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Selected AbstractsThe treatment of faecal incontinence following ileostomy takedown after rectal surgery for cancerJOURNAL OF NURSING AND HEALTHCARE OF CHRONIC ILLNE SS: AN INTERNATIONAL INTERDISCIPLINARY JOURNAL, Issue 3 2009Federico Attene MD Aim., The aim of this study was to assess the effectiveness of rehabilitative treatment of the pelvic floor on faecal incontinence after ileostomy take-down. Background., Several conditions can induce surgeons to fashion an excluding ileostomy. In our experience 40% of patients subjected to ileostomy takedown refer faecal incontinence which becomes a chronic condition if not treated. Design., Between 2006 and 2008 we observed fourteen patients with faecal incontinence after ileostomy takedown. Previous manometric assessment of the pelvic floor functionality they underwent rehabilitative treatment by electrostimulation of the anal sphincter. Methods., The rehabilitation program was organised in 10 sessions each of 15 minutes. In each session a double electrode probe was introduced through the anus which is able to conduct electric impulses at a frequency of 75 Hz with an intensity of 15,50 mA and duration of 150 ,s. Results., All patients showed important clinical and manometric improvement. Three patients needed a second rehabilitative treatment with subsequent clinical resolution of faecal incontinence. Conclusions., Improvement in all patients was found although the data are not statistically significant. Consideration of social and psychological implications of treatments is important. Patients need to acquire full control of their body and its functions. Considering that faecal incontinence is a pathology with high social costs it appears necessary to establish an effective and repeatable method of treatment. Electric stimulation seems to be the most adequate tool for this purpose. Relevance to clinical practice., The standardisation of parameters in the treatment protocol of incontinence could allow to extend this therapy to a lot of colo-proctological units. [source] Microwave-assisted solid-phase peptide synthesis at 60 °C: alternative conditions with low enantiomerization,JOURNAL OF PEPTIDE SCIENCE, Issue 12 2009Carina Loffredo Abstract Several conditions have been used in the coupling reaction of stepwise SPPS at elevated temperature (SPPS-ET), but we have elected the following as our first choice: 2.5-fold molar excess of 0.04,0.08 M Boc or Fmoc-amino acid derivative, equimolar amount of DIC/HOBt (1:1) or TBTU/DIPEA (1:3), 25% DMSO/toluene, 60 °C, conventional heating. In this study, aimed to further examine enantiomerization under such condition and study the applicability of our protocols to microwave-SPPS, peptides containing L -Ser, L -His, L -Cys and/or L -Met were manually synthesized traditionally, at 60 °C using conventional heating and at 60 °C using microwave heating. Detailed assessment of all crude peptides (in their intact and/or fully hydrolyzed forms) revealed that, except for the microwave-assisted coupling of L -Cys, all other reactions occurred with low levels of amino acid enantiomerization (<2%). Therefore, herein we (i) provide new evidences that our protocols for SPPS at 60 °C using conventional heating are suitable for routine use, (ii) demonstrate their appropriateness for microwave-assisted SPPS by Boc and Fmoc chemistries, (iii) disclose advantages and limitations of the three synthetic approaches employed. Thus, this study complements our past research on SPPS-ET and suggests alternative conditions for microwave-assisted SPPS. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. [source] The auricular impression: An alternate techniqueJOURNAL OF PROSTHODONTICS, Issue 2 2000Mark F. Mathews DDS Several conditions necessitate surgical or prosthetic ear reconstruction. If an auricular prosthesis is planned, accurate impressions of both the affected and unaffected ears are essential. This article describes a technique that uses a wax-customized, rigid impression tray and irreversible hydrocolloid to minimize distortion during the procedure. [source] Nondipolar Content of T Wave Derived from a Myocardial Source Simulation with Increased Repolarization InhomogeneityANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2009Milos Kesek M.D., Ph.D. Background: Several conditions with repolarization disturbances are associated with increased level of nondipolar components of the T wave. The nondipolar content has been proposed as a measure of repolarization inhomogeneity. This computer simulation study examines the link between increased nondipolar components and increased repolarization inhomogeneity in an established model. Methods: The simulation was performed with Ecgsim software that uses the equivalent double-layer source model. In the model, the shape of transmembrane potential is derived from biological recordings. Increased repolarization inhomogeneity was simulated globally by increasing the variance in action potential duration and locally by introducing changes mimicking acute myocardial infarction. We synthesized surface ECG recordings with 12, 18, and 300 leads. The T-wave residue was