ABSTRACT
HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17ß-estradiol. In untreated mice, E7 also induces skin tumors late in life albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes including signal transduction, transport, metabolic process, cell adhesion, apoptosis, cell differentiation, immune response and inflammatory response. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia including DMBT1, GLI1 and 17ßHSD2 in cervix, as well as MMP2, 12, 14, 19 and 27 in skin.
Subject(s)
Human papillomavirus 16/genetics , Human papillomavirus 16/pathogenicity , Papillomavirus E7 Proteins/genetics , Papillomavirus E7 Proteins/physiology , Animals , Base Sequence , Cervix Uteri/metabolism , Cervix Uteri/virology , Disease Models, Animal , Female , Genes, Viral , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/physiology , Human papillomavirus 16/physiology , Humans , Immunohistochemistry , Mice , Mice, Transgenic , Oligonucleotide Array Sequence Analysis , Papillomavirus Infections/etiology , Papillomavirus Infections/genetics , Papillomavirus Infections/virology , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , Real-Time Polymerase Chain Reaction , Skin/metabolism , Skin/virology , Transcriptome , Uterine Cervical Neoplasms/etiology , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/virologyABSTRACT
The typical form of hemolytic uremic syndrome (D+HUS) is a thrombotic microangiopathy that causes acute renal failure in children. The etiology of this disease is a toxin called Shiga-like toxin (Stx), present in certain strains of gram-negative bacteria. Vascular endothelial cell (EC) injury appears to be central in the pathogenesis of D+HUS. Thrombomodulin (TM) is a glycoprotein present in EC with anti-thrombogenic properties. The objective of this study was to investigate the effects of Stx on the surface expression of TM in EC using an in vitro culture of human glomerular microvascular endothelial cells. We also evaluated other inflammatory mediators [tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide], which are known to increase Stx receptor expression and are potentially involved in the pathogenesis of D+HUS. Stx2 induced a significant decrease of TM expression in this cell type after pre-incubation with TNF-alpha. This decrease could not be attributed to the inhibition of protein synthesis only, as cycloheximide, another inhibitor of protein synthesis, did not affect TM surface expression. These results suggest that the Stx2-induced decrease of TM expression in glomerular EC might contribute to the local procoagulant state present in D+HUS.
Subject(s)
Endothelium, Vascular/metabolism , Glomerular Mesangium/blood supply , Hemolytic-Uremic Syndrome/etiology , Hemolytic-Uremic Syndrome/metabolism , Thrombomodulin/metabolism , Cells, Cultured , Endothelial Cells/cytology , Endothelial Cells/metabolism , Endothelium, Vascular/cytology , Humans , Inflammation Mediators/metabolism , Leucine/pharmacokinetics , Microcirculation , Shiga Toxin 2/pharmacology , TritiumABSTRACT
En 1995, el Programa Mundial de Vacunas e Immunización de la OMS estableció un registro para ensayos con vacunas. En septiembre de 1996, este registro contenía 50 ensayos de vacunación patrocinados por la OMS, de los cuales 25 (50 por cien) eran estudios ya terminados. Las vacunas que se habían estudiado con mayor frecuencia fueron las de sarampión (9 ensayos), poliovirus (8 ensayos), cólera (8 ensayos), Escherichia coli enterotoxígena (4 ensayos) y neumococo (4 ensayos). Casi 80 por cien de estos ensayos se llevaron a cabo en países en desarrollo, principalmente en el Africa. En los 25 ensayos ya terminados, los resultados investigados fueron la respuesta inmunitaria (24 ensayos), las reacciones adversas (13 ensayos), la morbilidad (4 ensayos) y la mortalidad (1 ensayo). La OMS contribuyó a estos ensayos con el aporte indirecto de fondos, ayuda con el diseño metodológico, visitas a las localidades, el análisis de los datos, la adquisición de vacunas y la investigación de su potencia
Subject(s)
Clinical Trials as Topic , World Health OrganizationABSTRACT
Se publica en inglés en el Bull. WHO. Vol. 72:957-71, 1995
Subject(s)
Typhoid Fever , Typhoid-Paratyphoid Vaccines , VaccinationSubject(s)
Cell Adhesion Molecules/physiology , Cytokines/physiology , Malaria, Falciparum/physiopathology , Malaria/physiopathology , Plasmodium berghei , Animals , Child , Child, Preschool , Disease Susceptibility , Humans , Infant , Lymphocyte Subsets/immunology , Macrophages/immunology , Malaria, Cerebral/immunology , Malaria, Cerebral/physiopathology , Malaria, Falciparum/blood , Malaria, Falciparum/mortality , Mice , Mice, Inbred Strains , Plasmodium berghei/immunology , Severity of Illness Index , Tumor Necrosis Factor-alpha/physiologySubject(s)
Fat Necrosis/complications , Hypercalcemia/complications , Necrosis/complications , Alkaline Phosphatase/metabolism , Cyclic AMP/urine , Dihydroxycholecalciferols/metabolism , Fat Necrosis/enzymology , Fat Necrosis/metabolism , Female , Humans , Hydroxycholecalciferols/metabolism , Hypercalcemia/etiology , Hypercalcemia/metabolism , Infant , Parathyroid Hormone/blood , Phosphorus/metabolism , Prostaglandins E/urineABSTRACT
Después de examinar los conocimientos actuales de la morfología, multiplicación y transmisión del Trypanosoma cruzi, este artículo trata sobre los modelos animales que pueden servir para comprender los mecanismos inmunitarios que actúan en la enfermedad de Chagas. Se estudia la función de los anticuerpos circulantes y de la inmunidad por mediación celular en la protección contra el parásito, junto con la posibilidad de que algunas de las lesiones observadas en los pacientes con esta enfermedad se deban a mecanismos inmunopatológicos. Asimismo se mencionan los métodos de inmunodiagnóstico disponibles y la posibilidad de producir una vacuna para uso humano a la luz de los recientes resultados obtenidos en animales. Por último, se formula una serie de recomendaciones para investigaciones futuras (AU)