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  • 1
    ISSN: 1436-2813
    Keywords: concordant lung xenograft ; antidonor antibodies ; macrophages/monocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study was conducted to investigate the functional and morphological aspects of orthotopic lung xenograft rejection in a concordant hamster-to-rat donor-recipient species combination. By postoperative day (POD) 3, allotransplanted grafts demonstrated good aeration, but infiltrates were seen in all the xenotransplanted lungs. Antihamster lymphocytotoxic antibody titers increased to 5.2±1.1 by POD 3 (P〈0.05 vs POD 1) and reached 7.0±0.8 by POD 5 (P〈0.05 vs PODs 1 and 3). The CD4+/CD8+ ratio in peripheral blood lymphocytes increased significantly on POD 3 (P〈0.05 vs untransplanted), but decreased by POD 5 (P〈0.05). Histologically, on POD 3 the xenotransplanted grafts were characterized by perivascular cellular infiltrates and edema. Cytologically, the cells consisted of small round lymphocytes, monocytes, and occasional neutrophils. Immunohistochemical analysis showed heavy IgM and C3 deposits in the vascular endothelium, without any IgG deposits. Allotransplanted grafts showed moderate W 3/25+(28.3±17.3%) and MRC OX8+(38.7±0.7%) cellular infiltrations on POD 3, but ED1+(8.0±3.7%) cells were rare. Conversely, in the xenotransplanted grafts, ED1+(34.2±16.4%) cells were more prevalent than MRC OX8+(18.1±16.5%) cells on POD 3, at P〈0.01 and P〈0.05 vs allograft, respectively. These results indicate that both antidonor antibodies and macrophages/monocytes play an important role in the concordant lung xenograft rejection.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1436-2813
    Keywords: pulmonary hypertension ; rat ; monocrotaline ; single lung transplantation ; contralateral lung injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The hemodynamic effect and degree of damage in grafts of single lung transplants for pulmonary hypertension were studied in rats with monocrotaline-induced pulmonary hypertension. Inbred male Lewis rats (weight 200–230 g) were divided into two groups. Group 1 (control group,n = 16) underwent isogenic left lung transplantation, while group 2 (n = 15) received an intravenous administration of monocrotaline (80 mg/kg i.v.) and underwent isogenic left single lung transplantation 3 weeks later. Hemodynamic evaluations were performed prior to transplantation, at 1h postoperatively, and on days 3 and 7 after transplantation. Mean pulmonary arterial pressure (mPAP) rapidly declined after transplantation in group 2, from 39.3 ± 8.7 mmHg to 18.5 ±3.0 mmHg 1h after transplantation, and remained stable on day 7 after tranaplantation. No significant difference in the mPAP between the two groups was observed after tranaplantation. The extravascular lung water volume (ELWV: dry/wet ratio) in the right lung of group 2 significantly increased on day 3 (0.86 ± 0.02) (P 〈 0.01), and subsequently decreased to control levels on day 7 (0.83 ± 0.02). There was no significant difference in the ELWV in the grafted lungs between the two groups (0.84 ± 0.03 vs 0.86 ± 0.04), but there was tendency toward an increase in ELWV in group 2 on days 3 and 7. These data thus demonstrated that a hemodynamic improvement was obtained by single lung transplantation; however the degree of graft damage was remarkable in the pulmonary hypertension group.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2277
    Keywords: Xenotransplantation, lung, rat ; Rat, lung, xenotransplantation ; Splenectomy, deoxyspergualin, lung transplantation ; Deoxyspergualin, splenectomy, lung transplantation ; Lung transplantation, rat, xenografting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The efficacy of 15-deoxyspergualin (DSG), cyclosporin A (CyA), and splenectomy-alone or in combination-in prologing the survival of concordant lung xenotransplants was studied in the hamster-to-rat model. In the untreated group, rejection occurred within 3 days, with an elevation of lymphocytotoxic antibody titers. The rejected lung revealed that ED1+cells were more prevalent than MRC OX8+cells in the perivascular infiltrates. In the DSG group, the antibody response was suppressed and median survival increased to 7.5 days. The rejected lungs demonstrated a highly significant depression in ED1+cellular infiltration and a moderate MRC OX8+cellular infiltration. When maintenance CyA was combined with a short course of DSG, survival dramatically increased to beyond 100 days. There were no deposits of IgM, IgG, or C3 or of any cell infiltrate in the grafts of two animals sacrificed 107 and 119 days post-transplantation. We conclude that initial treatment with DSG combined with continuous CyA can suppress acute rejection in the hamster-to-rat lung xenograft model, resulting in longterm graft survival.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 43 (1994), S. 1118-1123 
