Differences In Activity Profiles Research Articles

Activity Profiles among Older Adults: Latent Class Analysis Using the Korean Time Use Survey.

This study empirically explored the activity profiles of Korean older adults by considering a wide range of activities simultaneously and further investigated the socioeconomic factors associated with activity profiles. Gender differences in activity profiles were examined in-depth. Latent class analysis (LCA) was used to identify activity profiles based on a nationally representative sample of older adults from the most recent two waves of the Korean Time Use Survey (n = 3034 for 2014 and n = 3960 for 2019). Multinomial logistic regression analysis was employed to further examine the factors associated with the activity profiles. The findings revealed four distinct activity groups, although there were differences in activity profiles between the two waves. Several sociodemographic factors, such as gender, age, assets and income, were significantly associated with the activity profiles. Findings from this study can inform policy makers seeking interventions that enhance the overall well-being of older adults through activity engagement.

The heterogeneity of European Higher Education Institutions: a configurational approach

ABSTRACT Classifications are a basic tool for research, which allow summarizing the diversity of objects in a number of categories that fits the cognitive abilities of the human mind. Their relevance for higher education is emphasized by the differentiation of institutional profiles. Yet, unlike in the US, there is currently no classification of European Higher Education Institutions (HEIs). This paper fills this gap by developing a classification of European HEIs, which focuses on differences in activity profiles and subject scope. To this aim, it uses data from an enriched version of the European Tertiary Education Register on a sample of more than 2000 HEIs in a large number of European countries. The classification comprises six classes that occupy distinct positions in a configuration space defined by two dimensions, i.e. research vs. educational orientation and subject specialization. Ex-post analysis shows that classes are identifiable and can be attributed meaningful labels; the class of research universities comprises most European HEIs competing in international rankings, while a class of generalist HEIs with lower research orientation that cuts across the traditional distinction between universities and Universities of Applied Sciences can be distinguished. Furthermore, three classes of specialist HEIs can be identified. The classification provides a meaningful representation of European higher education that is more fine-grained than the distinction between university and non-university sectors while remaining parsimonious. We, finally show how national categories map to the classification, displaying its potential to compare differences in national institutional settings across Europe.

Positional Demands and Physical Activity Profiles of Netball.

van Gogh, MJ, Wallace, LK, and Coutts, AJ. Positional demands and physical activity profiles of netball. J Strength Cond Res 34(5): 1422-1430, 2020-The aim of this study was to examine the activity profiles and physiological demands of netball. Eleven representative youth netball players participated in this study. Global positioning system, heart rate, and accelerometer data were collected during 8 competitive matches. Sport-specific skills were analyzed using notational methods. The main findings were that players traveled less distance during a match than previously reported. The center covered significantly greater distances than the other positions (p < 0.001). The goal shooter and goal keeper covered the least distance and endured lower accelerometer loads than other positions (p < 0.001). Very low levels of very high-speed running and sprint efforts were observed across all positions. The proportion of time spent in the high (>85% maximum heart rate [HRmax]) HR zone ranged from 7.0 to 62.6%, highlighting a high variation in cardiovascular demands between each position. The center and goal attack had the greatest cardiovascular demands spending significantly more time in the high (>85% HRmax) HR zone (p < 0.001). The goal shooter and goal keeper spent significantly more time in the low (<70% HRmax) HR zone (p < 0.001). Players in attacking positions were shown to pass/catch significantly more players than in defending positions (p < 0.001). Players in defending positions had higher number of deflections and intercepts compared with players in attacking positions (p < 0.001). These findings reveal significant positional differences in activity profiles and movement demands in netball. These data can be used to refine position-specific training practice and guide tactical strategies during competition.

Sensitivity of the Bacillus subtilis Xyn A Xylanase and Its Mutants to Different Xylanase Inhibitors Determines Their Activity Profile and Functionality during Bread Making.

