James L. Weemhoff
University of Kansas
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Featured researches published by James L. Weemhoff.
Liver Transplantation | 2014
Min Yang; Daniel J. Antoine; James L. Weemhoff; Rosalind E. Jenkins; Anwar Farhood; B. Kevin Park; Hartmut Jaeschke
Hepatic ischemia/reperfusion (IRP) injury is a significant clinical problem during tumor‐resection surgery (Pringle maneuver) and liver transplantation. However, the relative contribution of necrotic and apoptotic cell death to the overall liver injury is still controversial. To address this important issue with a standard murine model of hepatic IRP injury, plasma biomarkers of necrotic cell death such as micro‐RNA 122, full‐length cytokeratin 18 (FK18), and high‐mobility group box 1 (HMGB1) protein and plasma biomarkers of apoptosis such as plasma caspase‐3 activity and caspase‐cleaved fragment of cytokeratin 18 (CK18) coupled with markers of inflammation (hyperacetylated HMGB1) were compared by histological features in hematoxylin and eosin–stained and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick‐end labeling (TUNEL)–stained liver sections. After 45 minutes of hepatic ischemia and 1 to 24 hours of reperfusion, all necrosis markers increased dramatically in plasma by 40‐ to >10,000‐fold over the baseline with a time course similar to that of alanine aminotransferase. These data correlated well with histological characteristics of necrosis. Within the area of necrosis, most cells were TUNEL positive; initially (≤3 hours of reperfusion), the staining was restricted to nuclei, but it later spread to the cytosol, and this is characteristic of karyorrhexis during necrotic cell death. In contrast, the lack of morphological evidence of apoptotic cell death and relevant caspase‐3 activity in the postischemic liver correlated well with the absence of caspase‐3 activity and CK18 (except for a minor increase at 3 hours of reperfusion) in plasma. A quantitative comparison of FK18 (necrosis) and CK18 (apoptosis) release indicated dominant cell death by necrosis during IRP and only a temporary and very minor degree of apoptosis. These data suggest that the focus of future research should be the elucidation of necrotic signaling mechanisms to identify relevant targets, which may be used to attenuate hepatic IRP injury. Liver Transpl 20:1372‐1382, 2014.
Liver International | 2017
James L. Weemhoff; Benjamin L. Woolbright; Rosalind E. Jenkins; Mitchell R. McGill; Matthew R. Sharpe; Jody C. Olson; Daniel J. Antoine; Steven C. Curry; Hartmut Jaeschke
Hypoxic hepatitis is a clinical condition precipitated by prolonged periods of oxygen deprivation to the liver. It can have several underlying causes. Despite its prevalence in critically ill patients, which can reach upwards of 10%, very little is known about the mechanisms of injury. Thus, we set out to measure previously identified circulating biomarkers in an attempt to describe mechanisms of injury following hypoxic hepatitis.
Toxicology Letters | 2017
M. Maes; Sara Crespo Yanguas; Joost Willebrords; James L. Weemhoff; Tereza Cristina da Silva; Elke Decrock; Margitta Lebofsky; Isabel Veloso Alves Pereira; Luc Leybaert; Anwar Farhood; Hartmut Jaeschke; Bruno Cogliati; Mathieu Vinken
Historically, connexin hemichannels have been considered as structural precursors of gap junctions. However, accumulating evidence points to independent roles for connexin hemichannels in cellular signaling by connecting the intracellular compartment with the extracellular environment. Unlike gap junctions, connexin hemichannels seem to be mainly activated in pathological processes. The present study was set up to test the potential involvement of hemichannels composed of connexin32 and connexin43 in acute hepatotoxicity induced by acetaminophen. Prior to this, in vitro testing was performed to confirm the specificity and efficacy of TAT-Gap24 and TAT-Gap19 in blocking connexin32 and connexin43 hemichannels, respectively. Subsequently, mice were overdosed with acetaminophen followed by treatment with TAT-Gap24 or TAT-Gap19 or a combination of both after 1.5h. Sampling was performed 3, 6, 24 and 48h following acetaminophen administration. Evaluation of the effects of connexin hemichannel inhibition was based on a series of clinically relevant read-outs, measurement of inflammatory cytokines and oxidative stress. Subsequent treatment of acetaminophen-overdosed mice with TAT-Gap19 only marginally affected liver injury. In contrast, a significant reduction in serum alanine aminotransferase activity was found upon administration of TAT-Gap24 to intoxicated animals. Furthermore, co-treatment of acetaminophen-overdosed mice with both peptides revealed an additive effect as even lower serum alanine aminotransferase activity was observed. Blocking of connexin32 or connexin43 hemichannels individually was found to decrease serum quantities of pro-inflammatory cytokines, while no effects were observed on the occurrence of hepatic oxidative stress. This study shows for the first time a role for connexin hemichannels in acetaminophen-induced acute liver failure.
Food and Chemical Toxicology | 2015
Mitchell R. McGill; Kuo Du; James L. Weemhoff; Hartmut Jaeschke
Toxicological Sciences | 2016
Kuo Du; James L. Weemhoff; Hemantkumar Chavan; Yuchao Xie; Partha Krishnamurthy; Hartmut Jaeschke
Food and Chemical Toxicology | 2016
Luqi Duan; John S. Davis; Benjamin L. Woolbright; Kuo Du; Mala Cahkraborty; James L. Weemhoff; Hartmut Jaeschke; Mohammed Bourdi
Archives of Toxicology | 2017
M. Maes; Mitchell R. McGill; Tereza Cristina da Silva; Chloé Abels; Margitta Lebofsky; James L. Weemhoff; Taynã Tiburcio; Isabel Veloso Alves Pereira; Joost Willebrords; Sara Crespo Yanguas; Anwar Farhood; Alain Beschin; Jo A. Van Ginderachter; Silvia Penuela; Hartmut Jaeschke; Bruno Cogliati; Mathieu Vinken
Archives of Toxicology | 2018
Kuo Du; James L. Weemhoff; Benjamin L. Woolbright; Andrew H. Jaeschke; Xiaojuan Chao; Wen-Xing Ding; Hartmut Jaeschke
Journal of Hepatology | 2017
M. Maes; James L. Weemhoff; Joost Willebrords; Sara Crespo Yanguas; T.C. da Silva; Isabel Veloso Alves Pereira; Margitta Lebofsky; Hartmut Jaeschke; Bruno Cogliati; Mathieu Vinken
Food and Chemical Toxicology | 2017
Luqi Duan; John S. Davis; Benjamin L. Woolbright; Kuo Du; Mala Cahkraborty; James L. Weemhoff; Hartmut Jaeschke; Mohammed Bourdi