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Research Interests
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Regulation of liver microcirculation:
Role of stress-inducible
vasoactive mediators (endothelin, nitric oxide synthase, heme oxygenase)
in altering vascular responsiveness in the liver following oxidative
or inflammatory stress. Mechanisms of control of sinusoid perfusion
by hepatic stellate cells, especially related to components of phenotypic
transformation in response to injury.
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Hepatic metabolic response to infection.
Mechanisms
of altered carbohydrate metabolism during sepsis, especially related
to differentiation between inflammation-induced changes in gene
expression and perfusion supply/demand ratio as mediators of decreased
gluconeogenesis.
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Application of imaging techniques to biological research.
In vivo video microscopy for study of liver microcirculation;
application of quantitative fluorescence techniques to monitoring
of cellular processes in intact organs or in vivo.
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Engineered liver support systems:
Bioengineering
Research Partnership
BRP page
Professional Experience
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Research Scientist, Department of Surgery,Yale University, 1981-86
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Assistant Professor, Departments of Surgery and Physiology, Johns
Hopkins School of Medicine, 1986-91
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Associate Professor, Departments of Surgery and Physiology, Johns
Hopkins School of Medicine, 1992-96
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Robert Garrett Scholar, Johns Hopkins School of Medicine, 1986-96
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Director of Pediatric Surgery Research, Johns Hopkins School of
Medicine, 1986-96
Education
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B.S., Physical Therapy; St. Louis University, 1975
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Ph.D., Physiology; St. Louis University, 1979
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Postdoctoral Fellowship, Physiology and Metabolism; Yale University,
1980-81
Courses Taught (*offered for Graduate Credit)
Selected Recent Publications
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Mark G. CLEMENS, Walid KAMOUN, Amel KARAA, and
Sandra MERKEL.
Altered caveolae-associated signalling in liver
sinusoidal endothelial cells following
inflammation. Microcirculation Annual 21: 7-10,
2005
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Karaa A, Kamoun WS, Clemens MG. Chronic Ethanol
Sensitizes the Liver to Endotoxin via Effects on
Endothelial Nitric Oxide Synthase Regulation.
Shock 24(5):447-54, 2005
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Kamoun WS, Karaa A, Kresge N, M. Merkel S,
Korneszczuk K, Clemens MG. LPS Inhibits
Endothelin-1 Induced Endothelial Nitric Oxide
Synthase Activation through a Negative Feedback
Involving Caveolin-1. Hepatology
Jan;43(1):182-90, 2006
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Keller S, Karaa A, Paxian M, Clemens MG., and
Zhang J. Inhibition of Endothelin-1 Mediated
Upregulation of iNOS by Bosentan Ameliorates
Endotoxin-Induced Liver Injury in Cirrhosis.
Shock. Mar;25(3):306-13, 2006
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Clemens MG. What's new in shock, October
2005?Shock. 24(4):297-9, 2005
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Zinchenko YS,
Schrum LW, Clemens M, Coger RN.
Hepatocyte and kupffer cells co-cultured on
micropatterned surfaces to optimize hepatocyte
function.Tissue Eng. 2006 Apr;12(4):751-61
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Karaa A, Kamoun
WS, Xu H, Zhang J, Clemens MG.
Differential effects of oxidative stress on
hepatic endothelial and Kupffer cell eicosanoid
release in response to endothelin-1.
Microcirculation. 2006 Sep;13(6):457-66.
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Dreau D, Karaa A,
Culberson C, Wyan H, McKillop IH, Clemens MG.
