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Biomedical subjects

R Saunders

Publications and source records attributed to R Saunders.

At least 19 recordsLinked to original sources

Reassessment of the Ca2+ sensing property of a type I metabotropic glutamate receptor by simultaneous measurement of inositol 1,4,5-trisphosphate and Ca2+ in single cells.

Transient transfection of Chinese hamster ovary or baby hamster kidney cells expressing the Group I metabotropic glutamate receptor mGlu1alpha with green fluorescent protein-tagged pleckstrin homology domain of phospholipase Cdelta1 allows real-time detection of inositol 1,4,5-trisphosphate. Loading with Fura-2 enables simultaneous measurement of intracellular Ca(2+) within the same cell. Using this technique we have studied the extracellular calcium sensing property of the mGlu1alpha receptor. Quisqualate, in extracellular medium containing 1.3 mm Ca(2+), increased inositol 1,4,5-trisphosphate in all cells. This followed a typical peak and plateau pattern and was paralleled by concurrent increases in intracellular Ca(2+) concentration. Under nominally Ca(2+)-free conditions similar initial peaks in inositol 1,4,5-trisphosphate and Ca(2+) concentration occurred with little change in either agonist potency or efficacy. However, sustained inositol 1,4,5-trisphosphate production was substantially reduced and the plateau in Ca(2+) concentration absent. Depletion of intracellular Ca(2+) stores using thapsigargin abolished quisqualate-induced increases in intracellular Ca(2+) and markedly reduced inositol 1,4,5-trisphosphate production. These data suggest that the mGlu1alpha receptor is not a calcium-sensing receptor because the initial response to agonist is not sensitive to extracellular Ca(2+) concentration. However, prolonged activation of phospholipase C requires extracellular Ca(2+), while the initial burst of activity is highly dependent on Ca(2+) mobilization from intracellular stores.

Animals↗

Environmental influences, physical activity, and weight status in 8- to 16-year-olds.

OBJECTIVE: To assess the association between vigorous physical activity, participation on sport teams and in exercise programs, television watching, family environment, and weight status in youth. DESIGN: Cross-sectional data from the Third National Health and Nutrition Examination Survey. PARTICIPANTS: A group of 2791 youth between the ages of 8 and 16 years who were enrolled in the Third National Health and Nutrition Examination Survey. MAIN OUTCOME MEASURES: Overweight was defined using age- and sex-specific 85th percentile of body mass index using Center for Disease Control and Prevention growth charts. RESULTS: Both males and females who had an overweight mother and or father were more likely to be overweight compared with youth who did not have an overweight parent. Females who watched 4 or more hours of television were more likely to be overweight than those who watched less than 4 hours. Males and 14- to 16-year-old females who participated in sport team and exercise programs were less likely to be overweight than their counterparts who did not participate. Also, females with larger families and males from families with higher family incomes were less likely to be overweight. CONCLUSIONS: These results suggest that family environment is associated with overweight in youth and that sport and exercise program participants are less like to be overweight and that, for females, increased television watching is related to overweight.

Adolescent↗

A truly hybrid interventional MR/X-ray system: feasibility demonstration.

A system enabling both x-ray fluoroscopy and MRI in a single exam, without requiring patient repositioning, would be a powerful tool for image-guided interventions. We studied the technical issues related to acquisition of x-ray images inside an open MRI system (GE Signa SP). The system includes a flat-panel x-ray detector (GE Medical Systems) placed under the patient bed, a fixed-anode x-ray tube overhead with the anode-cathode axis aligned with the main magnetic field and a high-frequency x-ray generator (Lunar Corp.). New challenges investigated related to: 1) deflection and defocusing of the electron beam of the x-ray tube; 2) proper functioning of the flat panel; 3) effects on B0 field homogeneity; and 4) additional RF noise in the MR images. We have acquired high-quality x-ray and MR images without repositioning the object using our hybrid system, which demonstrates the feasibility of this new configuration. Further work is required to ensure that the highest possible image quality is achieved with both MR and x-ray modalities.

Brain↗

Measuring enjoyment of physical activity in adolescent girls.

