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Biomedical subjects

R Ross

Publications and source records attributed to R Ross.

At least 37 records · Page 2Linked to original sources
PubMed2000

Expression of the actin-bundling protein fascin in cultured human dendritic cells correlates with dendritic morphology and cell differentiation.

Dendritic cells are key players of the immune system as they efficiently induce primary immune responses by activating naive T cells. We generated human dendritic cells from CD14+ blood precursors and investigated expression of the actin-bundling protein fascin during maturation by western blotting, immunofluorescence, and cytofluorometry. Cells obtained by culture of CD14+ blood precursors in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4, which were only weakly positive for the maturation marker CD83, expressed low amounts of fascin. Addition of a cytokine cocktail including tumor necrosis factor alpha, interleukin-1beta, interleukin-6, and prostaglandin E2 induced maturation of the cells and enhanced fascin expression in parallel with CD83 expression. Isolated mature CD83+ cells displayed especially high fascin levels on western blots, as did gated CD83+ dendritic cells in cytofluorometry. Dendritic cells generated from CD34+ blood precursors expressed high levels of fascin as well. Confocal microscopy revealed that location of fascin within the cell was restricted to the area of the submembranous actin cytoskeleton and to the dendritic processes. Suppression experiments using antisense constructs of fascin hint at a retarded morphologic maturation of dendritic cells, supporting the view that fascin expression is pivotal for dendrite formation. Our data suggest that fascin could serve as a marker molecule to monitor the maturation state of in vitro generated dendritic cells for use in clinical trials.

Actins↗
PubMed2000

Paramedic success rate for blind nasotracheal intubation is improved with the use of an endotracheal tube with directional tip control.

STUDY OBJECTIVES: Blind nasotracheal intubation (BNTI) is used to secure the airway in patients who are spontaneously breathing. The success rate for BNTI is often lower than for orotracheal intubation. We conducted this study to determine whether the use of an endotracheal tube (ETT) capable of directional tip control can improve the BNTI success rate. METHODS: This prospective, experimental study was conducted by a state emergency medical services agency during 1997, 1998, and 1999. Consecutive patients undergoing attempted BNTI or orotracheal intubation were included. Five paramedic units were trained to use an ETT with triggeractivated distal tip directional control for BNTIs (intervention group). Ten units used conventional ETTs for BNTIs and served as concurrent controls (control group). Subjects in the 2 groups were enrolled concurrently with nonrandomized allocation based on the agency providing service. An intubation attempt was defined by tube passage, and success was defined as confirmed endotracheal placement. RESULTS: A total of 219 BNTIs were studied (141 in the control group and 78 in the intervention group). BNTI was successful in 82 (58%) of 141 cases using conventional ETTs, and in 56 (72%) of 78 cases using directional tip control (P =.04). The overall success rate was 63%. CONCLUSION: Use of ETTs with distal directional control is associated with a higher success rate for BNTI than conventional ETTs. Use of ETTs with directional tip control significantly improves the success rates for BNTIs.

Allied Health Personnel↗
PubMed2000

Total-body skeletal muscle mass: development and cross-validation of anthropometric prediction models.

BACKGROUND: Skeletal muscle (SM) is a large body compartment of biological importance, but it remains difficult to quantify SM with affordable and practical methods that can be applied in clinical and field settings. OBJECTIVE: The objective of this study was to develop and cross-validate anthropometric SM mass prediction models in healthy adults. DESIGN: SM mass, measured by using whole-body multislice magnetic resonance imaging, was set as the dependent variable in prediction models. Independent variables were organized into 2 separate formulas. One formula included mainly limb circumferences and skinfold thicknesses [model 1: height (in m) and skinfold-corrected upperarm, thigh, and calf girths (CAG, CTG, and CCG, respectively; in cm)]. The other formula included mainly body weight (in kg) and height (model 2). The models were developed and cross-validated in nonobese adults [body mass index (in kg/m(2)) < 30]. RESULTS: Two SM (in kg) models for nonobese subjects (n = 244) were developed as follows: SM = Ht x (0.00744 x CAG(2) + 0.00088 x CTG(2) + 0.00441 x CCG(2)) + 2.4 x sex - 0.048 x age + race + 7.8, where R:(2) = 0.91, P: < 0.0001, and SEE = 2.2 kg; sex = 0 for female and 1 for male, race = -2.0 for Asian, 1.1 for African American, and 0 for white and Hispanic, and SM = 0.244 x BW + 7.80 x Ht + 6.6 x sex - 0.098 x age + race - 3.3, where R:(2) = 0.86, P: < 0.0001, and SEE = 2.8 kg; sex = 0 for female and 1 for male, race = -1.2 for Asian, 1.4 for African American, and 0 for white and Hispanic. CONCLUSION: These 2 anthropometric prediction models, the first developed in vivo by using state-of-the-art body-composition methods, are likely to prove useful in clinical evaluations and field studies of SM mass in nonobese adults.

