Geert W Schmid-Schönbein

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc The Autodigestion Hypothesis for Shock and Multi-organ Failure
    Geert W Schmid-Schönbein
    Department of Bioengineering, The Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, 92093, USA
    Ann Biomed Eng 42:405-14. 2014
  2. ncbi request reprint Analysis of inflammation
    Geert W Schmid-Schönbein
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla, California 92093 0412, USA
    Annu Rev Biomed Eng 8:93-131. 2006
  3. ncbi request reprint A new hypothesis for microvascular inflammation in shock and multiorgan failure: self-digestion by pancreatic enzymes
    Geert W Schmid-Schönbein
    Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093, USA
    Microcirculation 12:71-82. 2005
  4. ncbi request reprint The second valve system in lymphatics
    Geert W Schmid-Schönbein
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla, California 92093 0412, USA
    Lymphat Res Biol 1:25-9; discussion 29-31. 2003
  5. ncbi request reprint The primary valves in the initial lymphatics during inflammation
    Patrick M Lynch
    Department of Bioengineering, University of California San Diego, La Jolla, California 92093 0412, USA
    Lymphat Res Biol 5:3-10. 2007
  6. pmc Biomechanical aspects of the auto-digestion theory
    Geert W Schmid-Schönbein
    Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, CA, 92093 0412, USA
    Mol Cell Biomech 5:83-95. 2008
  7. pmc 2008 Landis Award lecture. Inflammation and the autodigestion hypothesis
    Geert W Schmid-Schönbein
    Department of Bioengineering, University of California San Diego, La Jolla, California 92093 0412, USA
    Microcirculation 16:289-306. 2009
  8. ncbi request reprint Biomechanics of microcirculatory blood perfusion
    G W Schmid-Schonbein
    Department of Bioengineering and Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla, California 92093 0412, USA
    Annu Rev Biomed Eng 1:73-102. 1999
  9. ncbi request reprint Pancreatic enzymes and microvascular cell activation in multiorgan failure
    G W Schmid-Schonbein
    Department of Bioengineering, University of California, San Diego, La Jolla 92093 0412, USA
    Microcirculation 8:5-14. 2001
  10. ncbi request reprint Microvascular endothelial cell death and rarefaction in the glucocorticoid-induced hypertensive rat
    C J Vogt
    Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla 92093 0412, USA
    Microcirculation 8:129-39. 2001

Research Grants

  1. STRUCTURE AND FUNCTION OF THE MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2003
  2. Digestive Enzymes and Microvascular Inflammation in Shock
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2009
  3. STRUCTURE AND FUNCTION OF THE MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2005
  4. STRUCTURE AND FUNCTION OF MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2007
  5. Microvascular Injury and Pancreatic Enzyme Products
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2004
  6. STRUCTURE AND FUNCTION OF THE MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2004
  7. Microvascular Injury and Pancreatic Enzyme Products
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2003
  8. Microvascular Injury and Pancreatic Enzyme Products
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2005
  9. STRUCTURE AND FUNCTION OF THE MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2006
  10. 2006 Molecular Mechanisms in Lymphatic Function & Disease Gordon Conference
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2006

Collaborators

Detail Information

Publications87

  1. pmc The Autodigestion Hypothesis for Shock and Multi-organ Failure
    Geert W Schmid-Schönbein
    Department of Bioengineering, The Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA, 92093, USA
    Ann Biomed Eng 42:405-14. 2014
    ..Blockade of digestive enzymes in the lumen of the intestine in experimental forms of shock serves to reduce breakdown of the mucosal barrier and autodigestion of the intestine, organ dysfunctions and mortality. ..
  2. ncbi request reprint Analysis of inflammation
    Geert W Schmid-Schönbein
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla, California 92093 0412, USA
    Annu Rev Biomed Eng 8:93-131. 2006
    ..The inflammatory cascade offers a large number of opportunities for development of quantitative models that describe various aspects of human diseases...
  3. ncbi request reprint A new hypothesis for microvascular inflammation in shock and multiorgan failure: self-digestion by pancreatic enzymes
    Geert W Schmid-Schönbein
    Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093, USA
    Microcirculation 12:71-82. 2005
    ....
  4. ncbi request reprint The second valve system in lymphatics
    Geert W Schmid-Schönbein
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla, California 92093 0412, USA
    Lymphat Res Biol 1:25-9; discussion 29-31. 2003
    ..The primary valves, in conjunction with the secondary valves, provide a mechanism that facilitates the unidirectional flow during periodic compression and expansion of initial lymphatics...
  5. ncbi request reprint The primary valves in the initial lymphatics during inflammation
    Patrick M Lynch
    Department of Bioengineering, University of California San Diego, La Jolla, California 92093 0412, USA
    Lymphat Res Biol 5:3-10. 2007
    ..Thus, the opening dimension of the primary valves and their ability to prevent reflux into the interstitium during inflammation were investigated...
  6. pmc Biomechanical aspects of the auto-digestion theory
    Geert W Schmid-Schönbein
    Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, CA, 92093 0412, USA
    Mol Cell Biomech 5:83-95. 2008
    ..The hypothesis that multi-organ failure in shock may be due an auto-digestion process by pancreatic enzymes is ready to be tested in a variety of shock conditions...