Bosentan((R)) inhibits tumor vascularization and
bone metastasis in an immunocompetent skin-fold
chamber model of breast carcinoma cell
metastasis. Clin Exp Metastasis. 2006 Jul 7;
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Lee SH, Coger RN and Clemens MG. Antioxidant
functionality in hepatocytes using enhanced
collagen extracellular matrix under different
oxygen tensions. Tissue Engineering 2006 (in
press)
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Karaa A, Kamoun W and Clemens MG. Oxidative
stress disrupts nitric oxide synthase activation
in liver endothelial cells. Free Radical
Biology and Medicine (In Press)
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Kamoun WS, Shin MC., Keller S, Karaa
A, Huynh T, Clemens MG. Induction of Biphasic
Changes in Perfusion Heterogeneity of Rat Liver
Following Sequential Stress in Vivo. Shock (In
Press)
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Mark G. CLEMENS, Walid KAMOUN, Amel KARAA, and
Sandra MERKEL. Altered
caveolae-associated signalling in liver
sinusoidal endothelial cells following
inflammation. Microcirculation Annual 2005 (In
Press)
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Zinchenko YS., Schrum LW., Clemens M, and Coger
RN. Hepatocyte and Kupffer Cells Co-cultured
on Micropatterned Surfaces to Optimize
Hepatocyte Function. Tissue Engineering (In
Press)
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Merkel SM, Kamoun W, Karaa A, Korneszczuk K,
. Schrum LW and Mark G. Clemens.
LPS Inhibits Endothelin-1-Mediated eNOS
Translocation to the Cell Membrane in Sinusoidal
Endothelial Cells. Microcirculation 12:
433-442, 2005.
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Keller SA, Paxian M, Ashburn JH , Clemens MG,
and Toan Huynh. Kupffer Cell Ablation Improves
Hepatic Microcirculation after Trauma and Sepsis.
J. Trauma 58(4):740-9 2005.
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Keller SA, Paxian M, Lee SM,Clemens MG, and
Toan Huynh. Kupffer Cell Ablation Attenuates
Cyclooxygenase-2 Expression after Trauma and
Sepsis. J Surg Res 124(1): 126-33, 2005.
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Kamoun WS, Shin MC, Karaa A, Clemens MG.
Quantification of hepatic microcirculation
heterogeneity of perfusion: Effects of
endothelin-1. Microvasc Res. 2005
May;69(3):180-6.
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Xu H, Korneszczuk K, Karaa A , Lin T, Clemens
MG, and Jian X. Zhang
Thromboxane A2 from Kupffer cells
contributes to the hyperresponsiveness of
hepatic portal circulation to endothelin-1 in
endotoxemic rats. Am J
Physiol Gastrointest Liver Physiol 288:
G277-G283, 2005
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Jain S,
Lee CY,
Baicu S,
Duncan H,
Xu H,
Jones JW Jr,
Clemens MG,
Brassil J,
Taylor MJ,
Brockbank KG.
Hepatic function in hypothermically stored
porcine livers: comparison of hypothermic
machine perfusion vs cold storage. Transplant
Proc. 37(1):340-1, 2005.
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Xu H,
Zhang JX,
Jones JW,
Southard JH,
Clemens MG,
Lee CY.
Hypothermic machine perfusion of rat livers
preserves endothelial cell function. Transplant
Proc.37(1):335-7, 2005.
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Jain S, Xu H, Duncan H, Jones JW Jr, Zhang JX,
Clemens MG, Lee CY. Ex-vivo study of
flow dynamics and endothelial cell structure
during extended hypothermic machine perfusion
preservation of livers. Cryobiology. 2004
Jun;48(3):322-32
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Markus Paxian, Steve A. Keller, Rajiv Baveja,
Katarzyna Korneszczuk, Toan T. Huynh, and Mark
G. Clemens. Functional link between ETB
receptors and eNOS maintain tissue oxygenation
in the normal liver. Microcirulation
11(5):435-49, 2004
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Markus Paxian, Steve A. Keller, Toan T. Huynh,
and Mark G. Clemens Perflubron emulsion
improves hepatic microvascular integrity and
mitochondrial redox state following hemorrhagic
shock. Shock 20(5): 449-57, 2003 .
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Paxian M,. Keller S, Cross B, Huynh T, and Mark
G. Clemens. High resolution visualization of
oxygen distribution in the liver in vivo.
American Journal of Physiology 286(1): G37-44,
2004.
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Xu H, Lee CY, Clemens MG, Zhang JX. Prolonged
Hypothermic Machine Perfusion Preserves
Hepatocellular Function but Potentiates
Endothelial Cell Dysfunction in Rat Livers.
