RESUMEN
L-Glutamine is the most abundant free amino acid of the human body and is essential for the culture of many cell types. Clinically, reduction of glutamine by administration of glutaminase or the use of glutamine analogs is a common therapy for patients with acute lymphocytic leukemia. In the current study, we investigated the influence of glutamine concentrations on the human myelomonocytic cell line U937. Decreasing the glutamine concentration evoked a reduction in DNA synthesis (R2 = 0.9885, P < 0.0001), increased cell volume (P < 0.01) and the cytoplasm/nuclear ratio, and enhanced the development of vacuoles but did not influence cell viability. Culturing cells in reduced concentrations of glutamine augmented the percentage of cells expressing CD64 (Fc receptor for IgG/FcgammaRI, P < 0.01), CD11b (complement receptor type 3/CR3, P < 0.001) and CD71 (transferrin receptor, P < 0.05). The percentage of U937 cells expressing CD23 (low affinity receptor for IgE/FcepsilonRII) was increased at low concentrations of glutamine at both the protein (P < 0.01) and mRNA levels. The percentage of U937 cells phagocytizing opsonized E. coli (P < 0.001) or latex particles (P < 0.001) was enhanced by lowering the glutamine concentration. In conclusion, reducing glutamine concentration causes differentiation of the cell line U937 along the monocytic pathway. These effects may indicate a mechanistic basis for prior published evidence that glutaminase and glutamine antagonists are effective anti-tumor agents.
Asunto(s)
Glutamina/farmacología , Histiocitos/efectos de los fármacos , Monocitos/efectos de los fármacos , Anticuerpos Monoclonales/análisis , Anticuerpos Monoclonales/inmunología , Antígenos de Superficie/análisis , Antígenos de Superficie/metabolismo , Secuencia de Bases , Northern Blotting , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , División Celular/fisiología , Línea Celular , Cartilla de ADN/análisis , Cartilla de ADN/química , Cartilla de ADN/genética , Relación Dosis-Respuesta a Droga , Escherichia coli/inmunología , Citometría de Flujo , Glutamina/metabolismo , Histiocitos/patología , Histiocitos/fisiología , Humanos , Leucemia Mielomonocítica Aguda/patología , Microesferas , Monocitos/patología , Monocitos/fisiología , Ornitina/análogos & derivados , Ornitina/farmacología , Fagocitosis/efectos de los fármacos , Fenotipo , Receptores de IgE/análisis , Receptores de IgE/inmunología , Receptores de IgG/análisis , Receptores de IgG/inmunología , Factores de TiempoRESUMEN
Primary non-function (PNF) of renal allografts has been attributed to various risk factors, among them immunological ones, as well as unfavourable preservation conditions. To investigate the impact of these risk factory on the occurrence of PNF, 1335 consecutive kidney transplants performed at a single centre over a 10-year period were analysed. All patients received immunosuppression based on cyclosporine. As the method of analysis a conditional stepwise logistic regression model was chosen, comparing each graft suffering PNF with its partner kidney retrieved from the same donor. Thus, all donor-related variables could be omitted from the analysis, as they are the same in every pair of grafts. Risk factors analysed included panel-reactive antibodies, number of pretransplant transfusions, pregnancies, number of prior transplants, cold and second warm ischaemia time, mismatches on HLA loci A, B and DR and recipient age. The overall incidence of PNF was 87 grafts (6.5%). One patient suffered immediate rejection due to transplantation of an ABO incompatible graft. This case was excluded from further analysis. PNF occurred three times in recipients of living related grafts, twice in recipients of en-bloc grafts and four times in grafts, in which the paired kidney was either not transplanted or shipped outside the Eurotransplant region, so that no paired graft was available for matched case-control analysis. Of the remaining 77 pairs, twice both organs of one donor failed immediately. The remaining 73 complete pairs were analysed. Two of the investigated risk factors have independently a significant impact on the occurrence of PNF. Increasing the number of pretransplant transfusions raises the relative risk of graft failure up to six fold (P=0.02), while a history of prior transplants bears a relative risk of 0.21E05 (P=0.005). Ischaemia has no significant impact on the occurrence of PNF. Our data strongly suggest that immunological rather than donor risk factors are responsible for the non-function of kidney grafts.
