Shock cardiogénico por panhipopituitarismo / Cardiogenic shock due to panhypopituitarism

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Whitefly resistance traits derived from the wild tomato Solanum pimpinellifolium affect the preference and feeding behavior of Bemisia tabaci and reduce the spread of Tomato yellow leaf curl virus.

Breeding of tomato genotypes that limit whitefly (Bemisia tabaci) access and feeding might reduce the spread of Tomato yellow leaf curl virus (TYLCV), a begomovirus (genus Begomovirus, family Geminiviridae) that is the causal agent of tomato yellow leaf curl disease. TYLCV is restricted to the phloem and is transmitted in a persistent manner by B. tabaci. The tomato breeding line ABL 14-8 was developed by introgressing type IV leaf glandular trichomes and secretion of acylsucroses from the wild tomato Solanum pimpinellifolium accession TO-937 into the genetic background of the whitefly- and virus-susceptible tomato cultivar Moneymaker. Results of preference bioassays with ABL 14-8 versus Moneymaker indicated that presence of type IV glandular trichomes and the production of acylsucrose deterred the landing and settling of B. tabaci on ABL 14-8. Moreover, electrical penetration graph studies indicated that B. tabaci adults spent more time in nonprobing activities and showed a reduced ability to start probing. Such behavior resulted in a reduced ability to reach the phloem. The superficial type of resistance observed in ABL 14-8 against B. tabaci probing significantly reduced primary and secondary spread of TYLCV.

Multiple Resistance to Meloidogyne spp. and to Bipartite and Monopartite Begomovirus spp. in Wild Solanum (Lycopersicon) Accessions.

The Ty-1 locus confers tolerance to monopartite and bipartite Begomovirus spp. (genus Begomovirus, family Geminiviridae) and this phenotype is improved in homozygous tomato lines. However, the gene Mi (Meloidogyne spp. resistance) is in repulsion phase linkage with Ty-1, which hampers the large-scale development of multiresistant inbred lines. Seventy-one Solanum (section Lycopersicon) accessions were whitefly inoculated with the bipartite Begomovirus sp. Tomato rugose mosaic virus (ToRMV) and simultaneously infested with a mixture of Meloidogyne incognita and M. javanica under greenhouse conditions in Brazil. Accessions were then transplanted into a nematode-infested field with natural ToRMV infection. A severity index was used to evaluate ToRMV reaction. Nematode evaluation was done by counting the number of galls per root system. Seventeen accessions with Meloidogyne spp. and ToRMV resistance were selected and evaluated in Spain against three monopartite Begomovirus spp. associated with the tomato yellow leaf curl virus disease, using infectious clones. Systemic infection was monitored by DNA hybridization. Five S. peruvianum accessions (PI-306811, PI-365951, LA-1609, LA-2553, and CNPH-1194) displayed nematode and broad-spectrum resistance to all Begomovirus spp. tested in both continents. From the breeding standpoint, accessions combining resistance to Meloidogyne spp. and to bipartite and monopartite Begomovirus spp. would be useful for the development of elite lines expressing all traits in homozygous condition.

Phenotypic expression, stability, and inheritance of a recessive resistance to monopartite begomoviruses associated with tomato yellow leaf curl disease in tomato.

Tomato-infecting begomoviruses comprise a complex of monopartite and bipartite virus species that cause severe yield and quality losses worldwide. Therefore, the availability of wide spectrum resistance for begomovirus control is desirable. However, limited sources of resistance are available. In this study, three tomato inbred lines with resistance to bipartite begomoviruses of Brazil were tested for resistance to monopartite begomoviruses associated with the tomato yellow leaf curl disease (TYLCD). Stable resistance to Tomato yellow leaf curl virus was observed either by inoculation with Bemisia tabaci or with Agrobacterium tumefaciens using an infectious clone. The resistance resulted in a complete absence of TYLCD symptoms and restricted virus accumulation. Further studies performed with the line '468-1-1-12' indicated that the resistance was also effective against three other virus species associated with TYLCD, indicating wide spectrum resistance of this source. Quantitative genetics analyses suggested that a major recessive locus with epistatic interactions is controlling the resistance to TYLCD in '468-1-1-12', which could facilitate introgression of this trait into elite tomato lines. The resistance was stable under field conditions with high TYLCD pressure. Mild symptoms could be observed in these conditions, and recovery from disease and from virus infection suggested an active host antiviral defense mechanism. The differential reaction of '468-1-1-12' against a number of TYLCD-associated viruses and artificial chimeras between them allowed to identify a region of the virus genome that presumably contains a virus determinant for breaking the resistance to infection observed in '468-1-1-12'.

