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R K Johnson

Publications and source records attributed to R K Johnson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Exposure of mice to topical bovine thrombin induces systemic autoimmunity.

Bovine thrombin is used as an aid to hemostasis in medical and surgical procedures. At least 500,000 Americans are exposed to this therapeutic annually and reports suggest that exposure is associated with the development of autoreactive antibodies. To determine whether bovine thrombin can induce pathological autoimmunity we exposed nonautoimmune-prone galactose-alpha1-3-galactose-deficient mice to the two bovine thrombin preparations currently approved for use in the United States. We found that, like humans exposed to bovine thrombin, mice developed an immune response against the therapeutic and the xenogeneic carbohydrate galactose-alpha1-3-galactose, and some mice developed autoantibodies against clotting factors. Further, unexpectedly, a single exposure to this therapeutic also induced autoimmunity with features characteristic of systemic lupus erythematosus including antibodies against nuclear antigens, native DNA, double-stranded DNA, and cardiolipin. High levels of these autoantibodies correlated with glomerulonephritis in all mice evaluated. This autoimmune syndrome was detected in mice 15 weeks after a secondary exposure to bovine thrombin and female mice were found to develop the syndrome at a significantly greater frequency than males. Thus, these studies indicate that exposure to bovine thrombin preparations can induce a pathological systemic autoimmune syndrome with lupus-like serology.

Administration, Topical↗
PubMed2001

Choose beverages and foods to moderate your intake of sugars: the 2000 dietary guidelines for Americans--what's all the fuss about?

As part of the 2000 Dietary Guidelines for Americans, the public is advised to choose beverages and foods to moderate their intake of sugars. The term sugars is conventionally used to describe the mono- and disaccharides. However, the Dietary Guidelines for Americans distinguish between added sugars and other sources of carbohydrates. The concept of added sugars provides consumers with useful information, especially if they are trying to limit excessive use of caloric sweeteners. Added sugars are defined as sugars that are eaten separately at the table or used as ingredients in processed or prepared foods. Consumption of added sugars has increased steadily as documented by both food supply data and nationwide food consumption survey data. The largest source of added sugars in the U.S. diet is nondiet soft drinks, accounting for one third of total intake. Diets high in sugars have been associated with various health problems, including dental caries, dyslipidemias, obesity, bone loss and fractures, and poor diet quality. Research gaps are identified.

Adult↗
PubMed2001

Factors affecting population fluctuations of the glacial relict amphipod Monoporeia affinis (Lindström) in Sweden's largest lakes.

Factors affecting long-term (1982-2000) population densities of the glacial relict amphipod Monoporeia affinis were studied in Sweden's three largest lakes. Monoporeia showed large population fluctuations in all three lakes, with conspicuous peaks in density occurring in Lakes Vänern and Mälaren. In Lake Vänern, amphipod densities showed highly significant relationships with spring maximum diatom biovolume at a 1-yr lag. The lack of relationship between diatom biovolumes and Monoporeia densities in L. Vättern is likely due to the larger depth and the lower nutrient content of this lake. In eutrophic L. Mälaren, summer hypoxia (< 4 mg O2 L-1) is likely an important regulating factor. Hypolimnetic temperature showed a clear periodicity with relatively warm deep water occurring between 1989 and 1994. Hypolimnetic temperatures in Vänern and Vättern were correlated with total solar irradiance. However, neither hypolimnetic water temperature nor diatom biovolumes correlated with the North Atlantic Oscillation winter index. We speculate that variations in temperature and near-bottom oxygen concentrations negatively affect population densities by acting on recruitment success (reproduction) and juvenile (young-of-the-year) survival.

Animals↗
PubMed2001

Candidate gene analysis for loci affecting litter size and ovulation rate in swine.

