RESUMEN
Toxoplasma gondii is a protozoan that infects 30% of humans as intermediate hosts. T Sexual reproduction can occur only within the intestinal tract of felines, however, infection in other mammals and birds is associated with asexual replication and interconversion between the tachyzoite and bradyzoite stages. Bradyzoites are slow growing forms found in tissue cysts in latent infection. Recently, our group described the biological behavior of the EGS strain that forms thick walled cysts spontaneously in tissue culture, constituting a useful tool for examining the developmental biology of T. gondii. To further improve the usefulness of this model, we constructed genetically modified EGS parasites that express fluorescent tags under the control of stage specific promoters. The promoter regions for SAG-1 (tachyzoite specific), BAG-1 and LDH-2 (bradyzoite specific) were amplified by PCR and plasmids were constructed with mCherry (redT) and sfGFP (greenB) sequences, respectively. Strains of parasites were selected using FACS to arrive at single fluorescent and dual fluorescent strains of EGS expressing tags in a stage specific manner. In cell cultures, vacuoles labeled by immunofluorescence assay using anti-CST-1 a marker for T. gondii cyst wall contained parasites that were positive for BAG1-GFP and negative for SAG1-mCherry. Tachyzoites and bradyzoites harvested from the mice expressed stage specific mCherry and GFP proteins, respectively. These new dual fluorescent transgenic EGS strains are a promising tool to elucidate the mechanisms of T. gondii differentiation both in vitro and in vivo.
Asunto(s)
Células Epiteliales/parasitología , Fibroblastos/parasitología , Genes Reporteros , Coloración y Etiquetado/métodos , Toxoplasma/crecimiento & desarrollo , Animales , Fusión Artificial Génica , Técnicas de Cultivo de Célula , Línea Celular , Proteínas Fluorescentes Verdes/análisis , Proteínas Fluorescentes Verdes/genética , Humanos , Proteínas Luminiscentes/análisis , Proteínas Luminiscentes/genética , Regiones Promotoras Genéticas , Toxoplasma/genética , Proteína Fluorescente RojaRESUMEN
This study compared the hematological characteristics of diploid and triploid of jundia, Rhamdia quelen juveniles, an important freshwater fish cultured in south Brazil. Hematological morphometry of erythrocytes were determined in blood smears under a light microscope. The blood was used to measure the number of red blood cells (RBC) with a hemocytometer Neubauer chamber, and the numbers of white blood cells (WBC) and thrombocytes that were obtained using an indirect method. The results showed that triploidy increased (p < 0.01) the size and volume of the erythrocytes. Nevertheless, as expected, triploidy decreased (p < 0.01) the number of circulating erythrocytes, leucocytes and trombocytes in the blood of jundia. Moreover differential cell counts were different in diploids and triploids, suggesting that triploidy affects the number of cells and their proportion in blood. Lymphocytes were the most predominant cells in the differential counting of diploid fish (62.5%) while monocytes were predominant in triploid fish (49.6%). These results suggest performance differences between ploidies of jundia, and require future studies to evaluate the potential of triploid jundia in the culture conditions and resistance to infection.
Asunto(s)
Bagres/genética , Diploidia , Eritrocitos/citología , Triploidía , Animales , Bagres/sangre , Recuento de CélulasRESUMEN
Interferon-gamma (IFN-gamma) contributes to host resistance during acute infection with Trypanosoma cruzi, the causative agent of Chagas' disease. Inducibly expressed guanosine triphosphatase (IGTP), a 48-kDa guanosine triphosphatase (GTPase), is a member of a family of GTPase proteins inducibly expressed by IFN-gamma. The expression pattern of IGTP suggests that it may mediate IFN-gamma-induced responses in a variety of cell types. IGTP has been demonstrated to be important for control of Toxoplasma gondii infection but not for resistance against Listeria monocytogenes. We evaluated the role of IGTP in development of chronic chagasic cardiomyopathy in IGTP null mice and C57X129sv (wild type [WT]) mice infected with the Brazil strain for 6 mo. There was no significant difference in parasitemia or cardiac histopathology between null and WT mice. Right ventricular remodeling was observed in infected IGTP null mice, suggesting that IGTP does not significantly alter the course of T. cruzi infection.