Adult↗
PubMed2000

Distribution of protein turnover changes with age in humans as assessed by whole-body magnetic resonance image analysis to quantify tissue volumes.

We tested the hypothesis that nonmuscle lean tissue mass and its rate of protein catabolism remain constant with aging despite changes in the proportional contribution of these tissues to whole-body protein metabolism. Whole-body protein kinetics, using the 60-h oral [(15) N]glycine method, and muscle and nonmuscle protein catabolism, based on protein kinetic data, urinary N(tau)-methylhistine excretion and lean tissue volumes defined by whole-body magnetic resonance imaging, from eight healthy elderly subjects (5 females and 3 males, mean age 71.5 y) were compared with those of seven young persons (3 females and 4 males, mean age 28 y). There were no significant age or gender effects on rates of protein kinetics per L total lean tissue. There was a lower (P < 0.004) rate of muscle protein catabolism in the elderly (1.8 +/- 0.2 vs. 2.6 +/- 0.1 g. L(-1). d(-1)) and a trend (P = 0.08) for lower muscle volume (19.7 +/- 1.5 vs. 25.0 +/- 2.4 L). This contrasted with intraabdominal lean tissue, where the rate of protein catabolism (13. 8 +/- 0.6 vs. 13.2 +/- 0.9 g. L(-1 ). d(-1)) and volume (7.5 +/- 0.3 vs 8.0 +/- 0.5 L) did not differ between age groups. Thus, the decrease in the contribution by muscle to whole-body protein metabolism with age is associated with an increase from 62 to 74% (P < 0.001) in the contribution by nonmuscle lean tissues. These findings have potential implications for the nutrition of both normal and sick elderly persons.

Aged↗
PubMed2000

Detection of dissection and remodeling of atherosclerotic lesions in rabbits after balloon angioplasty by magnetic-resonance imaging.

OBJECTIVE: To assess the usefulness of magnetic-resonance imaging (MRI) for monitoring acute changes after angioplasty of preexisting lesions in rabbits with basal lesions similar to those observed in humans. METHODS: A combination of Fogarty balloon injury (1 week after initiation of diet) and a mildly hypercholesterolemic diet (0.2% cholesterol and 5% peanut oil) was used to promote the rapid formation of atherosclerotic lesions in 16 New Zealand white rabbits. After 5 months of the diet, angioplasty was performed on these lesions with a Grüntzig catheter in both iliac arteries and the abdominal aorta. MRI was used to monitor the initial formation of lesions after 3 and 5 months of the diet, and 2 days, 2 weeks, and 1 and 2 months after angioplasty. RESULTS: The combination of early Fogarty injury and mildly hypercholesterolemic diet induced fibroproliferative lesions similar to type Vb atherosclerotic lesions seen in humans. Angioplasty induced deep dissections at the shoulders of lesions in the majority of animals. These dissections often extended into the media. The cellular, proliferative response after angioplasty was localized and limited to sites of dissection. A significant increase in area of arterial wall was observed after angioplasty at sites of dissection without any loss of lumen. In contrast, proximal and distal to the sites of injury, there was no change in wall area but a transient reduction in lumen area. CONCLUSIONS: Comparison of MRI results with histology confirmed that changes in the wall and lumen, including small linear dissections in the lesions and arterial remodeling, are detectable by MRI.