A candidate gene approach was used to determine whether specific loci explain responses in ovulation rate (OR) and number of fully formed (FF), live (NBA), stillborn, and mummified pigs at birth observed in two lines selected for ovulation rate and litter size compared with a randomly selected control line. Line IOL was selected for an index of OR and embryonic survival for eight generations, followed by eight generations of two-stage selection for OR and litter size. Line C was selected at random for 16 generations. Line COL, derived from line C at Generation 8, underwent eight generations of two-stage selection. Lines IOL and C differed in mean EBV by 6.1 ova and 4.7 FF, whereas lines COL and C differed by 2.2 ova and 2.9 FF. Pigs of Generation 7 of two-stage selection lines were genotyped for the retinol binding protein 4 (RBP4, n = 190) and epidermal growth factor (EGF, n = 189) loci, whereas pigs of Generations 7 and 8 were genotyped for the estrogen receptor (ESR, n = 523), prolactin receptor (PRLR, n = 524), follicle-stimulating hormone beta (FSHbeta, n = 520), and prostaglandin-endoperoxide synthase 2 (PTGS2, n = 523) loci. Based on chi-square analysis for homogeneity of genotypic frequencies, distributions for PRLR, FSHbeta, and PTGS2 were different among lines (P < 0.005). Differences in gene frequencies between IOL vs C and COL vs C were 0.33 +/- 0.25 and 0.16 +/- 0.26 for PRLR, 0.35 +/- 0.20 and 0.15 +/- 0.24 for FSHbeta, and 0.16 +/- 0.16 and 0.08 +/- 0.18 for PTGS2. Although these differences are consistent with a model of selection acting on these loci, estimates of additive and dominance effects at these loci did not differ from zero (P > 0.05), and several of them had signs inconsistent with the changes in allele frequencies. We were not able to find significant associations between the polymorphic markers and phenotypes studied; however, we cannot rule out that other genetic variation within these candidate genes has an effect on the traits studied.

Animals↗
PubMed2001

Identification of quantitative trait loci affecting reproduction in pigs.

The objective of this research was to identify chromosomal regions harboring QTL affecting reproduction in pigs. A three-generation resource population was developed by crossing low-indexing pigs from a randomly selected control line (C) with high-indexing pigs of a line selected for increased index of ovulation rate and embryonic survival (I). Differences between Lines I and C at Generation 10 were 6.7 ova and 3.3 fetuses at 50 d of gestation and 3.1 fully formed and 1.6 live pigs at birth. Phenotypic data were collected on F2 females, born in three replicates, for ovulation rate (n = 423), age at puberty (n = 295), litter size (n = 370), and number of nipples (n = 428). Litter-size data included number of fully formed, live, stillborn, and mummified pigs. Grandparent, F1, and F2 animals were genotyped for 151 microsatellite markers distributed across all 18 autosomes and the X chromosome. Genotypic data were available on 423 F2 females. Average spacing between markers was 19.3 Kosambi centimorgans. Calculations of logarithms of odds (LOD) scores were by least squares, and fixed effects for sire-dam combination and replicate were included in the models. Genome-wide significance level thresholds of 5% and 10% were calculated using a permutation approach. There was evidence (P < 0.05) for QTL affecting ovulation rate on SSC9, age at puberty on SSC7 and SSC8, number of nipples on SSC8 and SSC11, number of stillborn pigs on SSC5 and SSC13, and number of fully formed pigs on SSC11. There was evidence (P < 0.10) for additional QTL affecting age at puberty on SSC7, SSC8, and SSC12, number born live on SSC11, and number of nipples on SSC1, SSC6, and SSC7. Litter size is lowly heritable and sex-limited. Therefore, accuracy of selection for litter size may be enhanced by marker-assisted selection. Ovulation rate and age at puberty are laborious to measure, and thus marker-assisted selection may provide a practical and efficient method of selection.

Animals↗
PubMed2001

Direct and correlated responses to two-stage selection for ovulation rate and number of fully formed pigs at birth in swine.

Our objectives were to estimate responses and genetic parameters for ovulation rate, number of fully formed pigs at birth, and other production traits following two-stage selection for increased ovulation rate and number of fully formed pigs. Eight generations of selection were practiced in each of two lines. One selection line was derived from a line that previously selected eight generations for an index to increase ovulation rate and embryonic survival (the IOL pigs). The other selection line was derived from the unselected control line of the index selection experiment (the COL pigs). The control line (C) was continued with random selection. Due to previous selection, Line IOL had greater ovulation rate (4.24 +/- 0.38 and 4.14 +/- 0.29 ova) and litter size (1.97 +/- 0.39 and 1.06 +/- 0.38 pigs) at Generation 0 of two-stage selection than did Lines COL and C. In Stage 1, all gilts from 50% of the largest litters were retained. Approximately 50% of them were selected for ovulation rate in Stage 2. Gilts selected for ovulation rate were mated to boars selected from the upper one-third of the litters for litter size. At Generations 7 and 8, differences in mean EBV for ovulation rate and litter size between Lines IOL and C were 6.20 +/- 0.29 ova and 4.66 +/- 0.38 pigs; differences between Lines COL and C were 2.26 +/- 0.29 ova and 2.79 +/- 0.39 pigs; and differences between Lines IOL and COL were 3.94 +/- 0.26 ova and 1.86 +/- 0.39 pigs. Regressions of line mean EBV on generation number were 0.27 +/- 0.07 ova and 0.35 +/- 0.06 pigs in Line IOL; 0.30 +/- 0.06 ova and 0.29 +/- 0.05 pigs in Line COL; and 0.01 +/- 0.07 ova and 0.02 +/- 0.05 pigs in Line C. Correlated responses were decreased age at puberty and increased number of pigs born alive, number of mummified pigs, prenatal loss, and individual and litter birth weight. Two-stage selection for ovulation rate and number of pigs per litter is a promising procedure to improve litter size in swine.