The importance of inhibition sensitivity for xylanase functionality in bread making was investigated using mutants of the wild-type Bacillus subtilis xylanase (XBSTAXI), sensitive to Triticum aestivum xylanase inhibitor (TAXI). XBSNI, a mutant with reduced sensitivity to TAXI, and XBSTI, a mutant sensitive to all wheat endogenous proteinaceous inhibitors (TAXI, Xylanase Inhibiting Protein and Thaumatin-like Xylanase Inhibitor) were used. The higher inhibition sensitivity of XBSTAXI and XBSTI compared to XBSNI was associated with a respective 7- and 53-fold increase in enzyme dosage required for a maximal increase in bread loaf volume. XBSTI and XBSTAXI were only active during the mixing phase and the beginning of fermentation, while XBSNI was able to hydrolyze arabinoxylan until the end of fermentation. In spite of this difference in activity profile, no differences in loaf volume were observed for the different xylanases at optimal concentrations. Dough extensional viscosity analysis suggests that increased water availability as a result of xylanase activity favors starch-starch and starch-gluten interactions and drives the improvement in bread loaf volume.

Activity profiles of full-match and substitution players in the 2018 FIFA World Cup

ABSTRACT In order to better understand the intensity of match activities of full-match and substitution football players, running performance of 527 players who generated 1167 match observations in the 2018 FIFA World Cup were analysed. Differences in activity profiles between groups (1st and 2nd half full-match, early and late substitutes) were quantified by the generalised mixed linear modelling. Results showed that: (1) Full-match players presented trivial changes (ES: 0.09–0.20) in the time spent (% of total playing time) and distance (m/min) covered at high intensity but substantial descents (ES: 0.33–0.61) at moderate and low intensity from the 1st to the 2nd half. (2) Early substitutes achieved substantially higher (ES: 0.27–0.65) numbers in time spent and distance covered at high and moderate intensity, but lower (ES: 0.27–0.46) numbers in walking and jogging time and distance than 1st and 2nd half full-match players. (3) Late substitutes achieved substantially higher (ES: 0.28–1.26) numbers in time spent and distance covered at high and moderate intensity but substantially lower (ES: 0.39–1.06) numbers in top speed (km/h), walking and jogging time and distance than 1st and 2nd half full-match players and early substitutes. Results of this study could provide insights to the design of post-match conditioning sessions.

Abstract P422: Accelerometer-Determined Sedentary Time and Physical Activity Across Employment Status Categories in CARDIA

Prolonged sedentary behavior and insufficient physical activity is a common activity profile, especially in modern workplaces. Describing activity profiles by employment status groups could identify target populations for sedentary and activity intervention. Methods: This cross-sectional analysis of Year 20 CARDIA data (2005-6), included participants who had valid accelerometry data (≥4 days with ≥10 hours), reported occupational status, and were not currently a student (n=2,068). Uniaxial accelerometry data (ActiGraph 7164) were expressed in 60 second epochs and summarized as: average counts per minute (cpm) and time spent (min/day) in prolonged sedentary behavior (≥30 continuous minutes, SED ≥30 ), less than 30-minute bouts of sedentary behavior of (SED &lt;30 ), light physical activity (LPA), less than 10-minute bouts of moderate-to-vigorous physical activity of (MVPA &lt;10 ), and bouted MVPA (≥10 minutes, MVPA ≥10 ) using Freedson cutpoints. Employment status was self-reported as full-time, part-time, unemployed/looking for work, keeping house, or raising children. Omnibus group differences were analyzed using ANCOVA adjusted for sex, race, age, education, wear time, center, and BMI. Least square means of activity time across groups were calculated and standardized to population average wear time (14.8 hours). Results: Figure 1 shows activity profiles of employment groups rank ordered by cpm. Cpm and most types of activity differed modestly but significantly across employment groups, except for MVPA ≥10 . Unemployed participants had the highest cpm, the most MVPA ≥10 and SED ≥30 , but the least SED &lt;30 . Participants working part-time had the most MVPA &lt;10 . Full-time workers had the least LPA. Those raising children had the least SED ≥30 and MVPA ≥10 , but the most LPA. Participants keeping house had the least cpm and MVPA &lt;10 . Conclusions: Public health intervention programing could consider differences in activity profiles across employment status groups.