  7. pmc 2008 Landis Award lecture. Inflammation and the autodigestion hypothesis
    Geert W Schmid-Schönbein
    Department of Bioengineering, University of California San Diego, La Jolla, California 92093 0412, USA
    Microcirculation 16:289-306. 2009
    ..The evidence suggests that uncontrolled proteolytic and lipolytic enzyme activity may trigger the mechanism for tissue injury. The significance of such mechanisms remain to be explored in human diseases...
  8. ncbi request reprint Biomechanics of microcirculatory blood perfusion
    G W Schmid-Schonbein
    Department of Bioengineering and Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla, California 92093 0412, USA
    Annu Rev Biomed Eng 1:73-102. 1999
    ..The application of biomechanical analysis of the microcirculation is starting to focus on diseases. The field is rich with problems of high significance...
  9. ncbi request reprint Pancreatic enzymes and microvascular cell activation in multiorgan failure
    G W Schmid-Schonbein
    Department of Bioengineering, University of California, San Diego, La Jolla 92093 0412, USA
    Microcirculation 8:5-14. 2001
    ..The evidence suggests that pancreatic enzymes in the ischemic intestine may attack several tissue components and generate cellular activators that are associated with multiorgan dysfunction in physiological shock...
  10. ncbi request reprint Microvascular endothelial cell death and rarefaction in the glucocorticoid-induced hypertensive rat
    C J Vogt
    Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla 92093 0412, USA
    Microcirculation 8:129-39. 2001
    ..Microvascular rarefaction, which has been shown in human and animal hypertension, may result from increased endothelial cell apoptosis...
  11. ncbi request reprint Mechanisms for cell activation and its consequences for biorheology and microcirculation: Multi-organ failure in shock
    G W Schmid-Schonbein
    Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla, CA, USA
    Biorheology 38:185-201. 2001
    ..Our current evidence suggests that pancreatic digestive enzymes and tissue enzymes may play a central role in humoral activator production...
  12. ncbi request reprint New advances in the understanding of the pathophysiology of chronic venous insufficiency
    G W Schmid-Schonbein
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla 92093 0412, USA
    Angiology 52:S27-34. 2001
    ....
  13. ncbi request reprint Pancreatic protease inhibition during shock attenuates cell activation and peripheral inflammation
    Florian Fitzal
    Department of Bioengineering, Whitaker Institute for Biomedical Engineering, Microcirculation Laboratory, University of California, La Jolla, Calif, USA
    J Vasc Res 39:320-9. 2002
    ..These results indicate that intestinal pancreatic protease inhibition significantly attenuates intestinal ischemia-induced shock by reducing SIRS and gut injury...
  14. ncbi request reprint Contribution of fluid shear response in leukocytes to hemodynamic resistance in the spontaneously hypertensive rat
    Shunichi Fukuda
    Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, Calif 92093 0412, USA
    Circ Res 95:100-8. 2004
    ..We conclude that in addition to enhanced vascular tone, pseudopod formation with lack of normal fluid shear response may serve as mechanisms for an elevated hemodynamic resistance in SHR...
  15. ncbi request reprint Enhancement of reperfusion injury by elevation of microvascular pressures
    Shinya Takase
    Department of Bioengineering and The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla, California 92093 0412, USA
    Am J Physiol Heart Circ Physiol 282:H1387-94. 2002
    ..These results indicate that an elevation of the venular blood pressure during occlusion/reperfusion exacerbates the inflammatory cascade and tissue injury. Venous occlusion may constitute an important mechanism for tissue injury...
  16. ncbi request reprint Leukocyte fluid shear response in the presence of glucocorticoid
    Shunichi Fukuda
    Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093 0412, USA
    J Leukoc Biol 75:664-70. 2004
    ..Thus, the reversal of leukocyte shear response by glucocorticoids may contribute to an enhanced incidence of circulating leukocytes with pseudopods, a process that affects the kinetics of these cells in the microcirculation...
  17. ncbi request reprint Protease inhibition in the intestinal lumen: attenuation of systemic inflammation and early indicators of multiple organ failure in shock
    Hiroshi Mitsuoka
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California, La Jolla 92093 0412, USA
    Shock 17:205-9. 2002
    ..Blockade of pancreatic enzymes in the lumen of the intestine may be a tool to interfere with inflammation and early indicators of multiorgan failure...
  18. pmc Regulation of CD18 expression on neutrophils in response to fluid shear stress
    Shunichi Fukuda
    Department of Bioengineering and The Whitaker Institute for Biomedical Engineering, University of California at San Diego, La Jolla, CA 92093 0412, USA
    Proc Natl Acad Sci U S A 100:13152-7. 2003
    ..The evidence suggests that physiological levels of fluid shear cause release of cysteine protease(s) including cathepsin B, leading to cleavage of the extracellular domain of CD18 molecules and possible membrane detachment...
  19. ncbi request reprint Microvascular display of xanthine oxidase and NADPH oxidase in the spontaneously hypertensive rat
    Frank A DeLano
    Department of Bioengineering and The Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla, 92093 0412, USA
    Microcirculation 13:551-66. 2006
    ..The aim of this study was to gain more detailed understanding of where oxidative enzymes are located in the microcirculation...
