A5063551206- Pediatric Hepatobiliary Diseases and Treatments
- Congenital Anomalies and Fetal Surgery
- Organ Transplantation Techniques and Outcomes
- Hepatocellular Carcinoma Treatment and Prognosis
- Gallbladder and Bile Duct Disorders
- Liver Disease and Transplantation
- Pancreatic and Hepatic Oncology Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Intestinal Malrotation and Obstruction Disorders
- Clinical Nutrition and Gastroenterology
- Renal Transplantation Outcomes and Treatments
- Neonatal Health and Biochemistry
- Organ Donation and Transplantation
- Viral gastroenteritis research and epidemiology
- Liver Disease Diagnosis and Treatment
- Infant Nutrition and Health
- Mitochondrial Function and Pathology
- Neuroblastoma Research and Treatments
- Pancreatitis Pathology and Treatment
- Muscle metabolism and nutrition
- Renal and related cancers
- Amoebic Infections and Treatments
- Liver Diseases and Immunity
- Urological Disorders and Treatments
- Polyamine Metabolism and Applications
Cincinnati Children's Hospital Medical Center
2016-2025
University of Cincinnati
2007-2025
University of Cincinnati Medical Center
1994-2024
E Ink (South Korea)
2022
Children's Medical Center
2016-2018
Dana-Farber Cancer Institute
2017
MSD K.K. (Japan)
2017
Children's Oncology Group
2017
Boston Children's Hospital
2017
UC Davis Comprehensive Cancer Center
2017
Previous studies provided evidence that sepsis-induced muscle proteolysis in experimental animals is caused by increased ubiquitin-proteasome-dependent protein breakdown. It not known if a similar mechanism accounts for patients with sepsis. We determined mRNA levels ubiquitin and the 20 S proteasome subunit HC3 Northern blot analysis tissue from septic (n = 7) non-septic 11) patients. Plasma amino acid concentrations urine of 3-methylhistidine (3-MH), creatinine, cortisol were measured at...
We tested the role of different intracellular proteolytic pathways in sepsis-induced muscle proteolysis. Sepsis was induced rats by cecal ligation and puncture; controls were sham operated. Total myofibrillar proteolysis determined incubated extensor digitorum longus muscles as release tyrosine 3-methylhistidine, respectively. Lysosomal assessed using lysosomotropic agents NH4Cl, chloroquine, leupeptin, methylamine. Ca(2+)-dependent absence or presence Ca2+ blocking proteases calpain I II....
Recent studies suggest that sepsis-induced increase in muscle proteolysis mainly reflects energy-ubiquitin-dependent protein breakdown. We tested the hypothesis glucocorticoids activate proteolytic pathway skeletal during sepsis. Rats underwent induction of sepsis by cecal ligation and puncture or were sham-operated breakdown rates measured 16 h later. The glucocorticoid receptor antagonist RU 38486 vehicle was administered to groups septic rats. In other experiments, dexamethasone (2.5 10...
The etiology and pathogenesis of bile duct obstruction in children with biliary atresia are largely unknown. We have previously reported that, despite phenotypic heterogeneity, genomic signatures livers from patients display a proinflammatory phenotype. Here, we address the hypothesis that production IFN-gamma is key pathogenic mechanism disease using mouse model rotavirus-induced atresia. found rotavirus infection neonatal mice has unique tropism to cells, it triggers hepatobiliary...
In Brief Objective: The goals of this study were to describe the clinical and anatomic features infants undergoing Kasai portoenterostomy (KPE) for biliary atresia (BA) examine associations between these parameters outcomes. Methods: Infants enrolled in prospective Childhood Liver Disease Research Education Network, who underwent KPE studied. Patients a blinded, interventional trial excluded from survival analysis. Primary endpoints successful surgical drainage (total bilirubin less than 2...
