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31.
L. A. DeFreest F. B. Mesfin L. Joseph D. J. McLeod A. Stallmer S. Reddy S. S. Balulad H. I. Jacobson T. T. Andersen J. A. Bennett 《Chemical biology & drug design》2004,63(5):409-419
Abstract: A synthetic peptide that inhibits the growth of estrogen receptor positive (ER+) human breast cancers, growing as xenografts in mice, has been reported. The cyclic 9‐mer peptide, cyclo[EMTOVNOGQ], is derived from α‐fetoprotein (AFP), a safe, naturally occurring human protein produced during pregnancy, which itself has anti‐estrogenic and anti‐breast cancer activity. To determine the pharmacophore of the peptide, a series of analogs was prepared using solid‐phase peptide synthesis. Analogs were screened in a 1‐day bioassay, which assessed their ability to inhibit the estrogen‐stimulated growth of uterus in immature mice. Deletion of glutamic acid, Glu1, abolished activity of the peptide, but glutamine (Gln) or asparagine (Asn) could be substituted for Glu1 without loss of activity. Methionine (Met2) was replaced with lysine (Lys) or tyrosine (Tyr) with retention of activity. Substitution of Lys for Met2 in the cyclic molecule resulted in a compound with activity comparable with the Met2‐containing cyclic molecule, but with a greater than twofold increase in purity and corresponding increase in yield. This Lys analog demonstrated anti‐breast cancer activity equivalent to that of the original Met‐containing peptide. Therefore, Met2 is not essential for biologic activity and substitution of Lys is synthetically advantageous. Threonine (Thr3) is a nonessential site, and can be substituted with serine (Ser), valine (Val), or alanine (Ala) without significant loss of activity. Hydroxyproline (Hyp), substituted in place of the naturally occurring prolines (Pro4, Pro7), allowed retention of activity and increased stability of the peptide during storage. Replacement of the first Pro (Pro4) with Ser maintains the activity of the peptide, but substitution of Ser for the second Pro (Pro7) abolishes the activity of the peptide. This suggests that the imino acid at residue 7 is important for conformation of the peptide, and the backbone atoms are part of the pharmacophore, but Pro4 is not essential. Valine (Val5) can be substituted only with branched‐chain amino acids (isoleucine, leucine or Thr); replacement by d ‐valine or Ala resulted in loss of biologic activity. Thus, for this site, the bulky branched side chain is essential. Asparagine (Asn6) is essential for activity. Substitution with Gln or aspartic acid (Asp), resulted in reduction of biologic activity. Removal of glycine (Gly8) resulted in a loss of activity but nonconservative substitutions can be made at this site without a loss of activity indicating that it is not part of the pharmacophore. Cyclization of the peptide is facilitated by addition of Gln9, but this residue does not occur in AFP nor is it necessary for activity. Gln9 can be replaced with Asn, resulting in a molecule with similar activity. These data indicate that the pharmacophore of the peptide includes side chains of Val5 and Asn6 and backbone atoms contributed by Thr3, Val5, Asn6, Hyp7 and Gly8. Met2 and Gln9 can be modified or replaced. Glu1 can be replaced with charged amino acids, and is not likely to be part of the binding site of the peptide. The results of this study provide information that will be helpful in the rational modification of cyclo[EMTOVNOGQ] to yield peptide analogs and peptidomimetics with advantages in synthesis, pharmacologic properties, and biologic activity. 相似文献
32.
甲胎蛋白、游离雌三醇及绒毛膜促性腺激素测定在产前诊断唐氏综合征中的应用 总被引:1,自引:0,他引:1
目的:探讨胎儿胎盘产物甲胎蛋白(AFP)、游离雌三醇(uE3)和β绒毛膜促性腺激素(β-hCG)水平与胎儿唐氏综合征发病的关系。方法:用放射免疫法测定17例妊娠唐氏综合征胎儿的孕妇(病例组)和131例妊娠正常胎儿孕妇(对照组)的外周血、羊水及脐血中AFP、uE3和β-hCG水平。结果:病例组孕妇外周血、羊水和脐血中AFP水平均低于对照组(P<0.05);uE3水平也均低于对照组(P<0.05);β-hCG水平均高于对照组(P<0.05)。结论:检测孕妇外周血中AFP、uE3、β-hCG可用于胎儿唐氏综合征的产前诊断 相似文献
33.
