5 research outputs found
Molecular and macromolecular alterations of recombinant adenoviral vectors do not resolve changes in hepatic drug metabolism during infection
No full textAbstract In this report we test the hypothesis that long-term virus-induced alterations in CYP occur from changes initiated by the virus that may not be related to the immune response. Enzyme activity, protein expression and mRNA of CYP3A2, a correlate of human CYP3A4, and CYP2C11, responsive to inflammatory mediators, were assessed 0.25, 1, 4, and 14 days after administration of several different recombinant adenoviruses at a dose of 5.7 × 1012 virus particles (vp)/kg to male Sprague Dawley rats. Wild type adenovirus, containing all viral genes, suppressed CYP3A2 and 2C11 activity by 37% and 39%, respectively within six hours. Levels fell to 67% (CYP3A2) and 79% (CYP2C11) of control by 14 days (p ≤ 0.01). Helper-dependent adenovirus, with all viral genes removed, suppressed CYP3A2 (43%) and CYP2C11 (55%) within six hours. CYP3A2 remained significantly suppressed (47%, 14 days, p ≤ 0.01) while CYP2C11 returned to baseline at this time. CYP3A2 and 2C11 were reduced by 45 and 42% respectively 6 hours after treatment with PEGylated adenovirus, which has a low immunological profile (p ≤ 0.05). CYP3A2 remained suppressed (34%, p ≤ 0.05) for 14 days while CYP2C11 recovered. Inactivated virus suppressed CYP3A2 activity by 25–50% for 14 days (p ≤ 0.05). CYP2C11 was affected similar manner but recovered by day 14. Microarray and in vitro studies suggest that changes in cellular signaling pathways initiated early in virus infection contribute to changes in CYP.</p
Approaching the uncultured endosymbiont of Riftia pachyptila by physiological proteomics
No full textAuthor Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of AAAS for personal use, not for redistribution. The definitive version was published in Science 315 (2007): 247-250, doi:10.1126/science.1132913.The bacterial endosymbiont of the deep-sea tube worm Riftia pachyptila has
never been successfully cultivated outside its host. In the absence of cultivation data we
have taken a proteomic approach based on the metagenome sequence to study the
metabolism of this peculiar microorganism in detail. As one result, we found that three
major sulfide oxidation proteins constitute ~12% of the total cytosolic proteome,
highlighting the essential role of these enzymes for the symbiont’s energy metabolism.
Unexpectedly, the symbiont uses the reductive tricarboxylic acid (TCA) cycle in addition
to the previously identified Calvin cycle for CO2 fixation.This work was supported by
the DFG, grant Schw595/3-1. Other funding sources were: NSF (OCE 04-52333) and NASA Astrobiology Institute (NNA04CC04A) for SMS, MH: postdoctoral
scholarship from WHOI, HF: Academic Senate (RF811S and RE518S)
Is Emergency Medicine the Right Choice for Me?
No full textOne of the hardest decisions a medical student has to make is the choice of specialty. Many studies have explored what influences the choice of emergency medicine (EM) as a specialty. In this article, we elaborate on the most important incentives, including the diversity in patients’ presentations, having a defined and flexible schedule, the plasticity in choosing and changing a practice location, and the acuity of care and trauma experience. Additionally, we tackle some of the challenges that emergency physicians face. For instance, having to follow a different thought process than most other physicians, as well as the patients’ quality and expectations. We also address some of the concerns regarding the specialty, specifically burnout, stress, and the fear associated with maintaining a career in EM. Finally, we provide students interested in EM with some resources that can provide them with further guidance to decide whether EM is the right choice for them. © 2018 The Author
Phase II study of dacarbazine given with modern prophylactic anti-emetics and growth factor support to patients with metastatic, resistant soft tissue, and bone sarcoma
No full textHistorically, administration of dacarbazine to sarcoma patients was limited by frequent treat-ment-related nausea/vomiting and neutropenia. These toxicities are now largely preventable with contemporary antiemetics and growth factor support. In this single-arm, phase II study, dacarbazine 850 mg/m 2 was given on day 1 of each 3-week cycle until disease progression or intolerance with prophylactic serotonin-3 receptor, neurokinin-1 antagonists, corticosteroids, and pegfilgrastim. Coprimary endpoints included clinical benefit rate (CBR), and any grade of nausea/vomiting and/or grade 3–4 neutropenia. With a sample size of 80 patients, >24 patients with clinical benefit would indicate that the CBR exceeds the historical (<20%) [Power 0.80; alpha 0.05]. In addition, we hypothesized that the rates of nausea/vomiting would be 27% and grade 3–4 neutropenia would be 1% (historical: 90% and 36%, respectively) [power 0.95; alpha 0.05]. The CBR was 30% (24 patients: PR-2 and stable-22). The rate of nausea/vomiting was 37.5% (31 patients) and grades 3–4 neutropenia was 10% (8 patients). Median time-to-progression was 8.1 weeks (95% CI 8–9.7) and median overall survival was 35.8 weeks (95% CI 26.2–55.4). PET scans demonstrated no association with response. Modern prophylactic anti-emetics and pegfilgrastim given with dacarbazine reduced the rates of treatment related nausea/vomiting and serious neutropenia
Large expert-curated database for benchmarking document similarity detection in biomedical literature search
No full textDocument recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH (RELISH) consortium consisting of more
than 1,500 scientists from 84 countries, who have collectively annotated the relevance of over 180,000 PubMed-listed articles with regard to their
respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The
collected data covers 76% of all unique PubMed Medical Subject Headings (MeSH) descriptors. No systematic biases were observed across different experience levels, research fields, or time spent on annotations. More
importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three
representative baseline methods used to generate recommended articles for evaluation [Okapi Best Matching 25 (BM25), Term Frequency–Inverse Document Frequency (TF-IDF), and PubMed Related Articles (PMRA)] had similar overall performances. Additionally we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind-testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science
