RXR antagonism induces G0 /G1 cell cycle arrest and ameliorates obesity by up-regulating the p53-p21(Cip1) pathway in adipocytes.

The peroxisome proliferator activated receptor-γ (PPARγ) agonist, pioglitazone (PIO), exerts anti-diabetic properties associated with increased fat mass, whereas the retinoid X receptor (RXR) antagonist HX531 demonstrates anti-obesity and anti-diabetic effects with reduced body weight and fat pad mass. The cell cycle abnormality in adipocytes has not been well-investigated in obesity or during treatment with modulators of nuclear receptors. We therefore investigated cell size and cell cycle distributions of adipocytes in vivo and examined the expression of cell cycle regulators in cultured human visceral preadipocytes. The cell size distribution and cell cycle analyses of in vivo adipocytes derived from OLETF rats demonstrated that HX531 brought about G0/G1 cell cycle arrest associated with the inhibition of cellular hypertrophy, which resulted in the reduction of fat pad mass. In contrast, PIO promoted proliferation activities associated with the increase in M + late M:G0 + G1 ratio and the appearance of both small and hypertrophied adipocytes. In cultured human visceral preadipocytes HX531 up-regulated cell cycle regulators, p53, p21(Cip1), cyclin D1, Fbxw7 and Skp2, which are known contributors towards G0 /G1 cell cycle arrest. The knockdown of p53 with a shRNA lentivirus reversed the HX531-induced up-regulation of p21(Cip1), which is one of the major p53-effector molecules. We conclude that HX531 exerts anti-obesity and anti-diabetes properties by up-regulating the p53-p21(Cip1) pathway, resulting in G0/G1 cell cycle arrest and the inhibition of cellular hypertrophy of adipocytes.

[Incorrect descriptions about Seicho Kamata in "Seishu Hanaoka and his surgery"].

"Seishu Hanaoka and his surgery" by Shuzo Kure is one of the most important books for the study of Seishu Hanaoka. However, several incorrect descriptions have been pointed out in the book. Therefore, we checked the content about Seicho Kamata, a distinguished disciple of Seishu Hanaoka (p.154-163) in the book, and found three incorrect descriptions. The figure being described as that of Seicho Kamata is his father's. His graveyard being described as "Nyohoji" is truly "Daizenji". Seicho Kamata is also described as the second distinguished disciple of Seishu Hanaoka ; however, authors think that he was the first distinguished disciple from his career. Further investigation into the content of the book is necessary.

Bilateral brachial plexus injury after liver transplantation.

We report a case of bilateral brachial plexus injury following living-donor liver transplantation. A 35-year-old man with hepatitis C cirrhosis underwent liver transplantation under general anesthesia, performed in the supine position with 90 degrees arm abduction. The surgery lasted for 14 h, and the anesthesia for 16 h. On postoperative day 1, it was noticed that he had brachial plexus injuries. We investigated the cause of the nerve injuries, in particular, the possible involvement of stretching, compression, or nerve ischemia, which can often result from excessive abduction, the use of shoulder braces, compression by the poles used in the operating theater or compression caused by surgeons leaning on the patient, or serious general status (e.g., hypotension or hypoxemia). Our findings were inconclusive, but we postulated that 90 degrees abduction of the arms per se may have resulted in excessive stretching of the brachial nerves, causing his injuries.

Elevated serum monocyte chemoattractant protein-4 and chronic inflammation in overweight subjects.

OBJECTIVE: Chronic inflammation observed in obesity has been reported to be implicated in the development of atherosclerosis. We screened candidate chemokines that link chronic inflammation and obesity. RESEARCH METHODS AND PROCEDURES: Japanese overweight (n = 39, BMI 28.7 +/- 0.65 kg/m(2)) and normal-weight (n = 24, BMI 22.3 +/- 0.45 kg/m(2)) subjects were enrolled. Using antibody-based protein microarray, spot intensities of monocyte chemoattractant protein (MCP)-4, eotaxin, and eotaxin-2 correlated with anthropometric parameters. We further measured serum concentration of these chemokines and mRNA levels in adipose tissues obtained from volunteers. RESULTS: Serum MCP-4 levels showed positive correlation with BMI (r = 0.318, p = 0.014), waist (r = 0.316, p = 0.018), and waist-to-hip ratio (WHR) (r = 0.264, p = 0.049). Furthermore, MCP-4 correlated with homeostasis model assessment of insulin resistance (r = 0.392, p = 0.002), high-sensitivity C-reactive protein (hsCRP) (r = 0.350, p = 0.006). In step-wise multiple regression analyses, hsCRP independently correlated with MCP-4 levels. The expression of MCP-4 mRNA in visceral adipose tissue positively correlates with BMI. Serum eotaxin levels correlate with BMI (r = 0.262, p = 0.045) and WHR (r = 0.383, p = 0.003). Serum eotaxin-2 levels correlated with BMI (r = 0.464, p < 0.001), waist (r = 0.333, p = 0.017), and WHR (r = 0.278, p = 0.048). However, eotaxin and eotaxin-2 levels did not show significant correlation with hsCRP. DISCUSSION: Serum levels of MCP-4, eotaxin, and eotaxin-2, which belong to CC chemokine family and share CC chemokine receptor 3, correlated with BMI. These chemokines, especially MCP-4, may be critical molecules that link obesity and chronic inflammation.