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31.
Barker JE Schuldt AJ Lessard ML Jude CD Vogler CA Soper BW 《Experimental hematology》2003,31(11):1112-1118
To block development of progressive childhood diseases, in utero transplantation (IUTx) requires immediate and significant donor peripheral blood (PB) cell amplification. To date, negligible and nontherapeutic donor PB cell levels have been observed postnatally, except in patients with immunodeficiency diseases. Donor cell fate in utero still is not clear. Ease of identifying and quantifying beta-glucuronidase (GUSB)-expressing donor cells in GUSB-null mucopolysaccharidosis type VII (MPSVII) mouse recipients allowed us to evaluate temporal donor cell engraftment and amplification post-IUTx. Like humans, MPSVII mice are unable to catabolize lysosomal glycosaminoglycans and progressively develop severe storage disease unless they are treated early in life.IUTx recipients were nonablated MPSVII fetuses and genetically stem cell-deficient, and hence myeloablated, W(41)/W(41) MPSVII fetuses. Donor GUSB+ cells were identified and counted in histochemical tissue sections. Quantitative results were confirmed by flow cytometry, enzyme analysis, and histopathology.Whereas GUSB+ cells engraft in most tissues in utero, significant amplification does not occur until the first postnatal week in the nonablated MPSVII hosts. In contrast, genetically myeloablated MPSVII recipients display widely distributed donor cell replacement accompanied by extensive amplification in utero. In both models, storage is alleviated in adult tissues with significant donor cell repopulation.To become therapeutic, IUTx must overcome the limitations of donor cell expansion in the highly competitive fetal environment. Fortunately, nonablative mechanisms to amplify cells in utero are coming on line. 相似文献
32.
Sposito G Skipper NT Sutton R Park S Soper AK Greathouse JA 《Proceedings of the National Academy of Sciences of the United States of America》1999,96(7):3358-3364
Clay minerals are layer type aluminosilicates that figure in terrestrial biogeochemical cycles, in the buffering capacity of the oceans, and in the containment of toxic waste materials. They are also used as lubricants in petroleum extraction and as industrial catalysts for the synthesis of many organic compounds. These applications derive fundamentally from the colloidal size and permanent structural charge of clay mineral particles, which endow them with significant surface reactivity. Unraveling the surface geochemistry of hydrated clay minerals is an abiding, if difficult, topic in earth sciences research. Recent experimental and computational studies that take advantage of new methodologies and basic insights derived from the study of concentrated ionic solutions have begun to clarify the structure of electrical double layers formed on hydrated clay mineral surfaces, particularly those in the interlayer region of swelling 2:1 layer type clay minerals. One emerging trend is that the coordination of interlayer cations with water molecules and clay mineral surface oxygens is governed largely by cation size and charge, similarly to a concentrated ionic solution, but the location of structural charge within a clay layer and the existence of hydrophobic patches on its surface provide important modulations. The larger the interlayer cation, the greater the influence of clay mineral structure and hydrophobicity on the configurations of adsorbed water molecules. This picture extends readily to hydrophobic molecules adsorbed within an interlayer region, with important implications for clay-hydrocarbon interactions and the design of catalysts for organic synthesis. 相似文献
33.
