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Biomedical subjects

M S Johnson

Publications and source records attributed to M S Johnson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Longitudinal changes in body fat in African American and Caucasian children: influence of fasting insulin and insulin sensitivity.

Obesity is associated with hyperinsulinemia and reduced insulin sensitivity, both risk factors for type 2 diabetes. However, it is not clear whether these risk factors occur as a result of obesity or whether they contribute to the development of obesity. The aims of this study were to determine whether baseline (first visit) or changes in insulin measures over time were associated with longitudinal changes in body fat mass during growth in children. The study group consisted of 137 children (83 Caucasian and 54 African American) with a mean age of 8.1 yr at baseline. The children returned for 3-6 annual visits for measurement of fasting insulin, insulin sensitivity (Si), and acute insulin response (AIR) from the tolbutamide-modified frequent sampling iv glucose tolerance test and for determination of body composition by dual energy x-ray absorptiometry. Data were analyzed using SAS Proc mixed growth models. Total fat mass increased with time by 15.6%/yr (P = 0.013), but the rate of increase was not significantly influenced by race, sex, or Tanner stage. However, fasting insulin (positive effect), Si (negative effect), and AIR (positive effect) were significantly associated with the rate of increase in fat mass. In conclusion, in this cohort of children, growth-related increases in body fat were significantly associated with increases in fasting insulin and AIR and decreases in Si.

Adipose Tissue↗
PubMed2001

Limits to sustained energy intake. I. Lactation in the laboratory mouse Mus musculus.

Laboratory mice (strain MF1) were used to determine whether sustainable rates of energy intake are limited during lactation. Mice raising natural-sized litters (N=71) reached an asymptote in their daily food intake between days 13 and 16 of lactation at 23.1 g x day(-1) and also between litter sizes of 9 and 15 pups (22.8 g x day(-1)). A second group of 37 females had their litter sizes manipulated at birth to raise more or fewer offspring than they gave birth to. When the litter size was increased, females did not increase their food intake to match their new litter size. However, when litter size was decreased, females decreased their asymptotic daily food intake during late lactation in relation to the extent of reduction in litter size. Therefore, it appeared that females were limited during late lactation and with large litter sizes. The milk energy exported amounted to 44% of the gross energy intake, and the estimated daily energy expenditure was therefore considerably lower than the sustained energy intake [8.0xRMR(gross), 6.6xRMR(assimilated)], and averaged 3.1xRMR, where RMR is resting metabolic rate. It was not possible to determine whether the apparent limit on sustained energy intake was acting centrally or peripherally because of the asymptotes in both food intake and milk energy output with increasing litter size.

Animals↗
PubMed2001

Limits to sustained energy intake. II. Inter-relationships between resting metabolic rate, life-history traits and morphology in Mus musculus.

Links between resting metabolic rate (RMR) and reproductive output have been previously sought at both inter- and intraspecific levels, but have only been found in some interspecific studies. We aimed to examine correlations between RMR measured both prior to breeding and at peak lactation with litter size and litter mass in Mus musculus. By manipulating the litter size of some females at birth, we aimed to establish the direction of causality in any correlation between litter size and RMR. Correlations between maternal morphology and RMR, litter size and litter mass were also examined. Neither pre-breeding RMR nor mass-independent pre-breeding RMR was correlated with litter size or litter mass. RMR at peak lactation, however, was positively correlated with litter size and negatively correlated with mean pup mass. After correcting for the effects of body mass, residual peak lactation RMR was not correlated with litter size or litter mass. Body size was the major morphological variable influencing litter mass, offspring mass and asymptotic food intake. Mammary tissue mass was correlated with litter size when only the data for mice raising unmanipulated litters were used. RMR at peak lactation was significantly related to the principal component of morphology dominated by carcass mass. This study confirms the findings of previous intraspecific and some interspecific studies that found no correlation between RMR and reproductive output after the effects of body mass had been removed.

Animals↗
PubMed2001

Limits to sustained energy intake. III. Effects of concurrent pregnancy and lactation in Mus musculus.

