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Selected AbstractsEnvironmental Risk Factors Predisposing to the Development of Basal Cell CarcinomaDERMATOLOGIC SURGERY, Issue 2004Malgorzata Zak-Prelich MD Background. Basal cell carcinomas (BCCs) are the most common malignancies in white people. The incidence varies depending on the region of the world, with the highest rate of 1% to 2% per year noted in Australia. It is estimated that BCC incidence increases by 5% annually. An increasing incidence of BCC is in line with the changes in the living style and exposure to various environmental factors. Objective. To present the environmental factors that may influence the development of BCCs. The influence of ultraviolet radiation exposure alone and in connection with immunosuppression, smoking, occupational factors, as well as arsenic and ionizing radiation exposure, was described. Conclusion. BCC is a very complex disease, with many factors influencing its development. Environmental factors are very important for the prevalence of BCC, and most of them can be avoided. The exposure to ultraviolet radiation is undoubtedly of great risk; therefore, the national campaigns against aggressive, seasonal sun exposure, especially in children and adolescents, as well as using sunscreens, are of great value in the fight against BCC development. [source] Beyond the Corporate SphereDESIGN MANAGEMENT REVIEW, Issue 1 2000Roger Sametz MUCH OF THE thinking and best practices related to branding and design in the corporate realm are of great value in the not-for-profit sector,particularly academia. Roger Sametz reframes fundamental branding strategies to better fit the academic culture, details the steps necessary to build a strong brand in this context, and shares examples of work Sametz Blackstone has done for several institutions. [source] ,-Methylacyl-CoA racemase (AMACR) in fine-needle aspiration specimens of prostate lesionsDIAGNOSTIC CYTOPATHOLOGY, Issue 11 2009Gordana Kai, M.D. Abstract The elevated expression of P504S gene and its product ,-methylacyl-CoA racemase (AMACR) can serve as a molecular marker for prostate cancer. The goal of this study is to investigate P504S/AMACR expression in fine-needle aspiration smears and correlate it with cytological diagnosis. Immunocytochemistry was performed in 35 patients with morphological diagnosis of prostate carcinoma (n = 16), atypia (n = 15), and benign hyperplasia (n = 4). Among 16 malignant cases there were two low-grade, eight intermediate, and six high-grade prostate carcinomas. Cytoplasmic positivity is analyzed qualitatively as predominantly diffuse or focal and quantitatively as <5%, 5,50%, and >50% of cells. Benign cases showed no P504S/AMACR expression. Positive staining was recorded in 75% of malignant cases, but in the majority of them it was weak and focal or diffuse and in a small amount of cells. The most intensive staining was seen in low-grade carcinomas and some atypical cases. This observation indicates a correlation between P504S/AMACR expression and differentiation of cells. P504S/AMACR staining might be of great value in cytodiagnosis of prostate lesions as well as an example of the characterization of cells at the molecular level using fresh tissue obtained by fine-needle aspiration. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Polymorphism in the sperm ultrastructure among four species of lizards in the genus Tupinambis (Squamata: Teiidae)ACTA ZOOLOGICA, Issue 4 2002L. Tavares-Bastos Abstract We describe, for the first time, the ultrastructure of the spermatozoa of four species of the genus Tupinambis (Squamata, Teiidae). We identified seven polymorphic characters within this genus: the presence and shape of the perforatorial base plate, the presence of the epinuclear lucent zone, the presence of a unilateral ridge in the acrosome, the presence of a central density within the proximal centriole, the number of mitochondria and dense-bodies sets, and the shape of mitochondria. We analysed the evolution of the seven polymorphic characters by mapping them onto a current phylogeny of the species of Tupinambis, using the teiids Ameiva ameiva and Cnemidophorus sexlineatus as outgroups. Our results indicate that sperm ultrastucture characters, although of great value for phylogeny at higher taxonomic levels in reptiles and other groups, are poor predictors of phylogeny when considering the species of Tupinambis studied here. We failed to identify evidences that homoplasy in sperm ultrastructure among the species of Tupinambis is due to convergent adaptation, suggesting that the polymorphism may be selectively neutral in this group. [source] Diffraction imaging in depthGEOPHYSICAL PROSPECTING, Issue 5 2008T.J. Moser ABSTRACT High resolution imaging is of great value to an interpreter, for instance to enable identification of small scale faults, and to locate formation pinch-out positions. Standard approaches to obtain high-resolution information, such as coherency analysis and structure-oriented filters, derive attributes from stacked, migrated images. Since they are image-driven, these techniques are sensitive to artifacts due to an inadequate migration velocity; in fact the attribute derivation is not based on the physics of wave propagation. Diffracted waves on the other hand have been recognized as physically reliable carriers of high- or even super-resolution structural information. However, high-resolution information, encoded in diffractions, is generally lost during the conventional processing sequence, indeed migration kernels in current migration algorithms are biased against diffractions. We propose here methods for a diffraction-based, data-oriented approach to image resolution. We also demonstrate the different behaviour of diffractions compared to specular reflections and how this can be leveraged to assess characteristics of subsurface features. In this way a rough surface such as a fault plane or unconformity may be distinguishable on a diffraction image and not on a traditional reflection