scispace - formally typeset
Search or ask a question
Institution

Eli Lilly and Company

CompanyIndianapolis, Indiana, United States
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 & Agonist. The organization has 17826 authors who have published 22835 publications receiving 946714 citations. The organization is also known as: Eli Lily.
Topics: Population, Agonist, Insulin, Placebo, Olanzapine


Papers
More filters
Journal ArticleDOI
TL;DR: A paracrine model in which hypoxia stimulates MP release of platelet-derived growth factor and a/bFGF, inducing EC proliferation and potentially promoting angiogenesis in hypoxic environments is suggested.
Abstract: Wound repair and tumor vascularization depend upon blood vessel growth into hypoxic tissue. Although hypoxia slows endothelial cell (EC) proliferation and suppresses EC basic fibroblast growth factor (bFGF) expression, we report that macrophages (MPs) exposed to PO2 approximately 12-14 torr (1 torr = 133.3 Pa) synthesize and release in a time-dependent manner platelet-derived growth factor (PDGF) and acidic/basic FGFs (a/bFGFs), which stimulate the growth of hypoxic ECs. Chromatography of hypoxic MP-conditioned medium on immobilized heparin with an ascending NaCl gradient resolved three peaks of mitogenic activity: activity of the first peak was neutralized by antibody to PDGF; activity of the second peak was neutralized by antibody to aFGF; and activity of the third peak was neutralized by antibody to bFGF. Metabolically labeled lysates and supernatants from MPs exposed to hypoxia showed increased synthesis and release of immunoprecipitable PDGF and a/bFGF in the absence of changes in cell viability. Possible involvement of a heme-containing oxygen sensor in MP elaboration of growth factors was suggested by the induction of bFGF and PDGF by normoxic MPs exposed to nickel or cobalt, although metabolic inhibitors such as sodium azide were without effect. These results suggest a paracrine model in which hypoxia stimulates MP release of PDGF and a/bFGF, inducing EC proliferation and potentially promoting angiogenesis in hypoxic environments.

254 citations

Journal ArticleDOI
TL;DR: The antibacterial activity of oritavancin is described, the evidence supporting the proposed mechanism of action for this agent and related analogs are examined, and the evidence support the proposed mechanisms of action is examined.
Abstract: Oritavancin (LY333328) is a semisynthetic glycopeptide antibiotic having excellent bactericidal activity against glycopeptide-susceptible and -resistant Gram-positive bacteria. Oritavancin is the N-alkyl-p-chlorophenylbenzyl derivative of chloroeremomycin (LY264826) and is currently in phase III clinical trials for use in Gram-positive infections. Studies show that oritavancin and related alkyl glycopeptides inhibit bacterial cell wall formation by blocking the transglycosylation step in peptidoglycan biosynthesis in a substrate-dependent manner. As with other glycopeptide antibiotics, including vancomycin, the effects of oritavancin on cell wall synthesis are attributable to interactions with dipeptidyl residues of peptidoglycan precursors. Unlike vancomycin, however, oritavancin is strongly dimerized and can anchor to the cytoplasmic membrane, the latter facilitated by its alkyl side chain. Cooperative interactions derived from dimerization and membrane anchoring in situ can be of sufficient strength to enable binding to either dipeptidyl or didepsipeptidyl peptidoglycan residues of vancomycin-susceptible and -resistant enterococci, respectively. This review describes the antibacterial activity of oritavancin, and examines the evidence supporting the proposed mechanism of action for this agent and related analogs.

