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Robert Frost
Title Associate Professor
Institution College of Medicine
Department Cellular and Molecular Physiology
Address 500 University Drive Hershey PA 17033
Mailbox: H166
Telephone 7175315346
Email
Background
PREFERRED TITLE/ROLE:

Associate Professor of Cellular and Molecular Physiology

GRADUATE PROGRAM AFFILIATIONS:

Physiology

EDUCATION:

Ph.D., State University of New York at Stony Brook (Cellular and Dev Biology)
Postdoctoral Training SUNY Stony Brook (Endocrinology)
Publications
1. Frost RA, Lang CH. Multifaceted role of insulin-like growth factors and mammalian target of rapamycin in skeletal muscle. Endocrinol Metab Clin North Am. 2012 Jun; 41(2):297-322, vi.
  View in: PubMed
 
2. Frost RA, Lang CH. mTor signaling in skeletal muscle during sepsis and inflammation: where does it all go wrong? Physiology (Bethesda). 2011 Apr; 26(2):83-96.
  View in: PubMed
 
3. Kazi AA, Pruznak AM, Frost RA, Lang CH. Sepsis-induced alterations in protein-protein interactions within mTOR complex 1 and the modulating effect of leucine on muscle protein synthesis. Shock. 2011 Feb; 35(2):117-25.
  View in: PubMed
 
4. Frost RA, Pereyra E, Lang CH. Ethyl pyruvate preserves IGF-I sensitivity toward mTOR substrates and protein synthesis in C2C12 myotubes. Endocrinology. 2011 Jan; 152(1):151-63.
  View in: PubMed
 
5. Lang CH, Frost RA, Bronson SK, Lynch CJ, Vary TC. Skeletal muscle protein balance in mTOR heterozygous mice in response to inflammation and leucine. Am J Physiol Endocrinol Metab. 2010 Jun; 298(6):E1283-94.
  View in: PubMed
 
6. Frost RA, Huber D, Pruznak A, Lang CH. Regulation of REDD1 by insulin-like growth factor-I in skeletal muscle and myotubes. J Cell Biochem. 2009 Dec 1; 108(5):1192-202.
  View in: PubMed
 
7. Frost RA, Nystrom GJ, Lang CH. Endotoxin and interferon-gamma inhibit translation in skeletal muscle cells by stimulating nitric oxide synthase activity. Shock. 2009 Oct; 32(4):416-26.
  View in: PubMed
 
8. Nystrom G, Pruznak A, Huber D, Frost RA, Lang CH. Local insulin-like growth factor I prevents sepsis-induced muscle atrophy. Metabolism. 2009 Jun; 58(6):787-97.
  View in: PubMed
 
9. Pruznak AM, Kazi AA, Frost RA, Vary TC, Lang CH. Activation of AMP-activated protein kinase by 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside prevents leucine-stimulated protein synthesis in rat skeletal muscle. J Nutr. 2008 Oct; 138(10):1887-94.
  View in: PubMed
 
10. Pruznak AM, Hong-Brown L, Lantry R, She P, Frost RA, Vary TC, Lang CH. Skeletal and cardiac myopathy in HIV-1 transgenic rats. Am J Physiol Endocrinol Metab. 2008 Oct; 295(4):E964-73.
  View in: PubMed
 
11. Vary TC, Frost RA, Lang CH. Acute alcohol intoxication increases atrogin-1 and MuRF1 mRNA without increasing proteolysis in skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2008 Jun; 294(6):R1777-89.
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12. Lang CH, Frost RA, Vary TC. Acute alcohol intoxication increases REDD1 in skeletal muscle. Alcohol Clin Exp Res. 2008 May; 32(5):796-805.
  View in: PubMed
 
13. Lang CH, Nystrom G, Frost RA. Beta-adrenergic blockade exacerbates sepsis-induced changes in tumor necrosis factor alpha and interleukin-6 in skeletal muscle and is associated with impaired translation initiation. J Trauma. 2008 Feb; 64(2):477-86.
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14. Frost RA, Lang CH. Regulation of muscle growth by pathogen-associated molecules. J Anim Sci. 2008 Apr; 86(14 Suppl):E84-93.
  View in: PubMed
 