  20. ncbi request reprint Pancreatic digestive enzymes are potent generators of mediators for leukocyte activation and mortality
    Stephen W Waldo
    Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California, La Jolla, California 92093, USA
    Shock 20:138-43. 2003
    ..We conclude that the intestine, as well as several other organs, may serve as a major source of inflammatory mediators during shock if exposed to digestive enzymes...
  21. ncbi request reprint Hypertension-induced venous valve remodeling
    Shinya Takase
    Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, School of Medicine, University of California San Diego, La Jolla, CA 92037, USA
    J Vasc Surg 39:1329-34. 2004
    ..Contralateral nonpressurized saphenous veins were used as control specimens...
  22. ncbi request reprint Control of neutrophil pseudopods by fluid shear: role of Rho family GTPases
    Ayako Makino
    Dept of Bioengineering, The Whitaker Institute of Biomedical Engineering, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA
    Am J Physiol Cell Physiol 288:C863-71. 2005
    ..These results suggest that deactivation of Rac activity by fluid shear plays an important role in stable circulation of leukocytes...
  23. ncbi request reprint Common genetic mechanisms of blood pressure elevation in two independent rodent models of human essential hypertension
    Ryan S Friese
    Department of Bioengineering, San Diego, California 92093 0838, USA
    Am J Hypertens 18:633-52. 2005
    ....
  24. ncbi request reprint Oxidative stress promotes endothelial cell apoptosis and loss of microvessels in the spontaneously hypertensive rats
    Nobuhiko Kobayashi
    Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093 0412, USA
    Arterioscler Thromb Vasc Biol 25:2114-21. 2005
    ..Endothelial cell apoptosis caused by oxidative stress may lead to the loss of microvessels (rarefaction) in hypertension. We examine here the effects of antioxidants on cell apoptosis and rarefaction...
  25. pmc Receptor cleavage and P-selectin-dependent reduction of leukocyte adhesion in the spontaneously hypertensive rat
    Angela Y Chen
    Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093 0412, USA
    J Leukoc Biol 92:183-94. 2012
    ..The impaired ability of SHR leukocytes to reduce rolling velocity upon inflammatory stimulation led to fewer firmly adhered leukocytes to the endothelium as a contributor to immune suppression...
  26. pmc Disruption of the mucosal barrier during gut ischemia allows entry of digestive enzymes into the intestinal wall
    Marisol Chang
    Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA
    Shock 37:297-305. 2012
    ..This study demonstrates that disruption of the mucosal epithelial barrier within minutes of intestinal ischemia allows entry of fully activated pancreatic digestive proteases across the intestinal barrier triggering autodigestion...
  27. ncbi request reprint Improvement in early symptoms of shock by delayed intestinal protease inhibition
    Florian Fitzal
    Microcirculation Laboratory, Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, USA
    Arch Surg 139:1008-16. 2004
    ..Herein we examine the effectiveness of delayed intestinal protease inhibition during reperfusion after SMAO...
  28. ncbi request reprint Microvascular cell death in spontaneously hypertensive rats during experimental inflammation
    Kyo C Mun
    Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California, San Diego La Jolla, CA 92093 0412, USA
    Microcirculation 9:397-405. 2002
    ..To clarify a possible underlying mechanisms, we examined leukocyte migration in the microcirculation and concomitant parenchymal cell death...
  29. ncbi request reprint Early capillary no-reflow during low-flow reperfusion after hind limb ischemia in the rat
    Florian Fitzal
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California San Diego, CA, USA
    Ann Plast Surg 49:170-80. 2002
    ..Instead, endothelial cell and/or tissue swelling in combination with luminal obstruction and leukocyte plugging may be responsible for the early capillary no-reflow phenomenon...
  30. ncbi request reprint An in-vivo analysis of capillary stasis and endothelial apoptosis in a model of hypertension
    Edward D Tran
    Department of Bioengineering, the Whitaker Institute for Biomedical Engineering Ulniversity of California San Diego, La Jolla 92093 0412, USA
    Microcirculation 14:793-804. 2007
    ..The objective of this study was to examine the early phase of endothelial apoptosis and capillary blood flow in the spontaneously hypertensive rat (SHR) and the normotensive Wistar-Kyoto (WKY) rat...
  31. ncbi request reprint Control of fluid shear response in circulating leukocytes by integrins
    Peter Marschel
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla 92093 0412, USA
    Ann Biomed Eng 30:333-43. 2002
    ..These results suggest that integrins may serve as a regulating mechanism for fluid shear response in human leukocytes. Attachment via beta1 integrins may lead to an abolishment of the fluid shear response...
  32. pmc Pseudopod projection and cell spreading of passive leukocytes in response to fluid shear stress
    Mark F Coughlin
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla, California 92093 0412, USA
    Biophys J 87:2035-42. 2004
    ..This behavior may contribute to cell spreading on endothelium and other cells as well as to transendothelial migration of leukocytes in the microcirculation...
  33. ncbi request reprint Activated leukocytes and endothelial cells enhance retention of ultrasound contrast microspheres containing perfluoropropane in inflamed venules
    Takanori Yasu
    Department of Bioengineering, University of California San Diego, La Jolla, CA 92093 0412, USA
    Int J Cardiol 98:245-52. 2005
    ..To characterize the flow dynamics of albumin ultrasound contrast microspheres containing perfluoropropane (PFP) in normal and inflamed microvasculature...