254 citations

Journal ArticleDOI
TL;DR: A general biosynthetic method has been developed which makes it possible to site-specifically incorporate unnatural amino acids with novel properties into proteins, used to study the stability, specificity, and catalytic properties of a number of proteins.
Abstract: A general biosynthetic method has been developed which makes it possible to site-specifically incorporate unnatural amino acids with novel properties into proteins. In this approach the codon encoding the amino acid of interest is replaced with the “blank” nonsense codon UAG by oligonucleotide-directed mutagenesis. A suppressor tRNA that recognizes this codon is generated by run-off transcription and then chemically aminoacylated with the desired unnatural amino acid. Addition of the mutagenized gene and the aminoacylated suppressor tRNA to an in vitro extract capable of supporting protein biosynthesis generates a mutant protein containing the unnatural amino acid at the specified position. This methodology has recently been used to study the stability, specificity, and catalytic properties of a number of proteins. In these studies amino acids and analogues possessing altered hydrogen-bonding, electronic, and steric properties and unique backbone conformations have all been site-specifically incorporated into proteins. In addition, photoactivatable amino acids, isotopically labeled amino acids, and amino acids bearing biophysical probes have been inserted site-specifically. This chemistry increases our ability to carry out detailed physical organic studies on this important class of macromolecules.

254 citations

Journal ArticleDOI
TL;DR: The evidence suggests people with schizophrenia can experience both hyper- and hypo-function of the HPA axis, and it is likely that this contributes to the pattern of poor physical health and premature mortality suffered byPeople with schizophrenia, in particular the high rates of cardiovascular and metabolic disturbance.
Abstract: There is convincing evidence that environmental stress plays a significant role in modifying both mental and physical health. The biological mechanisms linking stress to ill health are not fully understood, but significant evidence points to a central role of the stress axes; the hypothalamic- pituitary-adrenal (HPA) axis and the sympathetic nervous system. Together these two systems link the brain and the body and are crucial in maintaining homeostasis as well as improving an organism's survival chances in the face of environmental challenge. There is evidence of altered HPA axis function in people with a range of mental disorders, and this may in part explain the poor physical health of people with psychotic, mood and anxiety disorders. This paper systematically reviews HPA axis function in people with schizophrenia and relates this to the pattern of physical health seen in this disease. In summary, the evidence suggests people with schizophrenia can experience both hyper- and hypo-function of the HPA axis. It is likely that this contributes to the pattern of poor physical health and premature mortality suffered by people with schizophrenia, in particular the high rates of cardiovascular and metabolic disturbance.

253 citations

Journal ArticleDOI
TL;DR: A higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates.
Abstract: The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study. The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six chest clinics enrolled a total of 3,575 smokers. Subjects were allocated to one of five treatment arms: placebo and either standard or higher dose nicotine patches (15 mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately intensive support. The 12 month sustained success rates were: 25 mg patch for 22 weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22 weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0) 9.9% (placebo versus 15 mg, p<0.05; 25 mg versus 15 mg, p<0.03; 25 mg versus placebo, p<0.001, Chi- squared test). There was no significant difference in success rate between the two active treatment durations. Of the first week abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first week smokers, 2.7% of 1,877 subjects (p<0.001). In summary, a higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates. Eur Respir J 1999; 13: 238-246.

253 citations


Authors

Showing all 17866 results

NameH-indexPapersCitations
Mark J. Daly204763304452
Irving L. Weissman2011141172504
Eric J. Topol1931373151025
Tony Hunter175593124726
Xiang Zhang1541733117576
Jerrold M. Olefsky14359577356
Stephen F. Badylak13353057083
George A. Bray131896100975
Lloyd Paul Aiello13150685550
Levi A. Garraway12936699989
Mark Sullivan12680263916
James A. Russell124102487929
Tony L. Yaksh12380660898
Elisabetta Dejana12243048254
Hagop S. Akiskal11856550869
Network Information
Related Institutions (5)
Pfizer
37.4K papers, 1.6M citations

98% related

Merck & Co.
48K papers, 1.9M citations

97% related

Novartis
50.5K papers, 1.9M citations

97% related

Hoffmann-La Roche
43K papers, 1.6M citations

93% related

National Institutes of Health
297.8K papers, 21.3M citations

91% related

Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20236
202287
2021815
2020868
2019732
2018742