15. Lang CH, Frost RA, Vary TC. Regulation of muscle protein synthesis during sepsis and inflammation. Am J Physiol Endocrinol Metab. 2007 Aug; 293(2):E453-9.
  View in: PubMed
 
16. Frost RA, Lang CH. Protein kinase B/Akt: a nexus of growth factor and cytokine signaling in determining muscle mass. J Appl Physiol. 2007 Jul; 103(1):378-87.
  View in: PubMed
 
17. Krawiec BJ, Nystrom GJ, Frost RA, Jefferson LS, Lang CH. AMP-activated protein kinase agonists increase mRNA content of the muscle-specific ubiquitin ligases MAFbx and MuRF1 in C2C12 cells. Am J Physiol Endocrinol Metab. 2007 Jun; 292(6):E1555-67.
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18. Lang CH, Frost RA, Vary TC. Skeletal muscle protein synthesis and degradation exhibit sexual dimorphism after chronic alcohol consumption but not acute intoxication. Am J Physiol Endocrinol Metab. 2007 Jun; 292(6):E1497-506.
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19. Lang CH, Frost RA. Sepsis-induced suppression of skeletal muscle translation initiation mediated by tumor necrosis factor alpha. Metabolism. 2007 Jan; 56(1):49-57.
  View in: PubMed
 
20. Lang CH, Frost RA. Glucocorticoids and TNFalpha interact cooperatively to mediate sepsis-induced leucine resistance in skeletal muscle. Mol Med. 2006 Nov-Dec; 12(11-12):291-9.
  View in: PubMed
 
21. Frost RA, Nystrom GJ, Jefferson LS, Lang CH. Hormone, cytokine, and nutritional regulation of sepsis-induced increases in atrogin-1 and MuRF1 in skeletal muscle. Am J Physiol Endocrinol Metab. 2007 Feb; 292(2):E501-12.
  View in: PubMed
 
22. Lang CH, Huber D, Frost RA. Burn-induced increase in atrogin-1 and MuRF-1 in skeletal muscle is glucocorticoid independent but downregulated by IGF-I. Am J Physiol Regul Integr Comp Physiol. 2007 Jan; 292(1):R328-36.
  View in: PubMed
 
23. Lang CH, Krawiec BJ, Huber D, McCoy JM, Frost RA. Sepsis and inflammatory insults downregulate IGFBP-5, but not IGFBP-4, in skeletal muscle via a TNF-dependent mechanism. Am J Physiol Regul Integr Comp Physiol. 2006 Apr; 290(4):R963-72.
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24. Frost RA, Nystrom GJ, Lang CH. Multiple Toll-like receptor ligands induce an IL-6 transcriptional response in skeletal myocytes. Am J Physiol Regul Integr Comp Physiol. 2006 Mar; 290(3):R773-84.
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25. Lang CH, Frost RA, Summer AD, Vary TC. Molecular mechanisms responsible for alcohol-induced myopathy in skeletal muscle and heart. Int J Biochem Cell Biol. 2005 Oct; 37(10):2180-95.
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26. Krawiec BJ, Frost RA, Vary TC, Jefferson LS, Lang CH. Hindlimb casting decreases muscle mass in part by proteasome-dependent proteolysis but independent of protein synthesis. Am J Physiol Endocrinol Metab. 2005 Dec; 289(6):E969-80.
  View in: PubMed
 
