Search PubMedSearch

Biomedical subjects

D R Wagner

Publications and source records attributed to D R Wagner.

At least 19 recordsLinked to original sources

Porcine pancreatic phospholipase A2 stimulates secretin release from secretin-producing cells.

We have isolated, from canine pancreatic juice, two 14-kDa proteins with secretin-releasing activity that had N-terminal sequence homology with canine pancreatic phospholipase A2 (PLA2). In this study we have obtained evidence that secretin-releasing activity is an intrinsic property of pancreatic PLA2. Porcine pancreatic PLA2 from Sigma or Boehringer Mannheim was fractionated into several peaks by reverse phase high performance liquid chromatography. They were tested for stimulation of secretin release from murine neuroendocrine intestinal tumor cell line STC-1 and secretin cells enriched mucosal cell preparations isolated from rat upper small intestine. Each enzyme preparation was found to contain several components of secretin-releasing activity. Each bioactive fraction was purified to homogeneity by rechromatography and then subjected to mass spectral analysis and assays of PLA2 and secretin-releasing activities. It was found that the fraction with highest enzymatic activity also had the highest secretin-releasing activity and the same Mr as porcine pancreatic PLA2. Moreover, it also had the same N-terminal amino acid sequence (up to 30 residues determined) as that of porcine pancreatic PLA2, suggesting that it was identical to the enzyme. Purified porcine pancreatic PLA2 also stimulated secretin release concentration-dependently from both STC-1 cells and a mucosal cell preparation enriched in secretin-containing endocrine cells isolated from rat duodenum. Abolishment of the enzymatic activity by pretreatment with bromophenacyl bromide did not affect its secretin-releasing activity. The stimulatory effect of purified pancreatic PLA2 on secretin secretion from STC-1 cells was inhibited by an L-type Ca2+ channel blocker, by down-regulation of protein kinase C or by pretreatment of the cell with pertussis toxin. It is concluded that porcine pancreatic PLA2 possesses an intrinsic secretin-releasing activity that was independent of its enzymatic activity. This action is pertussis toxin-sensitive and is in part dependent on Ca2+ influx through the L-type channel and activation of protein kinase C.

Animals

Hyperhydrating with glycerol: implications for athletic performance.

Small decreases in hydration status can result in a dramatic decrement in athletic performance and greatly increase the risk of thermal injury. Because of its osmotic properties, which enable greater fluid retention than the ingestion of water alone, glycerol has been proposed as a hyperhydrating agent. In fact, glycerol is now commercially available and marketed as a sport supplement to be ingested with water or sport drinks; thus, dietitians need to be cognizant of this new addition to the sports nutrition table. The results of glycerol-induced hyperhydration research have been equivocal, most likely because of methodologic differences between studies, such as variations in the intensity of exercise, environmental conditions, and concentration or dose of glycerol administered. Although the suggested dosage of glycerol depends on body size and varies between manufacturers, 1 g/kg body weight with an additional 1.5 L fluid taken 60 to 120 minutes before competition is standard. Some test subjects reported feeling bloated or nauseated after ingesting glycerol. This review examines glycerol-induced hyperhydration research and the safety of ingesting glycerol, discusses commercial availability of glycerol, and makes recommendations for glycerol-induced hyperhydration research.

Dehydration

Techniques of body composition assessment: a review of laboratory and field methods.

Body composition is one of the major health-related components of fitness. Thus, it is important for health and fitness professionals to have a general understanding of the most commonly used techniques for assessing body composition. This review presents the developmental background and underlying principles and theory of four laboratory (hydrodensitometry, air displacement plethysmography, isotope dilution, and dual-energy x-ray absorptiometry) and four field (bioelectrical impedance analysis, near-infrared interactance, skinfolds, and anthropometry) methods of body composition assessment. In addition to a description of the methods, the validity, and reliability, strengths, and limitations of each measurement tool are examined. Highlights of the laboratory methods include the relatively new Bod Pod air displacement device, which is a promising assessment tool more convenient than hydrodensitometry but still lacking substantial validity testing and the ability of dual-energy x-ray absorptiometry to measure regional composition making it an attractive method for clinicians. Advancements in segmental and multifrequency bioelectrical impedance for compartmental analysis have enhanced the value of this field method, but research continues to show that commercially available near-infrared interactance units are invalid. With this knowledge, the clinician and researcher should be able to make an informed decision regarding the most appropriate measurement device for their body composition assessments.

Absorptiometry, Photon

Cross-validation of modified fatness-specific bioelectrical impedance equations.

The Segal fatness-specific bioelectrical impedance (BIA) equations are useful for predicting fat-free mass (FFM). Stolarczyk et al. Proposed a modified method of averaging the two equations for individuals who are neither lean nor obese, thus eliminating the need to know % BF a priori. To cross-validate this modification, we compared FFM determined using the averaging method versus hydrostatic weighing for 76 adults. Per the averaging method, accuracy for males was excellent (r =.91, SEE = 2.7 kg, E = 2.7 kg), with 78% of individuals within +/- .5% BF predicted by hydrostatic weighing. Accuracy for females was lower (r =.88, SEE = 3.0 kg, E = 3.1 kg), with % BF of 51% within +/- 3.5% of the reference method. The relative ease and practicality of the averaging method and the results of this study indicate this method may be useful with a diverse group.

Adipose Tissue

Differential regulation of cardiac expression of IL-6 and TNF-alpha by A2- and A3-adenosine receptors.

The proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 have been implicated in the development of congestive heart failure. Adenosine inhibits the expression of TNF-alpha and IL-6 in macrophages. We determined the effect of adenosine on cytokine expression in rat cardiomyocytes and trabecular muscles obtained from patients with cardiomyopathy. In myocytes, adenosine suppressed TNF-alpha mRNA by 40% (P < 0.05) and induced a 4.7-fold increase in IL-6 mRNA (P < 0.05) with a twofold increase in IL-6 protein release (P < 0.001). The effect on TNF-alpha could be replicated by A2 agonist. The effect on IL-6 could be replicated by A3 agonist, but not by A1 and A2 agonists, and was completely suppressed by A3 antagonist. In human trabecular muscles, A2 agonist suppressed TNF-alpha mRNA by 60% (P < 0.05), but adenosine had no effect on IL-6. In the failing heart, IL-6 was immunolocalized to inflammatory cells. Thus A2 and A3 receptors differentially regulate cardiac expression of TNF-alpha and IL-6. Rat cardiomyocytes and the failing human heart respond differently to adenosine.

Animals

Direct comparison of two widely used activity recorders.

Wrist actigraphy is increasingly used to track circadian rest-activity cycles and to identify states of wakefulness and sleep, yet the measurement characteristics of activity recorders have never been compared. Two widely used recorders are compared here: the MotionLogger from Ambulatory Monitoring, Inc (AM) and the Gaehwiler (G). They were worn together on the same wrist for periods averaging 41.5 hours by five members of a research team. Activity counts were stored every half-minute. Pairwise comparisons between recorders of each type showed both types to be reliable. Each also validly detected circadian rest/activity cycles. Both types suffered, however, from insensitivity. For the lower 75% of activity levels, the variance of data from the G was indeed so small as to be essentially uninformative. Since these levels include over 95% of all nocturnal data, the G must be less sensitive than the AM to small nocturnal movements, including those signifying arousal. An additional difference is that data from the AM but not the G were distributed in biphasic fashion. Biphasic activity levels are consistent with the common assumption that activity/wakefulness and rest/sleep are distinct neurobehavioral states. As the use of actigraphy increases, the important differences found here between two leading instruments point to an urgent need for standards by which activity recorders can be compared. Aspects of instrument design that could be quantitatively rated are reliability, validity, ruggedness and artifact rejection.

Circadian Rhythm

Adenosine inhibits lipopolysaccharide-induced secretion of tumor necrosis factor-alpha in the failing human heart.

BACKGROUND: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of congestive heart failure. Recent studies have shown that adenosine inhibits lipopolysaccharide (LPS)-induced expression of TNF-alpha in macrophages and rat cardiomyocytes. The aim of this study was to determine whether adenosine has a similar effect in the failing human heart. METHODS AND RESULTS: Left ventricular muscle strips were obtained from seven patients with end-stage congestive heart failure undergoing heart transplantation or insertion of a left ventricular assist device. The muscle strips were incubated at 37 degrees C in 95% O2/5% CO2 and stimulated with LPS (10 microg/mL). TNF-alpha release in the supernatant was measured with ELISA, and muscle sections were stained for TNF-alpha. Muscle strips released TNF-alpha in the absence of LPS (0.22+/-0.05 pg x mL(-1) x mg wet wt[-1]). TNF-alpha was immunolocalized to the cardiac myocyte, suggesting that the myocyte is a source for TNF-alpha production. Adenosine (10 micromol/L) decreased TNF-alpha by 40% (P<.05). The selective adenosine A2 receptor agonist DPMA (10 micromol/L) decreased TNF-alpha release by 87% (P<.001), whereas ITu (10 micromol/L), an adenosine-regulating agent that increases endogenous adenosine concentration, inhibited TNF-alpha release by 93% (P<.001). CONCLUSIONS: Adenosine can significantly diminish TNF levels in the failing human heart and may represent a new pharmacological intervention in congestive heart failure.

Adenosine

Predictive accuracy of BIA equations for estimating fat-free mass of black men.

This study assessed the predictive accuracy of previously published bioelectrical impedence analysis (BIA) equations in estimating the fat-free mass (FFM) of black men, 19 to 50 years. The reference method was hydrostatic weighing (HW) at residual lung volume. Body density (Db) was converted to relative body fat (%BF) for calculation of FFMHW using the Schutte et al. equation. Resistance and reactance were measured with a Valhalla bioimpedance analyzer. Age-specific, generalized, and fatness-specific BIA equations were cross validated using regression analysis. The Segal fatness-specific equations were modified using a method recommended by Stolarczyk. All of the equations significantly (P < 0.05) underestimated the average reference measure of FFMHW. However, the underestimation of FFM for the modified Segal fatness-specific equation was relatively small (-1.8 kg) and not likely to have much clinical significance. Furthermore, this equation had a high correlation with reference FFMHW (ry,y' = 0.97), low prediction errors (SEE = 2.1 kg; E = 2.7 kg), and accurately estimated the FFM within +/- 3.5 kg for 78% of the individuals in the sample. Thus, we recommend using the modified fatness-specific BIA equation for estimating the FFM of black men.

Adult

Exercise mode and gender comparisons of energy expenditure at self-selected intensities.

The purpose of this study was to compare oxygen consumption (VO2) and energy expenditure after 20 min of self-selected submaximal exercise for four modes of exercise. Eighteen subjects (9 male and 9 female) first completed a test of VO2max during treadmill running. On separate days, subjects then completed 20 min submaximal treadmill running (TR), simulated cross-country skiing (XC), cycle ergometry (CE), and aerobic riding (AR) exercise. Total VO2 and energy expenditure were significantly higher for TR than all other modes for both males and females (43.6 +/- 10.4, 39.1 +/- 9.7, 36.1 +/- 7.6, 28.4 +/- 6.1 LO2, for TR, XC, CE, and AR, respectively, P < 0.0001). For males and females, heart rate was similar during TR and XC and lower during CE and AR (154.8 +/- 14.2, 152 +/- 13.1, 143.4 +/- 14.9, and 126.2 +/- 12.0 beats.min-1 for TR, XC, CE, and AR, respectively, P < 0.0001). Compared with females, males had significantly greater VO2 (P < 0.005) and energy expenditure (P < 0.004), while females had higher heart rates (P < 0.003). Ratings of perceived exertion (RPE) were not different between TR, XC, and CE, but were significantly lower during AR (13.4 +/- 1.3, 13.6 +/- 0.8, 13.2 +/- 0.9, and 12.6 +/- 1.0 for TR, XC, CE, and AR, respectively, P < 0.003). TR elicited the greatest VO2 and energy expenditure during self-selected exercise despite and RPE similar to XC and CE. Therefore, treadmill exercise may be the modality of choice for individuals seeking to improve cardiorespiratory endurance and expend a larger number of kjoules.

