Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0403608 (ureter)
 9,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this work was to determine the role of the kidneys in the systemic clearance rate (CL) of interleukin-2 (IL-2). Rats received IL-2 by i.v. bolus and the pharmacokinetic data were found to be well described by a two-compartment, first-order elimination model. With administration of 0.2, 0.5 or 1.0 mg/kg of IL-2 (n = 3 per treatment), the median alpha and beta half-lives (T1/2 alpha, 2.3 min; T1/2 beta, 13.2 min, respectively), initial volume of distribution (V1, 93 ml/kg), volume of distribution at steady state (Vss, 198 ml/kg) and CL (16.8 ml min-1 kg-1) did not vary with the dose (P = .05). This demonstration of first-order kinetics suggested that renal CL remains constant over a range of doses. The pharmacokinetic properties of 1.0 mg/kg of IL-2 were examined after either single or double nephrectomy (n = 3 and 4, respectively), sham operation (n = 4) or no renal operation (n = 4; the "controls"). No difference in median T1/2 alpha, T1/2 beta, V1, Vss or CL was detected between control and sham-operated rats nor between single nephrectomy and sham operation. Compared with sham operation, double nephrectomy showed no significant change in V1 or Vss but the T1/2 alpha and T1/2 beta approximately doubled and CL was reduced by 75%. In a separate experiment, ureter-ligated rats were compared with sham-operated rats. With ureter ligation, T1/2 alpha, T1/2 beta, V1 and Vss were unchanged but CL was reduced by 36%.
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PMID:Quantitation of the renal clearance of interleukin-2 using nephrectomized and ureter-ligated rats. 781 24

In in vivo allogeneic bone marrow transplantation studies with the Brown Norway (BN) rat as recipient and the WAG/Rij rat as allogeneic donor a significant graft-versus-leukemia (GVL) effect is observed. Studies were performed to investigate whether lymphokine-activated killer (LAK) cells play a role in this GVL effect. Splenocytes from WAG/Rij and BN rats were activated in vitro by recombinant human interleukin-2 (rhIL-2) for 5-6 days. The cytolytic activity of these LAK cells was tested on four rat solid tumor cell lines, i.e. an ureter carcinoma, a rhabdomyosarcoma, and two lung tumors, and on leukemic cells derived from the BN rat acute myelocytic leukemia (BNML) and the WAG/Rij acute lymphocytic leukemia (L4415). The panel of target cells also included the murine cell lines P815 and YAC. Both WAG/Rij and BN LAK cells were not capable of lysing the leukemic cells in contrast to significant cytolytic activity on the rat solid tumor cell lines and P815 and YAC. BNML cells showed to be resistant to lysis by human NK cells. Phenotypical analysis of the rat LAK population revealed a decrease in the CD4/CD8 ratio compared to the unstimulated splenocyte population. Rat LAK cells displayed no antibody-dependent cellular cytotoxicity (ADCC) on the leukemic cells, whereas IL-2-stimulated human peripheral blood cells showed moderate ADCC activity on the leukemic cells. To investigate whether cytokines play a role in lysis of leukemic target cells, graded numbers of LAK cells and leukemic cells were co-cultivated for seven days in an agar-based colony culture system. This resulted in moderate suppression of leukemic colony formation. From the current in vitro studies it appears that the graft-versus-leukemia observed in in vivo allogeneic bone marrow transplantation studies is probably not due to a direct leukemic cell kill by LAK cells.
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PMID:In vitro resistance of the brown Norway rat acute myelocytic leukemia (BNML) to lymphokine-activated killer activity. 848 27