Activity Profiles by Position in Youth Elite Soccer Players in Official Matches.

In order to investigate activity profiles and external load patterns in elite youth soccer players, we studied high-intensity activity patterns, maximum running speed, and temporary and end-of-match decline in external load in 54 U17 players (96 match observations) over a full season of official match play.Wide midfielders covered most high-intensity running (HIR) distance (1044.2 m), most sprinting distance (224.4 m), and the highest number of accelerations (185.2); center defenders had the lowest values for these activities (508.3 m, 85.1 m, and 119.0), respectively. Wide midfielders had the highest and center defenders had the lowest maximum speed (30.3 km · h − 1 and 28.6 km · h − 1), respectively. During the matches, players in all playing positions displayed a significant drop in HIR distance, sprinting distance, and number of accelerations. This was especially pronounced in the 5 min following the 5-min peak period and in the last 5-min period for sprinting distance.There are substantial differences in activity profiles by positions, but all players show temporary and end-of-match drop in external load. The variation in activity profiles by playing position in this study may aid in the design of training programs. The considerable end-of-match drop in external load observed raises the question of the favorability of 90 min match times for U17 players.

The effects of urolithins on the response of prostate cancer cells to non-steroidal antiandrogen bicalutamide

BackgroundUrolithins are bioavailable products of gut microbiota metabolism of ellagitannins. Their biological activity includes anti-cancer effects. PurposeThe aim of this study was to explore the effects of urolithins on prostate cancer cells and activity of clinically used anti-androgen, bicalutamide. MethodsProstate cancer cells were treated with urolithin A, urolithin B, urolithin C or their combinations with bicalutamide. Cell proliferation was determined by DNA fluorescence with Hoechst 33258. The combination index method was used to examine interactions. Apoptosis and androgen receptor (AR) localization were analysed by flow cytometry. Prostate specific antigen (PSA) secretion was measured by ELISA. ResultsUrolithins inhibited proliferation of LNCaP prostate cancer cells. The mixtures of bicalutamide with uroA and uroB had additive anti-proliferative effect. All tested urolithins induced apoptosis of LNCaP cells. However, the combinations of bicalutamide with urolithin A and urolithin B had attenuated pro-apoptotic activity. UroA and uroC decreased DHT-induced PSA secretion. In contrast, uroB impaired PSA lowering effect of bicalutamide. UroA, individually and in combination with bicalutamide, promoted cytoplasmic localization of AR. ConclusionUrolithins might contribute to chemopreventive activity of ellagitannin rich preparations. Our results support use of ellagitannin rich preparations in prostate cancer chemoprevention, but advise caution in their potential use in complementary therapy of prostate cancer. The differences in activity profiles of urolithins indicate that possible health benefits and interactions will depend on the type of produced ellagitannins metabolite.

Gender Differences in the Association Between Leisure Activity in Adulthood and Cognitive Function in Old Age: A Prospective Longitudinal Population-Based Study.

ObjectivesTo examine the long-term association between leisure activities in adulthood and cognitive function in old age while recognizing gender differences in activity profiles.MethodsThe sample included 340 cognitively healthy twins enrolled in the OCTO-Twin Study, a longitudinal study on cognitive aging. Leisure activity was measured in midlife and cognitive function in old age (mean age 83). Leisure activities covered the domains of domestic, intellectual–cultural, and self-improvement activities. The cognitive assessments comprised 5 measurement occasions (2-year intervals) covering verbal ability, spatial ability, memory, and speed. The association between leisure activity and cognitive function was estimated separately for the genders using growth curve models, adjusting for age and education.ResultsMen and women had the same level of total leisure activity but differed in activity profiles and in the associations between activity and cognitive function. Higher engagement in self-improvement among men was related to higher level of cognitive functioning. Among women, intellectual–cultural activity was related to better verbal ability and memory. Concerning trajectories of cognitive function, domestic activity among men was related to less decline in speed, whereas for women it was related to steeper decline in spatial ability and memory. Further, higher intellectual–cultural activity among women was related to steeper decline in memory.DiscussionCognitively stimulating activities (i.e., self-improvement and intellectual–cultural), might increase cognitive reserve whereas less cognitively stimulating activities (i.e., domestic) do not. Gender differences should be considered when examining lifestyle factors in relation to cognitive aging.

Multiple Wearable Sensors in Parkinson and Huntington Disease Individuals: A Pilot Study in Clinic and at Home

Background: Clinician rating scales and patient-reported outcomes are the principal means of assessing motor symptoms in Parkinson disease and Huntington disease. However, these assessments are subjective and generally limited to episodic in-person visits. Wearable sensors can objectively and continuously measure motor features and could be valuable in clinical research and care. Methods: We recruited participants with Parkinson disease, Huntington disease, and prodromal Huntington disease (individuals who carry the genetic marker but do not yet exhibit symptoms of the disease), and controls to wear 5 accelerometer-based sensors on their chest and limbs for standardized in-clinic assessments and for 2 days at home. The study’s aims were to assess the feasibility of use of wearable sensors, to determine the activity (lying, sitting, standing, walking) of participants, and to survey participants on their experience. Results: Fifty-six individuals (16 with Parkinson disease, 15 with Huntington disease, 5 with prodromal Huntington disease, and 20 controls) were enrolled in the study. Data were successfully obtained from 99.3% (278/280) of sensors dispatched. On average, individuals with Huntington disease spent over 50% of the total time lying down, substantially more than individuals with prodromal Huntington disease (33%, p = 0.003), Parkinson disease (38%, p = 0.01), and controls (34%; p < 0.001). Most (86%) participants were “willing” or “very willing” to wear the sensors again. Conclusions: Among individuals with movement disorders, the use of wearable sensors in clinic and at home was feasible and well-received. These sensors can identify statistically significant differences in activity profiles between individuals with movement disorders and those without. In addition, continuous, objective monitoring can reveal disease characteristics not observed in clinic.

Insights into the structure-function relationship of Brugia malayi thymidylate kinase (BmTMK)

Lymphatic filariasis is a debilitating disease caused by lymph dwelling nematodal parasites like Wuchereria bancrofti, Brugia malayi and Brugia timori. Thymidylate kinase of B. malayi is a key enzyme in the de novo and salvage pathways for thymidine 5⿲-triphosphate (dTTP) synthesis. Therefore, B. malayi thymidylate kinase (BmTMK) is an essential enzyme for DNA biosynthesis and an important drug target to rein in filariasis. In the present study, the structural and functional changes associated with recombinant BmTMK, in the presence of protein denaturant GdnHCl, urea and pH were studied. GdnHCl and urea induced unfolding of BmTMK is non-cooperative and influence the functional property of the enzyme much lower than their Cm values. The study delineate that BmTMK is more prone to ionic perturbation. The dimeric assembly of BmTMK is an absolute requirement for enzymatic acitivity and any subtle change in dimeric conformation due to denaturation leads to loss of enzymatic activity. The pH induced changes on structure and activity suggests that selective modification of active site microenvironment pertains to difference in activity profile. This study also envisages that chemical moieties which acts by modulating oligomeric assembly, could be used for better designing of inhibitors against BmTMK enzyme.

Differences in the high speed match-play characteristics of rugby league players before, during and after a period of tramseridian transition

There is a paucity of information comparing competitive rugby league match play dynamics between northern and southern hemispheres. Notably, differences in the match demands of games played in an intensive period have not previously been reported. This study is the first to assess such demands, quantified using GPS/accelerometer technology, during a competitive three game period that comprised two games in England, interspersed with one game in Australia. The three games were completed over a period of 23 days. In-game data from fifteen elite level rugby league players were collected. The focus was to assess differences in activity profiles undertaken in each game. There were significant increases in the total number of high speed sprints, distance covered at high speed and acceleration/deceleration efforts undertaken in Australia when compared to England. No significant differences in other key performance indicators were observed. The current findings demonstrate minimal differences in the activity profiles of game play in elite professional rugby league, with the exception of high-speed activity and acceleration/deceleration efforts. The European team were defeated in their game in Australia, with clearly higher levels of total high speed sprints, acceleration and deceleration efforts being observed in that game when compared with games undertaken in England. Such findings emphasise the continuing use of GPS/accelerometer technologies in determining in-game performance characteristics associated with likely success, though the milieu of factors contributing to success must be considered in entirety.