血小板α颗粒膜蛋白140检测在“病”与“证的”特异性联系 总被引:9,自引:3,他引:9
应用血小板α颗粒膜蛋白140(GMPˉ140)为血小板活化指标,测定了74例糖尿病、36例心血管疾病、53例肾脏疾病患者的血浆GMPˉ140浓度,并分别按病种及按是否有血瘀证分组比较了各组间的GMPˉ140测定值。结果表明:GMPˉ140在各疾病组患者均较正常人升高,三组间则无明显差异;而在血瘀及非血瘀证明之间则有明显差异。认为GMPˉ140有可能作为诊断血瘀证的一项实验室指标。 相似文献
34.
乙型肝炎病毒相关性肾炎α-干扰素治疗后的病理变化 总被引:4,自引:0,他引:4
目的探讨乙型肝炎病毒相关性肾炎经α-干扰素治疗的临床病理变化。方法32例HBV相关性肾炎给予α-干扰素100~300万U,肌肉注射,6个月为一疗程,比较治疗前后血清白蛋白浓度,24h尿蛋白定量及肾组织乙肝抗原、HBV-DNA、IgG、IgM、IgA阳性率。结果α-干扰素治疗后血清白蛋白浓度升高、尿蛋白定量下降;肾组织乙肝抗原、HBV-DNA、IgA、IgM、IgG阳性率均显著下降(P<0.01)。结论乙型肝炎病毒相关性肾炎经α-干扰素治疗后临床病理有较显著改善。 相似文献
35.
目的 :观察拉米夫定和干扰素联合治疗HBeAg阳性慢性乙型肝炎的疗效及其影响因素。方法 :64例HBeAg阳性的慢性乙型肝炎患者随机分成治疗组和对照组。治疗组32例 ,同时使用α干扰素及拉米夫定9个月 ,随后单用拉米夫定15个月,对照组32例 ,单用拉米夫定24个月 ,定期检测丙氨酸转氨酶 (ALT)、HBeAg、抗 -HBe、HBVDNA ,并作YMDD变异检测 ,两组在治疗结束时进行疗效评价。结果 :治疗组ALT复常率为90.6 % (29/32) ,对照组ALT复常率为87.5 % (28/32) ,两组差异无显著性 (P>0.05),治疗组HBeAg阴转率为68.8 % (22/32) ,对照组HBeAg阴转率为37.5 % (12/32) ,两组比较差异有显著性 (P<0.05) ,治疗组HBeAg/抗 -HBe血清转换率为53.1 % (17/32) ,对照组HBeAg/抗 -HBe血清转换率为25 % (8/32) ,两组比较差异有显著性 (P<0.05),治疗组HBVDNA阴转率为78.1 % (25/32) ,对照组HBVDNA阴转率为59.4 % (19/32) ,两组比较差异无显著性 (P>0.05) ,治疗组YMDD变异率为21.9 % (7/32) ,对照组YMDD变异率为40.6 % (13/32) ,两组比较差异无显著性 (P>0.05) ,同时治疗组ALT复常率、HBeAg转换率、HBVDNA阴转率与治疗前ALT及HBVDNA基线水平有关。结论 :α干扰素联合拉米夫定治疗HBeAg阳性的慢性乙型肝炎对于ALT中度升高、HBVDNA高水平复制 相似文献
36.
