Androgen receptor CAG repeat length polymorphism in benign prostatic hyperplasia (BPH): correlation with adenoma growth.

BACKGROUND: The androgen receptor (AR) gene has a polymorphic CAG microsatellite encoding variable-length glutamine repeats in the AR protein. The purpose of this study was to evaluate the association between the growth of benign prostatic hyperplasia (BPH) and the AR gene CAG repeat length. METHODS: We determined CAG repeat lengths in 176 BPH patients who underwent simple prostatectomy and in 41 control subjects without benign prostatic enlargement (non-BPE group). RESULTS: A statistically significant (P < 0.02) trend for large adenoma size with short CAG repeat length was found among the adenoma quartiles. CAG repeat length in the fourth quartile (large adenoma, 21.5 +/- 2.7) was significantly shorter than in the first quartile (small adenoma, 23.3 +/- 2.1, P < 0.02). It tended to be shorter than in the non-BPE group (23.1 +/- 2.4), but CAG repeat lengths in the entire BPH (22.4 +/- 2.5) and non-BPE groups did not significantly differ. The relative risk of large BPH (the fourth quartile) was 2.75 (95% confidence interval, 1.05-7.24; P < 0.05) on comparing CAG repeats of < or = 22-> or = 23. CONCLUSIONS: Shorter CAG alleles may be a genetic factor that promotes the growth of BPH.     

Intracerebroventricular administration of mouse leptin does not reduce food intake in the chicken

Recently, it has been suggested that leptin plays an important role in regulation of food intake and metabolism in rats and mice, however, the effect of central administration of leptin on food intake in chicks has not been reported. We have investigated the anorexigenic effect of leptin administered by intracerebroventricular (i.c.v.) injection in chicks using mouse leptin, which shows 97% homology to chicken leptin. Three experiments were conducted. After being deprived of food for 3 h, male broiler chicks were administered leptin by i.c.v. injection at dose levels of 0, 0.2, 1.0 and 5.0 μg (Experiment 1) or 0, 2.5 and 5.0 μg (Experiment 2). The birds were allowed free access to the diet for 2 h (Experiment 1) and 24 h (Experiment 2) after treatment. Male Single Comb White Leghorn chicks were used in Experiment 3 and were treated in the same manner as in Experiment 1. In all experiments, central administration of mouse leptin did not influence food intake in the time periods examined. It appears that either mouse leptin does not bind to the chicken leptin receptor or in the chicken brain the leptin receptor may be absent.     

Peritumoral edema in osteoid osteoma on magnetic resonance imaging

Objective.To determine whether there is a relationship between the peritumoral edema caused by osteoid osteoma seen on magnetic resonance (MR) imaging and the patient’s age, duration of symptoms, or location of the lesion. Design and patients. All histologically proven osteoid osteomas seen in our institutions during a 5-year period in patients with known age, gender, duration of symptoms, and available radiological and MR imaging examinations were included in this study. The extent of the edema in the bone marrow and extraosseous soft tissue around the nidus of osteoid osteoma on T2-weighted MR imaging were graded from 1 (nonexistent) to 4 (extensive) by two masked observers. The relationships between the patient’s age, duration of symptoms, and location of lesions were evaluated by Pearson’s correlation coefficient and analysis of variance. Results.Twenty-seven cases met the inclusion criteria. The observer agreement on grading was good. Patients of 15 years of age or younger had significantly higher grades than patients older than 15 years. There was a moderate negative linear correlation between the patient’s age and peritumoral edema. No significant relationship was identified between edema and the duration of symptoms or the location of lesions. Conclusion. Osteoid osteomas in younger patients tend to be associated with more extensive peritumoral edema. Received: 13 March 1998 Revision requested: 3 August 1998 Revision received: 12 January 1999 Accepted: 2 March 1999     

Vascular endothelial growth factor and osteopontin in stage I lung adenocarcinoma.

Tumor growth and metastasis are angiogenesis-dependent processes initiated and regulated by a number of cytokines. Vascular endothelial growth factor (VEGF) is a potent angiogenic protein with a selective mitogenic effect on vascular endothelial cells. Osteopontin (OPN) induces endothelial cell migration and upregulates endothelial cell migration induced by VEGF. To clarify the cooperative role of VEGF and OPN in tumor angiogenesis, we stained VEGF, OPN, and CD34 immunohistochemically in 87 cases of stage I non-small cell lung cancer (adenocarcinoma, 55, and squamous cell carcinoma, 32). Of the 87 patients studied, 27 patients had postoperative relapse and 60 patients did not. VEGF was found in 34 of 55 cases of adenocarcinomas and 14 of 32 squamous cell carcinomas, and OPN was found in 30 of 55 adenocarcinomas and 10 of 32 squamous cell carcinomas. In adenocarcinoma, microvessel counts of VEGF-positive and OPN-positive tumors were significantly higher than VEGF-negative and OPN-negative tumors, respectively, whereas in squamous cell carcinoma they were not. More importantly, patients with VEGF- and OPN-positive stage I lung adenocarcinoma had significantly worse prognosis as compared with other groups. Cooperation of OPN is important in VEGF-mediated tumor angiogenesis in stage I lung adenocarcinoma.     