Asunto(s)
Cardiomiopatía Chagásica/patología , GTP Fosfohidrolasas/genética , Interferón gamma/inmunología , Animales , Brasil , Cardiomiopatía Chagásica/genética , Cardiomiopatía Chagásica/inmunología , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Masculino , Ratones , Parasitemia/parasitología , Trypanosoma cruzi/clasificaciónRESUMEN
OBJECTIVE: To compare circulating plasma levels of immunoinflammatory markers in patients with known de novo coronary artery disease and patients with postangioplasty restenosis. METHODS: Using enzymatic immunoabsorbent assay, we measured plasma levels of soluble interleukin-2 receptosr, tumor necrosis factor alpha, and soluble tumor necrosis alpha receptors I and II in 11 patients with restenosis postcoronary angioplasty (restenosis group), in 10 patients with primary atherosclerosis (de novo group) who were referred for coronary angiography because of stable or unstable angina, and in 9 healthy volunteers (control group). Levels of soluble interleukin-2 receptors were significantly higher in the de novo group compared with that in the restenosis and control groups. Levels were also higher in the restenosis group compared with that in the control group. Plasma levels of tumor necrosis alpha and receptor levels were significantly higher in the de novo group compared to with that in the restenosis and control groups, but levels in the restenosis group were not different from that in the controls. CONCLUSION: Coronary artery disease, either primary or secondary to restenosis, is associated with significant immunoinflammatory activity, which can be assessed by examining the extent of circulating plasma levels of inflammatory markers. Moreover, patients with de novo lesions appear to have increased inflammatory activity compared with patients with restenosis.
Asunto(s)
Angioplastia de Balón , Enfermedad de la Arteria Coronaria/sangre , Receptores de Interleucina-2/sangre , Factor de Necrosis Tumoral alfa/análisis , Análisis de Varianza , Biomarcadores/sangre , Estudios de Casos y Controles , Enfermedad Coronaria/sangre , Femenino , Humanos , Masculino , Recurrencia , Estadísticas no ParamétricasRESUMEN
During acute Trypanosoma cruzi infection in mice, many leucocytes undergo apoptosis. Although apoptosis has been ascribed to increased levels of nitric oxide (NO) and Fas-FasL interaction, the importance of this phenomenon in modulating the host response against T. cruzi is unknown. Herein, the role of NO- and Fas-FasL-induced apoptosis in modulating the immune response to T. cruzi was evaluated using mice deficient in Fas expression (MRL/MpJ-Fas lpr) and inducible nitric oxide synthase (iNOS) knockout mice (iNOS-/-). The results showed that besides decreasing apoptosis induction after infection, impairment of the Fas-FasL interaction resulted in decreased NO production, as a consequence of enhanced T helper 2 (Th2) cytokine production. Differently, blockage of NO-induced apoptosis resulted in uncontrolled cytokine production, rather than a biased Th2 cytokine pattern. Together, these results suggested that Fas and FasL-induced apoptosis could be implied in modulation of the immune response against T. cruzi by interfering with cytokine and NO production during the acute phase of the infection.
