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61.
Padmaja Yalamanchili Eric Wexler Megan Hayes Ming Yu Jody Bozek Mikhail Kagan Heike S. Radeke Michael Azure Ajay Purohit David S. Casebier Simon P. Robinson 《Journal of nuclear cardiology》2007,14(6):782-788
Background
BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention
mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02
was studied in vivo in mice.
Methods and Results
Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC50 of 16.6±3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC50 of 18.2±6.7 nmol/L, 19.8±2.6 nmol/L, and 23.1±1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers
of neonatal rat cardiomyocytes (10.3%±0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91%±2%)
and deguelin (89%±3%). In contrast, an inactive pyridaben analog, P-0 (IC50 value>4 μmol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics
for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t1/2) uptake was very rapid (approximately 35 seconds), and washout t1/2 for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02
had substatial myocardial uptake (9.5%±0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver
ratios of 14.1±2.5 and 8.3±0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization
and demonstrated sustained myocardial uptake through 55 minutes.
Conclusions
F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake
and slow washout. These characteristics allow fast and sustained accumulation in the heart. 相似文献
62.
Leena Joseph R. Anuradha R. Nathuram V. V. Shaha M. C. Abani 《Applied radiation and isotopes》2003,59(5-6):359-362
National intercomparisons of activity measurements of 131I, a radioisotope widely used for diagnosis and therapy of thyroid related ailments, were initiated in 1979 as a quality assurance program, towards improving radiation safety procedures and related dosimetry in Nuclear Medicine Centres (NMCs) in India. Oral administration of a known quantity of radioiodine to patients requires accurate radioactivity measurements to be performed on a well-calibrated isotope calibrators. Under or over estimation of the activity due to a faulty or uncalibrated isotope calibrator could provide misleading results. Calibration of isotope calibrators and the traceablity of subsequent measurements to the national standards laboratory is one of the essential basic radiation safety requirement of the IAEA. In view of the stringent quality assurance requirements for activity measurements imposed by Atomic Energy Regulatory Board, a National Intercomparison Program was initiated and to date ten such intercomparison programs have been conducted by the Radiation Safety Systems Division, of the Bhabha Atomic Research Centre. This program has benefited the participants by making their measurements traceable to the National Primary Standards. Over the years there has been a marked increase in the number of NMCs participating in the intercomparison programs. As a result, the number of institution showing large deviation from the correct value has decreased considerably over the years. This program thus, has enabled participating NMCs to check their isotope calibrators so as to ensure proper delivery of radiation dose to the patients and hence to optimise patient exposure. 相似文献
63.
目的 :探讨系统性红斑狼疮 (SLE)女性患者血清肿瘤标志物CA12 5 ,CA199含量变化及临床意义。方法 :用化学发光法测定 30例正常女性和 38例SLE女性患者血清中CA12 5 ,CA199含量。结果 :正常组CA12 5含量为 11.14± 6 .4 8U/ml,CA199含量为 3.75± 2 .89U/ml;SLE组CA12 5 ,CA199分别为 2 2 .5 6± 2 0 .4 6U/ml,9.5 7± 9.34U/ml。SLE患者CA12 5 ,CA199阳性率分别为 2 1.1% ,7.89%。结论 :SLE患者血清CAl2 5 ,CA199含量较正常组增高 (P <0 .0 5 )。CA12 5 ,CA199在SLE女性患者中可出现阳性 ,对临床诊断SLE有一定价值。 相似文献
64.