BACKGROUND: Enjoyment has been implicated as a determinant of physical activity among youth, but advances in understanding its importance have been limited by the use of measures that were not adequately validated. The present study examined: (1) the factorial validity of the Physical Activity Enjoyment Scale (PACES), and (2) the construct validity of PACES scores. METHODS: Adolescent girls (N=1797), who were randomly assigned to calibration (n=899) and cross-validation (n=898) samples, completed the PACES and measures of factors influencing enjoyment of physical education, physical activity, and sport involvement. The factorial validity of the PACES and the measure of factors influencing enjoyment of physical education was tested using exploratory and confirmatory factor analysis. The hypothesized relationships among the measures were tested using structural equation modeling. RESULTS: Unidimensional models fit the PACES and the measure of factors influencing enjoyment of physical education in the calibration and cross-validation samples. The hypothesized relationships between the PACES and the measures of factors influencing enjoyment of physical education, physical activity, and sport involvement were supported in the entire sample, were similar in African-American and Caucasian girls, and were independent of physical fitness. CONCLUSIONS: Evidence of factorial validity and convergent evidence for construct validity indicate that the PACES is a valid measure of physical activity enjoyment among adolescent girls, suitable for use as a mediator variable in interventions designed to increase physical activity.

Adolescent↗

Stress incontinence observed with real time sonography and dynamic fastscan magnetic resonance imaging--insights into pathophysiology.

Our concepts of pathophysiology of stress urinary continence have been greatly shaped by developments in radiographic imaging. Simple radiographs with and without contrast initially revealed the importance of urethral descent in pathogenesis. More recently, magnetic resonance imaging (MRI) and real time ultrasonography are showing soft tissue detail within both a global pelvic and a local urethral context. Careful examination of these studies can extend our concepts of pathophysiology and lead us beyond existing paradigms. We propose a unified theory of stress incontinence based on our dynamic fastscan MRI and real time ultrasonograms of stress incontinence, incorporating known details of pelvic anatomy, sphincteric location and function. The hypothesis introduces the concept of a continence threshold at which the urethra is subjected simultaneously to both shearing and explusive forces. If these forces are sufficient to overcome urethral coaptation at threshold, leakage results. The model proposes an anatomical sequence of changes through which the incontinent urethra cycles between periods of rest and increased abdominal pressure, and suggests a way in which repeated episodes of prolpase and urethral traction by shearing forces exerted by the vagina on the urethra may contribute to the development of intrinsic sphincteric deficiency.

Computer Systems↗

Alignment of a volumetric tomography system.

A test-bed system has been developed for imaging phantoms with tomosynthesis and volumetric computed tomography. This system incorporates an amorphous silicon flat panel detector on a movable gantry and a computer-controlled rotational positioning stage. In this paper, an analysis of the sensitivity of reconstructed images to geometrical misalignment is presented. Application of this method to circular digital tomosynthesis is examined, with spatial resolution in the focal plane as the criterion for evaluating the effect of misalignment. A software-based method is presented for correcting data for imperfect system alignment prior to image reconstruction. Experimental results yield reconstructed images with spatial resolution approaching the theoretical limit based on detector pixel size and accounting for data interpolation.

Algorithms↗

Impairment in motion discrimination tasks is unrelated to amount of damage to superior temporal sulcus motion areas.

The behavioral role of the middle temporal (MT/V5) area and its satellites in motion processing is still unclear, particularly the degree to which MT/V5 proper is critical for different types of motion processing. Therefore, effects of small and large lesions in the caudal part of the superior temporal sulcus of macaque monkeys were compared for two tasks requiring different types of motion processing: a direction and a kinetic orientation discrimination. The small lesion was restricted to the peripheral representation of MT/V5 but included V4t, whereas the large lesion included all of MT/V5 and the medial superior temporal (MST) area as well as substantial parts of the floor of the superior temporal (FST) area. Both lesions resulted in significant and long-lasting impairment of direction discrimination but had a lesser effect on kinetic orientation discrimination. Thus the effects of small STS lesions on motion perception are much stronger than expected.

Animals↗

A leptomycin B-sensitive homologue of human CRM1 promotes nuclear export of nuclear export sequence-containing proteins in Drosophila cells.