Células persistentemente infectadas por el virus del sarampión son más sensibles a la inducción de apoptósis por TRAIL: Base de una posible terapía para PES y otras encefalitis sarampionosas / Measles virus persistently infected cells are more sensitive to apoptosis induction by TRAIL: Basis for a potential therapy in SSPE and other measles virus encephalitis

Introducción y objetivos: El virus del sarampión (VS)aparte de producir complicaciones graves respiratorias,gastrointestinales, encefalitis, ceguera y sordera queacompañan al sarampión y hacen que mate anualmentecerca de un millón de niños en el mundo, es el causantede encefalitis lentas como la Panencefalitis esclerosantesubaguda (PES) o la Encefalitis sarampionosa de cuerposde inclusión (MIBE). Para estas encefalopatías subagudasprogresivas con desmielinización y atrofia cerebral, de curso mortal tras meses a décadas de evolución no se dispone actualmente de tratamiento efectivo. El objetivo de este estudio es la búsqueda de posibles tratamientos para eliminar selectivamente las células infectadas por el virus y así frenar el progreso de la infección y en último término la eliminación del virus del paciente.Métodos: Estudio de sensibilidad a la inducción de apoptosis por la proteína TRAIL (TNF-related-apoptosis inducing ligand) de células humanas en cultivo sin infectar y persistentemente infectadas por VS. Estudio de los mecanismos de inducción de la apoptosis en la línea celular MOLT3, en la que nuestro laboratorio mostró por primera vez que VS puede inducir apoptosis.Resultados: La infección persistente por VS hace que células humanas se hagan marcadamente más sensibles al suicidio celular inducido por TRAIL exógeno. El mecanismo de esta sensibilización podría explicarse por un aumento de la expresión en la superficie celular de las células infectadas de los receptores funcionales para TRAIL, junto con una reducción de la expresión de la proteína antiapoptótica Bcl2 y una estimulación de la quinasa Akt y del factor de transcripción NFkB, lo que provocaría el suicidio de las células infectadas.Conclusiones: Células persistentemente infectadas porVS son más sensibles a la inducción de suicidio por apoptosis mediado por TRAIL que la células no infectadas. El tratamiento con TRAIL al eliminar las células infectadas podría frenar la progresión del virus o incluso eliminarlo en pacientes con encefalitis subagudas causadas por VS como SSPE o MIBE

Introduction: Measles virus (MV) causes acute infectionswith severe respiratory, neurological, deafness, blindness and gastrointestinal complications that today still kill near one million children annually worldwide. The late measles complications Subacute Sclerosing Panencephalitis (SSPE) or Measles Inclusion Bodies Encephalitis (MIBE) show a protracted progressive and fatal course and for them no efficient treatment is currently available. This work aims to find a way to selectively destroy the infected cells, and doing so limit the progression of VS through the infectedbrain and eventually to eliminate the virus from the patient with SSPE or MIBE.Materials and Methods: Sensitivity to apoptosis induced by exogenous recombinant TRAIL was determined in steady-state MV persistently infected human cell line MOLT3 versus uninfected cells, by chromatin condensation, TUNEL, and caspases activation assays. Expression of TRAIL functional receptors (TRAIL-R1 y TRAIL-R2) and decoy receptors (TRAIL-R3 and TRAIL-R4) was determined by flow cytometry and western- blots. mRNAs of pro- and antiapopoptotic factors were quantitated by RT-PCR and RNAse protection assays. Activation of NFkB by EMSA and supershift electrophoretic assays.Results: MV persistently infected MOLT3 cells becamehighly sensitive to apoptosis induced by exogenous TRAIL.This sensitization could be explained by the observed MV infection up-regulation in the infected cells of the expression of TRAIL functional receptors TRAIL-R1 and TRAIL-R2 and down-regulation of the expression of antiapoptotic factor Bcl2 and activation of the protein-kinase Akt and NF-kB that would provoke the suicide of the infected cells.Conclusions: The high sensitization to induced apoptosisby exogenous TRAIL observed in MV persistently infectedcells suggest that treatment with recombinant TRAIL couldselectively eliminate MV infected cells in the CNS of patients and it could be possible to exploit this agent for the treatment of SSPE or MIBE encephalopaties (AU)

Toxicidad pulmonar por interleucina-2 / Pulmonary toxicity due to interleukin-2

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Neumotórax y pliegue cutáneo / No disponible

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[Virus and demyelination: why suspect that a virus may be involved in the aetiology of multiple sclerosis?]. / Virus y desmielinización: por qué sospechar la implicacion de virus en la etiología de la esclerosis múltiple?