Second-trimester double or triple screening for Down syndrome: a comparison of Chinese and Caucasian populations. 总被引:1,自引:0,他引:1
Yuan-Yuan Wang Jun Luo Ming-Wei Zhu Lan-Nv Liu Xu Ma 《International journal of gynaecology and obstetrics》2006,94(1):67-72
OBJECTIVES: To compare the performance of double screening (measuring maternal serum levels of alpha-fetoprotein [AFP] and total beta-human chorionic gonadotrophin [hCG] as markers for Down syndrome) with that of triple screening (also measuring levels of unconjugated estriol [uE3]) in the second trimester of pregnancy, and to compare ethnic variance between Chinese and Caucasian populations. METHODS: The study investigated 15096 normal singleton pregnancies and 24 pregnancies affected with Down syndrome. Frequency distributions of AFP, hCG, and uE3 levels were analyzed. Likelihood ratios (LRs) were calculated using the multiple of median value (MoM) of AFP, hCG, and uE3 as variables. After multiplying maternal age risk by the LR values for the markers used in double and triple screening, the specific risks obtained with double and triple screening were estimated. The detection rate (DR) and false-positive rate (FPR) were calculated at different cut-off points. The serum markers' levels were also compared with those of Caucasian women. RESULTS: The median MoM value of hCG was higher in women with affected pregnancies (1.40) than those with unaffected pregnancies (1.00). However, the median MoMs of AFP and uE3 (0.79 and 0.68) were lower in affected than in unaffected pregnancies. At a FPR of 5%, the detection rates reached with double and triple screening were 50% and 66.7%, respectively. Ratios of the 3 serum markers' medians to those in a study with Caucasian women were 1.06 (range=1.04-1.09) for AFP, 1.14 (range=1.10-1.17) for hCG, and 1.28 (range=1.23-1.41) for uE3 for the relevant gestational weeks. CONCLUSION: Triple screening performed better than double screening in the second trimester. Ethnic variance should be taken into account in Down syndrome screening. 相似文献
37.
Alessandro Mussa Kelly A. Duffy Diana Carli Giovanni Battista Ferrero Jennifer M. Kalish 《Pediatric blood & cancer》2019,66(1)
Patients with Beckwith‐Wiedemann spectrum (BWSp) undergo quarterly alpha‐fetoprotein measurement for hepatoblastoma (HB) screening up to 4 years of age, paralleling the epidemiology of nonsyndromic HB. However, specific data on the timing of HB development in BWSp are lacking. Here we compare the timing of presentation of HBs in BWSp with a control cohort of consecutive HB cases, demonstrating that halving screening duration of screening procedures in BWSp likely will not impact its effectiveness. 相似文献
38.
《Best Practice & Research: Clinical Gastroenterology》2014,28(5):783-793
When hepatocellular carcinoma presents with symptoms cure is seldom possible and death usually follows within months. However, it is possible to detect HCC early, at which stage it is curable. This requires a surveillance program. The components of such a program include: identification of the at risk population, provision of appropriate surveillance tests, and an appropriate method of determining whether the abnormalities found on screening are cancer or not. Surveillance for liver cancer meets all these criteria. Unfortunately high quality evidence showing benefit of liver cancer surveillance is lacking, but lesser quality evidence is plentiful, including several cost efficacy analyses that all show that surveillance does decrease mortality. Therefore all the continental liver disease societies and all national liver disease societies have recommended that surveillance should be undertaken. 相似文献
39.
Muge Gulen Yeliz Simsek Emre Oner Salim Satar 《The American journal of emergency medicine》2018,36(6):1126.e5-1126.e6
Alpha lipoic acid (ALA), which is an anti-oxidant acting as a scavenger for reactive oxygen species, is especially used to improve glycemic control and prevent polyneuropathies associated with diabetes mellitus. ALA is considered to be a safe drug and intoxication with ALA is extremely rare. However, this paper reports a 38-year-old young woman who was admitted to the emergency department after she had ingested ten pills of 600 mg ALA belonging to her diabetic parent, which led to delirium, metabolic acidosis, thrombocytopenia, and rhabdomyolysis. To the best of our knowledge, there are only four cases of ALA intoxication reported in the literature and all were observed in children. This report aims to present the first case of ALA related intoxication worldwide in an adult patient. 相似文献
40.
《Journal of cranio-maxillo-facial surgery》2014,42(4):333-339
AimsThe purpose of this study was to evaluate the expression of proteins that participate in the osteoinduction stage (VEGF, BMP2 and CBFA1) of the process of bone regeneration of defects created in rat calvariae and filled with autogenous bone block grafts.Materials and methods10 adult male rats (Rattus norvegicus albinus, Wistar) were used, who received two bone defects measuring 5 mm each in the calvariae. The bone defects constituted two experimental groups (n = 10): Control Group (CONT) (defects filled with a coagulum); Graft Group (GR) (defects filled with autogenous bone removed from the contralateral defect). The animals were submitted to euthanasia at 7 and 30 days post-operatively.ResultsQuantitative analysis demonstrated significantly greater bone formation in Group GR, but the presence of the studied proteins was significantly greater in the CONT Group in both time intervals of observation.ConclusionIt was not possible in this study in cortical bone block groups to detect the osteoinductive proteins in a significant amount during the repair process. 相似文献