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Rational Basis (rational + basis)
Selected AbstractsSolenoidal microcoil design,Part II: Optimizing winding parameters for maximum signal-to-noise performanceCONCEPTS IN MAGNETIC RESONANCE, Issue 3 2001Kevin R. Minard Abstract In high-field proton NMR, the signal-to-noise ratio (SNR) achieved with a close-fitting solenoidal microcoil is adversely affected by radio frequency (RF) losses in the coil, its leads, the capacitor used to tune it, and finally, the sample. In Part II, a rigorous description of these various losses is presented, and their severity is related to the details of coil design. Results not only provide a rational basis for defining a microcoil's optimal wire diameter and the number of turns, but also for evaluating how the SNR varies with coil size and NMR frequency in high-field proton NMR studies involving either conducting or non-conducting samples. © 2001 John Wiley & Sons, Inc. Concepts Magn Reson 13: 190,210, 2001 [source] Post-stroke depression, executive dysfunction and functional outcomeEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2002T. Pohjasvaara The early diagnosis of vascular cognitive impairment has been challenged and executive control function has been suggested to be a rational basis for the diagnosis of vascular dementia. We sought to examine the correlates of executive dysfunction in a well-defined stroke cohort. A group of 256 patients from a consecutive cohort of 486 patients with ischaemic stroke, aged 55,85 years, was subjected to a comprehensive neuropsychological examination 3,4 months after ischaemic stroke and 188 of them in addition to detailed psychiatric examination. Basic and complex activities of daily living (ADLs) (bADLs and cADLs) post-stroke were assessed. The DSM-III-R criteria were used for the diagnosis of the depressive disorders. Altogether 40.6% (n=104) of the patients had executive dysfunction. The patients with executive dysfunction were older, had lower level of education, were more often dependent, did worse in bADLs and cADLs, had more often DSM-III dementia, had worse cognition as measured by Mini Mental State Examination (MMSE) and were more depressed as measured by the BECK depression scale, but not with the more detailed psychiatric evaluation. They had more often stroke in the anterior circulation and less often in the posterior circulation. The independent correlates of executive dysfunction were cADLs (OR 1.1, 95% CI 1.03,1.16), each point of worsening in cognition by MMSE (OR 1.7, 95% CI 1.42,1.97) and stroke in the posterior circulation area (OR 0.4, 95% CI 0.18,0.84). Clinically significant executive dysfunction is frequent after ischaemic stroke and is closely connected with cADLs and to overall cognitive status but could be distinguished from depression by detailed neuropsychological examination. Executive measures may detect patients at risk of dementia and disability post-stroke. [source] Suspended sediment dynamics in a steep, glacier-fed mountain stream, Place Creek, CanadaHYDROLOGICAL PROCESSES, Issue 9 2003G. Richards Abstract This study examined suspended sediment concentration (SSC) during the ablation seasons of 2000 and 2001 in Place Creek, Canada, a steep, glacier-fed mountain stream. Comparison of stream flow in Place Creek with that in an adjacent, almost unglacierized catchment provided a rational basis for separating the ablation seasons into nival, nival,glacial, glacial and autumn recession subseasons. Distinct groupings of points in plots of electrical conductivity against discharge supported the validity of the subseasonal divisions in terms of varying hydrological conditions. Relationships between SSC and discharge (Q) varied between the two study seasons, and between subseasons. Hysteresis in the SSC,Q relationship was evident at both event and weekly time-scales. Some suspended sediment released from pro-glacial Place Lake (the source of Place Creek) appeared to be lost to channel storage at low flows, especially early in the ablation season, with re-entrainment at higher flows. Multiple regression models were derived for the subseasons using predictor variables including Q, Q2, the change in Q over the previous 3 h, cumulative discharge over the ablation season, total precipitation over the previous 24 h and SSC measured at 1500 hours as an index value for each day. The models produced adjusted R2 values ranging from 0·71 to 0·91, and provided tentative insights into the differences in SSC dynamics amongst subseasons. Introduction of the index value of SSC significantly improved the model fit during the nival,glacial and glacial subseasons for both years, as it adjusts the model to the current condition of sediment supply. Copyright © 2003 John Wiley & Sons, Ltd. [source] Constructing life-tables for the invasive maize pest Diabrotica virgifera virgifera (Col.; Chrysomelidae) in EuropeJOURNAL OF APPLIED ENTOMOLOGY, Issue 4 2006S. Toepfer Abstract:, The western corn rootworm (Diabrotica virgifera virgifera LeConte, Col.; Chrysomelidae) is an alien invasive species in Europe. It is a univoltine species with