INTRODUCTION: Epidemiological data indicate that environmental factors, possibly infections, are associated with the development of multiple sclerosis. Different viruses are known to produce demyelination in natural and experimental animal infections. In humans some virus cause acute or chronic diseases that course with central nervous system demyelination. A series of virus have been claimed to be etiological agents of multiple sclerosis, although a causal role for any of them has so far been demonstrated. METHOD: The mechanisms of viral demyelination are diverse,ranging from direct destruction of infected oligodendrocytes to triggering autoimmune responses without virus multiplication in target cells. The potential indirect mechanisms of viral demyelination and the heterogeneous histopathology shown in multiple sclerosis patients, suggesting an heterogeneus etiology, might explain why not a single virus has been as yet identified as the cause of this disease. CONCLUSIONS: Viral infections that cause demyelination in animals and humans are briefly reviewed, focusing on the potential myelin destruction mechanisms and obstacles to the identifying viruses that might cause multiple sclerosis.

Virus y desmielinización: ¿por qué sospechar la implicaciónde virus en la etiología de la esclerosis múltiple? / Virus and demyelination: why suspect that a virus may be involved in the aetiology of multiple sclerosis?

Introducción. La epidemiología de la esclerosis múltiple indica la existencia de uno o varios factores ambientales, posiblemente de origen infeccioso. Distintos virus producen desmielinización en infecciones naturales y experimentales de animales. En humanos se conocen virus causantes de enfermedades agudas o crónicas con desmielinización. Por otra parte, varios son los virus que se han asociado a esclerosis multiple sin que todavía se haya demostrado una relación causal para ninguno de ellos. Desarrollo. Los mecanismos por los que producen desmielinización pueden ser variados, desde destrucción directa de los oligodendrocitos a desencadenamiento de respuestas autoinmunes en ausencia de multiplicación vírica en las células diana. Esta diversidad de mecanismos, unido a que la patología de la esclerosis múltiple sugiere una etiología diversa, explica que haya sido difícil identificar los posibles virus conocidos o aún desconocidos implicados en este proceso. Conclusiones. Se revisan los virus animales y humanos causantes de desmielinización, los mecanismos de la misma y las dificultades en la identificación de posibles virus desencadenantes de esclerosis múltiple (AU)

[Risk of hepatitis B virus transmission from hepatitis B core antibody-positive liver donors]. / Riesgo de transmisión del virus de la hepatitis B de donantes de hígado anti-HBc positivos.

BACKGROUND: To study the hepatitis B virus (HBV) transmission from donors HBsAg-/AntiHBc+ to liver transplant recipients. PATIENTS AND METHOD: We studied retrospectively the HBV serological markers in 43 donors from our center and also the serological condition of the 41 recipients. The HBV serological markers were analyzed by ELISA and HBV DNA was detected by hybridation assays. RESULTS: 13 donors samples showed some HBV serological markers: 6 anti-HBc and anti- HBs (13.9%), 4 anti-HBc (9%) and 3 anti- HBs (6.9%). There were no cases of hepatitis B among liver recipients from donors with negative serological markers. Among the 13 recipients with HBV serological markers, 9 were followed during 39 (SD 17) months. The 5 recipients with no HBV markers, who received an anti- HBc+ with or without anti- HBs (100%) developed hepatitis B. The two liver recipients with anti-HBs solely, did not developed infection (0%). Of the 41 recipients, 15 had some HBV markers before transplant and two of them received an anti-HBc+ and did not develop the infection (0%). CONCLUSIONS: In our study, the prevalence of serological HBV infection in donors and recipients was of 30.2 and 31.7%, respectively. Anti-HBc with or without anti-HBs donors transmitted the HBV infection in all the cases (100%) to the susceptible recipients. The presence of anti-HBs in recipients protected these against the infection. Only the anti-HBs positive donors did not trasmit the HBV infection.

