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Dexamethasone induces gelsolin synthesis and altered morphology in L929 cells 总被引:1,自引:1,他引:0
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When L929 cells are exposed to 5 μg/ml dexamethasone, synthesis of a 90,000 M(r) polypeptide is induced within 12 h. Flattening of the cells begins at about this time and progresses to become quite prominent after 48 h of exposure. Two-dimensional PAGE and partial proteolytic fingerprints identify the 90,000 M(r) polypeptide as gelsolin, a Ca(++)-dependent inhibitor of actin polymerization. Thus, this system provides evidence that gelsolin may have a role in regulating cell shape in response to physiological agents such as glucocorticoids. 相似文献
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Serge D Steinfeld Laure Tant Gerd R Burmester Nick KW Teoh William A Wegener David M Goldenberg Olivier Pradier 《Arthritis research & therapy》2006,8(4):R129-11
This open-label, phase I/II study investigated the safety and efficacy of epratuzumab, a humanised anti-CD22 monoclonal antibody, in the treatment of patients with active primary Sjögren's syndrome (pSS). Sixteen Caucasian patients (14 females/2 males, 33–72 years) were to receive 4 infusions of 360 mg/m2 epratuzumab once every 2 weeks, with 6 months of follow-up. A composite endpoint involving the Schirmer-I test, unstimulated whole salivary flow, fatigue, erythrocyte sedimentation rate (ESR), and immunoglobulin G (IgG) was devised to provide a clinically meaningful assessment of response, defined as a ≥20% improvement in at least two of the aforementioned parameters, with ≥20% reduction in ESR and/or IgG considered as a single combined criterion. Fourteen patients received all infusions without significant reactions, 1 patient received 3, and another was discontinued due to a mild acute reaction after receiving a partial infusion. Three patients showed moderately elevated levels of Human anti-human (epratuzumab) antibody not associated with clinical manifestations. B-cell levels had mean reductions of 54% and 39% at 6 and 18 weeks, respectively, but T-cell levels, immunoglobulins, and routine safety laboratory tests did not change significantly. Fifty-three percent achieved a clinical response (at ≥20% improvement level) at 6 weeks, with 53%, 47%, and 67% responding at 10, 18, and 32 weeks, respectively. Approximately 40%–50% responded at the ≥30% level, while 10%–45% responded at the ≥50% level for 10–32 weeks. Additionally, statistically significant improvements were observed in fatigue, and patient and physician global assessments. Further, we determined that pSS patients have a CD22 over-expression in their peripheral B cells, which was downregulated by epratuzumab for at least 12 weeks after the therapy. Thus, epratuzumab appears to be a promising therapy in active pSS, suggesting that further studies be conducted. 相似文献
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Invasive hybrids and their spread dynamics pose unique opportunities to study evolutionary processes. Invasive hybrids of native Spartina foliosa and introduced S. alterniflora have expanded throughout San Francisco Bay intertidal habitats within the past 35 years by deliberate plantation and seeds floating on the tide. Our goals were to assess spatial and temporal scales of genetic structure in Spartina hybrid populations within the context of colonization history. We genotyped adult and seedling Spartina using 17 microsatellite loci and mapped their locations in three populations. All sampled seedlings were hybrids. Bayesian ordination analysis distinguished hybrid populations from parent species, clearly separated the population that originated by plantation from populations that originated naturally by seed and aligned most seedlings within each population. Population genetic structure estimated by analysis of molecular variance was substantial (FST=0.21). Temporal genetic structure among age classes varied highly between populations. At one population, the divergence between adults and 2004 seedlings was low (FST=0.02) whereas at another population this divergence was high (FST=0.26). This latter result was consistent with local recruitment of self-fertilized seed produced by only a few parental plants. We found fine-scale spatial genetic structure at distances less than ∼200 m, further supporting local seed and/or pollen dispersal. We posit a few self-fertile plants dominating local recruitment created substantial spatial genetic structure despite initial long-distance, human dispersal of hybrid Spartina through San Francisco Bay. Fine-scale genetic structure may more strongly develop when local recruits are dominated by the offspring of a few self-fertile plants. 相似文献
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Specific reduction of hepatic glucose 6-phosphate transporter-1 ameliorates diabetes while avoiding complications of glycogen storage disease 总被引:1,自引:0,他引:1
Sloop KW Showalter AD Cox AL Cao JX Siesky AM Zhang HY Irizarry AR Murray SF Booten SL Finger EA McKay RA Monia BP Bhanot S Michael MD 《The Journal of biological chemistry》2007,282(26):19113-19121
D-Glucose-6-phosphatase is a key regulator of endogenous glucose production, and its inhibition may improve glucose control in type 2 diabetes. Herein, 2'-O-(2-methoxy)ethyl-modified phosphorothioate antisense oligonucleotides (ASOs) specific to the glucose 6-phosphate transporter-1 (G6PT1) enabled reduction of hepatic D-Glu-6-phosphatase activity in diabetic ob/ob mice. Treatment with G6PT1 ASOs decreased G6PT1 expression, reduced G6PT1 activity, blunted glucagon-stimulated glucose production, and lowered plasma glucose concentration in a dose-dependent manner. In contrast to G6PT1 knock-out mice and patients with glycogen storage disease, excess hepatic and renal glycogen accumulation, hyperlipidemia, neutropenia, and elevations in plasma lactate and uric acid did not occur. In addition, hypoglycemia was not observed in animals during extended periods of fasting, and the ability of G6PT1 ASO-treated mice to recover from an exogenous insulin challenge was not impaired. Together, these results demonstrate that effective glucose lowering by G6PT1 inhibitors can be achieved without adversely affecting carbohydrate and lipid metabolism. 相似文献
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Michael J. Blum Christina M. Sloop Debra R. Ayres Donald R. Strong 《Molecular ecology resources》2004,4(1):39-42
The cordgrasses in the genus Spartina have become model organisms for studying biological invasions from both ecological and genetic perspectives. Here we characterize 11 disomic loci in Spartina alterniflora that show promise for population studies and for studying hybridization events between S. alterniflora and S. foliosa. Comparisons among invasive and native S. alterniflora populations showed that levels of allelic variation are lower in invasive populations. In addition, nearly all loci that amplified in S. foliosa populations and in a swarm of S. alterniflora×foliosa hybrids were polymorphic. We also found that several loci amplified successfully in other Spartina species. 相似文献
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