Animal Husbandry↗
PubMed2001

Has nonoperative management of solid visceral injuries adversely affected resident operative experience?

The purpose of this study was to assess the impact of increased use of nonoperative management of blunt injuries to the spleen or liver on surgical residents' operative experience with solid visceral injuries. We conducted a 10-year retrospective study of blunt spleen and liver injuries at a state-designated Level I trauma center and a survey of chief residents' operative experience with splenic and hepatic injuries from blunt trauma during the same time period. From 1990 through 1999, 431 patients were admitted with splenic injuries and 634 patients were admitted with liver injuries; 350 splenic injuries (81%) were due to blunt trauma; 317 liver injuries (50%) were caused by blunt mechanisms. In 1990 100 per cent of patients with splenic injuries and 93 per cent of those with liver injuries underwent surgery for those injuries. These rates were 19 and 28 per cent respectively in 1999. The number of patients with blunt solid visceral injuries increased more than fourfold from 1990 through 1999. The number of operations for splenic and hepatic injuries performed by chief residents did not decline significantly during this time period (5.5 cases per chief resident in 1990; 4.6 cases per chief resident in 1999). The increased numbers of patients with solid visceral injuries were due to two factors: increased proportion of blunt trauma admissions especially from motor vehicle collisions and improved recognition of spleen and liver injuries by expanded use of CT scans. We conclude that nonoperative management of blunt solid visceral injuries does not necessarily lead to a diminution of operations nor jeopardize resident education. However, trauma volumes must be high enough to support adequate operative experience.

Accidents, Traffic↗
PubMed2001

Applying functional genomics research to the study of pig reproduction.

Functional genomics is an experimental approach that incorporates genome-wide or system-wide experimentation, expanding the scope of biological investigation from studying single genes to studying potentially all genes at once in a systematic manner. This technology is highly appealing because of its high throughput and relatively low cost. Furthermore, analysis of gene expression using microarrays is likely to be more biologically relevant than the conventional paradigm of reductionism, because it has the potential to uncover new biological connections between genes and biochemical pathways. However, functional genomics is still in its infancy, especially with regard to the study of pig reproduction. Currently, efforts are centred on developing the necessary resources to enable high throughput evaluation and comparison of gene expression. However, it is clear that in the near future functional genomics will be applied on a large scale to study the biology and physiology of reproduction in pigs, and to understand better the complex nature of genetic control over polygenic characteristics, such as ovulation rate and litter size. We can look forward to generating a significant amount of new data on differences in gene expression between genotypes, treatments, or at various temporal and spatial coordinates within a variety of reproductively relevant systems. Along with this capability will be the challenge of collating, analysing and interpreting datasets that are orders of magnitude more extensive and complex than those currently used. Furthermore, integration of functional genomics with traditional genetic approaches and with detailed analysis of the proteome and relevant whole animal phenotypes will be required to make full use of this powerful new experimental paradigm as a beneficial research tool.

Animals↗
PubMed2000

In-person vs telephone-administered multiple-pass 24-hour recalls in women: validation with doubly labeled water.

OBJECTIVE: To determine the accuracy of energy intakes estimated with the multiple-pass 24-hour recall method in women by conducting in-person and telephone interviews. Doubly labeled water measurements of total energy expenditure were used for validation. SUBJECTS: Thirty-five weight-stable women (mean age = 30 years, range = 19 to 46 years) participated. DESIGN: Total energy expenditure was measured over a 14-day period using the doubly labeled water method. During this time, 4 multiple-pass 24-hour recalls were obtained from the women (2 in-person, 2 by telephone) who were provided 2-dimensional food models to estimate portion sizes. The Food Intake Analysis System was used to analyze recall data. STATISTICAL ANALYSES: Paired t tests were conducted to examine differences between energy intake estimated from the telephone and in-person interviews. Agreement between the energy intake estimates from the telephone recalls and the in-person recalls was assessed using the technique of Bland and Altman. Paired t tests were used to compare energy intake estimated from the telephone and in-person recalls to total energy expenditure. RESULTS: No significant difference in mean daily energy intake was found between the telephone (2,253 +/- 688 kcal) and in-person (2,173 +/- 656 kcal) interviews (P = .36). However, the mean energy intake from each interview method was significantly lower than total energy expenditure (2,644 +/- 503 kcal) (P = .006 and .001, respectively). APPLICATIONS/CONCLUSIONS: Underreporting of energy intake was widespread in the sample. Although the multiple-pass 24-hour recall method did not generate a group measure of energy intake that was accurate or unbiased, the telephone-administered multiple-pass 24-hour recall was just as effective in estimating energy intake as the recall administered in-person. Dietetics professionals should be aware of the pervasive and serious problem of under-reporting of self-reported food intakes.

