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91.
GX He SH Krawczyk S Swaminathan RG Shea JP Dougherty T Terhorst VS Law LC Griffin S Coutré N Bischofberger 《Canadian Metallurgical Quarterly》1998,41(13):2234-2242
2'-Deoxyguanosine (G) analogues carrying various hydrophobic substituents in the N2 and C8 positions were synthesized and introduced through solid-phase synthesis into 15-mer oligodeoxynucleotide, GGTTGGTGTGGTTGG, which forms a chairlike structure consisting of two G-tetrads and is a potent thrombin inhibitor. The effects of the substitutions at N2 and C8 of the G-tetrad-forming G residues on the thrombin inhibitory activity are relatively small, suggesting that these substitutions cause relatively small perturbations on the chairlike structure formed by the oligodeoxynucleotide. Introduction of a benzyl group into N2 of G6 and G11 and naphthylmethyl groups into N2 of G6 increased the thrombin inhibitory activity, whereas other substituents in these positions had almost no effect or decreased the activity. Particularly, the oligodeoxynucleotide carrying a 1-naphthylmethyl group in the N2 position of G6 showed an increase in activity by about 60% both in vitro and in vivo. Substitutions on the N2 position of other G residues had little effect or decreased the activity. Introduction of a relatively small group, such as methyl and propynyl, into the C8 positions of G1, G5, G10, and G14 increased the activity, presumably due to the stabilization of a chairlike structure, whereas introduction of a large substituent group, phenylethynyl, decreased the activity, probably due to the steric hindrance. 相似文献
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BACKGROUND: Mixed bone marrow chimerism reliably produces donor-specific transplantation tolerance for a variety of solid organ and cellular grafts. We used a rat heterotopic tracheal transplant model for chronic rejection to investigate whether mixed chimerism could successfully prevent obstructive airway disease. METHODS: Mixed allogeneic chimeras were prepared by reconstituting lethally irradiated Wistar-Furth (WF) recipients with a mixture of 5 x 10(6) T-cell-depleted syngeneic (WF) and 100 x 10(6) T-cell-depleted allogeneic (ACI) bone marrow cells (ACI + WF --> WF). Mixed chimerism was present in all animals 28 days after bone marrow transplantation. Donor-specific, syngeneic, or major histocompatibility complex (MHC)-disparate allogeneic tracheas were implanted in recipient's omentum and removed for histologic analysis 30 to 150 days after transplantation. RESULTS: At 30 days after implantation, median luminal obstruction grades (0=none, 4=complete) of syngeneic and allogeneic tracheas were 0 and 4, respectively. Donor-specific (ACI) tracheas implanted in chimeric (ACI + WF --> WF) recipients were remarkably free of obstruction (median luminal obstruction grade=0 at 150 days) and had excellent preservation of respiratory epithelium. Third-party F344 tracheas implanted in chimeric recipients developed progressive luminal obstruction (grade 2 at 30 days, grade 3 at 90 days). CONCLUSIONS: Mixed allogeneic chimerism induces donor-specific tolerance and prevents development of the characteristic fibroproliferative obstructive lesion of bronchiolitis obliterans in a rat heterotopic tracheal transplant model. Excellent preservation of tracheal structure and morphology was achieved across major and minor histocompatibility barriers. 相似文献
96.
AM Dvorak PF Weller VS Harvey ES Morgan HF Dvorak 《Canadian Metallurgical Quarterly》1993,101(2):136-142
The majority of equations used to predict values for basal metabolic rates (BMRs) are the result of indirect calorimetry measurements performed in the 1930s and 1950s. To assess the reliability of these equations in predicting the resting energy expenditure (REE) of the children in our community, indirect calorimetry was performed on 92 male and 107 female healthy children 2-3 h postprandial. Each individual was measured for a duration of 15-20 min. The data for analysis were obtained from 5-15 min steady-state periods. Subjects ranged in age from 5 to 16 years. The results were compared with BMRs calculated from the Harris-Benedict equation (Harris J, Benedict F. A biometric study of basal metabolism in man. Washington, DC: Carnegie Institute of Washington, publication no. 279, 1919.), the Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU) equations, and the equations proposed by Schofield for use by the 1985 FAO/WHO/UNU Nutrition Committee. The values predicted by the FAO/WHO/UNU and Schofield equations were consistent with the measured resting values for all the children in the study population. Ninety-two children weighed between 90-110% of their ideal body weight. When the measured REE and estimated BMR were compared by gender and age in these children, the Schofield equations provided the best estimates. Ninety-four of the study subjects weighed > 110% of their ideal body weight. The predicted estimates by all equations were consistent with the measured values in this subgroup of the population. We conclude that the FAO/WHO/UNU and Schofield equations are reliable estimates of metabolic rate in healthy children when measurement of REE is not possible. 相似文献
97.