calculated by singular value decomposition. The study examined the effects of the number of ECG leads, changes in definition of end of T wave and random noise added to the signal. Results: Normal myocardial source gave a low level of nondipolar content. Increased nondipolar content was observed in the two types of increased repolarization inhomogeneity. Noise gave a large increase in the nondipolar content. The sensitivity of the result to noise increased when a higher number of principal components were used in the computation. Conclusions: The nondipolar content of the T wave was associated with repolarization inhomogeneity in the computer model. The measure was very sensitive to noise, especially when principal components of high order were included in the computations. Increased number of ECG leads resulted in an increased signal-to-noise ratio. [source] Genetic engineering approach for the production of rhamnosyl and allosyl flavonoids from Escherichia coliBIOTECHNOLOGY & BIOENGINEERING, Issue 1 2010Dinesh Simkhada Abstract The main functions of glycosylation are stabilization, detoxification and solubilization of substrates and products. To produce glycosylated products, Escherichia coli was engineered by overexpression of TDP- L -rhamnose and TDP-6-deoxy- D -allose biosynthetic gene clusters, and flavonoids were glycosylated by the overexpression of the glycosyltransferase gene from Arabidopsis thaliana. For the glycosylation, these flavonoids (quercetin and kaempferol) were exogenously fed to the host in a biotransformation system. The products were isolated, analyzed and confirmed by HPLC, LC/MS, and ESI-MS/MS analyses. Several conditions (arabinose, IPTG concentration, OD600, substrate concentration, incubation time) were optimized to increase the production level. We successfully isolated approximately 24,mg/L 3- O -rhamnosyl quercetin and 12.9,mg/L 3- O -rhamnosyl kaempferol upon feeding of 0.2,mM of the respective flavonoids and were also able to isolate 3- O -allosyl quercetin. Thus, this study reveals a method that might be useful for the biosynthesis of rhamnosyl and allosyl flavonoids and for the glycosylation of related compounds. Biotechnol. Bioeng. 2010;107: 154,162. © 2010 Wiley Periodicals, Inc. [source] Progressive Hulls for Intersection ApplicationsCOMPUTER GRAPHICS FORUM, Issue 2 2003Nikos Platis Abstract Progressive meshes are an established tool for triangle mesh simplification. By suitably adapting the simplification process, progressive hulls can be generated which enclose the original mesh in gradually simpler, nested meshes. We couple progressive hulls with a selective refinement framework and use them in applications involving intersection queries on the mesh. We demonstrate that selectively refinable progressive hulls considerably speed up intersection queries by efficiently locating intersection points on the mesh. Concerning the progressive hull construction, we propose a new formula for assigning edge collapse priorities that significantly accelerates the simplification process, and enhance the existing algorithm with several conditions aimed at producing higher quality hulls. Using progressive hulls has the added advantage that they can be used instead of the enclosed object when a lower resolution of display can be tolerated, thus speeding up the rendering process. ACM CSS: I.3.3 Computer Graphics,Picture/Image Generation, I.3.5 Computer Graphics,Computational Geometry and Object Modeling, I.3.7 Computer Graphics,Three-Dimensional Graphics and Realism [source] When monocytes and platelets compete: The effect of platelet count on the flow cytometric measurement of monocyte CD36,CYTOMETRY, Issue 2 2010W.H. Dzik Abstract Background: Flow cytometric measurement of monocyte surface CD36 is relevant to several conditions including diabetes, cardiovascular disease, lipid disorders, platelet isoimmunization, and susceptibility to P falciparum malaria. CD36 is also strongly expressed on platelets where it is also known as platelet glycoprotein IV. Methods: Whole blood samples, containing identical monocyte concentrations, were adjusted to contain platelets ranging from 20,000/uL to 600,000/uL, were stained with fluorescent-labeled anti-CD36, and analyzed by flow cytometry. Results: CD36 median fluorescent intensity (MFI) observed on monocytes decreased as the platelet concentration in the sample increased with more than a 50% decline in monocyte MFI over the normal range of platelet values. The effect was not abolished by using larger volumes of monoclonal antibody and was observed with different clones of reagent anti-CD36. The findings were most consistent with competition by platelets for the CD36 reagent. Similar findings were observed with antibody to class I HLA. Under defined assay conditions, monocyte CD36 MFI declined with rising platelet concentration in a predictable fashion following an inverse linear relationship. Conclusions: Measurement of CD36 expression on monocytes by flow cytometry in whole blood samples is affected by the sample platelet count. When comparing the monocyte CD36 expression among different individuals, our approach can be used to adjust measured monocyte