The Lewin Group Study--what does it tell us and why does it matter? [ comment].
Explore the source record for details and available documents.
Cardiovascular Diseases↗
Biomedical subjects
R K Johnson
Publications and source records attributed to R K Johnson.
Synthesis of furanonaphthoquinones with hydroxyamino side chains.
Several furanonaphthoquinones have shown useful activity in a yeast assay for DNA-damaging agents and cytotoxicity in mammalian cell culture assays. These results, together with the planar aromatic character of the furanonaphthoquinones, suggested that they might be acting as DNA intercalators. In an attempt to improve this activity, various analogues containing a hydroxyamino side chain have been synthesized. The analogues were prepared by standard methods, but some unexpected reactions were observed nonetheless. Thus, 8-formyl-5-methoxy-4,9-dihydronaphtho[2,3-b]furan-4,9-dione (24) showed an unusual reactivity toward reductive amination, with the reaction proceeding further to give one of two different cyclized products, depending on the amination reagent used. Bioassay results indicated that only simple furanonaphthoquines showed activity in a yeast assay for DNA-damaging agents; compounds with a substituted hydroxyamino side chain were uniformly inactive in this assay. Most of the compounds with a substituted hydroxyamino side chain on the furan ring did, however, show cytotoxicity, although none of them was any more active than the simple aldehyde 2-formyl-4, 9-dihydronaphtho[2,3-b]furan-4,9-dione (14). This evidence tends to suggest that the furanonaphthoquinones do not serve primarily as DNA intercalators, because if this were the case, they would have been expected to show an increased activity on conversion to their hydroxyamino side chain derivatives.
Animals↗
Responses in ovulation rate, embryonal survival, and litter traits in swine to 14 generations of selection to increase litter size.
Eleven generations of selection for increased index of ovulation rate and embryonal survival rate, followed by three generations of selection for litter size, were practiced. Laparotomy was used to count corpora lutea and fetuses at 50 d of gestation. High-indexing gilts, approximately 30%, were farrowed. Sons of dams in the upper 10% of the distribution were selected. Selection from Generations 12 to 14 was for increased number of fully formed pigs; replacements were from the largest 25% of the litters. A randomly selected control line was maintained. Responses at Generation 11 were approximately 7.4 ova and 3.8 fetuses at 50 d of gestation (P < .01) and 2.3 fully formed pigs (P < .01) and 1.1 live pigs at birth (P < .05). Responses at Generation 14 were three fully formed pigs (P < .01) and 1.4 live pigs (P < .05) per litter. Number of pigs weaned declined (P < .05) in the index line. Total litter weight weaned did not change significantly. Ovulation rate and number of fetuses had positive genetic correlations with number of stillborn pigs per litter. Significantly greater rate of inbreeding and increased litter size at 50 d of gestation in the select line may have contributed to greater fetal losses in late gestation, greater number of stillborn pigs, and lighter pigs at birth, leading to lower preweaning viability. Heritabilities of traits were between 8 and 25%. Genetic improvement programs should emphasize live-born pigs and perhaps weight of live-born pigs because of undesirable genetic relationships of ovulation rate and number of fetuses with numbers of stillborn and mummified pigs and because birth weight decreased as litter size increased.
Animal Husbandry↗
Diaminobenzidine as a myelin stain in semithin plastic sections.
A diaminobenzidine (DAB) stain for myelin in glutaraldehyde fixed, osmicated, semithin epoxy sections is described. One or 1.5 microm sections, dried onto slides, are first etched with a 1:2 dilution of saturated sodium ethoxide:absolute ethanol, then incubated in 0.05% aqueous DAB with 0.01% hydrogen peroxide. DAB specifically stains osmium fixed myelinated nerve fibers. This permits high resolution light microscopic study of myelinated nerve fibers in semithin sections of tissues that also can be studied by electron microscopy.
3,3'-Diaminobenzidine↗
Concentrations of gonadotropins, estradiol and progesterone in sows selected on an index of ovulation rate and embryo survival.
