RESUMO
We report the case of a 58 year old man with occult obscure gastro-intestinal bleeding (OGIB) without other significant symptoms, in which systemic localisation of follicular B-cell non-Hodgkin lymphoma was discovered trough capsule endoscopy. This case reflects the clinical significance of performing capsule endoscopy in patients with OGIB.
Assuntos
Endoscopia por Cápsula , Neoplasias Intestinais/diagnóstico , Linfoma de Células B , Linfócitos B , Hemorragia Gastrointestinal , Humanos , Intestino Delgado , Linfoma de Células B/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
The induced expression of xanthine-guanine phosphoribosyl transferase (XGPRT) by low concentrations (-2 pg/ml) of interferon-alpha (IFN-alpha) or IFN-beta, in the 2fTPGH cell line caused a 50% cytotoxicity when these cells were grown in medium containing 6-thioguanine. We extended the application of this sensitive, reliable, and easy bioassay to other members of the cytokine family. To activate the IFN signaling pathway, we made receptor chimeras, consisting of the IFN type I receptor intracellular and transmembrane domains, fused to either the interleukin-5 (IL-5) receptors or erythropoietin (Epo) receptor extracellular domains as model systems. 2fTGH cells, stably transfected with these receptor chimeras, responded to very low concentrations of IL-5 or Epo (IC50 values of approximately 15 pg and 3 pg/ml, respectively) and thus can be used as a very sensitive bioassay for both ligands. Background activity of IL-5, Epo, tumor necrosis factor (TNF), IL-6, or leptin on cells that did not carry the receptor chimeras was very low. This methodology can in principle be extended to any ligand that acts via clustering of its receptors.
Assuntos
Bioensaio , Eritropoetina/análise , Interferon beta/farmacologia , Interleucina-5/análise , Pentosiltransferases/biossíntese , Agregação de Receptores , Transdução de Sinais , Corantes , Meios de Cultura/farmacologia , Indução Enzimática/efeitos dos fármacos , Eritropoetina/farmacologia , Fibrossarcoma/patologia , Violeta Genciana , Humanos , Interferon alfa-2 , Interferon-alfa/farmacologia , Interleucina-5/farmacologia , Interleucina-6/farmacologia , Leptina/farmacologia , Ligantes , Proteínas de Membrana , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Pentosiltransferases/genética , Agregação de Receptores/efeitos dos fármacos , Receptor de Interferon alfa e beta , Receptores da Eritropoetina/genética , Receptores da Eritropoetina/metabolismo , Receptores de Interferon/efeitos dos fármacos , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Receptores de Interleucina-5 , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/efeitos dos fármacos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes , Seleção Genética , Sensibilidade e Especificidade , Transdução de Sinais/efeitos dos fármacos , Tioguanina/toxicidade , Transfecção , Células Tumorais Cultivadas/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
We constructed chimeric receptors wherein the extracellular domain of the erythropoietin receptor (EpoR) was fused to the transmembrane and intracellular domains of the interferon (IFN) type I receptor subunits, IFNaR1 or IFNaR2-2. Transfection into 2fTGH and Tyk2-deficient 11,1 cells showed that EpoR/IFNaR2-2 alone was able to transduce a signal upon stimulation with erythropoietin (Epo), as judged by induction of the interferon type I-inducible 6-16 promoter. In contrast, protection against infection with encephalomyocarditis virus or vesicular stomatitis virus was reduced or absent, respectively. To further investigate the role of IFNaR1 in the induction of an antiviral state, we analyzed the Epo- versus IFNalpha-induced transcription of a set of genes, involved in antiviral protection. Up to 24 h after stimulation with Epo or IFNalpha, comparable transcription of the p56, dsRNA-dependent protein kinase, 2'-5'A synthetase, and MxA genes was seen. However, at later time points, only in the case of Epo induction, a sharp decrease of mRNA levels was observed. Western blotting analysis of dsRNA-dependent protein kinase showed a similar pattern at the protein level. Taken together, our results imply a role for IFNaR1 in the induction of sustained mRNA and protein levels that are likely required for optimal antiviral activity.
