Heterozygous familial hypobetalipoproteinemia (FHBL) is a semi-autosomal disorder that is caused mainly by an A 12-year-old boy was referred to our hospital after prolonged elevation of liver enzymes Show more
Heterozygous familial hypobetalipoproteinemia (FHBL) is a semi-autosomal disorder that is caused mainly by an A 12-year-old boy was referred to our hospital after prolonged elevation of liver enzymes was observed during health checkups in Kagawa Prefecture. Abdominal ultrasound showed a bright liver, and laboratory investigations revealed low low-density lipoprotein cholesterol and apolipoprotein B protein levels. His family history included fatty liver and hypolipidemia in his father, which led to a clinical diagnosis of FHBL. A liver biopsy was performed on suspicion of liver fibrosis based on biomarkers. The liver tissue showed fatty steatosis, inflammation, hepatocyte ballooning, and fibrosis, indicating NASH. Genetic testing detected the It is important to assess family history and liver dysfunction severity in non-obese patients with hypolipidemia and fatty liver. Show less
To investigate alterations in protein kinases and phosphatases that regulate the activity of mitogen activated protein kinase (MAPK) in sporadic inclusion body myositis (IBM). In vacuolated fibers in Show more
To investigate alterations in protein kinases and phosphatases that regulate the activity of mitogen activated protein kinase (MAPK) in sporadic inclusion body myositis (IBM). In vacuolated fibers in IBM, several studies reported upregulation of the extracellular regulated kinase (ERK) subclass of MAPK family. Whereas MAPK kinases (MKK) activate MAPK, MAPK phosphatases (MKP) inactivate MAPK. MKP-1 is involved in muscle fiber differentiation and it is downregulated during myotube formation. Immunolocalization of MKK1 through MKK4 and MKP-1 to MKP-3 was tested in muscle specimens from 10 patients with IBM and controls. In IBM, strong and focal deposits of MKP-1 were observed in vacuolated fibers. The MKP-1-positive deposits were colocalized with ERK. MKP-2, MKP-3, and MKK were not associated with vacuolated fibers. In IBM, MKP-1 is abnormally induced in vacuolated fibers probably to inactivate ERK. Although direct activators other than those tested in the current study might induce ERK, the absence of activation of MKK suggests that the aggregation of ERK protein itself causes the seeming upregulation of the protein kinase in IBM. Like ERK and its nuclear substrate, MKP-1 is an enzyme that forms aggregates in vacuolated fibers and is involved in myogenesis. Show less