Transplantation (in Press)
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Lee CY, Jain S, Duncan HM, Zhang JX, Jones JW Jr,
Southard JH, Clemens MG. Survival
transplantation of preserved non-heart-beating
donor rat livers: preservation by hypothermic
machine perfusion. Transplantation. 2003 Nov
27; 76(10): 1432-6.
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Yokoyama Y, Xu H, Kresge N, Keller S, Sarmadi
AH, Baveja R, Clemens MG, Zhang JX. Role of
thromboxane A2 in early BDL-induced portal
hypertension. Am J Physiol Gastrointest Liver
Physiol 2003 Mar;284(3):G453-60
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Rensing H, Bauer I, Zhang JX, Paxian M, Pannen
BH, Yokoyama Y, Clemens MG, Bauer M.
Endothelin-1 and heme oxygenase-1 as modulators of sinusoidal tone in
the stress-exposed rat liver. Hepatology 2002
Dec;36(6):1453-65
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Ashburn J H,. Rajiv Baveja, Nicole
Kresge, Katarzyna Korneszczuk, Steve Keller,
Amel Karaa, Yukihiro Yokoyama, Jian X. Zhang,
Toan Huynh, and Mark G. Clemens.
Remote trauma sensitizes hepatic
microcirculation to endothelin via caveolin
inhibition of eNOS activity. Shock (in press)
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Yokoyama Y, Alterman D, Sarmadi A, Baveja R,
Zhang J, Huynh T and Clemens MG. Hepatic
Vascular response to elevated intraperitoneal
pressure in the rat. J. Surg Res 2002 Jun
15;105(2):86-94
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Baveja R, Kresge N, Ashburn JH, Keller S,
Yokoyama Y, Sonin N, Zhang JX, Huynh T, Clemens
MG. Potentiated hepatic microcirculatory
response to endothelin-1 during polymicrobial
sepsis. Shock 2002 Nov;18(5):415-22
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Baveja R, Yokoyama Y, Korneszczuk K, Zhang JX,
Clemens MG. Endothelin 1 impairs oxygen
delivery in livers from LPS-primed animals.
Shock 2002 May;17(5):383-8
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Lee CY, Zhang JX, Jones JW Jr, Southard JH,
Clemens MG. Functional recovery of preserved
livers following warm ischemia: improvement by
machine perfusion preservation. Transplantation
2002 Oct 15;74(7):944-51
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Baveja R, Keller S, Yokoyama Y, Sonin N, Clemens
MG, Zhang JX. LPS-induced imbalanced expression
of hepatic vascular stress genes in cirrhosis:
possible mechanism of increased susceptibility
to endotoxemia. Shock 2002 Apr;17(4):316-21
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McConnell NA, Yunus RS, Gross SA, Bost KL,
Clemens MG, Hughes FM Jr. Water permeability
of an ovarian antral follicle is predominantly
transcellular and mediated by aquaporins.
Endocrinology 2002 Aug;143(8):2905-12
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Yukihiro Yokoyama, Rajiv Baveja, Nicole Kresge,
Natalie Sonin, Kazuya Nakanishi Jian X. Zhang,
Christopher A. Gitzelmann and Mark G. Clemens
Endothelin receptor remodeling induces the
portal venous hyper-response to endothelin-1
following endotoxin pretreatment Shock 2002
Jan;17(1):36-40
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Yokoyama, Y., A. Wawrzyniak, R. Baveja, N. Sonin,
M.G. Clemens, and J.X. Zhang. Altered
endothelin receptors in prehepatic portal
hypertension in the rat: predisposition of the
hepatic microcirculatory dysfunction. Journal of
Hepatology. 2001 Jul;35(1):29-36
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Baveja R, Zhang JX, Clemens MG.
