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Analogs of MCD peptide were synthesized by solid-phase methods. Positive charges were deleted at the N-and/or C-terminus, including the helical portion of the molecule. Four peptides were prepared by removing residues 16–18 (Arg-Lys-Ile), 1–2 (Lys), 1–2 and 16–18 and by acetylation of the amino end (Ile). Analogs were tested on mast cells for histamine-releasing activity. Although the helicity of these derivatives, determined by circular dichroism (CD), was not significantly different from the native MCD peptide, two analogs with C-terminal deletions showed a 5- to 10-fold decrease in activity. These findings suggest that the C-terminus is more important than the N-terminus in determining bioactivity of MCD peptide.  相似文献   
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The effect of increasing intravenous doses of synthetic salmon calcitonin (0.0044, 0.0088, 0.0175, and 0.0350 iu/kg per min) versus placebo on the fasted gall-bladder volume was assessed in seven normal subjects according to a double-blind study protocol. In addition, the action of calcitonin on meal-induced gall-bladder emptying was examined. Gall-bladder volumes were measured by means of real-time ultrasonography. Calcitonin evoked a dose-dependent relaxation of the fasted gall-bladder. A statistically significant increase of the fasted gall-bladder volume was observed with 0.0175 (23.4 +/- 5.5 cm3 placebo versus 33.9 +/- 7.7 cm3 calcitonin, P less than 0.001) and 0.0350 (21.4 +/- 4.6 cm3 placebo versus 36.1 +/- 8.4 cm3 calcitonin, P less than 0.01) iu/kg per min calcitonin, whereas a mean increase of the gall-bladder volume amounted to 32.1% and 46.5%, respectively. A significant delay of the gall-bladder emptying after calcitonin was reflected by a decrease of the ejection fraction: 23.2 +/- 8.3% calcitonin versus 57.8 +/- 6.9% placebo (P less than 0.02) at 20 min, and 40.5 +/- 8.8% calcitonin versus 67.2 +/- 3.8% placebo (P less than 0.02) at 30 min after the test meal. Calcitonin is concluded to have a potent relaxing effect on the human gall-bladder.  相似文献   
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The purpose of this study was to determine if PTCA of the infarct related coronary artery (IRA) in the late phase of myocardial infarction (MI) can improve autonomic regulation of sinus rhythm and electrical stability of the myocardium measured by heart rate variability (HRV), QT, QTc, and its dispersion (QTd) and if any correlation exists among these measures. The study was performed in 25 patients (21 male, age: 50 ± 9 years, EF: 52%± 11%) in the late phase of MI (2.5 ± 1.5 months). HRV parameters were calculated automatically. QT, QTc, and QTd were measured manually from a 12-lead surface ECG (50 mm/s). All measurements were made before and 3–5 days after PTCA. Day and night parameters of HRV were sampled over two periods: 2 pm to 10 pm (day) and 10 pm to 6 am (night). Parameters of HRV measured from whole recordings were significantly higher after successful PTCA: SDRR (116 31 vs 128 ± 38 ms), SD (55 ± 17 vs 62 ± 22 ms), rMSSD (30 ± 13 vs 36 ± 14 ms) and HF (246 ± 103 vs 417 ± 224 ms2). Significant differences were found during daytime for SD, rMSSD, and HF, and during nighttime for SDRR, SDANN. QT interval duration, QT corrected to the heart rate, and QT dispersion were significantly lower after PTCA (QTd: 54 ± 15 vs 39 ± 12 ms). There was no correlation between HRV and QT values before PTCA. High correlations were found after the procedure, particularly between QTd and nighttime HRV. Conclusions: PTCA of IRA in the late phase of MI enhances sympathovagal regulation of the cardiac rhythm and the electrical stability of the heart, which may be prognostically important.  相似文献   
