Eli Lilly and Company

About: Eli Lilly and Company is a company organization based out in Indianapolis, Indiana, United States. It is known for research contribution in the topics: Population & Receptor. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.

Genetic studies of quantitative MCI and AD phenotypes in ADNI: Progress, opportunities, and plans

Abstract: Introduction Genetic data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) have been crucial in advancing the understanding of Alzheimer's disease (AD) pathophysiology. Here, we provide an update on sample collection, scientific progress and opportunities, conceptual issues, and future plans. Methods Lymphoblastoid cell lines and DNA and RNA samples from blood have been collected and banked, and data and biosamples have been widely disseminated. To date, APOE genotyping, genome-wide association study (GWAS), and whole exome and whole genome sequencing data have been obtained and disseminated. Results ADNI genetic data have been downloaded thousands of times, and >300 publications have resulted, including reports of large-scale GWAS by consortia to which ADNI contributed. Many of the first applications of quantitative endophenotype association studies used ADNI data, including some of the earliest GWAS and pathway-based studies of biospecimen and imaging biomarkers, as well as memory and other clinical/cognitive variables. Other contributions include some of the first whole exome and whole genome sequencing data sets and reports in healthy controls, mild cognitive impairment, and AD. Discussion Numerous genetic susceptibility and protective markers for AD and disease biomarkers have been identified and replicated using ADNI data and have heavily implicated immune, mitochondrial, cell cycle/fate, and other biological processes. Early sequencing studies suggest that rare and structural variants are likely to account for significant additional phenotypic variation. Longitudinal analyses of transcriptomic, proteomic, metabolomic, and epigenomic changes will also further elucidate dynamic processes underlying preclinical and prodromal stages of disease. Integration of this unique collection of multiomics data within a systems biology framework will help to separate truly informative markers of early disease mechanisms and potential novel therapeutic targets from the vast background of less relevant biological processes. Fortunately, a broad swath of the scientific community has accepted this grand challenge.

The role of catecholamines in the release of anterior pituitary prolactin in vitro.

Abstract: Rat hypothalamic extracts, dopamine (DA), norepinephrine (NE), and epinephrine (EP), were incubated with rat pituitary tissue in medium 199. In all cases rat hypothalamic extracts significantly inhibited pituitary prolactin (PRL) release in vitro. When the hypothalamic extracts were subjected to preincubation with a rat brain monoamine oxidase enzyme preparation (MAO) or ot aluminum oxide (alumina) catecholamine adsorption, the hypothalamic extracts lost their ability to inhibit PRL release in vitro Pepsin pretreatment did not impair the inhibition of PRL release by hypothalamic extracts and iproniazid 10 μg/ml of medium blocked the effect of MAO on the hypothalamic extracts. The DA and NE content of MAO treated and untreated hypothalamic extracts was measured by a fluorometric technique. The catecholamine containing acid eluate from the alumina adsorption procedure was able to inhibit PRL release to the same degree as untreated hypothalamic extracts. Dopamine (5.26 × 10−9 to 5.26 × 10−7M) and NE (2.42 × ...

Hepatitis C therapeutics: current status and emerging strategies.

Abstract: Chronic infection with hepatitis C virus (HCV) is an emerging global epidemic. The development of effective HCV antiviral therapeutics continues to be a daunting challenge owing to the absence of adequate animal models and tissue-culture systems for analysis and propagation of the virus. Despite these obstacles, inhibitors of the replicative elements of HCV, immune modulators and non-specific hepatoprotective agents are being pursued and exciting progress has been made. Successful therapeutic intervention of HCV will probably require combination approaches and new approaches, including host drug discovery targets.

Homocysteine and methylmalonic acid: markers to predict and avoid toxicity from pemetrexed therapy.

Abstract: The purpose of this study was to identify predictive factors for severe toxicity caused by antifolate-chemotherapy using pemetrexed (ALIMTA, LY231514), as a model. Data on potential predictive factors for severe toxicity from pemetrexed were collected from 246 patients treated between 1995 and 1999. Multivariate stepwise regression methods were used to identify markers predictive of severe toxicity. Using a multiple logistic regression model allowed us to quantify the relative risk of developing toxicities and to generate a validated clinical hypothesis on ways to improve the safety profile of pemetrexed. Pretreatment total plasma homocysteine (tHcy) levels significantly predict severe thrombocytopenia and neutropenia with or without associated grade 3/4 diarrhea, mucositis, or infection. Pretreatment methylmalonic acid (MMA) levels significantly and independently predict grade 3/4 diarrhea and mucositis; however, these toxicities are still predicted by tHcy alone. Patients with elevated baseline levels of tHcy alone, or of both tHcy and MMA, were found to have a high risk of severe toxicity that led us to postulate that reducing tHcy would result in a reduction of severe toxicity with no harm to efficacy. This study points out for the first time the importance of pretreatment tHcy levels in predicting severe toxicity associated with an antifolate and sets the stage for a prospective clinical intervention to protect patients from pemetrexed-induced severe toxicity and possibly improve the drug's efficacy. Antifolates as a class have been associated with sporadic severe myelosuppression with gastrointestinal toxicity. Although infrequent, a combination of such toxicities can carry a high risk of mortality. This phenomenon had been unpredictable until now. Our work shows that by measuring tHcy, one can identify patients that are at risk of toxicity before treatment. Most importantly, decreasing homocysteine levels via vitamin supplementation leads to a better safety profile of pemetrexed and possibly to an improved efficacy.