To determine whether mice were limited in their capacity to absorb energy during late lactation, we attempted to increase the energy burden experienced by a group of female mice during late lactation by mating them at the postpartum oestrus, hence combining the energy demands of pregnancy and lactation. These experimental mice were therefore concurrently pregnant and lactating in their first lactation, and were followed through a normal second lactation. In a control group, females also underwent two lactations but sequentially, with the second mating after the first litter had been weaned. Maternal mass and food intake were measured throughout the first lactation, second pregnancy and second lactation. Maternal resting metabolic rate (RMR) was measured prior to the first mating and then at the peak of both the first and second lactations. Litter size and litter mass were also measured throughout both lactations. In the first lactation, experimental mice had a lower mass-independent RMR (F1,88=5.15, P=0.026) and raised significantly heavier pups (t=2.77, d.f.=32, P=0.0093) than the control mice. Experimental mice delayed implantation at the start of the second pregnancy. The extent of the delay was positively related to litter size during the first lactation (F1,19=4.58, P=0.046) and negatively related to mean pup mass (F1,19=5.78, P=0.027) in the first lactation. In the second lactation, the experimental mice gave birth to more (t=2.75, d.f.=38, P=0.0092) and lighter (t=-5.01, d.f.=38, P<0.0001) pups than did the controls in their second lactation. Maternal asymptotic daily food intake of control mice in the second lactation was significantly higher (t=-4.39, d.f.=37, P=0.0001) than that of the experimental mice and higher than that of controls during their first lactation. Despite the added burden on the experimental females during their first lactation, there was no increase in their food intake, which suggested that they might be limited by their capacity to absorb energy. However, control females appeared to be capable of increasing their asymptotic food intake beyond the supposed limits estimated previously, suggesting that the previously established limit was not a fixed central limitation on food intake. As RMR increased in parallel with the increase in food intake during the second lactation of control mice, the sustained energy intake remained at around 7.0xRMR.

Animals↗
PubMed2001

Limits to sustained energy intake. IV. Effect of variation in food quality on lactating mice Mus musculus.

Observations were made on 30 MF1 mice with their litters. The animals were fed either normal pelleted mouse food (SDS BP Nutrition Ltd) containing 13.4 kJ x g(-1) digestible energy or a specially formulated diet that provided 25% less digestible energy (9.75 kJ x g(-1)) but equivalent amounts of protein and essential minerals and vitamins per gram as the normal diet. Half the animals were switched to the low-energy diet during early pregnancy and half after parturition. The food intake of the two groups increased enormously following parturition, reaching an asymptote over the last few days of lactation. In both groups, the asymptotic food intake exceeded that previously observed across 71 litters of this strain of mice fed the normal diet throughout pregnancy and lactation; the intake of the group fed the low-energy diet from early lactation significantly exceeded that of the mice switched to the low-energy diet after parturition. The increased intakes of the experimental groups were, however, insufficient to offset the lower digestible energy content of the food during lactation. The body mass of the mothers at the end of lactation did not differ between the two experimental groups and the controls. Offspring mass at weaning was inversely related to litter size, but also did not differ between the three groups; pup mortality did not differ between the experimental and control groups. Behavioural observations showed that during both the dark and light phases the general activity of the mother declined enormously from early pregnancy to late lactation. In the dark phase, the time spent in general activity was replaced by time spent both feeding and resting (suckling young), but in the light phase it was replaced only by feeding. At peak lactation, the mice fed for 30-50% of the dark phase and for 30-40% of the light phase. The data indicate that a previously observed asymptote in food intake during peak lactation at 23 g x day(-1) is unlikely to be a limit mediated centrally by the alimentary tract. A higher central limit may exist, at 26.9 g x day(-1), but this is unlikely to reflect the time available for feeding. The data are consistent with limits on sustainable daily energy intake being mediated by the performance of the mammary glands. Animals appeared to accommodate the demands for milk production within a constrained total energy budget by compensating their behaviour, most notably by reductions in the time spent in 'general activity'.

Animals↗
PubMed2001

Limits to sustained energy intake. V. Effect of cold-exposure during lactation in Mus musculus.