Asunto(s)
Enfermedad de Chagas/inmunología , Glicoproteínas de Membrana/metabolismo , Óxido Nítrico/biosíntesis , Receptor fas/metabolismo , Enfermedad Aguda , Animales , Apoptosis/inmunología , Técnicas de Cultivo de Célula , Enfermedad de Chagas/metabolismo , Enfermedad de Chagas/patología , Citocinas/biosíntesis , Susceptibilidad a Enfermedades , Proteína Ligando Fas , Ligandos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
We examined the types of Epstein-Barr virus-associated nuclear antigen-1 (EBNA-1) gene carboxy (C)-terminal mutations occurring in Hodgkin's disease (HD) and reactive tissues from two different geographic regions. Previously reported EBNA-1 C-terminal region amino acid sequence variants, based on the amino acid at codon 487, include Prototype (P)-ala, which is found in the B95.8-derived prototype virus, P-thr, Variant (V)-leu, V-val, and V-pro. Using polymerase chain reaction (PCR) to amplify portions of the EBNA-1 gene, followed by DNA sequencing, we found a single EBNA-1 gene sequence variant in each tissue, whether reactive or neoplastic and whether from Brazil or the United States. Variant EBNA-1 gene sequences were more common in both neoplastic and non-neoplastic tissues from different geographic areas than the so-called prototype sequence. In the 17 Brazilian HD cases, 4 cases had P-thr variants and 13 had V-leu variants. In the six reactive tissues from Brazil, one had a P-ala variant, two had P-thr variants, and three had V-leu variants. In the 12 American HD cases, 2 had P-ala variants, 6 had P-thr variants, and 4 had V-leu variants. The 11 American reactive tissues included 2 P-ala variants, 5 P-thr variants, and 4 V-leu variants. In both countries, there were similar variant EBNA-1 sequences present in normal tissues and HD cases. Compared with the P-ala and P-thr cases, the V-leu cases were more likely to have the 30-bp latent membrane protein 1 (LMP1) gene deletion (P = 0.0075). In addition, cases of HD with the V-leu were statistically associated with a substitution of asparagine for glutamine at codon 322 of the C-terminal portion of the LMP1 gene. Our results suggest that any variation in EBNA-1 gene sequence is caused by a polymorphism present in pre-existing viral strains in the underlying population, and not a mutation occurring during oncogenesis.
Asunto(s)
Antígenos Nucleares del Virus de Epstein-Barr/genética , Genes Virales , Enfermedad de Hodgkin/genética , Brasil , Eliminación de Gen , Enfermedad de Hodgkin/virología , Humanos , Polimorfismo Genético , Análisis de Secuencia de ADN , Estados UnidosAsunto(s)
Aeromonas hydrophila/aislamiento & purificación , Enfermedades de los Bovinos/microbiología , Infecciones por Bacterias Gramnegativas/veterinaria , Vesículas Seminales/microbiología , Enfermedades Testiculares/veterinaria , Aeromonas hydrophila/patogenicidad , Animales , Bovinos , Enfermedades de los Bovinos/patología , Fibrosis/veterinaria , Infecciones por Bacterias Gramnegativas/patología , Masculino , Enfermedades Testiculares/microbiología , Enfermedades Testiculares/patologíaRESUMEN
A 30-bp deletion in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene has been reported in nasopharyngeal carcinoma and EBV-associated malignant lymphomas. Information on this deletion in EBV-associated gastric carcinoma (EBVaGC) is limited. The association of gastric carcinoma (GC) with EBV was examined by EBV-encoded RNA (EBER) in situ hybridization in 510 patients from Japan and 80 patients from Brazil. We studied the prevalence of 30-bp LMP1 gene deletion in EBVaGC in Japan (29 cases) and Brazil (four cases) in comparison with the corresponding EBER1-positive metastatic lesions in lymph nodes (10 cases) and EBV-infected reactive lymphocytes from dissected nonmetastatic lymph nodes (22 cases), microdissected non-neoplastic gastric mucosa of EBVaGC (five cases), and EBV-nonassociated GC (25 cases). We studied the status of the LMP1 gene by Southern blot hybridization of polymerase chain reaction products obtained after amplification with primers flanking the site of the deletion. We also performed EBV typing and LMP1 protein immunohistochemistry. EBV DNA was amplified by polymerase chain reaction in 30 of 33 EBVaGC cases, 8 of 10 metastatic carcinomas, 14 non-neoplastic tissues from 27 EBVaGC cases, and 12 of 25 non-EBV-associated GC cases with EBER1-positive lymphocytes. The 30-bp LMP1 gene deletion was observed in 23 of 26 (88.5%) cases of EBVaGC from Japan and two of four (50%) cases of Brazilian EBVaGC as compared with EBER1-positive reactive lymphocytes from 11 of 14 (78.6%) EBVaGC cases and 9 of 12 (75%) cases of non-EBV-associated GC. The variant type (the 30-bp deletion variant or nondeleted wild type) of LMP1 gene was the same among reactive lymphocytes, primary and secondary lesions of EBVaGC in all cases for which all three tissue types were studied (six of six). There was no correlation between the presence of the 30-bp deletion with depth of cancer invasion or presence of metastasis. Type A was detected in all available EBV-positive cases. The similar high incidence of 30-bp deletion in LMP1 gene in both carcinoma cells and reactive lymphocytes in EBVaGC cases suggests that this deletion may not be relevant to the pathogenesis of EBVaGC.