In vivo assessment of endothelin-induced
heterogeneity of hepatic tissue perfusion. Shock
2001 Mar;15(3):186-92
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Yokoyama Y, Baveja R, Sonin N, Clemens MG, Zhang
JX. Hepatic neovascularization after partial
portal vein ligation: novel mechanism of chronic
regulation of blood flow.Am J Physiol
Gastrointest Liver Physiol. 280(1): G21-G31,
2001
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DeMaio A, Gingalewski C, Theodorakis N, Clemens
MG. Interruption of hepatic gap junctional
communication in the rat during inflammation
induced by bacterial lipopolysaccharide. Shock
14(1):53-9, 2000.
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Lee S-M, M-J Park, T-S Cho and MG Clemens.
Hepatic injury and lipid peroxidation during
ischemia and reperfusion. Shock
2000;13(4):279-84
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Yokoyama Y, Baveja R, Sonin N, Nakanishi, Zhang
JX, and Clemens MG. The role of endothelin
receptor remodeling in microvascular response
after ischemia / reperfusion. Shock
13(1):72-8, 2000.
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St. John J, Barbee W, Sonin N, Clemens MG, Watts
JA. Inhibition of poly (ADP-ribose) synthetase
improves vascular contractile responses
following trauma-hemorrhage and resuscitation.
Shock 12: 188-195, 1999.
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Bauer M, Bauer I, Sonin NV, Kresge N, Baveja R,
Yokoyama Y, Harding D, Zhang JX, Clemens MG.
Functional significance of endothelin B
receptors in mediating sinusoidal and
extrasinusoidal effects of endothelins in the
intact rat liver.Hepatology 31(4):937-47, 2000
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Yutaka Morita, Toshikazu Yoshikawa, Satoshi
Takeda, Norimasa Yoshida, Mark G. Clemens and
Motoharu Kondo. Role of lipid peroxidation in
free fatty acid-induced isolated rat pancreatic
acinar cell injury. Pancreas 17: 383- 389, 1998
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Sonin NV, Garcia-Pagan JC, Nakanishi K, Zhang
JX, Clemens MG. Patterns of vasoregulatory gene
expression in the liver response to ischemia /
reperfusion and endotoxemia. Shock11: 175-179,
1999.
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Clemens, MG. Nitric Oxide in liver injury.
Hepatology 30: 1-5, 1999
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Clemens MG. Liver circulation in portal
hypertension. Hepato-Gastroenterology 46
(Supplement II): 1429-1433, 1999.
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Garcia-Pagán J-C, Zhang JX, Sonin N, Nakanishi
K, Clemens Mark G. Ischemia / reperfusion
induces an increase in the hepatic portal
vasoconstrictive response to endothelin-1. Shock
11: 325-329, 1999
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Susumu Kobayashi, Elizabeth Miescher, and Mark
G. Clemens A synergistic effect of extracellular
hypocalcemia for hyperoxic reoxygenation injury
in rat hepatocytes. Transplantation 67: 451-457,
1999
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Clemens, MG and JX Zhang. Regulation of
sinusoidal perfusion: in vivo methodology and
control by endothelins. Seminars in Liver
Disease 19(4):383-96, 1999
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Pannen BHJ, Geiger KK, Clemens MG, Bauer M, Al-Adili
F. Role of endothelins and nitric oxide in
hepatic reperfusion injury in the rat.
Hepatology 27:755-64, 1998.
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Clemens, MG. Does altered regulation of ecNOS in
sinusoidal endothelial cells determine increased
intrahepatic resistance leading to portal
hypertension? Hepatology 27:1745-1747, 1998.
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Pannen BHJ, Kohler N, Hole B, Bauer M, Clemens
MG, Geiger KK.
Protective Role of Endogenous Carbon Monoxide in
Hepatic Microcirculatory Dysfunction after
Hemorrhagic Shock in Rats J. Clin Invest. 102:
1220-1228, 1998.
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Yang SQ; Lin HZ; Lane MD; Clemens M; Diehl AM.
Obesity increases sensitivity to endotoxin liver
injury: implications for the pathogenesis of
steatohepatitis. Proc Natl Acad Sci U S A 1997
Mar 18;94(6):2557-62
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Clemens MG, Bauer M, Pannen BHJ, Bauer I, and JX
Zhang, Remodeling of hepatic microvascular
responsiveness after ischemia/reperfusion. Shock
8: 80-85, 1997
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Bauer I, Wanner G, Rensing H, Alte C, Miescher
E, Wolf B, Pannen BHJ, Clemens MG, and Bauer M.
