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  • 1
    ISSN: 1432-2277
    Keywords: Key words Immunosuppression ; FTY 720 ; rat ; small bowel transplantation ; FTY 720 ; immunosuppression ; rat ; small bowel transplantation ; Rat ; small bowel transplantation ; FTY 720 ; Small bowel transplantation ; rat ; FTY 720
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the present study, we examined the immunosuppressive effect of a new drug, FTY 720, on small bowel transplantation (SBT) in rats. Grafts from (LEW × BN) F 1-to-LEW rats treated with FTY 720 at 0.5 mg/kg from day 0 to 14 post-SBT survived significantly longer than untreated grafts. In addition, the administration of FTY 720 combined with cyclosporin (CyA; 5 mg/kg per day) had a synergistic effect on allograft survival. The graft-versus-host reaction (GVHR) that occurred in the LEW-to-F 1 rats was markedly reduced after the administration of FTY 720. FTY 720 combined with a low dose of CyA completely abrogated GVHR without any adverse reaction. FTY 720 treatment resulted in a significant decrease in the number of lymphocytes in the peripheral blood and the spleen, but the number of peripheral neutrophils was unchanged. Thus, FTY 720 would appear to be an ideal drug to combine with CyA in order to control the immune reaction after SBT.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2277
    Keywords: Key words Nitric oxide ; Near-infrared spectroscopy ; Nitrosyl hemoglobin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Near-infrared spectroscopy (NIRS) is a noninvasive biomeasurement system with rays in the near-infrared region that possess high permeability to biological tissues. NIRS was applied to liver allografts undergoing rejection in rats treated with deoxyspergualin (DSG) or tacrolimus (FK506). The nitrosyl hemoglobin (Hb) levels detected in the liver grafts increased 3 days and 5 days after grafting in both allogeneic and syngeneic transplantation. The levels on day 8 remained high in the allogeneic graft, but markedly decreased in the syngeneic graft. Although the serum levels of nitrite and nitrate were extremely low 8 days after grafting in allografted recipients treated with DSG or FK506, the nitrosyl-Hb level in DSG-treated graft was much higher than that in FK506-treated graft. There was no significant difference in survival time between DSG-treated and FK506-treated recipients. In conclusion, DSG and FK506 have a different effect on NO production in allografted liver with ongoing rejection, and circulating nitrite and /nitrate levels do not reflect the local levels of NO in the graft.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-5922
    Keywords: endoscopic examination ; hyperacute rejection ; second-set rejection ; sensitization ; small bowel transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In the presensitized recipient who has been exposed to donor antigens, second-set rejection takes the form of severe hyperacute graft rejection. Secondset allograft rejection was studied following small bowel transplantation in the rat. Heterotopic intestinal grafting was performed from DA (RT1a) donors to PVG (RT1c) recipients 4 weeks after DA skin sensitization. The endoscopic images and histological specimens were compared with those of syngeneic and firstset rejected grafts. Endoscopically, diffuse erosions of the graft were detected from day 1. Mucosal necrosis progressed rapidly, and was accompanied by massive bleeding on days 3–5. These findings were similar to the course of severe necrotizing hemorrhagic enteritis. Histologically, interstitial edema and hemorrhage with massive infiltrations of neutrophils were manifested from day 1. Mesenteric vessels were completely occluded by thrombi on days 3–5. The grafted intestine had became totally necrotic by day 5. Microscopic findings strongly suggested that destructive graft necrosis was due to vascular damage caused by humoral factors. All the presensitized rats (n=11) died showing systemic septic signs by day 11 after small bowel transplantation. We concludes that lethal hyperacute rejection occurred in presensitized recipients, even when the graft was transplanted heterotopically. Endoscopic evaluation is beneficial for the early diagnosis of graft rejection. Immediate graft removal should be mandatory as a rescue treatment in second-set rejection of the small intestine.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1436-2813
    Keywords: Key Words: graft-versus-host disease ; surgical damage ; endotoxin ; stress hormone ; cytokine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 8 or 1.5 × 108 cells/350 g body weight were injected via the tail vein into (LEW × BN)F1 rats. The injection of 4 × 108 of LEW rat splenocytes induced lethal GVHD in all nontreated F1 rats, while 1.5 × 108 of LEW splenocytes did not induce any signs of GVHD. However, when the F1 rats had received the same dose of parental LEW lymphocytes in combination with portal clamping, 14 recipients out of the 15 rats (93%) suffered GVHD and 10 rats (67%) died from GVHD. Interestingly, portal clamping 7 days after the injection enhanced the incidence of GVHD, whereas no GVHD was observed in the intervention group either 3 or 7 days prior to the cell transfusion. When 1.5 × 108 of allogeneic lymphocytes were injected intravenously togather with 0.1–1.0 mg/kg of endotoxin instead of portal clamping, the injection led the early death by GVHD, while the injection of methylpredonisolone did not enhance GVHD. These results thus indicate that either simultaneous or delayed surgical intervention has the potential to trigger a dormant state in transferred alloreactive lymphocytes.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1436-2813
    Keywords: graft-versus-host disease ; surgical damage ; endotoxin ; stress hormone ; cytokine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of surgical intervention on the incidence and augmentation of graft-versus-host disease (GVHD) were studied in the rat. To elicit GVHD, splenocytes from parental LEW rats at a dose of 4×108 or 1.5×108 cells/350g body weight were injected via the tail vein into (LEW×BN)F1 rats. The injection of 4×108 of LEW rat splenocytes induced lethal GVHD in all nontreated F1 rats, while 1.5×108 of LEW splenocytes did not induce any signs of GVHD. However, when the F1 rats had received the same dose of parental LEW lymphocytes in combination with portal clamping, 14 recipients out of the 15 rats (93%) suffered GVHD and 10 rats (67%) died from GVHD. Interestingly, portal clamping 7 days after the injection enhanced the incidence of GVHD, whereas no GVHD was observed in the intervention group either 3 or 7 days prior to the cell transfusion. When 1.5×108 of allogeneic lymphocytes were injected intravenously togather with 0.1–1.0 mg/kg of endotoxin instead of portal clamping, the injection led the early death by GVHD, while the injection of methylpredonisolone did not enhance GVHD. These results thus indicate that either simultaneous or delayed surgical intervention has the potential to trigger a dormant state in transferred alloreactive lymphocytes.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1573-0603
    Keywords: Dichloromethylene diphosphate ; Hepatic stellate cell isolation ; Liposome ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Hepatic perisinusoidal cell population consists of hepatic stellate cells, Kupffer cells, endothelial cells, and Pit cells. These cells are isolated by enzymic digestion and purified by density gradient centrifugation. With isolation of stellate cells, conventional method is unable to eliminate the contamination of Kupffer cells because the densities of these two cells are similar. We report here an improved method for isolation of highly purified hepatic stellate cells, using dichloromethylene diphosphate (CL2MDP), which has selective cytotoxicity of Kupffer cells. Three days after the single intravenous administration of liposome-encapsulated CL2MDP, the Kupffer cells disappeared almost completely from the liver. Following Percoll density gradient centrifugation, the purity of the hepatic stellate cells exceeded 98% without any contamination of the Kupffer cells. Kupffer cells are reported to affect the physiological functions of stellate cells. The availability of highly purified stellate cells will facilitate the investigation of their functions in primary culture.
    Type of Medium: Electronic Resource
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