小檗碱对兔颈动脉粥样硬化中内膜增生和巨噬细胞趋化作用的影响 总被引:6,自引:0,他引:6
目的观察小檗碱对家兔颈动脉粥样硬化的内膜中膜比和巨噬细胞变化的影响。方法24只雄性日本大耳白兔随机分为3个试验组,正常组每天肌肉注射生理盐水,普通饲料喂养,对照组高脂喂养,1周后行颈动脉内膜空气干燥术并每日肌肉注射生理盐水,小檗碱干预组高脂喂养,1周后行颈动脉内膜空气干燥术并肌肉注射小檗碱,5周时取手术侧的颈动脉做弹力纤维染色,计算内膜中膜比;巨噬细胞免疫组化检测巨噬细胞在颈动脉粥样硬化病变中的变化,计算巨噬细胞的阳性率。结果对照组内膜厚度明显增加,中膜萎缩变薄,经计算I/M为1.20±0.007,小檗碱组的I/M为0.65±0.008。两组间有显著差异(P<0.01);巨噬细胞免疫组化染色对照组内膜下和中膜有大量巨噬细胞,小檗碱干预组内膜和中膜下也可以见有巨噬细胞沉积,通过计算巨噬细胞阳性率,小檗碱干预组的巨噬细胞阳性率明显小于对照组(P<0.01)。结论小檗碱可以降低家兔颈动脉粥样硬化中的血管内膜厚度、减少粥样斑块中的巨噬细胞数目,从而干预颈动脉粥样硬化的形成。 相似文献
65.
B. Jahn-Schmid C. Harwanegg† R. Hiller† B. Bohle C. Ebner O. Scheiner M. W. Mueller† 《Clinical and experimental allergy》2003,33(10):1443-1449
BACKGROUND: The availability of recombinant allergens and recent advances in biochip technology led to the development of a novel test system for the detection of allergen-specific IgE. OBJECTIVE: To test the performance of this allergen microarray in a serological analytical study. METHODS: Standard allergens contained in grass pollen (Phl p 1, Phl p 2, Phl p 5 and Phl p 6) and tree pollen (Bet v 1 and Bet v 2) were used as a model system. The detection of allergen-specific serum IgE using microarrays was compared with standard test systems: CAP/RAST and an in-house ELISA. In order to test the analytical sensitivity of the assays, geometric dilutions of a serum pool containing high levels of pollen-specific IgE from allergic individuals were tested in each system. To assess the analytical specificity, the sera of 51 patients with presumptive allergic symptoms were collected before diagnosis. Thereafter, the results for grass/tree-pollen-specific IgE were compared. RESULTS: The microarray has a good dynamic range similar to the CAP/RAST system. Microarray and ELISA showed comparable analytical sensitivity exceeding the CAP/RAST system. With respect to the analytical specificity, no significant cross-reactivity of the allergens was observed. For two of the allergens tested, weak positive signals were detected in the microarray test system, whereas they were not detectable by CAP/RAST. CONCLUSION: A good correlation of presently used methods to detect serum IgE and the novel microarray test system was observed. As a next step, a careful validation of this method for a multitude of allergens and a thorough clinical evaluation has to be provided. Microarray testing of allergen-specific IgE can be presumed to be the method of choice for a prospective component-resolved diagnosis of Type I allergy, and the basis for the design and monitoring of a patient-tailored specific immunotherapy in the future. 相似文献
66.
Dr. W. Wörner A. Preissner N. Rietbrock 《European journal of clinical pharmacology》1992,43(1):97-100
Summary Sera from 17 patients with Type I diabetes and 19 healthy volunteers have been examined to evaluate whether the kinetics of the binding of drugs to Site II of serum albumin is altered in diabetes. Stopped-flow measurements showed that the association velocity and the affinity constants of the fluorescent marker dansylsarcosine were significantly lower in diabetics (160 s–1 and 2.0 × 105 l·mol–1) than in non-diabetics (196s–1 and 4.0 × 105 l·mol–1). The dissociation velocity was not different [20.3 s–1 vs. 19.4 s–1]. Although patients with a reduced albumin concentration were excluded the diabetics had significantly lower concentrations than the healthy volunteers. There was a significant correlation between decreased glycosylation of albumin and increased association velocity. The dissociation velocity constants were correlated with the molar concentration ratio of free fatty acids/human serum albumin. Thus, the extent of glycosylation and the amount of fatty acids bound per mole albumin can both affect the kinetics of drug binding to Site II. The lower affinity in patients with Type I diabetes is due to the increased in the glycoalbumin concentration. 相似文献
67.
