The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.
Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy
Open accessAbstract
An interferon-gamma, tumor necrosis factor, and interleukin-1-inducible, high-output pathway synthesizing nitric oxide (NO) from L-arginine was recently identified in rodents. High-dose interleukin-2 (IL-2) therapy is known to induce the same cytokines in patients with advanced cancer. Therefore, we examined renal cell carcinoma (RCC; n = 5) and malignant melanoma (MM; n = 7) patients for evidence of cytokine-inducible NO synthesis. Activity of this pathway was evaluated by measuring serum and urine nitrate (the stable degradation product of NO) during IL-2 therapy. IL-2 administration caused a striking increase in NO generation as reflected by serum nitrate levels (10- and 8-fold increase [P less than 0.001, P less than 0.003] for RCC and MM patients, respectively) and 24-h urinary nitrate excretion (6.5- and 9-fold increase [both P less than 0.001] for RCC and MM patients, respectively). IL-2-induced renal dysfunction made only a minor contribution to increased serum nitrate levels. Metabolic tracer studies using L-[guanidino-15N2]arginine demonstrated that the increased nitrate production was derived from a terminal guanidino nitrogen atom of L-arginine. Our results showing increased endogenous nitrate synthesis in patients receiving IL-2 demonstrate for the first time that a cytokine-inducible, high-output L-arginine/NO pathway exists in humans.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Importantly, during inflammatory reactions or infection involving increased iNOS expression large amounts of NO are produced resulting in significant increases in plasma nitrate and nitrite [42–44].”
From Inorganic nitrite therapy: historical perspective and future directions (2011) · cites this paper as [43]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Applied Multiple Regression/Correlation Analysis for the Behavioral Sciences
Cohen, P., Cohen, P., West, S. G., & Aiken, L. S. (2014) · Psychology Press eBooks · doi:10.4324/9781410606266 · Cited by 20,870
Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids
Green, L. C., Wagner, D. A., Glogowski, J. A., Skipper, P. L., Wishnok, J. S., & Tannenbaum, S. R. (1982) · Analytical Biochemistry · doi:10.1016/0003-2697(82)90118-x · Cited by 12,061
Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor
Palmer, R. M. J., Ferrige, A. G., & Moncada, S. (1987) · Nature · doi:10.1038/327524a0 · Cited by 10,704
Applied Multiple Regression/Correlation Analysis for the Behavioral Sciences.
Henry, N. W., Cohen, J., & Cohen, P. R. (1977) · Contemporary Sociology A Journal of Reviews · doi:10.2307/2064799 · Cited by 7,242
Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
Ignarro, L. J., Buga, G. M., Wood, K. S., Byrns, R. E., & Chaudhuri, G. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.24.9265 · Cited by 5,074
Vascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,786
Localization of nitric oxide synthase indicating a neural role for nitric oxide
Bredt, D. S., Hwang, P. M., & Snyder, S. H. (1990) · Nature · doi:10.1038/347768a0 · Cited by 2,981
Ding, A. H., Nathan, C., & Stuehr, D. J. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.141.7.2407 · Cited by 2,840
Garthwaite, J., Charles, S. L., & Chess‐Williams, R. (1988) · Nature · doi:10.1038/336385a0 · Cited by 2,540
Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia
Tracey, K. J., Fong, Y., Hesse, D. G., Manogue, K. R., Lee, A. T., Kuo, G. C., Lowry, S. F., & Cerami, A. (1987) · Nature · doi:10.1038/330662a0 · Cited by 2,448
Research works printed but not linked: 3
- Hibbs, J. B., Jr., R. R. Taintor, Z. Vavrin, D. L. Granger, J.-C. Drapier, I. J. Amber, and J. R. Lancaster, Jr. 1990. Synthesis of nitric oxide from a termi- nal guanidino nitrogen atom of L-arginine: a molecular mechanism regulating Cytokine-inducible Nitric Oxide Synthesis 875 cellular proliferation that targets intracellular iron. In Nitric Oxide from L-Argi- nine: A Bioregulatory System. S. Moncada and E. A. Higgs editors. Elsevier Science Publishers B. V. (Biomedical Division), New York. 189-223.
- Anon. 1981. Nitrate, nitrite and nitrogen oxides: environmental distribu- tion and exposure of humans. In The Health Effects of Nitrate, Nitrite, and N-Nitroso Compounds, Volume 1. F. M. Peter, editor. National Academy Press, Washington, DC. 3-52.
- Stoff, J. S., and D. M. Clive. 1983. Role of prostaglandins and thrombox- ane in acute renal failure. In Acute Renal Failure. B. M. Brenner and J. M. Lazarus, eds. W. B. Saunders Co., Philadelphia, pp. 157-174.
Cited by
Sorted by citations
Nitric oxide as a secretory product of mammalian cells
Nathan, C. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.12.1381691 · Cited by 4,350
Fang, F. C. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119473 · Cited by 1,139
Extensive Nitration of Protein Tyrosines in Human Atherosclerosis Detected by Immunohistochemistry
Beckman, J. S., Ye, Y. Z., Anderson, P. G., Chen, J., Accavitti, M. A., Tarpey, M. M., & White, C. R. (1994) · Biological Chemistry Hoppe-Seyler · doi:10.1515/bchm3.1994.375.2.81 · Cited by 1,122
Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions.
Förstermann, U., Closs, E. I., Pollock, J. S., Nakane, M., Schwarz, P., Gath, I., & Kleinert, H. (1994) · Hypertension · doi:10.1161/01.hyp.23.6.1121 · Cited by 1,122
Tsikas, D. (2006) · Journal of Chromatography B · doi:10.1016/j.jchromb.2006.07.054 · Cited by 897
Metadata
- Authors
- Hibbs, J. B., Westenfelder, C., Taintor, R., Vavrin, Z., Kablitz, C., Baranowski, R. L., Ward, J. H., Menlove, R. L., McMurry, M. P., & Kushner, J. P.
- Affiliations
- Veterans Health Administration (US)
- University of Utah (US)
- ORCID
- Westenfelder, C
- Venue
- Journal of Clinical Investigation
- Published
- 1992-03-01
- Volume
- 89
- Issue
- 3
- Pages
- 867-877
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC442932
- OpenAlex
- W2120872446
- Cited by
- 485
- References
- 80
- Citations by year
- 2026: 3 · 2025: 1 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 1 · 2018: 3 · 2017: 5 · 2016: 1 · 2015: 10 · 2014: 7 · 2013: 4 · 2012: 2
- FWCI
- 36.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- National Institutes of Health
- National Cancer Institute (CA42014, P30CA042014)
- National Center for Research Resources (RR 00064)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- nitric oxide production, L-arginine, interleukin-2 therapy, interferon-gamma, TNF-α, interleukin-1, nitrate, urinary nitrate excretion, renal cell carcinoma, melanoma, renal dysfunction, arginine metabolism
- MeSH terms
- Adult, Arginine, Carcinoma, Renal Cell, Female, Humans, Interferon-gamma, Interleukin-2, Kidney Neoplasms, Kidney Tubules, Male, Melanoma, Middle Aged, Nitric Oxide, Vascular Resistance
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
