Impacto de la vacuna del virus del papiloma humano en mujeres en edad fértil: revisión sistemática de literatura

Introducción. Con la creación de la vacuna contra el virus de papiloma humano en los años ochentas, se ha promovido su aplicación de manera sistemática para evitar el cáncer cervical, que es la segunda causa de mortalidad por cáncer en mujeres en edad fértil. Actualmente se desconoce el impacto de los resultados de su aplicación. Se pretendió evaluar la mejor evidencia relacionada con los resultados de la vacuna contra VPH en mujeres en edad fértil. Metodología Se realizó una revisión sistemática de literatura incluyendo los artículos con mejor evidencia en los últimos cinco años. Los términos mesH incluyeron HPV vaccine, women, efficacy entre otros. Todos los artículos fueron clasificados por evidencia antes de ser analizados. Resultados Se encontraron un total de 557 artículos relacionados con el tema de los cuales 21 cumplieron criterios para su selección. La mayoría de artículos fueron clasificados como evidencia II. Las causas más frecuentes de exclusión fueron por tema no acorde y título. Discusión Los resultados de la revisión sistemática permiten definir que la eficacia de la vacuna contra VPH, tanto y la vacuna bivalente como y la cuadrivalente supera el 97% cuando se completan tres dosis. No hay reportes de eventos adversos graves, la edad de aplicación ideal es entre 9-14 años de edad.

Perspectiva de la psicología de la salud infantil en programas holisticos de atención a pacientes pediátricos con leucemia: ilustración de una experiencia mexicana

Este artículo tiene como sustento teórico a la psicología de la salud, en general, y a la psicología de la salud infantil, en particular. La línea de investigación en la cual se enmarca es la de enfermedades crónicas, abordadas desde una perspectiva biopsicosocial. Se dan a conocer datos que demuestran la eficacia de las intervenciones psicológicas a nivel hospitalario.En esta investigación se muestra que los programas holísticos fomentan la calidad de vida del paciente pediátrico con leucemia. La razón fundamental para abordar esta neoplasia es porque es la más frecuente en la población pediátrica a nivel mundial y porque existen pocos programas de apoyo de orden psicológico para estos niños y sus familias. La creciente investigación en el área representa la posibilidad de incidir en diferentes instituciones logrando la inclusión del psicólogo y demostrando que una intervención multidisciplinaria es la opción más acertada.

Funció de l'educació en l'epidèmia del virus d'immunodeficiència humana. 'Función de la educación en la epidemia del virus de immunodeficiencia humana'.

Abordar la cuestión de como ha afectado la epidemia del VIH a la educación de sujetos con problemas de socialización y drogodependencia, concretamente los adictos por vía endovenosa. Se trata de ver cómo la epidemia del VIH comporta un nuevo objetivo de la intervención educativa en sujetos con problemas de adición a drogas, la adquisición de recursos para la prevención del contagio y la estigmatización social. Colectivo específico de la Oliva, una institución educativa para sujetos con problemas de drogodependencia. El colectivo tiene 10 plazas para sujetos en proceso de abandono de la drogadicción e inserción social, de los dos sexos y de edades comprendidas entre 18-40 años. La investigación se estructura en dos partes bien diferencidas. En la primera, de carácter más teórico, se realiza un estudio conceptual e historiográfico del virus de immunodeficiencia humana, incluyendo un punto dedicado al VIH visto desde la educación. Una segunda parte, de carácter más práctico, se centra en el estudio concreto del colectivo para drogodependientes de la Oliva, y la presentación de un proyecto de intervención educativa para abordar los problemas que comporta a la infección por el VIH. Observación, análisis de contenido de documentos sobre la filosofía y funcionamiento del centro. A lo largo de la investigación se ha podido ir comprobando como la epidemia del VIH, asismimo como su evolución hacia el SIDA en caso de que se produzca, es un grave problema de salud pública. El número de casos se duplica cada año en los países occidentales. Por otra parte, es urgente la realización de programas de educación sanitaria de la población para incidir en la programación de este virus y, por tanto, como forma de anticipación. La educación tiene un papel relevante, aunque sea todavía poco utilizado a nivel general. Asimismo, el educador ha de partir de una formación rigurosa, en este caso de una formación sanitaria científica, de manera que transmita informaciones y pautas válidas para la socialización del sujeto.