eggs that overwinter in the soil and larvae that hatch in spring. Three larval instars feed on maize roots, which can cause plant lodging and yield loss of economic importance. Adults emerge between mid-June and early August and can reduce yields through intensive silk feeding. In order to provide a thorough understanding of the population dynamics of this invasive pest species in the invaded European region, complete age specific life-tables were constructed in two maize fields in southern Hungary assessing the significance of natural mortality factors acting on D. v. virgifera populations. This information provides a rational basis for devising sustainable integrated pest management programmes, in particular, by enabling the identification of vulnerable pest age intervals for the timely application of various management tools. The life-table for D. v. virgifera in Europe resulted in a total mortality of about 99% from the egg stage in the autumn to the emergence of adult females in the following year (KTotal = 2.48), which is comparable with North America. The highest reduction of D. v. virgifera numbers resulted from the mortality in first instar larvae (94% marginal death rate) and from the unrealized fecundity (80%). However, only the variation in mortality between years can change the generational mortality and thus influence population growth. High variation in the marginal death rate between fields and years was found in the second and third instar larval stages, and in the overwintering egg stage. These mortality factors therefore have the potential to cause changes in the total generational mortality. Furthermore, the life-table suggested that a high fecundity could compensate for a high generational mortality and would lead to population increase. [source] A two-phase analysis of solute partitioning into the stratum corneumJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2006Johannes M. Nitsche Abstract An analysis is presented of partition coefficients KSC/w describing solute distribution into fully hydrated stratum corneum (SC) from dilute aqueous solution (w). A comprehensive database is compiled from the experimental literature covering more than eight decades in the octanol/water partition coefficient Ko/w. It is analyzed according to a two-phase model following that of Anderson, Raykar, and coworkers (1988, 1989), which accounts for uptake by intercellular lipid and corneocyte (keratin plus water) phases having inherently different lipophilicities, as characterized by an SC lipid/water partition coefficient Klip/w and a partition coefficient PCpro/w quantifying cornoeocyte-phase binding. Regression of 72 data points yields useful best-fit recalibrations of power laws (or linear free energy relationships) giving Klip/w and PCpro/w as functions of Ko/w. The specific conclusions of the analysis are as follows: (i) The two-phase model offers substantial improvements over previously proposed analytical representations of KSC/w, yielding an rms error in log10KSC/w of 0.30 limited by the scatter in the data. (ii) The best-fit description of the lipid phase is given by the power law Klip/w,=,0.43 (Ko/w)0.81, suggesting about half the absolute value of Klip/w relative to previous estimates. (iii) The best-fit description of corneocyte-phase binding differs negligibly from the correlation found by Anderson, Raykar, and coworkers for the more limited set of compounds studied by them. Explicit consideration of the two-phase nature of the SC also furnishes a rational basis for predicting the effects of varying hydration state upon KSC/w. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:649,666, 2006 [source] Stepping out of the box: broadening the dialogue around the organizational implementation of cognitive behavioural psychotherapyJOURNAL OF PSYCHIATRIC & MENTAL HEALTH NURSING, Issue 4 2005J. POOLE ba dip nursing (mh) The dissemination and uptake of cognitive behavioural interventions is central to the evidence-based mental health agenda in Britain. However, some policy and related literature, in and of itself social constructed, tends to display discursive naïvety in assuming a rational basis for the dissemination and organizational integration of cognitive behavioural approaches. Rational constructions fail to acknowledge that the practice settings of key stakeholders in the process are likely to be socially constructed fields of multiple meanings. Within these, the importance of evidence-based interventions may be variously contested or reworked. To illustrate this, a case example from the first author will discuss the hypothetical introduction of a cognitive behavioural group for voice hearers in a forensic mental health unit. This will highlight contradictions and local organizational problems around the effective utilization of postgraduate cognitive behavioural knowledge and skills. A synthesis of social constructionist with organizational theory will be used to make better sense of these actual and anticipated difficulties. From this basis, specific ways in which nurses and supportive stakeholders could move the implementation of cognitive behavioural psychotherapy agenda forward within a postmodern leadership context will be proposed. [source] Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudateJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2002F. SHOJAEE ALIABADI Aliabadi, F. S., Lees, P. Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate. J. vet. Pharmacol. Therap.25, 161,174. Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections. In this investigation the pharmacokinetics (PK) of marbofloxacin were determined after intravenous and intramuscular dosing at a dosage of 2 mg/kg. In addition the ex vivo pharmacodynamics (PD) of the drug were determined in serum and three types of tissue cage fluid (transudate, inflammatory exudate generated by carrageenan and exudate generated by lipopolysaccharide). Marbofloxacin PK was characterized by a high volume of distribution after dosing by both routes (1.28 L/kg intravenous and 1.25 L/kg intramuscular). Corresponding area under the concentration,time curve (AUC) and elimination half-life (t½el) values were 9.99 and 10.11 ,g h/mL and 4.23 and 4.33 h, respectively. Values of AUC for carrageenan-induced exudate, lipopolysaccharide-induced exudate and transudate were, respectively, 8.28, 7.83 and 7.75 ,g h/mL after intravenous and 8.84, 8.53 and 8.52 ,g h/mL after intramuscular dosing. Maximum concentration (Cmax) values were similar for the three tissue cage fluids after intravenous and intramuscular dosing. For in vivo PK data values of AUC: minimum inhibitory concentration (MIC) (AUIC) ratio for serum were 250 and 253, respectively, after intravenous and intramuscular dosing of marbofloxacin against a pathogenic strain of Mannheimia haemolytica (MIC=0.04 ,g/mL). For all tissue cage fluids AUIC values were >194 and >213 after intravenous and intramuscular dosing, and Cmax/MIC ratios were 9 or greater, indicating a likely high level of effectiveness in clinical infections caused by M. haemolytica of MIC 0.04 ,g/mL or less. This was confirmed by both in vitro (serum) and ex vivo (serum, exudate and transudate) measurements, which demonstrated a concentration-dependent killing profile for marbofloxacin against M. haemolytica. Ex vivo, after 24-h incubation, virtually all bacteria were killed (<10 cfu/mL) in all samples collected up to 9 h (serum), 24 h (carrageenan-induced exudate and transudate) and 36 h (lipopolysaccharide-induced exudate). Application of the sigmoid Emax equation to the ex vivo antibacterial data provided, for serum, AUIC24 h values of 37.1 for bacteriostasis, 46.3 for bactericidal activity and 119.6 for elimination of bacteria. These data may be used as a rational basis for setting dosing schedules which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms. [source] Profiling human gut bacterial metabolism and its kinetics using [U- 13C]glucose and NMRNMR IN BIOMEDICINE, Issue 1 2010Albert A. de Graaf Abstract This study introduces a stable-isotope metabolic approach employing [U- 13C]glucose that, as a novelty, allows selective profiling of the human intestinal microbial metabolic products of carbohydrate food components, as well as the measurement of the kinetics of their formation pathways, in a single experiment. A well-established, validated in vitro model of human intestinal fermentation was inoculated with standardized gastrointestinal microbiota from volunteers. After culture stabilization, [U- 13C]glucose was added as an isotopically labeled metabolic precursor. System lumen and dialysate samples were taken at regular intervals. Metabolite concentrations and isotopic labeling were determined by NMR, GC, and enzymatic methods. The main microbial metabolites were lactate, acetate, butyrate, formate, ethanol, and glycerol. They together accounted for a 13C recovery rate as high as 91.2%. Using an NMR chemical shift prediction approach, several minor products that showed 13C incorporation were identified as organic acids, amino acids, and various alcohols. Using computer modeling of the 12C contents and 13C labeling kinetics, the metabolic fluxes in the gut microbial pathways for synthesis of lactate, formate, acetate, and butyrate were determined separately for glucose and unlabeled background substrates. This novel approach enables the study of the modulation of human intestinal function by single nutrients, providing a new rational basis for achieving control of the short-chain fatty acids profile by manipulating substrate and microbiota composition in a purposeful manner. Copyright © 2009 John Wiley & Sons, Ltd. [source] A simple and effective model for cross-flow microfiltration and ultrafiltrationTHE CANADIAN JOURNAL OF CHEMICAL ENGINEERING, Issue 1 2002Anais (Alice) A. Makardij Abstract A semi-theoretical unsteady-state model for the flux in cross-flow microfiltration and ultrafiltration has been developed. The model predicts fouling behaviour for a wide range of particle sizes and foulant concentrations. The developed model uses only two coefficients, k1 and k2, incorporating both the influences of the cake formation and the shear cleaning of the membrane, to describe flux decline. These two parameters were found