Body Fat and Fat‐Free Mass and All‐Cause Mortality

Objective: To investigate whether the association between BMI and all‐cause mortality could be disentangled into opposite effects of body fat and fat‐free mass (FFM). Research Methods and Procedures: All‐cause mortality was studied in the Danish follow‐up study “Diet, Cancer and Health” with 27, 178 men and 29, 875 women 50 to 64 years old recruited from 1993 to 1997. By the end of year 2001, the median follow‐up was 5.8 years, and 1851 had died. Body composition was assessed by bioelectrical impedance. Cox regression models were used to estimate the relationships among body fat mass index (body fat mass divided by height squared), FFM index (FFM divided by height squared), and mortality. All analyses were adjusted for smoking habits. Results: Men and women showed similar associations. J‐shaped associations were found between body fat mass index and mortality adjusted for FFM and smoking. The mortality rate ratios in the upper part of body fat mass were 1.12 per kg/m² (95% confidence interval: 1.07, 1.18) in men and 1.06 per kg/m² (95% confidence interval: 1.02, 1.10) in women. Reversed J‐shaped associations were found between FFM index and mortality with a tendency to level off for high values of FFM. Discussion: Our findings suggest that BMI represents joint but opposite associations of body fat and FFM with mortality. Both high body fat and low FFM are independent predictors of all‐cause mortality.     

Use of an A-T-rich DNA clone for identification and detection of Peronosclerospora sorghi

A recombinant plasmid, pMLY12-1, screened from a Peronosclerospora sorghi library hybridizes only to DNA of P. sorghi, or to DNA from leaves infected with P. sorghi, not to DNA of P. sorghi Thailand isolate, P. philippinensis, P. sacchari, or P. maydis. The terminal sequences of the 1.3-kb insert, which appears to contain mitochondrial DNA, are 85% A and T. No polymorphisms were detected when the probe was hybridized to Southern blots containing DNA from P. sorghi pathotype 1, pathotype 3, or a Botswana isolate digested with any of the eight restriction endonucleases tested. The banding patterns were the same whether DNA was extracted directly from the fungus or from infected leaves.     

Synthesis of low molecular weight RNA components in cells with a temperature-sensitive polymerase II

AF 8 cells are a mutant cell line of baby hamster kidney cells with a temperature-sensitive polymerase II activity. When these cells grow at the non-permissive temperature (40 degrees C) the syntheseis of low molecular weight RNA components D, C and A is preferentially inhibited, whereas the synthesis of rRNA, tRNA, 5 S RNA and component L is affected only a little or not at all. These results indicate that polymerase II catalyzes the synthesis of components D, C and A.     

18F-FET MicroPET and MicroMRI for Anti-VEGF and Anti-PlGF Response Assessment in an Orthotopic Murine Model of Human Glioblastoma

BackgroundConflicting data exist for anti-cancer effects of anti-placental growth factor (anti-PlGF) in combination with anti-VEGF. Still, this treatment combination has not been evaluated in intracranial glioblastoma (GBM) xenografts. In clinical studies, position emission tomography (PET) using the radiolabeled amino acid O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) and magnetic resonance imaging (MRI) add complementary but distinct information about glioma growth; however, the value of ¹⁸F-FET MicroPET combined with MicroMRI has not been investigated preclinically. Here we examined the use of ¹⁸F-FET MicroPET and MicroMRI for evaluation of anti-VEGF and anti-PlGF treatment response in GBM xenografts.MethodsMice with intracranial GBM were treated with anti-VEGF, anti-PlGF + anti-VEGF or saline. Bioluminescence imaging (BLI), ¹⁸F-FET MicroPET and T2-weighted (T2w)-MRI were used to follow tumour development. Primary end-point was survival, and tumours were subsequently analysed for Ki67 proliferation index and micro-vessel density (MVD). Further, PlGF and VEGFR-1 expression were examined in a subset of the xenograft tumours and in 13 GBM patient tumours.ResultsAnti-VEGF monotherapy increased survival and decreased ¹⁸F-FET uptake, BLI and MVD, while no additive effect of anti-PlGF was observed. ¹⁸F-FET SUV_max tumour-to-brain (T/B) ratio was significantly lower after one week (114±6%, n = 11 vs. 143±8%, n = 13; p = 0.02) and two weeks of treatment (116±12%, n = 8 vs. 190±24%, n = 5; p = 0.02) in the anti-VEGF group as compared with the control group. In contrast, T2w-MRI volume was unaffected by anti-VEGF. Gene expression of PlGF and VEGFR-1 in xenografts was significantly lower than in patient tumours.Conclusion¹⁸F-FET PET was feasible for anti-angiogenic response evaluation and superior to T2w-MRI; however, no additive anti-cancer effect of anti-PlGF and anti-VEGF was observed. Thus, this study supports use of ¹⁸F-FET PET for response evaluation in future studies.