  34. pmc Acute venous occlusion enhances matrix metalloprotease activity: Implications on endothelial dysfunction
    Tom Alsaigh
    Department of Bioengineering, The Institute for Engineering in Medicine, University of California San Diego, La Jolla, CA 92093 0412, USA
    Microvasc Res 81:108-16. 2011
    ..We conclude that venous pressure elevation increases enzymatic activity which may contribute to inflammation and endothelial dysfunction associated with this disease by influencing critical surface receptors...
  35. ncbi request reprint Pancreatic enzymes generate cytotoxic mediators in the intestine
    Alexander H Penn
    Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, CA 92093 0412, USA
    Shock 27:296-304. 2007
    ..Cytotoxicity was significantly increased after digestion of food by luminal fluid compared with luminal fluid or undigested food. These results indicate the presence of a previously unknown mechanism for hemorrhagic necrosis in shock...
  36. pmc A journey with Tony Hugli up the inflammatory cascade towards the auto-digestion hypothesis
    Geert W Schmid-Schönbein
    Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California San Diego, 9500 Gilman Drive 0412 La Jolla, CA 92093 0412, USA
    Int Immunopharmacol 7:1845-51. 2007
    ..The auto-digestion hypothesis is in line with the century old observation that the intestine plays a special role on shock - indeed it is the organ for digestion. Auto-digestion may be the prize to pay for life-long nutrition...
  37. ncbi request reprint A model for mechanics of primary lymphatic valves
    Ernesto Mendoza
    Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla, CA 92093 0412, USA
    J Biomech Eng 125:407-14. 2003
    ..The model illustrates the mechanics of valve action and provides the first time a rational analysis of the mechanisms underlying fluid collection in the initial lymphatics and lymph transport in the microcirculation...
  38. pmc Impaired small-bowel barrier integrity in the presence of lumenal pancreatic digestive enzymes leads to circulatory shock
    Erik B Kistler
    Department of Anesthesiology and Critical Care, University of California, San Diego, CA 92093, USA
    Shock 38:262-7. 2012
    ..Digestive enzymes and their products, if allowed to penetrate the gut wall, may trigger multiorgan failure and death...
  39. pmc Enhanced matrix metalloproteinase activity in the spontaneously hypertensive rat: VEGFR-2 cleavage, endothelial apoptosis, and capillary rarefaction
    Edward D Tran
    Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla, Calif 92093 0412, USA
    J Vasc Res 47:423-31. 2010
    ..These results suggest elevated plasma MMP activities may cleave VEGFR-2, resulting in endothelial apoptosis and capillary rarefaction in the SHR...
  40. pmc MicroRNA-22 and promoter motif polymorphisms at the Chga locus in genetic hypertension: functional and therapeutic implications for gene expression and the pathogenesis of hypertension
    Ryan S Friese
    Department of Bioengineering, VA San Diego Healthcare System, University of California at San Diego, CA 92093, USA
    Hum Mol Genet 22:3624-40. 2013
    ..Accordingly, we demonstrated that in vivo administration of miR-22 antagomir to SHR causes substantial (∼18 mmHg) reductions in blood pressure, opening a novel therapeutic avenue for hypertension. ..
  41. ncbi request reprint An animal model of venous hypertension: the role of inflammation in venous valve failure
    Luigi Pascarella
    Department of Surgery, University of California, San Diego, USA
    J Vasc Surg 41:303-11. 2005
    ..Gross morphologic observation of venous valves in surgical specimens shows tearing, splitting, scarring, and disappearance of valves...
  42. ncbi request reprint Centrifugation attenuates the fluid shear response of circulating leukocytes
    Shunichi Fukuda
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0412, USA
    J Leukoc Biol 72:133-9. 2002
    ..It causes an impaired leukocyte behavior after reintroduction into the circulation, suggesting that shear response is a requirement for normal passage of leukocytes through the microcirculation...
  43. pmc Recoil and stiffening by adherent leukocytes in response to fluid shear
    Mark F Coughlin
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California at San Diego, La Jolla, California, USA
    Biophys J 94:1046-51. 2008
    ..This initial shear stress response may be particularly important in facilitating leukocyte attachment under sustained fluid shear stress by the flowing blood in the microcirculation...
  44. ncbi request reprint G protein-coupled receptors serve as mechanosensors for fluid shear stress in neutrophils
    Ayako Makino
    Dept of Bioengineering, The Whitaker Institute of Biomedical Engineering, Univ of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA
    Am J Physiol Cell Physiol 290:C1633-9. 2006
    ..These results suggest that GPCRs serve as mechanosensors for fluid shear stress in neutrophils by decreasing its constitutive activity and reducing pseudopod projection...
  45. ncbi request reprint Inhibition of intraluminal pancreatic enzymes with nafamostat mesilate improves clinical outcomes after hemorrhagic shock in swine
    Hubert D Kim
    Department of Surgery, University of California, Irvine Medical Center, Orange, California 92868, USA
    J Trauma 68:1078-83. 2010
    ..The objective of this study was to determine whether enteroclysis with NM would improve the clinical outcomes in swine after hemorrhagic shock and intestinal hypoperfusion...