Angioplasty, Balloon↗
PubMed2000

Magnetic resonance imaging in human body composition research. From quantitative to qualitative tissue measurement.

Incremental improvements in our knowledge of human body composition are abetted by advances in research technology. Indeed, magnetic resonance imaging (MRI) represents a technological advance that has profoundly influenced body composition research. Routine applications of MRI include the measurement of whole-body and regional adipose tissue distribution, quantification of lean tissue and its principal constituent skeletal muscle, and the measurement of visceral adipose tissue. MRI is now the method of choice for calibration of field methods designed to measure body fat and skeletal muscle in vivo. Common to these applications is the measurement of tissue quantity. More recently proton (1H) and sodium (23Na) MRI protocols have been developed that measure the quality (lipid and sodium concentration) of skeletal muscle tissue. These unique applications of MRI represent a major advance in the study of altered muscle composition in vivo, with numerous applications in both applied and clinical medicine. In this review we provide a brief overview of routine applications of MRI in body composition research, followed by a focus on more recent applications of MRI that employ fast-imaging sequences for qualitative measurement of human skeletal muscle.

Adipose Tissue↗
PubMed2000

Obesity reduction through lifestyle modification.

Obesity is a worldwide public health problem. One in three Canadians is overweight, a prevalence that is already high and increasing. Moreover, 54% of men and 37% of Canadian women are characterized as abdominally obese, the phenotype that is strongly associated with cardiovascular disease and type II diabetes. These observations underscore the importance of considering the efficacy of methods commonly used to reduce total and abdominal obesity. These strategies include a decrease in energy intake (diet), an increase in energy expenditure (exercise), or pharmacological intervention. The combination of diet and exercise is more commonly prescribed, with pharmacological intervention suggested only when lifestyle changes fail to achieve weight loss. The aim of this report is to review current knowledge regarding the influence of diet and exercise as treatment strategies for obesity reduction and provide recommendations for attaining and maintaining a healthy weight. The importance of diet composition in the treatment of obesity is also considered.

Abdomen↗
PubMed2000

Plasma leptin in moderately obese men: independent effects of weight loss and aerobic exercise.

The independent effects of weight loss and exercise on plasma leptin and total (AT), subcutaneous (SAT), and visceral (VAT) adipose tissue were investigated in 52 obese men. Subjects were randomly assigned to four 12-wk protocols: 1) control (C, n = 8), 2) diet-induced weight loss (DWL, n = 14), 3) exercise-induced weight loss (EWL, n = 14), and 4) exercise with weight maintenance (EWS, n = 16). Plasma leptin was unchanged in C (from 7.8 +/- 1.3 to 7.7 +/- 1.0 ng/ml). Equivalent weight loss (7.5 kg) decreased leptin significantly but similarly (DWL, from 8.5 +/- 1.0 to 4.8 +/- 0.6 ng/ml; EWL, from 10.1 +/- 1.0 to 5.0 +/- 0.6 ng/ml). Exercise in the absence of weight loss did not alter leptin levels (from 10.1 +/- 1. 3 to 9.2 +/- 1.2 ng/ml). Changes in leptin correlated with changes in AT and SAT (both P < 0.05) but not in VAT. We conclude that reduction in adipose tissue after weight loss results in a collateral decrease in circulating leptin, and exercise, independent of its effects on weight loss, has no profound influence on leptin secretion.

Adipose Tissue↗
PubMed2000

Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content.