The objective of this study was to determine concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P4) and 17beta-estradiol (E2) in sows from a line selected on an index which emphasized ovulation rate (Select) and from a control line. A further classification of the sows in each line was made according to the estimated number of ovulations during an estrous cycle. Sows in the Select line were ranked into a high (HI) or low group (LI) when their estimated number of ovulations were 25 or more and 14 to 15, respectively. Sows of the control line were classified into groups as high (HC) or low (LC) when the estimated values for ovulation rate were 14-15 and 8-9 ovulations, respectively. Blood samples were collected every 12 h during a complete estrous cycle and samples were analyzed for concentrations of FSH and LH. Samples collected every 24 h were assayed for P4 and E2. Mean concentrations of FSH, LH, P4 and E2 did not differ (P > 0.10) between lines or between HI and LI or HC and LC groups. Selection of pigs for ovulation rate and embryonal survival did not affect concentrations of FSH, LH, P4 and E2 in sows during the estrous cycle.
Animals↗
A small, nonpeptidyl mimic of granulocyte-colony-stimulating factor [see commetns].
A nonpeptidyl small molecule SB 247464, capable of activating granulocyte-colony-stimulating factor (G-CSF) signal transduction pathways, was identified in a high-throughput assay in cultured cells. Like G-CSF, SB 247464 induced tyrosine phosphorylation of multiple signaling proteins and stimulated primary murine bone marrow cells to form granulocytic colonies in vitro. It also elevated peripheral blood neutrophil counts in mice. The extracellular domain of the murine G-CSF receptor was required for the activity of SB 247464, suggesting that the compound acts by oligomerizing receptor chains. The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand.
Animals↗
Differential effects of camptothecin derivatives on topoisomerase I-mediated DNA structure modification.
The effects of eleven camptothecin derivatives on calf thymus topoisomerase I-mediated cleavage of synthetic DNA duplex have revealed that the A ring of camptothecin is very important for its biochemical activity. Depending on the type, number, and location of substituents, highly active or inactive analogues were obtained. The persistence of CPT-induced topoisomerase I-DNA covalent binary complexes was investigated by using as substrates DNA containing several good topoisomerase I cleavage sites, or else a synthetic DNA duplex of defined structure with a single high-efficiency cleavage site. The ligation kinetics at a given topoisomerase I cleavage site were sometimes quite different in the presence of CPT derivatives whose structures were closely related. Even in the presence of a single CPT analogue, topoisomerase I-DNA covalent binary complexes underwent ligation with different kinetics, presumably reflecting a dependence on DNA sequences flanking the individual topoisomerase I cleavage sites. Individual camptothecin derivatives also exhibited a spectrum of inhibitory potentials in blocking the topoisomerase I-mediated rearrangement of branched, nicked, and gapped DNA duplex substrates; in some cases the potencies of inhibition observed in these assays for individual camptothecin analogues were quite different than those determined for stabilization of the unmodified DNA-topoisomerase I binary complex.
Camptothecin↗
Dietary fat intake and the risk of coronary heart disease in women.
Explore the source record for details and available documents.
Bias↗
Literacy and body fatness are associated with underreporting of energy intake in US low-income women using the multiple-pass 24-hour recall: a doubly labeled water study.
OBJECTIVE: The accuracy of the multiple-pass 24-hour recall method for estimating energy intake in low-income women in the United States was ascertained by comparing the method with measurements of total energy expenditure. The multiple-pass 24-hour recall is designed to provide respondents with multiple cues and opportunities to report their food intake. It consists of 3 distinct passes: the quick list, detailed description, and review. Predictors of energy intake misreporting (energy intake--total energy expenditure) in the sample were determined. DESIGN: Four multiple-pass 24-hour recalls (2 in person, 2 by telephone) were obtained over a 14-day period to estimate energy intake. Total energy expenditure was measured over the same 14-day period using the doubly labeled water method. Body composition was measured using dual energy x-ray absorptiometry, and literacy was measured by the Wide Range Achievement Test (WRAT) for reading and spelling. SUBJECTS/SETTINGS: Thirty-five low-income women between the ages of 19 and 46 years were tested at the General Clinical Research Center at the University of Vermont, Burlington. Low income was defined as a household income at or below 130% of the federal poverty level. STATISTICAL ANALYSIS: Pearson product moment correlation coefficients, t tests, paired t tests, and stepwise multiple regression analysis were used to test the relationships among study variables. RESULTS: Mean energy intake was significantly lower than mean total energy expenditure (2,197 +/- 607 vs 2,644 +/- 503 kcal, P = .001) and the correlation between the 2 measures was poor (r = .22, P = .20). Percentage body fat and the combined age-adjusted reading and spelling WRAT scores were the best predictors of misreporting of energy intake (R = .52, P = .006). CONCLUSIONS: The multiple-pass 24-hour recall did not generate a group measure of energy intake that was accurate or unbiased in this sample. Underreporting was strongly associated with increased body fatness. The ability to read and spell as measured by the WRAT improved the accuracy of the women's recall of their food intake. APPLICATIONS: Dietetics professionals should take into consideration the problem of underreporting whenever conclusions are made about associations between diet and health and/or when evaluating the impact of food assistance programs on dietary intake.
