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Translational Research (translational + research)
Selected AbstractsBRIEF ALCOHOL INTERVENTION: TIME FOR TRANSLATIONAL RESEARCHADDICTION, Issue 6 2010EILEEN KANER No abstract is available for this article. [source] TRANSLATIONAL RESEARCH GOES BOTH WAYS: LESSONS FROM CLINICAL STUDIESCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2008John W Funder SUMMARY 1It is currently assumed that translational research goes from benchtop to bedside; that aldosterone elevates blood pressure via its effects on salt and water homeostasis; that mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) share a common immediate ancestor; and that aldosterone plays a deleterious role in essential hypertension and heart failure. 2Meta-analysis of clinical trials in essential hypertension, in which eplerenone was dose-titrated to attain diastolic blood pressure < 90 mmHg, showed no relationship between blood pressure response and electrolyte effects, as judged by change in plasma (K). 3Reexamination of sequence data, and insights from the S810L MR mutant gene causing juvenile hypertension exacerbated by pregnancy, suggest that MR were the first to branch off the primordial ancestor for MR, GR, androgen receptors (AR) and progesterone receptors (PR). 4In clinical trials of MR blockade in heart failure and essential hypertension baseline aldosterone levels are in the low to normal range and sodium status unremarkable. Under such circumstances cortisol appears to be responsible for MR activation, thus exculpating aldosterone in these conditions. 5On the basis of these clinical studies, there is need to revisit the basic biology of aldosterone and MR as translational research very clearly goes both ways. [source] A Vision for Growth: The Best of Basic, Clinical, and Translational ResearchJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2004FRACP Editor-in-Chief, John Eisman MBBS No abstract is available for this article. [source] Translational Research: Animal Models of Obliterative Bronchiolitis after Lung TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009M. Sato Obliterative bronchiolitis (OB) or chronic graft dysfunction remains the major limitation to long-term success of lung transplantation. Investigation using animal models is a critical component of research to understand the underlying pathological mechanisms and to develop novel preventive and therapeutic strategies for OB. Multiple animal models of OB exist, including orthotopic lung transplantation in rodents and large animals, orthotopic tracheal transplantation and heterotopic transplantation of a trachea in variable sites such as subcutaneous, intraomental and intrapulmonary sites. The most important issue for researchers is not specifically which model is the best but which is the most appropriate model to test their scientific hypothesis. For example, while orthotopic lung transplantation best mimics the overall surgical procedure, a question regarding fibrotic processes of OB may be better answered using heterotopic tracheal transplant models because of their reliable reproducibility of allograft obliterative airway fibrosis. Animal models should be continuously refined, modified and sometimes combined to fit the particular research purpose. We review the available animal models, their modifications and possible applications to assist researchers in choosing the appropriate model for their intended research. [source] Translational research in liver disease,HEPATOLOGY, Issue 4 2008Margaret James Koziel No abstract is available for this article. [source] Translational research to identify clinical applications of hepatocyte growth factorHEPATOLOGY RESEARCH, Issue 8 2009Akio Ido Hepatocyte growth factor (HGF), originally purified from the plasma of patients with fulminant hepatic failure, has been shown to carry out various physiological functions. HGF not only stimulates liver regeneration, but also acts as an antiapoptotic factor in in vivo experimental models. Therefore, HGF is a promising therapeutic agent for the treatment of fatal liver diseases, including fulminant hepatic failure. After performing a number of preclinical tests, our group began an investigator-initiated registered phase I/II clinical trial of patients with fulminant hepatic failure to examine the safety and clinical efficacy of recombinant human HGF. In this article, we will discuss the basic research results as well as the translational research that underpins current attempts to use HGF in various clinical settings. [source] Translational approaches to understanding anorexia nervosaINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue S1 2005Diane A. Klein MD Abstract Translational research has fostered significant gains in neuroscience and psychiatry and has been identified by the NIMH as a "priority area" for further funding. As applied to anorexia nervosa (AN), "translational research" describes the application of principles and methodologies employed in related fields to advance the understanding, and ultimately