27. Frost RA, Nystrom G, Burrows PV, Lang CH. Temporal differences in the ability of ethanol to modulate endotoxin-induced increases in inflammatory cytokines in muscle under in vivo conditions. Alcohol Clin Exp Res. 2005 Jul; 29(7):1247-56.
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28. Frost RA, Lang CH. Skeletal muscle cytokines: regulation by pathogen-associated molecules and catabolic hormones. Curr Opin Clin Nutr Metab Care. 2005 May; 8(3):255-63.
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29. Hong-Brown LQ, Pruznak AM, Frost RA, Vary TC, Lang CH. Indinavir alters regulators of protein anabolism and catabolism in skeletal muscle. Am J Physiol Endocrinol Metab. 2005 Sep; 289(3):E382-90.
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30. Lang CH, Frost RA. Endotoxin disrupts the leucine-signaling pathway involving phosphorylation of mTOR, 4E-BP1, and S6K1 in skeletal muscle. J Cell Physiol. 2005 Apr; 203(1):144-55.
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31. Lang CH, Pruznak AM, Frost RA. TNFalpha mediates sepsis-induced impairment of basal and leucine-stimulated signaling via S6K1 and eIF4E in cardiac muscle. J Cell Biochem. 2005 Feb 1; 94(2):419-31.
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32. Lang CH, Hong-Brown L, Frost RA. Cytokine inhibition of JAK-STAT signaling: a new mechanism of growth hormone resistance. Pediatr Nephrol. 2005 Mar; 20(3):306-12.
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33. Lang CH, Pruznak AM, Deshpande N, Palopoli MM, Frost RA, Vary TC. Alcohol intoxication impairs phosphorylation of S6K1 and S6 in skeletal muscle independently of ethanol metabolism. Alcohol Clin Exp Res. 2004 Nov; 28(11):1758-67.
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34. Lang CH, Deshpande N, Frost RA. Leucine acutely reverses burn-induced alterations in translation initiation in heart. Shock. 2004 Oct; 22(4):326-32.
  View in: PubMed
 
35. Frost RA, Nystrom GJ, Lang CH. Lipopolysaccharide stimulates nitric oxide synthase-2 expression in murine skeletal muscle and C(2)C(12) myoblasts via Toll-like receptor-4 and c-Jun NH(2)-terminal kinase pathways. Am J Physiol Cell Physiol. 2004 Dec; 287(6):C1605-15.
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36. Lang CH, Frost RA. Differential effect of sepsis on ability of leucine and IGF-I to stimulate muscle translation initiation. Am J Physiol Endocrinol Metab. 2004 Oct; 287(4):E721-30.
  View in: PubMed
 
37. Lang CH, Frost RA, Svanberg E, Vary TC. IGF-I/IGFBP-3 ameliorates alterations in protein synthesis, eIF4E availability, and myostatin in alcohol-fed rats. Am J Physiol Endocrinol Metab. 2004 Jun; 286(6):E916-26.
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38. Frost RA, Nystrom GJ, Lang CH. Epinephrine stimulates IL-6 expression in skeletal muscle and C2C12 myoblasts: role of c-Jun NH2-terminal kinase and histone deacetylase activity. Am J Physiol Endocrinol Metab. 2004 May; 286(5):E809-17.
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39. Frost RA, Lang CH. Alteration of somatotropic function by proinflammatory cytokines. J Anim Sci. 2004; 82 E-Suppl:E100-109.
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40. Lang CH, Frost RA, Vary TC. Thermal injury impairs cardiac protein synthesis and is associated with alterations in translation initiation. Am J Physiol Regul Integr Comp Physiol. 2004 Apr; 286(4):R740-50.
  View in: PubMed
 
41. Lang CH, Vary TC, Frost RA. Acute in vivo elevation of insulin-like growth factor (IGF) binding protein-1 decreases plasma free IGF-I and muscle protein synthesis. Endocrinology. 2003 Sep; 144(9):3922-33.
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42. Lang CH, Frost RA, Deshpande N, Kumar V, Vary TC, Jefferson LS, Kimball SR. Alcohol impairs leucine-mediated phosphorylation of 4E-BP1, S6K1, eIF4G, and mTOR in skeletal muscle. Am J Physiol Endocrinol Metab. 2003 Dec; 285(6):E1205-15.
  View in: PubMed
 
