Myoblasts respond to growth factor deprivation either by differentiating into multinucleated myotubes or by undergoing apoptosis; hence, the acquisition of apoptosis resistance by myogenic precursors is essential for their development. Here we demonstrate that the expression of the small heat shock protein ␣B-crystallin is selectively induced in C2C12 myoblasts that are resistant to differentiation-induced apoptosis, and we show that this induction occurs at an early stage in their differentiation in vitro. In contrast, the expression of several known anti-apoptotic proteins (FLIP, XIAP, Bclx L ) was not altered during myogenesis. We also demonstrate that ectopic expression of ␣B-crystallin, but not the closely related small heat shock protein Hsp27, renders C2C12 myoblasts resistant to differentiation-induced apoptosis. Furthermore, we show that the myopathy-causing R120G ␣B-crystallin mutant is partly impaired in its cytoprotective function, whereas a pseudophosphorylation ␣B-crystallin mutant that mimics stress-induced phosphorylation is completely devoid of anti-apoptotic activity. Finally, we demonstrate that ␣B-crystallin negatively regulates apoptosis during myogenesis by inhibiting the proteolytic activation of caspase-3, whereas the R120G and pseudophosphorylation mutants are defective in this function. Taken together, our findings indicate that ␣B-crystallin is a novel negative regulator of myogenic apoptosis that directly links the differentiation program to apoptosis resistance.During skeletal muscle development, a subset of proliferating myoblasts exit the cell cycle and become resistant to apoptosis; these surviving myoblasts fuse to form multinucleated myotubes and differentiate into mature myocytes, whereas apoptosis-sensitive myoblasts are eliminated (1). Although the acquisition of apoptosis resistance by myogenic precursors is a critical event in their differentiation, only a few genes that regulate this process have been identified. One such gene is the cyclin-dependent kinase inhibitor p21 whose expression is induced at an early stage of myogenesis by the skeletal musclespecific transcriptional regulator MyoD (2, 3). p21 expression in myoblasts promotes cell cycle withdrawal and confers resistance to apoptosis through its actions on its downstream target, the retinoblastoma (RB) protein (1, 4). The anti-apoptotic kinase Akt is also induced during skeletal muscle development and promotes the survival of differentiating myoblasts, although its anti-apoptotic mechanism(s) in muscle is unclear (5-7). Finally, Bcl-2, a protein that inhibits many of the mitochondrial events in apoptosis, is transiently expressed in myogenic precursors and promotes their clonal expansion (8). Nevertheless, given the complexity of the apoptotic cell death apparatus (9), it seems likely that other genes play important roles in myogenic apoptosis.One particularly intriguing candidate is ␣B-crystallin, a member of the small heat shock protein (HSP) 1 family that also includes ␣A-crystallin, Hsp27, Hsp20, Hsp22, myotoni...

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OBJECTIVEGreater accumulation of visceral fat is strongly linked to risk of cardiovascular disease. However, elevated waist circumference by itself does not always identify individuals with increased visceral fat.RESEARCH DESIGN AND METHODSWe examined 375 subjects with type 2 diabetes from the CHICAGO cohort for presence of hypertriglyceridemic waist phenotype (waist circumference >90 cm in men or >85 cm in women, in conjunction with a plasma triglyceride concentration of ≥177 mg/dl) to determine its usefulness for identifying subjects with increased amounts of visceral fat. We divided subjects into three groups: group 1 (low waist circumference and low triglycerides; waist circumference ≤90 cm in men or ≤85 cm in women and triglyceride <177 mg/dl, n = 18), group 2 (high waist circumference and low triglycerides; waist circumference >90 cm in men or >85 cm in women and triglycerides <177 mg/dl, n = 230), and group 3 (high waist circumference and high triglycerides; waist circumference >90 cm in men or >85 cm in women and triglycerides ≥177 mg/dl, n = 127).RESULTSSubjects in group 3 had significantly higher visceral fat (P < 0.0001), A1C (P < 0.01), and coronary artery calcium (P < 0.05) compared with group 2, despite similar age, BMI, and waist circumference. The relationship of the phenotype to atherosclerosis, however, was attenuated by adjustment for HDL cholesterol, triglyceride-rich lipoprotein cholesterol, apolipoprotein B, or LDL particle number.CONCLUSIONSThe presence of hypertriglyceridemic waist phenotype in subjects with type 2 diabetes identifies a subset with greater degree of visceral adiposity. This subset also has greater degree of subclinical atherosclerosis that may be related to the proatherogenic lipoprotein changes.

Cortisol levels were elevated in most patients with septic shock. Cortisol levels less than 552 nmol/l occurred in 30% of patients with septic shock but the mortality in these patients was not significantly increased. Serum cortisol levels > or = 1242 nmol/l were associated with significantly higher mortality.