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Articles by D. R Jacobs
Total Records ( 5 ) for D. R Jacobs
  P Gordon Larsen , J Boone Heinonen , S Sidney , B Sternfeld , D. R Jacobs and C. E. Lewis
 

Background  There is little research on the association of lifestyle exercise, such as active commuting (walking or biking to work), with obesity, fitness, and cardiovascular disease (CVD) risk factors.

Methods  This cross-sectional study included 2364 participants enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who worked outside the home during year 20 of the study (2005-2006). Associations between walking or biking to work (self-reported time, distance, and mode of commuting) with body weight (measured height and weight); obesity (body mass index [BMI], calculated as weight in kilograms divided by height in meters squared, ≥30); fitness (symptom-limited exercise stress testing); objective moderate-vigorous physical activity (accelerometry); CVD risk factors (blood pressure [oscillometric systolic and diastolic]); and serum measures (fasting measures of lipid, glucose, and insulin levels) were separately assessed by sex-stratified multivariable linear (or logistic) regression modeling.

Results  A total of 16.7% of participants used any means of active commuting to work. Controlling for age, race, income, education, smoking, examination center, and physical activity index excluding walking, men with any active commuting (vs none) had reduced likelihood of obesity (odds ratio [OR], 0.50; 95% confidence interval [CI], 0.33-0.76), reduced CVD risk: ratio of geometric mean triglyceride levels (trigactive)/(trignonactive) = 0.88 (95% CI, 0.80 to 0.98); ratio of geometric mean fasting insulin (FIactive)/(FInonactive) = 0.86 (95% CI, 0.78 to 0.93); difference in mean diastolic blood pressure (millimeters of mercury) (DBPactive) – (DBPnonactive) = –1.67 (95% CI, –3.20 to –0.15); and higher fitness: mean difference in treadmill test duration (in seconds) in men (TTactive) – (TTnonactive) = 50.0 (95% CI, 31.45 to 68.59) and women (TTactive) – (TTnonactive) = 28.77 (95% CI, 11.61 to 45.92).

Conclusions  Active commuting was positively associated with fitness in men and women and inversely associated with BMI, obesity, triglyceride levels, blood pressure, and insulin level in men. Active commuting should be investigated as a modality for maintaining or improving health.

  I Paur , T. R Balstad , M Kolberg , M. K Pedersen , L. M Austenaa , D. R Jacobs and R. Blomhoff
 

The transcription factor NF-B is a promising target for chemoprevention. Several dietary plants are efficient inhibitors of NF-B activation in vitro and could act synergistically on the NF-B signaling pathway. In this study, we tested whether dietary plant extracts could inhibit NF-B activation in a synergistic manner in vitro. Second, we investigated the potency of the same dietary plant extracts in the inhibition of NF-B activation in vivo. A combined extract of clove, oregano, thyme, walnuts, and coffee synergistically inhibited lipopolysaccaride (LPS)-induced NF-B activation in a monocytic cell line, compared with the sum of effects from the single extracts. Transgenic NF-B luciferase reporter mice were given a single dose of the combined extract and subsequently challenged with LPS. NF-B activation was monitored by in vivo imaging for 6 hours. In addition, NF-B activity in organs and the expression of immune-related genes in liver were investigated. Based on the area under the curve, the extract decreased whole body LPS-induced NF-B activity the first 6 hours by 35% compared with control mice. Organ-specific NF-B activation was inhibited in intestine, liver, testis, and epididymis of the mice receiving the combination extract. In addition, dietary plants reduced the expression of genes related to inflammation, cell migration, and proliferation in liver. This study shows that dietary plants may be potent modulators of NF-B signaling both in vitro and in vivo, and thus support further investigation of consumption of these plant foods as part of a healthy diet or as a mode of chemoprevention. Cancer Prev Res; 3(5); 653–63. ©2010 AACR.

  A. P Reiner , M. D Gross , C. S Carlson , S. J Bielinski , L. A Lange , M Fornage , N. S Jenny , J Walston , R. P Tracy , O. D Williams , D. R Jacobs and D. A. Nickerson
 

Background— The transcription factor hepatocyte nuclear factor (HNF)-1 regulates the activity of a number of genes involved in innate immunity, blood coagulation, lipid and glucose transport and metabolism, and cellular detoxification. Common polymorphisms of the HNF-1 gene (HNF1A) were recently associated with plasma C-reactive protein and -glutamyl transferase concentration in middle-aged to older European Americans (EA).

