The proteomic profile of hereditary inclusion body myopathy.

Hereditary inclusion body myopathy (HIBM) is an adult onset, slowly progressive distal and proximal myopathy. Although the causing gene, GNE, encodes for a key enzyme in the biosynthesis of sialic acid, its primary function in HIBM remains unknown. The goal of this study was to unravel new clues on the biological pathways leading to HIBM by proteomic comparison.

Focal liver necrosis appears early after partial hepatectomy and is dependent on T cells and antigen delivery from the gut.

Introduction: Progressive liver failure may develop following removal of a large part of the liver or transplantation of a small for size liver graft. The pathophysiology of this clinical syndrome is only partially understood.

Methods: We assessed liver damage and hepatocyte 5-bromo-2'-deoxyuridine (BrdU) incorporation following partial hepatectomy (PH) in C57BL/6, BALB/C and immune-deficient mice.

No overall hyposialylation in hereditary inclusion body myopathy myoblasts carrying the homozygous M712T GNE mutation.

Hereditary inclusion body myopathy (HIBM) is a unique group of neuromuscular disorders characterized by adult-onset, slowly progressive distal and proximal muscle weakness, which is caused by mutations in UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), the key enzyme in the biosynthetic pathway of sialic acid. In order to investigate the consequences of the mutated GNE enzyme in muscle cells, we have established cell cultures from muscle biopsies carrying either kinase or epimerase mutations. While all myoblasts carrying a mutated GNE gene show a reduction in their epimerase activity, only the cells derived from the patient carrying a homozygous epimerase mutation present also a significant reduction in the overall membrane bound sialic acid.

The AG1478 tyrosine kinase inhibitor is an effective suppressor of leiomyoma cell growth.

Background: Uterine leiomyomas are the most common benign smooth muscle cell tumours in women. Formation of leiomyomas, still not completely understood, is viewed as a multistep process, with involvement of ovarian steroid hormones, cytokines and growth factors. Our study aimed to identify tyrosine kinase inhibitors as potential 'signal transduction therapeutics' for leiomyomas, underlying the effect of ovarian steroidal hormones.

Tyrosine kinase inhibitors suppress the growth of non-hodgkin B lymphomas.

Non-Hodgkin lymphomas usually become resistant to chemotherapy and relapse due to the their intense antiapoptotic robustness. Furthermore, the slow growth of these malignancies limits the effectiveness of drugs aimed mainly at the proliferative pathways. Because protein tyrosine kinases (PTKs) play a key role in both proliferative and antiapoptotic pathways we screened our library of PTK inhibitors for agents that induce growth arrest and apoptosis in non-Hodgkin B cell lymphoma cell lines.