Expression pattern of heme oxygenase isoenzymes
1 and 2 in normal and stress exposed rat liver.
Hepatology 27: 829-838, 1998.
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Pannen PHJ, M Bauer, E Noldge-Schomburg, JX
Zhang, JL Robotham, MG Clemens , and KK Geiger.
Regulation of hepatic blood flw during resuscitation from
hemorrhagic shock: Role of nitric oxide and
endothelins. Am J Physiol Jun;272(6 Pt
2):H2736-45, 1997.
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Bauer M, BHJ Pannen, I Bauer, C Herzog, GA
Wanner, R Hanselmann, JX Zhang, MG Clemens and R
Larsen.
In vivo
evidence for a functional link between stress
response and vascular control in hepatic portal
circulation. Am. J. Physiol. 271: G929-G935,
1996
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Rai R, JX Zhang, MG Clemens and AM Diehl.
Gadolinium chloride alters acinar distribution
of phagocytosis and balance between pro- and
anti-inflammatory cytokines. Shock 6(4):243-7,
1996}
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Pannen BHJ, Bauer M, Zhang JX, Robotham J and
Clemens MG .
A time-dependent balance between endothelin and
nitric oxide regulates portal vascular
resistance following endotoxin. Am. J. Physiol .
271: H1953-H1961, 1996.
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Jaeschke H, Smith CW,Clemens MG, Ganey PE and
Roth RA. Mechanisms of inflammatory liver
injury: Adhesion molecules and cytotoxicity of
neutrophils. Toxicol Appl Pharmacol
139(2):213-26, 1996
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Gingalewski C, Wang K, Clemens MG, and DeMaio A.
Posttranscriptional regulation of the connexin
32 gene in liver during acute inflammation. J.
Cell Pysiol .166:461-467, 1996.
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Bauer I, Bauer M, Pannen BHJ, Leinwand MJ, Zhang
JX and Clemens MG .
Chronic ethanol consumption exacerbates liver
injury following hemorrhagic shock: Role of
sinusoidal perfusion failure. Shock4:324-331,
1995.
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Bauer M, Paquette NC, Zhang JX, Bauer I, Pannen
BHJ, Kleeburger SR and Clemens MG.
Chronic ethanol consumtion increases hepatic sinusoidal
contractile response to endothelin-1. Hepatology
22: 1565-1576, 1995.
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Pannen BHJ, Bauer M, Zhang JX, Robotham JL,
Clemens MG .
Endotoxin pretreatment enhances the portal
venous contractile response to endothelin-1. Am.
J. Physiol. 270:H7-15, 1996
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Zhang J, Bauer M, Clemens MG .
Vessel and target cell specific actions of
endothelin-1 and endothelin-3 in rat liver. Am J
Physiol 269:G269-G277, 1995
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Deutschman CS, DeMaio A, Clemens MG.
Sepsis-induced attenuation of glucagon and
8-bromo-cyclic AMP modulation of
phosphoenolpyruvate carboxykinase gene
expression. Am J Physiol 269:R584-R591, 1995.
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Wang K, Deutschman CS, Clemens MG, DeMaio A.
Reciprocal expression of phosphoenolpyruvate
carboxykinase (PEPCK) and acute phase genes
during acute inflammation. Shock 3:204-209, 1995
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Bauer M, Zhang J, Bauer I, Clemens MG.
Endothelin-1 induced alteration of hepatic
microcirculation: sinusoidal and presinusoidal
sites of action. Am J Physiol 267:G143-G149,
1994.
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Paidas CN, Clemens MG. Hormone effects on
hepatic substrate preference in sepsis. Shock
1:94-100, 1994.
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Zhang JX, Pegoli W, Clemens MG. Endothelin-1
induces direct constriction of hepatic
sinusoids. Am J Physiol 266:G624-G632, 1994.
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