Riesgo de transmisión del virus de la hepatitis B de donantes de hígado anti-hbc positivos / Risk of hepatitis B virus transmission from hepatitis B core antibody-positive liver donors

FUNDAMENTO: Estudiar el riesgo de transmitir el virus de la hepatitis B (VHB) a los receptores de hígados de donantes AgHBs negativos y anti-HBc positivos. PACIENTES Y MÉTODO: Se han analizado retrospectivamente los marcadores séricos del VHB (MHB) (AgHBs, anti-HBc y anti-HBs) de 43 donantes, junto con los 41 receptores de estos órganos.La determinación de MHB se realizó por ELISA, y el ADN del VHB por técnica de hibridación molecular. RESULTADOS: Trece sueros de donantes (30,2 por ciento) presentaron algún MHB: 6 anti-HBc y anti-HBs (13,9 por ciento), 4 anti-HBc (9 por ciento) y tres anti-HBs (6,9 por ciento). De los receptores que recibieron un injerto sin MHB, ninguno desarrolló infección después del trasplante de hígado. De los 13 receptores de órganos con MHB, 9 han sido controlados durante 39 (DE 17) meses. Los 5 receptores de un injerto anti-HBc positivo, con anti-HBs o sin él, y que no presentaban MHB desarrollaron hepatitis B (100 por ciento). Los dos receptores de órganos anti-HBs positivos únicamente y sin MHB no desarrollaron infección (0 por ciento). Entre los receptores 15 tenían algún MHB antes del trasplante de hígado (31,7 por ciento); 5 de ellos tenían anti-HBs positivo antes del trasplante. Los dos receptores de este grupo que recibieron un injerto anti-HBc positivo no desarrollaron infección (0 por ciento). CONCLUSIONES: En este estudio la prevalencia de MHB entre los donantes y receptores es del 30,2 y del 31,7 por ciento, respectivamente. Los injertos anti-HBc positivos con anti-HBs o sin él transmitieron la enfermedad en el 100 por ciento de los receptores. La presencia de anti-HBs en el receptor protegió de la infección. Los injertos únicamente positivos para anti-HBs no transmitieron la enfermedad (AU)

Clinical isolates of measles virus use CD46 as a cellular receptor.

Laboratory strains of measles viruses (MV), such as Edmonston and Halle, use the complement regulatory protein CD46 as a cell surface receptor. The receptor usage of clinical isolates of MV, however, remains unclear. Receptor usage by primary patient isolates of MV was compared to isolates that had been passaged on a variety of tissue culture cell lines. All of the isolates could infect cells in a CD46-dependent manner, but their tropism was restricted according to cell type (e.g., lymphocytes versus fibroblasts). The results indicate that patient isolates that have not been adapted to tissue culture cell lines use CD46 as a receptor. In addition, passaging primary MV patient isolates in B95-8 cells selected variants that had alternate receptor usage compared to the original isolate. Thus, changes in receptor usage by MV are dependent upon the cell type used for isolation. Furthermore, our results confirm the relevance of the CD46 receptor to natural measles infection.

Measles virus fusion protein is palmitoylated on transmembrane-intracytoplasmic cysteine residues which participate in cell fusion.

[3H]palmitic acid was metabolically incorporated into the viral fusion protein (F) of Edmonston or freshly isolated measles virus (MV) during infection of human lymphoid or Vero cells. The uncleaved precursor F0 and the F1 subunit from infected cells and extracellular virus were both labeled, indicating that palmitoylation can take place prior to F0 cleavage and that palmitoylated F protein was incorporated into virus particles. [3H]palmitic acid was released from F protein upon hydroxylamine or dithiothreitol treatment, indicating a thioester linkage. In cells transfected with the cloned MV F gene, in which the cysteines located in the intracytoplasmic and transmembrane domains (Cys 506, 518, 519, 520, and 524) were replaced by serine, a major reduction of [3H]palmitic acid incorporation was observed for F mutated at Cys 506 and, to a lesser extent, at Cys 518 and Cys 524. We also observed incorporation of [3H]palmitic acid in the F1 subunit of canine distemper virus F protein. Cell fusion induced by cotransfection of cells with MV F and H (hemagglutinin) genes was significantly reduced after replacement of Cys 506 or Cys 519 with serine in the MV F gene. Transfection with the F gene with a mutation for Cys 518 abolished cell fusion, although less mutant protein was detected on the cell surface. These results suggest that the F protein transmembrane domain cysteines 506 and 518 participate in structures involved in cell fusion, possibly mediated by palmitoylation.

Sequence divergence of measles virus haemagglutinin during natural evolution and adaptation to cell culture.