CD36 expression for the effect of the platelet concentration in the sample. Competition by platelets for monoclonal reagents may occur in other settings when whole blood assays are used and when the target antigen is strongly expressed on both platelets and leukocytes. © 2009 Clinical Cytometry Society [source] Time domain characteristics of hoof-ground interaction at the onset of stance phaseEQUINE VETERINARY JOURNAL, Issue 7 2006J. F. BURN Summary Reasons for performing study: Little is known about the interaction of the hoof with the ground at the onset of stance phase although is it widely believed that high power collisions are involved in the aetiopathology of several conditions causing lameness. Objectives: To answer 3 questions regarding the fundamental nature of hoof-ground collision: (1) is the collision process deterministic for ground surfaces that present a consistent mechanical interface (2) do collision forces act on the hoof in a small or large range of directions and (3) Is the hoof decelerated to near-zero velocity by the initial deceleration peak following ground contact? Methods: Hoof acceleration during the onset of stance phase was recorded using biaxial accelerometry for horses trotting on a tarmac surface and on a sand surface. Characteristics of the collision process were identified both from vector plots and time series representations of hoof acceleration, velocity and displacement. Results: The response of the hoof to collision with smooth tarmac was predominantly deterministic and consistent with the response of a spring-damper system following shock excitation. The response to collision with sand was predominantly random. The deceleration peak following ground contact did not decelerate the hoof to near-zero velocity on tarmac but appeared to on sand. On both surfaces, collision forces acted on the hoof in a wide range of directions. Conclusions: The study suggests the presence of stiff, visco-elastic structures within the foot that may act as shock absorbers isolating the limb from large collision forces. Potential relevance: The study indicates objectives for future in vivo and in vitro research into the shock absorbing mechanism within the equine foot; and the effects of shoe type and track surface properties on the collision forces experienced during locomotion. Studies of this nature should help to establish a link between musculoskeletal injury, hoof function and hoof-ground interaction if, indeed, one exists. [source] Transcriptional profiling of the early stages of germination in Candida albicans by real-time RT-PCRFEMS YEAST RESEARCH, Issue 3 2004Mika Toyoda Abstract By using real-time RT-PCR, we profiled the expression of CGR1, CaMSI3, EFG1, NRG1, and TUP1 in Candida albicans strains JCM9061 and CAI4 under several conditions, including induction of morphological transition, heat shock, and treatment with calcium inhibitors. Expression of CaMSI3 changed under these growth conditions except during heat shock. CGR1 expression increased during the early stages of hyphal growth in JCM9061, while expression was strain-dependent during heat shock. Both EFG1 and NRG1 were similarly expressed under hypha-inducing conditions and heat shock. Expression of TUP1 was slightly different from the expression of EFG1 or NRG1. [source] Staunch protections: the ethics of haemophilia gene transfer researchHAEMOPHILIA, Issue 1 2008J. KIMMELMAN Summary., Haemophilia has long been considered an ideal system for validating human gene transfer (GT). However, haemophilia GT trials present a particular ethical challenge because they involve subjects whose medical condition is stabilized by standard therapies. Below, I review the ethics and risks of haemophilia GT clinical research. I propose several conditions and practices that strengthen the ethical basis for such trials. These include consultation with haemophilia advocacy organizations as trials are designed and executed, high standards of supporting evidence before trials are initiated, pretrial publication of this evidence, and the offer of indemnification for participants. I further argue against the conduct of paediatric haemophilia GT studies at this time, and raise questions about the fairness of recruiting economically disadvantaged subjects into studies that are primarily directed towards the health needs of persons in the developed world. [source] The amazing universe of hepatic microstructure,HEPATOLOGY, Issue 2 2009Valeer J. Desmet An informal review is presented by the author of his 50 years of involvement in practice and research in hepatopathology. Some background for the author's attitude and meandering pathway into his professional career serves as introduction to a short discussion of the main topics of his interest and expertise. Histogenesis of liver cancer was the theme of early work for a Ph.D. thesis, the results of which were lost into oblivion due to local rules and circumstances, but were rescued three decades later. His conclusions about the cells of origin of liver cancer remain concordant with the newer concepts in the field after nearly half a century. Studies in the field of chronic hepatitis became a long saga, involving