The Rev protein of human immunodeficiency virus is a nuclear shuttling protein that promotes nuclear export of mRNAs that encode the viral structural proteins Gag, Pol, and Env. Rev binds to a highly structured RNA motif, the Rev-responsive element (RRE), that is present in all Rev-responsive viral transcripts and facilitates their entry into a nuclear export pathway by recruiting cellular export factors. In mammalian and yeast cells, the principal export receptor engaged by Rev has been identified as the importin/transportin family member CRM1/exportin 1. CRM1 binds directly to a leucine-rich nuclear export sequence (NES) present in Rev, and similar motifs have been identified in a variety of cellular nuclear shuttling proteins. We and our colleagues previously demonstrated that, in transfected Drosophila cells, HIV-1 Rev is fully functional and promotes expression of the viral envelope glycoprotein. We now demonstrate that the fundamental mechanism of Rev action in insect cells is identical to that observed in the mammalian systems. In particular, we show that Drosophila cells express a leptomycin B-sensitive homologue of human CRM1 that supports Rev-dependent gene expression and is required for nuclear export of NES-containing proteins in insect cells.

Amino Acid Sequence↗

The association between severity of sanction imposed for violation of tobacco policy and high school dropout rates.

This investigation explored the association between severity of sanctions imposed on students resulting from tobacco policy violation and the event dropout rate in South Carolina public high schools. The study employed a cross-sectional design (n = 132). Surveys were mailed to school principals to assess tobacco policy and sanctions for violation. Severe sanctions were categorized as those resulting in the student being denied onsite instruction, such as out-of-school suspension or expulsion. General linear regression models adjusting for SES, ethnicity, and rural/urban status, tested for an association between event dropout rate and severity of sanction imposed. The mean dropout rate in 1998 for high schools in South Carolina was 2.58% (+1.74). Suspension at first violation and expulsion were associated with lower dropout rates. Suspension at second violation was not associated with dropout behavior while suspension at third violation was associated with higher dropout rates. Results from the study provide preliminary evidence that severe sanctions imposed for violation of tobacco policy may help reduce high school dropout rates.

Adolescent↗

Complex involvement of pertussis toxin-sensitive G proteins in the regulation of type 1alpha metabotropic glutamate receptor signaling in baby hamster kidney cells.

Previously, we demonstrated that the coupling of the metabotropic glutamate receptor mGlu1alpha to phosphoinositide hydrolysis is enhanced by pertussis toxin (PTX) in stably transfected baby hamster kidney cells (BHK). Here, we show that the PTX effect on agonist-stimulated [(3)H]inositol phosphate accumulation can be resolved into two components: an immediate increase in agonist potency, and a more slowly developing increase in the magnitude of the response observed at maximally effective agonist concentrations. Using G(q/11)alpha- and G(i/o)alpha-selective antibodies to immunoprecipitate [(35)S]guanosine-5'-O-(3-thio)triphosphate-bound Galpha proteins, we also show that agonist stimulation of mGlu1alpha in BHK membranes increases specific [(35)S]guanosine-5'-O-(3-thio)triphosphate binding to both G(q/11) and G(i/o) proteins. Preincubation of BHK-mGlu1alpha with L-glutamate (300 microM) results in a progressive loss (60% in 30 min) of L-quisqualate-induced [(3)H]inositol phosphate accumulation (without a change in potency), providing evidence for agonist-induced receptor desensitization. Although such desensitization of mGlu receptor signaling was mimicked by a phorbol ester, agonist-induced phosphorylation of the receptor was not observed and protein kinase C inhibition by Ro 31-8220 did not prevent L-glutamate-mediated desensitization. In contrast, PTX treatment of the cells almost completely prevented L-glutamate-mediated desensitization. Together, these data provide evidence for a multifunctional coupling of mGlu1alpha to different types of G proteins, including PTX-sensitive G(i)-type G proteins. The latter are involved in the negative control of phospholipase C activity while also influencing the rate of desensitization of the mGlu1alpha receptor.

Adenylyl Cyclases↗

Isolation and characterization of unmyelinated axolemma from bovine splenic nerve.

Bovine splenic nerve was used as a source of axolemma-enriched fractions derived from mammalian unmyelinated axons. By electron microscopy, splenic nerve consisted entirely of fascicles of unmyelinated axons and associated Schwann cells. The epineurium and blood vessels were stripped from the dissected nerve, which was then homogenized followed by preparation of a microsomal fraction by differential centrifugation. The microsomes were fractionated on a 10% to 40% continuous sucrose gradient. The individual fractions were combined into six fractions based on sucrose concentration and each fraction was analyzed for membrane markers. The 20% to 23% region of the sucrose gradient was enriched approximately sevenfold in acetylcholinesterase activity and twofold enrichment in saxitoxin binding activity was noted in the same fraction. Relative to other microsomal fractions, this same fraction was less enriched in a microsomal marker (cytochrome c reductase) and only moderately enriched in the activity of a myelin membrane marker (2',3' cyclic nucleotide 3' phosphohydrolase, CNPase). Polyacrylamide electrophoresis of the axolemma-enriched fraction revealed five prominent peptides ranging in molecular weight from 40 kDa to 130 kDa. Lipids, comprising 59.4% of the dry weight, were enriched in cholesterol and sphingomyelin, consistent with the origin from a peripheral nervous system (PNS) plasma membrane. On a molar basis, the major gangliosides were G(T1b), G(D1a), and G(M1). As a whole, these molecular characteristics are consistent with the origin of the axolemma-enriched fraction in the unmyelinated splenic nerve axons. This membrane preparation should prove useful in future studies of the myelinogenic potential of mammalian unmyelinated axolemma.

Acetylcholinesterase↗

Correlates of objectively measured physical activity in preadolescent youth.

OBJECTIVE: The purpose of this study was to identify the psychosocial and environmental correlates of objectively measured physical activity behavior in a diverse sample of sixth-grade students. DESIGN: Cross-sectional. PARTICIPANTS AND SETTINGS: One hundred ninety-eight sixth-grade students from 4 public middle schools in Columbia, South Carolina. The study group was 52.0% female, 55.1% African-American, with a mean age of 11.4 +/- 0.6 years. MAIN OUTCOME MEASURES: Time spent in moderate physical activity (MPA) and vigorous physical activity (VPA) was assessed using a uniaxial accelerometer (CSA WAM 7164) (Computer Science and Applications Inc., Shalimar, FL). Determinant variables included: age, gender, race/ethnicity (demographic); physical activity self-efficacy, social norms related to physical activity, and beliefs regarding physical activity outcomes (psychosocial); and perceived physical activity habits of parents and peers, involvement in community physical activity organizations, involvement in community-based sports programs, access to fitness/sporting equipment at home, and self-reported hours spent watching television or playing video games (environmental). RESULTS: For boys, physical activity self-efficacy, social norms related to physical activity, and involvement in community physical activity organizations were salient predictors of MPA and VPA. Among girls, only physical activity self-efficacy emerged as a clear predictor of objectively measured physical activity. CONCLUSIONS: These findings are consistent with previous studies using self-reported physical activity and suggest that interventions to increase physical activity in preadolescent youth should endeavor to boost physical activity self-efficacy by offering a wide selection of enjoyable, developmentally-appropriate physical activity options.

Child↗

Secondary school tobacco policy and prevention curricula in South Carolina.