Phylogenetic analysis of the sequence of the H gene of 75 measles virus (MV) strains (32 published and 43 new sequences) was carried out. The lineage groups described from comparison of the nucleotide sequences encoding the C-terminal regions of the N protein of MV were the same as those derived from the H gene sequences in almost all cases. The databases document a number of distinct genotype switches that have occurred in Madrid (Spain). Well-documented is the complete replacement of lineage group C2, the common European genotype at that time, with that of group D3 around the autumn of 1993. No further isolations of group C2 took place in Madrid after this time. The rate of mutation of the H gene sequences of MV genotype D3 circulating in Madrid from 1993 to 1996 was very low (5 x 10(-4) per annum for a given nucleotide position). This is an order of magnitude lower than the rates of mutation observed in the HN genes of human influenza A viruses. The ratio of expressed over silent mutations indicated that the divergence was not driven by immune selection in this gene. Variations in amino acid 117 of the H protein (F or L) may be related to the ability of some strains to haemagglutinate only in the presence of salt. Adaptation of MV to different primate cell types was associated with very small numbers of mutations in the H gene. The changes could not be predicted when virus previously grown in human B cell lines was adapted to monkey Vero cells. In contrast, rodent brain-adapted viruses displayed a lot of amino acid sequence variation from normal MV strains. There was no convincing evidence for recombination between MV genotypes.

Identification of two amino acids in the hemagglutinin glycoprotein of measles virus (MV) that govern hemadsorption, HeLa cell fusion, and CD46 downregulation: phenotypic markers that differentiate vaccine and wild-type MV strains.

We have used site-directed mutagenesis of the hemagglutinin (H) glycoprotein of measles virus (MV) to investigate the molecular basis for the phenotypic differences observed between MV vaccine strains and recently isolated wild-type MV strains. The former downregulate CD46, the putative cellular receptor of MV, are positive for hemadsorption, and are fusogenic in HeLa cells, whereas the latter are negative for these phenotypic markers. CD46 downregulation in particular, could have profound consequences for the immunopathology of MV infection, as this molecule protects the cell from complement lysis. Mutagenesis of two amino acids, valine and tyrosine at positions 451 and 481, respectively, in the H protein from the vaccine-like Hallé MV strain to their counterparts, glutamate and asparagine, in the H protein from the wild-type Ma93F MV strain (creating the V451E/Y481N double mutation) abrogated CD46 downregulation, HeLa cell fusion, and hemadsorption. The converse double mutagenesis of the Ma93F H protein (E451V/N481Y) transferred the CD46-downregulating, fusogenic, and hemadsorption functions to this protein. The data provide the first mapping study of the functional domains of MV H. The consequences of these results for MV vaccine design and the role of CD46 in MV infection are discussed.

Molecular epidemiology of measles virus: identification of pathways of transmission and implications for measles elimination.

The nucleotide sequences of either the hemagglutinin or nucleoprotein genes from wild type measles viruses isolated in the United States between 1989 and 1992 differed by < 0.5%. This suggests that the majority of viruses associated with resurgence of measles in the United States belonged to a single indigenous genotype. In contrast, wild type viruses isolated from sporadic outbreaks of measles in the United States during 1994 were genetically heterogeneous. These viruses were more closely related to wild type viruses previously circulating in Europe, Africa, or Japan and were epidemiologically linked to importations or no known source. In addition to demonstrating the utility of genetic analysis in understanding the epidemiology of measles, these data suggest that the transmission of the indigenous virus was interrupted after the 1989-1992 epidemic. Measures to further reduce the incidence of measles in the United States should include efforts to control importation and subsequent spread of measles.

Temporal and geographical distribution of measles virus genotypes.

The nucleotide sequence encoding the C terminus of the nucleocapsid protein of measles virus (MV) is the most variable in the genome. The sequence of this region is reported for 21 new MV strains and for virus RNA obtained from cases of subacute panencephalitis (SSPE) tissue. The nucleotide sequence of a total of 65 MV strains has been analysed using the CLUSTAL program to determine the relationships between the strains. An unrooted tree shows that eight different genotypes can be discerned amongst the sequences analysed so far. The data show that the C-terminal coding sequence of the nucleocapsid gene, although highly variable between strains, is stable in a given strain and does not appear to diverge in tissue culture. It therefore provides a good 'signature' sequence for specific genotypes. The sequence of this region can be used to discriminate new imported viruses from old 'endemic' strains of MV in a geographical area. The different genotypes are not geographically restricted although some appear to be the mainly 'endemic' types in large areas of the world. In global terms there appears to be at least four cocirculating genotypes of MV. The low level of divergence in the Edmonston lineage group isolated before 1970 indicates that some isolates are probably laboratory contaminants. This applies to some SSPE isolates such as the Hallé, Mantooth and Horta-Barbosa strains as well as some wild-type isolates from that period.