the first classification of this syndrome by "the Gnomes" in 1968, histochemical investigations of viral antigens, lymphocyte subsets and adhesion molecules, and a quarter century later, the creation of a new classification presently in use. Cholestasis was a broadening field in diagnostic entities and involved the study of liver lesions, comprising pathways of bile regurgitation (including reversed secretory polarity of hepatocytes) and so-called ductular reaction. The latter topic has a high importance for the various roles it plays in modulating liver tissue of chronic cholestasis into biliary cirrhosis, and as the territory of hepatic progenitor cells, crucial for liver regeneration in adverse conditions and in development of liver cancer. Study of the embryology of intrahepatic bile ducts helped to clarify the strange appearance of the ducts in "ductal plate configuration" in several conditions, including some forms of biliary atresia with poor prognosis and all varieties of fibrocystic bile duct diseases with "ductal plate malformation" as the basic morphologic lesion. (HEPATOLOGY 2009;50:333,344.) [source] Use of dispersal,vicariance analysis in biogeography , a critiqueJOURNAL OF BIOGEOGRAPHY, Issue 1 2010Ullasa Kodandaramaiah Abstract Aim, Analytical methods are commonly used to identify historical processes of vicariance and dispersal in the evolution of taxa. Currently, dispersal,vicariance analysis implemented in the software diva is the most widely used method. Despite some recognized shortcomings of the method, it has been treated as error-free in many cases and used extensively as the sole method to reconstruct histories of taxa. In light of this, an evaluation of the limitations of the method is needed, especially in relation to several newer alternatives. Methods, In an approach similar to simulation studies in phylogenetics, I use hypothetical taxa evolving in specific geological scenarios and test how well diva reconstructs their histories. Results,diva reconstructs histories accurately when evolution has been simple; that is, where speciation is driven mainly by vicariance. Ancestral areas are wrongly identified under several conditions, including complex patterns of dispersals and within-area speciation events. Several potentially serious drawbacks in using diva for inferences in biogeography are discussed. These include the inability to distinguish between contiguous range expansions and across-barrier dispersals, a low probability of invoking extinctions, incorrect constraints set on the maximum number of areas by the user, and analysing the ingroup taxa without sister groups. Main conclusions, Most problems with inferences based on diva are linked to the inflexibility and simplicity of the assumptions used in the method. These are frequently invalid, resulting in spurious reconstructions. I argue that it might be dangerous to rely solely on diva optimization to infer the history of a group. I also argue that diva is not ideally suited to distinguishing between dispersal and vicariance because it cannot a priori take into account the age of divergences relative to the timing of barrier formation. I suggest that other alternative methods can be used to corroborate the findings in diva, increasing the robustness of biogeographic hypotheses. I compare some important alternatives and conclude that model-based approaches are promising. [source] Adrenarche and Bone Modeling and Remodeling at the Proximal Radius: Weak Androgens Make Stronger Cortical Bone in Healthy Children,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2003Thomas Remer Abstract Adrenarche, the physiological increase in adrenal androgen secretion, may contribute to better bone status. Proximal radial bone and 24-h urinary steroid hormones were analyzed cross-sectionally in 205 healthy children and adolescents. Positive adrenarchal effects on radial diaphyseal bone were observed. Obviously, adrenarche is one determinant of bone mineral status in children. Introduction: Increased bone mass has been reported in several conditions with supraphysiological adrenal androgen secretion during growth. However, no data are available for normal children. Therefore, our aim was to examine whether adrenal androgens within their physiological ranges may be involved in the strengthening of diaphyseal bone during growth. Methods: Periosteal circumference (PC), cortical density, cortical area, bone mineral content, bone strength strain index (SSI), and forearm cross-sectional muscle area were determined with peripheral quantitative computed tomography (pQCT) at the proximal radial diaphysis in healthy children and adolescents. All subjects, aged 6,18 years, who collected a 24-h urine sample around the time of their pQCT analysis (100 boys, 105 girls), were included in the present study, and major urinary glucocorticoid (C21) and androgen (C19) metabolites were quantified using gas chromatography-mass spectrometry. Results and Conclusions: We found a significant influence of muscularity, but not of hormones, on periosteal modeling (PC) before the appearance of pubic hair (prepubarche). Similarly, no influence of total cortisol secretion (C21) was