image. We outline some characteristic properties of diffractions and diffraction imaging, and present two novel approaches to diffraction imaging in the depth domain. The first technique is based on reflection focusing in the depth domain and subsequent filtering of reflections from prestack data. The second technique modifies the migration kernel and consists of a reverse application of stationary-phase migration to suppress contributions from specular reflections to the diffraction image. Both techniques are proposed as a complement to conventional full-wave pre-stack depth migration, and both assume the existence of an accurate migration velocity. [source] Paraoxonase-1 (PON1) activity as a risk factor for atherosclerosis in chronic renal failure patientsHEMODIALYSIS INTERNATIONAL, Issue 4 2008Saeed Abdelwhab SAEED Abstract Paraoxonase is a high-density lipoprotein-associated enzyme and has been shown to reduce the susceptibility to low-density lipoprotein peroxidation. This study aimed to investigate the activity of serum paraoxonase in uremic patients on hemodialysis (HD) and in the predialysis period, and to evaluate the correlations of vascular disease with paraoxonase activity. Thirty patients with chronic renal failure (CRF) undergoing HD (group 1), 30 patients with CRF under conservative treatment (group 2), and 30 healthy controls (group 3) were included. Basal, salt-stimulated, and arylesterase activity were tested by UV spectrophotometry. Serum lipid parameters were determined. B-Mode Doppler ultrasound was used to assess common carotid intima-media thickness (IMT). Basal paraoxonase, salt-stimulated, and arylesterase activity showed no significant difference between group 1 and group 2. However, it was significantly lower in group 1 and in group 2 than controls. Carotid IMT was significantly higher in group 1 than group 2 and both were significantly higher than controls. Basal paraoxonase-1 (PON1), salt-stimulated PON1, and arylesterase activity correlate with BUN, but only basal PON1 and salt-stimulated PON1 correlate with serum albumin. Linear regression showed that the most significant determinant of carotid IMT was PON1 arylesterase activity in group 1 and arylesterase activity and basal PON1 activity in group 2. Patients with CRF, whether under HD or conservative treatment, have reduced basal and stimulated paraoxonase activities, and this could be an important factor causing increased vascular disease in those patients. Modifying this factor can be of great value to protect against this common complication. [source] A dimensional option for the diagnosis of substance dependence in DSM-VINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue S1 2007John E. Helzer Abstract In this paper we discuss the creation of dimensional equivalents for categorically defined substance use disorders (SUDs) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), which now is being created. We begin with a review of the considerable literature that has accumulated on the dimensional properties of the SUDs. These studies have primarily examined the alcohol use disorders, but work relevant to other substances is reviewed as well. The weight of evidence indicates that SUDs fit well into a unidimensional concept. We next discuss potential advantages, drawbacks, and challenges in developing a dimensional alternative for the SUDs and highlight some issues for an ongoing research agenda to further explore the challenges. Finally we offer a specific proposal for a SUDs dimensional option for DSM-V. The model we propose is based on, and would relate directly back to, the categorical criteria that will be created for the SUDs by the substance use diagnostic workgroup. It is our contention that offering a dimensional equivalent for the DSM-V categories would be of great value, but that the categorical and dimensional definitions should be based on the same symptoms and closely linked. A dimensional scale that does not related directly to the categorical definition would be counterproductive. Copyright © 2007 John Wiley & Sons, Ltd. [source] Measuring the social impacts of local authority events: a pilot study for a civic pride scaleINTERNATIONAL JOURNAL OF NONPROFIT & VOLUNTARY SECTOR MARKETING, Issue 3 2006Emma H. Wood The provision of events and festivals by local government has become an expected, if non-mandatory, service. In many regions these events are organised in order to provide mainly social, rather than economic, benefits to the community and, as a consequence, the providing organisation may have difficulty in demonstrating a return on the budget invested. This paper suggests the use of multi-item attitude scales to quantify the intangible effects of the festival or event programme on the local community. The findings of a pilot study of one such scale are presented showing that reliable and valid methods can be developed, that they can be relatively low cost and simple to apply and that the data generated can be of great value in enhancing the evaluation of local authority service provision. Copyright © 2006 John Wiley & Sons, Ltd. [source] Mechanisms and management of gingival overgrowth in paediatric transplant recipients: a reviewINTERNATIONAL JOURNAL OF PAEDIATRIC DENTISTRY, Issue 4 2003D. Chabria Summary. Increasing numbers of children are receiving solid organ transplants namely kidney, liver, heart and lung. Patient survival rates following such transplants are essentially good with much of the success attributable to the development of Cyclosporine A (CyA), an immunosuppressive drug, that minimizes organ rejection. However the gingival overgrowth (GO) associated with the use of CyA is not only disfiguring but in paediatric recipients, may interfere with normal oral development and function. Objective. The aim of this review is to summarize current knowledge concerning the aetiology, pathogenesis and management of gingival overgrowth. Methods. Literature pertaining to gingival overgrowth is reviewed with particular reference to the paediatric population. Emphasis is placed on summarizing the evidence pertaining to the effectiveness of intervention. Conclusion. CyA undoubtedly causes gingival overgrowth, the effects and levels of which appears to be more severe in younger patients. There is conflicting evidence as to the effectiveness of oral hygiene regimes, antibiotics and surgery in reducing overgrowth. The introduction of an alternative immunosuppressive agent (Tacrolimus) offers potential as it does not appear to cause overgrowth, although research to date is limited by the small sample size of many of the studies. This is an area in which multicentre studies would be of great value. [source] ORIGINAL ARTICLE: Predicting species distributions from small numbers of occurrence records: a test case using cryptic geckos in MadagascarJOURNAL OF BIOGEOGRAPHY, Issue 1 2007Richard G. Pearson Abstract Aim, Techniques that predict species potential distributions by combining observed occurrence records with environmental variables show much potential for application across a range of biogeographical analyses. Some of the most promising applications relate to species for which occurrence records are scarce, due to cryptic habits, locally restricted distributions or low sampling effort. However, the minimum sample sizes required to yield useful predictions remain difficult to determine. Here we developed and tested a novel jackknife validation approach to assess the ability to predict species occurrence when fewer than 25 occurrence records are available. Location, Madagascar. Methods, Models were developed and evaluated for 13 species of secretive leaf-tailed geckos (Uroplatus spp.) that are endemic to Madagascar, for which available sample sizes range from 4 to 23 occurrence localities (at 1 km2 grid resolution). Predictions were based on 20 environmental data layers and were generated using two modelling approaches: a method based on the principle of maximum entropy (Maxent) and a genetic algorithm (GARP). Results, We found high success rates and statistical significance in jackknife tests with sample sizes as low as five when the Maxent model was applied. Results for GARP at very low sample sizes (less than c. 10) were less good. When sample sizes were experimentally reduced for those species with the most records, variability among predictions using different combinations of localities demonstrated that models were greatly influenced by exactly which observations were included. Main conclusions, We emphasize that models developed using this approach with small sample sizes should be interpreted as identifying regions that have similar environmental conditions to where the species is known to occur, and not as predicting actual limits to the range of a species. The jackknife validation approach proposed here enables assessment of the predictive ability of models built using very small sample sizes, although use of this test with larger sample sizes may lead to overoptimistic estimates of predictive power. Our analyses demonstrate that geographical predictions developed from small numbers of occurrence records may be of great value, for example in targeting field surveys to accelerate the discovery of unknown populations and species. [source] Quantitative Analysis of Cytokine mRNA Expression in Hearts from Patients with Nonischemic Dilated Cardiomyopathy (DCM)JOURNAL OF CARDIAC SURGERY, Issue 2003Akira Ukimura To evaluate the role of cytokines in nonischemic DCM, we analyzed the relative quantity of cytokine mRNA expression in the hearts from DCM patients with refractory heart failure, using the ABI PRISM7700 real-time PCR system. We used heart tissues resected from 32 DCM patients at the time of elective partial ventriculectomy (PLV), and five biopsy specimens with normal histological findings as control. Results and Discussion: Interleukin (IL)-1,, IL-10, and Tumor Necrosis Factor (TNF)-, mRNA were expressed at low levels in all normal hearts. The number of IL-10-positive DCM cases was significantly smaller than normal controls (P = 0.0036). One (10%) of 10 DCM patients with IL-10 mRNA expression died after PLV, and 10 (45%) of 22 DCM patients without IL-10 mRNA expression died. IL-1, mRNA was overexpressed (over twice the mean of control subjects) in 15 of 32, and TNF-, mRNA in 10 of 32 patients. We propose the classification of DCM patients into subgroups on the basis of cytokine mRNA expression. Anticytokine therapy or cytokine therapy may have potential in improving the condition of heart failure in certain subgroups of DCM patients. Conclusions: We suggest that DCM patients with heart failure deteriorate without IL-10 mRNA expression in the myocardium. The classification of DCM patients into subgroups on the basis of cytokine mRNA expression may have great value in considering the treatment of this heterogeneous disease state. (J CARD SURG 2003;18 (Suppl 2):S101-S108) [source] Comparison of potential protective effects of melatonin, indole-3-propionic acid, and propylthiouracil against lipid peroxidation caused by potassium bromate in the thyroid glandJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2005Malgorzata Karbownik Abstract Potassium bromate (KBrO3) is a prooxidant and carcinogen, inducing thyroid tumors. Melatonin and indole-3-propionic acid (IPA) are effective antioxidants. Some antioxidative effects of propylothiouracil (PTU),a thyrostatic drug,have been found. The aim of the study was to compare protective effects of melatonin, IPA, and PTU against lipid peroxidation in the thyroids, collected from rats treated with KBrO3, and in homogenates of porcine thyroids, incubated in the presence of KBrO3. Wistar rats were administered KBrO3 (110 mg/kg b.w., i.p., on the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w., i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for 10 days). Homogenates of porcine thyroids were incubated for 30 min in the presence of KBrO3 (5 mM) plus one of the antioxidants: melatonin (0.01, 0.1, 0.5, 1.0, 5.0, 7.5 mM), or IPA (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM), or