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John Hibbs (academic)

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John B. Hibbs Jr.
Hibbs in 2020
Born (1936-08-18) August 18, 1936 (age 88)
Uniontown, Pennsylvania
Other namesJohn Hibbs Jr
John B Hibbs Jr
CitizenshipUnited States
Known forNitric Oxide biochemistry
Academic background
EducationAB, History (1958)
MD (1962)
Alma materDartmouth College
University of Pittsburgh School of Medicine
Academic work
DisciplineInternal Medicine, Infectious Diseases, Investigation of macrophages in resistance to microbial pathogens and cancer cells
InstitutionsUniversity of Utah School of Medicine (1971-2011)
University of Utah

John B. Hibbs Jr. is an American physician-scientist and educator. He is Distinguished Professor Emeritus in the Department of Medicine at the University of Utah.

He is known for the discovery of the direct synthesis of L-citrulline and nitrogen oxides from L-arginine by murine activated macrophages, published in January 1987. This reaction was inhibited strongly by the non-toxic NG-monomethyl-L-arginine molecule.[1][2] These observations provided the biochemical tools needed to establish the new and unexpected field of nitric oxide biochemistry and made possible its rapid initial progress in cardiovascular and neural physiology. In 1988, he directly measured the gas nitric oxide,[3] simultaneously with Michael Marletta,[4] showing that it is the proximal nitrogen oxide produced during the biological oxidation of a terminal guanidino nitrogen atom of L-arginine.

Early life and education

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Hibbs was born in Uniontown, Pennsylvania in 1936 where his father was a scholarly practicing physician. Hibbs attended Dartmouth College (1954-1958) and the University of Pittsburgh School of Medicine (1958-1962). His internship was at the University of Oregon Hospitals (1962-1963). He then served as a medical officer in the U.S. Army. Following military service he returned to the University of Oregon as a resident in Internal Medicine (1966-1968). His training in clinical infectious diseases and in research examining host resistance to intracellular pathogens was at Stanford University Medical Center under the mentorship of Jack Remington (1969-1971).[5]

Career

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Hibbs joined the University of Utah School of Medicine faculty as an Assistant Professor in 1971. He rose through the academic ranks to become a Distinguished Professor in 1999. He served as Chief of the Infectious Diseases Division of the University affiliated Veterans Affairs Medical Center from 1971 to 1989 and Chief of Infectious Diseases Division of the University of Utah Health Sciences Center from 1989 to 2011.

Research

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In 1964, as a medical officer in the U.S. Army, Hibbs participated in the Bolivian hemorrhagic fever outbreak investigation directed by Karl Johnson.[5][6] This experience stimulated his interest in infectious diseases and in research. As a result, after completing training in Internal Medicine at the University of Oregon, he began Infectious Diseases Fellowship training at Stanford University in 1969. The research portion of the training was in the laboratory of Jack Remington. There he showed that mice with chronic infection with intracellular protozoan parasites, which act as a persistent stimulus for cytokine production and macrophage activation, had increased resistance to malignant cell growth.[7] In vitro activated macrophages from these mice expressed nonspecific cytotoxicity for malignant cells.[8] Prior to these experiments, macrophage mediated cytotoxicity for malignant cells was thought to be due only to immunologically specific mechanisms. After completing Infectious Diseases training in 1971, Hibbs joined the Infectious Diseases Division faculty at the University of Utah. There he began a search for a biochemical explanation for nonspecific cytotoxicity mediated by activated macrophages. These experiments led to the discovery of the synthesis of L-citrulline and nitrogen oxides, including nitric oxide per se, from L-arginine, by mouse activated macrophages.[1][2][3] He then, with colleagues, described a pattern of metabolic inhibition caused by nitric oxide in mammalian target cells and the involvement of nitric oxide in mouse activated macrophage antimicrobial activity.[9][10][11][12] This work established nitric oxide as an important component of the inflammatory response. He also showed that humans receiving the cytokine interleukin-2 for treatment of refractory malignant disease produced high levels of nitric oxide.[13] More recently he discovered extracellular energy producing metabolism carried out in highly diluted lysates of human peripheral blood leukocytes.[14]

Personal life

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Hibbs and his wife Françoise Arnaud have three children and three grandchildren. They live in Salt Lake City, Utah.[5]