¿Qué entienden los jóvenes universitarios por monogamia y sexo sin penetración, como estrategias preventivas de la transmisión sexual del virus del SIDA? = What university students understand by monogamy and sex without penetration as preventive strategies of sexual transmission of AIDS virus?

Monogamy and sex without penetration are behaviors recommended by the WHO to avoid AIDS virus sexual transmission. Seven hundred and fifty university students from 18 to 25 years (67.7% women) were surveyed and they were asked to give a maximum of three free definitions of the words monogamy and sex without penetration to prevent AIDS virus sexual transmission. Their participation was voluntary and anonymous. Although the majority of the answers was correct, there was a considerable percentage of wrong answers, either for monogamy (3.7% masturbation; 2.1% to have many partners; 0.9% homosexual relations), or for sex without penetration (20.5% oral sex; 1.1% anal coitus; 0.8% coitus without orgasm; 0.4% coitus interruptus). Some definitions or examples differ by gender. The amount of wrongs or incomplete answers put researchers on the alert about insufficient preventive knowledge in a population with a high educational level

Herpes Virus Bovino tipo 1 (BoHV-1) como posible causa de encefalitis en bovinos de la región del Magdalena Medio Colombiano. Estudio serológico y análisis epidemiológico

The bovine Herpesvirus type 1 and type 5 (BoHV-1 and BoHV-5), causing diseases and significant economic losses in farms of worldwide. Both affect the nervous system of cattle, although BoHV-5 has been the most associated with this type of pathogenesis. Given the death of animals with nervous symptoms and negative diagnoses for rabies virus in the area of study, this research focused on the detection of positive reactors to bovine herpes virus serum neutralization. We collected 518 blood samples from animals without Herpesvirus vaccine, in the municipalities of Caparrapi, Cimitarra, Honda and Victoria, in the Middle Magdalena River Region. In addition, epidemiological information useful to discuss neurological disease was collected through primary and secondary sources. For the analysis of data was used chi-square test by identification of relationship between evidence of viral infection and the variables recorded. The results revealed that 286 cases were positive for Herpesvirus infection, corresponding to a prevalence of 55.5%, however, there was no statistical relationship (p < 0.05) between the presence of antibodies and the variables analyzed. In conclusion, some cases of neurological disease in cattle in this region could be due to infection with herpes viruses. We discussed about the presence of BoHV-1 and BoHV-5 in the ambient, diagnosis and monitoring plans, as well as economic losses, which may cause in herds in this area.

Relationship between B-Cell-specific moloney murine leukemia virus integration site 1 (BMI-1) and homologous recombination regulatory genes in invasive ductal breast carcinomas

B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) is a Polycomb group protein that is able to induce telomerase activity, enabling the immortalization of epithelial cells. Immortalized cells are more susceptible to double-strand breaks (DSB), which are subsequently repaired by homologous recombination (HR). BRCA1 is among the HR regulatory genes involved in the response to DNA damage associated with the RAD51 protein, which accumulates in DNA damage foci after signaling H2AX, another important marker of DNA damage. Topoisomerase III beta (topoIII beta) removes HR intermediates before chromosomal segregation, preventing damage to cellular DNA structure. In breast carcinomas positive for BMI-1 the role of proteins involved in HR remains to be investigated. The aim of this study was to evaluate the association between BMI-1 and homologous recombination proteins. Using tissue microarrays containing 239 cases of primary breast tumors, the expression of Bmi-1, BRCA-1, H2AX, Rad51, p53, Ki-67, topoIII beta, estrogen receptors (ER), progesterone receptors (PR), and HER-2 was analyzed by immunohistochemistry. We observed high Bmi-1 expression in 66 cases (27.6%). Immunohistochemical overexpression of BMI-1 was related to ER (p=0.004), PR (p<0.001), Ki-67 (p<0.001), p53 (p=0.003), BRCA1 (p=0.003), H2AX (p=0.024) and topoIII beta (p<0,001). Our results show a relationship between the expression of BMI-1 and HR regulatory genes, suggesting that Bmi-1 overexpression might be an important event in HR regulation. However, further studies are necessary to understand the mechanisms in which Bmi-1 could regulate HR pathways in invasive ductal breast carcinomas.

