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MAREPALLI H. RAO WEI YANG HENRY JOSHUA JEFFREY M. BECKER FRED NAIDER 《Chemical biology & drug design》1995,45(5):418-429
In an effort to explore the effect of ring size on the biologically active conformation of cyclic analogs of the mating pheromone α-factor (WHWLQLKPGQPMY) from Saccharomyces cerevisiae, eight cyclic tetrapeptides corresponding to the KPGQ portion of α-factor were synthesized. These N-α-acetyl/carboxyl amide terminal cyclic tetrapeptides were prepared on a 4-methylbenzhydrylamine resin using orthogonal Boc, Frnoc, OFm and OtBut protecting groups and HOBt-DIPC accelerated active esters or urethane-protected N-carboxyanhydrides. On-resin cyclization of the side-chain amino and carboxyl groups of the first and fourth residues, respectively, was performed with the BOP reagent to generate lactams containing 14–18 atoms. HF cleavage resulted in two products, the desired cyclic tetrapeptide and a major side product. All peptides were purified to near homogeneity (>99%) by using reversed-phase HPLC and were characterized by FABMS and 1H NMR. Certain constrained cyclic tetrapeptides appear to be a mixture of isomers at room temperature as evidenced by HPLC and NMR. The major side product has been identified as a cyclo dimer, obtained as a consequence of interchain cyclization on the resin. CD analysis in several solvents gives evidence that some of the cyclic tetrapeptides exist in β-turn conformations. © Munksgaard 1995. 相似文献
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Dilevalol (SCH 19927) is an antihypertensive agent with directvasodilating properties due to ß2-adrenergic receptoragonist activity and nonselective ß-receptor blockingactivity. In acute (single dose) oral and parenteral studiesa low order of toxicity was observed. Clinical signs observedat the higher doses included salivation, prostration, tremors,and convulsions. In multidose oral studies dilevalol producedan increase in mean absolute and/or relative heart weights observedas early as 1 month in the high-dose (300 mg/kg) rats and atall dose levels (35, 90, 220 mg/kg) in rats treated for 1 year.There were no microscopic changes that could be associated withthe change in heart weight. Intraalveolar macrophages were observedin the lung tissue of rats treated for 3 months or 1 year withan increase in relative lung weights noted in the high-dose(220 mg/kg) group treated for 1 year. In a 2-year rat study,no evidence of oncogenicity was observed. On the basis of thesestudies, dilevalol has a low order of toxicity and lacks oncogenicpotential in the rat. 相似文献
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HUGH CALKINS RAFEL EL-ATASSI ANGEL LEON STEVEN KALBFLEISCH MARK BORGANELLI JONATHAN LANGBERG FRED MORADY 《Pacing and clinical electrophysiology : PACE》1992,15(5):771-778
Atrial arrhythmias occur frequently in the setting of increased atrial size and pressure. This may result from contraction-excitation feedback. The objective of this study was to investigate the effect of alterations in atrial pressure, induced by varying the atrioventricular (AV) interval, on atrial refractoriness, and on the frequency of induction of atrial fibrillation. Twenty-seven patients without structural heart disease participated in the study. In each patient the atrial effective (ERP) and absolute refractory period (ARP) were measured during AV pacing at a cycle length of 400 msec and AV intervals of 0, 120, and 160 msec. The ERP was defined as the longest extrastimulus coupling interval that failed to capture with an extrastimulus current strength of twice the stimulation threshold. The ARP was defined in a similar manner with an extrastimulus current strength of 10 mA. The ERP and ARP were determined during continuous pacing using the incremental extrastimulus technique. A subset of patients had the pacing protocol performed during autonomic blockade. As the AV interval was increased from 0 to 160 msec, the peak right atrial pressure decreased from 16 +/- 4 mmHg to 7 +/- 3 mmHg and the mean right atrial pressure decreased from 7 +/- 3 mmHg to 3 +/- 22 mmHg (P less than 0.001). The atrial ERP and ARP did not change with alterations in the AV interval. There was no difference in the frequency of induction of atrial fibrillation. Similar results were obtained during autonomic blockade. These findings suggests that the phenomenon of contraction-excitation feedback may not be of importance in the development of atrial arrhythmias in patients without structural heart disease. 相似文献
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FRED B. CHARATAN MD 《Special care in dentistry》1985,5(5):213-216
To achieve successful treatment in the geropsychiatric patient, the dentist should understand the difference between depression and dementia and be able to adapt his or her approach to the patient, depending on the diagnosis. The practitioner should also take time to review the geropsychiatric patient's clinical record and appreciate the patient's behavioral potentialities. Before starting dental treatment, the practitioner should plan appropriate psychotropic medications as a form of psychopharmacologic crisis intervention. This method reflects the team approach in geriatric medicine and dentistry. 相似文献
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FRED R. SMITH Ph.D. M.D. ARVEY I. ROGERS M.D. 《The American journal of gastroenterology》1980,74(3):282-284
A case of vasoactive intestinal peptide-producing adenoma of the tail of the pancreas (VIP) successfully managed by surgical resection is presented. Peripheral venous VIP levels correlated with the severity of the diarrhea. Intraoperatively, the VIP levels in the splenic and portal veins were 485 and 100 pg./ml, respectively. These data suggest that preoperative selective transhepatic venous catheterization for VIP sampling might be used to establish the site of VIP production and, thereby, direct surgical management. This technic requires further evaluation regarding its role in this clinical setting. 相似文献
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PAUL S. CASAMASSIMO DDS MS LARRY M. COFFEE DDS FRED J. LEVITON MPA 《Special care in dentistry》1988,8(2):77-81
Two mobile treatment programs using portable equipment transported in vans to serve homebound persons in Denver and Chicago are compared for types of patients treated, use by local dentists, types of services provided, fees generated, and costs involved in operation during the 2-year period (1985–86). Both programs treated a similar, largely nursing home-based white female population that was predominantly older. Volunteer dentist participation varied greatly, with more than twice the number of dentists using the service in Chicago. Both programs accomplished essentially the same number of visits for the biennium studied, with 1,324 for Chicago and 1,320 for Denver. The Denver program was more efficient, generating more visits each time a dentist used the program. The services provided in total were about the same for both programs, with Denver generating 4,887 procedures and Chicago 4,602 for the biennium, but Denver had a more favorable ratio of diagnostic to treatment services. The costs of both programs were close, averaging about $60,000 per year. Denver was able to generate far more in equivalent fees than Chicago for the biennium, but Chicago dentists donated a greater percentage of services (67) than did Denver dentists (62). 相似文献