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71.
DLA-identical bone marrow grafts after low-dose total body irradiation: effects of high-dose corticosteroids and cyclosporine on engraftment 总被引:2,自引:1,他引:2
Yu C; Storb R; Mathey B; Deeg HJ; Schuening FG; Graham TC; Seidel K; Burnett R; Wagner JL; Shulman H 《Blood》1995,86(11):4376-4381
Previous studies found that marrow allografts from DLA-identical littermates resulted in survival of 60% of recipient dogs after an otherwise lethal dose of 450 cGy of total body irradiation (TBI), either because of successful allografts or autologous recovery after rejection of the allografts. Forty percent of dogs died with marrow aplasia after allograft rejection. The current study asked whether allogeneic engraftment could be enhanced and survival improved by treating allograft recipients with high doses of corticosteroids or with cyclosporine (CSP), administered either before or after transplantation. Five dogs in group 1 received corticosteroids beginning on day -5 and ending on day 32 after transplant. The starting dose was 12.5 mg of prednisone per kilogram orally twice daily. All five dogs rejected their allografts; three died early with marrow aplasia and two showed endogenous marrow recovery. Nine dogs received CSP from day -6 to day -1 before transplantation at a dose of 20 mg/kg/d intravenously administered in divided doses. All nine dogs rejected the marrow allograft; six died with marrow aplasia and three survived with endogenous marrow recovery. Seven dogs received CSP after transplantation at a dose of 30 mg/kg/d orally from day -1 to day 35. All seven had sustained allografts (two mixed chimeras and five complete donor-type chimeras) and became healthy long-term survivors without graft-versus-host disease. These results extend previous observations and confirm that grafts of marrow from DLA-identical littermates improved survival of dogs exposed to low but otherwise lethal doses of TBI. Additional therapy with high-dose corticosteroids administered peritransplantation and posttransplantation or CSP administered before transplantation neither enhanced the rate of allogeneic engraftment nor improved survival; however, CSP administered after transplantation resulted in successful allografts and event-free survival in all cases. 相似文献
72.
FG K?ln 《MedR Medizinrecht》2008,26(5):320-322
Abstrakt Bedient sich ein Arzt nicht nur vorübergehend der Mithilfe eines Berufskollegen, so erzielt er
Einkünfte aus Gewerbebetrieb, wenn er nicht eigenverantwortlich dessen T?tigkeiten überwacht
und wenn der Berufskollege auch nicht als Mitunternehmer t?tig ist. 相似文献
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Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) by human cytochrome P4501B1 总被引:1,自引:1,他引:1
Cytochrome P4501B1 (CYP1B1) is the most recently identified member of the
dioxin-inducible CYP1 family. CYP1B1 is constitutively expressed in most
human tissues, including colon and breast, and can activate numerous
chemically diverse carcinogens. We evaluated the metabolism of the dietary
heterocyclic amine carcinogen 2-amino-1-methyl-6-
phenylimidazo[4,5-b]pyridine (PhIP) by microsomes from yeast expressing the
human CYP1B1 protein. PhIP metabolites were analysed by HPLC with
fluorescence and absorbance detection. We found that human CYP1B1
metabolizes PhIP to three products: N2-OH-PhIP, a mutagenic activation
product; 4'-OH-PhIP, a detoxification product; and 2-OH-PhIP, the mutagenic
potential of which is unknown. Metabolite identity was confirmed by
co-elution with authentic standards and synchronous fluorescence
spectroscopy. The identity of the 2-OH-PhIP standard was additionally
confirmed by mass spectrometry. Kinetic studies of the formation of
N2-OH-PhIP, 4'-OH-PhIP and 2-OH-PhIP by CYP1B1 indicated apparent Km values
of 5.7 +/- 1.3, 2.2 +/- 0.5 and 1.3 +/- 0.2 microM, respectively. Apparent
turnover rates were 0.40 +/- 0.03, 0.93 +/- 0.02 and 0.04 +/- 0.00 nmol
product/min nmol P450, respectively. At saturating levels of substrate,
CYP1B1-mediated formation of the non- mutagenic metabolite 4'-OH-PhIP was
favored two-fold over that of the mutagenic metabolite, N2-OH-PhIP and
>10-fold over that of 2-OH-PhIP. The formation of N2-OH-PhIP, a potent
mutagen implicated in the etiology of human colon and breast cancer,
indicates that CYP1B1 may play an important role in PhIP-mediated
carcinogenesis.