Asunto(s)
Carcinoma/virología , Eliminación de Gen , Herpesvirus Humano 4/genética , Metástasis Linfática/genética , Linfocitos/virología , Neoplasias Gástricas/virología , Proteínas de la Matriz Viral/genética , Adulto , Anciano , Anciano de 80 o más Años , Brasil/etnología , Carcinoma/etnología , Carcinoma/genética , Femenino , Humanos , Hibridación in Situ , Japón/etnología , Linfocitos/fisiología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Neoplasias Gástricas/etnología , Neoplasias Gástricas/genéticaRESUMEN
A 30-basepair (bp) deletion in the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) gene has been reported in nasopharyngeal carcinoma and EBV-associated malignant lymphomas. Prior studies have found the deletion in about 10% to 28% of cases of Hodgkin's disease (HD), particularly in cases with aggressive histology. We studied the prevalence of 30-bp LMP1 gene deletion in EBV-positive HD in the United States (US) (12 cases) and Brazil (26 cases) with comparison to reactive lymphoid tissues (21 cases) and HD without EBV-positive Reed-Sternberg cells (15 cases). We studied the status of the LMP1 gene by Southern blot hybridization of polymerase chain reaction (PCR) products obtained after amplification with primers spanning the site of the deletion. We also performed EBV typing, EBER1 in situ hybridization, and LMP1 protein immunohistochemistry. EBV was detected in 12/26 (46%) cases of HD from the US and 26/27 (96%) cases of Brazilian HD. The 30-bp LMP1 gene deletion was observed in 4/12 (33%) cases of EBV-positive HD from US, and 12/26 (46%) cases of Brazilian EBV-positive HD, including 3 cases of type B EBV, as compared with 12/21 (57%) reactive lymphoid tissues and 9/15 (60%) cases of EBV-negative HD. US and Brazilian HD showed a higher prevalence of the 30-bp LMP1 gene deletion, compared with studies of others. The unexpected finding of high incidence of 30-bp deletion in LMP1 gene in reactive lymphoid tissue and HD without EBV-positive Reed-Sternberg cells suggests that this deletion may not be relevant to HD pathogenesis in most cases.
Asunto(s)
Frecuencia de los Genes , Herpesvirus Humano 4/genética , Enfermedad de Hodgkin/genética , Enfermedad de Hodgkin/patología , Tejido Linfoide/patología , Eliminación de Secuencia , Proteínas de la Matriz Viral/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Composición de Base , Brasil/epidemiología , Cápside/genética , Femenino , Enfermedad de Hodgkin/epidemiología , Enfermedad de Hodgkin/virología , Humanos , Tejido Linfoide/virología , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estados Unidos/epidemiología , Latencia del Virus/genéticaRESUMEN
The occurrence of malignant lymphoma is an increasingly important cause of morbidity and mortality in AIDS patients. The incidence of AIDS-related lymphoma in some developing countries such as Brazil is increasing as the survival of HIV infection has improved. Although there is a clear association between several types of immunodeficiency-related lymphomas and Epstein-Barr virus (EBV), the association of EBV infection in AIDS-related lymphoma in Brazil, where the incidence of AIDS is high, is unknown. Formalin-fixed, paraffin-embedded tissue from 24 cases of AIDS-related lymphoma in Brazil were analyzed for morphologic classification, immunophenotype, and EBV association using in situ hybridization studies with an EBV-EBER1 biotinylated probe. Twenty cases of AIDS-related lymphoma were classified as non-Hodgkin's lymphoma and four cases were Hodgkin's disease. Eleven non-Hodgkin's lymphomas were classified as diffuse large cell type, five cases were small non-cleaved cell, Burkitt-type, and four cases were large cell immunoblastic non-Hodgkin's lymphoma. Eighteen cases were of B-cell phenotype; one was a T-cell lymphoma, and one was classified as null. Epstein-Barr virus (EBV) was demonstrated in the majority of tumor cells of 11 of 20 (55%) of the cases non-Hodgkin's lymphomas and in 3 of 4 (75%) cases of Hodgkin's disease. AIDS-related lymphomas in Brazil are usually of large cell/immunoblastic type, but Hodgkin's disease is also seen. Both non-Hodgkin's lymphoma and Hodgkin's disease are often associated with EBV infection. The non-Hodgkin's lymphoma is predominantly of B-cell phenotype.
