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排序方式: 共有598条查询结果,搜索用时 31 毫秒
1.
Sumei Ren Paul McNamara Pernilla Royster Jae Lee Surinderjit S. Saluja David Koharski Sharon Hendershot Van Truong 《Journal of labelled compounds & radiopharmaceuticals》2007,50(7):643-648
1‐Benzyl‐4‐hydroxy[2‐14C]piperidine, a useful intermediate in labeled compound synthesis, was prepared from [14C]formaldehyde in high yield. The distribution pattern of 14C in the product is consistent with a mechanism involving reversible iminium ion formation and rapid equilibration of the iminium ion through a cationic aza‐Cope rearrangement. These steps precede the rate‐determining intramolecular cyclization step. SCH 351125 is a potent, selective CCR5 receptor antagonist with potential as a treatment for HIV infection. [14C]SCH 351125, required for metabolism studies, was prepared from 1‐benzyl‐4‐hydroxy[2‐14C]piperidine in six steps. [14C]SCH 351125 is a mixture of four atropisomers. Preparation of [14C]SCH 351125 besylate salt of the desired atropisomer pair is also described. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
2.
Salnikov AV Roswall P Sundberg C Gardner H Heldin NE Rubin K 《Laboratory investigation; a journal of technical methods and pathology》2005,85(4):512-521
A pathologically elevated interstitial fluid pressure (IFP) is a characteristic of both clinical and experimental carcinoma. The soluble TGF-beta receptor type II-murine Fc:IgG2A chimeric protein (Fc:TbetaRII) lowers IFP in the KAT-4 experimental model for anaplastic thyroid carcinoma. Analyses of messenger RNA (mRNA) expressions by Affymetrix microarrays and RNase protection assays, as well as of protein expressions identified tumor macrophages as targets for Fc:TbetaRII. Treatment with Fc:TbetaRII reduced albumin extravasation, increased coverage of alpha-smooth muscle actin-positive cells and reduced expression of NG2, a marker of activated pericytes, in KAT-4 carcinoma blood vessels. Specific inhibition of interleukin-1 (IL-1), a major cytokine produced by activated macrophages, lowered carcinoma IFP to a similar degree as Fc:TbetaRII but had no significant effect on the parameters of blood vessel maturation. Neither Fc:TbetaRII nor inhibition of IL-1 changed blood vessel density. Finally, pretreatment of KAT-4 carcinomas with Fc:TbetaRII increased the antitumor efficacy of doxorubicin. Our data emphasize a potential role of tumor macrophages in carcinoma physiology and identify these cells as potential stromal targets for treatment aimed to improve efficacy of chemotherapy. 相似文献
3.
Pelin Sahlén Rapolas Spalinskas Samina Asad Kunal Das Mahapatra Pontus Höjer Anandashankar Anil Jesper Eisfeldt Ankit Srivastava Pernilla Nikamo Anaya Mukherjee Kyu-Han Kim Otto Bergman Mona Ståhle Enikö Sonkoly Andor Pivarcsi Carl-Fredrik Wahlgren Magnus Nordenskjöld Fulya Taylan Isabel Tapia-Páez 《The Journal of allergy and clinical immunology》2021,147(5):1742-1752
4.
Royster LH Driscoll DP Thomas WG Royster JD 《American Industrial Hygiene Association journal》1980,41(2):113-119
A nonindustrial noise exposed population (NINEP) that describes the age effects for a black male and female population has been established. The mean hearing threshold levels for the black NINEP are significantly lower (better hearing) than the previously established mean HTLs for a white NINEP when compared by sex. The availability of the black NINEP now makes it possible to more accurately evaluate a typical industrial noise exposed population (INEP). 相似文献
5.
Peter Gennemark Rasmus Jansson-Löfmark Gina Hyberg Maria Wigstrand Dorota Kakol-Palm Pernilla Håkansson Daniel Hovdal Peter Brodin Maria Fritsch-Fredin Madeleine Antonsson Karolina Ploj Johan Gabrielsson 《Journal of pharmacokinetics and pharmacodynamics》2013,40(6):651-667
Body composition and body mass are pivotal clinical endpoints in studies of welfare diseases. We present a combined effort of established and new mathematical models based on rigorous monitoring of energy intake (EI) and body mass in mice. Specifically, we parameterize a mechanistic turnover model based on the law of energy conservation coupled to a drug mechanism model. Key model variables are fat-free mass (FFM) and fat mass (FM), governed by EI and energy expenditure (EE). An empirical Forbes curve relating FFM to FM was derived experimentally for female C57BL/6 mice. The Forbes curve differs from a previously reported curve for male C57BL/6 mice, and we thoroughly analyse how the choice of Forbes curve impacts model predictions. The drug mechanism function acts on EI or EE, or both. Drug mechanism parameters (two to three parameters) and system parameters (up to six free parameters) could be estimated with good precision (coefficients of variation typically <20 % and not greater than 40 % in our analyses). Model simulations were done to predict the EE and FM change at different drug provocations in mice. In addition, we simulated body mass and FM changes at different drug provocations using a similar model for man. Surprisingly, model simulations indicate that an increase in EI (e.g. 10 %) was more efficient than an equal lowering of EI. Also, the relative change in body mass and FM is greater in man than in mouse at the same relative change in either EI or EE. We acknowledge that this assumes the same drug mechanism impact across the two species. A set of recommendations regarding the Forbes curve, vehicle control groups, dual action on EI and loss, and translational aspects are discussed. This quantitative approach significantly improves data interpretation, disease system understanding, safety assessment and translation across species. 相似文献
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There is now substantial evidence that the cytokine interleukin-17 orchestrates the accumulation of neutrophils in mammals
and thereby contributes to host defense. However, the role of IL-17 in controlling neutrophil turnover is not fully understood.
Here, we demonstrate that IL-17 stimulates the apoptosis of mouse neutrophils and, simultaneously, the release of the microbicidal
compound, myeloperoxidase. IL-17 also stimulates mouse macrophages to phagocytose aged neutrophils and latex beads, and it
induces an increase in a soluble form of the phagocytic receptor, lectin-like oxidized low-density lipoprotein receptor-1
as well. In contrast, IL-17 does not markedly increase the release of the archetype neutrophil-recruiting cytokine, macrophage
inflammatory protein-2 in mouse macrophages. Importantly, IL-17 also stimulates the phagocytosis of latex beads in human monocyte-derived
macrophages. Thus, IL-17 bears the potential to control both phagocytosis and neutrophil turnover during activation of host
defense. 相似文献