Efecto citotóxico de la melatonina en células de leucemia humana Molt-3

Programa de doctorado: Clínica e Investigación Terapéutica.

Interazioni tra le glicoproteine D, B, H ed L critiche per la fusione indotta dal virus Herpes simplex

Four glycoproteins (gD, gB, gH, and gL) are required for herpes simplex virus (HSV) entry into the cell and for cell-cell fusion in transfected cells. gD serves as the receptor-binding glycoprotein and as the trigger of fusion; the other three glycoproteins execute fusion between the viral envelope and the plasma or endocytic membranes. Little is known on the interaction of gD with gB, gH, and gL. Here, the interactions between herpes simplex virus gD and its nectin1 receptor or between gD, gB, and gH were analyzed by complementation of the N and C portions of split enhanced green fluorescent protein (EGFP) fused to the glycoproteins. Split EGFP complementation was detected between proteins designated gDN + gHC, gDN + gBC, and gHN + gBC + wtgD, both in cells transfected with two or tree glycoproteins and in cells transfected with the four glycoproteins, commited to form syncytia. The in situ assay provides evidence that gD interacts with gH and gB independently one of the other. We further document the interaction between gH and gB. To elucidate which portions of the glycoproteins interact with each other we generated mutants of gD and gB. gD triggers fusion through a specialised domain, named pro-fusion domain (PFD), located C-terminally in the ectodomain. Here, we show that PFD is made of subdomains 1 and 2 (amino acids 260–285 and 285–310) and that each one partially contributed to herpes simplex virus infectivity. Chimeric gB molecules composed of HSV and human herpesvirus 8 (HHV8) sequences failed to reach the cell surface and to complement a gB defective virus. By means of pull down experiments we analyzed the interactions of HSV-HHV8 gB chimeras with gH or gD fused to the strep-tag. The gB sequence between aa residues 219-360 was identified as putative region of interaction with gH or critical to the interaction.

Interazioni tra Glicoproteine che mediano la penetrazione del Virus Herpes Simplex nella cellula e disegno razionale di Peptidi Inibitori

Herpes simplex virus entry into cells requires a multipartite fusion apparatus made of gD, gB and heterodimer gH/gL. gD serves as receptor-binding glycoprotein and trigger of fusion; its ectodomain is organized in a N-terminal domain carrying the receptor-binding sites, and a C-terminal domain carrying the profusion domain, required for fusion but not receptor-binding. gB and gH/gL execute fusion. To understand how the four glycoproteins cross-talk to each other we searched for biochemical defined complexes in infected and transfected cells, and in virions. We report that gD formed complexes with gB in absence of gH/gL, and with gH/gL in absence of gB. Complexes with similar composition were formed in infected and transfected cells. They were also present in virions prior to entry, and did not increase at virus fusion with cell. A panel of gD mutants enabled the preliminary location of part of the binding site in gD to gB to the aa 240-260 portion and downstream, with T306P307 as critical residues, and of the binding site to gH/gL at aa 260-310 portion, with P291P292 as critical residues. The results indicate that gD carries composite independent binding sites for gB and gH/gL, both of which partly located in the profusion domain. The second part of the project dealt with rational design of peptides inhibiting virus entry has been performed. Considering gB and gD, the crystal structure is known, so we designed peptides that dock in the structure or prevent the adoption of the final conformation of target molecule. Considering the other glycoproteins, of which the structure is not known, peptide libraries were analyzed. Among several peptides, some were identified as active, designed on glycoprotein B. Two of them were further analyzed. We identified peptide residues fundamental for the inhibiting activity, suggesting a possible mechanism of action. Furthermore, changing the flexibility of peptides, an increased activity was observed,with an EC50 under 10μM. New approaches will try to demonstrate the direct interaction between these peptides and the target glycoprotein B.

