Two Novel CEBPA Mutations in a Turkish Patient with Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) was first categorized in 1976 by French, American and British researchers, and divided into eight subgroups (M0 to M7), depending on the cytochemical or histological changes in the leukemic cells. The gene mutations of FLT3-ITD, CEBPA and NPM1 are the most common that cooperate together in the prognosis of AML. The CEBPA gene that is a hematopoietic transcription factor, is located on chromosome 19q13.11, and its prevalence is between 5.0 and 14.0% in AML. The patient was referred to our clinic suffering from menorrhagia, unplanned weight loss in a month and low platelet levels, and was diagnosed with AML on clinical and laboratory examination. Here, we report a patient carrying two novel pathogenic mutations that create a frameshift mutation on the CEBPA gene, c.940_941insCCGTCG TGGAGACGA CGAAGG and c.221_222delAC by Sanger sequencing methodology.

Effects of cholesterol supplementation on antioxidant enzyme activities in rat hepatic tissues: possible implications of hepatic paraoxonase in atherogenesis.

BACKGROUND AND AIM: The effects of cholesterol supplementation on antioxidant enzyme activities were investigated hepatic tissue taken from Sprague Dawley rats. METHODS AND REULTS: The study involved 14 male Sprague Dawley rats: seven fed a normal laboratory diet and seven a normal diet plus cholesterol (3.6 g/kg/day) for three months, during which blood samples were obtained to measure serum cholesterol levels. At the end of the 3-month period, the livers were surgically removed in order to measure antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase and paraoxonase-1). At the end of the study period, serum total cholesterol and HDL-cholesterol levels were significantly higher in the cholesterol-fed group than the control group. There were no significant between-group differences in hepatic superoxide dismutase, catalase and glutathione peroxidase activities, but there was a significant decrease in hepatic paraoxonase-1 activity in the cholesterol-fed group. CONCLUSIONS: Cholesterol supplementation significantly decreases paraoxonase-1 activity in rat liver tissue without changing the activities of other antioxidant enzymes. These results suggest that cholesterol significantly suppresses hepatic paraoxonase-1 synthesis. It seems that the decreased paraoxinase-1 activity in the plasma HDL-fraction of atherosclerotic patients is associated with suppressed liver synthesis. A reduction in paraoxonase-1 activity may therefore lead to the more intensive exposure of LDL to oxidant attacks.

A phogrin-aequorin chimaera to image free Ca2+ in the vicinity of secretory granules.

Microdomains of high Ca2+ concentration ([Ca2+]) may be critical to the control of intracellular processes such as secretion and metabolism without compromising other cell functions. To explore changes in [Ca2+] in the outer mantle (< 30 nm deep) that surrounds the surface of dense-core secretory granules, we have designed a recombinant chimaera between the granule protein phogrin and aequorin. When expressed in populations of insulin-secreting MIN6 or phaeochromocytoma PC12 cells, the chimaera was targeted to secretory granules as expected. The recombinant protein reported a similar [Ca2+] at the granule surface to that in the bulk cytosol, measured with untargeted aequorin. This was the case both at rest (-Ca2+- = 80-120 nM) and after stimulation with agents that provoke Ca2+ entry or Ca2+ mobilization from intracellular pools, and during activated secretion. Thus depolarization of MIN6 cell populations with high K+ increased [Ca2+] both in the bulk cytosol and close to the granules to approx. 4 microM, with near-identical kinetics of increase and recovery. Similarly, stimulation of PC12 cells with ATP provoked an increase in -Ca2+- in either domain to 1.3 microM. These data argue that, in MIN6 and PC12 neuroendocrine cells (i) significant mobilization of Ca2+ from most secretory granules probably does not occur during activated Ca2+ influx or mobilization of internal Ca2+ stores, and (ii) agonist-stimulated Ca2+-dependent secretion can occur without development of a large gradient of [Ca2+] between the surface of most secretory vesicles and the rest of the cytosol.