Asunto(s)
Supervivencia de Injerto/fisiología , Trasplante de Riñón/fisiología , Sistema del Grupo Sanguíneo ABO , Análisis de Varianza , Anticuerpos/sangre , Incompatibilidad de Grupos Sanguíneos , Transfusión Sanguínea , Ciclosporina/uso terapéutico , Femenino , Estudios de Seguimiento , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/uso terapéutico , Riñón , Trasplante de Riñón/inmunología , Preservación de Órganos , Embarazo , Estudios Prospectivos , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos , Trasplante Homólogo , Insuficiencia del TratamientoRESUMEN
To detect the reasons for a massive decrease in the annual number of organ donors and as a means of evaluating the effectiveness of our information programme, a questionnaire was designed and sent to all intensive care units (ICUs) in our catchment area. We wished to obtain information about medical, organizational and capacity problems and negative occurrences that had happend during past retrievals. Although 60% of the answers we reiceved (87% feedback rate) mentioned the additional workload involved in treating an organ donor (and 88% had serious problems because of the shortage of nurses), less than 16% remembered a "lost" donor because of capacity problems. Eighty-six percent recognized our efforts to support them in any respect and were satisfied with the amount of "service" provided by the transplantation (TX) centre. About 45% remembered negative occurrences. More than 85% of all replies asked for more and continuing information related to organ donation and transplantation. We think that the key to a successful TX programme is a system of active care for the ICU staff in all peripheral hospitals; repeated mailing of updated information brochures, annual lectures about new developments, letters of thanks after each reported donor (including information on the fate of the organs), visiting donor ICU's accompanied by successfully transplanted recipients, etc.... The downwards trend of donor rates in our area clearly shows that it takes more than a stable legal situation to ensure the necessary amount of donor organs, even a very successful TX centre has to work hard to maintain a certain standard of knowledge, information and motivation amongst the staff of the peripheral hospitals. Moreover, the high turnover rate of ICU personnel requires a steady "flow of information" and cooperation between the "transplant people" and their coworkers outside to guarantee a permanent state of awareness concerning organ donation and transplantation. In fact, awareness seems to be the key issue: the activity of sending out the questionnaires was enough to raise the number of reported donors from 72 (estimated in July) to 96 (31 December 1992).
Asunto(s)
Unidades de Cuidados Intensivos/organización & administración , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/organización & administración , Austria , Hospitales Universitarios , Humanos , Cuerpo Médico de Hospitales , Personal de Enfermería en Hospital , Grupo de Atención al Paciente , Personal de Hospital , Relaciones Profesional-Familia , Encuestas y Cuestionarios , Donantes de Tejidos/estadística & datos numéricos , Obtención de Tejidos y Órganos/métodos , Recursos HumanosRESUMEN
The purpose of this study was to investigate the impact of prenephrectomy donor tissue typing on tissue typing quality and transplantation outcome in human kidney transplantation. We report on 680 consecutive kidney transplantations performed at the Vienna Transplantation Center from 1986 to June 1991. In 343 of them, HLA typing was performed using donor lymph node cells obtained in a small surgical procedure several hours before organ retrieval. The mean cold ischemia time (CIT) could be reduced to 17.7 h in these patients compared with 21.9 h in the control group (n = 337, conventional tissue typing using spleen lymphocytes obtained during the organ removal, P = 0.0001). There was a trend towards better initial and long-term function in the lymph node group; however, this did not reach statistical significance. The clarity of tissue typing results was significantly better when lymph nodes were used as the lymphocyte source. We conclude that prenephrectomy tissue typing is a feasable and inexpensive method of shortening CIT in renal transplantation and favors HLA typing, both likely to benefit transplantation outcome particularly within organ exchange programs.
Asunto(s)
Cadáver , Prueba de Histocompatibilidad , Ganglios Linfáticos/inmunología , Donantes de Tejidos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nefrectomía , Selección de Paciente , Reproducibilidad de los Resultados , Recolección de Tejidos y ÓrganosRESUMEN
Two hundred and eight orthotopic liver transplantations (OLT) were performed in 191 patients at the I Department of Surgery, University of Vienna from 1982-1990. The most frequent indications were hepatocellular carcinoma, alcoholic cirrhosis, posthepatic cirrhosis, primary biliary cirrhosis, and fulminant hepatic failure. Patients with malignancy constituted 33.8% of cases. The overall results showed a 64% one-year and 58% two-year survival; best results were seen in patients with primary biliary cirrhosis and the poorest long-term results were in malignancy. There were 23 postoperative deaths (11%). Primary non-function was seen in 14 (7%) cases; acute rejection episodes were seen in 62% of patients. The presence of a well organised cadaver organ procurement system in eastern Austria with upto 41 donors per million population per year ensures that the 57% growth rate in OLT achieved in 1990 will be maintained with even better results.