Proviral integration site for Moloney murine leukemia virus 1, but not phosphatidylinositol-3 kinase, is essential in the antiapoptotic signaling cascade initiated by IL-5 in eosinophils

BACKGROUND: Eosinophil differentiation, activation, and survival are largely regulated by IL-5. IL-5-mediated transmembrane signal transduction involves both Lyn-mitogen-activated protein kinases and Janus kinase 2-signal transducer and activator of transcription pathways. OBJECTIVE: We sought to determine whether additional signaling molecules/pathways are critically involved in IL-5-mediated eosinophil survival. METHODS: Eosinophil survival and apoptosis were measured in the presence and absence of IL-5 and defined pharmacologic inhibitors in vitro. The specific role of the serine/threonine kinase proviral integration site for Moloney murine leukemia virus (Pim) 1 was tested by using HIV-transactivator of transcription fusion proteins containing wild-type Pim-1 or a dominant-negative form of Pim-1. The expression of Pim-1 in eosinophils was analyzed by means of immunoblotting and immunofluorescence. RESULTS: Although pharmacologic inhibition of phosphatidylinositol-3 kinase (PI3K) by LY294002, wortmannin, or the selective PI3K p110delta isoform inhibitor IC87114 was successful in each case, only LY294002 blocked increased IL-5-mediated eosinophil survival. This suggested that LY294002 inhibited another kinase that is critically involved in this process in addition to PI3K. Indeed, Pim-1 was rapidly and strongly expressed in eosinophils after IL-5 stimulation in vitro and readily detected in eosinophils under inflammatory conditions in vivo. Moreover, by using specific protein transfer, we identified Pim-1 as a critical element in IL-5-mediated antiapoptotic signaling in eosinophils. CONCLUSIONS: Pim-1, but not PI3K, plays a major role in IL-5-mediated antiapoptotic signaling in eosinophils.

Upregulation of Reactive Oxygen Species During the Retrovirus Life Cycle and Their Roles in a Mutant of Moloney Murine Leukemia Virus, ts1-Mediated Neurodegeneration

Viral invasion of the central nervous system (CNS) and development of neurological symptoms is a characteristic of many retroviruses. The mechanism by which retrovirus infection causes neurological dysfunction has yet to be fully elucidated. Given the complexity of the retrovirus-mediated neuropathogenesis, studies using small animal models are extremely valuable. Our laboratory has used a mutant moloney murine leukemia retrovirus, ts1-mediated neurodegneration. We hypothesize that astrocytes play an important role in ts1-induced neurodegeneration since they are retroviral reservoirs and supporting cells for neurons. It has been shown that ts1 is able to infect astrocytes in vivo and in vitro. Astrocytes, the dominant cell population in the CNS, extend their end feet to endothelial cells and neuronal synapse to provide neuronal support. Signs of oxidative stress in the ts1-infected CNS have been well-documented from previous studies. After viral infection, retroviral DNA is generated from its RNA genome and integrated into the host genome. In this study, we identified the life cycle of ts1 in the infected astrocytes. During the infection, we observed reactive oxygen species (ROS) upregulations: one at low levels during the early infection phase and another at high levels during the late infection phase. Initially we hypothesized that p53 might play an important role in ts1-mediated astrocytic cell death. Subsequently, we found that p53 is unlikely to be involved in the ts1-mediated astrocytic cell death. Instead, p53 phosphorylation was increased by the early ROS upregulation via ATM, the protein encoded by the ataxia-telangiectasia (A-T) mutated gene. The early upregulation of p53 delayed viral gene expression by suppressing expression of the catalytic subunit of NADPH oxidase (NOX). We further demonstrated that the ROS upregulation induced by NOX activation plays an important role in establishing retroviral genome into the host. Inhibition of NOX decreased viral replication and delayed the onset of pathological symptoms in ts1-infected mice. These observations lead us to conclude that suppression of NOX not only prevents the establishment of the retrovirus but also decreases oxidative stress in the CNS. This study provides us with new perspectives on the retrovirus-host cell interaction and sheds light on retrovirus-induced neurodegeneration as a result of the astrocyte-neuron interaction.