Invited Commentary

Gruenwald and colleagues [1Gruenwald C.E. Manlhiot C. Abadilla A. et al.Heparin brand is associated with postsurgical outcomes in children undergoing cardiac surgery.Ann Thorac Surg. 2012; 93: 878-883Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar] have described a provocative association between the heparin brand used during pediatric cardiac operations, bleeding, and thromboembolism. Unfractionated heparin (UFH) is a heterogenous mixture of mucopolysaccharides of various molecular weights. About one-third of these molecules bind to antithrombin, vastly augmenting antithrombin-dependent inactivation of factors IIa (thrombin), IXa, Xa, XIa, and XIIa. Excess dosing or inadequate reversal may cause bleeding. Paradoxically, heparin can promote self-limiting platelet aggregation, but the rare, immunologic heparin-induced thrombocytopenia can be catastrophic. Heparin use, therefore, has been associated with adverse clinical outcomes, both hemorrhagic and thrombotic. This retrospective study compares a period when the authors exclusively used PPC heparin (Pharmaceutical Partners of Canada Inc, Richmond Hill, ON, Canada) with an earlier period using only Hepalean (Organon Teknika Corp, Durham, NC). Manufacturing problems affecting brand quality can alter clinical outcome [2Kishimoto T.K. Viswanathan K. Ganguly T. et al.Contaminated heparin associated with adverse clinical events and activation of the contact system.N Engl J Med. 2008; 358: 2457-2467Crossref PubMed Scopus (538) Google Scholar], but although PPC announced in January 2007 that latex had been removed from their heparin product [3Pharmaceutical Partners of Canada IncHeparin line now complete.http://ppcdrugs.com/en/news-june1b-07.phpGoogle Scholar], this is likely unrelated because study findings are not typical manifestations of latex allergy. Differences in activity profile or immunogenicity between the PPC and Hepalean (both porcine [4Francis J.L. Palmer 3rd, G.J. Moroose R. Drexler A. Comparison of bovine and porcine heparin in heparin antibody formation after cardiac surgery.Ann Thorac Surg. 2003; 75: 17-22Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar]) would be a more likely mechanism. An in vitro or in vivo evaluation of drug potency and adequacy of reversal [5Gruenwald C.E. Manlhiot C. Chan A.K. et al.Randomized, controlled trial of individualized heparin and protamine management in infants undergoing cardiac surgery with cardiopulmonary bypass.J Am Coll Cardiol. 2010; 56: 1794-1802Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar] or the development of heparin-induced thrombocytopenia antibodies may have helped explain the findings of increased bleeding and thromboembolism associated with the PPC heparin brand. Readers should always consider the limitations of a retrospective analysis, which determines association, not causation, as confounding factors are only partially addressed by model adjustment. In this study, there are too few binary outcome events (bleeding, thromboembolism, and reoperation) to support logistic regression analysis with 12 covariates, according to the general “rule-of-thumb” of 10 outcomes per covariate [6Peduzzi P. Concato J. Kemper E. Holford T.R. Feinstein A.R. A simulation study of the number of events per variable in logistic regression analysis.J Clin Epidemiol. 1996; 49: 1373-1379Abstract Full Text PDF PubMed Scopus (5038) Google Scholar], and details of the multivariate models are not provided. We encourage authors to carefully explain crucial model development steps, especially in retrospective analyses. However, this study was used to generate a hypothesis now being evaluated prospectively, a laudable example of an appropriate application of retrospective data. McMaster University is listed as sponsoring a prospective, randomized study [7ClinicalTrials.govComparison of heparin types; efficacy and safety.http://clinicaltrials.gov/ct2/show/NCT01343381Google Scholar] testing the anticoagulant effect and reversal of the two brands of heparin discussed here. We eagerly await the results. Heparin Brand Is Associated With Postsurgical Outcomes in Children Undergoing Cardiac SurgeryThe Annals of Thoracic SurgeryVol. 93Issue 3PreviewWe sought to determine whether the use of specific unfractionated heparin brands during cardiopulmonary bypass for pediatric cardiac surgery was associated with differences in postoperative outcomes, especially regarding the incidence of bleeding and thromboembolic complications. Full-Text PDF

Discrimination between the enzymatic activities of Candida albicans pleomorphic forms determined using the api® ZYM test

Enzymatic activity profiles for two morphotypes of 37 Candida albicans clinical isolates were compared. Yeast and hyphal forms were grown using yeast extract-peptone-glucose broth or undiluted human serum, respectively. Both morphotypes were documented under scanning electron microscopy. The api(®) ZYM (BioMérieux, France) test was used to evaluate the enzymatic activity profiles for particular pleomorphic forms. None of the examined enzymatic activities showed good agreement (kappa, κ > 0.80) for the two morphotypes of the tested strains. Only leucine arylamidase activity in blastoconidia and hyphae of 35 out of 37 strains appeared to be in significant agreement (κ = 0.770). This phenomenon should be explored further for clinical benefits. For morphotypes of all tested strains, activity profiles of 11 hydrolytic enzymes demonstrated weak agreement (κ = 0.044-0.197). Moreover, satisfactory (κ = 0.218-0.348) and moderate agreement (κ = 0.413-0.479) were noted for enzymatic activity values of five and two enzymes, respectively. The distinct differences in activity profiles of hydrolytic enzymes between hyphae and blastoconidia is suggested to be related to the specific roles of these two morphotypes in particular steps of pathogenesis. Moreover, both morphotypes should be examined by strain biotyping methods. Beta-N-hexosaminidase (HexNAcase) activity assessed by the api(®) ZYM test and on CHROMagar Candida(®) medium (Becton Dickinson, USA) is also discussed.

Developmental Activities That Contribute to High or Low Performance by Elite Cricket Batters When Recognizing Type of Delivery From Bowlers’ Advanced Postural Cues

We examined the developmental activities that contribute to the development of superior anticipation skill among elite cricket batters. The batters viewed 36 video clips involving deliveries from bowlers that were occluded at ball release and were required to predict delivery type. Accuracy scores were used to create two subgroups: high-performing and low-performing anticipators. Questionnaires were used to record the participation history profiles of the groups. In the early stages of development, hours accumulated in cricket and other sports, as well as milestones achieved, did not differentiate groups. Significant between-group differences in activity profiles were found between 13 and 15 years of age, with high-performing anticipators accumulating more hours in structured cricket activity, and specifically in batting, compared with their low-performing counterparts.

Abstract 1651: The use of ‘X-MAN’ isogenic cell lines to define PI3-kinase inhibitor activity profiles

Abstract The tumour microenvironment promotes selective outgrowth of cells carrying mutations in oncogenes or tumour suppressors, enabling the activated pathways to drive tumour growth. Two such pathways are the PI3-K/AKT and RAS/RAF/MEK signaling pathways, which demonstrate a high frequency of mutations in human cancer. These pathways represent important therapeutic targets, and a number of targeted agents are now in clinical trials. Despite being pertinent to the clinical situation, the role that the tumour microenvironment plays in modifying responsiveness to therapeutic agents targeted against these pathways is poorly understood. A major challenge faced during the development of PI3-K/AKT and RAS/RAF/MEK targeted agents is to demonstrate inhibitor selectivity and efficacy in a patient-relevant cell based system. Isogenic ‘X-MAN’ paired cell lines help address this by providing a system in which the endogenous wild-type or mutant alleles of the parental cell line are selectively activated or silenced via targeted homologous integration, providing a pair of human cell-lines in which the only difference between the cells is the mutation of interest. This approach therefore overcomes the issues that may occur when over-expression methods are employed. We therefore set out to investigate how changes in the tumour microenvironment altered cell responses to PI3-K and MEK inhibitors. We employed isogenic HCT116 human colon cancer cells where the parental cells harbor pre-existing H1047R PIK3CA and G13D KRAS alleles and compared these to isogenic clones that retain either the PIK3CA or KRAS wild-type alleles. Inhibitors were profiled under a range of defined conditions chosen to model the tumour microenvironment, including low glucose, low serum and hypoxia, and the activity of the compounds investigated. Under standard culture conditions, we found that PI3-K and MEK inhibitors showed minimal selectivity for cells with activating mutations compared to wild-type cells. When grown under defined culture conditions which more closely mimic the tumour microenvironment, the effects of the driving mutations became dominant and a differential between wild-type and mutant cell responses to inhibitors was observed. The selective PI3-K inhibitors GDC-0941 and PI-103 showed a &amp;gt;10-fold increase in potency when tested in anti-proliferative assays in mutant vs, wild-type cell lines. However, the dual PI3-K/mTOR inhibitor BEZ-235 did not show selectivity in this system. We show that by using isogenic cell lines under conditions which model the tumour microenvironment, differences in activity profiles between specific inhibitors can be quickly and definitively identified, highlighting the advantages of using this system in profiling molecularly targeted agents. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1651.