to be almost independent of the operating conditions. The model provides both a fundamental understanding of the key physical phenomena governing flux decline and a rational basis for the design of an improved and modified cross flow filters. Un modèle semi-théorique à l'état non permanent a été mis au point pour les écoulements en microfiltration tangentielle et en ultrafiltration. Le modèle prédit le comportement d'encrassement pour une large gamme de tailles de particules et de concentrations des salissures. Ce modèle emploie seulement deux coefficients, k1 et k2, incorporant les influences de la formation du gåteau et le nettoyage par cisaillement de la membrane, afin de décrire le déclin du flux. Ces deux paramètres s'avèrent quasi indépendants des conditions opératoires. Le modèle permet une compréhension fondamentale des principaux phénomènes physiques qui gouvernent le déclin du flux et fournit une base rationnelle en vue de la conception de filtres tangentiels améliorés et modifiés. [source] The capacity to be an analyst: A contribution from attachment research to the study of candidate selectionTHE INTERNATIONAL JOURNAL OF PSYCHOANALYSIS, Issue 6 2003Janice Halpern In this paper the author discusses how the study of candidate selection, once a topic of vibrant research, has unfortunately languished. Certain qualities were thought to characterize the successful candidate. However, they were never successfully operationalized nor empirically tested. Possibly because of this lack of empirical data, selectors today have difficulty articulating their criteria and are relying on intuition. In order to provide a more rational basis for contemporary selection, the author looks to the attachment literature. This makes sense because attachment theory shares some basic assumptions of contemporary psychoanalysis. The Adult Attachment Interview (AAI) is a research tool that predicts the ability of a parent to convey attachment security. It is scored by attending to how a person speaks about his early attachment experiences. The AAI appears to tap into similar qualities to those selection researchers have sought in their candidates. Further, the scoring method of the AAI appears to be similar to the last attempt by selection researchers to operationalize them. Given these similarities, the author recommends an empirical study using the AAI to operationalize these qualities in analytic candidates. The study would test their importance for success in the training program, thus offering selectors some empirical grounding for their choices. [source] Differential Classification of Acute Myocardial Infarction into ST- and Non-ST Segment Elevation Is Not Valid or RationalANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2010Brendan Phibbs M.D., F.A.C.C. Background: The distinction between ST elevation and nonST elevation infarcts is widely accepted and is employed as a guide to management. Aim: This is review of the world literature to assess the basis for this distinction, since the two studies on which it is based are seriously flawed in method and conclusions. Method: Pathologic and clinical studies were reviewed from the world literature. Finding: The pathology of the two subsets is identical as are the morbidity, mortality and clinical course. Non-ST elevation infarcts are likely to be subsequent, to occur in older patients and to involve the circumflex artery: this subset therefore includes a high-risk group. ST deviation in any part of the electric field of the heart will predictably be accompanied by reciprocal deviation if the entire field of the heart is mapped. Further, ST deviation of infarction is often transient, resolving in minutes so that infarcts will be predictably misclassified. ST deviation per se is therefore not a rational basis for classification of infarcts. In fact, invasive therapy is indicated in both subsets with identical results. Conclusion: The distinction between ST elevation and non-ST elevation infarcts is baseless. The high risk subgroup included in the non-ST elevation infarct set should not be denied the benefit of early invasive therapy. Ann Noninvasive Electrocardiol 2010;15(3):191,199 [source] CT31 HYPERBARIC OXYGEN IN POST-CARDIAC SURGERY STROKE PATIENTS , THE CHRISTCHURCH EXPERIENCEANZ JOURNAL OF SURGERY, Issue 2007A. J. Gibson Introduction Post-operative strokes occur in a small percentage of adult cardiac surgical patients and have devastating consequences for these patients. There is evidence to suggest that Cerebral Arterial Gas Embolism (CAGE) is an important aetiological factor in most of these cases. Hyperbaric Oxygen therapy (HBOT) is the administration of 100% oxygen at greater than atmospheric pressure. It is accepted as the definitive treatment for CAGE related to SCUBA diving accidents. The similarities between this and the pathophysiology of post cardiac-surgical strokes due to iatrogenic CAGE suggest that beneficial effects from HBOT may accrue to these patients. Purpose The purpose of this study is to review the experience of treating post cardiac-surgical stroke patients in our local hyperbaric oxygen facility, including their presentation, delay before treatment and outcomes. The current evidence base is reviewed. Method A retrospective case series analysis was conducted. Results Over a 10 year period, patients with post cardiac-surgical strokes and who presented within the first 48 hours were referred for HBOT, of whom 12 were treated. The neurological outcomes were excellent in all but one case who died. A review of the literature provides a rational basis for the potential benefits of HBOT in this scenario, but at present there is only limited clinical data to support its use. Conclusion The postulated mechanisms for the development of post cardiac-surgical strokes provide a sound theoretical basis for the suggestion that the use of HBOT is associated with improved outcomes. However there is no prospective data to support such a claim. Such a trial would be problematic and until more evidence is available, HBOT should be considered on a case by case basis. [source] Hepatitis C virus infection rates and risk factors in an Australian hospital endoscopy cohortAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 5 2009Karen Vickery Abstract Objective: To determine the reservoir and risk factors of HCV infection in a hospital population. Methods: The presence of anti-HCV in 2,119 endoscopy patients was related to putative risk factors for exposure using the SAS statistical package. Results: Most of the 4.7% of anti-HCV positive patients had multiple risk factors for HCV exposure. The risk was significantly increased in patients; with a previous history of hepatitis (36.4 fold), past history of injecting drugs (IDU) (32.1 fold), those born in North Africa, Middle East and Mediterranean countries (4.3 fold), had been tattooed before 1980s (3.3 fold), from 1980s-1990s (5.9 fold), had acupuncture before 1980s (3.8 fold), had a blood transfusion (3.6 fold), had clotting factors or growth hormone (4 fold), had contact with someone diagnosed with hepatitis in 1990s (4.1 fold). Of the anti-HCV patients 38 had a history of IDU, 43 were migrants and 10 were both. Conclusion: Anti-HCV prevalence was five times higher than predicted by the passive surveillance scheme and 20% of patients were unaware of their infection. Only one of these patients reported IDU. The evidence of HCV intersecting epidemics between developing and developed countries in Australia was strongly supported. Implications: The study provides a rational basis for targeted programs to identify asymptomatic HCV carriers who might benefit from the new antiviral treatment. [source] Regulation of XBP-1 signaling during transient and stable recombinant protein production in CHO cellsBIOTECHNOLOGY PROGRESS, Issue 2 2010Sebastian C. Y. Ku Abstract X-box binding protein 1 (XBP-1) is a key regulator of cellular unfolded protein response (UPR). The spliced isoform of XBP-1, XBP-1S, is a transcription activator, which is expressed only when UPR is induced. However, the impact of recombinant protein production on the regulation of XBP-1 signaling in CHO cells is not well understood. In this report, we cloned the Chinese hamster XBP-1 homolog to aid the investigation of the interplay between protein productivity, culture conditions, and endogenous XBP-1 signaling in CHO cells. Interestingly, expression of XBP-1S is detected in the non-producing and unstressed CHO-K1 cells. Transient expression of recombinant erythropoietin reveals a positive correlation between XBP-1 mRNA abundance and protein production level. However, such a correlation is not observed in batch cultivation of stable producing cell lines. The increased XBP-1 splicing is detected in late-phase cultures, suggesting that induction of XBP-1S may be a result of nutrient limitations or other environmental stresses rather than that of increased intracellular accumulation of recombinant proteins. Our data suggest that XBP-1 is a key determinant for the secretory capacity of CHO cells. Understanding its dynamic regulation hence provides a rational basis for cellular engineering strategies to improve recombinant protein secretion. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source] Recent Progress in Biomolecular EngineeringBIOTECHNOLOGY PROGRESS, Issue 1 2000Dewey D. Y. Ryu During the next decade or so, there will be significant and impressive advances in biomolecular engineering, especially in our understanding of the biological roles of various biomolecules inside the cell. The advances in high throughput screening technology for discovery of target molecules and the accumulation of functional genomics and proteomics data at accelerating rates will enable us to design and discover novel biomolecules and proteins on a rational basis in diverse areas of pharmaceutical, agricultural, industrial, and environmental applications. As an applied molecular evolution technology, DNA shuffling will play a key role in biomolecular engineering. In contrast to the point mutation techniques, DNA shuffling exchanges large functional domains of sequences to search for the best candidate molecule, thus mimicking and accelerating the process of sexual recombination in the evolution