Analysis of the Soehner-Dmochowski strain of Moloney murine sarcoma virus

The Soehner-Dmochowski strain of murine sarcoma virus (MuSV-SD) was derived from a bone tumor of a New Zealand Black (NZB) rat infected with the Moloney strain of MuSV, which carries the gene encoding the v-mos protein. Serial passage of cell-free tumor extracts both decreased the latent period and resulted in osteosarcomas. Cells from a late passage tumor were established in culture, cell-free extracts frozen, and later inoculated into newborn NZB rats. One of the resulting bone tumors was established in culture and clonal cell lines derived, of which S4 was selected for the present study. The objectives of the study were two-fold: an examination of the genetic organization of MuSV-SD, and an examination of the biochemical characteristics of the viral proteins, since this is an acutely transforming virus which may yield insights into the mechanism of transformation caused by the v-mos protein. Blot hybridization of digested S4 genomic DNA reveals three candidate MuSV-SD integrated viral DNAs. The largest of these, MuSV-SD-6.5, was cloned from an S4 cosmid library, and the complete MuSV-SD-mos sequence was determined. The predicted amino acid sequence of the v-mos protein was compared to that of MuSV-124 and Ht-1, which show a 96.5% and 97.1% similarity, respectively. To characterize the MuSV-SD-mos protein further, immunochemical assays were performed using anti-mos antisera. The immunoblot analysis and immunoprecipitation assays demonstrated that similar levels of the v-mos protein were present in cells chronically infected with either MuSV-SD or MuSV-124; however, the immune complex kinase assay revealed greatly reduced in vitro serine kinase activity of the MuSV-SD-mos protein compared to that of MuSV-124. Sequence analysis demonstrated that the serine at amino acid residue 358 of the MuSV-SD-mos protein, like that of MuSV-Ht-1, had been mutated to a glycine. Mutations of this serine residue have been shown to affect the detectable in vitro kinase activity, however, v-mos proteins containing this mutation still retain transforming properties. Therefore, although the characteristic in vitro kinase activity of the MuSV-SD-mos protein has not been demonstrated, it is clear that this virus is a potent transforming agent. ^

A cellular cleavage pathway for the Moloney murine leukemia virus precursor protein, Pr65$\rm\sp{gag}$: Identification of a new viral protein containing CAp30 and NCp10 sequences

The origin and structure of P55$\sp{\rm gag},$ a gag encoded polyprotein lacking the nucleocapsid protein, NCp10, have been explored. Evidence shows that P55$\sp{\rm gag}$ is formed by non-viral proteolytic cleavage of the Moloney murine leukemia virus (MoMuLV)gag precursor protein, Pr65$\sp{\rm gag}.$ P55$\sp{\rm gag}$ is produced in cells infected by a viral protease deletion mutant and by a recombinant murine sarcoma virus known to lack the protease gene, implying that a cellular protease is responsible for the cleavage. Structural and immunological studies show that the protein cleavage site is upstream of the CAp30-NCp10 viral proteolytic junction, implying that P55$\sp{\rm gag}$ lacks the carboxy-terminal residues of CAp30. During the course of studying P55$\sp{\rm gag},$ another protein was discovered, which I named nucleocapsid-related protein(NCRP). NCRP possesses the portion of CAp30 that is lacking in P55$\sp{\rm gag}.$ NCRP possesses antigenic epitopes present in CAp30 and NCp10. NCRP was observed in virus lysates and in nuclear lysates of MoMuLV infected cells; it was not detected in the cytoplasmic fractions of MoMuLV infected cells. Our results indicated that NCRP originates from Pr65$\sp{\rm gag},$ resulting from the same cellular proteolytic cleavage event that produces the viral cellular protein P55$\sp{\rm gag}.$ P55$\sp{\rm gag}$- and NCRP-like proteins also were observed in AKV murine leukemia virus (AKV MuLV) and feline leukemia virus (FeLV) infected cells and in their respective virus particles. The site of cleavage that yields P55$\sp{\rm gag}$ and NCRP is within the carboxy terminus of CAp30, likely within a motif highly conserved among mammalian type C retroviruses. This new motif, called the capsid conserved motif (CCM), overlaps a region containing both a possible bipartite nuclear targeting sequence and a region homologous with the U1 small nuclear ribonucleoprotein 70-kD protein. This domain, when intact, may act as a nuclear targeting sequence for the gag precursor proteins Pr65$\sp{\rm gag}$ and CAp30. Nuclei of cells infected with MoMuLV were examined for the presence of gag proteins. Both Pr65$\sp{\rm gag}$ and CAp30 were detected in the nuclear fraction of MoMuLV, AKV MuLV and FeLV infected cells. P55$\sp{\rm gag}$ was never detected in the nucleus of MoMuLV, AKV MuLV and FeLV infected cells or in their respective virus particles. I propose that NCRP may be involved in sequestering viral genomic RNA for the purposes of encapsidation and intracellular viral genomic RNA dimerization. ^

