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排序方式: 共有740条查询结果,搜索用时 15 毫秒
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Synthesis and mixed lineage kinase activity of pyrrolocarbazole and isoindolone analogs of (+)K-252a
Hudkins RL Johnson NW Angeles TS Gessner GW Mallamo JP 《Journal of medicinal chemistry》2007,50(3):433-441
Structural modification of the indolecarbazole natural product (+)K-252a identified structural requirements for MLK activity and a novel series of potent fused pyrrolocarbazole MLK1/3 inhibitors. The SAR revealed that the lactam regiochemistry, the shape of the heterocycle, and aryl rings B and F are important to MLK activity. Heteroatom and alkyl replacement of the N-12 and/or N-13 indole nitrogen atoms identified the nonplanar dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-7-one (8) and corresponding 5,7-dione (7) as potent cell-permeable MLK1/3 family-selective leads with in vitro activity comparable to that of (+)K-252a and determined them to be 2- to 3-fold more potent than the aglycone natural product K-252c. 相似文献
74.
Flavia Emilie Heimovski Juliana A. Simioni Thelma Larocca Skare 《Anais brasileiros de dermatologia》2015,90(6):837-840
BACKGROUND
Patients with systemic lupus erythematosus seem to belong to different serological and clinical subgroups of the disease. Genetic background can cause the appearance of these subgroups.OBJECTIVE
To determine whether Brazilian patients who have systemic lupus erythematosus and Raynaud''s phenomenon differ from those who do not.METHODS
Retrospective analysis of 373 medical records of systemic lupus erythematosus patients studied for demographic, clinical and serological data. A comparative analysis was performed of individuals with and without RP.RESULTS
There was a positive association between Raynaud''s phenomenon and age at diagnosis (p=0.02), presence of anti-Sm (p=0.01) antibodies and anti-RNP (p<0.0001). Furthermore, a negative association was found between Raynaud''s phenomenon and hemolysis (p=0.01), serositis (p=0.01), glomerulonephritis (p=0.0004) and IgM aCL (p=0.004) antibodies.CONCLUSION
Raynaud''s phenomenon patients appear to belong to a systemic lupus erythematosus subset with a spectrum of clinical manifestations located in a more benign pole of the disease. 相似文献75.
Thelma Canto-Cetina Samuel Canizales-Quinteros Elsa de la Chesnaye Ramón Coral-Vázquez Juan Pablo Méndez Patricia Canto 《Hypertension in pregnancy》2007,26(3):283-291
OBJECTIVE: To determine whether polymorphisms in the TNF-alpha promoter gene are associated with preeclampsia. METHODS: 105 women with preeclampsia and 200 controls were genotyped for the G-308A and C-850T polymorphisms by RFLP. Differences in allele, genotype, and haplotype frequencies between groups were assessed. RESULTS: The genotypic and allelic distribution of both polymorphisms was similar between groups. Moreover, the estimated overall pair of loci haplotype frequencies did not differ significantly. CONCLUSION: We did not find any association between these polymorphisms and the risk for preeclampsia. However, we found that both the genotypic and allelic distribution in our population differed from those reported in other populations. 相似文献
76.
Jerome H. Jaffe Maureen Kanzler Miriam Cohen Thelma Kaplan 《Addiction (Abingdon, England)》1978,73(3):271-281
Sixteen female smokers participated in a study of ‘safer cigarettes’ and bought their cigarettes from the experimenters at less than prevailing prices. Half received an economic incentive for purchasing cigarettes delivering progressively less tar and nicotine: the other half paid the same price regardless of brand purchased. Subjects were not required to change brands. Twelve of the sixteen subjects completed the twelve-week study. Significant reductions in tar and nicotine intake, which persisted for more than six months beyond the twelve-week study period, occurred in both groups. The differences between the two groups in tar and nicotine intake were not significant. A control group of seven female smokers showed little change in tar and nicotine intake over the same twelve-week period, and only modest changes in the subsequent six months. Neither the number of cigarettes smoked nor exhaled carbon monoxide levels (measured in a subsample of participants) increased as the subjects switched to lower nicotine levels. 相似文献
77.