PTU (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM). The level of lipid peroxidation products (MDA,+,4-HDA) was measured spectrophotometrically in thyroid homogenates. In vivo pretreatment with either melatonin or with IPA or with PTU decreased lipid peroxidation caused by KBrO3,injections in rat thyroid gland. Under in vitro conditions, PTU (5.0, 7.5, and 10.0 mM), but neither melatonin nor IPA, reduced KBrO3 -related lipid peroxidation in the homogenates of porcine thyroids. In conclusion, melatonin and IPA may be of great value as protective agents under conditions of exposure to KBrO3. © 2005 Wiley-Liss, Inc. [source] Beliefs of chronically ill Japanese patients that lead to intentional non-adherence to medicationJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2004N. Iihara BS Summary Objective:, To identify factors, associated with personal beliefs, involved in intentional non-adherence to prescribed medication of Japanese patients with chronic diseases. Methods:, A cross-sectional study of Japanese subjects with chronic, primarily liver, gastrointestinal, or nervous system diseases who had been prescribed oral medicines for regular use, was performed. The subjects were admitted to a university hospital and were interviewed face-to-face on admission. Intentional non-adherence was defined as experience of deliberate adjustment of self-managed prescription medicines during the few months prior to hospital admission. Patients' beliefs about taking medicines were assessed from the perspective of what the patient valued in order to take medicines without anxiety; whether the patient valued information about the medication such as its function and side-effects and/or mutual reliance on doctors. Using logistic multivariate regression analyses, factors associated with intentional non-adherence were identified. Results:, Among 154 subjects, 51 showed intentional non-adherence. Intentional non-adherence was associated with the following three factors: (a) the patients' beliefs with respect to taking medicines without anxiety, especially putting no value on mutual reliance on the patient,doctor relationship (P < 0·001) and putting great value on knowing the drug's side-effects (P < 0·001), (b) poor comprehension of general aspects of medication (P for trend <0·001), and (c) being in the prime of life (40,59 years) (P = 0·011). Comprehension of the function of each medicine, experience of side-effects, anxiety about taking medicines, and the number of types of medicines taken, were not associated with non-adherence. Conclusions:, Beliefs on which individual Japanese patients with chronic diseases attach value in order to take medicines without anxiety were potential factors for intentional non-adherence. This emphasizes the necessity of a patient-oriented approach to take account of patients' personal beliefs about medicines to increase adherence rate in Japan. [source] Applying marketing channel theory to food marketing in developing countries: Vertical disintegration model for horticultural marketing channels in kenyaAGRIBUSINESS : AN INTERNATIONAL JOURNAL, Issue 2 2001Tjalling Dijkstra This article shows that marketing channel theory, which has been extensively applied in developed countries, can also be of great value to the developing world. Notably, the channel approach makes it possible to explain the number of trade levels observed in food marketing systems. We propose here a vertical disintegration model for horticultural marketing channels in Kenya. It contains one dependent variable (the degree of vertical disintegration of a channel) and five independent variables (the population size of the market center served by the channel, the population density of the rural hinterland of that market center, the transport time from farm to market center, the turnover of the retailer involved, and the keeping quality of the commodity traded). Binomial and multinomial logit analyses show that the probability of encountering a more disintegrated horticultural marketing channel increases when the market center has more inhabitants, when the center's rural hinterland is more densely populated, and when the transport to the center takes more time. The probability of encountering a less disintegrated channel increases when the retailer in the channel has a larger turnover and when the traded commodity is a leafy vegetable. [EconLit classification: L190 market structure) © 2001 John Wiley & Sons, Inc. [source] An Overview of the Biology of Reaction Wood FormationJOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 2 2007Sheng Du Abstract Reaction wood possesses altered properties and performs the function of regulating a tree's form, but it is a serious defect in wood utility. Trees usually develop reaction wood in response to a gravistimulus. Reaction wood in gymnosperms is referred to as compression wood and develops on the lower side of leaning stems or branches. In arboreal, dicotyledonous angiosperms, however, it is called tension wood and is formed on the upper side of the leaning. Exploring the biology of reaction wood formation is of great value for the understanding of the wood differentiation mechanisms, cambial activity, gravitropism, and the systematics and evolution of plants. After giving an outline of the variety of wood and properties of reaction wood, this review lays emphasis on various stimuli for reaction wood induction and the extensive studies carried out so far on the roles of plant hormones in reaction wood formation. Inconsistent results have been reported for the effects of plant hormones. Both auxin and ethylene regulate the formation of compression wood in gymnosperms. However, the role of ethylene may be indirect as exogenous ethylene cannot induce compression wood formation. Tension wood formation is mainly regulated by auxin and gibberellin. Interactions among hormones and other substances may play important parts in the regulation of reaction wood formation. [source] Precursor synthesis and radiolabelling of [11C]ADAM: a potential