seen on the other bone variables. However, positive effects of C19 on cortical density (p < 0.01), cortical area (p < 0.001), bone mineral content (p < 0.001), and SSI (p < 0.001),reflecting, at least in part, reduction in intracortical remodeling,were observed in prepubarchal children after muscularity or age had been adjusted for. This early adrenarchal contribution to proximal radial diaphyseal bone strength was further confirmed for all cortical variables (except PC) when, instead of C19 and C21, specific dehydroepiandrosterone metabolites were included as independent variables in the multiple regression model. During development of pubic hair (pubarche), muscularity and pubertal stage rather than adrenarchal hormones seemed to influence bone variables. Our study shows that especially the prepubarchal increase in adrenal androgen secretion plays an independent role in the accretion of proximal radial diaphyseal bone strength in healthy children. [source] A review of the psychosocial issues for nurses in male genitalia-related careJOURNAL OF CLINICAL NURSING, Issue 8 2008MMed (Cardiovascular Surgery), Yu-Li Zang BMed (Nursing) Aim., This literature review aimed to highlight psychosocial issues for nurses in the practice of male genitalia-related care so as to guide the improvement of the teaching and practice of male genitalia-related care. Background., Male genitalia-related care is common in hospitals and in the community. In several conditions, e.g. incontinence, postradiotherapy or following operation for cancer of genitalia, bladder, colon or rectum, patients will require male genitalia-related care. Patients who require male genitalia-related care may encounter psychosocial and/or sexual dysfunction. In the holistic approach to men's health, nurses are expected to meet patients' psychosocial and sexual needs, while the literature suggests that nurses' perceptions and attitudes in providing certain male genitalia-related care, e.g. genital hygiene, sexual counselling, are negative. Method., Systematic literature review. Conclusion., Issues surrounding male genitalia-related care for nurses are complicated and may be related to privacy, intimacy, sexuality, dirty work and emotional discomfort. Age, gender, race and social class could compound these issues. Relevance to clinical practice., Nurses' negative perceptions, responses and attitudes towards male genitalia-related care may exacerbate patients' conditions under which male genitalia-related care is required. Appropriate strategies should be developed to overcome these problems. [source] Unusual hypersensitivity to warfarin in a critically ill patientJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 5 2004H. Konishi PhD Summary A patient was admitted to the intensive care unit because of respiratory failure, and warfarin therapy was started at 2 mg/day for the treatment of pulmonary embolism, together with other medications. Despite the low dosage of warfarin, international normalized ratio (INR) was markedly elevated from 1·15 to 11·28 for only 4 days, and bleeding symptoms concurrently developed. Vitamin K2 was infused along with discontinuation of warfarin. One day later, the INR was found to have decreased, and bleeding was also improved. An objective causality assessment indicated a probable relationship between clotting abnormality and warfarin administration, although the degree of elevation of the INR was unusual in the light of the daily warfarin dose and duration of its exposure. Based on the clinical status of the patient, it was suspected that several conditions contributed to the abnormal hypersensitivity to warfarin. Contributory factors probably included pharmacokinetic interactions with co-administrated drugs, vitamin K deficiency caused by decreased dietary intake, reduced gut bacterial production, impaired intestinal absorption and hepatic synthetic capacity, and increased consumption of clotting factors. In view of our experience in the present case, it should be stressed that close monitoring of coagulation capacity is necessary in critically ill patients in order to avoid fatal haemorrhage after initiating warfarin therapy regardless of the dosage. [source] Novel experiments and a mechanistic model for macroinstabilities in stirred tanksAICHE JOURNAL, Issue 2 2006A. Paglianti Abstract In this work a new experimental technique and a simple model for the identification and the analysis of macro-instabilities (MIs) in stirred tanks are presented. A pressure transducer is proposed for detecting the MIs that can take place inside a stirred vessel; its main advantages are the non-intrusivity, cheapness, and simplicity of installation and operation. Moreover, it can be used for both laboratory and industrial scale stirred tanks. The experimental technique and the time series analysis method, based on Fast Fourier Transform (FFT), are shown to provide reliable information on the frequency of MIs, through the comparison of the present data with those, from literature, obtained in similar systems. Its applicability to solid-liquid systems is also assessed. Afterwards, the data collected in several conditions differing by geometric characteristics