of life. The phage-display system of combinatorial peptide libraries will be extensively exploited to design and create many novel proteins, as a result of the relative ease of screening and identifying desirable proteins. Even though this system has so far been employed mainly in screening the combinatorial antibody libraries, its application will be extended further into the science of protein-receptor or protein-ligand interactions. The bioinformatics for genome and proteome analyses will contribute substantially toward ever more accelerated advances in the pharmaceutical industry. Biomolecular engineering will no doubt become one of the most important scientific disciplines, because it will enable systematic and comprehensive analyses of gene expression patterns in both normal and diseased cells, as well as the discovery of many new high-value molecules. When the functional genomics database, EST and SAGE techniques, microarray technique, and proteome analysis by 2-dimensional gel electrophoresis or capillary electrophoresis in combination with mass spectrometer are all put to good use, biomolecular engineering research will yield new drug discoveries, improved therapies, and significantly improved or new bioprocess technology. With the advances in biomolecular engineering, the rate of finding new high-value peptides or proteins, including antibodies, vaccines, enzymes, and therapeutic peptides, will continue to accelerate. The targets for the rational design of biomolecules will be broad, diverse, and complex, but many application goals can be achieved through the expansion of knowledge based on biomolecules and their roles and functions in cells and tissues. Some engineered biomolecules, including humanized Mab's, have already entered the clinical trials for therapeutic uses. Early results of the trials and their efficacy are positive and encouraging. Among them, Herceptin, a humanized Mab for breast cancer treatment, became the first drug designed by a biomolecular engineering approach and was approved by the FDA. Soon, new therapeutic drugs and high-value biomolecules will be designed and produced by biomolecular engineering for the treatment or prevention of not-so-easily cured diseases such as cancers, genetic diseases, age-related diseases, and other metabolic diseases. Many more industrial enzymes, which will be engineered to confer desirable properties for the process improvement and manufacturing of high-value biomolecular products at a lower production cost, are also anticipated. New metabolites, including novel antibiotics that are active against resistant strains, will also be produced soon by recombinant organisms having de novo engineered biosynthetic pathway enzyme systems. The biomolecular engineering era is here, and many of benefits will be derived from this field of scientific research for years to come if we are willing to put it to good use. [source] Molecular modelling of the androgen receptor axis: rational basis for androgen receptor intervention in androgen-independent prostate cancerBJU INTERNATIONAL, Issue 2005ROBERT J. FLETTERICK Androgen depletion in combination with antiandrogenic agents is initially highly effective for treating prostate cancer, and is the recommended treatment for more advanced or higher-grade tumours. However, many tumours eventually become insensitive to androgens, even though the androgen receptor (AR) continues to be expressed. Computational chemistry combined with structural analysis of nuclear receptors and determination of binding affinities of natural and designed coregulators (coactivators and corepressors) provides the theoretical framework for the rational design of novel therapeutic agents directed at the AR. Adding alternative groups to various sites throughout the receptor can alter the conformation of the molecule and its functional binding with coactivators or corepressors. Possible molecules can be identified thoroughly and systematically using intelligent high-throughput screening and FASTrack chemistry (three-dimensional crystallography). Applying these techniques should eventually result in therapeutic agents for androgen-independent prostate cancer that can block binding of AR coactivators while simultaneously increasing binding of AR corepressors. [source] Schedule-dependent Interactions between Raltitrexed and Cisplatin in Human Carcinoma Cell Lines in vitroCANCER SCIENCE, Issue 4 2000Yasuhiko Kano Raltitrexed (,Tomudex") is a new anticancer agent which inhibits thymidylate synthase. To provide a rational basis for clinical trial design of the combination of raltitrexed and cisplatin, we studied the cytotoxic effects of this combination using various schedules in vitro and four human colon cancer cell lines, Colo201, Colo320, LoVo, and WiDr. Cell growth inhibition after 5 days was determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of drug combinations at the concentration producing 80% cell growth inhibition (IC80) level were analyzed by the isobologram method. Simultaneous exposure to raltitrexed and cisplatin for 24 h, and sequential exposure to raltitrexed followed by cisplatin