radioligand for the serotonin transporter exploration by PETJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2001Johnny VERCOUILLIE Abstract The serotoninergic system is involved in a variety of neurological and psychiatric disorders. Exploration of the serotonin transporters (5-HTT) in living human brain by PET would be of great value for better understanding, diagnosis and therapeutic follow up of these diseases. In order to obtain a selective radioligand to explore the 5-HTT by PET we report the synthesis of [11C]N,N-dimethyl-2-(2-amino-4-iodophenylthio)-benzylamine ([11C]ADAM). The precursor for labelling N-demethyl ADAM, was obtained in five steps using 2,5-dibromonitrobenzene and 2-thio-N-methylbenzamide as starting material. [11C]ADAM was synthesised by N-alkylation of the precursor using [11C]methyl iodide in DMF. The incorporation yield of [11C]methyl iodide was in the range of 50 to 70%. Finally [11C]ADAM was obtained in 30 minutes synthesis time including HPLC and with a radiochemical purity better than 99%. Copyright © 2001 John Wiley & Sons, Ltd. [source] Accuracy of frozen section in the diagnosis of malignant ovarian tumorJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 5 2004Dittakarn Boriboonhirunsarn Abstract Aim:, To evaluate the diagnostic accuracy of frozen section for histopathologic diagnosis of ovarian tumors. Methods:, A total of 147 surgically removed ovarian tumors were studied. Each ovarian tumor sample was evaluated for histopathologic diagnosis using both frozen and paraffin sections. Interpretation was separate and blinded between each technique. Accuracy, diagnostic values and their 95% confidence intervals (CI) were estimated by comparing the results from both techniques, using paraffin section as a gold standard. Results:, Overall accuracy of frozen section was 89.8% (95% CI 83.4,94.0). Sensitivity was 90.4% (95% CI 78.2,96.4) for malignant, 33.3% (95% CI 6.0,75.9) for borderline, and 93.3% (95% CI 85.4,97.2) for benign tumors. The predictive value was 100% (95% CI 90.6,100) for malignant, 20% (95% CI 3.5,55.8) for borderline, and 92.2% (95% CI 84.1,96.5) for benign tumors. Most false negatives occurred in mucinous and borderline tumors. No benign tumor was misdiagnosed as malignant by frozen section. Accuracy and negative predictive value were significantly lower in epithelial rather than germ and other cell types. Excellent agreement with regard to histologic cell type was observed (Kappa 0.81). Conclusion:, Frozen section appears to be an accurate technique for the histopathologic diagnosis of ovarian tumors. Some limitations were observed among borderline and mucinous tumors; this emphasizes the great value of frozen section in the diagnosis of ovarian tumors. [source] Automatic quality assessment in structural brain magnetic resonance imaging,MAGNETIC RESONANCE IN MEDICINE, Issue 2 2009Bénédicte Mortamet Abstract MRI has evolved into an important diagnostic technique in medical imaging. However, reliability of the derived diagnosis can be degraded by artifacts, which challenge both radiologists and automatic computer-aided diagnosis. This work proposes a fully-automatic method for measuring image quality of three-dimensional (3D) structural MRI. Quality measures are derived by analyzing the air background of magnitude images and are capable of detecting image degradation from several sources, including bulk motion, residual magnetization from incomplete spoiling, blurring, and ghosting. The method has been validated on 749 3D T1 -weighted 1.5T and 3T head scans acquired at 36 Alzheimer's Disease Neuroimaging Initiative (ADNI) study sites operating with various software and hardware combinations. Results are compared against qualitative grades assigned by the ADNI quality control center (taken as the reference standard). The derived quality indices are independent of the MRI system used and agree with the reference standard quality ratings with high sensitivity and specificity (>85%). The proposed procedures for quality assessment could be of great value for both research and routine clinical imaging. It could greatly improve workflow through its ability to rule out the need for a repeat scan while the patient is still in the magnet bore. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [source] Matrix metalloproteinase 11 (MMP-11; stromelysin-3) and synthetic inhibitorsMEDICINAL RESEARCH REVIEWS, Issue 4 2007Magdalini Matziari Abstract Matrix metalloproteinase (MMP)-11, or Stromelysin 3, is a particular member of MMP family, a group of zinc-dependent endopeptidases involved in matrix degradation and tissue remodeling. Despite intense efforts since its first characterization 15 years ago, its role and target substrates in different diseases remain largely unknown. While mice with MMP-11 deficiency display no particular phenotype, analysis of different tumorigenesis models with these mice lead to the conclusion that MMP-11 promotes tumor development. In contrast with other MMPs, MMP-11 is unable to degrade any major extracellular matrix component and unlike most of other MMPs that are secreted as inactive proenzymes and activated extracellularly, MMP-11 is secreted under active form. MMP-11 may thus play a unique role in tissue remodeling processes, including those associated with tumor progression. Although MMP-11 and other MMPs have been considered as promising targets to combat cancer, a first series of clinical trials using broad-spectrum MMP inhibitors have not led to significant therapeutic benefits. These disappointing results highlight the need for better understanding of the exact role played by each MMP during the different stages of tumor progression. Among the different strategies to fill this gap, highly specific MMP inhibitors would be of great value. This review provides an update on the selectivity profile of phosphinic MMP-11 synthetic inhibitors developed and discusses the opportunities and limitations to identify inhibitors able to fully discriminate MMP-11 from the other MMPs. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 4, 528,552, 2007 [source] Therapeutic potential of sulfamides as enzyme inhibitorsMEDICINAL RESEARCH REVIEWS, Issue 6 2006Jean-Yves Winum Abstract Sulfamide, a quite simple molecule incorporating the sulfonamide functionality, widely used by medicinal chemists for the design of a host of biologically active derivatives with pharmacological applications, may give rise to at least five types of derivatives, by substituting one to four hydrogen atoms present in it, which show specific biological activities. Recently, some of these compounds started to be exploited for the design of many types of therapeutic agents. Among the enzymes for which sulfamide-based inhibitors were designed, are the carbonic anhydrases (CAs), a large number of proteases belonging to the aspartic protease (HIV-1 protease, ,-secretase), serine protease (elastase, chymase, tryptase, and thrombin among others), and metalloprotease (carboxypeptidase A (CPA) and matrix metalloproteinases (MMP)) families. Some steroid sulfatase (STS) and protein tyrosine phosphatase inhibitors belonging to the sulfamide class of derivatives have also been reported. In all these compounds, many of which show low nanomolar affinity for the target enzymes for which they have been designed, the free or substituted sulfamide moiety plays important roles for the binding of the inhibitor to the active site cavity, either by directly coordinating to a metal ion found in some metalloenzymes (CAs, CPA, STS), usually by means of one of the nitrogen atoms present in the sulfamide motif, or as in the case of the cyclic sulfamides acting as HIV protease inhibitors, interacting with the catalytically critical aspartic acid residues of the active site by means of an oxygen atom belonging to the HNSO2NH motif, which substitutes a catalytically essential water molecule. In other cases, the sulfamide moiety is important for inducing desired physico-chemical properties to the drug-like compounds incorporating it, such as enhanced water solubility, better bioavailability, etc., because of the intrinsic properties of this highly polarized moiety when attached to an organic scaffold. This interesting motif is thus of great value for the design of pharmacological agents with a lot of applications. © 2006 Wiley Periodicals, Inc. Med Res Rev [source] Development of microsatellite markers in polyploid persimmon (Diospyros kaki Lf) from an enriched genomic libraryMOLECULAR ECOLOGY RESOURCES, Issue 2 2006J. M. SORIANO Abstract The oriental persimmon (Diospyros kaki Lf) is believed to have originated in China with subsequent introduction into Japan and Korea in ancient times. The species was then brought to Europe, Brazil and the USA from Japan in the 19th century. Recent studies highlighted the poor state of identification of cultivars in these countries due to incorrect labelling and presence of synonyms among local varieties. Thus, molecular marker characterization of germplasm resources is of great value for genetic resource preservation and plant breeding of persimmon. Therefore, to identify accessions for further plant breeding and germplasm management, 37 microsatellite loci were developed from a CT/AG-enriched persimmon genomic library. [source] A case study in organizational change: Evaluation in Cooperative ExtensionNEW DIRECTIONS FOR EVALUATION, Issue 120 2008Roger A. Rennekamp This chapter examines how factors both internal and external to Cooperative Extension have influenced its commitment and capability to assess the quality and impact of its programs. The authors begin by documenting how the nature of Extension programming has changed dramatically in response to societal needs over the course of the organization's history. Because Extension's culture places great value on service to people, early attempts to measure organizational performance focused on the number of individuals reached and the quality of the interaction with those individuals. Over time, Extension educators began to turn their attention to program outcomes. But it wasn't until Extension was threatened with significant budget cuts that the organization responded with systemwide efforts to document the results of its programming. The authors conclude that so long as Extension educators consider program evaluation an obligation to be met rather than an opportunity to learn and grow, optimum levels of commitment and capability cannot be achieved. © Wiley Periodicals, Inc. [source] Clinical prediction rule to diagnose post-infectious bronchiolitis obliterans in childrenPEDIATRIC PULMONOLOGY, Issue 11 2009Alejandro J. Colom Abstract Rationale Infant pulmonary function testing has a great value in the diagnosis of post-infectious bronchiolitis obliterans (BOs), because of characteristic patterns of severe and fixed airway obstruction. Unfortunately, infant pulmonary function testing is not available in most pediatric pulmonary centers. Objective To develop and validate a clinical prediction rule (BO-Score) to diagnose children under 2 years of age with BOs, using multiple objectively measured parameters readily available in most medical centers. Methods Study subjects, children under 2 years old with a chronic pulmonary disease assisted at R. Gutierrez Children's Hospital of Buenos Aires. Patients were randomly divided into a derivation (66%) and a validation (34%) set. ROC analyses and multivariable logistic regression included significant clinical, radiological, and laboratory predictors. The main outcome measure was a diagnosis of BOs. The performance of the BO-Score was tested on the validation set. Results Hundred twenty-five patients were included, 83 in the derivation set and 42 in the validation set. The BO-Score (area under ROC curve,=,0.96; 95% CI, 0.9,1.0%) was developed by assigning points to the following variables: typical clinical history (four points), adenovirus infection (three points), and high-resolution computed tomography with mosaic perfusion (four points). A Score ,7 predicted the diagnosis of BOs with a specificity of 100% (95% CI, 79,100%) and a sensitivity of 67% (95% CI, 47,80%). Conclusions The BO-Score is a simple-to-use clinical prediction rule, based on variables that are readily available. A BO-Score of 7 or more predicts a diagnosis of post-infectious BOs with high accuracy. Pediatr Pulmonol. 