The purpose of this investigation was to validate that in vivo measurement of skeletal muscle attenuation (MA) with computed tomography (CT) is associated with muscle lipid content. Single-slice CT scans performed on phantoms of varying lipid concentrations revealed good concordance between attenuation and lipid concentration (r(2) = 0.995); increasing the phantom's lipid concentration by 1 g/100 ml decreased its attenuation by approximately 1 Hounsfield unit (HU). The test-retest coefficient of variation for two CT scans performed in six volunteers was 0.51% for the midthigh and 0.85% for the midcalf, indicating that the methodological variability is low. Lean subjects had significantly higher (P < 0.01) MA values (49.2 +/- 2.8 HU) than did obese nondiabetic (39.3 +/- 7.5 HU) and obese Type 2 diabetic (33.9 +/- 4. 1 HU) subjects, whereas obese Type 2 diabetic subjects had lower MA values that were not different from obese nondiabetic subjects. There was also good concordance between MA in midthigh and midcalf (r = 0.60, P < 0.01), psoas (r = 0.65, P < 0.01), and erector spinae (r = 0.77, P < 0.01) in subsets of volunteers. In 45 men and women who ranged from lean to obese (body mass index = 18.5 to 35.9 kg/m(2)), including 10 patients with Type 2 diabetes mellitus, reduced MA was associated with increased muscle fiber lipid content determined with histological oil red O staining (P = -0.43, P < 0. 01). In a subset of these volunteers (n = 19), triglyceride content in percutaneous biopsy specimens from vastus lateralis was also associated with MA (r = -0.58, P = 0.019). We conclude that the attenuation of skeletal muscle in vivo determined by CT is related to its lipid content and that this noninvasive method may provide additional information regarding the association between muscle composition and muscle function.

Adult↗
PubMed2000

Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr.

We employed a whole body magnetic resonance imaging protocol to examine the influence of age, gender, body weight, and height on skeletal muscle (SM) mass and distribution in a large and heterogeneous sample of 468 men and women. Men had significantly (P < 0.001) more SM in comparison to women in both absolute terms (33.0 vs. 21.0 kg) and relative to body mass (38.4 vs. 30.6%). The gender differences were greater in the upper (40%) than lower (33%) body (P < 0.01). We observed a reduction in relative SM mass starting in the third decade; however, a noticeable decrease in absolute SM mass was not observed until the end of the fifth decade. This decrease was primarily attributed to a decrease in lower body SM. Weight and height explained approximately 50% of the variance in SM mass in men and women. Although a linear relationship existed between SM and height, the relationship between SM and body weight was curvilinear because the contribution of SM to weight gain decreased with increasing body weight. These findings indicate that men have more SM than women and that these gender differences are greater in the upper body. Independent of gender, aging is associated with a decrease in SM mass that is explained, in large measure, by a decrease in lower body SM occurring after the fifth decade.

Adolescent↗
PubMed2000

Estimation of skeletal muscle mass by bioelectrical impedance analysis.

The purpose of this study was to develop and cross-validate predictive equations for estimating skeletal muscle (SM) mass using bioelectrical impedance analysis (BIA). Whole body SM mass, determined by magnetic resonance imaging, was compared with BIA measurements in a multiethnic sample of 388 men and women, aged 18-86 yr, at two different laboratories. Within each laboratory, equations for predicting SM mass from BIA measurements were derived using the data of the Caucasian subjects. These equations were then applied to the Caucasian subjects from the other laboratory to cross-validate the BIA method. Because the equations cross-validated (i.e., were not different), the data from both laboratories were pooled to generate the final regression equation SM mass (kg) = [(Ht 2 / R x 0.401) + (gender x 3.825) + (age x -0. 071)] + 5.102 where Ht is height in centimeters; R is BIA resistance in ohms; for gender, men = 1 and women = 0; and age is in years. The r(2) and SE of estimate of the regression equation were 0.86 and 2.7 kg (9%), respectively. The Caucasian-derived equation was applicable to Hispanics and African-Americans, but it underestimated SM mass in Asians. These results suggest that the BIA equation provides valid estimates of SM mass in healthy adults varying in age and adiposity.

Adolescent↗
PubMed2000

Racial differences in visceral adipose tissue but not anthropometric markers of health-related variables.

