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Biomedical subjects

R Saunders

Publications and source records attributed to R Saunders.

At least 37 records · Page 2Linked to original sources

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↗

Rejoinder to Mordock's critique of the Fort Bragg Evaluation Project: the sample is generalizable and the outcomes are clear.

The Fort Bragg Evaluation Project (FBEP) showed that children in a well implemented and expensive continuum of care had no better clinical outcomes than those experiencing more traditional and fragmented services. In an article published in this journal that was critical of the evaluation, Mordock argued that the FBEP results be viewed with skepticism because of what he perceived to be methodological, design, measurement, and analytic failures of this study. We think it is important to respond to Mordock's critique since it contributes to the great reluctance to seriously consider the study's findings and their implications.

Adolescent↗

Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method.

A major line of evidence that supports the hypothesis of dopamine overactivity in schizophrenia is the psychomimetic potential of agents such as amphetamine that stimulate dopamine outflow. A novel brain imaging method provides an indirect measure of in vivo synaptic dopamine concentration by quantifying the change in dopamine receptor radiotracer binding produced by agents that alter dopamine release but do not themselves bind to dopamine receptors. The purpose of this investigation is (i) to determine the sensitivity (i.e., amount of dopamine reflected in radiotracer binding changes) of this method by examining the relationship between amphetamine-induced changes in simultaneously derived striatal extracellular dopamine levels with in vivo microdialysis and striatal binding levels with the dopamine D2/D3 positron-emission tomography radioligand [11C]raclopride in nonhuman primates, and (ii) to test the hypothesis of elevated amphetamine-induced synaptic dopamine levels in schizophrenia. In the nonhuman primate study (n = 4), doubling the amphetamine dose produced a doubling in [11C]raclopride specific binding reductions. In addition, the ratio of percent mean dopamine increase to percent mean striatal binding reduction for amphetamine (0.2 mg/kg) was 44:1, demonstrating that relatively small binding changes reflect large changes in dopamine outflow. In the clinical study, patients with schizophrenia (n = 11) compared with healthy volunteers (n = 12) had significantly greater amphetamine-related reductions in [11C]raclopride specific binding (mean +/- SEM): -22.3% (+/-2.7) vs. -15.5% (+/-1.8),P = 0.04, respectively. Inferences from the preclinical study suggest that the patients' elevation in synaptic dopamine concentrations was substantially greater than controls. These data provide direct evidence for the hypothesis of elevated amphetamine-induced synaptic dopamine concentrations in schizophrenia.

Amphetamine↗

Physical activity and physical fitness in African-American girls with and without obesity.

Lack of physical activity and low levels of physical fitness are thought to be contributing factors to the high prevalence of obesity in African-American girls. To examine this hypothesis, we compared habitual physical activity and physical fitness in 54 African-American girls with obesity and 96 African-American girls without obesity residing in rural South Carolina. Participation in vigorous (> or = 6 METs) (VPA) or moderate and vigorous physical activity (> or = 4 METs) (MVPA) was assessed on three consecutive days using the Previous Day Physical Activity Recall. Cardiorespiratory fitness was assessed using the PWC 170 cycle ergometer test. Upper body strength was determined at two sites via isometric cable tensiometer tests. Relative to their counterparts without obesity, girls with obesity reported significantly fewer 30-minute blocks of VPA (0.90 +/- 0.14 vs. 1.3 +/- 0.14) and MVPA (1.2 +/- 0.18 vs. 1.7 +/- 0.16) (p < 0.01). Within the entire sample, VPA and MVPA were inversely associated with body mass index (r = -0.17 and r = -0.19) and triceps skinfold thickness (r = -0.19 and r = -0.22) (p < 0.05). In the PWC 170 test and isometric strength tests, girls with obesity demonstrated absolute scores that were similar to, or greater than, those of girls without obesity; however, when scores were expressed relative to bodyweight, girls with obesity demonstrated significantly lower values (p < 0.05). The results support the hypothesis that lack of physical activity and low physical fitness are important contributing factors in the development and/or maintenance of obesity in African-American girls.

Black People↗

Correlates of physical activity behavior in rural youth.

The purpose of this study was to identify correlates of physical activity behavior in a sample of rural, predominantly African American youth. Three hundred sixty-one fifth-grade students from two rural counties in South Carolina (69% African American, median age = 11 years) completed a questionnaire designed to measure beliefs and social influences regarding physical activity, physical activity self-efficacy, perceived physical activity habits of family members and friends, and access to exercise and fitness equipment at home. After school physical activity and television watching were assessed using the Previous Day Physical Activity Recall (PDPAR). Students were classified as physically active according to a moderate physical activity standard: two or more 30-min blocks at an intensity of 3 METs (metabolic equivalents) or greater, and a vigorous physical activity standard: one or more 30-min blocks at an intensity of 6 METs or greater. According to the moderate physical activity standard, 34.9% of students were classified as low-active. Multivariate analysis revealed age, gender, television watching, and exercise equipment at home to be significant correlates of low activity status. According to the vigorous physical activity standard, 32.1% of the students were classified as low-active. Multivariate analysis revealed age, gender, television watching, and self-efficacy with respect to seeking support for physical activity to be significant correlates of low activity status. In summary, gender and the amount of television watching were found to be the most important correlates of physical activity in rural, predominantly African American youth.

Black or African American↗

Enhanced type 1alpha metabotropic glutamate receptor-stimulated phosphoinositide signaling after pertussis toxin treatment.

The regulation of phosphoinositide hydrolysis by the type 1alpha metabotropic glutamate receptor (mGluR1alpha) was investigated in stably transfected baby hamster kidney (BHK) cells. Incubation of the cells with L-glutamate, quisqualate, and 1-aminocyclopentane-1S, 3R-dicarboxylic acid resulted in a marked accumulation of [3H]inositol monophosphate (InsP1) and inositol-1,4,5-trisphosphate [Ins(1,4,5)P3] mass in a time- and concentration-dependent manner. Pretreatment of BHK-mGluR1alpha cells with pertussis toxin [ 100 ng/ml, 24 hr] led to a dramatic 12-16-fold increase in the accumulation of [3H]InsP1 and a 2-fold increase in Ins(1,4,5)P3 in the absence of added agonist. Although only very low levels (</=1 microM) of L-glutamate could be detected in medium taken from control and PTX-treated cell monolayers, the PTX-elicited effect on basal [3H]InsP1 was fully reversed by preincubation of cells in the presence of glutamic-pyruvic transaminase and pyruvate, suggesting that an increased sensitivity to endogenous glutamate was responsible for the apparent agonist-independent activation of phosphoinositidase C (PIC) after PTX treatment. Consistent with this hypothesis, in the presence of glutamic-pyruvic transaminase/pyruvate, the maximal [3H]InsP1 response to quisqualate was increased by >/=75%, and the EC50 shifted leftward by 65-fold [-log EC50 values (molar), 7.26 +/- 0.23 versus 5.45 +/- 0.07; n = 4) in PTX-treated compared with control cells. In contrast, antagonist effects on agonist-stimulated [3H]InsP1 responses were similar in control and PTX-treated BHK-mGluR1alpha cells. These changes in the concentration-effect curves for mGluR agonists are consistent with a model in which the receptor associates with PTX-sensitive inhibitory (Gi/o) and PTX-insensitive stimulatory (Gq/11) G proteins that can each influence PIC activity. The present observations are consistent with a dual regulation of mGluR1alpha-mediated PIC activity that could be fundamental in controlling the output of phosphoinositide-derived messengers.

Amino Acid Sequence↗

Prospective study of the value of necropsy examination in early death after cardiac surgery.

OBJECTIVE: To assess the value of necropsy examination in patients dying soon after cardiac surgery, particularly the proportion of clinical questions answered by the necropsy, the frequency of major unexpected findings, and the limitations of the procedure. DESIGN: A three year prospective study of necropsy examinations in adult patients dying before discharge or within 30 days of cardiac surgery performed under cardiopulmonary bypass in one hospital. SETTING: Tertiary referral centre. RESULTS: 123 of 2781 patients (4.4%) died in the early postoperative period, and necropsy examination was performed in 108 of these (88%). The mortality after emergency procedures (18%) was much higher than after routine operations (2.6%). The main causes of death were cardiac failure (52%), haemorrhage (14%), cerebral disease (6%), and pulmonary emboli (5%). The necropsy changed the stated cause of death in 16 patients (15%), and answered clinical questions in 24 of 38 patients. In 15 patients necropsy examination did not provide a full explanation of death. Most of these patients died of cardiac failure soon after surgery or were sudden unexpected deaths. CONCLUSIONS: Necropsy examination in patients dying early after cardiac surgery is valuable as it answers the majority of clinical questions, and shows unexpected findings in a significant proportion of cases.

Adult↗

Gender differences in physical activity and determinants of physical activity in rural fifth grade children.

This study determined if gender differences in physical activity could be accounted for by differences in selected social-cognitive determinants of activity behavior. Some 334 fifth grade, predominantly African-American students provided information regarding after-school physical activity and the hypothesized determinants of activity behavior. Boys reported significantly greater participation in vigorous ( > or = 6 METs) and in moderate to vigorous ( > or = 4 METs). Relative to girls, boys demonstrated higher levels of physical fitness, greater self-efficacy in overcoming barriers to physical activity, greater amounts of television watching, and higher levels of participation in community sports and physical activity organizations. When mean physical activity scores for girls and boys were adjusted for the effects of these determinant variables, the significant gender difference in physical activity remained. However, adjustment for self-efficacy in overcoming barriers and community sports reduced the gender gap by 5% and 7%, respectively. In contrast, adjustment for television watching increased the gender gap by about 8%. Results indicated perceived confidence in overcoming barriers to physical activity and participation in community physical activity programs are factors related to the gender difference in physical activity.

Child↗

Predictors of alcohol use among rural adolescents.

There is increasing evidence that alcohol use is becoming more common during childhood and early adolescence. However, little is known about alcohol use among rural youths. This article reports a study of alcohol use among 367 fifth-grade students in two rural South Carolina school districts. More than one third (n = 131) of the fifth graders reported having used alcohol. Of these, 34 percent (n = 44) reported drinking during the previous month; 8 percent had been intoxicated during the previous two months; and 54 percent reported drinking in the home with or without parental approval. Logistic regression analysis was used to determine the predictors of alcohol use by fifth graders. The results indicated that gender (OR = 2.82), mother's alcohol use (OR = 1.86), father's alcohol use (OR = 2.13), and smoking (OR = 8.30) were significantly associated with alcohol use. The findings suggest that prevention programs address cigarette smoking and drinking behaviors of parents to reduce alcohol use and the acquisition of other health compromising behavior by youths. Early intervention approaches must go beyond the schools and target families as well as community populations.

Adolescent↗

Peptidergic regulation of chromatophore function in the European cuttlefish Sepia officinalis

Color patterning in cephalopod molluscs involves activation of a peripheral chromatophore system that is under neuromuscular control. The complex behavior of individual chromatophores is mediated by a specific set of muscles, the chromatophore muscles, that receive direct innervation from the central nervous system. To date, glutamate is the only excitatory transmitter that has been proposed to act at the chromatophore neuromuscular junction of cephalopods. We present data demonstrating that the chromatophore muscles in the European cuttlefish Sepia officinalis are also regulated by the FMRFamide family of neuropeptides. Using an in vitro chromatophore bioassay, it has been determined that several FMRFamide-related peptides (FaRPs) are potent excitors of the chromatophore muscles, causing chromatophore expansion. Immunocytochemical analyses of the central nervous system using an FMRFamide antibody revealed the presence of FMRFamide-like immunoreactive cell bodies in the posterior chromatophore lobes, the region of the brain containing the chromatophore motoneurons of the fin and mantle. FMRFamide-like immunoreactivity was also seen in the periphery, in the nerves around the chromatophores and in close apposition to the muscles in the chromatophore layer of the fin. HPLC analysis of the fin dermis isolated four bioactive peaks that were FMRFamide-immunoreactive when tested on an immunoblot assay. Two of these peaks co-eluted with known FaRPs, FMRFamide and ALSGDAFLRFamide, a decapeptide isolated from squid. Taken together, these data suggest that the FaRPs are likely to be endogenous excitors of the chromatophore muscles in cephalopods.

Journal Article↗

Fibrin and fibrinogen degradation products with an intact D-domain C-terminal gamma chain inhibit an early step in accessory cell-dependent lymphocyte mitogenesis.

Although the low molecular weight degradation products of fibrinogen (FgDP) and fibrin (FbDP) are known to inhibit lymphocyte blastogenesis, the effect of purified macro-molecular FgDP and FbDP (molecular weight, 90 to 200 Kd) is unclear. We have examined the effect of these latter FgDP and FbDP and find that products that contain the D domain inhibit lymphocyte proliferation in response to T-cell mitogens, allogeneic mononuclear leukocytes, and anti-CD3 in vitro. Plasmic digestion of D1 in the absence of calcium with removal of the C-terminal end of the gamma chain or disruption of the gamma-gamma C-terminal cross-link site of D-dimer (DD) by puffadder venom (PAV-D) abrogates their inhibitory potential. Prior incubation of monocytes with DD or D1 inhibits subsequent lymphocyte transformation. Binding studies with radiolabeled DD and PAV-D confirm that monocytes interact only with DD. This specific binding may be competitively inhibited by monoclonal antibodies to CD11b/CD18 or by peptide analogues of the C-terminal gamma chain of fibrinogen that mimic the adhesion recognition site of integrins. We postulate that DD and D1 bind to CD11b/CD18 on adherent monocytes and modulate lymphocyte activation. These products are typically present in the plasma of patients with disseminated intravascular coagulation with sepsis and could therefore influence inflammatory processes in vivo.

Antigen-Presenting Cells↗

Sequences of genes encoding naphthalene dioxygenase in Pseudomonas putida strains G7 and NCIB 9816-4.

The multicomponent enzyme, naphthalene dioxygenase, initiates the metabolism of naphthalene by Pseudomonas putida strains G7 (PpG7) and NCIB 9816-4 (Pp9816-4). The genes involved (nahAaAbAcAd) are encoded by the NAH7 and pDTG1 plasmids, respectively, and form part of the nah operon. The locations of the structural genes were determined on previously cloned fragments of DNA. The nucleotide (nt) sequences were determined for nahAaAb from Pp9816-4 and for nahAaAbAcAd from PpG7. The appropriate open reading frames were identified using N-terminal amino acid sequences determined from the purified proteins. The two nt sequences showed 93% homology, with the least homology seen upstream from the promoter region.

Amino Acid Sequence↗

Strategic capital planning scenarios for the future.

Hospitals have traditionally looked to income from operations, depreciation, debt, and philanthropy as their major source of revenue. This viewpoint, however, is changing as hospitals move from being the hub of the healthcare provider network to being spokes in an integrated delivery network (IDN), and the traditional tools of debt financing and revenue optimizing become less effective.

Capital Financing↗