RESUMEN
Mummified remains have been successfully studied radiologically since the end of the 19th century, giving rise to a specific field of research-paleoradiology. In this paper, we present the results of the first radiological investigation of a collection of Sicilian mummies found in a subterranean chamber beneath the Capuchin Church of Savoca. The chamber contains a number of preserved bodies, either held in special niches in the walls or interred within coffins. A recent detailed radiological examination of these mummies allowed the authors to determine information relating to the funerary treatment and some of the pathological alterations witnessed in the remains. Specifically, evidence of gout and DISH was identified, along with frequent degenerative joint disease, suggestive of rich dietary habits and a longer life expectancy. These findings were interpreted in the light of historical information and the social status of the subjects concerned.
Asunto(s)
Momias/diagnóstico por imagen , Historia del Siglo XVIII , Historia del Siglo XIX , Humanos , Masculino , Momias/historia , Momias/patología , Paleopatología , Radiografía , SiciliaRESUMEN
In this study we report on the establishment and characterization of two novel lymphoma cell lines (CRO-AP/3 and CRO-AP/5) which carry infection by human herpesvirus type-8 (HHV-8) and have derived from AIDS-related primary effusion lymphoma (PEL). These two cell lines are representative of different virologic subtypes of PEL, i.e. HHV-8+/EBV- PEL in the case of CRO-AP/3 and HHV-8+/EBV+ PEL in the case of CRO-AP/5. Consistent with the diagnosis of PEL, both CRO-AP/3 and CRO-AP/5 expressed indeterminate (i.e. non-B, non-T) phenotypes although immunogenotypic studies documented their B-cell origin. Both cell lines are devoid of genetic lesions of c-MYC, BCL-2 and p53 as well as gross rearrangements of BCL-6. Detailed histogenetic characterization of these novel PEL cell lines suggests that PEL may derive from a post-germinal centre B cell which has undergone pre-terminal differentiation. The CRO-AP/3 and CRO-AP/5 cell lines may provide a valuable model for clarifying the pathogenesis of PEL. In particular, these cell lines may help understand the relative contribution of HHV-8 and EBV to PEL growth and development and may facilitate the identification of recurrent cytogenetic abnormalities highlighting putative novel cancer related loci relevant to PEL.
Asunto(s)
Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 8/aislamiento & purificación , Linfoma Relacionado con SIDA/virología , Adulto , Moléculas de Adhesión Celular/metabolismo , Proteínas de Unión al ADN/genética , Células Madre de Carcinoma Embrionario , Infecciones por Herpesviridae/complicaciones , Humanos , Inmunofenotipificación , Cariotipificación , Linfoma Relacionado con SIDA/inmunología , Linfoma Relacionado con SIDA/patología , Masculino , Mutación , Células Madre Neoplásicas/patología , Células Plasmáticas/metabolismo , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-bcl-6 , Factores de Transcripción/genética , Células Tumorales Cultivadas , Infecciones Tumorales por Virus/complicacionesRESUMEN
Primary lymphomatous effusions are represented by cases of non-Hodgkin's lymphoma (NHL) which grow in liquid phase in the serous body cavities in the absence of solid tumour masses. Based on morphologic, immunophenotypic, virologic and genotypic features, primary lymphomatous effusions are distinguished into body cavity-based lymphoma (BCBL), Burkitt's lymphoma (BL) and immunoblastic large-cell lymphoma. The histogenesis and pathogenesis of primary lymphomatous effusions are virtually unclarified. In this study, we have established 2 cell lines (CRO-AP/1 and CRO-AP/2) representative of 2 distinct categories of primary lymphomatous effusion, BCBL (CRO-AP/2) and BL (CRO-AP/1). Both CRO-AP/1 and CRO-AP/2 carry monoclonal re-arrangements of the immunoglobulin genes which are identical to those of the respective parental tumours. Consistent with its BCBL origin, CRO-AP/2 is characterised by a non-B, non-T phenotype and harbours infection by HHV-8 (approx. 100 viral copies/cell) and Epstein-Barr virus. Conversely, CRO-AP/1 expresses several B cell-associated antigens, lacks HHV-8 infection and carries the genetic hallmark of BL, i.e., a chromosomal breakpoint of band 8q24. CRO-AP/1 and CRO-AP/2 may be valuable for the biologic characterization of primary lymphomatous effusions, particularly since the number of available cell lines derived from such lymphomatous effusions is extremely limited.
