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排序方式: 共有238条查询结果,搜索用时 19 毫秒
1.
William C. Groutas He Huang Jeffrey B. Epp Michael J. Brubaker Charles E. Keller Jerald J. McClenahan 《Bioorganic & medicinal chemistry letters》1992,2(12):1565-1570
A general approach toward the rational design of potential inhibitors of serine proteinases is described. The approach is exemplified and validated through the use of appropriate heterocyclic systems in inhibiting human leukocytes elastase (HLE). 相似文献
2.
Teruhiro Utsugi Colin P. N. Dinney Jerald J. Killion Isaiah J. Fidler 《Cancer immunology, immunotherapy : CII》1991,33(6):375-381
Summary We determined whether the intravenous administration of multilamellar vesicle liposomes (MLV) containing a lipopeptide analogue of a fragment from the cell wall of gram-negative bacteria (CGP 31 362) can render BALB/c mouse alveolar macrophages tumoricidal in situ and reduce the incidence of spontaneous lung metastasis of syngeneic renal carcinoma (RENCA) cells. Alveolar macrophages (a) incubated in vitro with MLV containing CGP 31 362 (MLV-31 362) and (b) harvested from mice injected i.v. with MLV-31 362 were rendered cytotoxic against the RENCA cells. Maximum cytotoxic activity of the macrophages was induced by injecting 5 µmol MLV consisting of 250 mg phospholipids and 0.5 mg CGP 31 362. The single i.v. injection of 5 µmol MLV-31 362 produced activation of macrophages that lasted for up to 4 days. Repeated i. v. injections of MLV-31 362 produced a continuous antitumor activity in alveolar macrophages. To study the lipopeptide's effects on metastasis, we injected the left kidneys of BALB/c mice with RENCA cells. The kidney with growing tumor was resected 10 days later and, after a further 2 days, groups of mice were injected i.v. with MLV-31 362 or with MLV-HBSS (twice weekly for 3 weeks). Treatment with MLV-31 362 significantly decreased the median number of spontaneous lung metastases. These data demonstrate that the systemic administration of MLV-31 362 can activate murine lung macrophages in situ and reduce the incidence of spontaneous RENCA lung metastases. 相似文献
3.
Adenosine triphosphate pool levels and endogenous metabolism in Arthrobacter crystallopoietes during growth and starvation 总被引:2,自引:0,他引:2
The adenosine triphosphate (ATP) content of Arthrobactery crystallopoietes was measured during growth, starvation and recovery from starvation. During exponential growth of the cells as spheres in a glucose salts medium, the level of ATP per cell remained constant at 8.0×10-10 g/cell. Morphogenesis to rodshaped cells and an increased growth rate following addition of casein hydrolysate was accompanied by an almost two-fold increase in the ATP level. As division of the rod-shaped cells proceeded, the level of ATP declined. After growing as rods for 12–14 h the cells underwent fragmentation to spheres during which time the ATP level again increased to the original value of 8.0×10-10 g/cell. As the spherical cells resumed growth on the residual glucose, their ATP content declined for a short period and then remained relatively constant. During starvation of sphere or rod-shaped cells for one week, the ATP level declined by approximately 70% during the first 40–50 h and then remained constant. The endogenous metabolism rate of spherical cells declined during the first 10–20 h of starvation and then remained constant at approximately 0.02% of the cell carbon being utilized per h. Addition of glucose to spherical cells which had been starved for one week increased both the ATP content per cell and their rate of endogenous metabolism. The ATP content fluctuated and then remained at a level higher than maintained during starvation while endogenous metabolism quickly declined.Non-Standard Abbreviations ATP
adenosine triphosphate
- GS
glucose mineral salts
- HC
casein hydrolysate
- PVP
polyvinylpyrrolidone
- DMSO
dimethylsulfoxide
- MOPS
morpholinopropane sulfonic acid
- EDTA
ethylene diaminetetraacetic acid 相似文献
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5.
Alphonse Ouédraogo Alfred B. Tiono Désiré Kargougou Jean Baptiste Yaro Esperance Ouédraogo Youssouf Kaboré David Kangoye Edith C. Bougouma Adama Gansane Noelie Henri Amidou Diarra Souleymane Sanon Issiaka Soulama Amadou T. Konate Nora L. Watson Valerie Brown Jenny Hendriks Maria Grazia Pau Isabella Versteege Edison Wiesken Jerald Sadoff Issa Nebie Sodiomon B. Sirima 《PloS one》2013,8(11)
Background
Ad35.CS.01 is a pre-erythrocytic malaria candidate vaccine. It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite (CS) surface antigen inserted in a replication deficient Adenovirus 35 backbone. A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe. The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa.Methods
A double blind, randomized, controlled, dose escalation, phase Ib trial was conducted in a rural area of Balonghin, the Saponé health district (Burkina Faso). Forty-eight healthy adults aged 18-45 years were randomized into 4 cohorts of 12 to receive three vaccine doses (day 0, 28 and 84) of 109, 1010, 5X1010, 1011 vp of Ad35.CS.01 or normal saline by intra muscular injection. Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events. Severe and serious adverse events were collected throughout the participant study duration (12 months from the first vaccination). Humoral and cellular immune responses were measured on study days 0, 28, 56, 84, 112 and 140.Results
Of the forty-eight subjects enrolled, forty-four (91.7%) received all three scheduled vaccine doses. Local reactions, all of mild severity, occurred in thirteen (27.1%) subjects. Severe (grade 3) laboratory abnormalities occurred in five (10.4%) subjects. One serious adverse event was reported and attributed to infection judged unrelated to vaccine. The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35.Conclusion
Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population. These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies.Trial Registration
ClinicalTrials.gov NCT01018459 http://clinicaltrials.gov/ct2/show/NCT01018459 相似文献6.