PIP: While there is a clear association between several types of immunodeficiency-related lymphomas and Epstein-Barr virus (EBV), the association of EBV infection in AIDS-related lymphoma in Brazil, where the incidence of AIDS is high, has remained unknown. The authors report their findings from an analysis of tissue samples from 24 cases of AIDS-related lymphoma in Brazil. The samples were analyzed for morphologic classification, immunophenotype, and EBV association. 20 cases were classified as non-Hodgkin's lymphoma, while 4 were Hodgkin's disease. 11 non-Hodgkin's lymphomas were classified as diffuse large cell type, 5 as small, non-cleaved cell, Burkitt-type, and 4 as large cell immunoblastic non-Hodgkin's lymphoma. 18 cases were of B-cell phenotype; one was a T-cell lymphoma and one was classified as null. EBV was demonstrated in the tumor cells of 11 of the 20 non-Hodgkin's lymphoma cases and in 3 of the 4 cases of non-Hodgkin's disease.
Asunto(s)
Infecciones por Herpesviridae/complicaciones , Herpesvirus Humano 4/aislamiento & purificación , Linfoma Relacionado con SIDA/patología , Linfoma Relacionado con SIDA/virología , Infecciones Tumorales por Virus/complicaciones , Adulto , Brasil , Femenino , Infecciones por Herpesviridae/virología , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/virología , Homosexualidad Masculina , Humanos , Inmunofenotipificación , Hibridación in Situ , Ganglios Linfáticos/patología , Linfoma Relacionado con SIDA/genética , Linfoma Relacionado con SIDA/inmunología , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/virología , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/virología , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/virología , ARN Viral/análisis , Trastornos Relacionados con Sustancias , Infecciones Tumorales por Virus/virologíaRESUMEN
The incidence of Burkitt's lymphoma (BL) in Brazil is intermediate between the endemic form of equatorial Africa and the sporadic form in the United States. To characterize these lymphomas, we evaluated the clinical, morphologic, and immunohistochemical features of 24 Brazilian cases of BL. We also analyzed the cases for the presence of Epstein-Barr virus (EBV)-RNA using a highly sensitive and specific method of in situ hybridization. Most cases presented with involvement of intraabdominal organs, similar to the sporadic form of BL. EBV-RNA was detected in 17 of 24 cases (71%) in all or virtually all the tumor cells. This prevalence of EBV-positivity in our cases is intermediate between the endemic form of BL in equatorial Africa (100%) and the sporadic form in the United States (30%). These findings suggest that EBV plays an important role in the pathogenesis of BL in Brazil. This intermediate incidence of EBV infection may explain in part the differences of incidence of BL in different geographic regions.
Asunto(s)
Linfoma de Burkitt/epidemiología , Linfoma de Burkitt/virología , Herpesvirus Humano 4/aislamiento & purificación , Adolescente , Adulto , Brasil/epidemiología , Linfoma de Burkitt/patología , Niño , Preescolar , Femenino , Herpesvirus Humano 4/genética , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , ARN Viral/genéticaRESUMEN
Both Epstein-Barr virus (EBV) types A and B are found in endemic Burkitt's lymphoma (BL) occurring in equatorial Africa. We studied 17 cases of Brazilian BL previously demonstrated to be EBV-positive to determine the EBV type as well as the presence of a characteristic 30 bp deletion within the 3' end of the latent membrane protein-1 (LMP-1) gene that may be important to the pathogenesis of several EBV-associated neoplasms. All cases in which the age was known were children. We found type A EBV in 13 of 14 (93%) evaluable cases, and type B in one case. The LMP-1 deletion was found in 12 of 15 (80%) evaluable cases, including the one case of type B EBV, and a similar high prevalence (59%) of the deletion was detected in EBV-positive normal and reactive lymphoid tissues from individuals from the same geographic region. The high proportion of cases associated with type A EBV suggests that immunodeficiency is not an important factor in the pathogenesis of Brazilian BL, in contrast to endemic African BL. The presence of the LMP-1 deletion in a high prevalence in the normal population in this region is unexplained.
