Vitamin K dependent formation of γ-carboxyglutamate residues in tumor microsomes

Vitamin K stimulated the incorporation of 14C into proteins when microsomes from melanoma, mammary gland, mast cell and lymphoma tumors were incubated with Na214CO3. The 14C label in the [14C] proteins was identified as [14C] γ-carboxyglutamate (Gla), which is formed by carboxylation of glutamic acid residues. Carboxylation in tumor microsomes ranged from 2 to 19% of the carboxylation in normal liver microsomes per mg of microsomal protein. Carboxylation in microsomes was completely blocked by 10 μM Warfarin. SDS-polyacrylamide gel analysis of the melanoma [14C] Gla protein(s) revealed one major peak of 14C with an apparent MW of less than 6,000. © 1982

Predictors of liver fat among children and adolescents from five different ethnic groups.

ObjectivesAs rates of obesity around the world have increased, so has the detection of high level of liver fat in children and adolescents. This may put them at risk for cardiovascular disease later in life. This analysis of a cross-sectional population-based study of children and adolescents evaluated demographic and lifestyle determinants of percent liver fat.MethodsHealthy participants (123 girls and 99 boys aged 5-17 years) recruited by convenience sampling in three locations completed questionnaires, anthropometric measurements, and dual X-ray absorptiometry and magnetic resonance imaging (MRI) assessment. General linear models were applied to estimate the association of demographic, anthropometric, and dietary factors as well as physical activity with MRI-based percent liver fat.ResultsThe strongest predictor of liver fat was body mass index (BMI; p < 0.0001); overweight and obesity were associated with 0.5% and 1% higher liver fat levels. The respective adjusted mean percent values were 2.9 (95% CI 2.7, 3.1) and 3.4 (95% CI 3.2, 3.6) as compared to normal weight (2.4; 95% CI 2.3, 2.6). Mean percent liver fat was highest in Whites and African Americans, intermediate in Hispanic, and lowest among Asians and Native Hawaiians/Pacific Islanders (p < 0.0001). Age (p = 0.67), sex (p = 0.28), physical activity (p = 0.74), and diet quality (p = 0.70) were not significantly related with liver fat.ConclusionsThis study in multiethnic children and adolescents confirms the strong relationship of BMI with percent liver fat even in a population with low liver fat levels without detecting an association with age, sex, and dietary or physical activity patterns

Subcutaneous and visceral fat assessment by DXA and MRI in older adults and children

ObjectiveGiven the importance of body fat distribution in chronic disease development, feasible methods to assess body fat are essential. This study compared dual-energy x-ray absorptiometry (DXA) in measuring visceral and subcutaneous adipose tissue (VAT and SAT) with magnetic resonance imaging (MRI).MethodsVAT and SAT were assessed using similar DXA and MRI protocols among 1,795 elderly participants of the Adiposity Phenotype Study (APS) and 309 children/adolescents in Shape Up! Kids (SKids). Spearman correlations, Bland-Altman plots, and coefficients of determination (R2 ) assessed agreement between DXA and MRI measures.ResultsDXA overestimated SAT values in APS (315 vs. 229 cm2 ) and SKids (212 vs. 161 cm2 ), whereas DXA underestimated VAT measures (141 vs. 167 cm2 ) in adults only. The correlations between DXA and MRI values were stronger for SAT than VAT (APS: r = 0.92 vs. 0.88; SKids: 0.90 vs. 0.74). Bland-Altman plots confirmed better agreement for SAT than VAT despite differences by sex, ethnicity, and weight status with respective R2 values for SAT and VAT of 0.88 and 0.84 (APS) and 0.81 and 0.69 (SKids).ConclusionThese findings indicate that SAT by DXA reflects MRI measures in children and older adults, whereas agreement for VAT is weaker for individuals with low VAT levels

Structural growth trajectories and rates of change in the first 3 months of infant brain development.

ImportanceThe very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders.ObjectiveTo assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth.Design, setting, and participantsSerial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013.Main outcomes and measuresWe segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms.ResultsWhole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10-13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development.Conclusions and relevanceNormative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders