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Reversal
Kinds of Reversal Terms modified by Reversal Selected AbstractsSEX REVERSAL: A FOUNTAIN OF YOUTH FOR SEX CHROMOSOMES?EVOLUTION, Issue 12 2009Nicolas Perrin Nonrecombining Y chromosomes are expected to degenerate through the progressive accumulation of deleterious mutations. In lower vertebrates, however, most species display homomorphic sex chromosomes. To address this, paradox I propose a role for sex reversal, which occasionally occurs in ectotherms due to the general dependence of physiological processes on temperature. Because sex-specific recombination patterns depend on phenotypic, rather than genotypic sex, homomorphic X and Y chromosomes are expected to recombine in sex-reversed females. These rare events should generate bursts of new Y haplotypes, which will be quickly sorted out by natural or sexual selection. By counteracting Muller's ratchet, this regular purge should prevent the evolutionary decay of Y chromosomes. I review empirical data supporting this suggestion, and propose further investigations for testing it. [source] RECONSTRUCTING PLUMAGE EVOLUTION IN ORIOLES (ICTERUS): REPEATED CONVERGENCE AND REVERSAL IN PATTERNSEVOLUTION, Issue 6 2000Kevin E. Omland Abstract. Several empirical studies suggest that sexually selected characters, including bird plumage, may evolve rapidly and show high levels of convergence and other forms of homoplasy. However, the processes that might generate such convergence have not been explored theoretically. Furthermore, no studies have rigorously addressed this issue using a robust phylogeny and a large number of signal characters. We scored the appearance of 44 adult male plumage characters that varied across New World orioles (Icterus). We mapped the plumage characters onto a molecular phylogeny based on two mitochondrial genes. Reconstructing the evolution of these characters revealed evidence of convergence or reversal in 42 of the 44 plumage characters. No plumage character states are restricted to any groups of species higher than superspecies in the oriole phylogeny. The high frequency of convergence and reversal is reflected in the low overall retention index (RI = 0.66) and the low overall consistency index (CI = 0.28). We found similar results when we mapped plumage changes onto a total evidence tree. Our findings reveal that plumage patterns and colors are highly labile between species of orioles, but highly conserved within the oriole genus. Furthermore, there are at least two overall plumage types that have convergently evolved repeatedly in the three oriole clades. This overall convergence leads to significant conflict between the molecular and plumage data. It is not clear what evolutionary processes lead to this homoplasy in individual characters or convergence in overall pattern. However, evolutionary constraints such as developmental limitations and genetic correlations between characters are likely to play a role. Our results are consistent with the belief that avian plumage and other sexually selected characters may evolve rapidly and may exhibit high homoplasy. The overall convergence in oriole plumage patterns is an interesting evolutionary phenomenon, but it cautions against heavy reliance on plumage characters for constructing phylogenies. [source] EVIDENCE-BASED CARIES REVERSAL USING OZONEJOURNAL OF ESTHETIC AND RESTORATIVE DENTISTRY, Issue 4 2008BDentSc, Edward Lynch MA, FDSRCSEd, FDSRCSLond Guest Expert, PhD Lond [source] ECOLOGICAL BISTABILITY AND EVOLUTIONARY REVERSALS UNDER ASYMMETRICAL COMPETITIONEVOLUTION, Issue 6 2002Fabio Dercole Abstract How does the process of life-history evolution interplay with population dynamics? Almost all models that have addressed this question assume that any combination of phenotypic traits uniquely determine the ecological population state. Here we show that if multiple ecological equilibria can exist, the evolution of a trait that relates to competitive performance can undergo adaptive reversals that drive cyclic alternation between population equilibria. The occurrence of evolutionary reversals requires neither environmentally driven changes in selective forces nor the coevolution of interactions with other species. The mechanism inducing evolutionary reversals is twofold. First, there exist phenotypes near which mutants can invade and yet fail to become fixed; although these mutants are eventually eliminated, their transitory growth causes the resident population to switch to an alternative ecological equilibrium. Second, asymmetrical competition causes the direction of selection to revert between high and low density. When ecological conditions for evolutionary reversals are not satisfied, the population evolves toward a steady state of either low or high abundance, depending on the degree of competitive asymmetry and environmental parameters. A sharp evolutionary transition between evolutionary stasis and evolutionary reversals and cycling can occur in response to a smooth change in ecological parameters, and this may have implications for our understanding of size-abundance patterns. [source] Reversal of End-Stage Heart Failure: Mechanical and Pharmacologic InterplayCONGESTIVE HEART FAILURE, Issue 1 2007Imran S. Virk MD No abstract is available for this article. [source] Reversal of trichotillomania with aripiprazoleDEPRESSION AND ANXIETY, Issue 6 2008B.Ed., Don Jefferys A.M., F.A.A.E.T.S, M.A.C.E., M.A.P.S., Ph.D. Abstract Trichotillomania (TTM) is a common psychiatric illness with marked chronicity and comorbidity that significantly impacts on psychosocial functioning and physical features of the sufferer. Treatment studies, to date, using behavioral and pharmacological interventions alone or simultaneously, are equivocal with few showing a sustained cessation of hair-plucking. In this report of a single patient with treatment resistant TTM, the sole use of the atypical neuroleptic Aripiprazole resulted in a cessation of hair-plucking maintained, at the time of reporting, for a period of 24 months. This finding, a first with Aripiprazole, warrants further investigation of this drug in the treatment of TTM. Depression and Anxiety 0:1,4, 2007. © 2007 Wiley-Liss, Inc. [source] Reversal of Laser-Induced Hypopigmentation with a Narrow-Band UV-B Light Source in a Patient with Skin Type VIDERMATOLOGIC SURGERY, Issue 10 2008ANETTA RESZKO MD First page of article [source] Contextual modulation of spatial discrimination reversal in developing ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 1 2005Jerome H. Pagani Abstract Reversal of discrimination learning is influenced by manipulation of the training context. In adult and developing rats, contextual changes made between acquisition and reversal aid the learning of the new discrimination, possibly by serving to release proactive interference from the originally acquired discrimination (M. E. Bouton & D. C. Brooks, 1993; N. Spear, G. Smith, R. Bryan, & W. Gordon, 1980). The present study sought to examine this effect in an appetitive T-maze task, as a function of different contextual manipulations. Rats of three ages, Postnatal Day (PND) 19, PND23, and PND30, were tested for their ability to acquire and reverse a position habit in a T-maze. Contextual changes were made between acquisition and reversal sessions and consisted of one of three manipulations: (a) texture; the texture of the maze floor was changed via the addition or subtraction of wire mesh; (b) maze; subjects were reversed in a different maze that was identical in construction to the training maze, but differed in spatial location; (c) texture and maze; subjects were shifted to the new maze, the floor of which differed in texture from the training maze but was otherwise identical in construction. Results showed that the texture,maze combination was an effective aid to reversal learning at all ages tested. The texture alone, however, was not effective at any age. The maze alone also was an effective cue for reversal, but proved to have the greatest effect for PND30 subjects. During ontogeny, the contextual modulation of reversal learning is importantly influenced by the nature and the salience of the contextual cue. © 2004 Wiley Periodicals, Inc. Dev Psychobiol 46: 36,46, 2005. [source] Reversal of cardiac complications in thalassemia major by long-term intermittent daily intensive iron chelationEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2003H. Miskin Abstract: Objectives: In patients with thalassemia major (TM) who are non-compliant with long-term deferoxamine (DFO) chelation, survival is limited mainly because of cardiac complications of transfusional siderosis. It was recently shown in a small group of TM patients with established cardiac damage that continuous 24-h DFO infusion via an indwelling intravenous (i.v.) catheter is effective in reversing cardiac toxicity. The aim of the present study was to evaluate the results with intermittent daily (8,10 h) i.v. DFO. Patients: Eight TM patients with cardiac complications treated with intensive intermittent DFO were retrospectively evaluated by the mean annual serum ferritin, radionucleated ventriculography and 24-h electrocardiography recordings. Results: The median age at diagnosis of cardiac disease was 17.5 yr (range 14,21), and the median follow-up time was 84 months (range, 36,120). In the majority of patients (seven of eight) high-dose DFO (mean 95 ± 18.3 mg/kg/d) was administered via a central venous line. During follow-up, there was a significant decrease in the mean ferritin levels (5828 ± 2016 ng/mL to 1585 ± 1849 ng/mL, P < 0.001). Both cardiac failure (mean ejection fraction 32 ± 5) and cardiac arrhythmias were resolved in four of five patients. One non-compliant patient died during the follow-up. Following discontinuation of the i.v. therapy, compliance with conventional DFO therapy improved. The complications of this regimen, mainly catheter-related infections and catheter-related thrombosis, were similar to those described earlier. Conclusions: These results with the longest follow-up period in the literature suggest that i.v. high-dose DFO for 8,10 h daily may be as effective as continuous 24-h infusion for the reversal of established cardiac disease in TM. [source] New approaches in the immunotherapy of haematological malignanciesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2003Régis T. Costello Abstract: Advances in the management of haematological malignancies have allowed to obtain improved remission rates. Nonetheless, relapses impair these results and justify the search for novel therapeutic strategies. Clinical data demonstrate that the immune system plays an important role in the control of haematological malignancies. An increased frequency of haematological malignancies is observed in immunodeficiency states. Reversal of the immunosuppression is sometimes sufficient to induce tumour regression (withdrawal of cyclosporine in post-transplant lymphoproliferations, highly active anti-retroviral treatment in human immunodeficiency virus related Kaposi's disease). Another line of evidence for the involvement of the immune system in the anti-tumour response comes from the observation of spontaneous anti-tumour responses that parallel the occurrence of paraneoplastic immune-mediated syndromes. Finally, the efficiency of allogeneic transplantation in the haematological field has been clearly demonstrated to depend on the immune-mediated graft vs. leukaemia effect. Nonetheless, tumours develop in immune competent patients because of various tumour escape mechanisms, such as loss of human leucocyte antigen class I antigens, absence of target recognition by deficient adhesion/co-stimulatory molecule expression, tumour cell counterattack against immune effectors, direct (contact-dependent) or indirect (cytokine-mediated) impairment of T-lymphocyte activation. Novel immunotherapy approaches are now orientated in a convergent direction, i.e. the reversal of immune escape mechanisms either via the correction of deficient phases of the immune response or by the amplification of physiological mechanisms. [source] "I was more her Mom than she was mine:" Role Reversal in a Community Sample,FAMILY RELATIONS, Issue 1 2004Ofra Mayseless Family processes associated with childhood role reversal and related adult outcomes were examined in a community sample (128 adults) using a semistructured interview exploring family, friend, and romantic relationships. Women showed stronger role reversal than men, and role reversal was stronger with mothers than with fathers. Role reversal of women with mothers was associated with parental divorce, neglect, and rejection. Only parental divorce was consistently associated with men's role reversal. Role reversal was not associated with current symptoms for either men or women, nor with attachment orientations for women. Three patterns with distinct family dynamics and outcomes,guardians/protectors, pleasers/compliants, and spousified,emerged from qualitative analyses of 16 women who experienced high levels of childhood role reversal. [source] 7,8-Diaminoperlargonic acid aminotransferase from Mycobacterium tuberculosis, a potential therapeutic targetFEBS JOURNAL, Issue 20 2006Characterization, inhibition studies Diaminopelargonic acid aminotransferase (DAPA AT), which is involved in biotin biosynthesis, catalyzes the transamination of 8-amino-7-oxononanoic acid (KAPA) using S -adenosyl- l -methionine (AdoMet) as amino donor. Mycobacterium tuberculosis DAPA AT, a potential therapeutic target, has been overproduced in Escherichia coli and purified to homogeneity using a single efficient step on a nickel-affinity column. The enzyme shows an electronic absorption spectrum typical of pyridoxal 5,-phosphate-dependent enzymes and behaves as a homotetramer in solution. The pH profile of the activity at saturation shows a single ionization group with a pKa of 8.0, which was attributed to the active-site lysine residue. The enzyme shows a Ping Pong Bi Bi kinetic mechanism with strong substrate inhibition with the following parameters: KmAdoMet = 0.78 ± 0.20 mm, KmKAPA = 3.8 ± 1.0 µm, kcat = 1.0 ± 0.2 min,1, KiKAPA = 14 ± 2 µm. Amiclenomycin and a new analogue, 4-(4c -aminocyclohexa-2,5-dien-1r -yl)propanol (referred to as compound 1), were shown to be suicide substrates of this enzyme, with the following inactivation parameters: Ki = 12 ± 2 µm, kinact = 0.35 ± 0.05 min,1, and Ki = 20 ± 2 µm, kinact = 0.56 ± 0.05 min,1, for amiclenomycin and compound 1, respectively. The inactivation was irreversible, and the partition ratios were 1.0 and 1.1 for amiclenomycin and compound 1, respectively, which make these inactivators particularly efficient. compound 1 (100 µg·mL,1) completely inhibited the growth of an E. coli C268bioA mutant strain transformed with a plasmid expressing the M. tuberculosis bioA gene, coding for DAPA AT. Reversal of the antibiotic effect was observed on the addition of biotin or DAPA. Thus, compound 1 specifically targets DAPA AT in vivo. [source] LATE-GLACIAL GLACIER EVENTS IN SOUTHERNMOST SOUTH AMERICA: A BLEND OF ,NORTHERN' AND 'SOUTHERN' HEMISPHERIC CLIMATIC SIGNALS?GEOGRAFISKA ANNALER SERIES A: PHYSICAL GEOGRAPHY, Issue 2 2005D.E. SUGDEN ABSTRACT. This paper examines new geomorphological, chronological and modelling data on glacier fluctuations in southernmost South America in latitudes 46,55°S during the last glacial,interglacial transition. Establishing leads and lags between the northern and southern hemispheres and between southern mid-latitudes and Antarctica is key to an appreciation of the mechanisms and resilience of global climate. This is particularly important in the southern hemisphere where there is a paucity of empirical data. The overall structure of the last glacial cycle in Patagonia has a northern hemisphere signal. Glaciers reached or approached their Last Glacial Maxima on two or more occasions at 25,23 ka (calendar) and there was a third less extensive advance at 17.5 ka. Deglaciation occurred in two steps at 17.5 ka and at 11.4 ka. This structure is the same as that recognized in the northern hemisphere and taking place in spite of glacier advances occurring at a time of high southern hemisphere summer insolation and deglaciation at a time of decreasing summer insolation. The implication is that at orbital time scales the,northern' signal dominates any southern hemisphere signal. During deglaciation, at a millennial scale, the glacier fluctuations mirror an antiphase 'southern' climatic signal as revealed in Antarctic ice cores. There is a glacier advance coincident with the Antarctic Cold Reversal at 15.3,12.2 ka. Furthermore, deglaciation begins in the middle of the Younger Dryas. The implication is that, during the last glacial,interglacial transition, southernmost South America was under the influence of sea surface temperatures, sea ice and southern westerlies responding to conditions in the 'southern' Antarctic domain. Such asynchrony may reflect a situation whereby, during deglaciation, the world is more sensitized to fluctuations in the oceanic thermohaline circulation, perhaps related to the bipolar seesaw, than at orbital timescales. [source] CHRONOLOGY OF THE LAST GLACIATION IN CENTRAL STRAIT OF MAGELLAN AND BAHÍA INÚTIL, SOUTHERNMOST SOUTH AMERICAGEOGRAFISKA ANNALER SERIES A: PHYSICAL GEOGRAPHY, Issue 2 2005R.D. McCULLOCH ABSTRACT. Glacier fluctuations in the Strait of Magellan tell of the climatic changes that affected southern latitudes at c. 53,55°S during the Last Glacial Maximum (LGM) and Late-glacial/Holocene transition. Here we present a revised chronology based on cosmogenic isotope analysis, 14C assays, amino acid racemisation and tephrochronology. We unpick the effect of bedrock-derived lignite which has affected many 14C dates in the past and synthesise new and revised dates that constrain five glacier advances (A to E). Advance A is prior to the LGM. LGM is represented by Advance B that reached and largely formed the arcuate peninsula Juan Mazia. Carbon-14and 10Be dating show it occurred after 31 250 cal yrs BP and culminated at 25 200,23 100 cal yrs BP and was then followed by the slightly less extensive advance C sometime before 22 400,20 300 cal yrs BP. This pattern of an early maximum is found elsewhere in South America and more widely. Stage D, considerably less extensive, culminated sometime before 17 700,17 600 cal yrs BP and was followed by rapid and widespread glacier retreat. Advance E, which dammed a lake, spanned 15 500,11770 cal yrs BP. This latter advance overlaps the Bølling-Allerød interstadials and the glacier retreat occurs during the peak of the Younger Dryas stadial in the northern hemisphere. However, the stage E advance coincides with the Antarctic Cold Reversal (c. 14800,12700 cal yrs BP) and may indicate that some millennial-scale climatic fluctuations in the Late-glacial period are out of phase between the northern and southern hemispheres. [source] Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats,HEPATOLOGY, Issue 4 2007Mercedes Fernandez Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) pathways are crucial to angiogenesis, a process that contributes significantly to the pathogenesis of portal hypertension. This study determined the effects of inhibition of VEGF and/or PDGF signaling on hyperdynamic splanchnic circulation and portosystemic collateralization in rats with completely established portal hypertension, thus mimicking the situation in patients. Portal vein,ligated rats were treated with rapamycin (VEGF signaling inhibitor), Gleevec (PDGF signaling inhibitor), or both simultaneously when portal hypertension was already fully developed. Hemodynamic studies were performed by transit-time flowmetry. The extent of portosystemic collaterals was measured by radioactive microspheres. The expression of angiogenesis mediators was determined by Western blotting and immunohistochemistry. Combined inhibition of VEGF and PDGF signaling significantly reduced splanchnic neovascularization (i.e., CD31 and VEGFR-2 expression) and pericyte coverage of neovessels (that is, ,-smooth muscle actin and PDGFR-, expression) and translated into hemodynamic effects as marked as a 40% decrease in portal pressure, a 30% decrease in superior mesenteric artery blood flow, and a 63% increase in superior mesenteric artery resistance, yielding a significant reversal of the hemodynamic changes provoked by portal hypertension in rats. Portosystemic collateralization was reduced as well. Conclusions: Our results provide new insights into how angiogenesis regulates portal hypertension by demonstrating that the maintenance of increased portal pressure, hyperkinetic circulation, splanchnic neovascularization, and portosystemic collateralization is regulated by VEGF and PDGF in portal hypertensive rats. Importantly, these findings also suggest that an extended antiangiogenic strategy (that is, targeting VEGF/endothelium and PDGF/pericytes) may be a novel approach to the treatment of portal hypertension. (HEPATOLOGY 2007.) [source] Reversal of expression of 15-lipoxygenase-1 to cyclooxygenase-2 is associated with development of colonic cancerHISTOPATHOLOGY, Issue 4 2007M Yuri Aims:, Two different pathways of linoleic acid (LA) metabolism have opposite effects on the development of colonic cancer: a protumoral prostaglandin cascade metabolized by cyclooxygenase (COX)-2, and an antitumoral peroxisome proliferator-activated receptor (PPAR)-, ligands metabolized by 15-lipooxygenase (LOX)-1. The aim was to examine the switching of the two LA metabolic pathways in colonic adenomas and carcinomas. Materials and methods:, The expression of 15LOX-1 mRNA and COX-2 protein was examined in 54 adenomas, 21 pTis carcinoma-in-adenoma lesions and 36 pT3/p Stage II carcinomas of the colon by in-situ hybridization and immunohistochemistry, respectively. Results:, 15LOX-1 expression was found in 89% (48 of 54) of adenomas, 43% (nine of 21) of adenomas and 10% (two of 21) of carcinomas in carcinoma-in-adenoma lesions, but not in pT3 carcinomas (P < 0.0001). In contrast, COX-2 production was found in 11% (six of 54) of adenomas, 52% (11 of 21) of adenomas and 71% (15 of 21) of carcinomas in carcinoma-in-adenoma lesions, and 92% (33 of 36) of pT3 carcinomas (P < 0.0001). Concurrence of 15LOX-1 down-regulation and COX-2 up-regulation was found in 6% (three of 54) of adenomas, 33% (seven of 21) of adenomas and 71% (15 of 21) of carcinomas in carcinoma-in-adenoma lesions, and 92% (33 of 36) of pT3 carcinomas (P < 0.0001). Conclusions:, These results suggest that switching of LA metabolism by reversal of the expression of 15LOX-1 and COX-2 is associated with acquisition of malignant potential in colonic neoplasia. [source] Reversal of pathogenic mutations in Hunter syndrome by an RNA-editing-like mechanism?HUMAN MUTATION, Issue 4 2010Lluÿsa Vilageliu No abstract is available for this article. [source] Sperm characteristics and teratology in rats following vas deferens occlusion with RISUG and its reversalINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2010N. K. Lohiya Summary The functional success of the reversal of vas occlusion by styrene maleic anhydride (RISUG), using the solvent vehicle, Dimethyl Sulphoxide (DMSO), has been investigated. Reversal with DMSO was carried out in Wistar albino rats 90 days after bilateral vas occlusion. The body weight, organ weight, sperm characteristics, fertility test and teratology, including skeletal morphology were evaluated in vas occlusion and reversal animals and in F1 progenies to assess the functional success of the occlusion and reversal. Body weight, organ weight and the cauda epididymal sperm characteristics of vas occlusion and reversal animals and of F1 progenies were comparable to control. Ejaculated spermatozoa in the vaginal smear showed detached head/tail, acrosomal damage, bent midpiece, bent tail and morphological aberrations in sperm head after vas occlusion, which returned to normal, 90 days after reversal. Monthly fertility test, post-injection showed 0% fertility, which improved gradually and 100% fertility was achieved 90 days after reversal. The fertility/pregnancy/implantation record and skeletal morphology of the offspring were comparable to control. The results suggest functional success and safety of vas occlusion reversal by DMSO. [source] Reversal of inflammation-associated dihydrodiol dehydrogenases (AKR1C1 and AKR1C2) overexpression and drug resistance in nonsmall cell lung cancer cells by wogonin and chrysinINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Hao-Wei Wang Abstract Dihydrodiol dehydrogenase (DDH) is a member of the aldo-keto reductases superfamily (AKR1C1,AKR1C4), which plays central roles in the metabolism of steroid hormone, prostaglandin and xenobiotics. We have previously detected overexpression of DDH as an indicator of poor prognosis and chemoresistance in human non-small lung cancer (NSCLC). We also found DDH expression to be closely related to chronic inflammatory conditions. The aim of this study was to investigate the links between inflammation, DDH expression and drug resistance in NSCLC cells. We showed that pro-inflammatory mediators including interleukin-6 (IL-6) could induce AKR1C1/1C2 expression in NSCLC cells and increase cellular resistance to cisplatin and adriamycin. This effect was nullified by Safingol, a protein kinase C inhibitor. Moreover, the expression of AKR1C1/1C2 was inversely correlated to NBS1 and apoptosis-inducing factor (AIF). We also showed that IL-6-induced AKR1C1/1C2 expression and drug resistance were inhibited by wogonin and chrysin, which are major flavonoids in Scutellaria baicalensis, a widely used traditional Chinese and Japanese medicine. In conclusion, this study demonstrated novel links of pro-inflammatory signals, AKR1C1/1C2 expression and drug resistance in NSCLC. The protein kinase C pathway may play an important role in this process. Overexpression of AKR1C1/1C2 may serve as a marker of chemoresistance. Further studies are warranted to evaluate wogonin and chrysin as a potential adjuvant therapy for drug-resistant NSCLC, especially for those with AKR1C1/1C2 overexpression. © 2007 Wiley-Liss, Inc. [source] Reversal of doxorubicin resistance in breast cancer cells by photochemical internalizationINTERNATIONAL JOURNAL OF CANCER, Issue 11 2006Pei-Jen Lou Abstract Multiple drug resistance (MDR) is a problem that seriously reduces the efficacy of many chemotherapy agents. One mechanism for MDR is increased acidification of endocytic vesicles and increased cytosol pH, so weak base chemotherapeutic agents, including doxorubicin, are trapped in endocytic vesicles and exhibit a drug resistant phenotype. Treatments that selectively reverse this accumulation may therefore reverse the MDR phenotype. Photochemical internalization (PCI) is a novel technology developed for site-specific enhancement of the therapeutic efficacy of macromolecules by selective photochemical rupture of endocytic vesicles and consequent release of endocytosed macromolecules into the cytosol. This study evaluates PCI for release of doxorubicin from endocytic vesicles in MDR cells. Two breast cancer cell lines, MCF-7 and MCF-7/ADR (the latter resistant to doxorubicin), were selected. They were found equally sensitive to photochemical treatment with the photosensitiser TPPS2a (disulfonated meso-tetraphenylporphine) and light. On exposure to doxorubicin alone, the IC50 (drug concentration for 50% reduction in colony formation) was 0.1 ,M for MCF-7 and 1 ,M for MCF-7/ADR. After PCI (photochemical treatment followed by doxorubicin), the IC50 concentration was 0.1 ,M for both cell lines. Comparable changes were seen with assay of cell viability using 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). On fluorescence microscopy in MCF-7/ADR cells, doxorubicin localised in granules identified as lysosomes. After PCI, doxorubicin was released into the cytosol and entered cell nuclei, as was seen in MCF-7 cells without PCI. In conclusion, PCI reversed the MDR phenotype of doxorubicin resistant breast cancer cells by endo-lysosomal release of the drug. The technique is a promising new approach to tackling the problem of MDR. © 2006 Wiley-Liss, Inc. [source] Electronic and charge aspects of potential endocrine disruptors: Applications to pharmacological clusteringINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4-5 2003James W. King Abstract Quantitative structure,activity relationships in a series of 37 substituted indoles with endocrine disruptor potential were performed using the structural indices FTe (electronic) and FTc (charge), in conjunction with a clustering technique, to relate substitution patterns to reported relative binding affinities for the calf estrogen receptor. Data clusters were generated by a primary numerically descending sort of the structure indices with a concurrent secondary numerically descending sort of the binding data. Reversal of the numerical descent of the latter served to delineate cluster boundaries. Analysis within the clusters defined the effect of substituents and their molecular positions on the pharmacological data. These results confirmed in detail a similar previous study in the same series using the more general FTm index and again suggested the same structure of a molecule with greater receptor binding ability than any in the database. The methodology used in these studies permits a rational presentation and subsequent interpretation of data that initially appear to be totally random and devoid of recoverable information content. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003 [source] Reversal of Fortunes or Continued Success?INTERNATIONAL MIGRATION REVIEW, Issue 2 2010Cohort Differences in Education, Earnings of Childhood Immigrants Using several years of Canadian census data, this study examines cohort differences in educational attainment and earnings among childhood immigrants who arrived in Canada between 1960 and 1989. Successive cohorts of childhood immigrants had increasingly higher university completion rates than their Canadian-born peers by age 25,34. We find that this lead was tempered by declining earnings of immigrant parents relative to Canadian-born parents, particularly among the 1980s cohort. Despite rising university completion rates, wages of male (but not female) childhood immigrants lagged behind those of their Canadian-born peers. This gap can be accounted for largely by the rising share of members of racial minority groups and the decreasing incidence of full-time employment. [source] A Chemical Approach Towards Understanding the Mechanism and Reversal of Drug Resistance in Plasmodium falciparum: Is it Viable?IUBMB LIFE, Issue 4-5 2002Kelly Chibale Abstract Genetic and biochemical approaches to studies of drug resistance mechanisms in Plasmodium falciparum have raised controversies and contradictions over the past several years. A different and novel chemical approach to this important problem is desirable at this point in time. Recently, the molecular basis of drug resistance in P. falciparum has been associated with mutations in the resistance genes, Chloroquine Resistance Transporter (PfCRT) and the P-glycoprotein homologue (Pgh1). Although not the determinant of chloroquine resistance in P. falciparum, mutations in Pgh1 have important implications for resistance to other antimalarial drugs. Because it is mutations in the aforementioned resistance genes rather than overexpression that has been associated with drug resistance in malaria, studies on mechanisms of drug resistance and its reversal by chemosensitisers should benefit from a chemical approach. Target-oriented organic synthesis of chemosensitisers against proteins implicated in drug resistance in malaria should shed light on mechanism of drug resistance and its reversal in this area. The effect of structurally diverse chemosensitisers should be examined on several putative resistance genes in P. falciparum to deal with antimalarial drug resistance in the broadest sense. Therefore, generating random mutations of these resistance proteins and subsequent screening in search of a specific phenotype followed by a search for mutations and/or chemosensitisers that affect a specific drug resistance pathway might be a viable strategy. This diversity-oriented organic synthesis approach should offer the means to simultaneously identify resistance proteins that can serve as targets for therapeutic intervention (therapeutic target validation) and chemosensitisers that modulate the functions of these proteins (chemical target validation). [source] Reversal of Electrical Remodeling After Cardioversion of Persistent Atrial FibrillationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2004MERRITT H. RAITT M.D. Introduction: In animals, atrial fibrillation results in reversible atrial electrical remodeling manifested as shortening of the atrial effective refractory period, slowing of intra-atrial conduction, and prolongation of sinus node recovery time. There is limited information on changes in these parameters after cardioversion in patients with persistent atrial fibrillation. Methods and Results: Thirty-eight patients who had been in atrial fibrillation for 1 to 12 months underwent electrophysiologic testing 10 minutes and 1 hour after cardioversion. At 1 week, 19 patients still in sinus rhythm returned for repeat testing. Reverse remodeling of the effective refractory period was not uniform across the three atrial sites tested. At the lateral right atrium, there was a highly significant increase in the effective refractory period between 10 minutes and 1 hour after cardioversion (drive cycle length 400 ms: 204 ± 17 ms vs 211 ± 20 ms, drive cycle length 550 ms: 213 ± 18 ms vs 219 ± 23 ms, P < 0.001). The effective refractory period at the coronary sinus and distal coronary sinus did not change in the first hour but had increased by 1 week. The corrected sinus node recovery time did not change in the first hour but was shorter at 1 week (606 ± 311 ms vs 408 ± 160 ms, P = 0.009). P wave duration also was shorter at 1 week (135 ± 18 ms vs 129 ± 13 ms, P = 0.04) consistent with increasing atrial conduction velocity. Conclusion: The atrial effective refractory period increases, sinus node function improves, and atrial conduction velocity goes up in the first week after cardioversion of long-standing atrial fibrillation in humans. Reverse electrical remodeling of the effective refractory period occurs at different rates in different regions of the atrium. (J Cardiovasc Electrophysiol, Vol. 15, pp. 507-512, May 2004) [source] Electrogram Polarity and Cavotricuspid Isthmus Block During Ablation of Typical Atrial FlutterJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 4 2001HIROSHI TADA M.D. Electrogram Polarity in Atrial Flutter Ablation.Introduction: The atrial activation sequence around the tricuspid annulus has been used to assess whether complete block has been achieved across the cavotricuspid isthmus during radiofrequency ablation of typical atrial flutter. However, sometimes the atrial activation sequence does not clearly establish the presence or absence of complete block. The purpose of this study was to determine whether a change in the polarity of atrial electrograms recorded near the ablation line is an accurate indicator of complete isthmus block. Methods and Results: Radiofrequency ablation was performed in 34 men and 10 women (age 60 ± 13 years [mean ± SD]) with isthmus-dependent, counterclockwise atrial flutter. Electrograms were recorded around the tricuspid annulus using a duodecapolar halo catheter. Electrograms recorded from two distal electrode pairs (E1 and E2) positioned just anterior to the ablation line were analyzed during atrial flutter and during coronary sinus pacing, before and after ablation. Complete isthmus block was verified by the presence of widely split double electrograms along the entire ablation line. Complete bidirectional isthmus block was achieved in 39 (89%) of 44 patients. Before ablation, the initial polarity of E1 and E2 was predominantly negative during atrial flutter and predominantly positive during coronary sinus pacing. During incomplete isthmus block, the electrogram polarity became reversed either only at E2, or at neither E1 nor E2. In every patient, the polarity of E1 and E2 became negative during coronary sinus pacing only after complete isthmus block was achieved. In 4 patients (10%), the atrial activation sequence recorded with the halo catheter was consistent with complete isthmus block, but the presence of incomplete block was accurately detected by inspection of the polarity of E1 and E2. Conclusion: Reversal of polarity in bipolar electrograms recorded just anterior to the line of isthmus block during coronary sinus pacing after ablation of atrial flutter is a simple, quick, and accurate indicator of complete isthmus block. [source] Reversal of aging-associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor functionAGING CELL, Issue 5 2010Yuan-Jian Yang Summary Deficits in learning and memory accompanied by age-related neurodegenerative diseases are closely related to the impairment of synaptic plasticity. In this study, we investigated the role of thiol redox status in the modulation of the N -methyl- d -aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) in CA1 areas of hippocampal slices. Our results demonstrated that the impaired LTP induced by aging could be reversed by acute administration of reductants that can regulate thiol redox status directly, such as dithiothreitol or ,-mercaptoethanol, but not by classical anti-oxidants such as vitamin C or trolox. This repair was mediated by the recruitment of aging-related deficits in NMDAR function induced by these reductants and was mimicked by glutathione, which can restore the age-associated alterations in endogenous thiol redox status. Moreover, antioxidant prevented but failed to reverse H2O2 -induced impairment of NMDAR-mediated synaptic plasticity. These results indicate that the restoring of thiol redox status may be a more effective strategy than the scavenging of oxidants in the treatment of pre-existing oxidative injury in learning and memory. [source] Satisfaction With Work and Family Life: No Evidence of a Cultural ReversalJOURNAL OF MARRIAGE AND FAMILY, Issue 1 2003K. Jill Kiecolt Hochschild (1997) argued that in recent decades the rewards of work