Asunto(s)
Linfoma de Burkitt/virología , Herpesvirus Humano 4/clasificación , Adolescente , Secuencia de Bases , Brasil/epidemiología , Linfoma de Burkitt/epidemiología , Niño , Femenino , Eliminación de Gen , Genes Virales/genética , Genotipo , Herpesvirus Humano 4/genética , Humanos , Tejido Linfoide/virología , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
This article focuses on clinical issues of taeniasis and cysticercosis, including a comprehensive review of the clinical data, standard and latest chemotherapy, modern concepts of pathogenesis, conventional and advanced diagnostic tests, current epidemiology, and effective means of control. Fundamental parasitology is covered to familiarize physicians and scientists with the latest concepts of parasites.
Asunto(s)
Cisticercosis , Teniasis , Corticoesteroides/uso terapéutico , Albendazol/uso terapéutico , Animales , Encéfalo/parasitología , Encéfalo/patología , Cisticercosis/diagnóstico , Cisticercosis/tratamiento farmacológico , Cisticercosis/epidemiología , Humanos , Praziquantel/uso terapéutico , Teniasis/diagnóstico , Teniasis/tratamiento farmacológico , Teniasis/epidemiologíaRESUMEN
The incidence of non-Hodgkin's lymphoma of the nasal region is much higher in Peru than in the United States and is similar to the incidence of sinonasal lymphomas in Asian countries. To characterize these lymphomas, we evaluated the clinical, morphologic, and immunohistochemical features of 14 cases and also analyzed the cases for Epstein-Barr virus (EBV) RNA using a sensitive and specific in situ hybridization method. Morphologically, the cases consisted of nine large cell immunoblastic lymphomas, one diffuse mixed cell lymphoma, one diffuse small cleaved lymphoma, one small noncleaved lymphoma, and two cases unclassifiable in the Working Formulation. Eleven cases demonstrated evidence of T lineage, two were of B lineage and one of indeterminate immunophenotype. In 13 of the lymphoma cases including all of the T-cell lymphomas, EBV RNA was detected in a high percentage of cells. Double-labeling immunohistochemical and in situ hybridization studies identified CD43 positivity in the cells labeling for EBV RNA. Much smaller amounts of EBV RNA were detectable in six of eight control benign nasopharyngeal biopsy specimens, and two were completely negative. These findings are similar to the prevalence of EBV-positive T-cell lymphomas in Asian countries and differ from the findings of the more common EBV-negative B-cell nasal lymphomas in the United States. These findings suggest that EBV plays a role in the development of nasal T-cell lymphomas and that the incidence of EBV infection may explain the reported "East-West" difference in the incidence of nasal T-cell lymphomas.
Asunto(s)
Herpesvirus Humano 4 , Linfoma/microbiología , Linfoma/patología , Neoplasias Nasales/microbiología , Neoplasias Nasales/patología , Linfocitos T/fisiología , Infecciones Tumorales por Virus/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Inmunofenotipificación , Hibridación in Situ , Incidencia , Linfoma/genética , Masculino , Persona de Mediana Edad , Neoplasias Nasales/genética , Infecciones Tumorales por Virus/epidemiologíaRESUMEN
The Epstein-Barr virus (EBV) has been implicated in the pathogenesis of Hodgkin's disease (HD). This study was undertaken to determine whether the association of EBV with HD showed geographical variation, as in Burkitt's lymphoma. We studied 32 formalin-fixed, paraffin-embedded cases of HD occurring in Peru. EBV DNA-RNA in situ hybridization was performed using a 30-base biotinylated antisense oligonucleotide complementary to the EBER1 gene of EBV. EBV immunohistochemistry was also performed, using a monoclonal antibody (MoAb) to the latent membrane protein (LMP1) of EBV. Identification of the precise cellular subset staining with EBV was accomplished via double-labeling with MoAbs directed against Reed-Sternberg cells (LeuM1/CD15) and B cells (L26/CD20). EBV RNA was identified in all or virtually all of the Reed-Sternberg cells and variants in 30 of the 32 (94%) cases of HD by in situ hybridization. LMP1 expression was identified in 83% of the EBER1-positive cases. Double-labeling studies confirmed the localization of EBV RNA to CD15-expressing Hodgkin's cells. This study found an extremely high prevalence of EBV in Peruvian HD, in contrast to the much lower percentage of EBV-associated cases of HD occurring in "Western" patients.
Asunto(s)
ADN Viral/análisis , Herpesvirus Humano 4/aislamiento & purificación , Enfermedad de Hodgkin/microbiología , ARN Viral/análisis , Células de Reed-Sternberg/microbiología , Proteínas Ribosómicas , Proteínas de la Matriz Viral , Adolescente , Adulto , Anticuerpos Monoclonales , Antígenos Virales/análisis , Niño , Preescolar , ADN Viral/genética , Femenino , Herpesvirus Humano 4/genética , Enfermedad de Hodgkin/clasificación , Enfermedad de Hodgkin/patología , Humanos , Hibridación in Situ , Masculino , Proteínas de la Membrana/análisis , ARN Viral/genética , Proteínas de Unión al ARN/análisis , Células de Reed-Sternberg/patología , Proteínas del Envoltorio Viral/análisisRESUMEN
BACKGROUND: Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative disease (PTLD) develops in 1 to 10 percent of transplant recipients, in whom it can be treated by a reduction in the level of immunosuppression. We postulated that the tissue expression of the small RNA transcribed by the EBER-1 gene during latent EBV infection would identify patients at risk for PTLD. METHODS: We studied EBER-1 gene expression in liver specimens obtained from 24 patients 2 days to 22 months before the development of PTLD, using in situ hybridization with an oligonucleotide probe. Control specimens were obtained from 20 recipients of allografts with signs of injury due to organ retrieval, acute graft rejection, or viral hepatitis in whom PTLD had not developed 9 to 71 months after the biopsy. RESULTS: Of the 24 patients with PTLD, 17 (71 percent) had specimens in which 1 to 40 percent of mononuclear cells were positive for the EBER-1 gene. In addition, 10 of these 17 patients (59 percent) had specimens with histopathological changes suggestive of EBV hepatitis. In every case, EBER-1-positive cells were found within the lymphoproliferative lesions identified at autopsy. Only 2 of the 20 controls (10 percent) had specimens with EBER-1-positive cells (P < 0.001), and such cells were rare. CONCLUSIONS: EBER-1 gene expression in liver tissue precedes the occurrence of clinical and histologic PTLD. The possibility of identifying patients at risk by the method we describe here and preventing the occurrence of PTLD by a timely reduction of immunosuppression needs to be addressed by future prospective studies.
Asunto(s)
Infecciones por Herpesviridae/transmisión , Herpesvirus Humano 4 , Trasplante de Hígado/efectos adversos , Hígado/química , Trastornos Linfoproliferativos/etiología , Proteínas/genética , ARN Mensajero/análisis , Proteínas de Unión al ARN , Proteínas Ribosómicas , Adolescente , Adulto , Niño , Preescolar , Femenino , Expresión Génica , Hepatitis Viral Humana/transmisión , Humanos , Hibridación in Situ , Lactante , MasculinoRESUMEN
The cases of 51 patients with malaria seen at the Albert Einstein College of Medicine hospitals from January 1986 to June 1991 are reviewed. Thirty-five patients acquired infection on journeys to their country of origin. Of these 35 patients, 83% of whom had lived in the United States for > or = 2 years, only 17% received antimalarial prophylaxis. Ten of the 51 patients were born and raised in the United States, and 70% received prophylaxis (P < .01). Six of the 51 patients were visitors to the United States from areas endemic for malaria. Overall, 64% of patients acquired malaria in West Africa, south of the Sahara; 20% in Asia; 8% in Ecuador; 6% in Haiti; and 4% in the Middle East. The majority of infections were due to Plasmodium falciparum. Six patients traveled to a zone endemic for malaria while pregnant, and none received prophylaxis. In nine of 13 patients who received prophylaxis, there was inadequate dosing or poor compliance. Individuals born in regions endemic for malaria are at high risk of acquiring malaria on return to their countries of origin and are less aware of the need for malaria prophylaxis than are other travelers.