Awards and honors

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  • 1979 - American Society for Clinical Investigation
  • 1981 - The Marie T. Bonazinga Award for Excellence in Research, Society for Leukocyte Biology
  • 1990 - Association of American Physicians
  • 1993 - The William S. Middleton Award for Outstanding Achievement in Medical Research, Department of Vetern Affairs
  • 1994, 1996, 1997, and 2002 - Outstanding Teacher Award, University of Utah
  • 2004 - Distinguished Scholarly and Creative Research Award, University of Utah
  • 2004 - The University of Pittsburgh Legacy Laureate Award, University of Pittsburgh

Books

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  • The Biology of Nitric Oxide 1. Physiological and Clinical Aspects. Edited by S. Moncada, M.A. Marletta, J.B. Hibbs Jr, and E.A. Higgs. Portland Press. London and Chapel Hill, 1992, ISBN 1-855-78-0127
  • The Biology of Nitric Oxide 2. Enzymology, Biochemistry, and Immunology. Edited by S. Moncada, M.A. Marletta, J.B. Hibbs Jr, and E.A. Higgs. Portland Press. London and Chapel Hill, 1992. ISBN 1-855-78-0135

References

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  1. ^ a b Hibbs Jr, J. B.; Vavrin, Z.; Taintor, R. R. (1987). "L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells". Journal of Immunology. 138 (2): 550–65. doi:10.4049/jimmunol.138.2.550. PMID 2432129. S2CID 442512.
  2. ^ a b Hibbs, J.; Taintor, R.; Vavrin, Z. (1987). "Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite". Science. 235 (4787): 473–476. Bibcode:1987Sci...235..473H. doi:10.1126/science.2432665. PMID 2432665.
  3. ^ a b "Nitric oxide: A cytotoxic activated macrophage effector molecule".
  4. ^ Marletta, Michael A.; Yoon, Poksyn S.; Iyengar, Radha; Leaf, Cynthia D.; Wishnok, John S. (1988). "Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate". Biochemistry. 27 (24): 8706–8711. doi:10.1021/bi00424a003. PMID 3242600.
  5. ^ a b c "Walking Before Dawn" (PDF).
  6. ^ Webb, P. A.; Johnson, K. M.; Hibbs, J. B.; Kuns, M. L. (1970). "Parana, a new tacaribe complex virus from Paraguay". Archiv für die Gesamte Virusforschung. 32 (4): 379–388. doi:10.1007/BF01250066. PMID 4993581. S2CID 24426347.
  7. ^ "Resistance to Murine Tumors Conferred by Chronic Infection with Intracellular Protozoa, Toxoplasma gondii and Besnoitia jellisoni".
  8. ^ "Possible Role of Macrophage Mediated Nonspecific Cytotoxicity in Tumour Resistance".
  9. ^ Hibbs JB Jr., Taintor RR., Vavrin Z, Granger DI., Drapier J-C, Amber IJ, Lancaster JR Jr., Synthesis of nitric oxide from a Terminal Guanidino Nitrogen Atom of L-argInine; a Molecular Mechanism Regulating Cellular Proliferation that targets Intracellular Iron. In Nitric Oxide from L-Arginine: A Bioregulatory System edited by Moncada S. and Higgs EA. The Netherlands, Elsevier Science Publishers BV, 1990, pp189-223. ISBN 0-444-81154-0
  10. ^ Hibbs JB Jr., 2002. Infection and Nitric Oxide. Journal of Infectious Diseases. 185 (Suppl 1) : S9-17. https://doi.org/10.1086/338005
  11. ^ Nathan CF., Hibbs JB Jr., 1991. Role of Nitric Oxide Synthesis in Macrophage Antimicrobial Activity. Current Opinion in Immunology. 3: 65-70. https://doi.org/10.1016/0952-7915(91)90079-G
  12. ^ Hibbs JB. Jr., 1991. Synthesis of Nitric Oxide from L-arginine: A Recently Discovered Pathway Induced by Cytokines with Antitumor and Antimicrobial Activity. Research in Immunology. 142: 565-569. https://doi.org/10.1016/0923-2494(91)90103-P
  13. ^ Hibbs JB Jr., Westenfelder C., Taintor RR. et al., 1992. Evidence for cytokine-inducible nitric oxide synthesis from L-arginine in patients receiving interleukin-2 therapy. J. Clin. Invest. 89: 867-877. https://doi.org/10.1172/JCI115666
  14. ^ Hibbs JB Jr., Vavrin Z., Cox JE. 2016. Complex coordinated extracellular metabolism: acid phosphates activate diluted human leukocyte proteins to generate energy flow as NADPH from purine nucleotide ribose. Redox Biology. 8: 271-284 http://dx.doi.org/10.1016/j.redox.2016.02.001
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