Adult↗
PubMed2000

Changing eating and physical activity patterns of US children.

The number of US children who are overweight has more than doubled over the last decade. This change has broadened the focus of dietary guidance for children to address nutrient overconsumption and physical activity patterns. Total fat consumption expressed as a percentage of energy intake has decreased among US children. However, this decrease is largely the result of increased total energy intake in the form of carbohydrates and not necessarily due to decreased fat consumption. The majority of children aged 5-17 years are not meeting recommendations for Ca intakes. Much of this deficit is attributed to changing beverage consumption patterns, characterized by declining milk intakes and substantial increases in soft-drink consumption. On average, US children are not eating the recommended amounts of fruits and vegetables. US adolescents become less active as they get older, and one-quarter of all US children watch > or = 4 h television each day, which is positively associated with increased BMI and skinfold thickness. There is an urgent need in the USA for effective prevention strategies aimed at helping children grow up with healthful eating and physical activity habits to achieve optimal health.

Adolescent↗
PubMed2000

Use of COMPARE analysis to discover new natural product drugs: isolation of camptothecin and 9-methoxycamptothecin from a new source.

Analysis of cytotoxicity data of extracts from the National Cancer Institute's Active Repository by the COMPARE protocol was carried out using camptothecin as a reference point. Extracts identified by this process were further characterized by a selective yeast bioassay for inhibitors of topoisomerase I and by a biochemical assay for compounds that stabilize the topoisomerase I-DNA covalent binary complex. Five of the extracts were positive in the yeast bioassay, and eight extracts showed activity on the assay that monitors stabilization of the topoisomerase I-DNA complex. Four of the latter extracts were inactive in the yeast bioassay, and thus would not have been identified as hits without the COMPARE preselection process. One of the extracts, from Pyrenacantha klaineana, was selected for detailed investigation, and fractionation of this extract yielded camptothecin and 9-methoxycamptothecin as the bioactive constituents.

Algorithms↗
PubMed2000

Bioactive compounds from Combretum erythrophyllum.

A methanol extract of Combretum erythrophyllum showed inhibitory bioactivities in a yeast-based microtiter assay for DNA-damaging agents. Bioassay-guided fractionation of this extract yielded two known bioactive compounds, combretastatin A-1 and (-)-combretastatin, and two new bioactive glucosides, combretastatin A-1 2'-beta-D-glucoside (1) and combretastatin B-1 2'-beta-D-glucoside (2). The structures of the new compounds were assigned by (1)H and (13)C NMR, DEPT, HMQC, and HMBC spectra.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Isolation and biochemical characterization of a new topoisomerase I inhibitor from Ocotea leucoxylon.

In a continuation of our search for potential tumor inhibitors from plants, we found that a crude extract from Ocotea leucoxylon showed selective activity typical of inhibitors of the enzyme topoisomerase I in a yeast assay for DNA-damaging agents. Using a bioassay-directed fractionation approach, the major bioactive compound was isolated and identified as the known aporphine alkaloid dicentrinone (4); the inactive alkaloid dicentrine (3) was also isolated. Compound 4 showed selective bioactivity against the rad52 repair-deficient yeast strain RS322 (IC(12) 49 microg/mL) and was inactive against the rad52- and topo1-deficient strain RS321 (IC(12) > 2000 microg/mL) and against the repair-proficient strain RJ03 (IC(12) > 2000 microg/mL). Biochemical studies with recombinant human topoisomerase I indicated that dicentrinone (4) is an inhibitor of the human enzyme. Colony formation studies suggest that it is weakly cytotoxic, but that its mechanism of toxicity differs from that of camptothecin and its derivatives.

Aporphines↗
PubMed2000

Influence of body composition on the accuracy of reported energy intake in children.