Development of left ventricular hypertrophy in adults in hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations 总被引:3,自引:0,他引:3
Maron BJ Niimura H Casey SA Soper MK Wright GB Seidman JG Seidman CE 《Journal of the American College of Cardiology》2001,38(2):315-321
OBJECTIVES: We sought to determine whether the development of left ventricular hypertrophy (LVH) can be demonstrated during adulthood in genetically affected relatives with hypertrophic cardiomyopathy (HCM). BACKGROUND: Hypertrophic cardiomyopathy is a heterogeneous cardiac disease caused by mutations in nine genes that encode proteins of the sarcomere. Mutations in cardiac myosin-binding protein C (MyBPC) gene have been associated with age-related penetrance. METHODS: To further analyze dormancy of LVH in patients with HCM, we studied, using echocardiography and 12-lead electrocardiography, the phenotypic expression caused by MyBPC mutations in seven genotyped pedigrees. RESULTS: Of 119 family members studied, 61 were identified with a MyBPC mutation, including 21 genetically affected relatives (34%) who did not express the HCM morphologic phenotype (by virtue of showing normal left ventricular wall thickness). Of these 21 phenotype-negative individuals, 9 were children, presumably in the prehypertrophic phase, and 12 were adults. Of the 12 adults with normal wall thickness < or = 12 mm (7 also with normal electrocardiograms), 5 subsequently underwent serial echocardiography prospectively over four to six years. Of note, three of these five adults showed development of LVH in mid-life, appearing for the first time at 33, 34 and 42 years of age, respectively, not associated with outflow obstruction or significant symptoms. CONCLUSIONS: In adults with HCM, disease-causing MyBPC mutations are not uncommonly associated with absence of LVH on echocardiogram. Delayed remodeling with the development of LVH appearing de novo in adulthood, demonstrated here for the first time in individual patients with prospectively obtained serial echocardiograms, substantiates the principle of age-related penetrance for MyBPC mutations in HCM. These observations alter prevailing perceptions regarding the HCM clinical spectrum and family screening strategies and further characterize the evolution of LVH in this disease. 相似文献
34.
35.
High-dose cytosine arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia 总被引:1,自引:1,他引:1
Hiddemann W; Kreutzmann H; Straif K; Ludwig WD; Mertelsmann R; Donhuijsen- Ant R; Lengfelder E; Arlin Z; Buchner T 《Blood》1987,69(3):744-749
In a clinical phase I/II study, high-dose cytosine arabinoside and mitoxantrone (HAM) were given in combination to 40 patients with refractory acute myeloid leukemia. All patients had received a 9-day combination of thioguanine, Ara-C, and daunorubicin (TAD-9) as standardized first-line treatment. Refractoriness was defined as (a) nonresponse against two TAD-9 induction cycles, (b) early relapse within the first 6 months on monthly maintenance or after TAD-9 consolidation, (c) relapse after 6 months with nonresponse against one additional TAD-9 cycle, and (d) second and subsequent relapses after successful TAD-9 therapy at the preceding relapse. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours on days 1 through 4; mitoxantrone was started at 12 mg/m2/day on days 3, 4, and 5 and was escalated to 4 and 5 doses of 10 mg/m2/day on days 2 through 5 and 2 through 6. Of the 40 patients, 21 achieved a complete remission (53%), 1 patient had a partial remission, and 5 patients were nonresponders. Thirteen patients died in aplasia due to infections (n = 11), pericardiac effusion, or acute cardiomyopathy. Nonhematologic side effects consisted predominantly of nausea and vomiting, mucositis, and diarrhea. Central nervous system (CNS) symptoms were observed during six treatment courses. Recovery of blood counts occurred at a median of 27 days from the onset of treatment; the median time to complete remission was 36 days. Two of the 21 responders underwent successful bone marrow transplantations. The median remission duration for the remaining 19 patients is 4.5 months, and the median survival time is 9 months. These data emphasize that HAM has high antileukemic activity in refractory AML and strongly suggest starting the combination at earlier stages in AML therapy. 相似文献
36.