The primary purpose of this study was to describe tobacco control policy in secondary schools in South Carolina, and sanctions imposed on students for violation of these policies; and to explore potential associations between policies and sanctions. A secondary purpose was to explore the use of tobacco education curricula in the state. This study employed a cross-sectional design in which two surveys were mailed to all secondary schools in South Carolina (n = 437): the School Principal Questionnaire (SPQ) and the Lead Health Education Teacher Questionnaire (LHETQ). The SPQ elicited information about tobacco control policies and the sanctions imposed on violators of such policies. The LHETQ was sent to lead health education teachers to elicit information about use of packaged curricula addressing tobacco use and prevention. Over 95% of respondents reported having school policies that prohibited use of tobacco inside buildings, and explicitly prohibited the use of cigarettes for students anywhere on school grounds. Sanctions imposed for violation of tobacco policy were severe. For a second offense, nearly 68% of students were suspended out-of-school or expelled, and for a third offense, almost 28% of students were expelled. There is some evidence to suggest that more stringent policies were associated with more severe sanctions. Cessation from tobacco programs were rarely used as a sanction, and in fact, tobacco education curricula were rarely used by health education teachers. In South Carolina secondary schools, tobacco policies are prevalent. Student violators of such policies are punished by means that potentially detract from their educational experience (e.g., out-of-school suspension, expulsion). It is recommended that school administrators and school health education teachers implement tobacco cessation programs as part of appropriate sanctions for violations of school tobacco use policy.

Adolescent↗

Determinants of physical activity in active and low-active, sixth grade African-American youth.

This study compared the determinants of physical activity in active and low-active African-American sixth grade students (N = 108, 57 F, 51 M). Objective assessments of physical activity over a seven-day period were obtained using the CSA 7164 accelerometer. Students were classified as active if they exhibited three or more 20-minute bouts of moderate to vigorous physical activity over the seven-day period. Relative to low-actives, active boys reported significantly higher levels of self-efficacy, greater involvement in community physical activity organizations, and were significantly more likely to perceive their mother as active. Relative to low-actives, active girls reported significantly higher levels of physical activity self-efficacy, greater positive beliefs regarding physical activity outcomes, and were significantly less likely to watch television or play video games for > or = 3 hrs/day. These observations provide preliminary guidance as to the design of physical activity interventions targeted at African-American youth.

Black or African American↗

The rough deal protein is a new kinetochore component required for accurate chromosome segregation in Drosophila.

Mutations in the rough deal (rod) gene of Drosophila greatly increase the missegregation of sister chromatids during mitosis, suggesting a role for this gene product in spindle or kinetochore function. The activity provided by rod also appears to be necessary for the recruitment of two known kinetochore components, Zw10 and cytoplasmic dynein. In this paper we describe the cloning of rough deal and an initial cytological characterization of its product. The Rod protein shares no identifiable structural motif with other known proteins, although apparent homologs exist in the genomes of nematode and man. By immunocytochemistry we show that Rod displays a dynamic intracellular staining pattern, localizing first to kinetochores in prometaphase, but moving to kinetochore microtubules at metaphase. Early in anaphase the protein is once again restricted to the kinetochores, where it persists until the end of telophase. This behavior is in all respects similar to that described for Zw10, and suggests that the proteins function together.

Amino Acid Sequence↗

Binge eating in gastric bypass patients before surgery.

BACKGROUND: Binge eating in the obese, specifically those undergoing bariatric surgery, has only recently been investigated. This study is a continuation of a long-term effort to determine the impact of eating disorders on the outcome of bariatric surgery. METHODS: Self-report questionnaires (Binge Eating Scale, Beck Depression Inventory, Questionnaire on Weight and Eating Patterns) were completed by 125 patients preparing to undergo gastric bypass surgery. RESULTS: Binge eating was clearly a problem in this population, with 33.3% showing severe binge eating problems on the Binge Eating Scale. Over half of patients engaged in bingeing or grazing, most reporting a frequency of two or more times per week. A high level of depression was associated with binge eating. CONCLUSIONS: Because postsurgical long-term weight loss maintenance is contingent on modifying eating behavior, the identification and treatment of such disorders may be critical to successful long-term outcome in these patients.

Adolescent↗

A modulatory effect of extracellular Ca2+ on type 1alpha metabotropic glutamate receptor-mediated signalling.

Increasing [Ca2+]e from 1.3 4 mM had little effect on basal phospholipase C activity in baby hamster kidney (BHK) cells stably expressing either type 1alpha metabotropic glutamate (mGlu1alpha) or M3-muscarinic (m3) receptors, but enhanced agonist-stimulated phosphoinositide hydrolysis in BHK-mGlu1alpha, but not BHK-m3 cells, demonstrating that Ca2+(e) selectively modulates phosphoinositide signalling stimulated by this receptor subtype.

Animals↗