  46. ncbi request reprint De-activation of neutrophils in suspension by fluid shear stress: a requirement for erythrocytes
    Yutaka Komai
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla, CA 92093 0412, USA
    Ann Biomed Eng 33:1375-86. 2005
    ..These results suggest that erythrocytes play an important role in neutrophil de-activation by reducing the superoxide level in plasma. Shear stress, rather than shear rate, is the key determinant that regulates neutrophil de-activation...
  47. pmc Pancreatic digestive enzyme blockade in the small intestine prevents insulin resistance in hemorrhagic shock
    Frank A DeLano
    Microcirculation Laboratory, Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, California
    Shock 41:55-61. 2014
    ..These results suggest that in hemorrhagic shock elevated microvascular extracellular digestive enzyme activity causes insulin receptor dysfunction, hyperglycemia, and reduced ability to regulate blood glucose values. ..
  48. doi request reprint Pancreatic digestive enzyme blockade in the intestine increases survival after experimental shock
    Frank A DeLano
    Department of Bioengineering, The Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093, USA
    Sci Transl Med 5:169ra11. 2013
    ....
  49. pmc Protease activity increases in plasma, peritoneal fluid, and vital organs after hemorrhagic shock in rats
    Angelina E Altshuler
    Department of Bioengineering, The Institute of Engineering in Medicine, University of California, San Diego, La Jolla, California, United States of America
    PLoS ONE 7:e32672. 2012
    ..Proteases, including pancreatic proteases, may be shock mediators and potential targets for therapy in shock...
  50. ncbi request reprint Intraluminal pancreatic serine protease activity, mucosal permeability, and shock: a review
    Jose A Acosta
    University of California San Diego School of Medicine, San Diego, CA, USA
    Shock 26:3-9. 2006
    ..We further hypothesize how these enzymes and/or their products may ultimately contribute to multiorgan failure and death...
  51. ncbi request reprint Fluid shear-induced activation and cleavage of CD18 during pseudopod retraction by human neutrophils
    Hainsworth Y Shin
    Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, California 92093 0412 USA
    J Cell Physiol 214:528-36. 2008
    ....
  52. ncbi request reprint Characterization of two classes of pancreatic shock factors: functional differences exhibited by hydrophilic and hydrophobic shock factors
    William J Kramp
    La Jolla Institute for Molecular Medicine, San Diego, California 92121, USA
    Shock 20:356-62. 2003
    ....
  53. doi request reprint The intestine as source of cytotoxic mediators in shock: free fatty acids and degradation of lipid-binding proteins
    Alexander H Penn
    Dept of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093 0412, USA
    Am J Physiol Heart Circ Physiol 294:H1779-92. 2008
    ..Breakdown of free fatty acid binding proteins by proteases causes release of free fatty acids to act as powerful cytotoxic mediators...
  54. pmc Integrated computational and experimental analysis of the neuroendocrine transcriptome in genetic hypertension identifies novel control points for the cardiometabolic syndrome
    Ryan S Friese
    Department of Bioengineering, University of California at San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093 0838, USA
    Circ Cardiovasc Genet 5:430-40. 2012
    ....
  55. pmc Matrix metalloproteinase activity causes VEGFR-2 cleavage and microvascular rarefaction in rat mesentery
    Edward D Tran
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla, California 92093 0412, USA
    Microcirculation 18:228-37. 2011
    ..These results spatially link MMP-induced VEGFR-2 cleavage and rarefaction in the mesentery of the SHR and thus support the hypothesis that MMPs serve as regulators of microvascular dysfunction in hypertension...
  56. ncbi request reprint Therapeutic management of chronic venous insufficiency: microcirculation as a target
    J J Bergan
    University of California San Diego, La Jolla 92037, USA
    Microcirculation 7:S23-8. 2000
    ..Currently, surgical attack is focused on correction of the sources of venous hypertension, but it is felt that this provides a crude method that hopefully wil be replaced by more precise pharmacological interventions...
  57. doi request reprint Pathogenesis of primary chronic venous disease: Insights from animal models of venous hypertension
    John J Bergan
    Department of Surgery, University of California San Diego, 9850 Genesee, La Jolla, CA 92037, USA
    J Vasc Surg 47:183-92. 2008
    ..Reflux of blood through incompetent venous valves is a major cause of the venous hypertension that underlies clinical manifestations of chronic venous disease, including varicose veins, lipodermatosclerosis, and venous ulcers...
  58. ncbi request reprint Mechanotransduction in leukocyte activation: a review
    Ayako Makino
    Department of Medicine, University of California, San Diego, La Jolla, CA 92093 0412, USA
    Biorheology 44:221-49. 2007
    ..We describe a disease model with chronic hypertension that suffers from an attenuated fluid shear-response with far reaching implications for microvascular blood flow...
  59. ncbi request reprint Enhancement of glucocorticoid and mineralocorticoid receptor density in the microcirculation of the spontaneously hypertensive rat
    Frank A DeLano
    Microcirculation Laboratory, Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, 9500 Gilman Dr, University of California San Diego, La Jolla, CA 92093, USA
    Microcirculation 11:69-78. 2004
    ..As background, this study was designed to examine the distribution of the glucocorticoid and mineralocorticoid receptors in a microvascular network...
  60. doi request reprint An elementary analysis of physiologic shock and multi-organ failure: the autodigestion hypothesis
    Geert W Schmid-Schönbein
    Department of Bioengineering, The Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA 92093 0412, USA
    Conf Proc IEEE Eng Med Biol Soc 2012:3114-5. 2012
    ..The consequence of autodigestion is multiorgan failure. We discuss the possibility to block the digestive enzymes in acute forms of shock as a potential therapeutic intervention...
  61. pmc Receptor cleavage reduces the fluid shear response in neutrophils of the spontaneously hypertensive rat
    Angela Y Chen
    Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093 0412, USA
    Am J Physiol Cell Physiol 299:C1441-9. 2010
    ..These results suggest that proteolytic cleavage of the FPR may interfere with normal fluid shear-induced pseudopod retractions in SHR neutrophils...
  62. ncbi request reprint Intrinsic disturbance of cellular redox balance enhances blood lymphocyte apoptosis in the spontaneously hypertensive rat
    Nobuhiko Kobayashi
    Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California at San Diego, La Jolla, CA 92093, USA
    Free Radic Biol Med 41:484-92. 2006
    ..The results suggest that blood lymphocyte apoptosis is enhanced in the SHR due to intrinsically disturbed cellular redox balance rather than altered activity in extracellular humoral factors...
  63. ncbi request reprint Xanthine oxidase activity in the dexamethasone-induced hypertensive rat
    Camille J Wallwork
    Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0412, USA
    Microvasc Res 66:30-7. 2003
    ..These results suggest that dexamethasone induces an elevated level of XO activity in the cremaster muscle. The enhanced XO activity can be attenuated by chronic allopurinol treatment...
  64. pmc Pancreatic trypsin increases matrix metalloproteinase-9 accumulation and activation during acute intestinal ischemia-reperfusion in the rat
    Henrique S Rosario
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla, California 92093, USA
    Am J Pathol 164:1707-16. 2004
    ..This process represents a powerful in vivo pathophysiological mechanism for trypsin-induced MMP-9 activation and is likely to play a central role in the development of acute intestinal inflammation and shock...
  65. pmc Fluid stresses on the membrane of migrating leukocytes
    Susan S Su
    Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0412, USA
    Ann Biomed Eng 36:298-307. 2008
    ....
  66. pmc Nuclear factor kappa B and matrix metalloproteinase induced receptor cleavage in the spontaneously hypertensive rat
    Kwan I Sharon Wu
    Department of Bioengineering, Institute for Engineering in Medicine, University of California San Diego, La Jolla, CA 92093 0412, USA
    Hypertension 57:261-8. 2011
    ..These results suggest NFκB is an important transcription factor in the SHR and may be involved in the enhanced MMP activity and, consequently, receptor cleavage...
  67. pmc Matrix metalloproteinase-1-mediated up-regulation of vascular endothelial growth factor-2 in endothelial cells
    Rafi Mazor
    Department of Bioengineering, The Institute of Engineering in Medicine, Veterans Affairs Medical Center, San Diego, California, USA
    J Biol Chem 288:598-607. 2013
    ..These results suggest a mechanism by which MMP-1 may prime or sensitize endothelial cell functions...
  68. pmc An emerging role of degrading proteinases in hypertension and the metabolic syndrome: autodigestion and receptor cleavage
    Geert W Schmid-Schönbein
    Department of Bioengineering, Institute of Engineering in Medicine, University of California San Diego, La Jolla, CA 92093 0412, USA
    Curr Hypertens Rep 14:88-96. 2012
    ..This work may open the opportunity for reassessment of old interventions and development of new interventions to manage hypertension and its comorbidities...
  69. pmc Matrix metalloproteinases: discrete elevations in essential hypertension and hypertensive end-stage renal disease
    Ryan S Friese
    Department of Medicine, University of California, San Diego, CA, USA
    Clin Exp Hypertens 31:521-33. 2009
    ..Our results suggest discrete patterns of MMP overexpression in hypertension, with MMP-9 elevated early, and MMP-2 and MMP-10 linked to target organ damage...
  70. pmc Digested formula but not digested fresh human milk causes death of intestinal cells in vitro: implications for necrotizing enterocolitis
    Alexander H Penn
    Department of Bioengineering, University of California, San Diego, La Jolla, California, USA
    Pediatr Res 72:560-7. 2012
    ..We hypothesized that after lipase digestion, formula, but not fresh breast milk, contains levels of unbound free fatty acids (FFAs) that are cytotoxic to intestinal cells...
  71. pmc Proteinase activity and receptor cleavage: mechanism for insulin resistance in the spontaneously hypertensive rat
    Frank A DeLano
    Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla CA 92093 0412, USA
    Hypertension 52:415-23. 2008
    ..The results suggest that elevated MMP activity leads to proteolytic cleavage of membrane receptors in the SHR, eg, cleavage of the insulin receptor-binding domain associated with insulin resistance...
  72. doi request reprint Systematic polymorphism discovery after genome-wide identification of potential susceptibility loci in a hereditary rodent model of human hypertension
    Ryan S Friese
    Department of Bioengineering, University of California at San Diego, USA
    Blood Press 20:222-31. 2011
    ..Our method for candidate gene identification is portable and can be applied to microarray data from any tissue, in any disease model with a QTL database...