    ISSN: 0006-3592
    Keywords: enzymatic synthesis ; peptide synthesis ; thermolysin ; immobilized enzyme ; aspartame precursor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: N-(Benzyloxycarbonyl)-L-aspartyl-L-phenylalanine methyl ester (Z-AspPheOMe), a precursor of the synthetic sweetner asparatame, was synthesized from N-(benzyloxycarbolyl)-L-aspartic acid (Z-Asp) and L-phenylalanine methyl ester (PheOMe) with an immobilized thermolysin in various organic solvents. We found that in tert-amyl alcohol containing a small amount of water the immobilized enzyme showed a high activity comparble to that in ethyl acetate with quite a high stability. The immobilized enzyme was fully stable up to 70°C in tert-amyl alcohol in the absence of the subatrate, and up to 50°C in the presence of the substrate. The high stability in the presence of the substrate was found due to the fact that the release of calcium ions, the stabilizing factor of thermolysin, is suppressed.The substrate concentration dependence of the initial synthetic rate with the immobilized enzyme was quite different from that with the free enzyme in the biphasic system, in contrast to that in ethyl acetate. Finally, Z-AspPheOMe was continuously synthesized in a column reactor using 200 mM PheOMe and 120 mM Z-Asp as the substrate for over 300 h at 45°C and a space velocity of 1 h-1 without any loss of acivity. © 1994 John Wiley & Sons, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 43 (1994), S. 1108-1117 
    ISSN: 0006-3592
    Keywords: enzymatic synthesis ; peptide synthesis ; thermolysin ; immobilized enzyme ; aspartame precursor ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: N-(Benzyloxycarbonyl)-L-aspartyl-L-phenylalanine methyl ester (Z-AspPheOMe), a precursor of the aspartame, and N-(benzyloxycarbonyl)-L-phenylalanyl-Lphenylalanine methyl ester (Z-PhePheOMe) were synthesized from the respective amino acid derivatives with an immobilized thermolysin (EC 3.4.24.4) in ethyl acetate. Various factors affecting the synthesis of these dipeptide precursors were clarified. The initial synthetic rate was the highest at the water content of 3.5% for both reactions. The substrate concentration dependencies of the initial synthetic rate of Z-AspkPheOMe and Z-PhePheOMe with the immobilized enzyme in ethyl acetate were different from those in an aqueous buffer solution saturated with ethyl acetate but similar to those in the aqueous/organic biphasic system using the free enzyme. Particularly, the initial synthetic rate of Z-AspPhOMe increased in order higher than first order with respect to the concentration of L-phenylalanine methyl ester (PheOMe), whereas it decreased sharply with the concentration of N-(benzyloxycarbonyl)-L-aspartic acid (Z-Asp). Such kinetic behavior could be explained by regarding the inside of the immobilized enzyme as being a biphasic mode composed from the organic phase and aqueous phase where the enzymatic reaction takes place. The reaction in the aqueous/organic biphasic system using the free enzyme could be simulated by taking into consideration the partition of the substrate and the initial rate of synthesis in the aqueous buffer saturated with ethyl acetate. Based on this analysis, the rate of reaction with the immobilized enzyme in ethyl acetate could also be predicted. Z-AsPheOMe and Z-PhePheOMe were synthesized by the fed-batch method where the acid component of the substrate was intermittently added during the course of reaction and by the batch method. In the synthesis of Z-AspPheOMe, the synthetic rate and maximum yield of reaction as well as the stability of the immobilized enzyme were higher in the fed-batch reaction than those in the batch reaction. In the synthesis of Z-PhePheOMe, the results obtained by both methods were similar. © 1994 John Wiley & Sons, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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