OBJECTIVE: Mis-reporting dietary intake is a substantial barrier to understanding the role of dietary behavior in disease. Work with adults indicates that heavier individuals under-report dietary intake and that under-reporting may be macronutrient-specific. Whether weight status and macronutrient intake influence the accuracy of dietary reports among children, however, is less clear. This research evaluated children's dietary reporting accuracy as a function of their relative weight, body composition, and macronutrient intake. RESEARCH METHODS AND PROCEDURES: Participants included 146 4- to 11-year-old children. Reported energy intake was determined by interviewing children in the presence of parents, using three multiple pass, 24-hour recalls. Children were classified as having had an under-reported, accurately reported, or over-reported dietary intake relative to total energy expenditure, as measured by doubly labeled water. Reporting accuracy was examined as a function of children's body weight, body composition (using dual energy x-ray absorptiometry), and macronutrient intake. RESULTS: Average reported intake was, on average, 14% greater than children's estimated expenditure (p < 0.01). Reporting accuracy varied as a function of children's relative weight and body composition; under-reporting tended to occur among heavier children, having the highest body fat content (p < 0.0001) and relative weight (p < 0.0001). DISCUSSION: These findings suggest that weight status influences the accuracy of dietary reports made by children and their parents. More research is needed to address possible psychological and social factors that introduce bias in reporting children's dietary data.

Absorptiometry, Photon↗
PubMed2000

Comparison of plasma FSH concentration in boars and gilts from lines selected for ovulation rate and embryonal survival, and litter size and estimation of (co)variance components for FSH and ovulation rate.

The objective of this research was to determine whether plasma concentration of FSH was genetically correlated with ovulation rate and thus was a useful trait for indirect selection. Blood samples were collected from 619 animals from five lines of pigs. Line I was selected for increased index of ovulation rate and embryonal survival, and Line C was its randomly selected control. Pigs sampled from Lines I and C were from generations 12 and 13. Pigs from three additional lines that were derived from eighth-generation pigs of Lines I and C also were used. These lines were Line C2, a randomly selected control derived from Line C, Line COL, derived from Line C, and Line IOL, derived from Line I; each of these lines was selected an additional five generations for increased ovulation rate and increased litter size. A single blood sample was collected from each pig between 46 to 63 (d 58), 86 to 98 (d 90), 110 to 133 (d 124), and 147 to 153 (d 150) d of age. The heritability of ovulation rate was .28 and heritabilities of plasma concentration of FSH at d 58, 90, 124, and 150 were .41, .25, .12, and 0, respectively. Genetic correlations between ovulation rate and d-58, d-90, and d-124 plasma concentration of FSH were .31, .23, and 0, respectively. Line I gilts had greater estimated breeding values for plasma concentration of FSH at d 58 and 90 than Line C gilts (P < .01). Line COL gilts had greater estimated breeding values for plasma concentration of FSH at d 58 than Line C2 gilts (P < .01). Line I boars had greater estimated breeding values for plasma concentration of FSH at d 90 than Line C boars (P < .05). Even though genetic correlations were low, selection for increased plasma concentration of FSH was estimated to be 93% as effective in changing ovulation rate as direct selection because selection for FSH can be practiced in both sexes. Thus, selection for increased plasma concentration of FSH seems to be a practical method for increasing ovulation rate in pig breeding programs without using laparoscopy.

Animals↗
PubMed1999

Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway.

In response to DNA damage and replication blocks, cells activate pathways that arrest the cell cycle and induce the transcription of genes that facilitate repair. In mammals, ATM (ataxia telangiectasia mutated) kinase together with other checkpoint kinases are important components in this response. We have cloned the rat and human homologs of Saccharomyces cerevisiae Rad 53 and Schizosaccharomyces pombe Cds1, called checkpoint kinase 2 (chk2). Complementation studies suggest that Chk2 can partially replace the function of the defective checkpoint kinase in the Cds1 deficient yeast strain. Chk2 was phosphorylated and activated in response to DNA damage in an ATM dependent manner. Its activation in response to replication blocks by hydroxyurea (HU) treatment, however, was independent of ATM. Using mass spectrometry, we found that, similar to Chk1, Chk2 can phosphorylate serine 216 in Cdc25C, a site known to be involved in negative regulation of Cdc25C. These results suggest that Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway. Activation of Chk2 might not only delay mitotic entry, but also increase the capacity of cultured cells to survive after treatment with gamma-radiation or with the topoisomerase-I inhibitor topotecan.

Alkylating Agents↗