RESUMO
The effects of the production of two closely related cytokines, oncostatin M (OSM) and leukaemia inhibitory factor (LIF), by astrocytoma cells were investigated using the stable cell line human U373-MG, which expressed and secreted both biologically active polypeptides. The expression of LIF by these cells caused resistance to this cytokine due to loss of the LIF receptor (LIFR), from the cell surface, suggesting its retention. In contrast, cells expressing OSM were stimulated by this cytokine, utilizing an autocrine mechanism, and possessed receptors for OSM, but not LIF, on the cell surface. In these cells the continuous up-regulation of OSM-induced gene expression was found even though the Janus kinase-signal transducer and activator of transcription ('JAK/STAT') pathway was almost exhausted due to long-term autocrine stimulation of the cells by OSM. The amount of LIFR was down-regulated in both LIF- and OSM-producing cells and this effect was not found in wild-type U373-MG cells treated with externally added cytokines. To investigate the mechanism of autocrine stimulation by OSM we constructed a stable cell line expressing a form of OSM that is retained in the endoplasmic reticulum (ER). This biologically active cytokine was not secreted, but was localized in the ER. In addition, it did not stimulate the astrocytoma cells in an autocrine manner. We conclude that expression of LIF causes resistance of astrocytoma cells to this cytokine, whereas expression of OSM leads to autocrine stimulation.
Assuntos
Astrocitoma/metabolismo , Inibidores do Crescimento/metabolismo , Interleucina-6 , Linfocinas/metabolismo , Peptídeos/metabolismo , Antígenos CD/metabolismo , Astrocitoma/patologia , Sequência de Bases , Receptor gp130 de Citocina , Primers do DNA , Retículo Endoplasmático/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Inibidores do Crescimento/fisiologia , Humanos , Janus Quinase 1 , Fator Inibidor de Leucemia , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Linfocinas/fisiologia , Glicoproteínas de Membrana/metabolismo , Oncostatina M , Peptídeos/fisiologia , Proteínas Tirosina Quinases/metabolismo , Receptores de Citocinas/metabolismo , Receptores de OSM-LIF , Fatores de Transcrição/metabolismo , Células Tumorais CultivadasRESUMO
A 29-year-old mentally ill farmer underwent microsurgery for the resuturing of the penis and testicles which he himself had chopped off with an ax. Microsurgery of the urethra, corpora cavernosa, arteries and veins was begun 10 h after the trauma. The veins, arteries and testicles were anastomosed and covered with a free flap of the scrotum skin. Three weeks after surgery, the anastomosed tested showed good healing. However, in 65% of the penis, necrosis had occurred.
Assuntos
Amputação Traumática/cirurgia , Pênis/cirurgia , Reimplante/métodos , Escroto/cirurgia , Adulto , Humanos , Masculino , Microcirurgia , Necrose , Pênis/lesões , Pênis/patologia , Escroto/lesõesRESUMO
Rare diseases of the posterior urethra and adjacent structures in adult men are presented. Anatomy and embryology of this segment of urethra, pathologies, diagnosis and therapy are also discussed.
Assuntos
Doenças Uretrais/diagnóstico , Humanos , Masculino , Doenças Uretrais/terapiaRESUMO
Two patients with penis fracture with urethral damage during sexual intercourse are reported. The patients were treated surgically although in one case the time after fracture was 28 hours and in the second case 12 hours. The therapeutic results were very good in both cases, and the authors believe that surgery is the treatment of choice in cases of penis fracture.