We have previously observed that female MF1 mice appeared to reach a limit in their food intake and milk production during late lactation, reaching a plateau between days 13 and 16 of lactation and between litter sizes of 9 and 15. These mice did not increase their food intake when forced to raise more offspring or when manipulated to be concurrently pregnant during late lactation, yet they did eat significantly more food at the peak of their second sequential lactation or when challenged with food of reduced energy content. These data suggest that apparent limits on sustained energy intake in this strain may not reflect central limitations but rather peripheral constraints at the mammary glands. In this study, we aimed to determine whether these were indeed limits by increasing the demands on the females during late lactation by cold-exposure (8 degrees C). Females responded to this manipulation by significantly increasing their food intake (F1,73=77.53, P<0.001) above that of lactating females kept in warmer conditions (21 degrees C). In addition, there was a significant reduction in the number of pups raised in the cold (t=2.36, d.f.=18, P=0.03), with the majority of the mortality occurring within the first 2 days of cold-exposure. The mean mass of the pups raised in the cold was significantly lower (F1,74=13.8, P<0.001) than that of those raised in the warm. Despite the cold-exposure and the increased food intake, there was no difference in the resting metabolic rates of the two groups of mothers or in the lengths of their small intestine. The greater food intake of lactating mice during cold-exposure supported our previous observations that they were capable of eating more food than the previously suggested limit of 23.1 g x day(-1). However, the milk energy output of females in the cold was also significantly higher than in the warm (F1,15=11.99, P=0.003), indicating that the asymptotic food intake of females in the warm was not mediated by limitations in their milk production. Sustained energy intake in these mice does not appear to be centrally or peripherally limited. Rather, the mice may restrain their use of energy during their first lactation because of life-history consequences for future reproductive attempts.

Acclimatization↗
PubMed2001

Barriers to follow-up of hypertensive patients.

Lack of follow-up care for hypertension adversely affects health in urban communities. The authors designed this study to (1) evaluate the effectiveness of a specialized intervention program for hypertension follow-up and (2) evaluate the associations with loss to follow-up. They evaluated factors related to loss to follow-up to either a routine care medical clinic or a special primary care intervention program (the Competitive Initiative Program [CIP]). They also conducted interviews to provide in-depth information on the barriers to this program. They found that patients referred through the CIP were significantly more likely to receive follow-up care through a primary care provider. Cost of care, long waiting times, lack of physician continuity, and more pressing priorities explained the lack of follow-up care. Despite a program to provide health care at no cost to patients, lack of insurance and worries about cost are described as barriers to adequate follow-up for hypertension treatment.

Continuity of Patient Care↗
PubMed2001

Effects of low birth weight on insulin resistance syndrome in caucasian and African-American children.

OBJECTIVE: To examine the effects of low birth weight (LBW) on the components of insulin resistance syndrome (IRS) in Caucasian and African-American children aged 4-14 years (n = 560 observations among 139 subjects). RESEARCH DESIGN AND METHODS: A linear random-effects modeling analysis with repeated measures (average four annual visits per child) was conducted to examine the associations between LBW and the components of IRS and their developmental trends over age. Fasting glucose, insulin, and lipids were assessed after an overnight fast; insulin action and secretion were determined by the tolbutamide-modified frequently sampled intravenous glucose tolerance test; and body composition was assessed by dual energy X-ray absorptiometry and computed tomography. RESULTS: LBW was significantly associated with increased fasting insulin concentration and visceral fat mass, decreased acute insulin response, beta-cell function, and HDL cholesterol among African-American children. Among children with LBW, there were significant differences in fasting insulin, insulin sensitivity, acute insulin response, and HDL cholesterol between Caucasians and African-Americans. LBW was significantly associated with faster decrease in acute insulin response and increase in triglycerides with regard to age. The hyperbolic function between insulin sensitivity and beta-cell function was retarded among children with LBW (P = 0.04). In addition, there was a significant interaction between LBW and ethnicity in relation to fasting insulin (P < 0.05) and visceral fat (P = 0.05). CONCLUSIONS: LBW may predict the risk of the IRS and its progression over age in childhood, and this effect may be more pronounced among African-American children.

Adipose Tissue↗
PubMed2000

When fold is not important: a common structural framework for adenine and AMP binding in 12 unrelated protein families.