This study sought to determine whether visceral adipose tissue (VAT) and/or its anthropometric surrogates could significantly predict health-related variables (HRV) in overweight Caucasian (CC) (n = 36) and African-American (AA) (n = 30) women. With the use of magnetic resonance imaging, findings showed significantly higher volume and area of VAT (P < 0.0001 for both) as well as higher triacylglycerol (P = 0.009) in CC compared with AA women. Furthermore, VAT volume, race, and VAT volume x race interaction could significantly predict triacylglycerol (P = 0.0094), high-density lipoprotein cholesterol (P = 0.0057), insulin (P = 0.0002), and insulin resistance (P < 0. 0001). Additionally, the VAT volume x race interaction for insulin (P = 0.040) and insulin resistance (P = 0.003) was significant. In a separate analysis, waist circumference and race predicted the identical variables. Our results support the use of volume or area of VAT in predicting HRV in CC women; however, its use in AA women appears limited. In contrast, waist circumference can provide a suitable VAT alternative for both CC and AA women; however, VAT clearly represents the more powerful predictor.

Adipose Tissue↗
PubMed2000

Rural at-risk drinkers: correlates and one-year use of alcoholism treatment services.

OBJECTIVE: The purpose of this study was to identify a community sample of rural and urban at-risk drinkers, to compare them in terms of sociodemographics, access measures and severity of illness, and to study them prospectively to identify rural/urban differences in use of 12-month alcoholism treatment services. METHOD: A brief telephone screening interview of over 12,000 respondents in six southern states identified a sample of at-risk drinkers. A baseline interview was administered to 733 individuals (67% men, 50% rural residents) that obtained information on substance use and psychiatric disorders, psychosocial factors, social support, four dimensions of access to alcoholism treatment services and prior alcoholism service use. Interviews at 6 and 12 months obtained self-reports of subsequent receipt of alcoholism treatment services. RESULTS: We identified modest differences between rural and urban at-risk drinkers. The rural sample was significantly less well-educated and reported significantly less affordability, accessibility and acceptability of some treatment services (p < .05). Rural at-risk drinkers also appeared to possess significantly greater illness characteristics, including more lifetime DSM-IV criteria for alcohol use disorders, more frequent recent alcohol disorders and more chronic medical problems (p < .05). The longitudinal sample comprised 579 participants, of whom 7% reported receiving some form of alcoholism treatment services in the year after the initial interview. In bivariate analysis, rural drinkers in the sample reported greater use of help for their drinking, more use of psychiatrists and more use of inpatient, outpatient and ER treatment settings than did their urban counterparts. However, significant independent predictors of 12-month alcoholism treatment use in multiple logistic regression were female gender (OR = 0.3), greater social support (OR = 2.2) and illness or severity characteristics including recent diagnosis of alcohol dependence (OR = 3.3), social consequences of drinking (OR = 1.7), concurrent medical problems (OR = 2.1) and prior treatment experience (OR = 4.4). CONCLUSIONS: We found modest differences among rural and urban at-risk drinkers and some evidence of greater barriers to treatment and greater illness severity among rural inhabitants. Further research is needed to know whether community interventions with social networks and other interventions to improve social support may help bring at-risk drinkers into treatment in both urban and rural settings as well as provide other support for sobriety.

Adult↗
PubMed2000

Exercise alone is an effective strategy for reducing obesity and related comorbidities.

The commonly held view that exercise alone is not a useful strategy for obesity reduction is drawn from studies with limitations that confound interpretation. Recent evidence counters the dogma that daily exercise produces only modest weight loss and suggests that exercise without diet restriction is an effective strategy for reducing obesity and related co-morbidities.

Adipose Tissue↗
PubMed1999

Degraded collagen fragments promote rapid disassembly of smooth muscle focal adhesions that correlates with cleavage of pp125(FAK), paxillin, and talin.

Active matrix metalloproteinases and degraded collagen are observed in disease states, such as atherosclerosis. To examine whether degraded collagen fragments have distinct effects on vascular smooth muscle cells (SMC), collagenase-digested type I collagen was added to cultured human arterial SMC. After addition of collagen fragments, adherent SMC lose their focal adhesion structures and round up. Analysis of components of the focal adhesion complex demonstrates rapid cleavage of the focal adhesion kinase (pp125(FAK)), paxillin, and talin. Cleavage is suppressed by inhibitors of the proteolytic enzyme, calpain I. In vitro translated pp125(FAK) is a substrate for both calpain I- and II-mediated processing. Mapping of the proteolytic cleavage fragments of pp125(FAK) predicts a dissociation of the focal adhesion targeting (FAT) sequence and second proline-rich domain from the tyrosine kinase domain and integrin-binding sequence. Coimmunoprecipitation studies confirm that the ability of pp125(FAK) to associate with paxillin, vinculin, and p130cas is significantly reduced in SMC treated with degraded collagen fragments. Further, there is a significant reduction in the association of intact pp125(FAK) with the cytoskeletal fraction, while pp125(FAK) cleavage fragments appear in the cytoplasm in SMC treated with degraded collagen fragments. Integrin-blocking studies indicate that integrin-mediated signals are involved in degraded collagen induction of pp125(FAK) cleavage. Thus, collagen fragments induce distinct integrin signals that lead to initiation of calpain-mediated cleavage of pp125(FAK), paxillin, and talin and dissolution of the focal adhesion complex.

Actinin↗
PubMed1999

NO synthase II in mouse skeletal muscle is associated with caveolin 3.

The inducible-type NO synthase (NOS II; iNOS) is constitutively expressed in slow-twitch skeletal muscle fibres of guinea-pigs [Gath, Closs, Gödtel-Armbrust, Schmitt, Nakane, Wessler and Förstermann (1996) FASEB J. 10, 1614-1620]. Here we studied the expression of NOS II in skeletal muscle of wild-type and NOS II-deficient mice and investigated the molecular basis for the membrane association of this NOS in muscle. A basal expression of NOS II mRNA and protein was detected in skeletal muscle from untreated wild-type mice; expression increased when mice were treated with bacterial lipopolysaccharide (LPS). No NOS II was found in any tissue of untreated or LPS-treated NOS II-deficient mice. Immunoprecipitation experiments were performed with homogenates of gastrocnemius muscle from untreated or LPS-treated wild-type mice. A NOS II-specific antibody precipitated caveolin 3 in all homogenates investigated, the effect being most pronounced in skeletal muscle from LPS-treated animals. Conversely, an antibody against caveolin 3 co-precipitated NOS II in muscle homogenates. Similarly, a weak co-precipitation of NOS II and caveolin 3 was seen in homogenates of untreated murine C2C12 myotubes; co-precipitation was markedly enhanced in cells stimulated with LPS/interferon gamma. The association of NOS II with caveolin 3 might have implications for the regulation of contraction of, and/or glucose uptake by, slow-twitch muscle fibres.

Animals↗
PubMed1999

Studies with a growth hormone antagonist and dual-fluorescent confocal microscopy demonstrate that the full-length human growth hormone receptor, but not the truncated isoform, is very rapidly internalized independent of Jak2-Stat5 signaling.

UNLABELLED: We have investigated trafficking of two negative regulators of growth hormone receptor (GHR) signaling: a human, truncated receptor, GHR1-279, and a GH antagonist, B2036. Fluorescent-labeled growth hormone (GH) was rapidly internalized by the full-length GHR, with >80% of the hormone internalized within 5 min of exposure to GH. In contrast, <5% of labeled GH was internalized by cells expressing truncated GHR1-279. Using another truncated receptor, GHR1-317 fused to enhanced green fluorescent protein (EGFP), we have exploited fluorescence energy transfer to monitor the trafficking of ligand-receptor complexes. The data confirmed that internalization of this truncated receptor is very inefficient. It was possible to visualize the truncated GHR1-317-EGFP packaged in the endoplasmic reticulum, its rapid movement in membrane bound vesicles to the Golgi apparatus, and subsequent transport to the cell membrane. The GH antagonist, B2036, blocked Jak2-Stat5-mediated GHR signaling but was internalized with a similar time course to native GH. THE RESULTS: 1) demonstrate the rapid internalization of GH when studied under physiological conditions; 2) confirm the hypothesis that internalization of cytoplasmic domain truncated human GHRs is very inefficient, which explains their dominant negative action; and 3) show that the antagonist action of B2036 is independent of receptor internalization.

Golgi Apparatus↗