The involvement of the strictly conserved tryptophan-25 (W25) residue in the structural stability and omega-amino acid ligand binding properties of the recombinant (r) kringle 2 (K2) domain of tissue-type plasminogen activator (tPA) has been investigated. Two conservative mutants were constructed and expressed that contained W25-->F and W25-->Y substitutions. The binding (dissociation) constants (Kd) for three ligands, viz., 6-aminohexanoic acid (EACA), 7-aminoheptanoic acid (7-AHpA), and L-lysine (Lys), to these polypeptides were determined by intrinsic fluorescence titrations. In the case of r-[K2tPA/W25F], the Kd values for these ligands were found to be 37, 16, and 89 microM for EACA, 7-AHpA, and Lys, respectively. For r-[K2tPA/W25Y], the Kd values for these same ligands were 64, 9, and 115 microM, respectively. The wild-type (wt) kringle domain possessed Kd values of 43, 6, and 85 microM for EACA, 7-AHpA, and Lys, respectively. The effect of these mutations on the stability of the r-[K2tPA] domain has been examined by differential scanning colorimetry. The temperature of maximum heat capacity (Tm) of wt-r-[K2tPA] (75.6 degrees C) was dramatically reduced to 50.8 and 58.0 degrees C for r-[K2tPA/W25F] and r-[K2tPA/W25Y], respectively. In the presence of EACA, the Tm values were increased to 86.1, 61.7, and 68.7 degrees C, respectively, indicating that EACA does interact with the r-[K2tPA] mutants and stabilizes their native conformations, similar to the case with wt-r-[K2tPA].(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
98.
AA Firsov VS Dombrovski? IB Kadenatsi EV Gagaeva LS Strachunski? 《Canadian Metallurgical Quarterly》1996,41(4):36-43
In the bioavailability studies with drugs biotransformed to biologically active metabolities only the concentrations of the parent drug (PD) are usually taken into account even when the pharmacokinetic data on the metabolite(s) (M) are available. However, such data may be useful as an alternative source for the bioavailability determination. Moreover, the clinical outcomes often depend on both the PD and M concentrations. The aim of the study performed with two rifampicin formulations, tablets and dragee, was to correlate the pharmacokinetic parameters of the PD and 25-O-deacetylrifampicin, a microbiologically active M of rifampicin, and to examine whether the bioavailability parameters based on the PD and M concentrations were compatible. The serum concentrations of the PD and M were determined in 8 healthy volunteers by HPLC. Despite different patterns of the PD and M pharmacokinetic profiles the PD peak concentration (Cmax) and especially the AUC correlated with Cmax or the AUC of the M (r = 0.76 and 0.92 respectively). Moreover, the extent of the absorption expressed as the AUC ratio for the PD correlated with the AUC ratio for the M (r = 0.86). However, neither the time to reach the maximum (tmax), nor the Cmax/AUC ratio, a measure of the absorption rate, based on the PD pharmacokinetic data correlated with the respective parameters calculated with using the M concentrations. Thus, only the estimates of the extent of the absorption and not of the absorption rate based on the PD and M data may be considered as compatible. 相似文献
99.
To survey the frequency of Lyme borreliosis (LB) and to evaluate its clinical presentation in Europe, we performed a questionnaire interview of a sample of physicians involved in the care of patients with LB. Reference laboratories in 15 European countries agreed to participate by distributing questionnaires to those clinicians who most frequently requested LB serology for their patients. The mean number of cases of LB per physician per country showed a longitudinal geographical gradient, with a higher number of patients seen in Eastern and Central Europe than in Western Europe. Skin involvement was seen in 58.9% of the patients, neurological involvement in 34.3%, joint involvement in 15.4% and cardiac involvement in 2%. About 30% of the patients had multisystem involvement. The frequency of the different manifestations varied greatly between countries. The frequency of diagnosis of LB and the number of serological tests requested were inversely correlated. 相似文献
100.
Biologic glue increases capillary ingrowth after cardiomyoplasty in an ischemic cardiomyopathy model
VS Chekanov GV Tchekanov MA Rieder R Eisenstein DM Wankowski DH Schmidt VV Nikolaychik PI Lelkes 《Canadian Metallurgical Quarterly》1996,42(5):M480-M487
The authors investigated the multi-step mechanism of healing after cardiomyoplasty, focusing on the process of angiogenesis. The authors contend that enhancement of angiogenesis and prevention of ischemia-reperfusion injuries immediately after muscle mobilization will be effective in improving cardiomyoplasty results. After cardiomyoplasty, autologous biologic glue (ABG) was administered between the latissimus dorsi muscle (LDM) and myocardium. By 2 months, a new pseudo interlayer was present that bridged the gap between the LDM and myocardium. Neovascularization was visible in the form of numerous small capillaries. Marked degeneration of the LDM was noted, possibly caused by muscle ischemia-reperfusion damage after mobilization. Pockets were created of ischemic and nonischemic LDM to test for angiogenesis. One was left free of ABG (control); one received ABG only; one received ABG and pyrrolostatin. Some of the capillaries were large and had erythrocytes inside. biopsy samples showed 9.4 +/- 1.9% of the sample was occupied by blood vessels (compared with 3.6 +/- 0.7% in control muscle). These preliminary studies prove the feasibility of the authors' concept and provide evidence that angiogenesis can accelerate the healing process and provide an organic bridge between the LDM and myocardium after cardiomyoplasty. 相似文献