treatment and prevention, of this disorder. Several promising areas of translational research in AN are identified. Such research, particularly when linked to a conceptual framework, offers the potential of lending much-needed novel insight into this challenging and enigmatic disorder. © 2005 by Wiley Periodicals, Inc. [source] NerveCenter: Translational research and the shifting landscape for physician,scientistsANNALS OF NEUROLOGY, Issue 3 2010Kathlyn Stone No abstract is available for this article. [source] Culture and in vitro hepatogenic differentiation of placenta-derived stem cells, using placental extract as an alternative to serumCELL PROLIFERATION, Issue 5 2010K. S. Shin Objectives:, Translational research using adult stem cells derived from various tissues has been highlighted in cell-based therapy. However, there are many limitations to using conventional culture systems of adult stem cells for clinically applicability, including limited combinations of cytokines and use of nutrients derived from animals. Here, we have investigated the effects of placental extract (PE) for culture of placenta-derived stem cells (PDSCs) as well as their potential for hepatogenic differentiation. Materials and methods:, Placental extract, extracted using water-soluble methods, was used as a supplement for culture of PDSCs. Cell viability was determined using the MTT assay, and cytokine assay was performed using Luminex assay kit. Gene expression, indocyanine green (ICG) up-take, PAS (Periodic Acid-Schiff) staining and urea production were also analysed. Results:, The placental extract contained several types of cytokine and chemokine essential for maintenance and differentiation of stem cells. Expression of stemness markers in PDSCs cultured with PE is no different from that of PDSCs cultured with foetal bovine serum (FBS). After hepatogenic differentiation, expression patterns for hepatocyte-specific markers in PDSCs cultured with PE were consistent and potential for hepatogenic differentiation of PDSCs cultured with PE was similar to that of PDSCs cultured with FBS, as shown by PAS staining and urea production assays. Conclusions:, Our findings revealed that placental extract could be used as a new component for culture of adult stem cells, as well as for development of human-based medium, in translational research for regenerative medicine. [source] THE MOLECULAR FUTURE IN CYTOLOGYCYTOPATHOLOGY, Issue 2006M. Salto-Tellez Molecular diagnosis is the application of molecular biology techniques and knowledge of the molecular mechanisms of disease to diagnosis, prognostication and treatment of diseases. Molecular Diagnosis is, arguably, the fastest growing area of diagnostic medicine. The US market for molecular testing generated $1.3 billion in 2000, which was predicted to increase to about $4.2 billion by 2007.1 We proposed the term Diagnostic Molecular Cytopathology to define the application of molecular diagnosis to cytopathology2. Diagnostic Molecular Cytopathology is essential for the following reasons: (i) Molecular testing is sometimes indispensable to establish an unequivocal diagnosis on cell preparations; (ii) Molecular testing provides extra information on the prognosis or therapy of diseases diagnosed by conventional cytology; (iii) Molecular testing provides genetic information on the inherited nature of diseases that can be directly investigated in cytology samples, by either exfoliation or by fine needle aspiration; (iv) Sometimes the cytopathology sample is the most convenient (or the only available) source of material for molecular testing; (v). Direct molecular interrogation of cells allows for a diagnostic correlation that would otherwise not be possible. Parallel to this direct diagnostic implication, cytopathology is increasing important in the validation of biomarkers for specific diseases, and in therefore of significant importance in the overall translational research strategies. We illustrate its application in some of the main areas of oncology molecular testing, such as molecular fingerprinting of neoplasms,3 lymphoreticular diseases,2 sarcomas4 and lung cancer,5 as well as translational research using diagnostic cytopathology techniques. The next years will see the consolidation of Diagnostic Molecular Cytopathology, a process that will lead to a change of many paradigms. In general, diagnostic pathology departments will have to reorganize molecular testing to pursue a cost-efficient operation. Sample preparation will have to take into account optimal preservation of nuclear acids. The training of technical staff and the level of laboratory quality control and quality assurance would have to follow strict clinical (not research) laboratory parameters. And, most importantly, those pathologists undertaking molecular diagnosis as a discipline would have to develop their professional expertise within the same framework of fellowships and professional credentials that is offered in other sub-specialties. The price to pay if this effort is not undertaken is too important for the