The etiology and pathogenesis of bile duct obstruction in children with biliary atresia are largely unknown. We have previously reported that, despite phenotypic heterogeneity, genomic signatures livers from patients display a proinflammatory phenotype. Here, we address the hypothesis that production IFN-γ is key pathogenic mechanism disease using mouse model rotavirus-induced atresia. found rotavirus infection neonatal mice has unique tropism to cells, it triggers hepatobiliary inflammation...
To evaluate the efficacy of nontransplant surgery for pediatric cholestasis, 58 clinically diagnosed children, including 20 with Alagille syndrome (ALGS), 16 familial intrahepatic cholestasis‐1 (FIC1), 18 bile salt export pump (BSEP) disease, and 4 others low γ‐glutamyl transpeptidase disease (levels <100 U/L), were identified across 14 Childhood Liver Disease Research Network (ChiLDReN) centers. Data collected retrospectively from individuals who collectively had 39 partial external...
The identification of new therapies for high-risk (HR) hepatoblastoma is challenging. Children's Oncology Group study AHEP0731 included a HR stratum to explore the efficacy novel agents. Herein, authors report response rate combination vincristine (V) and irinotecan (I) outcome patients with hepatoblastoma.Patients newly diagnosed metastatic or those serum α-fetoprotein (AFP) level <100 ng/mL were eligible. Patients received 2 cycles V at dose 1.5 mg/m2 /day intravenously on days 1 8 I 50 5....
The outcomes of hepatic undifferentiated embryonal sarcoma (HUES) have historically been limited by persistent, unresectable disease and the subsequent development resistance dissemination. We present our institutional experience with HUES assess current treatment trends in era liver transplantation. conducted a retrospective chart review cases presenting at institution over past 10 years. collected data included age, sex, symptoms, imaging associated Pretreatment Extent Disease (PRETEXT)...
Purpose To determine whether the pattern of lung nodules in children with metastatic hepatoblastoma (HB) correlates outcome. Methods Thirty-two patients HB were enrolled on Children’s Oncology Group Protocol AHEP0731 and treated vincristine irinotecan (VI). Responders to VI received two additional cycles intermixed six cisplatin/fluorouracil/vincristine/doxorubicin (C5VD), nonresponders C5VD alone. Patients imaged after every at conclusion therapy. All computed tomography scans pathology...
We tested the hypothesis that difference in response to sepsis of protein breakdown between fast- and slow-twitch skeletal muscle reflects differential activation energy-ubiquitin-dependent proteolytic pathway. In addition, we defined time course tissue specificity sepsis-induced changes expression ubiquitin Sepsis was induced rats by cecal ligation puncture; control were sham operated. Energy-dependent measured incubated extensor digitorum longus (EDL) soleus muscles. Ubiquitin mRNA levels...
Recent studies suggest that sepsis stimulates ubiquitin-dependent protein breakdown in skeletal muscle. The 20S proteasome is the catalytic core of proteolytic pathway. We tested effects vitro inhibitors N-acetyl-l-leucinyl-l-leucinal-l-norleucinal (LLnL) and lactacystin on incubated muscles from septic rats. LLnL resulted a dose- time-dependent inhibition Lactacystin blocked both total myofibrillar muscle breakdown. In addition to inhibiting breakdown, reduced synthesis increased ubiquitin...
The molecular basis for the embryonic and perinatal clinical forms of biliary atresia is largely undefined. In this study, we aimed to: 1) determine if can be differentiated at transcriptional level, 2) search mechanisms underlying phenotypic differences. To end, generated biotinylated cRNA probes from livers age-matched infants with (n = 5) 6) time diagnosis hybridized them against Affymetrix human HG-U133 A B microarrays containing 44,760 gene products. Data filtering two-way cluster...
Portal vein thrombosis (PVT) occurs in ≤12% of pediatric recipients liver transplantation (LT). Known complications PVT include portal hypertension, allograft loss, and mortality. The management is varied. A single-center, case-control study LT with (PV) changes after was performed. Cases were categorized as early (if detected within 30 days transplantation) or late more than if persisted beyond days). Two non-PVT control patients matched on the basis recipient weight, transplant indication,...