MONOCLONAL ANTIBODY CHARACTERIZATION OF RAT TRANSFORMATION ASSOCIATED PROTEINS INDUCED BY MOLONEY MURINE SARCOMA VIRUS

By the use of Moloney murine sarcoma virus (Mo-MSV)-induced rat bone tumor (RBT) cells as immunogens, and the hybridoma technique, a mouse hybridoma clone was isolated in Dr. Chan's lab (Chan et al., 1983), which produced a monoclonal antibody, designated MC. MC detected specific antigens in three different Mo-MSV-transformed rat cell lines: 78A1 WRC, RBT and 6M2 (NRK cells infected with the ts110 mutant of Mo-MSV), but not in their untransformed counterparts. These antigens are tentatively termed transformation associated proteins (TAP). In this study, TAP were hypothesized to be the rat specific proteins which are activated by Mo-MSV and play an important role in cellular transformation, and were further investigated. Their properties are summarized as follows: (1) TAP may represent cellular products localized in the cytoplasm of 6M2 cells. (2) The expression of TAP is temperature-sensitive and related to cellular transformation, and probably activated by the v-mos gene products. The optimal temperature for the expression of both P85('gag-mos), the only known viral transforming protein in 6M2 cells, and TAP was 28(DEGREES)C. The expression of both P85('gag-mos) and TAP was proportional to the degree of transformation of 6M2 cells. (3) There were four antigenically-related forms of intracellular TAP (P66, P63, P60 and P58) in 6M2 cells. After synthesis, the 58Kd TAP was probably converted to one of the other three forms. These three polypeptides (P66, P63 and P60) were rapidly converted to two (P68 and P64) and subsequently secreted to the extracellular medium with a 50% secretion rate of 78 min. The conversion of these molecular sizes of TAP is probably related to glycosylation. Inhibition of TAP glycosylation by 0.5 ug/ml of tunicamycin could retard the secretion rate of TAP by 39%. (4) TAP are phosphoproteins, but not associated with any protein kinase activity. (5) TAP have been purified, and found to be mitogenic NRK-2 cells. TAP can bind to the receptors of NRK-2 cells with a K(,d) of 1.4 pM and with about 2 x 10('5) binding sites for TAP per NRK-2 cell. (6) Some weak proteolytic activity was found to associate with purified TAP. ^

THE TRANSLATION PRODUCTS OF MOLONEY MURINE SARCOMA VIRUS 124 GENOMIC RNA

Murine sarcoma viruses constitute a class of replication-defective retroviruses. Cellular transformation may be induced by these viruses in vitro; whereas, fibrosarcomas may result in animals infected with them in vivo (Tooze, 1973; Bishop, 1978). Hybridization studies suggest that murine sarcoma viruses arose by recombination between nondefective murine leukemia virus sequences and certain cellular sequences present in uninfected mouse cells (Hu et al., 1977). A specific gene product, however, has not been implicated in murine sarcoma virus transformation.^ One line of murine sarcoma virus-producing cells, Mo-MuSV-clone 124, (Ball et al., 1973), was studied biochemically because it mainly produces the sarcoma virus as a pseudotype packaged with helper murine leukemia virus proteins. The sarcoma viral RNA was translated in a sophisticated cell-free protein synthesizing system (Murphy and Arlinghaus, 1978). The translation products were analyzed by a number of techniques, including electrophoresis in denaturing gels of SDS polyacrylamide, immunoprecipitation, and peptide mapping. The major products of the total RNA purified from the virus preparation were shown to have molecular weights of about 63,000 (P63('gag)), 42,000 (P42), 40,000 (P40), 38,000 (P38), and 23,000 (P23). The size class of mRNA coding for each of the cell-free products was estimated using a poly(A) selection technique and sucrose gradient fractionation. These analyses were used to localize the coding information related to each of the in vitro synthesized cell-free products within the sarcoma virus genome.^ The major findings of these studies were: (1) the 5' half of the sarcoma viral RNA codes for the 63,000 dalton polypeptide and 42,000 - 38,000 dalton polypeptides derived from the "gag" gene; and (2) the 3' half of the sarcoma viral RNA codes for a 38,000 dalton polypeptide and possibly derived from the cellular acquired sequences. ^