future of diagnostic pathology in general. The increasing characterization of molecular biomarkers with diagnostic, prognostic or therapeutic value is making the analysis of tissue and cell samples prior to treatment a more complex exercise. If cytopathologists and histopathologists allow others to take charge of molecular diagnosis, our overall contribution to the diagnostic process will be diminished. We may not become less important, but we may become less relevant. However, those within the discipline of diagnostic pathology who can combine the clinical background of diseases with the morphological, immunocytochemical and molecular diagnostic interpretation will represent bona fide diagnostic specialists. Such ,molecular cytopathologists' would place themselves at the centre of clinical decision-making. Reference:, 1. Liz Fletcher. Roche leads molecular diagnostics charge. Nature Biotechnol 20, 6,7; 2002 2. Salto-Tellez M and Koay ESC. Molecular Diagnostic Cytopathology - Definitions, Scope and Clinical Utility. Cytopathology 2004; 15:252,255 3. Salto-Tellez M, Zhang D, Chiu LL, Wang SC, Nilsson B, and Koay ESC. Immunocytochemistry Versus Molecular Fingerprinting of Metastases. Cytopathology, 2003 Aug; 14(4):186,90. 4. Chiu LL, Koay SCE, Chan NL and Salto-Tellez M. Molecular Cytopathology: Sequencing of the EWS-WT1 Gene Fusion Transcript in the Peritoneal Effusion of a Patient with Desmoplastic Small Round Cell Tumour. Diagnostic Cytopathology, 2003 Dec; 29(6): 341,3. 5. TM Chin, D Anuar, R Soo, M Salto-Tellez, WQ Li, B Ahmad, SC Lee, BC Goh, K Kawakami, A Segal, B Iacopetta, R Soong. Sensitive and Cost-Effective deptection of epidermal growth factor Receptor Mutations in Small Biopsies by denaturing High Performance Liquid Chromatography. (In press). [source] CLINICAL TRIALS AND SCID ROW: THE ETHICS OF PHASE 1 TRIALS IN THE DEVELOPING WORLDDEVELOPING WORLD BIOETHICS, Issue 3 2007JONATHAN KIMMELMAN ABSTRACT Relatively little has been written about the ethics of conducting early phase clinical trials involving subjects from the developing world. Below, I analyze ethical issues surrounding one of gene transfer's most widely praised studies conducted to date: in this study, Italian investigators recruited two subjects from the developing world who were ineligible for standard of care because of economic considerations. Though the study seems to have rendered a cure in these two subjects, it does not appear to have complied with various international guidelines that require that clinical trials conducted in the developing world be responsive to their populations' health needs. Nevertheless, policies devised to address large scale, late stage trials, such as the AZT short-course placebo trials, map somewhat awkwardly to early phase studies. I argue that interest in conducting translational research in the developing world, particularly in the context of hemophilia trials, should motivate more rigorous ethical thinking around clinical trials involving economically disadvantaged populations. [source] Challenges in translational researchEMBO MOLECULAR MEDICINE, Issue 2 2009Giulio Cossu No abstract is available for this article. [source] Sing the mind electric , principles of deep brain stimulationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2010Morten L. Kringelbach Abstract The remarkable efficacy of deep brain stimulation (DBS) for a range of treatment-resistant disorders is still not matched by a comparable understanding of the underlying neural mechanisms. Some progress has been made using translational research with a range of neuroscientific techniques, and here we review the most promising emerging principles. On balance, DBS appears to work by restoring normal oscillatory activity between a network of key brain regions. Further research using this causal neuromodulatory tool may provide vital insights into fundamental brain function, as well as guide targets for future treatments. In particular, DBS could have an important role in restoring the balance of the brain's default network and thus repairing the malignant brain states associated with affective disorders, which give rise to serious disabling problems such as anhedonia, the lack of pleasure. At the same time, it is important to proceed with caution and not repeat the errors from the era of psychosurgery. [source] New school in liver development: Lessons from zebrafish,HEPATOLOGY, Issue 5 2009Jaime Chu There is significant overlap in the genes and pathways that control liver development and those that regulate liver regeneration, hepatic progenitor cell expansion, response to injury, and cancer. Additionally, defects in liver development may underlie some congenital and perinatal liver diseases. Thus, studying hepatogenesis is important for understanding not only how the liver forms, but also how it functions. Elegant work in mice has uncovered a host of transcription factors and signaling molecules that govern the early steps of hepatic specification; however, the inherent difficulty of studying embryogenesis in utero has driven