43. Frost RA, Nystrom GJ, Lang CH. Lipopolysaccharide and proinflammatory cytokines stimulate interleukin-6 expression in C2C12 myoblasts: role of the Jun NH2-terminal kinase. Am J Physiol Regul Integr Comp Physiol. 2003 Nov; 285(5):R1153-64.
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44. Lang CH, Silvis C, Deshpande N, Nystrom G, Frost RA. Endotoxin stimulates in vivo expression of inflammatory cytokines tumor necrosis factor alpha, interleukin-1beta, -6, and high-mobility-group protein-1 in skeletal muscle. Shock. 2003 Jun; 19(6):538-46.
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45. Frost RA, Nystrom GJ, Lang CH. Tumor necrosis factor-alpha decreases insulin-like growth factor-I messenger ribonucleic acid expression in C2C12 myoblasts via a Jun N-terminal kinase pathway. Endocrinology. 2003 May; 144(5):1770-9.
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46. Hong-Brown LQ, Brown CR, Cooney RN, Frost RA, Lang CH. Sepsis-induced muscle growth hormone resistance occurs independently of STAT5 phosphorylation. Am J Physiol Endocrinol Metab. 2003 Jul; 285(1):E63-72.
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47. Lang CH, Kumar V, Liu X, Frost RA, Vary TC. IGF-I induced phosphorylation of S6K1 and 4E-BP1 in heart is impaired by acute alcohol intoxication. Alcohol Clin Exp Res. 2003 Mar; 27(3):485-94.
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48. Frost RA, Lang CH. Regulation of insulin-like growth factor-I in skeletal muscle and muscle cells. Minerva Endocrinol. 2003 Mar; 28(1):53-73.
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49. Kumar V, Frost RA, Lang CH. Alcohol impairs insulin and IGF-I stimulation of S6K1 but not 4E-BP1 in skeletal muscle. Am J Physiol Endocrinol Metab. 2002 Nov; 283(5):E917-28.
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50. Kumar V, Silvis C, Nystrom G, Deshpande N, Vary TC, Frost RA, Lang CH. Alcohol-induced increases in insulin-like growth factor binding protein-1 are partially mediated by TNF. Alcohol Clin Exp Res. 2002 Oct; 26(10):1574-83.
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51. Frost RA, Nystrom GJ, Lang CH. Lipopolysaccharide regulates proinflammatory cytokine expression in mouse myoblasts and skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2002 Sep; 283(3):R698-709.
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52. Lang CH, Frost RA. Role of growth hormone, insulin-like growth factor-I, and insulin-like growth factor binding proteins in the catabolic response to injury and infection. Curr Opin Clin Nutr Metab Care. 2002 May; 5(3):271-9.
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53. Lang CH, Frost RA, Nairn AC, MacLean DA, Vary TC. TNF-alpha impairs heart and skeletal muscle protein synthesis by altering translation initiation. Am J Physiol Endocrinol Metab. 2002 Feb; 282(2):E336-47.
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54. Frost RA, Nystrom GJ, Lang CH. Regulation of IGF-I mRNA and signal transducers and activators of transcription-3 and -5 (Stat-3 and -5) by GH in C2C12 myoblasts. Endocrinology. 2002 Feb; 143(2):492-503.
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55. Lang CH, Nystrom GJ, Frost RA. Burn-induced changes in IGF-I and IGF-binding proteins are partially glucocorticoid dependent. Am J Physiol Regul Integr Comp Physiol. 2002 Jan; 282(1):R207-15.
  View in: PubMed
 
56. Hong-Brown LQ, Frost RA, Lang CH. Alcohol impairs protein synthesis and degradation in cultured skeletal muscle cells. Alcohol Clin Exp Res. 2001 Sep; 25(9):1373-82.
  View in: PubMed
 
57. Lang CH, Nystrom GJ, Frost RA. Tissue-specific regulation of IGF-I and IGF-binding proteins in response to TNFalpha. Growth Horm IGF Res. 2001 Aug; 11(4):250-60.
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58. Lang CH, Silvis C, Nystrom G, Frost RA. Regulation of myostatin by glucocorticoids after thermal injury. FASEB J. 2001 Aug; 15(10):1807-9.
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59. Lang CH, Kimball SR, Frost RA, Vary TC. Alcohol myopathy: impairment of protein synthesis and translation initiation. Int J Biochem Cell Biol. 2001 May; 33(5):457-73.
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60. Lang CH, Frost RA, Kumar V, Vary TC. Impaired myocardial protein synthesis induced by acute alcohol intoxication is associated with changes in eIF4F. Am J Physiol Endocrinol Metab. 2000 Nov; 279(5):E1029-38.
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61. Svanberg E, Frost RA, Lang CH, Isgaard J, Jefferson LS, Kimball SR, Vary TC. IGF-I/IGFBP-3 binary complex modulates sepsis-induced inhibition of protein synthesis in skeletal muscle. Am J Physiol Endocrinol Metab. 2000 Nov; 279(5):E1145-58.
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62. Frost RA, Nystrom GJ, Lang CH. Stimulation of insulin-like growth factor binding protein-1 synthesis by interleukin-1beta: requirement of the mitogen-activated protein kinase pathway. Endocrinology. 2000 Sep; 141(9):3156-64.
  View in: PubMed
 
