-mediated upregulation of CD40 and CD54 was markedly impaired (by 60 to 90%) with CAO-LMP1 compared with B95.8-LMP1. In contrast, the function of AG876-LMP1 was indistinguishable from that of B95.8-LMP1 in two lines and was only slightly impaired in the other two lines. Activation of NF-kappaB by CAO-LMP1 was not impaired in any of the lines; rather, activation of an NF-kappaB reporter by CAO-LMP1 was consistently about twofold greater than the activation with B95.8- or AG876-LMP1. Therefore, while the CAO-LMP1 is functionally distinct from the prototype B95.8-LMP1 in human lymphocytes, the 10-amino-acid deletion appears not to be directly responsible. This conclusion was confirmed by using a B95.8-LMP1 mutant with codons 343 to 352 deleted and chimerae of CAO- and B95.8-LMP1 in which the CTAR-2 domains of these genes were exchanged. Sequences outside the CTAR-2 domain were implicated in the distinct functional characteristics of CAO-LMP1 in human lymphoid cells.
Asunto(s)
Variación Genética , Herpesvirus Humano 4/genética , Linfocitos/metabolismo , Eliminación de Secuencia , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/metabolismo , Secuencia de Aminoácidos , Composición de Base , Antígenos CD40/biosíntesis , China , ADN Viral , Genes Virales , Humanos , Molécula 1 de Adhesión Intercelular/biosíntesis , Linfocitos/virología , Datos de Secuencia Molecular , FN-kappa B/metabolismo , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
Moose (Alces alces) and reindeer (Rangifer tarandus) were experimentally cross-infected with Elaphostrongylus rangiferi and Elaphostrongylus alces, respectively. Both Elaphostrongylus species completed their development in the alternate hosts but produced fewer larvae than in their usual host species. Reindeer infected with Elaphostrongylus alces developed patent infections after 39-130 days. In moose, the prepatent period of this parasite was 39-73 days. Elaphostrongylus rangiferi infections were patent in moose after 133 days. The male morphological characteristic of E. alces in moose and reindeer, and E. rangiferi in moose and their migration pattern retained regardless of the host species. These results provide further evidence that E. alces and E. rangiferi are two distinct species.