Differential Expression of Cardiac Troponin T and I in a Patient with Isolated Skeletal Muscular Sarcoidosis.

A 49-year-old female was referred to our hospital due to high serum creatine kinase (CK) (2,605 IU/L) and serum cardiac troponin T (cTnT) (0.342 ng/mL) levels. She had no other complaints and further examinations suggested no signs of cardiac disease. Additionally, the serum cardiac troponin I (cTnI) levels were normal. She reported having gradually felt difficulty in walking upstairs. A biopsy indicated skeletal muscle sarcoidosis with positive staining for cTnT. Steroid therapy immediately resolved her muscular symptoms with a normalization of the serum CK levels. Since the serum levels of cTnI were normal, the concomitant measurement of cTnT/cTnI might be useful to diagnose skeletal muscular disease biochemically in such cases.

Expression of apolipoprotein C-IV is regulated by Ku antigen/peroxisome proliferator-activated receptor gamma complex and correlates with liver steatosis.

BACKGROUND/AIMS: We previously reported that hepatitis C virus (HCV) core protein up regulated transcription of apolipoprotein C-IV (ApoC-IV, 10.7-fold increase), a member of the apolipoprotein family implicated in liver steatosis. Here, we identified host transcription factors regulating the ApoC-IV gene expression. METHODS: Transcriptional regulators were identified by DNA affinity purification and steatosis was detected by oil red O staining and triglyceride assay. RESULTS: We defined a 163-bp ApoC-IV promoter as a core protein responsive element, and identified Ku antigen complex (Ku70 and Ku80) as well as nuclear receptors PPARgamma/RXRalpha as key regulators of ApoC-IV gene expression. Both Ku70 overexpression and PPARgamma agonist significantly increased ApoC-IV promoter activity; conversely, Ku70 silencing or mutation of PPARgamma binding site diminished the ApoC-IV promoter activity. Interestingly, transient transfection of ApoC-IV cDNA into a human hepatoma cell line was able to trigger moderate lipid accumulation. In agreement with this in vitro study, ApoC-IV transcript level was increased in HCV infected livers which correlated with triglyceride accumulation. CONCLUSIONS: ApoC-IV overexpression may perturb lipid metabolism leading to lipid accumulation. HCV core protein may modulate ApoC-IV expression through Ku antigen and PPARgamma/RXRalpha complex.

Hepatitis C virus core protein stimulates hepatocyte growth: correlation with upregulation of wnt-1 expression.

Hepatitis C virus (HCV) core protein has been implicated in the development of human hepatocellular carcinoma (HCC). Here we report that expression of HCV core protein by transient transfection increased cell proliferation, DNA synthesis, and cell cycle progression in Huh-7 cells, a human HCC-derived cell line. Culture supernatant from transfected cells also harbored a growth-promoting effect. Moreover, a full-length HCV replicon, but not a subgenomic replicon devoid of the core gene, significantly stimulated growth of transiently transfected Huh-7.5 cells. However, growth of the subgenomic replicon-containing Huh-7.5 cells could be stimulated by secondary transfection with core gene but not other structural genes present in the full-length replicon. Microarray analysis revealed threefold or more transcriptional changes in 372 of 12,500 known human genes in core protein expressing Huh-7 cells, with most genes involved in cell growth or oncogenic signaling, being upregulated rather than downregulated. Of particular interest is the marked upregulation of both wnt-1 and its downstream target gene WISP-2. Indeed, small interfering RNA against wnt-1 blunted growth stimulation by core gene, whereas transfection of Huh-7 cells with the wnt-1 gene sufficed to promote cell proliferation. Consistent with secretion of the wnt-1 protein, conditioned medium from wnt-1 transfected cells accelerated cell growth. In conclusion, HCV core protein induces Huh-7 cell proliferation whether alone or in the context of HCV replication, which is at least partly mediated by transcriptional upregulation of growth-related genes, in particular wnt-1.

Successful treatment of pure red cell aplasia and autoimmune cytopenia with cyclosporine and prednisolone in a patient with Sjögren's syndrome.

Abstract A 68-year-old woman was admitted to our hospital with xerophthalmia, xerostomia, leukopenia, and thrombocytopenia. She was diagnosed to have Sjögren's syndrome and autoimmune cytopenia. After 11 months, she was readmitted with severe anemia and reticulocytopenia. Mild hemolysis was seen, and bone marrow aspirate showed markedly decreased erythropoiesis. An association of pure red cell aplasia (PRCA) and autoimmune hemolytic anemia was diagnosed. After treatment with cyclosporine and prednisolone, her anemia dramatically improved. We discuss the mechanism of PRCA associated with Sjögren's syndrome.