produced additive effects in the Colo201, Colo320, and LoVo cells, and additive and synergistic effects in WiDr cells. Sequential exposure to cisplatin followed by raltitrexed produced additive effects in the Colo201 cells and antagonistic effects in other three cell lines. Simultaneous and continuous exposure to both agents for 5 days produced additive effects in all four cell lines. These findings suggest that the simultaneous administration of raltitrexed and cisplatin, or the sequential administration of raltitrexed followed by cisplatin, generally produce the expected cytotoxicity at the cellular level and are optimal schedules, while the sequential administration of cisplatin followed by raltitrexed produces antagonistic effects and is inappropriate for this combination. Further in vivo and clinical studies will be necessary to determine the toxicity and antitumor effects of this schedule. [source] Inner retinal ischaemia: current understanding and needs for further investigationsACTA OPHTHALMOLOGICA, Issue 4 2009Toke Bek Abstract. Inner retinal ischaemia is involved in the pathogenesis of major vision-threatening diseases such as retinal vein thrombosis, diabetic retinopathy and retinopathy of prematurity. However, the pathogenesis of inner retinal ischaemia has not been fully elucidated, which represents an impediment to the development and improvement of techniques to prevent and treat these diseases on a rational basis. This paper provides a comprehensive review of current knowledge of the pathophysiology of inner retinal ischaemia, including clinical, anatomical and physiological aspects of disease development. It is suggested that chronic inner retinal ischaemia caused by capillary occlusion may develop secondary to an increase in hydrostatic pressure in the vessels. Further knowledge of the pathophysiology of inner retinal ischaemia can be obtained by identifying the mechanisms that lead to increased hydrostatic pressure in the capillary bed and establishing the structural and functional basis for the different response patterns in the central and peripheral areas of the retina that develop secondary to this increased hydrostatic pressure. Further elucidation of these unknown response patterns requires both in vitro and in vivo studies of retinal vascular pathophysiology. It is conceivable that a more detailed knowledge of these response patterns may help in the design of new treatments for retinal ischaemia and its vision-threatening consequences. [source] Arteries in the posterior cervical triangle in manCLINICAL ANATOMY, Issue 8 2005Andreas H. Weiglein Abstract Due to frequent changes in the anatomical nomenclature of the arteries in the posterior cervical triangle (lateral cervical region), anatomical and surgical papers relating to these topics are sometimes difficult to understand and are hard to compare. These changes, coupled with improper knowledge of the gross anatomy and nomenclature of the arteries in the posterior cervical triangle, have presented difficulties in musculocutaneous flap planning, especially in plastic and reconstructive surgery. As an illustration of this concern, the term, transverse cervical artery (A. transversa colli [cervicis]), and its associated branches, have been used frequently over the past several decades with different meanings. In an effort to address this nomenclature challenge and to offer a rational basis for arguing specific name changes, a total of 498 neck-halves were investigated in Graz, Innsbruck, and Munich. Lateral neck dissections were carried out to expose the subclavian artery and those branches destined for the posterior cervical triangle, specifically, the superficial cervical artery, the dorsal scapular artery, and the suprascapular artery. The course of these arteries and details of their origins and branching patterns were documented. Several arose either as direct branches or from trunks. The convention used in labeling trunks was similar to that described for other trunk formations in the body (e.g., linguo-facial trunk). Four trunks were observed and named according to the branches that arose from each. A cervico-dorsal trunk gave origin to the superficial cervical and dorsal scapular arteries, and was found in 30% of cases. A cervico-scapular trunk gave rise to the superficial cervical and suprascapular arteries in 22% of cases, and a dorso-scapular trunk provided origins for the dorsal scapular and suprascapular arteries in 4% of cases. A cervico-dorso-scapular trunk gave origin to the superficial cervical artery, the dorsal scapular artery, and the suprascapular artery, and was found in 24% of cases. Each of these trunks, in turn, arose from either the subclavian artery or from the thyrocervical trunk. This labeling convention necessitated omitting the term, transverse cervical artery, because this term has become inherently imprecise and variously used over the years. This study describes a simple, uniform, and rational basis for standardizing the nomenclature of the arteries in the posterior cervical triangle. Clin. Anat. 18:553,557, 2005. © 2005 Wiley-Liss, Inc. [source] | ||||||||||||||||