78.
Edge cells are mechanoreceptive neurones located in the lateral tracts of the lamprey spinal cord. Phasic activation of these cells by lateral bending can entrain the activity of the locomotor central pattern generator. During fictive locomotion induced by bath-applied NMDLA (N-methyl-D,L-aspartate) or sensory stimulation, edge cells receive synaptic input. In this paper we provide evidence that the tonic inhibition received during sensory-induced fictive locomotion is glycinergic. We also show that during fictive locomotion induced by application of NMDLA to the spinal cord, bicuculline unveils phasic synaptic activity in edge cells. During sensory-evoked fictive locomotion, by contrast, only tonic synaptic activity is apparent in the presence of bicuculline. 相似文献
79.
Ojo B Rezaie P Gabbott PL Davies H Colyer F Cowley TR Lynch M Stewart MG 《Brain, behavior, and immunity》2012,26(5):778-788
Altered synaptic morphology, progressive loss of synapses and glial (astrocyte and microglial) cell activation are considered as characteristic hallmarks of aging. Recent evidence suggests that there is a concomitant age-related decrease in expression of the presynaptic protein, synaptophysin, and the neuronal glycoprotein CD200, which, by interacting with its receptor, plays a role in maintaining microglia in a quiescent state. These age-related changes may be indicative of reduced neuroglial support of synapses. FG Loop (FGL) peptide synthesized from the second fibronectin type III module of neural cell adhesion molecule (NCAM), has previously been shown to attenuate age-related glial cell activation, and to 'restore' cognitive function in aged rats. The mechanisms by which FGL exerts these neuroprotective effects remain unclear, but could involve regulation of CD200, modifying glial-synaptic interactions (affecting neuroglial 'support' at synapses), or impacting directly on synaptic function. Light and electron microscopic (EM) analyses were undertaken to investigate whether systemic treatment with FGL (i) alters CD200, synaptophysin (presynaptic) and PSD-95 (postsynaptic) immunohistochemical expression levels, (ii) affects synaptic number, or (iii) exerts any effects on glial-synaptic interactions within young (4 month-old) and aged (22 month-old) rat hippocampus. Treatment with FGL attenuated the age-related loss of synaptophysin immunoreactivity (-ir) within CA3 and hilus (with no major effect on PSD-95-ir), and of CD200-ir specifically in the CA3 region. Ultrastructural morphometric analyses showed that FGL treatment (i) prevented age-related loss in astrocyte-synaptic contacts, (ii) reduced microglia-synaptic contacts in the CA3 stratum radiatum, but (iii) had no effect on the mean number of synapses in this region. These data suggest that FGL mediates its neuroprotective effects by regulating glial-synaptic interaction. 相似文献
80.
The objective of this study was to analyze the usefulness of tumor necrosis factor-alpha and interleukin-6 cerebrospinal fluid concentrations for the differential diagnosis between bacterial and aseptic meningitis in children and in the prognostic evaluation. A cross-sectional study was performed on 35 children between 1 month and 12 years of age with suspected meningitis. Cytokines determination was performed by enzyme-linked immunosorbent assay technique. The Mann-Whitney test and Spearman's correlation coefficients were used for statistical analysis. Six children presented bacterial meningitis, 13 aseptic, and 16 had no meningitis. The tumor necrosis factor-alpha concentrations were significantly higher in the bacterial meningitis group as compared with the aseptic group (P = 0.001) and among groups with and without meningitis (P = 0.000). There was correlation between tumor necrosis factor-alpha and cerebrospinal fluid leukocytes (P = 0.019), protein (P = 0.000), and glucose (P = 0.038). There was no association between cytokines and complications of the meningitis. The tumor necrosis factor-alpha concentrations in the cerebrospinal fluid were useful markers for distinguishing bacterial from aseptic meningitis and were demonstrated to be useful in evaluating the intensity of the inflammatory process in the central nervous system. 相似文献