ATP is a ligand common to many proteins, yet it is unclear whether common recognition patterns do exist among the many different folds that bind ATP. Previously, it was shown that cAMP-dependent protein kinase, D-Ala:D-Ala ligase and the alpha-subunit of the alpha 2 beta 2 ribonucleotide reductase do share extensive common structural elements for ATP recognition although their folds are different. Here, we have made a survey of structures that bind ATP and compared them with the key features seen in these three proteins. Our survey shows that 12 different fold types share a specific recognition pattern for the adenine moiety, and 8 of these folds have a common structural framework for recognition of the AMP moiety of the ligand. The common framework consists of a tripeptide segment plus three additional residues, which provides similar polar and hydrophobic interactions between the protein and mononucleotide. Consensus interactions are represented by four key hydrogen bonds present in each fold type. Two of these four hydrogen bonds, together with three aliphatic residues, form a specific recognition pattern for the adenine moiety in all 12 folds. These similarities point to a structural-functional requirement shared by these different mononucleotide-binding proteins that represent at this time 28% of the adenine mononucleotide complexes found in the Brookhaven Protein Data Bank.

Adenine↗
PubMed2000

Fate and the biochemical effects of 2,4,6-trinitrotoluene exposure to tiger salamanders (Ambystoma tigrinum).

Biotransformation, metabolic enzyme profiles, and the glutathione antioxidant system in tiger salamanders (Ambystoma tigrinum) from a 14-day exposure to 2,4,6-trinitrotoluene (TNT) in situ were examined. Concentrations of parent compound and metabolites were measured in skin, kidney, and liver tissue. In addition, cytochrome P450 (P450) and cytochrome b5 content and their dependent isozyme activities, ethoxyresorufin O-dealkylation, pentoxyresorufin O-dealkylation, and the glutathione antioxidant system in the skin, liver, lung, kidneys, and blood were evaluated. Considerable differences were found in relative concentrations of TNT and its metabolites in the skin, relative to the liver and kidney. Trace amounts of TNT were detected only in the skin and liver of exposed animals while one of the secondary reduction metabolites, 2,6-diaminonitrotoluene, was found only in liver and kidney. Differences in the metabolite concentrations between systemic organs (liver, kidneys) and the skin suggest that the skin may be important in the primary reduction of TNT. In addition, measurable levels of these basal enzyme indicators were detected; yet of those evaluated only hepatic P450 content was affected by TNT exposure. The qualitative and quantitative differences in TNT and its metabolites in tissues suggest the fate and metabolism of the TNT in salamanders. Furthermore, results indicate that tiger salamanders possess considerable levels of xenobiotic metabolizing and antioxidant enzymes in these tissues but are not sensitive indicators of TNT exposure.

Ambystoma↗
PubMed2000

Local delivery of nadroparin via hydrogel-coated angioplasty balloon: effect on platelet deposition and smooth muscle cell proliferation--an experimental study.

PURPOSE: To assess the feasibility of intravascular delivery of nadroparin, a low-molecular-weight heparin, via hydrogel-coated angioplasty balloons, and the effects of nadroparin delivered in this manner on platelet deposition and smooth muscle cell (SMC) proliferation. MATERIALS AND METHODS: Tritiated nadroparin was used to determine the nadroparin-carrying capacity of the hydrogel-coating, kinetics of release from the balloons, and, in four pigs, delivery of the nadroparin to the iliac arterial wall. Platelet deposition in nadroparin-treated iliac arteries versus contralateral iliac arteries dilated with saline-loaded, hydrogel-coated balloons was quantified in seven pigs using 111Indium-labeled platelets. Smooth muscle cell proliferation in nadroparin and saline-treated iliac arteries in 10 pigs was evaluated 7 days after angioplasty with use of proliferating cell nuclear antigen. RESULTS: Approximately 98 international units of nadroparin were delivered by the hydrogel-coated balloon, the majority to the angioplasty site and distal vessel. There was a trend toward decreased platelet deposition in nadroparin-treated arteries, but statistical significance was not achieved (P = .1563). Medial SMC proliferation was decreased in the nadroparin-treated arteries in nine of 10 pigs (P = .0137). CONCLUSIONS: Hydrogel-coated balloons may be used to deliver nadroparin to the arterial wall, with measurable levels of the drug delivered to the site of angioplasty, and with resultant decrease in SMC proliferation.