developmental biologists to seek new systems. The rapidly developing vertebrate zebrafish is a favorite model for embryology. The power of forward genetic screens combined with live real-time imaging of development in transparent zebrafish embryos has highlighted conserved processes essential for hepatogenesis and has uncovered some exciting new players. This review presents the advantages of zebrafish for studying liver development, underscoring how studies in zebrafish and mice complement each other. In addition to their value for studying development, zebrafish models of hepatic and biliary diseases are expanding, and using these small, inexpensive embryos for drug screening has become de rigueur. Zebrafish provide a shared platform for developmental biology and translational research, offering innovative methods for studying liver development and disease. The story of hepatogenesis has something for everyone. It involves transcriptional regulation, cell-cell interaction, signaling pathways, control of cell proliferation and apoptosis, plus morphogenic processes that sculpt vasculature, parenchymal cells, and mesenchyme to form the multifaceted liver. Decades of research on liver development in mice and other vertebrates offer valuable lessons in how the multipotent endoderm is programmed to form a functional liver. Of equal importance are insights that have illuminated the mechanisms by which hepatic progenitors are activated in a damaged liver, how the adult liver regenerates, and, possibly, the basis for engineering liver cells in vitro for cell transplantation to sustain patients with liver failure. Moreover, processes that are key to liver development are often co-opted during pathogenesis. Therefore, reviewing hepatogenesis is informative for both basic and translational researchers. In this review, we bring to light the many advantages offered by the tropical freshwater vertebrate zebrafish (Danio rerio) in studying hepatogenesis. By comparing zebrafish and mice, we highlight how work in each system complements the other and emphasize novel paradigms that have been uncovered using zebrafish. Finally, we highlight exciting efforts using zebrafish to model hepatobiliary diseases. (HEPATOLOGY 2009.) [source] Translational research to identify clinical applications of hepatocyte growth factorHEPATOLOGY RESEARCH, Issue 8 2009Akio Ido Hepatocyte growth factor (HGF), originally purified from the plasma of patients with fulminant hepatic failure, has been shown to carry out various physiological functions. HGF not only stimulates liver regeneration, but also acts as an antiapoptotic factor in in vivo experimental models. Therefore, HGF is a promising therapeutic agent for the treatment of fatal liver diseases, including fulminant hepatic failure. After performing a number of preclinical tests, our group began an investigator-initiated registered phase I/II clinical trial of patients with fulminant hepatic failure to examine the safety and clinical efficacy of recombinant human HGF. In this article, we will discuss the basic research results as well as the translational research that underpins current attempts to use HGF in various clinical settings. [source] Are Australasian academic physicians an endangered species?INTERNAL MEDICINE JOURNAL, Issue 11 2007A. Wilson Abstract It has been stated that academic medicine is in a worldwide crisis. Is this decline in hospital academic practice a predictable consequence of modern clinical practice with its emphasis on community and outpatient-based services as well as a corporate health-care ethos or does it relate to innate problems in the training process and career structure for academic clinicians? A better understanding of the barriers to involvement in academic practice, including the effect of gender, the role and effect of overseas training, expectation of further research degrees and issues pertaining to the Australian academic workplace will facilitate recruitment and retention of the next generation of academic clinicians. Physician-scientists remain highly relevant as medical practice and education evolves in the 21st century. Hospital-based academics carry out a critical role in the ongoing mentoring of trainees and junior colleagues, whose training is still largely hospital based in most specialty programmes. Academic clinicians are uniquely placed to translate the rapid advances in medical biology into the clinical sphere, by guiding and carrying out translational research as well as leading clinical studies. Academic physicians also play key leadership in relations with government and industry, in professional groups and medical colleges. Thus, there is a strong case to assess the problems facing recruitment and retention of physician-scientists in academic practice and to develop workable solutions. [source] Translational approaches to understanding anorexia nervosaINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue S1 2005Diane A. Klein MD Abstract Translational research has fostered significant gains in neuroscience and psychiatry and