Neural Mechanisms Underlying Learning Following Semantic Mediation Treatment in a Case of Phonologic Alexia

Patients with phonologic alexia can be trained to read semantically impoverished words (e.g., functors) by pairing them with phonologically-related semantically rich words (e.g, nouns). What mechanisms underlie success in this cognitive re-training approach? Does the mechanism change if the skill is "overlearned", i.e., practiced beyond criterion? We utilized fMRI pre- and post-treatment, and after overlearning, to assess treatment-related functional reorganization in a patient with phonologic alexia, two years post left temporoparietal stroke. Pre-treatment, there were no statistically significant differences in activation profiles across the sets of words. Post-treatment, accuracy on the two trained sets improved. Compared with untrained words, reading trained words recruited larger and more significant clusters of activation in the right hemisphere, including right inferior frontal and inferior parietal cortex. Post-overlearning, with near normal performance on overlearned words, predominant activation shifted to left hemisphere regions, including perilesional activation in superior parietal lobe, when reading overlearned vs. untrained words.

Inhibition of PKC activity blocks the increase of ETB receptor expression in cerebral arteries

BackgroundPrevious studies have shown that there is a time-dependent upregulation of contractile endothelin B (ETB) receptors in middle cerebral arteries (MCA) after organ culture. This upregulation is dependent on mitogen-activated protein kinases and possibly protein kinase C (PKC). The aim of this study was to examine the effect of PKC inhibitors with different profiles on the upregulation of contractile ETB receptors in rat MCA. Artery segments were incubated for 24 hours at 37°C. To investigate involvement of PKC, inhibitors were added to the medium before incubation. The contractile endothelin-mediated responses were measured and real-time PCR was used to detect endothelin receptor mRNA levels. Furthermore, immunohistochemistry was used to demonstrate the ETB receptor protein distribution in the MCA and Western blot to measure which of the PKC subtypes that were affected by the inhibitors.ResultsThe PKC inhibitors bisindolylmaleimide I, Ro-32-0432 and PKC inhibitor 20–28 attenuated the ETB receptor mediated contractions. Furthermore, Ro-32-0432 and bisindolylmaleimide I decreased ETB receptor mRNA levels while PKC inhibitor 20–28 reduced the amount of receptor protein on smooth muscle cells. PKC inhibitor 20–28 also decreased the protein levels of the five PKC subtypes studied (α, βI, γ, δ and ε).ConclusionThe results show that PKC inhibitors are able to decrease the ETB receptor contraction and expression in MCA smooth muscle cells following organ culture. The PKC inhibitor 20–28 affects the protein levels, while Ro-32-0432 and bisindolylmaleimide I affect the mRNA levels, suggesting differences in activity profile. Since ETB receptor upregulation is seen in cerebral ischemia, the results of the present study provide a way to interfere with the vascular involvement in cerebral ischemia.