  73. ncbi request reprint Whole blood assay for trypsin activity using polyanionic focusing gel electrophoresis
    Roy B Lefkowitz
    Department of Bioengineering, University of California, San Diego, CA 92093 0448, USA
    Electrophoresis 31:2442-51. 2010
    ..This straightforward technique now allows for the rapid measurement of clinically relevant levels of trypsin activity in microliter volumes of whole blood, providing a useful tool for the development of novel point-of-care diagnostics...
  74. ncbi request reprint Discontinuous expression of endothelial cell adhesion molecules along initial lymphatic vessels in mesentery: the primary valve structure
    Walter L Murfee
    Department of Bioengineering, University of California San Diego, 9500 Gilman Drive, Mail Code 0412, La Jolla, CA 92093, USA
    Lymphat Res Biol 5:81-9. 2007
    ..The objective of this study was to evaluate the expression pattern of adhesion molecules at endothelial cell junctions in an adult initial lymphatic network...
  75. doi request reprint Whole blood assay for elastase, chymotrypsin, matrix metalloproteinase-2, and matrix metalloproteinase-9 activity
    Roy B Lefkowitz
    Department of Bioengineering, University of California San Diego, La Jolla, California 92093 0448, USA
    Anal Chem 82:8251-8. 2010
    ..Thus, these new substrates demonstrate broad applicability toward clinically relevant detection of important disease-relevant proteases...
  76. ncbi request reprint Orbital response indicates nasal pungency: analysis of biomechanical strain on the skin
    A A Jalowayski
    Chemosensory Perception Laboratory, Department of Surgery Otolaryngology, University of California, San Diego, La Jolla, California, USA
    Chem Senses 26:1005-13. 2001
    ..Comparison with psychophysical data showed that the strain became evident at concentrations just detectable as pungent. Maximum strain measured on the skin shows promise as an objective index of pungency...
  77. ncbi request reprint A mechanism for erythrocyte-mediated elevation of apparent viscosity by leukocytes in vivo without adhesion to the endothelium
    B P Helmke
    Department of Bioengineering, University of California, San Diego, La Jolla 92093 0412, USA
    Biorheology 35:437-48. 1998
    ..Thus, leukocytes influence the whole organ resistance in skeletal muscle to a significant degree only in the presence of erythrocytes...
  78. pmc Severe intestinal ischemia can trigger cardiovascular collapse and sudden death via a parasympathetic mechanism
    Alexander H Penn
    Department of Bioengineering, The Institute for Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA
    Shock 36:251-62. 2011
    ....
  79. pmc Global metabolic consequences of the chromogranin A-null model of hypertension: transcriptomic detection, pathway identification, and experimental verification
    Ryan S Friese
    Department of Bioengineering, University of California, La Jolla, CA 92093 0838, USA
    Physiol Genomics 40:195-207. 2010
    ..The Chga KO may constitute a unique model for studying the relationship between the CHGA locus and disease phenotypes of the metabolic syndrome...
  80. pmc Fluid shear attenuates endothelial pseudopodia formation into the capillary lumen
    Isgard S Hueck
    Department of Bioengineering, The Whitaker Institute for Biomedical Engineering, University of California San Diego, La Jolla, California 92093 0412, USA
    Microcirculation 15:531-42. 2008
    ..To examine mechanotransduction mechanisms, we investigated in vivo the hemodynamic conditions in capillaries that control endothelial pseudopod formation...
  81. ncbi request reprint An electrophoretic method for the detection of chymotrypsin and trypsin activity directly in whole blood
    Roy B Lefkowitz
    Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093 0448, USA
    Electrophoresis 31:403-10. 2010
    ..Thus, the new charge changing peptide substrates enable a simple electrophoretic assay format for the measurement of degradative enzyme activity, which is an important step toward the development of novel point-of-care diagnostics...
  82. ncbi request reprint Mechanisms in experimental venous valve failure and their modification by Daflon 500 mg
    L Pascarella
    Department of Surgery University of California San Diego, La Jolla, CA, USA
    Eur J Vasc Endovasc Surg 35:102-10. 2008
    ..To characterize the acute response of the vein wall to venous hypertension and associated altered fluid shear stress and to test the effect of micronized purified flavonoid fraction (MPFF, Daflon 500), on this response...
  83. ncbi request reprint Enhanced DNA fragmentation in the thymus of spontaneously hypertensive rats
    H Suzuki
    Department of Bioengineering and Institute for Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093 0412, USA
    Am J Physiol 276:H2135-40. 1999
    ..Thus increased DNA fragmentation represents one of the mechanisms associated with thymic atrophy, a feature that reflects immune suppression in SHR...
  84. pmc Proteolytic Activity Attenuates the Response of Endothelial Cells to Fluid Shear Stress
    Angelina E Altshuler
    Department of Bioengineering, The Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093 0412
    Cell Mol Bioeng 5:82-91. 2012
    ..Under shear, however, glucose uptake for protease-treated BAECs was greater than untreated controls. In conclusion, protease activity in plasma alters the exofacial membrane components of ECs and may interfere with mechanotransduction...
  85. ncbi request reprint Transport processes in biomedical systems: a roadmap for future research directions
    Geert W Schmid-Schönbein
    Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, University of California at San Diego, La Jolla, California, USA
    Ann Biomed Eng 33:1136-41. 2005
    ..Most central is the expanded integration of fundamental transport sciences into the understanding of living systems and the great potential of patient specific modeling in designing a broad array of medical procedures...