Methods and Results— We assessed whether common variants of HNF1A are associated with C-reactive protein, -glutamyl transferase, and other atherosclerotic and metabolic risk factors, in the large, population-based Coronary Artery Risk Development in Young Adults Study of healthy young EA (n=2154) and African American (AA; n=2083) adults. The minor alleles of Ile27Leu (rs1169288) and Ser486Asn (rs2464196) were associated with 0.10 to 0.15 standard deviation units lower C-reactive protein and -glutamyl transferase levels in EA. The same HNF1A coding variants were associated with higher low-density lipoprotein cholesterol, apolipoprotein B, creatinine, and fibrinogen in EA. We replicated the associations between HNF1A coding variants and C-reactive protein, fibrinogen, low-density lipoprotein cholesterol, and renal function in a second population-based sample of EA adults 65 years and older from the Cardiovascular Health Study. The HNF1A Ser486Asn and/or Ile27Leu variants were also associated with increased risk of subclinical coronary atherosclerosis in Coronary Artery Risk Development in Young Adults and with incident coronary heart disease in Cardiovascular Health Study. The Ile27Leu and Ser486Asn variants were 3-fold less common in AA than in EA. There was little evidence of association between HNF1A genotype and atherosclerosis-related phenotypes in AA.

Conclusions— Common polymorphisms of HNF1A seem to influence multiple phenotypes related to cardiovascular risk in the general population of younger and older EA adults.

  W Tang , G Apostol , P. J Schreiner , D. R Jacobs , E Boerwinkle and M. Fornage
 

Background— Genome-wide association studies in European Americans have reported several single-nucleotide polymorphisms (SNPs) in the lipoprotein lipase gene associated with plasma levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides. However, the influences of the lipoprotein lipase SNPs on longitudinal changes of these lipids have not been systematically examined.

Methods and Results— On the basis of data from 2045 African Americans and 2116 European Americans in the Coronary Artery Risk Development in Young Adults study, we investigated cross-sectional and longitudinal associations of lipids with 8 lipoprotein lipase SNPs, including the 2 that have been reported in genome-wide association studies. Plasma levels of HDL-C and triglycerides were measured at 7 examinations during 20 years of follow-up. In European Americans, rs328 (Ser447Stop), rs326, and rs13702 were significantly associated with cross-sectional interindividual variations in triglycerides and HDL-C (P<0.005) and with their longitudinal changes over time (P<0.05). The minor alleles in rs326, rs328, and rs13702 that predispose an individual to lower triglycerides and higher HDL-C levels at young adulthood further slow down the trajectory increase in triglycerides and decrease in HDL-C during 20 years of follow-up. In African Americans, these 3 SNPs were significantly associated with triglycerides, but only rs326 and rs13702 were associated with HDL-C (P<0.008). Rs328 showed a stronger association in European Americans than in African Americans, and adjustment for it did not remove all of the associations for the other SNPs. Longitudinal changes in either trait did not differ significantly by SNP genotypes in African Americans.

Conclusions— Our data suggest that aging interacts with LPL gene variants to influence the longitudinal lipid variations, and there is population-related heterogeneity in the longitudinal associations.

  J. Y Shin , Y. Y Choi , H. S Jeon , J. H Hwang , S. A Kim , J. H Kang , Y. S Chang , D. R Jacobs , J. Y Park and D. H. Lee
 

Although shortened telomeres have been found in many cancers, elongated telomere length has been observed as an early response after low-dose treatment with various chemical carcinogens in vitro and animal experiments, suggesting low-dose exposure to carcinogenic chemicals may function as a tumour promoter at the very early stage of carcinogenesis in humans. This cross-sectional study was performed to examine whether low-dose exposure to persistent organic pollutants (POPs), lipophilic xenobiotics that mainly bioaccumulate in adipose tissue, is associated with telomere length of peripheral blood leukocytes in apparently healthy persons. Telomere length was measured using quantitative polymerase chain reaction method in 84 apparently healthy Koreans. Among various POPs, serum concentrations of organochlorine (OC) pesticides, polychlorinated biphenyls (PCBs) and polybrominated diphenylethers were measured. Most OC pesticides and PCBs were positively and significantly associated with telomere length with correlation coefficients from about +0.25 to +0.35. The strongest associations were observed with p,p'-dichlorodiphenyldichloroethylene, PCB99, PCB153, PCB180, PCB183 and PCB187. When we examined adjusted means of telomere length by quintiles of POPs, the steeper increases of telomere length tended to be observed within relatively lower ranges of POPs. Besides serum concentrations of POPs, none of the other variables studied, including age, were associated with telomere length in this study. We found that telomere length was increasing across low doses of exposure to POPs in which the majority of study subjects were found, suggesting that low-dose POPs may act as a tumour promoter in carcinogenesis in humans.

 
 
 
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