has been identified by the NIMH as a "priority area" for further funding. As applied to anorexia nervosa (AN), "translational research" describes the application of principles and methodologies employed in related fields to advance the understanding, and ultimately treatment and prevention, of this disorder. Several promising areas of translational research in AN are identified. Such research, particularly when linked to a conceptual framework, offers the potential of lending much-needed novel insight into this challenging and enigmatic disorder. © 2005 by Wiley Periodicals, Inc. [source] Surgeons and scientists: Working together in embryo researchJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2009Alison P. Murdoch Abstract Most surgeons in academic hospitals will have had a request from an enthusiastic research scientist to take samples of tissue during an operation. It seems reasonable and most patients will respond positively. But of course it is not quite that simple. The regulation of donation of human tissue for basic research is clearly defined but usually less rigorous than that which covers translational research and clinical trials. An exception has been the donation of embryos for embryonic stem cell derivation. The specific issues related to obtaining cells from patients for this work has resulted in a different relationship between scientist and clinician. This will be considered. J. Cell. Biochem. 108: 1,2, 2009. © 2009 Wiley-Liss, Inc. [source] Emerging targets and novel strategies in the treatment of AIDS-related Kaposi's sarcoma: Bidirectional translational scienceJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2006Bruce J. Dezube Through the mentorship process, Dr. Arthur Pardee emphasized the critical importance of bidirectional translational research,not only advancing drug development from bench to bedside, but also bringing back precious clinical material to the laboratory to assess the biologic effects of therapeutic agents on their targets. This mini-review focuses on the signal transduction pathways of Kaposi's sarcoma (KS) and on how the knowledge of such pathways has led to the rational development of molecularly targeted pathogenesis-driven therapies. Acquired immune deficiency syndrome (AIDS) related-KS results from co-infection with human immunodeficiency virus and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8), which leads to the development of an angiogenic-inflammatory state that is critical in the pathogenesis of KS. KS is driven by KSHV/HHV8-specific pathways, which include viral G protein-coupled receptor (vGPCR), viral interleukin-6 (vIL-6), and viral chemokine homologues. In addition, cellular growth/angiogenic pathways, such as vascular endothelial growth factor (VEGF), insulin-like growth factor, platelet-derived growth factor (PDGF), angiopoietin and matrix metalloproteinases (MMPs) are "pirated" by KSHV/HHV8. As a very tangible example of how translational research has led to a marked improvement in patient outcome, the signal transduction inhibitor imatinib (a tyrosine kinase inhibitor of c-kit and PDGF) was administered to patients with KS whose tumors were serially biopsied. Not only did the patients' tumors regress, but also the regression was correlated with the inhibition of PDGF receptor (PDGFR) in the biopsy samples. Recent and future clinical trials of molecularly targeted therapy for the treatment of KS are a prelude to a shift in the paradigm of how KS is managed. J. Cell. Physiol. 209: 659,662, 2006. © 2006 Wiley-Liss, Inc. [source] From bench to bedside , translational research in psoriasisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2010JC Prinz Abstract For many years, psoriasis was firmly believed to be a disease of epidermal keratinocytes, but now is attributed to a combination of genetic and environmental factors that promote a T-cell mediated immune response in the skin. Psoriasis is now understood to be a systemic T-cell mediated autoimmune disease with the innate immune system playing an important role. Progress in understanding the pathogenesis of psoriasis has shown that following a stimulus, dendritic and T cell activation leads to the release of cytokines, chemokines and growth factors that initiate the proliferation and altered differentiation of keratinocytes. These factors subsequently lead to continuous activation of T cells and antigen-presenting cells, particularly dendritic cells, within the psoriatic plaque. This vicious cycle of psoriasis, in which the cytokines interleukin 12 (IL-12) and IL-23 play a pivotal role, is a logical target for biological therapy. [source] Cell therapies: realizing the potential of this new dimension to medical therapeuticsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 6 2008Pawanbir Singh Abstract Stem cells promise to treat conditions poorly served by conventional therapeutics. Cells from both embryonic and somatic tissues are being used to create cell therapies for genetic, traumatic and degenerative conditions. The current human, healthcare and fiscal costs