63. Lang CH, Liu X, Nystrom GJ, Frost RA. Acute response of IGF-I and IGF binding proteins induced by thermal injury. Am J Physiol Endocrinol Metab. 2000 Jun; 278(6):E1087-96.
  View in: PubMed
 
64. Lang CH, Frost RA, Jefferson LS, Kimball SR, Vary TC. Endotoxin-induced decrease in muscle protein synthesis is associated with changes in eIF2B, eIF4E, and IGF-I. Am J Physiol Endocrinol Metab. 2000 Jun; 278(6):E1133-43.
  View in: PubMed
 
65. Lang CH, Frost RA, Kumar V, Wu D, Vary TC. Impaired protein synthesis induced by acute alcohol intoxication is associated with changes in eIF4E in muscle and eIF2B in liver. Alcohol Clin Exp Res. 2000 Mar; 24(3):322-31.
  View in: PubMed
 
66. Lang CH, Liu X, Nystrom G, Wu D, Cooney RN, Frost RA. Acute effects of growth hormone in alcohol-fed rats. Alcohol Alcohol. 2000 Mar-Apr; 35(2):148-58.
  View in: PubMed
 
67. Lang CH, Wu D, Frost RA, Jefferson LS, Vary TC, Kimball SR. Chronic alcohol feeding impairs hepatic translation initiation by modulating eIF2 and eIF4E. Am J Physiol. 1999 Nov; 277(5 Pt 1):E805-14.
  View in: PubMed
 
68. Frost RA, Lang CH. Differential effects of insulin-like growth factor I (IGF-I) and IGF-binding protein-1 on protein metabolism in human skeletal muscle cells. Endocrinology. 1999 Sep; 140(9):3962-70.
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69. Mynarcik DC, Frost RA, Lang CH, DeCristofaro K, McNurlan MA, Garlick PJ, Steigbigel RT, Fuhrer J, Ahnn S, Gelato MC. Insulin-like growth factor system in patients with HIV infection: effect of exogenous growth hormone administration. J Acquir Immune Defic Syndr. 1999 Sep 1; 22(1):49-55.
  View in: PubMed
 
70. Lang CH, Wu D, Frost RA, Jefferson LS, Kimball SR, Vary TC. Inhibition of muscle protein synthesis by alcohol is associated with modulation of eIF2B and eIF4E. Am J Physiol. 1999 Aug; 277(2 Pt 1):E268-76.
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71. Lang CH, Nystrom GJ, Frost RA. Regulation of IGF binding protein-1 in hep G2 cells by cytokines and reactive oxygen species. Am J Physiol. 1999 Mar; 276(3 Pt 1):G719-27.
  View in: PubMed
 