Adult

Nocturnal interactions between community elders and caregivers, as measured by cross-correlation of their motor activity.

As the U.S. population ages, families must assume increasing responsibility for the care of elderly members. Disruptive nocturnal behaviors (DNBs) of elders, such as complaining and demanding help, may result in interactions with caregivers that threaten such arrangements. This study aimed to quantify such interactions by cross-correlating motor activity that was simultaneously recorded from the elders and caregivers. Forty-four elder-caregiver pairs reporting DNBs simultaneously kept sleep logs and wore activity recorders for 6 to 8 days. Day and night activity data were analyzed separately, because circadian variations would otherwise have overshadowed the elder-caregiver covariations of interest. An autoregressive model was fitted to each day and night data segment, and the data-model differences were used to calculate a cross-correlation function. Maximum significant values of the cross-correlation functions (rmax) exceeded .300 in 10 pairs of subjects. The unprocessed motor activity of these pairs looked so similar that rmax was interpreted as a measure of the subjects' interactions. The rmax was significantly larger for nighttime activity, especially in pairs who shared the same bed. It was smaller in pairs whose elders had high depression scores and in those with Parkinson's disease or related disorders. It was not affected by the presence of dementia. Analysis of the lags corresponding to significant values of rmax showed that, in cohabiting pairs, it was mainly the elders who initiated interactions. The findings provide unique, objective evidence that the night is a time of special difficulty for many caregivers of older Americans.

Aged

Oxygen consumption and energy expenditure of level versus downhill running.

OBJECTIVE: The purpose of this study was to assess and compare submaximal oxygen consumption (VO2) and energy expenditure (kJ) while running at 0, -1.8, -3.6, and -5.4% grades for three individually selected running speeds (9.4 + 0.79, 10.3 + 0.74, 11.3 + 0.73 km.h-1). EXPERIMENTAL DESIGN: Subjects completed the four grade conditions in random order via a modified Latin squares design at three self-selected submaximal running speeds for each condition. PARTICIPANTS: Thirteen (5 females and 8 males) recreational (< 35 km.wk-1) runners (age: 27.7 +/- 4.3 yrs) volunteered for the study. MEASURES: Two-way repeated measures ANOVA (Grade x Speed) was used to analyze steady-state VO2 and kJ expenditure. Stepwise linear multiple regression was used to develop an equation for predicting VO2 for running at recreational speeds on moderately negative grades. RESULTS: VO2 and kJ mean values were significantly different between all speed and % grade comparisons. Compared to level grade, the average reductions in VO2 and kJ expenditure ranged from approximately 9% at a grade of -1.8% to 22% at a grade of -5.4%. The relationship between VO2 and % grade for each running speed was linear. CONCLUSIONS: For a given speed, running at a modest negative grade can significantly decrease VO2 and kJ expenditure compared to level running. The following regression equation can be used to estimate VO2 (ml.kg-1.min-1) for running at recreational speeds on slight downhills: VO2 = 6.8192 + 0.1313 (speed in m.min-1) + 1.2367 (% grade).

Adult

Infrared emission spectra of candidate interstellar aromatic molecules.

Interstellar dust is responsible, through surface reactions, for the creation of molecular hydrogen, the main component of the interstellar clouds in which new stars form. Intermediate between small, gas-phase molecules and dust are the polycyclic aromatic hydrocarbons (PAHs). Such molecules could account for 2-30% of the carbon in the Galaxy, and may provide nucleation sites for the formation of carbonaceous dust. Although PAHs have been proposed as the sources of the unidentified infrared emission bands that are observed in the spectra of a variety of interstellar sources, the emission characteristics of such molecules are still poorly understood. Here we report laboratory emission spectra of several representative PAHs, obtained in conditions approximating those of the interstellar medium, and measured over the entire spectral region spanned by the unidentified infrared bands. We find that neutral PAHs of small and moderate size can at best make only a minor contribution to these emission bands. Cations of these molecules, as well as much larger PAHs and their cations, remain viable candidates for the sources of these bands.