of these conditions are significant. This review summarizes the use of stem cells for neurological and cardiac disorders and diabetes to determine the requirements for generic translational research to assist such therapies to be a reality. While there are multiple strategies in each disease area, with no clear favourite, there are clear opportunities in treatments that use a single cell type. A key requirement is to work with pluripotent progenitor cells to cultivate and differentiate a sufficiently large population of functioning cells. Challenges also arise in determining and achieving timely delivery of the correct dose of cells to where they can most effectively treat the disease and best benefit individual patients. Copyright © 2008 John Wiley & Sons, Ltd. [source] Translational experimental therapeutics: The translation of laboratory-based discovery into disease-related therapyMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2007Karl Kieburtz MD Abstract In the past decade, there has been an increasing emphasis on laboratory-based translational research. This has led to significant scientific advances in our understanding of disease mechanisms and in the development of novel approaches to therapy such as gene therapy, RNA interference, and stem cells. However, the translation of these remarkable scientific achievements into new and effective disease-modifying therapies has lagged behind these scientific accomplishments. We use the term "translational experimental therapeutics" to describe the pathway between the discovery of a basic disease mechanism or novel therapeutic approach and its translation into an effective treatment for patients with a specific disease. In this article, we review the components of this pathway, and discuss issues that might impede this process. Only by optimizing this pathway can we realize the full therapeutic potential of current scientific discoveries and translate the astounding advances that have been accomplished in the laboratory into effective treatments for our patients. Mt Sinai J Med 74: 7-14, 2007. Copyright © 2007 Mount Sinai School of Medicine [source] The role of the pathologist in translational and personalized medicineMOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 1 2007Daniel P. Perl MD Abstract Over the years, pathologists have served to make morphologic diagnoses for clinicians when provided with a biopsy or surgically resected tissue specimen. Traditionally, pathologists have used a series of morphologic techniques and relied on the microscopic appearance of resected tissues to determine a pathologic diagnosis and, with respect to neoplastic lesions, provide predictions of the potential growth pattern that might be anticipated. With the introduction of the techniques of molecular biology in medicine, the role of the pathologist has changed as have the tools available for characterizing pathologic specimens. With the pathologist's unique perspective on disease processes and access to tissue specimens from the operating room, he has become a key player in the area of translational and personalized medicine and the development of new approaches to diagnosis and translational research. Mt Sinai J Med 74:22,26, 2007. © 2007 Mount Sinai School of Medicine [source] Basic science and translational research in female pelvic floor disorders: Proceedings of an NIH-sponsored meetingNEUROUROLOGY AND URODYNAMICS, Issue 4 2004Anne M. Weber Abstract Aims To report the findings of a multidisciplinary group of scientists focusing on issues in basic science and translational research related to female pelvic floor disorders, and to produce recommendations for a research agenda for investigators studying female pelvic floor disorders. Methods A National Institutes of Health (NIH)-sponsored meeting was held on November 14,15, 2002, bringing together scientists in diverse fields including obstetrics, gynecology, urogynecology, urology, gastroenterology, biomechanical engineering, neuroscience, endocrinology, and molecular biology. Recent and ongoing studies were presented and discussed, key gaps in knowledge were identified, and recommendations were made for research that would have the highest impact in making advances in the field of female pelvic floor disorders. Results The meeting included presentations and discussion on the use of animal models to better understand physiology and pathophysiology; neuromuscular injury (such as at childbirth) as a possible pathogenetic factor and mechanisms for recovery of function after injury; the use of biomechanical concepts and imaging to better understand the relationship between structure and function; and molecular and biochemical mechanisms that may underlie the development of female pelvic floor disorders. Conclusions While the findings of current research will help elucidate the pathophysiologic pathways leading to the development of female pelvic floor disorders, much more research is needed for full understanding that will result in better care for patients through specific rather than empiric therapy, and