have increased relative to those of family life and that this cultural reversal has aggravated the time bind that families face by increasing working hours. To the contrary, pooled data from the 1973,1994 General Social Surveys indicate that in working families, women have shifted away from finding work more satisfying than home toward finding home a haven. Moreover, were it not for women's growing labor force participation and the changing distribution of marital status, the shift would have been even larger. Men's relative work,home satisfaction has been stable. Finally, finding work a haven is unrelated to weekly working hours, and it has not contributed to any increases in working hours over time. [source] The initiation and development of metamorphic foliation in the Otago Schist, Part 1: competitive oriented growth of white micaJOURNAL OF METAMORPHIC GEOLOGY, Issue 6 2005A. STALLARD Abstract The 3D shape, size and orientation data for white mica grains sampled along two transects of increasing metamorphic grade in the Otago Schist, New Zealand, reveal that metamorphic foliation, as defined by mica shape-preferred orientation (SPO), developed rapidly at sub-greenschist facies conditions early in the deformation history. The onset of penetrative strain metamorphism is marked by the rapid elimination of poorly oriented large clastic mica in favour of numerous new smaller grains of contrasting composition, higher aspect ratios and a strong preferred orientation. The metamorphic mica is blade shaped with long axes defining the linear aspect of the foliation and intermediate axes a partial girdle about the lineation. Once initiated, foliation progressively intensified by an increase in the aspect ratio, size and alignment of grains, although highest grade samples within the chlorite zone record a decrease in aspect ratio and reduction in SPO strength despite continued increase in grain size. These trends are interpreted in terms of progressive competitive anisotropic growth of blade-shaped grains so that the fastest growth directions and blade lengths tend to parallel the extension direction during deformation. The competitive nature of mica growth is indicated by the progressive increase in size and resultant decrease in number of metamorphic mica with increasing grade, from c. 1000 relatively small mica grains per square millimetre of thin section at lower grades, to c. 100 relatively large grains per square millimetre in higher grade samples. Reversal of SPO intensity and grain aspect ratio trends in higher grade samples may reflect a reduction in the strain rate or reduction in the deviatoric component of the stress field. [source] MRI Assessment Followed by Successful Mechanical Recanalization of a Complete Tandem (Internal Carotid/Middle Cerebral Artery) Occlusion and Reversal of a 10-Hour Fixed DeficitJOURNAL OF NEUROIMAGING, Issue 1 2008Catalina C. Ionita MD ABSTRACT BACKGROUND Mechanical clot extraction up to 8 hours after stroke onset is an alternative strategy for opening large vessels, especially for patients ineligible for intravenous thrombolysis. Safety beyond this therapeutic window is untested. METHODS An 81-year-old woman presented 8 hours after she developed left-sided weakness and dysarthria with a National Institutes of Health Stroke Scale (NIHSS) score fluctuating between 6 and 13. Neuroimaging revealed a large perfusion deficit with no diffusion abnormalities. An emergent cerebral angiogram revealed a complete internal carotid artery terminus occlusion. RESULTS Successful mechanical thrombectomy was performed without complication and resulted in almost complete reversal of the patient's deficit to an NIHSS score of 1, 10 hours after stroke onset. CONCLUSION Patients with large hypoperfused areas and minimal diffusion abnormalities on the MRI may benefit from mechanical thrombectomy beyond an 8-hour window. [source] Reversal of suppressed metabolism in prolonged cold preserved cartilageJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2008Tamara K. Pylawka Abstract Chondrocytes in cold preserved cartilage are metabolically suppressed. The goal of this study was to address this metabolic suppression and seek ways to reverse it. Specifically, we examined the roles of rewarming protocols and nitric oxide (NO) in this metabolic suppression. Bovine and canine full-thickness articular cartilage explants were cultured under various temperature conditions, and NO production, proteoglycan (PG) synthesis, and cell viability were measured. Nitric oxide was shown to be negatively correlated with PG synthesis following abrupt rewarming of cold preserved osteochondral allografts. Gradual rewarming of the allograft tissue decreased NO production with higher PG synthesis. Inhibition of nitric oxide synthases (NOS) led to a decrease in NO production and a concomitant increase in PG synthesis. We were able to partially reverse metabolic suppression of cold preserved osteochondral allograft material with gradual rewarming and decrease NO production with NOS inhibition. Chondrocytes in cold preserved allograft material may be metabolically suppressed predisposing the graft to failure in vivo. Minimizing this loss of metabolic function by gradual graft rewarming and decreasing NO production by NOS inhibition at the time of graft implantation may have implications on graft survival in vivo. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:247,254, 2008 [source] | ||||||||||||||||||||||||||||||||||||||||||||||||||||