2009; 44:1065,1069. ©2009 Wiley-Liss, Inc. [source] Utility of AFLP markers for the assessment of genetic diversity within Brassica nigra germplasmPLANT BREEDING, Issue 1 2004M. S. Negi Abstract Genetic diversity of 18 Brassica nigra accessions was estimated using amplified fragment length polymorphism (AFLP) marker technology. Two B. rapa and two B. juncea accessions were selected as outliers in the study. Eight AFLP primer combinations generated a total of 426 bands, of which 79% were polymorphic. The UPGMA method was employed to construct a dendrogram based on the Jaccard's similarity coefficient. The accessions of B. rapa separated from those of B. nigra at a genetic similarity coefficient of 0.27 while those of B. juncea did so at 0.5. The genetic similarity coefficients within the B. nigra accessions ranged from 0.58 to 0.86. Based on these coefficients it was concluded that the B. nigra accessions show high levels of genetic variation. These results have significant implications in the crop improvement programmes for the agronomically important crop B. juncea, an amphidiploid of B. nigra and B. rapa. Two incorrectly labelled B. nigra accessions were also identified. These accessions were found to cluster with those of B. juncea accessions. This result demonstrates the great value of AFLP markers in the management of genebanks. [source] Electrospray ionization tandem mass spectrometry fragmentation of protonated flavone and flavonol aglycones: a re-examinationRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 2 2009Gonçalo C. Justino Flavonoids are important phytochemicals which have been intensively studied in the last decades in view of their antioxidant activity, which is of particular importance in the case of flavones and flavonols, that differ in a single 3-OH group. Mass spectrometry has been used to elucidate the structures of many types of flavonoids and their metabolites. The work we present here is focused on the electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of flavone and flavonols aglycones. Their fragmentation mechanisms in the positive ion mode are described and compared with previously reported mechanisms. We analyzed flavonoid derivatives produced by reaction of the flavonoids with chemically synthesized hypohalous acids (HOCl, HOBr and HOI) and peroxynitrite, reactive species involved in the inflammatory response. All the proposed pathways have been analyzed using computational chemistry methods in order to seek for possible variations and establish the most plausible ones. We observed that the losses of one and two CO molecules can be useful in terms of antioxidant activity prediction. Losses of one and two C2H2O groups are also informative in terms of structure and activity predictions. The retro-Diels-Alder fragmentations, and subsequent neutral losses, were reviewed and, according to our calculations, the most plausible structures for the product ions were established. These fingerprints will be of great value for differentiating flavonoids from other compounds in complex biological mixtures and for a thorough structural identification of flavonoid aglycones and their invivo metabolites. Copyright © 2008 John Wiley & Sons, Ltd. [source] Alterations in sperm protein phosphorylation in male infertilityANDROLOGIA, Issue 5 2001M. L. Hortas Summary. Protein phosphorylation is involved in sperm capacitation, so the effect of protein phosphatase inhibitors on the capacitation of spermatozoa of males with unexplained infertility was investigated. d -mannose ligand specific receptor expression in fresh, living spermatozoa, capacitated or treated with calyculin A (an inhibitor of protein phosphatases 1 and 2A), was studied in three groups of men: pre-vasectomy (fertile) males, males in couples with male infertility, and males in couples with infertility of unknown aetiology. Flow cytometry showed significant differences between infertile couples with a male factor and fertile couples (P < 0.05), both after capacitation and after treatment with calyculin A. In the group of couples with infertility of unknown aetiology (n = 15), d -mannose receptor expression was diminished in six cases after classical capacitation. However, when the spermatozoa of these six men were treated with calyculin A, five showed an increased specific d -mannose receptor expression. From these results it is suggested that in vitro treatment of spermatozoa with inhibitors of protein phosphatases may be of great value in some cases of unexplained infertility. [source] Features and preliminary results of the Dutch centre of the ERSPC (Rotterdam, the Netherlands)BJU INTERNATIONAL, Issue 2003M.J. Roobol OBJECTIVE To describe the preliminary results of the Dutch section of a large multicentre study of screening for prostate cancer, the European Randomized study of Screening for Prostate Cancer (ERSPC), initiated in the Netherlands and Belgium in 1991. MATERIALS AND METHODS After a series of five pilot studies which started in 1991, full-capacity screening started in 1994 with the use of a serum prostate-specific antigen (PSA) determination, a digital rectal examination (DRE) and transrectal ultrasonography (TRUS) as screening tests. Depending on the results and the screening protocol used, men were referred for further examination by sextant biopsies (extended with a seventh biopsy if TRUS showed abnormality). The protocols used, efficiency of the different screening tests, number of cancers detected in the pilot studies, initial screening round and preliminary results of the second screening round are described. RESULTS After the pilot studies it became clear that a study of prostate cancer screening was feasible in the Rotterdam area. The screening protocol was workable and the recruitment