Correlations between the activities of 19 anti-tumor agents and the intracellular glutathione concentrations in a panel of 14 human cancer cell lines: comparisons with the National Cancer Institute data

The aim of this work was 2-fold: (i) to identify correlations between the activities of pairs of 19 anti-tumor agents in a mini-panel of 14 human cancer cell lines of diverse origins with the goal of validating the panel, and (ii) to look for correlations between the activities of 19 standard anti-tumor agents and the intracellular concentrations of glutathione (GSH). Validation with analogous data from the National Cancer Institute (NCI) Developmental Therapeutics Program was made. The cell growth inhibition potencies of the anti-tumor agents [cisplatin, carboplatin, oxaliplatin, DACH-Pt, melphalan, chlorambucil, thiotepa, busulfan, doxorubicin, etoposide, camptothecin, vinblastine, podophyllotoxin, colchicine, taxol, hydroxyurea, methotrexate, 5-azacytidine and 5-fluorouracil (5-FU)] were estimated in 14 cancer cell lines by their GI50 values. An enzymatic assay based on the method of Tietze was employed to measure intracellular total GSH concentrations. The Delta method was used to compare pairs of anti-tumor agents; similarities and differences in activity profiles (mean graphs) were evaluated by regression analysis. Most, but not all, of the correlations could be explained based on similarities in the mechanisms of action and many correlations/non-correlations were also observed in the NCI data. Some correlations were unexpected however, and not seen in the NCI data. For example, strong positive correlations (P < 0.01) were found between the GI50 values of melphalan/chlorambucil and the anti-mitotic agents. Similarly unexpected, a strong positive correlation was observed between methotrexate and cisplatin (P < 0.01). Interestingly, moderate to strong negative correlations (P < 0.01-0.05) were found between the GI50 values of 5-FU and the anti-mitotic agents/melphalan/chlorambucil. Significant positive correlations between intracellular GSH concentrations and GI50 values were found only for thiotepa (P < 0.05) and doxorubicin (P < 0.01). Data from a NCI panel of 34 cancer cell lines showed no correlations between GSH levels and the GI50 values of the same 19 compounds. In conclusion, a panel of 14 human cancer cell lines of diverse origin was used to identify similarities and differences in the activities of standard anti-tumor agents. The level of significance was stronger with the 34 cell lines of the NCI, however. Our results indicate that GSH intracellular concentrations correlate with resistance only with doxorubicin and thiotepa in these cell lines.

Interleukin‐6 inhibits cell proliferation in a rat model of hepatocellular carcinoma

Interleukin-6 (IL-6) plays a critical role in normal hepatic growth and liver regeneration. The aims of the present study are to determine the expression of components of IL-6 signaling in an in vivo model of hepatocellular carcinoma (HCC) and address the role of IL-6 signaling in the progression of HCC. An in vivo rat HCC model was established and IL-6 receptor (IL-6R) and downstream signaling pathway expression and activity were determined in HCC and normal liver specimens. Tumorigenic HCC cells from resected HCC samples and normal hepatocytes were then isolated and cultured in the presence and absence of recombinant human IL-6 (rhIL-6). HCC specimens demonstrated decreased IL-6Ralpha/gp130 expression as compared with the normal liver. In contrast, HCC samples had significantly increased IL-6 messenger RNA expression and signal transducers and activators of transcription (STAT)3 activity. Using in vitro cell cultures, we demonstrated that IL-6 stimulated STAT3 and extracellular regulated kinase (ERK) activity in both HCC cells and isolated hepatocytes. However, while STAT3 activation profiles were similar, IL-6 stimulated ERK activity in a biphasic manner in HCC cells and a monophasic, sustained ERK activation in hepatocytes. In HCC cells, a significant induction of cyclin-dependent kinase (CDK) inhibitors, p21(waf1/cip1) and p27(Kip1) occurred, an effect that was not observed in normal hepatocytes. Finally, we established that IL-6 acted to inhibit serum-stimulated DNA synthesis and cell mitogenesis in HCC cells in vitro. These data demonstrate altered expression of components of IL-6 signaling in HCC in vivo. IL-6 treatment of HCC cells inhibits serum-stimulated mitogenesis, possibly via differences in activation profiles of intracellular signaling pathways and their effect on CDK inhibitor expression/activity.