lead to the potential for prevention on primary and secondary levels. © 2004 Wiley-Liss, Inc. [source] Role of translational research advancing the understanding of the pathogenesis of light chain-mediated glomerulopathiesPATHOLOGY INTERNATIONAL, Issue 7 2007Jiamin Teng Glomerulopathic light chains engage in pathological interactions with mesangial cells resulting in alterations in glomerular homeostasis. The crucial pathological events are centered in the mesangium and, therefore, research dealing with pathogenesis of these disorders is focused on this glomerular compartment. Particular physicochemical characteristics of these light chains are responsible for their ability to alter mesangial milieu leading to glomerular damage. An in vitro model has been used to dissect the processes involved. This model has been instrumental in providing a solid platform from which to observe in a dynamic fashion how mesangial cells handle pathogenic light chains and the sequential steps that are involved in the progressive glomerular damage. Key steps amenable to possible modulation have been defined and should provide a solid platform to design and test therapeutic interventions. In the past significant difficulties have been encountered in the development of animal models of light chain-induced glomerular damage. However, in the last few years a new generation of animal models has emerged to address whether what has been documented in vitro retains significance in vivo. Preliminary observations appear to substantiate this. [source] Definitions of the phenotypic manifestations of sickle cell disease,AMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2010Samir K. Ballas Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD (,100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of SCD gathered to identify and categorize the most common complications. From this group, a formal writing team was formed that further reviewed the literature, sought specialist input, and produced definitions in a standard format. This article provides an overview of the process and describes 12 body system categories and the most prevalent or severe complications within these categories. A detailed Appendix provides standardized definitions for all complications identified within each system. This report proposes use of these definitions for studies of SCD complications, so future studies can be comparably robust and treatment efficacy measured. Use of these definitions will support greater accuracy in genotype,phenotype studies, thereby achieving a better understanding of SCD pathophysiology. This should nevertheless be viewed as a dynamic rather than final document; phenotype descriptions should be reevaluated and revised periodically to provide the most current standard definitions as etiologic factors are better understood, and new diagnostic options are developed. Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc. [source] Proteomics in rheumatology: The beginning of a fairy tale?PROTEOMICS - CLINICAL APPLICATIONS, Issue 3 2008Stijn Lambrecht Abstract One of the major challenges in proteome research is to translate its applications to the setting of human diseases. Proteomics in rheumatology is an area with marked potential including applications ranging from diagnostics, over therapeutic monitoring to discovery of new potential therapeutic targets. Biomarkers will be essential to discriminate between clinical similar rheumatic diseases, to monitor disease-states or to install the best appropriate therapy. Especially in the field of rheumatology, analysis of specific genes and/or their expression products by pharmacogenetics/-genomics or pharmacoproteomics could be necessary to enable an effective, patient-tailored therapy. In rheumatology, direct examination of proteins may be of utmost importance, as it is already known that PTMs, such as citrullination of proteins or peptides, may be involved in certain rheumatic diseases. The discovery and validation of antibodies directed against citrullinated proteins/peptides in rheumatic diseases using proteome analysis approaches has been described. Gel-free methods, SELDI-approaches and classic 2-DE approaches have been deployed on body fluids as well as on target tissues in different rheumatic diseases. Proteomics in rheumatology is on the rise and pilot studies have indicated that the application of proteomics-based technologies in rheumatic diseases appears to be an exciting example of translational research. [source] Why Current Breast Pathology Practices Must Be Evaluated.THE BREAST JOURNAL, Issue 5 2007A Susan G. Komen for the Cure White Paper: June 200 To this end, the organization has a strong interest and proven track record in ensuring public investment in quality breast health and breast cancer care. Recently, Susan G. Komen for the Cure identified major issues in the practice of pathology that have a negative impact on the lives of thousands of breast cancer patients in the United States. These issues were identified through a comprehensive literature review and