  86. ncbi request reprint Causes of telengiectasias, reticular veins, and varicose veins
    Luigi Pascarella
    Whitaker Institute of Biomedical Engineering, Department of Bioengineering, Jacobs School of Engineering, University of California San Diego, La Jolla, CA 92093 0412, USA
    Semin Vasc Surg 18:2-4. 2005
    ..Telangiectasias, reticular veins, and true varicose veins appear to be a consequence of the changes induced by venous hypertension and sheer stress...

Research Grants34

  1. STRUCTURE AND FUNCTION OF THE MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2003
    ..These studies serve to delineate mechanisms for the expression of key inflammatory mediators in hypertensive microvessels as a basis for development of new interventions against the injurious aspects of this syndrome. ..
  2. Digestive Enzymes and Microvascular Inflammation in Shock
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2009
    ..This research will provide essential information for development of a new intervention against multi-organ failure by transient blockade of the pancreatic digestive enzymes. ..
  3. STRUCTURE AND FUNCTION OF THE MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2005
    ..These studies serve to delineate mechanisms for the expression of key inflammatory mediators in hypertensive microvessels as a basis for development of new interventions against the injurious aspects of this syndrome. ..
  4. STRUCTURE AND FUNCTION OF MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2007
    ..The research program serves the first time to unify a diverse set of pathogenic mechanisms in the SHR under one mechanistic hypothesis and at the same time open the opportunity for new therapeutic approaches. ..
  5. Microvascular Injury and Pancreatic Enzyme Products
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2004
    ..Understanding the trigger mechanisms for inflammation in shock will lead to new treatment modalities in man. ..
  6. STRUCTURE AND FUNCTION OF THE MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2004
    ..These studies serve to delineate mechanisms for the expression of key inflammatory mediators in hypertensive microvessels as a basis for development of new interventions against the injurious aspects of this syndrome. ..
  7. Microvascular Injury and Pancreatic Enzyme Products
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2003
    ..Understanding the trigger mechanisms for inflammation in shock will lead to new treatment modalities in man. ..
  8. Microvascular Injury and Pancreatic Enzyme Products
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2005
    ..Understanding the trigger mechanisms for inflammation in shock will lead to new treatment modalities in man. ..
  9. STRUCTURE AND FUNCTION OF THE MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2006
    ..These studies serve to delineate mechanisms for the expression of key inflammatory mediators in hypertensive microvessels as a basis for development of new interventions against the injurious aspects of this syndrome. ..
  10. 2006 Molecular Mechanisms in Lymphatic Function & Disease Gordon Conference
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2006
    ..The conference plays an essential role in the advancement of lymphology and development of a new understanding of lymphatic diseases and treatments. ..
  11. STRUCTURE AND FUNCTION OF MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2009
    ..The research program serves the first time to unify a diverse set of pathogenic mechanisms in the SHR under one mechanistic hypothesis and at the same time open the opportunity for new therapeutic approaches. ..
  12. STRUCTURE AND FUNCTION OF MICROCIRCULATION
    GEERT W SCHMID SCHOENBEIN; Fiscal Year: 2010
    ..The research program serves the first time to unify a diverse set of pathogenic mechanisms in the SHR under one mechanistic hypothesis and at the same time open the opportunity for new therapeutic approaches. ..
  13. Microvascular Injury and Pancreatic Enzyme Products
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2002
    ..Understanding the trigger mechanisms for inflammation in shock will lead to new treatment modalities in man. ..
  14. STRUCTURE/FUNCTION OF THE MICROCIRCULATIOM
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2001
    ..Such a program will serve to clarify the pathogenesis of hypertension and is expected to stimulate the design of novel approaches for interventions. ..
  15. Microvascular Injury and Pancreatic Enzyme Products
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2001
    ..Understanding the trigger mechanisms for inflammation in shock will lead to new treatment modalities in man. ..
  16. STRUCTURE/FUNCTION OF THE MICROCIRCULATIOM
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 1999
    ..Such a program will serve to clarify the pathogenesis of hypertension and is expected to stimulate the design of novel approaches for interventions. ..
  17. STRUCTURE AND FUNCTION OF THE MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 1993
    ....
  18. STRUCTURE AND FUNCTION OF MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 1990
    ..This type of approach should enable us to evaluate the effectiveness of current therapeutic interventions and to identify potentially new departures...
  19. STRUCTURE AND FUNCTION OF MICROCIRCULATION
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 1991
    ..This type of approach should enable us to evaluate the effectiveness of current therapeutic interventions and to identify potentially new departures...
  20. STRUCTURE/FUNCTION OF THE MICROCIRCULATIOM
    GEERT SCHMID SCHOENBEIN; Fiscal Year: 2000
    ..Such a program will serve to clarify the pathogenesis of hypertension and is expected to stimulate the design of novel approaches for interventions. ..
  21. Digestive Enzymes and Microvascular Inflammation in Shock
    GEERT W SCHMID SCHOENBEIN; Fiscal Year: 2010
    ..This research will provide essential information for development of a new intervention against multi-organ failure by transient blockade of the pancreatic digestive enzymes. ..