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排序方式: 共有1465条查询结果,搜索用时 15 毫秒
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J B Press R Falotico Z G Hajos R A Sawyers R M Kanojia L Williams B Haertlein J A Kauffman C Lakas-Weiss J J Salata 《Journal of medicinal chemistry》1992,35(24):4509-4515
A series of purine derivatives was prepared and examined for selective inotropic activity in vitro and in vivo. Thioether-linked derivatives were superior to their oxygen and nitrogen isosteres. Substitution of electron-withdrawing groups on the benzhydryl moiety of these agents increased potency. The best compound of the study, 17 (carsatrin), was examined further and demonstrated selective oral activity as a positive inotrope. These compounds are presumed to act by affecting the kinetics of the cardiac sodium channel by analogy to the prototypic agent DPI 201106 (1). Their high selectivity for increasing contractile force and dP/dt without affecting blood pressure or heart rate is consistent with this mechanism. Carsatrin (17) was selected as a potential development candidate. 相似文献
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135.
Li-Qun Zhang Guangzhi Wang Gordon W Nuber Joel M Press Jason L Koh 《Journal of orthopaedic research》2003,21(3):565-571
Knee extension is always performed with coordinated contractions of multiple quadriceps muscle components; however, how the load is shared among them under normal and pathological conditions is unclear. We hypothesized that: the absolute moment generated by each quadriceps component increases with the total knee extension moment; the relative contribution and its dependence on the total knee extension moment are different for different quadriceps components; and the centrally located large vastus intermedius (VI) is favored by the central nervous system at low levels of activation. Electrical stimulation was used to activate each quadriceps component selectively in six human subjects. The relationship between the knee extension moment generated by an individual quadriceps component and the corresponding compound muscular action potential (M-wave) over various contraction levels was established for each quadriceps component. This relationship was used to calibrate the corresponding EMG signal and determine load sharing among quadriceps components during submaximal isometric voluntary knee extension. The VI contributed the most (51.8-39.6%) and vastus medialis the least (9.5-12.2%) to knee extension moment (P<0.05). As the knee extension moment increased, the relative contribution of the VI decreased (P=0.017) while the relation contribution of the vastus lateralis and medialis increased (P=0.012). The absolute moment generated by each quadriceps component always increased with the total knee extension moment (P<0.002). Our in vivo approach determined subject- and condition-specific load sharing among individual muscles and showed that the central nervous system utilized the centrally located, uniarticular VI in submaximal isometric knee extension. 相似文献
136.
Reduced cerebellar hemisphere size and its relationship to vermal hypoplasia in autism 总被引:10,自引:0,他引:10
J W Murakami E Courchesne G A Press R Yeung-Courchesne J R Hesselink 《Archives of neurology》1989,46(6):689-694
Cerebellar hemisphere size was calculated in 10 autistic and 8 normal control subjects by summing the cross-sectional areas of cerebellar hemisphere tissue measured on paramidline sagittal magnetic resonance images. The areas of two cerebellar vermal regions (lobules I through V and lobules VI through VII) were also measured using the midsagittal image. Our cumulative slice area measure of cerebellar hemisphere size was significantly smaller in the autistic subjects than in the control group. The cumulative slice area correlated positively with the area of vermal lobules VI through VII only in the autistic subjects. Our results indicated that the decreased size of the cerebellar hemispheres and vermal lobules VI through VII was associated with autism. 相似文献
137.
Michael F Press Dennis J Slamon Kerry J Flom Jinha Park Jian-Yuan Zhou Leslie Bernstein 《Journal of clinical oncology》2002,20(14):3095-3105
PURPOSE: To compare and evaluate HER-2/neu clinical assay methods. MATERIALS AND METHODS: One hundred seventeen breast cancer specimens with known HER-2/neu amplification and overexpression status were assayed with four different immunohistochemical assays and two different fluorescence in situ hybridization (FISH) assays. RESULTS: The accuracy of the FISH assays for HER-2/neu gene amplification was high, 97.4% for the Vysis PathVision assay (Vysis, Inc, Downers Grove, IL) and 95.7% for the the Ventana INFORM assay (Ventana, Medical Systems, Inc, Tucson, AZ). The immunohistochemical assay with the highest accuracy for HER-2/neu overexpression was obtained with R60 polyclonal antibody (96.6%), followed by immunohistochemical assays performed with 10H8 monoclonal antibody (95.7%), the Ventana CB11 monoclonal antibody (89.7%), and the DAKO HercepTest (88.9%; Dako, Corp, Carpinteria, CA). Only the sensitivities, and therefore, overall accuracy, of the DAKO Herceptest and Ventana CB11 immunohistochemical assays were significantly different from the more sensitive FISH assay. CONCLUSION: Based on these findings, the FISH assays were highly accurate, with immunohistochemical assays performed with R60 and 10H8 nearly as accurate. The DAKO HercepTest and the Ventana CB11 immunohistochemical assay were statistically significantly different from the Vysis FISH assay in evaluating these previously molecularly characterized breast cancer specimens. 相似文献
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139.
Comparison of anti-CD20 and anti-CD45 antibodies for conventional and pretargeted radioimmunotherapy of B-cell lymphomas 总被引:3,自引:2,他引:3
Pagel JM Hedin N Subbiah K Meyer D Mallet R Axworthy D Theodore LJ Wilbur DS Matthews DC Press OW 《Blood》2003,101(6):2340-2348
Radiolabeled anti-CD20 antibodies produce responses in 60% to 95% of patients with relapsed non-Hodgkin lymphoma (NHL); however, absorbed radiation ratios between tumors and normal organs are relatively low, and many patients have relapses. In this study we compared the abilities of anti-CD45 (BC8) and anti-CD20 (1F5) antibodies to target human Ramos lymphoma xenografts in athymic mice. When direct radioiodination was performed with conventional methods, BC8 delivered 2- to 4-fold more radioiodine to tumors than 1F5, with tumor-to-normal organ ratios as high as 20:1 using radiolabeled BC8 compared with a maximal ratio of 9.8:1 using radioiodinated 1F5. To optimize the biodistribution of radioactivity, we performed studies following a pretargeting method using streptavidin (SA)-conjugated BC8 and 1F5. Injection of a synthetic clearing agent decreased the circulating level of conjugates by 80% to 90% within 1 hour. Pretargeting with BC8-SA resulted in a 2- to 4-fold greater tumor uptake of radiolabeled biotin than with 1F5-SA, with maximal tumor-to-normal organ ratios of more than 80:1 and approximately 16:1, respectively. Therapy experiments demonstrated that 400 microCi (14.8 MBq) or more of yttrium-90-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin cured 100% of mice treated with BC8-SA and more than 90% of mice pretargeted with 1F5-SA, with complete remission occurring 8 to 10 days sooner in mice receiving BC8-SA. After treatment with 200 microCi (7.4 MBq) (90)Y-DOTA-biotin, 70% of the mice treated with BC8-SA were cured, but no mice were cured using 1F5-SA. Doses up to 800 microCi (29.6 MBq) (90)Y-DOTA-biotin were delivered with minor toxicity using either antibody conjugate. These lymphoma xenograft data suggest that pretargeted radioimmunotherapy using either anti-CD20 or anti-CD45 conjugates is highly effective and minimally toxic. 相似文献
140.
De novo metastasis in breast cancer: occurrence and overall survival stratified by molecular subtype
David J. Press Megan E. Miller Erik Liederbach Katherine Yao Dezheng Huo 《Clinical & experimental metastasis》2017,34(8):457-465
Breast cancer molecular subtypes, categorized jointly by hormone receptors (HR) and human epidermal growth factor-2 (HER2), are utilized to guide systemic therapy. We hypothesized distinct patterns of de novo metastasis and overall survival by molecular subtype using a retrospective cohort of 399,772 women in the National Cancer Database diagnosed with first primary invasive breast cancer between 2010 and 2014, of whom 13,924 were diagnosed with de novo metastasis from 2010 to 2013 and had follow up data. The relationship of molecular subtype with patient and tumor characteristics, including site of de novo metastasis, were examined using Chi-squared tests. Kaplan–Meier and Cox proportional hazards analyses were used to examine overall survival by molecular subtype. Bone was the most frequent de novo metastatic site for all molecular subtypes. Compared to HR+/HER2?, patients with HR?/HER2+ experienced 4.5, 3.0, and 6.0 times the de novo brain, lung, and liver metastasis respectively. In survival analyses of women diagnosed with de novo metastasis, the mortality risk relative to HR+/HER2? was twice as high for triple-negative (hazard ratio?=?2.02, 95% CI 1.89–2.16) and modestly lower for HR+/HER2+ (hazard ratio?=?0.83, 95% CI 0.78–0.88). The median survival difference between metastatic patients with and without chemotherapy was 28.6 months in HR+/HER2+ and 28.2 months in HR?/HER2+, but only 10.9 months in triple-negative and 5.2 months in HR+/HER2?. In conclusion, despite unfavorable patterns of de novo metastasis, HER2+ breast cancers had relatively better survival in recent years, probably due to treatment differences. Utilizing molecular subtype and site of de novo metastasis may predict prognosis and guide treatment. 相似文献