RESUMEN
T cells infected with human T-cell leukemia virus type 1 (HTLV-1) transform into malignant/leukemic cells and develop adult T-cell leukemia (ATL) after a long latency period. The tax (transactivator from the X-gene region) and HBZ (HTLV-1 bZIP factor) genes of HTLV-1 play crucial roles in the development of ATL. The process and mechanism by which HTLV-1-infected T cells acquire malignancy and develop ATL remain to be elucidated. Constitutive expression of interleukin-2 (IL-2) receptor α-chain (IL-2Rα/CD25), induced by the tax and HBZ genes of HTLV-1, on ATL cells implicates the involvement of IL-2/IL-2R pathway in the growth and development of ATL cells in vivo. However, the leukemic cells in the majority of ATL patients appeared unresponsive to IL-2, raising controversies on the role of this pathway for the growth of ATL cells in vivo. Here, we report the establishment of 32 IL-2-dependent T-cell lines infected with HTLV-1 from 26 ATL patients, including eight leukemic cell lines derived from five ATL patients, while no T-cell lines were established without IL-2. We have shown that the IL-2-dependent ATL cell lines evolved into IL-2-independent/-unresponsive growth phase, resembling ATL cells in vivo. Moreover, the IL-2-dependent non-leukemic T-cell lines infected with HTLV-1 acquired IL-2-independency and turned into tumor-producing cancer cells as with the ATL cell lines. HTLV-1-infected T cells in vivo could survive and proliferate depending on IL-2 that was produced in vivo by the HTLV-1-infected T cells of ATL patients and patients with HTLV-1-associated diseases and, acts as a physiological molecule to regulate T-cell growth. These results suggest that ATL cells develop among the HTLV-1-infected T cells growing dependently on IL-2 and that most of the circulating ATL cells progressed to become less responsive to IL-2, acquiring the ability to proliferate without IL-2.
Asunto(s)
Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Resistencia a Antineoplásicos , Inmunoglobulinas/genética , Factores Reguladores del Interferón/genética , Linfoma de Células B Grandes Difuso/genética , Antineoplásicos/uso terapéutico , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/deficiencia , Inhibidor p16 de la Quinasa Dependiente de Ciclina/deficiencia , Resultado Fatal , Eliminación de Gen , Expresión Génica , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana EdadRESUMEN
AIM: The number of hemodialysis (HD) patients is increasing along with their mean age in Japan. The assessment of their psychosocial status and quality of life (QOL) is therefore becoming more and more important along with laboratory data or comorbidities. METHODS: We examined the psychosocial status of 211 HD patients (72 elderly and 139 non-elderly) and compared the difference between elderly and non-elderly patients using a visual analogue scale (VAS). We then examined how QOL affected mortality rate in 3-year prospective follow up. We assessed 10 items of QOL: health condition, appetite, sleep, mood, memory, family relationships, friendship, economical status, life satisfaction in daily life, and happiness with qualified self-evaluating questionnaires along with laboratory data and comorbidities. Furthermore, we investigated the correlation between the scores of mood and geriatric depression scale (GDS)-15. RESULTS: There was no difference in VAS scores between elderly and non-elderly patients. Lower VAS scores for appetite and mood correlated with higher mortality in HD patients, especially in the non-elderly. VAS scores for mood correlated with GDS-15 in HD patients. CONCLUSIONS: More attention should be paid to appetite and the diagnosis and therapy of depressive mood to improve the prognosis of HD patients, especially for the non-elderly.
Asunto(s)
Afecto , Apetito , Trastorno Depresivo/psicología , Escalas de Valoración Psiquiátrica , Calidad de Vida/psicología , Diálisis Renal/psicología , Anciano , Trastorno Depresivo/diagnóstico , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/psicología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Skin pigmentation is a common problem for dialysis patients, but little is known about the factor responsible for the colour intensity. Middle-molecular-weight (MMW) substances have been suggested to be responsible for the skin colour. Several papers have reported that ß(2)-microglobulin (ß(2)-MG) correlates with the skin colour, and haemodiafiltration (HDF) is effective to reduce the skin hyperpigmentation. However, a quantitative skin colour follow-up on patients treated with online haemodiafiltration (online HDF) has not been performed. METHODS: Sixty-one patients were enrolled in this study. Quantification of skin colour was done using a reflected light colorimeter. Among them, 51 patients were under haemodialysis (HD), and the other 10 patients were under online HDF. Follow-ups to estimate the skin colour change were performed for 6 months. Among 10 patients under online HDF, four patients were also investigated by crossover way between HD and online HDF. RESULTS: Compared with controls, patients treated with HD had darker skin. The colour value was well correlated with age, haematocrit, sex, diabetes and ß(2)-MG but not with Kt/V. The skin colour got worse under HD treatment as well as the values of ß(2)-MG, but online HDF improved the hyperpigmentation and the ß(2)-MG values. CONCLUSIONS: Our data show the effectiveness of online HDF on skin colour and suggest that HD patients' skin colour can be improved by modality change.