Kaliappan Gopal Perumal Nagarajan Jose Jedy Avinash T. Raj S. Kalai Gnanaselvi Parveen Jahan Yogendra Sharma Esaki M. Shankar Jerald M. Kumar 《PloS one》2013,8(6)
Abdominal aortic aneurysm (AAA) is a common chronic degenerative disease characterized by progressive aortic dilation and rupture. The mechanisms underlying the role of α-tocopherol and β-carotene on AAA have not been comprehensively assessed. We investigated if α-tocopherol and β-carotene supplementation could attenuate AAA, and studied the underlying mechanisms utilized by the antioxidants to alleviate AAA. Four-months-old Apoe−/− mice were used in the induction of aneurysm by infusion of angiotensin II (Ang II), and were orally administered with α-tocopherol and β-carotene enriched diet for 60 days. Significant increase of LDL, cholesterol, triglycerides and circulating inflammatory cells was observed in the Ang II-treated animals, and gene expression studies showed that ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9 and MMP-12 were upregulated in the aorta of aneurysm-induced mice. Extensive plaques, aneurysm and diffusion of inflammatory cells into the tunica intima were also noticed. The size of aorta was significantly (P = 0.0002) increased (2.24±0.20 mm) in the aneurysm-induced animals as compared to control mice (1.17±0.06 mm). Interestingly, β-carotene dramatically controlled the diffusion of macrophages into the aortic tunica intima, and circulation. It also dissolved the formation of atheromatous plaque. Further, β-carotene significantly decreased the aortic diameter (1.33±0.12 mm) in the aneurysm-induced mice (β-carotene, P = 0.0002). It also downregulated ICAM-1, VCAM-1, MCP-1, M-CSF, MMP-2, MMP-9, MMP-12, PPAR-α and PPAR-γ following treatment. Hence, dietary supplementation of β-carotene may have a protective function against Ang II-induced AAA by ameliorating macrophage recruitment in Apoe−/− mice. 相似文献
7.
Brittany H. Gale Jerald B. Johnson G. Bruce Schaalje Mark C. Belk 《Ecology and evolution》2013,3(2):326-333
Variation in somatic growth rates is of great interest to biologists because of the relationship between growth and other fitness‐determining traits, and it results from both genetic and environmentally induced variation (i.e. plasticity). Theoretical predictions suggest that mean somatic growth rates and the shape of the reaction norm for growth can be influenced by variation in predator‐induced mortality rates. Few studies have focused on variation in reaction norms for growth in response to resource availability between high‐predation and low‐predation environments. We used juvenile Brachyrhaphis rhabdophora from high‐predation and low‐predation environments to test for variation in mean growth rates and for variation in reaction norms for growth at two levels of food availability in a common‐environment experiment. To test for variation in growth rates in the field, we compared somatic growth rates in juveniles in high‐predation and low‐predation environments. In the common‐environment experiment, mean growth rates did not differ between fish from differing predation environments, but the interaction between predation environment and food level took the form of a crossing reaction norm for both growth in length and mass. Fish from low‐predation environments exhibited no significant difference in growth rate between high and low food treatments. In contrast, fish from high‐predation environments exhibited variation in growth rates between high and low food treatments, with higher food availability resulting in higher growth rates. In the field, individuals in the high‐predation environment grow at a faster rate than those in low‐predation environments at the smallest sizes (comparable to sizes in the common‐environment experiment). These data provide no evidence for evolved differences in mean growth rates between predation environments. However, fish from high‐predation environments exhibited greater plasticity in growth rates in response to resource availability suggesting that predation environments may exhibit increased variation in food availability for prey fish and consequent selection for plasticity. 相似文献
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9.
Repeated evolution of local adaptation in swimming performance: population‐level trade‐offs between burst and endurance swimming in Brachyrhaphis freshwater fish 下载免费PDF全文
Spencer J. Ingley Henry Camarillo Hannah Willis Jerald B. Johnson 《Biological journal of the Linnean Society. Linnean Society of London》2016,119(4):1011-1026
Specialization is fundamentally important in biology because specialized traits allow species to expand into new environments, in turn promoting population differentiation and speciation. Specialization often results in trade‐offs between traits that maximize fitness in one environment but not others. Despite the ubiquity of trade‐offs, we know relatively little about how consistently trade‐offs evolve between populations when multiple sets of populations experience similarly divergent selective regimes. In the present study, we report a case study on Brachyrhaphis fishes from different predation environments. We evaluate apparent within/between population trade‐offs in burst‐speed and endurance at two levels of evolutionary diversification: high‐ and low‐predation populations of Brachyrhaphis rhabdophora, and sister species Brachyrhaphis roseni and Brachyrhaphis terrabensis, which occur in high‐ and low‐predation environments, respectively. Populations of Brachyrhaphis experiencing different predation regimes consistently evolved swimming specializations indicative of a trade‐off between two swimming forms that are likely highly adaptive in the environment in which they occur. We show that populations have become similarly locally adapted at both levels of diversification, suggesting that swimming specialization has evolved rather rapidly and persisted post‐speciation. Our findings provide valuable insight into how local adaptation evolves at different stages of evolutionary divergence. 相似文献
10.