Angioplasty, Balloon↗
PubMed2000

Kinetics of release of heparin from alginate hydrogel.

PURPOSE: Injected sodium alginate may be a useful perivascular drug delivery vehicle. This study was performed to determine the release rates of heparin from sodium alginate hydrogels cross-linked with varying amounts of calcium gluconate. MATERIALS AND METHODS: Six hydrogels, composed of 0.16 mEq sodium alginate and 4,000 units unfractionated heparin, were cross-linked with calcium gluconate to yield ion equivalence (IE) ratios (calcium:alginate) of 0.2, 0.4, 0.58, 0.8, 1.0, or 1.2. Two milliliters of normal saline was placed on top of each gel and allowed to remain in contact for up to 10 days. At set time intervals, the amount of heparin in the eluent was determined with use of high-performance liquid chromatography. RESULTS: Gels with 0.2 and 0.4 IE were partially liquid at 24 hours; the other gels solidified within 10 minutes. The 0.58 IE gel was slowest to solidify but immobilized the most heparin and released heparin slowest over 10 days. At 10 days, between 5.5% and 9.8% of the heparin immobilized was retained in the gel. CONCLUSION: This hydrogel shows promise as a vehicle for in vivo perivascular heparin delivery. The 0.58:1 IE ratio hydrogel has slowest release rate and the greatest immobilization despite its longer cross-linking time.

Alginates↗
PubMed2000

Accuracy of CO2 angiography in vessel diameter assessment: a comparative study of CO2 versus iodinated contrast material in an aortoiliac flow model.

PURPOSE: Precise vessel sizing prior to endovascular intervention is critical to achievement of technical success. Diameter measurements obtained with CO2 and iodinated contrast material in an aortoiliac flow model were compared. MATERIALS AND METHODS: Aortoiliac flow was simulated in a compliant, silicone elastomer phantom of the aortoiliac system using an autoperfusion pump (flow volume, approximately 1100 mL/min; mean arterial pressure, 70-80 mm Hg at 80-90 cycles/minute) and a glycerol solution (40% by weight; viscosity 3.7 centipoise at 20 degrees C). Digital subtraction angiography was performed with the phantom in the anteroposterior (AP) plane and in three oblique planes with both CO2 and iodinated contrast material. Five sets of images for both CO2 and iodinated contrast material were obtained for each projection. Two readers independently performed vessel diameter measurements at seven sites (distal abdominal aorta, bilateral proximal and distal common iliac, and mid-external iliac arteries). The model was then evaluated with intravascular ultrasound (IVUS) using a 20-MHz imaging catheter. Actual diameter measurements were taken from the inner wall to inner wall in orthogonal planes at the same locations within the model, as described previously. Analysis was performed to determine local difference in measurements (t tests), difference when compared to the standard AP projection with iodinated contrast material (Dunnett's test) and inter-reader variability (Pitman's test). RESULTS: The contralateral iliac vessel segment did not opacify when imaging with CO2 in the 45 degrees obliquities; thus, 22 of 28 sites were available for comparison. At 18 of 22 (81.8%) sites, there was significant difference in vessel measurements (P < .01), with CO2 yielding a significantly larger diameter at 17 of 22 (77.3%) of the sites. The difference in mean diameter ranged from -1.28 to 4.47 mm. With use of the AP iodinated contrast material run as the standard, there were significant differences (P < .05) in vessel diameter at 17 of 22 (77.3%) and four of 21 (19%) sites for CO2 and iodinated contrast material respectively, with CO2 tending toward greater diameter measurements. Significant differences (P < .05) in variance between the two readers were present but occurred primarily with CO2 in the AP projection and iodinated contrast material in the 45 degrees left obliquity. With use of IVUS as the standard, there were significant differences (P < .05) in the measured vessel diameters with CO2 at nine of 22 (40.9%) of the sites and with iodinated contrast material at 17 of 28 (60.7%) of the sites. Of the measurements made with CO2, seven of nine (77.8%) of the measurements were of larger diameter than those obtained with IVUS. By contrast, of the measurements made with iodinated contrast material angiography, IVUS measured larger diameters in 16 of 17 (94.1%). CONCLUSION: CO2 angiography consistently yielded significantly larger vessel measurements when compared to both iodinated contrast angiography and WVUS. These results have important implications in regards to planning intervention based solely on CO2 angiography. Further evaluation is needed before recommending CO2 for vessel sizing in clinical practice.