Extraterrestrial Environment

Disorders of the circadian sleep-wake cycle.

This article reviews several disorders of the circadian sleep-wake cycle, including delayed sleep phase syndrome, advanced sleep phase syndrome, non-24-hour sleep-wake syndrome, irregular sleep-wake pattern, time zone change (jet lag) syndrome, and shift work sleep disorder. For each disorder, the cause, diagnostic work-up, and management are outlined.

Activity Cycles

Cell-type specificity of inhibition of glycolysis by 5-amino-4-imidazolecarboxamide riboside. Lack of effect in rabbit cardiomyocytes and human erythrocytes, and inhibition in FTO-2B rat hepatoma cells.

The nucleoside AICAriboside (5-amino-4-imidazolecarboxamide riboside) has been shown to inhibit glycolysis in isolated rat hepatocytes [Vincent, Bontemps and Van den Berghe (1992) Biochem. J. 281, 267-272]. The effect is mediated by AICA-ribotide (ZMP), the product of the phosphorylation of AICA-riboside by adenosine kinase. To assess the cell-type specificity of the effect, studies were conducted in rabbit cardiomyocytes, human erythrocytes and rat hepatoma FTO-2B cells. AICA-riboside had no effect on glycolysis in cardiomyocytes, and a slight stimulatory effect in erythrocytes, but inhibited glycolysis by 65% at 250 microM concentration in FTO-2B cells, although only when tissue-culture medium was replaced by Krebs-Ringer bicarbonate buffer. At 500 microM AICAriboside, ZMP remained undetectable in cardiomyocytes, but reached 0.65 mM in erythrocytes and 5 mM in FTO-2B cells. In the latter, AICAriboside provoked up to 2-fold elevations of glucose 6-phosphate and fructose 6-phosphate, accompanied by a decrease in fructose 1,6-bisphosphate. This indicated inhibition of 6-phosphofructo-1-kinase (PFK-1). Accordingly, in FTO-2B cell-free extracts, the activity of PFK-1, measured under physiological conditions, was inhibited by approx. 70% by 5 mM ZMP. ZMP had a less pronounced effect on the activity of PFK-1 in normal rat liver; it did not influence the activity of PFK-1 in rat muscle, rabbit heart and human erythrocytes. It is concluded that the inhibitory effect of AICAriboside on glycolysis is dependent on both (1) the capacity of the cells to accumulate ZMP and (2) the presence of target enzymes which are sensitive to ZMP.

Adenosine Kinase

Evaluation of a new urease reagent strip for detection of Helicobacter pylori in gastric biopsy specimens.

OBJECTIVES: Determine sensitivity and specificity of a new urease reagent strip (URS) test for detection of Helicobacter pylori in gastric biopsy specimens. METHODS: Six paired biopsy specimens were obtained from the greater curvature of the distal antrum, the lesser curvature near the incisura, and the corpus along the greater curvature during 66 procedures on 59 patients with endoscopic findings of gastric antral mucosal erythema or erosions, or gastric or duodenal ulcers. One biopsy from each site was tested with the URS. The second was evaluated with histology. A final antral biopsy was evaluated with a urea/gel test. RESULTS: Twenty-eight of the 66 cases were histologically positive, with H. pylori observed in at least one of the three biopsy sites. The URS test correctly identified all 28. Of 193 individual biopsy specimens, 78 were positive for H. pylori. The URS correctly identified 77. Sensitivity was 0.99, specificity 0.95, positive predictive value 0.93, negative predictive value 0.99, and kappa 0.92. Average time to positive was 20 min. Twenty-seven antral biopsies were histologically positive for H. pylori. The URS test correctly identified all 27, whereas the urea/gel test correctly identified 21. For antral sites, URS sensitivity was 1.00 and specificity 0.95 versus urea/gel test sensitivity of 0.75 and specificity of 1.00. CONCLUSIONS: In this sample, the URS test is as accurate as histology in diagnosing H. pylori infections, and it provides results in less time and at a lower cost than histology.

Bacteriological Techniques