72. Lang CH, Frost RA, Ejiofor J, Lacy DB, McGuinness OP. Hepatic production and intestinal uptake of IGF-I: response to infection. Am J Physiol. 1998 Dec; 275(6 Pt 1):G1291-8.
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73. McNurlan MA, Garlick PJ, Frost RA, Decristofaro KA, Lang CH, Steigbigel RT, Fuhrer J, Gelato M. Albumin synthesis and bone collagen formation in human immunodeficiency virus-positive subjects: differential effects of growth hormone administration. J Clin Endocrinol Metab. 1998 Sep; 83(9):3050-5.
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74. Frost RA, Lang CH. Growth factors in critical illness: regulation and therapeutic aspects. Curr Opin Clin Nutr Metab Care. 1998 Mar; 1(2):195-204.
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75. McNurlan MA, Garlick PJ, Steigbigel RT, DeCristofaro KA, Frost RA, Lang CH, Johnson RW, Santasier AM, Cabahug CJ, Fuhrer J, Gelato MC. Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease. J Clin Invest. 1997 Oct 15; 100(8):2125-32.
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76. Frost RA, Lang CH, Gelato MC. Transient exposure of human myoblasts to tumor necrosis factor-alpha inhibits serum and insulin-like growth factor-I stimulated protein synthesis. Endocrinology. 1997 Oct; 138(10):4153-9.
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77. Lang CH, Pollard V, Fan J, Traber LD, Traber DL, Frost RA, Gelato MC, Prough DS. Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin. Am J Physiol. 1997 Jul; 273(1 Pt 2):R371-8.
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78. Bereket A, Wilson TA, Blethen SL, Fan J, Frost RA, Gelato MC, Lang CH. Effect of short-term fasting on free/dissociable insulin-like growth factor I concentrations in normal human serum. J Clin Endocrinol Metab. 1996 Dec; 81(12):4379-84.
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79. Samstein B, Hoimes ML, Fan J, Frost RA, Gelato MC, Lang CH. IL-6 stimulation of insulin-like growth factor binding protein (IGFBP)-1 production. Biochem Biophys Res Commun. 1996 Nov 12; 228(2):611-5.
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80. Frost RA, Nachman SA, Lang CH, Gelato MC. Proteolysis of insulin-like growth factor-binding protein-3 in human immunodeficiency virus-positive children who fail to thrive. J Clin Endocrinol Metab. 1996 Aug; 81(8):2957-62.
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81. Lang CH, Fan J, Frost RA, Gelato MC, Sakurai Y, Herndon DN, Wolfe RR. Regulation of the insulin-like growth factor system by insulin in burn patients. J Clin Endocrinol Metab. 1996 Jul; 81(7):2474-80.
  View in: PubMed
 
82. Frost RA, Fuhrer J, Steigbigel R, Mariuz P, Lang CH, Gelato MC. Wasting in the acquired immune deficiency syndrome is associated with multiple defects in the serum insulin-like growth factor system. Clin Endocrinol (Oxf). 1996 May; 44(5):501-14.
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83. Bereket A, Lang CH, Blethen SL, Fan J, Frost RA, Wilson TA. Insulin-like growth factor binding protein-3 proteolysis in children with insulin-dependent diabetes mellitus: a possible role for insulin in the regulation of IGFBP-3 protease activity. J Clin Endocrinol Metab. 1995 Aug; 80(8):2282-8.
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84. Bereket A, Lang CH, Blethen SL, Gelato MC, Fan J, Frost RA, Wilson TA. Effect of insulin on the insulin-like growth factor system in children with new-onset insulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1995 Apr; 80(4):1312-7.
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85. Wojnar MM, Fan J, Frost RA, Gelato MC, Lang CH. Alterations in the insulin-like growth factor system in trauma patients. Am J Physiol. 1995 Apr; 268(4 Pt 2):R970-7.
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86. Frost RA, Bereket A, Wilson TA, Wojnar MM, Lang CH, Gelato MC. Phosphorylation of insulin-like growth factor binding protein-1 in patients with insulin-dependent diabetes mellitus and severe trauma. J Clin Endocrinol Metab. 1994 Jun; 78(6):1533-5.
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87. Frost RA, Mazella J, Tseng L. Insulin-like growth factor binding protein-1 inhibits the mitogenic effect of insulin-like growth factors and progestins in human endometrial stromal cells. Biol Reprod. 1993 Jul; 49(1):104-11.
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88. Frost RA, Tseng L. Insulin-like growth factor-binding protein-1 is phosphorylated by cultured human endometrial stromal cells and multiple protein kinases in vitro. J Biol Chem. 1991 Sep 25; 266(27):18082-8.
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Keyword
Last Name
Institution
    
 
 
 
Keywords   
Insulin-Like Growth Factor I
Muscle, Skeletal
Sepsis
Muscle Proteins
Lipopolysaccharides
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Co-Authors  
Hong, Ly
Jefferson, Leonard
Kimball, Scot
Lang, Charles
She, Pengxiang
See all (7) people
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