Adipose Tissue↗
Limonoids showing selective toxicity to DNA repair-deficient yeast and other constituents of Trichilia emetica.
Bioactivity-directed fractionation of the MeCOEt extract of Trichilia emetica (Meliaceae) resulted in the isolation of the limonoids nymania 1 (1), drageana 4 (3), trichilin A (4), rohituka 3 (5), and Tr-B (7) and the novel seco-A protolimonoid 8. Of these, nymania 1 and Tr-B showed selective inhibitory activity toward DNA repair-deficient yeast mutants. The isolation, structure elucidation, 13C NMR spectral assignments, and biological activities of these compounds are reported.
Carbohydrate Sequence↗
Isolation and structure elucidation of new PKCalpha inhibitors from Pinus flexilis.
Bioassay-guided fractionation of the CH2Cl2-MeOH extract of Pinus flexilis using an assay for protein kinase C (PKC) inhibitory activity led to the isolation of the two new bioactive diarylheptanoids (3R)-1,7-bis(3, 4-dihydroxyphenyl)-3-(beta-D-glucopyranosyl)heptan-3-ol (1) and its aglycon (3R)-1,7-bis(3,4-dihydroxyphenyl)heptan-3-ol (2), together with the three known bioactive compounds, hirsutenone (3), oregonin (4), and hirsutanonol (5). The IC50 values of compounds 1-5 in the PKC assay were 1.4, 1.6, 1.4, 8.6, and 4.6 microg/mL, respectively.
Circular Dichroism↗
Phenylethanoid glycosides from Digitalis purpurea and Penstemon linarioides with PKCalpha-inhibitory activity.
In a continuation of our search for potential tumor inhibitors from plants, it was found that the CH2Cl2-MeOH (1:1) extracts from Digitalis purpurea and Penstemon linarioides both showed PKCalpha-inhibitory bioactivity. Bioassay-directed fractionation of the extract from D. purpurea yielded the new, weakly active phenylethanoid glycoside 2-(3-hydroxy-4-methoxy-phenyl)-ethyl-O-(alpha-L-rhamnosyl)-(1-->3) -O- (alpha-L-rhamnosyl)-(1-->6)-4-O-E-feruloyl-beta-D-glucopy ran oside (1) together with the four known compounds calceolarioside A (2), calceolarioside B (3), forsythiaside (4), and plantainoside D (5). The extract from P. linarioides yielded the three known glycosides leucosceptoside A (6), acteoside (7), and poliumoside (8), together with the iridoid plantarenaloside (9). All of the isolated compounds, except compound 9, showed inhibitory activity against PKCalpha with IC50 values (in microM) of 125 (1), 0.6 (2), 4.6 (3), 1.9 (4), 14.8 (5), 19.0 (6), 9.3 (7), and 24.4 (8).
Caffeic Acids↗
Effects of camptothecin analogues on DNA transformations mediated by calf thymus and human DNA topoisomerases I.
Camptothecin (CPT) and 10 structural analogues were studied to characterize their effects on specific rearrangements of DNA structure mediated by human and calf thymus DNA topoisomerases I. A 30 base pair DNA duplex containing a single high-efficiency topoisomerase cleavage site was incubated with each of the enzymes in the presence of the inhibitors. Individual inhibitors stabilized the covalent enzyme-DNA binary complex to different extents, as anticipated. However, for several of the inhibitors, the extent of ternary complex formation differed substantially for the human and calf thymus enzymes. In common with calf thymus topoisomerase I, the human enzyme was shown to mediate the rearrangement of branched, nicked, and gapped DNA substrates that constitute models for illegitimate recombination. However, some of these rearrangements proceeded with different rates and efficiencies in the presence of human topoisomerase I. When inhibition of three of the rearrangements by CPT analogues was studied, most of the analogues exhibited differential effects on a given transformation, depending on the source of the enzyme employed.