Possible role of IL-2 deficiency for hypogammaglobulinaemia in patients with common variable immunodeficiency. 下载免费PDF全文
J A Rump A Jahreis M Schlesier R Drger I Melchers H H Peter 《Clinical and experimental immunology》1992,89(2):204-210
Common variable immunodeficiency (CVID) patients are unable to produce specific immunoglobulins after antigen contact in vivo. The aim of this study was to investigate whether in some cases of CVID a decreased de novo synthesis of IL-2 might be the cause of immunodeficiency and whether this deficiency can be corrected by IL-2 supplementation in vitro. Mononuclear cells from 17 CVID patients and from 10 healthy controls were cultured with monoclonal anti-CD3 antibody OKT3, pokeweed mitogen (PWM) or tetanus toxoid (TT) to stimulate IL-2 synthesis. In parallel, in vitro IgG and IgM synthesis was stimulated with Staphylococcus aureus Cowan I (SAC), PWM or TT in the presence or absence of IL-2. While lymphocytes of 11 out of 17 patients produced low to normal amounts of IL-2 upon stimulation with anti-CD3, only three patients showed low IL-2 production in response to PWM and five in response to TT. Regarding immunoglobulin synthesis in vitro, five patients completely failed to produce IgM or IgG upon stimulation with PWM, SAC or TT irrespective of the addition of IL-2. By contrast, four patients did not show any defect in vitro and synthesized normal amounts of IgM and IgG with any of the three stimuli. Finally, eight patients could be reconstituted for PWM-, SAC- and TT-induced IgM and/or IgG synthesis in vitro, by adding IL-2 to the culture system. This enhancing effect of IL-2 could be blocked by adding anti-IL-2 receptor antibodies to the cultures. Our findings indicate that a defective IL-2 synthesis after antigen stimulation may be one reason for the impaired immunoglobulin production in some cases of CVID. 相似文献
68.
Nobutaka Eiraku Shinji Ijichi Shinji Yashiki Mitsuhiro Osame Shunro Sonoda 《Journal of neuroimmunology》1992,37(3):223-228
The in vitro proliferation of peripheral blood lymphocytes (PBLs) without any mitogenic stimulation is one of the hallmarks of human T lymphotropic virus type I (HTLV-I) infection. Recent evidence suggests a difference in the degree of the phenomenon between HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-I carriers (AC). In this article, we demonstrated several alterations in the features of the in vitro transformed lymphocytes between patients with HAM/TSP (n = 16) and AC (n = 8). The percentages of total CD8+ and CD8+CD28+ cells were significantly increased in the in vitro proliferating T lymphocytes derived from the patients with HAM/TSP when compared to those from AC. HAM/TSP was segregated from AC by the high degree of the proliferation of CD8+CD28+ cells. The expression of HTLV-I-specific antigens on the cultured PBLs was detected only in the subjects which showed low CD8+CD28+/CD4+ ratio of the in vitro proliferating lymphocytes. These findings suggest that this phenomenon distinguishes HAM/TSP from AC, not only in quantity but also in quality. 相似文献
69.
70.
The fixation of a distally ruptured ulnar collateral ligament of the MP 1 (Metacarpophalangeal) joint without a portion of ligament which can be sutured or a small bony fragment can be accomplished with a variety of methods, most of which require drillholes through borth cortices and a counter incision as well as the removal of the material at a second stage [1, 11, 13, 15]. The Mitek bone mini anchor (Ethicon-Mitek®) proved to be a reliable and quick alternative [10, 12, 16, 18, 19]. It was successfully used in eleven patients with excellent stability of the reconstructed joint. 相似文献