Angiography, Digital Subtraction↗
PubMed2000

PAS domain residues involved in signal transduction by the Aer redox sensor of Escherichia coli.

PAS domains sense oxygen, redox potential and light, and are implicated in behaviour, circadian rhythmicity, development and metabolic regulation. Although PAS domains are widespread in archaea, bacteria and eukaryota, the mechanism of signal transduction has been elucidated only for the bacterial photo sensor PYP and oxygen sensor FixL. We investigated the signalling mechanism in the PAS domain of Aer, the redox potential sensor and aerotaxis transducer in Escherichia coli. Forty-two residues in Aer were substituted using cysteine-replacement mutagenesis. Eight mutations resulted in a null phenotype for aerotaxis, the behavioural response to oxygen. Four of them also led to the loss of the non-covalently bound FAD cofactor. Three mutant Aer proteins, N34C, F66C and N85C, transmitted a constant signal-on bias. One mutation, Y111C, inverted signalling by the transducer so that positive stimuli produced negative signals and vice versa. Residues critical for signalling were mapped onto a three-dimensional model of the Aer PAS domain, and an FAD-binding site and 'active site' for signal transduction are proposed.

Amino Acid Sequence↗
PubMed2000

Environmental effects of radionuclides--observations on natural ecosystems.

To better quantify risk to non-human species from exposure to environmental radioactivity, understanding of the behaviour of radionuclides in the biosphere needs to be increased. This study outlines current thinking on ecological risk assessment (ERA) methodology and applies the indicator species or critical groups approach to biota inhabiting a semi-natural coniferous woodland contaminated with the radionuclides 137Cs, 238Pu, 239+240Pu and 241Am. The majority of these radionuclides originate from routine aerial emissions from the nuclear fuel reprocessing plant at BNFL, Sellafield, Cumbria, UK. Radionuclide activity concentrations have been determined in biota from the woodland and estimates of absorbed dose rates (mGy d(-1)) have been calculated using the dosimetric models outlined. Dose rates to the key indicator species, Oniscus asellus, Carabus violaceous and Apodemus sylvaticus (detritivorous invertebrate, predatory invertebrate and the granivorous wood mouse) have been determined at 3.0 x 10(-3) mGy d(-1), 2.2 x 10(-3) mGy d(-1) and 1.0 x 10(-3) mGy d(-1) respectively. The values are at least three orders of magnitude lower than the 1 mGy d(-1) level below which no observable effects on populations in a terrestrial ecosystem are thought to occur. Limitations of this approach are discussed.

Animals↗
PubMed2000

Differential activation of phospholipase D by VPAC and PAC1 receptors.

To investigate the phospholipase D (PLD) responses of the VIP/PACAP receptors, VPAC1 and VPAC2, and the PACAP-specific PAC1 receptors (short and "hop" intracellular loop 3 (i3) splice variants), stable CHO cell lines expressing similar levels of each wildtype receptor were generated (except for the VPAC1 receptor clone which showed considerably lower expression and lesser responses in signalling assays). All clones caused activation of PLD in response to agonists, as monitored by [3H]phosphatidylbutanol production. The PLD responses of the PAC1 "hop", but not the "null" receptor, were sensitive to the ARF inhibitor, brefeldin A (BFA) (as were VPAC1 and VPAC2 responses). Chimeric constructs of VPAC2 receptors containing i3 of either PAC1 hop or PAC1 null receptors were transiently expressed in COS 7 cells and PLD responses were measured. Only the PLD response of the hop construct was sensitive to BFA. This suggests that i3 motifs in certain Group II GPCRs may play a key role in determining their linkage to ARF-dependent PLD activation.

Amino Acid Sequence↗