interviews conducted in 2005,2006 with experts in oncology, breast pathology, surgery, and radiology. The interviewees practiced in community, academic, and cooperative group settings. Komen for the Cure has identified four areas that have a direct impact on the quality of care breast cancer patients receive in the United States, the accuracy of breast pathology diagnostics, the effects of current health insurance, and reimbursement policies on patients who are evaluated for a possible breast cancer diagnosis, the substantial decrease in tissue banking participation, particularly during a time of rapid advances in biologically correlated clinical science and the role for the Susan G. Komen for the Cure, pathology professional societies and the Federal government in ensuring that breast pathology practices meet the highest possible standards in the United States Concerns surrounding the quality and practice of breast pathology are not limited to diagnostic accuracy. Other considerations include, training and proficiency of pathologists who are evaluating breast specimens, the lack of integration of pathologists in the clinical care team, inadequate compensation for the amount of work required to thoroughly analyze specimens, potential loss in translational research as a result of medical privacy regulations, and the lack of mandatory uniform pathology practice standards without any way to measure the degree of variation or to remedy it. [source] The unique value of primate models in translational researchAMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009Carol A. Shively Abstract This special issue of AJP is focused on research using nonhuman primates as models to further the understanding of women's health. Nonhuman primates play a unique role in translational science by bridging the gap between basic and clinical investigations. The use of nonhuman primates in biomedical research challenges our resolve to treat all life as sacred. The scientific community has responded by developing ethical guidelines for the care and the use of primates and clarifying the responsibility of investigators to insure the physical and psychological well-being of nonhuman primates used in research. Preclinical investigations often involve the use of animal models. Rodent models have been the mainstay of biomedical science and have provided enormous insight into the workings of many mammalian systems that h ave proved applicable to human biological systems. Rodent models are dissimilar to primates in numerous ways, which may limit the generalizability to human biological systems. These limitations are much less likely in nonhuman primates and in Old World primates, in particular, Macaques are useful models for investigations involving the reproductive system, bioenergetics, obesity and diabetes, cardiovascular health, central nervous system function, cognitive and social behavior, the musculoskeletal system, and diseases of aging. This issue considers primate models of polycystic ovary syndrome; diet effects on glycemic control, breast and endometrium; estrogen, reproductive life stage and atherosclerosis; estrogen and diet effects on inflammation in atherogenesis; the neuroprotective effects of estrogen therapy; social stress and visceral obesity; and sex differences in the role of social status in atherogenesis. Unmet research needs in women's health include the use of diets in nonhuman primate studies that are similar to those consumed by human beings, primate models of natural menopause, dementia, hypertension, colon cancer, and frailty in old age, and dedicated colonies for the study of breast cancer. Am. J. Primatol. 71:715,721, 2009. © 2009 Wiley-Liss, Inc. [source] Embryo Stem Cell Research: Ten Years of ControversyTHE JOURNAL OF LAW, MEDICINE & ETHICS, Issue 2 2010John A. Robertson This overview of 10 years of stem cell controversy reviews the moral conflict that has made ESCs so controversial and how this conflict plays itself out in the legal realm, focusing on the constitutional status of efforts to ban ESC research or ESC-derived therapies. It provides a history of the federal funding debate from the Carter to the Obama administrations, and the importance of the Raab memo in authorizing federal funding for research with privately derived ESCs despite the Dickey-Wicker ban on federal funding of embryo research. It also reviews the role that scientists themselves have played in developing regulations for ESC research, the emergence of ESCROs as special review bodies for ESC research, and the thorough consent requirements for donation of IVF embryos to ESC research. With research now transitioning from the lab to the clinic, the article reviews the challenges of ensuring safety and consent in translational research. It concludes with a call for respecting those persons who have to using or working with ESC products and an account of how obtaining stem cells from a person's own cells will alleviate some but not all of the controversy surrounding ESC research. [source] | ||||||||||||||||||||||||||||||||||