相似文献
77.
Schultsz C van den Ende J Cobelens F Vervoort T van Gompel A Wetsteyn JC Dankert J 《Journal of clinical microbiology》2000,38(10):3550-3554
To determine the role of diarrheagenic Escherichia coli in acute and persistent diarrhea in returned travelers, a case control study was performed. Enterotoxigenic E. coli (ETEC) was detected in stool samples from 18 (10.7%) of 169 patients and 4 (3.7%) of 108 controls. Enteroaggregative E. coli (EAggEC) was detected in 16 (9.5%) patients and 7 (6.5%) controls. Diffuse adherent E. coli strains were commonly present in both patients (13%) and controls (13.9). Campylobacter and Shigella species were the other bacterial enteropathogens most commonly isolated (10% of patients, 2% of controls). Multivariate analysis showed that the presence of ETEC was associated with acute diarrhea (odds ratio [OR], 6.7; 95% confidence interval [CI], 1.5 to 29.1; P = 0.005), but not with persistent diarrhea (OR, 1.6; 95% CI, 0.4 to 7.4). EAggEC was significantly more often present in patients with acute diarrhea than in controls (P = 0.009), but no significant association remained after multivariate analysis. ETEC and EAggEC are frequently detected in returned travelers with diarrhea. The presence of ETEC strains is associated with acute but not with persistent diarrhea. 相似文献
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Nash RA; Schuening FG; Seidel K; Appelbaum FR; Boone T; Deeg HJ; Graham TC; Hackman R; Sullivan-Pepe M; Storb R 《Blood》1994,83(7):1963-1970
Recombinant canine granulocyte-macrophage colony-stimulating factor (rcGM-CSF) was studied in normal dogs and in dogs receiving otherwise lethal total body irradiation (TBI) without marrow transplant. Five normal dogs receiving 25 micrograms/kg of rcGM-CSF by subcutaneous (SC) injection twice daily (BID) for 14 days showed increases in peripheral blood neutrophil counts of three to five times the baseline. Platelet counts decreased during administration of rcGM-CSF to a mean nadir of 52,800. Ten dogs received 400 cGy TBI at 10 cGy/min from two opposing 60Co sources and no marrow graft. Within 2 hours of TBI, rcGM-CSF was begun at a dose of 50 micrograms/kg SC BID for 5 doses and then continued at 25 micrograms/kg SC BID for 21 days. Only 1 of the 10 dogs receiving rcGM-CSF survived with complete and sustained recovery of hematopoiesis. One of 13 historical control dogs survived after 400 cGy with no hematopoietic growth factor or marrow infusion. Results with rcGM-CSF were compared with previous and concurrent data with G-CSF studied in the same model. Of 10 dogs receiving G-CSF, 8 survived with complete and sustained hematopoietic recovery, a significantly better survival than that seen with rcGM-CSF (P = .006). Neutrophil counts were sustained at higher levels after TBI for the first 18 days in the G-CSF group (P < .016) and the neutrophil nadirs were higher. No differences in neutrophil nadirs were noted between the rcGM-CSF and control groups. Dogs treated with rcGM-CSF experienced a more rapid decline of platelet counts than G-CSF-treated or control dogs over the first 18 days (P < .001). The nadir of the platelet count was higher in the control group than in either the G-CSF or rcGM-CSF group and no significant difference was observed between the G-CSF and rcGM-CSF groups. After otherwise lethal TBI (400 cGy) in dogs, rcGM-CSF was not effective in promoting hematopoietic recovery or improving survival. 相似文献