rate acceptable (39.5%). An inventory of the population registries of Rotterdam and surrounding municipalities, and the known recruitment rate, made it clear that a contribution of 40 000 men (aged 55,74 years) from the Dutch centre to the ERSPC was feasible. The initial screening round started in December 1993 and lasted until December 1999 (protocol 5,10). In all, 42 376 men were randomized and 1014 cancers detected (5.1%). During this screening the protocol was simplified. After evaluating the different screening tests abnormal results of the DRE and TRUS were omitted as an indication for a sextant biopsy. Only a serum PSA level of , 3.0 ng/mL is now used as the indication. The second screening round started in December 1997 and continues. To December 2002, 9920 men were screened for the second time, 4 years after their initial screening visit. To date 446 cancers have been detected (4.5%); this round will last to December 2003. Further evaluation of the screening regimen and characteristics of the cancers detected are constantly assessed within the Dutch ERSPC. Meanwhile a third screening round has also been initiated, which will last to December 2007. CONCLUSION A prostate cancer screening study of the projected magnitude is feasible in Rotterdam; the recruitment rate is acceptable and the screening tests well tolerated. The study has generated many scientific publications and will be of great value in determining whether prostate cancer screening should be part of general healthcare. [source] A New Species of Gobiconodon (Mammalia) from Western Liaoning, China and its Implication for the Dental Formula of GobiconodonACTA GEOLOGICA SINICA (ENGLISH EDITION), Issue 2 2009Chongxi YUAN Abstract: A new species of Gobiconodon from the Early Cretaceous in the Lujiatun locality of western Liaoning is erected based on an almost complete skull and lower jaw. It has a flatten skull roof, the lambdoidal crest is strongly curved forward, and the sagittal crest is short and low. There is a protuberance near the anterior base of the zygoma. The preservation of the upper teeth is very rare in all known Gobiconodon, and this provides important information for the study on the formula of Gobiconodon. The new species is the fifth primitive mammal unearthed from the Lujiatun locality, and is of great value for the study of the geological age of the stratigraphy at Lujiatun by primitive mammal material. [source] Spectroscopic and perfusion magnetic resonance imaging predictors of progression in pediatric brain tumorsCANCER, Issue 6 2004A. Aria Tzika Ph.D. Abstract BACKGROUND In vivo biomarkers to predict progression of brain tumors are of great value in clinical practice. Therefore, the authors tested the hypothesis that changes in choline ratios by magnetic resonance (MR) spectroscopic imaging and/or relative tumor blood volume (rTBV) can differentiate clinically stable from progressive pediatric brain tumors. METHODS MR spectroscopic imaging examinations were performed on 27 children with neuroglial brain tumors during therapy on a 1.5-Tesla MR system. Normalized rTBV values were measured in 11 of 27 patients. Each examination was rated as stable or progressive by clinical and imaging criteria. RESULTS The percent change in normalized choline (Cho) was significantly greater in patients who had progressive examinations compared with patients who had stable examinations (P = 0.03). The percent change in Cho/N-acetylaspartate (Cho/NAA) was significantly higher in patients who had progressive outcomes (n = 18 patients) compared with patients who had stable outcomes (n = 32 patients; P < 0.001; sensitivity, 0.89; specificity, 0.88) and was identified as the most important prognostic indicator of tumor progression by logistic regression (likelihood ratio test, 33.4; P < 0.001). The odds of tumor progression were approximately 55 times greater for patients who showed at least a 20% change in Cho/NAA. rTBV distinguished between progressing and stable tumors (P = 0.03), and Cho/NAA and rTBV values showed interaction to predict the probability of a progressing clinical outcome. CONCLUSIONS The percent change in Cho/NAA by proton MR spectroscopic imaging, assisted by rTBV, was useful in predicting tumor progression in children with brain tumors. Cancer 2004. © 2004 American Cancer Society. [source] Protective effects of melatonin and indole-3-propionic acid against lipid peroxidation, caused by potassium bromate in the rat kidneyCELL BIOCHEMISTRY AND FUNCTION, Issue 6 2006gorzata Karbownik Abstract Potassium bromate (KBrO3) is classified as a carcinogenic agent. KBrO3 induces tumors and prooxidative effects in kidneys. Melatonin is a well known antioxidant and free radical scavenger. Indole-3-propionic acid (IPA), an indole substance, also reveals antioxidative properties. Recently, some antioxidative effects of propylthiouracil (PTU),an antithyroid drug,have been found. The aim of the study was to compare protective effects of melatonin, IPA, and PTU against lipid peroxidation in the kidneys and blood serum and, additionally, in the livers and the lungs, collected from rats, pretreated with KBrO3. Male Wistar rats were administered KBrO3 (110 mg/kg b.w., i.p., on the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w., i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for 10 days). The level of lipid peroxidation products,malondialdehyde,+,4-hydroxyalkenals (MDA,+,4-HDA),was measured spectrophotometrically in thyroid homogenates. KBrO3, when injected to rats, significantly increased lipid peroxidation in the kidney homogenates and blood serum, but not in the liver and the lung homogenates. Co-treatment with either melatonin or with IPA, but not with PTU, decreased KBrO3 -induced oxidative damage to lipids in the rat kidneys and serum. In conclusion, melatonin and IPA, which prevent KBrO3 -induced lipid peroxidation in rat kidneys, may be of great value as protective agents under conditions of exposure to KBrO3. Copyright © 2006 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||