of the stirred tanks and by the physical properties of the systems are presented. Finally, a new simplified model, based on the theory of impinging jets,1 is suggested for predicting the MI frequency. © 2005 American Institute of Chemical Engineers AIChE J, 2006 [source] Changes in the rRNA levels of specific microbial groups in activated sludge during sample handling and storageLETTERS IN APPLIED MICROBIOLOGY, Issue 2 2005J.E. Keith Abstract Aims:, To quantitatively analyse the changes in group-specific rRNA levels in activated sludge as a function of sample handling and storage procedure. Methods and Results:, Quantitative membrane hybridizations with 32P-labelled oligonucleotide probes were used to analyse the effects of different sample handling and storage conditions on the relative rRNA levels of the alpha, beta, and gamma-Proteobacteria, the Cytophaga-Flavobacteria group, and the mycolic acid-containing actinomycetes in activated sludge. Group-specific rRNA levels, expressed as percentages of total 16S rRNA detected with a universal probe, in samples maintained at room temperature significantly changed after 48 h. Group-specific rRNA levels in samples treated with chloramphenicol showed significant change after 72 h. Conclusions:, Sample storage at room temperature is a viable option if freezing or analysis can be performed within 24 h, while treatment with chlorampenicol can extend that time to at least 48 h. Significance and Impact of the Study:, Handling, shipping, and storage of environmental samples under several conditions may result in inaccurate determination of the microbial populations in microbial ecology studies. [source] A risk-factor model of epistatic interaction, focusing on autismAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 5 2002Marshall B. Jones Abstract Research to date on the genetics of autism has not uncovered a major susceptibility locus and indications are that a number of genes, perhaps as many as 15,20, may play detectable but minor roles in the etiology of the condition. To cope with this situation, a risk-factor model based on standard epidemiologic designs is proposed. The model supposes that adding a factor to a fixed set of existing factors always increases the total risk. Thus, according to the model genetic contributions cumulate but are not necessarily additive. A threshold, hence, epistasis is required. The model is applied to several conditions in which the risk of autism is elevated, some genetic (fragile X, tuberous sclerosis) and some exogenous (rubella and thalidomide embryopathies). Male gender is discussed as a risk factor. This approach is contrasted primarily with Gillberg and Coleman's view of autism as "a syndrome or series of syndromes caused by many different separate individual diseases." The principal point of difference is whether the effects of different causes cumulate or do not cumulate. In the present approach they do, in Gillberg and Coleman's they do not. © 2002 Wiley-Liss, Inc. [source] Crystallization and preliminary X-ray analysis of a DNA dodecamer containing 2,-deoxy-5-formyluridine; what is the role of magnesium cation in crystallization of Dickerson-type DNA dodecamers?ACTA CRYSTALLOGRAPHICA SECTION D, Issue 2 2001Masaru Tsunoda To investigate the role of divalent cations in crystal packing, four different crystals of a Dickerson-type dodecamer with the sequence d(CGCGAATXCGCG), containing 2,-deoxy-5-formyluridine at X, were obtained under several conditions with and without divalent cations. The crystal structures are all isomorphous. The octahedrally hydrated magnesium cations found in the major groove cement the two neighbouring duplexes along the b axis. In the Mg2+ -free crystals, a five-membered ring of water molecules occupies the same position as the magnesium site and connects the two duplexes similarly to the hydrated Mg2+ ion. It has been concluded that water molecules can take the place of the hydrated magnesium cation in crystallization, but the magnesium cation is more effective and gives X-ray diffraction at slightly higher resolution. In all four crystals, the 5-formyluracil residues form the canonical Watson,Crick pair with adenine residues. [source] Crystallization and diffraction patterns of the oxy and cyano forms of the Lucina pectinata haemoglobins complexACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 1 2009Carlos R. Ruiz-Martínez The native oxygen-carrier haemoglobins complex (HbII,III) is composed of haemoglobin II (HbII) and haemoglobin III (HbIII), which are found in the ctenidia tissue of the bivalve mollusc Lucina pectinata. This protein complex was isolated and purified from its natural source and crystallized using the vapour-diffusion and capillary counter-diffusion methods. Oxy and cyano derivatives of the complex crystallized using several conditions, but the best crystals in terms of quality and size were obtained from sodium formate pH 5 using the counter-diffusion method in a single capillary. Crystals of the oxy and cyano complexes, which showed a ruby-red colour and nonsingular prismatic shapes, scattered X-rays to resolution limits of 2.15 and 2.20,Ĺ, respectively, using a 0.886,Ĺ synchrotron-radiation source. The crystals belonged to the tetragonal system, space group P42212, with unit-cell parameters a = b = 74.07, c = 152.07 and a = b = 73.83, c = 152.49,Ĺ for the oxy and cyano complexes, respectively. The asymmetric unit of both crystals is composed of a single copy of the heterodimer, with Matthew coefficients (VM) of 3.08 and 3.06,Ĺ3,Da,1 for the oxy and cyano complexes, respectively, which correspond to a solvent content of approximately 60.0% by volume. [source] A review of Donnai-Barrow and facio-oculo-acoustico-renal (DB/FOAR) syndrome: Clinical features and differential diagnosisBIRTH DEFECTS RESEARCH, Issue 1 2009Barbara R. Pober Abstract Mutations in the gene LRP2 have recently been identified as the cause of Donnai-Barrow and Facio-oculo-acoustico-renal (DB/FOAR) syndrome. More than two dozen cases, the first reported more than 30 years ago by Holmes, have been published. Summarizing available information, we highlight the cardinal features of the disorder found in ,90% of published cases. These features include: agenesis of the corpus callosum, developmental delay, enlarged anterior fontanelle, high myopia, hypertelorism, proteinuria, and sensorineural hearing loss. Congenital diaphragmatic hernia and omphalocele are reported in only half of the patients. There is no evidence for genotype-phenotype correlation, though the sample size is too small to preclude this with certainty. Although several conditions to consider in the differential diagnosis are highlighted, the diagnosis of DB/FOAR syndrome should not be difficult to establish as its constellation of findings is strikingly characteristic. Birth Defects Research (Part A), 2009. © 2008 Wiley-Liss, Inc. [source] The molecular genetics of the genodermatoses: progress to date and future directionsBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2003A.D. Irvine Summary The Human Genome Mapping Project and allied rapid advances in genetic technology over the past decade have facilitated accurate association of allelic variations in several genes with specific skin phenotypes. Currently the genetic bases of the majority of the more common genodermatoses have been elucidated. In scientific terms this work has been extraordinarily successful and has yielded many new biological insights. These advances, although exciting, have yet to be translated into direct benefit for patients with these diseases. Genetic counselling has been greatly aided by gene identification, by the better understanding of genotype,phenotype correlation and by the disclosure of unexpected genetic mechanisms in some families. Knowledge of the molecular basis of these disorders has also been vital in enabling DNA-based prenatal diagnosis in several conditions and DNA-based preimplantation diagnosis has been used in a selected few. While this successful period of gene mapping is now nearing completion, progress towards the next goal, that of developing therapeutic strategies based on the knowledge of these underlying genetic mechanisms, has proven frustratingly slow. Despite the ready access to the skin compared with solid internal organs, the challenges of cutaneous gene therapy are legion and many technical issues need to be surmounted to enable gene replacement or modification of gene expression to have a useful role in these disorders. In this article we make a comprehensive review of progress to date in gene identification, genotype,phenotype correlation, prenatal diagnosis and cutaneous gene therapy, and we examine future directions for research in this field. [source] Animal models in urological disease and sexual dysfunctionBRITISH JOURNAL OF PHARMACOLOGY, Issue S2 2006Gordon McMurray There are several conditions associated with dysfunction of the lower urinary tract or which result in a reduction in the ability to engage in satisfactory sexual function and result in significant bother to sufferers, partners and/or carers. This review describes some of the animal models that may be used to discover safe and effective medicines with which to treat them. While alpha adrenoceptor antagonists and 5-alpha-reductase inhibitors deliver improvement in symptom relief in benign prostatic hyperplasia sufferers, the availability of efficacious and well-tolerated medicines to treat incontinence is less well served. Stress urinary incontinence (SUI) has no approved medical therapy in the United States and overactive bladder (OAB) therapy is limited to treatment with muscarinic antagonists (anti-muscarinics). SUI and OAB are characterised by high prevalence, a growing ageing population and a strong desire from sufferers and physicians for more effective treatment options. High patient numbers with low presentation rates characterizes sexual dysfunction in men and women. The introduction of ViagraÔ in 1998 for treating male erectile dysfunction and the success of the phosphodiesterase type 5 inhibitor class (PDE5 inhibitor) have indicated the willingness of sufferers to seek treatment when an effective alternative to injections and devices is available. The main value of preclinical models in discovering new medicines is to predict clinical outcomes. This translation can