George R. Douglas Jianli Jiao John D. Gingerich Lynda M. Soper Jan A. Gossen 《Environmental and molecular mutagenesis》1996,28(4):317-324
In order to help establish criteria for optimizing protocols for in vivo mutation studies, lacZ transgenic mice (Muta™ mouse) were treated with five consecutive daily doses of ethylnitrosourea (50 mg/kg), sampled at times up to 55 days after treatment, and mutant frequencies and DNA sequences determined for liver and bone marrow. In the bone marrow, the mutant frequency rose very rapidly in the first 5 days after treatment to 34 times the control frequency. Subsequently, there was a broad peak where the mutant frequency did not vary significantly, although it did appear to begin to decline after 45 days. In contrast, in the liver, the peak mutant frequency (11 times the control frequency) was not achieved until 35 days, after which there appeared to be a slow decline up to 55 days, which was not statistically significant. Once the maximum mutant frequency was reached, the mutation spectra in the two tissues were indistinguishable. In contrast to the G:C → A:T transitions in 5′-CpG sites characteristic of untreated mice, A:T → T:A transversions and A:T → G:C transitions were prominent in both liver and bone marrow of ENU-treated mice, suggesting the involvement of unrepaired O2-and O4-ethylthymine adducts. In addition, G:C → T:A transversions were induced in liver. This study demonstrates the possibility that although tissues may have different mutation fixation times, a single mutation fixation time equal to the longest time may be appropriate for in vivo mutation studies, provided that the mutation frequency does not decline appreciably after the peak is reached. This study also illustrates the necessity of ensuring that mutation characteristics are determined after optimal fixation has occurred. © 1996 Wiley-Liss, Inc. 相似文献
37.
定量组织速度成像技术评价阿霉素诱导兔心肌病模型:与常规经胸超声心动图比较 总被引:1,自引:0,他引:1
目的:采用定量组织速度成像技术评价阿霉素诱导兔心肌病模型,并与常规经胸超声心动图比较其评估优势。方法:实验于2005-06/2006-08在大连医科大学完成。①实验分组及处理:取纯种新西兰白兔22只,雌雄不限,随机分成阿霉素组12只,给予阿霉素每次2mg/kg,以1g/L耳缘静脉注射,每周1次,注射8周;对照组10只每周注射2mL/kg生理盐水,共8周。②实验评估:每周应用HPSonos5500型彩色多普勒超声诊断仪(美国Agilent公司生产)对两组兔心脏进行左室收缩末期和舒张末期内径明、室间隔厚度、E峰、射血分数、左室短轴缩短率等常规超声参数测量,使用GEVivid7型彩色多普勒超声诊断仪(美国GE公司生产)进行收缩期和舒张期峰值速度、收缩期加速度定量组织速度成像参数测定。结果:22只兔进入统计。①对照组1~12周各参数与阿霉素组基础状态下比较无明显差异(P>0.05)。②第4周阿霉素组二尖瓣环运动的平均收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P均<0.05)。③第7周阿霉素组二尖瓣环运动的收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P<0.01),E峰较基础状态明显减低(P<0.05)。④第8周阿霉素组二尖瓣环运动的收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P<0.01),E峰较基础状态明显减低(P<0.01),左室收缩末期和舒张末期内径明显增大(P<0.05)。⑤第12周阿霉素组二尖瓣环运动的收缩期和舒张期峰值速度、收缩期加速度较基础状态明显减低(P<0.01),左室收缩末期和舒张末期内径明显增大(P<0.01),室间隔厚度、左室后壁厚度明显变薄(P<0.05),射血分数、左室短轴缩短率和E峰明显减低(P<0.01)。结论:定量组织速度成像参数可有效评价阿霉素诱导心肌病模型兔心肌的病理变化,较常规超声参数更敏感。 相似文献
38.
39.
Nathaniel J. Soper 《Journal of gastrointestinal surgery》2011,15(6):1005-1006
Introduction
Since the introduction of laparoscopic cholecystectomy more than two decades ago, the incidence of bile duct injury has remained greater than that established during the era of open cholecystectomy. 相似文献40.
Robert T. Soper 《Postgraduate medicine》2013,125(5):523-529
Inguinal and umbilical hernias are extremely common in infants and children and should be considered minor incidents when health is otherwise good. Diagnosis may be difficult in inguinal hernia; the usual treatment is surgical repair. Umbilical hernia is easily diagnosed and seldom requires operation. Complications are rare in both of these childhood hernias. 相似文献