Association of serum creatinine-to-cystatin C ratio with skeletal muscle mass and strength in nonalcoholic fatty liver disease in the Iwaki Health Promotion Project

We evaluated the feasibility of using serum creatinine-to-cystatin C ratio in the assessments of muscle mass and strength in nonalcoholic fatty liver disease. In a community-based cross-sectional study, skeletal muscle mass and handgrip strength were assessed in 641 Japanese adults. Low skeletal muscle mass index and low handgrip strength were defined as indicated in the sarcopenia diagnostic criteria of the Japan Society of Hepatology. Nonalcoholic fatty liver disease was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. The creatinine-to-cystatin C ratio was useful for identifying the participants with low skeletal muscle mass index, with an area under the receiver-operating characteristic curve of 0.84 [95% confidence interval (CI), 0.77–0.91] in men and 0.72 in women (95% CI, 0.65–0.78), and those with low handgrip strength, with an area under the receiver-operating characteristic curve of 0.96 (95% CI, 0.93–0.99) in men and 0.79 (95% CI, 0.66–0.92) in women. Moreover, the creatinine-to-cystatin C ratio correlated with skeletal muscle mass index (r = 0.511, p<0.001) and handgrip strength (r = 0.657, p<0.001), whereas it did not correlate with exacerbation of hepatic steatosis. In this study, creatinine-to-cystatin C ratio correlated with muscle mass and strength in nonalcoholic fatty liver disease regardless of hepatic steatosis.     

NO-1886 (ibrolipim), a lipoprotein lipase activator, increases the expression of uncoupling protein 3 in skeletal muscle and suppresses fat accumulation in high-fat diet-induced obesity in rats

Although the lipoprotein lipase (LPL) activator NO-1886 shows antiobesity effects in high-fat-induced obese animals, the mechanism remains unclear. To clarify the mechanism, we studied the effects of NO-1886 on the expression of uncoupling protein (UCP) 1, UCP2, and UCP3 in rats. NO-1886 was mixed with a high-fat chow to supply a dose of 100 mg/kg to 8-month-old male Sprague-Dawley rats. The animals were fed the high-fat chow for 8 weeks. At the end of the administration period, brown adipose tissue (BAT), mesenteric fat, and soleus muscle were collected and levels of UCP1, UCP2, and UCP3 messenger RNA (mRNA) were determined. NO-1886 suppressed the body weight increase seen in the high-fat control group after the 8-week administration (585 +/- 39 vs 657 +/- 66 g, P < .05). NO-1886 also suppressed fat accumulation in visceral (46.9 +/- 10.4 vs 73.7 +/- 14.5 g, P < .01) and subcutaneous (43.1 +/- 18.1 vs 68.9 +/- 18.8 g, P < .05) tissues and increased the levels of plasma total cholesterol and high-density lipoprotein cholesterol in comparison to the high-fat control group. In contrast, NO-1886 decreased the levels of plasma triglycerides, nonesterified free fatty acid, glucose, and insulin. NO-1886 increased LPL activity in soleus muscle (0.082 +/- 0.013 vs 0.061 +/- 0.016 mumol of free fatty acid per minute per gram of tissue, P < .05). NO-1886 increased the expression of UCP3 mRNA in soleus muscle 3.14-fold (P < .01) compared with the high-fat control group without affecting the levels of UCP3 in mesenteric adipose tissue and BAT. In addition, NO-1886 did not affect the expression of UCP1 and UCP2 in BAT, mesenteric adipose tissue, and soleus muscle. In conclusion, NO-1886 increased the expression of UCP3 mRNA and LPL activity only in skeletal muscle. Therefore, a possible mechanism for NO-1886's antiobesity effects in rats may be the enhancement of LPL activity in skeletal muscle and the accompanying increase in UCP3 expression.     

Magnetic resonance cholangiopancreatography in assessing the cause of acute pancreatitis in children

Magnetic resonance cholangiopancreatography (MRCP) is a new noninvasive method of obtaining images of the pancreaticobiliary tract. Recent advances in MR technology and image quality have made it easy to diagnose structural abnormalities of the pancreaticobiliary tract (SAPBT) in children. To examine the usefulness of MRCP in assessing the cause of acute pancreatitis in children, we performed MRCP in 16 patients with acute pancreatitis. The study population was divided into two groups according to the cause of acute pancreatitis as follows: group 1 consisted of seven patients sonographically diagnosed with choledochal cysts; and group 2 consisted of nine patients with no obvious cause of acute pancreatitis. Non-breath-hold MRCP using the half-Fourier, single-shot, fast spin-echo imaging method was performed within 7 days after the onset of pancreatitis. Abnormal union of the pancreaticobiliary junction was detected in six of seven group 1 patients and in one of nine group 2 patients. Pancreatic divisum was detected in one patient of group 1, but could not be confirmed in one patient of group 2. Dilatation of the main pancreatic duct was detected in one patient of group 1 and in three patients of group 2. Our results suggest that MRCP is a useful, noninvasive method of identifying and ruling out SAPBT as a cause of acute pancreatitis in children with early-stage pancreatitis.