be established relatively easily in areas of medicine where there are a large number of drugs with different underlying pharmacological mechanisms in clinical usage. However, apart from, for example, the use of PDE5 inhibitors to treat male erectile dysfunction and the use of anti-muscarinics to treat OAB, this clinical information is limited. Therefore, current confidence in existing preclinical models is based on our understanding of the biochemical, physiological, pathophysiological and psychological mechanisms underlying the conditions in humans and how they are reflected in preclinical models. Confidence in both the models used and the pharmacological data generated is reinforced if different models of related aspects of the same disorder generate confirmatory data. However, these models will only be fully validated in retrospect once the pharmacological agents they have helped identify are tested in humans. British Journal of Pharmacology (2006) 147, S62,S79. doi:10.1038/sj.bjp.0706630 [source] Nonregenerative stimulation of hepatocyte proliferation in the rat: Variable effects in relation to spontaneous liver growth; a possible link with metabolic inductionCELL PROLIFERATION, Issue 5 2000C. Nadal Three procedures were used to stimulate hepatocyte proliferation in the rat without reducing liver mass, resulting in a supplementary growth which differs from the regenerative growth observed after loss of liver mass by hepatectomy or toxic necrosis. They were: (a) the ingestion of cyproterone, a cytochrome P450 inducing drug (b) the injection of an irritant which provokes glycogenesis and synthesis of acute-phase proteins (c) the injection of albumin-bound bilirubin leading to elimination of glucuronated bilirubin in bile. This ensuing supplementary growth was studied in the rat under several conditions of hepatic proliferation: 1In normal adult rats, in which hepatocyte proliferation is very low, the effect on proliferation was either weak or undetectable. 2In suckling rats, with a rapid body and liver growth, all the stimulants provoked a synchronized wave of proliferation with a steep increase of the percentage of S-phase hepatocytes from 4.5% in controls to 15,30% in treated rats. This increase was followed by a compensatory period of low proliferation during which a treatment with a second stimulant was much less effective. 3In 2/3 hepatectomized adult rats, the proliferation induced by cyproterone was higher than the spontaneous regenerative proliferation alone and additional to it during all of the regenerative process. The proliferation induced by acute inflammation was competitive with the synchronous spontaneous proliferation during the early period of synchronized proliferation following surgery, suggesting that both are similar acute responses. Differently, during the late period of lower and unsynchronized regenerative proliferation, the proliferation provoked by acute inflammation was additional to the spontaneous one. A stimulation of proliferation by injection of the albumin-bilirubin complex was observed during the late period after 2/3 hepatectomy. The highest level of stimulation occurred when the liver growth and the hepatocyte proliferation were already high. This suggests that these stimulants are not complete mitogenic stimuli and need cofactors which are present during the spontaneous growth or, alternatively, that the effect of stimulants is opposed by an inhibitory mechanism present in the adult rat. [source] Inspiration-induced vasoconstrictive responses in dominant versus non-dominant handsCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 2 2005Harvey N. Mayrovitz Summary Single rapid and deep inspirations (inspiratory gasps, IG) result in arteriolar vasoconstriction with concomitant transient decreases in skin blood flow that are most prominent in fingers and toes. Vascular responses (inspiratory gasp responses, IGR) are determined as the maximum percentage reduction in blood flow and have been used to assess sympathetic neurovascular function in several conditions. Previous studies have described various features of the response but there has been no reported systematic investigation of the degree of similarity between IGR obtained on dominant and non-dominant hands. This aspect is important in procedures that may use IGR to evaluate suspected unilateral sympathetic dysfunction of a limb-pair or to test the effectiveness of physiological interventions imposed on a single limb of a pair. Thus, the goal of our study was to compare IGR magnitudes that were simultaneously determined in paired-fingers of dominant and non-dominant hands. In 30 healthy seated subjects, skin blood perfusion via laser-Doppler (SBF) was measured on the dorsum of the middle finger of both hands while subjects performed three sequential IG at 3-min intervals. Analysis of variance for repeated measures revealed no significant difference in IGR between dominant (79·3 ± 11·2%) and non-dominant hands (81·9 ± 11·6%, P = 0·965) with an overall IGR of 80·6 ± 11·4%. These results indicate that hand-dominance is not a factor that is likely to significantly effect IGR differentials determined in paired-limbs. [source] |