Animals↗
Physical activity related energy expenditure in children by doubly labeled water as compared with the Caltrac accelerometer.
OBJECTIVE: The objective of this study was to determine whether the Caltrac accelerometer was a meaningful predictor of physical activity related energy expenditure (AEE) in free-living, pre-adolescent children. SUBJECTS: The sample consisted of 31 children (14 girls, 17 boys; 22 Caucasian, 9 Mohawk) with a mean age of 8.3 (+/- 2.0) y. MEASUREMENTS: AEE was measured by subtracting postprandial resting metabolic rate (RMR), measured via indirect calorimetry, from total daily energy expenditure (TDEE), derived from the doubly labeled water (DLW) method. Average daily activity counts (AC) were measured using a Caltrac accelerometer, which was worn for three days, two weekdays and one weekend day, within the DLW dosing period. RESULTS: AEE was related to gender (r = 0.42, P = 0.02), fat mass (FM, r = 0.32; P = 0.07), and fat free mass (FFM, r = 0.32; P = 0.07), but not to AC (r = -0.09; P = 0.63). After adjusting for gender, race, FM and FFM using multiple correlation regression analysis (R = 0.53), AC did not significantly increase the amount of variation explained in AEE. An estimate of the calories expended in physical activity was derived from AC using a formula developed by Sallis et al. This estimate was significantly higher than AEE (956 kcal/d vs 469 kcal/d, respectively, t = 5.9, P < 0.001). CONCLUSION: The Caltrac was not a meaningful predictor of AEE in our sample. The caloric estimates of energy expended in physical activity derived from the Caltrac AC, were significantly higher in comparison with measured AEE in these free-living children.
Asian People↗
Longitudinal changes in fatness in white children: no effect of childhood energy expenditure.
Reduced energy expenditure may predispose children to the development of obesity, but there are limited longitudinal studies to support this theory. We studied 75 white, preadolescent children over 4 y by taking annual measures of body composition and resting energy expenditure (by indirect calorimetry) and two annual measures of total energy expenditure and physical-activity-related energy expenditure (by doubly labeled water). Body composition of parents was assessed at the onset of the study with use of underwater weighing. The major outcome variable was the individual rate of change in fat mass (FM) adjusted for fat-free mass (FFM). The influence of sex, energy expenditure components, initial FM, and parental FM on the rate of change in FM was analyzed by hierarchical linear modeling and analysis of variance. The rate of change in absolute FM was 0.89 +/- 1.08 kg/y (range: -0.44 to 5.6 kg/y). The rate of change in FM adjusted for FFM was 0.08 +/- 0.64 kg/y (range: -1.45 to 2.22 kg/y) and was similar among children of two nonobese parents and children with one nonobese or one obese parent, but was significantly higher in children with two obese parents (0.61 +/- 0.87 kg/y). The major determinants of change in FM adjusted for FFM were sex (greater fat gain in girls), initial fatness, and parental fatness. None of the components of energy expenditure were inversely related to change in FM. The main predictors of change in FM relative to FFM during preadolescent growth are sex, initial fatness, and parental fatness, but not reduced energy expenditure.
Adipose Tissue↗
Breastfeeding practices of infants with Rubinstein-Taybi syndrome.
Rubinstein-Taybi Syndrome (RTS) is a rare disorder affecting 1 out of 300,000 people, characterized by broad thumbs and toes, distinctive facial features, hypotonia, and developmental delays. In this study, 180 members of an RTS parent group completed a survey that elucidated breastfeeding practices of infants with RTS. Fifty-nine percent of mothers initiated breastfeeding with an average duration of 7.1 months. Overall, 48% of the women reported that their child had a good to fair suck, and 50% were fairly to very pleased with the breastfeeding experience. Problems reported with breastfeeding included poor weight gain (46%), poor nipple grasp (35%), failure to thrive (34%), and infant fatigue (33%). In other populations of infants with special needs, many breastfeeding problems have been alleviated with instruction, proper positioning, close nutritional follow up, and strong encouragement by the health care team. With adequate support, mothers and their children with RTS can successfully carry out breastfeeding.
Adult↗