Asunto(s)
Linfoma de Burkitt/patología , Linfoma de Burkitt/virología , Herpesvirus Humano 8 , Linfoma Relacionado con SIDA/patología , Linfoma Relacionado con SIDA/virología , Células Tumorales Cultivadas/patología , Células Tumorales Cultivadas/virología , Ascitis/patología , Linfoma de Burkitt/genética , ADN de Neoplasias/genética , Herpesvirus Humano 8/genética , Humanos , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Derrame Pleural/patologíaRESUMEN
BACKGROUND: Even though the presence of a prominent tissue eosinophilia represents a common histopathologic feature of Hodgkin's disease (HD), eosinophils have been mainly regarded as 'innocent' bystanders recruited and activated during the cellular reaction typical of HD. To evaluate the putative role of eosinophils or eosinophil-derived cytokines on tumor-cell regulation in HD, we have analyzed these cells for the functional expression of surface ligands (L) of the tumor necrosis factor (TNF) superfamily, whose specific receptors are known to transduce proliferation signals at the surface of Hodgkin (H) and Reed-Sternberg (RS) cells. MATERIALS AND METHODS: Eosinophils from peripheral blood of healthy donors and patients with HD, primary hypereosinophilic syndrome (HES), or secondary hypereosinophilia (HE), were purified by density gradient centrifugation and immunomagnetic depletion of residual granulocytes. RESULTS: By immunostaining and mRNA analysis, we were able to show that eosinophils from normal donors and patients with HD, HES, and HE express a number of receptors and ligands of the TNF superfamily, including CD40, CD40L, CD30L, CD95/Fas, CD95/FasL and 4-1BB. In addition, we provide evidence that cytokines regulating eosinophil proliferation and activation, i.e., interleukin (IL)-5, IL-3, and granulocyte-macrophage colony-stimulating factor, are able to enhance the cellular density of several TNF superfamily ligands and/or receptors at the surface of cultured eosinophils. Finally, we have shown that native CD40L and CD30L at the surface of purified eosinophils are functionally active and able to transduce proliferative signals on CD40+ and CD30+ target cells, including cultured H-RS cells. CONCLUSIONS: Our data suggest that eosinophils may act as important elements in the pathology of HD by providing cellular ligands for TNF-superfamily receptors (CD40, CD30, CD95/Fas) able to transduce proliferation and antiapoptotic signals at the surface of H-RS cells. The presence on eosinophils of receptors for TNF ligands expressed by activated T cells (i.e., OX40L, FasL, CD40L, 4-1BBL), also suggest that eosinophils may contribute to the deregulated network of interactive signals between H-RS cells, T cells, and other surrounding reactive cells.
Asunto(s)
Eosinófilos/fisiología , Enfermedad de Hodgkin/sangre , Antígenos de Neoplasias/sangre , Apoptosis/fisiología , Antígenos CD40/sangre , Estudios de Casos y Controles , División Celular/fisiología , Eosinófilos/patología , Enfermedad de Hodgkin/patología , Humanos , Antígeno Ki-1/sangre , Ligandos , Receptores del Factor de Necrosis Tumoral/sangre , Valores de ReferenciaRESUMEN
The presence of a prominent tissue eosinophilia represents a typical histopathologic hallmark of Hodgkin's disease (HD). To evaluate the putative role of eosinophils on tumor cell regulation in HD, we have analyzed these cells for the functional expression of CD30 ligand (CD30L), a surface molecule able to transduce CD30-mediated proliferation signals on Hodgkin's (H) and Reed-Sternberg (RS) cells. The results demonstrate that circulating and tissue eosinophils from normal donors and patients with HD or hypereosinophilic syndrome (HES), display CD30L mRNA and express CD30L protein, as shown by immunostaining with a specific monoclonal antibody (M80) and with a biotinylated soluble CD30-Fc fusion protein. The surface density of CD30L on eosinophils from HD and HES patients was remarkably higher compared with healthy donors, probably reflecting a cytokine-mediated upregulation in these pathologic conditions. Accordingly, we provide evidence that cytokines regulating eosinophils proliferation and activation, ie, interleukin-5 (IL-5), IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF), are able to enhance the cellular density of CD30L on purified eosinophils from normal subjects. Finally, we show that native CD30L on human eosinophils is a functionally active surface structure able to transduce proliferative signals on CD30+ target cells, including cultured H-RS cells. Our data suggest that eosinophils may not merely represent innocent bystanders, but rather act as important elements in the pathology of HD by contributing to the deregulated network of CD30/CD30L-mediated interactive signals between H-RS cells and surrounding reactive cells.