Biomedical subjects

Bruce Wang

Publications and source records attributed to Bruce Wang.

4 recordsLinked to original sources

PubMed2025

Liver involvement in a large cohort of patients with erythropoietic protoporphyria or X-linked protoporphyria.

BACKGROUND: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are characterized by the accumulation of protoporphyrin in the marrow, erythrocytes, plasma, skin, and liver, and present clinically with painful cutaneous phototoxicity. Liver abnormalities have been reported in over 25% of patients with EPP. Further characterization of liver involvement in protoporphyria is needed. METHODS: Patients with EPP or XLP enrolled in the longitudinal studies of the NIH-supported Porphyrias Consortium were included. Medical history, laboratory, and liver histology data were abstracted and described. RESULTS: A total of 322 patients were enrolled; 28 (8.7%) had XLP, 52% were female, and the median age at enrollment was 33.3 years. Liver chemistries were available for 235 patients, and 132 (56.2%) had abnormalities, mostly mild. Abnormal liver enzymes were associated with higher erythrocyte protoporphyrin levels. Eleven patients had advanced protoporphyric hepatopathy. In total, 54 (16.8%) underwent cholecystectomy, 8 (2.5%) had a liver transplant, 4 (1.2%) had a bone marrow transplant, and 8 (2.5%) died. At least 4 deaths were caused by liver failure due to protoporphyric hepatopathy, 2 were complications of bone marrow transplant, and 1 from HCC, which developed in a patient with EPP without cirrhosis. Patients with XLP were more likely to develop liver-related complications compared to EPP. CONCLUSIONS: Liver abnormalities are common in patients with EPP and XLP. In this national registry, only 3.4% had protoporphyric hepatopathy, with most requiring a transplant. Of the deaths, 62.5% were attributable to liver disease. Further observations are needed for guiding hepatic evaluation and management of patients with protoporphyria with or without initial hepatic abnormalities.

Humans↗

PubMed2005

TWEAK induces liver progenitor cell proliferation.

Progenitor ("oval") cell expansion accompanies many forms of liver injury, including alcohol toxicity and submassive parenchymal necrosis as well as experimental injury models featuring blocked hepatocyte replication. Oval cells can potentially become either hepatocytes or biliary epithelial cells and may be critical to liver regeneration, particularly when hepatocyte replication is impaired. The regulation of oval cell proliferation is incompletely understood. Herein we present evidence that a TNF family member called TWEAK (TNF-like weak inducer of apoptosis) stimulates oval cell proliferation in mouse liver through its receptor Fn14. TWEAK has no effect on mature hepatocytes and thus appears to be selective for oval cells. Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia. A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus. Oval cell expansion induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) was significantly reduced in Fn14-null mice as well as in adult wild-type mice with a blocking anti-TWEAK mAb. Importantly, TWEAK stimulated the proliferation of an oval cell culture model. Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury. We conclude that TWEAK has a selective mitogenic effect for liver oval cells that distinguishes it from other previously described growth factors.

Adenoviridae↗

PubMed2005

A tumor-suppressor function for NFATc3 in T-cell lymphomagenesis by murine leukemia virus.

Nuclear factor of activated T cell (NFAT) transcription factors play a central role in differentiation, activation, and elimination of lymphocytes. We here report on the finding of provirus integration into the Nfatc3 locus in T-cell lymphomas induced by the murine lymphomagenic retrovirus SL3-3 and show that NFATc3 expression is repressed in these lymphomas. The provirus insertions are positioned close to the Nfatc3 promoter or a putative polyadenylated RNA (polyA) region. Furthermore, we demonstrate that NFATc3-deficient mice infected with SL3-3 develop T-cell lymphomas faster and with higher frequencies than wild-type mice or NFATc2-deficient mice. These results identify NFATc3 as a tumor suppressor for the development of murine T-cell lymphomas induced by the retrovirus SL3-3.

Animals↗

PubMed2004

FlyGEM, a full transcriptome array platform for the Drosophila community.

We have constructed a DNA microarray to monitor expression of predicted genes in Drosophila. By using homotypic hybridizations, we show that the array performs reproducibly, that dye effects are minimal, and that array results agree with systematic northern blotting. The array gene list has been extensively annotated and linked-out to other databases. Incyte and the NIH have made the platform available to the community via academic microarray facilities selected by an NIH committee.

Animals↗