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Background: Catalase is an intracellular antioxidant enzyme that is mainly located in cellular peroxisomes and in the cytosol. This enzyme plays a significant role in the development of tolerance to oxidative stress in the adaptive response of cells and tissues. The aim of the present study was to examine the association between the –262C/T polymorphism in the catalase gene and delayed graft function (DGF), acute rejection and chronic allograft nephropathy of kidney allografts. Methods: One hundred eighty‐seven recipients of first renal transplants were included in the study. The histories of the patients were analysed regarding DGF, acute rejection and chronic allograft nephropathy. The polymorphism –262C/T in the catalase gene was analysed using the polymerase chain reaction – restriction fragment length polymorphism (PCR‐RFLP) method. Results: The risk of DGF was significantly lower in T allele carriers compared with CC homozygotes: odds ratio = 0.34, 95% confidence interval = 0.17–0.67, P = 0.001. There were no statistically significant associations between the studied polymorphism and acute rejection or chronic allograft nephropathy. Conclusion: The results of this study suggest that –262C/T polymorphism in the catalase gene is associated with DGF in kidney allograft recipients.  相似文献   
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Using the solid-phase procedure, a linear 29-peptide with the reported sequence of trypsin inhibitor CMTI III was synthesized and oxidized to give three disulphide bridges. After affinity chromatography on an immobilized anhydrotrypsin column the synthetic product was shown by various physical techniques to be identical with the trypsin inhibitor CMTI III from squash seeds (Cucurbita maxima).  相似文献   
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We have previously shown that the substitution of 8-ornithine and 2-O-methyltyrosine alone and in combination in [1-deaminopenicillamine] oxytocin (dPOT) brought about enhancements in antagonistic potencies to responses to oxytocin in vivo. To explore the effects of these subtitutions in analogs of dPOT containing larger alkyl substitutents on the β carbon at position 1 and on the tyrosine residue at position two, the following six analogs were synthesized: [1-(β-mercapto-β, β-diethylpropionic acid), 8-ornithine] vasotocin (1, dEt2OVT); [1-β-mercapto-β, β-cyclopentamethylenepropionic acid), 8-ornithine] vasotocin [2, d(CH2)5OVT); [1-β-mercapto-β, β-diethylpropionic acid), 2-O-methyltyrosine, 8-ornithine]vasotocin [3, dEt2 Tyr(Me)OVT]; [1-(β-mercapto-β, β-diethylpropionic acid), 2-O-ethyltyrosine, 8-ornithine] vasotocin [4, dEt2 Tyr(Et)OVT]; [1-β-mercapto-β', β-cyclopentamethylenepropionic acid), 2-O-methyltyrosine, 8-ornithine] vasotocin [5, d(CH2)5 Tyr(Me)OVT]; [1-β-mercapto-β, β-cyclopentamethylenepropionic acid), 2-O-methyltyrosine, 8-ornithine] vasotocin [6, d(CH2)5 Tyr(Et)OVT]. The required protected intermediates were synthesized by a combination of solid-phase synthesis and by individual 8 + 1 couplings in solution. All six analogs antagonize the actions of oxytocin on the rat uterus in the absence of Mg2+, in the presence of 0.5 mM Mg2+ and in situ. They also antagonize milk ejection responses to oxytocin, and the vasopressor responses to arginine vasopressin, and all have very low antidiuretic activities. With pA2 values of 7.35 ± 0.08 and 7.37 ± 0.17, respectively, compounds 3 and 5 are the two most potent in vivo antagonists of oxytocin reported to date.  相似文献   
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Peptides containing phosphoserine or phosphothreonine were synthesized by solid phase methods. Phosphoserine and phosphothreonine were incorporated into peptides using Boc-diphenylphosphono esters of serine and threonine and standard DCC/HOBt coupling. The phenylphosphoesters were not removed when the peptides were cleaved from the resin by HF or by trifluoromethane sulfonic acid, but were subsequently removed by catalytic hydrogenation. Phosphopeptides were purified by HPLC and by Fe+3-Chelex chromatography and their identity verified by mass spectrometry. Two peptides, Leu-Arg-Arg-Ala-Ser(P)-Leu-Gly and Leu-Arg-Arg-Ala-Thr(P)-Leu-Gly, were prepared by both enzymatic and chemical methods and had identical properties.  相似文献   
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